Initial experience of bortezomib in cryptogenic new-onset refractory status epilepticus: a case series

Cryptogenic new-onset refractory status epilepticus (cNORSE) is a neurological emergency with limited evidence-based treatment options. Bortezomib, a proteasome inhibitor targeting plasma cells, has emerged as a potential immunomodulatory therapy in refractory autoimmune neurological disorders. It's additional inhibitory effects on interleukins make it a plausible therapeutic option in cNORSE.

We retrospectively evaluated patients with cNORSE treated with bortezomib at a tertiary epilepsy center between 2021 and 2026.

Five patients with cNORSE were identified in whom bortezomib was administered. All patients had failed multiple anti-seizure medications (ASMs), anesthetic agents, and immunotherapies before bortezomib. Median duration from status epilepticus onset to bortezomib administration was 15 days (range: 8-86 days). No additional ASMs were introduced after starting Bortezomib. Status epilepticus cessation occurred within three doses (80%) in four patients. Pneumonia and hematological cytopenias were the most common adverse events, occurring in four patients (80%), followed by sepsis in three patients (60%) and urinary tract infections in three patients (60%). The cessation of status epilepticus likely reflects the cumulative effect of all immunotherapies utilized, rather than bortezomib alone.

Bortezomib may represent a promising therapeutic option in immunotherapy-refractory NORSE. Larger prospective multicenter studies are needed to establish its efficacy, safety, and optimal timing of administration.