Neuromodulation in epilepsy: state-of-the-art approved therapies.

Three neuromodulation therapies have been appropriately tested and approved in refractory focal epilepsies: vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS), and closed-loop responsive neurostimulation of the epileptogenic zone or zones. These therapies are primarily palliative. Only a few individuals have achieved complete freedom from seizures for more than 12 months with these therapies, whereas more than half have benefited from long-term reduction in seizure frequency of more than 50%. Implantation-related adverse events primarily include infection and pain at the implant site. Intracranial haemorrhage is a frequent adverse event for ANT-DBS and responsive neurostimulation. Other stimulation-specific side-effects are observed with VNS and ANT-DBS. Biomarkers to predict response to neuromodulation therapies are not available, and high-level evidence to aid decision making about when and for whom these therapies should be preferred over other antiepileptic treatments is scant. Future studies are thus needed to address these shortfalls in knowledge, approve other forms of neuromodulation, and develop personalised closed-loop therapies with embedded machine learning. Until then, neuromodulation could be considered for individuals with intractable seizures, ideally after the possibility of curative surgical treatment has been carefully assessed and ruled out or judged less appropriate.