Since the original description by Taylor, the term focal cortical dysplasia has been used to refer to a wide range of alterations of the cortical mantle. More recently, these conditions have been described from neuroimaging, neuropathological and genetic standpoints, generating several classifications. It is widely recognized that these classifications are unsatisfactory. We propose a simplified classification of focal cortical dysplasias based on easily recognized neuropathological characteristics. We retrospectively re-examined histological sections of cortex from 52 of 224 (23%) patients operated on for drug-resistant partial epilepsy in which cortical dysplasia was present but not associated with other brain pathologies except hippocampal sclerosis. Three subgroups were identified: (i) architectural dysplasia (31 patients) characterized by abnormal cortical lamination and ectopic neurones in white matter; (ii) cytoarchitectural dysplasia (six patients) characterized by giant neurofilament-enriched neurones in addition to altered cortical lamination; and (iii) Taylor-type cortical dysplasia (15 patients) with giant dysmorphic neurones and balloon cells (all but two patients) associated with cortical laminar disruption. The patients with architectural dysplasia had lower seizure frequency than those with cytoarchitectural and Taylor-type dysplasia, and the epileptogenic zone was mainly in the temporal lobe. In patients with Taylor-type dysplasia, the epileptogenic zone was mainly extratemporal, and interictal stereo-EEG was distinctive. MRI was unrevealing in 34% of patients, but distinctive signal alterations characterized most patients with Taylor-type dysplasia, while focal hypoplasia with MRI abnormalities was found in architectural dysplasia. Patients with Taylor-type dysplasia had the best outcome, with 75% seizure-free (Engel class Ia) after at least a year of follow-up compared with 50% of cytoarchitectural dysplasia and 43% of architectural dysplasia patients seizure-free. This three-category classification is based on easily recognized histopathological characteristics and avoids complicated terminology, while the distinctive ensemble of other characteristics defines clinically homogeneous groups.

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We present the results of a retrospective study on 10 patients operated on for intractable epilepsy associated with nodular heterotopia as identified by high resolution MRI. Seven patients had unilateral heterotopia, one patient had symmetric bilateral heterotopia and two patients had asymmetric bilateral heterotopia. By stereo-electroencephalogram (SEEG) (nine patients) interictal activity within nodules was similar in all cases, and ictal activity never started from nodules alone but from the overlying cortex or simultaneously in nodules and cortex. Excellent outcomes (Engel class Ia, 1987) were achieved in the seven patients with unilateral heterotopia, showing that surgery can be highly beneficial in such cases when the epileptogenic zone is carefully located prior to surgery by MRI and particularly SEEG. For the bilateral cases surgical outcomes were Engel IIa (one patient) or Engel IIIa (two patients). Histological/immunohistochemical studies of resected specimens showed that all nodules had similar microscopic organization, even though their extent and location varied markedly. The overlying cortex was dysplastic in nine patients, but of normal thickness. We suggest that nodule formation may be the result of a dual mechanism: (i) failure of a stop signal in the germinal periventricular region leading to cell overproduction; and (ii) early transformation of radial glial cells into astrocytes resulting in defective neuronal migration. The intrinsic interictal epileptiform activity of nodules may be due to an impaired intranodular GABAergic system.

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.

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