Malformations of cortical development and epilepsies: neuropathological findings with emphasis on focal cortical dysplasia

Abstract

Structural brain abnormalities can be increasingly recognized in patients suffering from intractable focal epilepsies using high-resolution imaging techniques. Epilepsy surgery has become a successful treatment option for many of these patients. A broad spectrum of malformations of cortical development (MCD) can be histopathologically identified in resective surgical brain samples. Here, we discuss neuropathological findings and available classification systems in children and adult patients. Particular emphasis will be paid to the classification system for focal cortical dysplasias (FCD), which can be histopathologically distinguished as type I and II. Also mild forms of cortical malformations (mMCD) may be present, including heterotopic neurons in white matter location. However, different cohorts of epilepsy patients may present with similar histopathological findings and clinico-pathological correlations are not always comparable with respect to outcome prediction. We will, therefore, discuss also the difficulties to classify some FCD variants. Notwithstanding, the underlying pathomechanisms in all FCD entities need to be specified. A comprehensive approach taking all currently available data into consideration will be mandatory to further develop our current understanding of FCDs, and to continuously improve our concept for a reliable classification system.