Recent Advances in the Use of Focused Ultrasound as a Treatment for Epilepsy

Abstract

Epilepsy affects about 1% of the population. Approximately one third of patients with epilepsy are drug-resistant (DRE). Resective surgery is an effective treatment for DRE, yet invasive, and not all DRE patients are suitable resective surgery candidates. Focused ultrasound, a novel non-invasive neurointerventional method is currently under investigation as a treatment alternative for DRE. By emitting one or more ultrasound waves, FUS can target structures in the brain at millimeter resolution. High intensity focused ultrasound (HIFU) leads to ablation of tissue and could therefore serve as a non-invasive alternative for resective surgery. It is currently under investigation in clinical trials following the approval of HIFU for essential tremor and Parkinson’s disease. Low intensity focused ultrasound (LIFU) can modulate neuronal activity and could be used to lower cortical neuronal hyper-excitability in epilepsy patients in a non-invasive manner. The seizure-suppressive effect of LIFU has been studied in several preclinical trials, showing promising results. Further investigations are required to demonstrate translation of preclinical results to human subjects.

Emerging approaches in neurostimulation for epilepsy

“…tDCS has also been used following invasive stereo EEG evaluations [56 ▪ ] and for patient with Lennox-Gaustaut Syndrome [57 ▪ ]. Other approaches such as transcutaneous VNS [58], external trigeminal nerve stimulation [59] and focused ultrasound [60] are being explored as treatment options for epilepsy without any clear evidence for efficacy yet available.…”

“…Another recent pilot study evaluating the use of high definition tDCS in 10 adult patients with refractory status epilepticus demonstrated safety of the procedure with no reported adverse events and 50% median reduction of epileptiform discharges ]. Other approaches such as transcutaneous VNS [58], external trigeminal nerve stimulation [59] and focused ultrasound [60] are being explored as treatment options for epilepsy without any clear evidence for efficacy yet available.…”

Diagnostic and therapeutic approaches in refractory insular epilepsy

“…106 Low-intensity focused ultrasound (LIFU) is able to modulate the epileptic focus, whereas HIFU will ablate the epileptic focus as a noninvasive alternative to surgical resection. 106 Both LIFU and HIFU have been tested mostly in animal models of epilepsy and only in some cases of epileptic patients. 106 FUS has been tested for treatment of RFE in a phase 1 pilot study including a patient in whom the EZ, defined on SEEG, included the anterior part of the insular cortex.…”

“…106 Both LIFU and HIFU have been tested mostly in animal models of epilepsy and only in some cases of epileptic patients. 106 FUS has been tested for treatment of RFE in a phase 1 pilot study including a patient in whom the EZ, defined on SEEG, included the anterior part of the insular cortex. 107 A neuromodulation effect is suggested by changes in neural activities without structural brain lesions.…”

“…Low‐ and high‐intensity focused ultrasound (HIFU) could be effective as treatment of RFE 106 . Low‐intensity focused ultrasound (LIFU) is able to modulate the epileptic focus, whereas HIFU will ablate the epileptic focus as a non‐invasive alternative to surgical resection 106 . Both LIFU and HIFU have been tested mostly in animal models of epilepsy and only in some cases of epileptic patients 106 .…”