Focused Ultrasound Subthalamotomy Improves Motor Features in Asymmetrical Parkinson


Data from a small study showed patients experienced significant improvements in MDS-UPDRS III scores after 4 months of treatment with single-hemisphere FUS.

Raúl Martínez-Fernández, MD, PhD, researcher, Centro Integral de Neurociencias AC

Raúl Martínez-Fernández, MD, PhD

Recently published study data in The New England Journal of Medicine suggest that treatment with focused ultrasound (FUS) subthalamotomy in a single brain hemisphere is associated with improved motor features in individuals with Parkinson disease (PD) who had asymmetric signs of disease.

Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS III) motor scores improved for the treated group (n = 27) by 9.8 points (95% CI, 8.6-11.1) from a 19.9 baseline score. In comparison, the control sham-treatment group (n = 13) experienced an improvement of 1.7 points (95% CI, 0.0-3.5) from a baseline score of 18.7, with the between-group difference totaling 8.1 points (95% CI, 6.0-10.3; P <.001).

Lead author Raúl Martínez-Fernández, MD, PhD, researcher, Centro Integral de Neurociencias AC, and colleagues assessed 40 total patients who had motor signs which were uncontrolled by medication, or who were ineligible for deep brain stimulation (DBS) surgery to undergo FUS subthalamotomy on the opposite side of their main motor signs. In the active-treatment group, 16 patients underwent subthalamotomy in the left hemisphere and 11 in the right. In the control group, 7 patients underwent the sham procedure in the left hemisphere, and 6 in the right.

MDS-UPDRS III scores for the more affected side in the on-medication state decreased by 6.4 points (95% CI, 5.2-7.6) and 0.5 points (95% CI, –1.2 to 2.2) for the active group and control groups, respectively, for a between-group difference of 5.9 points (95% CI, 3.8-8.0). Reductions in levodopa dose equivalent (between-group difference, 0.3 points; 95% CI, –0.3 to 1.0) and dystonia in the OFF state (between-group difference, 0.4 points; 95% CI, –0.1 to 1.0), did not differ between groups at 4 months.

Martínez-Fernández and colleagues wrote that while this trial showed that the “comparison the change in the mean dose of dopaminergic medication between the active-treatment group and the control group was in the same direction as the primary outcome (i.e., the reduction from baseline in the dose of levodopa equivalent was greater in the active-treatment group than in the control group),” the outcome measures and confidence intervals were not adjusted for multiple comparisons. As such, “no definite conclusions can be drawn from these data.”

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Additionally, Patients’ Global Impression of Change (PGI-C) scores at 4 months were reported by 85% of patients (n = 23) in the active-treatment group, but only 15% (n = 2) of the control group. For the 25 patients with data, the change from baseline to 12 months in the MDS-UPDRS III score for the more affected side was 11.6 points (95% CI, 9.9.-13.3).

After the 4-month blinded follow-up was completed, the open-label phase of the trial began, with 12 of 13 control-group patients crossing over to receive FUS subthalamotomy. After 4 more months of assessment, 1 patient was lost to follow-up, and after 12 months, 4 more were lost. The mean MDS-UPDRS III score for the more affected side decreased from 19.5 (±3.9) at baseline to 8.1 (±5.3) at 4 months (n = 11) for a least-squares mean difference of 11.6 points (95% CI, 8.4 to 14.8), and to 9.7 (±6.4) at 12 months (n = 8) for a least-squares mean difference of 8.7 points (95% CI, 4.5 to 12.9).

New-onset dyskinesia developed in 3 patients in the crossover subgroup. One patient had hemiballismus, which was considered to be a serious adverse event (AE) that persisted as lower limb chorea in the OFF state at 4 months. Exacerbation of preexisting levodopa-induced dyskinesia occurred in 2 patients, isolated facial asymmetry in 1, speech disturbance in 5, and gait imbalance in 5.

Overall, after the first 4 months, AEs in the active-treatment group included dyskinesia in the OFF state in 6 patients and in the ON state in 6 (persisted in 3 and 1, respectively), weakness on the treated side in 5 patients (persisted in 2), speech disturbance in 15 patients (persisted in 3), facial weakness in 3 patients (which persisted in 1), and gait disturbance in 13 patients (persisted in 2). In 6 patients in the active group, some deficits were present after 1 year.

“Longer-term and larger trials are needed to determine the role of focused ultrasound subthalamotomy in the management of Parkinson’s disease and its effect as compared with other available treatments, including deep-brain stimulation,” Martínez-Fernández and colleagues concluded.

Martinez-Fernandez R, Manes-Miro JU, Rodriguez-Rojas R, et al. Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson’s Disease. N Engl J Med. 2020; 383:2501-2513. doi: 10.1056/NEJMoa2016311
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