Risk Factors Associated with Refractory Epilepsy in Patients with Tuberous Sclerosis Complex: A Systematic Review

Background: Epilepsy affects 70-90% of patients with tuberous sclerosis complex (TSC). In one-third of them, the seizures become refractory to treatment. Drug-resistant epilepsy (DRE) carries a significant educational, social, cognitive, and economic burden. Therefore, determining risk factors that increase the odds of refractory seizures is needed. We reviewed current data on risk factors associated with DRE in patients with tuberous sclerosis. Methods: The review was performed according to the PRISMA guidelines. Embase, Cochrane Library, MEDLINE, and ClinicalTrial.gov databases were searched. Only full-text journal articles on patients with TSC which defined risk factors related to DRE were included. Results: Twenty articles were identified, with a cohort size between 6 and 1546. Seven studies were prospective. Three factors appear to significantly increase DRE risk: TSC2 mutation, infantile spasms, and a high number of cortical tubers. Conclusions: A proper MRI and EEG monitoring, along with genetic testing, and close observation of individuals with early onset of seizures, allow identification of the patients at risk of DRE.