To determine the safety and feasibility of unilateral anterior thalamic nucleus ablation using focused ultrasound in patients with intractable partial-onset epilepsy.

Focused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. Here, we describe the feasibility and safety results of the first human application of anterior thalamic nucleus (ATN) ablation using FUSA in patients with treatment-refractory, focal onset epilepsy with secondary generalization.

A feasibility analysis was performed with simulations and phantom study. An investigational device exemption was obtained from the FDA to test the safety of unilateral ATN FUSA. Patients with medically intractable, focal-onset seizures with secondary generalization were screened and enrolled. Seizure frequency was determined using a seizure diary. Safety was determined based on clinical assessment, neuropsychology testing, and imaging.

The phantom study established the feasibility of ANT FUSA. Two patients were enrolled and treated with the targeting of the left ANT. Peak temperatures of >55 ⁰C were achieved during both treatments.The patients tolerated the procedure well without neurological deficits or serious adverse events. A detailed neuropsychological assessment at three months revealed a decline in verbal fluency, immediate verbal memory, and psychomotor speed in one patient. Seizure frequency reduced significantly in both patients: one patient remains seizure free at 12 months, and the frequency reduced from 3-4 seizures per day to 3 seizures in a month in the second patient.

This is the first report of ATN FUSA in patients with medically intractable epilepsy. The safety of this procedure will be carefully assessed in a larger cohort during this Phase-1 trial.