Transcranial Ultrasound Therapy of Essential Tremor

Summary

Context. Essential tremor (ET) is a common disease, disabling in severe forms and resistant to drug treatment. In patients with severe ET, invasive neurosurgical technique such as deep brain stimulation of the Ventral Intermediate (VIM) nucleus of the thalamus is used. Focused ultrasound therapy, creating a small lesion of VIM represents an effective therapeutic alternative of low morbidity with the advantage of not requiring the opening of the skull and penetration into the brain. This therapy is performed under stereotactic guidance. Validation of the target before lesioning is done by testing the clinical effect by a gradual increase in temperature, resulting in tremor reduction. However, the gradual temperature increase in the targeting phase is suboptimal because it can decrease the efficiency of the lesioning procedure. The aim of this research project is to test an innovation of fundamental physics developed by the Langevin Institute, which would allow the reversible modulation of nerve tissue by ultrasonic waves without heating, to predict the effectiveness of treatment of the chosen target within the VIM before creating an irreversible lesion.

Methodology: Fifteen patients with severe and resistant essential tremor will be included in the study. A multimodal MRI will be performed for target calculation using several targeting methods for VIM developed during step 1. For each target, the application of neuro-modulation by ultrasound will allow determine the effect obtained on the tremor (quantified with adequate clinical scales - as Tremor rating scale (CRST), and the recording of electromyographic activity of the upper limbs) and the absence of side effects. A definitive millimetric lesion will be performed at the level of the most relevant target in order to maintain the clinical effect obtained. The procedure will be controlled by thermal MRI sequences. Post-therapy clinical and MRI multimodal follow-up will take place on D1, D7, M1, M2, M3, M6, M12 and M24.

Perspectives and Innovation: This project will test clinically the low intensity ultrasound neuromodulation jointly developed by the Langevin Institute and the Brain and Spine Institute ( ICM) in order to refine the targeting procedure of high intensity transcranial focused ultrasound therapy. In perspective, reversible neuromodulation performed in vivo in humans represents a considerable advance in the exploration and future treatment of neurological and psychiatric diseases such as depression. The translational collaboration between the physicists of the Langevin Institute, the ICM and the medical services of the Pitié-Salpêtrière guarantees the feasibility and quality of this first joint therapeutic trial.

Conditions

• Essential Tremor

Interventions

DEVICE

Transcranial Ultrasound Therapy (Exablate® 4000 Type 1.1)

The Exablate® 4000 Type 1.1 model designed for noninvasive ablation of brain tissue is an MRI-guided transcranial ultrasound system (MRgFUS). The goal of the Exablate Neuro system is to precisely guide the focus of the ultrasound energy on the target region. The focused ultrasound energy is then repeatedly transmitted to the target until the desired result is achieved. Targeting is performed using MRI acquired during treatment. The treatment process is constantly monitored by closed-loop thermal feedback in real time, under the supervision of the treating physician. Once targeting is complete, the treatment outcome is confirmed by MRI sequences immediately after treatment. The Exablate Neuro is compatible with Siemens 3 Tesla MRI.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Nadya Pyatigorskaya, MD · Assistance Publique - Hôpitaux de Paris

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-01-07

Primary Completion

2023-01-10

Completion

2024-10-04

Countries

• France

Study Locations