Familial aggregation of seizure outcomes in four familial epilepsy cohorts.

OBJECTIVE: To assess the possible effects of genetics on seizure outcome by estimating the familial aggregation of three outcome measures: seizure remission, history of ≥4 tonic-clonic seizures, and seizure control for individuals taking antiseizure medication. METHODS: We analyzed families containing multiple persons with epilepsy in four previously collected retrospective cohorts. Seizure remission was defined as being 5 and 10 years seizure-free at last observation. Total number of tonic-clonic seizures was dichotomized at <4 and ≥4 seizures. Seizure control in patients taking antiseizure medication was defined as no seizures for 1, 2, and 3 years. We used Bayesian generalized linear mixed-effects model (GLMM) to estimate the intraclass correlation coefficient (ICC) of the family-specific random effect, controlling for epilepsy type, age at epilepsy onset, and age at last data collection as fixed effects. We analyzed each cohort separately and performed meta-analysis using GLMMs. RESULTS: The combined cohorts included 3644 individuals with epilepsy from 1463 families. A history of ≥4 tonic-clonic seizures showed strong familial aggregation in three separate cohorts and meta-analysis (ICC .28, 95% confidence interval [CI] .21-.35, Bayes factor 8 × 1016). Meta-analyses did not reveal significant familial aggregation of seizure remission (ICC .08, 95% CI .01-.17, Bayes factor 1.46) or seizure control for individuals taking antiseizure medication (ICC .13, 95% CI 0-.35, Bayes factor 0.94), with heterogeneity among cohorts. SIGNIFICANCE: A history of ≥4 tonic-clonic seizures aggregated strongly in families, suggesting a genetic influence, whereas seizure remission and seizure control for individuals taking antiseizure medications did not aggregate consistently in families. Different seizure outcomes may have different underlying biology and risk factors. These findings should inform the future molecular genetic studies of seizure outcomes.

Patient and provider attitudes regarding sudden unexpected death in epilepsy disclosure at a low-resource, minority community health center.

BACKGROUND: Sudden Unexpected Death in Epilepsy (SUDEP) is a complication of epilepsy responsible for approximately 1 death per 1000 patients. The literature has demonstrated minimal SUDEP disclosure between providers and patients, although patients have consistently reported desire to know about their risk. However, the majority of these studies has been conducted in Caucasian populations which did not seek to include lower socio-economic class individuals. Thus, the purpose of this study is to determine patient and provider attitudes regarding SUDEP disclosure at a community health center serving minority, predominantly Hispanic, patients. METHODS: This cross-sectional study utilized surveys distributed to patients with epilepsy (n = 20), patients with diabetes (n = 20), those with no chronic disease (n = 20) and providers (n = 13). Online surveys were distributed to 13 providers whereas phone surveys were conducted for patients with epilepsy. In-person surveys were distributed to patients with diabetes and no chronic disease to serve as comparison groups. Surveys were available in both Spanish and English. Patient surveys consisted of demographic information and questions evaluating their current knowledge and preferences regarding disclosure of a potentially fatal disorder. RESULTS: Twenty patients with epilepsy, 20 patients with diabetes, 20 patients without chronic diseases, and 9 providers responded to the online or in-person surveys. Of the patients with epilepsy, 90 % (n = 18/20) were Hispanic which was not significantly different from the comparison groups. 45 % (n = 9/20) believed they had a higher rate of death due to epilepsy with only 3 patients having heard of SUDEP prior to the survey, and only 1 learning this from a physician. All patients wanted to know everything there was to know regarding their condition, including a higher risk of unexpected death. Most patients (85%, n = 17/20) believe everyone with epilepsy should be informed of SUDEP and this information should come from their provider (90 %, n = 18/20). Results were similar for both comparison groups, except patients with diabetes unanimously desired to know about a theoretical risk of death at the time of diagnosis. Of the providers, 66.7% (n = 6/9) never discuss SUDEP, with the remaining 33.3% (n = 3/9) discussing SUDEP rarely. The primary reason for not discussing SUDEP was not knowing enough about it (66.7%, n = 5/9). CONCLUSION: Almost all patients with epilepsy had no knowledge of SUDEP, yet desired to know this information within the first two visits. Providers in the primary care setting rarely discuss SUDEP, most often due to lack of knowledge. These results are very similar to those found in mainly white, higher socioeconomic populations and indicate that race should not be a barrier to SUDEP disclosure.

Design and implementation of electronic health record common data elements for pediatric epilepsy: Foundations for a learning health care system.

OBJECTIVE: Common data elements (CDEs) are standardized questions and answer choices that allow aggregation, analysis, and comparison of observations from multiple sources. Clinical CDEs are foundational for learning health care systems, a data-driven approach to health care focused on continuous improvement of outcomes. We aimed to create clinical CDEs for pediatric epilepsy. METHODS: A multiple stakeholder group (clinicians, researchers, parents, caregivers, advocates, and electronic health record [EHR] vendors) developed clinical CDEs for routine care of children with epilepsy. Initial drafts drew from clinical epilepsy note templates, CDEs created for clinical research, items in existing registries, consensus documents and guidelines, quality metrics, and outcomes needed for demonstration projects. The CDEs were refined through discussion and field testing. We describe the development process, rationale for CDE selection, findings from piloting, and the CDEs themselves. We also describe early implementation, including experience with EHR systems and compatibility with the International League Against Epilepsy classification of seizure types. RESULTS: Common data elements were drafted in August 2017 and finalized in January 2020. Prioritized outcomes included seizure control, seizure freedom, American Academy of Neurology quality measures, presence of common comorbidities, and quality of life. The CDEs were piloted at 224 visits at 10 centers. The final CDEs included 36 questions in nine sections (number of questions): diagnosis (1), seizure frequency (9), quality of life (2), epilepsy history (6), etiology (8), comorbidities (2), treatment (2), process measures (5), and longitudinal history notes (1). Seizures are categorized as generalized tonic-clonic (regardless of onset), motor, nonmotor, and epileptic spasms. Focality is collected as epilepsy type rather than seizure type. Seizure frequency is measured in nine levels (all used during piloting). The CDEs were implemented in three vendor systems. Early clinical adoption included 1294 encounters at one center. SIGNIFICANCE: We created, piloted, refined, finalized, and implemented a novel set of clinical CDEs for pediatric epilepsy.

Preferred practices for rescue treatment of seizure clusters: A consensus-driven, multi-stakeholder approach.

BACKGROUND: Some of the most difficult issues in the care of people living with epilepsy (PWE) regard the definition, treatment, and communication of unexpected increase(s) in seizure frequency over a relatively short duration of time. In order to address this issue, the Epilepsy Foundation established the Rescue Therapy Project in Epilepsy to understand the gaps, needs, and barriers facing people with epilepsy who use or may benefit from rescue therapies (RTs) for "seizure clusters". The intent was to provide consensus-derived recommendations from a broad stakeholder group including PWE, their caregivers, epilepsy specialist physicians, nurses, pharmacists, and representatives of epilepsy & neurology advocacy and professional organizations. METHODS: During Phase 1, a group of epilepsy experts and stakeholders (N = 54) were divided into 3 workgroups that met by conference calls and in-person. Content of workgroups was developed into preferred practices related to RTs. In Phase 2, these recommendations were evaluated by a larger more diverse group of healthcare professionals, PWE, and caregivers. Agreement with recommended preferred practices at 80% or greater was set as the level to achieve consensus. RESULTS: The preferred practices were centered around four core themes identified by the experts and key stakeholders: the importance of a common language; when RTs should be prescribed; assessing the need for RTs; and education/communication about RTs. Consensus from experts and key stakeholders was reached for 27 recommended preferred practices using the Delphi method. "Rescue therapy" or "rescue medicine" was the preferred term to describe what to name a treatment intervention in this context, and seizure action plans was the preferred term to communicate how to respond to a seizure or SCs and the use of RTs. In Phase 2, 23 of the recommendations reached final consensus, including the need for a common language, and the need to consider RTs and seizure action plans in all PWE in an individualized manner, several circumstances in which RTs should be prescribed, and the importance of education regarding RTs and SAPs.

The rescue therapy in epilepsy project Part 2: Insights from people with epilepsy and families on expert-derived preferred practices.

BACKGROUND: The number and type of therapies available to treat seizure clusters (SCs) or periods of increased seizure activity have risen in recent years. Gaps still exist on defining SCs, when to use them, and educating patients and families. The Epilepsy Foundation developed and published expert-derived consensus on preferred practices for rescue therapies (RTs), 79% of which were agreed upon by a larger group of healthcare professionals (HCPs). This paper describes insights from people with epilepsy (PWE) and families/caregivers (FCGs) on these practices to assess similarities and trends between PWE, FCGs, an expert panel, and HCPs. METHODS: Online survey including expert-derived preferred practices for RT was completed by a convenience sample of 176 PWE/FCGs. Respondents rated agreement with each preferred practice using a 0-8 point Likert scale. Results were examined by relationship to epilepsy, prior use of RTs, and comparison to the expert panel and larger group of HCPs. RESULTS: 41.5% of respondents were PWE and 54.6% were FCGs; 70% represented PWE age 18 and over or those who cared for adults with epilepsy. Levels of agreement were similar to those of HCPs - consensus was obtained on 79% of preferred practices. Differences were noted on which items achieved consensus and strength of consensus for some items. Differences between PWE and FCG, and between those who had and had not previously used a RT were found. A proposed definition of SCs did not reach consensus, but there was strong consensus for individualized seizure action plans and more RT education.

Seizure documentation in people living with epilepsy.

Seizure documentation is an essential component of epilepsy management. Not all persons with epilepsy choose to document their seizures, but many view the practice as essential to managing their disease. While seizure documentation is a valuable aspect of patient care, clinicians and patients must remain aware that seizure underreport and overreport commonly occur due to lack of seizure awareness. Additionally, in rare cases, persons with epilepsy may intentionally conceal their seizures from clinicians. The continued development of electronic seizure diaries and epilepsy self-management software provides patients with new and expanding options for seizure documentation and disease management. In order for these tools to be utilized most effectively, patient input must be central to their development. Given the limitations of seizure documentation, the development of accurate, non-invasive seizure detection devices is crucial for accurate seizure monitoring.

Establishing a learning healthcare system to improve health outcomes for people with epilepsy.

OBJECTIVE: To describe the organization of the Epilepsy Learning Healthcare System (ELHS), a network that aims to improve care outcomes for people with epilepsy (PWE). MATERIALS AND METHODS: Patients and family partners, providers, researchers, epidemiologists, and other leaders collaborated to recruit epilepsy centers and community services organizations into a novel learning network. A multidisciplinary Coordinating Committee developed ELHS governance and organizational structure, including four key planning Cores (Community, Clinical, Quality Improvement, and Data). Through Quality Improvement (QI) methodology grounded in the Institute for Healthcare Improvement (IHI) model, including iterative Plan-Do-Study-Act (PDSA) rapid learning cycles and other learning and sharing sessions, ELHS equipped epilepsy centers and community organizations with tools to standardize, measure, share, and improve key aspects of epilepsy care. The initial learning cycles addressed provider documentation of seizure frequency and type, and also screening for medication adherence barriers. Rapid learning cycles have been carried out on these initial measures in both clinical centers and community-based settings. Additional key measures have been defined for quality of life, screening, and treatment for mental health and behavioral comorbidities, transition from pediatric to adult care, counseling for women and girls living with epilepsy, referral for specialty care, and prevention and treatment of seizure clusters and status epilepticus. RESULTS: It is feasible to adopt a learning healthcare system framework in epilepsy centers and community services organizations. Through structured collaboration between epilepsy care providers, community support organizations, PWE, and their families/caregivers we have identified new opportunities to improve outcomes that are not available in traditional care models.

Big data in epilepsy: Clinical and research considerations. Report from the Epilepsy Big Data Task Force of the International League Against Epilepsy.

Epilepsy is a heterogeneous condition with disparate etiologies and phenotypic and genotypic characteristics. Clinical and research aspects are accordingly varied, ranging from epidemiological to molecular, spanning clinical trials and outcomes, gene and drug discovery, imaging, electroencephalography, pathology, epilepsy surgery, digital technologies, and numerous others. Epilepsy data are collected in the terabytes and petabytes, pushing the limits of current capabilities. Modern computing firepower and advances in machine and deep learning, pioneered in other diseases, open up exciting possibilities for epilepsy too. However, without carefully designed approaches to acquiring, standardizing, curating, and making available such data, there is a risk of failure. Thus, careful construction of relevant ontologies, with intimate stakeholder inputs, provides the requisite scaffolding for more ambitious big data undertakings, such as an epilepsy data commons. In this review, we assess the clinical and research epilepsy landscapes in the big data arena, current challenges, and future directions, and make the case for a systematic approach to epilepsy big data.

Psychogenic nonepileptic seizures in children-Prospective validation of a clinical care pathway & risk factors for treatment outcome.

PURPOSE: The purpose of this study was to prospectively validate a care pathway for psychogenic nonepileptic seizures (PNES) in a pediatric setting. The pathway was developed based on a previous study of patients at our center, which demonstrated positive treatment outcomes of 80% full or partial remission. Sequentially referred patients with PNES in the validation cohort received care prospectively according to the pathway algorithm. It was hypothesized that the validation cohort would achieve outcomes similar to that of the development cohort as a result of standardized care. METHOD: We performed a retrospective chart review of 43 children sequentially referred, assessed, and treated within a specialized neurology psychology service for suspected PNES over a 5-year period. The majority of patients (n = 41, 95%) met diagnostic criteria for probable, clinically established, or documented PNES, according to the International League Against Epilepsy (ILAE) criteria. RESULTS: Ages ranged from 6 to 18 years of age at time of diagnosis, with the majority of patients being female (n = 29, 67%) and adolescent (n = 31, 72%). There was a high level of adherence to the care algorithm (n = 34, 84%). The development and validation cohorts were similar across demographic, clinical, and psychological characteristics. Standardized care resulted in high rates of full (n = 27, 63%) and partial (n = 12, 28%) remission, as self-reported at discharge. A 96% decrease in mean monthly frequency of total PNES events was also observed at discharge, as was a significant reduction in healthcare utilization related to PNES (74% fewer ambulance calls and 85% fewer emergency department (ED) visits). Post hoc analyses demonstrated that duration of PNES illness longer than 12 months (at diagnosis) increased odds of not achieving full remission by discharge (odds ratio = 5.94, p = 0.02). Developmental period of onset (child versus adolescent), having abnormal electroencephalogram (EEG) result, previous concussion, chronic versus acute stressor, more than one PNES event type, or additional functional neurological symptoms did not significantly impact treatment response. CONCLUSIONS: This study demonstrates, for the first time prospectively in a pediatric setting, that standardized care for PNES leads to improved clinical outcomes and reduced healthcare utilization. Delayed diagnosis and treatment of PNES longer than 12 months also appears to be associated with less favorable outcomes in children.

A feasibility assessment of functioning and quality-of-life patient-reported outcome measures in adult epilepsy clinics: A systematic review.

OBJECTIVE: The objective of the study was to identify functioning and quality-of-life (QOL) patient-reported outcome measurements (PROMs) feasible for use in the waiting room of adult epilepsy clinics. MATERIAL AND METHODS: We searched PubMed and Web of Science for articles on in English, Spanish, Portuguese, Italian, and French published by the end of February 15th, 2019. We screened retrieved titles and abstracts looking for publications that reported the use of PROMs to measure functioning and QOL in epilepsy. The authors, clinical experts, and patient advocates from the Epilepsy Foundation of America conceptualized a set of desirable feasibility attributes for PROMs implementation in the waiting room of adult epilepsy clinics. These attributes included brief time for completion (i.e., ≤3 min), free cost, coverage of four minimum QOL domains and respective facets, and good evidence of psychometric properties. We defined QOL domains according to the World Health Organization's classification and created psychometric appraisal criteria based on the Food and Drug Administration's (FDA) Guidance. RESULTS: Eighteen candidate instruments were identified and compared with respect to desirable attributes for use in adult epilepsy clinics. We found that the Quality-of-life in epilepsy (QOLIE)-10 and Patient-Reported Outcome Measurement Information System-10 (PROMIS-10) were the most feasible PROMs for implementation in adult epilepsy clinics based on our criteria. The QOLIE-10 and PROMIS-10 still lack ideal evidence of responsiveness in people with epilepsy. CONCLUSION: This is the first systematic review that aimed to assess feasibility properties of available functioning and QOL PROMs. The QOLIE-10 and PROMIS-10 are potentially feasible instruments for implementation in the waiting room of adult epilepsy clinics. Further studies assessing the responsiveness of these PROMs are needed and will contribute to the selection of the most appropriate instrument for longitudinal use in adult epilepsy clinical practice.

Clinical characteristics of psychogenic nonepileptic seizures across the lifespan: An international retrospective study.

PURPOSE: Previous studies from a few countries have reported semiological differences in younger children compared with adolescents or adults with psychogenic nonepileptic seizures (PNESs). This study tested the hypothesis that semiological, demographic, and historical risk factors vary with different ages of PNES onset in a large cohort from different countries. METHODS: In this retrospective study, we investigated patients consecutively referred for PNES, who were admitted to epilepsy monitoring units in Iran, Brazil, Venezuela, Canada, Argentina, and USA. Age, gender, age at seizure onset, seizure semiology, and factors predisposing to PNES (abuse, stressors) were documented according to routine diagnostic practices at each center. Participants were grouped according to their age at onset (i.e., childhood, adolescence, or adulthood). RESULTS: A total of 448 patients were studied. Female predominance was associated with adolescent- (85/122, 70%) and adult-onset (190/270, 70%) but not in childhood-onset PNES (28/56, 50%) (p = 0.011). Event frequency in the month preceding the diagnosis was higher in the childhood- [x¯â€¯= 50, standard deviation (sd) = 82, p = 0.025] versus adolescent- (x¯â€¯= 24, sd = 36) or adult-onset groups (x¯â€¯= 29, sd = 61). Significant between-group differences were observed for generalized body movements (p = 0.0001) and ictal injury (p = 0.027), suggesting more severe ictal presentations in adult-onset PNES compared with younger ages. Adult-onset patients were also more likely to be taking an unnecessary antiepileptic medication (p = 0.010). CONCLUSION: While PNES may present at any age, there appear to be notable differences across the lifespan with respect to some of the clinical characteristics. Further international and cross-cultural studies may reveal other interesting characteristics of PNES.

Psychogenic nonepileptic seizures in children and adolescents: An international cross-cultural study.

PURPOSE: We compared various clinical characteristics of psychogenic nonepileptic seizures (PNES) between young patients from Iran, Saudi Arabia, and Canada, three nations with significantly different socioeconomic and demographic characteristics. This international cross-cultural comparative study may advance our knowledge and understanding of PNES in children and adolescents across the cultures and borders. METHODS: In this retrospective study, we investigated all patients 16 years of age or younger, with PNES admitted to the epilepsy monitoring units at one center in Iran, one center in Saudi Arabia, and one center in Canada. Age, gender, age at seizure onset, seizure semiology, seizure frequency, factors potentially predisposing to PNES, and video-electroencephalography (EEG) recording of all patients were registered routinely and compared between the nations. RESULTS: Fifty-one patients were studied (22 from Iran, 14 from Saudi Arabia, and 15 from Canada). Age at the diagnosis was 13.4 ±â€¯2.2 years (range: 8-16 years), and age at the onset of seizures was 12.3 ±â€¯2.7 years (range: 5-16 years). Demographic and clinical characteristics of and associated factors in the patients among the three nations were not significantly different. Twenty-six (51%) patients were taking antiepileptic drugs at the time of diagnosis; the difference was not statistically significant between the nations (13 patients in Iran, 6 in Saudi Arabia, and 7 patients in Canada; P = 0.5). CONCLUSION: Young patients with PNES across borders and between cultures share more similarities than differences with regard to their demographic and clinical characteristics.

Signs and symptoms of the postictal period in epilepsy: A systematic review and meta-analysis.

OBJECTIVE: The postictal period has many physical, behavioral, and cognitive manifestations associated with it. These signs and symptoms are common, can be quite debilitating, and can have a continued impact long after the seizure has ended. The purpose of this systematic review was to quantify the occurrence of postictal signs and symptoms, along with their frequency and duration in persons with epilepsy. METHODS: Cochrane Database of Systematic Reviews, CINAHL, EMBASE, MEDLINE, PsycINFO, Web of Science, and Scopus were searched from inception to November 29, 2017. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting standards were followed. Search terms included subject headings and text words such as convulsion, epilepsy, seizure, postictal, post seizure, seizure recovery, seizure end, Todd's paresis, and Todd's paralysis. Standardized forms were used to collect various study variables. Abstract and full-text review, data abstraction, and quality assessment were all done in duplicate. Study heterogeneity was assessed using the I-squared test, and a random effects model was used to determine estimates. Publication bias was evaluated using funnel plots. RESULTS: From 7811 abstracts reviewed, 78 articles met eligibility criteria, with 31 postictal manifestations (signs and/or symptoms) described and 45 studies included in the meta-analysis. The majority of studies described postictal headaches, migraines, and psychoses, with mean weighted frequency of 33.0% [95% confidence interval (CI) 26.0-40.0], 16.0% [95% CI 10.0-22.0], and 4.0% [95% CI 2.0-5.0], respectively. The mean weighted proportions of manifestations ranged from 0.5% (subacute postictal aggression) to 96.2% (postictal unresponsiveness) with symptom duration usually lasting <24 h but up to 2 months for physical and cognitive/behavioral symptoms respectively. SIGNIFICANCE: Examining data on the various signs and symptoms of the postictal period will have practical applications for physicians by raising their awareness about these manifestations and informing them about the importance of optimizing their prevention and treatment in epilepsy.

Adult-onset psychogenic nonepileptic seizures: A multicenter international study.

PURPOSE: The aim of this multicenter international cross-cultural study was to compare clinical variables in a large sample of people with adult-onset psychogenic nonepileptic seizures (PNES). METHODS: In this retrospective study, we evaluated persons with documented PNES, who were older than 16 years of age at the onset, from four countries (i.e., Iran, Brazil, Venezuela, and Argentina) regarding their age, gender, PNES semiology, and possible predisposing factors. RESULTS: We included 389 patients (244 from Iran, 66 from Brazil, 51 from Venezuela, and 28 from Argentina). Age at diagnosis was 32 ±â€¯9 years (range: 17-64 years), and age at the onset of seizures was 27 ±â€¯8 years (range: 17-49 years). There was a female predominance in all countries. The demographic characteristics and factors associated with PNES were similar among the countries. However, there were significant semiological differences among the countries. CONCLUSION: This study corroborates the notion that PNES share more similarities than differences cross-culturally and across international borders. However, the background determined by cultural, ethnic, and religious differences may influence the semiology of PNES. Further cross-cultural studies involving more than two continents may advance our understanding of PNES.

Sex differences in demographic and clinical characteristics of psychogenic nonepileptic seizures: A retrospective multicenter international study.

PURPOSE: Sex-related differences have been reported in patients with neurological and psychiatric disorders. It is also plausible to assume that there might be differences between females and males with psychogenic nonepileptic seizures (PNES). METHODS: In this retrospective study, we investigated patients with PNES, who were admitted to the epilepsy monitoring units at centers in Iran, the USA, Canada, Brazil, Argentina, and Venezuela. Age, sex, age at seizure onset, seizure semiology, factors potentially predisposing to PNES, and video-electroencephalography recording of all patients were registered routinely. RESULTS: Four hundred and fifty-one patients had PNES-only and were eligible for inclusion; 305 patients (67.6%) were females. We executed a logistic regression analysis, evaluating significant variables in univariate analyses (i.e., age, age at onset, aura, presence of historical sexual or physical abuse, and family dysfunction). The only variables retaining significance were historical sexual abuse (p = 0.005) and presence of aura (p = 0.01); physical abuse was borderline significant (p = 0.05) (all three were more prevalent among females). CONCLUSION: Similarities between females and males outweigh the differences with regard to the demographic and clinical characteristics of PNES. However, notable differences are that females more often report lifetime adverse experiences (sexual and probably physical abuse) and auras. While social, psychological, and genetic factors may interact with lifetime adverse experiences in the inception of PNES, the link is not yet clear. This is an interesting avenue for future studies.

Heart rate variability in epilepsy: A potential biomarker of sudden unexpected death in epilepsy risk.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a tragic and devastating event for which the underlying pathophysiology remains poorly understood; this study investigated whether abnormalities in heart rate variability (HRV) are linked to SUDEP in patients with epilepsy due to mutations in sodium channel (SCN) genes. METHODS: We retrospectively evaluated HRV in epilepsy patients using electroencephalographic studies to study the potential contribution of autonomic dysregulation to SUDEP risk. We extracted HRV data, in wakefulness and sleep, from 80 patients with drug-resistant epilepsy, including 40 patients with mutations in SCN genes and 40 control patients with non-SCN drug-resistant epilepsy. From the SCN group, 10 patients had died of SUDEP. We compared HRV between SUDEP and non-SUDEP groups, specifically studying awake HRV and sleep:awake HRV ratios. RESULTS: The SUDEP patients had the most severe autonomic dysregulation, showing lower awake HRV and either extremely high or extremely low ratios of sleep-to-awake HRV in a subgroup analysis. A secondary analysis comparing the SCN and non-SCN groups indicated that autonomic dysfunction was slightly worse in the SCN epilepsy group. SIGNIFICANCE: These findings suggest that autonomic dysfunction is associated with SUDEP risk in patients with epilepsy due to sodium channel mutations. The relationship of HRV to SUDEP merits further study; HRV may eventually have potential as a biomarker of SUDEP risk, which would allow for more informed counseling of patients and families, and also serve as a useful outcome measure for research aimed at developing therapies and interventions to reduce SUDEP risk.

Introduction of Continuous Video EEG Monitoring into 2 Different NICU Models by Training Neonatal Nurses.

BACKGROUND: Continuous video electroencephalographic (EEG) (cvEEG) monitoring is emerging as the standard of care for diagnosis and management of neonatal seizures. However, cvEEG is labor-intensive and the need to initiate and interpret studies on a 24-hour basis is a major limitation. PURPOSE: This study aims at establishing consistency in monitoring of newborns admitted to 2 different neonatal intensive care units (NICUs) managed by the same neurocritical care team. METHODS: Neonatal nurses were trained to apply scalp electrodes, troubleshoot technical issues, and identify amplitude-integrated EEG abnormalities. Guidelines, checklists, and visual training modules were developed. A central network system allowed remote access to the cvEEGs by the epileptologist for timely interpretation and feedback. A cohort of 100 infants with moderate to severe hypoxic-ischemic encephalopathy before and after the training program was compared. RESULTS: During the study period, 192 cvEEGs were obtained. The time to initiate brain monitoring decreased by 31.5 hours posttraining; this, in turn, led to an increase in electrographic seizure detection (20% before vs 34% after), decrease in seizure clinical misdiagnosis (65% before and 36% after), and reduction in antiseizure medication burden. IMPLICATIONS FOR PRACTICE: Training experienced NICU nurses to set up, start, and monitor cvEEGs can decrease the time to initiate cvEEGs, which may lead to better seizure diagnosis and management. IMPLICATIONS FOR RESEARCH: Further understanding of practice bundles for best supporting infants at risk and being treated for seizures needs to be evaluated for integration into practice.Video Abstract Available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.

Experiences with premorbid SUDEP discussion among participants in the North American SUDEP Registry (NASR).

The North American SUDEP Registry (NASR) is a repository of clinical data and biospecimens in cases of sudden unexpected death in epilepsy (SUDEP), a leading cause of epilepsy-related deaths. We assessed whether bereaved families were aware of SUDEP before their family member's death and their preferences for SUDEP disclosure. At enrollment, next-of-kin of SUDEP cases completed an intake interview, including questions assessing premorbid SUDEP discussions. Only 18.1% of the 138 next-of-kin recalled a previous discussion of SUDEP with a healthcare provider or support resource. Of the 112 who did not recall such a discussion, 72.3% wished it was discussed, 10.7% were satisfied it was not discussed, and 17% were unsure. A history of status epilepticus predicted SUDEP discussion. Rates of SUDEP discussion were not significantly higher among SUDEPs after 2013 (the approximate study midpoint) compared with those before then. Our study suggests that SUDEP remains infrequently discussed with family members of persons with epilepsy. Nearly three-quarters of family members wished they had known of SUDEP before the death. However, some were indifferent or were satisfied that this discussion had not occurred. We must balance more systematic education of patients and families about SUDEP while respecting individual preferences about having this discussion.

The borderland of migraine and epilepsy in children.

OBJECTIVE: To provide a review on the spectrum of migraine-epilepsy disorders in children. BACKGROUND: The migraine-epilepsy continuum covers a fascinating array of disorders that share many clinical similarities but also differ fundamentally in pathophysiology. In the pediatric population, its study can be complicated by the young age of those affected and the lack of clear understanding of the neurobiology of these disorders within the developing brain. DISCUSSION: This review serves to discuss the borderland of migraine and epilepsy in children. It will focus on epidemiology and comorbidity of the two disorders, possible mechanisms for shared pathophysiology informed by basic and translational science, and an overview of clinical similarities and differences. It will also discuss differentiation of migraine aura from childhood occipital epilepsies. Finally, the review concludes with a discussion of current classification methods for capturing cases on the migraine-epilepsy spectrum and a call for a united approach towards a better definition of this spectrum of disorders. CONCLUSION: Recent advances examining the migraine-epilepsy spectrum show clinicopathological similarities between the two disorders in children. Epidemiology demonstrates reciprocally increased incidences of epilepsy in migraineurs and of migraines in children with epilepsy, however, prospective longitudinal in children are currently lacking. Clinically, the two disorders show similarity in preictal, ictal, and postictal phenomena, with close temporal association of the two conditions described by the controversial term of "migralepsy." Basic science research has contributed significant improvements in understanding the generation of both of these episodic neurological conditions, with common links seen at a cellular level involving synaptic glutamate release and the provocation of varying propagation methods including cortical spreading depression in migraine and the paroxysmal depolarizing shift in epilepsy. Despite these significant gains in understanding, improved classification methods are required to identify and further study these interrelated conditions and move towards improved diagnosis and treatment of disorders on the migraine-epilepsy continuum in children.

Familial risk of epilepsy: a population-based study.

Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935-94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives' medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7%, and risk was increased 3.3-fold (95% confidence interval 2.75-5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted 'prenatal/developmental cause' (standardized incidence ratio 4.3). Among relatives of probands with epilepsy without identified cause (including epilepsies classified as 'idiopathic' or 'unknown cause'), risk was significantly increased for epilepsy of prenatal/developmental cause (standardized incidence ratio 4.1). Similarly, among relatives of probands with prenatal/developmental cause, risk was significantly increased for epilepsies without identified cause (standardized incidence ratio 3.8). In relatives of probands with generalized epilepsy, standardized incidence ratios were 8.3 (95% confidence interval 2.93-15.31) for generalized epilepsy and 2.5 (95% confidence interval 0.92-4.00) for focal epilepsy. In relatives of probands with focal epilepsy, standardized incidence ratios were 1.0 (95% confidence interval 0.00-2.19) for generalized epilepsy and 2.6 (95% confidence interval 1.19-4.26) for focal epilepsy. Epilepsy incidence was greater in offspring of female probands than in offspring of male probands, and this maternal effect was restricted to offspring of probands with focal epilepsy. The results suggest that risks for epilepsies of unknown and prenatal/developmental cause may be influenced by shared genetic mechanisms. They also suggest that some of the genetic influences on generalized and focal epilepsies are distinct. However, the similar increase in risk for focal epilepsy among relatives of probands with either generalized (2.5-fold) or focal epilepsy (2.6-fold) may reflect some coexisting shared genetic influences.