High-Intensity Focused Ultrasonic Ablation of the Centromedian Thalamic Nucleus for Treatment of Medically Refractory Generalized Epilepsy in Patients Ages 18 Years to 89 Years

The primary purpose of this study is to evaluate the safety of thalamotomy targeting the centromedian thalamic nucleus (CMN) using magnetic resonance-guided high-intensity focused ultrasound (HIFU), an incisionless, ablative procedure that selectively delivers ultrasonic waves to brain regions with submillimeter precision, which is already FDA-approved for thalamotomy in essential tremor and in practice at many institutions, including that of the investigators. The proposed study aims to determine if ablation of CMN using HIFU can safely reduce generalized seizure burden in patients with medically refractory generalized epilepsy (MRGE) using success metrics commonly used in interventions for epilepsy and by the change in frequency of convulsive (generalized tonic-clonic) seizures before and after the intervention. Current literature suggests that thalamotomy with HIFU for essential tremor produces minimal and generally transient side effects, while targeted lesioning of CMN with other modalities such as radiofrequency ablation (RFA) produces similarly transient side effects in patients with MRGE. No mortality associated with treatment was reported in any study. Furthermore, the benefits for this patient population from RFA or from deep brain stimulation (DBS) of CMN ranged from 50-98% reduction in generalized seizures as long as 36 months post-operatively. Thus, we hypothesize that HIFU ablation of CMN will safely produce a similar durable reduction in generalized seizure burden for patients with MRGE. In the proposed study, patients will be evaluated for three months pre-intervention and followed for one year after Intervention 1. The same schedule will be followed by subjects who proceed to receive Intervention 2. Seizure freedom will be defined according to the International League Against Epilepsy (ILAE) outcome classification scale. The ILAE outcome scale includes six classes of outcome: Class 1 = seizure free; Class 2 = auras only; Class 3 = one to three seizure days/year and auras; Class 4 = four seizure days/year to 50% reduction in baseline and auras; Class 5 = \<50% reduction in baseline number of seizure days to 100% increase in baseline number of seizure days and auras; Class 6 = \>100% increase in baseline number of seizure days and auras. Only patients classified as ILAE Class 1 or Class 2 will be considered seizure-free. This is a proof-of-concept interventional study whose primary aims are as follows: Primary Aim 1: To characterize the safety of bilateral CMN ablation using HIFU in terms of both somatic and neuropsychological adverse events. Primary Aim 2: To determine the efficacy of bilateral CMN ablation using HIFU in reducing generalized seizure burden and effect on interictal Electroencephalogram (EEG) anomalies.