Morphological substrates of infantile spasms: studies based on surgically resected cerebral tissue

Extensive surgical resections of neocortical cerebral tissue (including hemispherectomies) from 13 infants and children with infantile spasms showed that 12 of 13 specimens contained either malformative and dysplastic lesions of the cortex and white matter (sometimes with associated hamartomatous proliferation of globular cells), or destructive lesions possibly acquired as a result of anoxic-ischemic injury, or a combination of the two. In brain tissue from 4 patients, coarse neuronal cytoplasmic fibrils resembling neurofibrillary tangles were seen in areas of dysplastic brain on silver-stained (Bielschowsky technique) sections. Immunohistochemical (immunoperoxidase) study of cortical lesions containing globular cells employing primary antibodies to glial fibrillary acidic protein and synaptophysin as markers of astrocytic and neuronal differentiation, respectively, revealed that many cells showed astrocytic and/or neuronal features, suggesting the local proliferation of primitive or multipotential neuroectodermal cells as one substrate for this seizure disorder. Morphological abnormalities of a severe degree and wide extent in the resected tissue (e.g., in one patient with hemimegalencephaly) often showed features to suggest that they may represent variants of tuberous sclerosis. These most likely result from abnormal movement and/or local proliferation of neuroectodermal precursors that have migrated from the germinal matrix to the cortical mantle. Cellular, molecular and neurophysiological study of these abnormalities is likely to yield information about basic molecular mechanisms of brain malformation and injury important in the pathogenesis of infantile spasms and other forms of focal or generalized epilepsy.