Neuromodulation in NORSE/FIRES

Neuromodulation is emerging as a promising adjunctive strategy for the management of new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES), conditions characterized by high morbidity, frequent treatment resistance, and a substantial risk of chronic epilepsy. This chapter presents a systematic review of reported neuromodulation interventions in NORSE/FIRES, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), responsive neurostimulation (RNS), electroconvulsive therapy (ECT), and repetitive transcranial magnetic stimulation (rTMS). Across the published literature, VNS was the most frequently reported technique and was generally well tolerated, with cases suggesting benefit in seizure termination, facilitation of anesthetic withdrawal, and longer-term seizure reduction. DBS and RNS were used predominantly in the chronic phase and showed signals of efficacy in selected patients, although the evidence base remains limited. ECT was associated with seizure reduction or cessation in several cases, particularly when applied in the acute phase, but cognitive adverse effects and heterogeneity of protocols were notable. rTMS was used infrequently and had inconsistent effects, while its safety profile remained favorable. Overall, the available evidence is limited to case reports and small case series, precluding direct comparison between techniques or firm treatment recommendations. Positive reporting bias is likely across all techniques. Nonetheless, neuromodulation appears feasible, generally safe, and potentially beneficial in carefully selected NORSE/FIRES patients. Further prospective studies are needed to define optimal timing, stimulation parameters, and patient selection, and to clarify the relative roles of acute versus chronic neuromodulation in improving both seizure and functional outcomes.