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

Abstract

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.

ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions

“…Etiology-specific syndromes can be identified, where there is a specific etiology for the epilepsy that is with a clearly defined, relatively uniform, and distinct clinical phenotype in most affected individuals (clinical presentation, seizure types, comorbidities, course of illness, and/or response to specific therapies), as well as consistent EEG, neuroimaging, and/or genetic correlates. 1 Our Task Force did not aim to identify and describe all Etiology-Specific Syndromes, but provided definitions on a limited number, including the DEEs associated with KCNQ2, CDKL5, PCDH19, SCL2A1, pyridoxine and pyridox(am)ine 5'-Phosphate-dependent epilepsy, Sturge-Weber syndrome, and Gelastic Seizures with Hypothalamic Hamartoma. KCNQ2-DEE KCNQ2-DEE causes a neonatal onset encephalopathy and is due to de novo missense variants that produce a disorder distinct from self-limited neonatal epilepsy.…”

“…Furthermore, we introduce the concept of epilepsy syndromes determined primarily by etiology. This group includes syndromes for which there is a specific etiology for the epilepsy that is associated with a clearly defined, relatively uniform, and distinct clinical phenotype in most affected individuals as well as consistent electroencephalography (EEG), neuroimaging, and/or genetic correlates 1 . With all novel associations, the phenotypic spectrum will become better defined with time.…”

“…Consistent electroclinical phenotypes have emerged, with examples including CDKL5 , 18 MeCP2 , 19,20 PCDH19 , 21–23 STXBP1 , 24 and inv dup 15 25 . Furthermore, some structural, metabolic, immune, and infectious etiologies also have characteristic electroclinical phenotypes 1 . Therefore, epilepsies due to specific genetic, structural, metabolic, immune, or infectious etiologies may also meet criteria for a syndrome, when they are associated with consistent electroclinical features and have management and prognostic implications.…”

ILAE definition of the Idiopathic Generalized Epilepsy Syndromes: Position statement by the ILAE Task Force on Nosology and Definitions

“…[1][2][3][4][5][6] We provide updated diagnostic criteria for the IGEs determined by a rigorous process to obtain the expert consensus opinion of the ILAE's Task Force on Nosology and Definitions (2017-2021). Details regarding methodology are found in a paper by Wirrell et al 7 Criteria for each syndrome were determined using a Delphi process, surveying all Task Force members and external recognized epilepsy syndromology experts. We incorporate current knowledge from rapid advances in genetic, imaging, and EEG studies, together with current terminology and classification of seizures and epilepsies.…”

International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE Task Force on Nosology and Definitions

“…• A combined generalized and focal epilepsy syndrome with polygenic etiology: epilepsy with reading-induced seizures (EwRIS). • Epilepsy syndromes with developmental encephalopathy (DE), epileptic encephalopathy (EE), or both, and epilepsy syndromes with progressive neurological deterioration: 1 progressive myoclonus epilepsies (PME) and febrile infection-related epilepsy syndrome (FIRES)…”