Understanding the Mechanism of Action of Vagus Nerve Stimulation in Epilepsy

Abstract

Epilepsy is a chronic neurological disorder characterised by recurrent, unprovoked seizures that can significantly affect morbidity, mortality, and quality of life (QoL). Around 30% of people with epilepsy develop drug-resistant epilepsy (DRE), meaning seizures persist despite treatment with two or more adequate trials of antiseizure medications (ASM). For these individuals, alternative therapeutic approaches are often required. Vagus nerve stimulation (VNS) is a well-established adjunctive neuromodulation therapy that has been used for more than 3 decades. Clinical evidence shows that it can reduce seizure frequency and burden, extend seizure-free intervals, and may also contribute to lowering the risk of sudden unexpected death in epilepsy (SUDEP). Evidence suggests that VNS works through the vagal afferent network to influence key brainstem nuclei and downstream brain circuits involved in seizure generation and propagation. Stimulation of the nucleus tractus solitarius (NTS) and locus coeruleus (LC) appears to increase the release of monoamines such as noradrenaline (NA) and 5-hydroxytryptamine (5-HT), better known as serotonin, which in turn modulate neurotransmission. Here, Raman Sankar, Professor of Neurology and Paediatrics and Chief of Paediatric Neurology, David Geffen School of Medicine, University of California, Los Angeles, USA, proposes and outlines the evidence for a monoamine hypothesis of VNS function. He also argues that a clearer understanding of this mechanism of action (MOA) can help clinicians work with patients to make more informed treatment decisions.