Everolimus in infants with tuberous sclerosis complex-related West syndrome: First results from a single-center prospective observational study

Tuberous sclerosis complex (TSC) is the most common cause of West syndrome (WS). Currently available treatment options are ineffective in the majority of affected infants and/or associated with potential serious side effects. Based on the assumption that mTOR overactivation results in increased neuroexcitability in TSC, mTOR inhibitors have been studied as antiseizure therapy. As a result, everolimus recently received approval for the adjunctive treatment of patients aged 2years with refractory TSC-associated focal and secondary generalized seizures. However, efficacy and safety data for infants with TSC-associated WS are still lacking. Therefore, a prospective open-label observational study was initiated at our center, to evaluate everolimus add-on treatment in infants with TSC-associated WS, previously refractory to standard treatment. For this preliminary report, data from four male infants with TSC2 and a median observation period of 13 (range = 8-42) months after treatment initiation were analyzed. Two infants showed electroclinical remission until day 14 after everolimus treatment initiation. In one additional infant, hypsarrhythmia resolved. No relapse after initial response was documented. Developmental progress improved in three infants. Tolerability was similar to that described in older children. According to our preliminary results, everolimus appears to have the potential to treat successfully both spasms and hypsarrhythmia in infants with TSC-associated WS, contributing to better developmental progress.