Magnetic resonance-guided focused ultrasound (MRgFUS) is an incisionless technique that enables focal brain lesioning, with demonstrated efficacy in refractory essential tremor (ET) and Parkinson's disease.1,2 Here, we describe the cases of 2 patients with multiple sclerosis (MS) and disabling tremor treated with MRgFUS thalamotomy.
Patient 1. A 52-year-old right-handed woman, diagnosed with relapsing-remitting MS (RRMS) at 36 years of age, developed severe bilateral upper limb action tremor at 38 years of age, which significantly impaired daily living activities. She presented a Clinical Rating Scale for Tremor (CRST) total score of 82 (A: 21, B: 35, C: 26). By the time, she had secondary progressive MS, with an Expanded Disability Status Scale (EDSS) score of 8.0.
Patient 2. A 34-year-old right-handed man, diagnosed with RRMS at 25 years of age (EDSS 6.0 at the time of diagnosis), developed progressive upper limb action tremor 6 years after diagnosis. His CRST total score was 88 (A: 28, B: 36, C: 24), and EDSS score was 6.5.
Both patients were refractory to pharmacological treatment and underwent left MRgFUS thalamotomy. Stereotactic planning was performed for the left ventralis intermedius (VIM) nucleus and tractography was used to localise the dentato-rubro-thalamic (DRT) tract, medial lemniscus, and corticospinal tract. The skull density ratio (SDR) was 0.56 in patient 1 and 0.65 in patient 2. After releasing each intermediate-energy sonication to verify the optimal treatment target, a clinical evaluation of transient clinical improvement and adverse events was performed. Two lesions were performed within the left VIM in patient 1 (coordinates relative to the posterior commissural point: L: 15 mm/A: 6.5 mm/S: 3 mm; L: 14 mm/A: 5.5 mm/S: 3 mm), with a total of 6 sonications (2 treatment sonications), delivering 43,837J over 111s. The maximum temperature reached was 62°C (range, 46–62) with a maximum mean temperature of 58°C (range, 45–58).
Three lesions were performed in patient 2 (L: 15 mm/A: 6.5 mm/S: 3 mm; L: 14 mm/A: 7 mm/S: 4 mm; L: 15 mm/A: 6 mm/S: 4 mm) (Fig. 1), with a total of 10 sonications (5 treatment sonications), delivering 29,221J over 66s. The maximum temperature reached was 62°C (range, 48–62), with a maximum mean temperature of 57°C (range, 4557).
Magnetic resonance images from 2 patients with refractory tremor secondary to multiple sclerosis, treated with MRgFUS thalamotomy. Top row, patient 1. Bottom row, patient 2. (A) Stereotactic planning. MRI images (axial, sagittal, and coronal views) with tractography. Corticospinal (pink); medial lemniscus (blue), and dentate-rubro-thalamic (DRT) tract (orange). (B) FLAIR sequence, axial plane, after thalamotomy. (C) Tractography showing the disappearance of the DRT tract after thalamotomy.
A significant reduction in tremor was observed in both patients, with an improvement of 59.4% and 54.4%, respectively, in CRST score on the treated side (sum of the 8 items of CRST parts A and B evaluating the treated side) after the procedure, remaining stable at 3 months. In patient 1, total CRST score decreased from 82 (baseline) to 41 points (at 3 months), with CRST-A score decreasing from 21 to 1, CRST-B score from 35 to 23, and CRST-C score (which evaluates the functional impact of tremor) from 26 to 17. For patient 2, total CRST score decreased from 88 to 75 points, with CRST-A decreasing score from 28 to 19, CRST-B score from 36 to 34, and CRST-C score from 24 to 22. Subjective improvement, assessed with the Patient Global Impression of Improvement (PGI-I), was rated as “much improved” and “minimally improved”, respectively. Both patients recovered independence for such daily living activities as eating and drinking. Adverse events were mild and transient. Patient 1 developed temporary dysarthria and right upper limb paresis, resolving within a month. Patient 2 experienced transient worsening of pre-existing dysarthria, right upper limb dysmetria, and tongue paraesthesia. No permanent side effects were reported. Regarding long-term follow-up, one patient died due to sudden nocturnal death 17 months after MRgFUS, an event that was unrelated to the procedure. The other patient experienced MS progression over 2 years, reaching an EDSS score of 8.0, with stability of MS-related lesions.
DiscussionWe report the cases of 2 patients with disabling tremor secondary to MS who were treated with MRgFUS thalamotomy, achieving significant tremor reduction without permanent adverse effects. Approximately 25%–58% of patients with MS present tremor, which is severe and refractory in some cases.3,4 The presence of cerebellar lesions and demyelination in neural pathways, such as the cerebello-thalamo-cortical network or the DRT tract, has been proposed to explain the tremor in these patients. VIM ablation reduces abnormal oscillatory signals propagating from damaged cerebellar regions to the motor cortex. Post-MRgFUS functional MRI in patients with ET shows normalisation of hyperconnectivity in motor networks.5,6
Previous reports of MRgFUS in MS-related tremor suggest that the procedure is safe in these patients, and achieves significant tremor control.3 Improvement in our patients was moderate, with smaller improvements than those reported previously (79%),3 although this may be explained by differences in the methods used to evaluate tremor and in the duration of tremor. Cases have also been reported of patients with essential tremor who later developed MS and were treated with MRgFUS, with moderate success.7 The subjective and functional improvements reported by the patients suggest that MRgFUS may still provide clinically meaningful benefits. The optimal time for this treatment should be investigated to improve patients’ quality of life for a longer time.
The safety of MRgFUS in MS deserves attention to avoid a worsening of their disability. Neither of our patients experienced permanent side effects after MRgFUS. Ataxia, the most common MRgFUS complication,8–10 was not a major concern, since both patients used wheelchairs. However, careful patient selection and adequate post-operative patient care are essential.
In conclusion, MRgFUS may be a safe and effective treatment for refractory MS-related tremor. Further studies with larger cohorts, longer follow-up periods, and safety monitoring are necessary to define the long-term efficacy and safety of MRgFUS in this population.
