Cortical dysplasia in Fukuyama congenital muscular dystrophy (FCMD): a Golgi and angioarchitectonic analysis

Abstract

The Golgi and vascular impregnation methods were applied to the abnormal cerebral cortex in Fukuyama congenital muscular dystrophy (FCMD). The cortical dysplasia in FCMD has been categorized into three patterns by the degrees of cytoarchitectural abnormalities. Cortical dysplasia type 1 is characterized by the presence of verrucose nodules in the otherwise normally stratified cortex. By the Golgi method, many neurons at the top of the verrucose nodules showed abnormal morphology and dendritic orientation, while the rest of pyramidal neurons appeared relatively normal. A single 'central blood vessel' often penetrated vertically at the axis of the verrucose nodules, so that it was suggested that such nodules were formed around the long perforating blood vessels. In type 2 dysplasia, or unlayered micropolygyria, individual cells showed relative paucity of lateral dendritic arborization. Despite mutual parallel alignment, neurons were often tilted in varying degrees. Concentration of relatively large blood vessels was seen at the microsulci. In the severest dysplastic pattern, or type 3 dysplasia, in addition to highly distorted cellular alignment, dendritic arborization of individual neurons were very poor. The cortical vasculature in type 3 consisted of two heterogeneous patterns; an extreme vascular distortion in the upper layer and a relatively well-preserved radial pattern in the deep layer. The upper layer is supposed to represent the extra-cortical gliomesenchymal layer intermixed with neuronal clusters seen in the 23-week FCMD fetus we reported previously. By that fetal case analysis, we had hypothesized that cortical dysplasia in FCMD has resulted from superficial heterotopia of migrating neurons related to diffuse proliferation of the extra-cortical gliomesenchymal tissue and focal or extensive defects of glia limitans. The abnormalities in cellular morphology, cellular alignment, and cortical vascular patterns shown in the present study seem to be compatible with our hypothesis.