Everolimus initiated in the neonatal period for refractory seizures associated with tuberous sclerosis complex: long-term clinical outcome

Objective: Everolimus is an established therapy for tumor manifestations and refractory focal seizures in tuberous sclerosis complex (TSC) in patients aged ≥2 years. Evidence regarding its use during the neonatal period, particularly for seizure control, remains extremely limited. Methods: We describe the clinical course, neuroimaging findings, treatment response, and developmental outcome of a neonate with genetically confirmed TSC who received early everolimus therapy for refractory seizures. Results: A term female neonate developed multifocal drug-resistant seizures beginning on day 3 of life. Brain magnetic resonance imaging demonstrated multiple cortical and subcortical tubers, and electroencephalography revealed multifocal epileptiform discharges. Despite treatment with phenobarbital, midazolam, and vigabatrin, seizures remained uncontrolled. Everolimus was initiated on day 30 of life. Seizure activity resolved completely within one week and remained controlled for over one year. The treatment was well tolerated, with no serious adverse events. Early developmental assessment at 12 months showed cognitive, language, and motor scores within the lower range of normal. Conclusion: This case suggests that early initiation of everolimus may represent a feasible adjunctive treatment option for selected neonates with TSC-associated refractory seizures.