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Turning up the current - optimizing stimulation parameters with vagus nerve stimulation in a nationwide Norwegian
Konstantin Hrisimirov Kostov1, Hrisimir Kostov2, Pål Gunnar Larsson3
1National Center for Epilepsy, Full Member of European Reference Network on Rare and Complex Epilepsies EpicCare, Sandvika, Oslo University Hospital, Norway; Institute for Clinical Medicine, University of Oslo, Norway.
Background:
Despite widespread use of vagus nerve stimulation (VNS), evidence regarding optimal stimulation titration and dosing remains limited. Significant inter-practice variability and deviation from guidelines, results in sub-optimal dosing.
Objective:
Identify optimal stimulation parameters and establish target dosing for VNS therapy in epilepsy.
Methods:
We linked long-term outcomes with dosing parameters in 415 patients from a VNS registry (median follow-up = 79.0 months). A generalized linear mixed model (GLMM) assessed relationships between stimulation parameters (Output Current (OC), Frequency, Pulse Width (PW), Duty cycle [DC]) and very good clinical response (≥75 % seizure frequency reduction from baseline).
Results:
Output current was the strongest predictor of seizure reduction (p = 0.001). Increasing OC by 1 mA more than doubled the probability of ≥75 % seizure reduction, peaking at 2.70 mA. Greatest likelihood of ≥50 % seizure reduction was at 2.1 mA. Post-hoc analysis supported GLMM findings, showing significantly more patients (46.3 %) receiving >2.0 mA OC achieved ≥75 % seizure reduction compared with 30.7 % (p = 0.01) among patients using lower OC. Although changes in DC were not significantly associated with seizure reduction, post-hoc analysis suggested benefits from other duty cycles. Standard 250 μs PW and 20 Hz frequency were associated with best effect. Longer follow-up improved seizure control (p < 0.001); intellectual disability negatively impacted response (p = 0.005). Seizure-free patients had significantly lower total charge (122.4 vs. 250.1 mC, p = 0.014) than patients with persistent seizures.
Conclusion:
Output current should be the primary focus when titrating VNS patients to optimal dose. We suggest a target range of 1.5-2.25 mA with 250 μs PW and 20 Hz frequency. Higher OC should be attempted if tolerated.
