Samuel Wiebe

Summary 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 .

The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.

To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.

Randomized trials of surgery for epilepsy have not been conducted, because of the difficulties involved in designing and implementing feasible studies. The lack of data supporting the therapeutic usefulness of surgery precludes making strong recommendations for patients with epilepsy. We conducted a randomized, controlled trial to assess the efficacy and safety of surgery for temporal-lobe epilepsy.

<h3>Objective:</h3> To review population-based studies of the prevalence and incidence of epilepsy worldwide and use meta-analytic techniques to explore factors that may explain heterogeneity between estimates. <h3>Methods:</h3> The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed. We searched MEDLINE and EMBASE for articles published on the prevalence or incidence of epilepsy since 1985. Abstract, full-text review, and data abstraction were conducted in duplicate. Meta-analyses and meta-regressions were used to explore the association between prevalence or incidence, age group, sex, country level income, and study quality. <h3>Results:</h3> A total of 222 studies were included (197 on prevalence, 48 on incidence). The point prevalence of active epilepsy was 6.38 per 1,000 persons (95% confidence interval [95% CI] 5.57–7.30), while the lifetime prevalence was 7.60 per 1,000 persons (95% CI 6.17–9.38). The annual cumulative incidence of epilepsy was 67.77 per 100,000 persons (95% CI 56.69–81.03) while the incidence rate was 61.44 per 100,000 person-years (95% CI 50.75–74.38). The prevalence of epilepsy did not differ by age group, sex, or study quality. The active annual period prevalence, lifetime prevalence, and incidence rate of epilepsy were higher in low to middle income countries. Epilepsies of unknown etiology and those with generalized seizures had the highest prevalence. <h3>Conclusions:</h3> This study provides a comprehensive synthesis of the prevalence and incidence of epilepsy from published international studies and offers insight into factors that contribute to heterogeneity between estimates. Significant gaps (e.g., lack of incidence studies, stratification by age groups) were identified. Standardized reporting of future epidemiologic studies of epilepsy is needed.

To systematically review outcomes in comatose survivors after cardiac arrest and cardiopulmonary resuscitation (CPR).The authors analyzed studies (1966 to 2006) that explored predictors of death or unconsciousness after 1 month or unconsciousness or severe disability after 6 months.The authors identified four class I studies, three class II studies, and five class III studies on clinical findings and circumstances. The indicators of poor outcome after CPR are absent pupillary light response or corneal reflexes, and extensor or no motor response to pain after 3 days of observation (level A), and myoclonus status epilepticus (level B). Prognosis cannot be based on circumstances of CPR (level B) or elevated body temperature (level C). The authors identified one class I, one class II, and nine class III studies on electrophysiology. Bilateral absent cortical responses on somatosensory evoked potential studies recorded 3 days after CPR predicted poor outcome (level B). Burst suppression or generalized epileptiform discharges on EEG predicted poor outcomes but with insufficient prognostic accuracy (level C). The authors identified one class I, 11 class III, and three class IV studies on biochemical markers. Serum neuron-specific enolase higher than 33 microg/L predicted poor outcome (level B). Ten class IV studies on brain monitoring and neuroimaging did not provide data to support or refute usefulness in prognostication (level U).Pupillary light response, corneal reflexes, motor responses to pain, myoclonus status epilepticus, serum neuron-specific enolase, and somatosensory evoked potential studies can reliably assist in accurately predicting poor outcome in comatose patients after cardiopulmonary resuscitation for cardiac arrest.

Assessment of long-term outcomes is essential in brain surgery for epilepsy, which is an irreversible intervention for a chronic condition. Excellent short-term results of resective epilepsy surgery have been established, but less is known about long-term outcomes. We performed a systematic review and meta-analysis of the evidence on this topic. To provide evidence-based estimates of long-term results of various types of epilepsy surgery and to identify sources of variation in results of published studies, we searched Medline, Index Medicus, the Cochrane database, bibliographies of reviews, original articles and book chapters to identify articles published since 1991 that contained ≥20 patients of any age, undergoing resective or non-resective epilepsy surgery, and followed for a mean/median of ≥5 years. Two reviewers independently assessed study eligibility and extracted data, resolving disagreements through discussion. Seventy-six articles fulfilled our eligibility criteria, of which 71 reported on resective surgery (93%) and five (7%) on non-resective surgery. There were no randomized trials and only six studies had a control group. Some articles contributed more than one study, yielding 83 studies of which 78 dealt with resective surgery and five with non-resective surgery. Forty studies (51%) of resective surgery referred to temporal lobe surgery, 25 (32%) to grouped temporal and extratemporal surgery, seven (9%) to frontal surgery, two (3%) to grouped extratemporal surgery, two (3%) to hemispherectomy, and one (1%) each to parietal and occipital surgery. In the non-resective category, three studies reported outcomes after callosotomy and two after multiple subpial transections. The median proportion of long-term seizure-free patients was 66% with temporal lobe resections, 46% with occipital and parietal resections, and 27% with frontal lobe resections. In the long term, only 35% of patients with callosotomy were free of most disabling seizures, and 16% with multiple subpial transections remained free of all seizures. The year of operation, duration of follow-up and outcome classification system were most strongly associated with outcomes. Almost all long-term outcome studies describe patient cohorts without controls. Although there is substantial variation in outcome definition and methodology among the studies, consistent patterns of results emerge for various surgical interventions after adjusting for sources of heterogeneity. The long-term (≥5 years) seizure free rate following temporal lobe resective surgery was similar to that reported in short-term controlled studies. On the other hand, long-term seizure freedom was consistently lower after extratemporal surgery and palliative procedures.

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

Summary Hippocampal sclerosis ( HS ) is the most frequent histopathology encountered in patients with drug‐resistant temporal lobe epilepsy ( TLE ). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. A task force reviewed previous classification schemes and proposes a system based on semiquantitative hippocampal cell loss patterns that can be applied in any histopathology laboratory. Interobserver and intraobserver agreement studies reached consensus to classify three types in anatomically well‐preserved hippocampal specimens: HS International League Against Epilepsy ( ILAE ) type 1 refers always to severe neuronal cell loss and gliosis predominantly in CA 1 and CA 4 regions, compared to CA 1 predominant neuronal cell loss and gliosis ( HS ILAE type 2), or CA 4 predominant neuronal cell loss and gliosis ( HS ILAE type 3). Surgical hippocampus specimens obtained from patients with TLE may also show normal content of neurons with reactive gliosis only (no‐ HS ). HS ILAE type 1 is more often associated with a history of initial precipitating injuries before age 5 years, with early seizure onset, and favorable postsurgical seizure control. CA 1 predominant HS ILAE type 2 and CA 4 predominant HS ILAE type 3 have been studied less systematically so far, but some reports point to less favorable outcome, and to differences regarding epilepsy history, including age of seizure onset. The proposed international consensus classification will aid in the characterization of specific clinicopathologic syndromes, and explore variability in imaging and electrophysiology findings, and in postsurgical seizure control.

Objectives/Methods: To examine evidence for effectiveness of anteromesial temporal lobe and localized neocortical resections for disabling complex partial seizures by systematic review and analysis of the literature since 1990.Results: One intention-to-treat Class I randomized, controlled trial of surgery for mesial temporal lobe epilepsy found that 58% of patients randomized to be evaluated for surgical therapy (64% of those who received surgery) were free of disabling seizures and 10 to 15% were unimproved at the end of 1 year, compared with 8% free of disabling seizures in the group randomized to continued medical therapy.There was a significant improvement in quantitative quality-of-life scores and a trend toward better social function at the end of 1 year for patients in the surgical group, no surgical mortality, and infrequent morbidity.Twenty-four Class IV series of temporal lobe resections yielded essentially identical results.There are similar Class IV results for localized neocortical resections; no Class I or II studies are available.Conclusions: A single Class I study and 24 Class IV studies indicate that the benefits of anteromesial temporal lobe resection for disabling complex partial seizures is greater than continued treatment with antiepileptic drugs, and the risks are at least comparable.For patients who are compromised by such seizures, referral to an epilepsy surgery center should be strongly considered.Further studies are needed to determine if neocortical seizures benefit from surgery, and whether early surgical intervention should be the treatment of choice for certain surgically remediable epileptic syndromes.

Summary Purpose: The estimated prevalence of mental health disorders in those with epilepsy in the general population varies owing to differences in study methods and heterogeneity of epilepsy syndromes. We assessed the population‐based prevalence of various psychiatric conditions associated with epilepsy using a large Canadian national population health survey. Methods: The Canadian Community Health Survey (CCHS 1.2) was used to explore numerous aspects of mental health in persons with epilepsy in the community compared with those without epilepsy. The CCHS includes administration of the World Mental Health Composite International Diagnostic Interview to a sample of 36,984 subjects. Age‐specific prevalence of mental health conditions in epilepsy was assessed using logistic regression. Results: The prevalence of epilepsy was 0.6%. Individuals with epilepsy were more likely than individuals without epilepsy to report lifetime anxiety disorders or suicidal thoughts with odds ratio of 2.4 (95% CI = 1.5–3.8) and 2.2 (1.4–3.3), respectively. In the crude analysis, the odds of lifetime major depression or panic disorder/agoraphobia were not greater in those with epilepsy than those without epilepsy, but the association with lifetime major depression became significant after adjustment for covariates. Conclusions: In the community, epilepsy is associated with an increased prevalence of mental health disorders compared with the general population. Epilepsy is also associated with a higher prevalence of suicidal ideation. Understanding the psychiatric correlates of epilepsy is important to adequately manage this patient population.

The inflammatory bowel diseases (IBDs) are chronic diseases that often require surgery. However, the risk of requirement of surgery over time has not been well characterized. We performed a systematic review and meta-analysis to establish the cumulative risk of surgery among patients with IBD and evaluated how this risk has changed over time.We searched Medline, EMBASE, PubMed, and conference proceedings (2009-2012) on May 8, 2013, for terms related to IBD and intestinal surgery. Two reviewers screened 8338 unique citations to identify 486 for full-text review. The analysis included population-based studies published as articles (n = 26) and abstracts (n = 4) that reported risks of surgery at 1, 5, or 10 years after a diagnosis of Crohn's disease and/or ulcerative colitis. The trend in risk of surgery over time was analyzed by meta-regression using mixed-effect models.Based on all population-based studies, the risk of surgery 1, 5, and 10 years after diagnosis of Crohn's disease was 16.3% (95% confidence interval [CI], 11.4%-23.2%), 33.3% (95% CI, 26.3%-42.1%), and 46.6% (95% CI, 37.7%-57.7%), respectively. The risk of surgery 1, 5, and 10 years after diagnosis of ulcerative colitis was 4.9% (95% CI, 3.8%-6.3%), 11.6% (95% CI, 9.3%-14.4%), and 15.6% (95% CI, 12.5%-19.6%), respectively. The risk of surgery 1, 5, and 10 years after diagnosis of Crohn's disease and 1 and 10 years after diagnosis of ulcerative colitis has decreased significantly over the past 6 decades (P < .05).Based on systematic review and meta-analysis of population-based studies, the risk of intestinal surgery among patients with IBD has decreased over the past 6 decades.

To provide evidence-based quantitative summary estimates of seizure outcomes in patients with non-lesional and lesional epilepsy treated with surgery, and to assess the consistency of results among published studies.An exhaustive literature search identified articles published since 1995, describing outcomes according to lesional status in patients of any age who underwent resective epilepsy surgery. Two reviewers independently assessed study eligibility and extracted the data. Disagreements were resolved through discussion. Random effects meta-analyses were used after assessing the dataset for heterogeneity.Forty articles fulfilled eligibility criteria and described outcomes in 697 patients with non-lesional epilepsy and 2860 patients with lesional epilepsy. Overall, the odds of being seizure-free after surgery were 2.5 times higher in patients with lesions on MRI or histopathology (OR 2.5, 95%CI 2.1, 3.0, p<0.001). In patients with temporal lobe epilepsy surgery the odds were 2.7 times higher in those with lesions (OR 2.7, 95%CI 2.1, 3.5, p<0.001). In patients with extratemporal epilepsy surgery the odds were 2.9 higher in those with lesions (OR 2.9, 95%CI 1.6, 5.1, p<0.001). Outcomes were similar in children, adults, and studies that used MRI or histopathology to identify lesions.Overall, the odds of seizure freedom after surgery are two to three times higher in the presence of a lesion on histopathology or MRI. The results are clinically and statistically significant, consistent across various subgroups, and quite homogeneous across studies.

We assessed the relative responsiveness of generic and specific quality of life instruments in 43 randomized controlled trials that compared head-to-head 31 generic and 84 specific instruments. Using weighted effect size as the metric of responsiveness, we assessed the impact of instrument type, disease category, and magnitude of underlying therapeutic effect on responsiveness, and assessed the responsiveness of specific instruments relative to the corresponding domains of generic measures. In studies with a nonzero therapeutic effect, specific instruments (mean = 0.57) were significantly more responsive than generic instruments (mean = 0.39, P =.01), and than the corresponding domains of generic instruments (mean = 0.40, P =.03). Studies with low, medium, and high therapeutic effects showed a corresponding gradation in responsiveness differences between specific and generic instruments. We conclude that, overall, specific instruments are more responsive than generic tools, and that investigators may come to misleading conclusions about relative instrument responsiveness if they include studies in which the magnitude of the underlying therapeutic effect is zero.

Epilepsy surgery is a safe surgical procedure, but it may be associated with cognitive changes. Estimates of the risk of decline in specific neuropsychological domains after epilepsy surgery would assist surgical decision making in clinical practice. The goal of this study was to conduct a systematic review to derive pooled estimates of the rate of losses and gains in neuropsychological functions after epilepsy surgery, using empirically based methods for quantifying cognitive change.An extensive literature search using PubMed, EmBase, and the Cochrane database was conducted, yielding 5,061 articles on epilepsy surgery, with 193 on neuropsychological outcomes (IQ, memory, language, executive functioning, attention, and subjective cognitive changes).Of these, 23 met final eligibility criteria, with 22 studies involving temporal surgery only. Key aspects of inclusion criteria were N ≥ 20 and use of reliable change index or standardized regression-based change estimates. In addition to the proportion of patients experiencing losses and gains in each individual test, a single pooled estimate of gains and losses for each cognitive domain was derived using a random effects model. Weighted estimates indicated a risk to verbal memory with left-sided temporal surgery of 44%, twice as high as the rate for right-sided surgery (20%). Naming was reduced in 34% of left-sided temporal patients, with almost no patients with gains (4%). Pooled data on IQ, executive functioning, and attention indicated few patients show declines post surgery, but a substantial rate of improvement in verbal fluency with left-sided temporal surgery (27%) was found. Self-reported cognitive declines after epilepsy surgery were uncommon, and gains were reported in some domains where losses were found on objective tests (i.e., verbal memory and language). Variations in surgical techniques did not appear to have a large effect on cognitive outcomes, except for naming outcomes, which appeared better with more conservative resections. Sensitivity to postoperative changes differed across visual memory tests, but not verbal memory tests. Few conclusions could be made regarding cognitive risks and benefits of extratemporal epilepsy surgery, or of epilepsy surgery in children.In sum, epilepsy surgery is associated with specific cognitive changes, but may also improve cognition in some patients. The results provide base rate estimates of expected cognitive gains and losses associated with epilepsy surgery that may prove useful in clinical settings.

The potential efficacy of temporal and extratemporal resection in patients with partial epilepsy uncontrolled by anti-epileptic drugs is undisputed. However, there are still uncertainties about which patients will benefit most. A systematic review of the available literature has been undertaken by four pairs of reviewers to assess the overall outcome of epilepsy surgery and to identify factors better correlated to seizure outcome. A Medline search for studies on epilepsy surgery published since 1984 was performed. Studies were included if they had a well-defined population and design, a sample size of at least 30 patients, an MRI performed in least 90% of cases, an expected duration of follow-up of at least one year, and a post-operative outcome measured as seizure remission. A good outcome was considered as seizure control or seizure-free status for at least one year or Engel class I. Based on the review of 47 articles meeting all the eligibility criteria, febrile seizures (odds ratio, OR, 0.48; 95% confidence interval, CI, 0.27-0.83), mesial temporal sclerosis (OR 0.47; 95% CI 0.35-0.64), tumors (OR 0.58; 95% CI 0.42-0.80), abnormal MRI (OR 0.44; 95% CI 0.29-0.65), EEG/MRI concordance (OR 0.52; 95% CI 0.32-0.83), and extensive surgical resection (OR 0.24; 95% CI 0.16-0.36) were the strongest prognostic indicators of seizure remission (positive predictors); by contrast, post-operative discharges (OR 2.41; 95% CI 1.37-4.27) and intracranial monitoring (OR 2.72; 95% CI 1.60-4.60) predicted an unfavorable prognosis (negative predictors). Firm conclusions cannot be drawn for extent of resection, EEG/MRI concordance and post-operative discharges for the heterogeneity of study results. Neuromigrational defects, CNS infections, vascular lesions, interictal spikes, and side of resection did not affect the chance of seizure remission after surgery. Despite a number of limitations, the results of the review provide some insight into the selection of the best surgical candidates in clinical practice but raise concerns on the quality of published reports, and may serve as the basis for the identification of better standards to assess surgical outcome in observational studies.

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy.Methods: Systematic review of relevant articles published between January

Objective: To estimate the prevalence of depression in persons with epilepsy (PWE) and the strength of association between these 2 conditions. Methods: The MEDLINE (1948–2012), EMBASE (1980–2012), and PsycINFO (1806–2012) databases, reference lists of retrieved articles, and conference abstracts were searched. Content experts were also consulted. Two independent reviewers screened abstracts and extracted data. For inclusion, studies were population-based, original research, and reported on epilepsy and depression. Estimates of depression prevalence among PWE and of the association between epilepsy and depression (estimated with reported odds ratios [ORs]) are provided. Results: Of 7,106 abstracts screened, 23 articles reported on 14 unique data sources. Nine studies reported on 29,891 PWE who had an overall prevalence of active (current or past-year) depression of 23.1% (95% confidence interval [CI] 20.6%–28.31%). Five of the 14 studies reported on 1,217,024 participants with an overall OR of active depression of 2.77 (95% CI 2.09–3.67) in PWE. For lifetime depression, 4 studies reported on 5,454 PWE, with an overall prevalence of 13.0% (95% CI 5.1–33.1), and 3 studies reported on 4,195 participants with an overall OR of 2.20 (95% CI 1.07–4.51) for PWE. Conclusions: Epilepsy was significantly associated with depression and depression was observed to be highly prevalent in PWE. These findings highlight the importance of proper identification and management of depression in PWE. CCHS= : Canadian Community Health Survey; CES-D= : Center for Epidemiologic Studies–Depression Scale; CI= : confidence interval; DSM-IV= : Diagnostic and Statistical Manual of Mental Disorders, 4th edition; HADS= : Hospital Anxiety and Depression Scale; HPA= : hypothalamic-pituitary-adrenal; ICD= : International Classification of Diseases; ICPC= : International Classification of Primary Care; K-6= : Kessler-6; OR= : odds ratio; PWE= : persons with epilepsy; WMH-CIDI= : World Mental Health–Composite Diagnostic Interview

Migraine is common, with an estimated lifetime prevalence of 7-17%. Population-based studies have reported an association between various psychiatric conditions and migraine. This is a population-based study exploring the association between migraine and psychiatric disorders in a large cohort and assessing various health-related outcomes.(1) Determine the prevalence of various psychiatric conditions in association with migraine; (2) describe the patterns of association of these comorbidities with a variety of health-related outcomes.Data from the 2002 Canadian Community Health Survey were used. This is a national health survey which included administration of the World Mental Health Composite International Diagnostic Interview to a sample of 36,984 subjects. Health-related outcomes included 2-week disability, restriction of activities, quality-of-life, and mental health care utilization.The prevalence of physician-diagnosed migraine (n=36,984) was 15.2% for females and 6.1% for males. Migraine was most common in those between ages 25 and 44 years and in those of lower income. Migraine was associated with major depressive disorder, bipolar disorder, panic disorder, and social phobia, all occurring more than twice as often in those with migraines compared with those without. Migraine was not associated with drug, alcohol, or substance dependence. The higher prevalence of psychiatric disorders in migraineurs was not related to sociodemographic variables. Psychiatric disorders were less common in those over 65 years, in those who were in a relationship, and in those of higher income whether migraine was present or not. Health-related outcomes were worst in those with both migraines and a psychiatric disorder and intermediate in those with either condition alone.Migraine is associated with major depressive disorder, bipolar disorder, panic disorder, and social phobia. Migraine in association with various mental health disorders results in poorer health-related outcomes compared with migraine or a psychiatric condition alone. Understanding the psychiatric correlates of migraine is important in order to adequately manage this patient population and to guide public health policies regarding health services utilization and health-care costs.

The 2017 International League Against Epilepsy classification has defined a three-tier system with epilepsy syndrome identification at the third level. Although a syndrome cannot be determined in all children with epilepsy, identification of a specific syndrome provides guidance on management and prognosis. In this paper, we describe the childhood onset epilepsy syndromes, most of which have both mandatory seizure type(s) and interictal electroencephalographic (EEG) features. Based on the 2017 Classification of Seizures and Epilepsies, some syndrome names have been updated using terms directly describing the seizure semiology. Epilepsy syndromes beginning in childhood have been divided into three categories: (1) self-limited focal epilepsies, comprising four syndromes: self-limited epilepsy with centrotemporal spikes, self-limited epilepsy with autonomic seizures, childhood occipital visual epilepsy, and photosensitive occipital lobe epilepsy; (2) generalized epilepsies, comprising three syndromes: childhood absence epilepsy, epilepsy with myoclonic absence, and epilepsy with eyelid myoclonia; and (3) developmental and/or epileptic encephalopathies, comprising five syndromes: epilepsy with myoclonic-atonic seizures, Lennox-Gastaut syndrome, developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep, hemiconvulsion-hemiplegia-epilepsy syndrome, and febrile infection-related epilepsy syndrome. We define each, highlighting the mandatory seizure(s), EEG features, phenotypic variations, and findings from key investigations.

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. Methods:A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007.Results: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs.There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications.Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important.Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts.Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative.

The Quality Standards Subcommittee of the American Academy of Neurology develops practice parameters as strategies for patient care based on analysis of evidence. For this practice parameter the authors reviewed available evidence relevant to evaluating adults presenting with an apparent unprovoked first seizure.Relevant questions were defined and addressed by multiple searches of medical literature. Each article was then reviewed, abstracted, and classified using an established evidence scoring system. Conclusions and recommendations were based on a standard three-tiered scheme of evidence classification.For adults presenting with a first seizure, a routine EEG revealed epileptiform abnormalities in approximately 23% of patients, and these were predictive of seizure recurrence. A brain imaging study (CT or MRI) was significantly abnormal in 10% of patients, indicating a possible seizure etiology. Laboratory tests such as blood counts, blood glucose, and electrolyte panels were abnormal in up to 15% of individuals, but abnormalities were minor and did not cause the seizure. Overt clinical signs of infection such as fever typically predicted significant CSF abnormalities on lumbar puncture. Toxicology screening studies were limited, but report some positive tests.EEG should be considered as part of the routine neurodiagnostic evaluation of adults presenting with an apparent unprovoked first seizure (Level B). Brain imaging with CT or MRI should be considered as part of the routine neurodiagnostic evaluation of adults presenting with an apparent unprovoked first seizure (Level B). Laboratory tests, such as blood counts, blood glucose, and electrolyte panels (particularly sodium), lumbar puncture, and toxicology screening may be helpful as determined by the specific clinical circumstances based on the history, physical, and neurologic examination, but there are insufficient data to support or refute recommending any of these tests for the routine evaluation of adults presenting with an apparent first unprovoked seizure (Level U).

Abstract The International League Against Epilepsy (ILAE) Task Force on Nosology and Definitions proposes a classification and definition of epilepsy syndromes in the neonate and infant with seizure onset up to 2 years of age. The incidence of epilepsy is high in this age group and epilepsy is frequently associated with significant comorbidities and mortality. The licensing of syndrome specific antiseizure medications following randomized controlled trials and the development of precision, gene‐related therapies are two of the drivers defining the electroclinical phenotypes of syndromes with onset in infancy. The principal aim of this proposal, consistent with the 2017 ILAE Classification of the Epilepsies, is to support epilepsy diagnosis and emphasize the importance of classifying epilepsy in an individual both by syndrome and etiology. For each syndrome, we report epidemiology, clinical course, seizure types, electroencephalography (EEG), neuroimaging, genetics, and differential diagnosis. Syndromes are separated into self‐limited syndromes, where there is likely to be spontaneous remission and developmental and epileptic encephalopathies , diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. The emerging class of etiology‐specific epilepsy syndromes, where there is a specific etiology for the epilepsy that is associated with a clearly defined, relatively uniform, and distinct clinical phenotype in most affected individuals as well as consistent EEG, neuroimaging, and/or genetic correlates, is presented. The number of etiology‐defined syndromes will continue to increase, and these newly described syndromes will in time be incorporated into this classification. The tables summarize mandatory features, cautionary alerts, and exclusionary features for the common syndromes. Guidance is given on the criteria for syndrome diagnosis in resource‐limited regions where laboratory confirmation, including EEG, MRI, and genetic testing, might not be available.

To compare standard anterior temporal lobectomy (ATL) with selective amygdalohippocampectomy (SAH) for postoperative seizure control in temporal lobe epilepsy (TLE).We searched MEDLINE and Embase using Medical Subject Headings and keywords related to ATL and SAH. We included original research that directly compared seizure outcomes in patients undergoing SAH or ATL for TLE. A fixed-effect model was used to derive a pooled risk ratio (RR) for either an Engel Class I (free of disabling seizures) or a composite of an Engel Class I and II (rare disabling seizures) outcome.Of 4,675 abstracts initially identified by the search, 65 were reviewed as full text. Thirteen studies containing data from 8 countries (5 continents) met our inclusion criteria. Eleven studies comprising 1,203 patients demonstrated that participants were statistically more likely to achieve an Engel Class I outcome after ATL compared with SAH (risk ratio 1.32, 95% confidence interval [CI] 1.12-1.57; p < 0.01). The summary risk difference of 8% (95% CI 3%-14%) translates to a number needed to treat of 13 (95% CI 7-33) for 1 additional patient to achieve an Engel Class I outcome after ATL. The result remained significant when 2 studies that contained fewer than 15 participants in at least 1 arm were excluded and in analyses restricted to hippocampal sclerosis.Standard ATL confers an improved chance of achieving freedom from disabling seizures in patients with TLE. Improved seizure freedom must be balanced against the neuropsychological impact of each procedure. A randomized controlled trial is justified.

Underutilization of epilepsy surgery remains a major problem and is in part due to physicians' misconceptions about the risks associated with epilepsy surgery. The purpose of this study was to systematically review the literature on complications of focal epilepsy surgery.A literature search was conducted using PubMed and Embase to identify studies examining epilepsy surgery complications. Abstract and full text review, along with data extraction, was done in duplicate. Minor medical and neurologic complications were defined as those that resolved completely within 3 months of surgery, whereas major complications persisted beyond that time frame. Descriptive statistics were used to report complication proportions.Invasive monitoring: Minor complications were reported in 7.7% of patients, whereas major complications were reported in only 0.6% of patients undergoing invasive monitoring. Resective surgery: Minor and major medical complications were reported in 5.1% and 1.5% of patients respectively, most common being cerebrospinal fluid (CSF) leak. Minor neurologic complications occurred in 10.9% of patients and were twice as frequent in children (11.2% vs. 5.5%). Minor visual field defects were most common (12.9%). Major neurologic complications were noted in 4.7% of patients, with the most common being major visual field defects (2.1% overall). Perioperative mortality was uncommon after epilepsy surgery, occurring in only 0.4% of temporal lobe patients (1.2%extratemporal).The majority of complications after epilepsy surgery are minor or temporary as they tend to resolve completely. Major permanent neurologic complications remain uncommon. Mortality as a result of epilepsy surgery in the modern era is rare.

To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy.A 20-member committee including general neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and February 2008.For WWE taking antiepileptic drugs, there is probably no substantially increased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84%-92%) of remaining seizure-free during pregnancy.Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%-92%) of remaining seizure-free during pregnancy (Level B). However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy (Level C).

To provide evidence-based recommendations for treatment of adults with an unprovoked first seizure.We defined relevant questions and systematically reviewed published studies according to the American Academy of Neurology's classification of evidence criteria; we based recommendations on evidence level.Adults with an unprovoked first seizure should be informed that their seizure recurrence risk is greatest early within the first 2 years (21%-45%) (Level A), and clinical variables associated with increased risk may include a prior brain insult (Level A), an EEG with epileptiform abnormalities (Level A), a significant brain-imaging abnormality (Level B), and a nocturnal seizure (Level B). Immediate antiepileptic drug (AED) therapy, as compared with delay of treatment pending a second seizure, is likely to reduce recurrence risk within the first 2 years (Level B) but may not improve quality of life (Level C). Over a longer term (>3 years), immediate AED treatment is unlikely to improve prognosis as measured by sustained seizure remission (Level B). Patients should be advised that risk of AED adverse events (AEs) may range from 7% to 31% (Level B) and that these AEs are likely predominantly mild and reversible. Clinicians' recommendations whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy, consider educated patient preferences, and advise that immediate treatment will not improve the long-term prognosis for seizure remission but will reduce seizure risk over the subsequent 2 years.

Summary A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost‐effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.

In 2017, the International League Against Epilepsy (ILAE) Classification of Epilepsies described the "genetic generalized epilepsies" (GGEs), which contained the "idiopathic generalized epilepsies" (IGEs). The goal of this paper is to delineate the four syndromes comprising the IGEs, namely childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We provide updated diagnostic criteria for these IGE syndromes determined by the expert consensus opinion of the ILAE's Task Force on Nosology and Definitions (2017-2021) and international external experts outside our Task Force. We incorporate current knowledge from recent advances in genetic, imaging, and electroencephalographic studies, together with current terminology and classification of seizures and epilepsies. Patients that do not fulfill criteria for one of these syndromes, but that have one, or a combination, of the following generalized seizure types: absence, myoclonic, tonic-clonic and myoclonic-tonic-clonic seizures, with 2.5-5.5 Hz generalized spike-wave should be classified as having GGE. Recognizing these four IGE syndromes as a special grouping among the GGEs is helpful, as they carry prognostic and therapeutic implications.

A bidirectional relationship exists between epilepsy and depression. However, any putative biological gradient between depression severity and the risk of epilepsy, and the degree to which depression mediates the influence of independent risk factors for epilepsy, has yet to be examined.To determine the effect of depression on the risk of epilepsy and seizure outcomes.An observational study of a population-based primary care cohort (all patients free of prevalent depression and epilepsy at 18-90 years of age who were active after the Acceptable Mortality Reporting date in The Health Improvement Network database) and a prospectively collected tertiary care cohort (all patients whose data were prospectively collected from the Calgary Comprehensive Epilepsy Programme). The analyses were performed on March 16, 2016.The hazard of developing epilepsy after incident depression and vice versa was calculated. In addition, a mediation analysis of the effect of depression on risk factors for epilepsy and the odds of seizure freedom stratified by the presence of depression were performed.We identified 10 595 709 patients in The Health Improvement Network of whom 229 164 (2.2%) developed depression and 97 177 (0.9%) developed epilepsy. The median age was 44 years (interquartile range, 32-58 years) for those with depression and 56 years (interquartile range, 43-71 years) for those with epilepsy. Significantly more patients with depression (144 373 [63%] were women, and 84 791 [37%] were men; P < .001) or epilepsy (54 419 [56%] were women, and 42 758 [44%] were men; P < .001) were female. Incident epilepsy was associated with an increased hazard of developing depression (hazard ratio [HR], 2.04 [95% CI, 1.97-2.09]; P < .001), and incident depression was associated with an increased hazard of developing epilepsy (HR, 2.55 [95% CI, 2.49-2.60]; P < .001) There was an incremental hazard according to depression treatment type with lowest risk for those receiving counselling alone (HR, 1.84 [95% CI, 1.30-2.59]; P < .001), an intermediate risk for those receiving antidepressants alone (HR, 3.43 [95% CI, 3.37-3.47]; P < .001), and the highest risk for those receiving both (HR, 9.85 [95% CI, 5.74-16.90]; P < .001). Furthermore, depression mediated the relationship between sex, social deprivation, and Charlson Comorbidity Index with incident epilepsy, accounting for 4.6%, 7.1%, and 20.6% of the total effects of these explanatory variables, respectively. In the Comprehensive Epilepsy Programme, the odds of failing to achieve 1-year seizure freedom were significantly higher for those with depression or treated depression.Common underlying pathophysiological mechanisms may explain the risk of developing epilepsy following incident depression. Treated depression is associated with worse epilepsy outcomes, suggesting that this may be a surrogate for more severe depression and that severity of depression is associated with severity of epilepsy.

Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition and classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 to identify existing gaps and provide a timely update. The following methodology was applied to achieve this goal: a survey of published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 and 06/30/2021 (n = 1349) in PubMed identified the knowledge gained since 2012 and new developments in the field. An online survey consulted the ILAE community about the current use of the FCD classification scheme with 367 people answering. The TF performed an iterative clinico-pathological and genetic agreement study to objectively measure the diagnostic gap in blood/brain samples from 22 patients suspicious for FCD and submitted to epilepsy surgery. The literature confirmed new molecular-genetic characterizations involving the mechanistic Target Of Rapamycin (mTOR) pathway in FCD type II (FCDII), and SLC35A2 in mild malformations of cortical development (mMCDs) with oligodendroglial hyperplasia (MOGHE). The electro-clinical-imaging phenotypes and surgical outcomes were better defined and validated for FCDII. Little new information was acquired on clinical, histopathological, or genetic characteristics of FCD type I (FCDI) and FCD type III (FCDIII). The survey identified mMCDs, FCDI, and genetic characterization as fields for improvement in an updated classification. Our iterative clinico-pathological and genetic agreement study confirmed the importance of immunohistochemical staining, neuroimaging, and genetic tests to improve the diagnostic yield. The TF proposes to include mMCDs, MOGHE, and "no definite FCD on histopathology" as new categories in the updated FCD classification. The histopathological classification can be further augmented by advanced neuroimaging and genetic studies to comprehensively diagnose FCD subtypes; these different levels should then be integrated into a multi-layered diagnostic scheme. This update may help to foster multidisciplinary efforts toward a better understanding of FCD and the development of novel targeted treatment options.

Epilepsy syndromes have been recognized for >50 years, as distinct electroclinical phenotypes with therapeutic and prognostic implications. Nonetheless, no formally accepted International League Against Epilepsy (ILAE) classification of epilepsy syndromes has existed. The ILAE Task Force on Nosology and Definitions was established to reach consensus regarding which entities fulfilled criteria for an epilepsy syndrome and to provide definitions for each syndrome. We defined an epilepsy syndrome as "a characteristic cluster of clinical and electroencephalographic features, often supported by specific etiological findings (structural, genetic, metabolic, immune, and infectious)." The diagnosis of a syndrome in an individual with epilepsy frequently carries prognostic and treatment implications. Syndromes often have age-dependent presentations and a range of specific comorbidities. This paper describes the guiding principles and process for syndrome identification in both children and adults, and the template of clinical data included for each syndrome. We divided syndromes into typical age at onset, and further characterized them based on seizure and epilepsy types and association with developmental and/or epileptic encephalopathy or progressive neurological deterioration. Definitions for each specific syndrome are contained within the corresponding position papers.

The goal of this paper is to provide updated diagnostic criteria for the epilepsy syndromes that have a variable age of onset, based on expert consensus of the International League Against Epilepsy Nosology and Definitions Taskforce (2017-2021). We use language consistent with current accepted epilepsy and seizure classifications and incorporate knowledge from advances in genetics, electroencephalography, and imaging. Our aim in delineating the epilepsy syndromes that present at a variable age is to aid diagnosis and to guide investigations for etiology and treatments for these patients.

Epilepsy surgery is the treatment of choice for patients with drug-resistant seizures. A timely evaluation for surgical candidacy can be life-saving for patients who are identified as appropriate surgical candidates, and may also enhance the care of nonsurgical candidates through improvement in diagnosis, optimization of therapy, and treatment of comorbidities. Yet, referral for surgical evaluations is often delayed while palliative options are pursued, with significant adverse consequences due to increased morbidity and mortality associated with intractable epilepsy. The Surgical Therapies Commission of the International League Against Epilepsy (ILAE) sought to address these clinical gaps and clarify when to initiate a surgical evaluation. We conducted a Delphi consensus process with 61 epileptologists, epilepsy neurosurgeons, neurologists, neuropsychiatrists, and neuropsychologists with a median of 22 years in practice, from 28 countries in all six ILAE world regions. After three rounds of Delphi surveys, evaluating 51 unique scenarios, we reached the following Expert Consensus Recommendations: (1) Referral for a surgical evaluation should be offered to every patient with drug-resistant epilepsy (up to 70 years of age), as soon as drug resistance is ascertained, regardless of epilepsy duration, sex, socioeconomic status, seizure type, epilepsy type (including epileptic encephalopathies), localization, and comorbidities (including severe psychiatric comorbidity like psychogenic nonepileptic seizures [PNES] or substance abuse) if patients are cooperative with management; (2) A surgical referral should be considered for older patients with drug-resistant epilepsy who have no surgical contraindication, and for patients (adults and children) who are seizure-free on 1-2 antiseizure medications (ASMs) but have a brain lesion in noneloquent cortex; and (3) referral for surgery should not be offered to patients with active substance abuse who are noncooperative with management. We present the Delphi consensus results leading up to these Expert Consensus Recommendations and discuss the data supporting our conclusions. High level evidence will be required to permit creation of clinical practice guidelines.

The global burden of neurological disorders is substantial and increasing, especially in low-resource settings. The current increased global interest in brain health and its impact on population wellbeing and economic growth, highlighted in the World Health Organization's new Intersectoral Global Action Plan on Epilepsy and other Neurological Disorders 2022-2031, presents an opportunity to rethink the delivery of neurological services. In this Perspective, we highlight the global burden of neurological disorders and propose pragmatic solutions to enhance neurological health, with an emphasis on building global synergies and fostering a 'neurological revolution' across four key pillars - surveillance, prevention, acute care and rehabilitation - termed the neurological quadrangle. Innovative strategies for achieving this transformation include the recognition and promotion of holistic, spiritual and planetary health. These strategies can be deployed through co-design and co-implementation to create equitable and inclusive access to services for the promotion, protection and recovery of neurological health in all human populations across the life course.

To examine evidence for effectiveness of anteromesial temporal lobe and localized neocortical resections for disabling complex partial seizures.Systemic review and analysis of the literature since 1990.One intention-to-treat Class I randomized controlled trial of surgery for mesial temporal lobe epilepsy found that 58% of patients randomized to be evaluated for surgical therapy (64% of those who received surgery) were free of disabling seizures and 10 to 15% were unimproved at the end of 1 year, compared with 8% free of disabling seizures in the group randomized to continued medical therapy. There was a significant improvement in quantitative quality-of-life scores and a trend toward better social function at the end of 1 year for patients in the surgical group, no surgical mortality, and infrequent morbidity. Twenty-four Class IV series of temporal lobe resections yielded essentially identical results. There are similar Class IV results for localized neocortical resections; no Class I or II studies are available.A single Class I study and 24 Class IV studies indicate that the benefits of anteromesial temporal lobe resection for disabling complex partial seizures is greater than continued treatment with antiepileptic drugs, and the risks are at least comparable. For patients who are compromised by such seizures, referral to an epilepsy surgery center should be strongly considered. Further studies are needed to determine if neocortical seizures benefit from surgery, and whether early surgical intervention should be the treatment of choice for certain surgically remediable epileptic syndromes.

Assessment of long-term outcomes is essential in brain surgery for epilepsy. Little information exists on long-term non-seizure outcomes after epilepsy surgery. We perform a systematic review and meta-analysis of the evidence on this topic. Our aim was to provide evidence-based estimates of antiepileptic drug, psychosocial, neuropsychological and mortality long-term outcomes following epilepsy surgery, and to identify sources of variation in published results. We searched Medline, Index Medicus, the Cochrane database, bibliographies of reviews, original articles, and book chapters, to identify articles published from 1991 to 2005, containing > or =20 patients of any age, undergoing resective or non-resective epilepsy surgery, and followed for a mean/median of > or =5 years. Two reviewers independently assessed study eligibility and extracted data, resolving disagreements through discussion. Standard meta-analytical techniques were used to pool data. Of the 159 potentially eligible articles reviewed in full-text, 35 (22%) fulfilled eligibility criteria; 6 (17%) were controlled studies; 15 (36%) explored antiepileptic drug outcome; 6 (17%) explored mortality; 11 (31%) reported psychosocial outcomes; and 7 (20%) explored neuropsychological outcomes. On an average, 14% [95% confidence interval (CI(95)) = 11-17] of the patients with temporal lobe surgery achieved long-term antiepileptic drug (AED) discontinuation, 50% (CI(95) = 45-55) achieved monotherapy, and 33% remained on polytherapy (CI(95 =) 29-38). In analyses including all types of surgery, on average, 20% (CI(95) = 18-23) achieved long-term AED discontinuation, while 41% (CI(95) = 37-45) were on monotherapy and 31% (CI(95) = 27-35) remained on polytherapy. Children achieved better AED outcomes than adults. Seizure freedom after surgery was associated with lower mortality, but inconsistent mortality outcomes precluded making strong inferences. Non-controlled studies consistently reported improved long-term psychosocial outcomes, but the effect was less clear in controlled studies. Intelligence was unchanged by surgery, but long-term memory outcomes were associated with seizure freedom and side of temporal lobe resection. Few long-term, controlled studies exist. Longer follow-up was associated with lower rates of AED discontinuation, reflecting lower seizure-free rates over time. Cognitive and psychosocial outcomes were similar to those of short-term studies, and the results were influenced by the presence of controls.

Summary: Purpose: There is a notion that people with epilepsy have substantial and often unrecognized comorbidity of chronic conditions. However, most studies focus on selected patient groups; population‐based studies are scarce. We compared the prevalence of chronic somatic conditions in people with epilepsy with that in the general population using Canadian, nationwide, population‐based health data. Method: We examined epilepsy‐specific and general population health data obtained through two previously validated, independently performed, door‐to‐door Canadian health surveys, the National Population Health Survey (NPHS, N = 49,000) and the Community Health Survey (CHS, N = 130882), which represent 98% of the Canadian population. The prevalence of epilepsy and 19 other chronic conditions was ascertained through direct inquiry from respondents about physician‐diagnosed illnesses. Weighted prevalence, prevalence ratios (PR), and 95% confidence intervals were obtained for the entire population and for males and females separately. Multivariate analyses assessed the strength of association of comorbid conditions with epilepsy as compared with the general population. Results: People with epilepsy had a statistically significant higher prevalence of most chronic conditions than the general population. Conditions with particularly high prevalence in epilepsy (prevalence ratio ≥ 2.0) include stomach/intestinal ulcers (PR, CHS 2.5, NPHS 2.7), stroke (PR, CHS 3.9, NPHS 4.7), urinary incontinence (PR, CHS 3.2, NPHS 4.4), bowel disorders (PR, CHS 2.0, NPHS 3.3), migraine (PR, CHS 2.0, NPHS 2.6), Alzheimer's disease (PR, NPHS 4.3), and chronic fatigue (PR, CHS 4.1). There were no gender‐specific differences in prevalence of chronic conditions among people with epilepsy. Conclusions: People with epilepsy in the general population, not only those actively seeking medical care, have a high prevalence of chronic somatic comorbid conditions. The findings are consistent across two independent surveys, which show that people with epilepsy in the general population have a two‐ to five‐fold risk of somatic comorbid conditions, as compared with people without epilepsy. This patient‐centered comorbidity profile reflects health aspects that are important to people with epilepsy, and indicate the need for a more integrated approach to people with epilepsy. The impact of epilepsy relative to other comorbid conditions requires further analysis, as does the contribution of comorbidity to epilepsy intractability and to differential health care needs. Similarly, it remains to be determined whether the observed comorbidity patterns are specific to epilepsy or simply reflect a pattern that is common to chronic illnesses in general.

<b>Background: </b> Adjustable, reversible therapies are needed for patients with pharmacoresistant epilepsy. Electrical stimulation of the hippocampus has been proposed as a possible treatment for mesial temporal lobe epilepsy (MTLE). <b>Methods: </b> Four patients with refractory MTLE whose risk to memory contraindicated temporal lobe resection underwent implantation of a chronic stimulating depth electrode along the axis of the left hippocampus. The authors used continuous, subthreshold electrical stimulation (90 μsec, 190 Hz) and a double blind, multiple cross-over, randomized controlled design, consisting of three treatment pairs, each containing two 1-month treatment periods. During each treatment pair the stimulator was randomly turned ON 1 month and OFF 1 month. Outcomes were assessed at monthly intervals in a double blind manner, using standardized instruments and accounting for a washout period. The authors compared outcomes between ON, OFF, and baseline periods. <b>Results: </b> Hippocampal stimulation produced a median reduction in seizures of 15%. All but one patient’s seizures improved; however, the results did not reach significance. Effects seemed to carry over into the OFF period, and an implantation effect cannot be ruled out. The authors found no significant differences in other outcomes. There were no adverse effects. One patient has been treated for 4 years and continues to experience substantial long-term seizure improvement. <b>Conclusion: </b> The authors demonstrate important beneficial trends, some long-term benefits, and absence of adverse effects of hippocampal electrical stimulation in mesial temporal lobe epilepsy. However, the effect sizes observed were smaller than those reported in non-randomized, unblinded studies.

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including antiepileptic drug (AED) teratogenicity and adverse perinatal outcomes. It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine (CBZ), and possibly compared to phenytoin (PHT) or lamotrigine (LTG). It is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. AED polytherapy probably contributes to the development of MCMs and reduced cognitive outcomes compared to monotherapy. Intrauterine exposure to VPA monotherapy probably reduces cognitive outcomes and monotherapy exposure to PHT or phenobarbital (PB) possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. If possible, avoidance of VPA and AED polytherapy during the first trimester of pregnancy should be considered to decrease the risk of MCMs. If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered and avoidance of PHT and PB throughout pregnancy may be considered to prevent reduced cognitive outcomes.

To provide an evidence-based analysis of the risk factors and incidence of SUDEP, and to assess methodological aspects and sources of variation in studies dealing with SUDEP.An expert in library resources and electronic databases comprehensively searched Medline, Index Medicus, and the Cochrane library. We included case-control or cohort studies focusing on SUDEP in children or adults, published in the English language. Two reviewers independently applied study eligibility criteria and extracted data, resolving disagreements through discussion.Of 404 citations identified, 83 potentially eligible articles were reviewed in full text and 36 studies fulfilled eligibility criteria (29 cohort and 8 case-control studies). In studies using non-SUDEP deaths as controls the most consistent risk factors were a seizure preceding death, and subtherapeutic antiepileptic drug levels. In studies that used persons living with epilepsy as controls the main risk factors for SUDEP were youth, high seizure frequency, high number of antiepileptic drugs and long duration of epilepsy. The annual incidence of SUDEP ranged from 0 to 10:1000. It was highest in studies of candidates for epilepsy surgery and epilepsy referral centers (2.2:1000-10:1000), intermediate in studies including patients with mental retardation (3.4:1000-3.6:1000), and lowest in children (0-0.2:1000). The incidence was similar in autopsy series (0.35:1000-2.5:1000) and in studies of epilepsy patients in the general population (0-1.35:1000). The median proportion of SUDEP in relation to overall mortality in epilepsy was 40 and 4% in high- and low-risk groups, respectively.Although studies on SUDEP are heterogeneous in methodology, consistent patterns in incidence and risk factors emerge. Low- and high-risk patient groups are identified, which determine the relative contribution of SUDEP to overall mortality in epilepsy. In addition to patient population, risk factors for SUDEP depend on the type of controls used for comparison (dead versus live patients with epilepsy). Risk factors found in different studies are not necessarily contradictory, but are often complementary.

Epilepsy is the most common serious neurological condition in the world, and an important cause of mortality and disability in developing countries. Because epidemiological and clinical characteristics of epilepsy vary by region, it is important to know the peculiarities of epilepsy in this area of the American continent. We searched MEDLINE, IMBIOMED, and LILACS (The Latin-American and Caribbean biomedical database) to identify community-based studies reporting on the prevalence and incidence of epilepsy in Latin America. Studies were included if a definition of epilepsy was given, if data were obtained through standardized questionnaires and if raw population numbers were available for data confirmation. Thirty-three studies fulfilled eligibility criteria, 32 reported on prevalence and three on incidence of epilepsy. The median lifetime prevalence in all countries was 17.8 (range 6–43.2) per 1000 people, and the range for incidence was 77.7–190 per 100,000 people per year. There were no differences between rural and urban areas, by gender, age-group (children, adult, all ages), ascertainment method, or year of study. Measuring the global burden of disease in Latin America requires adequate epidemiological information. This systematic review of epidemiological studies identifies higher prevalence and incidence rates of epilepsy in the general population of Latin America than in northern hemisphere countries. The remarkable heterogeneity found between and even within countries, could be explained by several factors, importantly, socioeconomic and methodological aspects.

Assess the validity of ICD-9-CM and ICD-10 epilepsy coding from an emergency visit (ER) and a hospital discharge abstract database (DAD).Two separate sources of patient records were reviewed and validated. (1) Charts of patients admitted to our seizure monitoring unit over 2 years (n = 127, ICD-10 coded records) were reviewed. Sensitivity (Sn), specificity (Sp), and positive and negative predictive values (PPV and NPV) were calculated. (2) Random sample of charts for patients seen in the ER or admitted to hospital under any services, and whose charts were coded with epilepsy or an epilepsy-like condition, were reviewed. Two time-periods were selected to allow validation of both ICD-9-CM (n = 486) and ICD-10 coded (n = 454) records. Only PPV and NPV were calculated for these records. All charts were reviewed by two physicians to confirm the presence/absence of epilepsy and compare to administrative coding.Sample 1: Sn, Sp, PPV, and NPV of ICD-10 epilepsy coding from the seizure monitoring unit (SMU) chart review were 99%, 70%, 85%, and 97% respectively. Sample 2: The PPV and NPV for ICD-9-CM coding from the ER database were, respectively, 99% and 97% and from the DAD were 98% and 99%. The PPV and NPV for ICD-10 coding from the ER database were, respectively, 100% and 90% and from the DAD were 98% and 99%. The epilepsy subtypes grand mal status and partial epilepsy with complex partial seizures both had PPVs >75% (ICD-9-CM and ICD-10 data).Administrative emergency and hospital discharge data have high epilepsy coding validity overall in our health region.

In North America, overall epilepsy incidence is approximately 50/100,000 per year, highest for children below five years of age, and the elderly. The best data suggest prevalence of 5-10/1000. Potential effects of gender, ethnicity, access to care and socioeconomic variables need further study. Studies of epilepsy etiology and classification mainly were performed without modern imaging tools. The best study found an overall standardized mortality ratio (SMR) for epilepsy relative to the general population of 2.3. There is evidence to suggest a greater increase in patients with symptomatic epilepsy, particularly children. People with epilepsy are more likely to report reduced Health-related Quality of Life than controls. They have reduced income, and are less likely to have full-time employment. They suffer from persistent stigma throughout the region, in developed as well as developing countries. Poor treatment access and health care disparities for people with epilepsy may be related to insufficient economic resources, rural isolation, gender, ethnicity, and lack of public and physician knowledge of modern approaches to epilepsy care. Despite high costs and severe disability, epilepsy may attract somewhat less research funding from public and private sources than other less common chronic neurological disorders. A Plan for Epilepsy in North America should address: basic and clinical research; primary prevention research; translation to care; stigma, quality of life, and self-management; industry relations; government and regional relations; and regional integration and resource sharing.

We performed a prevalence estimate of chronic pain with neuropathic pain (NeP) symptoms to determine its frequency and associations with morbidity.We conducted a telephone-based survey based upon a random sampling of both urban and rural households of the general population in one Canadian province to determine NeP prevalence and its impact upon financial well-being and quality of life.Telephonic use of the DN4 questionnaire (DN4Q), used to identify NeP symptoms in those patients with chronic pain, was validated within selected clinical populations of chronic pain. Epidemiological data was obtained for all subjects. EuroQoL (EQ)-5D data estimating quality of life was measured.Chronic pain was present in 35.0% of the surveyed population of 1,207 subjects, with NeP symptoms present in 17.9%. The NeP group had significantly more pain, was female predominant, had a greater belief of being economically disadvantaged, suffered from more restrictions in mobility and in usual activities, and had overall lower EQ-5D utility scores compared with subjects with non-NeP. DN4Q validation demonstrated that pain entities not normally defined as NeP are recorded as such using the DN4Q, and that a spectrum of NeP features may occur across a host of painful conditions.Despite limitations of the DN4Q, symptoms of NeP may be more prevalent in the general population than expected and has a greater impact upon patients' lives than non-NeP. Limitations of the DN4Q may relate to the concept of a spectrum of NeP existent amongst heterogenous NeP and non-NeP syndromes.

Abstract Objective Peripheral neuropathy (PN) is thought to be coincidental in patients with idiopathic Parkinson disease (IPD). We sought to examine the prevalence of PN in a population of IPD patients and a potential relationship to levodopa use and fasting methylmalonic acid (MMA) levels. Methods In a prospective cohort study, IPD patients randomly selected from a comprehensive database were compared to control subjects regarding the presence and severity of PN using clinical and electrophysiological measures. IPD severity was determined using the Unified Parkinson's Disease Rating Scale (UPDRS). We determined the relation of levodopa use with serum levels of cobalamin, MMA, and homocysteine (Hcy). We also explored the association between presence and severity of PN and age, duration of IPD, cumulative levodopa dosing, cobalamin, MMA, and Hcy levels. Results Fifty‐eight randomly selected IPD patients were compared to 58 age‐ and sex‐matched controls. PN was present in 55% of IPD patients and 9% of controls. Patients with IPD had greater prevalence of PN and fasting MMA/Hcy levels than controls. IPD patients with PN were older and exhibited higher UPDRS scores, fasting MMA/Hcy levels, and cumulative levodopa exposure. PN severity in IPD subjects positively correlated with both levodopa exposure and MMA levels. Interpretation IPD patients have a higher prevalence of PN than controls. Although causality is not established, levodopa exposure is associated with MMA elevation and sensorimotor neuropathy in IPD patients. Cobalamin replacement concurrent with levodopa therapy should be considered to protect against development of PN in IPD patients. ANN NEUROL 2010;67:28–36

Background: Few data exist on the frequency and burden of epilepsy in Canada and on the impact of self-reported epilepsy in the general population. We assess the frequency, general health, psychosocial function, and health care resource use among self-identified epileptic persons in the general population. Method: The 1990 Ontario Health Survey is an omnibus, extensive health survey of 61,239 subjects representing the Ontario population. Self-reported epileptic subjects are compared with three groups, ie., those with ≥1 other chronic illnesses, the general population, and those with no health problems. Results: The point prevalence of self-reported epilepsy was 5.8 per 1,000 population, a figure similar to that of active epilepsy in other studies. Quality of life, family function and social support were worse in epileptic than in other chronically ill subjects. Similarly, the epilepsy population had more disability days and limitations in activities, and lower annual income than all other groups, including the chronically ill. Accidents were no more common among epileptic subjects than among controls. Epileptic persons were high users of health care resources, including hospitalization, emergency room, psychological/social work, nursing services and telephone contact with health professionals. Barriers to health care were experienced infrequently. Small area variations in health status and care are explored. Conclusion: The health profile of self-reported epileptic subjects is similar to that obtained in studies involving defined epilepsy patients. In the general population, self-identification as having epilepsy carries a significant burden of illness, reflected in poorer health, psychosocial function, and quality of life, and higher health care resource use.

Health related quality of life (HRQOL) is increasingly recognised as an important outcome in epilepsy. However, interpretation of HRQOL data is difficult because there is no agreement on what constitutes a clinically important change in the scores of the various instruments.To determine the minimum clinically important change, and small, medium, and large changes, in broadly used epilepsy specific and generic HRQOL instruments.Patients with difficult to control focal epilepsy (n = 136) completed the QOLIE-89, QOLIE-31, SF-36, and HUI-III questionnaires twice, six months apart. Patient centred estimates of minimum important change, and of small, medium, and large change, were assessed on self administered 15 point global rating scales. Using regression analysis, the change in each HRQOL instrument that corresponded to the various categories of change determined by patients was obtained. The results were validated in a subgroup of patients tested at baseline and at nine months.The minimum important change was 10.1 for QOLIE-89, 11.8 for QOLIE-31, 4.6 for SF-36 MCS, 3.0 for SF-36 physical composite score, and 0.15 for HUI-III. All instruments differentiated between no change and minimum important change with precision, and QOLIE-89 and QOLIE-31 also distinguished accurately between minimum important change and medium or large change. Baseline HRQOL scores and the type of treatment (surgical or medical) had no impact on any of the estimates, and the results were replicated in the validation sample.These estimates of minimum important change, and small, medium, and large changes, in four HRQOL instruments in patients with epilepsy are robust and can distinguish accurately among different levels of change. The estimates allow for categorisation of patients into various levels of change in HRQOL, and will be of use in assessing the effect of interventions in individual patients.

Summary A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast‐milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.

Summary Purpose: We undertook a systematic review of the evidence on disparities in epilepsy with a focus on North American data (Canada, United States, and the English‐speaking Caribbean). Methods: We identified and evaluated: access to and outcomes following medical and surgical treatment, disability, incidence and prevalence, and knowledge and attitudes. An exhaustive search (1965–2007) was done, including: (1) disparities by socioeconomic status (SES), race/ethnicity, age, or education of subgroups of the epilepsy population; or (2) disparities between people with epilepsy (PWE) and healthy people or with other chronic illnesses. Results: From 1,455 citations, 278 eligible abstracts were identified and 44 articles were reviewed. Comparative research data were scarce in all areas. PWE have been shown to have lower education and employment status; among PWE, differences in access to surgery have been shown by racial/ethnic groups. Aboriginals, women, and children have been shown to differ in use of health resources. Poor compliance has been shown to be associated with lower SES, insufficient insurance, poor relationship with treating clinicians, and not having regular responsibilities. Discussion: Comprehensive, comparative research on all aspects of disparities in epilepsy is needed to understand the causes of disparities and the development of any policies aimed at addressing health disparities and minimizing their impact.

It remains unclear whether drug-resistant temporal lobe epilepsy (TLE) is associated with cumulative brain damage, with no expert consensus and no quantitative syntheses of the available evidence.We conducted a systematic review and meta-analysis of MRI studies on progressive atrophy, searching PubMed and Ovid MEDLINE databases for cross-sectional and longitudinal quantitative MRI studies on drug-resistant TLE.We screened 2,976 records and assessed eligibility of 248 full-text articles. Forty-two articles met the inclusion criteria for quantitative evaluation. We observed a predominance of cross-sectional studies, use of different clinical indices of progression, and high heterogeneity in age-control procedures. Meta-analysis of 18/1 cross-sectional/longitudinal studies on hippocampal atrophy (n = 979 patients) yielded a pooled effect size of r = -0.42 for ipsilateral atrophy related to epilepsy duration (95% confidence interval [CI] -0.51 to -0.32; p < 0.0001; I2 = 65.22%) and r = -0.35 related to seizure frequency (95% CI -0.47 to -0.22; p < 0.0001; I2 = 61.97%). Sensitivity analyses did not change the results. Narrative synthesis of 25/3 cross-sectional/longitudinal studies on whole brain atrophy (n = 1,504 patients) indicated that >80% of articles reported duration-related progression in extratemporal cortical and subcortical regions. Detailed analysis of study design features yielded low to moderate levels of evidence for progressive atrophy across studies, mainly due to dominance of cross-sectional over longitudinal investigations, use of diverse measures of seizure estimates, and absence of consistent age control procedures.While the neuroimaging literature is overall suggestive of progressive atrophy in drug-resistant TLE, published studies have employed rather weak designs to directly demonstrate it. Longitudinal multicohort studies are needed to unequivocally differentiate aging from disease progression.

A major limitation of intracranial electroencephalography (iEEG) is recording from a confined region. This may falsely localize seizure onset if the distinction between ictal onset zone, proximity, and spread is unclear, or if the ictal rhythm is not clearly identified. Delineation of the ictal onset zone is crucial for surgical success. We appraised the evidence to determine whether specific iEEG ictal patterns are associated with the ictal onset zone.We searched Embase for articles in English until September 30, 2014, with MeSH keywords related to intracranially implanted electrodes and seizures. Two authors independently screened abstracts, reviewed full text articles, and abstracted data. The association between seizure outcome and type of ictal onset pattern (IOP), and its extent, location, and spread were explored visually or by univariate analysis when sufficient data were provided. Methodologic quality of each study was assessed.We reviewed 1,987 abstracts from which 21 articles were analyzed. Fifteen IOPs were reported. Low frequency high amplitude repetitive spiking (LFRS) was the most frequently reported IOP by studies that dealt with mesial temporal lobe epilepsy (mTLE) and investigated with depth electrodes. In neocortical epilepsy, low voltage fast activity (LVFA) was the most commonly described IOP. Delta activity was an infrequently reported IOP and was described mostly as a spread pattern.LFRS is associated with good surgical outcome in mTLE and has a strong relation with mesial temporal pathology and its severity. LVFA is associated with neocortical temporal epilepsy and focal LVFA is associated with better surgical outcome. Electrodecrement may be associated with regional or widespread onsets. Rhythmic delta is a propagation rhythm rather than an IOP. Focal IOPs and slower propagation times are associated with better outcomes. The quality of the studies is suboptimal and there are methodological problems. Interobserver agreement is poorly documented.

Purpose: The objective of this systematic review was to identify: (1) prevalence and severity of psychiatric conditions before and after resective epilepsy surgery, (2) incidence of postsurgical psychiatric conditions, and (3) predictors of psychiatric status after surgery. Methods: A literature search was conducted using PubMed, EmBase, and the Cochrane database as part of a larger project on the development of an appropriateness and necessity rating tool to identify patients of all ages with potentially resectable focal epilepsy. The search yielded 5,061 articles related to epilepsy surgery and of the 763 articles meeting the inclusion criteria and reviewed in full text, 68 reported psychiatric outcomes. Thirteen articles met the final eligibility criteria. Key Findings: The studies demonstrated either improvements in psychiatric outcome postsurgery or no changes in psychiatric outcome. Only one study demonstrated deterioration in psychiatric status after surgery, with higher anxiety in the context of continued seizures post-surgery. One study reported a significantly increased rate of psychosis after surgery. The two main predictors of psychiatric outcome were seizure freedom and presurgical psychiatric history. De novo psychiatric conditions occurred postsurgery at a rate of 1.1–18.2%, with milder psychiatric issues (e.g., adjustment disorder) being more common than more severe psychiatric issues (e.g., psychosis). Significance: Overall, studies demonstrated either improvement in psychiatric outcomes postsurgery or no change. However, there is a need for more prospective, well-controlled studies to better delineate the prevalence and severity of psychiatric conditions occurring in the context of epilepsy surgery, and to identify specific predictors of psychiatric outcomes after epilepsy surgery.

Summary The effect of continuous electrical stimulation of the hippocampus bilaterally on seizures and memory was assessed in two subjects with seizures from both mesial temporal lobes who were not candidates for resective epilepsy surgery. A double blind, randomized, controlled, cross‐over trial design was utilized. Two electrodes with four contacts each were implanted along the axis of the hippocampus bilaterally. Simultaneous stimulation of all electrodes contacts was either on or off during each 3‐month interval. Seizure frequency decreased by 33% in the two patients during stimulation and remained lower by 25% for the 3 months after stimulation was turned off before returning to baseline (p &lt; 0.01). No consistent change in objective or subjective measures of memory occurred. No other adverse effects occurred. Seizure frequency is reduced both during and for a period after bilateral hippocampal stimulation, but the overall impact in this study is not as robust as has been previously reported.

Summary A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure‐free during pregnancy. The committee evaluated the available evidence according to a structured literature review and classification of relevant articles. For WWE who are taking antiepileptic drugs (AEDs), there is probably no substantially increased risk (&gt;2 times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (&gt;1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. WWE should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84–92%) of remaining seizure‐free during pregnancy. WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery.

Epilepsy surgery is an effective treatment in many patients with drug-resistant focal epilepsies. An early decision for surgical therapy is facilitated by a magnetic resonance imaging (MRI)-visible brain lesion congruent with the electrophysiologically abnormal brain region. Recent advances in the pathologic diagnosis and classification of epileptogenic brain lesions are helpful for clinical correlation, outcome stratification, and patient management. However, application of international consensus classification systems to common epileptic pathologies (e.g., focal cortical dysplasia [FCD] and hippocampal sclerosis [HS]) necessitates standardized protocols for neuropathologic workup of epilepsy surgery specimens. To this end, the Task Force of Neuropathology from the International League Against Epilepsy (ILAE) Commission on Diagnostic Methods developed a consensus standard operational procedure for tissue inspection, distribution, and processing. The aims are to provide a systematic framework for histopathologic workup, meeting minimal standards and maximizing current and future opportunities for morphofunctional correlations and molecular studies for both clinical care and research. Whenever feasible, anatomically intact surgical specimens are desirable to enable systematic analysis in selective hippocampectomies, temporal lobe resections, and lesional or nonlesional neocortical samples. Correct orientation of sample and the sample's relation to neurophysiologically aberrant sites requires good communication between pathology and neurosurgical teams. Systematic tissue sampling of 5-mm slabs along a defined anatomic axis and application of a limited immunohistochemical panel will ensure a reliable differential diagnosis of main pathologies encountered in epilepsy surgery.

Abstract BACKGROUND: Due to uncertain evidence, lumbar fusion for degenerative indications is associated with the greatest measured practice variation of any surgical procedure. OBJECTIVE: To summarize the current evidence on the comparative safety and efficacy of lumbar fusion, decompression-alone, or nonoperative care for degenerative indications. METHODS: A systematic review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (up to June 30, 2016). Comparative studies reporting validated measures of safety or efficacy were included. Treatment effects were calculated through DerSimonian and Laird random effects models. RESULTS: The literature search yielded 65 studies (19 randomized controlled trials, 16 prospective cohort studies, 15 retrospective cohort studies, and 15 registries) enrolling a total of 302 620 patients. Disability, pain, and patient satisfaction following fusion, decompression-alone, or nonoperative care were dependent on surgical indications and study methodology. Relative to decompression-alone, the risk of reoperation following fusion was increased for spinal stenosis (relative risk [RR] 1.17, 95% confidence interval [CI] 1.06-1.28) and decreased for spondylolisthesis (RR 0.75, 95% CI 0.68-0.83). Among patients with spinal stenosis, complications were more frequent following fusion (RR 1.87, 95% CI 1.18-2.96). Mortality was not significantly associated with any treatment modality. CONCLUSION: Positive clinical change was greatest in patients undergoing fusion for spondylolisthesis while complications and the risk of reoperation limited the benefit of fusion for spinal stenosis. The relative safety and efficacy of fusion for chronic low back pain suggests careful patient selection is required (PROSPERO International Prospective Register of Systematic Reviews number, CRD42015020153).

Depression affects approximately 25% of epilepsy patients. However, the optimal tool to screen for depression in epilepsy has not been definitively established. The purpose of this study was to systematically review the literature on the validity of depression-screening tools in epilepsy.MEDLINE, EMBASE, and PsycINFO were searched until April 4, 2016 with no restriction on dates. Abstract, full-text review and data abstraction were conducted in duplicate. We included studies that evaluated the validity of depression-screening tools and reported measures of diagnostic accuracy (e.g., sensitivity, specificity, and negative and positive predictive values) in epilepsy. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies Version 2. Medians and ranges for estimates of diagnostic accuracy were calculated when appropriate.A total of 16,070 abstracts were screened, and 38 articles met eligibility criteria. Sixteen screening tools were validated in 13 languages. The most commonly validated screening tool was the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) (n = 26). The Mini International Neuropsychiatric Interview (MINI) (n = 19) was the most common reference standard used. At the most common cutpoint of >15 (n = 12 studies), the NDDI-E had a median sensitivity of 80.5% (range 64.0-100.0) and specificity of 86.2 (range 81.0-95.6). Meta-analyses were not possible due to variability in cutpoints assessed, reference standards used, and lack of confidence intervals reported.A number of studies validated depression screening tools; however, estimates of diagnostic accuracy were inconsistently reported. The validity of scales in practice may have been overestimated, as cutpoints were often selected post hoc based on the study sample. The NDDI-E, which performed well, was the most commonly validated screening tool, is free to the public, and is validated in multiple languages and is easy to administer, although selection of the best tool may vary depending on the setting and available resources.

The objective of this study was to develop and validate coding algorithms for epilepsy using ICD-coded inpatient claims, physician claims, and emergency room (ER) visits. 720/2049 charts from 2003 and 1533/3252 charts from 2006 were randomly selected for review from 13 neurologists' practices as the "gold standard" for diagnosis. Epilepsy status in each chart was determined by 2 trained physicians. The optimal algorithm to identify epilepsy cases was developed by linking the reviewed charts with three administrative databases (ICD 9 and 10 data from 2000 to 2008) including hospital discharges, ER visits and physician claims in a Canadian health region. Accepting chart review data as the gold standard, we calculated sensitivity, specificity, positive, and negative predictive value for each ICD-9 and ICD-10 administrative data algorithm (case definitions). Of 18 algorithms assessed, the most accurate algorithm to identify epilepsy cases was "2 physician claims or 1 hospitalization in 2 years coded" (ICD-9 345 or G40/G41) and the most sensitive algorithm was "1 physician clam or 1 hospitalization or 1 ER visit in 2 years." Accurate and sensitive case definitions are available for research requiring the identification of epilepsy cases in administrative health data.

We systematically reviewed evidence-based determinants of health-related quality of life (QOL) in adults undergoing epilepsy surgery and assessed the effect of study methods. Medline, Embase, and the Cochrane library (1950-2008) were searched systematically. Two authors independently performed every step of the review. We obtained the proportion of studies reporting statistically significant positive or negative impact on QOL. Of 39 eligible studies, 32 assessed the impact of surgery on QOL and 29 (90.6%) found a significant positive effect. The most prevalent preoperative determinant was psychological function. Seizure freedom was the most prevalent postoperative determinant (80% of studies), followed by antiepileptic drug adverse events, employment status, and psychological function. Psychosocial (95%), physical (91%), and overall QOL (90%) domains improved most frequently, whereas role limitation (63%) and cognition (78%) improved least frequently. Methods, choice of instrument, and time of measurement influenced QOL outcomes and should be carefully chosen in future studies.

Summary The ILAE Task Force on Classification presents a road map for the development of an updated, relevant classification of the epilepsies. Our objective is to explain the process to date and the plan moving forward as well as to invite further discussion about the newly proposed terms and concepts. Here, we present our response to feedback about the 2010 Organization of the Epilepsies and clarify the reintroduction of the word “classification” to map out a framework for epilepsy diagnosis. We introduce some new concepts and suggest four diagnostic levels: seizure type, epilepsy category, epilepsy syndrome, and epilepsy with (specific) etiology to denote specific levels of diagnosis. We expand the etiological categories to six, focusing on those with treatment implications. Finally, we discuss the changes in terminology originally suggested and modifications in response to comments from the epilepsy community. We welcome feedback and discussion from the global epilepsy community, particularly for the new suggested terms, so that we can cement a classification that both reflects current thinking and scientific understanding and provides a dynamic, evolving framework.

<h3>Objectives:</h3> In the current study, we aim to assess potential neurologist-related barriers to epilepsy surgery among Canadian neurologists. <h3>Methods:</h3> A 29-item, pilot-tested questionnaire was mailed to all neurologists registered to practice in Canada. Survey items included the following: (1) type of medical practice, (2) perceptions of surgical risks and benefits, (3) knowledge of existing practice guidelines, and (4) barriers to surgery for patients with epilepsy. Neurologists who did not complete the questionnaire after the initial mailing were contacted a second time by e-mail, fax, or telephone. After this reminder, the survey was mailed a second time to any remaining nonresponders. <h3>Results:</h3> In total, 425 of 796 neurologists returned the questionnaire (response rate 53.5%). Respondents included 327 neurologists who followed patients with epilepsy in their practice. More than half (56.6%) of neurologists required patients to be drug-resistant and to have at least one seizure per year before considering surgery, and nearly half (48.6%) failed to correctly define drug-resistant epilepsy. More than 75% of neurologists identified inadequate health care resources as the greatest barrier to surgery for patients with epilepsy. <h3>Conclusions:</h3> A substantial proportion of Canadian neurologists are unaware of recommended standards of practice for epilepsy surgery. Access also appears to be a significant barrier to epilepsy surgery and surgical evaluation. As a result, we are concerned that patients with epilepsy are receiving inadequate care. A greater emphasis must be placed on knowledge dissemination and ensuring that the infrastructure and personnel are in place to allow patients to have timely access to this evidence-based treatment.

Background: There is a role for brief assessment instruments in detection and management of major depression in MS. However, candidate scales have rarely been validated against a validated diagnostic interview. In this study, we evaluated the performance of several candidate scales: Patient Health Questionnaire (PHQ)-9, PHQ-2, Center for Epidemiologic Studies Depression rating scale (CES-D), and Hospital Anxiety and Depression Scale (HADS-D) in relation to the Structured Clinical Interview for DSM-IV (SCID). Methods: The sample was an unselected series of 152 patients attending a multiple sclerosis (MS) clinic. Participants completed the scales during a clinic visit or returned them by mail. The SCID was administered by telephone within two weeks. The diagnosis of major depressive episode, according to the SCID, was used as a reference standard. Receiver-operator curves (ROC) were fitted and indices of measurement accuracy were calculated. Results: All of the scales performed well, each having an area under the ROC &gt; 90%. For example, the PHQ-9 had 95% sensitivity and 88.3% specificity when scored with a cut-point of 11. This cut-point achieved a 56% positive predictive value for major depression. Conclusions: While all of the scales performed well in terms of their sensitivity and specificity, the availability of the PHQ-9 in the public domain and its brevity may enhance the feasibility of its use.

<h3>Importance</h3> Levetiracetam is a commonly used antiepileptic drug, yet psychiatric adverse effects are common and may lead to treatment discontinuation. <h3>Objective</h3> To derive prediction models to estimate the risk of psychiatric adverse effects from levetiracetam use. <h3>Design, Setting, and Participants</h3> Retrospective open cohort study. All patients meeting the case definition for epilepsy after the Acceptable Mortality Reporting date in The Health Improvement Network (THIN) database based in the United Kingdom (inclusive January 1, 2000, to May 31, 2012) who received a first-ever prescription for levetiracetam were included. Of 11 194 182 patients registered in THIN, this study identified 7400 presumed incident cases (66.1 cases per 100 000 persons) over a maximum of 12 years’ follow-up. The index date was when patients received their first prescription code for levetiracetam, and follow-up lasted 2 years or until an event, loss to follow-up, or censoring. The analyses were performed on April 22, 2018. <h3>Exposure</h3> A presumed first-ever prescription for levetiracetam. <h3>Main Outcomes and Measures</h3> The outcome of interest was a Read code for any psychiatric sign, symptom, or disorder as reached through consensus by 2 authors. This study used regression techniques to derive 2 prediction models, one for the overall population and one for those without a history of a psychiatric sign, symptom, or disorder during the study period. <h3>Results</h3> Among 1173 patients with epilepsy receiving levetiracetam, the overall median age was 39 (interquartile range, 25-56) years, and 590 (50.3%) were female. A total of 14.1% (165 of 1173) experienced a psychiatric symptom or disorder within 2 years of index prescription. The odds of reporting a psychiatric symptom were significantly elevated for women (odds ratio [OR], 1.41; 95% CI, 0.99-2.01;<i>P</i>= .05) and those with a preexposure history of higher social deprivation (OR, 1.15; 95% CI, 1.01-1.31;<i>P</i>= .03), depression (OR, 2.20; 95% CI, 1.49-3.24;<i>P</i>&lt; .001), anxiety (OR, 1.74; 95% CI, 1.11-2.72;<i>P</i>= .02), or recreational drug use (OR, 2.02; 95% CI, 1.20-3.37;<i>P</i>= .008). The model performed well after stratified k = 5-fold cross-validation (area under the curve [AUC], 0.68; 95% CI, 0.58-0.79). There was a gradient in risk, with probabilities increasing from 8% for 0 risk factors to 11% to 17% for 1, 17% to 31% for 2, 30% to 42% for 3, and 49% when all risk factors were present. For those free of a preexposure psychiatric code, a second model performed comparably well after k = 5-fold cross-validation (AUC, 0.72; 95% CI, 0.54-0.90). Specificity was maximized using threshold cutoffs of 0.10 (full model) and 0.14 (second model); a score below these thresholds indicates safety of prescription. <h3>Conclusions and Relevance</h3> This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam. These algorithms can be used to guide prescription in clinical practice.

• This clinical practice guideline addresses automated seizure detection using wearable devices. • The guideline was developed by a working group of the ILAE and IFCN using the GRADE system. • Wearable devices are effective for accurate detection of generalized tonic-clonic seizures and focal-to-bilateral tonic-clonic seizures. • It is uncertain whether the detection alarms result in meaningful clinical outcomes for patients until further research is completed. • Wearable devices are recommended for detection of tonic-clonic seizures (weak / conditional recommendation). The objective of this clinical practice guideline (CPG) is to provide recommendations for healthcare personnel working with patients with epilepsy, on the use of wearable devices for automated seizure detection in patients with epilepsy, in outpatient, ambulatory settings. The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology developed the CPG according to the methodology proposed by the ILAE Epilepsy Guidelines Working Group. We reviewed the published evidence using The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and evaluated the evidence and formulated the recommendations following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We found high level of evidence for the accuracy of automated detection of generalized tonic-clonic seizures (GTCS) and focal-to-bilateral tonic-clonic seizures (FBTCS) and recommend use of wearable automated seizure detection devices for selected patients when accurate detection of GTCS and FBTCS is recommended as a clinical adjunct. We also found moderate level of evidence for seizure types without GTCs or FBTCs. However, it was uncertain whether the detected alarms resulted in meaningful clinical outcomes for the patients. We recommend using clinically validated devices for automated detection of GTCS and FBTCS, especially in unsupervised patients, where alarms can result in rapid intervention (weak/conditional recommendation). At present, we do not recommend clinical use of the currently available devices for other seizure types (weak/conditional recommendation). Further research and development are needed to improve the performance of automated seizure detection and to document their accuracy and clinical utility.

The coronavirus disease 2019 (COVID-19) pandemic has affected the care of all patients around the world. The International League Against Epilepsy (ILAE) COVID-19 and Telemedicine Task Forces examined, through surveys to people with epilepsy (PWE), caregivers, and health care professionals, how the pandemic has affected the well-being, care, and services for PWE. The ILAE included a link on their website whereby PWE and/or their caregivers could fill out a survey (in 11 languages) about the impact of the COVID-19 pandemic, including access to health services and impact on mental health, including the 6-item Kessler Psychological Distress Scale. An anonymous link was also provided whereby health care providers could report cases of new-onset seizures or an exacerbation of seizures in the context of COVID-19. Finally, a separate questionnaire aimed at exploring the utilization of telehealth by health care professionals since the pandemic began was available on the ILAE website and also disseminated to its members. Seventeen case reports were received; data were limited and therefore no firm conclusions could be drawn. Of 590 respondents to the well-being survey (422 PWE, 166 caregivers), 22.8% PWE and 27.5% caregivers reported an increase in seizure frequency, with difficulty in accessing medication and health care professionals reported as barriers to care. Of all respondents, 57.1% PWE and 21.5% caregivers had severe psychological distress (k score >13), which was significantly higher among PWE than caregivers (p<0.01). An increase in telemedicine use during the COVID-19 pandemic was reported by health care professionals, with 40% of consultations conducted by this method. Although 74.9% of health care providers thought that this impacted positively, barriers to care were also identified. As we move forward, there is a need to ensure ongoing support and care for PWE to prevent a parallel pandemic of unmet health care needs.

Abstract The objective of this clinical practice guideline (CPG) is to provide recommendations for healthcare personnel working with patients with epilepsy on the use of wearable devices for automated seizure detection in patients with epilepsy, in outpatient, ambulatory settings. The Working Group of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) developed the CPG according to the methodology proposed by the ILAE Epilepsy Guidelines Working Group. We reviewed the published evidence using The Preferred Reporting Items for Systematic Review and Meta‐Analysis (PRISMA) statement and evaluated the evidence and formulated the recommendations following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We found high level of evidence for the accuracy of automated detection of generalized tonic‐clonic seizures (GTCS) and focal‐to‐bilateral tonic‐clonic seizures (FBTCS) and recommend the use of wearable automated seizure detection devices for selected patients when accurate detection of GTCS and FBTCS is recommended as a clinical adjunct. We also found a moderate level of evidence for seizure types without GTCS or FBTCS. However, it was uncertain whether the detected alarms resulted in meaningful clinical outcomes for the patients. We recommend using clinically validated devices for automated detection of GTCS and FBTCS, especially in unsupervised patients, where alarms can result in rapid intervention (weak/conditional recommendation). At present, we do not recommend clinical use of the currently available devices for other seizure types (weak/conditional recommendation). Further research and development are needed to improve the performance of automated seizure detection and to document their accuracy and clinical utility.

<h3>Importance</h3> Enzyme-inducing antiseizure medications (eiASMs) have been hypothesized to be associated with long-term risks of cardiovascular disease. <h3>Objective</h3> To quantify and model the putative hazard of cardiovascular disease secondary to eiASM use. <h3>Design, Setting, and Participants</h3> This cohort study covered January 1990 to March 2019 (median [IQR] follow-up, 9 [4-15], years). The study linked primary care and hospital electronic health records at National Health Service hospitals in England. People aged 18 years or older diagnosed as having epilepsy after January 1, 1990, were included. All eligible patients were included with a waiver of consent. No patients were approached who withdrew consent. Analysis began January 2021 and ended August 2021. <h3>Exposures</h3> Receipt of 4 consecutive eiASMs (carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide, or topiramate) following an adult-onset (age ≥18 years) epilepsy diagnosis or repeated exposure in a weighted cumulative exposure model. <h3>Main Outcomes and Measures</h3> Three cohorts were isolated, 1 of which comprised all adults meeting a case definition for epilepsy diagnosed after 1990, 1 comprised incident cases diagnosed after 1998 (hospital linkage date), and 1 was limited to adults diagnosed with epilepsy at 65 years or older. Outcome was incident cardiovascular disease (ischemic heart disease or ischemic or hemorrhagic stroke). Hazard of incident cardiovascular disease was evaluated using adjusted propensity-matched survival analyses and weighted cumulative exposure models. <h3>Results</h3> Of 10 916 166 adults, 50 888 (0.6%) were identified as having period-prevalent cases (median [IQR] age, 32 [19-50] years; 16 584 [53%] female), of whom 31 479 (62%) were diagnosed on or after 1990 and were free of cardiovascular disease at baseline. In a propensity-matched Cox proportional hazards model adjusted for age, sex, baseline socioeconomic status, and cardiovascular risk factors, the hazard ratio for incident cardiovascular disease was 1.21 (95% CI, 1.06-1.39) for those receiving eiASMs. The absolute difference in cumulative hazard diverges by more than 1% and greater after 10 years. For those with persistent exposure beyond 4 prescriptions, the median hazard ratio increased from amedian (IQR) of 1.54 (1.28-1.79) when taking a relative defined daily dose of an eiASM of 1 to 2.38 (1.52-3.56) with a relative defined daily dose of 2 throughout a maximum of 25 years’ follow-up compared with those not receiving an eiASM. The hazard was elevated but attenuated when restricting analyses to incident cases or those diagnosed when older than 65 years. <h3>Conclusions and Relevance</h3> The hazard of incident cardiovascular disease is higher in those receiving eiASMs. The association is dose dependent and the absolute difference in hazard seems to reach clinical significance by approximately 10 years from first exposure.

The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography (iEEG) performed in difficult-to-localize drug-resistant focal epilepsy.The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit).Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE).In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939.

Abstract Objective To review the evidence of felt and enacted stigma and attitudes toward persons living with epilepsy, and their determining factors. Methods Thirteen databases were searched (1985–2019). Abstracts were reviewed in duplicate and data were independently extracted using a standardized form. Studies were characterized using descriptive analysis by whether they addressed “felt” or “enacted” stigma and “attitudes” toward persons living with epilepsy. Results Of 4234 abstracts, 132 met eligibility criteria and addressed either felt or enacted stigma and 210 attitudes toward epilepsy. Stigma frequency ranged broadly between regions. Factors associated with enacted stigma included low level of knowledge about epilepsy, lower educational level, lower socioeconomic status, rural areas living, and religious grouping. Negative stereotypes were often internalized by persons with epilepsy, who saw themselves as having an “undesirable difference” and so anticipated being treated differently. Felt stigma was associated with increased risk of psychological difficulties and impaired quality of life. Felt stigma was linked to higher seizure frequency, recency of seizures, younger age at epilepsy onset or longer duration, lower educational level, poorer knowledge about epilepsy, and younger age. An important finding was the potential contribution of epilepsy terminology to the production of stigma. Negative attitudes toward those with epilepsy were described in 100% of included studies, and originated in any population group (students, teachers, healthcare professionals, general public, and those living with epilepsy). Better attitudes were generally noted in those of younger age or higher educational status. Significance Whatever the specific beliefs about epilepsy, implications for felt and enacted stigma show considerable commonality worldwide. Although some studies show improvement in attitudes toward those living with epilepsy over time, much work remains to be done to improve attitudes and understand the true occurrence of discrimination against persons with epilepsy.

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English-language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease-modifying" effects. A more-refined terminology to describe precisely these actions needs to be developed.

To assess the point prevalence of self-described epilepsy in the general population nationally, provincially, and in different groups of interest.We analyzed data from two national health surveys, the National Population Health Survey (NPHS, N=49,000) and the Community Health Survey (CHS, N=130,882). Both surveys captured sociodemographic information, as well as age, sex, education, ethnicity, household income, and labor force status of participants. Epilepsy was ascertained with only one question in both surveys. "Do you have epilepsy diagnosed by a health professional?" (NPHS) and "Do you have epilepsy?" (CHS). Prevalences were age-adjusted by using national standard populations at the time of each survey. Exact 95% confidence intervals were obtained.In the NPHS, 241 of 49,026 subjects described themselves as having been diagnosed with epilepsy, yielding a weighted point prevalence of 5.2 per 1,000 [95% confidence interval (CI), 4.9-5.4]. In the CHS, 835 of 130,822 subjects described themselves as having epilepsy, yielding a weighted point prevalence of 5.6 per 1,000 (95% CI, 5.1-6.0). Trends in differences in prevalence among some Canadian provinces were observed. Prevalence was statistically significantly higher in groups with the lowest educational level, lowest income, and in those unemployed in the previous year. Prevalence also was higher in nonimmigrants than in immigrants.The overall and group-specific results are in keeping with those obtained in other developed countries by using different ascertainment methods. We discuss methodologic aspects related to the ascertainment of epilepsy in both surveys, and to the validity and implications of our findings.

To fulfill its task of informed clinical decision making and resource allocation, epidemiological studies in epilepsy must adhere to a series of methodological standards. These are reviewed. Because seizure and epilepsy classification systems may be viewed as extensions of the diagnosis, they have direct implications in the acquisition and interpretation of epidemiologic data. The International League Against Epilepsy (ILAE) classification systems are analyzed in this light. Finally, the lack of Canadian epidemiological studies is addressed, and the relevance and potential of Canadian epidemiological data in epilepsy is discussed.

To provide a descriptive analysis of the prevalence and pattern of psychiatric morbidity among 300 consecutive epileptic patients refractive to treatment and admitted during a six year period for evaluation of their candidature for surgery.Patients underwent detailed observation of their seizure and standardised psychiatric assessment. Patients were considered to be refractory to treatment if they continued to manifest seizures with an average frequency of at least once every month even with polytherapy using up to three different anti-convulsants for a period of at least two years. Of the 300 patients, 231 had a temporal lobe focus, 43 had a non-temporal lobe focus, and 26 patients had a generalised and multifocal seizure onset.With the DSM-III-R criteria 142 (47.3%) patients emerged as psychiatric cases. A principal axis I diagnosis was made in 88 (29.3%), and an axis II diagnosis (personality disorder) in another 54 (18.0%) patients. The most common axis I diagnosis was anxiety disorders (10.7%). A schizophrenia-like psychosis was seen in 13 (4.3%). Most patients with personality disorders showed dependent and avoidant personality traits. There was a significantly higher psychotic subscore on the present state examination in the temporal than with the non-temporal group of patients. These findings were not significant when compared with patients with a generalised and multifocal seizure disorder. There were no significant findings between the different seizure focus groups on the neurotic subscores. The findings with regard to laterality of seizure focus and the neurotic or psychotic subscores were not significant.

High frequency oscillations (HFOs) >200 Hz are believed to be associated with epileptic processes. The spatial distribution of HFOs and their evolution over time leading up to seizure onset is unknown. Also, recording HFOs through conventional intracranial electrodes is not well established. We therefore wished to determine whether HFOs could be recorded using commercially available depth macroelectrodes. We also examined the spatial distribution and temporal progression of HFOs during the transition to seizure activity.Intracranial electroencephalography (EEG) recordings of 19 seizures were obtained from seven patients with temporal lobe epilepsy using commercial depth or subdural electrodes. EEG recordings were analyzed for frequency content in five spectral bands spanning DC-500 Hz. We examined the spatial distribution of the different spectral bands 5 s before and 5 s after seizure onset. Temporal changes in the spectral bands were studied in the 30-s period leading up to seizure onset.Three main observations were made. First, HFOs (100-500 Hz) can be recorded using commercial depth and subdural grid electrodes. Second, HFOs, but not <100 Hz oscillations, were localized to channels of ictal onset (100-200, 400-500 Hz, p < 0.05; 300-400 Hz, p < 0.001). Third, temporal analysis showed increased HFO power for approximately 8 s prior to electrographic onset (p < 0.05).These results suggest that HFOs can be recorded by depth macroelectrodes. Also, HFOs are localized to the region of primary ictal onset and can exhibit increased power during the transition to seizure. Thus, HFOs likely represent important precursors to seizure initiation.

The American Epilepsy Society and the Epilepsy Foundation jointly convened a task force to assess the state of knowledge about sudden unexplained death in epilepsy (SUDEP). The task force had five charges: (1) develop a position statement describing if, when, what, and how SUDEP should be discussed with patients and their families and caregivers; (2) design methods by which the medical and lay communities become aware of the risk of SUDEP; (3) recommend research directions in SUDEP; (4) explore steps that organizations can take to perform large-scale, prospective studies of SUDEP to identify risk factors; and (5) identify possible preventive strategies for SUDEP. Some of the major task force recommendations include convening a multidisciplinary workshop to refine current lines of investigation and to identify additional areas of research for mechanisms underlying SUDEP; performing a survey of patients and their families and caregivers to identify effective means of education that will enhance participation in SUDEP research; conducting a campaign aimed at patients, families, caregivers, coroners, and medical examiners that emphasizes the need for complete autopsy examinations for patients with suspected SUDEP; and securing infrastructure grants to fund a consortium of centers that will conduct prospective clinical and basic research studies to identify preventable risk factors and mechanisms underlying SUDEP. For now, the principal effort in preventing SUDEP should be prompt and optimal control of seizures, especially generalized convulsive seizures.

The negative impact of epilepsy is disproportionate to its prevalence. Our objectives were to determine if health-related behaviors (HRBs) and health status differ between patients with epilepsy, migraine, or diabetes.The 2001-2005 Canadian Community Health Survey (N = 400,055) was used to explore health status and HRBs in patients with epilepsy, migraine, and diabetes and in the general population. Weighted estimates of association were produced as proportions with 95% confidence intervals (CIs). Logistic regression was used to explore the association between demographic variables and HRBs in epilepsy.The prevalence of active epilepsy, migraine, and diabetes was 0.6%, 8.4%, and 3.8%, respectively. Those with epilepsy and diabetes were more likely than migraineurs to perceive their health as poor and to be physically inactive. Obesity and comorbidities were more likely in all chronic conditions studied compared to the general population. Those with epilepsy or migraine were significantly more likely to smoke compared to the general population or to those with diabetes. Those with epilepsy were more likely to ever have consumed more than 12 alcoholic drinks per week. Health monitoring did not differ between groups. In the logistic regression analysis, epilepsy was associated with physical inactivity and lower alcohol consumption in the past 12 months compared to the general population.Our study demonstrated that those with epilepsy have a poorer pattern of HRBs and poorer health status compared to the general population. Screening for and managing comorbidities, and promoting exemplary HRBs, should improve overall health and quality-of-life in those with epilepsy.

The objective of this study was to systematically review the literature to assess social outcomes after epilepsy surgery.A systematic literature search was conducted as part of a larger project on the development of an appropriateness and necessity rating tool to identify patients with focal epilepsy that may benefit from an epilepsy surgery evaluation. Studies were included if they reported postsurgical data on social outcomes (employment, driving, social relationships, marriage, education, financial status, behavior, and social interactions) and had a follow-up period of at least 24 months. Our search strategy yielded 5,061 studies. Sixty-five of these studies addressed social outcomes, but only 19 met all eligibility criteria.In adults, a significant improvement in full-time employment postsurgery was documented. The ability to drive was significantly increased after surgery and was dependent on seizure freedom. Patients generally perceived improved relationships, independence, and overall lifestyle postsurgery. Marital status generally remained unchanged when compared to controls, education improved modestly, and income/financial status changes depended on how it was assessed (e.g., income level vs. receipt of disability pension). In children, a study examining behavior showed improved social interactions in those who underwent surgery compared to controls. The results for other social outcome categories were more variable.Overall, the majority of studies reported improvement in social outcomes after surgery. However, prospective controlled observational studies using objective social outcome measures are necessary prior to making specific conclusions about the influence of surgery on social outcomes other than employment or driving status in all age groups, but particularly in children and the elderly.

To assess health-related quality of life (HRQL) over 2 years in children 4-12 years old with new-onset epilepsy and risk factors.Data are from a multicenter prospective cohort study, the Health-Related Quality of Life Study in Children with Epilepsy Study (HERQULES). Parents reported on children's HRQL and family factors and neurologists on clinical characteristics 4 times. Mean subscale and summary scores were computed for HRQL. Individual growth curve models identified trajectories of change in HRQL scores. Multiple regression identified baseline risk factors for HRQL 2 years later.A total of 374 (82) questionnaires were returned postdiagnosis and 283 (62%) of eligible parents completed all 4. Growth rates for HRQL summary scores were most rapid during the first 6 months and then stabilized. About one-half experienced clinically meaningful improvements in HRQL, one-third maintained their same level, and one-fifth declined. Compared with the general population, at 2 years our sample scored significantly lower on one-third of CHQ subscales and the psychosocial summary. After controlling for baseline HRQL, cognitive problems, poor family functioning, and high family demands were risk factors for poor HRQL 2 years later.On average, HRQL was relatively good but with highly variable individual trajectories. At least one-half did not experience clinically meaningful improvements or declined over 2 years. Cognitive problems were the strongest risk factor for compromised HRQL 2 years after diagnosis and may be largely responsible for declines in the HRQL of children newly diagnosed with epilepsy.

We explored the association between magnetic resonance imaging (MRI) lesion, degree of seizure laterality on intracranial electroencephalography (iEEG), and seizure outcome in patients with ambiguous or presumed bilateral temporal lobe epilepsy (BiTLE) on scalp EEG. We systematically reviewed the literature using Embase and MEDLINE up to May 31, 2012. Patients with bilateral iEEG, temporal lobe surgery, and follow-up ≥1 year were included. We undertook three separate analyses on patients whose scalp EEG showed ambiguous onset or BiTLE (1) group data of those whose iEEG demonstrated unilateral TLE, (2) group data of those whose iEEG demonstrated BiTLE, (3) individual patient analysis in those with BiTLE for whom iEEG seizure laterality data were provided. Of 1,403 patients with ambiguous or presumed BiTLE on scalp EEG, 1,027 (73%) proved to have unilateral TLE on iEEG and contributed to the first analysis. Of these, 58% had Engel class I and 9% Engel class II outcomes. Of 132 patients in the second analysis (true BiTLE), Engel class I and II outcomes were achieved in 23% and 14%, respectively. Of 41 patients in the third analysis, 66% and 2% had Engel class I and II outcomes, respectively. The median proportion of seizures ipsilateral to the resection on iEEG did not differ between BiTLE patients with Engel class I-II (76%) and Engel III-IV (78%) outcomes (p = 0.87). Patients with ambiguous or independent bitemporal seizure onset on scalp EEG achieved good surgical outcomes. Overall, a significantly higher proportion of patients achieved good outcomes when iEEG showed unilateral TLE (67%) than when it showed true BiTLE (45%). However, the degree of seizure lateralization in those with BiTLE was not associated with seizure outcome, and it has a limited role in selecting the side of surgery.

To develop an epilepsy-specific comorbidity risk adjustment index for mortality outcomes research.Data were extracted from five linked administrative databases in Calgary, Canada from April 1, 1996 to March 31, 2004. Epilepsy patients were defined using a validated ICD-9-CM- and ICD-10-CA-based case definition. An epilepsy-specific comorbidity index was developed using comorbidities from the Charlson and Elixhauser indexes and other relevant epilepsy comorbidities. In the final model, 14 comorbidities significantly associated with mortality remained and each was assigned a value of 1-6 based on the hazard ratio from the survival analysis. Total prognostic scores were calculated and compared for all subjects using the epilepsy-specific index and the Charlson index. Crude mortality and survival curves of both indices were compared.We identified 7,253 subjects who met our case definition for epilepsy. The mean age of participants was 38 years (range 0.03-96), and 52% were male. The mortality rate was 7.9%. High rates of chronic pulmonary disease (20.3%), hypertension (19.6%), cerebrovascular disease (13.7%), fracture (12.1%), depression (28.2%), and alcohol abuse (10.1%) were noted. Patients with lower total prognostic scores were more likely to survive than patients with higher scores, using both indices. However, increasing prognostic scores were more strongly associated with reduced survival using the epilepsy-specific index compared to the Charlson index.A new comorbidity index for epilepsy, designed to include clinically relevant conditions, provided better discrimination of crude mortality in a population-based group of epilepsy patients compared with the Charlson index.

Summary Objective We examine improvement and worsening in quality of life ( QOL ) in terms of proportions achieving minimum clinically important change ( MCID ), and factors related to MCID , in patients with temporal lobe epilepsy randomized to medical or surgical treatment. Methods Eighty patients with temporal lobe epilepsy randomized to surgical (n 1 = 40) or medical (n 2 = 40) therapy were followed for 12 months, reporting QOL at baseline, and at 6 and 12 months. Previously established thresholds for MCID across various general and epilepsy‐specific QOL instruments were used to determine meaningful improvement (positive MCID ) or worsening (negative MCID ). Generalized linear mixed‐effects models were used to compare MCID in both groups. Results At 6 months, 56.0% of patients in the surgical group achieved positive MCID on the Quality of Life in Epilepsy ( QOLIE )‐89, as compared to 11.0% of those in the medical group (p &lt; 0.001). On the QOLIE ‐31, 62.0% of the surgical group and 17.0% of the medical group achieved positive MCID (p &lt; 0.001). Substantially more medically treated patients exhibited clinically significant worsening in QOL , as compared with those surgically treated. The respective medical versus surgical proportions with worsening were 36.67% versus 13.8% in QOLIE 31, 20% versus 15% in Health Utility Index‐III (HUI‐III), and 30% versus 19% in Short Form‐36 (SF‐36) Mental Composite Score ( MCS) . The number of patients who need to undergo surgery for one additional person to have a meaningful improvement in the QOLIE ‐31 is two ( number needed to treat = 2). The results also favored surgery using the generic HUI ‐ III instrument, but not with the mental of physical function subscales of the SF ‐36. Significance Significantly more patients in the surgical group achieved meaningful improvement in epilepsy‐specific measures of QOL at 6 and 12 months compared to those in the medical group. Substantially more patients in the medical therapy group exhibited clinically significant worsening in their QOL assessed with epilepsy‐specific and generic instruments. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .

Depression is a common comorbidity of epilepsy, and its timely identification in persons with epilepsy is essential. The use of screening tools to detect depression is common in epilepsy, but some scales in current use have not been validated using a gold standard in this population. The present study aims to validate three commonly used depression-screening scales and assess new cut points for scoring in those with epilepsy.Persons with epilepsy (n = 300) from the only epilepsy clinic in a large urban health region completed questionnaires (e.g., sociodemographics, adverse event profile) and three depression-screening tools (Hospital Anxiety and Depression Scale [HADS]; Patient Health Questionnaire [PHQ]-9 and PHQ-2). One hundred eighty-five patients participated in a gold-standard structured clinical interview to assess depression. The diagnostic accuracy of the depression scales was assessed comparing a variety of scoring cut points to the gold-standard diagnosis of depression.The prevalence of current depression in this population, according to the gold-standard, was 14.6%. The scale with the highest sensitivity (84.6%) was the HADS with a cut point of 6 and the scale with the highest specificity (96.2%) was the PHQ-9 algorithm scoring method. Overall, the PHQ-9 at a cut point of 9 and the HADS at a cut point of 7 resulted in the greatest balance of sensitivity and specificity (area under the curve: 88% and 90%, respectively).The PHQ-9 at a cut point of 9 and the HADS at a cut point of 7 had the best overall balance of sensitivity and specificity. However, for screening purposes the PHQ-9 algorithm method is ideal (optimizing specificity), whereas for case finding the HADS at a cut point of 6 performed best (optimizing sensitivity). Appropriate scale cut points should be chosen based on the study's goals and available resources. Disease-specific scale cut points are recommended for future studies assessing depression in persons with epilepsy.

The objectives of this study were to estimate the prevalence of, and factors associated with, anxiety in epilepsy. We conducted a cross-sectional analysis using data from the Neurological Disease and Depression Study. The prevalence of anxiety and associated factors were assessed using descriptive statistics and logistic regression. Of the total sample (n = 250 patients), nearly 40.0% of participants had anxiety according to the Hospital Anxiety and Depression Scale. The most prevalent symptom of anxiety was "worrying thoughts" (35.6%). After adjustment for age and sex, depression (odds ratio [OR] = 8.97, 95% confidence interval [CI] = 4.38-18.40), medication side effects (OR = 1.79, 95% CI = 1.04-3.05), smoking (OR = 4.35, 95% CI = 2.27-8.31), and illicit substance use (OR = 2.42, 95% CI = 1.18-4.96) were significantly associated with higher odds of anxiety, whereas higher education (OR = 0.47, 95% CI = 0.28-0.80) was associated with lower odds of anxiety. Furthermore, participants with anxiety reported more severe epilepsy, debilitating seizures, and overall lower quality of life. Evidence from our study reveals a high prevalence of anxiety in persons with epilepsy and that anxiety is associated with a variety of negative outcomes. These findings further emphasize the need for more studies to understand the impact of anxiety and its relationship with various sociodemographic and clinical factors.

ABSTRACT Teaching competency in the diagnosis and clinical management of epilepsy is of utmost importance for the ILAE. To achieve this mission, the Task Force for Epilepsy Education (EpiEd) developed a competency‐based curriculum for epileptology, covering the spectrum of skills and knowledge for best medical practice. The curriculum encompasses seven domains, 42 competencies, and 124 learning objectives, divided into three levels: entry (Level 1), proficiency (Level 2), and advanced proficiency (Level 3). A survey of the currently existing ILAE‐endorsed teaching activities identified a significant gap in education of basic knowledge of epileptology (Level 1). To bridge this gap, a web‐based educational tool is being developed. A virtual campus will be constructed around the curriculum, integrating the various educational activities of the ILAE. This paper describes the development of the curriculum and future tasks necessary to achieve the educational goal of the ILAE.

The International League Against Epilepsy (ILAE) Epilepsy Guidelines Task Force, composed of 14 international members, was established in 2011 to identify, using systematic review methodology, international epilepsy clinical care guidelines, assess their quality, and determine gaps in areas of need of development.A systematic review of the literature (1985-2014) was performed in six electronic databases (e.g. Medline, Embase) using a broad search strategy without initial limits to language or study design. Six gray literature databases (e.g., American Academy of Neurology [AAN], ILAE) were also searched to minimize publication bias. Two independent reviewers screened abstracts, reviewed full text articles, and performed data abstraction. Descriptive statistics and a meta-analysis were generated.The search identified 10,926 abstracts. Of the 410 articles selected for full text review, 63 met our eligibility criteria for a guideline. Of those included, 54 were in English and 9 were in other languages (French, Spanish, and Italian). Of all guidelines, 29% did not specify the target age groups, 27% were focused on adults, 22% included only children, and 6% specifically addressed issues related to women with epilepsy. Guidelines included in the review were most often aimed at guiding clinical practice for status epilepticus (n = 7), first seizure (n = 6), drug-resistant epilepsy (n = 5), and febrile seizures (n = 4), among others. Most of the guidelines were therapeutic (n = 35) or diagnostic (n = 16) in nature. The quality of the guidelines using a 1-7 point scale (7 = highest) varied and was moderate overall (mean = 4.99 ± 1.05 [SD]).We identified substantial gaps in topics (e.g., epilepsy in the elderly) and there was considerable heterogeneity in methodologic quality. The findings should offer a valuable resource for health professionals caring for people with epilepsy, since they will help guide the prioritization, development, and dissemination of future epilepsy-related guidelines.

It is unclear whether anxiety and depression impact health-related quality of life (HRQoL) equally across neurological diseases. This study examines the association between anxiety or depression and HRQoL in select neurological disorders. HRQoL was measured using the Short Form Health Survey (SF-12) in neurological patients: epilepsy (n = 279), migraine (n = 268), multiple sclerosis (MS) (n = 222), stroke (n = 204), and Parkinson's disease (PD) (n = 224). Depression and anxiety symptoms were assessed using the Patient Health Questionnaire (PHQ-9) and Hospital Anxiety and Depression Scale (HADS-A), respectively. Multiple linear regression was used to evaluate variables associated with the SF-12 mental health component (MCS) and physical health component scores (PCS). Pratt index was used to estimate the relative importance of anxiety and depression on HRQoL. Anxiety and depression had the largest contribution to PCS in stroke and to MCS in epilepsy. Overall, anxiety and depression had a larger contribution to MCS as compared to PCS, except in stroke patients. Different patterns were seen across neurological diseases, with mental health variables strongly affecting MCS in all conditions, with also a sizable contribution to PCS in migraine, MS, and stroke. Anxiety and depression have varying impacts on HRQoL across neurological diseases. It is important for clinicians to be aware of how these patterns differ in each condition.

Abstract Objective To evaluate the efficacy and tolerability of antiepileptic drugs ( AED s) in elderly individuals with epilepsy. Methods We searched four electronic databases as well as bibliographies and conference abstracts. Published and unpublished, randomized, or quasirandomized trials reporting the use of AED s in people aged at least 60 years with epilepsy were eligible for inclusion. Two authors independently carried out each stage of the review. Meta‐analyses were performed using random‐effects models. Results Three thousand four hundred seventeen titles and abstracts were reviewed. Eighteen studies evaluating 12 AED s met all eligibility criteria. Ten studies, comprising 1999 subjects, were suitable for meta‐analysis. Among the elderly with epilepsy, lamotrigine ( LTG ) is better tolerated relative to carbamazepine (pooled weighted risk ratio [ RR ] of experiencing withdrawal due to adverse events = 1.83, 95% confidence interval [ CI ] = 1.23‐2.43). There is a higher probability, although with a 95% CI of borderline importance, of seizure freedom when comparing levetiracetam to LTG ( RR = 0.83, 95% CI = 0.68‐0.97). Single studies provide evidence for the efficacy and/or tolerability of other AED s in the elderly, including brivaracetam, gabapentin, lacosamide, perampanel, and topiramate. The risk of bias of the included studies was frequently low or unclear, although there was on occasion a high risk of bias (especially with regard to selective reporting). Significance There is some evidence for AED use in the elderly with epilepsy. More evidence is required, comparing newer AED s to prior generations as well as examining the effects of determinants such as frailty, to guide clinicians when treating this rapidly growing patient population.

The identification of the aetiology of a patient's epilepsy is instrumental in the diagnosis, prognostic counselling and management of the epilepsies. Indeed, the aetiology can be important for determining the recurrence risk of single seizures and so for making a diagnosis of epilepsy. Here, we divide the aetiologies into six categories: structural, genetic, infectious, metabolic, immune (all of which are part of the International League Against Epilepsy [ILAE] classification system) and neurodegenerative (which we have considered separately because of its growing importance in epilepsy). These are not mutually exclusive categories and many aetiologies fall into more than one category. Indeed, genetic factors probably play a role, to varying degrees, in the risk of seizures in all people with epilepsy. In each of the categories, we discuss what we regard as the most important aetiologies; importance being determined not only by prevalence but also by clinical significance. The introduction contains information suitable for level 1 competency (entry level), whilst the subsequent sections contain information aimed at level 2 competency (proficiency level) as part of the new ILAE competency-based curriculum. As we move towards precision medicine and targeted therapies, so aetiologies will play an even greater role in the management of epilepsy.

Meningioangiomatosis (MA) is a rare, benign, focal lesion of the leptomeninges and underlying cerebral cortex characterized by leptomeningeal and meningovascular proliferation. It may occur sporadically or in association with neurofibromatosis type 2. Previous reports have emphasized histological and imaging features. Data on the management of these patients are sparse, and electrophysiological features of MA lesions have not been published. We assessed the clinical, electrophysiological, histopathological and imaging features as well as the surgical outcome in MA, and compared MA with and without neurofibromatosis. Seven patients with MA at our centre were investigated and their outcome was assessed. A review of the literature is included. MA exhibits a wide range of clinical, imaging, histopathological and electrophysiological features, making the diagnosis difficult. Sporadic MA cases are not associated with neurofibromatosis and the two disorders are genetically distinct. Medically refractory, localization-related epilepsy is the commonest presentation in sporadic cases, but atypical presentations also occur. Unlike sporadic cases, MA with neurofibromatosis is often found incidentally, does not produce seizures, occurs less frequently (ratio of 1:4), and is multifocal. MRI findings in MA correspond to the histological picture. However, the appearance on imaging is non-specific and may suggest cystic atrophy, angioma and tumours. Several abnormalities have been found in close proximity to MA lesions, i.e. meningioma, oligodendroglioma, arteriovenous malformation, encephalocoel and orbital erosion. In spite of histopathological diversity, MA lesions are either predominantly cellular or vascular. Immunohistochemical results are inconsistent among cases, add little to the diagnosis, and do not support a meningeal origin. Electrocorticographic recordings from the surface and within MA lesions revealed a spectrum of electrophysiological expressions. Intrinsic epileptogenicity of MA lesions was documented in some cases. Epileptogenicity was confined to the perilesional cortex in some patients and it was complex (extralesional, multifocal, generalized) in others. Only 43% of our patients became seizure-free postoperatively compared with 68% previously reported, and >70% of our patients and those in the literature continued to require antiepileptic drugs. This is in keeping with the diverse electrophysiology of MA and suggests a less optimistic postoperative outcome than previously recognized.

Our aim was to assess the outcome with regard to seizures and neurological function in unselected patients undergoing resective surgery involving the perirolandic area, with or without multiple subpial transections (MSTs). All patients who underwent perirolandic cortical resection or MSTs from 1979 to 2003 at the London Health Sciences Centre were identified. Patients were included if they had seizures originating in the perirolandic area, recorded with subdural electrodes, or if they had scalp recorded seizures and a congruent discrete epileptogenic lesion on MRI in the perirolandic area. Most patients had electrocorticography (ECoG) at the time of surgery. Data collected include pre-operative and post-operative neurological deficits, MRI findings, interictal and ictal scalp EEG, interictal and ictal subdural data, ECoG findings, type and extent of surgery, neuropathologic diagnoses, and seizure outcomes. We studied 52 patients (22 females). The average age at the time of surgery was 33 years, and the average post-operative follow-up was 4.2 years. The most frequent aetiologies were neoplastic in 26 patients (50%), vascular in eight (15%), malformations of cortical development in six (12%), Rasmussen's encephalitis in three (6%) and other aetiologies in nine (17%). Surgery involved the pre-central gyrus in 17 patients, pre- and post-central gyrus in 13, the inferior central region in 11, the post-central gyrus in 7, and the pre-central gyrus and mesial frontal area in 2. At last follow-up 16 patients were in Engel class I (31%), 8 (15%) in class II, 14 (27%) in class III and 14 (27%) in class IV. Residual neurological deficits were present in 26 patients (50%), occurred more frequently in patients > or =25 years old (P < 0.05) and were mild in 14 (54%) patients. In univariate analyses, better seizure outcomes (P < 0.05) occurred in patients whose ECoG showed infrequent post-resectional spikes and no spikes distant to the resection margin, and in resections involving the pre-central and inferior rolandic cortex. In unselected patients with intractable perirolandic epilepsy, many of whom have large, complex epileptogenic lesions, various levels of seizure improvement can be achieved in almost 75% through well-planned surgical resections. New, severe post-operative neurological deficits can occur in 23% of these patients and appear to be more frequent in older patients. Whereas scalp EEG provided limited information to guide surgery, findings on interictal ECoG predicted seizure outcome.

Summary: Purpose: Controversy exists about the relation of societal knowledge and attitudes regarding epilepsy. We conducted a survey to examine knowledge and attitudes, to note gender and occupational influences, and to examine the effect of an informational brochure. Methods: We administered a standardized questionnaire that noted demographics and examined knowledge and attitudes regarding epilepsy and persons with epilepsy, respectively, to a wide variety of Canadian college students. In a separate class we gave every other student a brochure regarding epilepsy and then administered the questionnaire to both the naïve and brochure‐exposed students. Results: Knowledge was patchy and weakest for the approximate prevalence of epilepsy in the population, hereditary epilepsy and several other etiologies, recognition of nonconvulsive seizures as a type of epilepsy, and knowledge of antiepileptic drug–induced teratogenicity. In contrast, attitudes were more uniformly favorable. However, 11 and 14%, respectively, showed negative bias against persons with epilepsy having children and equal opportunity for occupational employment. Women were slightly but significantly more tolerant than men. The brochure‐exposed group showed better knowledge but equivalent attitudes compared with the naïve group. Conclusions: Results compare favorably with surveys in other countries. Although knowledge was patchy, it could be easily improved on with an educational brochure. Attitudes were positive but show some discrepancies from knowledge and a gender effect.

The development and initial validity and reliability testing of a single-item, 7-point global rating scale designed for neurologists to assess the overall severity of epilepsy in children, the Global Assessment of Severity of Epilepsy (GASE) Scale, is described. The GASE Scale was quick and easy to use. Median epilepsy severity in the development sample was 3 (moderately severe), with a range from 1 ("not severe at all") in 36 patients (26.9%) to 7 ("extremely severe") in 7 patients (5.2%). Preliminary evidence of construct validity was found in support for our a priori predictions of associations between GASE scores and neurologists' ratings of seven individual clinical aspects of epilepsy and in a cumulative R(2) for the GASE score of 81% using ratings of the clinical aspects of epilepsy. Weighted kappa was 0.85 (95% CI: 0.79, 0.90) for inter-rater reliability and 0.90 (95% CI: 0.82, 0.98) and 0.95 (95% CI: 0.91, 0.98) for test-retest reliability for each of two raters. These promising initial results support continuation of the multistage process of testing the validity and reliability of the GASE Scale within various clinical contexts.

Little is known about subgroups of children with epilepsy who may experience less favorable outcomes over time. The objectives of this study were to document trajectories of health-related quality of life (HRQL) and to identify predictors of the trajectory group in children with new-onset epilepsy.Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study, a prospective multisite study of children 4-12 years old with new-onset epilepsy followed for 24 months. Health-related quality of life was measured using the Quality of Life in Childhood Epilepsy questionnaire. Trajectories of HRQL were investigated using latent class trajectory modeling. Multinomial logistic regression was used to identify child, parent, and family predictors of HRQL trajectories.A total of 374 families responded at baseline and 283 (76%) completed the study. Five HRQL trajectories were observed: low-increasing (4%), moderate-decreasing (12%), moderate-increasing (22%), high-increasing (32%), and high-stable (30%). Many children in the low-increasing, moderate-increasing, high-increasing, and high-stable had clinically meaningful improvements in HRQL: 82%, 47%, 63%, and 44%, respectively. In contrast, the majority of children in the moderate-decreasing group (56%) experienced clinically meaningful declines in their HRQL. Factors predicting trajectories were number of antiepileptic drugs prescribed, presence of comorbid behavior or cognitive problems, parent depression, and family functioning and demands.Results suggested that children with epilepsy are not homogenous but rather consist of groups with different trajectories and unique predictors of HRQL. Problems associated with child behavior and cognition were the strongest predictors identified. Given that several risk factors are modifiable, it is important to examine these as potential targets within a family-centered framework to improve HRQL of children with new-onset epilepsy.

Despite evidence that epilepsy surgery is more effective than medical therapy, significant delays between seizure intractability and surgery exist. We aimed to develop a new Web-based methodology to assist physicians in identifying patients who might benefit from an epilepsy surgery evaluation.The RAND/UCLA appropriateness method was used. Clinical scenarios were developed based on eligibility criteria from previously published surgical series. Thirteen national experts rated the scenarios for their appropriateness for an epilepsy surgery evaluation based on published evidence. All scenarios were rerated after a face-to-face meeting following a modified Delphi process. Appropriate scenarios were rerated for necessity to determine referral priority.Of the final 2646 scenarios, 20.6% (n = 544) were appropriate, 17.2% (n = 456) uncertain, and 61.5% (n = 1626) inappropriate for a surgical evaluation. Of the appropriate cases, 55.9% (n = 306) were rated as very high priority. Not attempting AED treatment was always rated as inappropriate for a referral. Trial of 2 AEDs was usually rated as appropriate unless seizure-free or not fully investigated Based on these data, a Web-based decision tool (www.epilepsycases.com) was created.Using the available evidence through 2008 and expert consensus, we developed a Web-based decision tool that provides a guide for determining candidacy for epilepsy surgery evaluations. The tool needs clinical validation, and will be updated and revised regularly. This rendition of the tool is most appropriate for those over age 12 years with focal epilepsy. The Rand/UCLA appropriate methodology might be considered in the development of guidelines in other areas of epilepsy care.

Using the most recent evidence, we provide an update on epilepsy surgery, focusing on its effectiveness, reasons for underutilization, considerations of candidacy and timing for referral for epilepsy surgery evaluation.The course of illness of epilepsy is being characterized. Well conducted studies describe the patterns of seizure remission and relapse with medical therapy and also in response to epilepsy surgery. Epilepsy surgery is highly effective in selected patients with drug-resistant epilepsy (DRE). The risk-benefit of epilepsy surgery is well known and consistent around the world. However, epilepsy surgery remains underutilized. A randomized controlled trial and Clinical Practice Guidelines (CPGs) supporting epilepsy surgery have had no discernible impact on referral rates for epilepsy surgery evaluation. Criteria and guidelines are being developed for identifying patients who need to be referred for epilepsy surgery evaluation. Quality indicators for epilepsy care now also include the need to consider surgical candidacy every 3 years in DRE. New developments in imaging and neurophysiology promise to help clinicians identify and treat patients more accurately.Surgery is effective but underused. Comprehensive interventions to translate evidence to practice in epilepsy surgery are urgently needed.

To systematically review primary research examining patient satisfaction with epilepsy surgery in order to obtain evidence-based estimates of this surgical outcome; to assess methods used to measure epilepsy surgery satisfaction, overall epilepsy surgery satisfaction ratings, and predictors of epilepsy surgery satisfaction.Systematic review of published studies in English up to June 2009, focusing on patient satisfaction with all types of epilepsy surgery in patients of all ages. We excluded studies that focused on satisfaction with epilepsy treatment in general, on quality of life without specific exploration of patient satisfaction with surgery, and on satisfaction with the process of health care delivery, rather than with surgery and its outcomes.Eight studies met inclusion criteria. Satisfaction was assessed using one or more global questions. Four epilepsy surgery satisfaction question content patterns emerged: (1) satisfied or dissatisfied, (2) perceived success or failure, (3) overall positive or negative impact, and (4) willingness to repeat surgery or regretting surgery. Overall 71% were satisfied; 64% considered it a success; it had a positive effect for 78%; and 87% would repeat surgery. Seizure freedom was the most common predictor of epilepsy surgery satisfaction, whereas postoperative neurologic deficit predicted dissatisfaction.Patient satisfaction with interventions is an important aspect of patient-centered care, but it has received little attention in epilepsy surgery. Future research is required to develop and validate epilepsy surgery satisfaction tools. We provide preliminary guiding principles for measuring satisfaction after epilepsy surgery.

The Global Assessment of Severity of Epilepsy (GASE) Scale is a single-item, 7-point global rating scale designed for neurologist-report of overall severity of epilepsy in children. Building on previous preliminary evidence of its validity and reliability for research and clinical use, this study evaluated the GASE Scale's construct validity, reliability, and responsiveness to changes in severity of epilepsy.Data used for the study arose from the Health-Related Quality of Life in Children with Epilepsy Study (HERQULES), a 2-year multicenter prospective cohort study (n = 374) with observations taken at baseline, and 6, 12, and 24 months after diagnosis. Construct validity and reliability were quantified using Spearman's correlation and intraclass correlation coefficient (ICC). Responsiveness was assessed using both distribution-based and anchor-based indices.The GASE Scale was at least moderately correlated (r ≥ 0.30) with several key clinical aspects and most strongly correlated with frequency and intensity of seizures and interference of epilepsy or drugs with daily activities (r > 0.30). Total variation in GASE Scale scores explained by seven core clinical aspects of epilepsy increased over time (R(2) = 28% at baseline to R(2) = 70% at 24 months). The GASE Scale had modest test-retest reliability (ICC range: 0.52-0.64) and was responsive to changes in clinical criteria (standardized response mean range: 0.49-0.68; probability of change range: 0.69-0.75; Guyatt's responsiveness statistic range: 0.56-0.84). The GASE Scale showed potential to discriminate "stable" and "changed" patients according to select criteria and to a composite score (area under the receiver operating characteristic [ROC] curve range: 0.50-0.67).Results offer additional evidence in support of the GASE Scale's validity, reliability, as well as responsiveness to changes in severity of epilepsy in children. We conclude that the GASE Scale is a potentially useful tool for assessing the severity of epilepsy in both clinical and research settings.

Clinical Practice Guidelines for depression and anxiety recommend cognitive-behavioral therapy (CBT) as an equivalent and sometimes more effective treatment than medication. The limited research investigating CBT for anxiety and depression in epilepsy demonstrates mixed results. Described here is a pilot project using an existing group CBT intervention for symptoms of depression and/or anxiety, CBT Basics II, in patients with epilepsy. Eighteen patients with epilepsy, referred by neurologists to address depression and/or anxiety symptoms, completed the 10-week group. Results demonstrated improvements in depression, anxiety, negative automatic thoughts, and cognitive therapy knowledge and skills. The group was generally acceptable to patients as indicated by good attendance rates and only one dropout. This pilot project demonstrates that group CBT is a feasible, acceptable, and promising intervention for patients with epilepsy and comorbid depression and anxiety symptoms.