Low-intensity focused ultrasound neuromodulation for drug-resistant epilepsy: A randomized, sham-controlled crossover trial.
TL;DR
Although the primary crossover analysis did not demonstrate a statistically significant antiseizure effect, delayed seizure reduction during the extended follow-up suggests potential sustained neuromodulatory effects.
Abstract
Objective
This study was undertaken to evaluate the safety, feasibility, and efficacy of low-intensity focused ultrasound (LIFU) as a noninvasive neuromodulation technique in patients with drug-resistant epilepsy (DRE).
Methods
In this pilot, single-blind, randomized sham-controlled crossover trial, 12 patients with DRE underwent both LIFU and sham stimulation in a randomized sequence, targeting the seizure onset zone (SOZ), each followed by a 4-week observation period. Seizure frequency was analyzed as proportional change from baseline using linear mixed-effects models. An open-label extension phase evaluated longitudinal seizure outcomes following LIFU. Safety assessments included neurological examinations, magnetic resonance imaging (MRI), and neuropsychological and quality of life (QOL) measures.
Results
During the crossover phase, LIFU did not significantly reduce seizure frequency compared with sham (estimate = .49, 95% confidence interval [CI] = -.04 to 1.01, p = .068). No period or sequence effects were observed. Conversely, during the open-label extension phase, seizure frequency demonstrated a significant longitudinal reduction following LIFU (β = -14.0 percentage points per month, 95% CI = -22.2 to -5.8, p = .001). Post-LIFU MRI showed no structural lesions. No significant changes were observed in anxiety, depression, or QOL scores. There were only transient mild-to-moderate adverse events reported, without serious complications.
Significance
LIFU neuromodulation targeting the SOZ is safe and well tolerated. Although the primary crossover analysis did not demonstrate a statistically significant antiseizure effect, delayed seizure reduction during the extended follow-up suggests potential sustained neuromodulatory effects. Larger parallel-group trials with longer observation periods are warranted.