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Despite improved ancillary investigations in epilepsy care, patients' narratives remain indispensable for diagnosing and treatment monitoring. This wealth of information is typically stored in electronic health records and accumulated in medical journals in an unstructured manner, thereby restricting complete utilization in clinical decision-making. To this end, clinical researchers increasing apply natural language processing (NLP) - a branch of artificial intelligence - as it removes ambiguity, derives context and imbues standardized meaning from free-narrative clinical texts. This systematic review presents an overview of the current NLP applications in epilepsy and discusses the opportunities and drawbacks of NLP alongside its future implications. We searched the PubMed and Embase databases with a "natural language processing" and "epilepsy" query (March 4

SummaryObjectiveGuidelines suggest considering antiseizure medication (ASM) discontinuation in patients with epilepsy who become seizure-free. Little is known about how discontinuation decisions are being made in practice. We measured the frequency of, and factors associated with, discussions and decisions surrounding ASM discontinuation.MethodsWe performed a multicenter retrospective cohort study at the University of Michigan (UM) and two Dutch centers: Wilhelmina Children’s Hospital (WCH) and Stichting Epilepsie Instellingen Nederland (SEIN). We screened all children and adults with outpatient epilepsy visits in January 2015 and included those with at least one visit during the subsequent two years where they were seizure-free for at least one year. We recorded whether charts documented 1) a discussion with the patient about possible ASM discontinuation and 2) any planned attempt to discontinue at least one ASM. We conducted multilevel logistic regressions to determine factors associated with each outcome.ResultsWe included 1,058 visits from 463 patients. Of all patients who were seizure-free at least one year, 248/463 (53%) had documentation of any discussion and 98/463 (21%) planned to discontinue at least one ASM. Corresponding frequencies for patients who were seizure-free at least two years were 184/285 (65%) and 74/285 (26%). The probability of discussing or discontinuing increased with longer duration of seizure-freedom. Still, even for patients who were ten years seizure-free, our models predicated that in only 49% of visits was a discontinuation discussion documented, and in only 16% of visits was it decided to discontinue all ASMs. Provider-to-provider variation explained 18% of variation in whether patients discontinued any ASM.SignificanceOnly approximately half of patients with prolonged seizure-freedom had a documented discussion about ASM discontinuation. Discontinuation was fairly rare even among low-risk patients. Future work should further explore barriers to and facilitators of counseling and discontinuation attempts.Key points boxWe performed a multicenter cohort study evaluating factors associated with discussions and decisions to discontinue antiseizure medications (ASMs).Of all patients seizure-free at least one year, 53% had documentation of any discussion and 21% planned to discontinue at least one ASM. Corresponding frequencies for patients seizure-free at least two years were 65% and 26%.While discussions and discontinuations increased with increasing seizure-free interval, even for patients who were ten years seizure-free, in only 49% of visits did providers discuss the possibility of discontinuation, and in only 16% of visits did patients decide to discontinue all ASMs.Provider-to-provider variation explained 18% of variation in whether patients discontinued any ASM.ASM discontinuation was fairly rare even among low-risk patients. Future work should further explore barriers to and facilitators of counseling and discontinuation attempts, including the role that differences in physician counseling play in determining whether patients discontinue.

Background and ObjectivesTo identify predictors of postoperative intelligence and developmental quotients (IQ/DQ) and develop and validate clinically applicable IQ/DQ prediction models.MethodsWe retrospectively analyzed neuropsychological outcomes and their possible determinants for children treated in Bethel and Utrecht since 1990. We performed separate analyses for patients with IQ and those with only DQ available. We developed prediction models based on presurgical determinants to predict dichotomized levels of performance (IQ ≥85, IQ ≥70, DQ ≥50).ResultsIQ/DQ data before and 2 years after surgery were available for 492 patients (IQ n = 365, DQ n = 127). At a cutoff level ±10 points, the chance of improvement was considerably higher than the chance of deterioration (IQ 37.3% vs 6.6% and DQ 31.5% vs 15.0%, respectively). Presurgical IQ/DQ was the strongest predictor of postoperative cognition (IQ r = 0.85, p r = 0.57, p DiscussionAfter epilepsy surgery in children, the risk of cognitive deterioration is very low. Presurgical development has a strong effect on the postoperative trajectory. The presented models can improve presurgical counseling of patients and parents by reliably predicting cognitive outcomes.Classification of EvidenceThis study provides Class II evidence that for children undergoing epilepsy surgery presurgical IQ/DQ was the strongest predictor of postoperative cognition.

BackgroundWe determined the prevalence, incidence, and risk factors for epilepsy in Nigeria.MethodsWe conducted a door-to-door survey to identify cases of epilepsy in 3 regions. We estimated age-standardized prevalence adjusted for nonresponse and sensitivity and the 1-year retrospective incidence for active epilepsy. To assess potential risk factors, we conducted a case-control study by collecting sociodemographic and risk factor data. We estimated odds ratios using logistic regression analysis and corresponding population attributable fractions (PAFs).ResultsWe screened 42,427 persons (age ≥6 years), of whom 254 had confirmed active epilepsy. The pooled prevalence of active epilepsy per 1,000 was 9.8 (95% confidence interval [CI] 8.6–11.1), 17.7 (14.2–20.6) in Gwandu, 4.8 (3.4–6.6) in Afikpo, and 3.3 (2.0–5.1) in Ijebu-Jesa. The pooled incidence per 100,000 was 101.3 (95% CI 57.9–167.6), 201.2 (105.0–358.9) in Gwandu, 27.6 (3.3–128.0) in Afikpo, and 23.9 (3.2–157.0) in Ijebu-Jesa. Children's significant risk factors included febrile seizures, meningitis, poor perinatal care, open defecation, measles, and family history in first-degree relatives. In adults, head injury, poor perinatal care, febrile seizures, family history in second-degree relatives, and consanguinity were significant. Gwandu had more significant risk factors. The PAF for the important factors in children was 74.0% (71.0%–76.0%) and in adults was 79.0% (75.0%–81.0%).ConclusionThis work suggests varied epidemiologic numbers, which may be explained by differences in risk factors and population structure in the different regions. These variations should differentially determine and drive prevention and health care responses.

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7–11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9–2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8–0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9–1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63–0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64–0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative antiseizure medication withdrawal. These multicentre-validated models may assist clinicians when discussing antiseizure medication withdrawal after surgery with their patients.

Objective The 1991 Medical Research Council (MRC) Study compared seizure relapse for seizure-free patients randomized to withdraw vs continue of antiseizure medications (ASMs). We re-analyzed this trial to account for crossover between arms using contamination-adjusted intention to treat (CA ITT) methods, to explore dose-response curves, and to validate predictions against external data. ITT assesses the effect of being randomized to withdraw, as-treated analysis assesses the confounded effect of withdrawing, but CA ITT assesses the unconfounded effect of actually withdrawing. Methods CA ITT involves two stages. First, we used randomized arm to predict whether patients withdrew their ASM (logistic) or total daily ASM dose (linear). Second, we used those values to predict seizure occurrence (logistic). Results The trial randomized 503 patients to withdraw and 501 patients to continue ASMs. We found that 316 of 376 patients (88%) who were randomized to withdraw decreased their dose at every pre-seizure visit, compared with 35 of 424 (8%) who were randomized to continue (p < .01). Adjusted odds ratios of a 2-year seizure for those who withdrew vs those who did not was 1.3 (95% confidence interval [CI] 0.9–1.9) in the as-treated analysis, 2.5 (95% CI 1.9–3.4) comparing those randomized to withdraw vs continue for ITT, and 3.1 (95% CI 2.1–4.5) for CA ITT. Probabilities (withdrawal vs continue) were 28% vs 24% (as-treated), 40% vs 22% (ITT), and 43% vs 21% (CA ITT). Differences between ITT and CA ITT were greater when varying the predictor (reaching zero ASMs) or outcome (1-year seizures). As-treated dose-response curves demonstrated little to no effects, but larger effects in CA ITT analysis. MRC data overpredicted risk in Lossius data, with moderate discrimination (areas under the curve ~0.70). Significance CA ITT results (the effect of actually withdrawing ASMs on seizures) were slightly greater than ITT effects (the effect of recommend withdrawing ASMs on seizures). How these findings affect clinical practice must be individualized.

Obsessive-compulsive disorder (OCD) is increasingly considered to be a neurodevelopmental disorder. However, despite insights in neural substrates of OCD in adults, less is known about mechanisms underlying compulsivity during brain development in children and adolescents. Therefore, we developed an adolescent rat model of compulsive checking behavior and investigated developmental changes in structural and functional measures in the frontostriatal circuitry. Five-weeks old Sprague Dawley rats were subcutaneously injected with quinpirole (n = 21) or saline (n = 20) twice a week for five weeks. Each injection was followed by placement in the middle of an open field table, and compulsive behavior was quantified as repeated checking behavior. Anatomical, resting-state functional and diffusion MRI at 4.7T were conducted before the first and after the last quinpirole/saline injection to measure regional volumes, functional connectivity and structural integrity in the brain, respectively. After consecutive quinpirole injections, adolescent rats demonstrated clear checking behavior and repeated travelling between two open-field zones. MRI measurements revealed an increase of regional volumes within the frontostriatal circuits and an increase in fractional anisotropy (FA) in white matter areas during maturation in both experimental groups. Quinpirole-injected rats showed a larger developmental increase in FA values in the internal capsule and forceps minor compared to control rats. Our study points toward a link between development of compulsive behavior and altered white matter maturation in quinpirole-injected adolescent rats, in line with observations in pediatric patients with compulsive phenotypes. This novel animal model provides opportunities to investigate novel treatments and underlying mechanisms for patients with early-onset OCD specifically.

Background and ObjectivesTo describe neurologist practice patterns, challenges, and decision support needs pertaining to withdrawal of antiseizure medications (ASMs) in patients with well-controlled epilepsy.MethodsWe sent an electronic survey to (1) US and (2) European physician members of the American Academy of Neurology and (3) members of EpiCARE, a European Reference Network for rare and complex epilepsies. Analyses included frequencies and percentages, and we showed distributions through histograms and violin plots.ResultsWe sent the survey to 4,923 individuals; 463 consented, 411 passed eligibility questions, and 287 responded to at least 1 of these questions. Most respondents indicated that they might ever consider ASM withdrawal, with respondents treating mostly children being more likely ever to consider withdrawal (e.g., medical monotherapy: children 96% vs adults 81%;p< 0.05). The most important factors when making decisions included seizure probability (83%), consequences of seizures (73%), and driving (74%). The top challenges when making decisions included unclear seizure probability (81%), inadequate guidelines (50%), and difficulty communicating probabilities (45%). Respondents would consider withdrawal after a median of 2-year seizure freedom, but also responded that they would begin withdrawal on average only when the postwithdrawal seizure relapse risk in the coming 2 years was less than 15%–30%. Wide variation existed in the use of words or numbers in respondents' counsel methods, for example, percentages vs frequencies or probability of seizure freedom vs seizure. The most highly rated point-of-care methods to inform providers of calculated risk were Kaplan-Meier curves and showing percentages only, rather than pictographs or text recommendations alone.DiscussionMost surveyed neurologists would consider withdrawing ASMs in seizure-free individuals. Seizure probability was the largest factor driving decisions, yet estimating seizure probabilities was the greatest challenge. Respondents on average indicated that they may withdraw ASM after a minimum seizure-free duration of 2 years, yet also on average were willing to withdraw when seizure risk decreased below 15%–30%, which is lower than most patients' postwithdrawal risk at 2-year seizure freedom and lower than the equivalent even of a first seizure of life. These findings will inform future efforts at developing decision support tools aimed at optimizing ASM withdrawal decisions.

Intraoperative electrocorticography is used to tailor epilepsy surgery by analysing interictal spikes or spike patterns that can delineate epileptogenic tissue. High-frequency oscillations (HFOs) on intraoperative electrocorticography have been proposed as a new biomarker of epileptogenic tissue, with higher specificity than spikes. We prospectively tested the non-inferiority of HFO-guided tailoring of epilepsy surgery to spike-guided tailoring on seizure freedom at 1 year.The HFO trial was a randomised, single-blind, adaptive non-inferiority trial at an epilepsy surgery centre (UMC Utrecht) in the Netherlands. We recruited children and adults (no age limits) who had been referred for intraoperative electrocorticography-tailored epilepsy surgery. Participants were randomly allocated (1:1) to either HFO-guided or spike-guided tailoring, using an online randomisation scheme with permuted blocks generated by an independent data manager, stratified by epilepsy type. Treatment allocation was masked to participants and clinicians who documented seizure outcome, but not to the study team or neurosurgeon. Ictiform spike patterns were always considered in surgical decision making. The primary endpoint was seizure outcome after 1 year (dichotomised as seizure freedom [defined as Engel 1A-B] vs seizure recurrence [Engel 1C-4]). We predefined a non-inferiority margin of 10% risk difference. Analysis was by intention to treat, with prespecified subgroup analyses by epilepsy type and for confounders. This completed trial is registered with the Dutch Trial Register, Toetsingonline ABR.NL44527.041.13, and ClinicalTrials.gov, NCT02207673.Between Oct 10, 2014, and Jan 31, 2020, 78 individuals were enrolled to the study and randomly assigned (39 to HFO-guided tailoring and 39 to spike-guided tailoring). There was no loss to follow-up. Seizure freedom at 1 year occurred in 26 (67%) of 39 participants in the HFO-guided group and 35 (90%) of 39 in the spike-guided group (risk difference -23·5%, 90% CI -39·1 to -7·9; for the 48 patients with temporal lobe epilepsy, the risk difference was -25·5%, -45·1 to -6·0, and for the 30 patients with extratemporal lobe epilepsy it was -20·3%, -46·0 to 5·4). Pathology associated with poor prognosis was identified as a confounding factor, with an adjusted risk difference of -7·9% (90% CI -20·7 to 4·9; adjusted risk difference -12·5%, -31·0 to 5·9, for temporal lobe epilepsy and 5·8%, -7·7 to 19·5, for extratemporal lobe epilepsy). We recorded eight serious adverse events (five in the HFO-guided group and three in the spike-guided group) requiring hospitalisation. No patients died.HFO-guided tailoring of epilepsy surgery was not non-inferior to spike-guided tailoring on intraoperative electrocorticography. After adjustment for confounders, HFOs show non-inferiority in extratemporal lobe epilepsy. This trial challenges the clinical value of HFOs as an epilepsy biomarker, especially in temporal lobe epilepsy. Further research is needed to establish whether HFO-guided intraoperative electrocorticography holds promise in extratemporal lobe epilepsy.UMCU Alexandre Suerman, EpilepsieNL, RMI Talent Fellowship, European Research Council, and MING Fund.

This population-based cross-sectional survey with a follow-up case-control study assessed the prevalence, incidence, and risk factors for epilepsy in a rural health district in the North-West Region of Cameroon. Community-based epilepsy screening targeted all inhabitants, six years and older, in all 16 health areas in the Batibo Health District. During door-to-door visits, trained fieldworkers used a validated questionnaire to interview consenting household heads to screen for epilepsy in eligible residents. Trained physicians subsequently assessed people with suspected seizures. After clinical assessment, they confirmed or refuted the diagnosis and estimated the date of epilepsy onset. A trained nurse interviewed people with epilepsy and randomly selected healthy individuals, obtaining relevant demographic details and information on exposure to risk factors for epilepsy. Out of 36,282 residents screened, 524 had active epilepsy. The age-standardized prevalence of active epilepsy was 33.9/1,000 (95% CI: 31.0-37.1/1,000). We estimated the one-year age-standardized epilepsy incidence at 171/100,000 (95%CI: 114.0-254.6). Active epilepsy prevalence varied widely between health areas, ranging between 12 and 75 per 1,000. The peak age-specific prevalence was in the 25-34 age group. In adults, multivariate analysis showed that having a relative with epilepsy was positively associated with epilepsy. Epilepsy characteristics in this population, geographical heterogeneity, and the age-specific prevalence pattern suggest that endemic neurocysticercosis and onchocerciasis may be implicated. Further investigations are warranted to establish the full range of risk factors for epilepsy in this population.

Despite clinical symptoms, a large majority of people with mild traumatic brain injury (TBI) have normal computed tomography (CT) and magnetic resonance imaging (MRI) scans. Therefore, present-day neuroimaging tools are insufficient to diagnose or classify low grades of TBI. Advanced neuroimaging techniques, such as diffusion-weighted and functional MRI, may yield novel biomarkers that may aid in the diagnosis of TBI. Therefore, the present study had two aims: first, to characterize the development of MRI-based measures of structural and functional changes in gray and white matter regions from acute to chronic stages after mild and moderate TBI; and second, to identify the imaging markers that can most accurately predict outcome after TBI. To these aims, 52 rats underwent serial functional (resting-state) and structural (T1-, T2-, and diffusion-weighted) MRI before and 1 h, 1 day, 1 week, 1 month and 3-4 months after mild or moderate experimental TBI. All rats underwent behavioral testing. Histology was performed in subgroups of rats at different time points. Early after moderate TBI, axial and radial diffusivities were increased, and fractional anisotropy was reduced in the corpus callosum and bilateral hippocampi, which normalized over time and was paralleled by recovery of sensorimotor function. Correspondingly, histology revealed decreased myelin staining early after TBI, which was not detected at chronic stages. No significant changes in individual outcome measures were detected after mild TBI. However, multivariate analysis showed a significant additive contribution of diffusion parameters in the distinction between control and different grades of TBI-affected brains. Therefore, combining multiple imaging markers may increase the sensitivity for TBI-related pathology.

Background Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling.Methods In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding.Findings 9147 patients were included, of whom seizure outcomes were available for 8191 (89.5%) participants at 2 years, and for 5577 (61.0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77.5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74.0% (328 of 443) for vascular malformation, and 71.5% (2108 of 2948) for hippocampal sderosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50.0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52.3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53.5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0-14% at 1 year and increased to 14-51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis.Interpretation Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

Introduction Epilepsy is a common yet misunderstood condition in Cameroon, including in the Batibo Health district. Methods This cross-sectional study describes epilepsy clinical characteristics, the treatment gap, and associated factors in a rural district in Cameroon. After screening for epilepsy using a door-to-door survey, physicians confirmed suspected cases of epilepsy. Detailed information on the medical, seizure, and treatment history was collected from everyone with epilepsy, followed by a general and neurological examination. Results We diagnosed 546 people with active epilepsy (at least one seizure in the previous 12 months). The mean age of people with active epilepsy was 25.2 years (SD: 11.1). The mean age at first seizure was 12.5 years (SD: 8.2). Convulsive seizures (uncertain whether generalized or focal) were the most common seizure types (60%), while 41% had focal-onset seizures. About 60% of people had seizures at least monthly. One-quarter of participants had had at least one episode of status epilepticus. Anti-seizure medication (ASM) was taken by 85%, but most were receiving inappropriate treatment or were non-adherent, hence the high treatment gap (80%). Almost a third had had seizure-related injuries. Epilepsy was responsible for low school attendance; 74% of school dropouts were because of epilepsy. Conclusion The high proportion of focal-onset seizures suggests acquired causes (such as neurocysticercosis and onchocerciasis, both endemic in this area). The high epilepsy treatment gap and the high rates of status epilepticus and epilepsy-related injuries underscore the high burden of epilepsy in this rural Cameroonian health district.

Functional outcome after stroke depends on the local site of ischemic injury and on remote effects within connected networks, frequently extending into the contralesional hemisphere. However, the pattern of large-scale contralesional network remodeling remains largely unresolved. In this study, we applied diffusion-based tractography and graph-based network analysis to measure structural connectivity in the contralesional hemisphere chronically after experimental stroke in rats. We used the minimum spanning tree method, which accounts for variations in network density, for unbiased characterization of network backbones that form the strongest connections in a network. Ultrahigh-resolution diffusion MRI scans of eight post-mortem rat brains collected 70 days after right-sided stroke were compared against scans from 10 control brains. Structural network backbones of the left (contralesional) hemisphere, derived from 42 atlas-based anatomical regions, were found to be relatively stable across stroke and control animals. However, several sensorimotor regions showed increased connection strength after stroke. Sensorimotor function correlated with specific contralesional sensorimotor network backbone measures of global integration and efficiency. Our findings point toward post-stroke adaptive reorganization of the contralesional sensorimotor network with recruitment of distinct sensorimotor regions, possibly through strengthening of connections, which may contribute to functional recovery.

Objective Intraoperative electrocorticography (ECoG) can be used to delineate the resection area in epilepsy surgery. High-frequency oscillations (HFOs; 80–500 Hz) seem better biomarkers for epileptogenic tissue than spikes. We studied how HFOs and spikes in combined pre- and postresection ECoG predict surgical outcome in different tailoring approaches. Methods We, retrospectively, marked HFOs, divided into fast ripples (FRs; 250–500 Hz) and ripples (80–250 Hz), and spikes in pre- and postresection ECoG sampled at 2,048 Hz in people with refractory focal epilepsy. We defined four groups of electroencephalography (EEG) event occurrence: pre+post− (+/−), pre+post+ (+/+), pre−post+ (−/+) and pre−post− (−/−). We subcategorized three tailoring approaches: hippocampectomy with tailoring for neocortical involvement; lesionectomy of temporal lesions with tailoring for mesiotemporal involvement; and lesionectomy with tailoring for surrounding neocortical involvement. We compared the percentage of resected pre-EEG events, time to recurrence, and the different tailoring approaches to outcome (seizure-free vs recurrence). Results We included 54 patients (median age, 15.5 years; 25 months of follow-up; 30 seizure free). The percentage of resected FRs, ripples, or spikes in pre-ECoG did not predict outcome. The occurrence of FRs in post-ECoG, given FRs in pre-ECoG (+/−, +/+), predicted outcome (hazard ratio, 3.13; confidence interval = 1.22–6.25; p = 0.01). Seven of 8 patients without spikes in pre-ECoG were seizure free. The highest predictive value for seizure recurrence was presence of FRs in post-ECoG for all tailoring approaches. Interpretation FRs that persist before and after resection predict poor postsurgical outcome. These findings hold for different tailoring approaches. FRs can thus be used for tailoring epilepsy surgery with repeated intraoperative ECoG measurements. Ann Neurol 2017;81:664–676

People with epilepsy often report seizures precipitated by stress. This is believed to be due to effects of stress hormones, such as cortisol, on neuronal excitability. Cortisol, regardless of stress, is released in hourly pulses, whose effect on epileptic activity is unknown. We tested the relation between cortisol levels and the incidence of epileptiform abnormalities in the electroencephalogram of people with focal epilepsy. Morning cortisol levels were measured in saliva samples obtained every 15 min. Interictal epileptiform discharges were determined in the same time periods. We investigated the relationship between cortisol levels and the epileptiform discharges distinguishing persons with from those without stress-precipitated seizures (linear mixed model), and analysed the contribution of individual, epilepsy and recording characteristics with multivariable analysis. Twenty-nine recordings were performed in 21 individuals. Cortisol was positively related to incidence of epileptiform discharges (β = 0.26, P = 0.002) in people reporting stress-sensitive seizures, but not those who did not report stress sensitivity (β = -0.07, P = 0.64). The relationship between cortisol and epileptiform discharges was positively associated only with stress sensitivity of seizures (β = 0.31, P = 0.005). The relationship between cortisol levels and incidence of interictal epileptiform discharges in people with stress-sensitive seizures suggests that stress hormones influence disease activity in epilepsy, also under basal conditions.

Objective Since the introduction of diffusion tensor imaging, white matter abnormalities in epilepsy have been studied extensively. However, the affected areas reported, the extent of abnormalities and the association with relevant clinical parameters are highly variable. We aimed to obtain a more consistent estimate of white matter abnormalities and their association with clinical parameters in different epilepsy types. Methods We systematically searched for differences in white matter fractional anisotropy and mean diffusivity, at regional and voxel level, between people with epilepsy and healthy controls. Meta-analyses were used to quantify the directionality and extent of these differences. Correlations between white matter differences and age of epilepsy onset, duration of epilepsy and sex were assessed with meta-regressions. Results Forty-two studies, with 1027 people with epilepsy and 1122 controls, were included with regional data. Sixteen voxel-based studies were also included. People with temporal or frontal lobe epilepsy had significantly decreased fractional anisotropy (Δ –0.021, 95% confidence interval –0.026 to –0.016) and increased mean diffusivity (Δ0.026 × 10–3 mm2/s, 0.012 to 0.039) in the commissural, association and projection white matter fibers. White matter was much less affected in generalized epilepsy. White matter changes in people with focal epilepsy correlated with age at onset, epilepsy duration and sex. Significance This study provides a better estimation of white matter changes in different epilepsies. Effects are particularly found in people with focal epilepsy. Correlations with the duration of focal epilepsy support the hypothesis that these changes are, at least partly, a consequence of seizures and may warrant early surgery. Future studies need to guarantee adequate group sizes, as white matter differences in epilepsy are small., Highlights • White matter FA and MD are more affected in focal than in generalized epilepsy. • Epilepsy subtypes show distinct patterns of affected white matter regions. • White matter integrity is altered both ipsi- and contralaterally in focal epilepsy. • White matter changes in focal epilepsy seem to be a consequence of seizures.

The mammalian brain is composed of densely connected and interacting regions, which form structural and functional networks. An improved understanding of the structure–function relation is crucial to understand the structural underpinnings of brain function and brain plasticity after injury. It is currently unclear how functional connectivity strength relates to structural connectivity strength. We obtained an overview of recent papers that report on correspondences between quantitative functional and structural connectivity measures in the mammalian brain. We included network studies in which functional connectivity was measured with resting-state fMRI, and structural connectivity with either diffusion-weighted MRI or neuronal tract tracers. Twenty-seven of the 28 included studies showed a positive structure–function relationship. Large inter-study variations were found comparing functional connectivity strength with either quantitative diffusion-based (correlation coefficient (r) ranges: 0.18–0.82) or neuronal tracer-based structural connectivity measures (r = 0.24–0.74). Two functional datasets demonstrated lower structure–function correlations with neuronal tracer-based (r = 0.22 and r = 0.30) than with diffusion-based measures (r = 0.49 and r = 0.65). The robust positive quantitative structure–function relationship supports the hypothesis that structural connectivity provides the hardware from which functional connectivity emerges. However, methodological differences between the included studies complicate the comparison across studies, which emphasize the need for validation and standardization in brain structure–function studies.

Following the results of the multicentre European retrospective "TimeToStop" cohort study, we initiated a randomised trial to determine cognitive benefits of early postoperative antiepileptic drug withdrawal. Unfortunately, the trial failed to recruit and was terminated, as almost all parents preferred early drug withdrawal. The objectives of the current survey were to obtain insight into current practices regarding drug withdrawal after paediatric epilepsy surgery among epileptologists, and better understand the reasons for difficulties in recruitment. A survey was sent to three international epilepsy surgery networks, questioning drug withdrawal policies. Forty-seven (19%) surveys were returned. For polytherapy, withdrawal was started at a median of three and six months by the TimeToStop collaborators and other paediatric epileptologists, respectively. Withdrawal was completed at a median of 12 and 20 months, respectively. For monotherapy, tapering was initiated at five and 11 months in these two groups, and ended at a median of seven and 12 months, respectively. Most TimeToStop collaborators believed that it was not justified to wait 12 months after surgery before reducing AEDs, regardless of the number of AEDs taken. Current AED policies in Europe have changed as a consequence of the retrospective TimeToStop results, and this accounts for why recruitment in a randomised trial was not feasible.

One of the challenges of brain network analysis is to directly compare network organization between subjects, irrespective of the number or strength of connections. In this study, we used minimum spanning tree (MST; a unique, acyclic subnetwork with a fixed number of connections) analysis to characterize the human brain network to create an empirical reference network. Such a reference network could be used as a null model of connections that form the backbone structure of the human brain. We analyzed the MST in three diffusion‐weighted imaging datasets of healthy adults. The MST of the group mean connectivity matrix was used as the empirical null‐model. The MST of individual subjects matched this reference MST for a mean 58%–88% of connections, depending on the analysis pipeline. Hub nodes in the MST matched with previously reported locations of hub regions, including the so‐called rich club nodes (a subset of high‐degree, highly interconnected nodes). Although most brain network studies have focused primarily on cortical connections, cortical–subcortical connections were consistently present in the MST across subjects. Brain network efficiency was higher when these connections were included in the analysis, suggesting that these tracts may be utilized as the major neural communication routes. Finally, we confirmed that MST characteristics index the effects of brain aging. We conclude that the MST provides an elegant and straightforward approach to analyze structural brain networks, and to test network topological features of individual subjects in comparison to empirical null models.

Treatment of epilepsy in low-income countries is a challenge considering the lack of resources, availability of antiepileptic drugs, and cultural beliefs. We used a community-based rehabilitation (CBR) service for the detection, monitoring, and treatment of epilepsy. A local network of trained community volunteers provided education, good quality antiepileptic drugs, and clinical follow-up for people with epilepsy (PWE). In a period of 2years, approximately 22,500 people were screened in central Guinea-Bissau, and 112 PWE were identified and registered. Monthly check-ups were offered to monitor treatment effect and increase compliance. Retrospective analysis on 81 records of patients under treatment in June 2016 showed a decrease of seizure frequency in 88.8% after treatment initiation and was maintained throughout the clinical follow-up of 15months. A conservative estimation of the treatment and monitoring of a single person with epilepsy revealed a daily cost of $0.73. Despite acknowledging epilepsy as a neglected condition by the World Health Organization (WHO), most PWE still lack appropriate treatment. Although CBR service has been suggested as efficient strategy to reduce the treatment gap, little information is available on the efficacy of the programs. Our experiences show that CBR service is a cost-effective approach to monitor treatment and increase compliance in PWE. This experience may be of value for other resource-poor settings.

Background This study assessed the epilepsy treatment gap (ETG) and factors associated with access to care and adherence from three sites of Afikpo, Ijebu-Jesa and Gwandu in the Southeast, Southwest and Northwest regions of Nigeria respectively. Methodology People with active epilepsy were recruited from a door-to-door survey undertaken between February and April 2018 using set criteria. The sociodemographic, pattern of care access and treatment-related information were obtained. ETG was defined according to International League Against Epilepsy criteria. Potential factors for ETG were examined using multivariate logistic regression with multiple imputations. Results A total of 252 subjects were recruited from the three sites. The self-reported therapeutic gap was 83.3% (95% CI:78.1–87.7), while the ETG was 94.4% (95% CI: 90.9, 96.9) considering the diagnostic gap with no difference across sites (P=0.230). The potential factors associated with failure to access to care include stigma (OR 0.16, 95% CI: 0.04–0.71; P=0.016), cultural beliefs (OR: 0.31, 95% CI: 0.16–0.62; P=0.001), difficulty reaching a health facility (OR 0.33, 95% CI: 0.14–0.75; P=0.008), and non-acceptance of diagnosis (OR 0.36, 95% 0.15–0.85; P=0.021). Factors associated with non-adherence include cultural beliefs (OR 28.68, 95% CI: 1.70– 483.97; P=0.020), afternoon seizures (OR 0.006, 95% CI: 0.001–0.58; P=0.029), learning difficulty (OR 0.16, 95% CI: 0.03–0.88; P=0.035), and difficulty reaching a health facility (OR 25.44, 95% CI: 0.88–735.88; P=0.059). Conclusion The treatment gap is high in Nigeria. The negative cultural belief can be improved by patient and community education.

Stroke is a major cause of disability; however, most patients experience spontaneous partial recovery of functions in subacute to chronic phases. Poststroke loss and recovery of functions have been increasingly correlated with brain-wide alterations in the connectivity of neural networks, which is described in this review. Elucidation of the mechanisms of functional brain remodeling could reveal targets and strategies for more effective neurorehabilitation.Data from recent resting-state functional MRI, electroencephalography, magnetoencephalography, and optical imaging studies in patients and animal models have demonstrated that loss of function after stroke is closely associated with disrupted connectivity in large-scale networks beyond the lesion territory. Restoration of functional connectivity in the surviving networks appears to be critical for functional recovery, and this may be promoted with specific therapeutic strategies, such as robot-assisted training and noninvasive brain stimulation. The adaptability of functional networks relies on the structural integrity of neuronal pathways, but the relationship between the two remains incompletely understood. Furthermore, disturbed neurovascular coupling after stroke can confound hemodynamically based measurements of functional connectivity.Identification of key network processes in adaptive brain plasticity can aid in the prediction of functional outcome and the development of therapeutic interventions to support and promote recovery after stroke.

Epilepsy is a common neurological disorder in Nigeria. Many individuals are affected in rural areas, although prevalence data is not available. In this study we aimed to establish the prevalence of epilepsy in a rural community in south-east Nigeria, a community suspected for having a high number of people living with epilepsy. We compared this with the prevalence in a nearby semi-urban community in north-central Nigeria. In both communities we identified potential causes of epilepsy and obtained information on the social beliefs regarding epilepsy. We used door-to-door surveys and focus group discussions. The epilepsy prevalence in the rural community was 20.8/1000 [95% confidence interval (CI): 15.7-27.4]. The prevalence in the semi-rural community was lower, namely 4.7/1000 [CI: 3.2-6.9]. The difference in prevalence was highly significant (χ(2)-test, p

Our aim was to evaluate Wikipedia page visits in relation to the most common neurological disorders by determining which factors are related to peaks in Wikipedia searches for these conditions. Millions of people worldwide use the internet daily as a source of health information. Wikipedia is a popular free online encyclopedia used by patients and physicians to search for health-related information. The following Wikipedia articles were considered: Alzheimer's disease; Amyotrophic lateral sclerosis; Dementia; Epilepsy; Epileptic seizure; Migraine; Multiple sclerosis; Parkinson's disease; Stroke; Traumatic brain injury. We analyzed information regarding the total article views for 90 days and the rank of these articles among all those available in Wikipedia. We determined the highest search volume peaks to identify possible relation with online news headlines. No relation between incidence or prevalence of neurological disorders and the search volume for the related articles was found. Seven out of 10 neurological conditions showed relations in search volume peaks and news headlines. Six out of these seven peaks were related to news about famous people suffering from neurological disorders, especially those from showbusiness. Identification of discrepancies between disease burden and health seeking behavior on Wikipedia is useful in the planning of public health campaigns. Celebrities who publicly announce their neurological diagnosis might effectively promote awareness programs, increase public knowledge and reduce stigma related to diagnoses of neurological disorders.

Background Community-based epilepsy care programs improve access to epilepsy treatment in resource-poor settings. Community volunteers are important to these services. Most studies on familiarity with, understanding of, and attitudes towards people with epilepsy (PWE), however, ignore these volunteers. Methods We explored these issues among 15 community volunteers involved in a community-based rehabilitation child epilepsy service recently initiated in Guinea-Bissau using face-to-face interviews. Results We found that the volunteers had a reasonable understanding of epilepsy, moderate attitudes towards PWE, and a good understanding of difficulties PWE encounter in society. Conclusion Evaluation of understanding and attitudes of community volunteers may be useful to improve low-cost community-based epilepsy programs. A correct understanding of epilepsy among community volunteers may increase effective treatment of and support to children with epilepsy through community-based epilepsy programs.

Background: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia and can severely disrupt behavior and decrease quality of life. Identification of areas with high functional connectivity (so-called hub regions) that are associated with the predisposition to hallucinate may provide potential targets for neuromodulation in the treatment of AVH. Methods: Resting-state fMRI scans during which no hallucinations had occurred were acquired from 29 nonpsychotic individuals with AVH and 29 matched controls. These nonpsychotic individuals with AVH provide the opportunity to study AVH without several confounds associated with schizophrenia, such as antipsychotic medication use and other symptoms related to the illness. Hub regions were identified by assessing weighted connectivity strength and betweenness centrality across groups using a permutation analysis. Results: Nonpsychotic individuals with AVH exhibited increased functioning as hub regions in the temporal cortices and the posterior cingulate/precuneus, which is an important area in the default mode network (DMN), compared to the nonhallucinating controls. In addition, the right inferior temporal gyrus, left paracentral lobule and right amygdala were less important as a hub region in the AVH group. Conclusions: These results suggest that the predisposition to hallucinate may be related to aberrant functioning of the DMN and the auditory cortices. Hum Brain Mapp 35:1436–1445, 2014. © 2013 Wiley Periodicals, Inc.

OBJECTIVE: To assess whether there is a difference in the background activity in the ripple band (80-200Hz) between epileptic and non-epileptic channels, and to assess whether this difference is sufficient for their reliable separation. METHODS: We calculated mean and standard deviation of wavelet entropy in 303 non-epileptic and 334 epileptic channels from 50 patients with intracerebral depth electrodes and used these measures as predictors in a multivariable logistic regression model. We assessed sensitivity, positive predictive value (PPV) and negative predictive value (NPV) based on a probability threshold corresponding to 90% specificity. RESULTS: The probability of a channel being epileptic increased with higher mean (p=0.004) and particularly with higher standard deviation (p

ObjectiveBlood–brain barrier (BBB) leakage may play a pro‐epileptogenic role after status epilepticus. In the accompanying contrast‐enhanced magnetic resonance imaging (CE‐MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activity during the chronic epileptic phase. Given rapamycin's role in growth and immune response, the potential therapeutic effects of rapamycin after status epilepticus with emphasis on brain inflammation and brain vasculature were investigated.MethodsSeven weeks after kainic acid–induced status epilepticus, rats were perfusion fixed and (immuno)histochemistry was performed using several glial and vascular markers. In addition, an in vitro model for the human BBB was used to determine the effects of rapamycin on transendothelial electrical resistance as a measure for BBB integrity.Results(Immuno)histochemistry showed that local blood vessel density, activated microglia, and astrogliosis were reduced in rapamycin‐treated rats compared to vehicle‐treated rats. In vitro studies showed that rapamycin could attenuate TNFα‐induced endothelial barrier breakdown.SignificanceThese data suggest that rapamycin improves BBB function during the chronic epileptic phase by a reduction of local brain inflammation and blood vessel density that can contribute to a milder form of epilepsy.

ObjectiveThe mammalian target of rapamycin (mTOR) pathway has received increasing attention as a potential antiepileptogenic target. Treatment with the mTOR inhibitor rapamycin after status epilepticus reduces the development of epilepsy in a rat model. To study whether rapamycin mediates this effect via restoration of blood–brain barrier (BBB) dysfunction, contrast‐enhanced magnetic resonance imaging (CE‐MRI) was used to determine BBB permeability throughout epileptogenesis.MethodsImaging was repeatedly performed until 6 weeks after kainic acid–induced status epilepticus in rapamycin (6 mg/kg for 6 weeks starting 4 h after SE) and vehicle‐treated rats, using gadobutrol as contrast agent. Seizures were detected using video monitoring in the week following the last imaging session.ResultsGadobutrol leakage was widespread and extensive in both rapamycin and vehicle‐treated epileptic rats during the acute phase, with the piriform cortex and amygdala as the most affected regions. Gadobutrol leakage was higher in rapamycin‐treated rats 4 and 8 days after status epilepticus compared to vehicle‐treated rats. However, during the chronic epileptic phase, gadobutrol leakage was lower in rapamycin‐treated epileptic rats along with a decreased seizure frequency. This was confirmed by local fluorescein staining in the brains of the same rats. Total brain volume was reduced by this rapamycin treatment regimen.SignificanceThe initial slow recovery of BBB function in rapamycin‐treated epileptic rats indicates that rapamycin does not reduce seizure activity by a gradual recovery of BBB integrity. The reduced BBB leakage during the chronic phase, however, could contribute to the decreased seizure frequency in post–status epilepticus rats treated with rapamycin. Furthermore, the data show that CE‐MRI (using step‐down infusion with gadobutrol) can be used as biomarker for monitoring the effect of drug therapy in rats.

Objective High frequency oscillations (HFOs; > 80 Hz), especially fast ripples (FRs, 250–500 Hz), are novel biomarkers for epileptogenic tissue. The pathophysiology suggests enhanced functional connectivity within FR generating tissue. Our aim was to determine the relation between brain areas showing FRs and ‘baseline’ functional connectivity within EEG networks, especially in the high frequency bands. Methods We marked FRs, ripples (80–250 Hz) and spikes in the electrocorticogram of 14 patients with refractory temporal lobe epilepsy. We assessed ‘baseline’ functional connectivity in epochs free of epileptiform events within these recordings, using the phase lag index. We computed the Eigenvector Centrality (EC) per channel in the FR and gamma band network. We compared EC between channels that did or did not show events at other moments in time. Results FR-band EC was higher in channels with than without spikes. Gamma-band EC was lower in channels with ripples and FRs. Conclusions We confirmed previous findings of functional isolation in the gamma-band and found a first proof of functional integration in the FR-band network of channels covering presumed epileptogenic tissue. Significance ‘Baseline’ high-frequency network parameters might help intra-operative recognition of epileptogenic tissue without the need for waiting for events. These findings can increase our understanding of the ‘architecture’ of epileptogenic networks and help unravel the pathophysiology of HFOs., Highlights • The epileptogenic area is functionally isolated in the gamma-band network. • The epileptogenic area seems functionally integrated in the high frequency network. • The ‘baseline’ signal contains clinically useful high frequency surrogate biomarker information.

Objective: The effectiveness of anthelminthic and corticosteroid drug therapy in parenchymal neurocysticercosis is well established. The treatment of parenchymal solitary cysticercus granuloma (SCG), however, remains controversial. We attempted to obtain a consistent estimate of the efficacy of anthelminthic and corticosteroid drug treatment in SCG. Methods: Randomized-controlled trials (RCTs) comparing rates of seizure freedom, granuloma resolution, and residual calcification in individuals with SCG treated with anthelminthic or corticosteroid drugs with those treated with antiepileptic drugs (AEDs) alone were systematically reviewed and quantified using fixed- or random-effects meta-analysis. Results: Fifteen RCTs were identified for inclusion. Ten RCTs assigned 765 people with SCG to AED treatment with or without anthelminthic drug (albendazole) treatment. A further 5 RCTs assigned 457 people with SCG to AED treatment with or without corticosteroid drugs. Anthelminthic treatment was associated with significantly increased rates of seizure freedom (nonevent odds ratio: 2.45; 95% confidence interval: 1.49–4.03; p = 0.0004) and significantly higher rates of granuloma resolution (odds ratio: 2.09; 95% confidence interval: 1.41–3.00; p = 0.0003), but did not alter the risk of residual calcification. Corticosteroid treatment was not significantly associated with any outcome. Conclusions: Anthelminthic treatment with albendazole provides improved rates of seizure freedom and hastens resolution of the granuloma. The role of corticosteroid treatment remains uncertain. The benefits (or lack thereof in the case of corticosteroids) are consistent when measured across different time points after treatment.

Summary Purpose: Extratemporal epilepsy often coincides with cognitive decline, which may be associated with hippocampal dysfunction. Severe hippocampal sclerosis can be detected with conventional neuroimaging in some patients with chronic extrahippocampal epilepsy (so-called dual pathology). However, subtle structural hippocampal changes may already develop at a much earlier phase, and in a larger number of patients. Our goal was to longitudinally characterize the development of bilateral hippocampal pathology in an experimental neocortical focal epilepsy model. Methods: Focal unilateral neocortical epilepsy was induced by microinjection of tetanus toxin in the primary motor cortex in adult male Sprague-Dawley rats. Another group of age-matched rats served as controls. In both groups, structural magnetic resonance imaging (MRI) was performed at 1, 3, 7, and 10 weeks of follow-up. Bilateral hippocampi were outlined and macroscopically analyzed using a state-of-the-art point-based morphometry model. Hippocampal microstructural changes at the end of follow-up, 10 weeks after epilepsy induction, were assessed with postmortem standard cresyl-violet, Fluoro-Jade, proteolipid protein 1, vimentin, glial fibrillary acidic protein, and ionized calcium binding adaptor molecule 1 stainings. Key Findings: All rats in the injected group developed seizures. The ipsilateral hippocampal volume was on average 8.76 (mean) ± 3.32% (standard deviation) smaller in the epileptic animals as compared to controls (p = 0.01) during the 10 weeks of follow-up. The contralateral hippocampus showed a similar reduction of 8.49 (mean) ± 3.27% (standard deviation) in total volume (p = 0.02). Clear hippocampal shape differences were found between the two groups. The most affected areas after epilepsy induction were the bilateral dorso-mediorostral, dorsolateral, and ventrolateral areas of the hippocampi. Normal developmental shape changes of the hippocampus, as detected in control rats, were largely absent in the ipsilateral hippocampus of epileptic rats. Quantitative histologic analysis revealed significant neuronal loss in the hippocampus, most pronounced in the hilar subregion, globally impaired myelination, reactive astrocytosis, and activated microglia. We found a weak but significant correlation between the number of neurons and hippocampal volume (r = 0.25, p = 0.0025). Significance: We found evidence of hippocampal pathology in both hemispheres following experimental focal neocortical epilepsy. The observed development of bilateral hippocampal pathology, with onset in the early stages of focal neocortical epilepsy, may be a significant factor in comorbidities, such as cognitive dysfunction, found in patients with extratemporal localization-related epilepsy.

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.

Many seizure-free patients consider withdrawal of antiepileptic drugs, both when seizure control is achieved by medication alone, or once they became seizure-free following epilepsy surgery. The risk of recurrence is consequently of very important prognostic value. However, estimations of recurrence risks are outdated for both populations. In addition, although many publications have reported predictors of seizure relapse, no comprehensive overview of prognostic factors is available.A systematic review of the databases of PubMed and EMBASE was conducted, identifying articles on antiepileptic drug withdrawal in patient cohorts. Recurrence risk meta-analyses were performed for both populations at one, two, three to four, and five or more years of follow-up. Within the selected articles, studies presenting multivariable analysis of predictors were identified; all studied predictors were listed, as well as all significant independent predictors. The quality of separate analyses of predictors was assessed.There was no significant difference of long-term cumulative recurrence risk between surgical and medication-only populations, with respectively 29% and 34% recurrences. In medication-only treated patients, 25 factors have been reported as significant independent predictors; 12 have been reported in surgical cohorts. The quality of most analyses of predictors was low to moderate. No predictor was consistently found among all analyses, and for most predictors, study results were contradictory.No consistent set of predictors could be identified because a large number of variables have been identified in the literature, many studies reported contradicting results, study populations varied considerably, and the quality of the original studies was often low. Meta-analysis of individual participant data is necessary, because it allows for (1) correction for differences in follow-up duration between subjects and studies, (2) a study of interaction effects, (3) calculation of more accurate estimates valid across several populations, and (4) the assessment of each predictor's effect size.

Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions.

There is a general need for high-quality, easily accessible, and comprehensive health-care information on epilepsy to better inform the general population about this highly stigmatized neurological disorder. The aim of this study was to evaluate the health literacy level of eight popular English-written websites that provide information on epilepsy in quantitative terms of readability. Educational epilepsy material on these websites, including 41 Wikipedia articles, were analyzed for their overall level of readability and the corresponding academic grade level needed to comprehend the published texts on the first reading. The Flesch Reading Ease (FRE) was used to assess ease of comprehension while the Gunning Fog Index, Coleman-Liau Index, Flesch-Kincaid Grade Level, Automated Readability Index, and Simple Measure of Gobbledygook scales estimated the corresponding academic grade level needed for comprehension. The average readability of websites yielded results indicative of a difficult-to-fairly-difficult readability level (FRE results: 44.0. ±. 8.2), with text readability corresponding to an 11th academic grade level (11.3. ±. 1.9). The average FRE score of the Wikipedia articles was indicative of a difficult readability level (25.6. ±. 9.5), with the other readability scales yielding results corresponding to a 14th grade level (14.3. ±. 1.7). Popular websites providing information on epilepsy, including Wikipedia, often demonstrate a low level of readability. This can be ameliorated by increasing access to clear and concise online information on epilepsy and health in general. Short "basic" summaries targeted to patients and nonmedical users should be added to articles published in specialist websites and Wikipedia to ease readability.

We aimed to relate the percentages of encountered epilepsy-related stigma in people with epilepsy with quantitative indicators of the quality of health systems and quality of life by country in Europe. The epilepsy-related stigma percentages were obtained from the largest population-based study in people with epilepsy available. We correlated percentages of people with perceived stigma per European country with data on the country's overall health system performance, health expenditure per capita in international dollars, and the Economist Intelligence Unit's quality-of-life index. Wefound a nonsignificant trend towards negative correlation between the epilepsy-related stigma percentage and the overall health system performance (r=-0.16; p= 0.57), the health expenditure per capita in international dollars (r = -0.24; p = 0.4), and the Economist Intelligence Unit's quality-of-life index (r = -0.33; p = 0.91). Living in a European country with a better health system performance and higher health expenditure per capita does not necessarily lead to a reduction in perceived epilepsy-related discrimination, unless the public health system invests on awareness programs to increase public knowledge and reduce stigma. (C) 2014 Elsevier Inc. All rights reserved.

In old and modern times and across cultures, recurrent seizures have been attributed to the lunar phase. It is unclear whether this relationship should be classified as a myth or whether a true connection exists between moon phases and seizures. We analyzed the worldwide aggregated search queries related to epilepsy health-seeking behavior between 2005 and 2012. Epilepsy-related Internet searches increased in periods with a high moon illumination. The overall association was weak (r=0.11, 95% confidence interval: 0.07 to 0.14) but seems to be higher than most control search queries not related to epilepsy. Increased sleep deprivation during periods of full moon might explain this positive association and warrants further study into epilepsy-related health-seeking behavior on the Internet, the lunar phase, and its contribution to nocturnal luminance.

Stress is the most often reported seizure-precipitant in epilepsy. As most evidence for the relation between stress and epilepsy is derived from human self-reports, observational studies including a larger part of the population could provide additional proof. A stressor often reported to increase seizure frequency in children with epilepsy in the Netherlands is the national celebration of Saint Nicholas' eve (December 5) and the weeks before; this is the main period of festivities for children in this country. To study the relation between stress and epilepsy, we analyzed epilepsy information-seeking behavior on the Internet, an indirect measure of seizure frequency, around this national children's celebration.Google Trends was used to extract relative search percentages for 'epilepsy' on Google in the Netherlands, the United States, and the United Kingdom between 2004 and 2013. Relative search percentages during the Saint Nicholas period were compared with baseline.Epilepsy searches increased by 14% in the Saint Nicholas period compared with baseline (p0.001). This effect was not found for searches performed in the same period in the United States or the United Kingdom, countries where this holiday is not celebrated.The increase in epilepsy information-seeking behavior in the Saint Nicholas period is possibly caused by an increased occurrence of epileptic seizures. This underscores the potential of health information-seeking behavior on the Internet to answer clinically relevant research questions and provides circumstantial evidence for a relation between stress and the occurrence of epileptic seizures.

Reducing the burden of epilepsy in low- and middle-income countries requires understanding of the cultural aspects of epilepsy. This cross-sectional study among individuals attending a clinic in an urban setting in Paramaribo, Suriname aimed to obtain information on the knowledge of and attitudes towards epilepsy and epilepsy treatment, comparing people with epilepsy (PWE) to those without epilepsy. This study also explored the help-seeking behavior and experience of having epilepsy in PWE. While the results of interviews with 49 PWE and 33 controls compared favorably to studies conducted in similar countries, a significant minority of PWE still rely on traditional remedies. Prejudices regarding social roles, schooling, and occupational choices of PWE also remain prevalent. Currently, the major source of information for both groups is the media, but there could be opportunities for the local epilepsy association to play a larger role. These findings, despite some selection bias, could be useful in bringing conventional medical treatment strategies to more PWE in Suriname, as well as empower patient organizations in designing stigma-reducing interventions.

OBJECTIVE: It remains unclear to what extent brain networks are altered at an early stage of epilepsy, which may be important to improve our understanding on the course of network alterations and their association with recurrent seizures and cognitive deficits.METHODS: 89 Drug-naïve children with newly diagnosed focal or generalized epilepsies and 179 controls were included. Brain networks were based on interictal electroencephalography recordings obtained at first consultation. Conventional network metrics and minimum spanning tree (MST) metrics were computed to characterize topological network differences, such integration and segregation and a hub measures (betweenness centrality).RESULTS: Network alterations between groups were only identified by MST metrics and most pronounced in the delta band, in which a loss of network integration and a significant lower betweenness centrality was found in children with focal epilepsies compared to healthy controls (pCONCLUSIONS: Interictal network alterations - only identifiable with the MST method - are already present at an early stage of focal epilepsy.SIGNIFICANCE: We argue that these alterations are subtle at the early stage and aggravate later as a result of persisting seizures.