LOW-INTENSITY FOCUSED ULTRASOUND FOR DRUG-RESISTANT EPILEPSY: NETWORK TARGETING, ACOUSTIC DOSE CONTROL, AND REVERSIBLE NONINVASIVE NEUROMODULATION

Аннотация

Background. Drug-resistant epilepsy remains associated with recurrent seizures, injuries, cognitive decline, psychosocial disability, and premature mortality. Resective surgery and implantable neurostimulation can be effective, but many patients have bilateral, deep, multifocal, eloquent-cortex, or poorly localized epileptogenic networks that limit invasive treatment. Low-intensity focused ultrasound offers nonthermal, incisionless, millimeter-scale modulation of cortical and subcortical circuits.

Materials and methods. A structured narrative review integrated prospective trials, pilot studies, preclinical experiments, technical investigations, safety consensus statements, and registered protocols available through July 2026. Evidence was organized by mechanism, acoustic dose, skull transmission, target selection, electrophysiological engagement, clinical efficacy, safety, reproducibility, and implementation. A prospective multicenter, randomized, double-blind, sham-controlled study is proposed for adults with drug-resistant focal epilepsy unsuitable for curative resection.

Results. Human pilot studies show that sonication can be delivered to seizure-onset tissue without radiographic injury and can alter intracranial electroencephalographic activity, but seizure outcomes remain preliminary and heterogeneous. Therapeutic direction depends on carrier frequency, pulse duration, pulse-repetition frequency, duty cycle, pressure, exposure duration, target geometry, and brain state. The proposed primary endpoint is the proportion of participants achieving at least fifty-percent reduction in disabling-seizure frequency during months four through six without treatment-related neurological deterioration. Secondary endpoints include seizure freedom, electrographic burden, cognition, mood, quality of life, target-engagement biomarkers, skull-adjusted acoustic exposure, adverse events, and durability.

Conclusion. Low-intensity focused ultrasound is an investigational network neuromodulation strategy rather than an established epilepsy treatment. Clinical translation requires individualized acoustic modeling, sham control, mechanistic biomarkers, standardized safety reporting, and independent multicenter validation before routine adoption.