Vagus nerve stimulation as an adjunctive therapy for super-refractory status epilepticus including NORSE: a...

Resistance to anti-seizure medications (ASMs) remains a major challenge in managing super refractory status epilepticus (SRSE), including new-onset refractory status epilepticus (NORSE). Vagus Nerve Stimulation (VNS) has emerged as a potential adjunctive therapy, but clinical evidence in SRSE is limited.

We retrospectively identified patients who underwent VNS implantation for SRSE during hospitalization within a large tertiary hospital system in New York City (July 2018 - June 2024). Electronic medical records were reviewed for demographic, clinical features, neuroimaging, EEG findings, medications, VNS parameters, and short- and long-term functional outcomes.

Fifteen patients (14 female; age 16-77 years) underwent VNS implantation for SRSE, including 8 with NORSE (6 cryptogenic; 2 with a later-identified etiology) and 7 non-NORSE patients. Compared to non-NORSE patients, NORSE patients received more ASMs (median 5 vs. 4) and anesthetic infusions (3 vs 2) for longer duration (14.5 vs. 11 days) before implantation. All but one patient was successfully weaned off anesthetics without SE recurrence; VNS output at weaning was higher in NORSE patients (0.88 vs. 0.50 mA). No complications were observed related to VNS implantation or titration. Despite longer hospitalization (86.5 vs 47 days) and similar ASM burden (4) and functional status at discharge (GOS-E 3), NORSE patients showed a trend toward better long-term functional outcomes (GOS-E 7 vs 1, p = 0.31), despite developing post-NORSE epilepsy. In exploratory analyses, earlier implantation showed non-significant trends toward shorter hospitalization (47 vs. 116 days, p = 0.09) and higher discharge GOS-E (4 vs. 2.5, p = 0.06).

Our findings suggest that VNS is likely a safe addition to the established treatment for SRSE. However, given the retrospective and uncontrolled design, efficacy of VNS cannot be determined. Prospective controlled studies are needed to assess clinical benefit and to define optimal implantation timing, titration strategies, and short-and long-term outcomes, including post-NORSE epilepsy.