Transcranial Ultrasound Therapy of Essential Tremor
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- The main objective is to evaluate the efficacy of Vim lesion produced by transcranial focused ultrasound on contralateral upper limb tremor at the 3-month procedure.
Study Overview
Brief 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.
Detailed Description
Context:
Essential tremor (ET) is the most common movement disorder, with a prevalence of 1-4% of the general population. ET is characterized by a rapid (6 and 12 Hz) attitude tremor with rhythmic oscillations of agonist and antagonist muscle groups. ET most often affects the upper limbs, the head and the voice but may involve the lower limbs in severe forms. The tremor worsens with age: it extends topographically towards the proximal end of the limbs. In severe forms, drug treatment is ineffective and tremor leads to impaired autonomy.
ET is due to dysfunction of neural networks including the cerebellum, bulbar olive, red nucleus and thalamus nuclei . At the thalamic level, the ventral intermediate thalamic nucleus (VIM), a relay of the cerebellar pathways, is a key structure. This VIM core receives output channels from the cerebellum and projects massively onto the primary motor cortex, the final effector of movement. In humans, imaging studies have shown the involvement of these cerebellar-thalamo-cortical circuits in the pathophysiology of tremor. When drug treatment is ineffective and tremor is disabling, surgical treatments are considered. Deep brain stimulation is the most used reversible and modulable method consisting in implantation of the electrodes in the VIM. However, patients are often elderly with much comorbidity. Thus, in these patients, the act of invasive neurosurgery (neurostimulation) may be contraindicated (anticoagulation treatment) or risky. Also, the peroperative risks such as hematoma of infection exist, even if they are rare.
As an alternative to Deep Brain Stimulation (DBS), radiosurgical thalamotomy was proposed. This method nevertheless has several major disadvantages, such as the use of radioactive sources, the fact that the dose actually delivered during irradiation of the patient cannot be controlled in terms of intensity. On the other hand, the biological effect on the tissues is not immediate and imposes a long waiting time (several months) to evaluate the effectiveness of the treatment. Finally, many cases of radionecrosis have been described with important clinical consequences, although transient in most cases.
Given the limitations inherent to deep brain stimulation and gamma knife thalamotomy, a new method of neuromodulation followed by injury without penetration into the brain would represent a considerable therapeutic hope. In addition, in patients in whom treatment is planned, pre-therapeutic neuromodulation would better determine the target of treatment.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Men and women, aged 18 to 80
- •Diagnosis of essential tremor according to the criteria of the Consensus Statement of the Movement Disorders Society (MDS)
- •Patients with significant disability related to their essential Tremor, despite well-conducted medical treatment
- •Stable essential tremor drug therapy for at least 30 days prior to inclusion
- •Contraindication or refusal or preference of deep brain stimulation
- •Patient receiving Social Security or Universal Medical Coverage or any equivalent plan
- •Person who voluntarily and knowingly agreed to participate in the study (signing of a written consent)
- •Exclusion criteria :
- •Inability to stop anticoagulant or antiplatelet therapy or any other medication that may increase the risk of bleeding during the 2 weeks prior to the procedure
- •Current state of health causing bleeding and / or abnormal coagulopathy
- •Unstable cardiac pathology or severe hypertension that cannot be controlled by medication (diastolic blood pressure> 100 with drugs).
- •Active epilepsy in the year preceding the inclusion
- •Contraindications to magnetic resonance imaging such as non-compatible implanted metal devices (including pacemakers), size limits, etc. including presence of implants in the brain or skull)
- •Known hypersensitivity to local anesthetics (Xylocaine 20mg / ml)
- •Important claustrophobia that cannot be managed with mild medication
- •Inability to maintain prolonged stationary supine position necessary for treatment (3-4 hours)
- •Woman of childbearing age without means of contraception
- •Pregnant or lactating woman
- •Major persons subject to a measure of legal protection (guardianship, curators or under the protection of justice)
- •Subject in exclusion period of another biomedical research or participating in any other biomedical stimulation or therapeutic trial
- •Patients under AME (state medical aid) (except if exemption from affiliation)
- •Patient cannot communicate with the doctor during the treatment procedure
- •Subjects with behavior compatible with the abuse of ethanol or psychoactive substances
- •Progressive neurological pathology other than TE, stroke or cerebral hemorrhage < 6 months, multiple stroke ATCD, brain tumor or intracranial aneurysm
- •Patients who have taken in the last 6 months drugs lowering the epileptogenic threshold significantly (CNS stimulants, sympathomimetics, neuroleptics, imipraminic antidepressants, amantadine, fampridine, fluoroquinolones, mefloquine)
- •Significant healing in an area on the path of the planned energy path to the treatment area
- •Recourse to neurosurgical treatments for essential tremor (deep brain stimulation or gamma knife
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
The main objective is to evaluate the efficacy of Vim lesion produced by transcranial focused ultrasound on contralateral upper limb tremor at the 3-month procedure.
Time Frame: 3 MONTHS
The primary endpoint is the reduction of the severity of essential tremor measured by the clinical assessment of contralateral upper limb tremor at the lesion quantified by CRST A and B at V5 (3 months) compared with V1.
Secondary Outcomes
- Adverse events(24 MONTHS)
- Interest of neuromodulation effect for the prediction of the final clinical effect(3 MONTHS)