The ILAE consensus classification of focal cortical dysplasia: An update proposed by an ad hoc task force of the ILAE diagnostic methods commission

Abstract

Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition and classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 to identify existing gaps and provide a timely update. The following methodology was applied to achieve this goal: a survey of published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 and 06/30/2021 (n = 1349) in PubMed identified the knowledge gained since 2012 and new developments in the field. An online survey consulted the ILAE community about the current use of the FCD classification scheme with 367 people answering. The TF performed an iterative clinicopathological and genetic agreement study to objectively measure the diagnostic gap in blood/brain samples from 22 patients suspicious for FCD and submitted to epilepsy surgery. The literature confirmed new molecular-genetic characterizations involving the mechanistic Target Of Rapamycin (mTOR) pathway in FCD type II (FCDII), and SLC35A2 in mild malformations of cortical development (mMCDs) with oligodendroglial hyperplasia (MOGHE). The electro-clinicalimaging phenotypes and surgical outcomes were better defined and validated for FCDII. Little new information was acquired on clinical, histopathological, or genetic characteristics of FCD type I (FCDI) and FCD type III (FCDIII). The survey identified mMCDs, FCDI, and genetic characterization as fields for improvement in an updated classification. Our iterative clinico-pathological and genetic agreement study confirmed the importance of immunohistochemical staining, neuroimaging, and genetic tests to improve the diagnostic yield. The TF proposes to include mMCDs, MOGHE, and "no definite FCD on histopathology" as new categories in the updated FCD classification. The histopathological classification can be further augmented by advanced neuroimaging and genetic studies to comprehensively diagnose FCD subtypes; these different levels should then be integrated into a multi-layered diagnostic scheme. This update may help to foster multidisciplinary efforts toward a better understanding of FCD and the development of novel targeted treatment options.

Unexpected Effect of IL-1β on the Function of GABAA Receptors in Pediatric Focal Cortical Dysplasia

“…Additionally, we also described the effect of IL-1β on two FCD IIa pediatric tissue samples, where we obtained the same results as the recordings in FCD IIb tissues. Indeed, FCD IIa and IIb represent two histopathological subtypes of FCD type II, and FCD IIb is further distinguished from FCD IIa by the additional presence of balloon cells [ 2 , 36 ]. This broadens the relevance of our findings, since we can hypothesize that the alteration in synaptic transmission by inflammatory mediators may be a general feature of FCD, at least of those forms frequently associated with drug-resistant epilepsy.…”

“…The cases included in this study were obtained from the archives of the Departments of Neuropathology of the Amsterdam UMC (Amsterdam, The Netherlands) and the University Medical Center Utrecht (UMCU, Utrecht, The Netherlands). Cortical brain samples were obtained from patients undergoing surgery for drug-resistant epilepsy and diagnosed with FCD type IIb (with brain somatic mutations in the MTOR gene) [ 2 ]. After resection, the tissue was immediately snap-frozen in liquid nitrogen and then part of the sample was used to perform the electrophysiology experiments.…”

“…Focal cortical dysplasias (FCDs) are a group of malformations of cortical development (MCD), frequently associated with drug-resistant epilepsy, and are predominant among the pediatric population [ 1 , 2 , 3 ]. FCDs type II are the most common MCD in epilepsy surgery case series [ 3 ].…”

Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: insights into disease mechanisms and tissue characterization

“…Samples from autopsies (control group) were submitted to the same protocol to exclude microscopic alterations. All histological analyses were performed at regions of gyri perpendicularly cut to the pial surface, as recommended by the FCD ILAE Classification (10, 13).…”

“…Recently, the International League Against Epilepsy (ILAE) has reviewed and updated its neuropathological classification system for FCD. Specifically, FCD type II refers to isolated lesions characterized by dyslamination of the cortex and dysmorphic neurons without (IIa) or with balloon cells (IIb) (10,11).…”