Pathology of cortical development and neuropsychiatric disorders

Epilepsy is a well-documented consequence of about 150 rare genetic syndromes and malformations of the central nervous system. These syndromes are generally associated with fairly gross defects within the central nervous system and they were thought to be responsible for a small minority of cases. However, improved methods of neuropathological investigations and extensive magnetic resonance imaging studies have revealed a range of disturbances in cortical cytoarchitecture in patients with epileptic seizures previously considered as idiopathic (up to 70% of epilepsy). Structural abnormalities have also been demonstrated in the brain in schizophrenia. These consist of disturbed cortical cytoarchitecture (best described in the temporal lobe) and a diffuse loss of grey matter. The absence of the pathological stigma characteristic of degenerative processes indicates that these structural changes are the result of an abnormal pattern of brain development. The relationship between the type and location of developmental abnormality and the subsequent clinical syndrome (e.g. generalized or localized epilepsy) and the effects of aberrant cortical development on the functional integrity of the adult brain require definition.