engleski

New diagnostic and therapeutic possibilities in tuberous sclerosis complex

Tuberous sclerosis complex (TSC), also known as Bourneville disease, is an autosomal dominant genetic disorder caused by mutations in either TSC1 encoding hamartin, or TSC2 encoding tuberin, the genes with high penetrance and variability. About two-thirds of TSC cases are sporadic, indicating the occurrence of new mutations. TSC is characterized by the development of multiple benign tumors in several organs such as the brain, lungs, heart, eyes, skin, kidneys and liver. The incidence of TSC is estimated as 1 case per 6000-10000 individuals. TSC proteins are involved in negative regulation of the mammalian target of rapamycin pathway (mTOR), which is involved in tumor cell proliferation and energy metabolism, cortical development and growth control. The pathognomonic cerebral lesions are cortical tubers, subependymal nodules and subependymal giant cell astrocytomas. Other brain abnormalities are white matter linear lesions that appear as radial bands, are composed of clusters of heterotopic cells and are indicative of a disorder of migration associated with abnormal cell diff erentiation. Epilepsy is the most common neurologic symptom in patients with TSC, and mental retardation in addition to multiple behavioral problems (including sleep disorder, hyperactivity, attention defi cit, aggressiveness and autism) are also frequent symptoms. Seizures are the initial manifestation in 90% of patients. Seizure onset is oft en within the fi rst 12 months of life ; one-third of patients present with infantile spasms, but also with a great number of diff erent seizure types. Seizures are oft en pharmacoresistant and the rate of refractory epilepsies is 50%-80%. Unfavorable prognostic factors are onset earlier than one year of age, presence of several clinical phenotypes (infantile spasms and partial motor or complex partial seizures, drop attacks and atypical absences), multifocal and/or bilateral discharges and the occurrence of new EEG foci. According to clinical recommendations from the Management of TSCassociated epilepsy made by a panel of European experts in March 2012, we selected patients who were good candidates for neurosurgery (we excluded patients with multiple seizure types), or candidates for vagus nerve stimulator implantation. In all patients, we prescribed ketogenic diet and we believe that in the near future a new drug (mTOR inhibitor) would show itself as a potential anti-seizure agent.

tuberous scerosis; epilepsy

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