MRI-guided Focused Ultrasound Thalamotomy for Patients with Medically-refractory Essential Tremor

Summary

High-intensity MRI guided focused ultrasound is an emerging noninvasive technique to precisely ablate brain tissue. It has been shown to be safe and effective in treating medically-refractory essential tremor. This article describes the protocol for thalamotomy from patient selection to equipment setup to post-treatment follow-up.

Abstract

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ET can have a significant impact on quality of life, mood, functional activities, and socialization. Patients suffering from ET not sufficiently treated with first line medications may be eligible for alternative strategies such as deep brain stimulation, radiofrequency ablation, and MRI guided focused ultrasound (MRgFUS). High-intensity MRgFUS is an emerging modality to treat ET, its attraction for patients being that it is noninvasive and associated with short recovery time, as patients are home the day after treatment. While MRgFUS centers are still limited, it will become important for clinicians to consider MRgFUS as a treatment alternative, particularly in the case of a patient for whom open surgery is contraindicated. This article outlines the steps of patient selection, equipment setup, sonication, and post-treatment follow-up, as well as critical steps to be aware of when performing a MRgFUS procedure.

Introduction

Essential tremor (ET) is the most common movement disorder, with a prevalence of up to 4% among individuals 40 year of age or older¹. It is characterized by a postural and intention tremor at a frequency of approximately 4 – 7 Hz. It typically affects the upper extremities as well as the head and voice but can also be seen in the legs. ET can be severely debilitating, affecting the ability to manage simple activities of daily living. 15 – 25% of patients are forced to retire prematurely as a result of ET, and 60% of patients do not apply for jobs or promotions due to uncontrollable shaking². Despite the effectiveness of first line medical therapies, such as propranolol or primidone³, a significant proportion of patients cannot tolerate or are resistant to medical treatments. Patients who remain symptomatic and significantly disabled after trying at least two medications, or who develop intolerable side effects, are considered medication-refractory.

Medically-refractory cases of ET are eligible for surgical interventions. Targeting of the ventralis intermedius (Vim) nucleus of the thalamus, a key cerebello-motor relay structure, with deep brain stimulation (DBS)⁴ electrodes or radiofrequency ablation can help alleviate tremors^5,6. However, both are open neurosurgical procedures, with potential complications including infection and hemorrhage. DBS further involves chronic implantation of an intracranial electrode and battery over the pectoralis major. Furthermore, patients require anesthetics, and in the case of DBS a general anesthetic, as well as hospital stays ranging from one to several days.

MR-guided Focused ultrasound (MRgFUS) is an emerging noninvasive technique to treat various neurologic and psychiatric disorders. The device consists of a helmet that focuses over 1000 ultrasound beams from independent transducers through the intact skull. High-intensity MRgFUS can generate heat at the target leading to coagulative necrosis. A multi-centered randomized sham-controlled trial of thalamotomy for essential tremor demonstrated 47% improvement in tremor score that was durable at 12 months⁷. This result has led to regulatory approval of MRgFUS as a treatment modality and the subsequent addition of MRgFUS to the clinician's armamentarium for tremor management. This protocol details the steps of patient selection, preparation, and sonication, as well as the important elements of patient follow-up.

Protocol

All human experiments were approved by the Institutional Research Ethics Board at Sunnybrook Health Sciences Centre. 1. Patient Identification Administer informed consent with the patient or substitute decision maker. Explain potential adverse events related to the procedure, such as bleeding and neurological deficits, to the patient. Assess the candidate patient for MRgFUS thalamotomy. A physician with expertise in movement disorder should perform the assessment. …

Representative Results

Long-term reduction in tremor in the treated extremity is on average 50% at 3 months and 40% at 12 months. Treatment success can be immediately evaluated after sonication through radiologic findings of a lesion at the Vim (Figure 1) and performance on clinical measures such as the hand-drawn spiral test (Figure 2). Additionally, intraoperative MR thermography provides real-time feedback to the target temperature. A permanent lesi…

Discussion

MRgFUS at high-intensity can noninvasively create an intracranial lesion. Current high-intensity MRgFUS with continuous wave mode at 650 kHz has been optimized for thermal ablation of deep brain structures, such as the Vim thalamus. The use of MRgFUS has some advantages over existing techniques such as DBS, gamma knife radiosurgery, or radiofrequency ablation for treatment-refractory ET. DBS is an open surgical procedure that can be associated with potential device-related complications, including hardware malfunctions, …

Materials

InSightec ExAblate Neuro system	InSightec		The ExAblate Neuro consists of a helmet transducer with 1,024 independent elements, each with central frequency 650 kHz and is integrated with a 3 Tesla MR scanner.
3 Tesla MRI scanner
MRI compatible Cosman-Roberts-Wells (CRW) stereotactic frame
20 mL of 1% lidocaine with 1:100,000 epinephrine
hair shaver/clipper
warming blanket
compression stockings