Epilepsy in tuberous sclerosis complex.

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder characterized by hamartomatous lesions involving skin, brain, kidneys, eyes and heart. Because of the wide variability of clinical expression and severity of TSC and the absence of a reliable molecular marker of the disease, diagnosis can be difficult in patients with only subtle manifestations. Genetic linkage studies indicate that about half of cases are due to TSC1, the gene on chromosome 9q34, and half are due to TSC2, the gene on chromosome 16p13. Clinical phenotypes associated with TSC1 vs TSC2 disease appear similar. Pathologically, TSC is a disorder of cell migration, proliferation and differentiation. Cell lineage and cell migration disorders in the developing cortex of TSC patients might produce very different neurological phenotypes. Cortical tubers constitute the hallmark of the disease and are pathognomonic of cerebral TSC. Epilepsy is the most common neurologic feature in TSC, occurring in 92% of patients. Seizures often begin in the first year of life and are frequently severe and intractable. The treatment of seizures has recently benefited from the advent of the new antiepileptic drugs (AEDs). However, current data suggest that despite the use of the new AEDs at the moment will still need a better treatment for at least 20 to 25% of TSC patients. Selected drug-resistant patients with TSC could be considered for surgical treatment. Clear localization of the most active epileptogenic focus and the zone of the cortical abnormality may lead to tuberectomy and improved seizure control in selective drug-resistant patients. The finding of multiple areas of cerebral involvement should not automatically preclude epilepsy surgery in a child with intractable seizures and a well-defined seizure origin.