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Presurgical long-term video-EEG monitoring (LT-VEEG) is an important part of the presurgical evaluation in patients with focal epilepsy. Multiple seizures need to be recorded, often in limited time and with the need to taper anti-seizure medication (ASM). The aim of this study was to systematically study the yield – in terms of success – and risks associated with presurgical LT-VEEG, and to identify all previously reported contributing variables.A systematic review of the databases of PubMed Medline, Embase, Cochrane Central, and the Cochrane Database of Systematic Reviews were searched following the Preferred Reporting Items for Systematic Reviews (PRISMA) guideline. Publications about presurgical LT-VEEG reporting on variables contributing to yield and risk were included. Study characteristics of all included studies were extracted following a standardized template. Within these articles, studies presenting multivariable analyses of factors contributing to the risk of adverse events or the success of LT-VEEG were identified.We found 36 articles reporting on LT-VEEG, including 4,703 presurgical patients, both children and adults. Presurgical LT-VEEG monitoring led to an average yield of 85%. Adverse events occurred with an averaged total event rate of 17%, but the type of included events was variable among studies. Factors reported to independently contribute to successful LT-VEEG were: baseline seizure frequency, a shorter interval from the most recent seizure, extratemporal lobe epilepsy, and no requirement for ASM reduction. Factors independently contributing to the occurrence of adverse events were: ASM tapering, a history of status epilepticus, a history of focal to bilateral tonic-clonic seizures, psychiatric comorbidity, and ASM taper rate.This study reveals that the data on factors contributing to yield and risk of adverse events is significant and variable, and often reported with inadequate statistics. Future research is warranted to develop guidelines for ASM withdrawal during presurgical video-EEG monitoring, taking predefined factors for success and risks of adverse events into account.

Objective We determined retention on open-label cenobamate therapy in the clinical development program to assess the long-term efficacy and tolerability of adjunctive cenobamate in individuals with uncontrolled focal seizures. Methods Data from two randomized, controlled cenobamate studies and one open-label safety and pharmacokinetic study were pooled. Based on the percentage of participants remaining on treatment, retention rates were estimated using Kaplan-Meier survival analyses. We performed two additional analyses to assess factors contributing to retention, stratifying a robust data set (through 2 years) by cenobamate modal dose and frequently used concomitant anti-seizure medications. Cenobamate discontinuations and treatment-emergent adverse events were summarized. Results Data from 1844 participants were pooled: 149 from a single-dose randomized trial, 355 from a multi-dose randomized trial, and 1340 from an open-label safety and pharmacokinetic study. Most participants from randomized trials continued in open-label extensions, and pooled data represent >95% of participants exposed to cenobamate. Baseline characteristics and disease and treatment histories were similar across studies. Median duration of cenobamate exposure was 34 months, with a median modal dose of 200 mg/day. Kaplan-Meier estimates of cumulative cenobamate retention rates were 80% at 1 year and 72% at 2 years. Once participants reached the maintenance phase, retention rates were consistently high in participants receiving ≥100 mg/day cenobamate, and concomitant anti-seizure medications did not affect long-term retention. By 2 years, 535 (29%) had actually discontinued cenobamate; the most common reasons for discontinuation were adverse events (37.6%), withdrawal of consent (21.1%), and other (16.8%). Significance Treatment retention rates provide a proxy measure for long-term efficacy, safety, tolerability, and adherence. The consistently high retention rates we found suggest that cenobamate may be an effective and well-tolerated new treatment option for people with drug-resistant focal seizures.

OBJECTIVE: This study was undertaken to investigate the COVID-19 vaccine uptake rate and possible postvaccination effects in adults with epilepsy. METHODS: We invited adults with epilepsy attending three centers in China from July 24 to August 31, 2021 to participate in this study. We also asked age- and sex-matched controls among people attending for other chronic neuropsychiatric conditions and healthy controls accompanying people with illness attending the hospitals to participate. We excluded people who, under the national guidelines, had evident contradictions to vaccination. Participants were interviewed face-to-face using questionnaires. Vaccine uptake and postvaccine adverse events among the people with epilepsy were compared with those with neuropsychiatric conditions and controls. We also compared the willingness and reasons for hesitancy among unvaccinated participants. RESULTS: We enrolled 981 people, of whom 491 had epilepsy, 217 had other neuropsychiatric conditions, and 273 were controls. Forty-two percent of those with epilepsy had had the first dose of a vaccine, compared with 93% of controls and 84% of the people with neuropsychiatric conditions (p

Accidente cerebrovascular isquémico; Tratamiento de reperfusión; Factores de riesgo Ischemic Stroke; Reperfusion treatment; Risk factors Accident cerebrovascular isquèmic; Tractament de reperfusió; Factor de risc Objective The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. Methods We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. Results In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. Interpretation Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy.

Objective: This study was undertaken to determine reasons for adults with drug-resistant focal epilepsy who undergo presurgical evaluation not proceeding with surgery, and to identify predictors of this course. // Methods: We retrospectively analyzed data on 617 consecutive individuals evaluated for epilepsy surgery at a tertiary referral center between January 2015 and December 2019. We compared the characteristics of those in whom a decision not to proceed with surgical treatment was made with those who underwent definitive surgery in the same period. Multivariate logistic regression was performed to identify predictors of not proceeding with surgery. // Results: A decision not to proceed with surgery was reached in 315 (51%) of 617 individuals evaluated. Common reasons for this were an inability to localize the epileptogenic zone (n = 104) and the presence of multifocal epilepsy (n = 74). An individual choice not to proceed with intracranial electroencephalography (icEEG; n = 50) or surgery (n = 39), risk of significant deficit (n = 33), declining noninvasive investigation (n = 12), and coexisting neurological comorbidity (n = 3) accounted for the remainder. Compared to 166 surgically treated patients, those who did not proceed to surgery were more likely to have a learning disability (odds ratio [OR] = 2.35, 95% confidence interval [CI] = 1.07‒5.16), normal magnetic resonance imaging (OR = 4.48, 95% CI = 1.68–11.94), extratemporal epilepsy (OR = 2.93, 95% CI = 1.82‒4.71), bilateral seizure onset zones (OR = 3.05, 95% CI = 1.41‒6.61) and to live in more deprived socioeconomic areas (median deprivation decile = 40%–50% vs. 50%–60%, p < .05). // Significance: Approximately half of those evaluated for surgical treatment of drug-resistant focal epilepsy do not proceed to surgery. Early consideration and discussion of the likelihood of surgical suitability or need for icEEG may help direct referral for presurgical evaluation.

Dravet syndrome (DS) is a rare severe epilepsy syndrome associated with slowed psychomotor development and behavioral disorders from the second year onward in a previously seemingly normal child. Among cognitive impairments, visuospatial, sensorimotor integration, and expressive language deficits are consistently reported. There have been independent hypotheses to deconstruct the typical cognitive development in DS (dorsal stream vulnerability, cerebellar-like pattern, sensorimotor integration deficit), but an encompassing framework is still lacking. We performed a scoping review of existing evidence to map the current understanding of DS cognitive and behavioral developmental profiles and to summarize the evidence on suggested frameworks. We searched PubMed, Scopus, PsycInfo, and MEDLINE to identify reports focusing on cognitive deficits and/or behavioral abnormalities in DS published between 1978 and March 15, 2020. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Twenty-one reports were selected and tabulated by three independent reviewers based on predefined data extraction and eligibility forms. Eighteen reports provided assessments of global intelligence quotients with variable degrees of cognitive impairment. Eleven reports analyzed single subitems contribution to global cognitive scores: these reports showed consistently larger impairment in performance scales compared to verbal ones. Studies assessing specific cognitive functions demonstrated deterioration of early visual processing, fine and gross motor abilities, visuomotor and auditory-motor integration, spatial processing, visuo-attentive abilities, executive functions, and expressive language. Behavioral abnormalities, reported from 14 studies, highlighted autistic-like traits and attention and hyperactivity disorders, slightly improving with age. The cognitive profile in DS and some behavioral and motor abnormalities may be enclosed within a unified theoretical framework of the three main hypotheses advanced: a pervasive sensorimotor integration deficit, encompassing an occipito-parietofrontal circuit (dorsal stream) dysfunction and a coexistent cerebellar deficit.

Objectives We ascertained the prevalence of ictal arrhythmias to explain the high rate of sudden unexpected death in epilepsy (SUDEP) in Dravet syndrome (DS). Methods We selected cases with clinical DS, ≥6 years, SCN1A mutation, and ≥1 seizure/week. Home‐based ECG recordings were performed for 20 days continuously. Cases were matched for age and sex to two epilepsy controls with no DS and ≥1 major motor seizure during video‐EEG. We determined the prevalence of peri‐ictal asystole, bradycardia, QTc changes, and effects of convulsive seizures (CS) on heart rate, heart rate variability (HRV), and PR/QRS. Generalized estimating equations were used to account for multiple seizures within subjects, seizure type, and sleep/wakefulness. Results We included 59 cases. Ictal recordings were obtained in 45 cases and compared to 90 controls. We analyzed 547 seizures in DS (300 CS) and 169 in controls (120 CS). No asystole occurred. Postictal bradycardia was more common in controls (n = 11, 6.5%) than cases (n = 4, 0.7%; P = 0.002). Peri‐ictal QTc‐lengthening (≥60ms) occurred more frequently in DS (n = 64, 12%) than controls (n = 8, 4.7%, P = 0.048); pathologically prolonged QTc was rare (once in each group). In DS, interictal HRV was lower compared to controls (RMSSD P = 0.029); peri‐ictal values did not differ between the groups. Prolonged QRS/PR was rare and more common in controls (QRS: one vs. none; PR: three vs. one). Interpretation We did not identify major arrhythmias in DS which can directly explain high SUDEP rates. Peri‐ictal QTc‐lengthening was, however, more common in DS. This may reflect unstable repolarization and an increased propensity for arrhythmias.

Summary Objectives A cluster‐randomized trial of home‐based care using primary‐care resources for people with epilepsy has been set up to optimize epilepsy care in resource‐limited communities in low‐ and middle‐income countries. The primary aim is to determine whether treatment adherence to antiepileptic drugs is better with home‐based care or with routine clinic‐based care. The secondary aims are to compare the effects of the two care pathways on seizure control and quality of life. Methods The home‐based intervention comprises epilepsy medication provision, adherence reinforcement, and epilepsy self‐management and stigma management guidance provided by an auxiliary nurse‐midwife equivalent. The experimental group will be compared to a routine clinic‐based care group using a cluster‐randomized design in which the unit of analysis is a cluster of 10 people with epilepsy residing in an area cared for by a single accredited government grass‐roots health care worker. The primary outcome is treatment adherence as measured by monthly tablet counts supplemented by two self‐completed questionnaires. The secondary outcomes include monthly seizure frequency, time to first seizure (in days) after enrollment, proportion of patients experiencing seizure freedom for the duration of the study, and quality of life measured by the “Personal Impact of Epilepsy Scale,” all assessed by an independent study nurse. Results The screening phase and neurologic evaluations and randomizations have been recently completed and follow‐up is underway. Significance The results of the trial are likely to have substantial bearing on the development of governmental policies and strategies to provide coverage and care for patients with epilepsy in resource‐limited countries.

This protocol for a Cochrane Review is out of date and has been withdrawn in order to adhere to Cochrane policy.

Our aim was to clarify the incidence and risk of acute symptomatic seizures in people with coronavirus disease 2019 (COVID‐19). This multicenter retrospective study enrolled people with COVID‐19 from January 18 to February 18, 2020 at 42 government‐designated hospitals in Hubei province, the epicenter of the epidemic in China; Sichuan province; and Chongqing municipality. Data were collected from medical records by 11 neurologists using a standard case report form. A total of 304 people were enrolled, of whom 108 had a severe condition. None in this cohort had a known history of epilepsy. Neither acute symptomatic seizures nor status epilepticus was observed. Two people had seizurelike symptoms during hospitalization due to acute stress reaction and hypocalcemia, and 84 (27%) had brain insults or metabolic imbalances during the disease course known to increase the risk of seizures. There was no evidence suggesting an additional risk of acute symptomatic seizures in people with COVID‐19. Neither the virus nor potential risk factors for seizures seem to be significant risks for the occurrence of acute symptomatic seizures in COVID‐19.

BACKGROUND AND PURPOSE: The International League against Epilepsy (ILAE) updated the classifications of seizures and epilepsies in 2017. The 2017 classifications were compared with the 1980s classifications in rural China. METHODS: People with epilepsy receiving treatment under the National Epilepsy Control Programme were recruited from rural areas in China. Their seizures and epileptic syndrome were classified using the 1980s ILAE classification system and then re-classified according to the 2017 system. Differences in seizure, epilepsy and aetiology classifications were identified. RESULTS: A total of 597 individuals (58% males, aged 6-78 years) were included. Amongst them 535 (90%) had a single seizure type, 57 (9.55%) had two types and five (0.84%) had three. There was complete agreement between the 1981 and 2017 classifications for the 525 individuals with focal seizures. Seizures originally classified as generalized in 10 of 65 individuals were re-classified as unknown in the 2017 classification. Compared to the 1980s classifications, the proportion of individuals with unknown seizures and unknown epilepsy increased from 1.2% (7/597) to 2.8% (17/597, P = 0.002), and unknown aetiology increased from 32% (189/597: 182 cryptogenic and seven unclassified) to 39% (230/597; P < 0.001) in the 2017 classifications. CONCLUSIONS: The 1980s and 2017 classifications had 100% agreement in classifying focal seizures and epilepsy in rural China. A small but significant proportion of generalized seizures and epilepsy and aetiologies classified in the old classifications were re-classified to unknown in the new classifications. These results highlight the need for improvement in clinical evaluation of people with epilepsy in resource-poor settings.

Background and purpose: Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome for which treatment response is generally assumed to be good. We aimed to determine the prevalence and prognostic risk factors for refractoriness of JME. Methods: We systematically searched PubMed and EMBASE and included 43 eligible studies, reporting seizure outcome after antiepileptic drug (AED) treatment in JME cohorts. We defined refractory JME as persistence of any seizure despite AED treatment and performed a random-effects meta-analysis to assess the prevalence of refractory JME and of seizure recurrence after AED withdrawal in individuals with well-controlled seizures. Studies reporting potential prognostic risk factors in relation to seizure outcome were included for subsequent meta-analysis of risk factors for refractoriness. Results: Overall, 35% (95% confidence interval, 29–41%) of individuals (n = 3311) were refractory. There was marked heterogeneity between studies. Seizures recurred in 78% (95% confidence interval, 52–94%) of individuals who attempted to withdraw from treatment after a period of seizure freedom (n = 246). Seizure outcome by publication year suggested that prognosis did not improve over time. Meta-analysis suggested six variables as prognostic factors for refractoriness, i.e. having three seizure types, absence seizures, psychiatric comorbidities, earlier age at seizure onset, history of childhood absence epilepsy and praxis-induced seizures. Conclusion: One-third of people with JME were refractory, which is a higher prevalence than expected. Risk factors were identified and can be used to guide treatment and counselling of people with JME.

Objective To pool observational data on the routine use of perampanel to obtain information on real-world outcomes and data in populations typically underrepresented in clinical trials. Methods Individual-level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1-year retention rate, 1-year seizure freedom rate (duration ≥6 months), and incidence of treatment-emergent adverse events (TEAEs). In addition, relationships were explored with logistic regression analyses. Results The full analysis set comprised 2396 people: 95% had focal seizures; median epilepsy duration was 27 years; median number of concomitant antiepileptic drugs (AEDs) was 2; and median prior AEDs was 6. One-year retention rate was 48% (1117/2332; 95% confidence interval [CI] 46-50%), and 1-year seizure-free rate (≥6-month duration) was 9.2% (74/803; 95% CI 7-11%). Median treatment duration was 11.3 months (1832 patient-years); median dose was 8 mg. In 388 individuals with available data at 3, 6, and 12 months, responder rates were 42%, 46%, and 39%, respectively. During the first year, TEAEs were reported in 68% of participants (1317/1497; 95% CI 66-70%). Logistic regression found higher age at perampanel initiation was associated with higher seizure-free rate, and higher number of prior AEDs with lower seizure-free rate and lower rates of somatic TEAEs. In 135 individuals aged ≥65 years, 1-year retention rate was 48% and seizure-free rate was 28%. Significance Across a large, treatment-resistant population, add-on perampanel was retained for ≥1 year by 48% of individuals, and 9% were seizure-free for ≥6 months. TEAEs were in line with previous reports in routine clinical use, and less frequent than in the clinical trial setting. No new or unexpected TEAEs were seen. Despite the limitations of observational studies, our data indicate that some individuals may derive a marked benefit from the use of perampanel.

Objective To investigate the effects of sodium channel-blocking antiepileptic drugs (AEDs) on functional magnetic resonance imaging (fMRI) language network activations in patients with focal epilepsy. Methods In a retrospective study, we identified patients who were treated at the time of language fMRI scanning with either carbamazepine (CBZ; n = 42) or lamotrigine (LTG; n = 42), but not another sodium channel-blocking AED. We propensity-matched 42 patients taking levetiracetam (LEV) as "patient-controls" and included further 42 age- and gender-matched healthy controls. After controlling for age, age at onset of epilepsy, gender, and antiepileptic comedications, we compared verbal fluency fMRI activations between groups and out-of-scanner psychometric measures of verbal fluency. Results Patients on CBZ performed less well on a verbal fluency tests than those taking LTG or LEV. Compared to either LEV-treated patients or controls, patients taking CBZ showed decreased activations in left inferior frontal gyrus and patients on LTG showed abnormal deactivations in frontal and parietal default mode areas. All patient groups showed fewer activations in the putamen bilaterally compared to controls. In a post hoc analysis, out-of-scanner fluency scores correlated positively with left putamen activation. Significance Our study provides evidence of AED effects on the functional neuroanatomy of language, which might explain subtle language deficits in patients taking otherwise well-tolerated sodium channel-blocking agents. Patients on CBZ showed dysfunctional frontal activation and more pronounced impairment of performance than patients taking LTG, which was associated only with failure to deactivate task-negative networks. As previously shown for working memory, LEV treatment did not affect functional language networks.

SummaryObjective Given that only the free non–protein-bound concentration of an antiepileptic drug (AED) crosses the blood–brain barrier, entering the brain and producing an antiepileptic effect, knowledge and measurement of the free drug fraction is important. Such data are sparse, particularly for newer AEDs, and have arisen from the use of disparate methodologies and settings over the past six decades. We report on the protein binding of 25 AEDs that are available for clinical use, along with two pharmacologically active metabolites (carbamazepine-epoxide and N-desmethyl clobazam), using standardized methodology and under set conditions. Methods The protein binding of the various AEDs was undertaken in sera of 278 patients with epilepsy. Separation of the free non–protein-bound component was achieved by using ultracentrifugation (Amicon Centrifree Micropartition System) under set conditions: 500 μl serum volume; centrifugation at 1,000 g for 15 min, and at 25°C. Free and total AED concentrations were measured by use of fully validated liquid chromatography/mass spectroscopy (LC/MS) techniques. Results Gabapentin and pregabalin are non–protein-bound, whereas highly bound AEDs (≥88%) include clobazam, clonazepam, perampanel, retigabine, stiripentol, tiagabine, and valproic acid as well as the N-desmethyl-clobazam (89%) metabolite. The minimally bound drugs (

Made available in DSpace on 2019-09-12T16:53:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2016 Programa Iberoamericano de Ciencia y Tecnologia para el Desarrollo (CYTED) Department of Health's NIHR Biomedical Research Centres funding scheme Dr. Marvin Weil Epilepsy Research Fund ObjectiveThe diagnosis of neurocysticercosis (NCC) remains problematic because of the heterogeneity of its clinical, immunological, and imaging characteristics. Our aim was to develop and assess a new set of diagnostic criteria for NCC, which might allow for the accurate detection of, and differentiation between, parenchymal and extraparenchymal disease. MethodsA group of Latin American NCC experts developed by consensus a new set of diagnostic criteria for NCC. A multicenter, retrospective study was then conducted to validate it. The reference standard for diagnosis of active NCC was the disappearance or reduction of cysts after anthelmintic treatment. In total, three pairs of independent neurologists blinded to the diagnosis evaluated 93 cases (with NCC) and 93 controls (without NCC) using the new diagnostic criteria. Mixed-effects logistic regression models were used to estimate sensitivity and specificity. ResultsInter-rater reliability (kappa) of diagnosis among evaluators was 0.60. For diagnosis of NCC versus no NCC, the new criteria had a sensitivity of 93.2% and specificity of 81.4%. For parenchymal NCC, the new criteria had a sensitivity of 89.8% and specificity of 80.7% and for extraparenchymal NCC, the new criteria had a sensitivity of 65.9% and specificity of 94.9%. InterpretationThese criteria have acceptable reliability and validity and could be a new tool for clinicians and researchers. An advantage of the new criteria is that they consider parasite location (ie, parenchymal or extraparenchymal), which is an important factor determining the clinical, immunological, and radiological presentation of the disease, and importantly, its treatment and prognosis. Ann Neurol 2016;80:434-442 [Fleury, Agnes] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Insurgentes Sur 3877, Mexico City 14269, DF, Mexico [Carpio, Arturo; Romo, Matthew L.] Univ Cuenca, Fac Ciencias Med, Cuenca, Ecuador [Carpio, Arturo] Columbia Univ, GH Sergievsky Ctr, New York, NY USA [Fleury, Agnes; Cardenas, Graciela; San-Juan, Daniel] Secretaria Salud Mexico, Inst Nacl Neurol & Neurocirugia, Mexico City, DF, Mexico [Romo, Matthew L.] CUNY, Grad Sch Publ Hlth & Hlth Policy, New York, NY 10021 USA [Abraham, Ronaldo] Universidade de Taubaté (Unitau), Sao Paulo, SP, Brazil [Fandino, Jaime] FIRE, Fdn Ctr Colombiano Epilepsia & Enfermedade Neurol, Cartagena, Colombia [Duran, Juan C.] Hosp Clin, Unidad Neurol, La Paz, Bolivia [Moncayo, Jorge] Univ Int Ecuador, Escuela Med, Quito, Ecuador [Rodrigues, Cleonisio Leite] Hosp Geral, Fortaleza, Ceara, Brazil [Serrano-Duenas, Marcos] Pontificia Univ Catolica Ecuador, Hosp Carlos Andrade Marin, Fac Med, Serv Neurol,IESS, Quito, Ecuador [Takayanagui, Oswaldo] Univ Sao Paulo, Fac Med, Ribeirao Preto, SP, Brazil [Sander, Josemir W.] UCL, Inst Neurol, NIHR Univ Coll London Hosp, Biomed Res Ctr, London, England [Sander, Josemir W.] SEIN, Heemstede, Netherlands

Background and purpose About a quarter of people with epilepsy have intellectual disability (ID). This group has communication issues, premature mortality, more treatment resistance, difficulties in making informed choices and greater risks of physical and mental health comorbidities. There is no specific prescribing guidance for this large and vulnerable group. The literature on prescribing for epilepsy in this group was reviewed, in particular examining how antiepileptic drugs (AEDs) work regarding their side effect profiles, effects on specific epilepsy syndromes associated with ID and their individual strengths and weaknesses based on the nature and degree of ID. Method This is a narrative review for which a comprehensive search was conducted to identify evidence for prescribing commonly used AEDs to people with ID including genetic syndromes specifically associated with epilepsy. Results A detailed analysis of the results has highlighted the urgent requirement for suitable and reliable evidence in AED prescribing amongst adults with epilepsy and ID as no studies taking account of the response to AEDs of the ID populations based on the WHO Diagnostic and Statistical Manual of Mental Disorders criteria of clinical severity of ID were identified. Conclusion There is a significant shortfall in suitably powered studies to provide sufficient evidence for safe prescribing of AEDs to people with ID.

A number of studies have suggested a pathophysiologic link between migraine and epilepsy. Our aim was to examine the relative lifetime prevalence of migraine in people with epilepsy (PWE) as well that of epilepsy in migraineurs. We carried out a systematic review, searching five electronic databases, specified bibliographies and conference abstracts in order to identify population-based studies that measured the lifetime co-prevalence of migraine and epilepsy. Two reviewers independently screened all titles and abstracts, carried out a risk of bias assessment and extracted the data. Meta-analyses were carried out using random effects models. Of the 3640 abstracts and titles screened, we identified 10 eligible studies encompassing a total of 1,548,967 subjects. Few of the studies used validated case ascertainment tools and there were inconsistent attempts to control for confounding. There was an overall 52% increase in the prevalence of migraine among PWE versus those without epilepsy [PR: 1.52 (95% CI: 1.29, 1.79)]. There was an overall 79% increase in the prevalence of epilepsy among migraineurs versus those without migraine [PR: 1.79 (95% CI: 1.43, 2.25)]. Subgroup analyses revealed that the method of ascertaining the epilepsy or migraine status of subjects was an important source of inter-study heterogeneity. Additional high quality primary studies are required, ones that use validated and accurate methods of case ascertainment as well as control for potential confounders.

Purpose: Detailed data on the mortality of epilepsy are still lacking from resource-poor settings. We conducted a long-term follow-up survey in a cohort of people with convulsive epilepsy in rural areas of China. In this longitudinal prospective study we investigated the causes of death and premature mortality risk among people with epilepsy. Methods: We attempted to trace all 2,455 people who had previously participated in a pragmatic assessment of epilepsy management at the primary health level. Putative causes of death were recorded for those who died, according to the International Classification of Diseases. We estimated proportional mortality ratios (PMRs) for each cause, and standardized mortality ratios (SMRs) for each age-group and cause. Survival analysis was used to detect risk factors associated with increased mortality. Key Findings: During 6.1 years of follow-up there were 206 reported deaths among the 1,986 people with epilepsy who were located. The highest PMRs were for cerebrovascular disease (15%), drowning (14%), self-inflicted injury (13%), and status epilepticus (6%), with probable sudden unexpected death in epilepsy (SUDEP) in 1%. The risk of premature death was 2.9 times greater in people with epilepsy than in the general population. A much higher risk (SMRs 28-37) was found in young people. Duration of epilepsy and living in a waterside area were independent predictors for drowning. Significance: Drowning and status epilepticus were important, possibly preventable, causes of death. Predictors of increasing mortality suggest interventions with efficient treatment and education to prevent premature mortality among people with epilepsy in resource-poor settings. Language: en

Summary Purpose: To evaluate the long-term outcome of phenobarbital treatment for convulsive epilepsy in rural China, and to explore factors associated with overall seizure outcomes. Methods: We carried out follow-up assessments of people who took part in an epilepsy community management program conducted in rural counties of six provinces in China. People with convulsive epilepsy who were previously untreated (or on irregular treatment) were commenced on regular treatment with phenobarbital. Information was collected using a standardized questionnaire by face-to-face interviews of the individuals (and their families where necessary). Information collected included treatment status, medication change, seizure frequency, and mortality. Key Findings: Among the 2,455 people who participated in the original program, outcomes were successfully ascertained during the follow-up assessment in 1986. Among them, 206 had died. Information on treatment response was obtained in 1,780 (56% male; mean age 33.9 years, range 3-84; mean duration of follow-up 6.4 years). Among them, 939 (53%) were still taking phenobarbital. The most common reasons for stopping phenobarbital were seizure freedom or substantial seizure reduction, socioeconomic reasons, and personal preference. Four hundred fifty-three individuals (25%) became seizure-free for at least 1 year while taking phenobarbital, 88% of whom did so at daily doses of 120 mg or below. Four hundred six (23%) reported adverse events, which led to withdrawal of phenobarbital in

Summary Purpose: Postictal generalized EEG suppression (PGES) seems to be a pathophysiologic hallmark in ictal recordings of sudden unexpected death in epilepsy (SUDEP). It has recently been suggested that presence and duration of PGES might be a predictor of SUDEP risk. Little is known about the etiology of PGES. Methods: We conducted a retrospective case-control study in 50 people with convulsive seizures (CS) recorded on digital video-electroencephalography (EEG). One CS per individual was reviewed for presence and duration of PGES by two independent observers: Preictal and postictal heart rate (HR) (1 min before seizure onset and 1, 3, 5, 15, and 30 min after seizure end) and frequency domain measures of heart rate variability (HRV), including the ratio of low frequency (LF) versus high frequency (HF) power, were analyzed. The relationship between PGES and periictal autonomic changes was evaluated, as well as its association with several clinical variables. Key Findings: Thirty-seven individuals (74%) exhibited PGES and 13 (26%) did not. CS resulted in a significant increase of periictal HR and the LF/HF ratio. PGES was associated with neither periictal HR (mean HR difference between PGES+ and PGES- seizures: -2 beats per minute [bpm], 95% confidence interval [CI] -10 to +6 bpm) nor HRV change. There was no association between the duration of PGES and periictal HR change. People with PGES were more likely to be asleep before seizure onset (odds ratio [OR] 4.7, 95% CI 1.2-18.3) and had a higher age of onset of epilepsy (median age 15 vs. 4 years). Significance: PGES was not associated with substantial changes in measures of cardiac autonomic instability but was more prevalent in CS arising from sleep. © Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

SUMMARY Purpose: To assess the association between epilepsy and exposure to the parasites, Toxocara canis and Taenia solium in a slum-community in India. Methods: A door-to-door survey to determine the prevalence of epilepsy was carried out by trained field workers. For every case, one age- and gender-matched control was selected from the same community. Serologic evaluation was carried out to detect antibodies against T. canis and T. solium. Key Findings: The crude prevalence of active epilepsy was 7.2 per 1,000. We enrolled 114 people with active epilepsy and 114 controls. The prevalence of antibodies to T. canis was similar in people with active epilepsy (4.7%; 5 of 106 people) and in controls (5.7%; 6 of 106 people). The prevalence of antibodies to T. solium was 25.5% (27 of 106) in people with active epilepsy, significantly higher than in controls (12.3%; 13 of 106 cases; p = 0.02). Adjusted conditional (fixed-effects) logistic regression estimated an odds ratio of 2.8 (95% confidence interval 1.2–6.8) for detection of T. solium antibodies. Nineteen people with active epilepsy demonstrated evidence of neurocysticercosis (NCC) on magnetic resonance imaging (MRI), including 7 (36.5%) with solitary cysticercus granuloma. Significance: Our findings do not support an association between epilepsy and exposure to T. canis in the community studied. A significant association between T. solium exposure and epilepsy was observed. Of those with active epilepsy and evidence of NCC on MRI, a large proportion demonstrated solitary cysticercus granuloma.

A range of medical and neurologic disorders occurs more frequently in people with epilepsy than in the general population and constitutes its somatic comorbidity. Common examples include cardiac, gastrointestinal, and respiratory disorders; stroke; dementia; and migraine. Alzheimer's disease and migraine are not only more common in epilepsy but are also risk factors for the development of seizures, suggesting a bidirectional association and shared disease mechanisms. Less well-appreciated associations with epilepsy include Parkinson's disease and obstructive sleep apnea. The association between epilepsy and other conditions can be due to a variety of interacting genetic, biologic, and environmental factors. We propose an etiologic classification of comorbidity into uncertain (coincidence or unknown), causal (cause), shared risk factors (common disease mechanisms or shared predisposing risk factors), and resultant (consequence). Co-occurrence of other conditions in a person with epilepsy can complicate diagnosis or have adverse prognostic implications. Management of these conditions may facilitate the treatment of epilepsy, as in the case of obstructive sleep apnea. The presence of somatic disorders in epilepsy is associated with increased health care needs, poorer health-related quality of life, and premature mortality. Prevention, identification, and adequate treatment of comorbid disorders in epilepsy should be an important part of epilepsy management at all levels of care.

Summary Purpose: Diffusion tensor imaging (DTI) is used increasingly to study white matter integrity in people with temporal lobe epilepsy (TLE). Most studies report fractional anisotropy (FA) decrease and mean diffusivity (MD) increase in multiple white matter regions. The disturbance of white matter integrity varies across studies and between regions. We aimed to obtain a more consistent estimate of white matter diffusion characteristics and relate these to the distance from the seizure focus. Methods: Studies comparing diffusion characteristics of people with epilepsy with those of healthy controls were systematically reviewed and quantified using random and mixed effects meta analysis. In addition to the overall meta-analysis, pooled FA and MD differences were determined per hemisphere and white matter category separately. Key Findings: We included 13 cross-sectional studies. The pooled FA difference for all white matter was −0.026 (95% confidence interval [CI] −0.033 to −0.019) and MD difference was 0.028 × 10−3 mm2/s (95% CI 0.015–0.04). FA was reduced significantly in people with TLE compared with healthy controls in both ipsilateral (mean difference −0.03) and contralateral white matter (−0.02). MD was significantly increased ipsilaterally and contralaterally. MD differed significantly between white matter connected to the affected temporal lobe and remote white matter. Significance: The meta-analysis provides a better estimation of the true diffusion characteristics. White matter structural integrity in TLE is disturbed more severely in the ipsilateral than in the contralateral hemisphere, and tracts closely connected with the affected temporal lobe are most disturbed. The exact underlying mechanisms remain to be elucidated.

Summary Purpose: Most people with epilepsy who die suddenly and whose death is attributed to sudden unexpected death in epilepsy (SUDEP) are found in or by the bed for unknown reasons. We assessed whether those with sleep-related SUDEP were more likely to have nocturnal seizures, and whether seizure patterns (diurnal vs. nocturnal) differed from people dying suddenly and living controls with epilepsy. Methods: Seizure patterns in a cohort of 154 people with epilepsy who died suddenly and after autopsy conformed to the definition of SUDEP and 616 controls living with epilepsy were classified as having “exclusively diurnal” or “nocturnal seizures.” Comparisons were made between the groups. SUDEP was classified as sleep-related or non–sleep-related based on eyewitness accounts and the circumstances surrounding death. Key Findings: SUDEP was primarily a sleep-related (58%) and unwitnessed (86%) event. If sleep-related, SUDEP was more likely to be unwitnessed [odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6–12]. Those with sleep-related SUDEP were more likely to have a history of nocturnal seizures than those who had non–sleep-related SUDEP (OR 3.6, 95% CI 1.4–9.4). Those who died were more likely to have a history of nocturnal seizures than living controls (OR 3.9, 95% CI 2.5–6.0). After correction for previously established SUDEP risk factors (Langan et al., 2005), the presence of nocturnal seizures remained significant (OR 2.6, 95% CI 1.3–5.0). Significance: Nocturnal seizures seem to be an independent risk factor for SUDEP. These findings underscore the importance of preventive measures, which may include night supervision.

Summary Purpose: In an analysis of four case–control studies of sudden unexpected death in epilepsy (SUDEP), we found that yearly frequency of generalized tonic–clonic seizures (GTCS) and antiepileptic drug (AED) polytherapy were associated with an increased risk for SUDEP. The prior analysis, however, did not evaluate AEDs and GTCS frequency concurrently. Methods: We combined data from the three case–control studies with information on the frequency of GTCS and AED therapy, that is, carbamazepine, phenytoin, valproic acid, and other AED therapy. Number of AEDs was also considered. Lamotrigine and GTCS frequency were considered separately in two of the case–control studies. Logistic regression analysis was used to evaluate GTCS frequency, each of the AEDs, and number of AEDs. Adjusted analysis of the different AEDs accounted for study, age at death, gender, and GTCS frequency. Key Findings: In crude analysis, GTCS frequency, AED polytherapy, and number of AEDs were associated with an increased risk for SUDEP. Analysis of individual AEDs and of number of AEDs, adjusting for GTCS frequency, revealed no increased risk associated with AEDs as monotherapy, polytherapy, or total number. GTCS frequency remained strongly associated with an increased risk for SUDEP. Significance: Our findings—that none of the AEDs considered were associated with increased SUDEP risk as monotherapy or as polytherapy when GTCS frequency was taken into account—provide a consistent message that number of GTCS increases SUDEP risk and not AEDs. These results suggest that prevention of SUDEP must involve increased efforts to decrease GTCS frequency in order to avert the occurrence of this devastating epilepsy outcome.

The ketogenic diet (KD) has been used to treat children with epilepsy who are resistant to antiepileptic drugs (AEDs) since the 1920s, and has undergone a resurgence in popularity over the last 15 years Its use in adolescents and adults has been more restrained. During the past few decades, more liberal regimens have emerged that may seem more attractive to older people while still proving effective, often independent of ketone levels. The KD and its variants may lead to similar reductions in seizure frequency in adolescents and adults as seen in children, although studies are limited and of poor quality. A total of only 122 adults and 82 adolescents have been included in open-label studies on the KD, and only 56 adults and 10 adolescents on the Modified Atkins Diet. Side effects appear similar to those encountered in children. Noncompliance may be higher in adolescents and adults than in children, but the main reason for discontinuation is lack of efficacy. A better understanding of the mechanisms underlying the effects of the KD might allow the same treatment effects to be achieved using novel, better-tolerated, nondietary approaches.

Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.