Abstract
Tuberous sclerosis complex (TSC) is associated with a high rate of epilepsy, which
often presents in the first month of life. An early diagnosis of TSC can allow a close
electroencephalography monitoring and a prompt detection of subtle or subclinical
seizures, thus guaranteeing a prompt treatment. Seizures in TSC are caused by an imbalance
between excitation and inhibition, which can be considered as the final step of the
genetic mutation and the subsequent overactivation of the mammalian target of rapamycin
pathway. Epilepsy is often associated with cognitive and behavioral comorbidities,
including learning disability, autism, and attention deficit/hyperactivity disorder.
A prompt treatment of early-onset seizures is able to reduce the risk of a subsequent
epileptic encephalopathy and cognitive and behavioral sequelae, but it cannot totally
revert the final outcome. Treatment options for epilepsy include antiepileptic drugs,
epilepsy surgery, ketogenic diet, and vagus nerve stimulation, but even after their
application about two-thirds of patients still continue to present seizures. All these
treatment options represent symptomatic treatment acting on seizures but not on the
underlying cause of epilepsy. Mammalian target of rapamycin inhibitors represent a
potential novel treatment strategy able to target the pathophysiologic mechanisms
underlying epilepsy and other TSC-related manifestations.
Keywords
tuberous sclerosis - epilepsy - mammalian target of rapamycin - everolimus - mTORopathy
- vigabatrin - neurocutaneous syndromes - autism - mental outcome
