Safety of Focused Ultrasound Neuromodulation in Humans with Temporal Lobe Epilepsy

Abstract

Objective: Low-Intensity Focused Ultrasound Pulsations (LIFUP) is a promising new potential neuromodulation tool. However, the safety of LIFUP neuromodulation has not yet been adequately assessed. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of LIFUP neuromodulation. Because the brain tissue in these patients will be removed, histological changes in tissue after LIFUP can be examined. Evidence of effective neuromodulation was assessed using functional MRI and EEG, while further potential safety concerns were assessed using neuropsychological testing. Methods: EEG, functional MRI, and neuropsychology were assessed in six patients before and 2 after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm . Using the BrainSonix Pulsar 1002, LIFUP was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. EEG was recorded using the Electrical Geodesics EGI 256 channel system. Histological changes were assessed using hematoxylin and eosin staining, among others. Results: LIFUP was not able to modulate the BOLD signal on fMRI in a reliable and consistent manner. The EEG data that was available did not demonstrate a change in activity after LIFUP in all but one subject. Likewise, the neuropsychology testing did not show any statistically significant changes in any test, except for a slight decrease in performance on the one test after LIFUP. Lastly, the histology did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive. Significance: The safety in the histology was the primary endpoint, and as such, longer exposure at the highest intensity levels will be administered moving forward.

Design, Development, and Operation of a Low-Intensity Focused Ultrasound Pulsation (LIFUP) System for Clinical Use

“…In a separate investigation, exposures up to 8 times the intensity limit (up to ISPTA.3 of 5760 mW/cm 2 ) failed to produce a measurable in-situ temperature rise via MR thermometry [41].…”

Timing of referral to evaluate for epilepsy surgery: Expert Consensus Recommendations from the Surgical Therapies Commission of the International League Against Epilepsy

“…RF‐TC is a less resource‐intensive alternative to LiTT. Focused ultrasound also has a potential use for neuromodulation in epilepsies 29 . There is compelling evidence of efficacy for these emerging minimally invasive approaches, 30,31 but recent meta‐analyses suggest waning seizure freedom over time across all types of epilepsy surgery, most noticeable in minimally invasive approaches 32,33 .…”

Emerging Trends in the Management of Cryptogenic Epilepsy

“…Abe et al in Japan reported the first case of transcranial magnetic resonance-guided FUS (MRgFUS) for mesial temporal lobe epilepsy [83]. Further study in UCLA group on eight temporal lobe epilepsy patients before and after treatment with FUS using intensities up to 5760 mW/cm showed that there was no detectable damage to the tissue in the histological analysis of the resected specimens, and the neuropsychological testing results showed no significant changes after the treatment [84].…”