Simultaneous Bilateral Radiofrequency Thalamotomy for Medication-Refractory Essential Tremor

Essential tremor (ET) is one of the most common movement disorders, characterized by kinetic and postural tremor, particularly of the upper limbs. While the pathophysiology of ET is not fully understood, the ventral intermediate nucleus (Vim) of the thalamus plays a key role as a relay center in the tremor-generating network, making it a validated target for surgical interventions. Although unilateral thalamotomy has long been recognized as an effective treatment for drug-refractory ET, bilateral procedures have been limited due to concerns regarding adverse effects, particularly speech disturbance, dysphagia, and gait imbalance.

Recently, staged bilateral thalamotomies, especially using magnetic resonance-guided focused ultrasound (MRgFUS), have shown promising results. However, simultaneous bilateral thalamotomy using radiofrequency lesioning has rarely been systematically evaluated. Given the shorter surgical burden and potential for immediate bilateral tremor suppression, simultaneous bilateral thalamotomy may represent a meaningful therapeutic option in selected patients with severe, symmetrical, medication-resistant tremor.

This investigator-initiated, prospective, single-arm clinical trial is designed to evaluate the feasibility, safety, and efficacy of simultaneous bilateral radiofrequency thalamotomy targeting the Vim in patients with medication-refractory essential tremor. A total of five participants will be enrolled and undergo stereotactic lesioning in a single operative session.

Preoperative evaluations include structural brain MRI, Clinical Rating Scale for Tremor (CRST), Quality of Life in Essential Tremor Questionnaire (QUEST), Scale for the Assessment and Rating of Ataxia (SARA), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Apathy Evaluation Scale (AES), and Mini-Mental State Examination (MMSE). Surgical planning is based on direct targeting of the Vim using high-resolution MRI. The procedure will be performed under local anesthesia, with frame-based stereotactic guidance, and intraoperative CT or MRI will be used to monitor safety.

Lesioning will begin on the side contralateral to the dominant hand. After completing the first side, intraoperative MRI will be performed to confirm the absence of hemorrhagic complications. Only if no bleeding is detected will the procedure proceed to the contralateral Vim. If hemorrhage or other significant adverse events are identified after the first lesion, the surgery will be terminated after unilateral treatment. If no adverse events are found, lesioning will continue on the second side. The expected lesioning time is approximately 30 minutes per side. Postoperative imaging will be performed immediately after the procedure and the following day.

Postoperative assessments will be performed at discharge, and at 1 month, 3 months, and 6 months. CRST will be evaluated at each follow-up point, while QUEST and SARA will be repeated at 1, 3, and 6 months. Mood scales and MMSE will be reassessed at 6 months. MRI will also be repeated at 3 months to evaluate lesion location and any potential structural changes. The primary endpoint is the change in CRST score at 6 months postoperatively. Secondary endpoints include quality of life, cerebellar symptoms, adverse events, and neuropsychiatric effects.

Participants will be closely monitored for adverse events, including intracranial hemorrhage, dysarthria, dysphagia, numbness, ataxia, or other neurological complications. The expected adverse event rates are based on prior publications and include transient dysarthria (~10%), swallowing difficulties (~5%), and mild sensory symptoms (~5%). Serious adverse events such as hemorrhage are considered rare (<1%).

This study is approved by the Institutional Review Board of Tokyo Women's Medical University and adheres to the ethical principles outlined in the Declaration of Helsinki and Japan's Clinical Research Act. Written informed consent will be obtained from all participants prior to enrollment.

The findings from this study are expected to contribute to the evidence base for bilateral surgical treatment of essential tremor and may help to define the role of simultaneous bilateral Vim thalamotomy in clinical practice.

Inclusion criteria

• Adults aged 20 to 70 years.
• Diagnosis of essential tremor by a neurologist or neurosurgeon specializing in movement disorders.
• Refractory to standard pharmacological therapy (e.g., propranolol, primidone, benzodiazepines, or alprenolol).
• Mini-Mental State Examination (MMSE) score ≥ 27.
• Able to undergo MRI.
• Provided written informed consent for participation in the study.

Exclusion criteria

• History or evidence of bleeding tendency.
• MRI contraindications (e.g., metallic implants, severe claustrophobia).
• Presence of intracranial pathology on preoperative MRI that would interfere with surgery.
• Pregnant or breastfeeding individuals.
• Any other condition that the principal investigator deems inappropriate for study participation.