Tuberous sclerosis (TSC) is a protean disease that affects many organs. producing focal derangements in the structure and assemblage of the cells that make them up. In most cases, the major source of concern is what it does to the central nervous system. because from the standpoint of patients with this disorder and all who have to do with them, its most distressing manifestations result from its effects on the brain. The name. tuberous sclerosis, is derived from the descriptive designation originally based on the particular anatomic abnormalities in the brain that are distinctive for the disease. Over R century has passed since these first were clearly described. and the literature devoted to the pathology of TSC is now voluminous. This presentation reviews the major neurop; ithologic features of TSC. features that can often be directly related to what patients may experience in the way of impediments to enjoyment of; I healthy life. With regard to the nervous system; IS a whole. I must emphasize that the only part that consistently and importantly shows structural abnormalities is the brain. The spinal cord and peripheral nerves are spared: in this way. TSC sharply differs from neurofibromatosis. with which it so often has been compared in the literature. Furthermore. the brain itself is not affected everywhere to the same degree; much of it is entirely normal, even in patients who are severely disabled. In a few patients who would then be considered to have the tuberous sclerosis complex rather than TSC itself. absolutely no abnormalities in the brain are discernible. Conversely. it is entirely possible for the characteristic; ibnormalities to be present in the brain without their producing any mental or neurologic impairment. As with other diseases. the clinical expression depends on the extent of neuropathologic alterations. and we have been presented at this conference with evidence that this is so.

When the brain from a patient with ‘I’SC is examined postmortem, its size, weight. and overall appearance are generally not remarkable. Inspection of the gyri and, even more. palpation. shows that scattered here and there. at random. but more or less equally on the two sides are circumscribed portions of gyri or convolutions that are a little paler than the rest ofthe cortex and of firmer consistency. These abnormal regions ofcortex. which vary greatly in size. are smoothly rounded and tend to project outward a little from the normal suil ‘ace. It was these cortical anomalies that Bourneville described and depicted in 1x80.’Their protuberance-like form led to his designating them as trihcwirs. whereas he gave recognition to their palpable firmness in the term.. sc~ lrro. sis (FIGS. I and 2). Startling though these tuberous foci may be on exxnination by touch and by the unaided eye, their remarkable qualities are best appreciated by microscopic study of stained sections. It becomes apparent then that the normal, orderly. laminated structure of the cerebral cortex is suddenly interrupted by cytoarchitectural near-chaos. Lamination is not lost entirely. but it becomes blurred. and the