Management of epilepsy in tuberous sclerosis complex.
Tuberous sclerosis complex (TSC) is an inherited disorder resulting from mutations in one of two genes, TSC1 (Hamartin) and TSC2 (Tuberin). These two proteins form a cytosolic complex that inhibits the mTOR pathway that controls cell growth and proliferation. Pathologically, abnormalities of neuronal migration, cellular differentiation and excessive cellular proliferation all contribute to the formation of the different brain lesions of TSC. Seizure is the most common presenting symptom. Seizures can be present in the first year of life and up to one third of children develop infantile spasms. Seizures usually have a focal or multifocal origin, are often resistant to antiepileptic drugs and have a negative impact on the neurocognitive development. Vigabatrin has proved to be effective against infantile spasms due to TSC. New evidence suggests that it is possible to noninvasively identify using multimodality techniques, TSC children who are likely to become seizure-free following surgical treatment. Understanding the mechanisms of epileptogenesis and the possible role of the mTOR pathway in this process might increase the availability of novel and targeted therapies.
Curatolo
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P
Tor Vergata University, Department of Neurosciences, Pediatric Neurology Unit, Rome, Italy. curatolo@uniroma2.it
D'Argenzio
L
L
Cerminara
C
C
Bombardieri
R
R
D000927:Anticonvulsants / Q000627:therapeutic use; D002648:Child; D004351:Drug Resistance; D004827:Epilepsy / Q000209:etiology / Q000628:therapy*; D015870:Gene Expression; D006801:Humans; D007223:Infant; D011379:Prognosis; D011494:Protein Kinases / Q000235:genetics; D011612:Psychosurgery; D013036:Spasms, Infantile / Q000209:etiology / Q000628:therapy; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics; D020888:Vigabatrin / Q000627:therapeutic use
D000927:Anticonvulsants; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020888:Vigabatrin