Assistant Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Sarva reports no financial relationships relevant to this field of study.
SYNOPSIS: Lesioning of the posterior portion of the VIM thalamus is most efficacious. Lesions extending beyond this portion can lead to adverse side effects in those with essential tremor treated with MRI-guided focused ultrasound.
SOURCE: Boutet A, Ranjan M, Zhong J, et al. Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor. Brain 2018;141:3405-3414.
Boutet et al studied 66 of 91 patients who received MRI-guided focused ultrasound thalamotomy (MRgFUS) for medically refractory essential tremor. Subjects were excluded if they received a sham procedure as part of a clinical trial, did not have essential tremor, or had treatment targets other than the thalamus. Post-procedure assessments were performed at one day, one week, one month, and three months after treatment. The investigators used the Clinical Rating Scale for Tremor (CRST) to compare the tremor in the treated arm at baseline and at three months. The most common side effects noted from both subjective report and physical examination were sensory symptoms, dysarthria, ataxia, and motor symptoms (clumsiness or weakness). Lesion mapping was performed and accounted for the percent improvement on CRST. Thalamotomy lesion maps of patients with and without adverse events were drawn to determine the extent of thalamic involvement.
Using diffusion-weighted imaging and tractography, the investigators determined that the area that bordered between the VIM and VC regions of the posterior portion of the thalamus produced the best tremor response. This area was significantly different from the regions that produced adverse effects. When comparing the lesion maps, those that included the lateral thalamus were more likely to produce motor side effects, whereas those in the inferolateral region were more likely to produce ataxic symptoms including abnormal gait. When the thalamic somatosensory relay nuclei were affected there was a 38-times higher likelihood of acute sensory side effects in the immediate period after the lesioning. Tractography confirmed that most of the lesions that resulted in a side effect overlapped the adjacent white matter tracts. Lesion volume > 170 mm3 had a higher risk of producing acute post-procedure adverse effects.
MRgFUS lesioning provides patients with medically refractory essential tremor a minimally invasive therapy as an alternative to deep brain stimulation. The lack of drilling and cutting makes the MRgFUS appealing to patients who do not want implantable hardware. FUS has been shown to reduce tremor by approximately 40% in studies that compared baseline CRST with three-month CRST after the procedure. Long-term studies have shown that the positive lesioning effects are maintained for at least two years. However, unlike DBS, MRgFUS is not reversible and does not have intraoperative electrophysiological recording to improve lesion accuracy. Even slight spread of the lesion can lead to unwanted side effects. This study allows for better localization of the optimal site for tremor control. Further study using DWI, DTI, and perhaps even PET studies can assist in better accurately mapping the targets precisely to reduce unwanted lesioning-related side effects. In addition, long-term studies of the lesions and any adverse events that persist past three months need to be performed to reduce not only immediate postoperative side effects but also potentially permanent negative effects. Longer-term studies also will allow us to understand how patients recover from any side effects.