From October 2013 to August 2014, 15 patients with intractable essential tremor were enrolled. Twelve of them completed clinical assessment through 4 years of postoperative follow-up. Tremor severity, task performance, and disability were measured using the Clinical Rating Scale of Tremor.
The mean age of the 12 patients was 61.7 ± 8.1 years. Maximally delivered energy was 15,552.4 ± 6574.1 joules. The mean number of sonications was 17.3 ± 1.6. The mean postoperative lesion volume was 82.6 ± 29.023 mm3 and in 1 year was a mean of 9.667 ± 8.573 mm3 . Four years postoperatively, improvement of the hand tremor score was 56%, that of the disability score was 63%, that of the postural score was 70%, and that of the action score was 63% compared with baseline; all improvements were significant and sustained over the 4-year period after thalamotomy. There was no permanent adverse effect throughout the 4-year follow-up period.
Magnetic resonance-guided focused ultrasound thalamotomy exhibits sustained clinical efficacy 4 years after the treatment of intractable essential tremor. Adverse events are generally transient. A large cohort of patients who have undergone magnetic resonance-guided focused ultrasound thalamotomy with longer follow-up is needed to confirm this findings 1).
Krishna et al., prospectively assessed the outcomes of Focused ultrasound thalamotomy (FUS-T) in 10 essential tremor (ET) patients using tractography-based targeting of the ventral intermediate nucleus (VIM).
VIM was identified at the intercommissural plane based on its neighboring tracts: the pyramidal tract and medial lemniscus. FUS-T was performed at the center of tractography-defined VIM. Tremor outcomes, at baseline and 3 months, were assessed independently by the Tremor Research Group. They analyzed targeting coordinates, clinical outcomes, and adverse events. The FUS-T lesion location was analyzed in relation to unbiased thalamic parcellation using probabilistic tractography. Quantitative diffusion weighted imaging changes were also studied in fiber tracts of interest.
The tractography coordinates were more anterior than the standard. Intraoperatively, therapeutic sonications at the tractography target improved tremor (>50% improvement) without motor or sensory side effects. Sustained improvement in tremor was observed at 3 mo (tremor score: 18.3 ± 6.9 vs 8.1 ± 4.4, P = .001). No motor weakness and sensory deficits after FUS-T were observed during 6-mo follow-up. Ataxia was observed in 3 patients. FUS-T lesions overlapped with the VIM parcellated with probablisitic tractography. Significant microstructural changes were observed in the white matter connecting VIM with cerebellum and motor cortex.
This is the first report of prospective VIM targeting with tractography for FUS-T. These results suggest that tractography-guided targeting is safe and has satisfactory short-term clinical outcomes 2).
Cerebellothalamic tractotomy (CTT) with (MR)-guided focused ultrasound (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 3).
Transcranial MRgFUS demonstrates a trend toward improvement in hand tremor, and a clinically significant reduction in mean UPDRS. A significant placebo response was noted in a randomized clinical trial 4).
With institutional review board approval, and with prospective informed consent, 15 patients with medication-refractory essential tremor were enrolled in a Health Insurance Portability and Accountability Act (HIPAA)-compliant pilot study and were treated with transcranial MR imaging-guided focused ultrasound surgery targeting the ventralis intermedius nucleus of the thalamus contralateral to their dominant hand. Fourteen patients were ultimately included. Diffusion tensor imaging (DTI) (DT MR imaging) studies at 3 Tesla were performed preoperatively and 24 hours, 1 week, 1 month, and 3 months after the procedure. Fractional anisotropy (FA) maps were calculated from the DT imaging data sets for all time points in all patients. Voxels where FA consistently decreased over time were identified, and FA change in these voxels was correlated with clinical changes in tremor over the same period by using Pearson correlation.
Ipsilateral brain structures that showed prespecified negative correlation values of FA over time of -0.5 or less included the pre- and postcentral subcortical white matter in the hand knob area; the region of the corticospinal tract in the semioval center, in the posterior limb of the internal capsule, and in the cerebral peduncle; the thalamus; the region of the red nucleus; the location of the central tegmental tract; and the region of the inferior olive. The contralateral middle cerebellar peduncle and bilateral portions of the superior vermis also showed persistent decrease in FA over time. There was strong correlation between decrease in FA and clinical improvement in hand tremor 3 months after lesion inducement (P < .001).
DT MR imaging after MR imaging-guided focused ultrasound thalamotomy depicts changes in specific brain structures. The magnitude of the DT imaging changes after thalamic lesion inducement correlates with the degree of clinical improvement in essential tremor 5).
In a pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized controlled trials will be required to assess the procedure's efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.) 6).
MR examinations were performed before and 2 days after the ultrasound functional neurosurgical treatment to visualize the targets on T2-weighted images and determine their coordinates. Thirty consecutive targets were reconstructed: 18 were in the central lateral nucleus of the medial thalamus (central lateral thalamotomies against neurogenic pain), 1 in the centrum medianum thalamic nucleus (centrum medianum thalamotomy against essential tremor), 10 on the pallido-thalamic tract (pallido-thalamic tractotomies against Parkinson's disease), and 1 on the cerebello thalamic tract (cerebello-thalamic tractotomy against essential tremor). We describe a method for reconstruction of the lesion coordinates on post-treatment MR images, which were compared with the desired atlas target coordinates. We also calculated the accuracy of the intra-operative target placement, thus allowing to determine the global, planning, and device accuracies. We also estimated the target lesion volume.
Moser et al. found mean absolute global targeting accuracies of 0.44 mm for the medio-lateral dimension (standard deviation 0.35 mm), 0.38 mm for the antero-posterior dimension (standard deviation 0.33 mm), and 0.66 mm for the dorso-ventral dimension (standard deviation 0.37 mm). Out of the 90 measured coordinates, 83 (92.2%) were inside the millimeter domain. The mean three-dimensional (3D) global accuracy was 0.99 mm (standard deviation 0.39 mm). The mean target volumes, reconstructed from surface measurements on 3D T1 series, were 68.5 mm(3) (standard deviation 39.7 mm(3)), and 68.9 mm(3) (standard deviation 40 mm(3)) using an ellipsoidal approximation 7).