Neurological Disorders

A Handbook for
Family Physicians
Neurological Disorders
A Handbook for Family
Physicians

Author :
Dr. Alok Sharma, M.S., M.Ch.

Co-Authors :
Dr. Vishal Chafale, MD, DM (Neurology), DNB (Neurology)
Dr. Hemangi Sane, M.D. (USA)
Dr. Anupama Desai, M.D.
Dr. Nandini Gokulchandran, M.D.
Dr. Richa Bansod, M.B.B.S., M.H.A

Scientic and Research Co-ordinator :

Ms. Pooja Kulkarni
Dr. Jasbinder Kaur Dr. Guneet Chopra
Dr. Sanjay Kukreja Dr. Zafar Shaikh
Neurological Disorders
A Handbook for Family Physicians
© 2018 by NeuroGen Brain and Spine Institute Pvt. Ltd.

All rights reserved.

This book is protected by copyright. No part of this book may be reproduced in

any form by any means, including photocopying, or utilized by any information
storage and retrieval system without written permission from the copyright
owner, except for the brief quotations embodied in critical articles and reviews.

This book is basically a compilation of information / literature available on the

topic, from various sources (which have been acknowledged duly). However,
this is by no means an exhaustive resource, since the eld is evolving at a very
rapid pace. Every effort is made to ensure accuracy of material, but the
publisher, printer and author will not be held responsible for any inadvertent
error(s).

Cover Designed by
Satish Narayan
Pooja Kulkarni

Printed by
Surekha Press,
A-20, Shalimar Industrial Estate,
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Tel.: 2409 3877, 2404 3877
 Author

Dr. Alok Sharma, M.S., M.Ch.

Dr. Alok Sharma is a Neurosurgeon and is presently
the [a] Professor & Head of Department of Neurosur-
gery at the LTMG Hospital & LTM Medical College in
Sion, Mumbai as well as the [b] Director of the
NeuroGen Brain & Spine Institute in Navi Mumbai and
[c] Consultant Neurosurgeon at the Fortis Hospital in
Mulund. He completed his graduate and post graduate
studies from the Seth G.S. Medical college and KEM
Hospital of Mumbai University. Subsequently he trained overseas in Sweden,
England, Germany, USA, & Japan. He has written/edited 15 books, has over 200
scientic publications in medical journals and has made over 300 scientic
presentations in India and overseas. He has conducted several national and
international trials and has been conferred with numerous honors and awards
in his distinguished career. He has been committed to both basic as well as
clinical research to nd an answer to the problems of paralysis and neurological
decits that occur following injury and diseases of the nervous system. He has
dedicated his life to research in incurable diseases and injuries of the brain and
spine and to provide the latest and most advanced treatments for patients who
are paralyzed and disabled. He is the pioneer of stem cell therapy in India. He
setup the stem cell and genetic research laboratory at the LTMG hospital & LTM
Medical College which was the rst of its kind in Mumbai. He has also created
India's rst dedicated Stem Cell Therapy and Neurorehabilitation center in
Navi Mumbai. He is a staunch believer that stem cell therapy can relieve suffer-
ing of neurological patients. He is one of the very few people in the world who
does psychosurgery which is a form of brain surgery for people with intractable
psychiatric problems. He has pioneered various forms of minimally invasive
neurosurgeries such as stereotactic surgery and neuroendoscopy alongwith
ground breaking work in the eld of spinal surgery and Neurotrauma and has a
special interest in revascularization microvascular surgery for cerebral
ischemia. He has a special personal interest in Neurobiology of the mind and
lectures extensively on the relationship of the brain/ mind to health and disease.
He is a strong advocate of the role of yoga, meditation, natural therapy and diet
in the prevention of various modern illnesses. In summary, he is a Neurosur-
geon, Medical Teacher and Scientist who is attempting to combine the best of
science, medicine and humanity to make a difference to the lives of people who
are suffering from neurological disorders.
 Co-Author

Dr Vishal A Chafale, MD (Medicine), DM (Neurology), DNB

(Neurology), Fellowship in Interventional Neurology
Dr. Vishal A Chafale is a Consultant and Interventional Neu-
rologist, practising in Navi Mumbai. Dr. Chafale has com-
pleted his MD (Medicine) from SS Medical College Rewa. Post
MD he has done his super specialisation in Neurology from
Bangur Institute of Neurosciences Kolkata and DNB Neurol-
ogy from National Board of Examinations. During his tenure
in Kolkata he developed special interest in vascular Neurology and to pursue it
he did his advanced fellowship in Interventional Neurology SNVI Mumbai. Dr
Vishal has 5 years of clinical experience as a Neurologist. He has peer reviewed
various publications in the eld of Neurology and Vascular Neurology. He has
many articles published in indexed Journals.

Dr. Hemangi Sane, M.D. (USA)

Dr. Hemangi Sane is the Deputy director and Head of the
research and development department at NeuroGen Brain
and Spine Institute, Navi Mumbai. Dr. Sane has completed her
MD Internal Medicine from the New York Medical College
and has clinical experience as an Internal medicine physician
in USA after graduating from Seth G.S Medical College. With
20 years of clinical experience, she has more than 78 scientic
peer reviewed publications to her name in the eld of stem cell therapy. She has
co-authored more than 12 medical books & multiple chapters in international
books. Recently she has been recognized as one of the 'Leading physicians of the
world' by The international association of internists, USA. She was awarded at
the International Women's day by the Mayor of Mumbai & “Iconic Women
creating a better world for all” by World Economic Forum . She is also the
founder of Asha Ek Hope foundation for ALS/MND in India.

Dr. Anupama Desai, M.D.

Dr. Anupama Desai is currently working as Associate Professor
in Dept. of Pharmacology at Surat Municipal Institute of Medical
Education & Research (SMIMER), Surat, Gujarat. She did her
MBBS & MD (Pharmacology) from Government Medical Col-
lege, Surat (GMCS). She started her teaching career as Tutor in
Department of Pharmacology at GMCS. She joined SMIMER in
the year 2003 and has a total teaching experience of 21 years in
the eld. In addition, she is secretary of the Drug Formulary
Committee & Prescription Auditing Committee, member secretary of Student
Mentorship Committee and an active member of the Teaching Coordination
Committee, Academic Cell, Medical Education Unit & Gymkhana Committee at
SMIMER.

Dr. Nandini Gokulchandran, M.D.

Dr. Nandini Gokulchandran is the deputy director, head
medical services and consultant regenerative medicine at
NeuroGen Brain and Spine Institute. After completing her MD
(Microbiology) from Government medical college and hospi-
tal, Nagpur; she has completed a 4 year post doctoral fellow-
ship in developmental neurobiology and stem cell research
from Tata institute of Fundamental Research, Mumbai. She has
more than 75 scientic peer reviewed publications to her name in the eld of
stem cell therapy. She has co-authored 'Stem cell therapy in neurological disor-
ders' and guidebooks for patients of neurological disorders.

Dr. Richa Bansod, M.B.B.S., M.H.A

Dr Richa Bansod is the Head of Surgery and Hospital Adminis-
tration at NeuroGen Brain and Spine Institute. After receiving
her medical degree in 1995, she trained in Neurosurgery at
Jaslok Hospital, Mumbai for DNB (Neurosurgery). She has
more than 10 years of experience in patient care in
neurosurgical and in neurological emergency settings. She
also holds a Master’s degree in Hospital Administration
(MHA) from Tata Institute of Social Sciences in Mumbai. Dr Richa Bansod’s
familiarity with healthcare spans many facets of health care, from direct patient
care to physician management and clinical quality indicator benchmarking
systems

Scientic and Research Co-ordinator :

Ms. Pooja Kulkarni
Dr. Jasbinder Kaur Dr. Guneet Chopra
Dr. Sanjay Kukreja Dr. Zafar Shaikh
 Special Contributors
Dr. Vrushali Mane
MBBS, DCH (Paediatrics),
Consultant Paediatrician

Grateful Acknowledgments
Dr. V. C. Jacob, Dr. Prerna Badhe, Dr. Joji Joseph, Dr. Hema Biju, Mrs. Vibhuti
Bhatt, Dr. Monali Dhanrale, Dr. Hema Sriram, Dr. Khushboo Bhagwanani, Dr.
Amruta Paranjape, Dr. Dhara Mehta,Dr. Shruti Shirke, Dr. Jasbinder Saini, Dr.
Vivek Nair, Dr. Rohit Das, Dr. Jidnyasa Koli, Dr. Sanket Inamdar, Dr. Nayana
Shet, Dr. Niranjana Kophrekar, Dr. Jyotsna Gaikwad, Dr. Sonali Parmar, Dr.
Naushin, Dr. Payal, Dr. Bhamini Waghela, Mr. Vishal Ganar, Ms. Ridhima
Sharma, Ms. Sukaina Lokhandwala, Ms. Smruthi Murali, Ms. Ashly Joseph, Ms.
Sonali Nalawade, Ms Zainab Ansari Mr. John Julius, Dr. Snehal Sontate, Dr.
Sushil Kasekar,Dr. Reena Jain, Dr. Kirti Lad, Dr. Abhishek Gupta, Dr. Shailesh
Patil, Dr. Shruti Pasi, Dr. Lata Thakur, Dr. Amol Salagre, Dr. Ajaz Khan, Dr. Ritu
Vargese, Mr. Samson Nivins, Ms. Alitta Jose, Ms. Nupur Jha, Ms. Shreya Madali,
Ms. Monica Chugh, Ms. Monica Vacchani, Mrs. Hridhika Rajesh, Ms. Larissa
Monteiro, Ms. Sharon Kinkar, Dr. Arushi Bhaumik, Dr. Ummeammara R K,Mr.
Aditya Nagaraja, Dr. Rajendra, Dr. Anup, Mr. Brain Pinto, Mr. Mandar Thakur,
Ms. Monica Vachhani, Ms. Sucheta, Mrs. Geeta Arora, Mrs. Kanchan Patil, Mr.
Kiran Pawar, Mr. Rajendra Patole, Mrs. Manjula Shete, Mrs. Daisy Devassy,Mr.
Sumedh Kedare, Mrs. Yasmeen Shaikh, Mr. Dinesh Desalae, Mr. Abhishek Patil,
Mrs. Mani Nair, Mrs. Chandra Bhatt , Mr. Udaykant Mishra, Ms. Anjali Avalusa,
Mrs. Amruta Kadam, Mr. Satish Pol, Mr. Roshan Salanki, Mr. Vikram
Chikne,Ms. Bhargavi Mamidi, Ms. Minal Vedante, Ms. Jigyasa Chabbria,Ms.
Namrata Katke, Mr. Roshan Solanki, Mr. Savio Agviour, Mr. Rohit Padale, Mr.
Kevin More, Ms. Sneha Khopkar, Mr. Rohan Awate, Ms. Neeta Thakur, Ms.
Prajakta Bhoir, Ms. Nanda Mane, Ms. Shweta Sathe, Mr. Satyavan More, Mr.
Sachin Jamble, John Julius Chettiar,Vikram Musale, Anup Mallick, Mr. Satish
 CONTENTS
A. Neurological symptoms & Their Management By The Family Physician

1. Headache.....................................................................................................25
2. Giddiness..................................................................................................... 38
3. Memory Problems...................................................................................... 49
4. Convulsions.................................................................................................59
5. Paralysis....................................................................................................... 66
6. Neuropathic Pain........................................................................................76
7. Physical Disabilties In Children............................................................... 79
8. Cognitive Disabilities In Children........................................................... 86
9. Behavioural issues in children..................................................................93

B. Neurological Investigations
I. Neuroradiology

10. Computed Tomography............................................................................105

11. Magnetic Resonance Imaging...................................................................111
12. Angiography............................................................................................... 117
13. Plain X Ray...................................................................................................122
14. Positron Emmission Tomography - Computed Tomography.............125
15. Functional MRI........................................................................................... 129

II. Electophysiolgical

16. Electroencephalography............................................................................133
17. Electromyography and Nerve Conduction Studies...............................138
18. Evoked Potentials........................................................................................144

III. Biochemical

19. Blood Tests...................................................................................................149

20. Cerebrospinal uid.....................................................................................159

C. Neurological Diseases & Their Comprehensive Management

21. Brain Stroke..................................................................................................167

22. Migraine....................................................................................................... 178
23. Spondylosis.................................................................................................. 183
24. Brain Tumors............................................................................................... 189
25. Head Injury.................................................................................................. 193
26. Spine Injury................................................................................................. 199
27. Dementia & Alzheimer’s Disease............................................................ 206
28. Movement Disorders................................................................................. 215
29. Demyelinating Disorders.......................................................................... 224
30. Infections of the CNS................................................................................. 233
31. Neuromuscular Disorders........................................................................ 245
32. Neurodevelopmental Disorders.............................................................. 262

D. Management of Neurological Emergencies

33. Acute Stroke................................................................................................ 273

34. Dellirium..................................................................................................... 275
35. Status Epilepticus....................................................................................... 277
36. Unconciousness.......................................................................................... 280
37. Head Trauma.............................................................................................. 283
38. Spine Trauma.............................................................................................. 288

E. Neuro Pharmacology

39. Drugs used for seizure disorders............................................................. 293

40. Analgesics....................................................................................................318
41. Drugs for Migraine.....................................................................................326
42. Drugs for Stroke......................................................................................... 331
43. Muscle Relaxants And Antispastic Drugs.............................................. 337
44. Antiparkinson And Other Drugs............................................................. 344
45. Neuroprotective Agents............................................................................ 348

F. Modern Developments In The Treatment Of Neurological Disorders

46. Use of tPA In Acute Stroke ....................................................................... 355

47. Role of HBOT in Neurological Disorders ............................................... 360
48. Comprehensive Neurorehabilitation.......................................................364
49. Recent Advances in Neurosurgery...........................................................373
50. Stem Cell Therapy in Incurable Neurological Disorders......................389
51. Interventional Neurology..........................................................................405
 Preface
When we were children, the word 'Doctor' meant only one thing - our "Local family
doctor." He was called family doctor because he in many ways was a part of the
family. He was a comforting gure who took care of our fevers, coughs, rashes,
diarrheas, pains and anything else we may have from bronchial asthma to chicken
pox. If there was any medical emergency at home he was the rst person to be
called. One was always sure that he would give us relief, whatever the reason and
whatever it was that we were suffering from. His mere presence was comforting.
He knew all about our family and kept track of all our health related issues.
However, in the recent past the community of family physicians is diminishing and
losing its relevance in the overall scheme of medical practice. Specialization, super-
specialization, fancy hospitals and access to medical information on the internet has
resulted in patient's directly reaching specialists and therefore bypassing the family
physician who in earlier years was the link between the family and the all aspects of
medical care. This has its disadvantages since the family physicians looked at the
patient's as a whole and in context to the rest of the family and therefore,
recommended medical advice in a more holistic fashion.
This book has therefore, been written for family physicians to update them on what
is happening in the eld of neurological disorders. Most serious neurological
conditions have early warning signs and it is important, that family physicians pick
up these signs so that early diagnosis through relevant investigations and correct
treatments through appropriate referrals can be made. These can be life saving in
many neurological conditions. Therefore, this book starts with a section on
symptoms and elaborates on what these symptoms can be due to. There have been
many rapid advances in the pharmacological treatments of neurological problems
and a whole lot of new investigations are now available. Therefore, separate
sections on these two important aspects have been included in the book. This will
help family physicians make better informed prescriptions and ask for more
focused investigations. There is a section on how to manage emergencies in the
clinic as well as a separate section on some of the important neurological conditions
such as stroke, brain tumors etc. The recent few years have also seen many new
developments in treatments of neurological conditions that were earlier considered
incurable. The availability of safer and more effective surgical techniques such as
Microneurosurgery and Minimally invasive neurosurgery along with the recent
evolution of revolutionary technologies such as Stem Cell Therapy have completely
changed the overall methods of management as well as prognosis in the
management of neurological disorders. We have therefore, included a section on
recent advances so that family physicians can guide their patient's as to what are the
best available treatments for their ailments. Wishing all our family physician
friends and colleagues - 'A Happy and Informative Reading'!
Dr. Alok Sharma
(9820046663 / alok276@gmail.com)
 Dedication
Dedicated to two outstanding human beings
(who also happened to be my grandfathers)

Dr. Gian Chand Sharma (New Delhi)

(1903 - 1972)
A Family Physician, General Practitioner from
Karol Bagh, New Delhi who became my role model
as to how a doctor should be.
From whom I learnt what is caring, compassion,
healing and seless service.
Whose words to me I still remember : "Never look at
a patient as a source of 5 rupees. Patients come to a
doctor in pain and suffering. Ease this suffering and
god will look after your needs”

Shri Sai Das Sharma, (Itarsi Madhya Pradesh)

(1887 -1966 )
A Police Ofcer from Itarsi, Madhya Pradesh
whose last wish inspired me to take up medicine as
a career.
From the story of whose life I learnt the meaning of
the words integrity, character, honesty, devotion
and commitment.
Whose suffering and death from a late diagnosed
malignancy taught me of the important role that a family physician
could make in the life’s of ordinary people by making early diagnosis of
serious conditions.

– Professor Alok Sharma

Scientic Publications on Stem Cell Therapy In
Neurological Disorders by the Authors

A) AUTISM:
1. Sharma A, et al., The baseline pattern and age related developmental meta-
bolic changes in the brain of children with autism as measured on positron
emission tomography/computed tomography scan. World J Nucl Med
2018;17 (In Press).
2. Alok Sharma, Nandini Gokulchandran, Hemangi Sane, Pooja Kulkarni,
Sarita Kalburgi, Ridhima Sharma, Prerna Badhe, Samson Nivins. PET CT
Scan Brain As A Monitoring Tool To Study The Effects Of Autologous Bone
Marrow Mononuclear Cell Transplantation In Autism Spectrum Disorder.
International Journal of Current Advanced Research. Sep 2017 (In Press).
3. Alok Sharma, Nandini Gokulchandran, Pooja Kulkarni, Sarita Kalburgi,
Shruti Kamat, Riddhima Sharma, Samson Nivins, Hemangi Sane, Prerna
Badhe. "Improvements in a case of autism spectrum disorder after cell ther-
apy as noted on PET CT brain scan" SJSC. May 2017
4. Alok Sharma, Nandini Gokulchandran, Hemangi Sane, Pooja Kulkarni,
Suhasini Pai, Vaishali Ganwir, Prerna Badhe. A case of autism showing
clinical improvements after cellular therapy along with PET CT evidence.
Journal of Stem Cell Research & Therapeutics. April 2017
5. Alok Sharma, Hemangi Sane, Nandini Gokulchandran, Prerna Badhe, Pooja
Kulkarni and Suhasini Pai. Stem Cell Therapy in Autism Spectrum Disorders.
Recent Advances in Autism. SMGroup. 2017
6. Alok Sharma, Hemangi Sane, Nandini Gokulchandran, Prerna Badhe,
Avantika Patil, Pooja Kulkarni, Amruta Paranjape PET- CT scan shows
decreased severity of Autism after autologous cellular therapy: A case report.
Autism Open Access 2016; 6:169.
7. Alok Sharma, Nandini Gokulchandran, Hemangi Sane, Avantika Patil,
Akshata Shetty, Hema Biju, Pooja Kulkarni, Prerna Badhe. Amelioration of
Autism by Autologous Bone Marrow Mononuclear Cells and
Neurorehabilitation: A Case Report. American Journal of Medical Case
Reports, 2015, Vol. 3, No. 10, 304-309
8. Alok Sharma, Nandini Gokulchandran, Hemangi Sane, Pradnya Bhovad,
Hema Biju, Akshata Shetty, Mrudula Kali and Prerna Badhe. Cell therapy
effects portrayed on positron emission tomography computerized tomogra-
phy scan of the brain serve as a new dimension for autism: A case report
(2014), Journal of Paediatric Neurology, 12:3.
9. Sharma A, Gokulchandran N, Shetty A, Kulkarni P, Sane H, Badhe P. Neuro-
psychiatric Disorder Tackled by Innovative Cell Therapy-A Case Report in
Autism. J Stem Cell Res Transplant. 2014;1(1): 4.
10. Alok Sharma, Nandini Gokulchandran, Hemangi Sane, Pooja Kulkarni,
Nancy Thomas, Amruta Paranjape, Prerna Badhe. Intrathecal autologous
bone marrow mononuclear cell transplantation in a case of adult autism.
Autism open access. 2013, 3:2.
11. Alok Sharma, Nandini Gokulchandran, Akshata Shetty, Hemangi Sane,
Pooja Kulkarni and Prerna Badhe. Autologous Bone Marrow Mononuclear
Cells may be Explored as a Novel. Potential Therapeutic Option for Autism. J
Clin Case Rep 2013, 3:7.
12. Alok Sharma, Nandini Gokulchandran, Prerna Badhe, Pooja Kulkarni, Priti
Mishra, Akshata Shetty and Hemangi Sane. An Improved Case of Autism as
Revealed by PET CT Scan in Patient Transplanted with Autologous Bone
Marrow Derived Mononuclear Cells. J Stem Cell Res Ther 2013, 3:2.
13. Alok SharAlok Sharma, Nandini Gokulchandran, Hemangi Sane, Anjana
Nagrajan, Amruta Paranjape, Pooja Kulkarni, Akshata Shetty, Priti Mishra,
Mrudula Kali, Hema Biju, Prerna Badhe. Autologous bone marrow
mononuclear cell therapy for autism – an open label proof of concept study.
Stem cell international. 2013 (2013), Article ID 623875, 13 pages.
14. Alok Sharma, Guneet Chopra, Nandini Gokulchandran, Mamta Lohia, Pooja
Kulkarni. Autologous Bone Derived Mononuclear Transplantation in Rett
Syndrome. Asian Journal of Paediatric Practice. 2011; 15 (1): 22-24.
B) CEREBRAL PALSY:
1. Alok Sharma, Pooja Kulkarni, Ritu Varghese, Hemangi Sane, Sanket Inamdar,
Jasbinder Kaur, Samson Nivins, Nandini Gokulchandran, Prerna Badhe.
Clinical translation of the benets of cell transplantation in a case of cerebral
Palsy. International Journal of Biological and Medical Research. Jan 2018.
2. Alok Sharma, Nandini Gokulchandran, Prerna Badhe, Vaibhav Lakhanpal,
Pooja Kulkarni, Suhasini Pai, Khushboo Bhagwanani, AmrutaParanjape and
Hemangi Sane. Multidisciplinary Approach of Cellular Therapy with
Neurorehabilitation in a Case of Mixed Cerebral Palsy. World J. Biol. Med.
Science Volume 4 (3) 70-74, 2017
3. Dr. Alok Sharma, Dr. Nandini Gokulchandran, Mrs. Suhasini Pai, Ms. Pooja
Kulkarni , Dr. Hemangi Sane , Dr. Khushboo Bhagwanani ,Dr. Prerna Badhe.
Diplegic dystonic Cerebral Palsy treated with cellular therapy: a case report.
Journal- International Journal of Case Studies. 2017
4. Sharma A, Sane H, Kalburgi S, Kulkarni P, Bhagwanani K, et al. Autologous
Bone Marrow Mononuclear Cell Transplantation with Neurorehabilitation
for Cerebral Palsy. J Stem Trans Bio 2017; 2(1): 110
5. Alok Sharma, Hemangi Sane, Suhasini Pai, Pooja Kulkarni, Meenakshi
Raichur , Sarita Kalburgi, Sanket Inamdar, Nandini Gokulchandran, Prerna
Badhe. Intrathecal administration of autologous bone marrow mononuclear
cells in a case of Cerebral Palsy coexisting with autistic features". Phys Med
Rehabil Int. 2017; 4(1): 1110.
6. Alok Sharma, Tongchao Geng, Hemangi Sane, Pooja Kulkarni. Clinical
neurorestorative progresses in cerebral palsy. Journal of Neurorestoratology
2016:4; 1-7
7. Alok Sharma, Hemangi Sane, Pooja Kulkarni, Myola D’sa, Nandini
Gokulchandran, Prerna Badhe. Improved Quality of Life in a Case of Cerebral
Palsy after bone marrow mononuclear cell transplantation. Cell J. 2015; 17(2):
389-394.
8. Alok Sharma, Hemangi Sane, Nandini Gokulchandran, Pooja Kulkarni,
Sushant Gandhi, Jyothi Sundaram, Amruta Paranjape, Akshata Shetty,
Khushboo Bhagawanani, Hema Biju and Prerna Badhe. A clinical study of
autologous bone marrow mononuclear cells for cerebral palsy patients: a new
frontier,” Stem Cells International, Volume 2015, Article ID 905874, 11 pages.
9. Alok Sharma, Hemangi Sane, Nandini Gokulchandran, Prerna Badhe, Pooja
Kulkarni and Amruta Paranjape. Stem Cell Therapy for Cerebral Palsy – A
Novel Option. Cerebral Palsy. Challenges for the future. 2014: 217-242.
10. Alok Sharma, Hemangi Sane, Amruta Paranjape, Nandini Gokulchandran,
Pooja Kulkarni and Anjana Nagrajan, Prerna Badhe. Positron Emission
Tomography – Computer Tomography scan used as a monitoring tool follow-
ing cellular therapy in Cerebral Palsy and Mental Retardation – A Case
Report. Case Reports in Neurological Medicine. Volume 2013, Article ID
141983, 6 pages.
11. Dr. Alok Sharma, Ms. Pooja Kulkarni, Dr. Hemangi Sane, Dr. Nandini
Gokulchandran, Dr. Prerna Badhe, Dr. Mamta Lohia, Dr. Priti Mishra. Posi-
tron Emission Tomography- Computed Tomography scan captures the
effects of cellular therapy in a case of cerebral palsy. Journal of clinical case
reports. 2012 J Clin Case Rep 2:195.
C) MUSCULAR DYSTROPHY:
1. Alok Sharma, Nandini Gokulchandran, Amruta Paranjape, Hemangi Sane,
Dr. Prerna Badhe. Stem cells as a therapeutic modality in Muscular Dystro-
phy. Chapter 2. Muscular Dystrophy. Avid Sciences. India. 2017
2. Alok Sharma, Amruta Paranjape, Hemangi Sane, Nandini Gokulchandran,
Dhanashree Sawant, Shruti Shirke, Vivek Nair, Sanket Inamdar, Prerna
Badhe. Effect of Cellular Therapy in a case of Limb Girdle Muscular Dystro-
phy. International Journal Of Current Medical And Pharmaceutical
Research, Vol. 3, Issue, 09, pp.2377-2381, September, 2017
3. Alok S, Amruta P, Ritu V, Hemangi S, Nandini G, et al. Functional Improve-
ments and Musculoskeletal Magnetic Resonance Imaging with Spectroscopy
Changes following Cell Therapy in a Case of Limb Girdle Muscular Dystro-
phy. Int J cell Sci & mol biol. 2017; 2(4) : 555595.
4. Alok Sharma, Hemangi Sane, Vaibhav Lakhanpal, Amruta Paranjape, Pooja
Kulkarni, Nandini Gokulchandran, Prerna Badhe. Stabilization of the disease
progression in a case of Duchenne Muscular Dystrophy with cellular trans-
plantation. Stem cell: Advanced research and therapy. 2017; 2017(3)
5. Alok Sharma , Dr. Prerna Badhe, Hemangi Sane, Suhasini Pai , Pooja
Kulkarni, Khushboo Bhagwanani, Dr. Nandini Gokulchandran. Halting of
functional decline in a case of Duchenne Muscular Dystrophy after cellular
therapy. International Journal of Recent Advances in Multidisciplinary
Research (IJRAMR), 2017 Jan
6. Sharma, A., Badhe, P., Sane, H., Gokulchandran, N., & Paranjape, A. Role of
Stem Cell Therapy in Treatment of Muscular Dystrophy. Muscular dystro-
phy. SMGebooks. July 2016. Dover, USA.
7. Alok Sharma, Hemangi Sane, Jasbinder Kaur, Nandini Gokulchandran,
Amruta Paranjape, Jayanti Yadav, Prerna Badhe Autologous Bone Marrow
Mononuclear Cell Transplantation Improves Function in a Case of Becker’s
Muscular Dystrophy. American Based Research Journal. 2016; 5 (2)
8. Sharma A, Sane H, Gokulchandran N, Sharan, R., Paranjape, A., Kulkarni, P.,
Yadav J, Badhe, P. Effect of Cellular Therapy in Progression of Becker’s
Muscular Dystrophy: A Case Study. European Journal of Translational
Myology. 2016;26(1):5522.
9. Sharma Alok, Sane Hemangi, Kulkarni Pooja, Mehta Dhara, Kaur Jasbinder,
Gokulchandran Nandini, Bhagwanani Khushboo, Badhe Prerna. Effect Of
Autologous Bone Marrow Mononuclear Cell Transplantation Coupled With
Rehabilitation In Limb Girdle Muscular Dystrophy – A Case Report. Int J
Med Res Health Sci. 2016, 5(12):1-7
10. Sharma A, Sane H, Gokulchandran N, Gandhi S, Bhovad P, Khopkar D,
Paranjape A, Bhagwanani K, Badhe P. The role of cell therapy in modifying
the course of limb girdle muscular dystrophy- A Longitudinal 5-year study.
Degenerative Neurological and Neuromuscular Disease 2015:5 93–102
11. Alok Sharma, Hemangi Sane, Amruta Paranjape, Khushboo Bhagwanani,
Nandini Gokulchandran, Prerna Badhe.Autologous bone marrow
mononuclear cell transplantation in Duchenne muscular dystrophy – a case
report. American journal of case reports 2014;15: 128-134.
12. Alok Sharma, Hemangi Sane, Prerna Badhe, Nandini Gokulchandran, Pooja
Kulkarni, Mamta Lohiya, Hema Biju, V.C.Jacob. A Clinical Study Shows
 Safety and Efcacy of Autologous Bone Marrow Mononuclear Cell Therapy
to Improve Quality Of Life in Muscular Dystrophy Patients. Cell Transplan-
tation. 2013 Vol. 22, Supplement 1, pp. S127–S138.
13. Sharma A., Sane, H., Paranjape, A., Badhe, P., Gokulchandran, N., & Jacob, V.
(2013). Effect of Cellular Therapy seen on Musculoskeletal Magnetic Reso-
nance Imaging in a Case of Becker’s Muscular Dystrophy. Journal of Case
Reports, 3(2), 440-447.
14. Sharma, Alok et al. “Cellular Transplantation Alters the Disease Progression
in Becker’s Muscular Dystrophy.” Case Reports in Transplantation 2013
(2013): 909328.
15. Dr. Suvarna Badhe, Ms. Pooja Kulkarni, Dr Guneet Chopra, Dr Nandini
Gokulchandran, Dr Alok Sharma Dystrophin Deletion mutation pattern and
Cardiac involvement in 46 cases of Dystrophinopathies. Asian journal of
clinical cardiology. Asian Journal of Clinical Cardiology, Vol. 15, No. 6,
October 2012: 211-214.
16. Dr. A. Sharma, Ms. P. Kulkarni, Dr. G. Chopra, Dr. N. Gokulchandran, Dr. M.
Lohia, Dr. P. Badhe. Autologous Bone Marrow Derived Mononuclear Cell
Transplantation In Duchenne Muscular Dystrophy-A Case Report. Indian
journal of Clinical Practice 2012; 23 (3): 169-72.
D) SPINAL CORD INJURY:
1. Alok S, Prerna B, Suhasini, Hemangi S, Samson N, Pooja K, Amruta P, Dhara
M, Nandini G.Functional Recovery and Functional Magnetic Resonance
Imaging changes Following Cellular Therapy in a Case of Chronic Complete
Spinal Cord Injury. Curr Trends Clin Med Imaging. 2017; 1(4): 555566.
2. Alok Sharma, Hemangi Sane, Suhasini Pai, Pooja Kulkarni, Amruta
Paranjape, V C Jacob, Joji Joseph, Sanket Inamdar, Sarita Kalburgi, Nandini
Gokulchandran, Prerna Badhe, Samson Nivins. Functional and symptomatic
improvement after cellular therapy in a pediatric case of chronic traumatic
incomplete SCI. J Stem Cell Regen Biol 2017; 3(1): 1- 7.
3. Alok Sharma, Hemangi Sane, Dipti Khopkar, Nandini Gokulchandran,
Varghese Chako Jacob, Joji Joseph, Prerna Badhe. Functional recovery in
chronic stage of spinal cord injury by Neurorestorative Approach. Case
Reports in Surgery 2014 Volume 2014, pages 1-4
4. Alok Sharma, Hemangi Sane, Dipti Khopkar, Nandini Gokulchandran, Hema
Biju, V C Jacob, Prerna Badhe. Cellular therapy targeting Functional outcome in
a case of Cervical Spinal Cord Injury. Advances in Stem Cells 2014 (2014)
5. Sharma A, Sane H, Gokulchandran N, Kulkarni P, Thomas N, et al. (2013)
Role of Autologous Bone Marrow Mononuclear Cells in Chronic Cervical
Spinal Cord Injury-A Longterm Follow Up Study. J Neurol Disord 1: 138.
6. Sharma A, Gokulchandran N, Sane H, Badhe P, Kulkarni P, Lohia M,
Nagrajan A, Thomas N. Detailed analysis of the clinical effects of cell therapy
for thoracolumbar spinal cord injury: an original study. Journal of
Neurorestoratology. 2013; 1:13-22.
7. Alok Sharma, Prerna Badhe, Pooja Kulkarni, Nandini Gokulchandran,
Guneet Chopra, Mamta Lohia, V.C.Jacob. Autologous Bone Marrow Derived
mononuclear cells for the treatment of Spinal Cord Injury. The Journal of
Orthopaedics. 2011; 1(1): 33-36.
E) STROKE:
1. Alok Sharma, Hemangi Sane, Nandini Gokulchandran, Pooja Kulkarni,
Rishabh Sharan, Amruta Paranjape, Prerna Badhe Effect of Cellular Therapy
Monitored on Positron Emission Tomography - Computer Tomography Scan
in Chronic Hemorrhagic Stroke: A Case Report. Archiv Neurol Neurosur-
gery, 2016 Volume 1(1): 22-25
2. Alok Sharma, Hemangi Sane , Amruta Paranjape, Nandini Gokulchandran ,
Sushant Gandhi, Prerna Badhe. Benets of Autologous Bone Marrow
Mononuclear Cell Transplantation in Chronic Ischemic Pontine Infarct.
Journal Of Case Reports 2016;6(1):80-85
3. Alok Sharma, Hemangi Sane, Nandini Gokulchandran, Dipti Khopkar,
Amruta Paranjape, Jyothi Sundaram, Sushant Gandhi, and Prerna Badhe.
Autologous Bone Marrow Mononuclear Cells Intrathecal Transplantation in
Chronic Stroke Stroke Research and Treatment, Volume 2014, pages 1-9.
4. Alok Sharma, Hemangi Sane, Anjana Nagrajan, et al., “Autologous Bone
Marrow Mononuclear Cells in Ischemic Cerebrovascular Accident Paves
Way for Neurorestoration: A Case Report,” Case Reports in Medicine, vol.
2014, Article ID 530239, 5 pages, 2014. doi:10.1155/2014/530239.
5. Dr. Alok Sharma, Dr. Hemangi Sane, Dr. Prerna Badhe, Ms. Pooja Kulkarni,
Dr. Guneet Chopra, Dr. Mamta Lohia, Dr. Nandini Gokulchandran.
Autologous Bone Marrow Stem Cell Therapy shows functional improvement
in hemorrhagic stroke- a case study. Indian Journal of Clinical Practice,
2012:23(2):100-105.
F) ALS/MND
1. Alok Sharma, Hemangi Sane, Sarita Kaliburgi, Amruta Paranjape, Nandini
gokulchandran, Prerna Badhe,“Potential Benets of Cellular Transplantation
in a Patient with Amyotrophic Lateral Sclerosis”. Current Opinions in
Neurological Science 1.2 (2017): 31-43
2. Sharma A, Sane H, Sawant D, Paranjape A, Inamdar S, Kaur J,
Gokulchandran N, Badhe P. Cellular Therapy in Amyotrophic Lateral Sclero-
sis: A Case Report; International Journal of Recent Advances in
Multidisciplinary Research. 2017;1(4):2605-2609
3. Hemangi Sane, Alok Sharma, Nandini Gokulchandran, Sarita Kalburgi,
Amruta Paranjape, Prerna Badhe Neurorestoration in Amyotrophic Lateral
Sclerosis - A case report. Indian Journal of Stem Cell therapy. 2016; 2(1):29-37
4. Alok K Sharma , Hemangi M Sane , Amruta A Paranjape , Nandini
Gokulchandran , Anjana Nagrajan , Myola D’sa , Prerna B Badhe. The effect of
autologous bone marrow mononuclear cell transplantation on the survival
duration in Amyotrophic Lateral Sclerosis - a retrospective controlled study.
Am J Stem Cells 2015;4(1).
5. Alok Sharma, Prerna Badhe, Omshree Shetty, Pooja Vijaygopal, Nandini
Gokulchandran, V.C. Jacob, Mamta Lohia, Hema Biju, Guneet Chopra.
Autologous bone marrow derived stem cells for motor neuron disease with
anterior horn cell involvement. Bombay hospital journal. 2011; 53(1): 71- 75.
F) MISCELLANEOUS:
1. Dr. Alok Sharma, Hemangi Sane, Nandini Gokulchandran, Prerna Badhe,
Mrs. Suhasini Pai, Pooja Kulkarni, Jayanti Yadav, Sanket Inamdar. Cellular
Therapy for Chronic Traumatic Brachial Plexus Injury-A case report.
Advanced Biomedical Research journal. (Ahead of Print)
2. Alok Sharma, Hemangi Sane, Nandini Gokulchandran, Suhasini Pai, Pooja
Kulkarni, Vaishali Ganwir, Maitree Maheshwari, Ridhima Sharma, Meenakshi
Raichur, Samson Nivins, MS; Prerna Badhe. An open label proof of concept
study of intrathecal Autologous Bone Marrow Mononuclear Cells transplanta-
tion in Intellectual Disability. Stem cell research and therapy. 2017
3. Sharma A, Gokulchandran N, Sane H, Pai S, Kulkarni P, et al. Cognitive
Changes after Cellular Therapy in a Case of Intellectual Disability. J
Transplant Stem Cel Biol. 2017;4(1): 4.
4. Alok Sharma, Hemangi Sane, Nandini Gokulchandran, Prerna Badhe, Pooja
Kulkarni, Suhasini Pai, Ritu Varghese, Amruta Paranjape. Stem cell therapy
in pediatric neurological disabilities In Physical disabilities. Intech 2017
5. Alok Sharma, Hemangi Sane , Sarita Kalburgi , Pooja Kulkarni , Sanket
Inamdar, Khushboo Bhagwanani ,Nandini Gokulchandran , Prerna Badhe.
Autologous Bone Marrow Mononuclear Cell Transplantation for Multiple
System Atrophy type C- A Case Report. American Based Research Journal.
2016.
6. Alok Sharma Hemangi Sane Pooja Kulkarni Nandini Gokulchandran
Dhanashree Sawant Samson Nivins Prerna Badhe. Effect of Cell
Transplantation in a Chronic Case of Traumatic Brain Injury.
Transplantation Open. 2016 Volume 1(1): 22-25
7. Alok Sharma, Ziad M Al Zoubi. Rethinking on ethics and regulations in cell
therapy as part of neurorestoratology. Journal of Neurorestoratology 2016:4 1–14
8. Alok Sharma, Hemangi Sane, Pooja Kulkarni, Nandini Gokulchandran,
Prerna Badhe Cellular therapy in Neurodevelopmental disorders. Indian
Journal of Stem Cell therapy. 2016; 2(1):64-73
9. Alok Sharma, Nandini Gokulchandran, Hemangi Sane, Prerna Badhe,
Amruta Paranjape. Current global trends in regulations for stem cell therapy
and the way ahead for India. Indian Journal of Stem Cell therapy. 2016;
2(1):5-16
10. Nandini Gokulchandran, Alok Sharma , Hemangi Sane , Prerna Badhe , Pooja
Kulkarni. Stem Cell Therapy as a Treatment Modality for Neurotrauma.
Indian Journal of Stem Cell therapy. 2015; 1(1):21-26.
11. Dr. Alok K. Sharma, Dr. Hemangi Sane , Dr. Nandini Gokulchandran , Dr.
Amruta Paranjape , Ms. Pooja Kulkarni , Dr. Prerna Badhe. The need to review
the existing guidelines and proposed regulations for stem cell therapy in
India based on published scientic facts, patient requirements, national
priorities and global trends. Indian Journal of Stem Cell therapy. 2015;
1(1):7-20.
12. Alok Sharma, Prerna Badhe, Nandini Gokulchandran, Pooja Kulkarni,
Hemangi Sane, Mamta Lohia, Vineet Avhad. Autologous bone marrow
derived mononuclear cell therapy for vascular dementia - Case report.
Journal of stem cell research and therapy. J Stem Cell Res Ther 2:129.
13. Sharma A, Sane H, Pooja K, Akshya N, Nandini G, Akshata S. (2015) Cellular
Therapy, a Novel Treatment Option for Intellectual Disability: A Case Report.
J Clin Case Rep 5:483. doi: 10.4172/2165- 7920.1000483.
14. Alok Sharma, Hemangi Sane, Pooja Kulkarni, Jayanti Yadav, Nandini
Gokulchandran, Hema Biju, Prerna Badhe. Cell therapy attempted as a novel
approach for chronic traumatic brain injury - a pilot study. SpringerPlus
(2015) 4:26.
15. Sharma A, Sane H, Paranjape A, Gokulchandran N, Takle M, et al. (2014)
Seizures as an Adverse Event of Cellular Therapy in Pediatric Neurological
Disorders and its Prevention. J Neurol Disord 2:164.
16. Alok Sharma, Hemangi Sane, Amruta Paranjape, Nandini Gokulchandran,
Hema Biju, Myola D’sa, Prerna Badhe. Cellular Transplantation May
Modulate Disease Progression In Spino-Cerebellar Ataxia – A Case Report.
Indian Journal Of Medical Research And Pharmaceutical Sciences. August
2014; 1(3).
17. Alok Sharma, Nandini Gokulchandran, Guneet Chopra, Pooja Kulkarni,
Mamta Lohia, Prerna Badhe, V.C. Jacob. Administration of autologous bone
marrow derived mononuclear cells in children with incurable neurological
disorders and injury is safe and improves their quality of life. Cell
Transplantation, 2012; 21 Supp 1: S1 – S12.
18. A. Sharma, P. Badhe, N. Gokulchandran, P. Kulkarni, V.C Jacob, M. Lohia, J.
George Joseph, H. Biju, G. Chopra. Administration of Autologous bone
marrow stem cells intrathecally in Multiple Sclerosis patients is safe and
improves their quality of life. Indian Journal of clinical Practice.
2011:21(11):622-625.
19. Sharma A, Gokulchandran N, Kulkarni P, Chopra G. Application of
autologous bone marrow stem cells in giant axonal neuropathy. Indian J Med
Sci 2010;64:41-4.
20. A Sharma, P Kulkarni, N Gokulchandran, P Badhe, VC Jacob, M Lohia, J
George Joseph, H Biju, G Chopra. Adult Stem Cells for Spinal Muscular
Atrophy. Bangladesh Journal Of Neuroscience. 2009; 25(2): 104- 107.
Neurological Disorders - A Handbook for Family Physicians 23

Section A

Neurological Symptoms &

Their Management by
the family physicians
24 Neurological Disorders - A Handbook for Family Physicians
 Neurological Disorders - A Handbook for Family Physicians 25

Headache
Headache is one of the most common presenting symptoms of neurological
disorders. Majority of them are innocuous and need only symptomatic
treatment, but some can be a sign of serious underlying disorders and therefore
headaches should always be taken seriously. A headache is a pain in the head
radiating above the eyes or the ears, behind the head or in the back of the upper
neck.
When treating a patient with headache the rst question in our mind should be -
is it Primary headache or is it a Secondary headache?
Primary headaches are not associated with any underlying major disease.
Examples of primary headaches are tension headaches, migraine and Cluster
headches. Secondary headaches are caused due to some other underlying
disease. These may be minor ones such as uncorrected ophthalmic refractory
error, sinusitis, withdrawal from caffeine and discontinuation of analgesics.
They may also be symptomatic of major illnesses such as brain tumors, strokes,
meningitis, and subarachnoid hemorrhages.

Fig. 1.1: Types of Headaches

 26 Neurological Disorders - A Handbook for Family Physicians

Common types of Headaches:

1. Tension Type Headache ( TTH ) :
It is the most common type of headache and occurs mostly due to emotional
stress causing muscle tension producing ischemia of the scalp and facial
muscles. This headache is usually bilateral , may have a band like discomfort
and is not associated by symptoms like nausea, vomiting, phonobhobia or
photophobia. Patient is able to continue his/her normal activity. This type of
headache builds slowly and may become severe.
These are generalized headaches of gradual onset and can be of mild to
moderate severity. They are described by the patients as aching or pressure type
of headache and are always non pulsatile. They last from one to two hours and
occur during the later part of the day. They may be associated with grinding of
the teeth, lack of sleep and difculty in concentration. There is always some
major underlying emotional or psychological cause which may be family or
work related. Neurological examination does not reveal any abnormality.
Investigations: None
Treatment:
1. Paracetamol 500mg 1 TDS for mild pain,
2. Combination of Paracetamol & Codeine 1 TDS for mild to moderate pain,
3. Paracetamol +Acelofenac 1BD for moderate pain
4. Naproxen 1 BD for moderate to severe pain
5. Amitriptyline 25 mg 1 QHS if difculty to sleep
6. Counseling / relaxation exercises / tranquilizers/ lifestyle changes may
be helpful.
Referal:
Non responsive headaches to regular treatment or persistent severe progressive
headache.
1. Migraine Headache
Migraine is a disorder of the brain and its blood vessels, which results in hyper
reactivity of the cerebral blood vessels. It is classied as a common migraine
(migraine without aura), classical migraine (migraine with aura) and complex
migraine. Classical migraine headaches are throbbing in nature, mostly unilat-
eral (60-75% cases) and often associated with ashes of light. Aura, nau
 Neurological Disorders - A Handbook for Family Physicians 27

sea/vomiting, photo/phonophobia, scalp tenderness is present in most of the

cases. Photophobia ( intolerance to sound) is more specic to migraine
headache.In the complicated migraine there are associated neurological signs
and symptoms caused by vasoconstriction of intracranial vessels such as confu-
sion, amnesia, transient monocular blindness, hemiparesis and limb
paraesthesias. Migraine can be precipitated by red wine, menses, hunger,
insomnia, perfumes, chocolates etc. A migraine typically lasts from 4 to 72
hours. Sometimes Patient of migraine may develop severe and persistent
headache which lasts for many days. Such condition then labelled as Status
Migranosus. Persistent vomiting associated with headache may cause dehydra-
tion.
Investigations:
None for common or classical migraine. In complex migraine CT Scan/MRI
scan may be done to rule out structural lesions if there is no relief.
Treatment:
Symptomatic relief (once attack starts). [1] Analgesics & NSAID’s [2] Rest in a
quiet, dark room if possible, [3] Triptans-are prescribed for acute attack in the
early stage. They should not be given in complicated migraine. (Sumatriptan
25mg, Zolmitriptan 5mg, Rizatriptan 5mg [4] Ergotamines (Dihydro
ergotamine preferred in status migraine), [5] Isometheptene [6] Sedatives, [7]
Antiemetics
Practical management for acute attack:- :[1] Rizatriptan 10 mg or Sumatriptan 6
mg stat followed by Naproxen and Tab Domperidone / Metoclopramide for 1-2
days) [ 2 ] steroid : Tab prednisolone 20 mg every 6 hours initially, followed
by a rapid tapering dose over 2 to 3 days may help abort status
migrainosus. [ 3] other agents : Dihydro-ergotamine, chlorpromazine,
Ketorolac, Prochlorperazine [ 4 ] Correction of dehydration.
Prevention:
1. Identify and avoid trigger factors such as exposure to sunlight, delayed
meals, delayed sleep, foods such as caffeine, cheese, chocolates, chinese
food etc.
2. Prophylactic medications-Those patients who have more than one
migraine per week should be put on prophylactic medications such as B-
blockers, calcium channel blockers, tricyclic antidepressants, SSRI’s
,anticonvulsants.
3. Practical management for migraine prophalaxis: Propranolol slow release
 28 Neurological Disorders - A Handbook for Family Physicians

40 mg one tablet in the morning for 3 months + Amitryptline 10mg 1 hs or

Flunarizine 10 mg HS. : Propranolol slow release 40 mg one tablet in the
morning Amitryptline 10mg 1 HS, Flunarizine 10 mg HS, Valproate 250-
500 mg / day, Topiramate 75-200 mg/day.
Referal:
Persistent migraine not responding to medications and migraine with
associated other signs.
3. Headache due to uncorrected refractory error
The headache comes as after watching TV, reading for long. Is dull, aching,
bilateral and may be bifrontal or generalized.
Investigations: None
Treatment: Analgesics
Referal:
Ophthalmologist or an optician for correction.
4. Headache due to Sinusitis
These are bifrontal headaches which are gradual in onset, moderate in severity,
dull and boring in nature and associated with pain or pressure in the face. There
is history of frequent cold with nasal discharge. Presence of tenderness on the
sinuses (frontal,maxillary), sides of the nose is noticed on examination.
Investigations:
[1] Plain X-ray of Paranasal sinuses (PNS), [2] CT Scan PNS
Treatment:
[1]Analgesics, [2]Antihistaminic, [3] Antibiotics – All For seven days.
Practical management:-a combination of diclofenac tds, sulfamethoxazole +
trimethoprim or amoxicillin and clavulanate – bd, fexofenadine (allegra) or
pheniramine (avil) –qhs is a good combination.
Referal:
If there is no improvement even after seven days of the above treatment then
refer to ENT surgeon for evaluation.
5. Headaches due to Hypertension
One of the early signs of Hypertension are Headaches. The classical feature of
 Neurological Disorders - A Handbook for Family Physicians 29

Hypertension headaches is that they occur early in the morning. They may
present as pressure just behind the eyes or as headaches at the back of the head.
They are sometimes associated by dizziness and palpitations . The headache
may be mild or severe and occur more commonly in women than men. Any
patient over 50 presenting with morning headaches should always have their
blood pressure checked.
Investigations:
1. Regular monitoring of BP.
2. ECG, 2 D Echo , Stress test , Lipid Prole and Other cardiac investigations
may be indicated in some cases.
Treatment :-
No analgesics
Medications for hypertension
Low salt diet
Counseling for Lifestyle changes to reduce stress levels- Relaxation techniques
and yoga

Referral
If despite the above the BP remains high and headaches persist then the patient
should be refereed to a cardiologist for further management.
It is important to note that Hypertension headaches are one type of headaches
for which painkillers should not be given since they suppress only the symp-
toms and do not take care of the serious issue of hypertension. The treatment of
hypertension headaches is control of hypertension and it has been noted that
once the blood pressure is lower, the headache get relieved.
6. Cluster headache
These are episodic pain attacks at periorbital region it is usually excrutiating and
deep and pulsatile in nature, pain is unilateral and lasts for 30 minutes to 2
hours. there are associated symptoms like lacrimation, redness of eye, nasal
stufness, ptosis, and nausea. Alcohol provokes the attack.
Treatment:
Acute attack- [1] 100% oxygen for 10-15 mins, [2] Sumatriptan 6mg subcutane-
ous injection stat.
 30 Neurological Disorders - A Handbook for Family Physicians

Prevention:
Prednisone 40mg/day for 5 days tapered over 3 weeks. [2] Indomethacin 75
mg/ day [3] Verapamil : starting dose is 80 mg TDS ( ECG should be normal ) 4 ]
others-lithium and ergotamine.
6) Trigeminal Neuralgia
Unilateral severe lancinating pain around the face, lips, gums. It is aggravated
by a tickle or touch, pain burst happen over seconds to minutes with a refractory
period afterwards. There may be associated ushing, salivation or lacrimation.
Investigation:
MRI/ CT scan must be done to rule out CP angle tumor. abberent loop of ves-
sels/ AV malformation.
Treatment:
[1] carbamazepine 100 - 200 mg BD [2] gabapentin 100-300 mg TDS [3] Others-
Antidepressants : Amitriptyline , uoxetine, clonazepam. [4] Avoid stimulation
of trigger zone by air, heat or cold [5] In some cases surgical intervention may be
required- nerve block, surgical decompression.
Treatment:
[1] carbamazepine 100 mg BD [2] gabapentin 100 mg TDS [3] Others- Antide-
pressants-Ametreptonin, uoxetine, clonazepam. [4] Avoid stimulation of
trigger zone by air, heat or cold [5] In some cases surgical intervention may be
required- nerve block, surgical decompression.
Referral:
Should be referred to neurophysician or neurosurgeon.
Maxillary Zone
Ophthalmic zone
Mandibular zone

Trigeminal
nerve

Fig. 1.2: Areas of the face covered by trigeminal nerve

 Neurological Disorders - A Handbook for Family Physicians 31

7) Headaches due to serious underlying conditions:

Conditions causing secondary headaches are brain stroke, subarachnoid
intracranial hemorrhage , brain tumors, meningitis, severe high blood pressure.
These can cause serious brain damage or even death. Thus, timely and accurate
diagnosis of secondary headaches is crucial. Special blood tests, brain scans, and
lumbar puncture (spinal tap) are necessary to establish these diagnoses. One
should rely upon information obtained from the initial patient history and
physical examination.
Common causes of serious headache:
1) Sentinel headache due to subarachnoid haemorrhage
Sentinel headache (SAH) is characterized as sudden (thunderclap headache),
intense, and persistent headache, preceding spontaneous subarachnoid
hemorrhage (SAH) by days or weeks. It is often described as the “worst
headache of my life”. It is the most common symptom to manifest 10-20 days
before rupture of an aneurysm. In addition to headaches, sentinel leaks may
produce nausea, vomiting, photophobia, malaise, or neck pain. These
symptoms can easily be ignored by a physician. Therefore, a high index of
suspicion is necessary to diagnose this type of headache due to subarachnoid
haemorrhage.
The diagnosis of SAH should be based upon the following seven characteristics:
Ÿ Aged >=40 years
Ÿ Witnessed loss of consciousness
Ÿ Complaint of neck pain or stiffness
Ÿ Onset of manifestations with exertion
Ÿ Arrival by ambulance
Ÿ Vomiting
Ÿ Diastolic blood pressure ≥ 100 mm Hg or systolic blood pressure ≥ 160
mm Hg
The possibility of SAH should be suspected if any one or more of these is present
along with acute nontraumatic headache which reaches maximum intensity
within one hour, and the patient be referred to a neurophysician and
hospitalized immediately.
 32 Neurological Disorders - A Handbook for Family Physicians

Fig 1.3: MRI T2-FLAIR sequence showing the presence of subarachnoid

hemorrhage in the left sylvian ssure

2) Meningitis
Acute to subacute severe type of headache with neck stiffness and fever sug-
gests meningitis. Meningitis may be mistaken as migraine sometimes due to the
chief symptoms like pounding headache, photophobia, nausea, vomiting, etc.
This requires hospitalisation and so patient should be referered to neurology
department.
3) Tumours
Profound pounding dull, aching, or throbbing headache of medium intensity
which worsens with exertion and change of position and may be associated with
nausea or vomiting may suggest an intracranial tumour. The headaches may
become more frequent, increasing in severity, and not easily relieved. Patient
gets disturbed from sleep. They can also be worsened by coughing or sneezing
and persistently occur on the same side often. Vomiting that precedes headache
is a characteristic of posterior fossa tumours. This type of headache should be
immediately investigated and brought to the concern of a neurophysician or
neurosurgeon.
4) Stroke
Headache with symptoms such as acute weakness and numbness in the limbs
and/or face, nausea, vomiting, an altered level of consciousness, may indicate
increased intracranial pressure and are more common with hemorrhagic
strokes and large ischemic strokes.
A detailed medical history of patient for identifying following risk factors of
stroke should be acquired to suspect a stroke:
 Neurological Disorders - A Handbook for Family Physicians 33

Ÿ Hypertension
Ÿ Diabetes mellitus
Ÿ Tobacco use
Ÿ High cholesterol
Ÿ History of coronary artery disease, coronary artery bypass, or atrial brilla-
tion
Ÿ Recent trauma
Ÿ Coagulopathies
Ÿ Illicit drug use (especially cocaine)
Ÿ Migraines
Ÿ Oral contraceptive use
In the presence of these risk factors and clinical presentation, the patient should
be immediately hospitalized to prevent stroke and its life threatening effects.
5) Temporal arteritis
It is an inammatory condition of arteries which involves the extracranial
c a r o t i d c i r c u l a t i o n . T e m p o r a l Inamed
arteritis presents with classical temporal Giant cell arterits
artery
symptoms - headache, jaw
claudication, scalp tenderness, and
visual disturbances. Fever, myalgia,
anorexia, weight loss, anemia, and
malaise may also occur as systemic
inammatory response. Temporal
arteritis should be distinguished
from systemic infections, connective
tissue diseases, and compressive Fig 1.4: Temporal arteritis
intracranial malignancies, etc by further clinical examination, blood and CSF
testing, and neuroimaging. Temporal arteritis usually occurs in older people
and is extremely rare in individuals younger than 50 years of age, and present
with visual changes. If not treated, patient may develop partial or complete
blindness due to involvement of ophthalmic artery or its branches. Therefore,
immediate hospitalisation and referral is a must in this case.
ESR should be done in all elderly with new onset headache.
If not treated, patient may develop partial or complete blindness due to involve-
ment of ophthalmic artery or its branches. Therefore, immediate hospitalisation
and referral is a must in this case.
 34 Neurological Disorders - A Handbook for Family Physicians

Information that should be taken by the doctor includes:

1. The mode of onset of the headache: For example, patients with a
subarachnoid hemorrhage typically report having a sudden onset of
severe headache (“the worst headache ever”).
2. The location of the headache: (on one side or both sides of the head). Head-
aches that persistently occur on the same side often are secondary head-
aches associated with one sided lesions such as brain tumors.
3. Associated fever and neck stiffness: Bacterial meningitis is a rapidly
progressive and life-threatening disease with fever, headaches, stiff neck,
and deterioration in mental function.
4. Associated mental deterioration, seizures, or weakness of the extremities
or face, which can be symptoms of brain tumors.
5. Associated temporary weakness of the extremities or facial muscles,
which can be symptoms of transient ischemic attacks.
6. Recent head injury: Headaches soon after injury to the head may be caused
by subdural or epidural hematomas.
7. The age of the patient: Temporal arteritis typically occurs in older people
and is extremely rare in individuals younger than 50.
Headaches those are different in severity and intensity need urgent attention,
investigations and reference.
Investigations:
[1] CT scan of the head. Should be done whenever the headache sis different in
severity and character and also for late onset headches. CT scan of the head is
useful for detecting accumulation of blood such as subdural hematomas and
subarachnoid hemorrhages. It is moderately useful in detecting brain tumors
and strokes not due to hemorrhage. [2] MRI scan of the head. An MRI scan of the
head can detect infections of the brain, strokes and tumors. It is not so useful for
acute hemorrhage. [3] Lumbar puncture. In some patients with subarachnoid
hemorrhage, CT scans are normal, and lumbar punctures are necessary to
demonstrate blood from the hemorrhage that has spread throughout the
cerebro-spinal uid(CSF). CSF is also useful for diagnosis of meningitis, it
shows decreased sugar levels, increased proteins and increased cells (if major
are polymorphs then it suggests Bacterial meningitis and if there are lympho-
cytes then it suggests Tubercular meningitis).
 Neurological Disorders - A Handbook for Family Physicians 35

Treatment:
Specic treatment of the cause of the headache.
Referal:
Refer to Neurophysician or Neurosurgeon.
Drugs useful in symptomatic treatment of headache:
(A) General
Paracetamol, [2] Paracetamol+ codeine, [3]Paracetamol +Acelofenac [4]
Naproxen
Diclofenac (Brufen is not useful in headaches, except those due to sinusitits, and
can in fact make some headaches worse)
(B) Specic
[1]Anti Migraine therapy, [2] Steroids, [3] Muscle relaxants, [4] Tricyclic anti
depressants, [5] Anticonvulsants
Warning signs
1. Headache with fever with neck stiffness.
2. Sudden serious acute headache associated with vomiting and neck stiff-
ness.
3. Headache after lumbar puncture which is relieved by lying down this type
of headache is called spinal headache which is relieved by analgesics and
plenty of uids.
4. Headache with projectile vomiting suspect for increased intracranial
pressure this type of headache may be worst on lying down.
5. Headache which is localised and aggravated on chewing temporal
arteritis.
6. Headache with neurodecit.
7. Headache with high BP. More than 160/100
 36 Neurological Disorders - A Handbook for Family Physicians

Sample Prescription

SUMMARY
[1] Sometimes a headache is a warning sign of something serious like stroke,
brain tumors etc. so it should not be taken lightly. One should act promptly
in diagnosing as well as treating the underlying cause. [2] Any patients
whose headaches do not get relieved or worsen within 3 days of initial
management should have a CT Scan done and should be referred to a
Neurosurgeon or Neurophysician. [3] Sudden onset severe headaches are a
sign of a possibly serious underlying disorder and must be investigated
with a scan or referred to a Neuro consultant immediately. [4] for mild
headaches the investigations to be done are (a) ESR, (b) Xrays PNS, (c) Check
up by optician / opthalmologist for refractory error, [5] for severe
headaches a CT Scan brain (plain & contrast) should be done.

Tension Headache
Rx
Tb Paracetamol 500mg 1—1—1 x 1 week (for mild headache) or
Tb Paracetamol (500mg) + Codeine (8mg) 1—1—1 x 1 week (for moderate)
or
Tb Paracetamol(500mg) + Aceclofenac(100mg) 1—0—1 x 1 week (for severe)
or
Tb Naproxen (500mg) 1—0—1 x 1 week (for severe headache)
Tb Amitriptyline 25 mg 0—0—1 x 1 week (if difculty in sleeping)
Tb Pantoprazole 40 mg 1—0—1 x 1 week

Migraine headache
Rx
Acute attack
Tb Rizatriptan 10mg 1 tablet stat followed by Tb Naproxen 250mg 8 hourly
with
Tab Domperidone 10 mg 1–0–1
Tb Pantoprazole 40 mg 1—0—1
Migraine prophylaxis
Tb Propranolol 40 mg(slow release) 1—0—0 x 3 months with
Tb Amitriptyline 10 mg 0—0—1 x 1 month or Tb Flunarizine 10 mg 0—0—1
x till relief is obtained
Tb Pantoprazole 40 mg 1—0—1 x 1 week
Neurological Disorders - A Handbook for Family Physicians 37

Cluster Headache
Rx
Tb Prednisone 40 mg 1—0—0 x 5 days (tapered over 3 weeks)
Tb Pantoprazole 40 mg 1—0—1 x 1 month
Refer to the neurologist.
 38 Neurological Disorders - A Handbook for Family Physicians

Giddiness
Giddiness or lightheadedness, a very common symptom seen in practise, is a
term used to describe a sensation of altered orientation in space usually
described by the patient as “chakkar”. Giddiness, lightheadedness, disequilib-
rium and syncope are often mistaken for one another; most often caused by
relative decrease in sensorium and are caused by different conditions.
The important enquires to be made are (a) whether there is a sense of the external
environment rotating or spinning, (b) whether there is an associated loss of
consciousness and (c) whether there are any preexisting medical, cardiac or
neurological disorders.
A) Vertigo/ Dizziness is hallucination of movements which results in sensation
of external environment spinning and rotating and is mostly caused by an
otological disorder and sometimes by CNS disorders.
B) Disequilibrium is a sense of imbalance observed while walking due to cere-
bellar or spinal disorders effecting sensory proprioception.
C) Syncope which is loss of consciousness occurs secondary to inadequate
cerebral perfusion, a common cause of which is postural hypertension and
cardiogenic factors.
Examination
1. Physician should check the blood pressure in all positions to see postural
hypotension.
2. Neurological examination to rule out any neurological decit and to rule
out secondary cause
3. ENT for otitis media or labyrinthitis, hearing loss
 Neurological Disorders - A Handbook for Family Physicians 39

4. Eye examination-to look for nystagmus, refractive error any visual decit
5. ECG to rule arrhythmias and other causes.
6. Basic blood tests- CBC, electrolytes etc.
7. See on what medications patient is on, medications as many of the drugs
itself can cause dizziness.
8. Clinical bedside maneuver : Dix Hallpike maneuver
Causes of Vertigo:
The three systems that are involved are the brain, the cervical spine and the
inner ear.
1. Inner ear or vestibular dysfunction:
a) BPPV (Benign paroxysmal positional vertigo):
It is caused by displacement of otoconia into the posterior semi circular canal
and it manifests as a rotational dizziness. The patient complains that the sur-
roundings seem to rotate.
The key distinguishing feature is that it is positional. There is severe vertigo only
in same positions of the head (i.e. right or left). In addition to vertigo, symptoms
of BPPV may include dizziness (lightheadedness), imbalance, difculty
concentrating, and nausea.
Provocative factors: Vertigo symptoms are precipitated by changing the head’s
position with respect to gravity like looking up, rolling over or getting out of bed.
Causes of BPPV in young adults include head injury, and age-related degenera-
tion of the otolithic membrane in older adults, surgical trauma, etc. It may also
develop after long periods of inactivity.
Diagnosis: BPPV is diagnosed based on medical history, physical examination,
vestibular and auditory tests. If vertigo does not respond to standard medicine
or there are other associated neurological signs, then workup needs to be done
to rule out other diagnoses.
1. Vestibular tests which include the Dix-Hallpike maneuver and the Supine
Roll test, observe the nystagmus elicited in response to a change in head
position. The semicircular canal involved in vertigo can be identied by
these tests.
2. Audiogram: if it shows sensory neural deafness then get the following
a. SISI: if positive suggests a cochlear problem.
 40 Neurological Disorders - A Handbook for Family Physicians

b. TDT testing: positive suggests a retrocochlear problem

3. An MRI scan will be needed to rule out other problems such as a stroke or
brain tumour. MRI brain with gadolinium contrast can be ordered to
evaluate for C P angle tumor.
4. Blood tests: CBC and serum electrolytes
Treatment:
1. Tb Meclizine 25 to 50 mg orally every 4 to 6 hours
2. Perform Epley’s maneuver:
Start with patient sitting on couch. Turn patient’s head (45 degrees) toward
affected side. Pause in this position for 30 seconds. Lie patient at, support the
head throughout. Head remains turned to affected side and is hanging off end of
couch. Pause in this position for 30 seconds. Turn the patient’s head (90 degrees)
towards the good ear. Pause in this position for 30 seconds. Keeping head look-
ing in same direction, ask patient to gently move to lie on shoulder of good side,
looking at oor, with chin close to shoulder. Pause in this position for 30 sec-
onds. Gently bring patient to sitting position. Ensure head position does not
change relative to trunk. Pause for 30 seconds. Finally, turn head to centre and
ex neck to put chin on chest in one movement. Pause for 30 seconds
3. Vestibular rehabilitation
THE EPLEY MANEUVER
Redistributed
particles
Particles in
semicircular
canal

The head may be rapidly turned

even further to almost face the oor. The clinician rotates the patients head lowaid the affected
The patient is returned to the ear, then lowers the patient backward to the supine
upright position. and the head is position with the head hanging over the table's edge.
rotated back to normal.

The head Is turne further, so that The head is turned to the other side.
the ear is parallel to the oor.
Fig. 2.1: The Epley Maneuver
 Neurological Disorders - A Handbook for Family Physicians 41

Precautions: The patient should be asked to sleep in an elevated position with

two or more pillows and not on the side of the treated ear. A cervical collar
should be given to avoid quick movements like looking up or down or head
rotation.
Referal : Refer to ENT consultant.
b) Meniere’s disease:
It is caused by collection of uid in the inner ear. Presents with a combination of
severe vertigo, tinnitus and nausea.
Causes
Cause is unknown, recent theory is intracranial compression of balance nerve by
blood vessel
Signs & symptoms
Ÿ Hearing loss
Ÿ Vertigo
Ÿ Ear fullness
Ÿ During severe attack there may be pallor, sweating, nausea, vomiting and
falling.
Investigations: Audiogram
Treatment: [1] Vertin TDS x 7 days. [2] Salt restriction (less than 1 to 2 gms
sodium/ day) [3] Others- diuretics (most commonly hydrochlorothia-
zide/triamterene) Intratympanic dexamethasone or gentamicin,[4] In severe
cases endolymphatic sac surgery
Referal: if no relief then refer to ENT consultant.
c) Labrinthitis:
Inammation of the vestibular labyrinth(a system of intercommunicating
cavities & canals in the inner ears). Clinically, patient experiences disturbances
of balance and hearing to varying degrees and may affect 1 or both ears.
Causes
Ÿ Physiological-mismatch of vestibular,visual and somatosensory systems
triggered by an external stimulus,such as a stop after whirling turns,
heights, motion sickness.
 42 Neurological Disorders - A Handbook for Family Physicians

Ÿ Pathological-imbalance in vestibular system caused by a lesion within

vestibular pathways
Ÿ Infections-especially viral, mumps
Ÿ Others-Tumors,Vasculitis,Infarction,Ototoxic drugs,Head injury
Investigations : CBC,LFT,blood sugar,creatinine etc Treatment
1. Tb Meclizine 25 to 50 mg orally every 4 to 6 hours
2. Tb Domperidone tds
3. In some cases, antibiotic or antiviral may be given
Referal: refer to ENT consultant.
d) Vestibular neuritis
Vestibular neuritis is acute, sustained dysfunction of the peripheral vestibular
system which presents as nausea, vomiting, and vertigo, and normal hearing.
Vestibular neuritis is generally distinguished from labyrinthitis by preserved
auditory function.
Treatment
Methylprednisolone initially 100 mg orally daily then tapered to 10 mg orally
daily over 3 weeks.
e) Migrainous vertigo:
Vertigo associated with migraine headache. Fairly common type of vertigo
especially in females. The cause of vertigo in migraine patients is not yet
known, but the diagnosis of migraine should be entertained in any patient
with chronic recurrent attacks of dizziness of unknown cause.
Treatment
1. Tb Meclizine 25 to 50 mg orally every 4 to 6 hours
2. Migraine prophylaxis with serotonin reuptake inhibitor 5-HT1 receptor
agonists(triptans)
2. Cervical Spine
a. Cervical spondylosis:
In the older age group the most common cause of giddiness is cervical
spondylosis. (this is the most commonly missed problem in routine practise). It
is associated with pain in the back of the neck radiating to head, one of the
 Neurological Disorders - A Handbook for Family Physicians 43

shoulders and upper limbs along with tingling and numbness of both hands. In
advanced stages wasting and weakness of the hands may occur.
Investigations:
1. Lateral and AP x-rays of cervical spine.
2. MRI cervical spine to be done if degenerative changes seen on the x-rays.
Treatment:
1. Analgesics and Anti inammatory combinations. (Brufen + paracetamol
or diclofenec sodium)
2. Muscle relaxants (a)Methocarbamol 1 tab TDS (b)Chlorozoxanone 1 tab
TDS (c) baclofen 10 mg TDS
3. Physiotherapy. (short wave diathermy, traction, neck exercises)
4. Soft cervical collar (till relief)
b. Other causes may include:
Cranio-vertebral junction anomalies, Atlanto-axial dislocation, Cervical spinal
tuberculosis /tumors
3. Brain:
a. Vertebrobasilar insufciency:
This results from decreased blood supply to brain from its posterior vascular
supply. There is a sudden onset of dizziness with imbalance while walking
along with nausea and vomiting. In advanced stages loss of consciousness may
occur.
Investigations: MRI brain with angiography.
Referal: Refer to neurosurgeon or neurophysician.
b. Other causes may include:
Cerebellar infarct, Brain stem infarct, C P angle tumor, Cerebellar hemorrhage,
Basilar migraine, Seizure
4. Other causes of vertigo:
1. Orthostatic hypotension
2. Cardiac arrhythmias/ other cardiac problems
3. Hypoglycemia / other manifestations of Diabetes
 44 Neurological Disorders - A Handbook for Family Physicians

4. Alcohol intoxication
5. Hyperventilation syndrome
6. Panic related
7. Drug toxicity(anticonvulsants,salicylates)
8. Medical conditions like Uremia.
Treatment
1. Orthostatic hypotension
2. Midodrine (promatine) titrated up to 10 mg orally 3 times a day
3. Fludrocortisone initially 0.1 mg orally daily,titrated up weekly until
peripheral edema develops or to a maximal dosages.
5. Hyperventilation syndrome
Breathing control exercises, rebreathing into small paper bag, beta
blockers,antianxiety agents eg serotonin reuptake inhibitors or short term
benzodiazepines.
6. Disequilibrium
Treatment of underlying cause is described in Section C.
7. Syncope and pre syncope:
When loss of consciousness is temporary and there is spontaneous recovery it is
called syncope. It may be preceded by symptoms like dizziness or faintness or
“the presyncope”. This occurs due to reduction of blood ow to the brain.
Presyncope symptoms vary in duration and may increase in severity until loss
of consciousness. Symptoms may include light headedness, sweating, pale skin,
blurred vision, nausea, vomiting, etc. These are usually brought about by
hypotension with reduction of cerebral blood ow. Three-fourths of the sys-
temic blood ow is contained in the venous bed and any interference in venous
return may result in reduction in cardiac output.
Syncope must be differentiated from vertigo, coma, drop attacks, dizziness,
sudden cardiac death, and seizures.
Neurological causes of syncope and pre syncope:
This condition is also known as ‘neurally mediated hypotension’, ‘the fainting
reex’, ‘vasodepressor syncope’, ‘vasovagal syncope’, or ‘autonomic dysfunc-
tion’. The brainstem structures are supplied by vertebrobasilar arteries, which is
 Neurological Disorders - A Handbook for Family Physicians 45

responsible to maintain consciousness and which may cause syncope due to

vascular disease.
Those who experience syncope may also have symptoms of focal neurologic
ischemia such as arm and leg weakness, diplopia, ataxia, dysarthria, etc. Neuro-
logical causes should be suspected if headache or dizziness occurs during
recovery from syncopal episodes.
In middle age, neurocardiogenic syncope remains the most frequent cause of
syncope.
Common causes of syncope in elderly persons include orthostatic hypotension,
postprandial hypotension, medications, carotid sinus hypersensitivity.
Other forms of neurocardiogenic syncope (so-called situational syncope)
related to deglutition, micturition, defecation, and cough are more common in
the middle-aged or elderly patients than in young patients.
Neurocardiogenic syncope may occur in the following situations:
Ÿ after prolonged periods of standing
Ÿ after being in a hot summer weather, a hot crowded room, or a hot shower
Ÿ immediately after exercise
Ÿ after emotionally stressful situations
Ÿ after having food (since blood ow shifts to the intestinal circulation
during the process of digestion)
How to diagnose
The Physician should look for emergency care in cases of massive internal
haemorrhage. The position of the patient is also important. If a patient has
syncope in supine position or loss of consciousness prolonged ( more than 3
mins) then it may be a seizure especially complex partial seizure.
Key clinical features of neurocardiogenic syncope
Ÿ It tends to be situational
Ÿ It is often recurrent
Ÿ It is often preceded by at least a few seconds of prodromal symptoms.
Ÿ It occurs when the patient is in the upright position, and is resolved and
can be aborted by assuming the supine position.
 46 Neurological Disorders - A Handbook for Family Physicians

Ÿ After recovery, patients with neurocardiogenic syncope often complain

of a “washed out” and tired feeling.
Examination
Ÿ Check the blood pressure in supine, sitting and lying down position.
Drop of systolic BP by more than 20 mm Hg and/ diastolic BP. Y more
than 10 mm Hg suggest that there is postural drop.
Ÿ Check the heart rate in supine, sitting and lying down position
Ÿ Cardiac and neurological examination
Investigations:
Tests involve serum electrolytes, glucose and haematocrit, creatinine, etc.
ECG and Echocardiogram to rule out cardiac causes
Head up tilt test, Autonomic function tests
In selected cases : MRI andMRA brain , EEG
Management
Non Pharmacological
Patients with frequent episodes of syncope should take extra precaution while
climbing stairs, swimming alone, operating heavy machines, driving. Patients
who have lost consciousness should be placed in recovery position which will
help to improve cerebral ow. Clothing that ts tight around the neck or waist
should be loosened.
Patients experiencing neurocardiogenic syncope should avoid situations that
predispose to syncope (e.g., dehydration, stress, alcohol consumption, pro-
longed standing, and extremely warm environments). Anxiety management
and coping skills should be taught. It is important to reassure the patient that
this is a benign condition.
Pharmacological
Metoprolol 25 to 50mg bid,
atenolol 25 to 50 qd.
Drug therapy is necessary in vasovagal syncope when the episodes are frequent
with associated risks.
paroxetine 20 to 40 mg qd, or sertraline 25 to 50 mg qd
Serotonin reuptake inhibitors in some patients is helpful.
Neurological Disorders - A Handbook for Family Physicians 47

Management for Neurological cause

Seizure-see chapter number 4
Stroke-see chapter number 21

Patient presents with doziness

Ask about medication regimen, caffeine, nicotine, and

alcohol intake, and history of head trauma or whiplash

What sensation does the patient describe?

False sense of motion Off•balance or wobbly Feeling of losing Vague symptoms,

or spinning sensation consciousness possibly feeling
or blacking out disconnected with
Dyseguilibrium the movement
Vertigo
Presyncope
Consider possible Lightheadedness
underlying conditions, such
as peripheral neuropathy Ask about history
Ask about migraine symptoms
and Parkinson disease of arrhythmias and Ask about history of
Recheck medication myocardial infarction anxiety or depression
regimen, especially in older Recheck medication Perform hyperventilation
Migrainous vertigo is diagnosed with
patients Examine gait and regimen, especially provocation test
history of episodic vertigo with a current
vision, perform Romberg in older patients
migraine or history of migraine and one of
test, screen for neuropathy Measure orthostatic
the following symptoms during at least two
blood pressures
episodes of vertigo: migraine headache,
photophobia, phonophobia, aura
Hearing loss?
Consider cardiac
testing in patients
Yes No with relevant history

Episodic vertigo? Episodic vertigo?

Yes No Yes No

Meniere Labyrinthitis Benign paroxysmal Vestibular

disease positional vertigo neuritis

Perform Dix-HatIpike maneuver (Figure 1)

Fig. 2.3
48 Neurological Disorders - A Handbook for Family Physicians

SUMMARY
Giddiness can be the presenting symptom of potentially life threatening
conditions. If in doubt get urgent CT scan or MRI and advise admission with
reference to the concerned consultant.
It is very important to differentiate whether the patient has dizziness/
vertigo or syncope because the causes & treatment will vary accordingly.
Syncope is a more serious symptom & therefore has to be evaluated by a
specialist Doctor & patient workup needs to be done immediately.
Vertigo is a common symptom encountered by a family physician. It is most
commonly caused by inner ear disturbances. Therefore, a thorough ENT
checkup is required if the symptoms do not resolve by standard medicines
or are recurrent.

Sample Prescription For Vertigo

Rx
Tb Meclizine 25 mg to 50 mg 4 to 6 hourly
Tb Domperidone 10 mg 1 – 0 – 1
Vestibular rehabilitation
 Neurological Disorders - A Handbook for Family Physicians 49

Memory Problems
Memory problems include inability to recall past experiences and are divided
into long term and short term memory loss. Loss of recent memory is an
important indication of age related cerebral degeneration and most often goes
undiagnosed. It is important to note that this is a symptom that patient would
never complain himself unless asked. It is the relatives who will conrm on
questioning that the patient forgets immediate past events. Since the patients
have very vivid recollection of the long term events they believe their memory is
good, therefore the distinction between long term and short term memory is
very important.
Therefore loss of recent memory is a symptom that all family physicians must
ask their patients (>60) and their relatives. A distinction should be made
between long term memory and short term memory, when obtaining the history
of memory loss.
Causes
1. Senile dementia
2. Normal pressure hydrocephalus
3. Multiple lacunar Infarcts
4. Alzheimer disease
5. Multiple sclerosis
6. Other rare degenerative disorders
Conditions in which memory problems can be reversed and treated:
1. Hypothyroidism
2. Vit B12 & folate deciency
3. Hepatic encephalopathy
 50 Neurological Disorders - A Handbook for Family Physicians

4. Uremic encephalopathy
5. Infections
- Meningitis
- Encephalitis
- Brain abscess
- Syphilis
6. Resectable tumours like small meningioma
7. Medicines
- Side effect of drug can cause memory loss Eg-Anticholinergic
8. Toxins
- Heavy metal
- Elicit drugs
9. Hypertension
- Hypertension encephalopathy
- Subdural hematoma
- Normal pressure hydrpcephalus
10. Depression
Conditions in which memory problems are irreversible:
1. Vascular dementia
2. Alzheimers
3. Fronto temporal dementia
4. Dementia with lewy body
5. Parkinson’s
6. Neurodegenerative disorders
7. Non resectable tumors
8. Progressive multifocal
9. leukoencephalopathy
10. HIV
11. Prion disease
-Crentzfeldt-Jakob disease
-Endocrine
12. Neuronal storage disorders
13. Leukodystrophy
 Neurological Disorders - A Handbook for Family Physicians 51

Mechanism of recent loss of memory

Ccerebral atrophy and degeneration of medial temporal lobe result in gradual
decline of memory function. A common triad of symptoms i.e. loss of recent
memory, urinary incontinence and ataxia denitely suggest cerebral atrophy
with increase in cerebral size resulting in a condition referring to normal
pressure hydrocephalus (NPH). Interestingly patients never tell about these
symptoms, however when asked they will answer in afrmation. Hence, it is
very important to enquire about these three symptoms whenever any patient
above sixty years presents with any neurological symptoms.
Investigations
1. MRI Brain - It would pick up small ischemic areas and other degenerative
neurological conditions if present.
2. CT scan Brain
3. Serum B12, folate, TSH , CBC and electrolytes
Chronic Memory Loss:
1. Senile dementia:
This is a clinical diagnosis and is made after
excluding normal pressure hydrocephalus
which may coexist. The most important
symptom in these patients is loss of recent
memory.
Treatment:
Donepezil – is available in 5 mg / 10 mg given
TDS. Patients report an instant improvement
within 48 hrs of starting the medication. Should
be taken for 6 wks and may be continued for
longer depending on the response. There are no
major side effects, though it is important to
follow up once every 15 days while on
Fig. 3.1: Normal
Donepezil.
pressure hydrocephalus
2. Normal pressure hydrocephalus:
Clinical diagnosis is by presence of triad of loss of recent memory, urinary
incontinence and ataxia. It coexists with dementia and is conrmed by a CT scan
or an MRI scan.
 52 Neurological Disorders - A Handbook for Family Physicians

Medical Treatment:
Treatment for NPH is surgical diversion of CSF, which is accomplished by
implanting a shunt to drain CSF from either the intracranial ventricular system
or the lumbar subarachnoid space to a distal site, such as the peritoneal or
pleural cavity or the venous system, where the CSF can be re absorbed. The
most common shunts utilized today are ventriculo peritoneal (VP) and
ventriculo atrial (VA) shunts Placement of a shunt is a neurosurgical procedure
performed under general anesthesia, taking less than an hour to complete.
Medical management has limited role in management of NPH. Trial of
Acetazolamide ( Dimox) can be given . Starting dose is 250 mg twice daily . It can
be gradually increased to 3-4 gm/day. Parenthesia is common and dose limiting
side effect. Hypokalemia is common with acetazolamide use. Close monitoring
of serum K+ level is recommended.
For associates behavioural disturbances antipsychotics like Quetiapin ( dose 25
mg /day can be increased up to 300 mg /day) should be given.
3. Multiple lacunar infarcts / Vascular
dementia :
These patients have multiple small infarcts,
none of which are big enough to cause neuro-
logical defects. However, there is cerebral
atrophy.
Treatment:
Fig 3.2: Vascular dementia
Treatment is similar to cerebral ischemia.
1. Aspirin
2. Clopidogrel
3. Pentoxyphyline
4. Neuroprotective drugs – Piracetum, Citicholine
5. Memory enhancers – Donepezil
6. Supportive therapy – Neuro protective vitamins (folic acid,
methylcobalamine, Biotin)

Practical management : In the authors experience the best combination of drugs

for the above are Donepezil 10 mg -TDS + Citicholine – 1 BD + neuroprotective
vitamins.
 Neurological Disorders - A Handbook for Family Physicians 53

Referral:
Patient with senile dementia can be managed by the family physician and need
not be referred, however if the CT /MRI shows NPH then refer to a neurosur-
geon. Patients with vascular infarcts should be referred to a neurophysician.
Memory clinics:
In the last 1-2 yrs many memory clinics have come up in the metros.
4. Alzheimer’s Disease:
It is characterized by progressive deterioration of higher mental functioning
with impaired short term and long term memory, impaired judgement and
abstract thinking, personality changes, sleep disturbances, mood disturbances
and affected speech. The rate of progression may be variable.

Basic principle
i. Ensure that dehydration, infections, metabolic disturbances, pain are
treated effectively.
ii. Correct hearing or visual loss
iii. Avoid anticholinergic agents
iv. Reduce the psychoactive medications with possible cognitive side effects
to the fewest at the lowest effective doses.
A) Pharmacologic therapy
i. Degenerative dementia
ii. Donepezil, Rivastigmine, Vitamin E are to be used
iii. Other alternative medications like Ginkgo biloba, Hydergine are also been
used nowadays.
iv. For behavioral symptoms like depression, selective serotonin reuptake
inhibitor is to be used.
 54 Neurological Disorders - A Handbook for Family Physicians

v. For anxiety, bupropion to be used

vi. For delusion, hallucinations, agitation medicines like donepezil,
rivastigmine, tacrine, respiridone, carbamazepine, valproic acid are to be
prescribed.
3) Non Pharmacologic therapy
i. Many of irreversible dementia needs multidisciplinary team which
includes:
ii. A neurologist, psychologist, physiotherapist, occupational therapist,
speech therapistii.
A physician should take charge in treating dementia patients and should
coordinate with other doctors of the team with regular follow ups.
iii. Psychological therapy- Behavior modication technique
iv. Rehabilitation: Research has shown that physical activity has slowed
down the progression of cognitive defects. Physiotherapy and
occupational therapy are few of the helpful therapies.
v. Environment changes : Modify the response, modify tasks
vi. Care for the caregivers : Counseling of the caretaker is very important as it
is stressful to handle dementia patients. Psychologists can give tips to the
care givers about handling the patient.
Pharmacology & supplements
i. Cholinesterase inhibitors
• Tablet Donepezil to give 1 tablet of 5 mg at bedtime may increase to 10 mg
in 4 to 6 weeks for mild to moderate disease
• Tablet Galantamine extended release start 8 mg every morning with food
may increase 16 mg after 4 weeks
• Tablet Rivastigmine 1.5 mg twice a day may increase to 3 mg twice a day
after 2 weeks
ii. NMDA receptor antagonist
Memantine start with tablet 5mg daily at weekly intervals to maximum 20
mg/ day doses greater than 5 mg should be divided in bid. Extended
release tablet start 7 mg per day, increase at weekly intervals to target dose
of 28mg/day, for renal impairment reduce to 14mg/day.
 Neurological Disorders - A Handbook for Family Physicians 55

iii. Neuroprotective drugs

iv. Tablet CO Q or Tablet Ubiquinol also tablet vitamin c, vitamin e,
multivitamin especially B complex including B12 & folic acid.
v. Other alternative medicines like gingko bibola are also being used.
Contraindications
i. Antipsycotics (haloperidol, risperidone) - severe depression, Parkinson’s
disease, hypo-hypertension
ii. Tricyclic antidepressants (nor tryptiline, desipramine) - acute recovery
phase following myocardial infarction
iii. Acute liver disease, peptic ulcers
Sun-downing, aggressive behavior
i. Antipsychotic drugs such as haloperidol or respiridone 0.5-1.0 mg a day
Sleep disturbance
ii. Tablet zolpidem Tb Restyl 0.2 mg, alprazolam 0.5mg
iii. Tb Temazepam 15 mg 0—0—1 at bedtime to be given
Acute memory loss
Warning signs
1. Acute onset of memory problem
2. Rapidly progressing memory problem
3. Dementia associated with other acute symptoms
If the patient has the above warning signs one should order the following
investigations
¡ CBC, LFT, Creatinine, electrolyte levels, ESR
¡ T3,T4, TSH, Vit B 12, Folic acid
¡ VDRL or Fluorescent treponemal antibody absorption test
¡ Toxin screening: heavy metal
Differential diagnosis of acute memory problem
i. Delirium
ii. Dementia
 56 Neurological Disorders - A Handbook for Family Physicians

iii. Electrolyte imbalance

iv. Heat stroke
v. Schizophrenia
vi. Depression
vii. Alcoholism
viii. Normal pressure hydrocephalus
Special investigations to be ordered to differentiate between various above
causes
1. CT Head (preferably with & without contrast) to rule out tumours or focal
neurological decit
2. MRI Brain –more sensitive than CT to diagnose brain soft tissue pathology
3. PET CT Brain-will show hypometabolism in various areas of brain
depending upon the cause.
4. CSF testing
(Findings are described in dementia chapter)
Below are the screening questions to differentiate various types of dementia:
1. Onset - sudden or gradual
2. Progression - rapid or slow
3. Severity - mild, moderate or severe
4. Any associated symptoms
a. Focal neurological decit
b. Infections - any history of fever, weight loss, gait impairment
Depending upon the associated symptoms, causes differ
1. In the presence of atypical course such as rapidly progressive, waxing
&waning, or series of abrupt changes in clinical course, consider causes
like vascular, infectious, inammatory/autoimmune, toxic/metabolic
processes, multiple sclerosis, Dementia with Lewy bodies,
Frontotemporal dementia, vascular dementia, Creutzfeldt–Jakob disease.
2. If there is presence of systemic symptoms such as headache, fever, dry eyes/
mouth, arthralgia, weight loss, or skin lesions then consider infectious,
inammatory/autoimmune, neoplastic, paraneoplastic processes.
 Neurological Disorders - A Handbook for Family Physicians 57

3. If there is presence of sleep disorder, such as excessive day time sleepiness,

loud snoring, restlessness, insomnia, leg jerks while sleeping then the
patient may have obstructive sleep apnoea, central sleep apnoea, restless
leg syndrome, periodic limb movement disorder.
4. Presence of neuropsychiatric symptoms such as behavior or personality
change, apathy, visual hallucinations, delusions, agitation may be due to
toxic or metabolic processes, infectious or inammatory conditions or
DLB, FTD
5. If there is presence of neurological symtoms or signs like diplopia,
dysphagia, face &limb weakness or numbness, gait unsteadiness, then
consider brain tumor or abscess.
6. In the presence of Parkinson’s signs such as masked facies, abnormal gait,
stooped posture, tremors, ridigity, suspect Parkinson’s disease, DLB,
NPH.
Examination
1. Check blood pressure, heart rate
2. Check for any signs of trauma (head injury)
3. Also look for nuchal rigidity, papilledema, focal facial or limb weakness,
abnormal deep tendon reexes, Parkinsonism, gait impairment,
fasciculations.
4. Mini mental status examination
Treatment
Treat the underlying cause.
 58 Neurological Disorders - A Handbook for Family Physicians

Sample Prescription

SUMMARY
Memory problems are very common in elderly population. Normal aging
beyond 65 years may be associated with memory loss called senile
dementia. It is very important to differentiate abnormal memory loss, for eg.
Alzheimer's dementia, etc. from normal aging as the prognosis will differ.
Early identication and treatment can help to preserve and slow down the
progression of dementia. Lifestyle modications, environmental
modications and rehabilitative techniques play a key role in the
management of dementia. MRI and PET scan are used as diagnostic and
monitoring tools. Anticholinesterase drugs (donepezil), neuroprotective
agents are used for pharmacotherapy.
In patients with acute memory loss, underlying causes need to be identied,
investigated and treated appropriately and immediately.

Rx
Cognitive impairment
Tb Donezepil 5mg 1-0-0 or Tb Rivastigmine 1.5mg 1-0-1 Or Tb
Galantamine 4mg 1-0-1
Sleep disturbance
Tb Temazepam 15 mg 0-0-1 or Tb Zolpidem 5 mg 0-0-1
Depression
Tb Nortriptyline 25 mg tds
Neuroprotection
Tb CoQ10 300 mg bd or Tb Ubiquinol 100 mg bd Tb Vit C 1-0-0, Cap Vit E
400 mg 1-0-0
Cap Mecobalamin 0-1-0, Tb folic acid 1-0-0, Tb Omega3 fatty acids 1-0-0
 Neurological Disorders - A Handbook for Family Physicians 59

Convulsions
These are the involuntary movements associated with loss of consciousness.
They may exist by themselves or present as an underlying neurological
disorder.
There are three phases of a seizure:
Aura – This is the unusual sensation of a start of a seizure. The person will
remain conscious but experience unusual feelings or sensations. The person
may experience sudden and unexplainable feelings of joy, anger, sadness, or
nausea. He or she also may hear, smell, taste, see, or feel things that are not real.
Ictus – Meaning the attack.
Postictal – Meaning after the attack and postictal refers to the after effects of the
seizure like loss of consciousness.
Causes of convulsions:
Ÿ Brain malformations or metabolic disorders.
Ÿ Lack of oxygen (hypoxic brain injury) or intracranial haemorrhage during
birth.
Ÿ Low levels of blood sugar, blood calcium, blood magnesium or other
electrolyte disturbances.
Ÿ Fever
Ÿ Congenital conditions (Down’s syndrome; Angelman’s syndrome;
tuberous sclerosis and neurobromatosis) and other genetic factors
Ÿ Head trauma
Ÿ Alcohol or drugs
Ÿ Brain tumours- Supratentorialtumours
Ÿ Drug withdrawal
 60 Neurological Disorders - A Handbook for Family Physicians

Ÿ Medications, Maternal use of drugs.

Ÿ Infection that could be viral, bacterial or parasitic
Ÿ Stroke
Ÿ Alzheimer’s disease

Fig. 4.1: Positioning a patient with an episode of convulsion

Investigations:
1. EEG
2. CT Brain /MRI
3. Blood Investigations- CBC, Electrolytes, LFT, Creatinine, Blood sugar,
Calcium, Magnesium.
Referal:
Should be made to a neurophysician or a pediatrician incase of children.
Treatment:
1. Treat the seizure episode with anticonvulsant as given below according to
the type.
2. Treat the underlying cause with medications for medical conditions and
surgery for operable cases.
3. Monitor and follow up regularly for repeat episodes. Ask the patient to
maintain record of seizure episode e.g. frequency of seizures, severity of
seizures, precipitating factors, etc. Adjust the current dose or add another
anticonvulsant if not under control.
 Neurological Disorders - A Handbook for Family Physicians 61

Types
A) Febrile:
Most commonly seen in children of 6 months – 6 years age group. It
presents as generalized convulsions with febrile episodes. Sometimes also
seen with administration of vaccines.
Treatment:
Single episode no treatment required. Repeated episodes with EEG
changes anticonvulsants should be started as advised by the pediatrician.
Sodium Valporate, Phenobarbitone, Levitiracetam.
B) Generalized Tonic – Clonic Seziures:
Most commonly seen in adults and are associated with loss of
consciousness. There is sustained contraction followed by rhythmic
contractions of all four extremities. Tonic clonic movements (stiffening of
limb along with jerking movements) last for a few seconds to a few
minutes. They invariably have post convulsive period of drowsiness or
stupor, lasting from a few minutes to a few hours.
Treatment:
Anti convulsants – any of the following
a. Phenytoin
b. Levitiracetam
c. Sodium valproate
d. Phenobarbitone (Gardinal)
e. Carbamezapine
f. Clonazepam
C) Absence Seizure:
These consist of a brief lapse of awareness, it may occur in children as well
as adults. These are divided into simple absence seizure (there is no limb
involvement and post icteric phase) and complex absence seizure (loss of
muscle tone).
Treatment:
Not all anticonvulsants are effective in this type of seizures e.g.
Carbamazepine is ineffective, whereas Phenytoin and Gardinal are not
very effective.
 62 Neurological Disorders - A Handbook for Family Physicians

Drugs used are: Sodium valproate, Ethosuximide, Lamotrigine,

Acetazolamide, Clonazepam
D) Partial Seizure:
There are of two types of partial seizures: simple partial (associated with
psychic phenomena known as Déjà vu, sense of unreality) which results in
focal motor movements without loss of consciousness. Complex partial,
there is alteration in consciousness, bizarre sensations such as dream like
state, automatism or olfactory sensations. Partial seizures occur due to
focal brain lesions such as tumors, infections, head injury and vascular
malformations.
Treatment:
Any one of the following anticonvulsants can be given
I. Phenobarbitone
ii. Phenytoin
iii. Levitiracetam
iv. Carbamazepine
v. Oxcarbazepine
vi. Clonazepam
If not responding to the above then the following should be given
1. Topiramate
2. Lamotrigine
Surgery if unresponsive to above treatment
E) Myoclonic Seizures:
These are characterised by repetitive jerking of large muscle groups. They
are clonic movements often conned to one limb, but may sometime
involve the axial musculature. They occur due to diffuse cerebral
condition such as infections, metabolic disorders such as uremia.
Treatment:
1. Sodium Valproate
2. Levitiracetam
3. Benzodiazepines (Diazepam)
4. Topiramate
5. Lamotrigine
 Neurological Disorders - A Handbook for Family Physicians 63

Surgery if unresponsive to above treatment

a) Removal of seizure focus
b) Temporal lobectomy
c) Vagal nerve stimulation.

Management of Acute Seizures

64 Neurological Disorders - A Handbook for Family Physicians

What questions should be asked by you?

¡ Age of onset?
¡ Precipitating factors?
¡ How often?
¡ What time of the day?
¡ Is its onset sudden? Or gradual?
¡ Was there loss of consciousness?
¡ Is it associated with sweating? Pallor? Mental disturbance? Involuntary
micturition?
¡ Was there any associated vomiting? Projectile vomiting?
¡ Does any family member suffer from epilepsy?
Neurological Disorders - A Handbook for Family Physicians 65
 66 Neurological Disorders - A Handbook for Family Physicians

Paralysis
Paralysis is the complete loss of muscle function for one or more muscle groups.
It can be associated with sensory loss along with the motor loss. It can occur on
one or both sides of the body. Paraplegia is the paralysis of lower half of the body
whereas paralysis of all four limbs is called quadriplegia. Hemiplegia
(sometimes called hemiparesis) is a condition that affects one side of the body.

What are the types?

Localised or generalized paralysis
Localized paralysis affects only a part of the body like facial paralysis – which is
usually limited to one side of the face or paralysis of the hand.
Generalized paralysis affects a wider area like monoplegia – where one limb is
paralysed; hemiplegia – where the arm and leg on one side of the body are
paralysed; paraplegia – where both legs, or sometimes the pelvis and some of
the lower body are paralyzed; quadriplegia where both the arms and legs are
paralysed

Fig. 5.1: Types of Paralysis

 Neurological Disorders - A Handbook for Family Physicians 67

Temporary and permanent paralysis

Paralysis can either be temporary or permanent. Bell’s palsy is a relatively
common type of temporary paralysis. Sometimes paralysis that occurs after a
stroke can also be temporary.
Paralysis caused by serious injury, such as a complete spinal cord section, is
usually permanent.
Partial or complete paralysis
Paralysis can be partial – where there is some muscle function and sensation; for
example, if a person can move one leg but not the other, or feel sensations such as
cold and heat.
It can be complete – where there is complete loss of muscle function and
sensation in affected limbs.
Spastic or accid paralysis
Paralysis can be spastic – where muscles in affected limbs are unusually stiff or
display spasms, and movements are not under the control of the individuals.
In accid paralysis, muscles in affected limbs are oppy and weak. Patients with
accid paralysis often experience muscle weakness without spasms.
In some conditions, such as motor neuron disease or cerebral palsy, it is possible
to experience episodes of spastic paralysis followed by accid paralysis, or the
other way around.
Depending on the levels of spinal cord injury
Spinal cord injury between C1 and C7 is likely to result in quadriplegia.
The extent of the paralysis and subsequent loss of muscle function will depend
on level of injury-C1 to C4 spinal cord injury will result in little or no movement
in limbs and patient will also need a ventilator to assist breathing. C7 spinal cord
injury patients will be able to extend their elbows and may have some
movement in their ngers.
T2 to T12 spinal cord injury will result in little or no function in lower limbs.
L1 to L5 injury may result in limited movement in the lower limbs.
The most common types of paralysis are-
a) Stroke where the blood supply to the brain is suddenly stopped or
there is haemorrhage in the surrounding brain tissue.
68 Neurological Disorders - A Handbook for Family Physicians

b) Spinal Cord Injury can cause damage to the nerves within the spinal
canal due to mostly trauma to the vertebral column, affecting
sensory, motor and autonomic function below the level of injury.

Fig. 5.2: Levels of Spinal cord injury

c) Amyotrophic Lateral Sclerosis ALS, also called Lou Gehrig’s disease,

is a progressive neurological disease where the progressive
degeneration of the motor neurons eventually leads to their death.
When the motor neurons die, the ability of the brain to initiate and
control muscle movement is lost. Patients in the later stages of the
disease may become totally paralyzed.
 Neurological Disorders - A Handbook for Family Physicians 69

d) Poliomyelitis (infantile paralysis) has been eradicated from almost

every country in the world since the vaccines have been used.
Paralytic polio occurs due to destruction of motor neurons within the
spinal cord, brain stem, or motor cortex.
e) Spina Bida is a type of neural tube defect leading to incomplete
closure in the spinal column.
f) Multiple Sclerosis is a disorder of the brain and spinal cord involving
decreased nerve function associated with scar formation on the
covering of neurons.
g) Guillain-Barre Syndrome is a disorder in which the body’s immune
system attacks part of the peripheral nervous system.
h) Cerebral Palsy is a group of conditions that affect control of
movement and posture.
i) Brachial plexus injury can be due to excessive stretching, tearing, or
other trauma to a network of nerves from the spine to the shoulder,
arm, and hand.
j) Muscular Dystrophy is a type of genetic diseases characterized by
progressive weakness and degeneration of the skeletal muscles that
control movement.
k) Syringomyelia/Tethered cord can include progressive deterioration
of the spinal cord, progressive loss of sensation or strength, profuse
sweating, spasticity, pain and autonomic dysreexia.
l) Transverse Myelitis is a neurological disorder caused by
inammation across one segment of the spinal cord.
The most common paralysis one is likely see in a practice are-
Bell’s palsy:
Localized paralysis occurs in Bell’s palsy where one side of the face may be
paralysed due to inammation of the facial nerve i.e. the seventh cranial nerve,
on that side. Patients present with following complaints:
1. Muscle weakness or paralysis
2. Forehead wrinkles disappear
3. Overall droopy appearance
4. Impossible or difcult to blink
 70 Neurological Disorders - A Handbook for Family Physicians

5. Nose is constantly stuffed

6. Difculty in speaking
7. Difculty eating and drinking
8. Sensitivity to sound (hyperacusis)
9. Excess or reduced salivation
10. Facial swelling
11. Diminished or distorted taste
12. Pain in or near the ear
13. Drooling
14. Eye closure difcult or impossible Fig 5.3 Bell's palsy - Drooping eye,
15. Dry eyes due to lack of tears drooping corner of mouth
16. Drooping of the eye brows
17. Lower eyelid droop
18. Sensitivity to light

Investigations:
After taking a history and carefully observing the symptoms, tests that may be
ordered include various blood tests, MRI, or CT scan. These tests will either add
conviction to a diagnosis of Bell’s palsy, or provide the information needed to
proceed in another direction.
Treatment:
1. Steroids (prednisone 80 mg once a day for three days, then 60 mg once a
day for three days, then 40 mg once a day for three days, then 20 mg once a
day for three days, then discontinue use.
2. Analgesics
3. Combination of steroids with antivirals
4. Vitamin B complex
5. Eye care
6. Surgery (decompression of the seventh nerve)
7. Physiotherapy
 Neurological Disorders - A Handbook for Family Physicians 71

Referal:
Refer to a neurophysician or an ENT surgeon.
Stroke (cerebro vascular accidents):
Brain strokes either present as Transcient ischemic attack(TIA) or as full blown
cerebro vascular accidents (CVA) causing hemiplegia (weakness on one side of
the body).
Most paralyses caused by nervous system damage are permanent in nature. The
paralysis of TIA is reversible whereas those of a CVA are irreversible. It is very
important to remember that most CVAs are preceded by TIA. If these TIA are
correctly diagnosed, investigated and treated, a full blown brain stroke can be
easily prevented.
Since majority of patients present initially to their family physician, it is very
important to be aware of this condition and treat it promptly. The role of the
family physicians in the prevention of CVA is therefore vital and crucial.
Common causes for brain stroke and TIA that should be kept in mind by the
physician are –
A. Anxiety
B. Body build
C. Cigarette Smoking
D. Diabetes/ Diet
E. Exercise lack
F. Family History
G. Gout
H. Hypertension

TIA’s: Patients present with one sided loss of sensations with limb weakness
along with blindness in one eye and difculty in talking with giddiness. One,
some or all of these may be present. These last for a few minutes and then resolve
by themselves.
Investigations:
1. CT scan or MRI of the brain with CT angiography or MR angiography
2. Carotid Doppler with 2D Echo
3. Lipid prole and diabetes screening.
Referal:
Urgent reference to a neurophysician or neurosurgeon.
 72 Neurological Disorders - A Handbook for Family Physicians

Treatment:
1. Identication and control of risk factors:
a. Control of hypertension with anti hypertensives
b. Intake of tobacco and smoking should be stopped.
c. Reduction of anxiety with help of meditation or counseling.
d. Weight reduction
e. Diet regulation or moderation.
f. Diabetic control if present.
2. The patient should be made aware to take care of the following –
A. Anxiety
B. Body Build
C. Cigarette Smoking
D. Diabetes/ Diet
E. Exercise lack
F. Family History
G. Gout
H. Hypertension

3. Identify if ischemia or hemorrhage with CT scan or MRI

4. In case of ischemia – Aspirin and clopidogrel should be started,

along with neuroprotective drugs – Piracetam or citicholine,
Methylcobalamin, Pyridoxine, Folic acid combinations.

5. Identication of the cause of ischemia- can be due to stenosis or

occlusion of large vessels such as carotid artery or smaller vessels
such as branches of middle and anterior cerebral artery.
Carotid stenosis:
If the stenosis is less than 50% then patient is treated medically. If 50% to 70%
then stenting is required. For stenosis of more than 70% surgical removal of the
atheroma is needed. The diagnosis of carotid stenosis can be made with a carotid
Doppler study.
Small vessel ischemia:
These are mostly treated medically. However in a few selected cases stenting or
the surgery of STA-MCA bypass are treatment options.
What is the management of chronic paralysis?
 Neurological Disorders - A Handbook for Family Physicians 73

Bladder and bowel management:

Almost all types of spinal cord injury result in the loss of normal bowel and
bladder function.
There are many methods that can be used to manage a paralysed bladder. It is
important to ensure the bladder is emptied regularly because an overly full
bladder can trigger a serious complication called autonomic dysreexia in high
spinal cord injuries.
There are two main types of catheter. They are:
Ÿ Intermittent catheter – the catheter is temporarily inserted into the bladder
and removed once the bladder is empty. This leads to lesser complications
then indwelling catheter.
Ÿ Indwelling catheter - remains in place for many days or weeks and is held in
position by a water-lled balloon in the bladder like the Foleys catheter,
silicon catheter. Indwelling catheters can be complicated by problems such
as bladder spasm, infection, blockage and leakage around the catheter,
urinary stones, etc.
Ÿ There are options to help people with paralysis empty their bowel:
Ÿ Bowel retraining – The aim is to improve the consistency of stools and
establish a regular time to empty bowel. Medications such as dulcolax
suppository can be regularly used.
Ÿ Enemas – liquid is injected into bowel to help stimulate it to empty.
Referral:
An Urologist should be consulted. Urodynamic studies may be required.
Neuropathic pain:
Neuropathic pain is pain caused by nerve damage. Neuropathic painrequires
alternative medications such as amitriptyline or pregabalin, a gaba analogue as
it does not usually respond to ordinary painkillers, such as paracetamol or
ibuprofen.
Breathing difculties:
Breathing assistance from a ventilator maybe required if the diaphragm is
paralysed. A positive pressure ventilator can either be invasive –tracheostomy
or non-invasive – bi-Pap or C-Pap
 74 Neurological Disorders - A Handbook for Family Physicians

Swallowing difculty:
Dietary advice would be helpful from a dietician, who can guide about
consistency and type of food for a particular problem. Ryle’s tube may be
required for some patients with no gag reexes. PEG tube is a long term option.
Spasticity and muscle spasms
Spasticity is a medical term that means abnormally stiff and rigid muscles.
Many people with paralysis develop spasticity and involuntary muscle spasms
(where muscles cramp and contract).
Treatment:
Muscle relaxants such as baclofen, tizanidine or dantrolene. If muscle relaxants
are not effective, an injection of botulinum toxin (Botox) may be given for
localised spasms. The effects of the injection usually last for up to three months.
Intrathecal baclofen therapy: surgically implanting a small pump on the outside
of the body connected to the spinal cord delivers regular doses of baclofen
directly to the spine.
Bed sore management:
Prevention: Special foam mattress or air mattress may be required for bed
ridden patients. Keep the skin dry by applying powder. Turn the patient on
sides every two hourly. Keep the perennial area clean and dry after urine or
motion.
Treatment:
Daily dressing with betadine. Dermatology referral. Medication- calendula,
permin gel, multivitamin and good nutrition will help in healing of bed sore.
Neurological Disorders - A Handbook for Family Physicians 75

SUMMARY
Early surgical intervention for spinal cord compression is mandatory so that
the neurological decit can be minimised. In case of Stroke patients,
management of hypertension and diabetes is of utmost importance. In acute
stroke management “Time is Brain” as earlier the proper treatment more is
the brain salvaged. Hence quick referral to neurologist / interventional
neurologists is necessary. In chronic stroke/ spinal cord injury
rehabilitation exercises are very important. Physiotherapy for stretching
and strengthening paralysed muscle. Bowel Bladder care training (catheter
care and diaper changing) to the care giver and to the patient is necessary.
Reduce risk of pressure ulcers by advising frequent positioning and
air/water mattress. Pain reduction/ management especially in patients
with transverse myelitis should be advised. Nutrition with adequate
hydration and protein and bre should be advised.

Treatment in case of Bell’s Palsy

Treatment:
1. Prednisone 80 mg once a day for three days,
• then 60 mg once a day for three days,
• then 40 mg once a day for three days,
• then 20 mg once a day for three days,
• then discontinue use.
2. Paracetamol 650mg thrice a day
3. Acyclovir 400mg ve times daily for 10 days
4. Vitamin B complex
5. Eye care with shield and eye drops
6. Physiotherapy
 76 Neurological Disorders - A Handbook for Family Physicians

Neuropathic Pain
Neuropathic pain generally results from damage to nerves or impairment in the
central nervous system. It is diagnosed when pain is out of proportion to the
injury. Pain generally presents itself in the form of burning or tingling.

Causes

Most common causes of neuropathic pain seen in practice are diabetes,herpes

zoster (shingles),alcoholism, B 12 deciency,trauma (nerve damage or spinal
cord injury), degenerative disc disease(spondylosis).

Other causes are trigeminal neuralgia, multiple sclerosis, HIV or AIDS, post
chemotherapy and due to toxins.

It can also present itself after surgeries such as mastectomy or amputation

(phantom limb). Phantom limb syndrome is a condition which occurs when
patient still feels the pain from the missing limb as the nerve ending misre and
send abnormal signal to the brain.

Pressure on nerves due to malignancy can also cause neuropathic pain.

Pain in movement disorders such as Parkinson’s disease and dystonia, pain

secondary to spasticity, pain in frozen shoulder secondary to stroke are all
categorized as neuropathic pain.

Signs & Symptoms

Burning or shooting or piercingpain is typical of neuropathic pain, but in some

 Neurological Disorders - A Handbook for Family Physicians 77

cases it may also be deep and aching. The pain may be radiating along the
damaged nerve.Tingling & numbness may be associated with the pain.

Increased sensitivity to touch and not alleviated by any of the normal pain
killers. The pain is long-lasting, typically persisting after the cause has been
removed. The pain is usually in the area of innervation of the damaged nerve,
but the surrounding areas may also be involved.

Investigation

Neuropathic pain is diagnosed on the basis of symptoms. Blood sugar &B 12

level may be checked.Look for compression of nerve, rash (herpes zoster).

Treatment
For treatment antidepressants and anticonvulsants are most commonly used as
regular analgesics do not work.
Diabetic neuropathy
Pregabalin75 mg bid & may increase to 150 mg bid & then maximum upto
300mg bid Or Gabapentin 300mg on day 1, 300mg bid on day 2, 300 mg tds on
day 3, & continue 300 tds for 1 week. If the pain is not getting controlled the dose
can be increased upto 600 mg tds gradually.
Post herpetic neuralgia
Antidepressants such as amitriptyline (Tryptomer) 25-75mg per day is
recommended.
Trigeminal neuralgia
Carbamazepine (Tegretol) start 100mg bid & can increase by 100mg each dose to
a maximum of 400mg bid in case of neuralgiacaused by pressure.
Post-surgical patients -Tramadol 50mg bid/tds then can increase to 100 bid/tds
maximum upto 200mg bid.
Localised pain
Local application of anaesthetic like xylocainegel or patch.
Surgical option may be required in non responding cases or severe cases.
Botox intradermal injections in case of focal pain can be used and is effective for
around 14 weeks.
 78 Neurological Disorders - A Handbook for Family Physicians

Surgery:
Epidural implantation of electrode in the spine for chronic leg pains has been
tried.Intrathecal pumps have also been tried in some patients.Nerve ablation
procedure in severe cases can be done.
Rehabilitation
Mobilization and physiotherapy are important to prevent disuse atrophy.
Patient must be protected from depression and appropriate counseling should
be provided.
Referal-pain management specialist, neurophysician or neurosurgeon.

SUMMARY
Most common causes of neuropathic pain seen in practice are diabetes,
herpes zoster, alcoholism, B 12 deciency, trauma (nerve damage or spinal
cord injury). Other causes are trigeminal neuralgia, multiple sclerosis, HIV
or AIDS, post chemotherapy and due to toxins. The type of pain points to the
treatment that will be most effective.

Sample treatment

Diabetic neuropathy
Pregabalin 150 mg twice a day
Or
Gabapentin 300mg on day 1,
300mg bid on day 2,
300 mg tds on day 3,
continue 300 tds for 1 week
Post herpetic neuralgia
Tryptomer 25mg once day – can be increased to 75mg gradually
Trigeminal neuralgia
Carbamazepine (Tegretol) 100mg twice a day to a maximum of 400mg
twice a day
Post-surgical patients
Tramadol 50mg thrice a day can be increased to 100 bid/tds maximum upto
200mg bid.
 Neurological Disorders - A Handbook for Family Physicians 79

Physical Disabilities in
Children
A physical disability is any condition that permanently prevents normal body
movement and/or control. There are many different types of physical
disabilities.
Below are some questions to be asked when a child suffering from any kind of
physical impairment or disability is brought to you:
1. Ask whether the illness or condition causing physical dysfunction is
congenital (present since birth) or acquired.
2. Ask about the course of illness and disability - the onset, duration and
progression; whether the disability, for e.g. weakness, is progressive or
non progressive.
3. Ask whether the child has any associated intellectual impairment (delays
in oral language development, self-help or self-care skills, developing
social skills, decits in memory and problem solving skills, etc), visual or
hearing problems.
4. Ask whether there is any delay in overall development of the child
(delayed sitting, crawling, walking, speaking, interacting with parents, etc
compared to normal typically developing child).
5. Ask the parents about a detailed birth history of the child, which includes -
Prenatal history (mother suffered from infection, hypertension during
pregnancy, on medications other than pregnancy related medicines, etc);
Perinatal history (whether the baby was full term or pre term, delivery was
 80 Neurological Disorders - A Handbook for Family Physicians

normal or assisted - Caesarean section or took too long, whether the baby
cried immediately after birth or not); Postnatal history (whether the baby
suffered from fever, jaundice, etc).
Causes of physical disabilities
There are many different causes for physical disabilities. These include:
1. Perinatal hypoxia: Injury to the brain due to problems during gestation
(prenatal), during childbirth (natal) or after birth (postnatal)
2. Serious infections affecting the brain, nerves or muscles, such as
poliomyelitis
3. Inherited or genetic disorders, such as muscular dystrophy,
leucodystrophy, glycogen storage disorders, etc.
4. Conditions present at birth (congenital birth defects), such as spina bida,
meningomyelocoele, etc.
5. Trauma: spinal cord injury and head injury
Some of the common ones include:
Cerebral palsy
Cerebral palsy is caused by damage to the parts of the brain which control
movement during the early stages of development. In most cases, this damage
occurs during pregnancy. However, damage can sometimes occur during birth
and from brain injuries in early infancy (such as lack of oxygen from near
drowning, meningitis, head injury or violent shaking of child).
Children with cerebral palsy may have:
• delayed development
• abnormal posture (the ability to put the body in a chosen position and
control it)
• difculty in movement of body parts or the whole body
• muscle weakness or tightness
• involuntary muscle movements (spasms)
• imbalance and incoordination
• difculty talking and eating. (motor component of speech and
swallowing)
 Neurological Disorders - A Handbook for Family Physicians 81

Children can have different types of cerebral palsy:

• Hemiplegic (involves muscle movements and weakness on one side of the
body)
• Diplegic (involves muscle movements and weakness in the lower part of
the body)
• Quadriplegic (involves muscle movements and weakness in both arms
and both legs)
• Ataxic (involves problems with balance and coordination).
• Dystonic/choreoathetoid (involuntary movements of hands ,legs and
head /neck/ face)

Fig 7.1: Types of cerebral palsy

Poliomyelitis
Poliomyelitis is an infectious disease caused by polio virus. A very few cases of
poliomyelitis develop a paralytic poliomyelitis. Paralytic poliomyelitis may be
clinically suspected in children experiencing a) acute onset of accid paralysis in
one or more limbs with b) decreased or absent tendon reexes in the affected
limbs that cannot be attributed to another apparent cause and c) without sensory
or cognitive loss. Minor symptoms such as fever, headache, vomiting, diarrhea,
neck stiffness and pain in the arms and legs may be present and last for few days.
There are many causes of acute accid paralysis (AFP); polio virus infection is
one of the main causes. Acute poliomyelitis affects the anterior horn motor
neurons of the spinal cord and brain stem causing severe muscle pain and
spasms, followed by accid asymmetric weakness and muscle atrophy.
 82 Neurological Disorders - A Handbook for Family Physicians

Paralysis is usually asymmetric,

begins in proximal extremities, and
progresses to distal muscle groups.
Paralysis remains for days or weeks
before slow recovery occurs over
months or years. Physical activity and
intramuscular injections during the
acute paralysis period should be
avoided since they are known to cause
exacerbation of the symptoms. There is
no cure for poliomyelitis, however, it
can be prevented by regular
immunization through vaccination as
per schedule. Therefore, family
practitioner plays a very important
role in prevention of polio. One should
emphasize compliance to vaccination
schedule.
Congenital defects
Spina bida
Sometimes, a baby's
spinal cord does not
develop normally
during pregnancy.
When this happens,
the child can have a
physical disability
called spina bida.
The type and amount
of disability caused by
spina bida will
depend upon the level Fig 7. 3: Spina Bida
of the abnormality of
the spinal cord. Children with spina bida may have:
• partial or full paralysis of the legs
• difculties with bowel and bladder control. They may also have:
• hydrocephalus (high pressure on the brain because of uid not being
drained away normally
 Neurological Disorders - A Handbook for Family Physicians 83

• bone and joint deformities (they may not grow normally)

• curvature (bending) of the spine.
Muscular dystrophies
When a child has muscular
dystrophy, the muscles show
progressive weakness. The
child may have difculty
running, walking, getting up
from the oor, etc. Children can
have different types of muscu-
lar dystrophy. The most com-
mon type is Duchenne Muscu-
lar Dystrophy which occurs
only in boys. All types of mus-
cular dystrophy are genetic
even though other family
members may not have the
condition. . (for details refer to
chapter 31 )
Multiple disabilities
Some children with physical Fig 7.4: Clinical Presentation in
disabilities will have other Duchenne Muscular Dystrophy
disabilities, such as intellectual,
visual or hearing impairments. They may also have communication difculties
or other medical conditions such as epilepsy, asthma, rickets, anemia, malnutri-
tion etc
Acquired brain and spinal injuries
Physical disabilities may result from permanent injuries to the brain, spinal cord
or limbs that prevent proper movement in parts of the body.
Investigations to be considered:
1. CT scan: A CT scan of the brain could be ordered as a screening tool to
identify the underlying CNS pathology.
2. MRI scan: An MRI brain or spinal cord could be ordered in highly
suspected cases of CNS disorders (h/o encephalitis, fever with siezures,
epilepsy, etc). It is also helpful in detecting congenital malformations of
the brain and spinal cord (meningomyelocele, spina bida, etc)
 84 Neurological Disorders - A Handbook for Family Physicians

3. Blood tests: Various blood tests to identify metabolic disorders

(phenylketonuria, juvenile diabetes, etc), electrolyte imbalance and
vitamin deciencies (hypokalemia, Vit B12 deciency, etc), hormonal
disorders (hypothyroidism), etc could be ordered.
4. EEG: An EEG is ordered to identify any coexisting epileptic foci in the
brain.
5. PET CT scan: PET CT scan can give areas of brain which are low or high
functioning than normal. It can be used when MRI ndings are normal but
patient is showing neurological decits related to the brain.
Treatment and management
Physical disabilities management involves a multidisciplinary approach.
Family physicians are the rst medical help sought by the patients/parents.
Early detection and timely intervention can drastically improve the quality of
life of these patients. The role of a family physician is to coordinate between
various specialties whenever needed. They have an important role to ensure
patient compliance to longterm therapies and prevention/early treatment of
complications.
• Refer to a paediatrician for medical treatment to relax muscles like
baclofen, tizanidine.
• Reference of orthopaedic surgeon for release of contractures or
dislocations.
• Physiotherapy: muscle charting and regular physical therapy.
• Occupational therapy: for ADL training, hand therapy, ne motor skill
development, etc.
• Neurosurgical treatment of underlying cause if possible.
• Urology reference to improve bladder dysfuction.
• Chest physiotherapy for adequate drainage of secretions.
• Diet and exercise for weight management.
• Splints , cast, callipers and wheel chair provision for ambulation.
• Motivation and counselling to prevent depression and low self esteem.
For details refer to chapters describing individual diagnosis.
Neurological Disorders - A Handbook for Family Physicians 85

SUMMARY
A physical disability is any condition resulting due to permanent injuries to
the brain, spinal cord or limbs that permanently prevents normal body
movement and/or control. Common causes of physical disability are
Perinatal hypoxia, Serious infections, Inherited or genetic disorders,
congenital conditions and trauma. Some of the physical disabilities include
cerebral palsy, poliomyelitis, muscular dystrophy and spina bida.
Investigations used for these disorders include Blood tests, CT scans, MRI,
PET CT scan and EEG. The treatment strategy involves a multidisciplinary
approach consisting of medical intervention, rehabilitation, assistive
devices, psychological counselling, dietary intervention, etc. If these
disorders are diagnosed and treated on time, it can improve the quality of
life of the patients. A family physician can help detect the disorder on time.
 86 Neurological Disorders - A Handbook for Family Physicians

Cognitive Disability in
Children
A cognitive impairment also known as intellectual disability is a term used
when a child has limitations in intellectual and thinking capacity.
It can be seen in various domains like delay in language development, decits in
memory skills, difculty in attaining social milestones, inappropriate social
behavior, problem solving difculties and delays in adaptive behavior like self-
help and self-care.
They may show lack of social inhibition also.
Physical capacities may be affected or preserved in such cases. Fine or gross
motor delays may be seen.
Common causes of intellectual disability are
Prenatal causes
• Consanguineous marriage
• Elderly mother
• Infections during pregnancy
• Hypertension or diabetes in mother
• Drugs and alcohol addictions in mother
• Folic acid deciency in mother
• Developmental anomalies in fetus like hydrocephalus or neural tube
defects
 Neurological Disorders - A Handbook for Family Physicians 87

Perinatal causes
• High risk twin pregnancy
• Preterm, premature baby
• Non progressive labor
• Low birth weight baby
• Fetal distress and hypoxia
• Seizures in mother (PIH)
• Seizures in baby
• Sepsis
• Hyperbilirubinemia
• Developmental anomalies like hydrocephalus
Postnatal
• Trauma or injury
• Infections in early neonatal period
• Malnutrition
• Neglect/abuse
• Heavy metal like lead toxicity
Hormonal or endocrine disorders
Hypothyroidism in mother /child (one of the treatable cause of intellectual
disability if diagnosed early)
Genetic conditions and metabolic errors
Ÿ Downs , Fragile X, Turners syndrome are common genetic conditions.
Ÿ Galatosemia, phenylketonuria, urea cycle disorders are metabolic errors
Assessment:
Cognitive disability can be measured by calculating intelligence quotient.
Some of the scales used for assessing intelligence are
- Weschler Intelligence Scale for Children
- Stanford-Binet Intelligence Scale
 88 Neurological Disorders - A Handbook for Family Physicians

Adaptive behaviour
To analyse adaptive behaviour the child's skills are observed and compared to
other children of the same age. Things that may be observed include how well
the child can feed or dress himself, how well the child is able to communicate
and understand others, and how the child interacts with family, friends and
other children of the same age. In children with severe or profound intellectual
disability, there may be other neurological problems as well. These problems
may include seizures, motor handicaps, vision problems or hearing problems.
Limitations in adaptive behaviour, covers three types of skills:
Ÿ Conceptual skills—language and literacy, money, time, and number
concepts and self-direction
Ÿ Social skills—interpersonal skills, social responsibility, self-esteem,
gullibility, naïveté, social problem solving, the ability to follow rules, obey
laws, and avoid being victimized
Ÿ Practical skills—activities of daily living (personal care), occupational skills,
healthcare, travel/transportation, schedules/routines, safety, use of
money, use of the telephone.
Learning disability: A child who has learning disability may have difculty
reading, writing, spelling, reasoning, recalling and/or organizing information.
 Neurological Disorders - A Handbook for Family Physicians 89

If taught in conventional ways or unsupported their scholastic performance

may be poor. Common types of learning disabilities include:
1. Dyscalculia:- difculty with math problems, understanding time and
using money
2. Dysgraphia :-Problems with handwriting, spellings and organizing ideas
in writing
3. Dyslexia:- Problems in reading, writing, spelling and speaking
4. Language processing disorders
5. Decits in auditory processing
6. Visual perceptual/ motor decit
7. Memory decits
A child with poor school performance may be an Attention Decit
Hyperactivity Disorder or they may have LD associated with ADHD . Children
with learning disabilities are of average or above average intelligence.
LDs should not be confused with learning problems which may be due to visual,
hearing, or motor handicaps; mental retardation; emotional disturbance and or
environmental, cultural or economic disadvantages.

Developmental Disabilities is an umbrella term that includes intellectual

disability but also includes other disabilities that are apparent during
childhood. Developmental disabilities are severe chronic disabilities that can be
cognitive or physical or both. The disabilities appear before the age of 2 and are
likely to be life-long. Some developmental disabilities are cerebral palsy ,
 90 Neurological Disorders - A Handbook for Family Physicians

kernicterus , fetal alcohol

syndrome , neural tube defects.
Maternal infections like
TORCH , genetic disorders like
Downs syndrome, fragile X
syndrome etc.
In case of Autism Spectrum
Disorders, children do not
generally have diminished
cognitive functioning. They
have normal or even above normal intelligence in some cases. The issue with
autistic children is their inability to function normally within the social
environment. They are unable to communicate with the outside world using
language. The classical triad of ASD shows: decits in socialization, language
and communication and stereotypical repetitive behavior.
Prevention:
Certain causes of cognitive disability are preventable. Nutritional causes and
problems during birth are the most common causes in India. Getting proper
prenatal care, taking pre-natal vitamins, folic acid and iron and getting
vaccinated against certain infectious diseases can also lower the risk of child
being born with cogniitive disabilities.
In families with a history of genetic disorders, genetic testing may be
recommended before conception.
Certain tests, such as ultrasound and amniocentesis, can also be performed
during pregnancy to look for any anomalies and genetic disorders. Although
these tests may identify problems before birth, they cannot correct them.
Diagnosis:
Cognitive disability may be suspected for many different reasons with a series
of supportive investigations such as:
• CT scan: A CT scan may help in identifying any structural abnormality or
damage to the brain.
• MRI scan: An MRI may help in diagnosing the disorder by helping
visualize tissues of the brain and their integrity.
• Blood tests: Blood tests may help identify metabolic disorders and
nutritional decits causing impaired mental function.
 Neurological Disorders - A Handbook for Family Physicians 91

• EEG: An EEG may help identify an underlying epileptic focus in the brain
even before the symptoms arise.
• PET: PET CT scan can identify areas of brain which are low or high
functioning as compared to normal. It can be used when MRI ndings are
normal but patient shows neurological decits related to the brain.
• Genetic testing: It is used to conrm the diagnosis by showing mutations
in various genes which may be hereditary or acquired during gestation.
• Diagnosis of autism is traditionally done by a developmental
paediatrician with inputs from psychologists. Clinical assessment scales,
based on an array of questions asked to the parents, forms the basis of
diagnosis. These scales are DSMV, CARS, ISAA.
Treatment
Diseases of the neurological system are the most challenging for the modern
medicine. Most of these remain incurable and lead to major neurological
decits. This affects the quality of life of patients and puts signicant burden on
the caregivers. Therefore, to provide good quality care and improve the
functional outcome, long term inpatient multidisciplinary neurorehabilitation
is required.
Medical interventions:
Serotonin reuptake inhibitors (SSRI's) such as uoxetine, sertraline are used for
treatment of anxiety and depression. They may also have the added benet of
increasing social interaction and inhibiting repetitive behavior.
Antipsychotic drugs such as thioridazine, uphenazine, chlorpromazine, and
haloperidol have shown to decrease behavioral abnormalities in autism.
Atypical antipsychotics such as risperidone, olanzapine and ziprasidone have
also demonstrated benecial effect at ameliorating behavioral problems.
Autism associated seizures are mainly treated by administration of
anticonvulsants such as carbamazepine, lamotrigine, topiramate, and valproic
acid.
Attention decient/hyperactivity is treated by agents such as methylphenidate.
Supplements such as vitamin B12, Vitamin E, Omega fatty acids, coenzyme Q10,
etc can also be used.
L-Carnosine is being used for autism disorders. It mainly helps in improving the
child’s behavior, language skills, and may enhance neurological functions. Use
of L-Carnosine is scientically approved. Studies have reported improvement
 92 Neurological Disorders - A Handbook for Family Physicians

in vocabulary, language comprehension, communication, socialization, object

recognition, awareness of surroundings, ne motor skills and auditory
processing. Dosage: 5 ml BD depending on age and weight of the patient.
Neurorehabilitation team consists of core participants like neurosurgeon,
neurologist, developmental pediatrician, urologist, nurse, physical therapist,
aquatic therapist, occupational therapists, speech therapist, psychologist,
dietitian and family members or caregivers of the patient. Multiple other
professionals like, plastic surgeons, orthopedic surgeons, andrologists,
cardiologists, ophthalmologist, gastroenterologist and ENT specialists form the
secondary team and may be given appropriate referrals when required.
Process of neurorehabilitation is to reintegrate the patient in community.
Therefore, the most important aim of the neurorehabilitation is to facilitate
maximum neurological recovery and functional independence

SUMMARY
Someone with intellectual disability has limitations in two areas.
Intellectual functioning: Also known as IQ, this refers to a person's ability to
learn, reason, make decisions, and solve problems.
Adaptive behaviours: These are skills necessary for day-to-day life, such as
being able to communicate effectively, interact with others, and take care of
oneself.
The causes can be prenatal, perinatal or postnatal. The detection of these
disorders may be missed at birth. Therefore, family physician should
carefully examine children for developmental delay. At the earliest sign one
should refer the patient to a paediatrician. Treatment includes
pharmacological intervention and rehabilitation. Few drugs and
supplements have shown to manage the overall symptoms in these
disorders. Rehabilitation at early age can accelerate development of these
children. Though there is no cure for these conditions, the patient's family
should be educated about various options like specialized rehabilitation
centres, vocational rehabilitation centres, support groups, special schools,
etc. Care of caregivers is also essential.
 Neurological Disorders - A Handbook for Family Physicians 93

Behavioral Issues in Children

Behaviour is the manner of conducting oneself in conjunction with oneself or the
environment that includes norms, beliefs, systems and other organisms as well
as inanimate objects and physical environment. It can be learnt and unlearnt,
and the learning of behaviour is relatively permanent change in the mannerism.
Behaviour issues are subjected to hindrance in functioning of self with respect to
the environment that are not in conjunction with the norms and society. The
hindrance caused can be harm to self or the environment or both. This leads to a
breech in the normal functioning within acceptable level.
Often parents will approach the family physician or paediatrician with
complaints of inappropriate behaviour and complaints from school or peers.
Child may show poor interpersonal relation, adjustment problems, fear,
hyperactivity, aggression and so on.
Teacher may convey the problem through a letter addressing the poor
performance, inability to interact, any difculty with learning like spellings or
math.
Often children may be noticed lying, fear or low self-esteem to cover up their
decits in learning disability.
Autism spectrum disorders
How to suspect Autism spectrum disorders needing further evaluation?
• Age should be upto 3 yrs
• Withdrawal from others, not social
• Only indulging in self
 94 Neurological Disorders - A Handbook for Family Physicians

• All motor milestones age appropriate but speech grossly affected

• Not communicating needs
• Repetitive behaviour like rocking, going in circles, hand apping etc
All these may raise a doubt to evaluate further, especially a speech delay beyond
2 and half years must raise concern.
What is Autism Spectrum Disorder?
Autism Spectrum Disorder is a neuro-developmental disorder that impacts on
how an individual perceives the world and socializes with others leading to
problems related to social interaction and communication. The disorder is
accompanied with limited pattern, restrictive and or repetitive behaviour. The
term spectrum indicates the varied symptoms and its severity.
Autism spectrum disorder includes autism and Asperger’s syndrome,
childhood disintegrative disorder and unspecied pervasive developmental
disorder as per DSM V. The symptoms of ASD can be identied in early life. The
disorder produces impaired functionality in the society. There is no cure for
ASD but early identication and intervention can make a signicant difference.
Pathophysiology In Autism
Brain hypoperfusion and immune dysfunctions have been characterized as the
two main brain pathologic alterations in autism cases. Research on animal brain
to study the etiology of autism has shown that a major dysfunction of the autistic
brain resides in neural mechanisms of the structures in the medial temporal
lobe, anterior cingulate gyrus, reticular activating system, prefrontal and
temporal lobe and perhaps more specically the amygdaloid complex. Distinct
patterns of memory loss and socioemotional abnormalities emerge as a result of
extent of dysfuction to the medial temporal lobe structures.
Symptoms:
The symptoms can be identied as early as 2 years and are listed below.
1. Reduced eye contact
2. Lack of response to their name
3. Initial normal development with sudden withdrawal or aggressive or loss
of language skills
4. Difculty in learning
5. Lower than normal intelligence or normal to high intelligence
6. Quick learning but difcult in communication and execution
 Neurological Disorders - A Handbook for Family Physicians 95

Not all the symptoms are seen in every patient of ASD but a combination of
these symptoms may occur.
Signs:
Social communication and interaction and behavioural patterns.

Social communication and Pattern of Behaviour

interaction 1. Repetitive movements
1. Failure to respond to call (rocking, spinning or hand
2. Resistance to cuddle,prefer apping)
playing alone 2. Self harming behaviour
3. Poor eye contact 3. Follows routine and rituals that
4. Lack in facial expression are rigid and get disturbed
when changed
5. No speech, delayed speech or
lost acquired speech 4. Incordination of movements or
has odd movement pattern
6. Cannot initiate or keep on the
conversation 5. Difculty in understanding the
overall function of an object
7. Abnormal tone or rhythm of
speech 6. Poor or no imitation
8. Repeats words or phrases 7. Lack of imaginative play
verbatim 8. Fixative nature to an object
9. Lack of emotional expression 9. Specic food preference
10. Lack in understanding simple
question
11. Do not point out objects or
share interest
12. Inappropriate initiation to
social interaction
13. Difculty in recognising non
verbal cues

Diagnosis:
Rule out other causes of behavioural disorders.
Laboratory tests for heavy metal :- heavy metal panel can be ordered to r/o
arsenic, lead or mercury toxicity
Complete blood count to look for anemia , child with iron deciency can present
with irritability and changed behaviour
Stool routine also to look for worm infestation, leading to anemia and irritability
 96 Neurological Disorders - A Handbook for Family Physicians

MRI to look for any neurodegenerative disease or tumors or CNS infestation

with tuberculoma or neurocystisercosis, leading to behaviour changes and
neurological symptoms or seizures. This can also help to look for any
developmental anomalies or migration defects of brain
EEG to r/o epilepsy or absence seizures causing behaviour changes and
regression.
This can also help to look for any developmental anomalies or migration defects
of brain
Because ASD varies widely in symptoms and severity, making a diagnosis may
be difcult. Keen observation of parents and complains from school are the
usual route of early identication.
Diagnosis is as per DSM V. Severity can be established by Indian Scale for
Assessment of Autism (ISAA), Childhood Autism Rating Scale (CARS).
Medical Intervention:
Risperidone is a antipsychotic medication and very helpful in controlling
inappropriate behavior or hyperactivity . A 0.5mg tablet is available and syp
risdone of 1ml/1mg. It can be started at a dose of ½ tab of 0.5mg or 0.5ml at night
time or sos.
Aripiprazole can be initiated for irritability in paediatric patients with autism at
dose of 2mg / day, increasing weekly upto 5mg/day.Go upto 10-15 mg/day to
control symptoms.
Other medications for hyperactivity and attention decit are methylphenidate
and atomoxetine preferably to be started after a neurological evaluation. These
can be omitted on weekends where no attention is needed as child is off school.
Therapeutic Interventions:
Behaviour and communication therapies, Occupational therapy,
physiotherapy, Educational therapies, Vocational instructor and medication
and regenerative medicine can provide assistance to independent living.
Intervention strategies are set based on the assessment and most suitable
intervention strategy the child can respond. Few of the commonly practiced
interventions are
1. Neuro-cognitive therapy:
2. Cognitive Rehabilitation Therapy (CRT):
3. Behaviour therapy:
 Neurological Disorders - A Handbook for Family Physicians 97

Attention Decit Hyperactivity Disorder

Attention Decit Hyperactivity Disorder (ADHD) is a neurological disorder
with an on-going pattern of hyperactivity and inattention that interferes with
the normal functioning and development.
Inattention: wandering off task, lack of focus, disorganised but not due to lack
of comprehension
Hyperactivity: move constantly always even in inappropriate situations and
dgeting. In adults, extreme restlessness with constant activity.
Impulsivity: hasty decisions and actions that may have potential harm.
How to suspect ADHD?
Poor school performance
Inability to complete task at hand
TWO COMPONENTS
Child could have lack of attention and focus or
Hyperactivity (on the go kind of behaviour) or
both attention decit and hyperactivity.
Signs and symptoms
Inattention:
1. Overlook or make careless mistake at school, work or during activities
2. Difculty in sustenance in attention in tasks like play, conversation
lectures, lengthy reading
3. Does not seem to listen when spoken directly
4. Does not follow instruction and fail to nish school work or duties at work
place
5. Dislike task that demands mental effort
6. Lose things that are task essential
7. Easily distracted
8. Forgetful in daily activities
 98 Neurological Disorders - A Handbook for Family Physicians

Hyperactivity-Impulsivity
1. Fidget and squirm at their seats
2. Leaves seats in situations where being seated is expected
3. Run, dash and climb in inappropriate situations
4. Teens and adults feel restless
5. Unable to engage in hobbies and play quietly
6. Being constantly in motion
7. Have trouble waiting or taking their turn
8. Interrupt and intrude in conversations and activities
9. Talking non stop
Diagnosis:
Labs
A comprehensive evaluation by a psychologist, psychiatrist and paediatrician
will lead to early diagnosis of ADHD.
ADHD symptoms can appear early as 3 and 6 years persisting till adolescence
and adulthood and can be mistaken for emotional or disciplinary problems.
ADHD missed in diagnosis may have history of poor academic performance
and difcult or failed relationships.
Treatment:
Medications: in detail
Psychiatrist or neurologist can help to prescribe appropriate medications
Methylphenidate and atomoxetine are two medications commonly used.
These are preferred at school going age or atleast above 6 yrs of age
Dosage titration and timing adjustment is individual based.
Methylphenidate is a stimulant and may have side effects like anorexia, sleep
disturbance, headache and irritability.
Dosage ranges from 5mg to 20mg twice or thrice daily.
Atomoxetine is a non stimulant
Dosage is 0.5mg/kg/day and increased to 1.2-1.4mg/kg/day after 4 days may
have side effects like nausea, dyspepsia, decreased appetite and weight loss.
 Neurological Disorders - A Handbook for Family Physicians 99

Various therapeutic inputs including behavioural therapy, behaviour training,

meta-cognitive skill training, cognitive behaviour therapy, counselling, parents
counselling, peer group training, social skill training, emotional management,
social understanding along with self awareness training.
Childhood Schizophrenia:
When to suspect childhood schizophrenia?
Hallucinations:- abnormal visual, auditory or sensory perception (like voices
speaking, insects crawling over body)
Delusions :- abnormal belief contrary to reality (perceiving rope as snake)
Catatonic behaviour:- abnormal postures for long time
Blunted affect:- blunted emotional response
Childhood schizophrenia is a severe mental disorder wherein the Child
misinterprets reality. It involves a range of problems from cognitive (Thinking),
behaviour, or emotion.
Childhood schizophrenia is the same as in adults, but occurs early in life. The
diagnosis is a challenge as it overlaps with childhood development and
behaviour. The challenge is not restricted to diagnosis but also in treatment,
education, emotion and social development.
The treatment is lifelong for schizophrenia and is not different to children. Early
identication and treatment has a signicant improvement observed in long
term.
Symptoms:
Symptoms involve range of problems from thinking, emotions and behaviour.
Early onset occurs before 18yrs for childhood Schizophrenia but children
younger than 13 years of age is a rare occurrence. Types and severity may vary
with periods of worsening and remission of symptoms.
The symptoms may overlap with pervasive developmental disorders such as
autism spectrum disorders, ruling out these disorders is the rst step to
childhood schizophrenia.
Teenager symptoms:
Teenager symptoms are closely linked to adult. Challenge is that there is an
overlap of typical development. Enlisted below are the symptoms.
1. Withdrawal from family and friends
100 Neurological Disorders - A Handbook for Family Physicians

2. Drop in school performances

3. Lack of motivation
4. Trouble to sleep
5. Substance use
6. Strange behaviour
7. Disturbed eating patterns
8. Increased aloofness
Note: children with schizophrenia are less likely to have delusion but more
likely to have visual hallucinations in contrast to adults with schizophrenia.
Later Signs and symptoms:
1. Delusions: False believing that are not based on reality
2. Hallucinations: Unusual seeing or having things that do not exist
3. Disorganised Thinking: inferred as disorganised speech. Presence of
ineffective communication observed as used of words that are
meaningless to the content and that cannot be understood.
4. Abnormal Motor behaviour: Behaviour is not task driven which makes
execution difcult. Inappropriate posture, lack of responses, excessive
movements along with resistance to instruction makes functioning
difcult in daily living.
5. Negative symptoms: lack of ability to function normally is a key issue that
is followed by many other issues like negligence on personal hygiene, no
eye contact, doesn’t change facial expression, monotone speech, No
gestural movements when communicated to, reduced engagement in
activities due to withdrawal or lack of interest.
There is greatest possibility to attribute childhood schizophrenia as
developmental issues. Keen watching for few months will help diagnosing the
child with schizophrenia.
Diagnosis:
Diagnosis of childhood schizophrenia is as per DSM V, similar to adults with
schizophrenia.
A physical examination to rule out the possible complications and symptoms.
Neurological Disorders - A Handbook for Family Physicians 101

A comprehensive Psychological evaluation will render information on

behaviour, mood, thoughts, feelings, ability to function, ruling out other
pervasive developmental disorders, age appropriate development. Assessing
mood, anxiety and possible psychotic symptoms can assist in diagnosis.
Other investigations from the lab and imaging studies will rule out substance
use of any sort.
Treatment:
Medications: Psychiatrist or neurologist can help to prescribed appropriate
antipsychotic medications. haloperidol (Haldol), thioridazine (Mellaril),
risperidone (Risperdal), aripiprazole (Abilify), quetiapine (Seroquel),
olanzapine (Zyprexa), and ziprasidone (Geodon) are some of the medications
used.
The starting dose of aripiprazole for pediatric patients is 2 mg/day, increasing
to 5 mg/day, with gradual weekly increase to 10 or 15 mg/day as per patient
need. Dose adjustments of up to 5 mg/day can be made at intervals of 1 week or
greater.
Risperidone o.5mg half tab at night for hyperactivity also will sedate the child
Other sedatives to be used is emergency situations are midazolam spray starting
with 1 puff in each nostril, dose being 0.2mg/kg. max dose is 10mg, to calm a
very hyperactive or aggressive child, or immediate control of seizures if any.
Syp pedichloryl can be used at night time for sleep and sedation during travel
2.5ml for 10kg, upto 5ml for 20 kg, 10ml for 35 to 40kg child can be used.
Psychotherapy: Various psychotherapies including behavioural therapy,
behaviour training, meta-cognitive skill training, cognitive behaviour therapy,
counselling, parents counselling, peer group training, social skill training,
emotional management, social understanding along with self awareness
training.
Life skill education/training: Decision making, creative thinking, group
involvement, recreational and time management, hobby development &
management, emotional management, study techniques and other required life
skill can help children with schizophrenia.
Hospitalization: We can recommend few of the children with schizophrenia at
sever condition for hospital based rehabilitation, where they can receive
comprehensive treatment including medicinal intervention, psychotherapies,
social skill training, and educational inputs along with parents or family
102 Neurological Disorders - A Handbook for Family Physicians

training. Assistance in physical and educational need can mention signicant

contribution toward total quality rehabilitation.
A comprehensive rehabilitation team can promote to independent living.

SUMMARY
This chapter discusses the behavioural issues in few commonly seen
neurodevelopmental disorders such as Autism spectrum disorder,
Attention decit hyperactivity disorder and childhood schizophrenia.
The behaviour of the patient is trainable and early identication along with a
comprehensive program, can lead to a great outcome in these patients.
As a primary contact with many patients being a family physician,
knowledge of these conditions can play a crucial role towards the patient
and the whole family.
Neurological Disorders - A Handbook for Family Physicians 103

Section B

Neurological Investigations
(I) Neuroradiology
104 Neurological Disorders - A Handbook for Family Physicians
Neurological Disorders - A Handbook for Family Physicians 105

10

Computed Tomography (CT)

Neurological CT scans are used to view the brain and spine. They can detect
bone and vascular irregularities, certain brain tumors and cysts, herniated discs,
epilepsy, encephalitis, spinal stenosis, a blood clot or intracranial bleeding in
patients with stroke, brain damage from head injury, and other disorders. It can
also be used to guide biopsies.
Computed tomography, also known as a CT scan, is a noninvasive, painless, X-
ray imaging procedure used to produce rapid, clear two-dimensional images of
organs, bones, and tissues. The cross-sectional images generated during a CT
scan can be reformatted in multiple planes, and can even generate three-
dimensional images. Depending on the clinical indication, the scan can be
performed with or without intravenous contrast injection.
When to order CT v/s MRI?
• CT scan is used in emergency neurological conditions, as it is quick, takes
lesser time and easily available.
• CT is very good for imaging bony structures. Therefore, in all head trauma
cases and accidents with multiple injuries, CT scan should be ordered as a
screening test.
• CT scan can easily and quickly distinguish between ischaemic and
haemorrhagic stroke. Thus, in all suspected stroke cases CT brain scan
should be ordered immediately.
• In cases of severe headache or atypical headache or headache with
warning signs, CT brain scan should be ordered.
• In any cases of altered mental status or coma, CT brain should be ordered.
106 Neurological Disorders - A Handbook for Family Physicians

• CT scan is used as a screening tool for migraine, tumours, transient

ischaemic attacks (TIA), dizziness, seizures, congenital deformities of the
skull or brain, etc.
• Patients having metallic implants, pacemakers cannot receive an MRI but
can have a CT scan.
• CT scan may be done as a pre-requisite for surgical procedures of the brain
and spinal cord (for e.g. CT guided biopsy).
Four basic steps of CT scanning:
1. X-Ray Production
2. Data Acquisition
3. Data Processing
4. Image Display
CT scan works much like other X-ray examinations in which different parts of
the part being scanned absorb X-rays in varying degrees. It is this crucial
difference in absorption that allows the body parts to be distinguished from one
another on an X-ray lm or CT electronic image.
The CT scanner takes X-ray images at various angles around the body with the
help of rotating X-ray beams and X-ray detectors. These images are processed by
a computer to produce cross-sectional pictures of the body. These pictures are
seen as an X-ray ‘slice’ of the body, which is recorded on a lm and called as a
tomogram. Three-dimensional models of the body area also can be created by
stacking the slices together.
Certain exams require a special dye, called contrast, to be delivered into the
person’s body through intravenous injection, orally or per rectum. Contrast CT
scan helps to highlight structures such as blood vessels and obtain functional
information about specic tissues.
CT scanning is used in medicine as a diagnostic tool and as a guide for
interventional procedures.
Indications for head CT examination include the following:
Ÿ Head trauma
Ÿ Stroke
Ÿ Headaches
Ÿ Initial evaluation for space-occupying lesions, tumors
Ÿ Unexplained change in mental status
Neurological Disorders - A Handbook for Family Physicians 107

Ÿ Seizures
Ÿ Suspected hydrocephalus
Ÿ Suspected intracranial hematoma, infections
Ÿ Psychiatric disorders
Ÿ Dizziness
Ÿ Vascular occlusive disease and aneurysm evaluation
Ÿ Diseases or malformations of the skull
Ÿ Guide the biopsy of the brain

Indications for spine CT examination include the following:

• Guide diagnostic procedures such as the biopsy of a suspicious area to
detect cancer, or the removal of uid from a localized infection (abscess)
• Congenital anomalies of the spine
• Tumors of the spinal cord, spinal pain
• Spinal injury
• Detection of spinal canal stenosis, vertebral fracture, and infection of the
spine and spinal cord.
• When MRI is not available/possible.
Special precautions to be taken for CT examination include the following:
• CT should be performed for pregnant patients only in critical situations
and only after discussion of the potential risks and benets.
• Repeated X-ray exposure may increase the patient’s risk for cancer.
However, the risk from any one scan is small, with the benet of an
accurate diagnosis outweighing the risks.
• In certain clinical situations, intravenous contrast administration is
indicated. Contrast media is safe in most patients. However, adverse
reactions may occur in patients who have an allergy to the IV contrast
media, or patients suffering from renal impairment, hyperthyroidism,
phaeochromocytoma, myasthenia gravis, etc.
• Checklist to be considered before ordering a CT scan with contrast:
a. Presence of renal failure (as in alcohol abuse, angina, heart failure,
kidney problems, liver disease, severe infection).
b. If taking diabetes medication Metformin, medicine may need to be
stopped temporarily for 48 hours (Since contrast medium affects the
108 Neurological Disorders - A Handbook for Family Physicians

kidneys temporarily and kidneys are involved in removal of

metformin, contrast medium can greatly increase the levels of
metformin in the blood which increases the risk of lactic acidosis.)
c. Any previous reaction to contrast.
d. It is recommended that nursing mothers should wait 24 hours after
contrast administration to resume breastfeeding.
Advantages of CT scan:
• The time taken for total testing is shorter in CT than for MRI. Thus, CT is
used in emergency settings as well as a screening method for detecting
suspected brain and spine disorders, wherein use of MRI is not possible
due o unavailability and/or time constraints.
• MRI cannot be done on patients who are claustrophobic as the patient has
to remain inside the noisy machine for about 20-45 minutes. CT is more
comfortable.
• CT scan is cheaper than an MRI.
• CT is less sensitive to patient motion than MRI.
Disadvantages of CT scan:
• Risk of ionizing radiations is always there in CT scan.
• CT does not differentiate well between bone, soft tissue and blood vessels.
It also does not give inter soft tissue differentiation.
• Contrast medium used in CT contains iodine, while MRI uses non iodine
contrast medium.
• CT scan does not visualize the spinal cord adequately.
Common CT brain ndings:

Fig 10.1: CT ndings reveal the presence of Bilateral subdural haemorrhage

Neurological Disorders - A Handbook for Family Physicians 109

Fig 10.2: CT Axial, and sagittal sections showing Chance fracture

Fig 10.3: CT ndings reveal the presence of Extradural, subdural and

subarchanoid haemorrhage

Fig 10.4: CT ndings reveal the presence of Intracranial haemorrhage

Fig 10.5: CT shows the presence of right Meningioma with shift in midline
110 Neurological Disorders - A Handbook for Family Physicians

Fig 10.6: CT ndings reveal, right MCA Acute stroke

Fig 10.7: CT ndings reveal, right MCA Chronic stroke

Fig 10.8: CT Brain ndings reveal the presence of right

frontal subdural haematoma
Neurological Disorders - A Handbook for Family Physicians 111

11

Magnetic Resonance Imaging

(MRI)
Magnetic Resonance Imaging (MRI) is a medical imaging technique that uses a
powerful magnetic eld and radio waves to produce detailed images of body
structures including tissues, organs, bones, and nerves to study the anatomy
and physiology of the body in both health and disease. An MRI differs from a CT
scan, in that it does not use radiation. Brain and spine MRI is an excellent
diagnostic and prognostic tool for various neurological and neuromuscular
disorders like cerebrovascular diseases, tumours, demyelinating and infectious
diseases of the brain and spinal cord.
When to order an MRI scan instead of CT scan?
• MRI is done once CT scan has already detected a brain tumour. MRI
visualizes the brain and soft tissues very well, so, the extent, spread, type
and staging of the tumour can be done in detail.
• MRI is done as a follow up scan in cases of stroke to know the area of
damage and prognosis.
• In cases of spinal cord injury, degenerative disc disease, spinal cord
tumour, meningioma, meningomyelocoele, transverse myelitis, infections
of the spine, MRI is done. Spinal cord is visualized better with MRI than
with CT scan.
• MRI is an imaging modality of choice in cases where a denitive diagnosis
is suspected clinically or through previous imaging like CT scan. It is used
to conrm the diagnosis and to better visualize the soft tissues and their
abnormalities.
112 Neurological Disorders - A Handbook for Family Physicians

• In neurodegenerative conditions, for e.g. dementia, multiple sclerosis,

multi system atrophy (MSA), Parkinson's disease, cerebellar ataxia, etc, an
MRI scan is preferred.
• MRI is ordered in cases of behavioral problems and psychiatric disorders.
Principle of MRI
The hydrogen protons contained in water molecules of the body exhibit tiny
magnetic elds which normally move around randomly. During an MRI scan,
when short bursts of radio waves are applied to the body, these tiny magnetic
elds of the hydrogen protons align to the magnetic eld and realign back into
place alternately. This makes the protons' magnetic elds spin round in unison
and emit a weak radio signal in resonance. The protons in different tissues of the
body realign at different speeds and thus, emit signals of varying intensities.
This forms the basis of differentiation of various soft and hard tissues of the part
being scanned. A receiving device receives and transmits the resonance signals
to a computer, where clear, cross-sectional black and white images of the body
are created. Each of these images shows a thin slice of the body and differentiates
between bone, soft tissues and uid-lled spaces by their water content and
structural properties. These images can be converted into three-dimensional (3-
D) pictures of the scanned area. The eld strength of the magnet is measured in
tesla, and the majority of systems operate at 1.5T (nowadays 3 T). T1 image
weighting is useful for assessing the cerebral cortex and identifying fatty tissue,
while T2 image weighting is useful for detecting edema and revealing white
matter lesions.
Contrast MRI scanning
Chelates of gadolinium are the most commonly used intravenous contrast
agents.
• These agents are safer than the iodinated contrast agents used in X-ray
radiography or CT.
• Gadolinium agents are safe in patients with renal impairment, though
precautions have to be taken before administering these agents in specic
cases.
• In patients with severe renal failure requiring dialysis there is a risk of
nephrogenic systemic brosis. Therefore, dialysis patients should receive
gadolinium agents only when essential.
• Dialysis should be performed as soon as possible after the scan to remove
the agent from the body promptly.
Neurological Disorders - A Handbook for Family Physicians 113

Indications of MRI brain

• To check for causes of muscle weakness, numbness and tingling.
• To check for causes of symptoms such as change in consciousness,
confusion, or abnormal movements. These symptoms may be caused by
brain diseases, such as Huntington's disease, multiple sclerosis,
Parkinson's disease, or Alzheimer's disease.
• To look for tumors, infections, abscess, or conditions of the brain or brain
stem, such as encephalitis or meningitis.
• To investigate birth defects and developmental anomalies.
• To investigate causes of epilepsy (seizure).
• To check for integrity of brain and other cranial structures in head trauma.
• To diagnose a stroke or blood vessel problems in the head.
• To investigate psychiatric disorders.
• To look for causes of hearing loss, memory loss, headaches, speaking
difculties, vision problems and dizziness.
• To diagnose vascular occlusive disease and aneurysm.
Indications of MRI spine
• To assess the spinal anatomy and alignment in injury and birth defects.
• To look for causes of muscle weakness in the limbs, numbness and
tingling, abnormal movements.
• To look for problems in controlling or emptying urinary bladder.
• To assess intervertebral disc and joint for diagnosing sciatica, nerve root
entrapment, spinal cord indentation.
• To assess compression of spinal cord and nerves.
• To help plan and monitor spinal surgical procedures, such as
decompression of compressed spinal cord and nerves or spinal fusion.
• To image spinal infection or tumors.
• To assess inammation of the spinal cord or nerves.
Contraindications of MRI scan
• Patients with metal implants (brain aneurysm clips , prosthetic metal heart
114 Neurological Disorders - A Handbook for Family Physicians

valves, eye implants, intrauterine device, articial joints, dental llings

and braces, tubal ligation clips, surgical clips or staples) and implanted
electronic device (cardiac debrillator, pacemaker, retained leads,
implanted nerve stimulators, implantable cardioverter-debrillator) can
experience excess MRI related heating during the scanning procedure.
• These implants can also interfere with the MR signaling and produce
artifacts which deteriorate the quality of images and also may produce
false and misleading images of the inside of the scanned body part.
• The patients need to inform about these implants to the referring doctor
and staff carrying out MRI scanning so that they are aware of the risks
associated with MRI scanning and measures are taken to ensure the scan is
as safe as possible.
• Some tattoo ink contains traces of metal, but most tattoos are safe in an
MRI scanner.
• MRI scans are not usually recommended during pregnancy, particularly
in the rst three months.
Advantages of MRI scan
• MR images of the brain and other cranial structures are clearer and more
detailed than with other imaging methods. Thus, MRI should be preferred
for imaging if available.
• MRI uses non iodine contrast medium which is safer than iodine
containing contrast media used in X-ray and CT imaging.
• Risk of ionizing radiations is absent in MRI scan.
• MRI is the most sensitive means to detect and evaluate brain tumors.
• MRI can detect stroke at a very early stage (within less than 30 minutes) by
mapping the motion of water molecules in the tissue.
• The MRI examination poses almost no risk to the average patient when
appropriate safety guidelines are followed.
Disadvantages of MRI scan
• Implanted medical devices that contain metal may malfunction or cause
problems in obtaining clear images during an MRI exam.
• Metallic implants, pacemakers may malfunction or cause problems
during an MRI exam.
Neurological Disorders - A Handbook for Family Physicians 115

• Nephrogenic systemic brosis may occur as a complication of MRI caused

by the injection of high doses of gadolinium-based contrast material in
patients with very poor kidney function.
• A person who is very obese and large may not t into the opening of
certain types of MRI machines.
• The time taken for MRI scanning is longer than for CT. Also, traction
devices and life support equipment used in emergency settings have to be
kept away from the area to be imaged. Thus, MRI cannot be used in
emergency settings.
• MRI is many a time uncomfortable for patients who are claustrophobic
and cannot remain in the noisy machine for such long testing time.
• MRI costs more than CT.
• MRI is sensitive to patient motion. Patient motion can give rise to bad
quality images.
MRI with DTI
Diffusion tensor imaging (DTI) is an MRI technique used to noninvasively
visualize anatomical connections between different parts of the brain. It is used
to study abnormalities in white matter ber structure (location and orientation)
and brain connectivity. DTI is useful in the investigation of stroke, epilepsy,
multiple sclerosis, brain abscesses, brain tumors (localization, inltration), mild
traumatic brain injury (dening the severity), and hypertensive
encephalopathy. It is used in surgical planning of brain tumors, to determine the
proximity and relative position of the corticospinal tracts and a tumor.
DTI tractography is a 3D modeling technique used to visualize neural tracts. It
can also visualize very short connections present among cortical and subcortical
regions. It is used for measuring decits in white matter (such as in aging),
differentiation of brain tumour, distinguishing between acute-ischemic changes
and chronic-ischemic changes in cases of stroke, diagnosing and follow up of
MS lesions, determining the location and extent of epileptic foci, etc. It helps in
preoperative planning in terms of determining the extent of diffuse inltration
of pathologic tissue (for e.g. tumour, abscess) to minimize functional damage
and residual tumor volume.
116 Neurological Disorders - A Handbook for Family Physicians

Fig. 11.1 MRI Axial T1 with and without contrast showing

presence of right Meningioma with brain invasion

Fig. 11.2 MRI-T2 Sagittal sequences showing enhanced lesion in the spine

Fig 11.3: T1-W MSK-MRI shows characteristic patterns of muscular fatty

inltration in DMD patients. Affected muscles demonstrate high
T1-weighted signal as compared to normal muscles MRI MSK
Neurological Disorders - A Handbook for Family Physicians 117

12

Angiography
Angiography is a very specialized test which is ordered by a neurologist or a
neurosurgeon. Angiography is a minimally invasive medical test that uses X-
rays or MRI technology and an iodine or gadolinium containing contrast
material to produce pictures of the blood vessels. Imaging of the vascular
architecture of the brain is termed as Neuro-angiogaphy.
Angiography can be performed using:
• Digital X-ray technology (DSA)
• Computed Tomography (CT)
• Magnetic Resonance Imaging (MRI)
Digital subtraction angiography (DSA) is a type of uoroscopy technique used
to clearly visualize blood vessels in a bony or dense soft tissue environment.
Procedure: A pre-contrast image which includes all the structures within the
head like skull, brain, CSF, meninges, blood vessels, etc. is acquired rst by a
digital X-ray using technology. In catheter angiography a catheter is introduced
into the supercial femoral artery of the patient after giving local anaesthesia
(general anaesthesia in children) and navigated under X-ray guidance up to the
carotid artery where an iodine containing contrast material is injected and
multiple X-ray images are taken. In IV-DSA, radiopaque iodine based dye is
injected intravenously into the body. The contrast material ows along with the
blood to the cerebral arteries and highlights the blood vessels on the X-ray.
These images are simultaneously stored in the computer which then subtracts
the 'pre-contrast image' from the 'post-contrast image'. Tissues and blood
vessels on the rst image are digitally subtracted from the second image, leaving
a clear picture of the artery or vein for assessing the integrity of these blood
118 Neurological Disorders - A Handbook for Family Physicians

vessels and abnormalities in them.

CT angiography uses a CT scanner to produce detailed images of both blood
vessels of the brain. An iodine containing contrast is through intravenous route.
A CT scan is then performed while the contrast ows through the blood vessels
to the blood vessels of the brain. After scanning, the images are processed on a
computer and reviewed in different planes and projections. In Digital
Subtraction Angiography (DSA), images are electronically manipulated to
remove (subtract) bones and other structures obscuring the images taken to
make the blood vessels stand out.
Magnetic resonance angiography (MRA) uses magnetic resonance imaging
(MRI) technology to image blood vessels.
Various MRI techniques include:
• Flow-dependent angiography
–Time-of-ight (TOF) or inow angiography
–Phase-contrast (PC-MRA)
• Flow-independent angiography
–Contrast-enhanced Magnetic Resonance Angiography
–Subtraction less Contrast-enhanced Magnetic Resonance Angiography
–Non-enhanced magnetic resonance angiography
Indications of cerebral angiography
To diagnose and evaluate diseases of blood vessels and related conditions such
as:
• Cerebral aneurysm
• Brain arteriovenous Malformation (AVM)
• Dural arteriovenous stula
• Intracerebral Hemorrhage
• Dissections of arteries
• High-grade intracranial stenosis
• Acute stroke
• Multiple sub cortical strokes in cerebral vasculitis
Neurological Disorders - A Handbook for Family Physicians 119

• Intracranial tumor and its blood supply

• Cerebral venous thrombosis
• Congenital abnormalities in blood vessels
Indications of spinal angiography
Evaluating and diagnosing diseases of blood vessels and related conditions of
the spine including:
• Bleeding into the blood vessels of the spinal cord.
• AVM
• Aneurysm
• Stenosis, thrombosis of spinal blood vessels
• Spinal stroke due to blockage of blood vessel
• Stroke due to blood vessel inammation
• Suspected rupture of blood vessels of the spine
• Spinal tumour and its blood supply
• Suspected spinal dural stula
• Unexplained spinal disease
Contraindications of angiography
DSA and CT angiography:
• Patients with bleeding disorders
• Patients who have an allergy to the IV contrast media
• Patients suffering from renal impairment, hyperthyroidism,
phaeochromocytoma, myasthenia gravis, etc.
• Presence of renal failure (as in alcohol abuse, angina, heart failure, kidney
problems, liver disease, severe infection).
• Patients taking diabetes medication Metformin. Medicine may need to be
stopped temporarily for 48 hours
• Pregnant females should have the scan done only in critical situations after
discussion of benets and risks.
• Complications such as an allergic reaction to the anesthetic or the contrast
120 Neurological Disorders - A Handbook for Family Physicians

medium, blockage or damage to the vessel punctured, thrombosis and

embolism formation, bleeding or bruising at the site of
puncture/injection, and anywhere along the vessel during passage of the
catheter, increased risk of ionizing radiation can also occur.
MR Angiography:
• Patients with metal implants and implanted electronic device (cardiac
debrillator, pacemaker)
• Pregnancy (especially in the rst trimester)
Advantages of DSA
• Results from cerebral angiography are more accurate than those produced
by carotid Doppler ultrasound or other noninvasive imaging of the blood
vessels.
• Use of a catheter makes it possible to combine diagnosis and treatment in a
single procedure.
Disadvantages of DSA
• Risk of ionizing radiations and allergic reaction to iodine containing
contrast is present.
• Risk to the foetus in pregnant females.
• Risk of catheter introduction causing damage to the vessels is present.
• Risk of stroke occurring due to dislodged thrombus from artery into the
vessels supplying brain by the catheter is present.
Advantages of MR angiography
• It is a non-invasive technique not involving introduction of catheter into
any blood vessel.
• It does not use ionizing radiations.
• Contrast medium used in MRA does not contain iodine and is less toxic
and can be used in patients with renal impairment.
Disadvantages of MR angiography:
• It is unsafe and cannot be used for patients having metal and electronic
implants.
• High cost of MRA makes it a less frequently used diagnostic test.
Neurological Disorders - A Handbook for Family Physicians 121

Common DSA ndings

Fig 12.2 DSA showing occlusion of

right middle carotid artery by a clot

Fig 12.1 DSA showing right posterior

communicating artery aneurysm (arrow)

Common CT angiography ndings:

Fig 12.3 Cerebral CT angiogram showing

occlusion of left middle carotid artery

Fig 12.4 Cerebral MR angiogram Fig 12.5 Cerebral MR angiogram

showing multiple aneurysms showing bilateral transverse
cerebral venous stenosis
122 Neurological Disorders - A Handbook for Family Physicians

13

Plain X-Ray
X-rays are a type of radiation called electromagnetic waves. When the body is
exposed to X-rays, different parts of the body absorb different amounts of
radiation and allow varying amounts of the X-rays to pass through depending
on their densities.
X-rays pass through body tissues onto specially treated plates and a 'negative'
type picture is made. Images are produced in degrees of light and dark,
depending on the amount of X-rays that penetrate the tissues. The soft tissues in
the body (such as blood, skin, fat, and muscle) allow most of the X-ray to pass
through and appear dark gray on the lm. A bone, metal or a tumor, which is
denser than the soft tissues, allows few of the X-rays to pass through and
appears white on the X-ray. At a break in a bone, the X-ray beam passes through
the broken area and appears as a dark line in the white bone.
Radiographs are useful in the detection of pathology of the skeletal system as
well as for detecting some disease processes in soft tissue of brain and spinal
cord. Radiographs may show fractures, presence of foreign body intracranial
air, midline shift of structures through shift of calcied pineal gland, etc.
For some types of X-ray tests, a contrast medium such as iodine or barium is
introduced into the patient's body, either orally, intravenously, rectally or
intrathecally (myelogram). In some people, the injection of a contrast medium
can cause side effects such as feeling of warmth or ushing, a metallic taste in the
mouth, lightheadedness, nausea, itching and rarely, severe reactions which
include severe hypotension, anaphylactic shock and cardiac arrest.
Though X-rays of the skull are not used as often as in the past, due to the use of
newer technologies such as computed tomography (CT scans) and magnetic
resonance imaging (MRI), they remain valuable for evaluating the bones of the
Neurological Disorders - A Handbook for Family Physicians 123

skull and spine for fractures and detecting other conditions of the skull, spine
and their contents.
Indications of X-ray imaging
• Head trauma
• Spine trauma
• Suspected non-accidental injuries to detect previous injuries

Fig. 13.1: X-Ray Brain Fig. 13.2: X-Ray Spinal Cord

• To detect tumors
• Congenital anomalies of the cranial vault and spine
• Headache
• Certain metabolic and endocrine disorders that cause bone defects of the
skull.
• Detect cerebral calcication
• Migration of the soft tissues inside the skull
Contraindications of X-ray imaging
• Risks associated with radiation exposure may be related to the cumulative
number of X-ray examinations and/or treatments over a long period of
time.
• Radiation exposure during pregnancy may lead to birth defects. When
taking a skull X-ray, special precautions should be made to minimize the
radiation exposure to the foetus.
124 Neurological Disorders - A Handbook for Family Physicians

• Patients having allergy to iodine or barium contrast agents are

contraindicated for contrast induced X-ray imaging.
• Contrast media is safe in most patients. However, adverse reactions may
range from mild to severe in patients suffering from renal impairment,
hyperthyroidism, phaeochromocytoma, myasthenia gravis, etc
Neurological Disorders - A Handbook for Family Physicians 125

14

Positron Emission
Tomography-Computer
Tomography (PET-CT)
Positron emission tomography (PET) scanning is a very specialized scanning
procedure, which is used only in specialized cases, where apart from structural
imaging, a functional imaging of the body part is required (for e.g. tumours,
Alzheimer's disease, epilepsy, behavioral disorders, etc.). PET is a functional
imaging technique that produces a three-dimensional image of functional
processes in the body.
Procedure: A positron-emitting radionuclide (tracer), usually
uorodeoxyglucose (FDG), an analogue of glucose is introduced into the body
on a biologically active molecule intravenously, which is taken up by active
tissues of the body. Gamma rays are created during the emission of positrons
from these active tissues, and the scanner then detects the gamma rays. A
computer then analyzes the gamma rays and uses the information to create an
image map of the organ or tissue being studied.
Principle: PET neuroimaging is based on the principle that areas of high
radioactivity are associated with brain activity. The amount of the radionuclide
collected in the tissue affects how brightly the tissue appears on the image, and
indicates the level of organ or tissue function. If blood ow and perfusion of an
organ or tissue has to be studied, the radionuclide chosen may be a type of
radioactive oxygen, carbon, nitrogen, or gallium.
Functional imaging obtained by PET can be more precisely aligned or correlated
126 Neurological Disorders - A Handbook for Family Physicians

with anatomic imaging obtained by CT scanning. In modern PET-CT scanners,

three dimensional imaging is often accomplished with the aid of a CT X-ray scan
performed on the patient during the same session, in the same machine.
Uses of PET-CT scans
PET and PET-CT scans are performed to:
• To detect suspected brain and spinal tumours.
• To detect cancer metastasis and recurrence of tumors.
• To determine staging of patients with tumours where staging is difcult
clinically, and also to help in radiotherapy planning.
• To evaluate the prognosis of a treatment plan, such as cancer therapy.
• To evaluate and diagnose memory disorders (Alzheimer's disease) and
other central nervous system disorders such as Parkinson's disease,
Huntington's disease, epilepsy, and cerebrovascular accident.
• To localize epileptic foci.
• To evaluate the perfusion (blood and oxygen ow) of the brain tissue using
the tracer oxygen-15.
• To examine links between specic psychological processes or disorders
and brain activity.
• To locate the specic surgical site prior to surgical procedures of the brain.
• To facilitate PET-image guided surgery of intracranial tumors,
arteriovenous malformations and other surgically treatable conditions.
• To map normal human brain for research purposes.
• To compare the effects of a treatment intervention on brain function, using
a pre and post intervention PET scan.
Contraindications of PET-CT scan
• Pregnant females should not undergo the scan since radiation is believed
to be unsafe for developing fetuses.
• Recent chemotherapy or radiotherapy can make interpretation difcult.
• Patients having allergies or who are sensitive to radionuclide, contrast
dyes, or iodine.
• Very obese people may not t into the opening of a PET-CT scanner.
Neurological Disorders - A Handbook for Family Physicians 127

Precautions for PET-CT scan

• Other imaging methods should be considered for pregnant patients.
• Patients who are claustrophobic may nd the test uncomfortable.
• High blood glucose levels in diabetics may interfere with the accuracy of a
PET scan, since high levels lower the FDG tracer uptake in tissues and
tumour cells. A diabetic patient may be instructed to take pre-procedure
insulin dose with a meal several hours prior to the procedure. Also, fasting
for a certain period of time prior to the procedure may be required. If
plasma glucose level is <120 mg/dl the FDG PET study can be performed.
If plasma glucose level is >120 mg/dl the FDG PET study may be
rescheduled or the patient excluded depending on the patient
circumstances and the need for the test being conducted.
• Since medications such as tranquilizers and sedatives, and alcohol act as
CNS depressants, while caffeine and nicotine in tobacco and smoking act
as CNS stimulants, their consumption should be avoided a day prior to
testing to avoid false results on scans.
• Some of the administered FDG might be excreted in small amounts in
breast milk. Therefore, milk should be collected and discarded for 2 hours
after the scan following which normal breast feeding can be resumed.
Advantages of PET-CT scan
• PET-CT scan provides information on both function and anatomic
structure of the brain and spinal cord that is unattainable using other
imaging procedures.
• PET-CT scan results help in more accurate diagnosis of various
neurological disorders.
• PET-CT scans are less expensive than exploratory surgery and yield more
precise information.
• By identifying changes in the body at the cellular level, PET imaging may
detect the early onset of disease before it is evident on other imaging tests
such as CT or MRI.
Disadvantages of PET CT scan
• Injection of the radiotracer may cause pain and inammation.
• PET CT scans are time consuming.
128 Neurological Disorders - A Handbook for Family Physicians

• Test results of diabetic patients or patients who have eaten within a few
hours prior to the examination can be adversely affected because of altered
blood sugar or blood insulin levels.
• Because the radioactive substance decays quickly and is effective for only a
short period of time, late arrival of the patient for the test may require
rescheduling the procedure for another day.

Fig 14.1: PET ndings show hypometabolism in halamus, medial

temporal cortex and cerebellum in autism

Fig 14.2: PET findings show hypometabolism in Basal ganglia,

thalamus, medial temporal cortex and cerebellum

Fig 14.3: PET findings show hypometabolism in the regions of left MCA,
ACA and right PICA terriotory
Neurological Disorders - A Handbook for Family Physicians 129

15

Functional MRI
Functional Magnetic Resonance Imaging (fMRI) is a very specialized imaging
test which is ordered by a neurologist or a neurosurgeon. It is a functional
neuroimaging procedure that uses MRI technology to measure activity of
neurons in the brain and spinal cord by detecting associated changes in blood
ow in the area of activation. When neurons of a particular brain or spinal cord
area become active, blood ow to that area increases bringing in more
oxygenated haemoglobin which is diamagnetic (resistant to magnetism) than
deoxygenated haemoglobin which is paramagnetic (attracted to magnetism).
While performing an MRI scan, this difference in rising oxygenated
haemoglobin level gives rise to an improved MR signal, since diamagnetic
blood interferes less with the magnetic MR signal. This improvement is mapped
and represented graphically by color coding according to the strengths of
activation, to show which neurons are active at the time of a particular task
during MRI scanning.

Procedure

fMRI detects differences in brain activity involved in a sensory, motor, cognitive

function or a behavioral function. During the fMRI procedure, the patient is
asked to alternatively perform a specic task or is stimulated to trigger several
processes or emotions. The stimuli can be grouped in blocks (e.g. 30s-long) or
presented as events. Each of the conditions is repeated several times and
separated by rest periods. The combination of these conditions is called an fMRI
paradigm. Tasks like tapping the ngers, toes, moving feet up and down are
commanded to perform to study activation of the areas involved in motor
function. To study areas of activation in sensory function, sensory stimuli like
stroking with a brush along a particular dermatome (cutaneous), viewing
130 Neurological Disorders - A Handbook for Family Physicians

pictures (visual), listening to an audio (auditory), smelling an odour (olfactory),

tasting a substance (gustatory) may be presented. Many cognitive and language
paradigms also exist, which include word generation (prompted by a letter),
semantic decision making (e.g., is the displayed word a vegetable?), and even
simple auditory presentation of words. Though motor tasks and cutaneous
sensory stimuli are mainly used in clinical fMRI studies, other tasks and stimuli
are used in studies conducting research.

Uses of brain fMRI

• To examine the anatomy of the brain.

• To help assess the effects of stroke, trauma or degenerative diseases (such
as Alzheimer's disease) on brain function.
• Assessment of patients with disorders of consciousness (coma, vegetative
state, minimally conscious state, locked-in syndrome).
• To determine precisely which part of the brain is handling critical
functions such as thought, speech, movement and sensation, called brain
mapping.
• To check the neural correlates of a seizure.
• To study how the brain recovers partially from a stroke, test how well a
drug or behavioral therapy works, detect the onset of Alzheimer's, and
note the presence of disorders like depression.
• To monitor the growth and function of brain tumors.
• To guide the planning of surgery, radiation therapy, or other surgical
treatments for the brain so that damage to important functional areas of
the brain is avoided and that primary functions (motor, language, etc.) are
preserved as much as possible.
• To compare the effects of a treatment intervention with respect to function
using a pre intervention and a post intervention fMRI.
Uses of spinal fMRI
• To map neuronal activity at different levels of the spinal cord in response
to various stimuli, such as touch, vibration, and thermal changes, and with
motor tasks.
• To detect a neuronal response in the spinal cord caudal to the injury site
during both active and passive lower limb movement tasks, and in
Neurological Disorders - A Handbook for Family Physicians 131

response to a noxious stimulus, even when subjects could not feel the
stimulus. This is useful for revealing areas of impaired and preserved
activity in spinal cord injured patients.
• To identify the pathogenesis of many chronic pain conditions such as
irritable bowel syndrome, chronic lower back pain, or bromyalgia.
• To determine whether the breakdown causing muscle weakness is at the
spinal level, neuromuscular junction or within the muscle bers
themselves, as in muscular dystrophies.
• To track disease progression and prognosis.
• To localize function in pre-surgical mapping, in cortical tissue near areas
intended for any spine surgery or resection.
• To study normal sensory and motor function and the effects of trauma to
the spinal cord and multiple sclerosis for research purposes.

Fig. 15.1: Brain regions showing activation following task based fMRI

• To compare the effects of a treatment intervention with respect to function

using a pre intervention and a post intervention fMRI.
Contraindications of fMRI
• Patients who are contraindicated for MRI scanning are also
contraindicated for fMRI.
• Patients with metal and electronic implants
• Pregnant females, especially in the rst trimester.
132 Neurological Disorders - A Handbook for Family Physicians

(II) Electrophysiological
Neurological Disorders - A Handbook for Family Physicians 133

16

Electroencephalography
Electroencephalography is the neurophysiologic measurement of the electrical
activity of the brain OBTAINED by recording from electrodes placed on the
scalp or, in special cases, subdurally or in the cerebral cortex. The resulting
traces are known as an electroencephalogram (EEG) and represent an electrical
signal (postsynaptic potentials) from a large number of neurons.

Clinical use

EEG in various forms is most useful as a tool for monitoring and diagnosis in
certain clinical situations:

• Seizure and epilepsy: to detect seizure focus and monitor the effects of
treatment

• Disorders with coexisting seizures: in cases of autism, cp, etc, where the
patient may not have experienced a seizure attack or shown symptoms,
EEG can efciently detect a possible underlying epileptic focus

• Sleep disorders

• Eating disorders

• Coma and brain death

• Dementia
134 Neurological Disorders - A Handbook for Family Physicians

Procedure

In conventional scalp EEG, the recording is obtained by placing electrodes on

the scalp, after preparing the scalp area BY applying a conductive gel to reduce
impedance. Modern EEG systems have the subject wear a plastic cap where the
electrodes are inserted in small holes.

Electrode placement is determined by measuring and marking the scalp using a

system called the 10-20 system. Each electrode is connected to an input of a
differential amplier (one amplier per pair of electrodes), which amplies the
voltage between them (typically 1,000-100,000 times, or 60-100 dB of voltage
gain). The resulting voltage signal is ltered by a high-pass lter and a low-pass
lter, typically set at 0.5 Hz and 35-70 Hz, respectively. The high-pass lter
typically lters out slow electrogalvanic signals, whereas the low-pass lter
lters out electromyographic signals.
The ltered signal is then output on paper (in older systems), or displayed on a
computer screen. The amplitude of the EEG is about 100 μV when measured on
the scalp, and about 1-2 mV when measured on the surface of the brain.
Standard EEG: During a standard EEG, the patient is asked to breathe deeply for
some minutes, look at a ashing light, etc. These activities change the electrical
activity in the brain which shows on the computer. The patient is asked to keep
as still as possible during the test. Any movement can change the electrical
activity in the brain, which can affect the results.
Advantages
• Less expensive than other functional imaging tests.
• The time resolution is very high.
• EEG measures the electrical activity of the brain directly.
Limitations
• Scalp electrodes are not sensitive enough to pick UP individual action
potentials.
• It cannot differentiate whether the resulting electrical activity is releasing
inhibitory, excitatory or modulatory neurotransmitters.
• EEG has limited anatomical specicity when compared with other
functional brain imaging techniques such as functional magnetic
resonance imaging (fMRI).
Neurological Disorders - A Handbook for Family Physicians 135

Activity types
The EEG activity is of two types: (1) rhythmic activity and (2) transients.
Rhythmic activity is divided into the following bands depending on the
frequency:
• Delta: These waves are normally found only when a person is asleep or in
young children. abnormal activity may indicate subcortical lesions,
diffuse lesions, metabolic encephalopathy hydrocephalus, deep midline
lesions
• Theta: These waves are normally found only when a person is asleep or in
young children. abnormal activity may indicate focal subcortical lesions,
metabolic encephalopathy, deep midline disorders, hydrocephalus
• Alpha: Alpha waves are present only in the waking state when eyes are
closed but the person is mentally alert. present abnormally in coma
• Beta: Abnormal activity present in patients on benzodiazepines
• Gamma: A decrease in gamma band activity may indicate cognitive
decline
• Mu: Limited Mu activity may indicate working of motor mirror neurons
(as in autism).
136 Neurological Disorders - A Handbook for Family Physicians

Fig. 15.1: EEG – Seizures

Fig. 15.2: EEG – Autism

Neurological Disorders - A Handbook for Family Physicians 137

Sleep EEG
Sleep EEG is ordered in cases where seizures occur during sleep, or in fatigued
state, or when the awake EEG is normal.
Sleep-deprived EEG
A sleep-deprived EEG is done when standard awake EEG did not show any
unusual electrical activity.
Normal EEG
• In adults who are awake, the EEG shows mostly alpha waves and beta
waves.
• The two sides of the brain show similar patterns of electrical activity.
• There are no abnormal bursts of electrical activity.
• On photic stimulation, one area of the brain (the occipital region) shows a
brief response after each ash of light, the brain waves being normal.
Abnormal EEG
• If the two sides of the brain show different patterns of electrical activity, it
may indicate a problem in one area or side of the brain.
• Sudden bursts of electrical activity (spikes) or sudden slowing of brain
waves may be caused by a brain tumor, infection, injury, stroke, or
epilepsy. In many patients with epilepsy, the EEG may appear completely
normal between seizures.
• Presence of delta waves or too many theta waves in awake EEG of adults
may indicate presence of a brain injury or a brain illness.
• The EEG which shows no electrical activity in the brain (a at or straight
line EEG) means that the brain function has stopped. This may be due lack
of oxygen or blood ow to the brain, or when a person is in coma, or even in
cases of severe drug induced sedation.
138 Neurological Disorders - A Handbook for Family Physicians

17

Electromyography and Nerve

Conduction Studies
Electromyography (EMG) is an electrodiagnostic technique used for recording
the electrical activity produced by skeletal muscles. An electromyograph is used
to detect the electrical potentials generated by muscle cells when they are
neurologically or electrically activated. These signals are then analyzed to
evaluate normal or abnormal activation level and recruitment of muscle bers in
various disorders of muscles and nerves of central nervous system as well as
peripheral nervous system.
There are two kinds of EMG: surface EMG and intramuscular (needle and ne-
wire) EMG using surface electrodes and needle electrodes respectively. Surface
EMG is unable to assess the same muscle activity as when the needle is inserted
through a muscle. Therefore, needle EMG is commonly used in clinical settings.
The activities recorded during an EMG are: A) Insertional activity - Normal
muscles at rest generate some normal electrical signals when the needle is
inserted into them.
Spontaneous activity at rest - Nil muscle activity is seen normally. Abnormal
spontaneous activity might indicate some nerve and/or muscle pathology. C)
Voluntary recruitment - The patient is asked to contract the muscle and electrical
activity is recorded. The shape, size, and frequency of the resulting electrical
signals are analyzed.
EMG characteristics in neuropathies and myopathies.
1. Neuropathic disease shows the following EMG characteristics:
Neurological Disorders - A Handbook for Family Physicians 139

• An action potential amplitude that is twice normal due to the increased

number of bers per motor unit because of reinnervation of denervated
bers
• An increase in duration of the action potential
• A decrease in the number of motor units in the muscle
2. Myopathic disease shows the following EMG characteristics:
• A decrease in duration of the action potential
• A reduction in the area to amplitude ratio of the action potential
• A decrease in the number of motor units in the muscle
• Dementia
Abnormal EMG nding
• Insertional activity:
This activity is decreased in atrophied muscle or fatty tissue. Whereas, it is
increased in conditions that cause membrane instability, such as neuropathies,
radiculopathies, and inammatory myopathies.
• Spontaneous activity at rest:
Abnormal brillation potentials result from motor axonal loss that is not
balanced by reinnervation in conditions such as inammatory myopathies and
direct muscle injury. Low-amplitude brillation potentials suggest that
denervation has occurred in the remote past, whereas high-amplitude
brillation potentials suggest an ongoing active denervation process.
• Voluntary muscle recruitment:
Reduced recruitment signies motor axonal loss or focal demyelination or
conduction block. Whereas, increased recruitment with a small voluntary force
suggests a myopathy.
Interpretation:
EMG study is combined with nerve conduction studies for better interpretation
of results.
Uses
• To identify neuromuscular disorders
• To diagnose peripheral nerve compression or injury (eg. Carpal tunnel
syndrome, Cubital tunnel syndrome)
140 Neurological Disorders - A Handbook for Family Physicians

• To identify nerve root compression or injury (eg. due to herniated

intervertebral disc, sciatica)
• To check for causes of muscle weakness and wasting and help differentiate
between neuropathy and myopathy
• To diagnose muscle disorders such as muscular dystrophy
• To evaluate motor problems such as involuntary muscle twitching (eg.
Motor neuron disease)
• To diagnose disorders those affect the motor neurons in the spinal cord,
such as amyotrophic lateral sclerosis or polio
• To diagnose diseases affecting the neuromuscular junction such as
myasthenia gravis
Indications
EMG is indicated when there is:
• Weakness in the limb/s
• Pain in the limb/s
• Suspected spinal nerve compression
• Suspected neurologic injury or disorder affecting peripheral nerves
Contraindications
• Patients with bleeding disorders (eg. haemophilia) and patients receiving
anticoagulant therapy, since the needle electrodes may cause bleeding
within the muscle.
• Patients with skin infections, since there is a risk of spreading infection
from the skin to the muscle.
• Patients on medications such as skeletal muscle relaxants, cholinergics,
and anticholinergics, since they affect muscle activity and EMG may show
false test results. These medications may need to be stopped at least three
days prior to EMG testing.
• Patients with impaired consciousness or cognition, who cannot
understand commands given during the procedure.
Precautions
• In patients with gross oedema, skin puncture by needle electrodes may
result in leakage of serous uid for a long time. The uid may also contain
Neurological Disorders - A Handbook for Family Physicians 141

bacteria which may increase the risk of cellulitis. So, EMG study should be
avoided or postponed.
• Swelling or bleeding in muscles or excess fat (obesity) may interfere with
the transmission of electrical waves to the electrodes, and thereby alter the
EMG results.
Limitations
• Excess of adipose tissue (fat) affects the EMG recordings.
• Needle and wire introduction into the muscles is painful.
• Even if surface EMG technique is used, it only measures potentials of
supercial muscles and provide comparatively less information about the
state of diseased muscle.
Nerve Conduction Studies
A nerve conduction study (NCS) is an electrodiagnostic test used to evaluate the
electrical conduction, and thus the function of the motor and sensory nerves of
the body.
Uses
• Uses of sensory NCS include evaluating parasthesias (numbness, tingling,
burning sensations) in a limb or a part of the limb (eg. Carpal tunnel
syndrome, Guyon's canal syndrome, peroneal neuropathy), in two or
more limbs or parts of the limbs (eg. Guillain-Barré syndrome, diabetic
neuropathy)
• Uses of motor NCS include evaluating weakness in muscle/s of limb/s
(eg. nerve root compression due to herniated disc, motor neuron disease,
muscular dystrophy, poliomyelitis)
Indications
NCS is indicated when there is:
• Weakness in the limb/s
• Parasthesias in the limb/s
• Pain in the limb/s
• Suspected spinal nerve compression
• Suspected neurologic injury or disorder affecting peripheral nerves
142 Neurological Disorders - A Handbook for Family Physicians

The nerve conduction study consists of the following components:

• Motor NCS
• Sensory NCS
• F wave study
• H-reex study
Nerve conduction velocity (NCV) is a common measurement made during this
test. NCV refers to the speed with which electrical impulses travel through a
particular nerve.
Procedure: Flat electrodes are placed on the skin at intervals along the nerve
course. Low-intensity electrical impulses are passed through these electrodes to
stimulate the nerve. The impulses (sensory/motor) produced by this electrical
current are recorded and viewed on an oscilloscope or computer screen. The
recorded impulses are then evaluated to determine the speed with which the
impulses travel through the nerves.
Motor NCS
Motor NCS are performed by electrical stimulation of a peripheral nerve and
recording from a muscle supplied by this nerve. The time taken by the electrical
impulse to travel from the stimulation site to the recording site is called the
latency and is measured in milliseconds (ms). The size of the response
(amplitude) is measured in millivolts (mV). Stimulation is carried out at two or
more different locations along the same nerve to determine difference in
latencies. The distance between the different stimulating electrodes and the
difference in latencies are used to calculate the velocity.
Sensory NCS
Sensory NCS are performed by electrical stimulation of a peripheral nerve and
recording from a purely sensory portion of the nerve, such as on a nger. The
sensory NCV is also calculated the same way as for motor NCV.
F-wave study
F-wave study uses supramaximal current intensity to stimulate a motor nerve,
action potentials of which travel through the nerve in an anti-dromic direction,
from the site of the stimulating electrode in the limb to the spinal cord's ventral
horn and back to the limb in the same nerve that was stimulated. Action
potentials from a muscle supplied by the nerve are recorded. The F-wave
latency is used to derive the conduction velocity of nerve between the limb and
spinal cord.
Neurological Disorders - A Handbook for Family Physicians 143

H-reex study
H-reex study uses stimulation of a nerve and recording the reex action
potential from a muscle in the limb. This also evaluates conduction between the
limb and the spinal cord, but in this case, the afferent impulses are in sensory
nerves while the efferent impulses are in motor nerves.
Interpretation
Different pathological processes result in changes in latencies, amplitudes of the
motor and/or sensory nerves or slowing of the conduction velocities to differing
degrees.
Possible causes for abnormal result:
• axonopathy (damage to the nerve cell)
• conduction block (an obstacle to the impulse conduction within the nerve)
• demyelination (damage to the myelin sheath)
Contraindications
There are no specic contraindications for this test. But, precautions need to
be taken in the following cases:
• In patients with pacemakers, deep brain stimulators or spinal cord
stimulators, stimulating electrodes placed in close proximity to these
devices could induce a voltage of sufcient amplitude to inhibit the
functioning of these devices. Thus, special precautions must be taken
while performing NCS on them.
• Patients with impaired consciousness or cognition, who cannot
understand commands given during the procedure and who cannot bear
the electrical stimulations.
144 Neurological Disorders - A Handbook for Family Physicians

18

Evoked Potentials
Evoked potential (EP) tests measure the electrical activity in the brain in
response to stimulation of specic sensory nerve pathways such as sight, sound,
or touch. Minute electrical signals are evoked in the brain in response to these
sensory stimuli. These signals travel along the sensory nerves and through
afferent pathways of the spinal cord to respective regions of the brain and are
picked up by electrodes, amplied, and displayed on a computer. EPs, thus, are
able to detect the slowing or blockage of electrical conduction (eg.
demyelination) along these pathways.

Uses of SSEP test:

• Primary use is to determine compromised central nervous system (CNS)

conduction.

• To diagnose nerve entrapment syndromes such as carpal tunnel

syndrome/ulnar nerve entrapment syndrome.

• To diagnose spondylytic myeloradiculopathy

• To diagnose thoracic outlet syndrome

• To diagnose and manage acquired metabolic disorders (e.g., lead toxicity,

B12 deciency)

• To help reveal asymptomatic lesions, for example in case of suspected

multiple sclerosis.
Neurological Disorders - A Handbook for Family Physicians 145

• To conrm presence of demyelinating diseases such as multiple sclerosis;

diagnosis of which requires evidence of demyelination in two distinct
areas of the central nervous system.

• Abnormalities of trigeminal SSEPs may guide towards diagnosis of MS,

Wallenberg syndrome, cerebellopontine angle tumors, trigeminal
neuromas, or meningeal sarcoidosis with facial paralysis.

• To help conrm symptoms when few physical ndings are noted

• To establish an anatomic region where the conduction disturbance or

block occurs.

• To detect tumors or other problems affecting the brain and spinal cord.

• To check prognosis in comatosed patients in anoxic brain injury

• To study fundamental aspects of sensory physiology for research
purposes.
Indications
• To assess patients with acute spinal cord injury
• To evaluate acute anoxic encephalopathy
• To evaluate patients with suspected stroke
• To conrm or reject the presence of a suspected conduction block.
• To identify clinically silent brain lesions such as multiple sclerosis
suspects, in whom neurological signs and other objective ndings (brain
plaques on MRI and/or positive oligoclonal bands in CSF) are present.
• To assess and follow up for prognosis in patients with spinocerebellar
degeneration (e.g. Friedreich's ataxia, olivopontocerebellar degeneration)
• In unexplained myelopathy
• To evaluate radiculopathy, neuropathy
Different types of evoked potentials studies
• Somatosensory evoked potential (SSEP) test: This test helps detect problems
with cutaneous sensations which may be due to segmental innervation
disturbances, disturbances in the spinal cord, demyelination, etc.
146 Neurological Disorders - A Handbook for Family Physicians

• Visual evoked potential (VEP) test: This test helps detect problems with
the optic nerves that affect sight.
• Brainstem auditory evoked potential (BAEP) test: This test helps detect
problems with hearing due to nerve damage or brain stem tumors and
multiple sclerosis.
Somatosensory evoked potential (SSEP) testing is commonly used in clinical
settings. During the procedure, electrodes are attached to the wrist, the back of
the knee, or other locations depending on the dermatome to be studied. A mild
electrical stimulus is applied through the electrodes. Electrodes placed on the
scalp then pick up the response from corresponding brain area and the time
taken for the current to travel along the nerve to the brain is recorded.
Abnormalities may include prolonged latencies or lack of development of the
SSEP. The stimulation sites commonly used for clinical diagnostic SSEP studies
are the median nerve at the wrist, the common peroneal nerve at the knee, and
the posterior tibial nerve at the ankle.
The dorsal columns in the spinal cord are mainly responsible for conduction of
the electrical activity that generates the SSEP. While in the brain, the lemniscal
and thalamocortical pathways are involved. Because the diagnosis of multiple
sclerosis requires evidence of demyelination in two distinct areas of the central
nervous system, EP testing can help conrm multiple sclerosis.
Visual evoked potential (VEP) testing
Visual stimuli used in VEP testing are strobe ash, ashing light-emitting
diodes (LEDs), transient and steady state pattern reversal and pattern
onset/offset. The most common stimulus used is a checkerboard pattern, which
reverses every half-second. The VEP is used to identify impaired transmission
along the optic nerve pathways, which is a common early nding in MS, even in
some patients who have never experienced any visual symptoms. It is used to
detect problems with the conducting nerves and areas of the brain involved in
vision in cases of optic neuritis, occipital trauma, or neurobromatosis, etc.
Brainstem auditory evoked potential (BAEP) testing
In BAEP testing, broad-band clicks as stimuli are used for the neurologic
applications of auditory evoked potentials. BAEPs reect neuronal activity in
the auditory nerve, cochlear nucleus, superior olive, and inferior colliculus of
the brainstem. Abnormal test results may be a sign of hearing loss, multiple
sclerosis, acoustic neuroma, brainstem stroke, or brainstem degenerative
disorders, etc. BAEP testing may also be used for outcome prediction in cases of
coma.
Neurological Disorders - A Handbook for Family Physicians 147

Contraindications
There are no specic contraindications for this test. But, precautions need to be
taken in the following cases:
• In patients with pacemakers, deep brain stimulators or spinal cord
stimulators, stimulating electrodes placed in close proximity to these
devices could induce a voltage of sufcient amplitude to inhibit the
functioning of these devices. Thus, special precautions must be taken
while performing SSEP testing on them.
• Patients with impaired consciousness or cognition, who cannot
understand commands given during the procedure and who cannot bear
the electrical stimulations.
Advantages
• SSEP testing may help diagnose a problem even when the neurologic
change is too subtle to be noticed by the patient or to show up on
neurological examination.
Limitations
• Abnormalities demonstrated by these tests are etiologically nonspecic
and do not guide towards a specic diagnosis. Therefore, the test results
should be integrated carefully into the clinical situation by the concerned
physician.
• Though evoked potential studies are considered safe procedures, the test
may cause discomfort in hyperalgesic patients and children.
148 Neurological Disorders - A Handbook for Family Physicians

(III) Biochemical
Neurological Disorders - A Handbook for Family Physicians 149

19

Blood Tests
In neurological disorders, clinical history and examination is the key to identify
the diagnosis. Radiological investigations, for e.g. CT, MRI, are required to
conrm the diagnosis and differentiate between various causes. Blood tests are
adjunctive and offer added information about systemic causes or effects of
neurological disorders. Blood tests are especially important in CNS infections,
seizures, nutritional deciencies and metabolic disorders. Here we have
described the commonly used blood tests in patients presenting with
neurological complaints.
I. Routine blood tests
Complete blood count
White blood cells (WBC)
Normal ranges
• WBC - 4-10 x 109/L
• Neutrophils - 2.0-7.0×109/L
• Lymphocytes - 1.0-3.0×109/L
• Monocytes - 0.2-1.0×109/L
• Eosinophils - 0.02-0.5×109/L
• Basophils - 0.02-0.1×109/L
• Peripheral WBC count increases signicantly after a generalized seizure
and is probably transient in nature.
150 Neurological Disorders - A Handbook for Family Physicians

• High WBC count (consisting predominantly of PMNs) in bacterial

meningitis.
• Higher than normal numbers of lymphocytes or monocytes - some types
of cancers.
• Neutropenia - in cancer, viral infections such as inuenza, bacterial
infections such as tuberculosis, or deciencies of vitamin B12 or folate
(folic acid).
• Neutrophil granulocytes - May indicate bacterial infection. May also be
raised in acute viral infections
• Monocytes - May be raised in bacterial infection, tuberculosis, malaria
• Eosinophil granulocytes - increased in parasitic infections, or allergic
reaction.
Platelet
Platelet abnormalities could be the underlying cause of some of the neurological
disorders.
Normal value: 150-400 × 109
• Thrombocytosis (increased platelet count) may present as:
–Headache, transient ischaemic episodes, paraesthesias
–Other transient symptoms may include dizziness, dysarthria, syncope,
migraine, seizures, etc.
• Thrombocytopenia (low platelet count) may cause bleeding in the brain
leading to stroke or hematoma.
• Thrombotic thrombocytopenic purpura may present as:
–hallucinations, bizarre behavior, altered mental status, stroke, headaches
Haemoglobin level
Normal ranges:
• Men: 13.8 to 18.0 g/dL
• Women: 12.1 to 15.1 g/dL
• Children: 11 to 16 g/dL
• Pregnant women: 11 to 14 g/dL
Neurological Disorders - A Handbook for Family Physicians 151

Headache may be a symptom of anemia due to decreased oxygenation of the

brain tissues.
Polycythemia vera (increased RBC count) may present as headaches, lack of
concentration, fatigue and thromboembolic stroke (due to increased blood
clotting tendencies).
Creatinine level
Normal value: 0.5 to 1.2 mg/dL
Renal failure can lead to increased levels of creatinine, which in turn can cause
electrolyte imbalance leading to seizures. Also, drug dosing errors in patients
with renal impairment can cause adverse effects and poor outcomes. Dosages of
drugs cleared renally should be adjusted according to creatinine clearance or
glomerular ltration rate.
Prothrombin time tests (PT-INR)
The prothrombin time (PT) test and international normalized ratio (INR) test
examine the integrated function of all of the coagulation factors.
Normal PT:
12-13 seconds, Normal INR: 0.8-1.2
PT-INR should be checked in haemorrhagic stroke (bleeding tendencies).
Regular PT-INR check up will be required in patients with ischemic stroke who
are on anti-coagulants.
ESR
Normal ranges:
0-22 mm/hr for men and 0-29 mm/hr for women
Elevated ESR should raise suspicion of tuberculosis and malignancies. In these
conditions, there is very high ESR level. A borderline increased ESR may be non-
specic due to chronic inammation.
II. Vitamins
Vitamin B12
Normal value: 130-700 ng/L
A full blood count which shows anaemia and macrocytosis should prompt the
practitioner to look for a deciency of vitamin B12 or folate. Tests commonly
used for the detection of these vitamin deciencies are serum folate, red cell
folate and serum B12 concentrations.
152 Neurological Disorders - A Handbook for Family Physicians

Deciency may cause:

• unexplained neurological or neuropsychiatric abnormalities.
• peripheral neuropathy and sub-acute combined degeneration of the spinal
cord
• paraesthesias, weakness, clumsiness, and an unsteady gait (ataxia)
• senile dementia or Alzheimer disease; memory loss, irritability, and
personality changes in elders
B12 toxicity may present with similar complaints of deciency. For e.g.
numbness, paresthesias, headaches, giddiness, etc. Therefore, B12 level is
required to distinguish between toxicity and deciency. Also, history of
whether the patient was on B12 supplements will help to differentiate.
Vitamin E
Normal value: 5.5-17 μg/mL
Deciency may cause:
• Ataxia
• Progressive spinocerebellar syndrome
• Peripheral neuropathy
• Cranial neuropathy with ophthalmoplegia
• Dysarthria
• Psychomotor impairment
• Myopathy
III. Serum Immunoglobulins
IgG is increased in chronic phases of inammatory diseases of CNS, multiple
sclerosis, Lyme disease, neuromyelitisoptica, neurosarcoidosis and GBS
Oligoclonal bands are bands of immunoglobulins that are seen in patient's
blood serum or cerebrospinal uid on protein electrophoresis. IgG in normal
CSF migrates as a faint diffuse zone, but in demyelinating diseases, IgG
migrates as discrete oligoclonal bands. The presence of oligoclonal bands in
cerebrospinal uid combined with their absence in blood serum often indicates
that immunoglobulins are produced in central nervous system resulting from
viral and bacterial infections, and autoimmune diseases. Therefore, when
investigating CNS diseases, bands in serum are subtracted from bands in CSF.
Presence of oligoclonal bands in serum as well as CSF may indicate presence of
multiple sclerosis, myelitis, neoplastic meningitis and CNS inammatory
disorders.
Neurological Disorders - A Handbook for Family Physicians 153

IV. Disease specic tests

• Myasthenia gravis
The anti-acetylcholine receptor (AChR) antibody test is the most reliable test for
diagnosing autoimmune myasthenia gravis (MG) in most of the patients.
The anti-striated muscle (anti-SM) Ab is present in about 84% of patients with
thymoma who are younger than 40 years and less often in those without
thymoma. Thus, a positive test result should guide towards checking the pres-
ence of thymoma in patients younger than 40 years.
Seronegative (negative for anti-AChR Ab) patients should be referred for anti-
bodies to muscle-specic kinase (MuSK) testing. Anti-MuSK-positive individu-
als tend to have more pronounced bulbar weakness and may have tongue and
facial atrophy. They may have neck, shoulder and respiratory involvement
without ocular weakness. Also, response to acetylcholine esterase (AChE)
inhibitors is oftenly less, with chances of symptoms getting worse.
Striational antibodies are found in almost all the patients with thymoma and
MG, and late-onset MG patients; while rarely in anti-AChR-negative patients.
Presence of these antibodies should raise a strong suspicion of thymoma in a
young patient with MG.
Testing for rheumatoid factor and antinuclear antibodies (ANAs) is indicated to
rule out systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
• Muscular dystrophy
Increased Creatine phosphokinase (CPK) levels are indicative of muscle dis-
ease. Thus, CPK testing is the most specic test for muscular dystrophy. CPK
levels are 50-300 times greater than normal levels in the early phases of disease,
but the levels decrease as the muscle mass decreases. The CPK level is highest in
Duchenne MD, with comparatively lesser level in Becker MD.
• GuillianBarre syndrome
Antibodies to glycolipids and gangliosides are observed in the sera of most of
the patients with GBS during the acute phase.
Antibodies to GM1 are frequently found in the sera of patients with the acute
motor axonal neuropathy (AMAN) or acute demyelinating
polyradiculoneuropathy (AIDP) variants of GBS.
Anti-GM1 antibodies titers may be elevated with C jejuni infections.
Anti-GQ1b antibodies are found in GBS patients with ophthalmoplegia and the
Miller-Fisher variant.
154 Neurological Disorders - A Handbook for Family Physicians

Assays for antibodies to C jejuni, Cytomegalovirus, Epstein-Barr virus, Herpes

simplex virus, HIV, and Mycoplasma pneumonia infections may be considered
in GBS. HIV has been reported to precede GBS. Thus, testing should be done in
high-risk patients to check for possible infection with this agent.
• Cerebral malaria
Rapid diagnostic tests (RDTs) are being used for emergency medical screening
and in medical facilities with limited resources. These tests target antigen HRP-2
from P. falciparum.
Immunochromatographic tests detect antibodies to histidine-rich protein-2
(PfHRP2), parasite LDH (pLDH), or Plasmodium aldolase, and are very specic.
Polymerase chain reaction (PCR) tests target the detection of small-subunit 18S
rRNA and circumsporozoite (CS) genes. In patients with low levels of
parasitemia, PCR-based technique is the most reliable test for detecting malaria
parasites.
V. Peripheral smears
• Cerebral malaria
Manifestations of cerebral malaria include impairment of consciousness (confu-
sion, delirium, obtundation, stupor, or coma), convulsions, focal neurologic
decit, and psychosis.
Demonstration of asexual form of P. falciparum in peripheral blood smear, in
thick and thin blood smear lms stained by Giemsa stain is required for the
diagnosis. Absence of parasites in some patients may be due to sequestration of
parasitized RBCs in cerebral circulation or earlier treatment with antimalarial
drugs. In such a situation, at least 3 smears 6 hours apart should be examined. At
least 3 smears should be negative before excluding cerebral malaria.
• Tuberculous meningitis
AFB testing is used to identify an active tuberculosis (TB) infection caused by the
Mycobacterium tuberculosis. An AFB smear is used as a rapid test to detect
mycobacteria. A molecular test for TB called nucleic acid amplication test
(NAAT) may be done in conjunction with an AFB smear.
AFB blood and CSF cultures are used to diagnose active M. tuberculosis infec-
tions, infections due to nontuberculous mycobacteria, or to determine whether
TB-like symptoms are due to another cause. Susceptibility testing is done to
determine the most effective antibiotic to treat the mycobacterial infection.
Neurological Disorders - A Handbook for Family Physicians 155

VI. Specic biomarkers

• Homocysteine
–Signicant in cases of stroke
–Homocystinuria- causes mental retardation, seizures
–Hyperhomocystinemia - associated with arterial and venous thrombosis
and should be distinguished from autosomal recessive homocystinuria.
–Elevated homocysteine levels are found in the elderly, in patients with
vitamin B6 and B12 deciency; and in renal insufciency. Testing should
be done in young adults in case of stroke. Fasting homocysteine level is
measured by high-performance liquid chromatography (HPLC) with
uorescence detection.
Normal levels:
• Age 0-30 years: 4.6-8.1 μmol/L
• Age 30-59 years: 6.3-11.2 μmol/L (males); 4-5-7.9 μmol/L (females)
• Age >59 years: 5.8-11.9 μmol/L
VII. Thyroid hormones test
• Hyperthyroidism: Neurological manifestations can include tremors,
chorea, myopathy, and) periodic paralysis.
• Hypothyroidism: seizures, coma
• Typical adult limits for these hormones are: TSH (units): 0.45 - 4.50
uIU/mL; T4 Free/Direct (nanograms): 0.82 - 1.77 ng/dl; and T3
(nanograms): 71 - 180 ng/dl.
VIII. Electrolytes
Common electrolytes include:
1. Calcium (Normal: 2-2.6 mmol/L)
• Hypocalcemia: Convulsions, Arrhythmias, Tetany and numbness/
parasthesias in hands, feet, around mouth and lips.
• Hypercalcemia: Psychiatric overtones (Depression 30-40%, anxiety,
cognitive dysfunction, insomnia, coma)
2. Magnesium (Normal: 1.5-2 mEq/L)
• Hypomagnesemia: increased irritability of the nervous system with
156 Neurological Disorders - A Handbook for Family Physicians

tremors, athetosis, jerking, nystagmus and an extensor plantar reex. In

addition, there may be confusion, disorientation, hallucinations, depres-
sion, epileptic ts, hypertension, tachycardia and tetany.
3. Potassium (Normal: 3.5-5 mmol/L)
• Hypokalemia: muscle weakness, myalgia, tremor, and muscle cramps
(owing to disturbed function of skeletal muscle). With more severe
hypokalemia, accid paralysis and hyporeexia may result.
• Hyperkalemia: muscle weakness
4. Sodium (Normal: 135-145 mmol/L)
• Hyponatremia: headache, nausea, vomiting, confusion, seizures, brain
stem compression and respiratory arrest
• Hypernatremia: neuromuscular excitability, and edema. With more
severe elevations of the sodium level, seizures and coma may occur.
5 Chloride (Normal: 95-105 mmol/L)
• Levels decrease in metabolic acidosis which shows neurological symp-
toms like lethargy, stupor, coma, seizures.
IX. Blood sugar
• Hypoglycaemia manifestations - headache, cognitive disturbance,
hemiplegia, coma, and seizures.
• Diffuse peripheral neuropathy primarily affects the limbs, damaging the
nerves of the feet and hands. Autonomic neuropathy is the other form of
diffuse neuropathy and it affects the heart and other internal organs.
• Focal or localized diabetic neuropathy affects specic nerves, most
commonly in the torso, leg, or head.
Normal ranges:
• Fasting plasma glucose: 70-99 mg/dL
• Postprandial plasma glucose at 2 hours: Less than 140 mg/dL
• Random plasma glucose: Less than 140 mg/dL
X. Lipid prole
Hyperlipidaemia is a major risk factor of stroke. Therefore, it is very important
to check the lipid prole and do preventive measures.
Neurological Disorders - A Handbook for Family Physicians 157

High LDL and Total cholesterol, low HDL signicantly increase the chances of
stroke.
Normal ranges:
• Triglycerides: 50-150 mg/dL
• Total cholesterol: 3-5.5 mmol/L
• High-density lipoprotein (HDL): 40-80 mg/dL
• Low-density lipoprotein (LDL): 85-125 mg/dL
XI. Liver function tests
• Hepatic encephalopathy manifestations - forgetfulness, confusion, irrita-
bility, altered level of consciousness, and coma
• These tests include serum liver transaminases (AST or SGOT and ALT or
SGPT), albumin and bilirubin (direct and indirect), ammonia.
Normal ranges
• Alanine aminotransferase (ALT): 5-30 U/L
• Aspartate aminotransferase (AST): 5-30 U/L
• Total bilirubin: 2-20 μmol/L
• Albumin: 35-50 g/L
• Ammonia: 15-50 μmol/L
XII. Uremia
• Normal Blood urea: 5 to 20 mg/dl
Increased levels of blood urea cause: Central nervous system - Diurnal somno-
lence, Night insomnia, Memory and concentration disorders, Asthenia, Head-
ache, Confusion, Fatigue, Seizures, Coma, Encephalopathy Peripheral nervous
system - Polyneuritis, Restless legs, Cramps, Peripheral neuropathy, Oxidative
stress.
XIII. Genetic testing
• Congenital myopathies - muscular dystrophies
The PCR method rapidly screens for deletions of the dystrophin gene at exons 3-
30 and at exons 44-55. PCR can be used to detect more than 98% of existing
deletions, and it can be performed within 24 hours.
158 Neurological Disorders - A Handbook for Family Physicians

• Spinal muscular atrophy

Homozygous SMN1 gene deletion is highly specic and sensitive for the
diagnosis of SMA. In patients with suspected disease and no gene deletion,
SMN1copy testing with sequencing of coding regions of SMN1 copy is sug-
gested.
• Epileptic seizures
Mutations in one of several genes can cause or increase susceptibility to juvenile
myoclonic epilepsy. The genes commonly studied are the GABRA1 gene and
the EFHC1 gene.
Potassium channel subunit gene mutation (KCNQ2, KCNQ3) is found in benign
familial neonatal seizures; while, mutations of LGI1 gene is found in autosomal
dominant epilepsy with auditory features.
Patients with the syndrome of epilepsy with myoclonic-atonic seizures show
GLUT1 deciency. The gene tested for the cause of deciency is SLC2A1.
• Huntington's disease
Huntington disease (HD) is an adult-onset, autosomal dominant inherited
disorder. Genetic testing may not be necessary in a patient with a typical clinical
picture and a family history of HD. However, in the absence of a family history
of HD, patients should undergo genetic testing to exclude or conrm HD. In
normal individuals, CAG - tri-nucleotide repeat occurs between 11 and 29 times.
In people with Huntington's disease, the repeat occurs over and over again,
from 40 times to more than 80. Genetic testing, thus detects CAG repeat number
for each allele.
• Hereditary ataxias
Various genes responsible for ataxia have been identied in spinocerebellar
ataxia types 1, 2, 3, 5, 6, 7, 8, 10, 12, 13, 14, 17, 28; dentatorubropallidoluysian
atrophy (DRPLA); ataxia-telangiectasia (A-T); Friedreich's ataxia (FRDA);
ataxia with oculomotor apraxia types 1 and 2; Marinesco-Sjogren Syndrome;
ataxia with Vitamin E deciency; fragile X associated tremor/ataxia syndrome;
mitochondrial recessive ataxia syndrome; autosomal recessive spastic ataxia of
Charlevoix-Saguenay (ARSACS); and episodic ataxia types 1 and 2.
• Amyotrophic lateral sclerosis
Various specic gene mutations have been described in familial ALS. Mutation
in the copper/zinc superoxide dismutase 1 (SOD1) gene, also known as ALS1 is
the most common nding in genetic testing. Other genes most commonly
involved in familial ALS are C9orf72, FUS (ALS6) and TARDBP (ALS10).
Neurological Disorders - A Handbook for Family Physicians 159

20

Cerebrospinal Fluid
Cerebrospinal uid (CSF) is a vital uid found in the brain and spinal cord. CSF
is examined to diagnose a variety of neurological disorders. CSF is collected by a
method called lumbar puncture.
Procedure
Lumbar puncture is carried out under sterile conditions by inserting a needle
into the subarachnoid space, usually between the third and fourth lumbar
vertebrae. CSF is extracted through the needle, and tested for cell count, and
physical, chemical and microbiological characteristics.
Risks
Risks associated with lumbar puncture include:
• bleeding from the puncture site into the spinal uid (traumatic tap)
• discomfort during and after the procedure
• allergic reaction to the anaesthetic
• infection at the puncture site
• headache after the test
• adhesive arachnoiditis
• trauma to the spinal cord or spinal nerve roots resulting in weakness or
loss of sensation, or even paraplegia
Indications
CSF testing is done in the presence of following signs and symptoms:
160 Neurological Disorders - A Handbook for Family Physicians

• severe, unremitting headache

• stiff neck
• hallucinations, confusion, or dementia
• seizures
• fever that persist or intensies
• fatigue, lethargy, muscle weakness
• changes in consciousness
• severe nausea
• light sensitivity
• numbness or tremor
• dizziness
• speaking difculties
• trouble walking or poor coordination
• severe mood swings
• intractable clinical depression
• In infants - when they are irritable, cry when they are held, have body
stiffness, refuse food, and have bulging fontanelles
Contraindications
Lumbar puncture should not be performed in the following situations:
• Idiopathic increased intracranial pressure (ICP), because it can lead to
brain herniation.
• Age >65, reduced GCS, recent history of seizure- A CT or MRI scan is
indicated instead
• Bleeding disorders
• Skin infection at puncture site
• Sepsis
• Hypertension with bradycardia and deteriorating consciousness
• Cardiorespiratory compromise
Neurological Disorders - A Handbook for Family Physicians 161

• Skeletal deformities of the spine (scoliosis or kyphosis)

Common ndings
Physical Characteristics
v Pressure of the CSF can be measured when starting CSF collection.

§ Normal: 90-180 mm H2O

§ Increased CSF pressure may indicate tumour, infection, hydrocephalus,
or bleeding
§ Decreased pressure may be due to dehydration, shock, or leakage of CSF
through an abnormal opening.
v Colour of the uid - normally it is clear and colourless.
• Yellow, orange, or pink CSF may indicate the breakdown of blood
cells due to bleeding into the CSF or the presence of bilirubin.
• Green CSF may indicate presence of bilirubin or infection.
v Turbidity - Cloudy or turbid CSF may indicate the presence of white or red
blood cells, microorganisms, or an increase in protein levels.
v Viscosity - Normal CSF will have the same consistency as water. Thicker
consistency of CSF may indicate certain types of cancers or meningitis.
Chemical Tests
• CSF glucose -Normal: 50-80 mg/dL (or greater than two-thirds of
blood glucose). Glucose levels may decrease in the presence of
bacteria or inammatory cells (WBCs) or tumour cells.
• CSF protein - only a small amount is normally present in CSF. Nor-
mal: 15-60 mg/dL. Decreases in CSF protein are not generally con-
sidered signicant. Increases in protein are most commonly seen
with:
–Meningitis and brain abscess
–Brain or spinal cord tumors
–Multiple Sclerosis
–Guillain-Barré Syndrome
–Syphilis
162 Neurological Disorders - A Handbook for Family Physicians

Additional CSF testing includes:

v CSF protein electrophoresis - specic types of proteins are detected. For e.g.
Oligoclonal bands may be seen with multiple sclerosis and Lyme disease.
Normal: 0 or 1 band present normally
• CSF IgG - increased in some conditions, such as multiple sclerosis,
herpes encephalitis, connective tissue diseases.
• Myelin basic protein - seen in myelin breakdown, such as with
multiple sclerosis.
§ • CSF lactic acid - often used to distinguish between viral and bacterial
meningitis. The level will usually be increased with bacterial and
fungal meningitis while it will remain normal or only slightly elevated
with viral meningitis. Normal: 10-25 mg/dL
§ • CSF lactate dehydrogenase (LDH) - used to differentiate between
bacterial and viral meningitis; the level is usually increased with
bacterial meningitis and not with viral meningitis; may also be elevated
with leukemia or stroke. Normal: <2.0-7.2 U/mL
• CSF glutamine - may be increased with liver disease, hepatic
encephalopathy or Reye syndrome. Normal: 6-15 mg/dL
• CSF C-reactive protein (CRP) - elevated with inammation. It is
markedly increased with bacterial meningitis.
• Tumor markers - Carcinoembryonic antigen (CEA), alpha-
fetoprotein (AFP), and hCG may be increased in metastatic cancers.
Infectious Disease Tests
These tests may be performed to look for microorganisms if meningitis or
encephalitis is suspected.
• CSF gram stain for direct observation of bacteria and fungi present in CSF
under a microscope
• CSF culture and sensitivity is used to detect any microorganisms which
will grow in the culture and to select antimicrobial therapy for the affected
person and prophylaxis. Some amoebae, single cell parasites, may also be
detected with a culture.
Additional CSF testing includes:
• Detection of viruses - detection of viral genetic material (DNA, RNA) by
polymerase chain reaction (PCR) testing; for example, herpes virus and
Neurological Disorders - A Handbook for Family Physicians 163

enteroviruses. The presence of viral antibodies and their increase over time
indicates a recent infection by that virus.
• CSF Cryptococcal antigen - to detect a fungal infection caused by the yeast
Cryptococcus neoformans.
• Other CSF antigen and antibody tests - may be done depending on which
organism(s) are suspected.
Other CSF tests for infectious diseases that are less commonly done include:
• CSF AFB smear and culture may be positive with tuberculosis and with
other mycobacteria
• CSF syphilis testing (VDRL) positive with neurosyphilis.
Microscopic tests
• CSF total cell counts
–Red blood cell (RBC) count -Normally no red blood cells are present in the
CSF. The presence of red blood cells may indicate bleeding into the CSF or
may indicate a "traumatic tap" - blood that leaked into the CSF sample
during collection.
–White blood cell (WBC) count- Normally less than 5 cells are present in
the adult. A signicant increase in white blood cells in the CSF is seen with
infection or inammation of the central nervous system.
• CSF WBC differential
Small numbers of lymphocytes, monocytes are normal in a sample of CSF. There
may be:
–an increase in neutrophils with a bacterial infection
–an increase in lymphocytes with a viral or fungal infection, immune
disorders (multiple sclerosis)
–sometimes an increase in eosinophils with a parasitic infection
• CSF cytology
A cytocentrifuged sample is treated with a special stain and examined under a
microscope for tumour cells.
–abnormal cells may be present with cancerous tumors
164 Neurological Disorders - A Handbook for Family Physicians

CSF analysis
Neurological Disorders - A Handbook for Family Physicians 165

Section C

Neurological Diseases and their

Comprehensive Management
166 Neurological Disorders - A Handbook for Family Physicians
Neurological Disorders - A Handbook for Family Physicians 167

21

Brain Stroke
Stroke is a focal neurological decit which occurs due to disruption of blood
supply. The blood vessels are either blocked by a clot (ischemia) or they are
ruptured leading to a hemorrhage. This further affects the oxygen supply to the
brain causing brain damage.
Risk Factors:
A– Age and Anxiety and Atrial brillation
B – Body built (obesity)
C – Cigarette Smoking and Cardiac disease
D – Diabetes/ Diet
E – Exercise lack
F – Family History
G – Gout
H – Hypertension and hypercholesterolemia and homocystinemia
antiphospholipid antibodies, metabolic syndrome (obesity, hypertension and
hyperlipidemia) are also risk factors for stroke.
Types
There are three main types of strokes namely ischemic stroke, hemorrhagic
stroke and TIA (transient ischemic attack).
TIA (transient ischemic attack)
The sudden onset of a focal and transient (<24 hours) neurological decit due to
brain ischemia. This type of stroke is called a mini stroke. It is usually caused due
168 Neurological Disorders - A Handbook for Family Physicians

to a temporary clot. However, it should be taken seriously as there are chances of

it leading to ischemic stroke.
Warning Signs
• Numbness or weakness that starts suddenly, either on the left or right side
of the body (face, arms, or legs are often affected)
• Confusion, difculty comprehending language, or trouble talking that
begins without warning
• Sudden vision problems (in one eye or both)
• Severe, piercing headache, with no clear cause, that starts suddenly
• Difculty walking because of sudden loss of balance or dizziness
• In a TIA, symptoms generally last only about one minute, according to the
American Stroke Association (ASA). Some can last up to ve minutes.
• Blood pressure more than 180/110
• Any neurodecit, headache with projectile vomiting.
Ischemic stroke :
This type of stroke occurs due to formation of a clot in the blood vessel obstruct-
ing the blood supply to the brain. 87% of all strokes are ischemic type. There are
two sub-types of ischemic stroke. Embolic stroke in which, the blood clot forms
in any part of the body and eventually reaches the brain. Thrombotic stroke is
caused due to a clot formed in an artery which supplies blood to the brain called
thrombosis. Thrombosis either results due to large vessel thrombosis or small
vessel disease also called lacunar infarction.
Hemorrhagic stroke:
This type of stroke occurs when a weak blood vessel ruptures resulting in bleed-
ing. Hemorrhagic stroke is further divided into two types. Intracerebral hemor-
rhage, wherein a blood vessel in the brain bursts and spills into the surrounding
brain tissue, damaging brain cells. Subarachnoid hemorrhage, wherein the
artery which is on or near the surface of the brain bursts and spills into the space
between the surface of the brain and the skull. This bleeding is often signaled by
a sudden, severe headache.
Causes of stroke:
Ischemic strokes are caused due to clots in the blood supplying arteries. These
clots are formed in the already narrowed arteries due to atherosclerosis. Life-
style risk factors for atherosclerosis include high cholesterol, smoking, heavy
Neurological Disorders - A Handbook for Family Physicians 169

drinking, high blood pressure, diabetes, etc.

Hemorrhagic stroke is often caused due to conditions like high blood pressure,
trauma, vascular malformations, overtreatment with anticoagulants and
aneurysms and arteriovenous malformations (AVMs).
Examination
The F.A.S.T. test is often an easy way to examine and diagnose stroke
Using the F.A.S.T. test involves asking these simple questions:
Face : Check the patients face. Has their mouth drooped?
Arms: Can the patient lift both arms?
Speech: Is the patient’s speech slurred? Do they understand what the doctor
speaks?
Time: Is critical. When was the patient normal? When did the symptoms start?
Basic examination of all patients includes a neurological and cardiovascular
exam which includes vital signs and carotid auscultation. Check blood sugar by
a nger prick test. The doctor should identify current medications, especially
anticoagulants, and recent illnesses, surgery, or trauma. The patients should be
immediately referred to the specialized hospital.
Differential Diagnosis
Differential Diagnosis for suspected stroke can include: hypoglycemia,
hyperglycemia, hypercalcemia, seizure, migraine, brain tumor, peripheral
vertigo, syncope, subdural hematoma, acute confusional state (delirium),
vasculitis, drug side effect, transient global amnesia, encephalitis, functional
disorder and paroxysmal symptoms of other neurological disorders including
MS, upper cord lesions, radiculopathies and acute peripheral neuropathies.
Investigation
• CT Scan of brain
• MRI Brain
• Blood test (CBC, Electrolytes, blood sugar, lipid prole, creatinine)
• EEG in some cases where you suspect seizures
170 Neurological Disorders - A Handbook for Family Physicians

Fig. 21.1: CT Scan of brain

Fig. 20.1: MRI Scan of brain

Management
Acute ischemic stroke:
The only FDA approved treatment for ischemic strokes is tissue plasminogen
activator which is given through IV to the patient. tPA dissolves the clot and
improves blood ow to the brain. However, it should be administered within 3 -
4 hours to improve the chances of recovery. A signicant number of stroke
victims don't get to the hospital in time for tPA treatment; this is why it's so
important to identify a stroke immediately. Refer to Section F for more details
regarding tPA use.
The goal for the acute management of patients with stroke is to stabilize the
patient and to complete initial evaluation and assessment, including imaging
and laboratory studies, within 60 minutes of patient arrival. Critical decisions
focus on the need for intubation, blood pressure control, and determination of
risk/benet for thrombolytic intervention.
Acute antiplatelet therapy (for secondary stroke prevention; patient assessed
individually).
After intracranial hemorrhage exclusion - for patients not given tPA an immedi-
ate one time dose of 160mg ASA is recommended.
Neurological Disorders - A Handbook for Family Physicians 171

For patients who have been given tPA withhold antiplatelet or anticoagulant
therapy for rst 24hrs, after which, ASA (50-325mg) should be given daily.
Initial Management:
• Temperature (treat >38°C, as fever may contribute to further brain injury
or indicate complication such as pneumonia)
• Initial neurological vital signs (Q4H)
• O2 saturation
• Blood sugar (treat hypo and hyperglycemia)
• BP (treat >220 systolic or >120 diastolic cautiously in rst 48hrs; aim for
reduction by 10-15% unless otherwise indicated by medical conditions)
• Heart rhythm (to assess for atrial brillation)
• Swallowing screen (if fails keep NPO until full swallowing assessment)
172 Neurological Disorders - A Handbook for Family Physicians

Standard haematological and biochemical tests such as a full blood count,

erythrocyte sedimentation rate, blood glucose, renal biochemistry and choles-
terol level should be performed on patients with a stroke or TIA as a minimum.
Thrombolytic therapy with rt-PA (alteplase 0.9 mg/kg up to maximum 90 mg)
administered within four and a half hours of stroke onset according to protocols
stated in the product licence signicantly reduces death and disability at 90
days.
Patients admitted with stroke within four and a half hours of denite onset of
symptoms, who are considered suitable, should be treated with 0.9 mg/kg (up
to maximum 90 mg) intravenous rt-PA.
Streptokinase should not be used for treatment of patients in the acute phase of
stroke.
Recently Tenecteplase (Tenectase) has got approval in India by DGCA in acute
stroke of < 3 hrs duration. Its dose is 0.25 mg/kg, given as bolus.
Aspirin 300 mg daily should be commenced within 48 hours of ischaemic stroke
and continued for at least 14 days. In patients with dysphagia aspirin (300 mg)
should be administered rectally or by enteral tube.
Aspirin should be avoided within 24 hours of IV or IA thrombolytic therapy.
Anticoagulants - Low molecular weight heparin (LMWH)
Dosage: 40 mg of enoxaparin subcutaneously daily or 5,000 U unfractionated
heparin subcutaneously every 12 hours.
Indications:
a) If early anticoagulation after ischemic stroke is indicated but UFH is
contraindicated because of large brain infarctions, hemorrhagic
infarctions, or pronounced microangiopathic changes in the brain, LMWH
(in a body-weight-adapted dose) could be used since it carries lower
bleeding risk.
b) Conditions with potential high risk of early cardiogenic reembolization,
such as atrial brillation with proven intracardial thrombus on
echocardiography, articial valves, left atrial or ventricular thrombi, or
myocardial infarction during the last 4 weeks
c) Symptomatic dissection of the arteries supplying the brain (after exclusion
of subarachnoid hemorrhage on CT scan)
Neurological Disorders - A Handbook for Family Physicians 173

d) Symptomatic extracranial or intracranial arteriosclerotic stenosis with

crescendo TIAs or early progressive stroke
e) Basilar artery occlusion before or after intra-arterial pharmacological or
mechanical thrombolysis.
f) Known hypercoagulable states (eg, protein C and S deciencies, activated
protein C [APC] resistance, antithrombin deciency, relevant titer of
antiphospholipid antibodies)
g) Cerebral venous sinus thrombosis
Contraindications:
Patients with acute ischemic stroke treated with IV recombinant tPA should not
be treated with anticoagulants for at least 24 hours post thrombolysis.
The use of LMWHs should be avoided in patients with known allergies to
LMWHs, heparin, sultes or benzyl alcohol, in patients with active major
bleeding, or patients with a history of heparin-induced thrombocytopenia.
Advantages: Compared with UFH, LMW heparins display improved
bioavailability and a more predictable dose response. LMWHs have fewer
serious side effects, such as heparin-induced thrombocytopenia, heparin-
induced osteopenia and severe bleeding.
Anti-Platelets and Anti-Coagulants:
They are effective at reducing the risk of another Ischaemic stroke in the future.
These are long term treatments. They are contraindicated after a Haemorrhagic
Stroke.
The anti-platelet medications used are:
Aspirin
Dosage - 75-325 mg daily.
Side effects: bleeding, low platelet, peptic ulcers
Clopidogrel
Dosage- Prophylaxis of Thromboembolic Events: Recommended Dose: 75 mg
once daily.
Side effects: gastrointestinal hemorrhage, neutropenia, palpitation, syncope,
asthenia, neuralgia, paresthesia and vertigo.
174 Neurological Disorders - A Handbook for Family Physicians

Warfarin
Warfarin is the most commonly prescribed anticoagulant. Warfarin is an antico-
agulant used to reduce the risk of death, recurrent MI, and thromboembolic
events such as stroke or systemic embolization after MI. Monitoring of INR
(International Normalised Ratio) is necessary. The anticoagulant effect of
warfarin should be kept at an international normalised ratio (INR) of about 2.5
(desirable range, 2.0-3.0).
Indications: Warfarin is recommended for Ischaemic stroke with atrial brilla-
tion and those who are at high risk of recurrent ischemic stroke.
Contraindications:
Absolute Contraindications to Warfarin
a) Current active bleeding or bleeding disorders
b) Platelet count <50,000
c) Blood pressure consistently >160/90
d) Noncompliance with medication or monitoring
Dosage: Initial: 2 to 5 mg orally or intravenously once a day for 1 to 2 days, then
adjust dose according to results of the International Normalized Ratio (INR) or
prothrombin time (PT).
Maintenance: the usual maintenance dose ranges from 2 to 10 mg orally once a
day.
Side effects: bleeding, jaundice, oliguria
Dagibatran
It is a new type of anti-coagulant which acts by direct inhibition of thrombin. The
main advantage offered by dagibatran is that it does not require INR monitor-
ing. It is a tablet which is taken every day, but it more expensive that other
treatments. One of the side effects of anticoagulants is bleeding and dyspepsis.
Rivaroxaban and Apixaban are also newer anticoagulants which act by Factor X
a inhibition. Risk of intracranial bleeding is less and these agents do not need
INR monitoring.
Management of acute Haemorrhagic stroke is discussed in detail in Section D.
Management of Chronic Stroke
• Reduction of high risk factors: Reduce anxiety, and stress
Neurological Disorders - A Handbook for Family Physicians 175

Lifestyle modications- healthy diet and exercise regularly, quit smoking

Control diabetes by diet and antidiabetic medicines
Control blood pressure by diet, exercise and antihypertensive medicines
Control cholesterol levels by low fat and low carbohydrate diet, and
anticholesterol medicines
• Comprehensive neurorehabilitation:
In the chronic stage of stroke, neurorehabilitation plays a key role in recovery.
Physiotherapy, occupational therapy, speech therapy and psychological coun-
seling will help in faster and higher degree of recovery.
• Medicine:
Antiplatelet or anticoagulant therapy may be required to prevent recurrent
ischemic stroke. Aspirin, clopidogrel may be prescribed by the neurologist for
long term after ischemic stroke. Warfarin may have been started in the hospital
by a specialist if there is an underlying cause of recurrent thromboembolic
episode. In these cases, family doctor should keep a close watch on occurrence of
side effects like bleeding. They should also closely monitor INR levels. In case of
any episode of bleeding or high INR, patient should be referred to a neurologist
immediately.
In cases of haemorrhagic stroke, blood pressure monitoring is very important.
Blood pressure should be maintained around 120/80 mm Hg. Antihypertensive
drugs should be prescribed. ACE inhibitors, beta blockers, angiotensin receptor
blockers are prescribed according to the coexisting factors.
• Prevention of stroke related complications such as:
a. Deep vein thrombosis - Regular rehabilitation, maximize mobility
and in some cases DVT prophylaxis may be required
b. Spasticity or contracture - Regular rehabilitation will ensure that the
range of motion and tone of the muscles are maintained which will
prevent contracture formation. If the spasticity is hampering the
ambulation or day to day activities, small dose of antispastic medi-
cines may be tried.
c. Shoulder displacement - It may happen because of accid shoulder
girdle muscles which may lead to subluxation of shoulder joint.
Therefore, it has to be prevented by giving appropriate shoulder
braces and rehabilitation by a physical or occupational therapist.
176 Neurological Disorders - A Handbook for Family Physicians

d. Pneumonia - In bulbar weakness, aspiration is common which leads

to recurrent pneumonia. Regular speech and swallow therapy is
required. Chest physiotherapy is needed in bed ridden patients.
e. Urinary tract infection - In case of bowel bladder incontinence,
proper care and the catheter hygiene is needed.
f. Pressure ulcer - Pressure ulcers are the common complication in bed
ridden patients, which has to be taken care of by advising proper
positioning and skin hygiene. Special mattresses like foam mattress,
water or air bed which prevent pressure on pressure prone areas are
required. The patient needs to be turned every two hourly. Keep the
skin dry by powder application.
g. Depression - Psychological counseling and family support are
necessary to help the patient develop coping skills and improve his
quality of life.

SUMMARY
• Acute stroke is a medical emergency which needs immediate attention
and treatment. Identify the signs and symptoms of acute stroke by
FAST. Obtain a history regarding stroke in the past or a recent TIA.
Identify the risk factors of stroke. Conrm the diagnosis of stroke by
signs and symptoms, and exclude other stroke mimics like hypoxia,
hypoglycemia, or hypotension. On suspicion of stroke, immediately
hospitalize the patient and get a CT scan done to differentiate between
an ischemic and hemorhhagic stroke.
• Post-stroke involves care for a patient who has had a stroke recently
which includes comprehensive neurorehabilitation, prevention of
complications, and medical treatment (antiplatelet, anticoagulants for
ischemic and antihypertensive for hemorrhagic stroke and medicines
to control other risk factors).
• Stroke prevention involves measures to prevent a rst or recurrent
stroke. This includes compliance to medical management and
neurorehabilitation. Also, control of high risk factors is of utmost
importance (lifestyle changes, diet, exercise, weight control,
antidiabetic and anticholesterol medications).
Neurological Disorders - A Handbook for Family Physicians 177

Sample prescription for chronic ischemic stroke

Rx
1) Tb Aspirin 75 mg po 1-0-0
2) Tb Atorvastatin 20 mg po 0 - 0 - 1 (if the patient has high
cholesterol)
3) Tb Lisinopril 5 mg po 1 - 0 - 0 (if the patient has high
BP)
4) Tb Metformin 500 mg po 1 - 0 - 0 (if the patient has high
blood sugar)
5) Low fat, low carbohydrate, low cholesterol diet
6) Low salt diet if hypertensive
7) Rehabilitation
178 Neurological Disorders - A Handbook for Family Physicians

22

Migraine
Migraine is a complex disorder characterized by recurrent episodes of
headache, most often unilateral and in some cases associated with visual or
sensory symptoms. It is severe paroxysmal headache which is throbbing in
nature preceded by an aura.
It may be associated with nausea and vomiting. Migraine can be precipitated by
red wine, menses, hunger, insomnia, perfumes. Symptoms accompanying
migraine may be photophobia,s calp tenderness, paraesthesias, vertigo, syn-
cope, seizures, etc.
Signs and symptoms
• Throbbing or pulsatile headache, with moderate to severe pain that inten-
sies with movement or physical activity.
• Headache lasts 4-72 hours. Also the patient is sensitive to light and sound.
• Unilateral and localized pain in the frontotemporal and ocular area, but
the pain may be felt anywhere around the head or neck.
• Pain builds up over a period of 1-2 hours, progressing posteriorly and
becoming diffuse.
• Nausea and vomiting, including anorexia and food intolerance, and light-
headedness.
• Features of migraine aura may precede or accompany the headache phase
or may occur in isolation. Usually develops over 5-20 minutes and lasts
less than 60 minutes. Most commonly visual but can be sensory, motor, or
any combination of these.
Neurological Disorders - A Handbook for Family Physicians 179

• Visual symptoms may be positive or negative

Examination
• Cranial/cervical muscle tenderness
• Horner's syndrome (ie, relative miosis with 1-2 mm of ptosis on the same
side as the headache)
• Tachycardia or bradycardia
• Hypertension or hypotension
• Hemisensory or hemiparetic neurologic decits (ie, complicated
migraine)
• Pupils may be poor in light reactivity, with near dissociation from light
Diagnosis
The diagnosis can be made on patient's history. International Headache Society
diagnostic criteria are that patients must have had at least 5 headache attacks
that lasted 4-72 hours (untreated or unsuccessfully treated) and that the head-
ache must have had at least 2 of the following characteristics.
• Unilateral location
• Pulsating quality
• Moderate or severe pain intensity
• Aggravation by or causing avoidance of routine physical activity (eg,
walking or climbing stairs)
• In addition, during the headache the patient must have had at least 1 of the
following:
• Nausea and/or vomiting
• Photophobia and phonophobia
The most common positive visual phenomenon is the scintillating scotoma, an
arc or band of absent vision with a shimmering or glittering zigzag border.
Investigations
1) MRI
Neuroimaging is indicated in cases of:
• Worst severe headache
180 Neurological Disorders - A Handbook for Family Physicians

• Change in the pattern of previous migraine

• Abnormal neurologic examination
• Onset of migraine after age 50 years
• New onset of headache in an immunocompromised patient (eg, one with
cancer or HIV infection)
• Headache with fever
• Migraine and epilepsy
• New daily, persistent headache
• Escalation of headache frequency/intensity in the absence of medication
overuse headache
• Posteriorly located headaches (especially in children, but also in adults)
2) CT (Is done when MRI is not available or is contraindicated)
Management
Management of migraine involves treatment of acute attack and prevention of
recurrence.
Treatment of acute attack
Hospital admission for migraine is indicated for:
• Treatment of severe nausea, vomiting, and subsequent dehydration
• Treatment of status migrainosus
• Detoxication from overuse of combination analgesics, ergots, or opioids
Simple analgesics alone or in combination with other drugs are benecial in
cases of mild to moderately severe headaches. Acute treatment is most effective
when given within 15 minutes of pain onset.
Analgesics used in migraine include acetaminophen, NSAIDs, and narcotic
analgesics (eg, oxycodone, morphine sulfate).
(5-HT1) agonists (triptans) or opioid analgesics are used, for more severe pain,
either alone or in combination with dopamine antagonists (eg,
prochlorperazine).
Some commonly used triptans: Sumatriptan, Rizatriptan, Zolmitriptan,
Naratriptan, Almotriptan, Eletriptan, Fovatriptan
Neurological Disorders - A Handbook for Family Physicians 181

All the triptans are most effective when taken early during a migraine. They may
be repeated in 2 hours as needed, with a maximum of 2 doses daily. Triptans
should not be taken by patients with known or suspected coronary artery
disease, as they may increase risk of myocardial ischemia, infarction, or other
cardiac or cerebrovascular events. Do not administer vasoconstrictors - ergots or
triptans, to patients with known complicated migraine.
(The drugs with dosages are explained in detail in Section E and a quick refer-
ence in Section A [Chapter 1])
Antiemetics (eg, chlorperazine, promethazine) are used to treat vomiting
associated with acute migraine attacks. Intravenous prochlorperazine can be
given in patients with severe nausea and vomiting at the onset of an attack.
Adequate hydration should be maintained.
Prophylactic migraine therapy: It is indicated if -
• Frequency of migraine attacks is greater than 2 /month
• Duration of each attack is longer than 24 hours
• The headaches cause signicant disability that lasts 3 or more days
• Abortive therapy fails or is overused
• Symptomatic medications are contraindicated or ineffective
• Use of abortive medications more than twice a week
• Migraine variants such as hemiplegic migraine pose risk of permanent
neurologic injury
The goals of preventive therapy are to reduce attack frequency, severity, and/or
duration, improve responsiveness to acute attacks and reduce disability.
An immediate neurologist referral should be made in case of status
migrainosus, complicated migraine or if there is no response to previous treat-
ment.
Prevention of migraine attacks
Reduction of Migraine Triggers: Patients should avoid factors that precipitate a
migraine attack (eg, lack of sleep, fatigue, stress, certain foods, use of vasodila-
tors). Patients may need to discontinue any medications that exacerbate their
headaches. If an oral contraceptive is suspected to be a trigger, the patient
should be advised to modify, change, or discontinue.
Biofeedback, cognitive-behavioral therapy, and relaxation therapy are also
benecial for migraine headaches.
182 Neurological Disorders - A Handbook for Family Physicians

SUMMARY
Migraine is a very common form of headache. It is important to differentiate
migraine from other serious headaches. Migraine can be triggered by
various factors which should be identied. Investigations are not usually
required unless other causes are suspected or patient is not responding to
treatment. Management of migraine consists of treating the acute attack,
and patient education to reduce further attacks. In unresponsive cases or
status migrainosus or complicated migraine, neurologist referral needs to
be sought.

Sample prescription

Rx
Migraine headache
1) Tb Rizatriptan 10mg 1 tablet stat followed by Tb Naproxen 250mg 8
hourly
with Tb Pantoprazole 40 mg 1-0-1
Migraine prophylaxis
1) Tb Propranolol 40 mg (slow release) 1-0-0 x 3 months with
2) Tb Amitriptyline 10 mg 0-0-1 x 1 month or
3) Tb Flunarizine 10 mg 0-0-1 x till relief is
obtained
4) Tb Pantoprazole 40 mg 1-0-1 x 1 week
Neurological Disorders - A Handbook for Family Physicians 183

23

Spondylosis
Spondylosis is a spinal degeneration of the discs or spinal joints and is
universally present in all people above 50 years. However, in some cases it
becomes severely symptomatic and requires investigations and treatment
accordingly.
Degenerative changes in the vertebrae may occur at cervical or lumbar level
with subsequent impingement of neural elements in the canal.
There are 2 types of spondylosis: cervical and lumbar spondylosis
When to Suspect Spondylosis
Cervical
• Neck pain radiating to arms (1 or both), the pain is almost always on the
outer aspect of the arm(cardiac pain is almost always at the inner aspect of
the arm)
• Restricted neck movements-loss of neck extension & lateral exion
• Scapular pain may or may not be associated with neck pain
• Tingling & numbness of upper limb (1 or both)
• Dizziness or vertigo or tinnitus or blurring of vision - these symptoms are
exacerbated by extremes of movement or minor neck jerk in case of cervi-
cal spondylosis.
• Arm weakness with pain
Examination
• Tenderness of posterior neck region, scapular muscles & trapezius, biceps,
pectoralis major, and triceps
184 Neurological Disorders - A Handbook for Family Physicians

• Reduction in or loss of sensation of touch, prick or hypersensitiveness in

the area of distribution of cervical segments
• decreased power in upper or lower limb, poor grip, difculty in raising
arms against resistance, diiculty raising legs against resistance,foot drop.
• Brisk reexes-biceps,triceps, brachioradialis & sometimes in lower limb,
knee jerk & ankle jerk
• Babinski sign positive
• Imbalance on Romberg's test positive on eyes closed only (when eyes are
open patient has good balance)
Lumbar Spondylosis
• Gait disturbance
• low back pain, radiating pain from back to thighs
• Sciatica
• tingling & numbness of lower limb only
• weakness in lower limb only
• bladder or bowel - difculty in control or incontinence in case of lumbar
spondylosis
Examination
• Tenderness of lumbar & paraspinal muscles, sacro-iliac region,
• Straight leg raise test (SLR) -positive
• Reduced power in lower limb
• Brisk lower limb reexes, Babinski-absent,
• Sensory decit in lower limb
• Bowel bladder incontinence
• Restricted back movement ,bending, extending & lateral movements
Warning Signs
• Neck pain or low back pain with weakness in upper limb or lower limb
(neurodecit)
• Sensory loss in cervical or lumbar segment innervation
• Severe imbalance with nausea, vomiting associated with neck pain
Neurological Disorders - A Handbook for Family Physicians 185

• Severe blackout associated with neck pain

• Severe back pain with restricted movements
• Bowel bladder incontinence
IF ABOVE WARNING SIGNS ARE PRESENT DO IMMEDIATE INVESTIGA-
TION THAT IS MRI OF CERVICAL SPINE OR LUMBAR SPINE & URGENT
REFERENCE TO NEUROLOGIST OR NEUROSURGEON
• MRI of cervical / lumbar spine with whole spine screening. MRI is the
preferred & diagnostic imaging technique for spondylosis.
Findings may show either posterior osteophytes compressing the cord or
the nerve roots, disc prolapse compressing the cord and reduced canal size
(canal stenosis).
MRI will show the presence of disc pathology & severity. I t depicts cord
changes, enlargement, compression, or atrophy.
This investigation will guide to make decision about management choices,
conservative or surgical.

Fig. 22.1: X-Ray of Cervical

Fig. 22.2: X-Ray of Lumbar spondylosis spondylosis

• X ray cervical / lumbar spine

This is a basic investigation which will show loss of cervical lordosis,
osteophytes reduction in joint space or spur formation, etc.
• CT spine
CT spine to be done only if MRI is not available
186 Neurological Disorders - A Handbook for Family Physicians

• EMG/NCV
EMG and nerve study is done if above warning signs are present. It is also
done if the MRI ndings are not conclusive. The study shows the level of
nerve root compression. It will conrm the diagnosis and rule out other
differential diagnoses.
• Blood routine -Blood tests are done to rule out infection & to check kidney
& liver function, so that appropriate medication or side effect of any
analgesic medicines can be monitored.
If Creatinine levels are high, then NSAIDS are to be avoided & other pain
medications are prescribed.
Management:
A. Conservative
• Medication
• Analgesics - Acetaminophin, NSAIDS like Tb (diclofenac
50+paracetamol 500) 1-0-1,
Or Tb (ibuprofen 400mg +paracetamol 325mg) 1-0-1 Tb (naproxen
250mg +domperidone 10mg) 1-0-1,
If creatinine at higher side give Tb Tramadol 100 mg 1-0-1
If the pain is neuropathic in nature, then Amitriptyline or Pregabalin
or Gabapentin should be prescribed. (Dosages mentioned in Section
E)
• Muscle relaxants- Chlorzoxazone (250/500mg 3-4 times a day),
methocarbomol (1.5 g four times a day in divided doses)
• Sedative- Sedatives like Tb Alprazolam 0.25mg or Tb Amitriptyline
25 mg can be give in the night before bed .
• Cervical (neck) support collar
• Rehabilitation-Physiotherapy: gentle exercises, passive manipulation
techniques
• Avoidance of lifting heavy weights
• Yoga under supervision
• Traction may be considered in severe cases.
Neurological Disorders - A Handbook for Family Physicians 187

B. Surgery
If no relief with the above mentioned then surgery is considered. Also, if there
are signs of cord compression, surgery
should be considered early and neurosurgery referral should be done immedi-
ately. Options are anterior or posterior fusion of spinal vertebrae and decom-
pression only or decompression along with stabilization.
Anterior approach: This is the most preferred one now days.
Indications:
• Single level disc protrusion
• Anterior cord compression
Procedure: Is done under general anesthesia. A transverse 4 to 5 cm incision is
made in the neck. The disk is removed along with the posterior osteophytes and
the cord is decompressed. The empty space is lled either with a bone graft from
the iliac bone or a titanium cage. Some cases require additional xation with
plates and screws.

Fig 23.2: Laminectomy

Result and complications: Majority of patients report an immediate relief of

symptoms after the surgery. Complications are rare and include displacement
of the graft and neurological deterioration of power in all or some of the limbs.
Post op: Patient can start walking within one to two days of surgery (with a
collar on). Patient can resume normal work after three weeks. The collar has to
be worn for three to six months.
188 Neurological Disorders - A Handbook for Family Physicians

Posterior Approach: This involves doing a laminectomy, in which the spinal

process and lamina on either side are removed.
Indications: Done in cases of cervical canal stenosis.
In this operation the spinal cord is decompressed. Post operatively the patient
has to wear a collar for three to six months.
Results and complications: It is a safe procedure if done with correct indica-
tions. If not done properly it can cause severe neurological complications such
as weakness of all four limbs.

SUMMARY
Spondylosis is a degenerative condition of the spine, observed commonly in
the age group of 40 years and above. Most of the cases are treated
conservatively, however if the patient does not show any sign of relief with
the conservative management, surgery should be considered. Also, if any
warning signs of cord compression are suspected, patient should be
hospitalized and immediate MRI is warranted along with neurosurgery
consultation.

Sample Prescription For Spondylosis

Rx
Tb Diclofenac sodium + paracetemol 1-0-1,
Tb Pantoprazole 40 mg 1-0-1,
Tb Chlorzoxazone 250/500mg 1-0-1,
Tb Amitryptiline 25 mg 1-0--1
Neurological Disorders - A Handbook for Family Physicians 189

24

Brain Tumors
Brain tumors are broadly classied into two types.
Benign Tumors: grow slowly and are curable, once totally excised surgically.
• Meningiomas: are very vascular tumors that can grow to a very large size.

Fig 24.1 CT shows the presence of right Meningioma with shift in midline

• Acoustic Neuromas: arise from the 8th cranial nerve, in the angle between
the cerebellum and pons, so are called CP angle tumors. They are slow
growing and present with one sided hearing loss with tinnitus, along with
difculty in walking, headache, giddiness. In most of the patients the
hearing loss is permanent. Patients present with decrease hearing in one
ear along with tinnitus. At this stage the tumor is very small, can be
removed easily. If not diagnosed early, it grows very large in size. Hence
should be diagnosed early by doing a CTscan and a MRI scan.
190 Neurological Disorders - A Handbook for Family Physicians

• Pituitary tumors: arise from the pituitary gland and are slow growing.
They initially cause hormonal and then visual symptoms. In women an
early manifestation is ammenhorea or galactorhea. In men, it may present
with thickened face and jaw bones, along with visual disturbances with
restriction of the eld of vision i.e. they can see only what is straight ahead
and not on the sides (bitemporal hemianopia). Gradually they present
with headaches and other signs of raised intracranial pressure. Hence
early diagnosis is very essential as larger the tumor the more difcult it
gets to excise it completely.

Acromegalic hand

Normal hand

Tumors can be divided into primary tumors that started within the brain and
those that spread from somewhere else i.e. brain metastasis.
Malignant tumors: grow very rapidly and hence a complete cure is difcult,
since they recur after surgery and other treatments. The symptoms may include
headaches, seizures, problem with vision, vomiting, and mental changes. The
headache is classically worst in the morning and goes away with vomiting
indicating raised intracranial pressure. Other symptoms may be difculty in
walking, speaking and altered sensorium.The most common malignant brain
tumors are called gliomas or astrocytomas. They have 4 grades i.e. 1 to 4. Grades
1 and 2 are slow growing and have a relatively good prognosis. Grades 3 and 4
are fast growing and have a poor prognosis. Grade 4 astrocytomas are also
called glioblastomamultiforme, these are the most malignant tumors of the
brain. The average survival of the patients with grade 1 and 2 is 5 Years and that
of grade 3 and 4 is 10 - 12 months.
Neurological Disorders - A Handbook for Family Physicians 191

Brain Metastasis
The most common brain tumor in older people is metastasis from another
malignancy.
After the lungs and the liver the brain is the most common site for malignancy.
Malignancy can be single or multiple, can be detected early as well as late. The
symptoms are headache, severe and generalized with one sided limb weakness.
Note: Headache in any known case of malignancy should always be taken
seriously and an urgent CT scan or MRI should be requested. Single large metas-
tasis causing pressure effects on the brain need surgical excision. Small multiple
metastases are treated with radiation and chemotherapy.
Investigations: Urgent CT scan of the brain (contrast and plain) or MRI brain.
Reference: Urgent reference to a neurosurgeon.
Treatment:
All brain tumor patients should be admitted once diagnosed.
Anticonvulsants (Eptoin 100 mg iv 8 hrly), antioedema measures (mannitol 100
mg iv 8 hrly with dexamethasone 4 mg iv 6 hrly)
Surgery:
Craniotomy: open surgery with attempt to totally excise the tumor. Done for all
benign tumor as well as all large malignant tumors that are causing severe brain
compression and increase of the intracranial pressure. Done under general
anaesthesia, multiple holes are drilled in the skull using an electric drilling
system. The bone between these holes is cut and removed (measuring 6 cm to 12
cm in size).Then the dura lining the brain is cut. Surface tumors are visible at this
point and are removed. For deep tumors we have to delicately go through
normal brain to reach the tumor. The use of advanced modern operating micro-
scopes and sophisticated tumor removal devices such as CUSA (Cavitory
ultrasonic suction aspiration) has made brain tumor removal very safe and
satisfactory.
Stereotactic biopsy: with this the skull is not opened completely but with a
small hole a needle is put in the brain and a biopsy is done. To do this a frame has
to be put on the head and the patient is taken to the CT scan or the MRI Scan.
Where the coordinates are obtained as to where the tumor is. These are then set
on the frame to get accurate biopsy. It is done under local anaesthesia and only
two to three days hospitalization is required with less of complications and
patient discomfort. It is indicated and deep seated or small malignant tumors or
infected lesions such as suspected tuberculomas.
192 Neurological Disorders - A Handbook for Family Physicians

Overall the procedure is cost effective.

Endoscopic Surgery: Pituitary tumors can be removed from the nose with an
endoscope. It is a stitchless surgery which takes care of the patient comfort and
safety. Tumors within the ventricles can also be easily removed with a neuro
endoscope.
Adjuvant Therapy:
Benign brain tumors require no adjuvant therapy however malignant tumors
may require, radiation therapy and chemotherapy. Radiation therapy is given
over six weeks (5 times a week). Chemotherapy is given for grade 3 and grade 4
malignant tumors. Presently 2 regimes are commonly used PCV and
Temozolamide. PCV's to be given in an injectable form and has side effects, but
is cheaper. Temozolamide is the preferred one which is available as tablets and
has much less side effects but is expensive. In selected types of tumors
radiosurgery can be done using the gamma knife or X-knife. This is a one-time
treatment with focused radiation. The advantage is absence of any side effects
but the limitations are that it works only in selected indications, in only certain
size tumors and is very expensive.
Follow Up:
All Brain tumors patients need to be on anti convulsant medications regularly
(One year to lifelong)
Since possibilities of recurrence are high family physicians should take all
symptoms of these patients seriously.
If any doubt get a CT Scan or an MRI done and refer back to neurosurgeon.
Counseling and rehabilitation are important to the patients.

SUMMARY
• Brain tumours can be either benign or malignant.
• Most common tumours are gliomas in adults
• Second most common are meningiomas
• Common symptoms are headache, vomiting and seizures
• Diagnosed by CT scan or MRI scan
• Management is generally surgery followed by chemotherapy or
radiotherapy
Neurological Disorders - A Handbook for Family Physicians 193

25

Head Injury
A head injury is any trauma that leads to injury of the scalp, skull, or brain. These
injuries can range from a minor bump on the skull to a very serious brain injury.
The most common cause of which are vehicular accident, falls, assaults, etc.
Head injury can be classied as either closed or penetrating. In a closed head
injury, the head sustains a blunt force by striking against an object. A concussion
is a type of closed head injury that involves the brain.
In a penetrating head injury, an object breaks through the skull and enters the
brain. (This object is usually moving at a high speed like a windshield or another
part of a motor vehicle).
Symptoms
The signs of a head injury can occur immediately or develop slowly over a few
hours. Even if the skull is not fractured, the brain can bang against the inside of
the skull and be bruised. (This is called a concussion.) The head may look ne,
but complications could result from bleeding inside the skull.

Fig 24.1: Depressed fracture of the skull

194 Neurological Disorders - A Handbook for Family Physicians

When a person who just had a head injury comes to you, try to nd out what
happened. Try to take the full history from the patient or the person accompany-
ing him. In any serious head trauma, always assume the spinal cord is also
injured.
Serious head injury
The following symptoms suggest a more serious head injury that requires
emergency medical treatment:
1. Loss of consciousness, confusion, or drowsiness
2. Low breathing rate or drop in blood pressure
3. Convulsions
4. Fracture in the skull or face: Usually the break occurs at the site of impact.
Skull fractures are generally linear or depressed. Typically, if the skull is
fractured, the underlying brain has been injured. Fracture of the skull vault
may be linear or depressed.

Fig .2 Linear Fracture of the skull

• Linear Fracture of the skull:The most common sites of linear fractures
involve the temporal and parietal bones. If the auditory meatus is injured
in a temporo-pareital fracture, the patient may have hearing loss, tinnitus
or even vertigo.
• Fracture of the skull base: This is rare and if present may result in injury to
the cranial nerves.
• Open Fracture (with scalp defect): If the dura is torn the brain is often
injured as well. Moreover, if the dura has been torn the patient becomes
vulnerable to infection, particularly if pieces of hair or other debris enter, it
may give rise to a host of symptoms including the possible development of
meningitis.
Neurological Disorders - A Handbook for Family Physicians 195

5. Facial bruising, swelling at the site of the injury, or scalp wound

6. Discharge from nose, mouth, or ears (may be clear or bloody):If the
cribriform plate is damaged, itmay result in a laceration of the meninges
leading to cerebrospinal uidleak into the nose. The only symptom may be
a continually "running nose". This may eventually lead to meningitis and
therefore has to be treated in emergency.
7. Severe headache: This may occur due to intracranial haemorrhage.
8. Initial improvement followed by worsening symptoms
9. Irritability (especially in children), personality changes, or unusual behavior
10. Restlessness, clumsiness, lack of coordination
11. Slurred speech or blurred vision
12. Inability to move one or more limbs
13. Stiff neck or vomiting - signs of meningeal irritation.
14. Pupil changes: size is unequal or one of the pupils is not reacting.
15. Inability to hear, see, taste, or smell
Investigations:
CT scan should be done and should be admitted immediately or shifted to
another hospital.

Fig 24.3: CT Scan Brain

after a head injury

Fig 25.4: Axial CT showing the presence of multiple cerebral contusions

196 Neurological Disorders - A Handbook for Family Physicians

Fig 25.5: MRI-SWI showing diffused axonal injury

Treatment:
1. If you suspect a skull fracture, do not apply direct pressure to the bleeding
site, and do not remove any debris from the wound. Cover the wound with
sterile gauze dressing.
a. Linear Fracture: No Surgical treatment required, analgesics, needs 24
hours observations admission.
• Closed Fractures (No Scalp Defect)
b. Depressed Fractures: Have to be operated and surgically evaluated, anti
convulsants to be started. These patients have high chances of post injury
epilepsy.
c. Fractures of Cranial Base: Require hospitalization, to be treated with high
antibiotics as there might be the case of CSF leak and meningitis.
2. Management of CLW's: Even if the patient is referred to another hospital, it
is always advisable to suture the CLW of the scalp. If patient is not shifted
to another hospital then start with broad spectrum antibiotics and con-
tinue till suture removal. That is after 10 days.
Reference: refer the patient urgently to a neurosurgeon.
For a moderate to severe head injury, take the following steps:
• Check the person's airway, breathing, and circulation. If necessary, begin
rescue breathing and CPR.
• If the person's breathing and heart rate are normal but the person is uncon-
scious, treat as if there is a spinal injury. Stabilize the head and neck by plac-
ing your hands on both sides of the person's head, keeping the head in line
with the spine and preventing movement.
• Stop any bleeding by rmly pressing a clean cloth on the wound. If the injury
is serious, be careful not to move the person's head. If blood soaks through
the cloth, DO NOT REMOVE it. Place another cloth over the rst one.
Neurological Disorders - A Handbook for Family Physicians 197

For a mild head injury, no specic treatment may be needed. Advice to, closely
watch the patient for any concerning symptoms over the next 24 hours.
Patient's relatives should watch for -
• Vomiting
• Headache not relieved after a few hours
• Drowsiness
• Irritability
• Seizure
• Unusual or confused behaviour
• Bleeding or discharge from the ear or nose
• Weakness or numbness in arm or leg
• Altered vision
The symptoms of a serious head injury can be delayed. While the person is
sleeping, wake him or her every 2 to 3 hours and ask simple questions to check
alertness, such as "What is your name?"
Treatment: Analgesics may be used for a mild headache. Do not advice aspirin,
because it can increase the risk of bleeding.
Brain Hemorrhage
Can be classied as three types that is
• Extradural: Extradural hematomas are often secondary to a skull fracture
and tear of the meningeal arteries below the site of primary impact.
• Subdural: Subdural haemorrhagedevelops immediately at the time of
injury, or slowly thus causing symptoms few days after the original head
injury also.
• Intracerebral: They are uncommon after a head injury except in case of
gunshots or penetrating injuries.
In most cases a patient will lose consciousness for a little interval. He may seem
lucid on waking up but then as the hematoma develops begins to increasingly
complain of headache, irritability, confusion. If these haematomasare large and
are causing increase in the ICP they have to be removed surgically by
craniotomy.
Hematomas are potentially life threatening and can cause extensive brain
198 Neurological Disorders - A Handbook for Family Physicians

injury, including coma, and even death. This is due to the effects of compression
and raised ICP.Because of the compression the brain will press the
varioustentorial compartments, or even be forced down into the foramen
magnum at the base of the skull (herniation)thus compressing the brainstem,
which can lead to death.
Usually the oculomotor nerve becomes compressed resulting in pupillary
dilation, and loss of eye movement. As the brainstem gets compressed, patient
begins to experience rapid changes in conscious-awareness, becomes stupor-
ous, and may become comatose with irregular respiration. It may result
inhemiplegia or decerebrate rigidity (i.e. extension of the extremities).
Brain Injury
These are further two types contusions that occur in the outer part of the brain
and diffuse axonal injury that occur in the central part of the Brain. These require
ICU management with ventilator support for upto 48 hours, and are treated
medically with
• Mannitol 100cc IV 8 hrly
• Dexamethasone 4 mg IV 6 hrly
• Eptoin 100 mg IV 8 hrly
Brain Death
Occurs when the brain is irreversibility damaged. These patients can be
declared dead for the purpose of organ transplantation. The clinical signs of
Brain death are:
a. Deep unconsciousness
b. Fully dilated and non-reacting pupils.
c. Absent doll's eye movements
d. No motor response, to deep central pain.
e. No spontaneous respiration.

SUMMARY
Priority should be given to immediate assessment and stabilizing airway
breathing and circulation. Look out for signs and symptoms that suggest
immediate hospitalization is required. If sending the patient home, give a
list of warning signs to the care taker, so that the patient can be brought back
to the doctor immediately. See management of neurological emergencies for
acute head injury management.
Neurological Disorders - A Handbook for Family Physicians 199

26

Spine Injury
Spinal injury is a devastating event that occurs suddenly and whose
consequences range from minimal symptomatic pain to a tragic quadriplegia
(total paralysis of all four limbs). The key element in management is prevention
of secondary neurological damage occurring during transportation, so
whenever a family physician sees a patient with suspected spinal injury the rst
thing to be done is immobilize the spine which is done with cervical color and
belts for thoracic and lumbar spine.

Fig 26..1 Immobilization of Spine

Classication :
1. Region wise:
a. Cranio - ertebral junction
b. Cervical
c. Thoracic
d. Lumbar
200 Neurological Disorders - A Handbook for Family Physicians

2. Type:
a. Fracture
b. Dislocation
c. Fracture dislocation
3. Complete / Incomplete
In complete spinal cord injury the entire cross section of the spinal cord has
been injured resulting in loss of all sensory & motor function below the
level of injury
In incomplete spinal cord injury the spinal cord has been partially injured
preventing some communication between brain & spinal cord below the
level of injury. There is some preservation of either motor or sensory
function
4. Cause of injury
The spinal cord can be injured by transection, distraction, compression,
bruising, haemorrhage or ischaemia of the cord or by injury to blood
vessels supplying it. These injuries can all result in permanent cord injury
and may be complete or incomplete.
5. Concussion of the spinal cord can result in temporary loss of function for
hours to weeks
Cause of spinal cord injury
Injury results from primary & secondary insults Primary injury occurs at
the time of the traumatic insult
Secondary injury occurs over hours to days as a result of a complex inam-
matory process, vascular changes and intracellular calcium changes
leading to oedema and ischemia of the spinal cord. Irreversible damage
occurs to nerve cells leading to permanent disability
Symptoms of an acute spinal injury are-
• Flaccid paralysis below level of injury
• Loss of spinal reexes below level of injury
• Loss of sensation (pain, touch, proprioception, temperature) below level of
injury
• Loss of sweating below level of injury
Neurological Disorders - A Handbook for Family Physicians 201

• Loss of sphincter tone and bowel & bladder dysfunction

Investigations:
1. Plain X-rays - AP and Lateral views
2. MRI - best diagnostic tool for spinal injury, as it shows the exact damage to
the spinal cord nerves and help in deciding whether surgery is required
along with what type of surgery to be done.
Note that CT scan is not useful diagnostic tool, since structures cannot be visual-
ized and should be done only if MRI is not available

Fig 26.1: CT Axial, and sagittal sections showing Burst fracture

Fig 26.2: MRI T2 Fig 26.3: MRI T2 Sagittal

Sagittal section sections showing spine
showing cord contusion traumatic injury
202 Neurological Disorders - A Handbook for Family Physicians

In order to conrm the level of injury, neurological assessment is required

• Assess the sensory level
• Assess the motor function
• After 72 hours, use the ASIA guidelines -
ASIA Scale:
A = Complete : No motor or sensory function (for denitions, see note below) is
preserved in the sacral segments S4-S5
B = Incomplete : Sensory but not motor function is preserved below the neuro-
logical level and includes the sacral segments S4-S5
C = Incomplete : Motor function is preserved below the neurological level, and
more than half of key muscles below the neurological level have a muscle grade
of less than 3
D = Incomplete : Motor function is preserved below the neurological level, and
at least half of the key muscles below the neurological level have a muscle grade
of 3 or more
E = Normal : Motor and sensory function are normal.
Treatment:
1. At the site of accident / clinic of the family physician :
• Patient should be immobilized with the help of sand bags, plastic IV
bottles along the neck/head and should be fastened to the stretcher.
• Airway, breathing should be assessed and maintained. Regurgitation and
aspiration should be managed accordingly.
• Patient should be transported with no spinal movements and care should
be taken while doing so, three persons should help in shifting / lifting the
patient, they should lift the patient from the same side only.
• For family physicians having to manage in their clinics due to transporta-
tion problem 2gm of Methyl prednisolone sodium succinate (MPSS) in 200
ml of normal saline should be given over a period of 1/2 hr .
2. In the hospital :
• Resuscitation and maintaining the airway with intubation / ventilation if
required.
• Hemodynamic state is maintained.
Neurological Disorders - A Handbook for Family Physicians 203

• Methyl prednisolone sodium succinate (MPSS) -Should be started within 3

hrs. of the injury and should be continued for next 24 hrs. If started within
3-8 hrs of injury then it should be given for 48 hrs. MPSS is given as a
loading bolus dose of 30 mg/kg over ½ hr and a maintenance dose of 5.4
mg/kg/hr for the required period accordingly.
• In dislocation patients traction needs to be applied by the neurosurgeon.
• If patient has no evidence of spinal cord compression on MRI and shows
improvement on MPSS and traction then there is no need for the surgery.
However in patients with spinal cord compression or progressive neuro-
logical deterioration surgery must be considered.
• Physiotherapy - is given for rehabilitation.
3. Surgery : Basic aims of surgery are decompression of the neural elements,
reduction of misalignment and restoration of spinal stability.
• Anterior /Posterior
• Decompression / Stabilization
4. Operative procedure in spinal injury:
• Cranio - Vertebral junction :
i. Anterior surgery - Trans oral excision of odontoid
ii. Posterior surgery - Cranio cervical decompression and or stabilization.
• Cervical spine :
i. Anterior Corpectomy /Disc excision with anterior stabilization.
ii. Posterior Decompressive Laminectomy
• Thoracic spine :
i. Trans thoracic Anterior Corpectomy with screws and rods/plate xation.
ii. Posterior Decompressive Laminectomy and stabilization using pedicular
screws and rods /plate xation.
• Lumbar spine :
i. Trans abdominal Anterior Corpectomy.
ii. Posterior Decompressive Laminectomy and stabilization using
pedicular screws and rods /plate xation.
204 Neurological Disorders - A Handbook for Family Physicians

Many patients require both anterior as well as posterior surgery so it is done as a

single and a two stage procedure.
5. Recent Advances: Availability and development of stem cell therapy is
slowly revolutionizing the management of spinal cord injury. All the
surgeries listed above are focused on the musculo skeletal system and
none of them correct the neurological injury. The central nervous system
(CNS) i.e. the brain and the spinal cord is the only tissue in the body which
is incapable of degeneration, therefore any damage to CNS is irreversible.
However, with availability of the stem cells this is now no longer valid.
Despite the surgery many patients are left with neurological decits and
are given rehabilitation in form of physiotherapy. The main aim of rehabil-
itation is to get the patient back to activities of daily living and achieve
maximum possible degree of functional independence, therefore when
stem cells are implanted to damage spinal cord they help to reestablish
broken connections and thereby help in return the loss neurological
functions.
Complications to watch for
• Pressure sores
Patients who have a spinal cord injury are at high risk of damage to their
skin. The spinal cord injury causes loss of sensation of pain, pressure &
temperature. They also have lost motor control and have poor autonomic
nervous system function. Pressure mattress should be used for such
patients Air mattress should not be used for unstable spines. Change
position 2 hourly of the patient.
• Pneumonia
Regular ches physiotherapy and assisted coughing will help the patient.
• Urinary tract infections
Long term management includes clean intermittentcatheterisation; con-
dom drainage suprapubic catheter. Reduce bladder spasm by prescribing anti-
cholinergics.Watch for recurrent UTI, renal & bladder calculi by maintaining
good hydration and good hygiene of theperineal area to reduce infection.
• Constipation
Increased uid and bre in diet.
• Deep venous thrombosis
Thromboprophylaxis to be carried out so that DVT is averted.
Neurological Disorders - A Handbook for Family Physicians 205

SUMMARY
Patients with spinal cord injury usually have distressing neurologic decits
and disability. Priority should be given to immediate assessment and
stabilizing airway breathing and circulation. Patients with suspected spinal
cord injury should be given a collar and transported on a hard back board.
Watch out for hypotension, neurogenic shock and breathing in spinal cord
injury patients. Patients with spinal cord injury should receive a
comprehensive program of physical and occupational therapy as a part of
management.
206 Neurological Disorders - A Handbook for Family Physicians

27

Dementia and Alzheimer's

Disease
Denition:
Dementia is dened as an impairment in memory and atleast one other
cognitive domain that is sufciently severe to impair social and occupational
functioning.
What are the early signs of dementia?
• Forgetfulness-forgets name & context
• Language & communication problem-difculty to nd correct words
while speaking
• Personality hanges-agitated, anxious, apathetic, depressed, irritable,
suspicious
• Difculty in performing familiar tasks
• Confusion & disorientation
• Odd behavior
• Difculty in following strong lines
What is MMSE
Mini mental state examination is a sensitive reliable 30 questionnaire that is
used in clinical and research settings to measure cognitive impairment. It is also
used to estimate the severity and progression of cognitive impairment and to
follow the course of cognitive changes in an individual over time & makes it an
effective way to document an individual's response to the treatment given.
Neurological Disorders - A Handbook for Family Physicians 207

What are the types of dementia?

1) Mild Cognitive Impairment(MCI)
This is a condition which involves mild cognitive impairment, but is not
signicant to interfere with the daily activities.
Mild cognitive impairment (MCI) is an intermediate stage between the expected
cognitive decline of normal aging and the more serious decline of dementia. It
involves problems with memory, language, thinking and judgment that are
greater than normal age-related changes. More than the patient, the family and
friends will notice the memory lapses. But, it is not very evident as the patient
continues to do the daily activities routinely.
On MMSE score 25 to 28
Investigations:
MRI shows bilateral hippocampal atrophy
Management:
Conservative management:
• Treat the associated conditions that can also affect the memory. For eg.
Treat hypertension or depression or sleep disturbances if present.
• Start neuroprotective vitamins. For eg. Vit B12, folic acid, CoQ10, omega3
fatty acids
• Start cognitive rehabilitation. Refer to a psychologist for specialized
rehabilitation. Studies have shown computer use, playing games, reading
books and other intellectual activities may help preserve function and
prevent cognitive decline.
• Regular physical exercise may also help prevent or slow cognitive decline.
• Dietary advice: A diet low in fat and rich in fruits and vegetables
• Social engagement may help to preserve mental function and slow mental
decline.
2) Alzheimers Disease
Alzheimers is a condition of behavior and cognitive impairment which inter-
feres with social and occupational functioning. It is a progressive brain disease
which is irreversible in nature. This is characterized by development of amyloid
plaques and neurobrillary tangles,these plaques are seen on hippocampus(a
structure which helps to encode memory) also the plaques are seen on other
areas of cerebral cortex which helps in thinking and making decisions.
208 Neurological Disorders - A Handbook for Family Physicians

Signs and symptoms:

The most prominent feature is memory impairment for recent events,language
dysfunction, apraxia, behavioral disturbance.
MMSE- 12 TO 24

Mild Alzheimer Moderate Alzheimer Severe Alzheimer

Memory loss Loss ofimpulse control cannot recognize family

through behavior or loved ones and cannot
communicate in any way

Takinglonger accomplish Shortened attention span completely dependent on

normal, daily tasks others for care

Confusionabout Difcultyorganizing All sense of self seems to

location of familiar places thoughtsand logically vanish.

Compromised judgment, Increasing memory loss Other symptoms may

often leading to and confusion include Groaning,
decisions moaning, or grunting

Mood and personality Restlessness, agitation, Seizures, skin infections,

changes;increased anxiety anxiety,wandering difculty swallowing
especiallyin the late
afternoon or at night

Trouble handling money Problemsrecognizing Lack of bowel bladder

and paying bills friends and members control

Loss of spontaneity and Perceptual-motor pro-

sense of initiative blems: Such as trouble
getting out of a chair or
setting the table

Etiology
-family history, advancing age, vascular factors, inammatory markers, APOE 4
genotype, insulin resistance, dyslipidemia, hypertension, downs syndrome,
traumatic brain injury.
Prognosis
Patients with alzheimers can display with anxiety, agitation, depression, insom-
nia, paranoia.Patients with alzheimers requires assistance for their ADLS that is
Neurological Disorders - A Handbook for Family Physicians 209

for dressing, bathing, toileting they may also have symptoms of dyphagia and
they may require the feeding tube to be inserted also they may have difculty in
walking.

Fig. 27.1: 3D-SSP projection of controls, MCI and AD patients

Fig. 27.2 : Comparative amyloid PET, FDG-PET and

MRI in controls, AD and FTD patients
210 Neurological Disorders - A Handbook for Family Physicians

Fig 27.4: T2 Axial FLAIR showing cerebral infarct in Vascular dementia

Investigations:
i. MRI - medial temporal lobe atrophy (MTA) and parietal atrophy, bilateral
hippocampal atrophy, eventual atrophy in temporal,parietal,and frontal
cortex.
• mild atrophy: opening of sulci
• moderate atrophy: volume loss of gyri
• severe (end-stage) atrophy: 'knife blade' atrophy.
ii. PET CT brain: FDG-PET can show hypometabolism in the
temporoparietal regions and/or the posterior cingulum, or the hippocam-
pus.
• This may help differentiate AD from FTD, which shows frontal
hypometabolism on FDG-PET.
iii. CT: CT should be done only if MRI is contraindicated (for eg. Presence of
metallic implants)
Management of Alzheimers Disease
Pharmacology
1. Cholinesterase inhibitors
Tablet Donepezil to give 1 tablet of 5 mg at bedtime may increase to 10 mg
in 4 to 6 weeks for mild to moderate disease.
Neurological Disorders - A Handbook for Family Physicians 211

Tablet Galantamine extended release start 8 mg every morning with food

may increase 16 mg after 4 weeks
Tablet Rivastigmine 1.5 mg twice a day may increase to 3 mg twice a day
after 2 weeks
2. NMDA receptor antagonist
Memantine start with tablet 5mg daily at weekly intervals to maximum 20
mg/ day doses greater than 5 mg should be divided in bid.
Extended release tablet start 7 mg per day,increase at weekly intervals to
target dose of 28mg/day,for renal impairment reduce to 14mg/day
Management of the associated symptoms & non pharmacological treat-
ment given in the end of this chapter(pg number )
3. Vascular Dementia
This is also called as multi-infarct dementia,and this occurs because the
blood supply to the brain is affected typically due to a series of minor
strokes.Here the features of cognitive decline is associated with atleast one
cerebral infarct which is temporary in nature.
Investigations:
Radiological ndings may show one or more cerebral infarcts of varying sizes,or
severe diffuse white matter abnormalities
• MRI may show global atrophy, diffuse white matter lesions, lacunes and
'strategic infarcts' (infarcts in regions that are involved in cognitive func-
tion).
• PET CT: Hypometabolism in the areas of infarct
• CT: Multiple lacunar infarcts
Management of vascular dementia
a. Control blood pressure with antihypertensives like tablet amlodepin 5mg
od or tablet telmisartan 20 mg od or Tb Lisinopril 5 mg od
b. Control diabetes with antidiabetic medicines like tablet metformin,
glyboride
c. Control cholesterol levels by medications like tablet atorvastatin 40 mg at
night, tablet rosuvastatin 20mg at night.
d. Anticholinesterase medicines like Donepezil is also used as cognitive enhancer.
212 Neurological Disorders - A Handbook for Family Physicians

Management of the associated symptoms & non-pharmacological treat-

ment given in the end of this chapter.
4. Dementia with Lewy Bodies (DLB)
This is a type of dementia closely associated with parkinsons disease, this
is characetrised by presence of lewy bodies which are clumps of alpha-
synuclein & ubiquitin proteins in neurons.
Features like Impaired attention, concentration are seen, whereas
visuospatial functioning, memory and naming is preserved.
Parkinsonism,uctuations and visual hallucinations are highly suggestive
of DLB.
Behavioural disturbances worsen with typical antipsychotics. Thus drugs
like haloperiodol should not be given in this dementia.
MMSE 15 to 28
Investigations:
§ MRI may often be normal or may have hippocampal and cortical
atrophy if coexisting Alzheimers disease
§ Management of DLB
§ medications such as tablet donepezil or tablet rivastigmine or tablet
carbidopa or levodopa
Management of the associated symptoms & non pharmacological treatment
given in the end of this chapter.
5. Frontotemporal Dementia
This is a type of dementia where the frontotemporal area of brain is
affected.
It may be associated with motor neuron disease.
Prominent features are personality/behavioural change,apathy or lan
guage dysfunction.
MMSE score-30 in initial 3 years
Investigations:
§ MRI -Frontal or/and temporal cortical atrophy
§ PET CT - Hypometabolism in frontal and temporal lobes
Neurological Disorders - A Handbook for Family Physicians 213

§ Treatment of FTD
§ medications such as tablet donepezil or tablet rivastigmine or tablet
carbidopa or levodopa
§ Management of the associated symptoms & non pharmacological treatment
given in the end of this chapter(pg number )
§ Normal pressure hydrocephalus or NPH ia also and important differential
diagnosis which is described in Section A.
Management of Associated Symptoms With Dementia
Sun-downing, Aggressive Behavior
Antipsychotic drugs such as haloperidol or respiridone 0.5-1.0mg at bedtime to
be given
Depression
Amitriptyline 25 mg bd, or Nortryptyline 20-50 mg twice a day or serotonin
reuptake inhibitors like sertraline to be given.
Sleep Disturbance
Tablet zolpidem 5 mg qhs, or Tb alprazolam 0.2 mg, or Tb Temazepam 15 mg 0-
0-1
Neuroprotective Drugs (Supplements)
As Supplements are very helpful along with the medicines
Tablet CO Q or Tablet Ubiquinol also tablet vitamin c,vitamin e,multivitamin
especially B complex including B12 & folic acid.
Other alternating medicines like gingko biloba are also being used.
Non Pharmacological Management is discussed in detail in Section A

SUMMARY
The major types of dementia are Alzheimer's, vascular, FTD and DLB. The
clinical history, examination remain the mainstay of diagnosis. MRI and
PET CT scans' ndings are used to conrm the diagnosis and differentiate
between the various types of dementia. Treatment of dementia needs a
multidisciplinary approach which includes medications, rehabilitation,
neuroprotection, environmental modications and caregiver education
214 Neurological Disorders - A Handbook for Family Physicians

Sample prescription

1. COGNITIVE IMPAIRMENT
TB Donezepil 5MG 1-0-0 OR
TB Rivastigmine 1.5MG 1-0-1 OR
TB Galantamine 4MG 1-0-1
2. SLEEP DISTURBANCE
TB Temazepam 15 MG 0-0-1 OR
TB Zolpidem 5 MG 0-0-1
3. DEPRESSION
TB Nortriptyline 25 MG TDS
4. NEUROPROTECTION
Tb COQ10 300 mg bd or TB Ubiquinol 100 mg bd
TB VIT C 1-0-0,
CAP VIT E 400 MG 1-0-0
CAP Mecobalamin 0-1-0,
TB Folic Acid 1-0-0,
TB Omega- 3 Fatty Acids 1-0-0
Neurological Disorders - A Handbook for Family Physicians 215

28

Movement Disorders
Movement disorders are the disorders which affect uency, speed, quality, and
ease of movements. Abnormal uency or speed of movement is called
dyskinesia. It may involve excessive or involuntary movements known as
hyperkinesias; or slowed or absent voluntary movements known as
hypokinesia.
Common Types of Movement Disorders
– Tremors
– Parkinson's
– Tics
– Dystonia
– Chorea
– Ataxia
– Restless leg syndrome
1. Tremors
Tremors could occur at rest or are intentional (on performing activity). If they
are at rest it could be-
• Essential tremors - these are also called as benign tremors & are aggra-
vated on activity. In old patients they are called senile tremors.
• Secondary tremors - these occur due to anxiety, alcohol, hyperthyroidism ,
secondary to medications (eg-salbutamol, amytryptilin), etc
216 Neurological Disorders - A Handbook for Family Physicians

• Parkinson's tremors- these are resting pill rolling tremors reduced with
activity & sleep &may be associated with other features of Parkinson's
such as bradykinesia (slow movement) and rigidity (stiffness).
• Intentional tremors - These tremors are absent at rest & present only on
doing activity. They may be associated with other cerebellar signs.
Management of Essential Tremors
• Assure the patient that the tremors are benign
• Tremors characteristically improve with alcohol intake.
• Tab Primidon ( mysoline) 25 mg OD
• Propanalol 10-40 mg twice a day
• Neuracetam 400 mg 1 tablet tds
• B complex 1 daily
• Rehabilitation: physiotherapy and Occupational therapy
If the above treatment is not responding then give gabapentin, alprazolam or
clozapine
If medications are unable to suppress the tremors then consider referring the
patient to neurologist or neurosurgeon for further management.
2. Parkinson's Disorder
Parkinson's is a degenerative disorder of the nervous system involving degener-
ation of dopamine generating cells. In the early stages of Parkinson's disease, the
face may show little or no expression or the arms may not swing on walking. The
speech may become soft or slurred. Symptoms worsen as the condition pro-
gresses over time.
Although Parkinson's disease cannot be cured, medications may markedly
improve the symptoms.
Signs and symptoms
§ Symptoms are related to movement disorders like shaking, rigidity, dif-
culty walking.
§ Resting pill rolling tremors.
§ Bradykinesia-slow handwriting, slow shufing gait, slow daily activity,
slow speech.
Neurological Disorders - A Handbook for Family Physicians 217

§ Rigidity-lead pipe type (stiffness throughout exion,extension of the

elbow)or cogwheel type (intermittent)
§ Associated
§ Gait-no arm,swing,mass turning,freezing episode, slow shufing gait,short
steps
§ Mask faces-decreased expression on the face
§ Leaning posture
§ Blapharospasm or decreased blinking
§ Dementia
Investigations
Blood tests may be done to check for abnormal thyroid hormone levels or liver
damage. An imaging test (such as a CT scan or an MRI) may be used to check for
signs of a stroke or brain tumor.
PET CT sometimes may detect low levels of dopamine in the brain, a key feature
of Parkinson's.

Fig 28.1: Dopa PET shows the decreased retention of Dopamine in

Parkinsons and PSP as compared to controls

Fig 28.2: MRI of cerebellar ataxia showing atrophy in the cerebellum

218 Neurological Disorders - A Handbook for Family Physicians

Fig 28.3: FDG-PET of cerebellar ataxia showing

hypometabolism in the cerebellum
Risk factors for Parkinson's
Age : Young adults rarely experience Parkinson's disease. It ordinarily begins in
middle or late life, and the risk increases with age. People usually develop the
disease around age 60 or older.
Sex: Men are more likely to develop Parkinson's disease than are women
Heredity: Having a close relative with Parkinson's disease increases the chances
of developing the disease.
Exposure to toxins: Ongoing exposure to herbicides and pesticides may be a risk
factor of Parkinson's.
Management
Pharmacologic treatment of Parkinson disease can be divided into symptomatic
and neuroprotective (disease modifying) therapy.
A. Symptomatic treatment
• Levodopa, coupled with carbidopa, remains the gold standard of symp-
tomatic treatment for Parkinson disease. Carbidopa allows for greater
levodopa distribution into the central nervous system. The time when
medication is providing benet for bradykinesia, rigidity, and tremor is
called "on" time, and the time when medication is not providing benet is
called "off" time.
For details regarding Levodopa and Carbidopa dosage refer to Section E.
Levodopa provides the greatest benets for motor signs and symptoms, with
only few adverse effects. However, its long-term use is associated with the
development of motor uctuations ("wearing-off") and dyskinesias.
Dopamine agonists (ropinirole, pramipexole) provide moderate symptomatic
benet and delay the development of dyskinesia compared with levodopa.
Neurological Disorders - A Handbook for Family Physicians 219

Levodopa in combination with a dopa decarboxylase inhibitor is started at a low

dose and slowly titrated to control clinical symptoms. Most patients experience
a good response on a daily levodopa dosage of 300-600 mg/day (usually
divided 3 or 4 times daily) for 3-5 years or longer.
• Anticholinergic agents are used when tremors are not adequately con-
trolled with dopaminergic medication. However, they have limited
efcacy and may cause neuropsychiatric side effects.
One of the most commonly used anticholinergic is trihexyphenidyl. The initial
dose of trihexyphenidyl should be low and gradually increased. It is recom-
mended to begin therapy with a single 1-mg dose. Dosage can be titrated by 1
mg each week or so, until a total of 4-6 mg is given daily or until satisfactory
control is achieved. Some patients may require higher doses. Benztropine
(Cogentin) is also commonly used, with an initial dose of 0.5-1 mg daily at
bedtime. Dose can be titrated at weekly intervals in increments of 0.5 mg to a
maximum of 6 mg/day.
• Amantadine is an antiviral agent that has antiparkinsonian activity.
Amantadine offers additional benet in patients experiencing waxing or
waning effects from levodopa.
Amantadine is commonly introduced at a dose of 100 mg per day and
slowly increased to an initial maintenance dose of 100 mg 2 or 3 times
daily. Potential side effects of amantadine are confusion and hallucina-
tions.
Possible strategies for advanced stage or when the response time for
levodopa is decreasing include the following:
• Adding a dopamine agonist, COMT inhibitor, or MAO-B inhibitor
• Dosing levodopa more frequently
• Increasing the levodopa dose
• Switching from immediate release to sustained release levodopa /
carbidopa / entacapone
Surgical treatment includes deep brain stimulation and neuroablative
surgeries. This may be an option for advanced stages. A neurosurgeon
referral is thus required for uncontrolled advanced cases.
Rehabilitation - A comprehensive neurorehabilitation consisting of phys-
iotherapy, occupational therapy, and psychological counseling is
required.
220 Neurological Disorders - A Handbook for Family Physicians

• Neuroprotective therapy aims to slow down or reverse the disease pro-

gression. This includes CoQ 10 and multivitamin prescription. For details
refer Section E.
3. TICS
Rapid repetitive involuntary contractions of a group of muscles are known
as tics.
They are of two types-
i. Motor tics (involving bodily movement)such as facial twitching,
grimacing, binking& shrugging the shoulders.
ii. Phonic or vocal tics (involving sounds) such as coughing, grunting,
clearing the throat &snifng
Causes
Anxiety, stress,excitement,fatigue,medications, other diseases like CP
Treatment
• Habit reversal therapy-this therapy concentrates on other movements
which compete with the tic movement.
• Exposure with response prevention-this teaches techniques to suppress
unpleasant feelings proceeding a tic.
In severe cases where day to day life is affected a new surgical treatment
option of deep brain stimulation can be discussed by a neurosurgeon.
4. Dystonia
This is a syndrome of involuntary sustained or spasmodic muscle spasm
&the movements are slow, sustained & often occur in a repetitive & pat-
terned manner but are unpredictable & uctuant. There may be abnormal
posturing & twisting. Causes-dystonia occurs due to
–damage to basal ganglia
–infection, stroke, drug interactions, CP,brain trauma.
Common types are writers cramp,cervical dystonia or torticollis,tardive
dystonia-due to medication
Treatment
• Medicine-Pacitane,levodopa,syndopa,clonazepam,lorazepam,baclofen
Neurological Disorders - A Handbook for Family Physicians 221

• Sensorytrick-Control the movement by touching or stimulating affected or

nearby body part.
• Rehabilitation-Occupational and physical therapies
Stress management
In severe cases deep brain stimulation (Refer to a neurosurgeon)
5. Chorea
Excessive, spontaneous, irregular, non repetitive, random movements of
arms or legs with unstable (dance like gait) are called chorea.
Causes
Levodopa induced Huntington's disease, Wilson's disease, and Syden-
ham's chorea-in acute rheumatic fever
Investigations
TSH & PTH, serum copper & ceruloplasmin level, serum ammonia, anti
streptococcal antibody titers.
MRI brain, PET CT brain.
Treatment
• Neuroleptics-Fluphenazine, risperidone, olanzapine, clozapine &
quetiapine Or
• Gaba ergic -gabapentin& valproate & clonazepam.
• CoQ 10
6. Ataxias
Common types of ataxia:
Cerebellar ataxia, spinocerebellar ataxia, Friedreichs ataxia, ataxia
teleangectesis, ataxia with vit E deciency.
Investigations :
Basic routine blood tests-TSH,VIT E levels,Co Q 10 levels,vit B 12 levels,
metabolic screening.
MRI brain, PET CT brain
Genetic testing
222 Neurological Disorders - A Handbook for Family Physicians

Treatment-
vit E, Co Q 10, B complex
Multivitamin (treat the specic cause)
Propanalol or primadone,clonazepam,baclofen for spasticity,amantadine,
acetazolamide for episodic ataxia.
Treat any underlying secondary cause if present.
Rehabilitation : Occupational and physical therapy
7. Restless Leg Syndrome
This is a neurological movement disorder of the limbs which is associated
with a sleep complaint. Patient has irresistible urge to move legs.
Signs and symptoms :
An urge to move the legs that occurs due to uncomfortable and unpleasant
sensations in the legs which may worsen during periods of rest or inactiv-
ity and worsens in evening & at night. This urge is partially relieved by
movement.
These symptoms are not attributed to any mental disorder.
Other features associated with RLS are sleeplessness,daytime
fatigue,involuntary repetitive jerky movements either during sleep or
while awake or at rest.
Diagnosis:
The patients of RLS should be tested for iron deciency anemia.
If any secondary cause is suspected on the basis of initial history, abnormal
neurological ndings, other laboratory tests which include CBC,
creatinine, fasting blood glucose, magnesium, TSH, vit b12, folate should
be done.
EMG, NCV should be considered if suspected for polyneuropathy or
radiculopathy
Management
a. Pharmacology
Medications for primary RLS can be given on the basis of the symptoms. In
case of secondary RLS Dopaminergic agents, benzodiazepines, opiods,
anticonvulsants are to be given accordingly.
Neurological Disorders - A Handbook for Family Physicians 223

b. Non Pharmacology
To avoid caffenine, alcohol, nicotine
Sleep hygiene measure
Medications which exacerbate RLS such as like Serotonin reuptake inhibi-
tors, dopamine antagonists should be discontinued if possible.
Physical modalities before bedtime such as hot or colds water bath.

SUMMARY
One of the common movement disorder is Parkinson's disorder. It is caused
by dysfunction of dopaminergic neurons. It is important to distinguish
between Parkinson's tremors from benign tremors as the management will
differ. Family physician plays a key role in multidisciplinary treatment of
Parkinson's. Monitor for dose response and side effects of medications. CT
or MRI may be normal in early stages of Parkinson's. Therefore, if there is
suspicion of Parkinson's , referral to a neurologist is required.
Ataxias can be very debilitating and affect the daily and social life of the
patient. They are progressive and can affect the lifespan. Rehabilitation
plays a major role and should be started at early stage.

Sample prescription for Parkinson's tremors

Rx
Tb Levodopa / Carbidopa 100 mg / 25 mg one Tb 1 - 1 - 1 (empty
stomach)
Tb Pan 40 mg 1 - 0 - 1
Tb CoQ 10 300 mg 1 - 0 - 1
Tb multivitamin 0 - 1 - 0
Rehabilitation
Neurologist referral
224 Neurological Disorders - A Handbook for Family Physicians

29

Demyelinating Disorders
Demyelinating disorders are characterized by loss or dysfunction of myelin in
the central or peripheral nervous system which occurs due to damage to the
myelin sheath of neurons. This damage impairs the conduction of signals in the
affected nerves. In turn, the reduction in conduction ability causes deciency in
sensation, movement, cognition, or other functions depending on which nerves
are involved.
The most common demyelinating disorder is multiple sclerosis.
1. CNS :
Here the demyelinating process involves the central nervous system. The
cause can be primary or secondary.
Primary
In primary demyelinating disorders, cause is unknown, but an
autoimmune mechanism is suspected, since the disorder sometimes
follows a viral infection or viral vaccination.
a. Multiple sclerosis
b. Neuromyelitis optica
c. optic neuritis
d. acute transverse myelitis
e. acute disseminated encephalomyelitis,
f. acute hemorrhagic leukoencephalitis
Neurological Disorders - A Handbook for Family Physicians 225

Secondary
Demyelination is secondary to an infectious, ischemic, metabolic, or hereditary
disorder or to a toxin (eg, alcohol, ethambutol)
a. toxins-alcohol, ethambutol
b. infections-JC virus causes progressive multifocal leukoencephalopathy
c. nutritional- Vit B12 deciency, Vit E,Vit B6, Thiamine ,osmotic
demyelination syndrome.
d. hypoxic
e. hereditary - Adrenoleukodystrophies, metabolic storage disorders.
2. Peripheral demyelination:
Here the demyelinating process occurs within the peripheral nervous system.
The most common type is Polyneuropathy.
When to suspect a demyelinating disorder
• diffuse or multifocal neurological decit
• sudden onset,particularly in young adults
• onset within weeks of an infection or vaccination
• neurodecits that wax & wane
• symptoms suggesting a specic demyelinating disorder
Signs and symptoms
Visual- Blurred vision, unilateral loss of vision, Oscillopsia, Diplopia Motor--
Trunk/limb weakness, Spasticity, Hyperreexia.
Gait disturbance & Balance problems.
Sensory- Numbness, paraesthesias, dysesthesias, trigeminal neuralgia,
hyperpathia, proprioception decits.
Cerebellar- Tremor, ataxia, incoordination.
Genitourinary- Urgency/frequency/retention of urine, Incontinence, consti-
pation, impotence, dyspareunia.
Neuropsychiatric- Impairment of memory, concentration, attention, Depres-
sion, irritability, anxiety.
226 Neurological Disorders - A Handbook for Family Physicians

Other symptoms- Prominent intractable fatigue with no other cause Here we

describe the most common demyelinating disorders.
Multiple Sclerosis
Multiple sclerosis is an autoimmune disorder that affects the central nervous
system and optic nerves by causing destruction of the myelin sheaths. This is a
life-long chronic disease diagnosed primarily in young adults. During an MS
attack, inammation occurs in areas of the white matter of the central nervous
system in random patches called plaques. This process is followed by destruc-
tion of myelin. Myelin destruction causes nerve conduction defects.
Usually a young adult will present with diplopia or other visual disturbance,
weakness in limbs, fatigue, paraesthesia or sensory loss, incoordination, gait
imbalance, bladder and bowel dysfunction. Memory problem and speech
disturbance may also be present. These symptoms may wax and wane.
Multiple sclerosis is of four types
• Benign multiple sclerosis
• Relapsing remitting multiple sclerosis
• Secondary progressive multiple sclerosis
• Primary progressive multiple sclerosis
Investigations
• MRI - MRI typically shows more than one hyperintense white matter
lesions (plaques) particularly in periventricular white matter, corpus
callosum, brainstem, cerebellum and/ or spinal cord. Ovoid lesions
perpendicular to the ventricles (Dawson's bar or ngers) may be seen. In
chronic advanced stage, global cerebral atrophy is seen.
Gadolinium enhanced T1 weighted MRI scans may show enhancing white
matter lesion which depict acute active MS lesions.
Newer FLAIR MRI and MR spectroscopy have increased the sensitivity for
detection of MS lesions.
MRI also helps in excluding any other cause of neurological complaints.
MRI is also an efcient monitoring tool to study the progression of the
disease and also useful for treatment.
• CT scan - In MS CT scan may show enhanced white matter lesion but the
appearance is nonspecic. Therefore, it is used only to rule out other
causes of neurodecit.
Neurological Disorders - A Handbook for Family Physicians 227

• Lumbar puncture - LP is not routinely done in MS. It is done only if the

MRI ndings are non diagnostic.
CSF abnormalities found in MS include a mononuclear cell pleocytosis
and an increased level of intrathecally synthesized IgG. The total CSF
protein is usually normal or slightly elevated. Oligoclonal bands are
detected in the CSF.
• Evoked Potentials- EP testing assesses function in afferent (visual,
auditory,and somatosensory) or efferent (motor) CNS pathways. VEP
may show delay in latencies, SSEP may show delayed latencies in poste-
rior column conduction of the spinal cord, the brainstem and cerebral
cortex.
BAEP may show delayed auditory pathways.
• In Neuromyelitis optica serum antibodies aquaporin 4 may be present.
Treatment
Goals of therapy
i. Minimizing the effect of acute attack
An exacerbation of MS is the appearance of the new neurologic decit or
reappearance and/or worsening of an old decit due to MS that lasts
longer than 24 hours and is not due to fever or other systemic process.
Methylprednisolone- IV 1g for 5 days followed by tapered oral
prednisolone for acute attacks.
ii. Modify the course of the disease (to prevent the relapse) Interferon is given
nowadays to modify the disease progression. Interferons are listed below
a. Interferon Beta-1b
Dose-8 MIU (250mcg) to be given subcutaneously on alternate days
Side effects-Flu like symptoms may be seen, elevated liver enzymes
can be seen. Leukopenia and psychiatric symptoms can be seen.
b. Interferon Beta-1a
Dose- 6 MIU (30 mcg) to be given intramuscularly weekly. Side
effects-Flu like symptoms can be seen
c. Glatiramer acetate
Dose- 20 mcg to be given subcutaneously daily
228 Neurological Disorders - A Handbook for Family Physicians

Side effect-mild injection site reaction may occur,transient

ushing,chest tightness,shortness of breath.
iii. Symptomatic management
a. Bladder dysfunction-to treat and prevent incontinence and urinary
retention,hyperreexic bladder(urgency,frequency,urge inconti-
nence) it is better to keep a cathether after taking advice of a urologist.
Tb Oxybutynin 5 mg thrice a day, Tb Tolterodine (long acting) 2mg
once a day
b. Spasticity
Simple exercises should be tried for example stretching,riding a
bicycle. When physical measures fail, start on tb baclofen, tizanidine,
benzodiazepines
c. Constipation-Stool softner or laxatives for example lactulose,
bisacodyl
d. Fatigue -Multivitamins ,rehabilitation,dietary advice
e. Depression or emotional lability- Amitryptiline 25 mg qhs
f. Musculoskeletal pain - NSAIDs.
g. Paraesthesia-Carbamazepine 100-200 mg once or twice a day.
iv. long term rehabilitation including visual rehabilitation is important
Transverse myelitis
Transverse myelitis is a sudden onset of acute inammation of the spinal cord.
This inammation damages nerve bers, and causes them to lose their myelin
coating, thereby leading to decreased electrical conductivity in the spinal cord.
Causes
The disease is presumed to be caused by viral infections, spinal cord injuries,
immune reactions, schistosomiasis or insufcient blood ow through spinal
cord vessels.
This condition may be associated with
Bacterial Infections - Mycoplasma pneumoniae, Lyme borreliosis, syphilis
(tabes dorsalis), tuberculosis
Neurological Disorders - A Handbook for Family Physicians 229

Viral Infections - herpes simplex, herpes zoster, cytomegalovirus, Epstein-Barr

virus, enteroviruses (poliomyelitis, Coxsackie virus, echovirus), human T-cell,
leukemia virus, human immunodeciency virus, inuenza, rabies
Post-Vaccination - Rabies, cowpox
Paraneoplastic syndromes
Vascular - thrombosis of spinal arteries, vasculitis secondary to heroin abuse,
spinal arteriovenous malformations
Signs and symptoms
Symptoms typically develop over the course of hours or days and may progress
over weeks. There is sudden onset of weakness and numbness of the limbs along
with bladder bowel incontinence or dysfunction. Patient experiences pain and
there may be associated fever. Typically, the patient suddenly falls down due to
paralysis in both lower limbs.
Sensory symptoms of transverse myelitis may include a sensation of pins and
needles traveling up from the feet. Back pain can occur at the level of the
inamed segment of the spinal cord. The degree and type of sensory loss will
depend upon the extent of the involvement of the various sensory tracts, but
there is often a sensory level. Motor weakness occurs due to involvement of the
pyramidal tracts and mainly affects the muscles that ex the legs and extend the
arms. Involvement of the autonomic nervous system is common and frequently
leads to impaired function of the bladder and bowel and can also lead to epi-
sodes of high blood pressure. Bladder paralysis often occurs and urinary reten-
tion is an early manifestation.
Examination
If all the four limbs are involved this means the upper cervical cord is involved.
And also there is risk of respiratory paralysis (segments C3, 4, 5 to the abdominal
diaphragm).
A lesion of the thoracic spinal cord (T1-12) will produce upper motor neuron
signs in the lower limbs, presenting as a spastic diplegia.
A lesion of the lower part of the spinal cord (L1-S5) often produces a combina-
tion of upper and lower motor neuron signs in the lower limbs.
Differential diagnosis
Acute spinal cord trauma, Lyme disease, acute compressive lesions of the spinal
cord such as epidural metastatic tumour and infarction of the spinal cord (eg.
due to insufciency of the anterior spinal artery).
230 Neurological Disorders - A Handbook for Family Physicians

Investigation
i. MRI Spinal cord-The T1 weighted images show decreased signal intensity
and myelomalacia in chronic stage.MRI is preferred as it is diagnostic. It
also shows the severity and extent of spinal cord involvement.
ii. If MRI is not available CT SCAN is done to rule out any compression of
spinal cord by abscess or tumor.
Management
Stabilise the patient after checking the vitals
If you suspect tranverse myelitis then neurophysician consultation is required
immediately.
1. ABC Airway breathing Circulation
Start O2, IV uids, and shift the patient to nearby hospital.
2. In hospital management
Methylprednisolone - IV 1g for 5 days followed by tapered oral
prednisolone for acute attacks or Dexamethasone is used as an acute line of
treatment
3. Plasma exchange is used for moderate or severe cases who do not improve
with IV steroids.
4. If any infective cause is found it is treated with Antibiotics and in case of
herpes zoster treatment should be with acyclovir.
In chronic patients of demyelinating diseases long term care is required.
Pulmonary care-Patient should be ventilated properly if the saturation is low,
also aspiration precaution needs to be taken care.
1. Bedsore prophylaxis needs to be taken care.
2. Urinary rehabilitation in consultation with a urologist.
3. Comprehensive neurorehabilitation should be started at the earliest.
Polyneuropathy
The demyelination of peripheral nerves leads to polyneuropathy.
Polyneuropathy
Neurological Disorders - A Handbook for Family Physicians 231

Fig.29.1: MRI Brain of Multiple sclerosis

Fig.29.2: MRI of Spine of transverse myelitis

may affect primarily motor bres or primarily sensory bres or it may be mixed
(sensory & motor).
Causes
Toxic - Alcohol, lead toxicity
Infections - Lyme disease, Diphtheria, leprosy, AIDS
Diabetes
Cancer
Medications - Colchicine, ethambutol, chloroquine, amiodarone.
Vasculitis
Signs and symptoms
One should suspect polyneuropathy when a patient has diffuse or multifocal
sensory decit, weakness without hyperreexia. If the ndings are diffuse but
had asymmetrical onset, then it may suggest multiple mononeuropathy.
The patient may have distal symmetric stocking-glove distribution of loss of
sensation.
Acute neuropathies suggest an autoimmune cause,a toxin,infection or a
postinfectious cause
232 Neurological Disorders - A Handbook for Family Physicians

Symmetric distal neuropathies suggests toxic or metabolic

Rash, skin ulcers, and Raynaud's syndrome with polyneuropathy suggest
vasculitis.
Weight loss,lymphadenopathy, with polyneuropathy suggests paraneoplastic
syndrome.
Investigations
EMG/NCV is a diagnostic tool which gives information about the sensory and
motor bres.
Blood tests- CBC, Electrolytes, Renal prole, Blood sugar, VIT B12,Folate
levels,TSH.
Coagulation studies,ProteinC & S, antithrombin III,anticardiolipin antibody
and homocystine levels if one suspects vasculitits or hypercoagulable state as a
cause of polyneuropathy.
Urine toxicology for heavy metal.
Treatment
1. For neuropathy amitryptiline 25 mg once a day or gabapentin 100 mg tds
2. Rehabilitation - Physiotherapy & Occupational therapy can minimize the
disability and pain .
3. Treat the underlying cause - Remove the toxins, correct the nutritional
deciency
4. Vitamin B12, folic acid can be given for neuroprotection.
5. Corticosteroids for acute polyneuropathy.

SUMMARY
The common demyelinating disorders include multiple sclerosis,
transverse myelitis and peripheral polyneuropathy. Multiple sclerosis is a
progressive disorder and eventually affects the whole body rendering the
patient bed ridden. Recent advances in disease modifying agents have
somewhat improved the prognosis. MRI of the brain and spine is diagnostic
and can be used as a monitoring tool. A multidisciplinary team of specialists
from the eld of medicine, surgery, rehabilitation and nursing would be
required. Family physician serves as an important link between the patient
and the members of this team.
Neurological Disorders - A Handbook for Family Physicians 233

30

Infections of CNS
Infection of the central nervous system (CNS) can be viral, bacterial, fungal, or
parasitic in origin. Infectious microorganisms most often enter the CNS by
direct penetration after trauma or by travelling in the bloodstream.
The common types of infections involving the CNS are described below
• Meningitis
• Encephalitis
• Brain abscess
• Cerebral malaria
1. MENINGITIS
The protective membranes covering the brain and the spinal cord are called
meninges. Infection of the meninges is called meningitis. The infection may
occur due to bacteria, virus, fungus or protozoa.
They are classied according to the cause which has been described below.
Causes
i. Bacterial -a) pyogenic & b) tuberculous
ii. Viral
iii. Fungal
iv. Protozoal
234 Neurological Disorders - A Handbook for Family Physicians

Bacterial meningitis
The most common bacteria that cause meningitis is S. pneumoniae and N.
meningitidis. They initially colonize the nasopharynx by attaching to
nasopharyngeal epithelial cells. Once in the bloodstream, the blood borne
bacteria can reach the intraventricular choroid plexus, directly infect choroid
plexus epithelial cells, and gain access to the CSF.
Signs & Symptoms
The classic triad of bacterial meningitis consists of the following:
• Fever
• Headache
• Neck stiffness
Other symptoms can include nausea, vomiting, photophobia, sleepiness,
confusion, irritability, delirium, and coma.
Risk Factors
Otits media, immunocompromised, trauma, exposure to drugs,recurrent
meningoencephalitis or meningitis,history of recent resection of acoustic
neuroma, recent injection into subarachnoid space.
Tuberculous Meningitis
Tuberculous meningitis (TBM) develops in 2 steps. Mycobacterium tuberculo-
sis bacilli enter the host by droplet inhalation. Localized infection escalates
within the lungs, with dissemination to the regional lymph nodes. In persons
who develop TBM, bacilli seed in to the meninges or brain parenchyma.
The second step in the development of TBM is an increase in size of a Rich focus
until it ruptures into the subarachnoid space. The location of the expanding
tubercle (ie, Rich focus) determines the type of CNS involvement
This can also occur after a primary infection in childhood or as a part of miliary
tuberculosis.
Unlike bacterial meningitis Tuberculous meningitis in adults does not develop
acutely from hematogenous spread of tuberculous bacilli to the meninges.
Rather, millet seed-size (miliary) tubercles form in the parenchyma of the brain
during hematogenous dissemination of tubercle bacilli in the course of primary
infection. These tubercles enlarge and are usually caseating. The propensity for
a caseous lesion to produce meningitis is determined by its proximity to the
Neurological Disorders - A Handbook for Family Physicians 235

subarachnoid space and the rate at which brous encapsulation develops.

Subependymal caseous foci cause meningitis via discharge of bacilli and tuber-
culous antigens into the subarachnoid space.
Signs & Symptoms
TBM may have an acute presentation. Sometimes it may present with cranial
nerve decits, or it may have a more indolent course involving headache,
meningismus, and altered mental status. The prodrome is usually nonspecic;
including headache, vomiting, photophobia, and fever also symptoms such as
lassitude, depression, papilloedema, occulomotor palsies can also be seen.
Viral meningitis
Viral meningitis is inammation of the meninges as a manifestation of central
nervous system (CNS) infection. Viral meningitis is also often referred to as
aseptic meningitis.
In uncomplicated viral meningitis, the clinical course is usually self-limited,
with complete recovery in 7-10 days. However, when the viral pathogen causes
meningoencephalitis or meningomyelitis, the course can be signicantly more
protracted.
Based only on clinical symptoms, viral meningitis cannot be differentiated from
bacterial meningitis. Both appear as headache, fever, and neck stiffness but viral
meningitis has no evidence of bacterial presence in CSF. However, viral menin-
gitis is less serious than bacterial meningitis. Therefore, CSF analysis is needed
to identify the disease. In general, there are no medications to ght the virus that
cause meningitis, so treatment is usually aimed at relieving the patient's symp-
toms by having rest and fever-reducing medication.(IV Acyclovir may be used
in few cases.)
Investigations of Meningitis
1. CSF Finding:
It is one of the most important tests which helps us in diagnosing the cause
and type of meningitis
CSF ndings-
a. Pyogenic - presence of polymorphonuclear (PMN) leukocytosis,
decreased glucose concentration, increased protein concentration,
increased opening pressure.
b. Tubercolous- increased CSF pressure, it is usually clear but if
allowed to stand may form a clot, AFB seen on staining
236 Neurological Disorders - A Handbook for Family Physicians

c. Viral-Typical prole is lymphocytic pleocytosis, a normal or slightly

elevated protein concentration, organisms are not seen on gram or
AFB stain.
d. Fungal-the CSF ndings are similar to tuberculous with culture
positive for fungal infection.

2. CT scan
The CTscan may show Watershed and lacunar infarcts and may show
cerebral oedema in patient with bacterial meningitis, also it may show
subdural effusion.
Contrast-enhanced CT scans may also help in detecting complications
such as venous thrombosis, infarction, and ventriculitis. Ventriculitis is a
complication of bacterial meningitis that is seen commonly in neonates.
Ependymal enhancement can be seen on contrast-enhanced CT scans.
In case of tuberculous meningitis the scan may show hydrocephalus or
may show tuberculoma.
3. MRI ndings
MRI helps to detect the presence and extent of inammatory changes in
the meninges as well as complications. Noncontrast MRI of patient with
uncomplicated acute bacterial meningitis may demonstrate obliterated
cisterns and the distention of the subarachnoid space with widening of the
interhemispheric ssure, cortical hyperintensities that represent edema.
Neurological Disorders - A Handbook for Family Physicians 237

In complicated cases with seizures and evolving focal signs, MRI is supe-
rior to CT in demonstrating parenchymal lesions due to
meningoencephalitis or vasculitic complications. MRI helps in diagnosing
intraventricular rupture of pyogenic abscess.
4. Blood tests
Complete blood count (CBC) with differential counts Serum electrolytes
Serum glucose (which is compared with the CSF glucose) Blood urea
nitrogen (BUN) or creatinine and liver prole Blood culture
Complications
¡ Hypotension or shock
¡ Hypoxemia
¡ Hyponatremia
¡ Cardiac arrhythmias and ischemia
¡ Stroke
¡ Exacerbation of chronic disease
Management of Bacterial Meningitis
Firstly to check the vitals & stabilize the patient, if the patient is dehydrated due
to vomiting or the BP is low start him on IV uids immediately.
If you suspect meningitis in the patient the patient has to be referred for hospital-
ization.
Antibiotics
After CSF testing start on empiric antibiotics
Ceftriaxone-1-2 g BD or 12 hrly or
Cefotaxime- 1-2 g BD or 12 hrly.
Vancomycin - Starts with 0.5-2 g/day maximum is till 500 mg 6 hrly
Gentamicin - starts with 3-5 mg/kg/day in divided doses
Meropenum - starts with 500 mg
Augmentin -1.2 gm
238 Neurological Disorders - A Handbook for Family Physicians

Management Of Tuberculous Meningitis

Standard therapy nowadays includes combination of Rifampicin, isoniazid and
pyrazinamide (rifampicin 120 mg, isoniazid 50 mg and pyrazinamide 300 mg:
<40 kg: 3 tab/day;
40-49 kg: 4 tab/day; 50-64 kg: 5 tab/day; 65 kg: 6 tab/day)
Ethambutol dosage is 15-30mg/kg.
Blood tests are to be done such as liver proling as these medicines are
hepatotoxic in nature.Other routine blood tests should also be done like Renal
function tests, CBC, Electrolytes.
Compliance to medications is necessary in these conditions.
Also see post infection chronic care at the end of this chapter.
Encephalitis
Encephalitis means infection of the brain parenchyma .The causes are similar to
meningitis.Encephalitis presents as diffuse or focal neuropsychological dys-
function.
Sign & Symptoms
Fever,confusion,behavior abnormality,altered level of consciousness,evidence
of either focal or diffuse neurological symptoms, Neck pain, stiffness,
photophobia, lethargy, accid paralysis .
Acute confusion or amnestic states.
Patients may also have hallucination,agitation,personality changes,behavior
change,focal or generalized seizures may also occur.
Investigations
1. Blood tests-Complete blood count (CBC),Serum electrolyte levels,Serum
glucose level,Blood urea nitrogen (BUN) and creatinine levels.
2. Urine electrolyte levels,Urine or serum toxicology screening Blood cul-
tures for bacterial pathogens.
3. Lumbar puncture-A lumbar puncture (LP) should be performed in all
cases of suspected viral encephalitis.
Examination of the cerebrospinal uid reveals increased amounts of protein
and white blood cells with normal glucose, though in a signicant percentage of
patients, the cerebrospinal uid may be normal.
Neurological Disorders - A Handbook for Family Physicians 239

Bleeding is also uncommon except in patients with herpes simplex type 1

encephalitis.
4. CT SCAN
CT scan without contrast reveals marked hypodensity representing
edema within the frontal and temporal lobes with sparing of the basal
ganglia and cerebellum. The ndings are typical of herpes encephalitis.
5. MRI scan
MRI offers better resolution in patients with herpes simplex encephalitis.
Characteristic MRI ndings in viral encephalitis - FLAIR sequence shows
bilateral thalamic, globus pallidus and caudate involvement, bilateral
midbrain involvement
6. EEG- electroencephalograph may show sharp waves in one or both of the
temporal lobes.
Management
To refer the patient to neurology department for hospitalization Specic
treatment to be started according to the cause
Supportive management-Stabilize the patient by checking the vitals like
blood pressure, SPO2,pulse,HGT and accordingly giving O2,IV uids,
antihypertensives and immediate shifting of the patient for hospitaliza-
tion.
IV acyclovir dose-
Adult: 10 mg/kg every 8 hr for 10 days.
Child: 3 months: 20 mg/kg every 8 hr for 10 days
Also see post infection chronic care at the end of this chapter.
Brain Abscess
Brain abscesses are uncommon, serious, life-threatening infections. Brain
abscess is Focal suppurative lesion in brain parenchyma.
Brain abscesses can originate from infection of contiguous structures (eg, otitis
media, dental infection, mastoiditis, sinusitis) secondary to hematogenous
spread from a remote site (especially in patients with cyanotic congenital heart
disease), after skull trauma or surgery
Signs & Symptoms
240 Neurological Disorders - A Handbook for Family Physicians

The clinical presentation depends upon its location.

More than an infectious process this presents as expanding intracranial lesion.It
presents with headache which is of dull, constant character either hemicranial or
generalized and is progressive in nature.Headache may be associated with
nausea and projectile vomiting .
There may be focal or generalized seizure,focal neurological decit including
hemiparesis,aphasia or visual eld defects.
Signs of raised intracranial pressure may be seen-Change in mental state and
Papilloedema.
Investigations
1. MRI
MRI scan in an abscess patient will show a mass effect with surrounding
edema.
Gadolinium-enhanced coronal T1-weighted MRI in a patient also shows
the midline shift by the abscess.
On T1 contrast-enhanced MRI the abscess may be seen as an irregular mass
with moderate peripheral enhancement.
2. CT scan
Brain abscess will appear as an ill-dened hypodensity on non-contrast CT
scan. They are frequently ring-enhanced with the addition of intravenous
contrast.
The CT scan will show the cerebral oedema and also it will show the
thickness of cerebral abscess wall.
3. Lumbar puncture-LP should not be performed in patients with known or
suspected intracranial infections,since it increases the risk of herniation.
4. Blood prole- Complete blood count, Serum electrolytes
Serum glucose, Blood urea nitrogen (BUN) and creatinine and liver prole.
Management
Treatment involves high dose parenteral antibiotics & neurosurgical drainage.
Third generation cephalosporins such as cefotaxime & ceftriaxone are being
used. Meropenum & vancomycin are also being used.
Neurological Disorders - A Handbook for Family Physicians 241

Dosages-
Ceftriaxone2gm IV BD or Cefepime 6 gm/day or Cefotaxime 12 gm/day or
caftazidime 6 gm/day
Cefotaxime- 1-2 g 4-12 hrly
Vancomycin - Starts with 0.5-2 g/day maximum is till 500 mg 6 hrly
Gentamicin - starts with 3-5 mg/kg/day in divided doses
Meropenum - starts with 500 mg
Augmentin -1.2 gms
Also see post infection chronic care at the end of this chapter.
Cerebral Malaria
Cerebral malaria refers to a life-threatening infection of the cerebrum caused by
protozoa plasmodium falciparum.
The earliest manifestation is nonspecic fever. Loss of appetite, vomiting and
cough are common. The history of symptoms preceding coma may be as brief as
one to two days.
The primary symptoms which are seen in Cerebral Malaria are:
i. Impaired consciousness with non-specic fever.
ii. Generalised convulsion and neurological sequelae and
iii. Coma, initially arousable which becomes unarousable later.
Cerebral malaria manifests as diffuse symmetric encephalopathy accompanied
by focal neurologic signs. Some passive resistance to head exion may be
detected.
Examination
In cerebral malaria the tendon reexes are variable, and the plantar reexes may
be exor or extensor; the abdominal reexes are absent. Flexor or extensor
posturing may be documented.Patients are seen to have retinal hemorrhages
with pupillary dilatation.
Funduscopic abnormalities include discrete spots of retinal opacication,
papilledema, cotton wool spots, and decolorization of a retinal vessel or seg-
ment of vessel (occasional cases).
Convulsions may be generalized and often repeated, commonly seen in children.
242 Neurological Disorders - A Handbook for Family Physicians

History and clinical ndings of convulsion, coma and altered sensorium are
important.
Investigations
1. Blood tests -These include CBC,creatinine,Liver prole, electrolyte,
bleeding time clotting time, PT, INR, BUN, also blood tests for malarial
parasite, malarial antigen, blood culture.
2. Peripheral smear: Asexual form of P. falciparum is seen in peripheral
blood smear, in thick and thin blood smear lms stained by Giemsa stain.
In some patients with prior antimalarial treatment or sequestration of
parasitized RBCs in cerebral circulation, peripheral smear may not show
any parasites. In such a situation, atleast 3 smears 6 h apart should be
examined. At least 3 smears should be negative before excluding cerebral
malaria.
3. The rapid diagnostic test (antigen detection test) and PCR may be helpful.
4. CSF examination is necessary to exclude other causes of febrile
encephalopathy. CSF is generally normal in cerebral malaria, however,
mild pleocytosis (10-50 cells/mm3) and protein rise up to 200 mg/dL may
be seen.
5. CT and MRI are usually normal or show edema and cortical or subcortical
infarcts in watershed zone in 15%-20% patients.
6. EEG shows nonspecic abnormalities, such as diffuse slowing, spike wave
discharges, and burst suppression pattern.
Management
Cerebral malaria is a serious condition. If cerebral malaria is suspected admit the
patient in a hospital immediately. Stabilize the patient and transfer the patient to
a hospital.
In hospital management
1. Antimalarial therapy
2. Fluids and nutrition
3. Treatment of seizures
4. Respiratory status
5. Anaemia
6. Coagulopathy
Neurological Disorders - A Handbook for Family Physicians 243

Following are the dosages of antimalarials-

a) IV Chloroquine - initial dose 10mg/kg over a period of not less than 8
hours, preferable by slow intravenous infusion, Subsequent infusions of
5mg/kg should be administered every 8 hours until a total dose of
25mg/kg is given.
b) Artemether- adults and children over 6 months 3.2 mg/kg as a loading
dose by Intrmuscular injection, followed by 1.6 mg/kg daily until the
patient is able to tolerate oral medications for a maximum of 7 days.
c) Artesunate- A loading dose of 2mg/kg should be followed by 1mg/kg
after 4 hours and 24 hours,thereafter a dose of 1mg/kg should be given
daily until the patient is able to tolerate oral medications for a maximum of
7 days.
d) IV quinine is also used but it is associated with lot of side effects.
Supportive & Adjunctive Therapy:
• Comatose patient should be given meticulous nursing care.
• A Nasogastric tube should be inserted to aspirate the stomach contents
• Urethral catheter to be inserted and attached to a urobag which will mea-
sure output
§ Fluid intake and output chart should be maintained.
§ Level of coma should be monitored along with temperature, respiratory
rate and depth, blood pressure and vital signs.
• Antipyretics - Paracetamol is effective in reducing fever.
• Anticonvulsants - It is crucial to control or prevent seizure, as they can
cause neural damage and are associated with a fatal outcome. A slow
Intravenous dose of 0.15mg /kg of Diazepam is effective in controlling
convulsion and it can be repeated if required.
• Reduction of Intracranial Pressure - Raised ICP can cause death by
transtentorial herniation or by compromising cerebral blood ow.
Mannitol is used to reduce cerebral edema.
• Correction of Hypoglycaemia - This can be done by using hypertonic
glucose.
• Anemia should be treated with blood transfusion.
244 Neurological Disorders - A Handbook for Family Physicians

• Acidosis - Correction of anaemia, dehydration and control of seizures

reduces acidosis.
• Thrombocytopenia needs to be monitored and corrected.
• Exchange transfusion is justied when parasitemia exceeds 10% of
circulating RBCs.
• Microcirculatory Flow - Pentoxifylline reduces red cell deformability,
blood viscosity, systemic vascular resistance and platelet aggregation
which improve microcirculatory ow.
• Desferroxamine - An iron chelator which reduces formation of reactive
oxygen by reducing amount of free iron.
Post Infection Chronic Care
• Tuberculosis- To monitor whether the patient is taking his medications
regularly especially the AKT.
• Compliance & monitoring for side effects is an important task of the
physician
• Improve the nutrition-which includes High protein diet with dietary
advice is very important. Also multivitamins should be given as it may
give extra nutrition which may be skipped from diet.
• Rehabilitation- Physical and occupational therapy to improve weakness.
• Post surgical care in case of surgery for eg- In Case of abscess, the wound
needs to be checked for pus.
In bed ridden patients skin care, DVT prophylaxis needs to be monitored to
prevent DVT, bedsores, also the ryle's tube, catheter tracheostomy care needs to
be taken care of.

SUMMARY
CNS infections are serious conditions which require hospitalization. Early
diagnosis and treatment will prevent complications. The common CNS
infections encountered are meningitis, abscess and cerebral malaria.
Tuberculous meningitis needs long term treatment. Therefore, compliance
to treatment needs to be monitored.
Neurological Disorders - A Handbook for Family Physicians 245

31

Neuromuscular Disorders
The brain controls the movements of skeletal (voluntary) muscles via
specialised nerves. The combination of the nervous system and muscles,
working together to permit movement, is known as the neuromuscular system.
There are many separate diseases that are classied as neuromuscular
disorders.
Some of the major diseases affecting the neuromuscular system are classied
into three groups:
a) Disorders affecting primarily the muscles
• Muscular dystrophies
• Inammatory myopathies
• Toxic myopathy
b) Disorders affecting primarily the nerves
• Motor neuron disease
• Spinal muscle atrophy
• Poliomyelitis
• Guillian Barre syndrome
c) Disorders affecting primarily the neuromuscular junction
• Myaesthenia gravis
Muscular Dystrophies
Muscular dystrophy is characterized by progressive muscle degeneration
246 Neurological Disorders - A Handbook for Family Physicians

causing muscle weakness. Muscle degeneration occurs due to disruption of the

cell wall of muscle cell. It is caused by a genetic abnormality that leads to faulty
production or absence of the proteins essential for the structural integrity of the
cell wall. Subnormal functioning of these walls therefore makes those more
prone to damage even with forces of day to day muscle contraction. This leads to
accelerated damage of the tissue which cannot be repaired by existing cells. As
the difference between number of damaged cells and number of cells available
for repair increases muscles grow weaker and weaker.
Various investigations are recommended for the diagnosis of muscular
dystrophy.
Diagnosis of muscular dystrophy can be conrmed using following steps:
Diagnosis
• Points to note from the history of the patient:
• History of progressive muscle weakness in the patient
• Weakness progressing in different regions of the body like UEs, LEs
and Trunk
• History of progressive functional decits
• History of consanguinity of parents
• Strong family history
Assessment and evaluation
• Manual muscle testing shows weakness of the muscles, the pattern of
weakness changes as per the type of muscular dystrophy
• Tendon jerks are usually diminished or in early stage of the disease
will be normal
• Tone of the muscles is normal however sometimes you may nd
hypotonia
• Posture and gait assessment will show compensatory mechanisms
like increased lumbar lordosis, waddling and toe walking etc.
• Easy fatigability will be observed during assessment
• Some dyspnoea may be present depending on the involvement of
cardiac and respiratory systems
Neurological Disorders - A Handbook for Family Physicians 247

Investigations
• Blood serum testing will show increased serum CPK levels
• Muscle biopsy will show histopathological changes in the muscles
and soft tissues
• Electromyography - EMG shows difference in the muscle unit
potentials of dystrophic muscles. It shows features of primary mus-
cle disease.
• Musculoskeletal MRI -It possesses diagnostic capabilities similar to
muscle biopsy and may be preferred over EMG and Biopsy due to its
non-invasive nature. It may show muscle degeneration, necrosis and
brosis.
• Genetic testing - Genetic testing is the gold standard test for conrm-
ing the type of muscular dystrophy. Patients should be encouraged
to undergo genetic testing as well as counseling.
Common types of muscular dystrophies
Duchenne Muscular Dystrophy (DMD), Becker's Muscular Dystrophy (BMD)
and Limb Girdle muscular dystrophy (LGMD). The less common forms are
FacioScapulo Humeral dystrophy (FSHD), Congenital muscular dystrophy
(CMD), Myotonic muscular dystrophy, Occulopharyngeal muscular dystro-
phy, distal muscular dystrophy, Emery Dreiufuss muscular dystrophy.
• Duchenne muscular dystrophy : This is the most common and the most
severe type of muscular dystrophy with rapid progression of muscle
weakness. This affects young boys only. It is an X- linked recessive disor-
der, which results in an absence of dystrophin. Deciency of dystrophin
leads to degeneration of the muscle bers with resultant muscle weakness.
The rst symptoms are decreased motor skills, clumsy walking, calf
pseudohypertrophy, lumbar lordosis. Hip extensions are often the rst
muscle group affected.
Gower's maneuver positive - Gower's sign is when the patient makes use
of his hands to climb up on his body while getting up from the oor.
Frequent falls while walking, running or jumping, easy fatiguability,
difculty climbing stairs, poor balance, waddling gait, toe walking, etc.
The patients gradually lose independent ambulation and are wheelchair
bound and become bedridden later, owing to the resultant spinal defor-
mity. Symptoms start by the age of 7 years and they become wheelchair
248 Neurological Disorders - A Handbook for Family Physicians

bound by the age of 10-12 years. Later on cardiorespiratory complications

develop which lead to early mortality by the age of 22 years.
• Becker muscular dystrophy: It is an X linked recessive disorder involving
genetic mutation which leads to abnormal dystrophin protein production
(not completely absent dystrophin as in DMD). The disease progresses in
the same stages as DMD. The muscle weakness, postural and structural
deviations and compensations remain identical. The functional loss is also
same as observed in DMD. However the rate of progression of the disease
is much slower. The life expectancy is much more that in DMD.
• Limb girdle muscular dystrophy: Limb Girdle muscular dystrophy
(LGMD) is one of the slow progressive muscular dystrophies, where the
muscles of the hip and shoulder region are involved earlier than other
muscles. Slowly the muscles undergo thinning causing severe weakness in
other parts of the body as well. The patient has difculty in getting up from
the oor without support, climbing up the stairs, walking, lifting arms,
overhead activities and poor balance with frequent falls.
• Facioscapulohumeral dystrophy: As the name suggests the disease affects
the muscles of arms, shoulder, neck and face. In the later stages of the
disease other muscles may also get involved and severely limit the func-
tion. The patient has asymmetric facial muscle weakness (eyelid drooping,
inability to whistle, decreased facial expression), asymmetric shoulder
muscle weakness, inability to chew and swallow, speak, difculty breath-
ing, etc.
• Myotonic muscular dystrophy: The characteristic of the disease is
Myotonia, which means delayed relaxation of the muscle after voluntary
action or prolonged contraction. Along with myotonia and muscle weak-
ness it presents with cataract, heart conduction defects, hormonal varia-
tions and mental retardation.
• Congenital muscular dystrophy: It presents with muscle weakness at birth
or during infancy. Children typically appear "oppy" due to low muscle
tone and lack of spontaneous movement. Although muscle weakness can
stabilize short term, it progresses with time. This leads to rigidity of spine,
contractures and spinal deformities. In later stage respiratory complica-
tions may arise. These affect quality of life and life span.
• Emery-Dreifuss Muscular Dystrophy: One of the characteristic features of
the disease is involvement of the cardiovascular system by the third decade
of life leading to cardiomyopathy along with generalized muscle weakness.
Neurological Disorders - A Handbook for Family Physicians 249

Management
The management of muscular dystrophy is multidisciplinary.
Medical management:
Muscular dystrophy is medically incurable at the moment. Various medicines
and newer drugs are under investigation but none have given a conclusive
nding.
Medical management aims to:
a) Completely halt or slow down the disease progression
b) Lengthen the period of independent walking
c) Symptomatic improvements
d) Functional improvements to ease activities of daily living
e) Prevent complications of contractures and deformities
f) Preserve cardio-respiratory functions
Standard medical therapy at the moment is steroid therapy
Corticosteroids and glucocorticoids are routinely used in the treatment of
muscular dystrophy. Although it is not a mainstay of treatment in India, it is
integral in the management of muscular dystrophies in western countries.
However, there are side effects of steroids which must be monitored.
Side effects of steroids: Weight gain, Behavioral changes- irritability, hyperac-
tivity, euphoria, mood lability (mood swings), depression, Excessive hair
growth,Growth failure with short stature, Cushingoid appearance- swollen
puffy face, Acne, Hypertension, Hyperglycemia/ glycosuria, Hypokalemia
(low potassium), stress ulcers, Cataracts, Osteoporosis- fractures
Rehabilitative management:
Due to the progressive and incurable nature of the disease, rehabilitation is the
crux of the management of dystrophies. Clinicians must emphasize benets of
rehabilitation.
Rehabilitative management includes various disciplines like physiotherapy,
aquatic therapy, occupational therapy, speech therapy, Diet and nutrition and
psychological intervention. All these are equally important and the requirement
may differ depending upon how advanced the disease is.
• Physiotherapy - The aim of physiotherapy treatment is to prevent second
250 Neurological Disorders - A Handbook for Family Physicians

ary musculoskeletal complications, training the muscles at a moderate

intensity to slow down the process of brosis and muscle degeneration, to
facilitate functional independence and to prevent secondary cardio-
respiratory impairment.
Stretching and exercises are the key components of physiotherapy for
muscular dystrophy. Physiotherapists will prescribe tailored exercises to
all the patients and may prescribe assistive devices like knee and ankle
braces, close contact braces to facilitate standing, walking and prevent
scoliosis.
• Aquatic therapy - The aim aquatic therapy is same as that of physiotherapy
but with more emphasis on the cardio-respiratory endurance of the
patients. Aquatic therapy refers to performing exercises in the water with a
trained therapist. Exercises are tailor made according to the abilities of the
patient.
• Occupational Therapy - Occupational therapy aims to maintain the func-
tion of the patients and provide assistive devices or alternate techniques
for activities of daily living and vocational activities.
Occupational therapists will also provide assistive devices that are key in
improving independence in daily activities.
• Speech therapy - Patients with muscular dystrophy may present with
hypertrophy of tongue and in later stages dysarthria and dysphagia due to
muscle weakness. Speech therapists will address these impairments and
prevent further complications like aspiration and recurrent respiratory
infections.
• Diet and nutrition management - Due to lack of activity and sluggishness
of bowel movements children and adults with muscular dystrophy may
develop nutritional decits and reduced intake. A proper diet and nutri-
tion advice and timely monitoring and assessments are therefore key in
their management.
• Psychological counseling - Psychological counseling is required not only
for the patients but also for the care givers. Patients develop negative
emotional and behavioral problems as the disease progresses and need to
taught and made aware of the strategies for the management of these.
Some common psychological problems are emotional sensitivity, anger
management, depression, anxiety, temper tantrums and learned helpless-
ness. Care givers should also be made aware as to how to deal with such
problems.
Neurological Disorders - A Handbook for Family Physicians 251

Surgical management :
Due to progressive muscle weakness and imbalance, children develop
contractures of the muscles, and skeletal deformities.
Surgical corrections may be required for these deformities. Surgical corrections
are mainly of three types tendon release surgeries to prevent contractures of the
muscles.
bony corrections in case of xed contracture and scoliosis prevention surgeries
and spinal xation.
Surgical intervention is decided based on the functional improvement that the
patient will gain after surgery and the severity of secondary complications that
may develop in absence of surgical management.
Genetic Counselling:
Once diagnosed the patients should be sent for genetic counseling, wherein the
nature, prognosis of the disease and possibilities and patterns of inheritance will
be discussed with the patient. They will also be given further information about
the management of the disease and prevention in subsequent generations.
Inammatory Myopathy
These are autoimmune diseases in which the skeletal muscles are damaged by
an inammatory immune mechanism.
1. Polymyositis - Polymyositis is an idiopathic inammatory myopathy that
causes symmetrical, proximal muscle weakness; elevated skeletal muscle
enzyme levels. Myalgias, arthralgias and dysphagia may also be associ-
ated. The patient has difculty kneeling, climbing or descending stairs,
raising arms, lifting objects, combing hair, holding the head up. Pelvic
girdle involvement is usually greater than upper body involvement.
Cardiac involvement may cause symptoms of pericarditis or
cardiomyopathy.
Signs and symptoms:
• Fatigue
• Anorexia
• Morning stiffness
• Fever (associated with antisynthetase antibodies such as anti-Jo-1)
• Eight loss
252 Neurological Disorders - A Handbook for Family Physicians

• On examination - muscle tenderness and nodular feel on palpation

2. Dermatomyositis - this myositis is associated with erythematous skin
changes over extensor surfaces of the joints and a facial rash. The muscle
weakness is similar to polymyositis
3. Inclusion body myositis - this type of myositis is seen after the age of 50
years and it involves the ngers, forearm exors and leg extensors.Muscle
biopsy shows inammatory inltrates,with characteristic rimmed
inclusion vacuoles & amyloid deposits.

Fig 31.1: MRI-MSK of DMD

Neurological Disorders - A Handbook for Family Physicians 253

Investigations
• Complete blood count (CBC) - May show leukocytosis or thrombocytosis;
leukocytosis is present in more than 50% of patients.
• Erythrocyte sedimentation rate or C-reactive protein level - Elevated in
50% of patients with polymyositis.
• Elevated muscle enzyme levels
• Myoglobinuria
• Autoantibodies - Antinuclear antibody assay - Positive in polymyositis;
Myositis-specic antibodies; anti-Jo-1 antibodies in polymyositis
• Positive rheumatoid factor results
• MRI scan: shows signal intensity abnormalities of muscle due to inam-
mation, edema, or scarring.
• Electromyography: It may show evidence of membrane irritability,
increased insertional activity, brillation potentials, positive sharp waves
at rest. The EMG may show a typical myopathic picture - decreased ampli-
tude and duration; increased polyphasic potentials. Chronic changes such
as evidence of denervation-reinnervation may also be seen.
• Muscle biopsy: It shows muscle ber inammation with focal endomysial
inltration by mononuclear cells, endothelial cell damage, and increased
amounts of connective tissue. Later in the course of polymyositis it may
show muscle ber degeneration, brosis, and regeneration.
Treatment
• Corticosteroids
Prednisone is the rst-line treatment of choice for polymyositis.
Dosage 1 mg/kg/day, either as a single or divided dose. This high dose is
continued for 4-8 weeks, until the creatine kinase level returns to normal.
Taper the dose by 5-10 mg on a monthly basis until the lowest effective
dose.
• Immunosuppressants
Intravenous immunoglobulin (IVIG) is used for the short-term treatment
of steroid-resistant cases of polymyositis.
• Diet
254 Neurological Disorders - A Handbook for Family Physicians

Patients with polymyositis may benet from a high-protein diet. Monitor

patients to avoid excessive weight gain due to corticosteroid use.
• Activity
Encourage patients to start an exercise program as early as possible.
During the acute stage, passive range of motion exercises and splints are
given to avoid contractures.
Once acute inammation is under control, the rehabilitation program is
started.
Toxic Myopathy
Major common causes are-
• Steroid myopathy
• Statin induced myopathy
These medicines are commonly encountered by a family physician. Any
patient who is already on steroids or statins; develops muscular weakness
which is non specic, generalized, and recent onset should raise a suspi-
cion for side effect of this medicine. Statin should be held for few weeks
and if the weakness reverses it is diagnostic. In case of steroids, one should
taper the dose in consultation with a specialist physician.
Management
If detected early and if the medications are stopped, weakness may be reversed.
Motor Neuron Disease
Motor neuron disease (MND) is a neuromuscular disease caused due to selec-
tive degeneration of the motor neurons. The degeneration is progressively
noted in the upper motor neuron (cortex) or lower motor neurons (Medulla and
anterior horn cells) or both. It is characterized by progressive degeneration of
neurons causing progressive muscle weakness. The cause is unknown. There
are various types of MND, based on region affected, rate of progression of the
disease and UMN or LMN involvement. The prognosis of each type differs
signicantly.
Neurological Disorders - A Handbook for Family Physicians 255

Types of Motor Neuron Disease

1. Amyotrophic lateral sclerosis:

ALS is the most common variant of MND. Disease manifests due to both
UMN and LMN degeneration.
Symptoms are of UMN type like progressive muscle weakness, brisk
reexes, increased tone of the muscles, cramps, and LMN type like
wasting, fasciculations, hypotonia, severe weakness in different regions of
the body. There are two types- a) limb onset where the weakness begins in
the upper limb or lower limb, b) bulbar onset where there is difculty in
speech, swallow and breathing at the onset.
The prognosis of this condition is the worst with life expectancy of up to 3 -
5 years from diagnosis. The weakness progresses all over the body and the
patient becomes bed ridden and will need ventilator support.
2. Primary lateral sclerosis:
PLS is a relatively uncommon variant of MND. It manifests mainly in the
form of UMN degeneration.
The symptoms are mainly the UMN signs in limb and bulbar region but
with lesser wasting and weakness of the limbs as compared to ALS. The
progression of the disease is slower than in ALS and the prognosis and life
expectancy is more (6-7 years).
3. Progressive bulbar palsy:
Progressive bulbar palsy is also a rare variant of MND. It is caused by
256 Neurological Disorders - A Handbook for Family Physicians

degeneration of lower motor neurons in bulbar region. It may develop into a

bulbar onset ALS.
Symptoms include dysarthria (difculty or slurring of speech) , dysphagia
(difculty or slowness of swallowing and chewing food), breathing
difculty, exertion dyspnoea and orthopnoea.
4. Progressive spinal muscular atrophy:
Progressive spinal muscular atrophy is also a rare variant of MND.
The progression is relatively slower and mainly exhibits lower motor
neuron symptoms.
Diagnosis:
Diagnosis of MND is a diagnosis of exclusion.
There are set criteria, Revised Eorld federation of neurology El-escorial criteria
for the diagnosis of Amyotrphic Lateral Sclerosis as this is the most common
type of motor neuron disease. However the other types are differentiated and
diagnosed using clinical features, physical assessment and electromyography.

Investigations
• Electromyography and nerve conduction studies (EMG/NCV) is the gold
standard in the diagnosis of MND which shows anterior horn cell involvement.
• MRI brain and spine screening: It helps to exclude any focal spinal or cerebral
disease. MRI report will be normal in MND.
• PET CT scan: It is done in patients where paraneoplastic syndrome is suspected. It
rules out presence of malignancies anywhere in the body. PET CT scan will be
normal in MND.
Neurological Disorders - A Handbook for Family Physicians 257

• Lumbar puncture: It is done to rule out any other causes of muscular

weakness. CSF study will be normal in MND.
• Blood tests: Routine and heavy metal screening. Blood tests will be normal
in MND.
• Genetic testing: SOD1 gene abnormality may be detected.
Management
As the disease manifests in multiple body systems over a long period of time and
affects quality of life of the patient, multidisciplinary management is the best
approach.
Pharmacological management
• Riluzole is the only approved medicine that has shown signicant effect on
the survival duration. Riluzole inhibits the glutamate release and modu-
lates some of the post synaptic effects of glutamate. Dosage: 50 mg bd. Side
effects: nausea, vomiting, vertigo, liver dysfunction, renal dysfunction,
anemia. Monitoring: Monitor hemoglobin, LFT and serum creatinine
levels.
• Neuroprotective drugs: Ubiquinol/CoQ10, vitamin B12, Thiamine,
Vitamins C, E, omega3 fatty acids. For details refer to Section E.
• Antispastic drugs and muscle relaxants may be required for severe muscle
spasticity and muscle cramps. Refer to Section E for more details.
Non Pharmacological management
Exercise: Regular moderate intensity physical exercise has several benets in
MND. It prevents rapid damage to the muscles and functional deterioration.
Exercise also has an anti-inammatory effect. Exercise also helps prolong
respiratory insufciency, dysphagia and dysarthria.
Multidisciplinary rehabilitation for MND consists of following disciplines:
• Neurorehabilitation: Physiotherapy, Occupational Therapy, Speech
therapy, Psychological counseling, Aquatic therapy.
• Diet and nutrition: High protein diet is recommended. In patients where
swallowing is affected, dietitian and swallow therapist should be con-
sulted to modify the diet consistency, regularity, food items, etc. Some
patients may require nutritional supplements.
• In late stages PEG (Percutaneous endoscopic gastrotomy) may be
required. PEG is a surgical technique that has shown signicant effect of
258 Neurological Disorders - A Handbook for Family Physicians

the survival in MND by preventing dysphagia related complications.

Refer to gastroenterologist for PEG.
• Respiratory management: Articial ventilator support in the later stages
of the disease which has signicantly prolonged the survival of MND
patients. Chest physician should be involved in the care of MND patient to
assess requirement for non invasive ventilation for eg. Bipap machine, etc.
Spinal Muscle Atrophy
The spinal muscular atrophies (SMAs) comprise a group of autosomal-recessive
disorders which involve progressive weakness of the lower motor neurons.
Different types of spinal muscular atrophies have been described based on age
of onset. The most common types are acute infantile (SMA type I, or Werdnig-
Hoffman disease, present before 6 months of age), chronic infantile (SMA type
II, present between the ages of 6 and 18 months), chronic juvenile (SMA type III
or Kugelberg-Welander disease, appears after age 18 months), and adult onset
(SMA type IV, Onset is typically in the mid 30s) forms.
The genetic defects associated with SMA types I-III are localized on chromo-
some 5q11.
Patients with spinal muscular atrophy present with weakness and muscle
wasting in the limbs, respiratory, and bulbar or brainstem muscles. LMN signs
are present i.e. decreased tone, diminished reexes, atrophy. Patients with
spinal muscular atrophy often have above-average intelligence quotients (IQs)
and demonstrate high degrees of intelligence.
Investigations:
• EMG and NCV: They are diagnostic and show anterior horn cells involve-
ment.
• MRI brain and spine are normal.
• CSF study is normal.
• Serum CPK level may be normal or slightly elevated.
• Blood tests: Routine and heavy metal screening is normal.
• Genetic testing reveals SMN1 gene abnormality.
Management:
Supportive treatment should be aimed at improving the patients' quality of life
and minimizing disability, particularly in patients with slow progression. Refer
to MND management as given above.
Neurological Disorders - A Handbook for Family Physicians 259

Poliomyelitis
A viral infection which, at its worst destroys the anterior horn cells in the spinal
cord and brain stem motor nuclei, causing paralysis. The disease can be mild,
severely disabling, or fatal. A feature of polio is that normal sensation accompa-
nies the muscle weakness. For details refer to Section A.
Guillain Barre Syndrome
Here the complaints begin with respiratory or gastric illness and progressive
muscle weakness from hours to days.It involves limbs & may be associated with
tingling,numbness in the arms.
On examination
Complaints start with progressive weakness of 2 or more limbs with neuropa-
thy & areexia
Types
Ascending-Weakness starts with lower limb & then progresses upwards to the
trunk, upper limb, respiratory muscles.
Descending-Weakness will start in the cranial nerves or upper limb or bulbar
muscles & then progress downwards involving the respiratory muscles.
Investigations
• CSF-High protein without pleocytosis. CSF may be normal in early hours
• GBS antibody (Gm1)
• Blood tests like electrolytes,LFT,CPK,ESR
• EMG/NCV
• PFT
Management
If you suspect GBS immediately hospitalize the patient. ICU management will
be required in case of respiratory failure.
Immunoglobulins, corticosteroids, plasmapheresis will be needed.
Chronic care and Rehabilitation.
Myasthenia Gravis
It is a condition which is characterized by progressive weakness of facial, bulbar,
neck, and ocular muscles. This occurs due to production of antibodies to the
260 Neurological Disorders - A Handbook for Family Physicians

acetylcholine receptors on the post synaptic junction membrane, which block

conduction across the neuromuscular junction. Myasthenia symptoms can be
improved by inhibiting the acetylcholinesterase which normally removes the
acetylcholine.
Here the patient may initially have ptosis, diplopia, weakness,fatigue which
becomes worse by repeated activity and which is improved by rest.Also there
may be difculty in chewing,swallowing,breathing; combing hair, raising the
arms above shoulder level. . Limb weakness is more in proximal muscles than
distal muscles. There are no sensory nerve involvement, and the disorder is
purely motor.
Bulbar muscle weakness is also common, along with weakness of head exten-
sion and exion. Aspiration may occur if the cough is ineffective. Patients
progress from mild to more severe disease over weeks to months. Weakness
tends to spread from the ocular to facial to bulbar muscles and then to truncal
and limb muscles. Exposure to bright sunlight, surgery, immunization, emo-
tional stress, menstruation, and physical factors might trigger or worsen exacer-
bations. The symptoms can be quickly precipitated by various factors which is
called 'myaesthenic crisis' and is a medical emergency.
Investigations:
Laboratory testing includes Anti-AChR radioimmunoassay-85% positive in
generalized MG, 50% in ocular MG.
Anti musk antibody, anti striated muscle antibody Single -ber
electromyography-blocking & jitter with normal ber. For ocular or cranial MG-
exclude intracranial lesions by CT OR MRI. Other tests for RA Factor & ANA &
TSH to rule out other diseases. D/D
Lambert syndrome (LEMS): Muscle weakness is similar to myasthenia but is
associated with tumors. It can be differentiated from myasthenia by EMG
ndings.
Treatment
Pharmacology:
• Anticholinesterase inhibitors - Pyridostigmine is used for long-term
maintenance.
• Immunosuppressants: Corticosteroids,
• Immunomodulators: Immunoglobulin, azathioprine, cyclosporine
• Plasmapheresis
Neurological Disorders - A Handbook for Family Physicians 261

Non pharmacology:
• Chronic care is required for long term.
• Rehabilitation is very important.
• Diet advice is required if any difculty in chewing.
• Yoga helps in improving breathing capacity.
262 Neurological Disorders - A Handbook for Family Physicians

32

Neurodevelopmental
Disorders
Any perinatal event (before, during, after the time of birth) could cause damage
to the brain. This could lead to mental as well as physical disabilities. These
group of disorders are known as neurodevelopmental disorders. These are
sometimes noticed immediately after birth or later in early childhood as the
parents notice that the child is not reaching the expected/appropriate
developmental milestones.
Neurodevelopmental disorders are a broad spectrum or an umbrella, which
covers multiple conditions. Some common disorders are:
• Cerebral palsy
• Mental Retardation/Intellectual disability
• Autism Spectrum disorders
• Others; would include, genetic disorders, such as Downs syndrome,
learning disability, ADHD, Slow learners
Symptoms
These disorders have a diverse clinical picture. Signs and symptoms vary
depending on the type and severity of brain damage. However, a simple guide-
line or yard stick could be comparison with a normal/neurotypical child of the
same age.
Development scales used by paediatricians give a perfect understanding to
know that the milestone is delayed. However parents may give history of com-
parison with previous child or another normal child.
Neurological Disorders - A Handbook for Family Physicians 263

• Motor milestones such as neck holding, sitting, standing and walking,

either delayed or not achieved. child is either oppy or has very
tight(spastic) muscles or has uncontrolled movements (dystonia
/choreoathetoid movements)
• Speech delay: child is not able to speak or can speak few words as com-
pared to age. This could also be accompanied with swallowing, chewing
difculties (oromotor dysfunction)
• Not responding to being called or not tracking toys or light (hearing and
vision defect, as comorbidities)
• Cognitive impairment: has difculty in understanding or learning new
activities
Causes
Causes can be divided broadly into when the event has occurred:
• Prenatal(before birth):
Abnormal development of the brain is seen if the mother has infections
(TORCH) which gets transmitted intrauterine, nutritional deciency in
mother, consumption of medicines/teratogens or hypoxia just before
birth(cord around neck, meconium aspiration, prolonged labour) or
genetic mutations.
• Natal(at birth):
Prematurity, low birth weight, delayed cry (indicating hypoxia or lack of
oxygen),multiple births(twins,triplets,etc), septicemia in mother or pla-
cental tissue/umbilical cord sepsis, birth injury ( such as which may
happen during forceps/ vacuum assisted delivery)
• Postnatal (after birth):
Birth asphyxia (lack of oxygen due to respiratory or cardiac disorders,
pathological jaundice (kernicterus), seizures/epilepsy or morphological
abnormalities, such as hydrocephalus (if uncorrected)
• Early childhood:
Trauma to the head and brain, infections such as meningitis, encephalitis,
seizures/ epilepsy
• No obvious cause; sometimes, no cause can be identied (developmental
delay needing investigation like endocrine, metabolic or genetic cause)
264 Neurological Disorders - A Handbook for Family Physicians

Neurodevelopmental disorders are a broad spectrum or an umbrella,which

covers multiple conditions. Broadly, they can be divided as :
• Cerebral palsy
• Intellectual disability
• Autism Spectrum disorders
• Others; this would include, genetic disorders, such as Downs syndrome,
learning disability, ADHD, Slow learners
Cerebral Palsy:
Cerebral palsy is a disorder causing inability to movements, incoordination,
excessive tightness, due to damage to the brain during the developmental
stage(around the time of birth and early childhood).This damage may also lead
to impairments in understanding , cognition, learning, intellect, behavior,
communication, speech ,hearing and vision.
Cerebral palsy is the leading cause of childhood disabilities in India.3 in every
100 births are diagnosed with cerebral palsy.
Types of cerebral palsy:
a. Based upon extent of impaired/affected function;
§ Quadriplegic (all the four limbs affected)
§ Diplegic (both legs affected)
§ Hemiplegic (an arm and leg on one side affected)
§ Monoplegic (only anyone limb affected)
§ Triplegic (both legs and one arm affected)
b. Based on area of the brain damaged:
§ Spastic (increased stiffness in all muscles) - the cerebral cortex, espe-
cially, the motor cortex is affected
§ Dyskinetic (abnormal movements of the body) - the basal ganglia is
affected (part of the brain controlling the voluntary movements)
§ Dystonic (uctuating muscle tension) or athetoid (uncontrollable jerky
movements)
§ Ataxic (clumsy movements and poor balance)- cerebellar affection
Neurological Disorders - A Handbook for Family Physicians 265

§ Hypotonic (Floppy muscles) - this is the opposite of spastic. Muscles

are loose here and may mimic muscle weakness. Injury to cerebellum
may manifest as this ( hypothyroidism is also a common reason for
hypotonia)
§ Here child achieves most milestones, but very late and Needs support
for most activities.
c. Mixed:
Two or more forms may coexist.
Investigations:
• MRI Brain +DTI (diffusion tensor imaging) : this imaging will in most
cases clarify where the problem, the extent and also give an indication
whether there is a hypoxic injury.
Typically, a MRI Brain of a child with CP would show periventricular
leukomalacia (PVL), with a variation in degree and severity.
• EEG: In a child with co morbid seizures/ts, it is important to do an EEG.
Even otherwise, a routine EEG may give an indication of potential
epileptogenic focus, which has not manifested yet. Caution about future
possibility of seizure can be exerted.
• PET CT Scan: PET imaging helps in detecting metabolic abnormalities,
changes in blood ow and in receptor expression at much earlier stage,
before the development of structural and morphological abnormalities.
Treatment:
Conventional treatment consists of-
Surgical :
• Correction of anomalies, such as hydrocephalus using surgical means (VP
shunts, etc..)
• Correction of deformities (tenotomies) or use of Botox to reduce spasticity
• Correction of squint surgically
• Cochlear implants for hearing decit (if indicated)/hearing aids
Rehabilitation: which includes physiotherapy, occupational therapy, speech
therapy, visual rehabilitation program etc..
Medications: Medications are generally used to treat comorbid conditions such
as seizures, dystonia, hyperactivity/aggression.
266 Neurological Disorders - A Handbook for Family Physicians

Antiepileptics drugs
(AEDS generally used in children are sodium valproate (20mg/kg/day in two
divided doses), as starting dose , can go upto 40mg/kg/day
leveracitam (20mg/kg/day in two divided doses) (levipil, Keppra available
brands) max upto 60mg/kg/day
In uncontrolled seizures, these are combined with Frisium, clobazam,etc..
Tablet frisium can be started at 0.2 to 0.3mg/kg/day or 5mg at night then 5mg
twice a day if required.
Clobazam is an ad on drug for uncontrolled seizures0.5 mg/kg/day once/
twice a day Other antiepileptics, used are phenobarbitone ( gardenal ) 3-5
mg/kg/day once or twice a day and Carbemezepine (tegritol) 8-10 mg/kg/day
recommended for absent seizures maintenance at 30mg/kg/day
In emergency situations midazolam spray starting with 1 puff in each nostril,
dose being 0.2mg/kg can be used, max dose is 10mg,
Pacitane/levodopa-carbidopa is now used for control of dystonia/involuntary
movements in gradually increasing doses, titrated to need.
Pacitane is 2mg tablet can be started at ¼ to ½ twice a day and gradually
increased to control dystonia , maximum of 15mg/day
Levodopa carbidopa dose 1/0.25 mg/kg thrice or twice a day for dystonia or
involuntary movements.
Baclofen also helps to relieve spasticity and dystonia , 5mg and 10 mg tablets and
syrup available
Can be started at 2.5mg twice or thrice a day and increased gradually
Dose is 10-40 mg/kg/day
Hyperactivity:
Resperidone 0.5mg start with half tablet at night to twice a day if more daytime
sypmtoms.
Target to 3mg/day. Max dose is 6mg/day
Methylphenidate is a stimulant and may have side effects like anorexia, sleep
disturbance, headache and irritability.
Dosage ranges from 5mg to 20mg twice or thrice daily.
Neurological Disorders - A Handbook for Family Physicians 267

Atomoxetine is a non stimulant

Dosage is 0.5mg/kg/day and increased to 1.2-1.4mg/kg/day after 4 days may
have side effects like nausea, dyspepsia, decreased appetite and weight loss.
Intellectual Disability
ID is a developmental disability, where intellectual functioning of an individual
is below average (as measured by standard intelligence tests). This results in
signicant limitations in the persons daily living skills (adaptive functioning).
Such skills include, the ability to communicate, home living skills, self care,
social skills, functional academic skills/scholastic performance and job related
skills. In intellectual disability, the IQ(Intelligence quotient) is blow 70-
75%.These children in addition to intellectual dysfunction, may also have
comorbid seizures/convuslsions and aggressive behaviours.
Apart from the common causes of neurodevelopmental disorders mentioned
earlier, MR/ID can also be caused by hereditary factors, such as genetic defect
(Fragile X syndrome), single gene defects like Phenylketonuria(PKU).
Diagnosis:
Psychological assessment: To properly scale the IQ is mandatory. This helps in
understanding the level of dysfunction and plan out rehabilitative measures
accordingly.
Investigations:
The investigations for MR remain broadly similar to that in Cerebral Palsy,
i.e.MRI Brain and EEG.
MRI Brain may not reveal any abnormality. Hence, PET CT Scan Brain is recom-
mended which reveals the areas of the brain which are functioning less and
thereby contributing to the intellectual disability.
Genetic tests (Fragile X syndrome) ,tests for metabolic defects and inborn error
of metabolism are optional.
Treatment:
Conventional treatment:
The treatment for MR/ID ,so far, conventionally, has been only rehabilitative.
These children need to be trained in special schools, to be able to use their abili-
ties to the optimum to achieve some functional independence.
268 Neurological Disorders - A Handbook for Family Physicians

Medications:
Medications are used to treat comorbid conditions, such as seizures/ epilepsy,
hyperactivity and aggression .
Autism spectrum disorders
Autism spectrum disorders is a neurodevelopmental disorder characterized by
impairments or delays in social interaction,communication and language,as
well as , by repitive routines and behaviours.
They are called spectrum disorders because of wide range and severity of
symptoms. The prevalence of autism has increased radically over the few
decades.Currently, the gures are 1 in 68 children in USA and 1 in 250 in India.
This expotential rise, could partly be attributed to increasing awareness and
diagnosis of this disorder. Traditionally, till very recently, these children were
misdiagnosed as Mental retardation, which in turn lead to lack of intervention
and bad prognostication.
Like other neurodevelopmental disorders, the cause of autism is
multifactorial,hence no specic diagnostic blood investigations/biomarkers are
available.
The diagnosis, is mostly clinical,based on analysis of behavioral symptoms.
Apart from the causes common to other neurodevelopmental disorders,
increasing association with some genetic causes is being seen, such as Fragile X
syndrome, maternal duplication 0f 15q1-q13,and deletions and duplications of
16p11.
Clinical symptoms:
Clinical symptoms , typically, consist of the triad of symptoms: Lack of commu-
nication, social interaction and abstract thinking.
These lead to other secondary characteristics, like, hyperactivity, no eye contact,
low attention span, no verbalization or repetition of speech(echolalia),inability
to concentrate and learn.
socioemotional abnormalities emerge as a result of extent of damage to the
medial temporal lobe structures.
Diagnosis and investigations
Diagnosis of autism is traditionally done by a developmental pediatrician with
inputs from psychologists. Clinical assessment scales, based on an array of
questions asked to the parents, forms the basis of diagnosis.
Neurological Disorders - A Handbook for Family Physicians 269

These scales are DSM V, CARS, ISAA.

Investigations
• EEG: Routinely only EEG is carried out by neurologists, to rule out poten-
tial epileptiform activity, which is associated with a subset of autistic
children.
• MRI Brain: grossly,MRI Brain is expected to be normal.However, it is
important to be carried out, in order to rule out correctable causes,such as
brain tumor or know the possible underlying cause, such as coexisting
neurobromatosis, corpus callosum agenesis,hypoxia related injury,etc.
• PET CT Scan: PET CT scan detects areas of brain which are low or high
functioning than normal. It can be used when MRI ndings are normal but
patient is showing neurological decits related to the brain.
Treatment:
Conventional therapies:
Rehabilitation : Early intensive behavioral intervention -designed to facilitate
development and learning, promoting socialization, self awareness, reducing
maladaptive behaviors and educating and supporting families.
Occupational therapy, sensory integration techniques, speech therapy help in
overall development of the child.
Nutritional interventions restrict allergy associated dietary components, as well
as to supplement minerals or vitamins which may be lacking. Autistic children
tend to have problems with digestion, including food sensitivity - particularly to
casein and gluten in dairy and wheat products.
Medical interventions usually treat specic activities associated with autism.
Risperidone and Aripiprazole are the two drugs approved by US FDA for
treatment of hyperactivity in autism
Serotonin reuptake inhibitors (SSRI's) such as uoxetine, uvoxamine,
sertraline, and clomipramine, are used for treatment of anxiety and depression.
They may also have the added benet of increasing social interaction and
inhibiting repetitive behavior.
Antipsychotic drugs such as thioridazine, uphenazine, chlorpromazine, and
haloperidol have been showed to decrease behavioral abnormalities in autism.
Atypical antipsychotics such as risperidone, olanzapine and ziprasidone have
also demonstrated benecial effect at ameliorating behavioral problems.
270 Neurological Disorders - A Handbook for Family Physicians

Autism associated seizures are mainly treated by administration of

anticonvulsants such as carbamazepine, lamotrigine, topiramate, and valproic
acid.
Risperidone is a antipsychotic medication and very helpful in controlling
inappropriate behavior or hyperactivity . A 0.5mg tablet is available and syp
risdone of 1ml/1mg. It can be started at a dose of ½ tab of 0.5mg or 0.5ml at night
time or sos.
Aripiprazole can be initiated for irritability in paediatric patients with autism at
dose of 2mg / day, increasing weekly upto 5mg/day.Go upto 10-15 mg/day to
control symptoms.
Attention decient/hyperactivity is treated by agents such as methylphenidate
or atomoxetine.
Other treatments include psychiatric care, neurodevelopmental therapies, and
treatment for co-occurring medical conditions.

SUMMARY
Neurodevelopmental disorders cause delayed development of the child in
motor, sensory, speech, intellectual, and social domains. The causes can be
prenatal, perinatal or postnatal. The detection of these disorders may be
missed at birth. Therefore, family physician should carefully examine
children for developmental delay. At the earliest sign one should refer the
patient to a pediatrician. Treatment involves a multidisciplinary approach.
Medicines can help manage the symptoms of these disorders to a certain
extent. Rehabilitation at early age can accelerate development of these
children. Though there is no cure for these conditions, the patient's family
should be educated about various options like specialized rehabilitation
centres, vocational rehabilitation centres, support groups, special schools,
etc. Care of caregivers is also essential.
Neurological Disorders - A Handbook for Family Physicians 271

Section D

Management of
Neurological Emergencies
272 Neurological Disorders - A Handbook for Family Physicians
Neurological Disorders - A Handbook for Family Physicians 273

33

Acute Stroke
Strokes can be either ischemic or hemorrhagic. In an ischemic stroke, the blood
supply to part of the brain is cut off because a vessel is blocked due to either
atherosclerosis or a blood clot. Past medical history helps in diagnosing
strokelike a history of prior stroke, diabetes mellitus, hypertension, and atrial
brillation.
What to Examine ?
Ask for age, as it is more prevalent in over 50, history of hypertension, Diabetes,
smoking, and TIA in the last month.
Look for -
• Loss of sensations in an arm, leg or one side of the body
• Weakness or paralysis
• Partial loss of vision or hearing
• Double vision
• Dizziness
• Slurred speech
• Confused state
• Imbalance and falling
Neurological Examination and GCS scoring should be done to establish the
diagnosis.
Investigations-
274 Neurological Disorders - A Handbook for Family Physicians

• CT brain and MRI

• Blood glucose
• Oxygen saturation
• Serum electrolytes/renal function tests
• Complete blood count
• Prothrombin time/INR
• PTT
• ECG
• Liver function tests
• ABG
• Chest X-ray
How to manage?
Airway, Breathing and Circulation to be established. Elevate head end by 30
degrees. Acute management of stroke
Blood glucose
• Treat hyperglycemia with insulin if serum glucose >200 mg/dL
• Treat hypoglycemia with D50
Blood pressure
Continuous cardiac monitoring for ischemic changes or atrial brillation
Intravenous uids
• Avoid D5W and excessive uid administration
• IV isotonic sodium chloride solution at 50 mL/h unless otherwise
indicated
Stop oral intake
Oxygen
• Start O2 if Saturation less than 94%
Temperature
• Control temperature to avoid high fever
Refer to the hospital at the earliest.
Neurological Disorders - A Handbook for Family Physicians 275

34

Delirium
Delirium is a common clinical syndrome characterized by disturbed
consciousness, confusion and decreased awareness.
Delirium may occur due to dementia, old age, fever and acute infection,
particularly in children. Poor nutrition or dehydration, severe, chronic or
terminal illness, alcohol or drug abuse or alcohol withdrawals are some of the
causes for delirium.
A number of medications like analgesics or sedatives or combinations of
medications can trigger delirium. Medications for mood disorders, such as
anxiety and depression and Parkinson's disease medications can also cause
delirium.
WHAT TO EXAMINE?
Physical and neurological examination
Look for
• Dehydration
• Infection
• Alcohol withdrawal
A neurological exam - check vision, balance, coordination and reexes to rule
out stroke.
Investigations
• CT brain and MRI
• Blood glucose
276 Neurological Disorders - A Handbook for Family Physicians

• Oxygen saturation
• Serum electrolytes/renal function tests
• Complete blood count
• Prothrombin time/INR
• PTT
• ECG
• Liver function tests
• Thyroid function tests
• Serum vitamin B12 and folate levels.
• Chest X-ray
How to manage?
Identify and manage the underlying cause or combination of causes.
In case the patient appears confused and violent-
• Give clear, brief, assertive instructions and attempt to establish a rapport
• Avoiding threat and appear reassuring, caondent with eye contact and
allowing greater space around the patient than normal
Look for dementia, Alzheimer's or Parkinsonism and treat appropriately
Communicate and provide reassurance.
Haloperidol can be started for a short duration
Refer to psychiatrist
Neurological Disorders - A Handbook for Family Physicians 277

35

Status Epilepticus
278 Neurological Disorders - A Handbook for Family Physicians

Anti pyretics
Neurological Disorders - A Handbook for Family Physicians 279
280 Neurological Disorders - A Handbook for Family Physicians

36

Unconsciousness
Unconsciousness or altered state of consciousness:When patient is unable to
respond appropriately to stimuli or is drowsy and confused.
Potential Causes - "AEIOU TIPS”
• A - Alcohol ( Drugs & Toxin
• E - Endocrine, Exocrine, Electrolyte
• I - Insulin
• O - Opiates, Overdose
• U - Uremia
• T - Trauma, Temperature
• I - Infection
• P - Psychiatric disorder
• S - Seizure , Stroke, Shock, Space occupying lesion
What to Examine?
Attempt to get full history.
Smell the breath - ketones or alcohol,
Look for abnormal posturing like decorticate (exion of UE with extension of
LE) or decerebrate (extension of all limbs)
• Look for cyanosis, jaundice
• Look for signs of trauma
Neurological Disorders - A Handbook for Family Physicians 281

• Look for respiratory rate and patterns (Cheyne-Stokes)

• Temperature
• Heart rate; Blood pressure; Auscultation and examination of the heart
(cardiovascular)
• Abdomen for trauma
• Neck Stiffness
• Fundal examination
• Glasgow Coma Scale
–Eye opening
–Motor response
–Verbal response
• Brain stem function
–Pupillary reactions
–Corneal responses
–Spontaneous eye movements
–Oculocephalic responses
–Oculovestibular responses
–Respiratory pattern
• Motor function
–Motor response
–Muscle tone
–Tendon reexes
–Seizures
How to Manage?
Always assess & stabilize ABC rst
• A-Airway
• B-Breathing
• C-Circulation
282 Neurological Disorders - A Handbook for Family Physicians

Especially airway with Cervical Spine immobilization / protection in case of

trauma.
• Start Oxygen
• IV line: IV Fluids, Thiamine 100mg IV, 1 amp D 50
• Complete history and physical exam after stabilization
• Check X-ray cervical spine for spinal cord injury
Investigations:
• ECG
• Blood sugar
• Serum Electrolyte
• Liver function tests
• Urinalysis
• Thyroid function tests
• CT Head
• Lumbar Puncture
• USG Abdomen
Quickly manage
• Low glucose level - IV dextrose
• Hypoxia - give oxygen
• Pinpoint pupils not breathing - Ivnalaxone
• Seizure -IV Lorazepam
• Hypothermia - warm up
• Infection- IV antibiotic
Neurological Disorders - A Handbook for Family Physicians 283

37

Head Trauma
What To Ask?
• Loss of Consciousness
• Vomiting
• Amnesia
• Seizures
• Disorientation and confusion
What To Examine?
Neurological examination:
First rate the head injury by Glasgow Coma Scale (GCS)
Glasgow Coma Scale
Eye Opening

Score 1 Year or Older 0-1 Year

4 Spontaneously Spontaneously

3 To verbal command To shout

2 To pain To pain

1 No response No response
284 Neurological Disorders - A Handbook for Family Physicians

Best Motor Response

Score 1 Year or Older 0-1 Year

6 Obeys command

5 Localizes pain Localizes pain

4 Flexion withdrawal Flexion withdrawal

3 Flexes upper limbs extends Flexes upper limbs extends

lower limbs (decorticate) lower limbs (decorticate)

2 Extension (decerebrate) Extension (decerebrate)

1 No response No response

Best Verbal Response

Score >5 Years 2-5 Years 0-2 Years

5 Oriented and Appropriate Cries appropriately
converses words
4 Disoriented and Inappropriate Cries
converses words
3 Inappropriate words; Screams Inappropriate crying/
cries screaming
2 Incomprehensible Grunts Grunts
sounds

1 No response No response No response

Denition of mild, moderate and severe head injury by GCS score

Degree of head injury GCS score
Mild 13-15
Moderate 9-12
Severe 8 or less
Neurological Examination should include
Neck and cervical spine
Neurological Disorders - A Handbook for Family Physicians 285

• Deformity
• Tenderness
• Muscle spasm
Head
• Scalp bruising
• Lacerations
• Swelling
• Tenderness
Raccoon eyes-Refer to nearest hospital
Bruising behind the ear (Battledore sign) -Refer to nearest hospital
Eyes
• Pupil size
• Equality
• Reactivity
Fundoscopy for retinal haemorrhage
Ears
• Blood behind the ear drum-Refer to nearest hospital
• CSF leak-Refer to nearest hospital
Nose
• Deformity
• Swelling
• Bleeding
• CSF leak-Refer to nearest hospital
Mouth
• Dental trauma
• Soft tissue injuries
286 Neurological Disorders - A Handbook for Family Physicians

Face
• Focal tenderness
• Crepitus-Refer to nearest hospital Motor function
• Reexes present

No history of loss Normal No CT scan. Give a warning

of consciousness, Neurological Monitoring sign list to
no vomiting or Examination at home. Parace- the caregiver
amnesia, a normal tamol for headache.
and minimal if any
subgaleal swelling

Brief loss of Normal CT Scan Give a warning

consciousness, Neurological Monitor for a few signs list to the
post-traumatic Examination hours if CT scan caregiver for
amnesia, a normal. If CT scan monitoring at home
single episode of not available then
vomiting or X-ray Skull and
signicant look for fracture
subgaleal swelling CTscan required if
there is a fracture
on X-ray. If X-ray
normal, monitor
for few hours and
then monitor at
home.

Loss of Neurological CT scan Antibiotics and

consciousness, Decits compulsory analgesics
repeated episodes Admit patient to a as indicated. No
of vomiting, hospital for sedatives
blood from the ear, monitoring for 48 should be given.
CSF from the ear, hours. Watch
CSF from the nose, for warning signs.
seizures,
penetrating or
perforating
wounds, non-
cooperative patient,
patients who have
undergone
previous brain
surgery, patient
who has been on
anticoagulant
therapy, epileptic
or alcoholic patients
Neurological Disorders - A Handbook for Family Physicians 287

Unconscious Neurological Resuscitation. CT Apply oxygen 10

patients Decits, scan compulsory. l/min by
Decorticate or Refer to an face mask.Establish
Decerebrate emergency care intravenous access.
response hospital Transfer patient
preferably on spi-
nal board and with
neck collar in place.

Most minor head injuries make a full recovery within a short period and just
cause bruising and pain for a short while. Scalp injuries generally require sutur-
ing asw they tend to bleed a lot. In case of closed injuries with swelling on the
scalp application of ice to the injured area to helps reduce the swelling.
Headache - Give paracetamol 6hrly to relieve pain.
Warning signs list to be handed to patient caregivers to bring the patient back to
the doctor-
• Vomiting
• Headache not relieved after a few hours
• Drowsiness
• Irritability
• Seizure
• Unusual or confused behaviour
• Bleeding or discharge from the ear or nose
• Weakness or numbness in arm or leg
• Altered vision
288 Neurological Disorders - A Handbook for Family Physicians

38

Spine Trauma
Post traumatic spinal cord injury is often seen in road trafc accidents and
construction sites-
On receiving the patient assess for
• Airway/Breathing: Intubation may be required but it would need
sedation (Lorazepam 1-2 mg IV) with constant monitoring
• Circulation: Start IV access to begin IV Fluids, preferably Normal
Saline
• Immobilize the spine
What to examine?
• Neurological assessment
• Note the sensory level
• Assess the motor function
• Use the Glasgow coma score to assess the sensorium
Autonomic Control
Vital signs can be quite abnormal following spinal cord injury due to loss of
autonomic control which occurs particularly in cervical or thoracic spine inju-
ries-
• Note the heart rate - watch for bradycardia, the physician can use
atropine if it is not contraindicated by a head injury.
Neurological Disorders - A Handbook for Family Physicians 289

• Note blood pressure and watch out for hypotension to rule out
neurogenic shock. Patient may need intravenous uids to maintain
BP.
• Loss of temperature control - watch for hypothermia.
• Respiratory difculty depends on injury level and should be moni-
tored by asking the patient to cough and monitoring oxygen satura-
tion
• Watch abdomen for distension
Investigation
• Plain X-ray of the entire cervical, thoracic and lumbar spines
• MRI spine can be planned once the patient is stable
• CBC ABG Serum Electrolytes
How to manage?
First 24 hours
• Conrm ABC
• Immobilize the neck spine with neck collar. If a neck collar is not available
then plastic IV uid bottles can be secured on either side of the head with a
tape, so that there is no movement of the cervical spine.
• In case the patient needs to be resuscitated, the spinal immobilization
should be maintained. To move the patient log roll should be used.
• Take care with water temperature for washes, and use of hot or cold
devices against skin in case ofspinal cord injury patients.
• Bladder function depends on the level of spinal cord injury. It is better to
catheterize the patient to avoid neurogenic bladder where the loss of
bladder function is obvious in the initial stages.
• Refer to a neurosurgeon.
“It is important to note that injection methyl prednisolone if started within 8 hrs.
of spine cord injury has a signicantly benecial effect on the overall recovery. It
is therefore, important to shift a spine injured patient as soon as possible to a
specialized trauma hospital. if there is likely to be delay in transfer then injection
methyl prednisolone may be started as 30 mg/ kg may be given over 30 mins.
and then 5.4 mg/kg per hour, continued till the patient is shifted to a specialized
center.”
290 Neurological Disorders - A Handbook for Family Physicians

38.1: Log Roll a patient of spinal cord injury

Step 1 : Four persons to help. The person at the head end calls out the
instructions.
Step2 : Secure and hold the patients neck with both forearms as shown.
Step 3 : Turn the patient as called out by the head end togather.
Step 4 : Roll the patient back on to a spinal board.
Neurological Disorders - A Handbook for Family Physicians 291

Section E

Neuropharmacology
292 Neurological Disorders - A Handbook for Family Physicians
Neurological Disorders - A Handbook for Family Physicians 293

39

Drugs used for Seizure

Disorders
The anticonvulsants, sometimes also called antiepileptics, belong to a diverse
group of drugs used in treatment or prevention of the occurrence ofseizures.
The goal of an anticonvulsant is to suppress the rapid and excessive ring of
neurons that start a seizure. A good anticonvulsant would prevent the spread of
the seizure within the brain.
Antiseizure drugs act by blocking sodium (Na+) channels, calcium (Ca2+)
channels, AMPA receptors or NMDA receptors. Some antiseizure drugs inhibit
the metabolism of GABA or increase its release. Some drugs act by inhibition of
Brain Carbonic Anhydrase.
Classication:
A. Classical
Ÿ Phenytoin
Ÿ Phenobarbital
Ÿ Primidone
Ÿ Carbamazepine
Ÿ Ethosuximide
Ÿ Valproate (valproic acid)
B. Newer
Ÿ Levetiracetam
Ÿ Fosphenytoin
Ÿ lamotrigine
Ÿ Topiramate
294 Neurological Disorders - A Handbook for Family Physicians

Ÿ Gabapentin
Ÿ Tiagabine
Ÿ Vigabatrin
Ÿ Oxycarbazepine
Ÿ Felbamate
Ÿ Clobazam
Ÿ Clonazepam
Ÿ Runamide
Ÿ Zonisamide
Ÿ Lacosamide
Ÿ Ezogabine

Benzodiazepines
The benzodiazepines are a class of drugs with anticonvulsant, hypnotic, anxio-
lytic, amnestic and muscle relaxant properties. Long-term use can lead to the
development of tolerance and dependence.
Mechanism of action
Benzodiazepines act by increasing neuronal membrane permeability to Cl- ions
by binding to stereospecic benzodiazepine receptors on the postsynaptic
GABA neuron within the CNS and enhancing the GABA inhibitory effects,
which in turn result in hyperpolarisation and stabilisation.
Indications : Insomnia, anxiety, tension, epilepsy, muscle spasm, psychoso-
matic & behaviour disorders, general anaesthesia/preanaesthetic medication,
drug dependence.
Contraindications: Severe hepatic impairment; respiratory depression; acute
narrow-angle glaucoma; pregnancy and lactation.
Special Precautions need to be taken in cases of hepatic and renal dysfunction;
pulmonary insufciency; and myasthenia gravis. These drugs may impair the
ability to drive or operate machinery.
Adverse Drug Reactions: Drowsiness, headache, dizziness, confusion; blurred
vision; weakness; unsteadiness. Respiratory depression is a serious complica-
tion.
Drug Interactions: Potentiation of CNS depression produced by alcohol; gen-
eral anaesthetics; narcotic analgesics; TCAs; MAOIs; phenothiazines;
antipsychotics; barbiturates; scopolamine. Drugs like Erythromycin &
Fluconazole (CYP3A4 inhibitors) inhibit the metabolism of benzodiazepines
and thus prolong their action.
Neurological Disorders - A Handbook for Family Physicians 295

Diazepam
It is preffered in acute panic states & anxiety associated with organic disease
Onset of action: Almost immediate (IV); rapid (oral).
Duration: IV: 20-30 min.
Absorption: Time to peak plasma concentration: Approx 30-90 min (oral);
approx 10-30 min (rectal). Bioavailability is nearly 100%
Distribution: Plasma protein binding: 98-99%.
Metabolism: Extensively hepatic via CYP3A4 and CYP2C19 isoenzymes to
desmethyldiazepam (active metabolite).
Excretion: Via urine (as free or conjugated metabolites). Biphasic half-life: Rapid
(initial), 1 or 2 days (terminal), 2-5 days (desmethyldiazepam).
Contraindications : acute narrow angle glaucoma, hypersentivity to
benzodiazepines.
myasthenia gravis.
Special precautions to be taken in patients with hepatic & renal impairment.
Side effects : drowsiness, altered activeness, vertigo, increased appetite &
weight gain
Dosage
Parenteral
Seizures
Adult: Initially, 5-10 mg IV repeated at 10- to 15-min intervals up to max 30 mg.
On stoppage of seizures, appropriate maintenance therapy to be started. Initial
dose at 2-4 hr interval may be started. IM administration is advised if IV is not
possible.
Child: 30 days to 5 yr: Initially, 0.1-0.5 mg IV, may be repeated every 2-5 min up
to max 5-10 mg; >5 yr Initially, 1 mg, may be repeated every 2-5 min up to max 10
mg. Followed by maintenance treatment.
Elderly: dosage should not exceed half the adult dose.
Dose reduction may be required in hepatic impairment.
Lorazepam
296 Neurological Disorders - A Handbook for Family Physicians

Lorazepam is a short acting benzodiazepine. Lorazepam enhances the inhibi-

tory effect of GABA on neuronal excitability by modulating GABA receptors.
Onset of action: Hypnosis: anticonvulsant: 5 min (IV), 30-60 min (oral).
Duration: 6-8 hr.
Absorption: peak plasma concentrations after 2 hr.
Distribution: Crosses the placenta and blood-brain barrier; enters breast milk.
Protein-binding: 85%.
Metabolism: Hepatic; converted to inactive metabolites.
Excretion: Urine and faeces; 10-20 hr (elimination half-life).
Indications: anxiety, status epilepticus, sedation
Dosage:-
Adult: 4 mg injected slowly, may be repeated once after 10 minutes if seizures
recur.
Dose should be given at a rate not >2 mg/minute into a large vein.
Child: Neonates and children up to 12 yr: 0.1 mg/kg (max: 4 mg) as a single
dose; may be repeated once after 10 minutes if needed.
Containdications: Severe hepatic impairment; respiratory depression; acute
narrow-angle glaucoma; pregnancy and lactation.
Midazolam
Midazolam is a short-acting benzodiazepine.
Absorption: Rapidly absorbed (any route); peak plasma concentrations after 20-
60 min (depending on route).
Distribution: Protein-binding: 96%
Metabolism: Extensively hepatic via CYP3A4 isoenzyme; converted to
hydroxymethylmidazolam.
Excretion: Urine (as glucuronide conjugates); 2 hr (elimination half-life), pro-
longed in neonates, elderly and hepatic impairment.
Indications: The midazolam nasal spray is only used when an epileptic seizure
lasts more than ten minutes. Seizures that last this long can cause status
epilepticus. Midazolam nasal sprays are also used to stop the seizures as soon as
possible.
Neurological Disorders - A Handbook for Family Physicians 297

Dosage
The midazolam nasal spray is very easy to use, even for someone that has never
used it before. For new sprays a few pumps are required to clear the spray of air.
During epileptic seizures, generally one spray per nostril is sufcient for the
patient to recover. As each spray contains 2,5 mg midazolam, this sums up to a
total dosage of 5 mg. For some patients 10 mg of midazolam is used.
Alprazolam
It is a triazolo analogue of benzodiazepine,which is indicated in anxiety
Mechanism of action:
Alprazolam has anxiolytic, muscle-relaxant, anticonvulsant, antidepressant
and sleep-modifying effects. It binds to the Gama aminobutyric acid (GABA)-
specic sites throughout the CNS, leading to an increase in the inhibitory effect
of GABA on neuronal excitability.
Absorption: peak plasma concentrations after 1-2 hrs.
Distribution: Protein-binding: 70-80%
Metabolism: Hepatic; converted to α-hydroxyalprazolam and benzophenone.
Excretion: Urine (as unchanged drug and metabolites); 11-15 hrs (elimination
half-life).
Indications- anxiety disorders,anxiety associated depression, sedation (mild)
Dosage
Oral
Short-term management of anxiety
Adult: 0.25-0.5 mg tid, increased to 3-4 mg daily if necessary.
Elderly: Initially, 0.25 mg bid/tid.
Hepatic impairment: Avoid in severe impairment.
Oral
Panic attacks
Adult: Up to 10 mg daily.
Contraindications : acute narrow angle glaucoma, hypersentivity to
benzodiazepines, acute pulmonary insufciency or sleep apnoea, severe
hepatic impairment; pregnancy, lactation. CNS depressants are not recom-
mended in children.
298 Neurological Disorders - A Handbook for Family Physicians

Side effects : drowiness, psychological and physical dependence, withdrawal

seizures, anorexia, musculoskeletal weakness, ataxia, dizziness, confusion and
depression. Blood dyscrasias being a serious adverse effect.
Drug Interactions: Potentiates action of alcohol and CNS depressants. Cigarette
smoking reduces concentration by 50%.
Zolpidem
This is a non benzodiazepine sedative belonging to imidazopyridine class.
Dosage
Oral
Short-term management of insomnia
Adult: As immediate release tab: 5-10 mg immediately before bedtime; Max: 10
mg/
day. As extended release tab: 6.25-12.5 mg immediately before bedtime; Max:
12.5
mg/day. Max duration of treatment: 4 weeks which includes tapering.
Elderly: As immediate release tab: 5 mg immediately before bedtime. As
extended release tab: 6.25 mg immediately before bedtime. Max duration of
treatment: 4 weeks including tapering.
Hepatic impairment: As immediate release tab: 5 mg immediately before
bedtime.
As extended release tab: 6.25 mg immediately before bedtime. Max duration of
treatment: 4 weeks including tapering.
Indications : short term treatment for insomnia.
Contraindication : obstructive sleep apnoea, myasthenia, severe hepatic insuf-
ciency, acute pulmonary insufciency.
Special precaution to be taken in neonates, nursing mothers, pregnancy and
depression.
Patients should be advised not to drive after taking medication.
Side effects
Atypical thinking and behaviour, hallucinations, nightmares, somnolence,
headache, dizziness, vertigo, drowsiness, asthenia, ataxia, rebound insomnia,
Neurological Disorders - A Handbook for Family Physicians 299

amnesia, upper and lower respiratory tract infection, fatigue, visual distur-
bances, increased ALT serum concentrations; while Hepatitis, anaphylactic
reactions, angioedema are the more serious complications.
Hydantoins
Phenytoin
Phenytoin is available at a relatively low cost, making it one of the most afford-
able seizure control medications. It is available in extended release capsules and
injectable forms.
Mechanism of action
Phenytoin acts as an anticonvulsant by increasing efux or decreasing inux of
sodium ions across cell membranes in the motor cortex, thus stabilising
neuronal membranes and decreasing seizure activity. At higher doses Ca2+ and
K+ uxes are affected and also facilitates the GABA receptor effect and inhibits
effect of glutamate.
Pharmacokinetics
It is well absorbed by the oral route but exhibits phenomenon of
bioinequivalence i.e the bioavailablity of different pharmaceutical preperations
may be different.
Distribution: Widely distributed. Protein-binding: 90%.
Metabolism: Extensively hepatic; converted to inactive metabolites.
Excretion: Via urine as hydroxylated metabolite; elimination half life at steady
state:
22 hr
Dosage
Oral
Epilepsy
Adult: Initially, 3-4 mg/kg daily as single dose or in divided doses. Alterna-
tively, 150-300 mg daily increased gradually to 600 mg daily if necessary. Main-
tenance: 200-500 mg daily.
Child: Initially, 5-6 mg/kg daily in 2-3 divided doses. Maintenance: 4-8 mg/kg
daily in divided doses. Max dose: 300 mg daily.
Intravenous
Tonic- clonic status epilepticus
300 Neurological Disorders - A Handbook for Family Physicians

Adult: Adjunctive therapy with a benzodiazepine (e.g. diazepam): 10-15 mg/kg

by slow inj or intermittent infusion at a max rate of 50 mg/min. Maintenance:
100 mg IV (or orally) given every 6-8 hr.
Child: Neonates: 20 mg/kg as a loading dose, then 2.5-5 mg/kg bid; 1 mth-12 yr:
18 mg/kg as a loading dose, then 2.5-5 mg/kg bid; >12 yr: 18 mg/kg as a loading
dose, then up to 100 mg 3-4 times daily.
Phenytoin has a narrow therapeutic window. Hence, a ne balance must be
maintained between its efcacy and dose-related side effects. Phenytoin
demonstrates non-linear pharmacokinetics, which causes the enzyme system
involved to become saturated with phenytoin, even with a small change in dose
and can lead to a large change in phenytoin levels. Thus, monitoring phenytoin
plasma levels regularly is necessary to decide the next appropriate dosage.
Target plasma range of phenytoin: 10-20 mg/L
Indications: All types of epilepsy except petit mal epilepsy, status epilepticus,
trigeminal neuralgia.
Contraindications : Pregnancy, IV administration in sinus bradycardia, heart
block, or Stokes-Adams syndrome.
Special precautions - Precautions should be taken while administering intrave-
nously in patients with hypotension, heart failure, Patient's BP and ECG should
be monitored during therapy. IV must be given slowly (too rapid administra-
tion may cause hypotension, CNS depression, cardiac arrhythmias and
impaired heart conduction). Therapy should not be discontinued abruptly as it
may increase seizure frequency.
Side effects- headache, dizziness, tremor, insomnia, tenderness and hyperpla-
sia of the gums, acne, hirsutism, osteomalacia and megaloblastic anemia.
Phenytoin toxicity is manifested as a syndrome of cerebellar, vestibular, ocular
effects, notably nystagmus, diplopia, slurred speech, and ataxia; also with
mental confusion, dyskinesias, exacerbations of seizure frequency, hypergly-
caemia. Prolonged use may affect mental function and cognition in children.
Toxic epidermal necrolysis, Stevens-Johnson syndrome could occur in serious
adverse events.
Fosphenytoin
Mechanism of action
Fosphenytoin is converted to phenytoin in the liver. It modulates voltage-
dependent Na channels of neurons.
Absorption: Plasma concentrations peak after 30 minutes (IM).
Neurological Disorders - A Handbook for Family Physicians 301

Distribution: Displaces phenytoin from binding sites. Protein-binding: 95-99%.

Metabolism: Complete; hydrolysed to phenytoin, phosphate and formalde-
hyde.
Excretion: Urine (as inactive metabolites).
Dosage:
Parenteral
Tonic-clonic status epilepticus
Adult: As Phenytoin sodium equivalents (PSE): Loading dose: 15 mg/kg, given
via IV infusion at a rate of 100-150 mg/minute. Maintenance: Initially, 4-5 mg
PSE/kg/ day by IM inj or IV infusion at a rate of 50-100 mg PSE/minute; subse-
quent doses depend on patient's response and trough-plasma phenytoin levels.
Child: As Phenytoin sodium equivalents (PSE): Loading dose: 15 mg/kg, given
via IV infusion at a rate of 2-3 mg/kg/minute. Maintenance: Initially, 4-5
mg/kg/day by IM inj or IV infusion at a rate of 1-2 mg/kg/minute; subsequent
doses depend on patient's response and trough-plasma phenytoin levels.
Hepatic impairment: Dose reduction or slower infusion may be needed.
Parenteral
Seizures
Adult: Except status epilepticus: As Phenytoin sodium equivalents (PSE):
Loading. dose: 10-15 mg/kg, given via IM inj or IV infusion at a rate of 50-100
mg/minute. Maintenance: Initially, 4-5 mg/kg/day by IM inj or IV infusion at a
rate of 50-100 mg/minute; subsequent doses depend on patient's response and
trough-plasma phenytoin levels.
Child: ?5 yr: As Phenytoin sodium equivalents (PSE): Loading dose: 10-15
mg/kg, given via IM inj or IV infusion at a rate of 1-2 mg/kg/minute. Mainte-
nance: Initially, 4-5 mg/kg/day by IM inj or IV infusion at a rate of 1-2
mg/kg/minute; subsequent doses depend on patient's response and trough-
plasma phenytoin levels.
Hepatic impairment: Dose reduction or slower infusion may be needed.
Indications: status epilepticus, as a substitute for phenytoin
Contraindications: Porphyria; sinus bradycardia; SA block; 2nd- and 3rd-
degree heart block; Stokes-Adams syndrome; pregnancy, lactation.
302 Neurological Disorders - A Handbook for Family Physicians

Special Precautions: Hepatic or renal impairment; elderly; patients requiring

phosphate restriction. Monitor ECG, BP and respiratory function during infu-
sion; observe patient for at least 30 minutes after infusion. IV infusion rate
should not exceed 150 mg PSE/minute in adults or 3 mg PSE/kg/minute in
children ?5 yr.
Side effects: Burning, itching and paraesthesia in the groin area following IV
administration; asystole, ventricular brillation, hypotension, bradycardia,
heart block which could be fatal.
Fatty acids
The valproates - valproic acid, sodium valproate, and divalproex sodium are
anticonvulsant and mood-stabilizing drugs
Mechanism of Action:
Valproate is a carboxylic acid anticonvulsant which increases levels of α-
aminobutyric acid (GABA) in the brain, maintains Na+channels in inactivated
state
Absorption: Time to peak plasma concentration: Oral: Approx 4 hr; extended
release:
4-17 hr.
Distribution: Plasma protein binding (concentration dependent): 80-90%; free
fraction: Increases from approx 10% at 40 mcg/mL to approx 18.5% at 130
mcg/mL; decreases in the elderly and patients with hepatic or renal impair-
ment. Crosses the placenta; enters breast milk.
Metabolism: Valpromide is almost completely and rapidly metabolised in the
liver to valproic acid. Valproic acid is extensively metabolised by liver, via
glucuronidation and mitochondrial beta oxidation.
Excretion: Excreted in urine (30-50% as glucuronide conjugate; <3% as
unchanged drug), small amounts in faeces and expired air. Elimination half-life:
Adult: 5-20 hr;
>2 mth: 7-13 hr.
Sodium valproate
It is a broad spectrum anticonvulsant producing little sedation
Oral
Complex partial seizures
Neurological Disorders - A Handbook for Family Physicians 303

Adult: Given as valproic acid or valproate semisodium: ?10 yr Initially 10-15

mg/kg/day in 2-4 divided doses, increased by 5-10 mg/kg/wk. Max: 60
mg/kg/day. Given as sodium valproate: 600 mg/day in 2 divided doses,
increased by 150-300 mg every 3 days. Usual range: 1-2 g/day (20-30
mg/kg/day). Max: 2.5 g/day.
Child: Given as sodium valproate: >20 kg: 400 mg/day in 2 divided doses,
increased gradually until control is achieved. Usual range: 20-30 mg/kg/day.
Max: 35 mg/kg/ day. <20 kg: 20 mg/kg/day in 2 divided doses, increased to 40
mg/kg/day.
Elderly: Initiate at lower dose and increase slowly.
Hepatic impairment: Contraindicated.
Oral
Simple and complex absence seizures
Adult: As monotherapy, conversion to monotherapy or adjunctive therapy.
Given as valproic acid or valproate semisodium: ?10 yr Initially 15 mg/kg/day
in 2-4 divided doses, increased by 5-10 mg/kg/wk. Max: 60 mg/kg/day.
Child: Given as sodium valproate: >20 kg: 400 mg/day in 2 divided doses,
increased gradually until control is achieved. Usual range: 20-30 mg/kg/day.
Max: 35 mg/kg/ day. <20 kg: 20 mg/kg/day in 2 divided doses, increased to 40
mg/kg/day.
Elderly: Initiate at lower dose and increase slowly.
Hepatic impairment: Contraindicated.
Oral
Bipolar disorder
Adult: As valpromide: 600-1800 mg/day in 2 divided doses. Usual dose: 1200
mg/ day. Initiate at required dose or dosage may be increased every 2-3 days to
reach optimal dose in 2 wk w/ simultaneous and progressive dose reduction of
concurrent psychotropic drugs.
Intravenous
Complex partial seizures
Adult: As monotherapy, conversion to monotherapy or adjunctive therapy.
Given as sodium valproate: ?10 yr Initially 10-15 mg/kg/day in 2-4 divided
doses, increased by 5-10 mg/kg/wk. Usual dose: 20-30 mg/kg/day. Each dose
304 Neurological Disorders - A Handbook for Family Physicians

to be given as slow IV inj over 3-5 min or by infusion in 0.9% saline, 5% dextrose
or lactated ringer's inj over 60 min (Max rate: 20 mg/min). Max: 2.5 g/day.
Child: As monotherapy, conversion to monotherapy or adjunctive therapy.
Given as sodium valproate: Initially 10 mg/kg/day in 2-4 divided doses,
increased until control is achieved. Usual range: 20-30 mg/kg/day. Max: 40
mg/kg/day w/ plasma valproic acid levels monitoring.
Elderly: Initiate at lower dose and increase slowly.
Hepatic impairment: Contraindicated.
Intravenous
Simple and complex absence seizures
Adult: As monotherapy, conversion to monotherapy or adjunctive therapy.
Given as sodium valproate: ?10 yr Initially 10-15 mg/kg/day in 2-4 divided
doses, increased by 5-10 mg/kg/wk. Usual dose: 20-30 mg/kg/day. Each dose
to be given as slow IV inj over 3-5 min or by infusion in 0.9% saline, 5% dextrose
or lactated ringer's inj over 60 min (Max rate: 20 mg/min). Max: 2.5 g/day.
Child: As monotherapy, conversion to monotherapy or adjunctive therapy.
Given as sodium valproate: Initially 10 mg/kg/day in 2-4 divided doses,
increased until control is achieved. Usual range: 20-30 mg/kg/day. Max: 40
mg/kg/day w/ plasma valproic acid levels monitoring.
Elderly: Initiate at lower dose and increase slowly.
Hepatic impairment: Contraindicated.
Monitoring sodium valproate plasma levels regularly is necessary to decide the
next appropriate dosage. Target plasma rangeof sodium valproate: 50-100
mg/L
Indications: epilepsy and bipolar disorder, migraine, schizophrenia, treatment
of status epilepticus alternatively to phenytoin.
Contraindications - liver impairment, concurrent administration of
clonazepam, active liver disease, porphyria; mitochondrial and urea cycle
disorders, pregnancy.
Special precautions need to be taken in mentally retarded children with epi-
lepsy.
Dose should be reduced in children.
Neurological Disorders - A Handbook for Family Physicians 305

Side effects- anorexia, drowsiness, ataxia,tremor, nystagmus, somnolence,

dizziness, fatigue, hyperammonaemic encephalopathy, hypothermia, halluci-
nations, pancreatitis, blood dyscrasias. Fatal hepatotoxicity could occur in
children less than 2 years of age. Transient alopecia is seen in some patients.
Divalproex
A combination of sodium valproate and valproic acid (1:1). It has slower absorp-
tion and lesser CNS and GI side effects.
Dosage
Oral
Primary generalised seizures
Adult: Initially, 10-15 mg/kg/day in 2-4 divided doses, if necessary, increase at
5-10 mg/kg/wk. Max: 60 mg/kg/day.
Child: 10 yr: Initially, 10-15 mg/kg/day in 2-4 divided doses, if necessary,
increase at 5-10 mg/kg/wk. Max: 60 mg/kg/day.
Oral
Partial seizures
Adult: Initially, 10-15 mg/kg/day in 2-4 divided doses, if necessary, increase at
5-10 mg/kg/wk. Max: 60 mg/kg/day.
Child: 10 yr: Initially, 10-15 mg/kg/day in 2-4 divided doses, if necessary,
increase at 5-10 mg/kg/wk. Max: 60 mg/kg/day.
Oral
Prophylaxis of migraine
Adult: 500 mg once daily for 1 wk, may increase to 1000 mg once daily.
Indications: Petit mal epilepsy,alternative/adjuvant drug for grand mal,
psychomotor, myoclonic & temporal lobe epilepsy.
Contraindications : liver impairment,concurrent administration with
clonazepam
Special precaution: major surgery,mental retarded children with epilepsy,
pregnancy.
Side effects: anorexia, drowsiness, ataxia, tremor, hairloss, hyperammonaemia;
pancreatitis, thrombocytopenia, weight gain.
306 Neurological Disorders - A Handbook for Family Physicians

Barbiturates
Barbiturates are drugs that act as central nervous system (CNS) depressants,
and bring about mild sedation to anesthesia. The following are classied as
anticonvulsants:
Phenobarbital - it is the most widely used anticonvulsant. It also has sedative
and hypnotic properties.
Mechanism of action:
Phenobarbitone is a short- acting barbiturate. It depresses the sensory cortex,
reduces motor activity, changes cerebellar function, and produces drowsiness,
sedation and hypnosis. Its anticonvulsant property is exhibited at high doses.
Onset: Hypnosis: Oral: 20-60 min; IV: Approx 5 min.
Duration: Oral: 6-10 hr; IV: 4-10 hr.
Absorption: peak plasma concentrations in about 2 hr (oral), and within 4 hr
(IM).
Distribution: Crosses the placenta; enters breast milk. Protein-binding: 45-60%.
Metabolism: Partly hepatic.
Excretion: Via urine (as unchanged drug). Plasma half-life: 75-120 hr (adult),
greatly prolonged (neonates), 21-75 hr (children).
Dosage
Oral
Partial seizures
Adult: 60-180 mg daily taken at night. Titrate dose according to patient's needs
to achieve adequate control of seizures. Plasma concentrations of 15-40 mcg/ml
(65-170 micromol/l) are usually required.
Child: 1 mth-12 yr: Initially, 1-1.5 mg/kg bid. Increase by 2 mg/kg daily, as
required, to a maintenance dose of 2.5-4 mg/kg once or bid. 12-18 yr: Initially,
60-180 mg bid.
Maintenance: 60-180 mg once daily.
Renal impairment: CrCl: <10 ml/min- Administer every 12-16 hr.
Hepatic impairment: Severe: Monitor plasma levels and adjust dose as neces-
sary.
Oral
Neurological Disorders - A Handbook for Family Physicians 307

Generalised tonic- clonic seizures

Adult: 60-180 mg daily taken at night. Titrate dose according to patient's needs
to achieve adequate control of seizures. Plasma concentrations of 15-40 mcg/ml
(65-170 micromol/l) are usually required.
Child: 1 mth-12 yr: Initially, 1-1.5 mg/kg bid. Increase by 2 mg/kg daily, as
required, to a maintenance dose of 2.5-4 mg/kg once or bid. 12-18 yr: Initially,
60-180 mg bid.
Maintenance: 60-180 mg once daily.
Renal impairment: CrCl: <10 ml/min- Administer every 12-16 hr
Hepatic impairment: Severe: Monitor plasma levels and adjust dose as neces-
sary.
Oral
Intravenous
Status epilepticus
Adult: Doses of 10 mg/kg to a max of 1 g.
Child: As sodium: Neonates and children up to 12 yr: Initially, 20 mg/kg by
slow IV inj then 2.5-5 mg/kg once or bid. 12-18 yr: Initially 20 mg/kg (max 1 g)
by slow IV inj then 300 mg bid.
Intravenous
Generalised tonic-clonic seizures
Child: As sodium: Neonates: Loading dose is 20 mg/kg by slow IV inj followed
by 2.5-5 mg/kg once daily either by slow IV inj or orally.
Intravenous
Partial seizures
Child: As sodium: Neonates: Loading dose is 20 mg/kg by slow IV inj followed
by 2.5-5 mg/kg once daily either by slow IV inj or orally.
Intramuscular
Sedation
Adult: As sodium: 30-120 mg/day in 2-3 divided doses.
Renal impairment: CrCl: <10 ml/min- Administer every 12-16 hr.
308 Neurological Disorders - A Handbook for Family Physicians

Hepatic impairment: Severe: Monitor plasma levels and adjust dose as neces-
sary.
Indications- mania, delirium, insomnia, anti convulsant. Phenobarbital sodium
injection can be used to stop acute convulsions or status epilepticus.
Contraindications- concurrent administration with CNS deppresants, renal &
hepatic impairment, pulmonary insufciency, porphyria, pregnancy.
Side effects: Bradycardia, hypotension, syncope; drowsiness, lethargy,
impaired judgement, hangover effect, confusion, somnolence, agitation,
hyperkinesia, ataxia, nervousness, headache, insomnia, nightmares, hallucina-
tions, anxiety, dizziness; agranulocytosis, thrombocytopenia, megaloblastic
anaemia; thrombophlebitis (IV); respiratory depression. Long term administra-
tion may produce behavioral abnormalities, megaloblastic anemia, hyperactiv-
ity in children.
Carboxamides
Carbamazepine
Mechanism of Action
Carbamazepine Slows the rate of recovery of Na+ channels, reduces
polysynaptic responses and blocks post-tetanic potentiation
Distribution: Crosses the placenta; enters breast milk. Protein-binding: 75%.
Well distributed in the body.
Metabolism: Hepatic; converted to its metabolites.
Excretion: Urine (as metabolites), faeces; 5-26 hr (elimination half-life).
Dosage
Oral
Epilepsy
Adult: Initially, 100-200 mg once or bid gradually increased by increments of
100-200 mg every 2 wk. Maintenance: 0.8-1.2 g daily in divided doses. Max dose:
2 g daily.
Child: 1 yr: 100-200 mg daily, 1-5 yr: 200-400 mg daily, 5-10 yr: 400-600 mg daily,
10-15 yr: 0.6-1 g daily. Alternatively, 10-20 mg/kg daily in divided doses.
Rectal
Epilepsy
Neurological Disorders - A Handbook for Family Physicians 309

Adult: 250 mg every 6 hr for patients incapable of oral treatment.

Oral
Carbamazepine level should be considered if toxicity is suspected (>12mg/L) or
in presence of possible noncompliance. The therapeutic reference range of
carbamazepine is 4-12 mg/L. The minimum toxic level is 10 mg/kg.
Indications: epilepsy, partial seizures, primary epilepsy or secondary general-
ised forms of seizure with a tonic clonic component.
Contraindications : AVblock, bone marrow depression; porphyria, pregnancy,
hepatic and renal impairment.
Side effects - leucopenia, proteinuria, renal failure, heart failure and
hyponatraemia loss of appetite, dry mouth, headache, dizziness, ataxia,
diplopia
Levetiracetam
Mechanism of action
The drug binds to a synaptic vesicle glycoprotein, SV2A and inhibits
presynaptic calcium channels reducing neurotransmitter release. This impedes
impulse conduction across synapses.
Onset: 1 hr
Distribution: Not signicantly protein bound (<10%). Distributed in breast
milk.
Metabolism: Not extensively metabolised (24% into inactive metabolite);
primarily by enzymatic hydrolysis.
Excretion: Excreted in the urine as both unchanged drug (66%) and metabolites.
Plasma half life of 6-8 hr.
Dosage
Oral
Adjunct in partial seizures
Adult: Initially, 500 mg bid on the 1st day, increase in steps of 1 g at 2-4 wk
intervals until effective antiepileptic control is achieved. Max: 3 g/day.
Child: 4-15 yr (<50 kg): Initially 10 mg/kg bid. May be increased by 10 mg/kg
bid at 2-wk intervals. Adolescents ?16 yr or 50 kg initially 500 mg bid. May be
increased by 500 mg bid at 2-4 wk intervals. Max: 60 mg/kg/day.
310 Neurological Disorders - A Handbook for Family Physicians

Renal impairment: Suitable total daily dose (given as 2 divided doses) based on
CrCl.
Cr Cl: 50-79ml/min: 1-2 g, 30-49 ml/min: 500 mg - 1.5 g, <30 ml/min: 500 mg - 1 g
Oral
Monotherapy for partial seizures with or without secondary generalisation
Adult: Initially 500 mg daily, increased after 2 wk to 1 g daily. May further
increase in steps of 500 mg at 2 wk intervals. Max: 3 g/day.
Renal impairment: Suitable total daily dose (given as 2 divided doses) based on
CrCl.
Cr Cl: 50-79ml/min: 1-2 g, 30-49 ml/min: 500 mg - 1.5 g, <30 ml/min: 500 mg - 1 g
Intravenous
Adjunct in partial seizures
Adult: Initially, 500 mg bid on the 1st day. May increase in steps of 1 g at 2-4 wk
intervals until effective antiepileptic control is achieved. Max: 3 g/day. No
safety and efcacy data for IV usage >4 days.
Child: 4-15 yr (<50 kg): Initially 10 mg/kg bid via IV infusion over 15 min. May
be increased by 10 mg/kg bid at 2-wk intervals. Adolescents ?16 yr or 50 kg
initially 500mg bid via IV infusion over 15 min. May be increased by 500 mg bid
at 2-4 wk intervals. Max: 60 mg/kg/day.
Renal impairment: Suitable total daily dose (given as 2 divided doses) based on
CrCl.
Cr Cl: 50-79ml/min: 1-2 g, 30-49 ml/min: 500 mg - 1.5 g, <30 ml/min: 500 mg - 1 g
Intravenous
Monotherapy for partial seizures with or without secondary generalisation.
Adult: Initially 500 mg daily, increased after 2 wk to 1 g daily. May further
increase in steps of 500 mg at 2 wk intervals. Max: 3 g/day. No safety and ef-
cacy data for IV usage >4 days.
Renal impairment: Suitable total daily dose (given as 2 divided doses) based on
CrCl.
Cr Cl: 50-79ml/min: 1-2 g, 30-49 ml/min: 500 mg - 1.5 g, <30 ml/min: 500 mg - 1 g
Indications - partial onset seizures, myoclonic seizures,primary tonic-clonic
seizures
Neurological Disorders - A Handbook for Family Physicians 311

Contraindications : pregnancy,lactation and children less than 4 years of age

Special precautions should be taken in patients with renal and hepatic impair-
ment; patients undergoing haemodialysis. If psychotic symptoms (eg hallucina-
tion) and behavioural symptoms (eg agitation, anxiety) occur, reduce dosage.
Abrupt withdrawal may result in increased seizure frequency. May impair
ability to drive or operate machinery during initial therapy.
Side effects : somnolence, dizziness, vertigo, ataxia,hairloss,depression,
tremor, amnesia, headache, diplopia.
Topiramate
This is used for seizures including refractory seizures,simple & complex partial
seizures.
Mechanism of Action
Topiramate is a sulfamate-substituted monosaccharide. It acts by blocking
voltage-dependent sodium channels; augmenting the activity of ?-
aminobutyric acid (GABA) at GABA-A receptor; antagonising AMPA gluta-
mate receptors; and inhibiting carbonic anhydrase.
Absorption: peak plasma concentrations after 2 hr. Bioavailability unaffected
by food.
Distribution: Protein-binding: 9-17%. Volume of distribution in man is double
that in woman. Crosses the placenta, distributed into breast milk.
Metabolism: Not extensively metabolised.
Excretion: Excreted by urine (as unchanged drug and metabolites); elimination
half-
life: 21 hr. Children has a higher clearance and shorter elimination half-life than
adults.
Dosage
Oral
Adjunct for seizures associated with the Lennox-gastaut syndrome
Adult: Initially, 25 mg at night for 1 wk, thereafter increase in steps of 25-50 mg
at intervals of 1-2 wk until effective dose is achieved. Doses >25 mg/day should
be taken in 2 divided doses. Usual dose: 200-400 mg daily. Max: 800 mg daily.
Child: 2-16 yr: Initially, 25 mg nightly for the 1st wk increased at intervals of 1-2
wk by increments of 1-3 mg/kg daily according to response. Daily doses of >25
mg should be taken in 2 divided doses. Usual dose: 5-9 mg/kg daily. Max: 30
mg/kg/ day.
Hepatic impairment: Dosage adjustment may be needed.
Oral
Epilepsy
312 Neurological Disorders - A Handbook for Family Physicians

Adult: Monotherapy: Initially, 25 mg at night for 1 wk, thereafter increase in

steps of 25-50 mg at intervals of 1-2 wk. Doses >25 mg/day should be taken in 2
divided doses. Usual dose: 100-400 mg daily. Max: 400 mg daily. Adjunctive
treatment: Initially, 25 mg at night for 1 wk, thereafter increase in steps of 25-50
mg at intervals of 1-2 wk until effective dose is achieved. Doses >25 mg/day
should be taken in 2 divided doses. Usual dose: 200-400 mg daily. Max: 800 mg
daily.
Child: 10-16 yr: Initially, 0.5-1 mg/kg at night for the 1st wk, increased at inter-
vals of 1-2 wk by increments of 0.5 to 1 mg/kg daily. Usual dose: 3-6 mg/kg
daily. Daily doses >25 mg should be taken in 2 divided doses. Max: 16
mg/kg/day.
Hepatic impairment: Dosage adjustment may be needed.
Oral
Indications- adjunctive treatment of partial seizures,with or without secondary
generalisation. primary generalised tonic clonic seizures.
Contraindications : lactation
Special precautions should be taken in cases of renal or hepatic impairment,
pregnancy. Drug may impair ability to drive or operate machinery. Adequate
hydration should be maintained to reduce the risk of renal calculi especially in
predisposed patients. Abrupt withdrawal should be avoided; decrease dose by
100 mg daily at weekly intervals.
Side effects : weight los,impaired cognition & memory,confusion,mood disor-
ders, dizziness, drowsiness, fatigue, migraine, visual disturbances,
oligohidrosis, hyperthermia and hyperammonaemic encephalopathy.
GABA analogs
Gabapentin- used as an adjunctive medication to control partial seizures (effec-
tive when added to other antiseizure drugs). Gabapentin is well tolerated in
most patients, has a relatively mild side-effect prole, and passes through the
body unmetabolized.
Mechanism of Action
Gabapentin is structurally related to the neurotransmitter GABA but is neither a
GABA agonist nor antagonist. High afnity gabapentin binding sites are located
throughout the brain. These sites correspond to the presence of voltage-gated
Ca channels particularly controlling the ?-2/?-1 subunit. This channel appears
to be located presynaptically and may modulate the release of excitatory
neurotransmitters which participate in epileptogenesis and nociception.
Neurological Disorders - A Handbook for Family Physicians 313

Absorption: Absorbed from the GI tract. Bioavailability may be increased w/

food esp high-fat meals. Time to peak plasma concentration: W/in 2-3 hr; 5 hr in
fasting state and 7.3 hr (as enacarbil).
Distribution: Enters breast milk. Volume of distribution: 58 ± 6 L. Plasma
protein
binding: <3%.
Metabolism: As enacarbil: Undergoes extensive rst-pass metabolism mainly
in enterocytes and liver (to a lesser extent) to form gabapentin, CO2,
acetaldehyde and isobutyric acid.
Excretion: Via urine (as unchanged drug) and the remainder in the faeces.
Elimination
half-life: Approx 5-7 hr.
Dosage
Oral
Epilepsy
Adult: Initially, 300 mg on the 1st day, 300 mg bid on the 2nd day and 300 mg tid
on the 3rd day. Thereafter, may increase dose until effective antiepileptic control
is achieved. Usual maintenance range: 0.9-3.6 g daily; daily dose to be taken in 3
equally divided doses and max dosing interval: 12 hr. Max: 4.8 g daily.
Child: 6 yr Initially, 10-15 mg/kg daily, titrated over a period of approx 3 days
until effective antiepileptic control is achieved, usually w/in 25-35 mg/kg daily
in 3 divided doses w/ max interval of 12 hr. Max: 50 mg/kg daily.
Renal impairment: Haemodialysis: Loading dose: 300-400 mg followed by 200-
300 mg after each 4 hr of haemodialysis.
CrCl (ml/min): <15: 300 mg on alternate days to 300 mg daily, 15-29: 300 mg on
alternate days to 600 mg daily, 30-49: 300-900 mg daily, 50-79: 600-1,800 mg
daily.
Oral
Indications: epilepsy, neuropathic pain
Special precautions should be taken in patients with mixed seizures including
absences, renal impairment undergoing haemodialysis, children, pregnancy
and lactation. To discontinue therapy if acute pancreatitis develops. Abrupt
withdrawal may cause rebound seizures. Drug impairs the ability to drive or
operate machinery
314 Neurological Disorders - A Handbook for Family Physicians

Side effects
Somnolence/sedation, blood glucose uctuation, , elevated creatine kinase and
LFTs, jaundice, fever, hyponatraemia, movement disorder, Stevens-Johnson
syndrome, pneumonia, viral and respiratory infection, otitis media, leucopenia,
anorexia, behavioral disturbances; dizziness, ataxia, convulsions, hyperkine-
sias, dysarthria, amnesia, tremor, insomnia, headache, amblyopia, diplopia,
vertigo, dry mouth or throat, atulence, dental abnormalities, hypersensitivity,
musculoskeletal pain, twitching, impotence, decreased WBC.
Succinimides
Ethosuximide
It is a succinimide anticonvulsant, used mainly in absence seizures.
Mechanism of action
It binds to T-type voltage sensitive calcium channels and blocks them.
Distribution : Widely distributed throughout the body, but not signicantly
bound to plasma proteins.
Metabolism : Extensively hydroxylated in the liver to its principal metabolite
which is inactive.
Excretion : Excreted in the urine mainly as metabolite, either free or conjugated.
Dosage
Oral
Absence seizures
Adult: Initially, 500 mg daily, may increase in steps of 250 mg at intervals of 4-7
days. Usual dose: 1-1.5 g daily. Optimum plasma concentration: 40-100 mg/L
(300-700 micromol/L). Max: Up to 2 g in some patients. Strict supervision is
recommended if dose >1.5 g daily.
Child: <6 yr: Initially, 250 mg daily, may increase gradually to usual dose of 20
mg/kg daily. 6 yr: Initially, 500 mg daily, may increase in steps of 250 mg at
intervals of 4-7 days. Usual dose: 1-1.5 g daily. Max: <6 yr: Up to 1 g/day and ?6
yr: 2 g/day .
Max Dosage:
Indications: absence (petite mal) seizures; ineffective in partial seizures with
complex symptomatology or tonic-clonic seizures.
Contraindications: Hypersensitivity, pregnancy and lactation.
Neurological Disorders - A Handbook for Family Physicians 315

Side effects: Blood toxicities and disorders; headache, fatigue, lethargy, drowsi-
ness, dizziness, ataxia, hiccup and mild euphoria; more rarely, psychotic states,
rashes, hepatic and renal changes, SLE, erythema multiforme. Gum hypertro-
phy, irritability, hyperactivity, sleep disturbances, night terrors, inability to
concentrate, aggressiveness, increased libido, myopia.
Special Precautions: Hepatic or renal impairment, porphyria. Complete blood
cell count, liver function tests, and urinalysis should be performed periodically.
Drug increase the risk of grand mal seizures when used alone in mixed types of
epilepsy. Avoid sudden withdrawal. May impair ability to drive or operate
machinery.
Clobazam
Mechanism of action
Clobazam binds to one or more specic GABA receptors at several sites within
the CNS. Increased permeability of neuronal membrane to chloride ions results
in GABA's inhibitory effect leading to hyperpolarisation and stabilisation.
Absorption: peak plasma concentrations after 1-4 hr.
Distribution: Rapidly crosses the blood-brain barrier. Protein-binding: 85%.
Metabolism: Hepatic by demethylation and hydroxylation.
Excretion: Urine (as unchanged drug and metabolites); 18-42 hr (elimination
half-life).
Dosage
Oral
Short- term management of anxiety, Adjunct in epilepsy
Adult: 20-30 mg as a single dose at night or as daily divided doses, increased to
60 mg/day in severe conditions.
Child: 3-12 yr: 125 mcg/kg bid increased every 5 days. Usual maintenance dose:
250 mcg/kg bid. Max: 500 mcg/kg bid.
Elderly: or debilitated patients: 10-20 mg daily.
Hepatic impairment: Dose adjustment may be needed.
Indications- typical or atypical absence seizures,in those who have myoclonic
jerks and secondary generalised tonic/clonic seizure.
Contraindications: Hypersensitivity; history of drug dependence; myasthaenia
316 Neurological Disorders - A Handbook for Family Physicians

gravis; pregnancy (1st trimester), lactation; serious liver damage; sleep apnoea
syndrome; impaired respiratory function.
Side effects: dizziness, ne tremors; worsening of respiratory symptoms in
predisposed individuals; ataxia, drowsiness, headache, confusion; loss of
libido, motor dysfunction; dependence; visual disturbances and weight gain.
Felbamate:
Trade name : Felbatol
Principle seizure type: focal onset, tonic-clonic, LGS
Dose : 2400-3600 mg/day
Half life : 16-22 hrs
Adverse events:
Dizziness, sedation, Headache, aplastic anaemia, hepatic failure, weight loss
Drug interaction : no known drug interactions
Lacosamide:
Trade name : Vimpat, Lacoset
Principle seizure type: focal onset
Dose : 200-400 mg/day
Half life : 13 hrs
Adverse events:
Dizziness, ataxia, diplopia, vertigo GI irritation, PR interval prolongation
Drug interaction : levels are decreased by enzyme inducing agents
Runamide :
Trade name : Benzel
Principle seizure type: Lennox-Gastaut syndrome
Dose : 3200 mg/day, 45 mg/kg
Half life : 2-5 hrs
Adverse events:
Psychomotor slowing, sedation, speech and language problems, fatigue,
paresthesias, renal stones, glaucoma, weight loss, hypohydrosis.
Neurological Disorders - A Handbook for Family Physicians 317

Drug interaction : levels are decreased by enzyme inducing agents

Tiagabine :
Trade name : Gabitril
Principle seizure type: focal onset
Dose : 32-36 mg/day,
Half life : 20 hrs
Adverse events:
Confusion, depression, sedation, speech and language problems, dizziness,
paresthesias, psychosis GI irritation
Drug interaction : levels are decreased by enzyme inducing agents
Zonisamide :
Trade name : Zonegran
Principle seizure type: Focal onset, tonic-clonic
Dose : 200-400 mg/day,
Half life : 50-68 hrs
Adverse events:
Confusion, sedation, headache, psychosis, anorexia, renal stones, hypohydrosis
Drug interaction : levels are decreased by enzyme inducing agents
Ezogabine:
Trade name : Potiga
Principle seizure type: focal onset
Dose : 800-1200 mg/day
Half life : 7-11 hrs
Adverse events:
Dizziness, fatigue, sedation, confusion, vertigo, tremors, retinal abnormalities,
skin discoloration, QT prolongation, urinary retention.
Drug interaction : levels are decreased by enzyme inducing agents
318 Neurological Disorders - A Handbook for Family Physicians

40

Analgesics
An analgesic (commonly known as a painkiller) is any member of the diverse
group of drugs used to relieve pain. Analgesic drugs act in various ways on the
peripheral and central nervous system; they include paracetamol
(acetaminophen), the nonsteroidal anti-inammatory drugs (NSAIDs) such as
salicylates (like aspirin), acetic acid derivatives like diclofenac, narcotic drugs
such as morphine, synthetic drugs with narcotic properties such as tramadol,
and various others. Some other classes of drugs not normally considered
analgesics are used to treat neuropathic pain syndromes; these include tricyclic
antidepressants and anticonvulsants.
Paracetamol
Mechanism of action
Paracetamol exhibits analgesic action by peripheral blockage of pain impulse
generation. It has good antipyretic activity. Its weak anti-inammatory activity
is related to inhibition of prostaglandin synthesis in the CNS.
Onset: Oral: <1 hr. IV: 5-10 min (analgesia); w/in 30 min (antipyretic).
Duration: 4-6 hr (analgesia). IV: 6 hr (antipyretic).
Absorption: Time to peak plasma concentration: Approx. 10-60 min (oral).
Distribution: Distributed into most body tissues; crosses the placenta and
enters breast milk. Plasma protein binding: Approx. 25%.
Metabolism: Hepatic via glucuronic and sulfuric acid conjugation. N-acetyl-p-
benzoquinoneimine (minor hydroxylated metabolite), is usually produced in
very small amounts by CYP2E1 and CYP3A4 isoenzymes in the liver and
kidneys.
Neurological Disorders - A Handbook for Family Physicians 319

Excretion: Mainly via urine (as glucuronide and sulfate conjugates, <5% as
unchanged drug). Elimination half-life: Approx. 1-3 hr.
Dosage
Oral
Mild to moderate pain and fever
Adult: 0.5-1 g 4-6 hrly. Max: 4 g daily.
Child: 3 to <6 mth 60 mg; 6 mth to <2 yr 120 mg; 2 to <4 yr 180 mg; 4 to <6 yr 240
mg; 6 to <8 yr 240 or 250 mg; 8 to <10 yr 360 or 375 mg; 10 to <12 yr 480 or 500 mg;
12-16 yr 480 or 750 mg. Given 4-6 hrly if necessary. Max: 4 doses in 24 hr.
Intravenous
Mild to moderate pain and fever
Adult: 33-50 kg: 15 mg/kg as a single dose, at least 4 hrly. Max: 60 mg/kg (up to
3 g) daily; >50 kg: 1 g as a single dose, at least 4 hrly. Max: 4 g daily. Admin by
infusion over 15 min.
Child: <10 kg: 7.5 mg/kg as a single dose, at least 4 hrly. Max: 30 mg/kg daily;
10-33 kg: 15 mg/kg as a single dose, at least 4 hrly. Max: 60 mg/kg (up to 2 g)
daily; >33-50 kg: 15 mg/kg as a single dose, at least 4 hrly. Max: 60 mg/kg (up to
3 g) daily. Admin by infusion over 15 min.
Renal impairment: CrCl (ml/min);- ≤ 30: Increase dosing interval to 6 hrly
Hepatic impairment : Max: 3 g/day.
Rectal
Mild to moderate pain and fever
Adult: As supp: 0.5-1 g 4-6 hrly. Max: 4 g daily.
Child: 3 mth to <1 yr 60-125 mg; 1 to <5 yr 125-250 mg; 5-<12 yr 250-500 mg.
Given 4-6 hrly if necessary, up to 4 times daily.
Side effects: thrombocytopenia, leucopenia, pancytopenia, neutropenia,
agranulocytosis, rarely, hypotension and tachycardia.
Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalised
exanthematous pustulosis, acute renal tubular necrosis and hepatotoxicity
could be fatal complications.
NSAIDS
320 Neurological Disorders - A Handbook for Family Physicians

Mechanism of action
NSAIDS inhibit cyclooxygenase, leading to a decrease in prostaglandin produc-
tion; this reduces pain and inammation.
Diclofenac Sodium
Dosage: 100-150mg daily in 2-3 divided doses
Indications: headache, migraine, rheumatoid arthritis, osteoarthritis, tooth-
ache, tendonitis postoperative pain etc.
Contraindications: active or recurrent peptic ulcers, hypersensitivity, asthma
Special precaution: patients having history of GI bleeding, haematemesis or
malena, ulcerative colitis, retention of uid
Side effects : epigastric pain, sodium and water retention (use its potassium salt
in hypertensive patients)
Aceclofenac
Dosage : 100mg orally bd. Dosage reduction to be considered in hepatic impair-
ment
Indications : for pain relief and inammation
Contraindications : moderate to severe renal impairment; pregnancy (3rd
trimester); history of peptic ulceration or GI bleed; patients with infections.
Special precautions : Cautiously administer to patients with GI disease, ulcer-
ative colitis, Crohn's disease, haematological abnormalities, hepatic porphyria;
history of bronchial asthma; history of heart failure or hypertension; mild renal,
hepatic or cardiac impairment. May impair ability to drive or operate machin-
ery.
Side effects : dizziness, nephrotoxicity; blood dyscrasias could be fatal.
Opiates and Morphinomimetics
Morphine, the archetypal opioid, and various other substances (e.g. Codeine,
oxycodone, hydrocodone, diamorphine, pethidine) all exert a similar inuence
on the cerebral opioid receptor system. Tramadol and buprenorphine are
thought to be partial agonists of the opioid receptors. Dosing of all opioids may
be limited by opioid toxicity (confusion, myoclonic jerks and pinpoint pupils),
but there is no dose ceiling in patients who tolerate this.
Mechanism of action
Neurological Disorders - A Handbook for Family Physicians 321

Morphine is a phenanthrene derivative which acts mainly on the CNS and

smooth muscles. It binds to opiate receptors in the CNS altering pain perception
and response. Analgesia is thought to be due to its action at the mu-1 receptors.
Onset: Approx 30 min (conventional tab); 5-10 min (IV).
Duration: 4 hr (conventional tab); 8-24 hr (extended-release tab/cap).
Distribution: Distributed throughout the body mainly in the kidneys, liver,
lungs and spleen, w/ lower concentrations in the brain and muscles. Crosses the
blood-brain barrier and placenta; enters breast milk. Volume of distribution: 1-6
L/kg. Plasma protein binding: Approx 35%.
Metabolism: Metabolised in the liver and gut via glucuronidation to produce
morphine-3-glucoronide and morphine-6-glucoronide; undergoes extensive
rst-pass metabolism.
Excretion: Via urine (approx 90%) and through the bile into the faeces (10%)
mainly as conjugates. Mean plasma elimination half-life: Approx 2 hr (mor-
phine); 2.4-6.7 hr (morphine-3-glucoronide).
Dosage
Oral
Moderate to severe pain
Adult : 5-20 mg 4 hrly. Extended-release: 5-20 mg 12 hrly. Dosage is dependent
on the severity of pain.
Child : 3-5 yr 5 mg 4 hrly; 6-12 yr 5-10 mg 4 hrly.
Hepatic impairment : Dosage may need to be reduced.
Parenteral
Moderate to severe pain
Adult: IM/SC: 5-20 mg; 2.5-10 mg via slow IV inj over 4-5 min w/ patient in
recumbent position or a starting dose of 1-2 mg/hr via continuous IV infusion
(max: 100 mg/ day; 4 g/day in cancer patients). Doses may be adjusted accord-
ing to severity of pain and patient's response.
Hepatic impairment: Dosage may need to be reduced.
Rectal
Severe pain
Adult : 10-20 mg 4 hrly. Dosage may be increased as required.
322 Neurological Disorders - A Handbook for Family Physicians

Intraspinal or intrathecal administration could be done in cases of severe pain.

This should be done by a pain management specialist, a neurosurgeon or a
anaesthesiologist.
Contraindications: Respiratory depression, obstructive airway disease,
delayed gastric emptying, heart failure, chronic lung disease, known or sus-
pected paralytic ileus, phaeochromocytoma. It is also contraindicated in
undiagnosed acute abdomen (as it may worsen biliary colic/spasm) and in head
injury. Concurrent administration with MAOI or within 2 weeks after treat-
ment.
Side-effects : anorexia, taste disturbance, dyspepsia, respiratory depression,
sedation, dizziness, confusion, insomnia, headache, somnolence, involuntary
muscle contractions, hyperhidrosis, asthenic conditions, HTN, bronchospasm,
seizures, amenorrhoea, rhabdomyolysis, nystagmus.
Gradual tapering of the dose is required to avoid withdrawal symptoms.
Specic agents
In patients with chronic or neuropathic pain, various other substances may have
analgesic properties. Tricyclic antidepressants, especially amitriptyline, have
been shown to improve pain in what appears to be a central manner. The exact
mechanism of carbamazepine, gabapentin and pregabalin is similarly unclear,
but these anticonvulsants are used to treat neuropathic pain.
Amitriptyline
Mechanism of action
Amitriptyline is a dibenzocycloheptadiene tricyclic antidepressant. It increases
synaptic concentration of serotonin and/or norepinephrine in the CNS by
blocking the neuronal reuptake of norepinephrine and serotonin.
Absorption: Time to peak plasma concentration: Approx 6 hr.
Distribution: Crosses the placenta and is distributed into breast milk.
Volume of distribution: Approx 18-22 L/kg. Extensively bound to plasma
protein.
Metabolism: Undergoes extensive rst-pass metabolism and is demethylated
hepatically by CYP3A4, CYP2C9 and CYP2D6 isoenzymes to nortriptyline
(active metabolite). Other paths involve hydroxylation by CYP2D6 and N-
oxidation.
Excretion: Via urine (mainly as metabolites, either free or conjugated). Elimina-
tion half-life: Approx 9-25 hr.
Neurological Disorders - A Handbook for Family Physicians 323

Dosage
Oral
Adult: Initially, 50-75 mg/day as a single dose (at bedtime) or in divided doses,
may increase gradually to 150 mg/day. Max: 300 mg/day in severe depression.
Child: Adolescent: Initially, 25-50 mg/day as a single dose (at bedtime) or in
divided doses.
Elderly: Initially, 25-50 mg/day as a single dose (at bedtime) or in divided
doses.
Contraindications: Recent MI, arrhythmias (particularly heart block), mania.
Concomitant use with MAOI or within 14 days of discontinuing the MAOI;
linezolid, IV methylene blue.
Side effects
Hypotension, HTN, tachycardia, palpitation, MI, arrhythmias, heart block,
stroke, changes in AV conduction and ECG, confusion, paraesthesia;
incoordination, dysarthria, extrapyramidal symptoms (e.g. tardive dyskinesia);
seizures; tinnitus, dry mouth, blurred vision, paralytic ileus, hyperpyrexia,
urinary retention, bone-marrow depression including agranulocytosis,
eosinophilia, leucopenia, thrombocytopenia, fatigue, headache, parotid swell-
ing, alopecia. Gynaecomastia and galactorrhoea, impotence and altered liver
function.
Pregabalin
Mechanism of action
Pregabalin is an analog of the neurotransmitter GABA. It binds to the ?2-?
subunit resulting in modulation of Calcium channels and reduction in the
release of several neurotransmitters, including glutamate, norepinephrine,
serotonin, dopamine, calcitonin gene-related peptide and substance P.
Absorption: Time to peak plasma concentration: W/in 1.5 hr.
Distribution: Volume of distribution: 0.5 L/kg. Not bound to plasma protein.
Metabolism: Negligible metabolism.
Excretion: Via urine (approx 98%) as unchanged drug). Elimination half-life: 6.3 hr.
Dosage
Oral
324 Neurological Disorders - A Handbook for Family Physicians

Neuropathic pain
Adult: Initially, 150 mg/day, may increase to 300 mg/day after 3-7 days. Max:
600 mg/day after a 7-day interval. All doses to be given in 2 or 3 divided doses.
Renal impairment: Dose adjustment required in renal impairment CrCl
(ml/min): - 30 to <60: 75 mg/day. Max: 300 mg/day. All doses to be given in 2 or
3 divided doses, 15 to <30: Initially, 25-50 mg/day. Max: 150 mg/day. All doses
to be given as a single dose or in 2 divided doses, <15: Initially, 25 mg/day. Max:
75 mg/day. All doses to be given as a single dose.
Side effects: Somnolence, dizziness, blurred vision, muscle cramp, insomnia,
amnesia, paraesthesia, increased appetite, wt gain, euphoria, confusion,
reduced libido, erectile dysfunction; attention, memory, coordination and gait
disturbances; fall, feeling drunk, abnormal feeling. Rarely, Stevens-Johnson
syndrome, rhabdomyolysis, breast enlargement, gynaecomastia.
Potentially Fatal : Angioedema.
Carbamazepine is also used in treatment of Trigeminal neuralgia
Dosage
Adult: Initially, 100 mg once or bid gradually increased as necessary. Mainte-
nance: 400-800 mg daily in 2-4 divided doses. Max: 1.2 g daily.
Gabapentin
Neuropathic pain
Adult: Initially, 300 mg on the 1st day, 300 mg bid on the 2nd day and 300 mg tid
on the 3rd day; alternatively, 900 mg daily in 3 divided doses. Dose may increase
in increments of 300 mg every 2-3 days. Max: 3,600 mg daily.
Renal impairment: Haemodialysis: Loading dose: 300-400 mg followed by 200-
300 mg after each 4 hr of haemodialysis.
CrCl (ml/min): <15: 300 mg on alternate days to 300 mg daily, 15-29: 300 mg on
alternate days to 600 mg daily, 30-49: 300-900 mg daily, 50-79: 600-1,800 mg
daily.
Oral
Postherpetic neuralgia
Adult: As gabapentin enacarbil: Modied-release preparation: Initially, 600 mg
in the morning for 3 days, then increased to 600 mg bid.
Neurological Disorders - A Handbook for Family Physicians 325

Renal impairment: As gabapentin enacarbil: Modied-release preparation:

Haemodialysis: 300 mg after each dialysis session, may increase to 600 mg if
needed.
CrCl (ml/min): - <15: 300 mg in the morning on alternate days, may increase to
300 mg daily in the morning., 15-29: 300 mg in the morning on days 1 and 3
followed by 300 mg daily in the morning, may increase to 300 mg bid., 30-59: 300
mg in the morning for the 1st 3 days followed by 300 mg bid, may increase to 600
mg bid.
Combinations
Analgesics are frequently used in combination, such as the paracetamol and
codeine preparations found in many non-prescription pain relievers. They can
also be found in combination with vasoconstrictor drugs such as
pseudoephedrine for sinus-related patients.the use of paracetamol, as well as
aspirin, ibuprofen, naproxen, and other nsaids concurrently with weak to mid-
range opiates has been shown to have benecial effects.
Topical
Topical analgesia is generally recommended to avoid systemic side-effects.
Painful joints, for example, may be treated with an ibuprofen- or diclofenac-
containing gel. Lidocaine and steroids may be injected into painful joints for
longer-term pain relief.
Atypical and/or adjuvant analgesics
Orphenadrine, cyclobenzaprine, scopolamine, atropine, gabapentin, rst-
generation antidepressants and other drugs possessing anticholinergic and/or
antispasmodic properties are used in many cases along with analgesics to
potentiate centrally acting analgesics such as opioids when used against pain
especially of neuropathic origin and to and modulate the effects of many other
types of analgesics by action in the parasympathetic nervous system.
Ibuprofen, naproxen
Indication : analgesic, antipyretic, musculo skeletal disorders.
Dosage : ibuprofen 200-600 mg thrice daily naproxen-250 mg twice daily
Contraindication : pregnancy, active peptic ulcer, gi bleeding, lactation
Special precaution : asthma, bleeding tendencies, cardiovascular disorder
Side effect : jaundice,thrombocytopenia
326 Neurological Disorders - A Handbook for Family Physicians

41

Drugs for Migraine

Migraine treatment depends on the duration and severity of pain, associated
symptoms, degree of disability, and initial response to therapy. Drugs can be
used to decrease the frequency/ intensity of migraine. Many of these have
actions in the serotonergic system.
Propanolol
Mechanism of action
Propranolol inhibits the norepinephrine transporter and stimulates
norepinephrine release.It causes vasodilation, leading to improved blood
supply to the brain and relief of headache and migraine.
Dosage
Prophylaxis of migraine
Adult: As conventional tab or oral soln: Initially, 40 mg bid or tid. Usual range:
120-240 mg/day. As extended release cap: 80 mg once daily, may be increased to
160 mg once daily. Max: 240 mg/day.
Child: As conventional tab or oral soln: ?12 yr 10-20 mg bid or tid. >12 yr
Initially, 40 mg bid or tid increased at weekly intervals up to 160 mg/day. Max:
240 mg/day.
Hepatic impairment: Severe: 20 mg tid.
Contraindications :
Sinus bradycardia, cardiogenic shock, sick sinus syndrome, Raynaud's
syndrome, 2nd and 3rd degree heart block, overt CHF, bronchial asthma,
COPD, untreated phaeochromocytoma, Prinzmetal's angina; severe peripheral
Neurological Disorders - A Handbook for Family Physicians 327

arterial disease, metabolic acidosis. Concomitant use with thioridazine.

Side effects :
Bradycardia, hypotension, syncope, shock, angina pectoris. giddiness, ataxia,
dizziness, irritability, sleepiness, hearing loss, and visual disturbances to vivid
dreams, hallucinations, and confusion. Hypoglycaemia, transient eosinophilia,
thrombocytopenic and nonthrombocytopenic purpura; elevated levels of K,
transaminases, and BUN. Rarely, Peyronie's disease and dry eyes.
Flunarizine
Mechanism of action:
Flunarizine has H1-receptor blocking action and calcium-channel blocking
effect.
Distribution: Highly lipophilic. Protein-binding: >90%.
Metabolism: Extensive.
Excretion: Via bile (as metabolites); 18 days (elimination half-life).
Dosage
Oral
Adult: 5-10 mg daily at bedtime.
Contraindications: Pregnancy, lactation, GI or urinary tract obstruction, acute
porphyrias.
Side effects : Drowsiness, headache, depression, insomnia, extrapyramidal
reactions, galactorrhoea.
Prophylaxis treatment:
Beta-adrenergic blockers: propronolol- starting with 40 mg bd may be increased
to 160mg if required.
Calcium channel blockers: verapamil, unarizine 5rmg od
Treatment of acute attack:
For mild to moderate migraine attacks or severe attacks that have been respon-
sive in the past to similar agents, use the following options:
NSAIDS (oral)
Combination analgesics containing caffeine
328 Neurological Disorders - A Handbook for Family Physicians

Isometheptene combinations
For moderate to severe migraine or mild to moderate migraines that respond
poorly to nsaids, use:
Migraine-specic drugs (i.e., triptans [naratriptan, rizatriptan, sumatriptan,
zolmitriptan], dhe)
Or
Combination drug therapy (e.g., aspirin plus acetaminophen* plus caffeine)
Or
Other drugs such as ergotamine
For migraine accompanied by nausea or vomiting, use a non-oral route of
administration.
Sumatriptan
Mechanism of action
Sumatriptan is a selective serotonin agonist that acts at 5-HT1 receptors. It
causes vasoconstriction of cranial arteries and inhibition of neurogenic inam-
matory processes in the CNS.
Onset: Oral: 30 min; Intranasal: 15 min; subcutaneous: 10-15 min.
Absorption: peak plasma concentrations reached in 2 hr (oral), 25 min (subcuta-
neous), 1.5 hr (intranasal).
Distribution: Enters breast milk. Protein-binding: 14-21%
Metabolism: Extensive rst-pass metabolism by MAO type A
Excretion: Mainly via urine (as inactive indole acetic acid derivative and its
glucuronide), via faeces (as unchanged drug and metabolites). Elimination half-
life: 2hr.
Dosage
Oral
Migraine
Adult: >18 yr: 50-100 mg repeated at 2-hr intervals if migraine recurs. Max: 300
mg/ 24 hr.
Hepatic impairment: Max single dose: 50 mg.
Neurological Disorders - A Handbook for Family Physicians 329

Nasal
Migraine
Adult: 12-17 yr: 10 mg into 1 nostril, repeated at least 2 hr after the 1st dose if
symptoms recur. Max: 20 mg/24 hr. >18 yr: 20 mg into 1 nostril, repeated at least
2 hr after the 1st dose if symptoms recur. Max: 40 mg/24 hr.
Hepatic impairment: Dose reduction needed.
Subcutaneous
Migraine
Adult: >18 yr: 6 mg as a single dose inj, repeated at least 1 hr after the 1st dose if
symptoms persist. Max: 12 mg/24 hr.
Hepatic impairment: Dose reduction needed.
Subcutaneous
Cluster headache
Adult: >18 yr: 6 mg as a single dose inj, repeated at least 1 hr after the 1st dose if
symptoms persist. Max: 12 mg/24 hr.
Hepatic impairment: Dose reduction needed.
Indications- migraine, cluster headache.
Contraindications - Not to be used prophylactically and in patients with basilar
or hemiplegic or ophthalmoplegic migraine. History of MI or stroke, severe
hepatic impairment, ischaemic heart disease, uncontrolled hypertension,
peripheral vascular disease, hypersensitivity to sulphonamides, not to be used
alongwith or within 24 hrs of using ergot alkaloids or any other triptan.
Special precaution- paediatrics,pregnancy,lactation not recommended, IHD,
hepatic impairment.
Side effects - Transient hypertension, hypotension, dizziness, ushing, fatigue,
drowsiness, weakness, seizures, heat, tightness in any part of body,
paraesthesia, seizures, irritation of nasal mucosa and epistaxis. Rebound head-
ache with frequent use.
Potentially Fatal: Cardiac arrhythmias, MI.\
Sodium Valproate
Dosage
330 Neurological Disorders - A Handbook for Family Physicians

Oral
Prophylaxis of migraine
Adult: Initially, 250 mg bid. Max: 1 g/day; extended release: 500 mg once daily
for 7 days then increase to 1 g once daily. Usual range: 500-1000 mg/day.
Elderly: Initiate at lower dose and increase slowly.
Hepatic impairment: Contraindicated
Topiramate
Prophylaxis of migraine
Adult: >16 yr: Initially 25 mg daily at night for 1 wk, increased in steps of 25-mg
at wkly intervals. Usual dose: 50-100 mg daily in 2 divided doses. Daily doses
>25 mg should be taken in 2 divided doses.
Hepatic impairment: Dosage adjustment may be needed.
Neurological Disorders - A Handbook for Family Physicians 331

42

Drugs for Stroke

Aspirin
It is acetylsalicylic acid
Mechanism of action
It inhibits cyclooxygenase, which is responsible for the synthesis of
prostaglandin and thromboxane. It also inhibits platelet aggregation.
Duration: 4-6 hr.
Absorption: Peak plasma concentrations after 1-2 hr.
Distribution: Widely distributed; crosses the placenta; enters breast milk.
Protein-
binding: 80-90%.
Metabolism: Hepatic; converted to metabolites.
Excretion: Via urine by glomerular ltration, active renal tubular secretion and
passive tubular reabsorption (as unchanged drug); via haemodialysis; 15-20
minutes (elimination half-life, parent drug).
Dosage - post stoke patients-50- 350mg daily depending upon the age.
Contraindications - peptic ulcer, liver disease, bleeding tendencies, pregnancy
(3rd trimester), children <12 yr, patients with haemophilia or haemorrhagic
disorders, gout, severe renal or hepatic impairment, lactation.
Side effects - tinnitus,vertigo, impairment of hearing & vision, excitement &
mental confusion, electrolyte imbalance. Reye's syndrome (children <12 yr).
Hepatotoxicity; CNS depression which may lead to coma; CV collapse and
332 Neurological Disorders - A Handbook for Family Physicians

respiratory failure; paroxysmal bronchospasm and dyspnoea.

Clopidogrel
Mechanism of action
Clopidogrel inhibits adenosine diphosphate (ADP) from binding to its receptor
sites on the platelets and subsequent activation of glycoprotein GP IIb/IIIa
complex thus preventing brinogen binding, platelet adhesion and
aggregation.
Distribution: Protein-binding: Extensive.
Metabolism: Hepatic: Extensive; converted to inactive carboxylic acid deriva-
tive and thiol derivative (active).
Excretion: Via urine and faeces (as metabolites and unchanged drug).
Dosage - prophylaxis of thromboembolic events 75 mg once daily.
Contraindications - Active pathological bleeding. Administration within 7
days after MI and ischaemic stroke, coagulation disorders, lactation.
Precautions - patients at risk of increased bleeding from trauma, surgery, or
other pathological conditions; ulcer; renal and hepatic impairment; history of
bleeding or haemostatic disorders.
Side effects - paraesthesia, vertigo, headache, dizziness.
Potentially Fatal: Bleeding disorders including GI and intracranial haemor-
rhage.
Blood dyscrasias.
Dipyridamole :
It is a relatively weak antiplatelet agent on its own, but an extended-release
formulation of dipyridamolle combined with low dose aspirin ( Aggrenox) is
available and is used for prevention of stroke in patients with TIAs.
It acts by inhibition of phosphodiesterase.
Dose : Aggrenox is given twice daily . it contains 200 mg dipyridamole and 25
mg aspirin.
Side effects: used with caution in patients with coronary artery disease as it may
cause coronary steal phenomenon due to its vasodilatory property.
Prasugrel:
Neurological Disorders - A Handbook for Family Physicians 333

Its a Thienopyridines like clopidogrel and acts by selectively inhibiting ADP

induced platelet aggregation. It is 10 fold more potent than clopidogrel.
Dose : Loading dose of 60 mg owed by 10 mg /day ( if weight <60 kg reduce
dose to 5mg/day)
Ticagrelor :
It is an orally active inhibitor of P2Y12. It produce reversible inhibition of ADP
receptor. It does not require metabolic activation.
Dose : Ticagrelor is initiated with loading dose of 180 mg followed by 90 mg
twice daily. While using with aspirin, daily aspirin dose should not exceed 100
mg.
Side effects :
Dyspepsia occurs in 15 % cases.
Statins
These are dyslipidemic drugs which are administered for controlling of
cholestrol, rosuvasatin and atorvastatin are commonly being used.
Atorvastatin
Mechanism of action
Atorvastatin inhibits HMG - CoA reductase, the enzyme that catalyses the
conversion of HMG-CoA to mevalonate. This results in the induction of the LDL
receptors and stimulation of LDL catabolism, leading to lowered LDL-
cholesterol levels.
Distribution : Volume of distribution: Approx 381 L. Plasma protein binding:
98%.
Metabolism: Metabolised by CYP3A4 isoenzyme to active ortho- and
parahydroxylated derivates and an inactive ?-oxidation product.
Excretion: Via faeces (as metabolites); urine (<2% as unchanged drug). Elimina-
tion
half-life: Approx 14 hr.
Dosage - 20 mg- 80 mg daily
Contraindications: Active liver disease or unexplained persistent elevations of
serum transaminases. Concomitant use w/ciclosporin, gembrozil, telaprevir,
tipranavir. Pregnancy and lactation.
334 Neurological Disorders - A Handbook for Family Physicians

Side effects - Headache, anorexia. Pain in extremity, musculoskeletal and

pharyngolaryngeal; myopathy, muscle spasms, myalgia, arthralgia,
nasopharyngitis, insomnia, UTI. Increased serum aminotransferase,
glycosylated haemoglobin and fasting serum glucose levels.
Potentially Fatal: Severe rhabdomyolysis w/ acute renal failure. Hepatitis,
pancreatitis. Rarely, Stevens-Johnson syndrome, anaphylaxis, toxic epidermal
necrolysis.
Rosuvastatin
Mechanism of action
Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase,
the rate-limiting enzyme in cholesterol synthesis. It increases the number of
hepatic LDL receptors on the cell surface, enhancing uptake and catabolism of
LDL. It also decreases apolipoprotein B, triglycerides and increases HDL.
Absorption: Time to peak plasma concentration: Approx 5 hr.
Distribution: Volume of distribution: 134 L. Plasma protein binding: Approx
90%.
Metabolism: Limited metabolism via CYP2C9 isoenzyme.
Excretion: Via faeces (approx 90%); urine (approx 5% as unchanged drug).
Elimination
half-life: Approx 19 hr.
Dosage - 20 mg- 80 mg daily
Contraindications: Active liver disease or unexplained persistent elevated
serum transaminases. Severe renal impairment. Concomitant use w/
ciclosporin and gembrozil. Pregnancy and lactation.
Side effects - Headache, dizziness, myalgia, chest pain, peripheral oedema,
depression, insomnia, rash, paraesthesia, asthenia, abnormal LFT, elevated
serum transaminase levels.
Potentially Fatal: Severe rhabdomyolysis w/ acute renal failure. Hepatitis,
pancreatitis.
Rare: Stevens-Johnson syndrome, anaphylaxis, toxic epidermal necrolysis.
Anticoagulants
Coumarins (Warfarin)
Neurological Disorders - A Handbook for Family Physicians 335

These are anticoagulants, antiplatelets & brinolytics (thrombolytics)

Mechanism of action – Warfarin inhibits synthesis of vit K-dependent coagula-
tion factors VII, IX, X and II and anticoagulant protein C and its cofactor protein
S. Extension of the clot can be prevented. Secondary embolic phenomena are
avoided.
Onset: 24 hr
Duration: 2-5 days.
Absorption: Peak plasma concentration: within rst 4 hr.
Distribution: Protein binding: Extensive (99%) to albumin. Crosses placenta.
Metabolism: Hepatic;
Excretion: Via urine (as metabolites after reabsorption from the bile); 37 hr
(elimination half-life).
Dosage
Oral
Treatment and prophylaxis of venous thromboembolism
Adult: Initially, 5 mg daily. Rapid anti-coagulation: Initially, 10 mg daily for 2
days.
Adjust subsequent doses based on PT/INR. Usual maintenance dose: 2-10 mg
daily.
Elderly: Lower initial dose.
Hepatic impairment: Severe: Avoid.
Containdications - haemorrhagic tendencies; recent surgery; peptic ulcer;
severe hypertension; senility; aneurysms; alcoholism; severe renal and hepatic
impairment; pregnancy.
Side effects - drop in haematocrit, purple toes syndrome, skin necrosis, hepatic
dysfunction, pancreatitis.
Potentially Fatal : Haemorrhage (narrow therapeutic index).
Low molecular weight heparin
Enoxaparin
Enoxaparin is a low molecular weight heparin w/ anticoagulant properties.
336 Neurological Disorders - A Handbook for Family Physicians

Mechanism of action
It acts by enhancing the inhibition rate of activated clotting factors including
thrombin and factor Xa through its action on antithrombin III.
Onset: 3-5 hr.
Duration: Approx 12 hr.
Absorption: Peak plasma concentrations: 1-5 hr.
Distribution: Volume of distribution: 4.3 L. Plasma protein binding: Does not
bind to heparin binding proteins.
Metabolism: Hepatically metabolised.
Excretion: Via urine (40% as unchanged drug; 10% as active metabolites).
Elimination.
half-life: Approx 4-5 hr.
Dosage
Acute stroke
1 mg/kg subcutaneously bid
Contraindications: Patients with active major bleeding, acute bacterial
endocarditis, recent haemorrhagic stroke, active gastric or duodenal ulceration,
thrombocytopenia.
Side effects : Haemorrhage (including at the inj site), peripheral or unspecied
oedema, anaemia, haematuria, ecchymosis, fever, confusion.
Potentially Fatal: Major haemorrhagic complications (e.g. retroperitoneal and
intracranial bleeding).
Neurological Disorders - A Handbook for Family Physicians 337

43

Muscle Relaxants and

Antispastic Drugs
Muscle Relaxants
Muscle relaxants are drugs which affect skeletal muscle function and decrease
the muscle tone. They are used to alleviate symptoms such as muscle spasms,
pain, and hyperreexia.
Some commonly used muscle relaxants are:
Chlorzoxazone
Mechanism of action
Chlorzoxazone inhibits multisynaptic areas at the level of the spinal cord and
subcortical areas of the brain. These areas are involved in producing and
maintaining skeletal muscle spasm of varied etiology. Thus it helps in relieving
painful muscle spasms.
Onset: 1 hr.
Duration: 3-4 hr.
Absorption: peak plasma concentrations after 1-2 hr.
Metabolism: Hepatic; yielding 6-hydroxychlorzoxazone.
Excretion: Via urine (mainly as glucuronide); 1 hr (elimination half-life).
Dosage
Oral
338 Neurological Disorders - A Handbook for Family Physicians

Painful muscle spasm associated with musculoskeletal conditions

Adult: Initially, 500 mg 3-4 times daily, may subsequently reduce to 250 mg 3-4
times daily. Max: 750 mg 3-4 times daily.
Indications: painful muscle spasms associated with musculoskeletal or
neuromuscular problems.
Contraindications: Liver disease. Porphyria. Lactation.
Special Precautions: Pregnancy. Tasks requiring mental alertness may be
impaired.
Monitor liver function while administering the drug.
Side effects: Drowsiness, dizziness, lightheadedness, headache, excitement,
restlessness, irritability, Jaundice, liver damage.
Serious side effects: Anaphylactoid reactions, angioedema, fatal hepatocellular
toxicity.
Methocarbamol
Methocarbamol is a centrally acting skeletal muscle relaxant.
Mechanism of action
Methocarbamol is involved in the inhibition of carbonic anhydrase and it is
known to cause general depression of the central nervous system. It is also
known to prolong muscle refractory period. Absorption: Peak plasma
concentration in 1-2 hr (oral).
Metabolism: Metabolised by dealkylation and hydroxylation.
Excretion: Via urine as metabolites and unchanged drug. 1-2 hr (elimination
half-life).
Dosage
Oral
Painful muscle spasm associated with musculoskeletal conditions.
Adult: Initially: 1.5 g 4 times daily, reduced according to response after 2-3 days.
Maintenance: 2.25-4 g daily in divided doses. Max dose 8 g daily.
Elderly: Dose may need to be reduced by half.
Intravenous
Neurological Disorders - A Handbook for Family Physicians 339

Painful muscle spasm associated with musculoskeletal conditions

Adult: 1 g administered by slow inj or infusion at a rate not faster than 300
mg/min. In cases where patients are not able to continue with oral therapy,
additional doses of 1 g every 8 hr may be used for up to 3 consecutive days. Max
3 g daily.
Elderly: Dose may need to be reduced by half.
Intramuscular
Painful muscle spasm associated with musculoskeletal conditions
Adult : Up to 500 mg into each gluteal region at intervals of 8 hr. In cases where
patients are not able to continue with oral therapy, additional doses of 1 g every
8 hr may be used for up to consecutive 3 days. Max 3 g daily.
Elderly: Dose may need to be reduced by half.
Intravenous
Tetanus
Adult: Initial total dose: 3 g with 1-2 g via direct inj at a rate of 300 mg/minute
and the remainder 1-2 g may be administered via infusion. Repeat infusion of 1-
2 g every 6 hr until a nasogastric tube can be inserted. Tablets may be crushed
and suspended in water or saline solutions and administered through the
nasogastric tube. Total oral dosage of up to 24 g daily may be needed.
Child: 15 mg/kg or 500 mg/m2 given by IV inj (suggested rate 180
mg/m2/min). Dose may be repeated every 6 hr if necessary by IV inj or infu-
sion. Max dose 1.8 g/ m2 daily for 3 consecutive days.
Indications: painful muscle spasms associated with musculoskeletal or
neuromuscular problems.
Contraindications: Coma or pre-coma states, brain damage, myasthenia gravis.
Do not admin parenteral solutions in patients with renal impairment, epilepsy
or history of epilepsy.
Special Precautions: Renal or hepatic impairment; acidosis. Pregnancy and
lactation.
May impair ability to drive or operate machinery. Children ?12 yr.
Side effects: anorexia, lassitude, drowsiness, dizziness, restlesness, anxiety,
confusion, fever, headache, blurred vision, convulsions; Parenteral: Flushing
and a metallic taste; incoordination, diplopia, nystagmus, vertigo; sloughing
and thrombophloebitis at the site of inj.
340 Neurological Disorders - A Handbook for Family Physicians

Serious side effects: Parenteral: Syncope, hypotension, bradycardia,

anaphylaxis.
Antispastic drugs
Antispastic drugs aid in improving muscle hypertonicity and involuntary jerks.
Following are commonly used antispastic drugs:
Baclofen
Baclofen is a gama -aminobutyric acid (GABA-B) agonist.
Mechanism of action
It inhibits both monosynaptic and polysynaptic reexes at spinal level.
Absorption: peak plasma conc after 1-3 hr.
Distribution: Blood-brain barrier, CSF (equivalent to 12% conc found in
plasma).
Protein- binding: 30%.
Metabolism: Hepatic (15% of the dose).
Excretion: Via urine (70-80% as unchanged drug); elimination half-life (Via
urine (70-80% as unchanged drug); elimination half-life (t1/2): 3-4 hr (plasma), 5
hr (CSF). 3-4 hr (plasma), 5 hr (CSF).
Dosage
Oral
Severe chronic spasticity
Adult: Initially, 5 mg tid for 3 days increased to 10 mg tid for 3 days, then in
similar increments and intervals until either 20 mg tid is reached or until desired
effect is obtained. Max: 100 mg daily.
Child: 0.75-2 mg/kg daily. May initiate with 2.5 mg 4 times daily, increased
gradually every 3 days until desired effect is obtained. Maintenance: 6-10 yr: 30-
60 mg daily; 2- 6 yr: 20-30 mg daily; 12 mth-2 yr: 10-20 mg daily. Max: >10 yr: 2.5
mg/kg daily.
Elderly: Initiate with lower doses.
Intrathecal administration may be done by a neurosurgeon or pain management
specialist in severe chronic spasticity.
Contraindications: Active peptic ulcer disease.
Neurological Disorders - A Handbook for Family Physicians 341

Special Precautions: Cerebrovascular disorders, epilepsy, severe psychotic

disorders, confusional states, history of peptic ulcer, respiratory depression,
diabetes (DM), hepatic or renal impairment, elderly, pregnancy. Avoid sudden
withdrawal.
Side effects: Sedation, drowsiness, ataxia, dizziness, headache, confusion,
hallucinations, enuresis.
Serious side effects: Respiratory or CV depression, seizures.
Tolperisone
Tolperisone is a centrally acting muscle relaxant.
Mechanism of action
It acts at the reticular formation in the brain stem by blocking voltage-gated
sodium and calcium channels.
Dosage
Oral
Spasticity, Muscle spasms
Adult : 50-150 mg tid.
Child : <6 yr: 5 mg/kg daily in 3 divided doses; 6-14 yr: 2-4 mg/kg daily in 3
divided doses.
Contraindications : Myasthenia gravis.
Side effects : Muscular weakness, headache, hypotension.
Tizanidine
Tizanidine is a centrally acting 2-agonist.
Mechanism of action
It exerts its antispastic effect by causing presynaptic inhibition of motor neuron
hyperactivity.
Absorption: peak plasma concentrations in 1-2 hr.
Distribution: Protein-binding: 30%. Elimination half-life: 2-4 hr.
Metabolism: Extensive hepatic rst-pass metabolism mainly via the
cytochrome P450 isoenzyme CYP1A2.
Excretion: Via urine (mainly as inactive metabolites).
342 Neurological Disorders - A Handbook for Family Physicians

Dosage
Oral
Spasticity
Adult: >18 yr: Initially, 2 mg once daily increased according to response by 2-mg
increments at intervals of at least 3-4 days up to 24 mg daily in 3-4 divided doses.
Max: 8 mg/dose. Max: 24 mg/day.
Elderly: Not recommended.
Renal impairment: Depending on creatine clearance- CrCl: <25 (ml/min)-
Initially, 2 mg once daily, gradually increasing the dose before increasing the
frequency of admin.
Hepatic impairment: Avoid or use with extreme caution.
Contraindications: Severe hepatic dysfunction.
Special Precautions: Hepatic or renal insufciency. Children, elderly, preg-
nancy and lactation. Monitor LFT regularly. Stop treatment if liver enzymes are
raised persistently >3 times upper limit of normal range. Avoid abrupt with-
drawal of therapy.
Side effects: Drowsiness, fatigue, dizziness, insomnia, headache, anxiety,
hypotension, bradycardia, muscle pain and weakness, transient increase in
serum transaminases, hallucinations.
Serious side effects : Hepatitis.
Botox
Botulinum toxin is a protein and neurotoxin produced by the bacterium
Clostridium botulinum.
Botulinum toxin Type A (BTX-A) is a common treatment for muscles affected by
the upper motor neuron syndrome which causes spasticity in a group of mus-
cles. Botox injections inhibit muscle spasticity by weakening or paralyzing
certain muscles or by blocking the nerves involved in hypertonicity.
Mechanism of action
BTX-A inhibits the release of acetylcholine (the neurotransmitter that activates
muscles). Botox paralyzes muscle by stopping acetylcholine release. BTX-A
reduces both voluntary and involuntary motor activity of the muscles.
Neurological Disorders - A Handbook for Family Physicians 343

Indications:
• Severe spascticity in a muscle or muscle groups due to UMN lesions.
• Spasticity not improved by antispastic drugs and other measures.
• Cervical dystonia (spasmodic torticollis)
• Local intradermal injection of BTX-A in chronic focal neuropathies.
• Idiopathic and neurogenic detrusor overactivity
• Pediatric incontinence, incontinence due to overactive bladder, and
incontinence due to neurogenic bladder
• Movement disorders associated with stroke, multiple sclerosis, Parkin-
son's disease, or cerebral palsy
• Focal dystonias affecting the limbs, face, jaw, or vocal cords
Contraindications: pregnancy, lactation
Side effects : paralysis of the wrong muscle group and allergic reaction, pain,
swelling, or bruising at the injection site, u-like symptoms, headache.
Advantages : The advantage of Botox is its ease of administration. The effects of
Botox last for about three to twelve months. Botox injection can be given to a
single muscle or muscle group; where focal a action is required. Local injections
act locally, and thus, a widespread action is prevented.
Disadvantages : Injections have to be repeated every six months. Botox para-
lyzes both voluntary and involuntary muscle activity. The weakness due to
botox may contribute to further dysfunction in patients who anticipate to use
the muscles. The side-effects and the development of immune responses to the
toxin are signicant drawbacks of repeated injections. It is not suitable for
treatment of widespread spasticity, spasms, and other abnormal activity affect-
ing many muscle groups.
Alternatives to Botox injections are available and used when injections of Botox
are contraindicated or may cause serious adverse effects. These are surgical
methods, such as lengthening of tendons of spastic and shortened muscles,
denervation of the spastic muscles, etc.
344 Neurological Disorders - A Handbook for Family Physicians

44

Antiparkinson and Other

Drugs
Drugs controlling tremors
Levodopa
Levodopa is a dopaminergic agent which is used in the treatment of parkinson's
disease.
Mechanism of action
Levodopa increases dopamine levels in the brain leading to the stimulation of
dopamine receptors.
Absorption: Peak plasma concentrations within 2 hr.
Distribution: Protein-binding: 10-30%. Penetrates the blood-brain barrier;
crosses the placenta; distributed into breast milk.
Metabolism: Metabolised in the gut, liver and kidney; decarboxylated by L-
aminodecarboxylase to dihydrophenylacetic acid (DOPAC) and homovanillic
acid (HVA). Other routes: O-methylation, transamination, oxidation.
Excretion: Via urine within 24 hr (80% as metabolites); via faeces (minimal
amounts).
30-60 min (elimination half-life).
Dosage
Oral
Neurological Disorders - A Handbook for Family Physicians 345

Parkinsonism
Adult: Initially, 125 mg bid; increase gradually every 3-7 days according to
response.
Max dose: 8 g daily in divided doses.
Contraindication- acute narrow angle glaucoma, severe pyschosis, history of
malignant ,melanoma.
Special precaution – elderly ,IHD ,psychiatric,endocrine,hepatic & renal
impairment.
Side effect - Orthostatic hypotension, cardiac arrhythmias. Psychiatric
symptoms (especially the elderly). Abnormal involuntary movements or
dyskinesias, delirium, hallucinations. Slight elevation of liver enzymes, BUN
and uric acid. Transient leucopenia and thrombocytopenia.
Levodopa and Carbidopa
Levodopa, a precursor of dopamine, crosses the blood-brain barrier and gets
converted to dopamine in the basal ganglia while carbidopa is a dopa-
decarboxylase inhibitor. The latter prevents conversion of L-dopa to dopamine
outside the brain and minimises side effects.
Dosage
Oral
As monotherapy in Parkinson's disease
Adult: Per tablet contains L-dopa 100 mg and carbidopa 25 mg. Initially, 1 tab
tid. Increase by 1 tab/day every 1-2 days up to a max. of 8 tabs of any
strength/day. If the patient has been taking L-dopa alone, the combination
should be started after a gap of at least 8 hr after stopping L-dopa.
Levodopa and Benserazide
Levodopa is the metabolic precursor of dopamine. Only a small amount of
administered Levodopa enters blood-brain barrier unaltered and the remainder
is converted peripherally to dopamine by dopa-decarboxylase. Benserazide is a
peripheral decarboxylase inhibitor that reduces the peripheral conversion of
Levodopa; concurrent admin enables dosage of Levodopa to be reduced and
may diminish peripheral side effects such as nausea and vomiting.
Dosage
Oral
346 Neurological Disorders - A Handbook for Family Physicians

Parkinson's disease
Adult: Standard forms or Dispersible form available in Levodopa
(mg)/Benserazide (mg) formulations 50/12.5, 100/25, 200/50. Doses expressed
as Levodopa: Initially 50 mg 3 or 4 times daily (100 mg tid in advance stage
disease); gradually increase by 100 mg daily once or twice wkly. Effective dose
range: 400-800 mg daily in divided doses; most require < 600 mg daily. Patients
previously on levodopa monotherapy: Initiate with 10-15% of the usual dose
previously taken. Patient previously on other levodopa/dopa-decarboxylase
combination therapy: Withdraw previous therapy for 12 hr before initiating
therapy at 50 mg 3 or 4 times daily.
Controlled - release form as Levodopa (mg)/Benserazide (mg) 100/25 cap:
Initially.
1 cap tid. Max initial dose: 6 caps/day. Patients previously on immediate-
release Levodopa/Benserazide preparations: Initially dose should substitute
every 100 mg of Levodopa with 1 controlled-release cap, given at same dosage
frequency as before. Increase every 2-3 day.
Elderly: Standard forms or Dispersible form Doses expressed as Levodopa:
Initially 50 mg once or twice daily, gradually increase by 50 mg every 3-4 days
according to response.
Donepezil
Mechanism of action
Donepezil reversibly and noncompetitively inhibits centrally-active
acetylcholinesterase. It is used for the symptomatic treatment of Alzheimer's
disease.
Absorption: Plasma levels peak within 3-4 hr after oral admin.
Distribution: Protein binding: About 95% (mainly albumin).
Metabolism: Partially metabolised in the liver mainly by CYP3A4 to 4 major
metabolites.
Excretion: Elimination half-life: About 70 hr. Steady-state concentrations are
achieved within 3 wk of treatment initiation.
Dosage
Oral
Mild to moderately severe dementia in Alzheimer's disease
Neurological Disorders - A Handbook for Family Physicians 347

Adult: Initially, 5 mg daily at bedtime, increase if necessary up to 10 mg once

daily at bedtime after 4-6 wk.
Elderly: Initially, 5 mg daily at bedtime, increase if necessary up to 10 mg once
daily at bedtime after 4-6 wk.
Side effects: anorexia, wt loss, insomnia, fatigue, muscle cramps; headache and
dizziness; syncope, bradycardia; convulsions; increased liver transaminases;
hallucinations, agitation and aggressive behavior; urine retention.
Immunoglobulins
IVIG
Dosage : The initial dose of IVIg for MG and other neuromuscular diseases is
usually 2 g/kg. This is generally administered over 2 to 5 days. Slower rates of
infusion are preferable in older patients and those with renal insufciency or
congestive heart failure. Intravenous immunoglobulin is often used for treat-
ment of MG outpatients refractory to other immunomodulating therapies.
Side effects : adverse effects are related to the rate of infusion and include
headache, light-headedness, and chills. Other side effects include
nephrotoxicity, hypertension, thrombotic events, myocardial infarction and
stroke.
348 Neurological Disorders - A Handbook for Family Physicians

45

Neuroprotective Agents
Neuroprotective Drugs
Neuroprotective agents are used in an attempt to save ischemic neurons in the
brain from irreversible injury. Studies in animals indicate a period of at least 4
hours after onset of complete ischemia in which many potentially viable
neurons exist in the ischemic penumbra (ie, the rim of the infarct). In humans,
the ischemia may be less complete, and the time window may be longer, but
human patients also tend to be older, with comorbidities that may limit benet.
2 types of neuroprotective agents, one that prevents early ischemic injury and
another that prevents reperfusion injury.
I. Prevention of early ishemic injury
N-methyl-D-aspartate receptor antagonists
By preventing excitatory neurotransmitter release, neuroprotective agents may
reduce deleterious effects of ischemia on cells.
A. Memantine
Memantine, a derivative of amantadine, is a noncompetitive N-methyl-D-
aspartate (NMDA)-receptor antagonist. It affects transmission of glutamate, the
primary excitatory neurotransmitter in the CNS. Glutamate may contribute to
the pathogenesis of Alzheimer's disease by overstimulating various glutamate
receptors resulting in excitotoxicity and neuronal cell death.
Dosage
Oral
Neurological Disorders - A Handbook for Family Physicians 349

Moderate to severe dementia in Alzheimer's disease

Adult: As hydrochloride: Initially, 5 mg daily in the morning for the 1st wk;
increase dose wkly in steps of 5 mg. Max: 20 mg daily. Wait for at least 1 wk
between dose changes. Doses ?10 mg/day should be given in 2 divided doses.
Suggested titration: 5 mg daily for ?1 wk; 5 mg bid for ?1 wk; 15 mg daily given in
5- and 10-mg separated doses for ?1 wk; then 10 mg bid.
Renal impairment : Depending on creatine clearance; 40-60 ml/min: Max dose:
10 mg/day.
Side effects : Dizziness, confusion, headache, somnolence, hallucinations,
tiredness, anxiety, abnormal gait, hypertonia, cystitis and increased libido.
B. Magnesium
Magnesium is another agent with actions on the NMDA receptor and a low
incidence of adverse effects. It may reduce ischemic injury by increasing
regional blood ow, antagonizing voltage-sensitive calcium channels, and
blocking the NMDA receptor. In myocardial infarction and small stroke studies,
patients tolerated the drug.
Dosage : 400 to 800 mg orally once a day.
II. Prevention of reperfusion injury
Citicoline
Citicoline is an exogenous form of cytidine-5'-diphosphocholine (CDP-choline)
used in membrane biosynthesis. Citicoline may reduce ischemic injury by
stabilizing membranes and decreasing free radical formation. Citicoline
increases blood ow and O2 consumption in the brain. It is also involved in the
biosynthesis of lecithin.
Dosage
Oral
Adult: 200-600 mg daily in divided doses.
Piracetam
It is a nootrophic agent and used as a cognitive enhancer.
Indication - cerebral vascular accidents and cerebral insufciency, ischemic or
even haemorrhagic acute accidents,mental retardation in children,behaviour &
psychotic problems.
Dosage - adult-800 mg 3 times a day.
350 Neurological Disorders - A Handbook for Family Physicians

Children - 50mg/kg body weight

Contraindication - severe renal impairment or hepatic functions and Cerebral
haemorrhage.
Special precaution - impaired renal or hepatic functions,cardiac disorders.
Side effects: Hyperkinesia, nervousness, depression, CNS stimulation, sleep
disturbances, dizziness, excitement, wt gain.
Ginkgo biloba
Indication - cerebral impairment due to organic degeneration of cortex,multiple
vascular infarcts, headache, sleep disturbances, dizziness, tinnitus.
Dosages - 40 mg 3 times a day.
Contraindication - acute phase of cerebrovascular accidents, acute myocardial
infarction, hypotension, pregnancy & hypersensitivity to ingrediants.
Special precautions - nausea, gi, upsets, heart, palpitation
Vitamins
Vitamins like vitamin B1, B6, B12 and folate are also used for neuroprotection.
Vitamin B6 (Pyridoxine)
It is a water soluble vitamin, important for metabolism of carbohydrates, pro-
teins and fats. It helps in GABA synthesis in the CNS and release of glycogen
stored in muscles.
Dosage : 150 mg daily
Vitamin B12
Vitamin B12 plays a signicant role in the synthesis and maintenance of myelin.
The neurological problems caused by vitamin B12 deciency are due to the
damage caused to the myelin sheath.
Thus, Vit B12 medications and supplements are given in the treatment of
peripheral neuropathy, diabetic neuropathy and to prevent neurological distur-
bances. Methylcobalamin is known to help repair the damage caused by dia-
betic neuropathy by modulating the protein kinase C signaling pathway or
activating chemical signals. Vitamin B12 also helps protect against brain atro-
phy or shrinkage associated with Alzheimer's disease and impaired cognitive
function.
Dosage : 1500 mcg/day
Neurological Disorders - A Handbook for Family Physicians 351

Vitamin C
Vitamin C is one of many antioxidants. Antioxidants are nutrients that Prevent
damage caused from free radicals. Intracellular ascorbate in the CNS provides
antioxidant protection, peptide amidation, myelin formation, synaptic
potentiation, and protection against glutamate toxicity. Thus, it protects neu-
rons from the oxidant damage associated with neurodegenerative diseases such
as Alzheimer's, Parkinson's, and Huntington's disease.
Dosage : 500mg/day
Vitamin E
Vit E is important for the maintenance of the integrity and stability of biological
membranes, and for the protection of the phospholipids of biological mem-
branes from peroxidation. Vit E deciency has been known to cause degenera-
tion and loss of sensory axons in the posterior columns, sensory roots, and
peripheral nerves. This degeneration results from axonal membrane injury and
then develops as an axonopathy.
Dosage : 400 mg/day
Folate
Folic acid is known to have some roles in the production of neurotransmitters
necessary for nerve conduction. Folate deciency may lead to cognitive impair-
ment, dementia, depression, peripheral neuropathy and subacute combined
degeneration of the spinal cord.
Dosage : 1.5 mg/day
Vitamin B1 (Thiamine)
Thiamine is a water soluble vitamin. It is an essential coenzyme in carbohydrate
metabolism.
Dosage : As a prophylaxis: 10-25 mg daily
In Thiamine deciency: 300 mg daily
Wernicke - Korsakoff syndrome: 100 mg by slow IV over 10 minutes; then 50-
100 mg/day IM or IV until he can take oral
CoQ10 or Ubiquinone
CoQ10 acts as an antioxidant and membrane stabilizer. It is also involved in the
electron transport chain, and is an important component for production of ATPs
(energy) for cell functions. It is used in the treatment of mitochondrial
352 Neurological Disorders - A Handbook for Family Physicians

cytopathies, Huntington's disease, Parkinson's disease, muscular dystrophies,

migraine headaches and myopathies.
CoQ10 is used as a cardioprotective agent in cases of muscular dystrophy. In
multiple studies, CoQ10 was found to be safe and well tolerated up to 1200
mg/day.
Dosage :
Adult: 300 mg bid, maximum 1200 mg/day
Children : 300 mg once a day
Ubiquinol
Ubiquinol is an oxidized form of CoQ10 and acts as an antioxidant. It is the most
common form of CoQ10 and accounts for more than 80% of the total ubiquinol
and ubiquinone pool in human plasma. It is used in neurodegenerative disor-
ders, for e.g. Parkinson's disease, dementia, etc. Indications of ubiquinol use are
same as of CoQ10. The bioavailability of ubiquinol is higher than CoQ10.
Dosage : Adults: 100 mg bid
Children: 50 mg bid or 100 mg od
Omega 3 fatty acids
These are essential fatty acids which act as antioxidants. They decrease inam-
mation and boost the immunity of the individual. There are three types: EPA,
DHA (found in sh oil) and ALA (found in plants). Omega 3 fatty acids are used
in neurodegenerative, cognitive disorders, ADHD, etc. for neuroprotection.
Dosage: 1 tablet three times a day
Neuroprotective hormones:
Hormones such as estrogen, progesterone, testosterone, etc also have
neuroprotective properties and its use as therapeutic measure is being vigor-
ously explored.
Neurological Disorders - A Handbook for Family Physicians 353

Section F

Modern Developments
in the Treatment of
Neurological Disorders
354 Neurological Disorders - A Handbook for Family Physicians
Neurological Disorders - A Handbook for Family Physicians 355

46

Use of tPA in Acute Ischemic

Stroke
Stroke most often occurs as a result of acute vascular occlusion, and therefore
acute revascularization is crucial. Prompt revascularization to restore perfusion
minimizes the extent of infarction and improves neurologic outcome.
Importance of tPA
Intravenous administration of rtPA is a valuable treatment of patients with
acute ischemic stroke. tPA use has shown improved outcomes in patients who
can be treated within 3 hours of symptom onset. Earlier treatment results in
better outcomes.
Inclusion and Exclusion Characteristics of Patients with Ischemic Stroke Who
Could Be Treated With IV rtPA Within 3 Hours (in some cases upto 4.5 hours)
From Symptom Onset
Inclusion criteria
• Diagnosis of ischemic stroke causing measurable neurological decit
• Onset of symptoms <3 hours before beginning treatment
• Age more than 18 years
Exclusion criteria
• Signicant head trauma or prior stroke in previous 3 months
• Symptoms suggest subarachnoid hemorrhage
• Arterial puncture at noncompressible site in previous 7 days
356 Neurological Disorders - A Handbook for Family Physicians

• History of previous intracranial hemorrhage

• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Recent intracranial or intraspinal surgery
• Elevated blood pressure (systolic >185 mmHg or diastolic >110 mmHg)
• Active internal bleeding
• Acute bleeding diathesis, including but not limited to
• Platelet count <100 000/mm³
• Heparin received within 48 hours, resulting in abnormally elevated aPTT
greater than the upper limit of normal
• Current use of anticoagulant with INR >1.7 or PT >15 seconds
• Current use of direct thrombin inhibitors or direct factor Xa inhibitors with
elevated sensitive laboratory tests (such as aPTT, INR, platelet count, and
• ECT; TT; or appropriate factor Xa activity assays)
• Blood glucose concentration <50 mg/dL (2.7 mmol/L)
• CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemi-
sphere)
Relative exclusion criteria
• Only minor or rapidly improving stroke symptoms (clearing spontane-
ously)
• Pregnancy
• Seizure at onset with postictal residual neurological impairments
• Major surgery or serious trauma within previous 14 days
• Recent gastrointestinal or urinary tract hemorrhage (within previous 21
days)
• Recent acute myocardial infarction (within previous 3 months)
Consider risk to benet of IV rtPA administration carefully in any of above
cases.
Additional Inclusion and Exclusion Characteristics of Patients With Acute
Ischemic Stroke Who Could Be Treated With IV rtPA Within 3 to 4.5 Hours
From Symptom Onset.
Neurological Disorders - A Handbook for Family Physicians 357

Inclusion criteria
• Diagnosis of ischemic stroke causing measurable neurological decit
• Onset of symptoms within 3 to 4.5 hours before beginning treatment
Relative exclusion criteria
• Aged >80 years
• Severe stroke (NIHSS>25)
• Taking an oral anticoagulant regardless of INR
• History of both diabetes and prior ischemic stroke
Mechanism of Action
Recombinant human tissue-type plasminogen activator (t-PA) produces local
brinolysis and promotes thrombolysis by converting plasminogen to plasmin
which degrades brin and brinogen.
Absorption: Onset: Coronary thrombolysis occurs in 30 min; reaches peak
response at 60 min
Peak plasma time: 20-40 min
Metabolism : Rapidly cleared from circulation by liver
Elimination: Initial half-life: 5 minutes (free, unbound form), Terminal half-life:
72 minutes, Total body clearance: 34.3-38.4 mL/hr, Excretion: Urine
Dosage: Acute Ischemic Stroke
0.9 mg/kg IV infused over 1 hour
100 kg: Administer 10% of total dose as initial bolus over 1 minute; THEN 0.81
mg/kg as continuous infusion over 60 min; not to exceed total dose of 90 mg
>100 kg: Administer 9 mg (10% of 90 mg) as IV bolus over 1 min; THEN 81 mg as
a continuous infusion over 60 min
Dosing considerations
• Treatment should be initiated only within 3 hours after onset of stroke
symptoms.
• Exclude intracranial hemorrhage by cranial computerized tomography
(CT) scan or other diagnostic imaging method sensitive for the presence of
hemorrhage.
358 Neurological Disorders - A Handbook for Family Physicians

Side effects: Accelerated idioventricular rhythm, Pulmonary edema, Arterial

embolism, Bruising, Bleeding, DVT, Hypotension, Intracranial hemorrhage,
GI/GU hemorrhage, Pulmonary embolism, Fever / chills, Nausea / vomiting,
Sensitivity reaction, Sepsis,Shock
Recommendations
• Intravenous rtPA (0.9 mg/kg, maximum dose 90 mg) is recommended for
selected patients who may be treated within 3 hours of onset of ischemic
stroke.
• In patients eligible for intravenous rtPA, benet of therapy is time depend-
ent, and treatment should be initiated as quickly as possible. The door-to-
needle time (time of bolus administration) should be within 60 minutes
from hospital arrival.
• Intravenous rtPA is reasonable in patients whose blood pressure can be
lowered safely (to below 185/110 mmHg) with antihypertensive agents,
with the physician assessing the stability of the blood pressure before
starting intravenous rtPA.
• In patients undergoing brinolytic therapy, physicians should be aware of
and prepared to emergently treat potential side effects, including bleeding
complications and angioedema that may cause partial airway obstruction.
• Use of intravenous brinolysis in patients with conditions of mild stroke
decits, rapidly improving stroke symptoms, major surgery in the
preceding 3 months, and recent myocardial infarction may be considered,
and potential increased risk should be weighed against the anticipated
benets.
• The intravenous administration of streptokinase for treatment of stroke is
not recommended
Monitoring of the patient
Admit the patient to an intensive care or stroke unit for monitoring.
If the patient develops severe headache, acute hypertension, nausea, or vomit-
ing or has a worsening neurological examination, discontinue the infusion (if IV
rtPA is being administered) and obtain emergent CT scan.
Measure blood pressure and perform neurological assessments every 15 min-
utes during and after IV rtPA infusion for 2 hours, then every 30 minutes for 6
hours, then hourly until 24 hours after IV rtPA treatment.
Neurological Disorders - A Handbook for Family Physicians 359

Increase the frequency of blood pressure measurements if systolic blood pres-

sure is >180 mmHg or if diastolic blood pressure is >105 mmHg; administer
antihypertensive medications to maintain blood pressure at or below these
levels.
Delay placement of nasogastric tubes, indwelling bladder catheters, or
intraarterial pressure catheters if the patient can be safely managed without
them.
Obtain a follow-up CT or MRI scan at 24 hours after IV rtPA before starting
anticoagulants or antiplatelet agents.
For mechanical thrombectomy in acute ischemic stroke refer to chapter 51.
360 Neurological Disorders - A Handbook for Family Physicians

47

Role of Hyperbaric Oxygen

Therapy in Neurological Dis-
orders
Hyperbaric oxygen therapy (HBOT) is a medical treatment which enhances the
body's natural healing process by inhalation of 100% oxygen in a total body
chamber, where atmospheric pressure is increased and controlled. It is used for
a wide variety of treatments usually as a part of an overall medical care plan.

Under normal circumstances, oxygen is transported throughout the body only

by red blood cells. With HBOT, oxygen is dissolved into all of the body's uids,
the plasma, the central nervous system uids, the lymph, and the bone and can
be carried to areas where circulation is diminished or blocked. In this way, extra
oxygen can reach all of the
damaged tissues and the
body can support its own
healing process. The
increased oxygen greatly
enhances the ability of white
blood cells to kill bacteria,
reduces swelling and allows
new blood vessels to grow
more rapidly into the affected
areas. It is a simple, non-
invasive and painless treat-
ment.
Neurological Disorders - A Handbook for Family Physicians 361

Indications:
FDA has approved HBOT for treatment of brain abscess and acute traumatic
ischemia.
Off label indications for neurological disorders are:
• Brain injury
• Autism
• Cerebral palsy
• Migraine
• Alzheimer's disease
• Attention decit hyperactive disorder
• Multiple sclerosis
• Motor neuron disease
• Neuropathies
• Dementia
• Depression
• Coma
• Parkinson's disease
• Epilepsy/Seizure disorders
• Encephalomyelitis
• Spinal cord injury
• Stroke

Process or Procedure:
The patient is on a table that slides into the transparent chamber which is about 7
feet long.
The pressure inside the chamber is increased slowly. Children can be accompa-
nied with a parent and can play or drink inside the chamber. One can see and
talk to the technician at all times. The chamber is sealed and lled with 100%
oxygen and pressure is increased to 1.5 to 2.5 times the normal air pressure
which may cause some ear popping or mild discomfort. Pure, 100 percent
oxygen is continuously maintained and circulated throughout the chamber
during the treatment. The session will last anywhere from 45 minutes to one
hour. At the end slow decompression of the chamber is carried out to avoid
decompression sickness. Usually, 40 hourly sessions are conducted.
Benets :
Healing in most areas of the body requires appropriate oxygen levels in the
tissue. Most illnesses and injuries occur, and often linger, at the cellular or tissue
362 Neurological Disorders - A Handbook for Family Physicians

level. In many cases, such as: circulatory problems; non-healing wounds; and
strokes, adequate oxygen cannot reach the damaged area and the body's natural
healing ability is unable to function properly. Hyperbaric oxygen therapy
provides this extra oxygen naturally and with minimal side effects.
Hyperbaric oxygen therapy improves the quality of life of the patient in many
areas when standard medicine is not working. Many conditions such as stroke,
cerebral palsy, head injuries, and chronic fatigue have been reported to respond
favorably to HBOT.
Hyperbaric oxygen is used to treat all conditions which benet from increased
tissue oxygen availability either as the primary therapy, or in conjunction with
other drugs.
HBOT in brain injury or stroke:
Following an injury to the brain, either from trauma or lack of oxygen, cellular
plasma leaks out into surrounding brain tissue causing swelling and reducing
blood ow. The pressure on these cells,hampers their normal function,due to
inadequate oxygenation.HBOT facilitates increase in the oxygen carrying
capacity of the blood.
• Plasma, making oxygen available to heal damaged capillary walls, pre-
venting plasma leakage and reducing swelling. As the swelling decreases,
blood ow can be restored to the dormant tissue (neovascularization) and
these cells then have the potential to function again.
A clinical trial, aimed to evaluate whether increasing the level of dissolved
oxygen by Hyperbaric Oxygen Therapy (HBOT) could activate neuroplasticity
in patients with chronic neurologic deciencies due to stroke was carried out
and published in 2013 by Shai Efrati,,et al.,from Israel.The results indicate that
HBOT can lead to signicant neurological improvements in post stroke patients
even at chronic late stages. The observed clinical improvements implied that
neuroplasticity can still be activated long after damage onset in regions where
there is a brain SPECT/CT (anatomy/physiology) mismatch.
HBOT in a child with cerebral palsy (CP)
In CP patients, some of the injured brain tissues may be "dormant" and non-
functioning.
HBOT can stimulate these "dormant" tissues and return them to more normal
function.
In young children, cognitive function and spasticity can be improved.
Neurological Disorders - A Handbook for Family Physicians 363

Hyperbaric oxygen therapy, used in conjunction with other therapies, ensures

the best recovery possible for children with cerebral palsy and traumatic brain
injury.
HBOT in autism:
the pathogenetic mechanisms postulated are cerebral hypoperfusion, inam-
mation, oxidative stress, and immune dysregulation. Studies have shown that
children with autism may have decreased blood ow through the social brain
(mesial temporal, amygdala, etc). Less blood ow results in decreased oxygen
supply to these areas. The chances of the hypoxic tissue to receive more oxygen
increases by enhanced supply. HBOT not only increases the oxygen in the blood
but also allows the oxygen to effortlessly cross cell membranes and enter all of
the other body's uid systems. This cumulatively improves the transport of
oxygen in the body. It stimulates angiogenesis, reduces oxidative stress by
stimulating superoxide dismutase, reduces inammation and stimulates local
stem cells. This improves the neuronal functions. HBOT thus reverses the
neurological abnormalities. Clinically, this leads to improvement in cognition,
socialization, language, behavior, eye contact, etc in children with autism.
Contraindications: (for children and their parents): Absolute: pneumothorax
and severe congestive heart failure. Relative: History of seizures, febrile illness
(lower threshold for seizures and prolonged removal time due to slow decom-
pression incase of an event), recent ear surgery, chronic sinusitis, active upper
respiratory infection, (due to inability to equalize the ear pressure). Asthma,
emphysema (lung barotrauma), congenital spherocytosis (fragile RBCs), claus-
trophobia (anxiety), optic neuritis (blindness), active cancer, pacemaker and
pregnancy.
Possible Complications: One should be vigilant for possible complications of
HBOT, that includes barotrauma injury (to middle ear, nasal sinuses, inner ear,
lung, teeth), oxygen toxicity (central nervous system, lung), connement
anxiety, and ocular effects (myopia, cataract growth) and seizures.
364 Neurological Disorders - A Handbook for Family Physicians

48

Comprehensive
Neurorehabilitation
Neurorehabilitation is the clinical specialty that aims to restore and maximize
functions that have been lost due to impairments caused by injury or disease of
nervous system. The goal of neurorehabilitation is to help patients with impair-
ments and disabilities be functionally independent, which requires team of
rehabilitation specialists, such as nurses, physiotherapists, occupational thera-
pists, aquatic therapists, speech therapist, psychologist, special educators and
caregivers.
Importance of Rehabilitation:
Once the acute pathology of the injury or disease is over, neurorehabilitation
aims to recover the lost function of patients during the sub-acute and chronic
stage of recovery. The rehabilitation team sets short term goals (generally
considered to be two to three weeks) and long-term goals (longer than 3 weeks)
which should be objective, measurable and time limited. Neurorehabilitation
team has an understanding of neural regulation of movement patterns and
sensory inputs and outputs. Some of the common principles used by
neurorehabilitation therapist are motor learning, sensory facilitation and neural
plasticity. Motor learning is a process where permanent changes occur in the
neural structures in response to repetitive motor tasks and the ability of the
brain to adapt, form and reroute the neural circutary is called brain plasticity.
Neuroplasticity is dened as brain's ability to adapt or use cellular adaptations
to learn or relearn functions which are previously lost as result of cellular death
by trauma or disease at any age. Neuronal sprouting is thought to be primary
mechanism, allowing injured neurons, to reconnect in new ways and allowing
Neurological Disorders - A Handbook for Family Physicians 365

intact undamaged neurons to form new connection and to enhance function.

Motor learning will continue throughout life as long as environment asks for
change and central nervous system has pliability and desire to learn. The
rehabilitation team promotes this learning and facilitates neural plasticity.
The philosophic foundation of rehabilitation team is to promote purposeful
activity thereby preventing dysfunction and eliciting maximum adaptation.
These goal-oriented activities are meant to be culturally meaningful and
important to the needs of patient and their families. Activities include daily life
and work skills, exercise, recreation and crafts. Exercise tasks in animal models,
have shown that specically skilled type of exercises lead to increased
angiogenesis in damaged cortical areas whereas unskilled activities did not
show this positive change. It is believed that in humans too rehabilitation
techniques would enhance neuroplastic changes.
How rehabilitation augments the effects of stem cell therapy
The concept of Neuro Regenerative Rehabilitation Therapy (NRRT) at
NeuroGen promotes a multidisciplinary and holistic approach to bring about
recovery of neural function with a close integration of Neuro regenerative
(including stem cell therapy), Neuro protective (medications) and
neurorehabilitative therapies. Thus, it combines the best neurobiological repair
technologies and neurorestorative techniques. The rehabilitation protocol is
then individualized to the specic requirements of each patient emphasizing on
functional recovery and independence in activities of daily living (ADL).
Inspite of neurorehabilitation and neural plasticity degenerated or damaged
nervous system leads to permanent disability in many individuals. There is
signicant neurodecit. Regenerative therapies like stem cell therapy help to
reduce this neurodecit and therefore enhance the functional recovery of the
patients. Paracrine effects of stem cells also secrete neuroprotective chemicals
and aid in improving the outcome of neurorehabilitation. Neurorehabilitation
complements regenerative therapies and facilitate better recovery.
Neurorehabilitation facilitates neural plasticity and improves neural
connectivity. It stimulates neurons to function at their optimum capacity. It also
activates the local resident stem cells to help repair the damaged areas. Similarly
exercise also stimulates the injected stem cells and guides them towards their
targeted functions. It helps the regenerated cells to gain maximum function.
Neurorehabilitation has also been postulated to release growth factors, improve
oxygenation and increase blood supply. Thus, the synergistic effect of stem cell
therapy and neurorehabilitation brings about maximum benets.
366 Neurological Disorders - A Handbook for Family Physicians

Studies have suggested that the combination of bone marrow stem cell therapy
and exercise training result in signicant functional improvement in
neurological disorders.
Physical therapy
As an important member of rehabilitation team a, physical therapist has a
crucial role to play which includes, bed mobility, ambulation and transfer
activities like, transfers from bed to chair or from chair to commode or from
wheelchair to car and so on. Their assessments emphasize measures of
voluntary movement, sensory appreciation, ROM, strength, balance,
fatigability, mobility, gait and functional status.
Practices in Physical Therapy includes
Ÿ Therapeutic exercise and re-education
Ÿ Neurofacilitation techniques
Ÿ Proprioceptive neuromuscular facilitation
Ÿ Bobath
Ÿ Brunnstrom
Ÿ Rood
Ÿ Motor skills learning
Ÿ Task-oriented practice
Ÿ Forced use
Ÿ Massed Practice
Ÿ Biofeedback
Ÿ Virtual environment training.
Ÿ Musculoskeletal techniques.
Ÿ Electromyogram-triggered
neuromuscular stimulation.
Ÿ Orthosis and assistive devices.

Fig 48.1: Physiotherapy

Neurological Disorders - A Handbook for Family Physicians 367

Occupational Therapy
Occupational Therapists bring expertise to the rehabilitation team in enhancing
the independence and personal satisfaction of patients in their activities of daily
living (ADL), community and leisure activities, social integration, and work
performance. They play integral part in evaluating the need for a range of
assistive devices and training patients to make them independent in eating,
dressing, bathing combing and other ADL.
In the patient's home and workplace, the therapist provide grab bars, rails,
ramps, environmental controls, computer interfaces, architectural changes such
as widening a doorway to allow wheelchair access and emergency remote-
control calling systems. Along with the physical and recreational therapist,
occupational therapist seek out the environmental, personal, and activity-
specic equipment and technologies that enhance the quality of life of patients
Success in retraining during rehabilitation depends on diverse variables that
include the characteristics of a task, changing contexts and environments when
performing a task, psychological reinforcements including positive contextual
factors like motivation, attention, memory for carryover of what is taught and
negative contextual factors like environmental distractions, anxiety, sleep
deprivation and family support play a signicant role.

Fig 48.2: Occupational Therapy

Psychology
The word psychology is derived from the Greek words Psyche (which means
soul) and logos (which means study). Hence, psychology could be dened as a
"study of the soul". However, today it is dened as the scientic study of the
behaviour of individuals and their mental processes (American Psychological
368 Neurological Disorders - A Handbook for Family Physicians

Association). Neuropsychological testing and evaluation is to identify the

pattern of cognitive, behavioural, and emotional strengths and weaknesses and
to provide specic treatment recommendations or clarify diagnostic questions.
The domains and tests specied.

Fig 48.3: Psychological counselling

Psychological Counseling:
The purpose of counseling is to broadly empower the client to cope with life
situations, to reduce emotional stress, to engage in growth producing activity, to
have meaningful interpersonal relationships and to make effective decisions.
Counseling increases the control over present circumstances and enhances
present and future opportunities.
There are several main broad systems of psychotherapy:
Psychoanalytic: It encourages the verbalization of all the patient's thoughts,
including free associations, fantasies, and dreams, from which the analyst
formulates the nature of the unconscious conicts which are causing the
patient's symptoms and character problems.
Behaviour Therapy: This focuses on changing maladaptive patterns of behav-
ior to improve emotional responses, cognitions, and interactions with others.
Cognitive Behavioural Therapy: Seeks to identify maladaptive cognition,
appraisal, beliefs and reactions with the aim of inuencing destructive negative
emotions and problematic dysfunctional behaviours.
Psychodynamic: Primary focus is to reveal the unconscious content of a client's
psyche in an effort to alleviate psychic tension.
Existential Therapy: This is based on the existential belief that human beings are
alone in the world. This isolation leads to feelings of meaninglessness, which can
be overcome only by creating one's own values and meanings.
Neurological Disorders - A Handbook for Family Physicians 369

Humanistic: The task of Humanistic therapy is to create a relational environ-

ment where this the self-actualizing tendency might ourish.
Transpersonal Therapy: Addresses the client in the context of a spiritual under-
standing of consciousness.
Body Psychotherapy: Addresses problems of the mind as being closely corre-
lated with bodily phenomena, including a person's sexuality, musculature,
breathing habits, physiology etc. This therapy may involve massage and other
body exercises as well as talking.
Play Therapy, Gestalt Therapy, Rational Emotive Behaviour Therapy, Solution
based therapies and Reality Therapy some other forms of psychotherapy.
Speech therapy:
Speech therapy focuses on receptive language, or the ability to understand
words spoken and expressive language or the ability to express. It also deals
with the mechanics of producing words, such as articulation, uency and voice.
Speech therapy also deals with rehabilitation of language in children who do not
speak congenitally due to hearing impairment, mental retardation, autism or
attention decit hyperactivity disorder.
Speech and language therapy is benecial in neurogenic disorders of non -
progressive and progressive origin.
Aphasia: Aphasia is dened as loss of reception or expression of language as a
result of brain stroke. It can be classied as Broca's aphasia (patient presents
with intact comprehension with affected expression), Wernicke's (patient
presents with affected comprehension with jargon speech), Anomia or nominal
aphasia (patient presents with naming difculties).
Recovery from aphasia depends on many prognostic factors like age, site and
extent of lesion, concomitant problems and time lapsed between the stroke and
initiation of therapy. Rehabilitation in aphasia focuses on the following:
Improving auditory comprehension using pointing tasks "point to the spoon".
Encouraging verbal utterances voluntarily.
Improving sentence formation.
Improving naming
A study done on aphasics concluded that combination of two inout channels -
auditory plus visual, auditory plus gestural may facilitate better comprehension
and performance by the patient.
370 Neurological Disorders - A Handbook for Family Physicians

Many of the cases of do not improve with traditional speech and language. In
such cases, nonverbal modalities can be used to augment or alternate patient's
communication. The most commonly used AAC are communication boards,
gestures and use of written modality.
According to Collins (1986), severly aphasic patient may rely more on pictures
for basic need that cannot be readily expressed by pointing or natural gesturing
(as cited in Davis,2000) (5)
Dysarthria: The literal denition of dysarthria is disordered utterance (dys
means disordered or abnormal; arthria means to utter distinctly). A more com-
prehensive denition is that dysarthria is the impaired production of speech
because of disturbances in the muscular control of the speech mechanism (as
cited in Freed, 2000). Dysarthria can be classied as spastic dysarthria (due to
upper motor neuron lesion), accid dysarthria (due to lower motor neuron
involvement), ataxic dysarthria (due to cerebellar involvement), hypokinetic
and hyperkinetic dysarthria (due to basal ganglionic involvement) and mixed
dysarthria.
Common causes of dysarthria are stroke, motor neuron disorder, multiple
sclerosis, head injury and Parkinson's disease to name a few.
Most of the patients with dysarthria present with inability to produce sounds
clearly, reduced loudness and monotonous or robotic speech. In cases of accid
and spastic dysarthria, oro - motor structures and functions are restricted.
Treatment of dysarthria depends on the severity of speech problem. Speech and
language pathologist aim to improve speech intelligibility (overall clarity of
speech) by:
Ÿ PNF (proprioceptive and neuromuscular facilitation).
Ÿ Improving loudness levels.
Ÿ Improving articulatory precision by using exaggerated consonants.
Apraxia: According to Darley (1969), apraxia is an articulatory disorder result-
ing from impairment, as a result of brain damage of the capacity to program the
positioning of speech musculature and the sequencing of muscle movement for
the volitional production of phonemes. No signicant weakness, slowness, or
incoordination in reex and automatic acts is seen (as cited in Freed, 2000).
Treatment of apraxia of speech involves phonemic drills, giving proprioceptive
and kinesthetic cues to the patients. MIT (melodic intonation therapy) is another
technique used (as cited in Freed, 2000).
Neurological Disorders - A Handbook for Family Physicians 371

Darley (1975) stated that the goal of treating apraxia of speech is to help patients
relearn the motor sequences needed to produce phonemes accurately.
Dysphagia: Dysphagia means disordered swallowing. Swallowing disorders
occur in all age groups from newborns to the elderly, and can occur as a result of
CVA, presence of tumors and/ or progressive neurologic conditions. Swallow-
ing consists of 4 stages namely oral preparatory, oral, pharyngeal and esopha-
geal stage. Depending upon the stage affected, a swallowing therapist needs to
make a judgement on the treatment modality.
A swallowing therapist aims to work on:
Strengthening the oral and pharyngeal structures for swallowing.
Modify the bolus in order to facilitate adequate swallowing.
Recommend postures and maneuvers like chin tuck/ chin down postures
according to the nature of disorder. During swallowing therapy, the therapist
should ensure airway safety and rule out any silent aspiration. Children with
autism, cerebral palsy, hearing impairment or mental retardation present with
either absence of speech or decient speech and language skills as compared to
their age. The main aim of the speech therapist is to bridge the gap between the
chronological age and the language age of the child. The speech and language
pathologist tries to explore the areas which the child would respond in and
facilitate communication within child's impairment. Most widely used tech-
niques for language learning are repetitions, modeling utterances, expanding a
topic and role play. However, children with higher grade of severity may have
to rely on alternative and augmented communication (AAC) in order to reduce
the communicative burden on the caregivers.
Aquatic therapist
Aquatic therapist makes use of different properties of water and hydrodynamic
principles of water in bringing about physical, physiological, psychological and
therapeutic changes in an individual to maintain, improve or restore body
structure & function, to overcome activity limitations and facilitate participa-
tion to full their roles independently in daily life. There are different tech-
niques used in aquatic therapists which are water specic therapy, bad ragaz
ring method, clinical aai chi and passive relaxation techniques. Benecial effects
of aquatic therapy include improved Posture, co-ordination, body Control,
reduced sensory issues, improved social skills, improved cognition, memory
and learning, improved attention and concentration.
372 Neurological Disorders - A Handbook for Family Physicians

Fig 48.4: Aquatic Therapy

Neuro-rehabilitation is a holistic approach towards improving function and

increasing social and vocational participation of patients suffering from incur-
able neurological disorders, by means of employing strategies to improve
motor, sensory and cognitive functions. Neurorehabilitation is an educational
process that reduces the level of disability experienced by a patient and
increases the level of participation. Neurological disorders affect multiple body
systems and lead to physical, cognitive and functional disability. Therefore, a
team of qualied professionals with expertise in treating neurological disorders
is required to work as an integrated unit with a patient centered approach to
provide quality care.
Neurological Disorders - A Handbook for Family Physicians 373

49

Recent Advances in
Neurosurgery

Modern Neurosurgical facilities have made the cures for serious Brain and
Spine problems safer and more denitive. We now have better results with
fewer complications, total cures, lower risks, lesser discomfort and shorter and
lesser treatments. The modern neurosurgical advances include better and more
specic pre-operative investigations more precise surgery in the form of micro-
neuro surgery, minimally invasive surgery, and advanced technological assis-
tance. The post-operative care has been improved by sophisticated intensive
care monitoring and treatments. For conditions, where neurological decits
persists despite all medical and surgical interventions there is now the availabil-
ity of stem cell therapy and aggressive neuro-rehabilitation. Together all of
these, have resulted in signicantly better outcomes in the present as compared
to what the results were several years ago.
374 Neurological Disorders - A Handbook for Family Physicians

The recent advances in neurosurgery may be divided into following :

• Micro neurosurgery
• Minimally invasive neurosurgery
• Stereotactic and functional neurosurgery
• Neuroendoscopy
• Interventional Neuroendovascular treatment
• Radiosurgery
• Neuromodulation and Neurostimulation
• Advanced Spinal Surgery
Microneurosurgery
The availability of sophisticated operating microscope which have high magni-
cation, have resulted in more accurate, rened and safer neurosurgery since
the visualization of vital brain structures as well as normal areas is signicantly
enhanced. There is less blood loss as well as less damage to normal structures.
The following procedures are now regularly done with the operating micro-
scope. Large as well as difcult to access tumours are now much more easily
resected through microneurosurgery. These include malignant as well as
benign tumours.
A few examples of micro neurosurgery are shown below in pictures :
Brain Tumour surgery
Brain tumors may be malignant or benign and when they are large need to be
removed without causing damage to the surrounding normal brain.
Microneurosurgery has made this possible now with good overall results.
People can lead normal lives after major brain tumor surgery.
• This is a highly malignant brain tumour which has been totally excised.

A highly brain tumour (glioma)

Neurological Disorders - A Handbook for Family Physicians 375

Tumour removal being done with the microscope and CUSA

(Cavitron Ultrasonic Suction Aspirator)

Total tumour removal done

Vascular Surgery
Aneurysms and Arteriovenous malformations can rupture and cause intra-
cranial hemmorhage and therefore need to be treated. The 2 options are:
Microsurgical clipping for aneurysms/Excisions of AVMs or interventional
coiling.
This is a decision that the treating neurosurgeon makes in consultation with the
family.
376 Neurological Disorders - A Handbook for Family Physicians

Clipping of Aneurysm

Intracranial aneurysm Aneurysm successfully

which had bled clipped with micro
Intracranial aneurysm
which had bled
Neurosurgery

Intracranial AVM Successful

which had bled micro-neurosurgical
removal of AVM

Carotid Endartrectomy
Surgery for Carotid Artery Stenosis due to atherosclerotic plaque (Carotid
Endareterectomy) effectively reduces the relative risk of stroke by 55% in
patients with more than 70% carotid stenosis and by 35% in patients with steno-
sis between 50% and 69%. The surgery involves opening the carotid artery and
removal of the plague. Interventional stenting is also an option if the stenosis is
not very severe.
Neurological Disorders - A Handbook for Family Physicians 377

Athero matus plaque in the carotid artery removed microsurgically

Pre-operative DSA showing the plaque obstructing the

carotid and post operative DSA shows restoration of the blood supply

STA - MCA Bypass

The supercial temporal artery to middle cerebral artery by pass surgery is
indicated in some special cases. It helps revascularize the ischemic brain when
the MCA blood supply is compromised.

Supercial artery dissected from below the scalp

378 Neurological Disorders - A Handbook for Family Physicians

The skull opened and middle cerebral artery identied

An anastamosis done of the supercial temporal artery to

the middle cerebral artery bypassing the block in the middle
cerebral artery and restoring blood circulation to the ischemic brain
Excision of Hydatid Worm Cysts in the Brain

Large intracranial collection of hydatid cyst

Total microsurgical removal of the intracranial worm cyst

Neurological Disorders - A Handbook for Family Physicians 379

Removal of spinal tumour

Spinal tumprs by causing compression on the spinal cord can cause paraplegia
or quadriplegia and so need to be surgically excised. The removal of these
tumors microsurgically gives very good results.

Intradural Spinal Tumours are safely removed through micro-neural surgery

Minimally Invasive Neurosurgery

This includes neuroendoscopy, stereotactic surgery, interventional
endovascular therapy and radiosurgery
Neuroendoscopy
Neuroendoscopy involves the surgical treatment of disorders of the brain and
the spine, using keyhole techniques and the use of specially designed endo-
scopes. There are three main areas where neuroendoscopy can be used. These
are for intraventicular lesions and the treatment of hydrocephalus, surgical
excision of pituitary tumors, spinal surgery in cases of prolapsed discs
removal.Brain tumors and lesions within the ventricles can be removed with an
endoscope through a small hole instead of opening the whole skull through a
craniotomy. A major indication for intraventicular endoscopy is in the manage-
ment of selected cases of hydrocephalus. The conventional treatment of the
same involves the operation of the ventriculo-peritoneal shunt. This has many
complications such as blockages and infections. Endoscopic cranial base Sur-
gery for tumors on the base of the skull can be removed through the nose, via the
endoscope in a stitch less surgery i.e. no external incisions are made. It is mainly
useful for pituitary tumors and occasionally other tumors such as
angiobromas and clival chordomas. Complications are much less and patient
can go home in 4 to 5 days.
380 Neurological Disorders - A Handbook for Family Physicians

Operating with the help of a neuroendsocope, surgery can be done

through a small opening in the skull instead of opening the entire skull

Difference between the skull opening made in open surgery

versus endoscopic surgery

Conditions that can be treated with the endoscope include

hydrocephalus and intraventricular cysts
Neurological Disorders - A Handbook for Family Physicians 381

The operation of endoscopic 3rd ventriculostomy is modern replacement

operation for the conventional VP shunt surgery in selective cases.

Large pituitary tumour successfully removed through the nose endoscopically

Stereotactic neurosurgery
With the use of the Leksell Stereotactic frame surgeries can be done from a small
hole in the head instead of opening the whole skull. Stereotactic Surgery is
useful for :-
• Brain tumors
• Brain Hemorrhage
• Brain infections
• Brain cysts
• Parkinson's disease
• Psychiatric disorders
• Pain
382 Neurological Disorders - A Handbook for Family Physicians

Stereotactic biopsy can be done of malignant brain tumours

Intracranial Haematomas can be evacuated through minimally

invasive method using Stereotactic frame.

Electrodes can be inserted into the brain to make lesions as part of functional
Stereotactic Surgery such as Bilateral Anterior Cingulotomy for Obsessive
Compulsive neurosis.(OCD)
Neurological Disorders - A Handbook for Family Physicians 383

Differences between Stereotactic Surgery v/s Open surgery are as follows :-

Stereotactic Surgery Open surgery
• Opening: Small hole • Opening: Whole skull
• Time 30 minutes • Time: 5-6 hours
• Local Anesthesia • General Anesthesia
• Stay in hosp - 3 days • Stay in hosp - 10 days
• Less complications • More complications
• Less expensive • More expensive
Interventional endovascular therapy

Interventional therapy is done by passing a catheter from a puncture in the thigh

and sending it through the blood vessels all the way into the brain vessels.
Similar to the way angioplasty & similar procedures are done in cardiac
patients. The Advantages of Interventional therapy are that they are very
signicantly less complications as compared to open surgery. Many cases that
are untreatable by open surgery can be treated with Interventional. Sometimes
supplements open surgery and the hospital stay is shorter.
The indications for Interventional therapy are :-
• Aneurysms of the brain
• AVM's in the brain
• Carotid artery stenosis / block
• Blockage of Intracranial blood vessels
• Vascular brain tumours
384 Neurological Disorders - A Handbook for Family Physicians

Interventional endovascular treatment of intracranial using coils

Radio Surgery
Radio Surgery is a treatment technique that use external radiation to treat
certain type of brain tumours and vascular malformations. There are 3 types of
radio surgery available :
• Gama knife
• X knife
• Cyber knife
All these have comparable results but for specic indications one may be better
than the other. Since this is an external treatment , it is completely non-invasive
and therefore, totally safe. However its limitations are not all brain tumours can
be treated with radio surgery. Availability as well as high cost are also the
limitations.
Neuromodulation & Neurostimulation
Neurostimulation is the implantation of electrodes into the brain or spinal cord
along with an internal pacemaker and an external handheld programmable
device. Neuromodulation and neurostimulation can be used for many condi-
tions such as intractable pain, Parkinsons disease, movement disorders, coma,
spasticity, psychiatric disorders, etc

Motor cortex stimulation being done for intractable pain

Neurological Disorders - A Handbook for Family Physicians 385

Electrodes within the brain

External programmer being used to program the stimulation

Dorsal column spinal stimulation being done for persistent

vegetative state (coma)

Electrodes placed on the spine

386 Neurological Disorders - A Handbook for Family Physicians

Implantation of intrathecal baclofen pump through which

continuous drugs (baclofen for spasticity ormorphine for pain) can be
infused directly into the CSF surrounding the spinal cord and the brain.

Spine Surgery
Spine Surgery for degenerative spinal conditions, trauma, infections, etc has
become much safer and much effective due to two main reasons :-
• The availability of sophisticated instrumentation using titanium implants
• The possibility of minimal invasive spinal surgery
Neurological Disorders - A Handbook for Family Physicians 387

Decompression and Stabilization for the cranio vertebral junction

Anterior decompression and fusion surgery for the cervical spine

Stabilization Surgery for the dorsal spine injury

Microlumbar discectomy surgery for lumbar spine prolapse disc

388 Neurological Disorders - A Handbook for Family Physicians

Percutaneous spine surgery (kyphoplasty) for vertebral

collapse in dorsal spine done under local anaethesia.

Conclusion
Advanced technology has made available to the neurosurgeon micro neurosur-
gery, minimally invasive surgery and sophisticated implants which have
resulted in much safer and more effective neurosurgical treatments for various
brain and spine disorders.
Neurological Disorders - A Handbook for Family Physicians 389

50

Stem Cell Therapy for

Incurable Neurological
Disorders
“We are not made of drugs, we are made of cells” – Cade Hildreth. Stem cell
therapy is one of the biggest breakthroughs in the eld of medicine. In the mid
1800s it was discovered that cells were the building blocks of life and that some
cells had the ability to produce other cells. Since then we have come a long way
in discovering the therapeutic use of these cells in treating debilitating diseases
which were once thought to be incurable. Stem cells not only revolutionized the
treatment for incurable disorders but also laid the foundation for regenerative
medicine. Remarkable research is happening all over the world with numerous
studies published each year in scientic journals. Researchers like Martin Evans
in the year 2007 and John Gurdon and Shinya Yamanaka in 2012 have been
awarded the Nobel Prize in physiology or medicine for their contribution to the
eld of stem cells.
Now, the stem cell research has translated into clinical medicine. Stem cell
therapy has been used to treat many diseases for eg: autism, cerebral palsy,
intellectual disability, muscular dystrophy, traumatic brain injury, brain stroke
and motor neuron disease. This chapter gives an overview of stem cells and their
use in these neurological disorders.
What are stem cells?
Stem cells are blank cells which are the foundation of every tissue/ organ in the
human body. They can divide, self-renew and differentiate into specialized
390 Neurological Disorders - A Handbook for Family Physicians

cells. When a stem cell divides, each new cell can either remain a stem cell or
become another type of cell with a more specialized function, such as a brain cell,
nerve cell, muscle cell, or a red blood cell. They can be acquired from different
areas of the body and are capable of healing, and replenishing the lost or dam-
aged cells.

Fig 50.1 Stem cell differentiation

What are different Types of Stem Cells?

Embryonic stem cells:
These cells are derived from 3-4 days old waste embryos in the IVF clinics. These
are most potent, but their use involves ethical and moral issues. Side effects
include potential teratoma formation. They are still not used for therapeutic
purpose.
Umbilical cord blood cells: Umbilical cord blood is a rich source of stem cells.
These cells are stored in cord blood banks and can be revived when required.
Adult stem cells: These cells are derived from adult tissues such as bone mar-
row, adipose tissue, dental pulp, etc, and are the most used in clinical practice.
They have no ethical issues or controversies, are safe for use, especially the
autologous cells which are cells from the same patient.
Neurological Disorders - A Handbook for Family Physicians 391

For which disorders can stem cells be used as treatment?

Various incurable neurological disorders such as cerebral palsy, autism, intel-
lectual disability, brain stroke/paralysis, head injury, cerebellar
ataxia/atrophy, cerebral atrophy, dementia, spinal cord injury, muscular
dystrophy, amyotrophic lateral sclerosis, genetic neurological disorders,
neuromuscular disorders, etc.
How do stem cells work in patients with neurological disorders?
In neurological disorders, neurons get damaged or are dead. They stimulate the
endogenous stem cells to initiate the repair process. However, these existing
stem cells have a limited ability to carry out the repair on their own. Hence, stem
cell therapy, which involves administration of stem cells, enhances the overall
repair and regeneration process.
Stem cells carry out the repair process by either direct replacement of damaged
or lost cells or via paracrine mechanisms. On transplantation, they migrate
towards the damaged areas of the nervous system and differentiate into the host
tissue cells and replace the damaged/ dead neuronal tissue. They also secrete
various growth factors which are responsible for anti-inammation, modulat-
ing the immune system, angiogenesis (forming new blood vessels), halting
further damage of the cells, etc. It has recently been suggested that stem cells
also promote tissue repair through secretion of microvesicles or exosomes. The
exosomes arise from the endosomal membrane cell compartment and are
important mediators of cell to cell communication. Their secretion may result in
horizontal transcript transfer from the stem cells to the injured cells, inducing
cell cycle re-entry facilitating tissue repair.
Via these mechanisms, stem cells help in establishing lost neuronal connections
and improve information processing. Therefore, they help in restoring the lost
functions, regain functional independence and improving the quality of life of
patients with incurable neurological disorders. In progressive disorders, they
may either slow the disease progression or completely halt it along with delay-
ing loss of ambulation and increasing their life span. The benets of stem cells
multiply in combination with multidisciplinary rehabilitation.
392 Neurological Disorders - A Handbook for Family Physicians

Figure 50.2: Mechanism of action of stem cells

Figure 50.3: Mechanism of action of stem cells

How is Stem cell therapy performed in NeuroGen Brain and Spine Institute?
We use autologous bone marrow mononuclear cells which are extremely safe
and effective and involves a very simple and a minimally invasive procedure.
The procedure involves 3 steps:
1. Aspiration: 100-120 ml of bone marrow is aspirated from the hip bone.
2. Purication and Isolation: Mononuclear cells are separated and isolated from
the bone marrow sample by density gradient centrifugation method.
Neurological Disorders - A Handbook for Family Physicians 393

3. Stem cell injection: The isolated cells are immediately injected intrathecally
into the cerebro spinal uid of the patient. In special cases, such as patients with
muscular dystrophy, stem cells are also injected intramuscularly.
The stem cell therapy is followed by an extensive personalized
neurorehabilitation program.

Fig 50.4: Aspiration of cells Fig 50.5: Separation and purication

from the bone marrow of stem cells

Fig 50.6: Intrathecal administration Figure 50.7: Intramuscular Injection

of stem cells

What are our results of stem cell therapy?

At NeuroGen Brain and Spine Institute, we have treated more than 6000 patients
with various neurological disorders. These patients are followed up at regular
intervals and the outcome of the therapy is analysed in detail.
394 Neurological Disorders - A Handbook for Family Physicians

Our results have been published in the form of 78 scientic publications in

numerous peer reviewed, national and international medical journals. All our
publications can be found on www.stemcellspublications.com
Autism spectrum disorders
Overall we have treated around 800 patients with autism. We have published 14
scientic publications showing evidence that stem cells benet children with
autism.
In our preliminary study conducted on 193 patients of ASD treated with
autologous BMMNCs intrathecal administration, common symptoms such as
social interaction, eye contact, hyperactivity, aggressive behaviour, self
stimulatory behaviour, speech, attention, stereotypical behaviour and commu-
nication were analysed. On follow up we found that, 89.12% of patients showed
improvements while 10.88% did not show any change after intervention. No
major adverse events were recorded. Children showed improvements on
objective scales like CGI – II and III, ISAA and CARS. PET-CT scans also
revealed improvements which correlated well with the clinical improvements.
Improvements in Autism After Stem Cell Therapy (N=193)
33.67%

29.53%

25.90%

10.88%

Figure 50.8: Graph representing improvements in Autism after Stem cell Therapy

Figure 50.9: Signicant improvement in metabolism is observed in caudate

head, thalamus, medial temporal cortex and cerebellum.
Neurological Disorders - A Handbook for Family Physicians 395

Cerebral Palsy
Overall we have treated more than 750 cases of cerebral palsy. We have pub-
lished 11 scientic publications demonstrating the effect of stem cell therapy in
cerebral palsy.

Improvements in CP After Stem Cell Therapy (N=267)

120

100 41%

80 30%

60

40 9% 20%

20

Figure 50.10: Graph demonstrating improvements after

stem cell therapy in cerebral palsy.
Our preliminary study included 267 patients diagnosed with cerebral palsy
who underwent stem cell therapy. The improvements were graded as no
change, mild improvements, moderate improvements and signicant improve-
ments. Analysis revealed that out of 267 patients, Overall 91 % patients showed
symptomatic improvements on follow up in common symptoms like
oromotor/speech, balance, trunk activity, upper limb activity, lower limb
activity, muscle tone, ambulation and Activities of Daily Living. Improvements
were recorded in objective scales such as FIM and GMFCS. PET CT scan also
showed improvement in brain metabolism in the areas responsible for the above
mentioned functions.

Figure 50.11: The blue damaged areas seen in the pre SCT image have almost
disappeared after SCT. This shows improvement in the metabolism /
functioning of the damaged areas after SCT.
396 Neurological Disorders - A Handbook for Family Physicians

Muscular Dystrophy
Overall we have treated more than 1150 patients with different types of muscu-
lar dystrophies such as Duchenne, Limb girdle, Becker, Facioscapulohumeral,
Congenital, etc. We have published 16 scientic publications showing evidence
that stem cell therapy is benecial in muscular dystrophy.
Our published pilot study which had 332 patients diagnosed with different
types of muscular dystrophies. On follow up, 85.74% of patients showed
improvements in ambulatory status, hand functions, balance, stamina/fatigue,
trunk activation and standing while 14.25% of patients remained stable without
deterioration in any of the symptoms.

Improvements in Muscular Dystrophy After Stem Cell Therapy (N=332)

40

35
35.74%
30 29.68%

25 20.31%

20

15
14.25%
10

0
Figure 50.12: Graph demonstrating improvement in
muscular dystrophy after stem cell therapy

Fig 50.13: Post MRI-MSk following cellular therapy, slows or halts the
progression of the pathology in Gluteal, and Mid thigh muscles
Neurological Disorders - A Handbook for Family Physicians 397

Intellectual Disability
Overall we have treated around 300 cases with intellectual disability.
In our preliminary study including 56 patients who underwent autologous stem
cell therapy ,on follow up, we found that 86.21 % of patients showed improve-
ments in symptoms such as cognition, remote memory, problem solving, under-
standing, social inhibition and toilette training. No adverse events were
recorded.

Improvements in ID After Stem Cell Therapy

45
39.65%
40
35 20.68%
30
25.86%
25
20
15 13.79%
10
5
0

Figure 50.14: Improvements seen with intrathecal administration of

autologous BMMNCs in patients with intellectual disability.

Figure 50.15: (A) Pre Stem cell

therapy PET CT scan showing
blue areas with hypometabolism
(B) Post Stem cell therapy PET
CT scan showing signicant
improvement in metabolism in
bilateral frontal cortex, cingulate
cortex, medial temporal cortex
and temporal cortex.
398 Neurological Disorders - A Handbook for Family Physicians

Traumatic Brain Injury

We have treated around 100 cases of Traumatic Brain Injury. In our published
pilot study including 30 patients of TBI, we found that 66.67 % of patients
showed improvements in balance, voluntary control, memory, upper and lower
limb activity, ambulation, posture, muscle tone, speech , cognition and ADLs.
No adverse events were recorded.
Improvements in TBA After Stem Cell Therapy

70
66.67%
60

50

40

30

20 33.33%

10

Figure 50.16: Graph showing overall improvement in the

TBI patients after stem cell therapy

Figure 50.17: (A) Pre stem cell therapy PET CT scan showing reduced
metabolism in Bilateral precuneus, left posterior cingulate, cerebellum, left
basal ganglia, thalamus, Left temporal cortex, left occipital lobe, L Superior
frontal cortex and superior parietal regions. (B) Post stem cell therapy PET
CT showing improvement in cingulate cortex, cerebellum, right basal
ganglia, right thalamus, right occipital temporal lobe.
Neurological Disorders - A Handbook for Family Physicians 399

Spinal Cord Injury

We have treated around 500 cases of Spinal Cord injury and published 7 scien-
tic papers.
Thoracic Spinal Cord Injury:
We analyzed 184 patients with chronic thoracic spinal cord injury to study the
effect of stem cell therapy. Analysis revealed that out of 184, 96.19% patients
showed improvements in symptoms like muscle tone, lower limb activity,
sensory changes, bowel/bladder function, trunk activity, balance, standing,
ambulation and activities of daily living. Improvements were also recorded in
objective scales such as FIM.

Improvements in Thoracolumbar SCI After Stem Cell Therapy

120
56.52%
100

80

24.46%
60

40
15.21%
20 3.80%

Figure 50.18: Improvements seen in thoracolumbar SCI

after intrathecal administration of autologous BMMNCs.

Cervical Spinal Cord Injury:

104 patients with cervical spinal cord injury were included in the analysis. The.
Analysis revealed that out of 104 patients, 96.19% patients showed improve-
ments in symptoms such as muscle tone, upper limb activity, lower limb activ-
ity, sensory changes, bowel/bladder function, trunk activity, balance, standing,
ambulation and activities of daily living. Improvements were also recorded in
objective scales such as FIM
400 Neurological Disorders - A Handbook for Family Physicians

Improvements in Cervical SCI After Stem Cell Therapy

60
56.52%
50

40

24.46%
30

20
15.21%
10 3.80%

Figure 50.19: Improvements seen in cervical SCI

after intrathecal administration of autologous BMMNCs.

Fig 50. 20: Post fMRI in Spinal cord injury after cellular therapy showing
increased activation in the associated regions of the brain

Brain Stroke
We have treated around 150 patients with brain stroke and published 5 publica-
tions demonstrating the results of stem cell therapy in stroke. On analysing the
data of 47 patients, it was observed that 77% showed improvements in symp-
toms such as standing and walking balance, ambulation, hand functions and
activities of daily living. Improvements were recorded on FIM scale, Berg
Balance scale, Reach test and Modied Rankin Scale. PET CT brain also showed
metabolic improvements after stem cell therapy.
Neurological Disorders - A Handbook for Family Physicians 401

Improvements in Brain Stroke After Stem Cell Therapy (N=47)

25

48.93%
20

15

23%
10
19.14%

5 8.51%

Figure 50.21: Graph demonstrating improvements in

brain stroke after stem cell therapy

Amyotrophic Lateral Sclerosis

We have treated around 250 patients of ALS and published 5 publications. Our
previously published preliminary study included 84 patients who underwent
stem cell therapy. Their survival duration was compared with that of 20 patients
who did not undergo stem cell therapy. Both patient groups shared similar
baseline demographics. The mean survival duration of the patients who
received treatment was 90.96 ± 9.27 months and those who did not was 57.38
±5.31. A clinically signicant difference of 34 months in the survival duration
was recorded.
We also noted that patients who were given Lithium and were young had better
survival than the others. This could be attributed to better survival and growth
of the transplanted cells. Hence, this study suggests that in addition to the
standard treatment with Riluzole and neurorehabilitation, there is a possibility
that early intervention with combination of stem cell therapy and Lithium may
have a positive effect on the duration of survival in ALS.
402 Neurological Disorders - A Handbook for Family Physicians

Figure 50. 22: .Comparitive Kaplan-Meier Analysis of ALS patients with

and without stem cell transplantation

Cerebellar Ataxia
We have treated around 140 patients of cerebellar ataxia. In our preliminary
study of 91 patients, improvements were recorded in 93.4% of patients. Symp-
toms such as co-ordination, ambulation, hand functions, stamina/fatigue, trunk
balance and standing showed improvements. Changes were also recorded in
outcome measures such as FIM scale, MICARS and BARS. PET CT scan brain
also showed improved metabolic activity after stem cell therapy.
Neurological Disorders - A Handbook for Family Physicians 403

Improvements in Cerebellar Ataxia After Stem Cell Therapy (N=91)

45
42.85%
40 39.5%

35
30
25
10
15
10 6.6%

Moderate
6.5%
4.3%
5
Mild
No

0
Deteriororate Significant

Figure 50.23: Graph demonstrating improvements in

cerebellar ataxia after stem cell therapy

Figure 50.24: PET CT Scan

showing improved metabolic
activity in the cerebellum
after stem cell therapy.

How safe is stem cell therapy?

At NeuroGen Brain and Spine Institute, we use autologous bone marrow
mononuclear cells which are the safest form of cells used for clinical purposes.
Since they are autologous i.e. patient’s own cells there is no risk involved in their
use. Procedural side effects such as headache, pain at the site of aspira-
tion/injection, fever, nausea, vomiting is seen in few patients. However, they
are self-limiting and easily treated with medications before discharge. Some
patients with history of seizures or an abnormal EEG are at risk of having sei-
zures after stem cell therapy. Therefore, our protocol includes administration of
prophylactic anti-epileptic medications before the therapy to avoid the occur-
rence of seizures. Thus, overall autologous stem cell therapy has no major long-
term side effects.
404 Neurological Disorders - A Handbook for Family Physicians

“Stem cell research can revolutionize medicine more than anything since antibi-
otics”- Ron Reagan. Adult stem cells such as autologous bone marrow derived
cells have shown promising outcome in various neurological disorders paving a
way for newer treatments. They are safe with no major side effects and have no
ethical or moral issues associated with them. They repair the neurological
damage or slow down/ halt the disease progression by neuroprotection,
neurorepair and neuroregeneration.. In combination with multidisciplinary
rehabilitation, they further enhance the outcome of standard treatment. Their
therapeutic effects are demonstrated as improvements in clinical symptoms as
well as objective neuroimaging studies such as PET CT scan, MRI MSK, func-
tional MRI, etc. Though not a cure, stem cell therapy is a safe treatment and can
make the patient functionally independent, promote development of mile-
stones in children and improve their quality of life. It can bridge the gap between
normalcy and current condition of the patient. If stem cell therapy is done at
young age or in early stage of the disease then the results of the treatment seen
are much better. Hence with all this supporting background scientic evidence,
stem cell therapy should be considered for treatment of incurable neurological
disorders.
Neurological Disorders - A Handbook for Family Physicians 405

51

Interventional Neurology
Interventional neurology refers to endovascular, catheter-based techniques
using uoroscopy and angiography to diagnose and treat vascular disease of
the central nervous system. Interventional Neurology has evolved (and still
evolving) into a complex eld, with a set of techniques and a knowledge base
that are distinct from other elds of medicine. Rapid advances in the eld of
interventional neurology and the development of minimally invasive tech-
niques have resulted in a great expansion of potential therapeutic applications.
Here is a brief view of current endovascular treatments available for various
vascular disorders of brain and spine and also future of Interventional neurol-
ogy.
Diagnostic Cerebral Catheter Angiography -
Also called as Digital subtraction angiography (DSA). Typical indications
include the diagnosis of cerebral aneurysms, arteriovenous malformations,
cerebral vasospasm, intracranial stenosis, arteriovenous stula or small vessel
vasculopathy including vasculitis. It is often performed just prior to a planned
neurosurgical or neurointerventional procedure, as well as immediately after a
neurosurgical case. Despite alternative imaging modalities and safety concerns,
the actual indications for catheter angiography have not signicantly decreased
because of the increasing numbers of suspicious vascular ndings seen on the
very studies (CTA and MRA) thought to supplant it. Furthermore, since mini-
mally invasive endovascular techniques have gained prominence and some-
times replaced open surgical techniques, catheter angiography remains an
indispensable modern imaging modality. Spinal DSA is useful tool in diagnosis
and treatment planning of spinal AVM, spinal Dural AV stula.
406 Neurological Disorders - A Handbook for Family Physicians

3D rotational angiography allows evaluation of the opacied artery and its

branches from any angle. The technique facilitates understanding of complex
vascular anatomy and is a frequently used application in modern diagnostic as
well as therapeutic neurovascular care especially in aneurysm and AVM treat-
ment planning.
Cerebral DSA is gold standard for diagnosis of various vascular disorders like
intracranial stenosis, posterior circulation stenosis, Dural AV stulas etc. DSA is
indicated when distinctions affecting treatment are unclear; for example,
angiography can assist in cases in which differentiation between carotid
and vertebrobasilar TIA or evolving stroke is uncertain on clinical grounds
and noninvasive imaging only.
Although the risks associated with cerebral angiography have been gradually
decreasing, the risk for any complication is approximately 1% to 5%, of which
half are minor groin hematomas. Renal function should be normal as iodinated
contrast dye used for DSA is nephrotoxic.
Referral : Referral to Interventional Neurologist/Neurosurgen/Radiologist
Who should be referred: Patients with recurrent Stroke, Young Stroke,
intracranial bleeding of unknown cause, subarachnoid hemorrhage, suspected
spinal vascular malformation.
Endovascular Treatment of Acute Ischemic Stroke:
The corner stone of the treatment in acute ischemic stroke (AIS) is
revascularization. It was only in 1995 when National Institute of Neurological
Disorders and Stroke rtPA Stroke Trial (NINDS Study Group) revolutionalized
the management of AIS using recombinant tissue plasminogen activator (rtPA)
within 3hrs reducing the stroke morbidity by 30%. Eventually the window
period was increased to 4.5 hrs after ECASS III. Inj rtPA (Actilyse) and
Tenectaplase (Tenectase) are the IV thrombolytic agents approved for acute
Ischemic Stroke and both are available in India. Dose of Inj Actilyse is 0.9 mg/kg
(10 % as bolus and remaining as IV infusion over 60 mins). It can be given upto
4.5 hrs from symptom onset. Inj Tenectaplase is approved by DGCA, India. It
can be given upto 3 hrs from symptom onset and its dose is 0.25 mg/kg (given as
bolus dose). Unfortunately, intravenous thrombolysis (IVT) has higher failure
rate in large vessel occlusion (LVO).
Intra-arterial urokinase achieved 66% recanalization in LVO and also prolonged
the window period for acute stroke intervention upto 6 hours. In this procedure ,
drug (urokinase or rtPA) is administered through microcatheter at the site of
occlusion. This targeted delivery of drug also minimises systemic side effects of
Neurological Disorders - A Handbook for Family Physicians 407

drug. But there is minimal increase of risk of hemorrhagic complications.

Though FDA has not approved intraarterial rtPA , it can be used in selected
cases within 6 hrs of Stroke onset. American Stroke Association (ASA) has given
Class 2 recommendation for this treatment. Thus, while both these therapies
improved stroke outcomes, a proportion of patients having large vessel occlu-
sions were not amenable to these measures.
Mechanical thrombectomy (MT) with newer thrombectomy devices have many
advantages compared to thrombolysis in LVO stroke. A recent review of litera-
ture of ve randomized control trials (RCT) proved superiority of MT using
stent retrievers over best medical management using IVT. Recently published
study of Mechanical Thrombectomy in Acute Ischemic Stroke due to large
vessel occlusion by Singh et al showed results comparable with Published RCTs
and shows feasibility of this procedure in real world scenario like India. The
Merci Retrieval system was the rst FDA approved treatment option for
embolectomy in cerebral arteries. The Penumbra Stroke System (Penumbra,
Alameda) was also approved by FDA in 2008 and is the most widely used
thromboaspiration device in the US. Newer generation stent retrievers avail-
able give more success rate with fewer complications. Solitaire, Trevo, Eric etc
are the stentrivers available in India. With the use of ballon guide catheters (
Merci, Cello, Flowgate) with stentrivers , recanalization rate is over 80%.
Recanalization rates with thromboaspiration or stentrivers are comparable and
both techniques are equally efcacious. Sometimes both techniques has to be
used ( Solumbra technique).
Mechanical Thrombectomy is recommended upto 6 hours of symptom onset.
But according to new ASA/AHA 2018 guidelines, in selected cases it can be
done in patients with 6-24 hours of symptom onset! Patients with large vessel
occlusion requiring mechanical Thrombectomy should also receive IV
thrombolysis and then shifted to Cathlab for mechanical Thrombectomy (Bridg-
ing Thrombolysis ). Procedure of mechanical Thrombectomy:
Procedure is performed through femoral artery access. 8F balloon guide cathe-
ter is navigated over Guide wire and placed in the ipsilateral cervical internal
carotid artery. The microcatheter is navigated distal to the clot over microwire.
Solitaire stentriver is then delivered through the microcatheter and deployed
over the thrombus. Solitaire serves dual function, namely, immediate ow
restoration by creating temporary bypass through the thrombus and also acts as
a clot retriever, trapping thrombus into its cells. The balloon of guide catheter is
inated with contrast to provide proximal ICA occlusion and ow arrest during
the recovery of the stent retriever. Subsequently, the Solitaire and microcatheter
are slowly recovered as a unit under constant aspiration with 50-mL syringe
through the balloon guide catheter.
408 Neurological Disorders - A Handbook for Family Physicians

Investigations in acute stroke: Urgent CT-CTA brain or MRI stroke protocol

(DW, ADC, FLAIR, MRA). Rule out hemorrhagic on imaging. If patient is in
time window period (4.5 hrs) and no contraindication for intravenous
thrombolysis then IV rtPA should be started. Patient should be immediately
referred to higher centre with facility of Thrombectomy if large vessel occlusion
(ICA, Procimal M1, Basilar artery) is present.
Referral: To Neurologist and Interventional Neurologist/ Neurosurgen /
Radiologist
Who should be referred: Acute Stroke in window period.
Endovascular Aspects of Secondary Stroke Prevention:
Carotid Angioplasty-Stenting (CAS )
Current surgical interventions to lower the risk of stroke among people with
carotid artery stenosis include carotid endarterectomy (CEA) as well as carotid
angioplasty and stent placement (CAS).
Carotid angioplasty with stent placement (CAS) was resurrected as an alterna-
tive treatment for revascularization of carotid artery stenosis in high-risk surgi-
cal candidates. Several Randomized control studies and comparisons with CEA
have increased the popularity of CAS. These studies have focused on the safety
and effectiveness of CAS. With improving devices and techniques, CAS has
become safer than and as effective as surgical treatment.
Patients undergoing CAS have small embolic showers occurring frequently
during the procedure. These microemboli are composed of thrombotic and
plaque substances. This underlies the importance of using a distal protection
device to prevent the microemboli from being released into cerebral circulation
during carotid angioplasty and stenting. Distal protection devices include
occlusive balloons, lter devices, and ow reversal devices.
Progressive improvements in technology and increasing operator experience
and encouraging results from clinical trials have led to a broader acceptance of
CAS even in patients not considered high risk for carotid endarterectomy.
Procedure of CAS:
Procedure is performed through femoral artery access. 8F guide catheter or 6 F
long sheath is navigated over Guide wire and placed in the common carotid
artery. Stenosis is crossed with microwire. Over microwire distal embolization
protection device (Spider) is placed into ICA. Angioplasty is done using
noncompliant Balloon at desired pressure. Inj atropine is given to counteract
bradycardia due to carotid body stimulation during angioplasty.Then stent is
deployed across the stenosis. This procedure is done generally under local
anaesthesia.
Neurological Disorders - A Handbook for Family Physicians 409

Vertebral artery stenting:

Most common site of stenosis is at origin of vertebral arteries, also called as
osteal stenosis. In some cases, traumatic / spontaneous dissection of vertebral
artery results in ow-limiting narrowing necessitating stenting. Stenting is
generally required in patients with severe stenosis causing symptoms of
Vertebro-Basilar insufciency. Procedure of vertebral artery stenting is gener-
ally done under local anaesthesia and stents used are balloon mounted drug
eluting stents.
Angioplasty-stenting of intracranial Stenosis :
Intracranial stenosis is responsible for 8–10% of all ischemic strokes. There is a
high yearly rate of recurrent strokes in patients with intracranial stenosis that
has been estimated at approximately 8–12% and in those not taking
antithrombotic treatment, the rate of recurrent ischemic stroke events can be
even higher and has been estimated at 52%.
Percutaneous transluminal angioplasty with possible stent placement has been
recommended for treatment of intracranial stenosis especially for patients not
responding to medical treatment. The long-term follow-up has suggested
ipsilateral stroke prevention of up to 96% for the rst year and approximately
87% for up to the third year after interventional treatment.
For symptomatic patients with >50% intracranial stenosis who have failed
medical therapy, balloon angioplasty with or without stenting should be
considered. Patients who have an asymptomatic intracranial arterial stenosis
should rst be counseled regarding optimizing medical therapy. There is
insufcient evidence to make denite recommendations regarding
endovascular therapy in asymptomatic patients with severe intracranial athero-
sclerosis. Contraindications for intracranial stenting are inability to have
antiplatelet therapy and/or anticoagulation and highly calcied lesions or
anatomy that prevents endovascular access. In India balloon mounted drug
eluting stents are available and widely used for intracranial stenosis. Advantage
of these stents are lower rate of restenosis.
Procedure of Intracranial stenting :
Procedure is performed through femoral artery access. 6F guide catheter is
navigated over Guide wire and placed in the internal carotid artery / vertebral
artery. Stenosis is crossed with microwire. Angioplasty is done using
noncompliant ballloon slowly and carefully at desired pressure. Then stent is
placed across the stenosis under uoroscopic guidance.
410 Neurological Disorders - A Handbook for Family Physicians

Referral : To Interventional Neurologist/Neurosurgen/Radiologist

Whom should be referred: Patients with recurrent stroke/ TIAs with docu-
mented stenosis on CTA/ MRA.
Endovascular treatment of Cerebral venous thrombosis (CVT):
Cerebral venous thrombosis (CVT) can occur in the form of cortical venous
thrombosis, venous sinus thrombosis, deep venous thrombosis, jugular venous
thrombosis, or various combinations of the above. CVT has high mortality rate
ranging from 5–30%. The interruption of outow in the brain circulation leads to
augmentation in the pressure of the entire system with venous hypertension,
intracranial hypertension, and hemorrhagic events.
The main goal of the treatment of CVT should be the recanalization of venous
drainage system with complete reestablishment of normal brain circulation. The
treatment of choice is IV anticoagulation followed by local thrombolysis where
indicated. Endovascular treatment is indicated for patients unable to receive
antico-agulation and for those who deteriorate despite anticoagulation heparin.
Endovascular therapy is also indicated in high-risk categories including those
with seizures, coma, disturbed consciousness, deep cerebral vein thrombosis,
posterior fossa involvement, and/or pro-gressive focal decits.
The endovascular route used is transvenous through the femoral vein, navigat-
ing the catheter into the venous circulation and nal placement in the matrix of
thrombus. The thrombolytics are given as bolus dose followed by infusion over
a period of hours for a better recanalization. The rate of recanalization (partial
and total) ranges from 70–95%. Drugs used are urokinase and rtPA.
Endovascular treatment of aneurysms :
Intracranial aneurysms (IAs) are localized dilations of the cerebral arteries wall
and are prone to rupture, resulting in bleeding. The overall prevalence of
unruptured IAs is between 2% and 3.2% in the general population with a male to
female ratio of 1:2.1 It is the leading cause of hemorrhagic stroke, responsible for
85% of subarachnoid hemorrhages (SAH).
The outcome for patients with SAH remains poor, with overall mortality rates of
25% and signicant morbidity among approximately 50% of survivors.
Long-term follow-up in the International subarachnoid aneurysm (ISAT) trial
evaluating exclusively ruptured aneurysm, with a mean follow-up of nine
years, has demonstrated the effectiveness of coil embolization in essentially
eliminating the risk of future subarachnoid hemorrhage.
Neurological Disorders - A Handbook for Family Physicians 411

Considerable advances have been made in the ability to use coils for
endovascular treatment of intracranial aneurysms in situations that might have
appeared unsuitable a few years ago. The new designs of coils, including the
three-and two-dimensional congurations, have improved results. Focusing on
the anatomy of the aneurysm and on the neck and dome ratio, as well as its
packing with coils in a step-wise manner, has led to remarkable success in
coiling of aneurysms previously considered to be difcult.
Simple Coiling:
Detachable coils were invented by Guglielmi in the 1990s, and transluminal
embolization techniques were gradually developed since then.Simple coiling
refers to transluminal navigation of a microcatheter into the aneurysmal dome
with the help of microguidewires and the delivery and packing of detachable
coils within the aneurysmal sac. The goal in coiling is to achieve dense packing
and induce rapid blood clot formation within the aneurysmal sac, hence isolat-
ing it from active circulation.
Balloon-Assisted Coiling Balloon-assisted coiling (BAC):
BAC was initially described by Moret et al in 1997 in treating IAs with a wide
neck. It is described as using 1 or multiple nondetachable temporarily inated
balloons to block the aneurysmal neck during coil placement . For difcult
situations or complex cases, multiple balloon technique is used. Besides multi-
ple balloon technique, special balloons are also being developed, such as
hypercompliant, roundshaped, and double lumen balloons. The BAC was used
frequently in IAs with unfavorable dome-to-neck ratio (1.5, >1.0).
Stent-Assisted Coiling :
The SAC can overcome the limitations of wide-necked, gigantic, fusiform, and
some other complex IAs.56 Similar to BAC, a stent is deployed to block the
aneurysmal neck before coil packing. The IAs wit an extremely unfavorable
dome-to-neck ratio (1.0) require SACgenerally due to the need of permanent
support to prevent coil prolapse and migration
Y-stenting technique is developed for treating bifurcation IAs, where 1 or more
microcatheter are in place with 2 stents blocking the aneurysmal neck (Figure
6B).61 It is by far the best technique for treating bifurcation basilar artery
aneurysms.
Flow-Diverting Stent Flow-diverting stents (FDSs) are a new generation of
stents designed to treat IAs by isolating the aneurysmal lumen from the circula-
tion via recanalization.
412 Neurological Disorders - A Handbook for Family Physicians

Flow Diverters:
The FDSs are suitable for both wide-necked and fusiform IAs. For large
aneurysms it is also advisable to put some coils to prevent imminent rupture
due to ow diversion. The main concern with FDSs is the risk of perforator
blockage and stent thrombosis.
WEB:
WEB ow disruption is a new, innovative endovascular technique dedicated to
the treatment of ruptured and unruptured wide-neck bifurcation aneurysms.
Referral: To Interventional Neurologist/Neurosurgen/Radiologist
Whom should be referred: All Patients with subarachnoid hemorrhage
Chemical angioplasty:
Cerebral vasospasm
Despite all therapeutic possibilities, a large number of patients develop
angiographic or clinical vasospasm responsible for high morbidity and mortal-
ity. Usually the vasospasm is delayed and has a typical temporal course, with
onset 3–5 days after the hemorrhage, maximal narrowing at 5–14 days, and
gradual resolution over 2–4 weeks. In about half the patients, vasospasm is
manifested by the occurrence of a delayed neurological ischemic decit which
can lead to stroke, disability and death.
Endovascular therapy offers an additional treatment for patients who continue
to experience delayed ischemic neurological decits despite optimal medical
therapy. Presently, the most commonly employed treatments are PTA and/or
intraarterial vasodilation with nicardipine, verapamil, nimodipine, amrinone,
or milrinone.
Referral: To Interventional Neurologist/Neurosurgen/Radiologist
Who should be referred: Patients of subarachnoid hemorrhage with suspected
vasospasm. Vasospasm should be suspected if patient of SAH developed
worsening of headache, neurodecit despite Nimodipine and triple H therapy.
Endovascular treatment of AVMs:
Arteriovenous malformations (AVMs) are congenital vascular lesions that may
appear throughout the central nervous system. They consist of direct connec-
tions between arteries and veins, without an intervening capillary bed. There is
a rate of approximately 4% hemorrhagic conversion per year for cerebral AVMs.
They carry a combined morbidity and mortality rate of 2.7% per year.
Neurological Disorders - A Handbook for Family Physicians 413

The risk of haemorrhage from an AVM depends strongly on whether there has
been a previous haemorrhage. AVMs can cause headaches, seizures, ischemia
and developemental learning disorders due to changes in surrounding brain
parenchyma by AVM.
The treatment of AVMs is challenging and multifaceted. Surgical excision ,
radiosurgery and endovascular embolization are the treatment modalities
available. They pose a unique problem and often require a combination of
therapeutic modalities. Embolization has been used for the following purpose:
1) adjunct to surgery; 2) reduction of size before radiation; 3) palliation; and 4)
embolization alone for cure. In cases with large AVMs, generally staged
embolization is done.
The ARUBA trial (2014) showed that medical management alone is superior to
medical management with interventional therapy for the prevention of death or
stroke in patients with unruptured brain arteriovenous malformations followed
up for 33 months. This is for unruptured AVMs. But if AVMs have weak spots
on angiography like intranidal aneurysms it is better to treat them as they have
high chance of rupture in near future.
Advancements in catheter design in the 1980s permitted selective
catheterization of AVM pedicles. The introduction of the ow-directed Magic
catheter was a major breakthrough. With the additional availability of 0.010-in.
wires and the addition of hydrophilic coating to the catheters, intranidal
catheterization was possible. n-BCA and polyvinyl alcohol ( Glue ) emerged as
the most popular embolization materials for AVMs. Ethylene vinyl alcohol
copolymer in dimethyl sulfoxide solution (Onyx, Micro Therapeutics, Inc.,
Irvine, CA) was introduced in 1990.
Other liquid embolizing materials available are SQUID, PHIL. Sometimes after
injection of embolizing material into AVM , retrieval of microcatheter can
become problematic as it may got stuck into cast. This problem is overcome by
detachable tip microcatheters ( Apollo, Sonic).
With advancement in techniques and materials, more and more AVMs can be
treated with endovascular embolization with increasing cure rate. Embolization
is generally done through arterial route and aim of treatment remains oblitera-
tion of nidus with foot of draining vein. In some cases venous route can be used
for embolization. Recently developed Pressure Cooker Technique, use of multi-
ple catheters offer promise of complete cure in difcult and complex AVMs.
Referral : To Interventional Neurologist/Neurosurgen/Radiologist
Who should be referred: Patients with atypical intracranial bleed, suspected
414 Neurological Disorders - A Handbook for Family Physicians

AVM/ ow voids on imaging. Once ruptured chances of rerupture is high in

immediate few days. Weak spots should be identied by DSA and treated with
embolization/ surgical excision.
Endovascular embolization of Dural Arteriovenous Fistulas :
Intracranial dural AV stulas (dAVF, dural arteriovenous stulous malforma-
tion) are acquired lesions that usually involve one of the intracranial venous
sinuses. They comprise about 10% of all intracranial vascular malformations.
Numerous branches of the ECA, ICA, and/or vertebral artery form direct
connections to a venous sinus and/or intracranial veins. Any intracranial
venous sinus may be involved. Symptoms and physical ndings are highly
variable and depend on the location and anatomy of the lesion. DAVF can give
rise to Pulsatile tinnitus, Haemorrhage, Intracranial venous hypertensionl.
Neurological symptoms attributable to elevated intracranial venous pressure
include: Progressive dementia, pseudotumor cerebri, Parkinsonism, Cervical
myelopathy. Lesions causing arterialization of intradural veins are classically
associated with intracranial haemorrhage.
Management options for patients with a dAVFs are Conservative management,
endovascular techniques, Surgery, Radiosurgery and combined approach.
Conservative management is reasonable in certain situations like asymptomatic
or minimally symptomatic lesions.
Generally the most effective treatment of dAVFs is occlusion of the draining
vein. In most cases, obliteration of the lesion can only be accomplished by treat-
ment of the venous side of the lesion. Transvenous techniques appear to carry
the highest success rates among endovascular techniques. Successful arterial
embolization usually occurs only when the microcatheter is positioned well
within or adjacent to the nidus, so that embolic material can be pushed through
the nidus into the venous side. If only feeding arteries are occluded and not the
draining vein, collateral vessels usually develop and the stula will recur.
Conversely, it is equally important to ensure that normal venous drainage is
preserved after embolization to avoid exacerbated venous hypertension and
risk of haemorrhage.
With availability of good microcatheters (ow guided microcatheters, detach-
able tip microcatheters), liquid embolizing agents (Glue, Onyx, SQUID, PHIL)
and advancements in techniques, more and more dAVFs can be safely treated
with endovascular route with good results.
Referral: To Interventional Neurologist/Neurosurgen/Radiologist
Who should be referred: Patients with atypical intracranial bleed, suspected AV
Neurological Disorders - A Handbook for Family Physicians 415

stula/ ow voids on imaging. Once ruptured chances of rerupture is high in

immediate few days. Weak spots, cortical venous reux, venous stenosis should
be identied by DSA and treated with embolization/ surgery.
Carotico-cavernous stula (CCF):
CCF is characterized by a direct shunt between the intracavernous segment of
the internal carotid artery (ICA) and the surrounding venous plexus of the
cavernous sinus. The pathogenesis is commonly a rupture of the artery and vein,
after a penetrating or blunt trauma. Spontaneous stulas can also occur.
Carotid–cavernous stulas are characterized by a typical cavernous sinus
syndrome with ophthalmoplegia, pulsating exophthalmos, chemosis, and
bruit. The symptoms can appear acutely or slowly, progressively days or weeks
after the trauma, or have a spontaneous onset. Sometimes presentation is with
signs of venous hypertension if there is cortical venous reux. Treatment is
endovascular embolization with detachable balloons, coils, coils + liquid
embolizing agents, covered stents. Both arterial and or venous approaches can
be used. Parent vessel occlusion is also a valid option.
Referral : To Interventional Neurologist/Neurosurgeon/Radiologist
Who should be referred: Patients with unilateral/ bilateral proptosis, chemosis,
external ophthalmoplegia.
Traumatic neurovascular injury:
Transcatheter occlusion of traumatically injured vessels to control life-
threatening bleeding represents some of the earliest endovascular
procedures.Penetrating injury to the arteries of the head and neck may lead to
dissection and pseudoaneurysm formation with the dreaded consequence of
high-pressure arterial hemorrhage. Endovascular stenting of dissected intimal
aps aids in tacking down the affected vessel wall and preventing downstream
dissection. Aside from endovascular stenting, coil embolization of traumati-
cally induced bleeding stulas and pseudoaneurysms of the head and neck may
also be performed using liquid embolic agents, Bernstein liquid coils, particles
(polyvinyl alcohol), Detachable balloons, detachable coils .
Role of endovascular therapy in head and neck tumors:
Endovascular neurointervention offers a means for preoperative embolization
of highly vascular tumors, thus reducing the complexity and complications of
blood loss during surgery. In addition to neurovascular tumors that may benet
from embolization, hemangiomas, vascular malformations, and lymphovenous
malformations of the head and neck may also benet from endovascular
416 Neurological Disorders - A Handbook for Family Physicians

therapy. Methods of embolization involve a standard angiographic

transfemoral approach to the cranial vasculature. Though embolization is
usually restricted to the external carotid artery (ECA) system, the internal
carotid artery (ICA) is often studied to assess important orbital anastomoses
between the ECA and ICA. Superselective catheterization using microcatheters
is then undertaken to localize the territory targeted for treatment. Embolization
is then performed using 150–250 m polyvinyl alcohol particles, Gelfoam powder
or strips, or ethanol. Direct injection of absolute alcohol (dehydrated alcohol,
98% ethylalcohol), or sodium tetradecyl sulfate for the treatment of supercially
accessible lesions such as hemangiomas, vascular malformations, and
lymphovenous malformations of the head and neck may be performed.
Recent endovascular intervention has involved clinical trials aimed at deliver-
ing chemotherapeutic agents directly to the tumor region, with the hypothesis
that intra-arterial (IA) delivery would increase the concentration of the medica-
tion at the tumor site while minimizing side effects of systemic administration.
Many trials are on going with equivocal results.
Endovascular treatment of Spinal Vascular Lesions :
Spinal arterio-venous vascular lesions are entities with serious consequences if
untreated. Spinal vascular lesions include dural arteriovenous stula (dAVF) ,
intramedullary arteriovenous malformation (AVM) , Juvenile AVM, intradural
perimedullary AVF, Extradural arteriovenous stulas, Spinal cord aneurysms,
Intramedullary cavernous malformations , Vascular spinal tumours Spinal
cord ischaemic stroke. dAVFs are the most common spinal vascular lesion,
representing approximately 70% of spinal vascular malformations. Catheter
angiography is the gold standard for the workup of most of spinal vascular
lesions.
Endovascular embolization should be done when the anatomy of the lesion
permit obliteration of the nidus and proximal part of the vein. Embolization is
feasible in some 75% of cases. Barriers to embolization include advanced athero-
sclerosis, arterial feeders too small to catheterize and collateralization of the
feeding vessel with normal spinal cord vessels. Embolization is most effective
when the glue penetrates the proximal portion of the draining vein; if the glue
does not reach the draining vein, the stula may persist or recanalize.
Embolization is particularly useful in patients who are poor candidates for
surgery, or in some cases as a temporizing measure, to reduce venous conges-
tion until a denitive surgical procedure can be performed. The embolization
agent of choice is N-butyl cyanoacrylate (Glue). Other liquid embolizing agents
also can be used.
Neurological Disorders - A Handbook for Family Physicians 417

Referral : To Interventional Neurologist/Neurosurgen/Radiologist

Who should be referred: Patients with paraplegia/ quadriplegia with suspected
spinal AVM/ ow voids on MRI spine. Spindle shapes edema of cord is typical
nding in spinal AVF.
Future applications :
Endovascular therapy for acute and chronic cerebrovascular diseases and
interventional neuroimaging is evolving at a rapid pace. The safety and efcacy
of endovascular procedures is expected to improve with new technologies.
Stem cell therapy :
Despite the fact that numerous paths of stem cell transport to the brain in acute
ischemic stroke exist, the intra-arterial route of stem cell transport is most attrac-
tive and has great potential for clinical translation. Intra arterial delivery of stem
cells derived from bone marrow in autologous or transplanted stem cell deliv-
ery may help repair damaged regions of the brain. Experimental study on rat
model by Watanabi et al suggested optimum timing and Maximum tolerated
dose (MTD) of stem cells through Intra arterial route in acute Ischemic stroke.
According to their study, administration of stem cells at MTD of 1 x 10 ^5
through the Intra arterial route will not obstruct MCA blood ow and adminis-
tration during subacute period will more effectively stimulate neuroprotection
following cerebral ischemia

Figure 50.1 : Mechanical Thrombectomy . 79 yrs old female presented with acute
onset left hemiplegia due to MCA occlusion. Mechanical Thrombectomy done
using solitaire stentriver with retrieval of multiple clots with complete opening
of artery. Patient improved dramatically. Red Arrows indicate the sight of
occlusion before and after the procedure.
418 Neurological Disorders - A Handbook for Family Physicians

SUMMARY
- Field of Interventional Neurology is evolving. With advancement of
techniques and better catheters/ material availability procedure has
become more safe and previously untreatable vascular lesions can also
be treated safely.
- Mechanical Thrombectomy for acute Ischemic Stroke has class 1
recommendation and all Patients with acute Ischemic Stroke with
large vessel occlusion should be offered this treatment.
- Carotid and vertebral artery angioplasty-stenting and in selected cases
intracranial stenting can be done if stenosis is severe and Patient is
symptomatic despite optimum medical management.
- All Patients with atypical intracranial bleed should undergo cerebral
DSA to nd out underlying causes like AVM, AVF and if found can be
safely treated with endovascular embolization/surgery.
- All subarachnoid hemorrhage Patients should undergo cerebral DSA
to nd out aneurysm/ dissection and if found, can be treated with
Endovascular coiling or surgical clipping. Resistant vasospasm can be
managed with chemical angioplasty.