Under the microscope the tubers are seen to be composed of interlacing rows of plump, fibrous astrocytes (much like an astrocytoma, though lacking in glial fibrillar protein). In the cerebral cortex and ganglionic structures, derangements of architecture result from the presence of abnormal-appearing cells: greatly enlarged “monstrous,” or “balloon” neurons and glia cells—often difficult to distinguish from one another. Also, displaced normal-sized neurons contribute to the chaotic histologic appearance. Gliomatous deposits may obstruct the foramina of Monro or the aqueduct or floor of the fourth ventricle, causing hydrocephalus. Neoplastic transformation of abnormal glia cells, a not infrequent occurrence, usually takes the form of a large-cell astrocytoma, less often of a glioblastoma or meningioma. Recently, certain relationships have been drawn between the balloon cells of this disease and similar cells in focal cortical dysplasias (see Crino for details).
The phakomas of the retina are also composed mainly of neuronal and glial components, but occasionally there is an admixture of fibrous tissue.
When the full combination of seizures and mental and dermal abnormalities is conjoined, the diagnosis is self-evident. It is the early stage of the disease and the formes frustes that give trouble, and here the experienced dermatologist can be of great help. Epilepsy—that is, flexion spasms in infancy—and delay in psychomotor development are by no means diagnostic of tuberous sclerosis, as they occur in many diseases. It is in these cases, and also in every sizable population of the epileptic or developmentally delayed, especially when the family history is unrevealing, that a search for the dermal equivalents of the disease—the hypomelanotic ash-leaf spots, adenoma sebaceum, collagenous skin patch, phakoma of the retina, or subungual or gingival fibromas—is so rewarding. The finding of any one of these lesions provides confirmation of the partial and atypical case. Adenoma sebaceum may occasionally occur alone and is easily confused with acne vulgaris in the adolescent. The history of epilepsy or demonstration of developmental delay is helpful but neither is a requisite for the diagnosis of tuberous sclerosis (see the monograph by Gomez).
The most useful laboratory measures for corroborating the disease are CT and MRI (see Fig. 37-7). The calcific tuber lesions tend to be periventricular and are particularly well shown on CT, whereas MRI is more sensitive in detecting the hamartomatous giant cell subependymal and subcortical lesions. There is an absence of edema in the surrounding tissue. Roach and colleagues have indicated that an increasing number of cortical lesions demonstrated with MRI appear to correlate with an increased impairment of neurologic function. Clinics that treat large numbers of these patients recommend imaging of the kidneys and lungs and, in children, echocardiography. Serial examinations to detect enlargement of the subependymal tumors is advised annually for those younger than age 21 years and every 2 to 3 years thereafter, but the best course of action if a glioma emerges has not been clearly established.
Nothing can be offered in the way of prevention other than genetic counseling. Antiepileptic therapy of the standard type suppresses the convulsive tendency more or less effectively and should be applied. Adrenocorticotropic hormone (ACTH) suppresses the flexor spasms in infancy and tends to normalize the EEG for a time.