Norwegian Population-Based Study of Long-Term Effects, Safety, and Predictors of Response of VNS Treatment in Drug-Resistant Epilepsy: The NORPulse Study

Background: Vagus nerve stimulation (VNS) is used for patients with drug-resistant epilepsy not amenable to epilepsy surgery. However, the efficacy of VNS treatment over time, and which patients with which etiologies derive most benefit from VNS, is uncertain.  Methods: We report long-term outcomes of VNS in 436 epilepsy patients (52·8% adults, 47·2% children), with median follow-up of 75 months (six to 254). Patients were stratified into constant responders, fluctuating responders, and non-responders. We used regression analysis to identify predictors of response. Findings: The cumulative probability of ≥50% seizure reduction was 60%, however 15% of patients showed a fluctuating course. Of those becoming responders, 89·5% (230/257) did so within two years. A steady increase in effect was observed among constant responders, with 48·7% (19/39) of those becoming seizure-free, and 29·3% (39/133) with ≥75% seizure reduction achieving these effects within between two and five years. Some effect (<50%) at six months was a positive predictor of becoming a responder (OR=10·18, CI 5·50–18·87, p<0·0001) and having ≥75% reduction at two years (OR=3·34, CI 1·50-7·45, p=0.03). Patients without intellectual disability had OR of 3·34 and 3·11 of having ≥75% reduction at two and five years, respectively. Among these patients, the OR of being seizure-free at last control of follow-up was 6·22. Patients with unchanged anti-seizure medication over observation period showed better responder rates at two years (63·0% vs. 43·1%, p=0·002) and five years (63·4% vs. 46·3%, p= 0·031) than patients whose anti-seizure medication was modified. Responder rates were higher for post-traumatic (70·6%, p=0·048) and post-stroke epilepsies (75·0%, p=0·05) than other etiologies (46·5%). Interpretation VNS is a viable treatment option for refractory epilepsy. Our data provide information about effects over time and for different patient groups and epilepsy etiologies. Funding Information: This work was done at and internally funded by the National Center for Epilepsy in Sandvika, Norway. Declaration of Interests: Dr. Peltola reports grants, personal fees and other from Eisai, grants, personal fees and other from UCB, grants, personal fees and other from Livanova, grants, personal fees and other from Medtronic, other from Bial, personal fees and other from Orion Pharma, other from Arvelle, other from Novartis, other from Phizer, outside the submitted work; all other authors have nothing to disclose. Ethics Approval Statement: The study was approved by the Regional Committee for Medical and Health Research Ethics (REK; ref. number 2018/2183) and the Norwegian Centre for Research Data (Personvernombud; ref. number 18/19827).