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Focused ultrasound thalamotomy for tremor treatment impacts the cerebello-thalamo-cortical network.

Authors: Dahmani L, Bai Y, Li M, Ren J, Shen L, Ma J, Li H, Wei W, Li P, Wang D, Du L, Cui W, Liu H, Wang M

High-intensity Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a recent, non-invasive line of treatment for medication-resistant tremor. We used MRgFUS to produce small lesions in the thalamic ventral intermediate nucleus (VIM), an important node in the cerebello-thalamo-cortical tremor network, in 13 patients with tremor-dominant Parkinson's disease or essential tremor. Significant tremor alleviation in the target hand ensued (t(12) = 7.21, p < 0.001, two-tailed), which was strongly associated with the functional reorganization of the brain's hand region with the cerebellum (r = 0.91, p < 0.001, one-tailed). This reorganization potentially reflected a process of normalization, as there was a trend of increase in similarity between the hand cerebellar connectivity of the patients and that of a matched, healthy control group (n = 48) after treatment. Control regions in the ventral attention, dorsal attention, default, and frontoparietal networks, in comparison, exhibited no association with tremor alleviation and no normalization. More broadly, changes in functional connectivity were observed in regions belonging to the motor, limbic, visual, and dorsal attention networks, largely overlapping with regions connected to the lesion targets. Our results indicate that MRgFUS is a highly efficient treatment for tremor, and that lesioning the VIM may result in the reorganization of the cerebello-thalamo-cortical tremor network.

Introduction

Purpose Other
Study Objective To evaluate if MRgFUS VIM lesioning alleviates hand tremor and changes functional connectivity in patients with tremor-dominant Parkinson's disease or essential tremor
Animal model / Human subject Human (Homo sapiens); strain: not applicable; age: adults — patients: 13 clinical participants (10 tremor-dominant Parkinson’s disease, 3 essential tremor), exact ages not reported in excerpt (control group n=48 age-matched to patients); note: GSP dataset used for thalamus mapping comprised healthy young adults (mean age 20.88 ± 3.01 years); sex: both sexes (patients and controls matched for sex)
Disease model tremor-dominant Parkinson's disease and essential tremor
MRI or image guidance method MR thermometry with T2-weighted MRI localization
Targeted brain region(s) Thalamus
Target coordinates Approximate target: on the AC–PC plane at 75% of the AC–PC line (along the AC–PC axis), 14 mm lateral to the AC–PC line. If third-ventricle enlargement: 11.5 mm lateral to the third-ventricle wall. (No DV coordinate reported.)
Cargo name and characteristics Not specified in the provided paper text.
Route of administration not reported

Outcomes and Safety

Summary of Outcomes Unilateral MRgFUS lesioning of the thalamic VIM in 13 patients produced rapid and sustained tremor improvement up to 12 months and was associated with reorganization of cerebello-thalomo-cortical functional connectivity
Duration of biological effect 12 months
Safety-related matter Transient adverse effects included gait disturbance in 3/13 patients and paresthesia/numbness in 5/13 at one month, with one patient showing inflexible/slowed movement and another slight leg shaking at six months, and all adverse effects resolved by 12 months.

Brain Region

Ultrasound Parameters

Ultrasound instrument ExAblate Neuro (InSightec, Haifa, Israel) — ExAblate Transcranial therapy table with a half-spherical helmet containing focused ultrasound transducer elements; no transducer aperture or diameter specified in the text.
FUS Frequency Not reported
FUS Intensity Not reported in the provided text
FUS Pressure Not reported in the provided text
FUS Mode continuous
Pulse duration Not reported
Duration of a single FUS session Not reported in provided text
Focal Characteristics Not reported
Treatment frequency single session

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