Meningitis

Definition
• Meningitis is defined as inflammation of the meninges.
• Meningitis can be caused by infectious and non-infectious processes (
autoimmune disorders, cancer/paraneoplastic syndromes, drug
reactions).
• The infectious etiologic agents of meningitis include bacteria, viruses,
fungi, and less commonly parasites.
• World meningitis day is celebrated on 5th October.
Epidemiology
• It is the most common form of suppurative CNS infection with an
annual incidence of >2.5 cases / 1 lakh population. The organisms
most often responsible for community acquired bacterial meningitis
are Streptococcus pneumonia ( 50% ), Neisseria meningitides (25%) ,
Group b Streptococci (15%), Listeria monocytogenes (10%).
Haemophilus influenza type b is accounting for <10 % cases of
bacterial meningitis.
• Neisseria meningitidis is the causative organism of recurring
epidemics of meningitis every 8-12 years.
Types of meningitis based on
duration of illness
• Acute : sudden onset, severe symptoms
• Subacute : presentation of symptoms over weeks
• Chronic : over >4months.
 Causes of acute meningitis
• Bacterial
VIRAL MENINGITIS PARASITIC
MENINGITIS
• ENTEROVIRUS • NAEGLERIA FOWLERI
• HERPESVIRUS • BALAMUTHIA MANDRILLARIS
• HIV
• ARBOVIRUS
Pathogenesis of bacterial meningitis
• Streptococcus which is the most common cause usually colonises in
nasopharynx. It posseses pili and capsules which migrate to blood
vessels and attach to vessel wall , and then migrate across blood brain
barrier to reach choroid plexus and subarachnoid space.
• The bacterial products like endotoxins and lipopolysaccharide of cell
wall are released there thereby initiating inflammation and causing
meningitis.
Result of inflammation
• It leads to increased vascular permeability thereby causing edema.
• Exudation is seen due to increased protein thereby reducing CSF
resorption and causing obstructive hydrocephalus.
• There can also be vascular changes leading to ischemia / stroke
because of vasospasm , vasculitic changes.
Types of oedema in meningitis
• It is usually of 3 types
1) Vasogenic edema: it is the main culprit in meningitis. Steroids are
used to reduce vasogenic edema.
2) Cytotoxic edema: seen in cases of cell rupture. Mannitol is used for
this. Steroids don’t help in such cases.
3) Interstitial edema: seen in obstructive hydrocephalus. Mannitol and
steroids both are used together here.
Cranial neuropathies can occur due to formation of exudates.
Clinical features
• Fever
• Headache
• Altered sensorium
• Meningismus: headache + neck stiffness + photophobia, neck stiffness
occurs due to meningeal irritation.
• Altered mental status needs to be differentiated from encephalitis
which has features like focal seizures, focal neurological deficits, severe
behavioural abnormalities.
• Cushing’s reflex can also be present due to raised ict. ( hypertension ,
bradycardia, irregular respiration )
Signs of meningeal irritation
• Neck stiffness: pain on neck flexion
• Kernig’s sign: patient lies supine and then 90 degree flexion at hip and
knee is done followed by knee extension which causes painful spasm
of posterior compartment ( hamstring muscles ).
• Brudzinki’s sign: neck flexion leads to knee flexion of both legs.
Investigations
• Blood culture: it should be obtained within 60mins of patient’s arrival
and antibiotics started empirically within 60mins.
• Csf analysis and culture: it is the gold standard for diagnosis of
bacterial meningitis.
• Neuroimaging
• Cxr, procalcitonin, cbc.
Situations where neuroimaging is
required before csf analysis
• Signs of raised ICT and papilledema
• Altered level of consciousness
• Focal signs like seizures
• Immunocompromised patients
• In these situations, a space occupying lesion should also be
suspected.
Relative contraindications of LP
• Herniation
• Large space occupying lesion / abscess
• High inr, bleeding disorder
• Local infection at LP site
• Platelet count < 50k according to American guidelines
• In some situations, a guarded LP can be done.
Csf findings in meningitis
Treatment
• Empirical therapy must be started within 60mins of patient’s arrival in
hospital if clinical suspicion is high.
• Vancomycin is given to cover penicillin resistant streptococci.
• Higher doses of drugs are to be given as they need to surpass the blood
brain barrier to reach CSF.
• Dexamethasone exerts is beneficial effect by inhibiting the synthesis of tnf-
alpha and IL-1 , decreasing csf outflow resistance and stabilizing the blood
brain barrier.
• The rationale of giving dexamethasone 20mins before antibiotic therapy is
that it inhibits tnf-alpha production by macrophages and microglia only if it
is administered before these cells are activated by endotoxin.
Viral meningitis
• Most common causes
1.Enteroviruses (>85%): coxsackievirus, echovirus , enterovirus-70
2. Varicella zoster virus
3. Herpes simplex virus 2
4. Epstein barr virus
5. HIV
Diagnosis
• Polymerase chain reaction amplification of viral nucleic acid from CSF
is the most single important method for diagnosing it. It is more
sensitive than viral cultures.
• Viral cultures sensitivity is comparatively poor as compared to
bacterial meningitis. This is because specific viruses may be isolated
from throat swabs, stool , blood and urine. Enteroviruses and
arbovirus can be seen in stool. Mumps and CMV can be seen in urine.
Treatment of viral meningitis
• Oral or intravenous acyclovir may be of benefit in patients with
meningitis caused by HSV-1 or HSV-2 and in severe cases of EBV or
VZV infection.
• Seriously ill patients should receive iv acyclovir (15-30mg/kg per day
in 3 divided doses) followed by oral drug such as acyclovir( 800mg five
times daily ), or valacyclovir (1000mg tid) for a total course of 7-14
days.
• Analgesics, antipyretics and antiemetics should be given as supportive
care.
Vaccination
• Vaccination is an effective method of preventing the development of
meningitis and other neurological complications associated with
poliovirus, mumps, measles, rubella and varicella infection.
• A live attenuated vaccine for VZV ( Varivax ) is available in US. Clinical
studies indicate 70-90% efficacy for this vaccine, but a booster is
generally required to maintain immunity.
Tubercular meningitis
• It is the most common cause of subacute and chronic meningitis.
• It does not develop acutely from hematogenous spread of tubercle bacilli to the
meninges, rather millet seed sized tubercles form in the parenchyma of the
brain during hematogenous dissemination during the course of primary
infection. These tubercles enlarge and are primarily caseating.
• The propensity for a caseous lesion to produce meningitis is determined by its
proximity to the SAS and the rate at which fibrous encapsulation develops.
Subependymal caseous foci cause meningitis via discharge of bacilli and
tuberculous antigens into the SAS. Mycobacterial antigens produce an intense
inflammatory reaction that leads to production of thick exudate that fills the
basilar cisterns and surrounds the cranial nerves and major blood vessels at the
base of brain.
Lab diagnosis of TB meningitis
• The last tube of fluid collected at LP is the best tube to send for a
smear for AFB. If there is a pellicle in the CSF or a cobweb like clot on
the surface of the fluid, AFB is best demonstrated in the cobweb or
pellicle.
• Positive smears are demonstrated only in 10-40% of cases.
• Culture remains the gold standard of diagnosis of TB meningitis.
Culture of csf takes around 4-8 weeks to identify the organism and are
positive in 50% of adults.
• PCR for the detection of M.TB dna should be sent
Treatment of TB meningitis
• Anti-tubercular therapy is the cornerstone of treatment. It is given for
minimum 18 months.
• First 2 months: HRZE+S+ steroids , followed by HRZE for next 1 month,
f/b HRE for 3 months f/b HR for 12 months.
• Streptomycin is given only for first 2 months.
• Dexamethasone is the preferred steroid, started at dose of
0.4mg/kg/day for first 2 weeks and then tapered every weekly.
• Mri brain with contrast is to be repeated after 3 months of therapy to
look for decrease in size of lesions. It also helps to look for
antimicrobial resistance.
Fungal meningitis
• Risk factors include use of immunosuppresants like for organ
transplantation, HIV/AIDS and loss of immunity associated with
ageing.
• The most common cause of fungal meningitis is Cryptococcus
neoformans.
• Other less common pathogenic fungi which can cause meningitis
include: Coccidioides immitis, Histoplasma capsulatum, Blastomyces
dermatitidis, and Candida species.
Laboratory investigations for fungal
meningitis
• India ink preparation on CSF studies is the gold standard for diagnosis.
If encapsulated yeasts are seen, the test is positive.
• In cases of histoplasmosis and blastomyces, exposure history should
be taken to certain regions of USA. Csf culture is the gold standard of
diagnosis for such patients.
Fungal meningitis
• Meningitis due to Cryptococcus neoformans in non-HIV, non
transplant patient is treated by
1) induction therapy with amphotericin B (0.7mg/kg iv per day) plus
flucytosine (100mg/kg per day in four divided doses) for atleast 4
weeks if CSF culture results are negative after 2 weeks of treatment.
2) Consolidation therapy with fluconazole is given for 8 weeks
( 400mg/day dose ).
In patients who are HIV +ve, we give AMP-B + flucytosine for 2 weeks ,
followed by fluconazole for minimum 8 weeks. Some patients require
indefinite maintenance therapy with fluconazole 200mg/day.
Syphilitic meningitis
• Treated with aqueous penicillin G in a dose of 3-4 million units iv
every 4hrly for 10-14 days.
• This is followed by 2.4 million units of benzathine penicillin G im once
a week for 3 weeks.
• The standard criteria for treatment success is re-examination of the
CSF.
Non infectious causes of chronic
meningitis
• Malignancy : metastatic cancer of breat, lung, stomach or pancreas,
melanoma, lymphomas, leukemia.
• Neurosarcoidosis: cranial nerve palsy ( CN VII ,II ) including optic
chiasma is involved. Serum ace levels and chest radiograph should be
obtained.
• Autoimmune disorders such as SLE, Behcets syndrome, Wegener’s
granulomatosis can also manifest as meningitis.