Video Analyses of Sudden Unexplained Deaths in Toddlers Gould L, Reid CA, Rodriguez AJ, Devinsky O; for SUDC Video Working Group. Neurology . 2024;102(3):e208038. doi: 10.1212/WNL.0000000000208038 . PMID: 38175965 Background and objectives: More than 2,900 US children aged younger than 4 years die from unknown causes each year, accounting for more than 219,000 life years lost annually. They are mostly sleep-related and unwitnessed with unremarkable autopsies, limiting our understanding of death mechanisms. We sought to understand potential mechanisms of death by evaluating videos of sudden deaths in toddlers. Methods: In our registry of 301 sudden unexplained child deaths, a series of 7 consecutively enrolled cases with home video recordings of the child’s last sleep period were independently assessed by 8 physicians for video quality, movement, and sound. Results: Four boys and 3 girls (13-27 months at death) with terminal videos shared similar demographic features to the 293 other registry cases without video recordings. Five video recordings were continuous and 2 were triggered by sound or motion; 2 lacked audio. All continuous recordings included a terminal convulsive event lasting 8-50 seconds; 4 children survived for >2.5 minutes postconvulsion. Among discontinuous videos, time lapses limited review; 1 suggested a convulsive event. Six were prone with face down, and 1 had autopsy evidence of airway obstruction. Primary cardiac arrhythmias were not supported; all 7 children had normal cardiac pathology and whole-exome sequencing identified no known cardiac disease variants. Discussion: Audio-visual recordings in 7 toddlers with unexplained sudden deaths strongly implicate that deaths were related to convulsive seizures, suggesting that many unexplained sleep-related deaths may result from seizures. Exome Analysis Focusing on Epilepsy-Related Genes in Children and Adults With Sudden Unexplained Death Buerki SE, Haas C, Neubauer J. Seizure . 2023;113:66-75. doi: 10.1016/j.seizure.2023.11.002 . PMID: 37995443 Purpose: Genetic studies in sudden infant death syndrome (SIDS) and sudden unexplained death (SUD) cohorts have indicated that cardiovascular diseases might have contributed to sudden unexpected death in 20% to 35% of autopsy-negative cases. Sudden unexpected death can also occur in people with epilepsy, termed as sudden unexpected death in epilepsy (SUDEP). The pathophysiological mechanisms of SUDEP are not well understood, but are likely multifactorial, including seizure-induced hypoventilation and arrhythmias as well as genetic risk factors. The sudden death of some of the SIDS/SUD victims might also be explained by genetic epilepsy, therefore this study aimed to expand the post-mortem genetic analysis of SIDS/SUD cases to epilepsy-related genes. Methods: Existing whole-exome sequencing data from our 155 SIDS and 45 SUD cases were analyzed, with a focus on 365 epilepsy-related genes. Nine of the SUD victims had a known medical history of epilepsy, seizures or other underlying neurological conditions and were therefore classified as SUDEP cases. Results: In our SIDS and SUD cohorts, we found epilepsy-related pathogenic/likely pathogenic variants in the genes OPA1, RAI1, SCN3A, SCN5A and TSC2. Conclusion: Post-mortem analysis of epilepsy-related genes identified potentially disease-causing variants that might have contributed to the sudden death events in our SIDS/SUD cases. However, the interpretation of identified variants remains challenging and often changes over time as more data is gathered. Overall, this study contributes insight in potentially pathophysiological epilepsy-related mechanisms in SIDS, SUD and SUDEP victims and underlines the importance of sensible counselling on the risk and preventive measures in genetic epilepsy.

The 2023 American Epilepsy Society Annual Course "It's About Time" addressed timing in epilepsy evaluation and treatment with respect to health disparity and vulnerable populations and diagnostic, clinical, and epilepsy surgery evaluation. This comprehensive course included topics on gaps in epilepsy care and optimization of behavioral health for patients with epilepsy. The summary details current knowledge in areas of seizure forecasting and epileptogenesis. Intricacies and controversies over timing were discussed for treatment of nonconvulsive seizures and ictal-interictal patterns, acute symptomatic seizures, neuromodulation versus surgery, and epilepsy surgery in status epilepticus. Timing regarding clinical care in autoimmune-associated epilepsy, developmental and epileptic encephalopathy, and dietary therapy were examined. Additionally, salient topics on using novel biomarkers and collaboration with neuropsychological outcomes were also tackled in this all-encompassing lecture series.

Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized EpilepsyIrelli EC, Cocchi E, Morano A, Gesche J, Caraballo RH, Lattanzi S, Strigaro G, Catania C, Ferlazzo E, Pascarella A, Casciato S, Quarato P, Pizzanelli C, Pulitano P, Giuliano L, Viola V, Mostacci B, Fortunato F, Marini C, Di Gennaro G, Gambardella A, Labate A, Operto FF, Giallonardo AT, Baykan B, Beier CP, Di Bonaventura C; Women With Epilepsy Treatment Options and Research (WETOR) Study Group. JAMA Neurol. 2023;80(11):1174-1181. doi:10.1001/jamaneurol.2023.3400Importance:After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors’ knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients.Objective:To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE.Design, Setting, and Participants:This was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription.Exposures:Levetiracetam or lamotrigine as initial monotherapy.Main Outcomes and Measures:Inverse probability of treatment weighting (IPTW)–adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy.Results:A total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95%CI, 0.59-0.99; P = .04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR, 0.47; 95%CI, 0.32-0.68; P < .001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95%CI, 0.65-1.23; P = .60).Conclusions and Relevance:Results of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.

Diagnostic Accuracy of Ambulatory EEG vs Routine EEG in Patients With First Single Unprovoked SeizureHernandez-Ronquillo L, Thorpe L, Feng C, Hunter G, Dash D, Hussein T, Dolinsky C, Waterhouse K, Roy P, Jette N. Neurol Clin Pract. 2023;13(3). doi:10.1212/CPJ.0000000000200160Background and Objective:To evaluate the diagnostic accuracy of the ambulatory EEG (aEEG) at detecting interictal epileptiform discharges (IEDs)/seizures compared with routine EEG (rEEG) and repetitive/second rEEG in patients with a first single unprovoked seizure (FSUS). We also evaluated the association between IED/seizures on aEEG and seizure recurrence within 1 year of follow-up.Methods:We prospectively evaluated 100 consecutive patients with FSUS at the provincial Single Seizure Clinic. They underwent 3 sequential EEG modalities: first rEEG, second rEEG, and aEEG. Clinical epilepsy diagnosis was ascertained based on the 2014 International League Against Epilepsy definition by a neurologist/epileptologist at the clinic. An EEG-certified epileptologist/neurologist interpreted all 3 EEGs. All patients were followed up for 52 weeks until they had either second unprovoked seizure or maintained single seizure status. Accuracy measures (sensitivity, specificity, negative and positive predictive values, and likelihood ratios), receiver operating characteristic (ROC) analysis, and area under the curve (AUC) were used to evaluate the diagnostic accuracy of each EEG modality. Life tables and the Cox proportional hazard model were used to estimate the probability and association of seizure recurrence.Results:Ambulatory EEG captured IED/seizures with a sensitivity of 72%, compared with 11% for the first rEEG and 22% for the second rEEG. The diagnostic performance of the aEEG was statistically better (AUC: 0.85) compared with the first rEEG (AUC: 0.56) and second rEEG (AUC: 0.60). There were no statistically significant differences between the 3 EEG modalities regarding specificity and positive predictive value. Finally, IED/seizure on the aEEG was associated with more than 3 times the hazard of seizure recurrence.Discussion:The overall diagnostic accuracy of aEEG at capturing IED/seizures in people presenting with FSUS was higher than the first and second rEEGs. We also found that IED/seizures on the aEEG were associated with an increased risk of seizure recurrence.Classification of Evidence:This study provides Class I evidence supporting that, in adults with First Single Unprovoked Seizure (FSUS), 24-h ambulatory EEG has increased sensitivity when compared with routine and repeated EEG.

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This brief review summarizes presentations at the Temporal Lobe Club Special Interest Group session held in December 2022 at the American Epilepsy Society meeting. The session addressed newer methods to treat temporal epilepsy, including methods currently in clinical use and techniques under investigation. Brief summaries are provided for each of 4 lectures. Dr Chengyuan Wu discussed ablative techniques such as laser interstitial thermal ablation, radiofrequency ablation, focused ultrasound; Dr Joon Kang reviewed neuromodulation techniques including electrical stimulation and focused ultrasound; Dr Julia Makhalova discussed network effects of the aforementioned techniques; and Dr Derek Southwell reviewed inhibitory interneuron transplantation. These summaries are intended to provide a brief overview and references are provided for the reader to learn more about each topic.

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Cognitive Outcomes at Age 3 Years in Children With Fetal Exposure to Antiseizure Medications (MONEAD Study) in the USA: A Prospective, Observational Cohort StudyMeador KJ, Cohen MJ, Loring DW, Matthews AG, Brown C, Robalino CP, Birnbaum AK, Voinescu PE, Kalayjian LA, Gerard EE, Gedzelman ER, Hanna J, Cavitt J, Sam M, French JA, Hwang S, Pack AM, Pennell PB; MONEAD Investigator Group. Lancet Neurol. 2023;22(8):712-722. doi:10.1016/S1474-4422(23)00199-0Background:The neurodevelopmental effects of fetal exposure to most antiseizure medications are unclear. We aimed to investigate the effects of fetal exposure to commonly used antiseizure medications on neuropsychological outcomes at age 3 years.Methods:The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicenter cohort study at 20 specialty epilepsy centers in the USA. We have investigated pregnancy outcomes in women (aged 14-45 years) with and without epilepsy who were enrolled during pregnancy (≤20 weeks’ gestational age), and their children. The primary outcome for children at age 3 years was a blindly assessed Verbal Index score, which was calculated by averaging scores on the Naming Vocabulary and Verbal Comprehension subtests of Differential Ability Scales-II, Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale-5, and Peabody Picture Vocabulary Test-4. Children of women with and without epilepsy were compared, and the associations of medication exposures to outcomes in exposed children were assessed. The MONEAD study is registered with ClinicalTrials.gov, NCT0730170, and is ongoing.Findings:Between Dec 19, 2012, and Jan 13, 2016, 456 pregnant women (351 with epilepsy and 105 without epilepsy) were enrolled into the study. 345 children were born to women with epilepsy and 106 children were born to women without epilepsy. Verbal Index scores at age 3 years did not differ for children of women with epilepsy (n = 284; adjusted least-square mean 102.7, 95% CI 101.4 to 103.9) versus those without epilepsy (n = 87; 102.3, 99.8 to 104.7). Significant risk factors for reduced Verbal Index scores included maternal intelligence quotient, maternal education, post-birth anxiety, gestational age at enrolment, child’s sex, and child’s ethnicity. For Verbal Index scores, antiseizure medication exposure effects were not seen for maximum third trimester blood concentrations (n = 258; adjusted parameter estimate −2.9, 95% CI −6.7 to 1·0). However, in secondary analyses, exposure-dependent effects were present on multiple cognitive measures, which varied by medication.Interpretation:We found no difference in neurodevelopmental outcomes between children with fetal exposure to newer antiseizure medications compared with unexposed children. However, some exposure-dependent antiseizure medication effects were seen in secondary analyses. The adverse effects of maternal post-birth anxiety emphasize the importance of screening mothers during pregnancy and postpartum and implementing interventions. Additional studies are needed to clarify the exposure-dependent effects.

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With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia.