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Incisionless transcranial MR-guided focused ultrasound in essential tremor: cerebellothalamic tractotomy.

Authors: Gallay MN, Moser D, Rossi F, Pourtehrani P, Magara AE, Kowalski M, Arnold A, Jeanmonod D

Already in the late 1960s and early 1970s, targeting of the "posterior subthalamic area (PSA)" was explored by different functional neurosurgical groups applying the radiofrequency (RF) technique to treat patients suffering from essential tremor (ET). Recent advances in magnetic resonance (MR)-guided focused ultrasound (MRgFUS) technology offer the possibility to perform thermocoagulation of the cerebellothalamic fiber tract in the PSA without brain penetration, allowing a strong reduction of the procedure-related risks and increased accuracy. We describe here the first results of the MRgFUS cerebellothalamic tractotomy (CTT). Twenty-one consecutive patients suffering from chronic (mean disease duration 29.9 years), therapy-resistant ET were treated with MRgFUS CTT. Three patients received bilateral treatment with a 1-year interval. Primary relief assessment indicators were the Essential Tremor Rating Scale (Fahn, Tolosa, and Marin) (ETRS) taken at follow-up (3 months to 2 years) with accent on the hand function subscores (HF16 for treated hand and HF32 for both hands) and handwriting. The evolution of seven patients with HF32 above 28 points over 32 (group 1) differentiated itself from the others' (group 2) and was analyzed separately. Global tremor relief estimations were provided by the patients. Lesion reconstruction and measurement of targeting accuracy were done on 2-day post-treatment MR pictures for each CTT lesion. The mean ETRS score for all patients was 57.6 ± 13.2 at baseline and 25.8 ± 17.6 at 1 year (n = 10). The HF16 score reduction was 92 % in group 2 at 3 months and stayed stable at 1 year (90 %). Group 1 showed only an improvement of 41 % at 3 months and 40 % at 1 year. Nevertheless, two patients of group 1 treated bilaterally had an HF16 score reduction of 75 and 88 % for the dominant hand at 1 year after the second side. The mean patient estimation of global tremor relief after CTT was 92 % at 2 days and 77 % at 1-year follow-up. CTT with MRgFUS was shown to be an effective and safe approach for patients with therapy-refractory essential tremor, combining neurological function sparing with precise targeting and the possibility to treat patients bilaterally.

Introduction

Purpose Thermal ablation
Study Objective To evaluate the safety and efficacy of MR-guided focused ultrasound cerebellothalamic tractotomy (CTT) for treating patients with therapy-refractory essential tremor.
Animal model / Human subject Human (Homo sapiens), strain: N/A, age: mean 69.1 ± 9.2 years, sex: 6F/15M (21 patients)
Disease model Essential tremor
MRI or image guidance method MR-guided (MRgFUS) with ExAblate Neuro using MR imaging and MR thermometry; stereotactic targeting using the Morel multiarchitectonic thalamic atlas and stereotactic head frame fixation; pre- and post-op MRI co-registration for target reconstruction.
Targeted brain region(s) Cerebellothalamic Tract (Posterior Subthalamic Area, Psa)
Target coordinates AP: 5.0 mm posterior to the mid-commissural line; ML: 8.0 mm lateral to the thalamo-ventricular border; DV: 3 mm below the intercommissural plane.
Route of administration oral (per os)

Outcomes and Safety

Summary of Outcomes MRgFUS cerebellothalamic tractotomy (CTT) produced substantial and sustained reduction of essential tremor (mean ETRS 57.6 → 25.8 at 1 year, ≈55% reduction), with HF16 improvement ≈90% in less-severe patients and ≈40% in the most severe group; patient-reported global tremor relief was 92% at 2 days and 77% at 1 year, and bilateral complementation improved outcomes in some patients without major persistent side effects. The study did not report testing or comparing different focused ultrasound parameter sets (no parameter variations were reported).
Duration of biological effect 1 year
Safety-related matter The authors report MRgFUS CTT to be effective and safe, with no procedure-related side effects apart from a slight worsening of pre‑existing gait instability in 5/21 patients (increase ~0.5/4), only one of which persisted at 1 year (2.5/4 vs 2/4 preoperatively) and may have been related to concomitant polyneuropathy and cervical canal stenosis.

Brain Region

Ultrasound Parameters

Ultrasound instrument ExAblate Neuro device (InSightec, Haifa, Israel); transducer aperture/diameter: None
Duration of a single FUS session 4.45 ± 1.1 h
Focal Characteristics focal depth: None; focal length: None; aperture size: None
Treatment frequency multiple

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