Adjunctive transcranial direct current stimulation in super-refractory status epilepticus: a prospective case series

Super-refractory status epilepticus (SRSE) is a life-threatening neurological emergency characterized by persistent seizures despite anesthetic therapy, with high associated mortality and limited treatment options. Transcranial direct current stimulation (tDCS) has emerged as a potential neuromodulatory intervention in refractory epilepsy; however, evidence in SRSE remains limited. This study aimed to evaluate the feasibility, safety, and exploratory clinical response associated with adjunctive tDCS in patients with SRSE. In this investigator-initiated prospective single-center interventional case series, 20 adult patients with convulsive SRSE admitted to a tertiary referral center between 2021 and 2025 received adjunctive cathodal tDCS (2 mA for 20 min) applied bilaterally over temporal–frontal regions while standard medical therapy was continued. Clinical and electroencephalographic (EEG) assessments were performed 30 min before and after stimulation. Feasibility and safety were primary outcomes, while short-term clinical response was assessed as an exploratory endpoint. Written informed consent for study participation and publication of anonymized clinical data and EEG recordings was obtained from legally authorized representatives prior to enrollment, and the trial was registered in the Iranian Registry of Clinical Trials (IRCT20230209057371N1; retrospectively registered on October 21, 2023). Four patients (20%; 95% CI: 6–44%) demonstrated short-term clinical and EEG improvement within 30 min of stimulation. No serious adverse events were observed; one patient experienced a mild, self-limited erythematous skin reaction. Hospital mortality was 50%. Exploratory subgroup differences were observed between responders and non-responders. Adjunctive tDCS was feasible and well tolerated in patients with SRSE, with short-term clinical and EEG improvement observed in a subset of patients. These preliminary findings warrant further evaluation in controlled, adequately powered studies to determine efficacy and identify predictors of response. This study was registered in the Iranian Registry of Clinical Trials (IRCT) under registration number IRCT20230209057371N1 on October 21, 2023. The trial was registered while participant recruitment was ongoing (retrospective registration relative to study initiation).