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Genetic variants in relevant genes coexisting with MRI lesions in children with drug-resistant epilepsy (DRE) can negatively influence epilepsy surgery outcomes. Still, presurgical evaluation does not include genetic diagnostics routinely. Here, we report our presurgical evaluation algorithm that includes routine genetic testing. We analyzed retrospectively the data of 68 children with DRE operated at a mean age of 7.8 years (IQR: 8.1 years) at our center. In 49 children, genetic test results were available. We identified 21 gene variants (ACMG III: n = 7, ACMG IV: n = 2, ACMG V: n = 12) in 19 patients (45.2%) in the genes TSC1, TSC2, MECP2, DEPDC5, HUWE1, GRIN1, ASH1I, TRIO, KIF5C, CDON, ANKD11, TGFBR2, ATN1, COL4A1, JAK2, KCNQ2, ATP1A2, and GLI3 by whole-exome sequencing as well as deletions and duplications by array CGH in six patients. While the results did not change the surgery indication, they supported counseling with respect to postoperative chance of seizure freedom and weaning of antiseizure medication (ASM). The presence of genetic findings leads to the postoperative retention of at least one ASM. In our cohort, the International League against Epilepsy (ILAE) seizure outcome did not differ between patients with and without abnormal genetic findings. However, in the 7/68 patients with an unsatisfactory ILAE seizure outcome IV or V 12 months postsurgery, 2 had an abnormal or suspicious genetic finding as a putative explanation for persisting seizures postsurgery, and 3 had received palliative surgery including one TSC patient. This study highlights the importance of genetic testing in children with DRE to address putative underlying germline variants as genetic epilepsy causes or predisposing factors that guide patient and/or parent counseling on a case-by-case with respect to their individual chance of postoperative seizure freedom and ASM weaning. PLAIN LANGUAGE SUMMARY: Genetic variants in children with drug-resistant epilepsy (DRE) can negatively influence epilepsy surgery outcomes. However, presurgical evaluation does not include genetic diagnostics routinely. This retrospective study analyzed the genetic testing results of the 68 pediatric patients who received epilepsy surgery in our center. We identified 21 gene variants by whole-exome sequencing as well as deletions and duplications by array CGH in 6 patients. These results highlight the importance of genetic testing in children with DRE to guide patient and/or parent counseling on a case-by-case with respect to their individual chance of postoperative seizure freedom and ASM weaning., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Although epilepsy surgery is the only curative therapeutic approach for lesional drug-resistant epilepsy (DRE), there is reluctance to operate on infants due to a fear of complications. A recent meta-analysis showed that epilepsy surgery in the first 6 months of life can achieve seizure control in about two thirds of children. However, robust data on surgical complications and postoperative cognitive development are lacking. We performed a retrospective multicenter study of infants who underwent epilepsy surgery in the first 6 months of life. 15 infants underwent epilepsy surgery at a median age of 134 days (IQR: 58) at four centers. The most common cause was malformation of cortical development, and 13 patients underwent a hemispherotomy. Two thirds required intraoperative red blood transfusions. Severe intraoperative complications occurred in two patients including death in one infant due to cardiovascular insufficiency. At a median follow-up of 1.5 years (IQR: 1.8), 57% of patients were seizure-free. Three patients where reoperated at a later age, resulting in 79% seizure freedom. Anti-seizure medication could be reduced in two thirds, and all patients improved in their development. Our findings suggest that early epilepsy surgery can result in good seizure control and developmental improvement. However, given the perioperative risks, it should be performed only in specialized centers., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Epilepsy surgery is currently the only way to cure drug-resistant epilepsy (DRE). The loss of epileptic activity or its propagation in the developing brain may not only result in seizure freedom but also be associated with further positive effects. Here, we analyzed the cognitive development of children and adolescents with DRE after epilepsy surgery., Methods: We evaluated retrospectively the cognitive development of children and adolescents before and after epilepsy surgery., Results: Fifty-three children and adolescents underwent epilepsy surgery at a median age of 7.62 years. Overall seizure freedom was 86.8% at a current median observation period of 20 months. Presurgically, 81.1% had the clinical diagnosis of cognitive impairment, which was confirmed by standardized tests in 43 of 53 patients (76.7%). Further 10 patients had severe cognitive impairment rendering a standardized test impossible. The median intelligence quotient (IQ)/development quotient value was 74. After surgery, caretakers reported developmental progress in all patients, whereas the median IQ decreased slightly (P = 0.404). In eight patients the IQ points decreased after surgery; however, their individual raw scores increased in line with their reported increase in cognitive abilities., Conclusions: We did not detect any cognitive deterioration in children following epilepsy surgery. A loss of IQ points did not correspond to a real loss of cognitive abilities. These patients developed more slowly than age-matched peers with an average development speed but profited individually as seen in their raw scores. Therefore, an individual analysis of raw scores is relevant to assess the cognitive development after surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Family burden (FB) in pediatric patients with drug-resistant epilepsy (DRE) is significantly higher than that in children with non-DRE. Epilepsy surgery is an established approach to treat DRE, and this study examines the impact of pediatric epilepsy surgery on FB., Methods: We retrospectively analyzed data of families and pediatric patients with focal structural DRE treated with epilepsy surgery at our epilepsy center from April 2018 to November 2021. We examined the relationship between cognitive, behavioral, and epilepsy-specific data and the FB measured with the German version of the Impact on Family Scale before and after epilepsy surgery., Results: The study cohort included 31 children with DRE at a mean age of 9 years at surgery (range = 0-16) and a mean epilepsy duration of 3 years (range = 0-14). Cognitive impairment correlated with FB in children with DRE prior to surgery. At the last assessment, 14.5 months (mean, range = 6-24) after epilepsy surgery, 87.2% of patients were seizure-free, FB values had decreased by 75.0%, and behavioral problems had decreased by 85,7%. Cognitive functions remained stable following epilepsy surgery., Conclusion: In children with DRE, epilepsy surgery reduces FB. Given the considerable impact of families on the development and wellbeing of their children, the impact of epilepsy surgery should be communicated to affected families., Competing Interests: None declared., (Thieme. All rights reserved.)

Background and Objectives: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice., Methods: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes., Results: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years ( p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years ( p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported., Discussion: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation., Classification of Evidence: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy., Trial Registration Information: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Focal cortical dysplasias (FCDs) are malformations of cortical development and one of the most common pathologies causing pharmacoresistant focal epilepsy. Resective neurosurgery yields high success rates, especially if the full extent of the lesion is correctly identified and completely removed. The visual assessment of magnetic resonance imaging does not pinpoint the FCD in 30%-50% of cases, and half of all patients with FCD are not amenable to epilepsy surgery, partly because the FCD could not be sufficiently localized. Computational approaches to FCD detection are an active area of research, benefitting from advancements in computer vision. Automatic FCD detection is a significant challenge and one of the first clinical grounds where the application of artificial intelligence may translate into an advance for patients' health. The emergence of new methods from the combination of health and computer sciences creates novel challenges. Imaging data need to be organized into structured, well-annotated datasets and combined with other clinical information, such as histopathological subtypes or neuroimaging characteristics. Algorithmic output, that is, model prediction, requires a technically correct evaluation with adequate metrics that are understandable and usable for clinicians. Publication of code and data is necessary to make research accessible and reproducible. This critical review introduces the field of automatic FCD detection, explaining underlying medical and technical concepts, highlighting its challenges and current limitations, and providing a perspective for a novel research environment., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Some patients unexpectedly display an unfavorable cognitive course after epilepsy surgery subsequent to any direct cognitive sequelae of the surgical treatment. Therefore, we conducted in-depth neuropathological examinations of resective specimens from corresponding patients to provide insights as to the underlying disease processes., Methods: In this study, cases with significant cognitive deterioration following a previous postoperative assessment were extracted from the neuropsychological database of a longstanding epilepsy surgical program. An extensive reanalysis of available specimens was performed using current, state-of-the-art neuropathological examinations. Patients without cognitive deterioration but matched in regard to basic pathologies served as controls., Results: Among the 355 operated patients who had undergone more than one postoperative neuropsychological examination, 30 (8%) showed significant cognitive decline in the period after surgery. Of the 24 patients with available specimens, 71% displayed further neuropathological changes in addition to the typical spectrum (ie, hippocampal sclerosis, focal cortical dysplasias, vascular lesions, and low-grade tumors), indicating (1) a secondary, putatively epilepsy-independent neurodegenerative disease process; (2) limbic inflammation; or (3) the enigmatic pathology pattern of "hippocampal gliosis" without segmental neurodegeneration. In the controls, the matched individual principal epilepsy-associated pathologies were not found in combination with the secondary pathology patterns of the study group., Interpretation: Our findings indicate that patients who unexpectedly displayed unfavorable cognitive development beyond any direct surgical effects show rare and very particular pathogenetic causes or parallel, presumably independent, neurodegenerative alterations. A multicenter collection of such cases would be appreciated to discern presurgical biomarkers that help with surgical decision-making. ANN NEUROL 2023;93:536-550., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Topiramate (TPM) is effective for treating epilepsy, but executive dysfunction is a common side effect that could significantly affect everyday life. Additionally, previous studies have suggested that patients might be unaware of these changes., Objective: To evaluate a rapid TPM titration scheme for the early detection of adverse cognitive side effects., Methods: In this retrospective study, we assessed changes in objective cognitive performance (EpiTrack ® ) after rapidly titrating TPM (50 mg per day during an inpatient stay) in 49 epilepsy patients and compared those results with an outpatient control group that underwent the recommended standard titration (n = 23 with 25-50 mg per week)., Results: Using Bayesian statistics, analyses revealed decisive evidence of a negative effect on cognitive performance when TPM was introduced (BF 31480000000) independent of the titration speed (BF 0.739). When using a fast titration rate, deficits in executive function increased from a baseline of 53.1 to 73.5% at follow-up, and 55.1% experienced a statistically significant intraindividual decline. When using the standard titration scheme, impairments increased from 52.2 to 65.2%, with an intraindividual deterioration found in 52.2% of the patients., Conclusion: Physicians might be able to detect adverse cognitive side effects sooner in epilepsy patients if TPM is administered using a faster titration rate while applying repeated cognitive assessments within days. This approach might help prevent any unnoticed intolerance and eventual negative consequences for the patient. Therefore, we recommend monitoring early on for adverse changes instead of withholding a potentially effective treatment option because of anticipated side effects., (© 2022. The Author(s).)

Objective: Epilepsy surgery can potentially cure drug-resistant epilepsy, but careful presurgical evaluation is vital to select patients who will profit from such an intervention. Many epilepsy surgery programs offer extensive presurgical evaluation including several days of video-EEG monitoring. Non-lesional epilepsy cases are rare among epilepsy surgery patients. We set up a lesion-orientated paediatric epilepsy surgery program for patients with clearly localized lesions with limited presurgical diagnostics, in particular, with a maximum of 48 hours of non-invasive EEG monitoring that did not necessarily include ictal EEGs., Methods: We retrospectively evaluated the outcome of patients who were operated on within our epilepsy surgery program with respect to seizure freedom., Results: Fifty-two children and adolescents with MRI lesions at a mean age of 8.27 ±4.83 years (range: 0.17-18.87) underwent a resective procedure. The most frequent surgery was a hemispherotomy. Overall seizure freedom was 81.8% after 12 months and 85.6% after a median observation period of 20.45 months. Seizure frequency was reduced >50% in all other patients. Preoperative recording of an ictal EEG on the side of surgery had no effect on postoperative seizure outcome (p= 0.697), nor did recording of epileptiform discharges on the ipsilateral (p= 0.538) and contralateral side (p= 0.147)., Significance: Our findings highlight the high success rate using a lesion-orientated epilepsy surgical approach with reduced presurgical video-EEG monitoring in the paediatric epilepsy population. Our data show that it is possible to reduce the complex pre-surgical work-up for epilepsy in children and adolescents by asking the basic question: "Is there any reason why the lesion should not be resected".

Introduction: Nearly one-third of all infants with epilepsy develop drug-resistant epilepsy. Although epilepsy surgery is a well-established therapy across all age groups, there might be a reluctance to operate on infants in the first six months of life due to unique surgical and anesthesiologic difficulties., Methods: We performed a meta-analysis and systematic review to assess the outcome and complication rate of epilepsy surgery in infants operated on ≤ six months of life., Results: 158 infants underwent epilepsy surgery, most frequently a hemispherotomy rather than focal surgery. Overall seizure freedom after surgery was 65.6% [CI: 0.5785; 0.7261], with higher seizure-free rates following hemispherotomy (71%) than after focal surgery (58%). Complications occurred in 27.7% [0.1794; 0.4004] of patients. Most prevalently, a hydrocephalus developed in 20 out of 136 cases (14.71%). Anti-seizure medication (ASM) was discontinued in 21.5% [0.1431; 0.3100] and reduced in 85.9% [0.515; 0.9721] of 93 patients postoperatively. 84.6% of infants displayed cognitive impairment (development quotient (DQ) <85) preoperatively. After surgery, there was a trend toward a cognitive gain. However, cognitive gain was seen almost exclusively in seizure-free patients., Discussion: Excellent seizure control can be achieved with epilepsy surgery in the first six months of life, a large proportion of patients are able to reduce or discontinue ASM. Data regarding cognitive outcome are promising, but also show that the primary goal should be to achieve seizure freedom. Given the more difficult surgical conditions, epilepsy surgery in the first six months of life should only be performed in specialized epilepsy centers., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Status epilepticus (SE) can occur in persons with or without epilepsy and is associated with high morbidity and mortality., Methods: This survey aimed to record self-reported frequency of SE in persons with epilepsy, its association with clinical characteristics and patient level of information on SE and rescue medication. 251 persons with epilepsy at a tertiary epilepsy center were included in the study., Results: 87 (35%) had a history of SE defined as seizure duration of more than 5 min. These patients were less likely to be seizure-free, and had a higher number of present and past anti-seizure medication. Female sex, cognitive disability, younger age at epilepsy onset, defined epilepsy etiology, and focal epilepsy were associated with a history of SE. On Cox regression analysis, female sex, defined etiology and focal classification remained significant. 67% stated that they had information about prolonged seizures, and 75% knew about rescue medication. 85% found it desirable to receive information about SE at the time of initial diagnosis of epilepsy, but only 16% had been offered such information at the time., Conclusion: SE is frequent among persons with epilepsy and there remain unmet needs regarding patient education., (© 2021. The Author(s).)

Objective: To identify non-EEG-based signals and algorithms for detection of motor and non-motor seizures in people lying in bed during video-EEG (VEEG) monitoring and to test whether these algorithms work in freely moving people during mobile EEG recordings., Methods: Data of three groups of adult people with epilepsy (PwE) were analyzed. Group 1 underwent VEEG with additional devices (accelerometry, ECG, electrodermal activity); group 2 underwent VEEG; and group 3 underwent mobile EEG recordings both including one-lead ECG. All seizure types were analyzed. Feature extraction and machine-learning techniques were applied to develop seizure detection algorithms. Performance was expressed as sensitivity, precision, F 1 score, and false positives per 24 hours., Results: The algorithms were developed in group 1 (35 PwE, 33 seizures) and achieved best results (F 1 score 56%, sensitivity 67%, precision 45%, false positives 0.7/24 hours) when ECG features alone were used, with no improvement by including accelerometry and electrodermal activity. In group 2 (97 PwE, 255 seizures), this ECG-based algorithm largely achieved the same performance (F 1 score 51%, sensitivity 39%, precision 73%, false positives 0.4/24 hours). In group 3 (30 PwE, 51 seizures), the same ECG-based algorithm failed to meet up with the performance in groups 1 and 2 (F 1 score 27%, sensitivity 31%, precision 23%, false positives 1.2/24 hours). ECG-based algorithms were also separately trained on data of groups 2 and 3 and tested on the data of the other groups, yielding maximal F 1 scores between 8% and 26%., Significance: Our results suggest that algorithms based on ECG features alone can provide clinically meaningful performance for automatic detection of all seizure types. Our study also underscores that the circumstances under which such algorithms were developed, and the selection of the training and test data sets need to be considered and limit the application of such systems to unseen patient groups behaving in different conditions., (© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Here, we describe four patients suffering from a rather broad spectrum of epilepsy-related disorders, ranging from developmental and epileptic encephalopathy with intellectual disability (DEE) to genetic generalized epilepsy (GGE), which all harbor novel KCNH1 mutations. In one family, we found a weak association of a novel nonsense mutation with epilepsy, suggesting reduced penetrance, and which shows, in agreement with previous findings, that gain-of-function effects rather than haploinsufficiency are important for the pathogenicity of mutations. De novo missense variants in the pore region of the channel result in severe phenotypes presenting usually with DEE with various malformations. The potential pathogenicity of a novel KCNH1 germline mutation located outside of the critical pore domain observed in a GGE patient with a milder phenotype is supported by the fact that the very same amino acid exchange was detected as a somatic mutation in the resected brain tissue of a patient suffering from a focal cortical dysplasia type IIb. Thus, our case series broadens the phenotypic spectrum of KCNH1 -associated diseases.

Objective: To ascertain factors that are related to the antiepileptic drug load in epilepsy., Methods: In this cross-sectional study, we analyzed a large cohort of conservatively treated patients with epilepsy (n = 1135) and a smaller homogeneous group of presurgical patients with neuropathologically confirmed unilateral hippocampal sclerosis (n = 91). Considered clinical variables comprised (1) presence of an underlying cerebral lesion, (2) onset and (3) duration of epilepsy, (4) seizure frequency, (5) generalized or focal to bilateral tonic-clonic seizures, (6) ictal impairment of awareness, and (7) a history of convulsive status epilepticus. In the presurgical sample, we additionally considered (8) the degree of pathology (hippocampal neuronal cell densities) instead of (1) presence of a cerebral lesion and (9) an overall rating of epilepsy severity (GASE scale). Drug load was quantified as (a) the number of concomitant antiepileptic drugs (AEDs) and (b) the total defined daily dose (DDD)., Results: Analyses disclosed only small correlations between clinical variables and drug load indices. In the conservatively treated cohort, the multiple regression analyses revealed that epilepsy onset, cerebral lesion, history of convulsive status epilepticus, and seizure frequency combined explained only 6%-10% of variance in drug load. Nearly the same variance (5%-8%) could be explained by duration of epilepsy alone. Degree of hippocampal pathology and the epilepsy severity ratings were not related to drug load indices., Significance: Clinical markers of epilepsy severity were only marginally associated with drug load. Findings rather indicate that patients seem to accumulate drugs due to the chronicity of epilepsy. Overall, the drug load remained largely unexplained. The findings nevertheless call for scrutinizing multidrug therapies in patients with long-lasting epilepsies., (© 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Limbic encephalitis (LE) forms a spectrum of autoimmune diseases involving temporal lobe epilepsy and memory impairment. Imaging features of LE are known to depend on the associated antibody and to occur on the brain network level. However, first studies investigating brain networks in LE have either focused on one distinct antibody subgroup or on distinct anatomical regions. In this study, brain graphs of 17 LE patients with autoantibodies against glutamic acid decarboxylase 65 (GAD-LE), four LE patients with autoantibodies against leucine-rich glioma-inactivated 1, five LE patients with autoantibodies against contactin-associated protein-like 2, 26 age- and gender-matched healthy control subjects, and 20 epilepsy control patients with hippocampal sclerosis were constructed based on T1-weighted structural magnetic resonance imaging scans and diffusion tensor imaging. GAD-LE showed significantly altered global network topology in terms of integration and segregation as compared to healthy controls and patients with hippocampal sclerosis (P < .01, analysis of variance with Tukey-Kramer post hoc tests). Linear regression linked global network measures with amygdala volume and verbal memory performance (P < .05). Alterations of local network topology show serotype dependence in hippocampus, amygdala, insula, and various cortical regions. Our findings reveal serotype-dependent patterns of structural connectivity and prove the relevance of in silico network measures on clinical grounds., (© 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: The cognitive outcome of pediatric epilepsy surgery has mainly been examined on the basis of standardized tests. Here, we analyzed the outcome in six cognitive domains from the parents' view., Methods: Included were consecutive surgical pediatric patients whose parents filled-in a comprehensive questionnaire on cognitive problems in children and adolescents (Kognitive Probleme bei Kindern und Jugendlichen (KOPKIJ); Gleissner et al. 2006) at the preoperative baseline (T1) as well as twelve months thereafter (T2). All children also underwent standard neuropsychological assessments at T1 and T2., Results: Parents of 96 patients provided pre- and postoperative KOPKIJ data. Overall, 80% of the children became seizure-free at the follow-up. Group means indicated a strong positive effect of time on KOPKIJ and neuropsychological performance. We found postoperative improvements in five out of six cognitive domains (language, memory, executive functions, attention, school; unchanged: visuospatial abilities). Individually, improvements were twice as likely as declines. However, 33 patients (35%) experienced significant decline in at least one cognitive domain. Later onset of epilepsy resulted in better performance but had no effect on change scores. Seizure-free status, lower antiseizure drug load, and stronger drug reduction after surgery contributed to postoperative cognitive improvements as perceived by the parents; no other effects of clinical factors were obtained (e.g., localization/lateralization). Despite their similar outcome patterns, change scores as derived from parental ratings and neuropsychological assessment were not correlated., Conclusions: Parents acknowledged the overall positive neurocognitive development after pediatric epilepsy surgery as previously shown by standardized tests. Seizure freedom and lower antiseizure drug load contributed to the beneficial cognitive outcome. Even if cognitive improvements outweighed declines, a risk for cognitive decline with impact on everyday functioning does exist., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the accuracy of expert estimations of achieving seizure freedom after epilepsy surgery in the context of presurgical patient counseling., Method: The retrospective study comprised a random sample of 200 patients who underwent any type of resective epilepsy surgery at the University of Bonn Epilepsy Center and the routine 1-year postoperative control visit in the years from 2008-2016. The prediction by a team of epileptologists and the actual seizure outcome were extracted from the pre- and postsurgical medical files, respectively. A deviation of >10% was a priori defined as a relevant discrepancy., Results: Estimated chances of achieving seizure freedom ranged from 30 to 90% (mean: 67%). The actual seizure freedom rate was 66% (Engel Ia/ ILAE 1a). Nine of 12 estimation categories showed a tolerable deviation of ≤10%, none of these with a worse than expected outcome. Two estimation categories (40-50%, and 80%) showed a worse actual seizure outcome with deviations of -40% (n = 3); and -17% (n = 30), respectively. All in all, for 83% of the patients a correct prediction was provided., Conclusions: For the vast majority of surgical patients, the expert prediction of postsurgical seizure freedom at the 1-year follow-up was accurate despite the heterogeneity of patients and surgical procedures., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Seizures and epilepsy may substantially add to the burden of disease in multiple sclerosis (MS), whereas the exact prevalence and prognosis of seizures and epilepsy in patients with MS remains largely unknown., Objectives: We aimed to investigate the epidemiology and prognosis of seizures and epilepsy in MS., Methods: We retrospectively analyzed a cohort of 4078 MS patients from a single tertiary referral clinic., Results: After excluding 37 patients with unconfirmed MS and alternative seizure etiologies, we found seizures attributable to MS in 1.5% and epilepsy in 0.9% of patients. 40.4% of patients with a follow-up of at least twelve months experienced only a single seizure and 59.6% had recurring seizures. 39% of patients with recurrent seizures were considered drug-resistant, with 9.7% experiencing status epilepticus. Seizure recurrence after a first seizure depended significantly on the MS subtype and was seen more often if the first seizure occurred simultaneously with a MS relapse than in the absence of a relapse., Conclusion: Our study shows a lower number of seizures and epilepsy in MS than previously reported. While a single seizure in MS usually has a good prognosis, relapse-associated seizures and established epilepsy in MS may not be as benign as previously assumed.

Epilepsy has been associated with a dysfunction of the blood-brain barrier. While there is ample evidence that a dysfunction of the blood-brain barrier contributes to epileptogenesis, blood-brain barrier dysfunction as a consequence of single epileptic seizures has not been systematically investigated. We hypothesized that blood-brain barrier dysfunction is temporally and anatomically associated with epileptic seizures in patients and used a newly-established quantitative MRI protocol to test our hypothesis. Twenty-three patients with epilepsy undergoing inpatient monitoring as part of their presurgical evaluation were included in this study (10 females, mean age ± standard deviation: 28.78 ± 8.45). For each patient, we acquired quantitative T1 relaxation time maps (qT1) after both ictal and interictal injection of gadolinium-based contrast agent. The postictal enhancement of contrast agent was quantified by subtracting postictal qT1 from interictal qT1 and the resulting ΔqT1 was used as a surrogate imaging marker of peri-ictal blood-brain barrier dysfunction. Additionally, the serum concentrations of MMP9 and S100, both considered biomarkers of blood-brain barrier dysfunction, were assessed in serum samples obtained prior to and after the index seizure. Fifteen patients exhibited secondarily generalized tonic-clonic seizures and eight patients exhibited focal seizures at ictal injection of contrast agent. By comparing ΔqT1 of the generalized tonic-clonic seizures and focal seizures groups, the anatomical association between ictal epileptic activity and postictal enhancement of contrast agent could be probed. The generalized tonic-clonic seizures group showed significantly higher ΔqT1 in the whole brain as compared to the focal seizures group. Specific analysis of scans acquired later than 3 h after the onset of the seizure revealed higher ΔqT1 in the generalized tonic-clonic seizures group as compared to the focal seizures group, which was strictly lateralized to the hemisphere of seizure onset. Both MMP9 and S100 showed a significantly increased postictal concentration. The current study provides evidence for the occurrence of a blood-brain barrier dysfunction, which is temporally and anatomically associated with epileptic seizures. qT1 after ictal contrast agent injection is rendered as valuable imaging marker of seizure-associated blood-brain barrier dysfunction and may be measured hours after the seizure. The observation of the strong anatomical association of peri-ictal blood-brain barrier dysfunction may spark the development of new functional imaging modalities for the post hoc visualization of brain areas affected by the seizure.

Purpose: This retrospective longitudinal study aims to compare the longer-term cognitive and behavioral side effects of adjunctive antiepileptic treatment with perampanel (PER) and lacosamide (LCM), two third generation antiepileptic drugs with suggested favorable cognitive profiles. The two drugs were monitored according to a previously established routine diagnostic protocol (Helmstaedter et al. E&B 2013;26:182-7) which facilitates the retrospective comparison of antiepileptic drug tolerability in a naturalistic outpatient setting., Methods: Records from 94 patients were evaluated who underwent neuropsychological assessment before and under adjunctive treatment with either PER (n = 57) or LCM (n = 37). Cognition was assessed using the EpiTrack screening for executive functions and a VLMT short form for verbal memory. Subjective assessments included a German QOLIE-10 adaptation (quality of life) and an extended Adverse Events Profile (AEP). The median follow-up interval was 36 weeks., Results: Multivariate repeated measures statistics revealed a non-significant trend towards an interaction effect "time - treatment arm" on both executive function and memory. When analyzed separately executive functions and memory scores significantly improved under LCM (t = -2.76 p < 0.01 and t = -2.44 p < 0.05 respectively). Subjectively, PER was associated with improvements in 2/18 physiological domains and in the LCM group 1/9 cognitive domains deteriorated. Seizure freedom was achieved for five patients treated with LCM (14%) and 15 treated with PER (26%, χ 2  = 2.2, n.s.)., Conclusion: In a naturalistic outpatient setting, chronic adjunctive treatment with PER and LCM did not negatively affect cognition and LCM may even improve cognition. Neither drug increased self-reported irritability or aggression. This suggests favorable longer-term tolerability., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: The age at epilepsy onset in patients with inborn or very early acquired brain lesions depends on the epileptogenic potential of the lesion and the patients' individual "susceptibility" to epileptic seizures. To gain insight into these determinants, we analysed the case history of patients with focal cortical dysplasias (FCDs) and neuroglial tumours., Methods: In a systematic, retrospective analysis comprised of 233 patients who underwent surgery (116 with FCDs and 117 with neuroglial tumours), we evaluated the age at epilepsy onset according to histopathologic subgroups, lesion location and family history., Results: Epilepsy onset was significantly earlier in patients with FCD than for those with neuroglial tumours (FCDs: 8.06 ± 0.74 years, gangliogliomas: 15.86 ± 1.24 years, dysembryoplastic neuroepithelial tumours (DNTs): 19.18 ± 2.47 years; p < 0.00001). FCDs were most frequently located in the frontal, whereas neuroglial tumours most frequently in the temporal lobe. For FCD patients, the age at epilepsy onset was not dependent on lesion location, whereas DNTs in a temporal location were associated with a later epilepsy onset than gangliogliomas and extratemporal DNTs. A positive family history for epilepsy or epileptic seizures was found more frequently among patients with FCDs (FCDs: 20.4%, neuroglial tumours: 8.1%; p = 0.013)., Conclusion: We postulate that the age difference at epilepsy onset between patients with FCDs and neuroglial tumours can be attributed - at least partially - to unidentified genetic factors underlying the epileptogenic potential of the brain tissue. Additionally, the large variance in the age at epilepsy onset is possibly also genetically determined., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Neurosurgery is an underutilized treatment that can potentially cure drug-refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drug-refractory focal epilepsies. Ann Neurol 2018;83:676-690., (© 2018 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Purpose of Review: MRI has a crucial position in the diagnostic routine of epilepsy patients. It relevantly contributes to etiological diagnostics and is indispensable in presurgical evaluation. As modern MRI research has been a boon to clinical neuroscience in general, it also holds the promise of enhancing diagnostics of epilepsy patients; i.e. increasing the diagnostic yield while decreasing the number of MRI-negative patients. Its rapid progress, however, has caused uncertainty about which of its latest developments already are of clinical interest and which still are of academic interest. It is the purpose of this review to clarify what, to the authors' mind, good practice of MRI in epilepsy patient care is today and what it might be tomorrow., Recent Findings: Progress of diagnostic MRI in epilepsy patients is driven by development of scanner hardware, scanner sequence and data postprocessing. Ultra high-field MRI and elaborate sequences provide datasets of novel quality which can be fed into postprocessing programs extracting pathognomonic features of structural or functional anatomy. The integration of these features by means of computerized classifiers yield previously unsurpassed diagnostic validity. Enthusiasm about Diffusion Tensor Imaging and functional MRI in the evaluation before epilepsy surgery is quelled., Summary: The application of an epilepsy tailored MRI protocol at 3 Tesla followed by meticulous expert evaluation early after the onset of epilepsy is most crucial. It is hoped that future research will result in MRI workups more standardized than today and widely used postprocessing routines analyzing co-registered three-dimensional volumes from different modalities.

Background: There is evidence that the sudden unexpected death in epilepsy (SUDEP) risk can be reduced by good seizure control, nocturnal supervision, and by early cardiopulmonary resuscitation if cardiorespiratory arrest occurs in the aftermaths of generalized tonic-clonic seizures (GTCS). These measures, however, may critically depend on the knowledge of patients and relatives on SUDEP. Here, we assessed the basic knowledge on SUDEP of people with epilepsy at a tertiary epilepsy center in Germany., Methods: Adult patients with epilepsy and relatives or caregivers of patients with epilepsy aged 16years or older attending our outpatient clinic from January to March 2014 were given the opportunity to participate in a (assisted or unassisted) written survey. In the anonymized questionnaire, people were asked if they had already heard about SUDEP, by what means and if they wish to learn (more) about SUDEP. Furthermore, age, sex, epilepsy duration, highest degree of education, number of GTCS during the last year, and estimation of subjective impairment by their disease were assessed. Statistics were done using mixed linear or logistic regression models., Results: A total of 372 patients' questionnaires were included in this survey. More than 87% of the participants had never heard of SUDEP before. Whereas about 50% of the participants wanted to learn more about SUDEP, about 40% did not. Only the age at survey was significantly associated with both being informed and the desire of learning more about SUDEP: Younger patients had more often heard (p=0.022) and wanted to know more about SUDEP (p=0.020). Thirty-nine patients were considered at high risk for SUDEP. Of these, only 6 patients (15%) knew about SUDEP prior to this survey, but 18 patients (46%) wanted to learn more about this fatal complication., Conclusion: Our data suggest that the level of information on SUDEP among people with epilepsy is poor in Germany regardless of sex, school education, or epilepsy severity. Additionally, a considerable proportion of people with epilepsy seems to prefer not getting detailed information on SUDEP. More efforts are required to understand the potential barriers of the education of patients and relatives on sudden death with the ultimate goal of decreasing the risk of SUDEP., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Epileptic seizures vary greatly in clinical phenomenology and can markedly affect the patient's quality of life. As therapeutic interventions focus on reduction or elimination of seizures, the accurate documentation of seizure occurrence is essential. However, patient self-evaluation compared with objective evaluation by video-electroencephalography (EEG) monitoring or long-term ambulatory EEG revealed that patients document fewer than 50% of their seizures, on average, and that documentation accuracy varies significantly over time. For good clinical practice in epilepsy, novel and feasible seizure detection techniques for ambulatory long-term use are needed. Generalised tonic-clonic seizures can already be detected reliably by methods that rely on motion recording (eg, surface electromyography). However, the automatic detection of other seizure types, such as complex partial seizures, will require multimodal approaches that combine the measurement of ictal autonomic alterations (eg, heart rate) and of characteristic movement patterns (eg, accelerometry). Innovative and feasible tools for automatic seizure detection are likely to advance both monitoring of the outcome of a treatment in a patient and clinical research in epilepsy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Epilepsy is one of the most common primary brain disorders. Nonparaneoplastic autoimmune encephalitis is increasingly recognized as an important cause of adult onset epilepsy. However, only in rare cases an initiating factor of the syndrome can be identified. Autoantibody detection after central nervous herpesvirus infection indicates a postviral etiology in a subgroup of patients. In order to analyze a possible underrecognition of postinfectious autoimmunity we performed a large-scale analysis of herpesvirus DNA in cerebrospinal fluid samples from patients with clinical signs of autoimmune encephalitis., Methods: Real time PCR for HSV 1/2, CMV, EBV, VZV, HHV-6A, HHV-6B, HHV-7 and HHV-8 was performed in cerebrospinal fluid samples from 113 patients with epilepsy and suspected autoimmune encephalitis. Indirect immunofluorescence analysis was used for autoantibody analysis., Results: Antineuronal autoantibodies could be identified in 48 patients with definite autoimmune encephalitis. No autoantibodies were detected in 65 additional patients with probable or possible autoimmune encephalitis. Real-time PCR analysis revealed in three autoantibody-negative patients positive results for HSV, but no evidence for further virus DNA., Conclusion: The findings argue against longstanding herpesvirus infection of the CNS as frequent trigger for autoimmunity. However, appearance of autoantibodies after a short period of active virus infection cannot be excluded., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the recurrence risk of ictal asystole (IA) and its determining factors in people with epilepsy., Methods: We performed a systematic review of published cases with IA in 3 databases and additionally searched our local database for patients with multiple seizures simultaneously recorded with ECG and EEG and at least one IA. IA recurrence risk was estimated by including all seizures without knowledge of the chronological order. Various clinical features were assessed by an individual patient data meta-analysis. A random mixed effect logistic regression model was applied to estimate the average recurrence risk of IA. Plausibility of the calculated IA recurrence risk was checked by analyzing the local dataset with available information in chronological order., Results: Eighty patients with 182 IA in 537 seizures were included. Recurrence risk of IA amounted to 40% (95% confidence interval [CI] 32%-50%). None of the clinical factors (age, sex, type and duration of epilepsy, hemispheric lateralization, duration of IA per patient) appeared to have a significant effect on the short-term recurrence risk of IA. When considering the local dataset only, IA recurrence risk was estimated to 30% (95% CI 14%-53%). Information whether IA coincided with symptoms (i.e., syncope) or not was given in 60 patients: 100 out of 142 IAs were symptomatic., Conclusion: Our data suggest that in case of clinically suspected IA, the recording of 1 or 2 seizures is not sufficient to rule out IA. Furthermore, the high short-term recurrence risk favors aggressive treatment, including pacemaker implantation if seizure freedom cannot be achieved., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Besides other innovative stereotactic procedures (radiofrequency thermocoagulation, focused ultrasound, gamma knife) laser interstitial thermotherapy (LiTT) provides minimally invasive destruction of pathological soft tissues which could be especially relevant for epilepsy surgeries involving adult and pediatric patients. Unlike standard resections, no craniotomy is required; just a tiny borehole trepanation is sufficient. Damage to cortical areas when accessing deep lesions can be minimized or completely avoided, and treating epileptogenic foci near eloquent or even vital brain areas becomes possible. Here, we briefly describe the history and rationale of laser neurosurgery as well as the technical key features of the two currently available systems for magnetic resonance-guided LiTT (Visualase ® , NeuroBlate ® ; CE marks pending for both). We also discuss the published clinical experience with LiTT in the field of epilepsy surgery (approximately 200 cases) with regard to complications, LiTT-induced, long-term brain structural alterations, seizure outcome, preliminary neuropsychological findings and first estimates of treatment costs. Overall, the seizure outcome appears to be slightly worse than for resective surgery. Due to insufficient research methods (e.g. non-established measures, lack of a control condition), the expected neuropsychological superiority over resective surgery has not been unambiguously demonstrated thus far. Also, the cost-benefit ratio requires further critical evaluation. Clinical, multi-center and adequately controlled outcome studies of high quality should also accompany the imminent introduction of LiTT into the field of epilepsy surgery and therewith permit critical scientific evaluation and rational, individual, clinical decisions., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

At least one third of patients with active epilepsy suffer from significant impairment of their emotional well-being. A targeted examination for possible depression (irrespective of any social, financial or personal burdens) can identify patients who may benefit from medical attention and therapeutic support. Reliable screening instruments such as the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) are suitable for the timely identification of patients needing help. Neurologists should be capable of managing mild to moderate comorbid depression but referral to mental health specialists is mandatory in severe and difficult-to-treat depression, or if the patient is acutely suicidal. In terms of the therapeutic approach, it is essential first to optimize seizure control and minimize unwanted antiepileptic drug-related side effects. Psychotherapy for depression in epilepsy (including online self-treatment programs) is underutilized although it has proven effective in ten well-controlled trials. In contrast, the effectiveness of antidepressant drugs for depression in epilepsy is unknown. However, if modern antidepressants are used (e.g. SSRI, SNRI, NaSSA), concerns about an aggravation of seizures and or problematic interactions with antiepileptic drugs seem unwarranted. Epilepsy-related stress ("burden of epilepsy") explains depression in many patients but acute and temporary seizure-related states of depression or suicidality have also been reported. Limbic encephalitits may cause isolated mood alteration without any recognizable psychoetiological background indicating a possible role of neuroinflammation. This review will argue that, overall, a bio-psycho-social model best captures the currently available evidence relating to the etiology and treatment of depression as a comorbidity of epilepsy., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To better understand the mechanisms that lead to the sudden and unexpected occurrence of seizures, with the neuronal correlate being abnormally synchronous discharges that disrupt neuronal function., Methods: To address this problem, we recorded single neuron activity in epilepsy patients during the transition to seizures to uncover specific changes of neuronal firing patterns. We focused particularly on neurons repeatedly firing discrete groups of high-frequency action potentials (so called bursters) that have been associated with ictogenesis. We analyzed a total of 459 single neurons and used the mean autocorrelation time as a quantitative measure of burstiness. To unravel the intricate roles of excitation and inhibition, we also examined differential contributions from putative principal cells and interneurons., Results: During interictal recordings, burstiness was significantly higher in the seizure onset hemisphere, an effect found only for principal cells, but not for interneurons, and which disappeared before seizures., Conclusion: These findings deviate from conventional views of ictogenesis that propose slowly-increasing aggregates of bursting neurons which give rise to seizures once they reach a critical mass., Significance: Instead our results are in line with recent hypotheses that bursting may represent a protective mechanism by preventing direct transmission of postsynaptic high-frequency oscillations., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: The eradication of epileptogenic lesions (e.g. focal cortical dysplasia) can be used for treatment of drug-resistant focal epilepsy, but in highly eloquent cortex areas it can also lead to a permanent neurological deficit. In such cases the neuromodulation effect of low-dose high-precision irradiation of circumscribed lesions may represent an alternative therapy., Method: A total of 10 patients with eloquent localized lesions causing pharmacoresistant focal epilepsy were prospectively identified. After informed consent, six patients agreed and were treated with risk adapted low-dose radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (hfSRT). Comprehensive data concerning treatment modalities and outcome after short-term follow up (mean=16.3 months) were prospectively collected and evaluated., Results: From the six patients, two patients were treated with hfSRT (marginal dose 36 Gy) and four with SRS (marginal dose 13 Gy). Clinical target volume (CTV) ranged from 0.70 ccm to 4.32 ccm. The short-term follow-up ranged from 6 to 27 months. There were no side effects or neurological deficits after treatment. At last available follow-up two patients were seizure-free, one of them being off antiepileptic drugs. The seizure frequency improved in one and remained unchanged in three patients., Conclusion: Treatment of eloquent localized epileptogenic lesions by SRS and hfSRT showed no adverse events and an acceptable seizure outcome in this small prospective patient series. The relatively short-term follow-up comprises one of the study's drawbacks and therefore a longer follow-up should be awaited in order to evaluate the neuromodulation effect of the treatment. These preliminary results may however justify the initiation of a larger prospective trial investigating whether focused low-dose stereotactic irradiation could be an option for lesions in eloquent brain areas., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

In the recent years, several neurological syndromes related to defects of the glucose transporter type 1 (Glut1) have been descried. They include the glucose transporter deficiency syndrome (Glut1-DS) as the most severe form, the paroxysmal exertion-induced dyskinesia (PED), a form of spastic paraparesis (CSE) as well as the childhood (CAE) and the early-onset absence epilepsy (EOAE). Glut1, encoded by the gene SLC2A1, is the most relevant glucose transporter in the brain. All Glut1 syndromes respond well to a ketogenic diet (KD) and most of the patients show a rapid seizure control. Ketogenic Diet developed to an established treatment for other forms of pharmaco-resistant epilepsies. Since we were interested in the question if those patients might have an underlying Glut1 defect, we sequenced SLC2A1 in a cohort of 28 patients with different forms of pharmaco-resistant epilepsies responding well to a KD. Unfortunately, we could not detect any mutations in SLC2A1. The exact action mechanisms of KD in pharmaco-resistant epilepsy are not well understood, but bypassing the Glut1 transporter seems not to play an important role., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Neural representations of specific stimuli rely on activity patterns in distributed neural assemblies [1-4]. According to one influential view, these assemblies are characterized by synchronized gamma-band activity (GBA) [5-11] that reflects stimulus-specific representations [12-14]. However, recent studies have shown that GBA is closely correlated with the overall amount of cellular activity and may be detrimental for precise representations of specific stimuli [15, 16]. Until now, the role of GBA for the formation of dynamically changing representations has been unknown. Here, we applied representational similarity analysis (RSA) [17] to intracranial electroencephalogram (iEEG) data from ten presurgical epilepsy patients to identify stimulus-specific neural representations. Patients first learned and then retrieved their paths through virtual houses. Dynamic representations were identified by the rapidly changing distributions of frequency-specific global (spatial) activity patterns across the brain. We found that GBA patterns during successful (but not unsuccessful) retrieval of one sequence were more similar to activity during encoding of that same sequence compared to other sequences. The contribution of individual electrodes to these global representations was correlated with local similarity in individual electrodes (i.e., with RSA across time). Moreover, time-resolved RSA values were negatively correlated with the magnitude of iEEG gamma power: RSA values were higher at time points when gamma power was reduced. Both global and local representations relied on a small proportion of electrodes. These results show that behaviorally relevant neural representations of specific dynamically changing stimuli can be tracked by iEEG recordings and that they are associated with reductions of gamma power., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: A novel vagus nerve stimulation (VNS) device was recently approved in Europe which rapidly detects increases in heart rates (HR) and applies an additional stimulus if HR-increases exceed a given threshold. The effects of HR-triggered VNS-pulses on seizures were not reported yet under controlled conditions. Here, we quantified the effects of HR-triggered VNS-pulses on the seizure duration in one patient., Methods: The novel VNS device was implanted in a 29-year old man with refractory epilepsy. After implantation, the patient underwent video-EEG telemetry for 68h with no changes in anticonvulsant drugs. On the first day the patient only received sham-stimulation. During the following 46h HR-related VNS-stimulation was set to 2mA. Seizure duration was determined based on clinical signs., Results: Twelve stereotypical seizures were recorded (six during sham- and six during the active stimulation). The VNS device recognised a total of 139 events as a seizure and correctly identified 11 seizures. The HR-triggered VNS-stimulation significantly reduced the total seizure duration from 33.2±4.8s to 26.5±5s and the remaining seizure duration after the onset of the extra-stimulation from 27.8±4.3s to 16.2±3.2s. With the given configuration in this patient, sensitivity and specificity of HR-based seizure-detection amounted to 92% and 13.5%, respectively., Conclusions: This case illustrates that VNS-stimulation in response to seizure-related HR-increases is able to significantly reduce seizure duration. Despite the limitations of our case, its promising results should prompt larger studies to confirm the clinical benefit of this novel device., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study used an electronic practice management software in daily routine to gather long-term disease and cost-of-illness (COI) data in patients with epilepsy in Germany., Methods: Data on socio-economic status, course of epilepsy as well as direct and indirect costs were recorded using practice software-based questionnaires., Results: In 2011 we enrolled 359 patients (170 male (47.4%); mean age 50.5±20.7 years) in six neurological practices. The majority of patients had been in long-term seizure remission for more than one year (n=200, 55.7%) and in more than two-thirds the anti-epileptic drug (AED) monotherapy (n=248, 69.1%) was used. Levetiracetam (31%), lamotrigine (26%) and valproate (24%) were the drugs prescribed most frequently. Total annual direct costs amounted to €1698 per patient with anticonvulsants (59.9% of total direct costs) and hospitalization (30.0%) as the main cost factors. Of the patients enrolled 252 (70.2%) were of working age and indirect annual costs due to absenteeism amounted to €745 per patient. Potential cost-driving factors were seizure frequency and a recent diagnosis of epilepsy associated with higher costs. Anticonvulsant treatment in patients aged 65 years and older was associated with lower drug costs due to prescription of older AEDs., Conclusion: We were able to demonstrate that electronic practice management software can easily be used to perform long-term health economic evaluations with a bottom-up approach. The combination of both physician- and patient-based electronic databases will facilitate performing less expensive studies, but at the same time simplify large, prospective and multicentre clinical trials., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Object: The purpose of this study was to retrospectively assess the objective and subjective neuropsychological outcome after epilepsy surgery in patients with bilateral Ammon's horn sclerosis (AHS)., Methods: Memory and executive functions were evaluated at baseline and at follow-up in 11 surgically treated patients and compared with 8 pharmacologically treated patients with temporal lobe epilepsy and bilateral AHS. The median follow-up duration was 16 months in the surgically treated patients and 80.5 months in the pharmacologically treated group. Subjective outcome was evaluated by questionnaires and included mood, quality of life, subjective memory, and activities of daily living., Results: At the follow-up assessment, 82% of the surgically treated patients as opposed to 0% of the nonsurgery patients were seizure free. In the surgical group, nonverbal memory performance did not change significantly in any patient after surgery, but there was a floor effect in 55% of the surgical patients. Regarding verbal memory, 9% of the surgical patients improved while 73% declined, despite severe impairments already evident at baseline. In the nonsurgery control group, 13% of the patients declined in nonverbal memory (floor effect in 63%) and 25% declined in verbal memory (floor effect in 25%) at follow-up. None of the controls improved at follow-up. Executive functions remained unchanged on an impaired level in both groups. At follow-up, the patient groups did not differ significantly with respect to mood, quality of life, subjective memory, or activities of daily living. However, in most aspects, surgically treated patients reported a slightly better subjective outcome than pharmacologically treated patients and a significantly improved quality of life., Conclusions: These results suggest that beyond benefits concerning seizure control, surgically treated patients with bilateral AHS, despite already poor baseline performance, are still at risk for severe postoperative decline in memory. In the light of predominantly minor benefits on a subjective level, the findings put the overall outcome of epilepsy surgery in bilateral AHS patients into perspective.

Introduction: Spike-based magnetoencephalography (MEG) source localization is an established method in the presurgical evaluation of epilepsy patients. Focal cortical dysplasias (FCDs) are associated with focal epileptic discharges of variable morphologies in the beta frequency band in addition to single epileptic spikes. Therefore, we investigated the potential diagnostic value of MEG-based localization of spike-independent beta band (12-30Hz) activity generated by epileptogenic lesions., Methods: Five patients with FCD IIB underwent MEG. In one patient, invasive EEG (iEEG) was recorded simultaneously with MEG. In two patients, iEEG succeeded MEG, and two patients had MEG only. MEG and iEEG were evaluated for epileptic spikes. Two minutes of iEEG data and MEG epochs with no spikes as well as MEG epochs with epileptic spikes were analyzed in the frequency domain. MEG oscillatory beta band activity was localized using Dynamic Imaging of Coherent Sources., Results: Intralesional beta band activity was coherent between simultaneous MEG and iEEG recordings. Continuous 14Hz beta band power correlated with the rate of interictal epileptic discharges detected in iEEG. In cases where visual MEG evaluation revealed epileptic spikes, the sources of beta band activity localized within <2cm of the epileptogenic lesion as shown on magnetic resonance imaging. This result held even when visually marked epileptic spikes were deselected. When epileptic spikes were detectable in iEEG but not MEG, MEG beta band activity source localization failed., Discussion: Source localization of beta band activity has the potential to contribute to the identification of epileptic foci in addition to source localization of visually marked epileptic spikes. Thus, this technique may assist in the localization of epileptic foci in patients with suspected FCD., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age-dependent epilepsy syndrome but are now past the applicable age or who have remained seizure-free for the last 10 years and off antiseizure medicines for at least the last 5 years. "Resolved" is not necessarily identical to the conventional view of "remission or "cure." Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Purpose: Magnetic resonance imaging (MRI) is a key technology in the presurgical evaluation of patients with epilepsy. Already at early outpatient stages it can contribute to the identification of patients who are, in the case of pharmacoresistance, good candidates for epilepsy surgery. Yet, "standard head" MRI examinations often fail to displaying therapeutically relevant epileptogenic lesions. The purpose of this study is to identify an epilepsy-specific MRI protocol, which is likewise sensitive for even small epileptogenic lesions and economical enough to be applied outside specialized epilepsy centers., Methods: Based on a large European presurgical epilepsy program comprising 2,740 patients we identified the spectrum of common epileptogenic lesions and determine the set of MRI sequences that are required for their reliable detection. Relying on a series of small, therapeutically particularly relevant lesions we determined the required slices thickness, slice angulations, and orientations for an epilepsy-specific MRI protocol., Key Findings: Indispensable for early outpatient epilepsy specific MRI are fluid attenuated inversion recovery (FLAIR), T(2) -weighted, T(1) -weighted, and hemosiderin/calcification-sensitive sequences. Slice thickness for T(2) and FLAIR must not exceed 3 mm. The T(1) image should be acquired in three-dimensional technique at 1 mm isotropic voxels size. For T(2) and FLAIR, at least two slice orientations each must be demanded in hippocampal angulation. We suggest no adaption to a clinical focus hypothesis. The resulting "essential 6" sequence protocol allows the detection of virtually all common epileptogenic lesion entities., Significance: The creation of a broadly accepted and abundantly applied MRI protocol for epilepsy outpatients can contribute to improved and earlier identification of potential candidates for epilepsy surgery. Our systematic analysis of MRI requirements for the detection of epileptogenic lesions can serve as basis for protocol negotiations between epileptologists, radiologists, and health care funders., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Objective: To determine the consistency and facilitating cofactors of postictal generalized EEG suppression (PGES) of >20 seconds after convulsive seizures (CS), a suggested predictor of sudden unexpected death in epilepsy risk., Methods: We retrospectively reviewed video-EEG data of people with ≥2 recorded CS. Presence and duration of PGES were assessed by 2 independent observers blinded to patient status. Intraindividual consistency of PGES >20 seconds was determined and correlations with clinical characteristics were analyzed after correction for individual effects and the varying number of seizures., Results: One hundred fifty-four seizures in 59 people were analyzed. PGES >20 seconds was found in 37 individuals (63%) and 57 (37%) of CS. The proportion of persons in whom PGES occurred consistently (presence or absence of PGES >20 seconds in all CS) was lower in those with more CS. PGES of >20 seconds was more frequent in seizures arising from sleep (odds ratio 3.29, 95% confidence interval 1.21-8.96) and when antiepileptic medication was tapered (odds ratio 4.80, 95% confidence interval 1.27-18.14)., Conclusion: Apparent PGES consistency was less frequent in people with more CS recorded, suggesting that PGES is an inconsistent finding in any one individual. Thus, we believe that PGES >20 seconds is not a reliable predictor of sudden unexpected death in epilepsy. Sleep and antiepileptic drug reduction appear to facilitate the occurrence of PGES.

Purpose: Precise outcome data about the surgical therapy of cerebral cavernous malformation (CCM)-associated epilepsy is scarce regarding different epilepsy types, surgical approach, and outcome. Long-term outcome in patients with CCM-associated epilepsy is analyzed in a large single-center series., Methods: Seizure outcome data >24 months was available in 118 patients. The influence of different parameters of preoperative workup and surgical technique was analyzed with regard to seizure outcome., Key Findings: The study cohort comprised 76 patients with drug-resistant epilepsy (DRE), 20 patients with chronic epilepsy that did not meet the definition of DRE, as well as 22 patients with sporadic seizures. Temporal localization of CCMs predisposed to develop DRE. Detailed epileptologic workup was performed in 85 patients; invasive monitoring was done in 23 (37%) of 76 DRE cases. In 84% of DRE cases more extensive resections were performed. Mean follow-up varied between 107 and 137 months for the three groups. Seizure freedom in DRE was 88%, in chronic epilepsy 80%, and in sporadic seizures was 91%. Longer symptom duration was associated with worse seizure outcome. Outcome of patients who underwent invasive monitoring was not worse. The outcome in CCM-associated DRE can be good if more extensive resections are used and if noninvasive and/or invasive presurgical epileptologic workup is used whenever indicated. DRE was considerably more frequent in the temporal lobe, suggesting that temporal localization predisposes development of DRE. Seizure freedom rates were stable over a long period., Significance: Surgical therapy of CCM-associated seizures and epilepsy can be successful if different surgical techniques according to presurgical evaluation are realized. To prevent clinical worsening into DRE, surgical intervention in CCM-associated epilepsy may be considered early., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Purpose: Resection of the seizure focus leads to sustained seizure-freedom in intractable focal epilepsy in up to 80% of selected populations. However, surgery fails to help in a considerable proportion of patients. Reevaluation and reoperation may be considered in a selected group of patients with an unfavorable postsurgical outcome. Here, we reviewed 15 case series on reoperation after failed resective epilepsy surgery in adults in order to identify factors associated with a good chance of benefitting from a second operation., Methods: Literature review of case series describing the outcome of epilepsy surgical re-operations., Results: Overall, 3.8-14% of all patients who had resective epilepsy surgery underwent a second operation. A total of 402 reoperated patients were included. Reoperation was performed in average between 2 and 5.5 years after the first surgery. 36.6% of all patients were seizure-free with a minimal follow-up of 6 months to 4 years after the second operation. Postsurgical complications were observed in 13.5% and mainly consisted of visual field defects and, less frequently, of hemiparesis. The causes of failed first epilepsy surgery were heterogeneous and included incorrect localization or incomplete resection of the seizure focus, presence of additional seizure foci or progression of the underlying disease. Some features appear to indicate successful reoperation, such as concordance of postsurgical imaging and electroclinical findings as well as absence of brain trauma and cerebral infection prior to epilepsy onset., Conclusion: Reoperation after thorough assessment of all available clinical, imaging and EEG findings can be an efficacious and reasonably safe treatment option which can achieve sustained seizure control after failed resective epilepsy surgery., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

In refractory temporal lobe epilepsy with unilateral ammon's horn sclerosis (uAHS) resective epilepsy surgery is an established treatment option whereas little evidence exists about the consequences of unilateral hippocampal resection in patients with bilateral ammon's horn sclerosis (bAHS). The aim of this study was to evaluate the post-surgical outcome of patients with bAHS after selective amygdalo-hippocampectomy (SAH) in comparison to uAHS patients. For this purpose, all bAHS and uAHS patients, identified at our center between 2003 and 2009 were analyzed retrospectively. Thirty-one bAHS patients and 291 uAHS patients were identified. Only 55% of the bAHS, but 80% of the uAHS patients were referred for formal pre-surgical diagnostics (p=0.001). Eleven bAHS and 127 uAHS patients underwent SAH. There was no difference in seizure-free outcome (Engel IA) at 12 months (bAHS 82% vs. 69%, p=0.40) and 24 months follow up (bAHS 57% vs. 60%, p=0.80). None of the bAHS patients became globally amnesic post-surgically. The favorable outcome in these highly selected bAHS patients suggests that bAHS patients may have a fair chance of becoming seizure-free after SAH. However, due to the large number of bAHS patients not undergoing formal presurgical evaluation, the results cannot be extrapolated to bAHS patients in general., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The aim of this study was to investigate the change of health related quality of life (HRQoL), anxiety and depression in adult patients in whom an adjunctive treatment with levetiracetam (LEV) was converted to a LEV monotherapy. A prospective, open, investigator initiated multicenter study enrolled 140 patients in whom LEV was added to the existing antiepileptic medication. A total of 65 patients who benefited from the 16-week add-on treatment with LEV (≥50% seizure reduction) were converted to LEV monotherapy (16-week follow-up). In LEV responders, HRQoL, anxiety and depression improved after add-on of LEV. The subsequent conversion to LEV monotherapy did not lead to a significant change in HRQoL, anxiety and depression. However, comparing baseline with LEV monotherapy, the improvements remained significant for most dimensions of HRQoL and for anxiety and depression. Patients' ratings of efficacy of LEV were related with their HRQoL after the conversion to monotherapy. Add-on therapy of LEV improved HRQoL, anxiety and depression in LEV responders. Conversion to a LEV monotherapy did not inevitably improve HRQoL in LEV responders, but the positive effect was maintained in the majority of the patients. The effects were highly related to seizure reduction., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose: In the treatment of epilepsy, the recommendation to add vagus nerve stimulation (VNS) to the best available drug therapy (BDT) mostly relies on uncontrolled studies which provide limited information about VNS-specific benefits. We report findings from a retrospective matched pairs case-control study comparing the long-term (>2 years) outcomes of BDT with or without VNS., Methods: Included were adult patients with therapy-refractory epilepsy who had undergone the pre-surgical work-up (baseline) and subsequently received BDT with VNS (BDT+VNS) or BDT alone (BDT group). Patients were matched in pairs for age, gender and follow-up. Health outcomes were assessed at least 24 months after the baseline by comprehensive postal surveys and included established psychometric scales., Results: We obtained data from 20 matched pairs of case and control patients. In both groups, seizures, health-related quality of life and mood improved over time. More BDT patients experienced a complete cessation of "major" seizures (12/20 vs. 4/20) whereas, in non-seizure free patients, BDT+VNS patients showed better seizure frequency reduction (>50% reduction: 12/19 vs. 7/16). BDT+VNS patients experienced equal drug related and additional VNS related side effects. No clinically relevant effect of VNS treatment was found on any psychological/psychosocial outcome measure., Conclusion: This retrospective study provided no positive evidence for therapeutic benefits of adding VNS to BDT. The follow-up health status of BDT+VNS patients was slightly worse than in patients receiving BDT alone. Despite minor group differences at baseline the two patient groups who had failed presurgical evaluation were comparable. Therapeutic improvements during long-term BDT alone are often underestimated resulting in a misattribution of positive changes to VNS in uncontrolled studies and reviews. Currently, there is no incontrovertible evidence for the clinical effectiveness of adding VNS to BDT., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)