There is an urgent need for more informative quantitative techniques that non-invasively and obje... more There is an urgent need for more informative quantitative techniques that non-invasively and objectively assess strategies for epilepsy surgery. Invasive intracranial electroencephalography (iEEG) remains the clinical gold standard to investigate the nature of the epileptogenic zone (EZ) before surgical resection. However, there are major limitations of iEEG, such as the limited spatial sampling and the degree of subjectivity inherent in the analysis and clinical interpretation of iEEG data. Recent advances in network analysis and dynamical network modeling provide a novel aspect toward a more objective assessment of the EZ. The advantage of such approaches is that they are data-driven and require less or no human input. Multiple studies have demonstrated success using these approaches when applied to iEEG data in characterizing the EZ and predicting surgical outcomes. However, the limitations of iEEG recordings equally apply to these studies—limited spatial sampling and the implici...
Volumetric MRI permits acquisition of fine, contiguous slices with excellent tissue contrast, and... more Volumetric MRI permits acquisition of fine, contiguous slices with excellent tissue contrast, and is ideal for detailed morphometric studies of the hippocampus.
Fibre- and sphere-based microcapsules have been developed, exhibiting controllable uniform morpho... more Fibre- and sphere-based microcapsules have been developed, exhibiting controllable uniform morphologies, predictable drug release profiles, and neuro-cytocompatibility.
The serendipitous discovery of triggered autobiographical memories and eventual memory improvemen... more The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation in 2008 paved the way for several phase I and phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzheimer's disease. In this article, we summarize clinical trials and case reports on fornix deep brain stimulation for Alzheimer's disease and review experiments on animal models evaluating the physiological or behavioral effects of this intervention. Based on information from these reports and studies, we identify potential translational challenges of this approach and determine practical and ethical considerations for clinical trials, focusing on issues regarding selection criteria, trial design, and outcome evaluation. Based on initial results suggesting greater benefit for those with milder disease stage, we find it essential that participant expectations are ...
Diabetes/metabolism research and reviews, Jan 10, 2015
This study assesses the autonomic function of patients who have regained awareness of hypoglycaem... more This study assesses the autonomic function of patients who have regained awareness of hypoglycaemia following islet cell or whole pancreas transplant. Five patients with type 1 diabetes and either islet cell (four patients) or whole pancreas (one patient) transplant were assessed. These patients were age and gender matched to five patients with type 1 diabetes without transplant and preserved hypoglycaemia awareness, and five healthy control participants without diabetes. All participants underwent: i. A battery of five cardiovascular autonomic function tests, ii. Quantitative sudomotor axonal reflex testing (QSART), and iii. Sympathetic skin response (SSR) testing. Total recorded hypoglycaemia episodes per month fell from 76 pre-transplant to 13 at 0-3 months post-transplant (83% reduction). The percentage of hypoglycaemia episodes that patients were unaware of decreased from 97% to 69% at 0-3 months (p<0.001, Fisher's Exact Test) and to 20% after 12 months (p<0.0001, Fis...
Non-viral gene transfer into skeletal muscle is enhanced by electroporation and myotoxin precondi... more Non-viral gene transfer into skeletal muscle is enhanced by electroporation and myotoxin preconditioning of muscle following plasmid injection. We investigated in vivo delivery of naked DNA to mdx mouse muscle, utilising enhanced green fluorescent protein reporter vector (pEGFP) and a corrective nucleic acid to promote targeted corrective gene conversion at the mutant mdx mouse dystrophin (DMDmdx) locus. Electroporation, myoablation with bupivacaine and a combined protocol, were applied to mdx muscle. We report up to 90% EGFP expression in electroporated mdx tibialis anterior muscle. Muscles preconditioned with bupivacaine showed low transgene expression with or without EP. Single EGFP+ve muscle fibre explants showed EGFP expression in mature fibres in preference to satellite cells. We observed a two-fold increase (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.005; t) in dystrophin protein, accompanied by wild-type (wt) DMD transcript in muscles injected with corrective nucleic acid over contralateral saline-injected TAs. By targeting the muscle fibres in preference to the satellite cells, plasmid-bourne transgenes delivered to dystrophic muscle will not penetrate the regenerative component of muscle. Whether in the context of targeted corrective gene conversion or therapeutic non-viral transgenes, under these conditions periodic re-administration will be required to promote phenotypic benefits in dystrophic muscle.
Abstract Researchers have emphasized a need for ongoing rehabilitation and support for individual... more Abstract Researchers have emphasized a need for ongoing rehabilitation and support for individuals with traumatic brain injury FBI), yet there are few detailed descriptions of long-term outcome, and many people with long-standing TBI do not or cannot access support services. HB and NL, two men who sustained severe TBI, presented for neuropsychological consultation for the first time more than 20 years post-injury. Referral was prompted by significant mood and relationship disturbances, and ongoing mnemonic and cognitive ...
ABSTRACTBACKGROUND AND PURPOSEThe difficulty of distinguishing disorders of consciousness from ce... more ABSTRACTBACKGROUND AND PURPOSEThe difficulty of distinguishing disorders of consciousness from certain disorders of communication leads to the possibility of false diagnosis. Our aim is to communicate with patients with disorders of consciousness through asking them to answer questions with “yes/no” by performing mental imagery tasks using functional magnetic resonance imaging (fMRI).METHODSA 1.5 T fMRI study with 5 patients and a control group is presented. Speech comprehension, mental imagery, and question–answer tests were performed.RESULTSThe imagery task of mental calculation produced equally distinct activation patterns when compared to navigation and motor imagery in controls. For controls, we could infer answers to questions based on imagery activations. Two patients produced activations in similar areas to controls for certain imagery tasks, however, no activations were observed for the question–answer task.CONCLUSIONSThe results from 2 patients provide independent support ...
Journal of Clinical and Experimental Neuropsychology, 2006
Controversy surrounds the question of whether there is a specific pattern of psychopathology or p... more Controversy surrounds the question of whether there is a specific pattern of psychopathology or personality style observed in patients with temporal lobe epilepsy (TLE) or whether the symptoms of psychological distress reflect a common disorder such as depression. Measurement equivalence was examined to test the hypothesis that the latent variable model underlying scores on the Beck Depression Inventory (BDI) was equivalent across samples of patients with TLE (n = 187) and patients with heterogeneous neurological disorders (n = 150). A well-replicated model of depression or psychological distress comprising three related variables, negative attitude, performance difficulty, and somatic elements, displayed a pattern of strict metric invariance. This result suggests that the same set of latent variables is measured with the same metric relationship between item scores and latent variables in patients with TLE and in patients with heterogeneous neurological disorders.
Epilepsy is characterised by recurrent seizures, which are manifestations of aberrant cortical ne... more Epilepsy is characterised by recurrent seizures, which are manifestations of aberrant cortical neuronal firing. It is unclear whether oxidative stress is a cause or consequence of seizure-related hippocampal neuronal loss or whether it occurs concomitantly with the initiation of cell death pathways. We utilised the rapid electrical amygdala kindling (REAK) model which does not induce cell death to examine early seizure-induced oxidative stress in wildtype and superoxide dismutase 2 (Sod2) +/- mice, which lack 50% of Sod2 activity and are therefore known to be more susceptible to mitochondrial oxidative stress. A significant increase in lipid peroxidation and superoxide production was noted in the hippocampi of wildtype mice and a more delayed response observed in Sod2 +/- mice at early time-points post-seizures, but protein carbonylation levels appeared unchanged. A 10-fold increase in superoxide production was seen in the Sod2 +/- CA2 neurons, indicating that Sod2 plays an important role in protecting the CA2 region of the hippocampus from seizure-induced free radical damage. Early hippocampal cell death was undetectable in wildtype or Sod2 +/- mice post-seizures. We were able to demonstrate that hippocampal oxidative stress occurred as a direct consequence of seizures rather than downstream of activation of cell death pathways. We were also able to show that this increase in oxidative stress was not sufficient to cause cell death within the time window investigated. Our data indicates that a possible upregulation of endogenous antioxidant activity might exist within selective hippocampal sectors in the Sod2 +/- mice that are as yet unknown.
SummaryThe incidence of constipation as an adverse effect of pregabalin has previously been repor... more SummaryThe incidence of constipation as an adverse effect of pregabalin has previously been reported as low, with all cases described as either mild or moderate. From the experience of a tertiary referral epilepsy hospital center, we report several cases of severe and disabling constipation after initiating pregabalin, and resolving only on drug withdrawal. Of 80 consecutive patients, six (7.5%) developed significant constipation within 1–2 weeks of commencing pregabalin. Constipation was the most frequent adverse effect that required pregabalin to be withdrawn (6.3% of patients). The severity of symptoms was dose dependent. Pregabalin can cause marked constipation in some patients, and can lead to multiple unnecessary investigations and procedures if the clinician is not aware of this entirely reversible side effect.
Summary: Patients with reflex epilepsies may provide insights into cerebral pathophysiology. We r... more Summary: Patients with reflex epilepsies may provide insights into cerebral pathophysiology. We report a patient with an unusual form of reflex epilepsy in whom seizures are induced by tooth brushing. Magnetic resonance imaging (MRI) demonstrated a right posterior frontal low‐grade tumor predominantly involving the precentral gyrus. Video‐telemetry demonstrated right‐sided epileptiform activity during a typical induced complex partial seizure. An ictal single photon emission computed tomography (SPECT) scan showed an area of hyperfusion that corresponded to the MRI lesion on coregistration with a surface‐matching technique. A subsequent coregistered interictal SPECT scan demonstrated hypoperfusion in the same region. Ours is the first report to demonstrate a structural focus in this unusual form of reflex epilepsy. Possible mechanisms to explain the induction of the seizures are discussed.
Inpatient video-EEG monitoring (VEM) is widely used for the diagnosis, seizure classification, an... more Inpatient video-EEG monitoring (VEM) is widely used for the diagnosis, seizure classification, and presurgical evaluation of patients with seizure disorders. It is resource intensive and relatively expensive, so its utility continues to be debated. Few studies have specifically evaluated the utility of inpatient VEM in altering diagnosis or management of patients with seizure disorders. We sought to assess the proportion of patients for whom the preadmission diagnosis and management were altered after inpatient VEM of patients admitted for diagnostic and presurgical evaluation of seizure disorders. Data from a consecutive cohort of patients admitted over a 3-year period to an inpatient VEM unit in a tertiary referral hospital were retrospectively analyzed. The preadmission diagnosis and management by the referring neurologist was compared with the diagnosis and management after the VEM. Of 131 patients, 91 (70%) were admitted for diagnostic evaluation and 39 (30%) for a presurgical workup. Mean evaluative period was 5.6 days. Mean number of seizures recorded was 2.9. No seizures were recorded in 31% of patients. Interictal EEG showed epileptiform changes in 56 (43%). In 76 (58%), the diagnosis was altered as a result of the VEM, with the greatest change being an increase in the nonepileptic diagnosis group (7% to 31%) and the generalized diagnosis group (5% to 11%). Management was changed after the VEM in 95 (73%). The results of this study demonstrate that inpatient VEM has a high yield in changing diagnosis and management. Future long-term cost-benefit studies of the management changes resulting from VEM evaluation will aid in further reinforcing its role.
The most common temporal lobe pathology is Ammons Horn sclerosis (AHS), and several different ima... more The most common temporal lobe pathology is Ammons Horn sclerosis (AHS), and several different imaging techniques have been utilized to detect this with varying success. We describe the clinical application of magnetic resonance imaging (MRI) using a three-dimensional volume technique which allows total hippocampal volume to be measured and symmetry evaluated. Hippocampal surface area was calculated in sequential 1.5 mm thick contiguous images, using a GE IC workstation. Total volumes and surface areas were calculated. The cross-sectional surface area at 1.5 mm intervals was displayed graphically, permitting morphometric analysis of the hippocampus throughout its length. Focal atrophy within any part of the hippocampal formation (HF) and its extent could thus be assessed. Patients with well-lateralized temporal lobe epilepsy (TLE) (n = 20) and well-defined frontal lobe epilepsy (FLE) (n = 20) were studied, and volumes compared with normal values derived from 10 neurologically normal controls. Asymmetric hippocampal volume loss was demonstrated in all 20 patients with clinically typed TLE, but not in normal controls or patients with FLE. Volume loss distribution was anterior in 12 patients, posterior in one patient and widespread in seven patients. Secondarily generalized seizures were strongly associated with widespread loss. This method of surface area and volumetric analysis of the hippocampus in TLE can demonstrate asymmetry and focal involvement, and help distinguish between hippocampal and frontal pathologies.
There is an urgent need for more informative quantitative techniques that non-invasively and obje... more There is an urgent need for more informative quantitative techniques that non-invasively and objectively assess strategies for epilepsy surgery. Invasive intracranial electroencephalography (iEEG) remains the clinical gold standard to investigate the nature of the epileptogenic zone (EZ) before surgical resection. However, there are major limitations of iEEG, such as the limited spatial sampling and the degree of subjectivity inherent in the analysis and clinical interpretation of iEEG data. Recent advances in network analysis and dynamical network modeling provide a novel aspect toward a more objective assessment of the EZ. The advantage of such approaches is that they are data-driven and require less or no human input. Multiple studies have demonstrated success using these approaches when applied to iEEG data in characterizing the EZ and predicting surgical outcomes. However, the limitations of iEEG recordings equally apply to these studies—limited spatial sampling and the implici...
Volumetric MRI permits acquisition of fine, contiguous slices with excellent tissue contrast, and... more Volumetric MRI permits acquisition of fine, contiguous slices with excellent tissue contrast, and is ideal for detailed morphometric studies of the hippocampus.
Fibre- and sphere-based microcapsules have been developed, exhibiting controllable uniform morpho... more Fibre- and sphere-based microcapsules have been developed, exhibiting controllable uniform morphologies, predictable drug release profiles, and neuro-cytocompatibility.
The serendipitous discovery of triggered autobiographical memories and eventual memory improvemen... more The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation in 2008 paved the way for several phase I and phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzheimer's disease. In this article, we summarize clinical trials and case reports on fornix deep brain stimulation for Alzheimer's disease and review experiments on animal models evaluating the physiological or behavioral effects of this intervention. Based on information from these reports and studies, we identify potential translational challenges of this approach and determine practical and ethical considerations for clinical trials, focusing on issues regarding selection criteria, trial design, and outcome evaluation. Based on initial results suggesting greater benefit for those with milder disease stage, we find it essential that participant expectations are ...
Diabetes/metabolism research and reviews, Jan 10, 2015
This study assesses the autonomic function of patients who have regained awareness of hypoglycaem... more This study assesses the autonomic function of patients who have regained awareness of hypoglycaemia following islet cell or whole pancreas transplant. Five patients with type 1 diabetes and either islet cell (four patients) or whole pancreas (one patient) transplant were assessed. These patients were age and gender matched to five patients with type 1 diabetes without transplant and preserved hypoglycaemia awareness, and five healthy control participants without diabetes. All participants underwent: i. A battery of five cardiovascular autonomic function tests, ii. Quantitative sudomotor axonal reflex testing (QSART), and iii. Sympathetic skin response (SSR) testing. Total recorded hypoglycaemia episodes per month fell from 76 pre-transplant to 13 at 0-3 months post-transplant (83% reduction). The percentage of hypoglycaemia episodes that patients were unaware of decreased from 97% to 69% at 0-3 months (p<0.001, Fisher's Exact Test) and to 20% after 12 months (p<0.0001, Fis...
Non-viral gene transfer into skeletal muscle is enhanced by electroporation and myotoxin precondi... more Non-viral gene transfer into skeletal muscle is enhanced by electroporation and myotoxin preconditioning of muscle following plasmid injection. We investigated in vivo delivery of naked DNA to mdx mouse muscle, utilising enhanced green fluorescent protein reporter vector (pEGFP) and a corrective nucleic acid to promote targeted corrective gene conversion at the mutant mdx mouse dystrophin (DMDmdx) locus. Electroporation, myoablation with bupivacaine and a combined protocol, were applied to mdx muscle. We report up to 90% EGFP expression in electroporated mdx tibialis anterior muscle. Muscles preconditioned with bupivacaine showed low transgene expression with or without EP. Single EGFP+ve muscle fibre explants showed EGFP expression in mature fibres in preference to satellite cells. We observed a two-fold increase (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.005; t) in dystrophin protein, accompanied by wild-type (wt) DMD transcript in muscles injected with corrective nucleic acid over contralateral saline-injected TAs. By targeting the muscle fibres in preference to the satellite cells, plasmid-bourne transgenes delivered to dystrophic muscle will not penetrate the regenerative component of muscle. Whether in the context of targeted corrective gene conversion or therapeutic non-viral transgenes, under these conditions periodic re-administration will be required to promote phenotypic benefits in dystrophic muscle.
Abstract Researchers have emphasized a need for ongoing rehabilitation and support for individual... more Abstract Researchers have emphasized a need for ongoing rehabilitation and support for individuals with traumatic brain injury FBI), yet there are few detailed descriptions of long-term outcome, and many people with long-standing TBI do not or cannot access support services. HB and NL, two men who sustained severe TBI, presented for neuropsychological consultation for the first time more than 20 years post-injury. Referral was prompted by significant mood and relationship disturbances, and ongoing mnemonic and cognitive ...
ABSTRACTBACKGROUND AND PURPOSEThe difficulty of distinguishing disorders of consciousness from ce... more ABSTRACTBACKGROUND AND PURPOSEThe difficulty of distinguishing disorders of consciousness from certain disorders of communication leads to the possibility of false diagnosis. Our aim is to communicate with patients with disorders of consciousness through asking them to answer questions with “yes/no” by performing mental imagery tasks using functional magnetic resonance imaging (fMRI).METHODSA 1.5 T fMRI study with 5 patients and a control group is presented. Speech comprehension, mental imagery, and question–answer tests were performed.RESULTSThe imagery task of mental calculation produced equally distinct activation patterns when compared to navigation and motor imagery in controls. For controls, we could infer answers to questions based on imagery activations. Two patients produced activations in similar areas to controls for certain imagery tasks, however, no activations were observed for the question–answer task.CONCLUSIONSThe results from 2 patients provide independent support ...
Journal of Clinical and Experimental Neuropsychology, 2006
Controversy surrounds the question of whether there is a specific pattern of psychopathology or p... more Controversy surrounds the question of whether there is a specific pattern of psychopathology or personality style observed in patients with temporal lobe epilepsy (TLE) or whether the symptoms of psychological distress reflect a common disorder such as depression. Measurement equivalence was examined to test the hypothesis that the latent variable model underlying scores on the Beck Depression Inventory (BDI) was equivalent across samples of patients with TLE (n = 187) and patients with heterogeneous neurological disorders (n = 150). A well-replicated model of depression or psychological distress comprising three related variables, negative attitude, performance difficulty, and somatic elements, displayed a pattern of strict metric invariance. This result suggests that the same set of latent variables is measured with the same metric relationship between item scores and latent variables in patients with TLE and in patients with heterogeneous neurological disorders.
Epilepsy is characterised by recurrent seizures, which are manifestations of aberrant cortical ne... more Epilepsy is characterised by recurrent seizures, which are manifestations of aberrant cortical neuronal firing. It is unclear whether oxidative stress is a cause or consequence of seizure-related hippocampal neuronal loss or whether it occurs concomitantly with the initiation of cell death pathways. We utilised the rapid electrical amygdala kindling (REAK) model which does not induce cell death to examine early seizure-induced oxidative stress in wildtype and superoxide dismutase 2 (Sod2) +/- mice, which lack 50% of Sod2 activity and are therefore known to be more susceptible to mitochondrial oxidative stress. A significant increase in lipid peroxidation and superoxide production was noted in the hippocampi of wildtype mice and a more delayed response observed in Sod2 +/- mice at early time-points post-seizures, but protein carbonylation levels appeared unchanged. A 10-fold increase in superoxide production was seen in the Sod2 +/- CA2 neurons, indicating that Sod2 plays an important role in protecting the CA2 region of the hippocampus from seizure-induced free radical damage. Early hippocampal cell death was undetectable in wildtype or Sod2 +/- mice post-seizures. We were able to demonstrate that hippocampal oxidative stress occurred as a direct consequence of seizures rather than downstream of activation of cell death pathways. We were also able to show that this increase in oxidative stress was not sufficient to cause cell death within the time window investigated. Our data indicates that a possible upregulation of endogenous antioxidant activity might exist within selective hippocampal sectors in the Sod2 +/- mice that are as yet unknown.
SummaryThe incidence of constipation as an adverse effect of pregabalin has previously been repor... more SummaryThe incidence of constipation as an adverse effect of pregabalin has previously been reported as low, with all cases described as either mild or moderate. From the experience of a tertiary referral epilepsy hospital center, we report several cases of severe and disabling constipation after initiating pregabalin, and resolving only on drug withdrawal. Of 80 consecutive patients, six (7.5%) developed significant constipation within 1–2 weeks of commencing pregabalin. Constipation was the most frequent adverse effect that required pregabalin to be withdrawn (6.3% of patients). The severity of symptoms was dose dependent. Pregabalin can cause marked constipation in some patients, and can lead to multiple unnecessary investigations and procedures if the clinician is not aware of this entirely reversible side effect.
Summary: Patients with reflex epilepsies may provide insights into cerebral pathophysiology. We r... more Summary: Patients with reflex epilepsies may provide insights into cerebral pathophysiology. We report a patient with an unusual form of reflex epilepsy in whom seizures are induced by tooth brushing. Magnetic resonance imaging (MRI) demonstrated a right posterior frontal low‐grade tumor predominantly involving the precentral gyrus. Video‐telemetry demonstrated right‐sided epileptiform activity during a typical induced complex partial seizure. An ictal single photon emission computed tomography (SPECT) scan showed an area of hyperfusion that corresponded to the MRI lesion on coregistration with a surface‐matching technique. A subsequent coregistered interictal SPECT scan demonstrated hypoperfusion in the same region. Ours is the first report to demonstrate a structural focus in this unusual form of reflex epilepsy. Possible mechanisms to explain the induction of the seizures are discussed.
Inpatient video-EEG monitoring (VEM) is widely used for the diagnosis, seizure classification, an... more Inpatient video-EEG monitoring (VEM) is widely used for the diagnosis, seizure classification, and presurgical evaluation of patients with seizure disorders. It is resource intensive and relatively expensive, so its utility continues to be debated. Few studies have specifically evaluated the utility of inpatient VEM in altering diagnosis or management of patients with seizure disorders. We sought to assess the proportion of patients for whom the preadmission diagnosis and management were altered after inpatient VEM of patients admitted for diagnostic and presurgical evaluation of seizure disorders. Data from a consecutive cohort of patients admitted over a 3-year period to an inpatient VEM unit in a tertiary referral hospital were retrospectively analyzed. The preadmission diagnosis and management by the referring neurologist was compared with the diagnosis and management after the VEM. Of 131 patients, 91 (70%) were admitted for diagnostic evaluation and 39 (30%) for a presurgical workup. Mean evaluative period was 5.6 days. Mean number of seizures recorded was 2.9. No seizures were recorded in 31% of patients. Interictal EEG showed epileptiform changes in 56 (43%). In 76 (58%), the diagnosis was altered as a result of the VEM, with the greatest change being an increase in the nonepileptic diagnosis group (7% to 31%) and the generalized diagnosis group (5% to 11%). Management was changed after the VEM in 95 (73%). The results of this study demonstrate that inpatient VEM has a high yield in changing diagnosis and management. Future long-term cost-benefit studies of the management changes resulting from VEM evaluation will aid in further reinforcing its role.
The most common temporal lobe pathology is Ammons Horn sclerosis (AHS), and several different ima... more The most common temporal lobe pathology is Ammons Horn sclerosis (AHS), and several different imaging techniques have been utilized to detect this with varying success. We describe the clinical application of magnetic resonance imaging (MRI) using a three-dimensional volume technique which allows total hippocampal volume to be measured and symmetry evaluated. Hippocampal surface area was calculated in sequential 1.5 mm thick contiguous images, using a GE IC workstation. Total volumes and surface areas were calculated. The cross-sectional surface area at 1.5 mm intervals was displayed graphically, permitting morphometric analysis of the hippocampus throughout its length. Focal atrophy within any part of the hippocampal formation (HF) and its extent could thus be assessed. Patients with well-lateralized temporal lobe epilepsy (TLE) (n = 20) and well-defined frontal lobe epilepsy (FLE) (n = 20) were studied, and volumes compared with normal values derived from 10 neurologically normal controls. Asymmetric hippocampal volume loss was demonstrated in all 20 patients with clinically typed TLE, but not in normal controls or patients with FLE. Volume loss distribution was anterior in 12 patients, posterior in one patient and widespread in seven patients. Secondarily generalized seizures were strongly associated with widespread loss. This method of surface area and volumetric analysis of the hippocampus in TLE can demonstrate asymmetry and focal involvement, and help distinguish between hippocampal and frontal pathologies.
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Papers by Mark J Cook