Focused Ultrasound Shown to Improve Motor Symptoms in Parkinson Disease

Focused ultrasound subthalamotomy was shown to improve motor features among patients with Parkinson disease (PD) who present with asymmetric symptom severity, according to study findings published in The New England Journal of Medicine.

As a minimally invasive image-guided procedure, focused ultrasound for PD involves creating therapeutic lesions in deep-brain structures through focusing on sound waves inside the body.

“This allows doctors to interrupt faulty brain circuits or destroy unwanted tissue,” explains an accompanying press release. “Magnetic-resonance imaging allows doctors to monitor the procedure in real time, and to make adjustments as needed to obtain the best patient outcomes.”

Notably, deep-brain structures influenced by the procedure include the subthalamic nucleus, which researchers say is the preferred neurosurgical target for deep brain stimulation (DBS) in treating motor symptoms of PD. They sought to examine whether the technology would benefit patients with asymmetrical Parkinson symptoms, in which symptoms present much more severe on 1 side of the body.

Collaborating with the Centro Intregral de Neurociencias in Spain, researchers of the University of Virginia (UVA) Department of Neurology recruited 40 volunteers in the randomized, double-blind study. At a 2:1 ratio, participants with asymmetric PD who had motor signs not fully controlled by medication or who were ineligible for DBS received either focused ultrasound subthalamotomy (n = 27) on the side opposite their main motor signs or a sham procedure (n = 13).

In the study, researchers assessed the primary efficacy outcome of between-group difference in the change from baseline to 4 months in the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale III (MDS-UPDRS) motor score for the more affected body side in the off-medication state, in which higher scores on a scale of 1–44 indicate worse parkinsonism. The primary safety outcome, procedure-related complications, was assessed at 4 months.

For participants given the procedure, the mean MDS-UPDRS III score for the most affected side showed a decrease from 19.9 at baseline to 9.9 at 4 months (least-squares mean difference (LSMD) = 9.8 points; 95% CI, 8.6–11.1), compared with a decrease from 18.7 to 17.1 in the control group (LSMD = 1.7 points; 95% CI, 0.0–3.5), exhibiting a significant between-group difference of 8.1 points (95% CI, 6.0–10.3; P < .001).

Addressing the safety aspects of the procedure, adverse events in the treatment group included dyskinesia, weakness on the treated side, speech disturbance, facial weakness, and gait disturbance. “In 6 patients in the active-treatment group, some of these deficits were present at 12 months,” noted researchers.

"This small brain region, the subthalamic nucleus, had a very strong and potent effect on parkinsonian symptoms when we targeted it with precise, focused ultrasound energy," said study author Jeff Elias, MD, neurosurgeon at UVA Health, in a statement. "The key for the ultimate adoption of this new procedure will be further refinements of the technology to ensure reliability and safety."

Reference

Martínez-Fernández R, Máñez-Miró JU, Rodríguez-Rojas R, et al. Randomized trial of focused ultrasound subthalamotomy for Parkinson disease. N Engl J Med. Published online December 24, 2020. doi:10.1056/NEJMoa2016311