Central Nervous System Pathology of Tuberous Sclerosis in Children

Abstract

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.

Characteristics of Abnormal Diffusivity in Normal-Appearing White Matter Investigated with Diffusion Tensor MR Imaging in Tuberous Sclerosis Complex

“…[46][47][48] There is evidence for astrogliosis from histopathology in human TSC lesions, 8,49,50 but this has not been described in NAWM. Uhlmann et al 48 reported that heterozygosity for TSC2 resulted in a 1.5-fold increase in the numbers of astrocytes in mice in vivo.…”

A circuitry and biochemical basis for tuberous sclerosis symptoms: from epilepsy to neurocognitive deficits

“…SENs are among the most common brain lesions associated with TSC (95% of the patients) and are contiguous with the lateral ventricles (LVs) (Bender and Yunis, 1980). SENs contain enlarged neurons and glia as well as giant or multinucleated cells similar to those observed in tubers.…”

Loss of function of the tuberous sclerosis 2 tumor suppressor gene results in embryonic lethality characterized by disrupted neuroepithelial growth and development

“…The underlying pathology, cortical tubers and subependymal giant cell astrocytomas (SEGAs), is characterized by focal disorganized arrays of dysplastic and proliferating cellular elements, most notably giant cells of indeterminate origin (17,18). Although early studies have shown a lower than expected frequency of loss of heterozygosity in brain lesions (19), recent immunoanalysis of SEGAs in TSC patients has confirmed the lack of tuberin expression within the spindle and epithelioid cells in these lesions (20).…”