Central nervous system pathology of tuberous sclerosis in children.

Ten cases of tuberous sclerosis involving the central nervous system (CNS) in children aged 2 days to 15 years were studied. The abnormal cells found in subependymal, cortical, and white matter lesions were examined by light and electron microscopy. Histochemistry and immunohistochemistry were also employed. The results were similar in all lesions. Approximately one-third of the abnormal cells were positive by glial fibrillary acidic protein (GFAP), one-half by Nissl, and one-quarter by Holzer's stains. The intensity and pattern of GFAP staining varied from cell to cell and could not be predicted before staining. Ultrastructurally the cytoplasm of abnormal cells contained moderate to large numbers of 9- to 12-nm diameter fibrils and frequent dense bodies with crystalline appearance. Stacked rough endoplasmic reticulum was variable. Cell junctions and glycogen were rare. Nuclei were usually vesicular with a prominent nucleolus. Individual cells of tuberous sclerosis have features of both neurons and astrocytes. The disease may affect cells before differentiation. The predominant abnormal features of the cells in tuberous sclerosis are a great increase in fibrils and the presence of dense bodies, which may be a nonspecific reaction or result from a metabolic defect affecting the cells.