Therapeutic use of transcranial ultrasound for epilepsy: A review

Up to 40 % of people with epilepsy (PwE) suffer from drug-resistant epilepsy (DRE). Despite the approval of novel anti-seizure medication (ASM), a significant treatment gap persists, emphasizing the need for alternative therapies. Transcranial delivery of ultrasound waves or focused ultrasound (FUS) is a promising novel non-invasive technique for PwE, capable of targeting deep brain regions at millimeter resolution. High-intensity Focused Ultrasound (HiFU) is used for focal ablation and Low-intensity Focused Ultrasound (LiFU) for non-invasive neuromodulation. Transcranial delivery of ultrasound waves can also be used for targeted drug delivery by either transiently opening the blood-brain barrier (BBB), or increasing focal drug uptake without BBB opening, through mechanisms such as reducing plasma protein binding or drug uncaging. An update on the current state of the art of LiFU, HiFU and ultrasound waves for targeted drug delivery in epilepsy is timely in view of recently performed clinical trials. We provide scientific background and discuss its added value for PwE. The limitations are addressed, and the technique is discussed in the context of currently available therapies for DRE.