The 2017 International League Against Epilepsy classification has defined a three‐tier system with epilepsy syndrome identification at the third level. Although a syndrome cannot be determined in all children with epilepsy, identification of a specific syndrome provides guidance on management and prognosis. In this paper, we describe the childhood onset epilepsy syndromes, most of which have both mandatory seizure type(s) and interictal electroencephalographic (EEG) features. Based on the 2017 Classification of Seizures and Epilepsies, some syndrome names have been updated using terms directly describing the seizure semiology. Epilepsy syndromes beginning in childhood have been divided into three categories: (1) self‐limited focal epilepsies, comprising four syndromes: self‐limited epilepsy with centrotemporal spikes, self‐limited epilepsy with autonomic seizures, childhood occipital visual epilepsy, and photosensitive occipital lobe epilepsy; (2) generalized epilepsies, comprising three syndromes: childhood absence epilepsy, epilepsy with myoclonic absence, and epilepsy with eyelid myoclonia; and (3) developmental and/or epileptic encephalopathies, comprising five syndromes: epilepsy with myoclonic–atonic seizures, Lennox–Gastaut syndrome, developmental and/or epileptic encephalopathy with spike‐and‐wave activation in sleep, hemiconvulsion–hemiplegia–epilepsy syndrome, and febrile infection‐related epilepsy syndrome. We define each, highlighting the mandatory seizure(s), EEG features, phenotypic variations, and findings from key investigations.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/epi.17241

International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions

Since 1992, the Eilat Conferences have provided a forum for all stakeholders in the epilepsy community to appraise the latest data on new antiepileptic drugs and emergency seizure treatments, including, in recent years, updates on progress with the development of novel monitoring and therapeutic devices. Because of the COVID-19 pandemic, the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV) was held as a fully virtual conference on July 27-30, 2020 for the sessions on drugs and on August 3, 2020 for the sessions on devices, and was attended during the 5 days by >500 participants from 63 countries. This progress report summarizes key preclinical and initial (phase 1) clinical data on eight investigational treatments that are currently in early development, including 2-deoxy-D-glucose, GAO-3-02, JNJ-40411813, NBI-921352, NTX-001, sec-butylpropylacetamide, XEN1101, and XEN496. This report provides an overview of current scenarios in the area of treatment discovery and development. The information presented illustrates a variety of innovative strategies, including exploration of compounds with novel mechanisms of action, transplantation of interneurons into epileptogenic brain regions, and the targeting of rare, previously neglected syndromes.

Progress report on new antiepileptic drugs: A summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV). I. Drugs in preclinical and early clinical development.

Febrile infection–related epilepsy syndrome (FIRES) is a severe epileptic encephalopathy with presumed inflammatory origin and lacking effective treatments. Anakinra is the human recombinant interleukin 1 receptor antagonist clinically used in autoinflammatory or autoimmune conditions. We report a case of FIRES for which the spatial and temporal match between electroencephalography (EEG) and magnetic resonance imaging (MRI) focal alterations provides support for the detrimental synergic interplay between seizures and inflammation that may evolve to permanent focal lesions and progressive brain atrophy in weeks to months. Brain biopsy showed aspects of chronic neuroinflammation with scarce parenchymal lymphocytes. We report the novel evidence that anakinra reduces the relapse of highly recurrent refractory seizures at 1.5 years after FIRES onset. Our evidence, together with previously reported therapeutic effects of anakinra administered since the first days of disease onset, support the hypothesis that interleukin 1β and inflammation-related factors play a crucial role in seizure recurrence in both the acute and chronic stages of the disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/epi4.12317

Therapeutic effect of Anakinra in the relapsing chronic phase of febrile infection–related epilepsy syndrome

New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) are relatively rare clinical presentations. They are characterized by de novo onset of refractory status epilepticus (RSE) without clearly identifiable acute or active cause (structural, toxic, or metabolic). We reviewed the literature using PubMed reports published between 2003 and 2019 and summarized the clinical, neurophysiological, imaging, and treatment findings. Focal motor seizures, which tend to evolve into status epilepticus, characterize the typical presentation. Disease course is biphasic: acute phase followed by chronic phase with refractory epilepsy and neurological impairment. Aetiology is unknown, but immune-inflammatory-mediated epileptic encephalopathy is suspected. Electroencephalograms show variety in discharges (sporadic or periodic, focal, generalized, or more frequently bilateral), sometimes with a multifocal pattern. About 70% of adult NORSE have abnormal magnetic resonance imaging (MRI); in paediatric series of FIRES, 61.2% of patients have a normal brain MRI at the beginning and only 18.5% during the chronic phase. No specific therapy for FIRES and NORSE currently exists; high doses of barbiturates and ketogenic diet can be used with some effectiveness. Recently, anakinra and tocilizumab, targeting interleukin pathways, have emerged as potential specific therapies. Mortality rate is around 12% in children and even higher in adults (16-27%).

New-onset refractory status epilepticus and febrile infection-related epilepsy syndrome.

The evolution of the pilocarpine animal model of status epilepticus

Purpose To understand the long-term neurological outcomes and chronological changes of brain MRIs in patients with febrile infection-related epilepsy syndrome (FIRES) Methods From December 2000 to May 2016, 29 patients diagnosed with FIRES were collected retrospectively The demographic distribution, clinical manifestations, neuroimaging findings, and treatment methodology were described Follow-up clinical outcomes and chronological evolution of neuroimaging findings were analyzed Results The median age of disease onset was 89 years The median duration of hospitalization was 87 days During the period of hospitalization, more than 50% of patients exhibited complications such as skin rash, liver function impairment, and arrhythmia Abnormal findings were found in 38% of neuroimaging studies in the initial study and in 87% of the follow-up brain MRI Focal abnormal signal changes over the periventricular white matter suggested the more extensive lesions would be associated with a poorer clinical outcome The median duration of follow-up was 5 years in 23 patients In total, 87% of patients exhibited residual and/or refractory epilepsy Regarding cognitive function, 26% of patients had normal intelligence quotient, 26% had learning disability and mild to moderate mental retardation, and 48% had severe mental retardation or vegetative status The mortality rate at acute stage was 10%, and that at chronic stage was 13% Conclusions Liver function impairment, skin rash, and arrhythmia are frequently seen during hospitalization for FIRES at the acute stage of disease course The higher grade of periventricular white matter lesions suggested poorer neurological outcomes Studies on the pathomechanism of FIRES are crucially needed so that new treatment strategies for FIRES can be developed, which may improve long-term outcomes

Hsiu-Fen Lee

Papers

Febrile infection-related epilepsy syndrome (FIRES): therapeutic complications, long-term neurological and neuroimaging follow-up.