Transcutaneous vagus nerve stimulation in the treatment of drug-resistant epilepsy

Epilepsy is a common chronic neurological disease with a high burden of illness. Invasive vagus nerve stimulation (iVNS) is a well-established treatment option in patients with epilepsy (PWE). More recently, transcutaneous vagus nerve stimulation (tVNS) was introduced, an alternative option which is particularly interesting because it does not require surgery and is instantaneously removable. Here, we thoroughly reviewed clinical data on efficacy and safety of tVNS in epilepsies. Five prospective trials in 118 patients with drug-resistant epilepsies and 3 randomized controlled trials in 280 patients with drug-resistant epilepsies were carried out. Study protocols were heterogeneous in terms of patients' characteristics, used device, stimulation parameters, study duration and endpoints. Seizure reduction amounted up to 64%, with responder rates (seizure reduction ≥50%) up to 65%. Seizure freedom was reached in up to 24%, and even to 31% in a small pediatric study group. Seizure severity scores were provided in 4 studies, showing significant improvement in two of them. Adverse side effects were mostly headache, ear pain and skin alteration and rated as mild to moderate. Drowsiness might be depend on stimulation intensity. Quality of life scores reflecting burden of illness showed significant improvement in two studies. Efficacy and safety of tVNS in PWE has to be interpreted as promising. Multicenter randomized double-blind clinical trials with standardized stimulation protocols and long-term follow-up studies are necessary to finally assess tVNS treatment outcome in drug-resistant epilepsies.