Focused Ultrasound in the Treatment of Epilepsy: Current Applications and Future Directions

Introduction: Epilepsy is the fourth most common neurological disorder, affecting almost 1% of the world’s population. Despite medical advances, one-third of patients prove medically refractory, necessitating surgical interventions. One rapidly developing minimally invasive technique is the use of magnetic resonance imaging-guided focused ultrasound (FUS). In this systematic review, we categorize and present pre-clinical and clinical advances in various FUS techniques for treating epilepsy.

Methods: A systematic review was conducted via PRISMA guidelines. PUBMED, Web of Science, and Clinical Trials.gov (CT.gov) search engines were searched using keywords: “Ultrasound” AND “Seizure.” Inclusion criteria included: pre-clinical experiment, case study, case series, cohort studies, and clinical trials involving therapeutic application of focused ultrasound for treatment of epilepsy of any etiology. Studies were classified as ablative (HIFU), neuromodulatory (modulatory LIFU), or blood brain barrier opening (BBB LIFU).

Results: 781 abstracts were screened, 79 selected for full text review, and 47 met criteria for data extraction. Additionally, 15 clinical trials were identified and screened after keyword search of which 9 were included as part of the review. For HIFU therapies, 10 studies were identified: 3 pre-clinical studies, 3 case reports, 1 clinical pilot study, and 3 ongoing Phase I-Phase II clinical trials. For neuromodulatory LIFU 30 studies were identified: 19 pre-clinical studies, 1 case report, 4 clinical pilot studies, and 6 ongoing Phase I-Phase II clinical trials. Lastly, for PING, 15 were identified, all of which were pre-clinical.

Conclusion : FUS is rapidly emerging as a clinical tool for safely and effectively treating epilepsy. HIFU and LIFU have achieved early promising results in safety, feasibility, and efficacy in case reports with more robust trials ongoing. Furthermore, PING has a strong pre-clinical foundation of evidence and recent success in facilitating drug delivery directly to intracranial targets. The next steps for HIFU and LIFU are comparative studies to existing standards of care, while FUS assisted/augmented drug delivery through PING needs human pilot studies for clinical safety and efficacy. MR-guided FUS provides a new and exciting frontier for minimally invasive epilepsy treatment.