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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. [ABSTRACT FROM AUTHOR]

The article discusses the progress and achievements of the journal Advanced NanoBiomed Research in 2023 and looks ahead to the coming year. The journal has become a go-to source for research on nanomedicine, nanotechnology, biomaterials, and other related topics. It has received over 500 submissions and published more than 250 articles from authors around the world. The journal received its first Journal Impact Factor of 3.4, establishing its reputation as a high-quality open access platform. It has also been accepted for listing in SCOPUS and has seen a significant increase in downloads. The article expresses gratitude to the authors, reviewers, and readers for their support and looks forward to bringing more exciting research findings in the field in 2024. [Extracted from the article]

Objective: To describe the development of the Pediatric Epilepsy Outcome‐Informatics Project (PEOIP) at Alberta Children's Hospital (ACH), which was created to provide standardized, point‐of‐care data entry; near‐time data analysis; and availability of outcome dashboards as a baseline on which to pursue quality improvement. Methods: Stakeholders involved in the PEOIP met weekly to determine the most important outcomes for patients diagnosed with epilepsy, create a standardized electronic note with defined fields (patient demographics, seizure and syndrome type and frequency and specific outcomes‐ seizure type and frequency, adverse effects, emergency department visits, hospitalization, and care pathways for clinical decision support. These were embedded in the electronic health record from which the fields were extracted into a data display platform that provided patient‐ and population‐level dashboards updated every 36 hours. Provider satisfaction and family experience surveys were performed to assess the impact of the standardized electronic note. Results: In the last 5 years, 3,245 unique patients involving 13, 831 encounters had prospective, longitudinal, standardized epilepsy data accrued via point‐of‐care data entry into an electronic note as part of routine clinical care. A provider satisfaction survey of the small number of users involved indicated that the vast majority believed that the note makes documentation more efficient. A family experience survey indicated that being provided with the note was considered "valuable" or "really valuable" by 86% of respondents and facilitated communication with family members, school, and advocacy organizations. Significance: The PEOIP serves as a proof of principle that information obtained as part of routine clinical care can be collected in a prospective, standardized, efficient manner and be used to construct filterable process/outcome dashboards, updated in near time (36 hours). This information will provide the necessary baseline data on which multiple of QI projects to improve meaningful outcomes for children with epilepsy will be based. [ABSTRACT FROM AUTHOR]

Objectives: This International League Against Epilepsy (ILAE) Report: (a) summarizes the literature about "driving and psychogenic nonepileptic seizures (PNES)"; (b) presents the views of international experts; and (c) proposes an approach to assessing the ability of persons with PNES (PwPNES) to drive. Methods: Phase 1: Systematic literature review. Phase 2: Collection of international expert opinion using SurveyMonkey®. Experts included the members of the ILAE PNES Task Force and individuals with relevant publications since 2000. Phase 3: Joint analysis of the findings and refinement of conclusions by all participants using email. As an ILAE Report, the resulting text was reviewed by the Psychiatry Commission, the ILAE Task Force on Driving Guidelines, and Executive Committee. Results: Eight studies identified by the systematic review process failed to provide a firm evidence base for PNES‐related driving regulations, but suggest that most health professionals think restrictions are appropriate. Twenty‐six experts responded to the survey. Most held the view that decisions about driving privileges should consider individual patient and PNES characteristics and take account of whether permits are sought for private or commercial driving. Most felt that those with active PNES should not be allowed to drive unless certain criteria were met and that PNES should be thought of as "active" if the last psychogenic seizure had occurred within 6 months. Significance: Recommendations on whether PwPNES can drive should be made at the individual patient level. Until future research has determined the risk of accidents in PwPNES a proposed algorithm may guide decisions about driving advice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitors currently confer the greatest survival gain for nonsmall cell lung cancer (NSCLC) patients with actionable genetic alterations. Simultaneously, the increasing number of targets and compounds poses the challenge of reliable, broad and timely molecular assays for the identification of patients likely to benefit from novel treatments. Here, we demonstrate the feasibility and clinical utility of comprehensive, NGS‐based genetic profiling for routine workup of advanced NSCLC based on the first 3,000 patients analyzed in our department. Following automated extraction of DNA and RNA from formalin‐fixed, paraffin‐embedded tissue samples, parallel sequencing of DNA and RNA for detection of mutations and gene fusions, respectively, was performed using PCR‐based enrichment with an ion semiconductor sequencing platform. Overall, 807 patients (27%) were eligible for currently approved, EGFR‐/BRAF‐/ALK‐ and ROS1‐directed therapies, while 218 additional cases (7%) with MET, ERBB2 (HER2) and RET alterations could potentially benefit from experimental targeted compounds. In addition, routine capturing of comutations, e.g. TP53 (55%), KEAP1 (11%) and STK11 (11%), as well as the precise typing of fusion partners and involved exons in case of actionable translocations including ALK and ROS1, are prognostic and predictive tools currently gaining importance for further refinement of therapeutic and surveillance strategies. The reliability, low dropout rates (<5%), minimal tissue requirements, fast turnaround times (6 days on average) and lower costs of the diagnostic approach presented here compared to sequential single‐gene testing, highlight its practicability in order to support individualized decisions in routine patient care, enrollment in molecularly stratified clinical trials, as well as translational research. What's new? Next‐generation sequencing (NGS) is an attractive option in the molecular workup of non‐small cell lung cancer (NSCLC). However, large‐scale implementation for routine diagnostics is a non‐trivial task. Here, the authors present the largest cohort of advanced NSCLC tested for mutations and translocations by combined targeted RNA‐ and DNA‐sequencing in routine diagnostics to date. The integrated approach exceeds current international guidelines and illustrates the performance and clinical impact of one‐stop shop NGS profiling. Due to amplification‐based sequencing, dropout rates are minimal and turnaround times low. By facilitating better patient stratification, such an approach can improve oncologic management and boost translational research. [ABSTRACT FROM AUTHOR]

Assessment of Tumor Mutational Burden (TMB) for response stratification of cancer patients treated with immune checkpoint inhibitors is emerging as a new biomarker. Commonly defined as the total number of exonic somatic mutations, TMB approximates the amount of neoantigens that potentially are recognized by the immune system. While whole exome sequencing (WES) is an unbiased approach to quantify TMB, implementation in diagnostics is hampered by tissue availability as well as time and cost constrains. Conversely, panel‐based targeted sequencing is nowadays widely used in routine molecular diagnostics, but only very limited data are available on its performance for TMB estimation. Here, we evaluated three commercially available larger gene panels with covered genomic regions of 0.39 Megabase pairs (Mbp), 0.53 Mbp and 1.7 Mbp using i) in silico analysis of TCGA (The Cancer Genome Atlas) data and ii) wet‐lab sequencing of a total of 92 formalin‐fixed and paraffin‐embedded (FFPE) cancer samples grouped in three independent cohorts (non‐small cell lung cancer, NSCLC; colorectal cancer, CRC; and mixed cancer types) for which matching WES data were available. We observed a strong correlation of the panel data with WES mutation counts especially for the gene panel >1Mbp. Sensitivity and specificity related to TMB cutpoints for checkpoint inhibitor response in NSCLC determined by wet‐lab experiments well reflected the in silico data. Additionally, we highlight potential pitfalls in bioinformatics pipelines and provide recommendations for variant filtering. In summary, our study is a valuable data source for researchers working in the field of immuno‐oncology as well as for diagnostic laboratories planning TMB testing. What's new? Tumor mutational burden (TMB) is an emerging biomarker to predict response to immune checkpoint inhibitors. While TMB can be measured by whole exome sequencing (WES), costs, turn‐around time, and tissue availability currently favor a panel sequencing approach using FFPE tissue for routine diagnostics. However, performance remains to be clarified. Our study is the first worldwide that analyses three major commercial gene panels by comparing TMB approximation across panels as well as against the technical reference standard WES. The data suggest that TMB approximation using gene panel sequencing of FFPE tumor tissue is feasible and can be implemented in routine diagnostics. [ABSTRACT FROM AUTHOR]

Tumor mutational burden (TMB) represents a new determinant of clinical benefit from immune checkpoint blockade that identifies responders independent of PD‐L1 expression levels and is currently being explored in clinical trials. Although TMB can be measured directly by comprehensive genomic approaches such as whole‐genome and exome sequencing, broad availability, short turnaround times, costs and amenability to formalin‐fixed and paraffin‐embedded tissue support the use of gene panel sequencing for approximating TMB in routine diagnostics. However, data on the parameters influencing panel‐based TMB estimation are limited. Here, we report an extensive in silico analysis of the TCGA data set that simulates various panel sizes and compositions. We demonstrate that panel size is a critical parameter that influences confidence intervals (CIs) and cutoff values as well as important test parameters including sensitivity, specificity, and positive predictive value. Moreover, we evaluate the Illumina TSO500 panel, which will be made available for TMB estimation, and propose dynamic, entity‐specific cutoff values based on current clinical trial data. Optimizing the cost–benefit ratio, our data suggest that panels between 1.5 and 3 Mbp are ideally suited to estimate TMB with small CIs, whereas smaller panels tend to deliver imprecise TMB estimates for low to moderate TMB (0–30 muts/Mbp), connected with insufficient separation of hypermutated tumors from non‐hypermutated tumors. What's new? While the immune system can fight cancer, tumor clones may hijack the body's own mechanisms of dampening immune responses by expressing immune‐checkpoint proteins. Tumor mutational burden (TMB) is an emerging selection biomarker for patients who would benefit from immune checkpoint inhibitor therapy. Unification of TMB estimation and driver mutation detection in a single panel sequencing assay is highly desirable but challenging, however. Combinatorial calculations and simulations in the TCGA dataset show that panel sizes greater than 1.5 Mbp are recommendable, and–although not immunogenic–synonymous and nonsense mutations can be included in TMB estimation together with cancer‐type specific correction factors. [ABSTRACT FROM AUTHOR]

Abstract: Most antidiabetic drugs treat disease symptoms rather than adipose tissue dysfunction as a key pathogenic cause in the metabolic syndrome and type 2 diabetes. Pharmacological targeting of adipose tissue through the nuclear receptor PPARg, as exemplified by glitazone treatments, mediates efficacious insulin sensitization. However, a better understanding of the context‐specific PPARg responses is required for the development of novel approaches with reduced side effects. Here, we identified the transcriptional cofactor Cited4 as a target and mediator of rosiglitazone in human and murine adipocyte progenitor cells, where it promoted specific sets of the rosiglitazone‐dependent transcriptional program. In mice, Cited4 was required for the proper induction of thermogenic expression by Rosi specifically in subcutaneous fat. This phenotype had high penetrance in females only and was not evident in beta‐adrenergically stimulated browning. Intriguingly, this specific defect was associated with reduced capacity for systemic thermogenesis and compromised insulin sensitization upon therapeutic rosiglitazone treatment in female but not male mice. Our findings on Cited4 function reveal novel unexpected aspects of the pharmacological targeting of PPARg. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

In order to identify anaplastic lymphoma kinase‐driven non‐small cell lung cancer (ALK+ NSCLC) patients with a worse outcome, who might require alternative therapeutic approaches, we retrospectively analyzed all stage IV cases treated at our institutions with one of the main echinoderm microtubule‐associated protein‐like 4 (EML4)‐ALK fusion variants V1, V2 and V3 as detected by next‐generation sequencing or reverse transcription‐polymerase chain reaction (n = 67). Progression under tyrosine kinase inhibitor (TKI) treatment was evaluated both according to Response Evaluation Criteria in Solid Tumors (RECIST) and by the need to change systemic therapy. EML4‐ALK fusion variants V1, V2 and V3 were found in 39%, 10% and 51% of cases, respectively. Patients with V3‐driven tumors had more metastatic sites at diagnosis than cases with the V1 and V2 variants (mean 3.3 vs. 1.9 and 1.6, p = 0.005), which suggests increased disease aggressiveness. Furthermore, V3‐positive status was associated with earlier failure after treatment with first and second‐generation ALK TKI (median progression‐free survival [PFS] by RECIST in the first line 7.3 vs. 39.3 months, p = 0.01), platinum‐based combination chemotherapy (median PFS 5.4 vs. 15.2 months for the first line, p = 0.008) and cerebral radiotherapy (median brain PFS 6.1 months vs. not reached for cerebral radiotherapy during first‐line treatment, p = 0.028), and with inferior overall survival (39.8 vs. 59.6 months in median, p = 0.017). Thus, EML4‐ALK fusion variant V3 is a high‐risk feature for ALK+ NSCLC. Determination of V3 status should be considered as part of the initial workup for this entity in order to select patients for more aggressive surveillance and treatment strategies. [ABSTRACT FROM AUTHOR]

Summary: Ketogenic dietary therapies (KDTs) are established, effective nonpharmacologic treatments for intractable childhood epilepsy. For many years KDTs were implemented differently throughout the world due to lack of consistent protocols. In 2009, an expert consensus guideline for the management of children on KDT was published, focusing on topics of patient selection, pre‐KDT counseling and evaluation, diet choice and attributes, implementation, supplementation, follow‐up, side events, and KDT discontinuation. It has been helpful in outlining a state‐of‐the‐art protocol, standardizing KDT for multicenter clinical trials, and identifying areas of controversy and uncertainty for future research. Now one decade later, the organizers and authors of this guideline present a revised version with additional authors, in order to include recent research, especially regarding other dietary treatments, clarifying indications for use, side effects during initiation and ongoing use, value of supplements, and methods of KDT discontinuation. In addition, authors completed a survey of their institution's practices, which was compared to responses from the original consensus survey, to show trends in management over the last 10 years. [ABSTRACT FROM AUTHOR]

Objective Health-related quality of life ( HRQL) is compromised in children with epilepsy. The current study aimed to identify correlates of HRQL in children with drug resistant epilepsy. Methods Data came from 115 children enrolled in the Impact of Pediatric Epilepsy Surgery on Health-Related Quality of Life Study ( PEPSQOL), a multicenter prospective cohort study. Individual, clinical, and family factors were evaluated. HRQL was measured using the Quality of Life in Childhood Epilepsy Questionnaire ( QOLCE), a parent-rated epilepsy-specific instrument, with composite scores ranging from 0 to 100. A series of univariable linear regression analyses were conducted to identify significant associations with HRQL, followed by a multivariable regression analysis. Results Children had a mean age of 11.85 ± 3.81 years and 65 (56.5%) were male. The mean composite QOLCE score was 60.18 ± 16.69. Child age, sex, age at seizure onset, duration of epilepsy, caregiver age, caregiver education, and income were not significantly associated with HRQL. Univariable regression analyses revealed that a higher number of anti-seizure medications (p = 0.020), lower IQ (p = 0.002), greater seizure frequency (p = 0.048), caregiver unemployment (p = 0.010), higher caregiver depressive and anxiety symptoms (p < 0.001 for both), poorer family adaptation, fewer family resources, and a greater number of family demands (p < 0.001 for all) were associated with lower HRQL. Multivariable regression analysis showed that lower child IQ (β = 0.20, p = 0.004), fewer family resources (β = 0.43, p = 0.012), and caregiver unemployment (β = 6.53, p = 0.018) were associated with diminished HRQL in children. Significance The results emphasize the importance of child cognition and family variables in the HRQL of children with drug-resistant epilepsy. The findings speak to the importance of offering comprehensive care to children and their families to address the nonmedical features that impact on HRQL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective The yield of epileptiform abnormalities in serial electroencephalography (EEG) studies has not been addressed in a population-based setting for subjects with incident epilepsy or a single unprovoked seizure, raising the possibility of methodologic limitations such as selection bias. Our aim was to address these limitations by assessing the yield and predictors of epileptiform abnormalities for the first and subsequent EEG recording in a study of incident epilepsy or single unprovoked seizure in Rochester, Minnesota. Methods We used the resources of the Rochester Epidemiology Project to identify all 619 residents of Rochester, Minnesota, born in 1920 or later with a diagnosis of incident epilepsy (n = 478) or single unprovoked seizure (n = 141) between 1960 and 1994, who had at least one EEG study. Information on all EEG studies and their results was obtained by comprehensive review of medical records. Results Among subjects with epilepsy, the cumulative yield of epileptiform abnormalities was 53% after the first EEG study and 72% after the third. Among subjects with a single unprovoked seizure, the cumulative yield was 39% after the first EEG study and 68% after the third. Young age at diagnosis and idiopathic etiology were risk factors for finding epileptiform abnormalities across all EEG recordings. Significance Although the cumulative yield of epileptiform abnormalities increases over successive EEG recordings, there is a decrease in the increment for each additional EEG study after the first EEG study. This is most evident in incident epilepsy and in younger subjects. Clinically it may be worthwhile to consider that the probability of finding an epileptiform abnormality after the third nonepileptiform EEG recording is low. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Several studies indicate a higher occurrence than might be expected of seizures in intensive care unit patients, many of which are not clinically apparent. Few of these studies are devoted exclusively to pediatric patients. The purpose of this study is to determine the occurrence of seizures in a cohort of pediatric and neonatal intensive care unit patients. Long-term video electroencephalography (EEG) monitoring studies performed in the pediatric and neonatal intensive care units were reviewed. Age, gender, diagnosis, EEG background, epileptiform activity, time of onset and duration of seizures, presence of electroclinical or electrographic seizures, and survival were collected. One hundred thirty-eight recordings encompassing 122 patients were identified. Thirty-four percent of the sessions identified seizures in the first 24 h (38% of the cohort experienced a seizure at some time during monitoring, which ranged from 1-22 days): 17% captured only electroclinical seizures, 49% were electrographic only, and 34% had both electroclinical and electrographic seizures. Seventy percent of those patients experiencing seizures had their first seizure within the first hour of EEG recording. Younger age and epileptiform activity (including periodic) were associated with the occurrence of seizures. Diagnoses of head trauma and status epilepticus/recent prior seizure were more likely than other at-risk diagnoses to be associated with seizures; cardiac arrest managed with hypothermia was less likely to be associated with seizures. One-fourth of the recordings identified nonepileptic events. Seizures occurred in one-third of critically ill pediatric patients at risk for seizures who underwent video-EEG monitoring, and many of these seizures did not have a clinical correlate. In those at risk for seizures in intensive care units, there should be a low threshold for obtaining long-term monitoring. [ABSTRACT FROM AUTHOR]

The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy. Generalized and focal are redefined for seizures as occurring in and rapidly engaging bilaterally distributed networks (generalized) and within networks limited to one hemisphere and either discretely localized or more widely distributed (focal). Classification of generalized seizures is simplified. No natural classification for focal seizures exists; focal seizures should be described according to their manifestations (e.g., dyscognitive, focal motor). The concepts of generalized and focal do not apply to electroclinical syndromes. Genetic, structural–metabolic, and unknown represent modified concepts to replace idiopathic, symptomatic, and cryptogenic. Not all epilepsies are recognized as electroclinical syndromes. Organization of forms of epilepsy is first by specificity: electroclinical syndromes, nonsyndromic epilepsies with structural–metabolic causes, and epilepsies of unknown cause. Further organization within these divisions can be accomplished in a flexible manner depending on purpose. Natural classes (e.g., specific underlying cause, age at onset, associated seizure type), or pragmatic groupings (e.g., epileptic encephalopathies, self-limited electroclinical syndromes) may serve as the basis for organizing knowledge about recognized forms of epilepsy and facilitate identification of new forms. [ABSTRACT FROM AUTHOR]

To validate a brief screening instrument for identifying people with epilepsy in epidemiologic or genetic studies. We designed a nine-question screening instrument for epilepsy and administered it by telephone to individuals with medical record–documented epilepsy (lifetime history of ≥2 unprovoked seizures, n = 168) or isolated unprovoked seizure (n = 54), and individuals who were seizure-free on medical record review (n = 120), from a population-based study using Rochester Epidemiology Project resources. Interviewers were blinded to record-review findings. Sensitivity (the proportion of individuals who screened positive among affected individuals) was 96% for epilepsy and 87% for isolated unprovoked seizure. The false positive rate (FPR, the proportion who screened positive among seizure-free individuals) was 7%. The estimated positive predictive value (PPV) for epilepsy was 23%, assuming a lifetime prevalence of 2% in the population. Use of only a single question asking whether the subject had ever had epilepsy or a seizure disorder resulted in sensitivity 76%, FPR 0.8%, and estimated PPV 66%. Subjects with epilepsy were more likely to screen positive with this question if they were diagnosed after 1964 or continued to have seizures for at least 5 years after diagnosis. Given its high sensitivity, our instrument may be useful for the first stage of screening for epilepsy; however, the PPV of 23% suggests that only about one in four screen-positive individuals will be truly affected. Screening with a single question asking about epilepsy yields a higher PPV but lower sensitivity, and screen-positive subjects may be biased toward more severe epilepsy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research. [ABSTRACT FROM AUTHOR]

The aims of this retrospective study were: (1) to compare the demographics, clinical characteristics, etiology, and EEG findings of status epilepticus aborted with medication (ASE) and refractory status epilepticus (RSE), (2) to describe the treatment response of status epilepticus (SE), and (3) to determine predictors of long-term outcome in children with SE. Medical records and EEG lab logs with ICD-9 diagnostic codes related to SE were reviewed. Patients younger than 18 years of age, hospitalized in 1994–2004 at the Mayo Clinic, Rochester, were included. One hundred fifty-four children had SE; 94 (61%) had ASE, and 60 (39.0%) had RSE. Family history of seizures, higher seizure frequency score, higher number of maintenance antiepileptic drugs (AEDs), nonconvulsive SE, and focal or electrographic seizures on initial EEG were associated with RSE by univariate analysis. In-hospital mortality was significantly higher in RSE (13.3%) than in ASE (2.1%). In the long term, survivors with RSE developed more new neurological deficits (p < 0.001) and more epilepsy (p < 0.004) than children with ASE. Children treated in a more aggressive fashion appeared to have better treatment responses (p < 0.001) and outcomes (p = 0.03). Predictors of poor outcome were long seizure duration (p < 0.001), acute symptomatic etiology (p = 0.04), nonconvulsive SE (NCSE) (p = 0.01), and age at admission <5 years (p = 0.05). Several patient and clinical characteristics are associated with development of RSE and poor outcome. Prospective, randomized trials that assess different treatment protocols in children with SE are needed to determine the optimal sequence and timing of medications. [ABSTRACT FROM AUTHOR]

Objective: The concept of “rational polypharmacy” has been associated with anticonvulsant management for decades, but the term has not been applied to nonpharmacologic therapies. Methods: We conducted a multicenter, retrospective study of children who received concurrent diet (ketogenic or modified Atkins) and vagus nerve stimulation (VNS) treatment for medically intractable epilepsy. Results: Thirty children in total from six epilepsy centers were treated over a 6-yr period. The median age at the initiation of combination therapy was 10 yr (range, 4–24 yr). Sixteen (53%) received dietary therapy followed by VNS; no differences were noted between centers. After 3 months, 21 (70%) had seizure reduced by >50% over the previous single nonpharmacologic treatment, of whom 13 (62%) had improvement within the first month. A 5-min VNS off-time correlated with >90% seizure reduction (p = 0.02). The median duration of nonpharmacologic polytherapy was 12 months (range, 0.5–96 months); 17 (57%) remain on dual therapy at this time. No side effects were noted. Most patients who discontinued combination therapy did so because of a lack of efficacy rather than restrictiveness. Conclusions: In this small group, the combined use of diet and VNS appeared synergistic and yielded rapid benefits. It may be more effective with longer VNS off-times. Further prospective studies of this combination in refractory pediatric epilepsy are needed to help guide optimal use. [ABSTRACT FROM AUTHOR]

The article discusses the use of various pharmacotherapies on patients with cancer due to smoking in the U.S. The estimated number of deaths related to cigarette smoking, is discussed. Thus, significant reduction of health risks by smoking cessation is conducted with varying outcomes across medical conditions.

Cigarette smoking causes cancer and disease, yet people find quitting difficult due to aversive symptoms that accompany tobacco abstinence. Understanding how to suppress these symptoms is critical in developing effective smoking cessation treatments. Pharmacologically, pure nicotine suppresses tobacco abstinence symptoms partially, and non-nicotine, smoking-related stimuli suppress these abstinence symptoms fully, at least for 24 hours. The current study was designed to clarify the impact of smoking-related stimuli on tobacco withdrawal, and to explore the duration of their ability to suppress withdrawal in smokers.Three double-blind, within-subjects, Latin square-ordered, 5-day conditions in which participants smoked nicotinized, denicotinized or no cigarettes.Out-patient laboratory at Virginia Commonwealth University.Thirteen women and 19 men.Subjective, physiological and performance measures were collected daily and compliance with study conditions was verified objectively.Smoking-related stimuli are sufficient for suppressing some symptoms of tobacco abstinence over a 5-day period[i.e. Questionnaire of Smoking Urges (QSU) factor 1,‘Desire for sweets’,‘Hunger’ and‘Urges to smoke’], while in this study a combination of nicotine and smoking-related stimuli suppressed other symptoms (i.e.‘Difficulty concentrating’,‘Increased eating’,‘Restlessness’ and‘Impatient’).These results indicate that, while some tobacco abstinence symptoms may be suppressed with nicotine, suppressing others may also require strategies that address the absence of smoking-related stimuli. [ABSTRACT FROM AUTHOR]

Epilepsy surgery has emerged as an important option in the treatment of children with epilepsy that is refractory to antiepileptic drug management. The cornerstone of successful surgery is accurate localization of the brain region of seizure onset. Traditional techniques of seizure onset localization, e.g. surface electroencephalography (EEG) recording and magnetic resonance imaging (MRI), allow accurate localization in a significant number of patients. When the focus of seizure onset is not apparent from these non-invasive techniques, other methods of localization, e.g. intracranial EEG recording, may be needed before resection of the focus. Single-photon emission computed tomography (SPECT) is a nuclear medicine blood-flow technique that has been used to identify a region of epileptogenic brain associated with low blood flow in the resting state (interictal SPECT) or increased blood flow at the time of seizure activity (ictal SPECT). This report describes the validation and utility of a computer-assisted method of subtracting the interictal from the ictal SPECT scans and co-registering the difference image on the MRI. This method, called subtraction ictal SPECT co-registered on MRI (SISCOM), is used in guiding the location and the extent of intracranial electrode implantation, or in obviating the need for the implantation in some cases. [ABSTRACT FROM AUTHOR]

Summary: Purpose: To determine the frequency and prognostic features of acute postoperative seizures (APOSs), within the first postoperative week, in a group of children undergoing surgery for the treatment of medically refractory epilepsy. Methods: Patients younger than 18 years who underwent surgery for the relief of medically intractable epilepsy at the Mayo Clinic between 1985 and 1998 with a minimum of 12 months of follow-up were eligible. A retrospective chart review was conducted to abstract information regarding demographics, epilepsy history, and preoperative, intraoperative, and postoperative risk factors, APOSs, and outcome. A multivariate analysis was conducted to control for confounding variables. Results: The study group was composed of 148 patients (mean age at surgery, 13 years; range, 5 months to 18 years). Twenty-five percent of patients experienced APOSs. Risk factors associated with a statistically significant (p < 0.05) greater likelihood of experiencing APOS were non–complex partial seizure type, extratemporal surgery, postoperative fever, non–temporal lobe epilepsy, and postoperative interictal epileptiform activity. At last follow-up, patients who did not experience APOSs had a significantly greater chance of being seizure free (80 vs. 51%; p < 0.001). With a multivariate analysis, APOS was found to be an independent predictor of outcome. Conclusions: This study indicates that APOSs are predictive of a less favorable outcome in the pediatric postsurgical patient; however, 51% remained seizure free at last follow-up. Finally, the effects of APOSs on outcome were shown to be stable over a 12-month follow-up period. [ABSTRACT FROM AUTHOR]

A variety of symptoms that accompany migraine in the child and adult are mediated by the autonomic nervous system. Significant effects on cardiac rhythm are uncommon, but can be life threatening. We describe a 3-year-old girl in whom migraine-associated vomiting precipitated cardiac asystole which was effectively treated with a cardiac pacemaker. [ABSTRACT FROM AUTHOR]

Sudden unexpected death in epilepsy (SUDEP) is the most tragic potential outcome of epilepsy. Despite recommendations from epilepsy organizations in the United Kingdom and the United States, many neurologists choose not to discuss the risk of SUDEP with their patients with epilepsy. Yet, the literature clearly demonstrates that people with epilepsy and their caregivers want to know more about SUDEP. When health care providers do not provide information, people with epilepsy turn to other sources, risking misinformation and potentially increasing anxiety and distress. Sharing accurate information about SUDEP can optimize epilepsy self-management and engage the person with epilepsy as a partner in their own care. Information about SUDEP must be part of the comprehensive education given to all people with epilepsy. [ABSTRACT FROM AUTHOR]

Purpose: Ictal single-photon emission computed tomography (SPECT) may be a reliable indicator of the ictal onset zone in patients with intractable partial epilepsy who are being considered for epilepsy surgery. The rationale for the illustrated case report is to evaluate the use of an innovation in SPECT imaging in a patient with nonlesional extratemporal epilepsy. Methods: We investigated the presurgical evaluation and operative outcome in a patient with intractable partial epilepsy. The ictal semiology indicated a “hypermotor” seizure with bipedal automatism. The electroclinical correlation and magnetic resonance imaging (MRI) did not suggest the appropriate localization of the epileptogenic zone. A subtraction periictal SPECT coregistered to MRI (SISCOM) was peformed. Results: SISCOM revealed a region of localized hyperperfusion in the right supplementary sensorimotor area. Chronic intracranial EEG monitoring confirmed the relationship between the localized SISCOM alteration and the ictal onset zone. The patient was rendered seizure free after surgical treatment. Conclusions: SISCOM may be used to identify potential candidates for surgical treatment of nonlesional extratemporal epilepsy. Periictal imaging may also alter the strategy for intracranial EEG recordings and focal cortical resection. [ABSTRACT FROM AUTHOR]

The author comments on the article "Epilepsy informatics and an ontology-driven infrastructure for large database research and patient care in epilepsy," by S. Sahoo and colleagues. He emphasizes the application of modern informatics techniques in the classification of epilepsy. He describes the approach of the International League Against Epilepsy (ILAE) Commission on Classification and Terminology (CTC) in the classification of seizures.

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Prabhakar H, Bindra A, Singh GP, Kalaivani M. Propofol versus thiopental sodium for the treatment of refractory status epilepticus. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD009202. DOI: 10.1002/14651858.CD009202.pub2. [ABSTRACT FROM AUTHOR]