Tumor excision is generally not undertaken, especially in severely affected individuals (with the exception of renal hamartomas that impair kidney function). However, sirolimus, which suppresses the mTOR signaling pathway, causes slight regression of the bodily angiolipomas (Bissler et al) and, of greater interest to the neurologist and neurosurgeon, the similar drug rapamycin has been shown in a report by Franz and colleagues to shrink subependymal giant cell astrocytomas in some patients, and its efficacy has been supported by more recent studies. Everolimus, another mTOR inhibitor has been found to be useful in the same way and in suppressing the status epilepticus associated with some cases of tuberous sclerosis (Krueger et al).
Some patients undergo dermabrasion of the facial lesions for cosmetic reasons, with the knowledge that these slowly regrow. To an increasing degree, neurosurgeons are excising single epileptogenic cortical tubers in otherwise relatively normal children. There are about 15 specialized centers in the United States, and several abroad, that are expert at caring for these patients and establishing a regimen of radiologic surveillance. (See http://www.tsalliance .org as well as the International Tuberous Sclerosis
Complex Consensus Group for further information including guidelines for testing, surveillance, and management.)
In general, the disease advances so slowly that years must elapse before one can be sure of progression. Of the severe cases, approximately 30 percent die before the fifth year, and 50 to 75 percent before attaining adult age. Worsening is mainly in the cognitive sphere. Status epilepticus accounted for many deaths in the past, but improved medication therapy has reduced this hazard. Neoplasias take their toll; the authors have had several such patients who died of malignant gliomas arising in striatothalamic regions.
Neurofibromatosis of von Recklinghausen
Neurofibromatosis (NF) is a comparatively common hereditary disease in which the skin, nervous system, bones, endocrine glands, and sometimes other organs are the sites of a variety of congenital abnormalities, often taking the form of benign tumors. The typical clinical picture, usually identifiable at a glance, consists of multiple circumscribed areas of increased skin pigmentation accompanied by dermal and neural tumors of various types.
The condition known as multiple idiopathic neuromas was the subject of a monograph by R.W. Smith in 1849; even at that time, he referred to examples recorded by other writers. It was von Recklinghausen, however, who, in 1882, gave the definitive account of its clinical and pathologic features. The subsequent studies of the disease by Yakovlev and Guthrie; Lichtenstein; Riccardi; and Martuza and Eldridge; and more recently by Créange and colleagues; and the comprehensive monographs of Crowe and colleagues and of Riccardi and Mulvihill are informative references that provide a complete analysis of the clinical, pathologic, and genetic data pertaining to the disease.
Epidemiology Crowe and associates calculated the prevalence of the disease to be 30 to 40 per 100,000, with the expectancy of 1 case in every 2,500 to 3,300 births over 50 years ago and these rates pertain in the all series from the current era. Approximately half of their cases had affected relatives, and in all instances the distribution of cases within a family was consistent with an autosomal dominant mode of inheritance. The disease has been observed in all races in different parts of the world, and males and females are about equally affected.