Vagus nerve stimulation for refractory status epilepticus: A systematic review

Refractory status epilepticus (RSE) is associated with high morbidity and mortality; however, evidence supporting standardized, effective medical treatments remains limited, and the role of vagus nerve stimulation (VNS) remains unclear. This systematic review aims to synthesize updated evidence on VNS therapy for RSE and evaluate its efficacy and functional outcomes.

This review included VNS outcome studies for any acute-to-subacute RSE (≤ 90 days from onset), excluding transcutaneous VNS, epilepsia partialis continua, and electrical status epilepticus in slow-wave sleep. The primary endpoint was RSE cessation, and the secondary endpoints were seizure freedom (International League Against Epilepsy Class 1) and functional outcome (modified Rankin Scale [mRS]).

This review included 23 articles comprising 61 patients, with a pediatric predominance (79%, 48/61). All included patients (100%, 61/61) had super-refractory status epilepticus (SRSE). Sixty-nine percent (42/61) were diagnosed with new-onset refractory status epilepticus (NORSE). The median RSE duration before VNS implantation was 18.9 days (interquartile range [IQR]: 18.9-25.5). The RSE cessation rate after VNS was 90% (55/61), with a median implantation-to-cessation duration of 12.7 days (IQR: 7.0-12.7). Among responders with follow-up of ≥ 12 months, 38% (13/34) achieved seizure freedom. Of the patients with a documented functional status, 61% (33/54) had unfavorable functional outcomes (mRS ≥ 4) and 31% (17/54) died. Excluding one case lacking a reported titration rate, all analyzed cases utilized fast VNS titration.

VNS implantation may be considered a treatment option for patients with acute-to-subacute SRSE who do not respond to medical treatment. However, functional disability remains substantial, and the likelihood of long-term seizure freedom is uncertain. Given the potential for publication bias and the exploratory nature of the subgroup analyses, the findings of this review should be interpreted cautiously and validated in large prospective studies.