As the years pass, the seizures change pattern. In the first year or two they take the form of massive flexion spasms with hypsarrhythmia (irregular dysrhythmic bursts of high-voltage spikes and slow waves in the EEG). As many as 25 percent of patients with these types of seizures have been found to have tuberous sclerosis. Later, the seizures change to more typical generalized motor and psychomotor attacks or atypical absence spells. Any one of the seizure types may be brief, especially if the patient is receiving anti-epileptic medication. Focal neurologic abnormalities, which one might expect to occur from the size and location of some of the lesions, are distinctly uncommon.
Cognitive function continues to deteriorate slowly. Exceptionally there is a spastic weakness or mild choreoathetosis of the limbs and in a few cases an obstructive hydrocephalus develops. As in any state of severe developmental delay, a variety of nonspecific motor peculiarities—such as constant crying, muttering, stereotypical rocking and swaying movements, and digital mannerisms—may be observed. In nearly half of the cases, affective and behavioral derangements, often of hyperkinetic and aggressive type, are added to the intellectual deficiency.
The lack of parallelism in the severity of the epilepsy, the cognitive deficit, and cutaneous abnormalities has been noted by all clinicians who have wide experience with this disease. Some patients are subject to recurrent seizures while retaining relatively normal mental function; in others, trivial skin lesions or a retinal phakoma (see below) may suggest the diagnosis in a mentally normal person with few seizures. In such cases, recognition may elude neurologists and dermatologists. As a general rule, early onset of seizures is predictive of developmental delay. Gomez and colleagues suggested that the seizures damage the brain, a point with which we tend to agree in part. However, it seems likely that both the epilepsy and developmental delay are the product of severe involvement of the brain by the lesions of tuberous sclerosis.
Limitation of space allows no more than a catalogue of the other visceral abnormalities in tuberous sclerosis. In about half the cases, gray or yellow plaques (in reality gliomatous tumors) may be found in the retina in or near the optic disc or at a distance from it. It is from this lesion, called a phakoma, that van der Hoeve derived the term that is applied to all neurocutaneous diseases of this class. About half of all benign rhabdomyomas of the heart are associated with tuberous sclerosis; if located in the wall of the atrium, they may cause conduction defects. Other benign tumors of mixed cell type (angiomyolipomas) have been found in the kidneys, liver, lungs, thyroid, testes, and gastrointestinal tract. Cysts of the pleura or lungs, bone cysts in digits, and zones of marbling or densification in bones are some of the less common abnormalities.