Faculty Bibliography

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

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

OBJECTIVE:A recent FDA warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurological community. This warning was based on in vitro studies, but no clinically relevant risk was considered. This rapid systematic review aims to elucidate the risk of lamotrigine on sudden death or electrocardiogram abnormalities. METHODS:We conducted a systematic search of Ovid Medline and Ovid Embase, including randomized controlled trials and observational studies, studies of people with or without epilepsy, with one of the following outcome measures: SUDEP and sudden cardiac death, as well as the development or worsening of electrocardiogram abnormalities. All titles and abstracts were independently screened, and the full texts of relevant studies were obtained. We re-evaluated the sudden death definitions used in all included studies, as some could have used unclear or overlapping definitions. We used the American Academy of Neurology risk of bias tool to evaluate the class of evidence and the GRADE approach to evaluate our confidence in the evidence. RESULTS:We included 26 studies with 24,962 participants, of whom 2,326 used lamotrigine. Twelve studies showed no significant risk of SUDEP for lamotrigine users. One study reporting on sudden cardiac death and three studies with unclear sudden death definitions did not report an elevated risk of death in lamotrigine users compared to controls. In 10 studies reporting on electrocardiogram parameters, there was no statistically significant increased risk among lamotrigine users except for two studies. These two studies reported either "slight increases" in PR interval or an increased PQ interval that the primary study authors felt to be more related to structural cardiac differences rather than an effect of lamotrigine. One study was rated class II while all others were class III or IV. We had "very low confidence" in the evidence following the GRADE assessment. None of the studies examined the risk of lamotrigine in people with pre-existing cardiac conditions. CONCLUSION/CONCLUSIONS:There is insufficient evidence to support or refute that lamotrigine is associated with sudden death or electrocardiogram changes, in people with or without epilepsy as compared to ASM or placebo. This is due to the high risk of bias in most studies and low precision and inconsistency in the reported results.

Light flashes, patterns, or color changes can provoke seizures in up to 1 in 4000 persons. Prevalence may be higher because of selection bias. The Epilepsy Foundation reviewed light-induced seizures in 2005. Since then, images on social media, virtual reality, three-dimensional (3D) movies, and the Internet have proliferated. Hundreds of studies have explored the mechanisms and presentations of photosensitive seizures, justifying an updated review. This literature summary derives from a nonsystematic literature review via PubMed using the terms "photosensitive" and "epilepsy." The photoparoxysmal response (PPR) is an electroencephalography (EEG) phenomenon, and photosensitive seizures (PS) are seizures provoked by visual stimulation. Photosensitivity is more common in the young and in specific forms of generalized epilepsy. PS can coexist with spontaneous seizures. PS are hereditable and linked to recently identified genes. Brain imaging usually is normal, but special studies imaging white matter tracts demonstrate abnormal connectivity. Occipital cortex and connected regions are hyperexcitable in subjects with light-provoked seizures. Mechanisms remain unclear. Video games, social media clips, occasional movies, and natural stimuli can provoke PS. Virtual reality and 3D images so far appear benign unless they contain specific provocative content, for example, flashes. Images with flashes brighter than 20 candelas/m² at 3-60 (particularly 15-20) Hz occupying at least 10 to 25% of the visual field are a risk, as are red color flashes or oscillating stripes. Equipment to assay for these characteristics is probably underutilized. Prevention of seizures includes avoiding provocative stimuli, covering one eye, wearing dark glasses, sitting at least two meters from screens, reducing contrast, and taking certain antiseizure drugs. Measurement of PPR suppression in a photosensitivity model can screen putative antiseizure drugs. Some countries regulate media to reduce risk. Visually-induced seizures remain significant public health hazards so they warrant ongoing scientific and regulatory efforts and public education.

The International League Against Epilepsy (ILAE) seizure classification scheme has been periodically updated to improve its reliability and applicability to clinicians and researchers alike. Here, members of the Epilepsy Study Consortium propose a pragmatic seizure classification, based on the ILAE scheme, designed for use in clinical trials with a focus on outcome measures that have high reliability, broad interpretability across stakeholders, and clinical relevance in the context of the development of novel antiseizure medications. Controversies around the current ILAE classification scheme are discussed in the context of clinical trials, and pragmatic simplifications to the existing scheme are proposed, for intended use by investigators, industry sponsors, and regulatory agencies.

OBJECTIVE/UNASSIGNED:Little is known about psychiatric symptoms among patients with migraine and newly diagnosed focal epilepsy. The investigators compared symptoms of depression, anxiety, and suicidality among people with newly diagnosed focal epilepsy with migraine versus without migraine. METHODS/UNASSIGNED:The Human Epilepsy Project is a prospective multicenter study of patients with newly diagnosed focal epilepsy. Depression (measured with the Center for Epidemiologic Studies Depression Scale), anxiety (measured with the 7-item Generalized Anxiety Disorder scale), and suicidality scores (measured with the Columbia-Suicide Severity Rating Scale [C-SSRS]) were compared between participants with versus without migraine. Data analysis was performed with the Kolmogorov-Smirnov test for normality assessment, the Mann-Whitney U test, chi-square test, and linear regression. RESULTS/UNASSIGNED:Of 349 patients with new-onset focal epilepsy, 74 (21.2%) had migraine. There were no differences between the patients without migraine versus those with migraine in terms of age, race, and level of education. There were more women in the group with migraine than in the group without migraine (75.7% vs. 55.6%, p=0.0018). The patients with epilepsy and comorbid migraine had more depressive symptoms than the patients with epilepsy without migraine (35.2% vs. 22.7%, p=0.031). Patients with epilepsy with comorbid migraine had more anxiety symptoms than patients with epilepsy without migraine, but this relation was mediated by age in logistic regression, with younger age being associated with anxiety. Comorbid migraine was not associated with C-SSRS ideation or behavior. CONCLUSIONS/UNASSIGNED:Among a sample of patients with newly diagnosed focal epilepsy, 21.2% had migraine. Migraine comorbidity was associated with higher incidence of depressive symptoms. Future studies should be performed to better assess these relationships and possible treatment implications.

OBJECTIVE:To update a 1996 American Academy of Neurology practice parameter. METHODS:The authors systematically reviewed literature published from January 1991 to March 2020. RESULTS:The long-term (24-60 months) risk of seizure recurrence is possibly higher among adults who have been seizure-free for 2 years and taper antiseizure medications (ASMs) vs those who do not taper ASMs (15% vs 7% per the 1 Class I article addressing this issue). In pediatric patients, there is probably no significant difference in seizure recurrence between those who begin tapering ASMs after 2 years vs 4 years of seizure freedom, and there is insufficient evidence of significant difference in risk of seizure recurrence between those who taper ASMs after 18 months of seizure freedom and those tapering after 24 months. There is insufficient evidence that the rate of seizure recurrence with ASM withdrawal following epilepsy surgery after 1 year of seizure freedom vs after 4 years is not significantly different than maintaining patients on ASMs. An epileptiform EEG in pediatric patients increases the risk of seizure recurrence. ASM withdrawal possibly does not increase the risk of status epilepticus in adults. In seizure-free adults, ASM weaning possibly does not change quality of life. Withdrawal of ASMs at 25% every 10 days to 2 weeks is probably not significantly different from withdrawal at 25% every 2 months in children who are seizure-free in more than 4 years of follow-up. RECOMMENDATIONS/CONCLUSIONS:Fourteen recommendations were developed.