Neuropathology of lissencephalies

The neuropathological findings at autopsy in four cases of type I and three of type II lissencephaly are presented. Type I lissencephaly is characterized by agyriapachygyria with a markedly thickened cerebral cortex with four coarse histological layers. The normally myelinated white matter, often with neuronal heterotopias, is very narrow, and the gray-to-white matter ratio is inverted (about 4:1); there are no white-gray interdigitations. Claustrum and capsula extrema are absent. Ventricular dilatation is present, especially of the occipital horns. In the hypoplastic brain stem large olivary heterotopias can often be observed. Severe cerebellar malformations, obstructive hydrocephalus, severe eye abnormalities, and congenital muscular dystrophy are not seen. Clinically, type I lissencephaly presents as "isolated lissencephaly sequence" or as "Miller-Dieker syndrome" with characteristic facial dysmorphism. The long survival of 20 years achieved by one of our patients is very uncommon. Type II lissencephaly is characterized by widespread agyria. Usually, obstructive hydrocephalus is present with a thin cerebral mantle showing a slightly thickened cortex and a narrow, hypomyelinated white matter often with neuronal heterotopias (gray-to-white matter ratio about 1:1). The border between gray and white matter is blurred. Claustrum and capsula extrema are absent. Histologically, the cortex appears disorganized without layering; widespread leptomeningeal gliomesenchymal proliferations and glioneuronal heterotopias are present.(ABSTRACT TRUNCATED AT 250 WORDS)