Early-Onset Epileptic Encephalopathies: Ohtahara Syndrome and Early Myoclonic Encephalopathy

AbstractOhtahara syndrome and early myoclonic encephalopathy are the earliest presenting of the epileptic encephalopathies. They are typically distinguished from each other according to specific clinical and etiologic criteria. Nonetheless, considerable overlap exists between the two syndromes in terms of clinical presentation, prognosis, and electroencephalographic signature. Newer understandings of underlying etiologies of these conditions may support the previously suggested concept that they represent a single spectrum of disease rather than two distinct disorders. We review both syndromes, with particular focus on the underlying genetics and pathophysiology and implications regarding the classification of these conditions

The ILAE classification of seizures and the epilepsies : Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic-only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic-only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non-motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group.Peer reviewe

Why monitor the neonatal brain-that is the important question

A key goal of neonatal neurocritical care is improved outcomes, and brain monitoring plays an essential role. The recent NEST trial(1) reported no outcome benefits using aEEG monitoring compared to clinical seizure identification among neonates treated for seizures. However, the study failed to prove the effects of monitoring on seizure treatment in the first place.Non peer reviewe

Methodology for classification and definition of epilepsy syndromes with list of syndromes: Report of the ILAE Task Force on Nosology and Definitions

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

Sex-specific consequences of early life seizures

WOS: 000345198200006PubMed ID: 24874547Seizures are very common in the early periods of life and are often associated with poor neurologic outcome in humans. Animal studies have provided evidence that early life seizures may disrupt neuronal differentiation and connectivity, signaling pathways, and the function of various neuronal. networks. There is growing experimental evidence that many signaling pathways, like GABA(A) receptor signaling, the cellular physiology and differentiation, or the functional maturation of certain brain regions, including those involved in seizure control, mature differently in males and females. However, most experimental studies of early life seizures have not directly investigated the importance of sex on the consequences of early life seizures. The sexual dimorphism of the developing brain raises the question that early seizures could have distinct effects in immature females and males that are subjected to seizures. We will first discuss the evidence for sex-specific features of the developing brain that could be involved in modifying the susceptibility and consequences of early life seizures. We will then review how sex-related biological factors could modify the age-specific consequences of induced seizures in the immature animals. These include signaling pathways (e.g., GABA(A) receptors), steroid hormones, growth factors. Overall, there are very few studies that have specifically addressed seizure outcomes in developing animals as a function of sex. The available literature indicates that a variety of outcomes (histopathological, behavioral, molecular, epileptogenesis) may be affected in a sex-, age-, region-specific manner after seizures during development. Obtaining a better understanding for the gender-related mechanisms underlying epileptogenesis and seizure comorbidities will be necessary to develop better gender and age appropriate therapies. (C) 2014 Elsevier Inc. All rights reserved.NINDS [NS078333, NS020253, NS043209, NS045911]; CURE; Autism Speaks; Department of Defense; Heffer Family Foundation; Siegel Family FoundationA.S.G. acknowledges research grant funding from NINDS (NS078333), CURE, Autism Speaks, Department of Defense, and the Heffer Family and Siegel Family Foundations. A.S.G. has received royalties from Morgan & Claypool Publishers and John Libbey Eurotext Ltd., and consultancy honorarium from Viropharma. S.L.M. received grants from NINDS (NS020253, NS043209, NS045911, and NS078333), Department of Defense, CURE, the Heffer Family and Siegel Family Foundations, and consultancy honorarium from Lundbeck and UCB Pharma

Application of the International League Against Epilepsy Neonatal Seizure Framework to an international panel of medical personnel

Objective The International League Against Epilepsy (ILAE) Neonatal Seizure Framework was tested by medical personnel.Methods Attendees at the 2016 ILAE European Congress on Epileptology in Prague, the International Video-EEG Course in Pediatric Epilepsies in Madrid 2017, and a local meeting in Utrecht 2018, were introduced to the proposed ILAE neonatal classification system with teaching videos covering the seven types of clinical seizures in the proposed neonatal classification system. Five test digital video recordings of electroencephalography (EEG)-confirmed motor neonatal seizures were then shown and classified by the rater based on their knowledge of the proposed ILAE Neonatal Seizure Framework. A multi-rater Kappa statistic was used to assess the agreement between observers and the true diagnosis.Results The responses of 194 raters were obtained. There was no single predominant classification system that was currently used by the raters. Using the ILAE framework, 78%-93% of raters correctly identified the clinical seizure type for each neonate; the overall inter-rater agreement (Kappa statistic) was 0.67. The clonic motor seizure type was most frequently accurately identified (93% of the time; ? = 0.870). EEG technicians correctly identified all presented motor seizure types more frequently than any other group (accuracy = 0.9).Significance The ILAE Neonatal Seizure Framework was judged by most raters to be better than other systems for the classification of clinical seizures. Among all seizure types presented, clonic seizures appeared to be the easiest to accurately identify. Average accuracy across the five seizure types was 84.5%. These data suggest that the ILAE neonatal seizure classification may be used by all healthcare professionals to correctly identify the predominant clinical seizure type.Peer reviewe