Sanjay Sisodiya

Publications of Sanjay Sisodiya

• Psychogenic nonepileptic seizure manifestations reported by patients and witnesses.

  Authors: Markus Reuber, Jenny Jamnadas-Khoda, Mark Broadhurst, Richard Grunewald, Steve Howell, Matthias Koepp, Sanjay Sisodiya, Matthew Walker

  Epilepsia. 07/2011; 52(11):2028-35.

  Psychogenic nonepileptic seizures (PNES) continue to represent a serious diagnostic challenge for neurologists. Video-electroencephalography (EEG) studies have provided detailed knowledge of thePsychogenic nonepileptic seizures (PNES) continue to represent a serious diagnostic challenge for neurologists. Video-electroencephalography (EEG) studies have provided detailed knowledge of the spectrum of visible PNES manifestations. However, little is known about how patients or seizure witnesses experience PNES, although many diagnoses in seizure clinics are made on the basis of self-reported information rather than video-EEG observations. This study describes the range of PNES manifestations as they are reported by patients or seizure witnesses. Three hundred eight candidates for this study were consecutively diagnosed with PNES on the basis of video-EEG recordings of habitual seizures involving impairment of consciousness without epileptic ictal EEG activity at the Royal Hallamshire Hospital in Sheffield and the National Hospital for Neurology in London, United Kingdom. One hundred patients responded to a postal questionnaire and participated in this study. Eighty-four of the questionnaires completed by patients were accompanied by questionnaires completed by seizure witness. The patient questionnaire contained 12 demographic and clinical questions and the 86-item Paroxysmal Event Profile (PEP), asking patients to rate statements about their attacks on a five-point Likert scale ("always,"frequently,"sometimes,"rarely,"never"). The Paroxysmal Event Observer (PEO) questionnaire uses 34-items with the same Likert scale. The PEP questionnaire includes inquiries about symptoms of panic or dissociation as well as symptoms previously found to distinguish between generalized tonic-clonic seizures and syncope or thought to differentiate between epilepsy and PNES. The item-by-item analysis revealed the inter- and intraindividual variability of PNES experiences. The majority of patients with PNES reported some phenomena, which have traditionally been attributed to epilepsy (such as seizures from sleep, experiencing a rising sensation in their body, postictal myalgia). Although most PNES were experienced as striking without warning and reported to cause loss or impairment of consciousness, most patients also reported seizure warnings in at least some of the seizures. Despite the clinical heterogeneity apparent from these findings, a correlation matrix showed that symptoms were not randomly distributed. Significant correlations were seen between duration of seizures and seizures from reported sleep (r = -0.28, p = 0.006), seizure-related motor activity and seizures from reported sleep (p = -0.48, p < 0.001), flashbacks and anxiety (p = 0.44, p < 0.001) or dissociation (p = 0.66, p < 0.001), and anxiety and dissociation (r = 0.53, p < 0.001). The comparison of similarly worded items on the PEP and PEO questionnaires showed that witnesses were more often aware of seizure triggers and a relationship between PNES and emotional stress than were patients (p = 0.001/p < 0.001). These findings based on the self-report of patients with well-characterized PNES and witnesses of their seizures demonstrate why it can be difficult to distinguish descriptions of PNES from those of epilepsy on the basis of factual items. The differences between patient and witness reports suggest that clinicians have to take note of the source of information they use in their diagnostic considerations. The intra- and interindividual variability of reported PNES manifestations demonstrates the clinical heterogeneity of PNES disorders. The positive correlation of symptoms of dissociation and anxiety in these patients may reflect psychopathologic differences between subgroups of PNES patients.

• Epilepsy: the new order-classifying focal cortical dysplasias.

  Authors: Sanjay Sisodiya

  Nature reviews. Neurology. 03/2011; 7(3):129-30.

• Early progenitor cell marker expression distinguishes type II from type I focal cortical dysplasias.

  Authors: Ksenia A Orlova, Victoria Tsai, Marianna Baybis, Gregory G Heuer, Sanjay Sisodiya, Maria Thom, Kevin Strauss, Eleonora Aronica, Phillip B Storm, Peter B Crino

  Journal of neuropathology and experimental neurology. 08/2010; 69(8):850-63.

  Type I and type II focal cortical dysplasias (FCDs) exhibit distinct histopathologic features that suggest different pathogenic mechanisms. Type I FCDs are characterized by mild laminarType I and type II focal cortical dysplasias (FCDs) exhibit distinct histopathologic features that suggest different pathogenic mechanisms. Type I FCDs are characterized by mild laminar disorganization and hypertrophic neurons, whereas type II FCDs exhibit dramatic laminar disorganization and cytomegalic cells (balloon cells). Both FCD types are associated with intractable epilepsy; therefore, identifying cellular or molecular differences between these lesion types that explains the histologic differences could provide new diagnostic and therapeutic insights. Type II FCDs express nestin, a neuroglial progenitor protein that is modulated in vitro by the stem cell proteins c-Myc, sex-determining region Y-box 2 (SOX2), and Octamer-4 (Oct-4) after activation of mammalian target of rapamycin complex 1 (mTORC1). Because mTORC1 activation has been demonstrated in type II FCDs, we hypothesized that c-Myc, SOX2, and Oct-4 expression would distinguish type II from type I FCDs. In addition, we assayed the expression of progenitor cell proteins forkhead box G1 (FOXG1), Kruppel-like factor 4 (KLF4), Nanog, and SOX3. Differential expression of 7 stem cellproteins and aberrant phosphorylation of2mTORC1 substrates, S6 andS6 kinase 1 proteins, clearly distinguished type II from type I FCDs(n = 10 each). Our results demonstrate new potential pathogenic pathways in type II FCDs and suggest biomarkers for diagnostic pathology in resected epilepsy specimens.

• Does the primary literature provide support for clinical signs used to distinguish psychogenic nonepileptic seizures from epileptic seizures?

  Authors: Andreja Avbersek, Sanjay Sisodiya

  Journal of neurology, neurosurgery, and psychiatry. 07/2010; 81(7):719-25.

  Psychogenic non-epileptic seizures (PNES) represent a diagnostic challenge. When trying to distinguish between PNES and epileptic seizures (ES), clinicians rely on the presence or absence of severalPsychogenic non-epileptic seizures (PNES) represent a diagnostic challenge. When trying to distinguish between PNES and epileptic seizures (ES), clinicians rely on the presence or absence of several clinical signs. The purpose of this review is to establish the extent to which these signs are supported by primary data from the literature. A Medline search was used to identify primary studies that used video-EEG to define the presence or absence of different clinical signs in PNES and ES. The methodological quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. 34 studies matched the inclusion criteria. A specific sign was considered well supported by the data from the primary literature if we were able to identify at least two controlled studies demonstrating its usefulness and if the data from other studies were supportive. There is good evidence from the literature that long duration, occurrence from apparent sleep with EEG-verified wakefulness, fluctuating course, asynchronous movements, pelvic thrusting, side-to-side head or body movement, closed eyes during the episode, ictal crying, memory recall and absence of postictal confusion are signs that distinguish PNES from ES. Postictal stertorous breathing proved to distinguish convulsive PNES from generalised tonic clonic seizures (GTCS) and should be added to the list of useful clinical signs. The final clinical diagnosis should encompass all available data and should not rely on any single sign alone.

• Temporal Lobe Sclerosis Associated With Hippocampal Sclerosis in Temporal Lobe Epilepsy: Neuropathological Features.

  Authors: Maria Thom, Sofia Eriksson, Lillian Martinian, Luis Caboclo, Andrew McEvoy, John Duncan, Sanjay Sisodiya

  Journal of neuropathology and experimental neurology. 09/2009; 68(8):928-938.

  Widespread changes involving neocortical and mesial temporal lobe structures can be present in patients with temporal lobe epilepsy and hippocampal sclerosis. The incidence, pathology, and clinicalWidespread changes involving neocortical and mesial temporal lobe structures can be present in patients with temporal lobe epilepsy and hippocampal sclerosis. The incidence, pathology, and clinical significance of neocortical temporal lobe sclerosis (TLS) are not well characterized. We identified TLS in 30 of 272 surgically treated cases of hippocampal sclerosis. Temporal lobe sclerosis was defined by variable reduction of neurons from cortical layers II/III and laminar gliosis; it was typically accompanied by additional architectural abnormalities of layer II, that is, abnormal neuronal orientation and aggregation. Quantitative analysis including tessellation methods for the distribution of layer II neurons supported these observations. In 40% of cases, there was a gradient of TLS with more severe involvement toward the temporal pole, possibly signifying involvement of hippocampal projection pathways. There was a history of a febrile seizure as an initial precipitating injury in 73% of patients with TLS compared with 36% without TLS; no other clinical differences between TLS and non-TLS cases were identified. Temporal lobe sclerosis was not evident preoperatively by neuroimaging. No obvious effect of TLS on seizure outcome was noted after temporal lobe resection; 73% became seizure-free at 2-year follow-up. In conclusion, approximately 11% of surgically treated hippocampal sclerosis is accompanied by TLS. Temporal lobe sclerosis is likely an acquired process with accompanying reorganizational dysplasia and an extension of mesial temporal sclerosis rather than a separate pathological entity.

• Long-term Monitoring in Refractory Epilepsy: The Gowers Unit Experience.

  Authors: Mahinda Yogarajah, H W Robert Powell, Shelagh Smith, Dominic Heaney, J S Duncan, Sanjay Sisodiya

  Journal of neurology, neurosurgery, and psychiatry. 11/2008;

  INTRODUCTION: Guidelines from NICE and the International League Against Epilepsy recommend long-term EEG monitoring (LTM) in patients in whom seizure or syndrome type is unclear, and in patients inINTRODUCTION: Guidelines from NICE and the International League Against Epilepsy recommend long-term EEG monitoring (LTM) in patients in whom seizure or syndrome type is unclear, and in patients in whom it is proving difficult to differentiate between epilepsy and non-epileptic attack disorder (NEAD). The purpose of this study was to evaluate this recommended use of LTM in the setting of an epilepsy tertiary referral unit. METHODS: We reviewed the case notes of all admissions to the Sir William Gowers Unit at the National Society for Epilepsy in the years 2004 and 2005. We recorded the type, duration and result of all LTM performed both prior to and during the admission. Pre- and post-admission diagnoses were compared, and patients were divided according to whether LTM had resulted in a change in diagnosis, refinement in diagnosis or no change in diagnosis. The distinction between change and a refinement in the diagnosis was made on the basis of whether or not this alteration resulted in a change of management. RESULTS: A total of 612 patients were admitted during 2004 and 2005, 230 of whom were referred for diagnostic clarification. Of these, LTM was primarily responsible for a change in diagnosis in 133 (58%), and a refinement of diagnosis in 29 (13%). In 65 (29%) patients the diagnosis remained the same after LTM. In those patients in whom there was a change in diagnosis the most common change was in distinguishing epilepsy from NEAD in 73 (55%) and in distinguishing between focal and generalised epilepsy in 47 (35%). LTM was particularly helpful in differentiating frontal lobe seizures from generalized seizures and non-epileptic attacks. In-patient ambulatory EEG proved as effective as video telemetry (VT) in helping to distinguish between NEAD, focal and generalised epilepsy. DISCUSSION: Our study revealed that LTM led to an alteration in the diagnosis of 71% of patients referred to a tertiary centre for diagnostic clarification of possible epilepsy. Although LTM is relatively expensive, time consuming and of limited availability, this needs to be balanced against the considerable financial and social cost of misdiagnosed and uncontrolled seizures. Our service evaluation supports the use of performing LTM (either video or ambulatory) in a specialist setting in patients who present diagnostic difficulty.

• Brain structure, function, and genetics revealed by studies of the eye and face.

  Authors: Sanjay Sisodiya

  Current opinion in neurology. 09/2008; 24(4):404-9.

  PURPOSE OF REVIEW: Understanding the structure and function of the human brain is intrinsically interesting and fundamental to improved diagnosis, treatment, and prevention of human neurologicalPURPOSE OF REVIEW: Understanding the structure and function of the human brain is intrinsically interesting and fundamental to improved diagnosis, treatment, and prevention of human neurological diseases, which constitute an increasing global burden. The intimate connections between brain and face, and brain and eye, have been utilized to access brain structure and function. Concepts and recent progress are reviewed here. RECENT FINDINGS: Continued work on biological links between brain and eye or face has uncovered further genetic abnormalities causing facial or eye anomalies, which in either case may clearly indicate changes in the underlying brain. Cause and effect can be difficult to disentangle, but the use of conditional animal models can help establish whether brain changes are the result of face or eye changes or the result of a parallel influence on brain and eye or face. The application of newer methods and technologies such as parameterization of facial characteristics and comparative genomic hybridization has led to new discoveries and insights. SUMMARY: Further interdisciplinary studies into brain structure and function through the windows of the face and the eye, with the application of genome-wide studies in larger cohorts, will potentially enable more discovery and critically may reveal unsuspected therapeutic targets in human disease.

• The role of the interhemispheric pathway in hearing.

  Authors: Doris-Eva Bamiou, Sanjay Sisodiya, Frank E Musiek, Linda M Luxon

  Brain research reviews. 12/2007; 56(1):170-82.

  The corpus callosum consists of heavily myelinated fibres connecting the two hemispheres. Its caudal portion and splenium contain fibres that originate from the primary and second auditory cortices,The corpus callosum consists of heavily myelinated fibres connecting the two hemispheres. Its caudal portion and splenium contain fibres that originate from the primary and second auditory cortices, and from other auditory responsive areas. The anterior commissure in humans is much smaller than the corpus callosum, and it also contains interhemispheric fibres from auditory responsive cortical areas. The corpus callosum is exclusively present in placental mammals, while in acallosal mammals, most of the corpus callosum-related functions are carried out by the anterior commissure. The exact contribution of these two structures and of interhemispheric transfer in hearing in humans is still a matter of debate. In more recent years, human behavioural studies which employ psychoacoustic tasks designed to tap into interhemispheric transfer, combined with sophisticated neuroimaging paradigms, have helped to interpret information from animal experiments and post-mortem studies. This review will summarize and discuss the available information of the contributions of the human interhemispheric pathway in hearing in humans from behavioural, neuroimaging and histopathological studies in humans.

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• Inherited PAX6, NF1 and OTX2 mutations in a child with microphthalmia and aniridia.

  Authors: R Alex Henderson, Kathy Williamson, Sally Cumming, Michael P Clarke, Sally Ann Lynch, Isabel M Hanson, David R Fitzpatrick, Sanjay Sisodiya, Veronica van Heyningen

  European journal of human genetics : EJHG. 09/2007; 15(8):898-901.

  A girl with aniridia, microphthalmia, microcephaly and café au lait macules was found to have mutations in PAX6, NF1 and OTX2. A novel PAX6 missense mutation (p.R38W) was inherited from her motherA girl with aniridia, microphthalmia, microcephaly and café au lait macules was found to have mutations in PAX6, NF1 and OTX2. A novel PAX6 missense mutation (p.R38W) was inherited from her mother whose iris phenotype had not been evident because of ocular neurofibromatosis. Analysis of the NF1 gene in the proband, prompted by the mother's diagnosis and the presence of café au lait spots, revealed a nonsense mutation (p.R192X). Subsequently an OTX2 nonsense mutation (p.Y179X) was identified and shown to be inherited from her father who was initially diagnosed with Leber's congenital amaurosis. Since individual mutations in PAX6, OTX2 or NF1 can cause a variety of severe developmental defects, the proband's phenotype is surprisingly mild. This case shows that patients with complex phenotypes should not be eliminated from subsequent mutation analysis after one or even two mutations are found.

• Etiology and management of refractory epilepsies.

  Authors: Sanjay Sisodiya

  Nature clinical practice. Neurology. 07/2007; 3(6):320-30.

  The epilepsies are an important, common and diverse group of symptom complexes characterized by recurrent spontaneous seizures. Although many patients with epilepsy have their seizures controlledThe epilepsies are an important, common and diverse group of symptom complexes characterized by recurrent spontaneous seizures. Although many patients with epilepsy have their seizures controlled effectively by antiepileptic drugs (AEDs), about one-third of patients continue to have seizures, despite trying a range of AEDs. Such patients bear the heaviest burden of epilepsy, with increased morbidity and risk of premature mortality. Our current understanding of the refractory epilepsies--the most common of which are focal--is limited; even their definition is problematic. Standard treatments for refractory epilepsies include optimization of existing AED regimens, trials of further AEDs, and, for some patients, therapeutic resective neurosurgery. Recent basic research has explored possible underlying causes of refractory epilepsy, and two main hypotheses have emerged to account for the failure of AED treatment. According to one hypothesis, AEDs might fail because of alterations in the properties of their usual targets. Alternatively, they might fail because multidrug transporter mechanisms limit concentrations of the drugs at their targets. The refractory epilepsies can be viewed as offering remarkable insights into biological processes in the epilepsies, and their effective treatment remains an important aim; treatment would potentially bring much-needed relief to hundreds of thousands of patients across the world.

• Genetics of epilepsy: epilepsy research foundation workshop report.

  Authors: Sanjay Sisodiya, J Helen Cross, Ingmar Blümcke, David Chadwick, John Craig, Peter B Crino, Paul Debenham, Norman Delanty, Frances Elmslie, Mark Gardiner [......] Lina Nashef, Jeffrey L Noebels, Ruth Ottman, Munir Pirmohamed, Asla Pitkänen, Ingrid Scheffer, Simon Shorvon, Graeme Sills, Nicholas Wood, Sameer Zuberi

  Epileptic disorders : international epilepsy journal with videotape. 07/2007; 9(2):194-236.

  The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians toThe Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.

• Auditory and verbal working memory deficits in a child with congenital aniridia due to a PAX6 mutation.

  Authors: Doris-Eva Bamiou, Nicole G Campbell, Frank E Musiek, Rachael Taylor, W K Chong, Anthony Moore, Veronica van Heyningen, Samantha Free, Sanjay Sisodiya, Linda M Luxon

  International journal of audiology. 05/2007; 46(4):196-202.

  PAX6 encodes a transcriptional regulator that is essential for brain morphogenesis. Heterozygous PAX6 mutation is associated with aniridia and abnormalities of the interhemispheric pathway in humans.PAX6 encodes a transcriptional regulator that is essential for brain morphogenesis. Heterozygous PAX6 mutation is associated with aniridia and abnormalities of the interhemispheric pathway in humans. We present the case of a 12 year old boy with a known mutation of the PAX6 gene. There were parental concerns regarding his hearing, but repeated pure-tone audiograms were normal. He had a battery of standard central auditory tests, which gave abnormal results in tests which required auditory interhemispheric transfer (dichotic digits and pattern tests). A speech and language assessment, which yielded age-appropriate scores for speech, receptive and expressive language, revealed impaired verbal working memory. These test results were interpreted as indicating impaired auditory sensory and higher order interhemispheric transfer, consistent with reported findings in adults with mutations in PAX6, and correlated with his parent-reported hearing difficulties. This is the first report of central auditory and verbal working memory deficits in a child with a PAX6 mutation. Further research is needed to assess how these deficits impact on academic performance particularly in childhood.

• A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose.

  Authors: Sarah Tate, Rinki Singh, Chin-Chuan Hung, John Tai, Chantal Depondt, Gianpiero Cavalleri, Sanjay Sisodiya, David Goldstein, Horng-Huei Liou

  Pharmacogenetics and genomics. 10/2006; 16(10):721-726.

  OBJECTIVES: A broad range of phenytoin doses is used in clinical practice, with the final 'maintenance' dose normally determined by trial and error. A common functional polymorphism in the SCN1A geneOBJECTIVES: A broad range of phenytoin doses is used in clinical practice, with the final 'maintenance' dose normally determined by trial and error. A common functional polymorphism in the SCN1A gene (one of the genes encoding the drug target) has been previously associated with maximum dose of phenytoin used clinically, and also maximum dose of carbamazepine, another antiepileptic drug with the same drug target. METHODS: We have related variation at the SCN1A IVS5-91 G>A polymorphism to maximum dose and to maintenance dose of phenytoin in 168 patients with epilepsy treated with phenytoin. We also related genotype to phenytoin serum levels at maximum dose and at maintenance dose of phenytoin. We genotyped the polymorphism using an Applied Biosystems Taqman assay. RESULTS: The polymorphism is associated with phenytoin serum concentration at maintenance dose (P=0.03). In a reduced cohort of 71 patients receiving phenytoin monotherapy this association is also significant (P=0.03). Neither association remains significant after Bonferroni correction for multiple testing. CONCLUSIONS: These results are not a replication of the original study. They do, however, support the hypothesis that this polymorphism influences the clinical use of phenytoin. They also demonstrate the utility of using multiple phenotypes in pharmacogenetics studies, particularly when attempting to separate pharmacokinetic and pharmacodynamic effects. As the SCN1A polymorphism affects phenytoin pharmacodynamics, it is particularly useful to obtain data on serum levels in addition to dose because association of a pharmacodynamic variant may be stronger with serum levels than dose as the serum level may eliminate or reduce pharmacokinetic variability.

• Quantitative post-mortem study of the hippocampus in chronic epilepsy: seizures do not inevitably cause neuronal loss.

  Authors: Maria Thom, Jiemin Zhou, Lillian Martinian, Sanjay Sisodiya

  Brain : a journal of neurology. 07/2005; 128(Pt 6):1344-57.

  Hippocampal sclerosis describes a pattern of neuronal loss and gliosis involving the medial temporal structures most often encountered in patients with epilepsy. It is still a matter for debate as toHippocampal sclerosis describes a pattern of neuronal loss and gliosis involving the medial temporal structures most often encountered in patients with epilepsy. It is still a matter for debate as to whether this lesion is acquired during the course of the patient's seizure history or is present at the outset. Early febrile seizures, episodes of status epilepticus as well as repetitive brief seizures may all contribute to the evolution of hippocampal sclerosis. In addition, genetic factors and developmental abnormalities of the hippocampus may both increase vulnerability to seizures and hippocampal injury. Recent human studies have addressed neuropathological changes in young adults and children undergoing surgery for refractory seizures with hippocampal sclerosis. Post-mortem examination, however, provides the opportunity to evaluate the effect of a lifetime of seizures on both left and right hippocampi, and the presence of any co-existing malformation. Post-mortem stereological analysis of 28 patients with poorly controlled seizures has confirmed a subgroup with absence of significant hippocampal neuronal loss despite decades of generalized seizures, including status epilepticus. The presence of granule cell dispersion correlated to the severity of hippocampal neuronal loss. Furthermore, in patients with confirmed hippocampal sclerosis at post-mortem examination, stereological assessment of the neocortex failed to confirm significant white matter neuronal heterotopia that might indicate an underlying developmental abnormality. In conclusion, seizures do not invariably lead to hippocampal injury and white matter heterotopia is not invariably associated with hippocampal sclerosis.

• Stroke in the developing brain and intractable epilepsy: effect of timing on hippocampal sclerosis.

  Authors: Waney Squier, Helen Salisbury, Sanjay Sisodiya

  Developmental medicine and child neurology. 10/2003; 45(9):580-5.

  A detailed study was made of the pathology of specimens removed by hemispherectomy for the treatment of intractable epilepsy in children with unilateral middle cerebral artery stroke.A detailed study was made of the pathology of specimens removed by hemispherectomy for the treatment of intractable epilepsy in children with unilateral middle cerebral artery stroke. Neuropathological criteria were used to differentiate strokes that occurred in early intrauterine development (before 28 weeks gestational age) from those occurring in the last trimester, at birth, or after birth: 19 children had early strokes and 21 late. There was no difference in seizure history or occurrence of febrile convulsions in these two groups. Hippocampal tissue was available in 20 patients; pathology in the hippocampus, remote from the infarcted area, showed a marked difference between early-onset and late-onset groups. Hippocampal sclerosis was uncommon in children with early-onset strokes but developed in most of the children whose strokes were of later origin. However, hippocampal sclerosis was more closely related to a clinical history of a late initial precipitating insult irrespective of infarct timing. These findings demonstrate the changing vulnerability of the developing brain and show that hippocampal pathology is more closely related to the timing of an insult than seizure history or the occurrence of febrile convulsions.

• Drug resistance in epilepsy: not futile, but complex?

  Authors: Sanjay Sisodiya

  Lancet neurology. 07/2003; 2(6):331.