TUBEROUS SCLEROSIS COMPLEX

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder resulting from mutations in TSC1 (9q34) or in TSC2 (16p13), respectively encoding for hamartin and tuberin. TSC is inherited in an autosomal dominant fashion, although up to two thirds of cases result from spontaneous mutations. The hamartin-tuberin complex plays an important role during cortical development. New schemes of CNS malformations that integrate molecular genetic and morphologic criteria have resulted in a reclassification of TSC as a disorder of cellular lineage. 90% of individuals with TSC exhibits at least one supratentorial brain lesion. Abnormalities of cellular differentiation, proliferation and migration all contribute to the formation of the various brain lesions of the TSC and to the production of very different neurological phenotypes, including seizures, mental impairment, learning disabilities and autism. About 80–90% of individuals with TSC experiences seizures. Epilepsy in TSC seems to arise from the interaction between multiple areas, all of which have increased excitability and reduced inhibition (changes in GABA-A receptors). Advances in understanding mechanisms and genetics underlying infantile spasms and catastrophic epilepsy associated with TSC may facilitate more effective interventions. Early effective seizures control could significantly reduce the adverse developmental effects of chronic epilepsy in tuberous sclerosis. Vigabatrin is the first choice drug in the short term treatment of infantile spasms. However, some individuals develop seizures that remain highly intractable. The factors that influence the intractability of epilepsy associated with TSC remain poorly understood. Multimodality neuroimaging has improved detection of epileptogenic foci, allowing an increased number of individuals to be evaluated for resective surgery. New evidences suggest that it is possible to non-invasively identify children with tuberous sclerosis who are highly likely to become seizure free following surgical treatment. Epilepsy surgery is often associated with significant improvement of the neurologic outcome.

Key-words: tuberous sclerosis, intractable seizures, outcome, surgery