Parkinson’s Motor Symptoms Improve With Focused Ultrasound

Focused ultrasound in one brain hemisphere improved motor function on the opposite side of the body in people with Parkinson’s disease, but led to frequent, persistent adverse events, a small sham-controlled trial showed.

In a select group of patients with markedly asymmetric Parkinson’s signs, focused ultrasound subthalamotomy led to a significant improvement in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale motor scores (MDS-UPDRS III) at 4 months compared with sham treatment, with a between-group difference of 8.1 points (95% CI 6.0-10.3, P<0.001), reported Raul Martinez-Fernandez, MD, PhD, of CEU San Pablo University in Mostoles, Spain, and co-authors.

“This randomized, sham-controlled trial showed that focused ultrasound subthalamotomy performed in one hemisphere improved the motor features of Parkinson’s disease on the more affected side at 4 months,” they wrote in the New England Journal of Medicine.

“Adverse events such as dyskinesias, motor weakness, and gait and speech disturbances were frequent and persisted in several patients,” Martinez-Fernandez and colleagues noted. “These results are similar to outcomes in uncontrolled series of stereotactic radiofrequency subthalamotomy for the treatment of Parkinson’s disease.”

Changes from baseline MDS-UPDRS motor scores for the more affected side varied, ranging from 5% to 95%, and were more apparent for tremor and rigidity reduction than bradykinesia.

Among 27 patients treated with focused ultrasound subthalamotomy, adverse events included:

• Dyskinesia in the off-medication state in six patients and on-medication state in six patients, which persisted in three patients and one patient, respectively, at 4 months
• Weakness on the treated side in five patients, which persisted in two patients at 4 months
• Speech disturbance in 15 patients, which persisted in three patients at 4 months
• Facial weakness in three patients, which persisted in one patient at 4 months
• Gait disturbance in 13 patients, which persisted in two patients at 4 months

Some of these deficits were present in six patients at 12 months.

Deep-brain stimulation (DBS) to treat Parkinson’s disease predominantly has targeted the subthalamic nucleus or the internal segment of the globus pallidus, but some patients are wary of DBS surgery and hardware, noted Joel Perlmutter, MD, and Mwiza Ushe, MD, both of Washington University in St. Louis, in an accompanying editorial. Focused ultrasound, which has been approved to treat intractable essential tremor, “has the advantage of producing lesions without the need for craniotomy,” they observed.

But in this small trial, patients who had focused ultrasound subthalamotomy had almost five times as many adverse events as those who had the sham procedure, Perlmutter and Ushe pointed out.

“These adverse events in a group of relatively young patients and the lack of ability to modulate treatment over time to treat prominent tremor raise questions about the appropriate implementation of focused ultrasound-produced lesions for the treatment of Parkinson’s disease,” they wrote.

The trial included 40 adults with markedly asymmetric Parkinson’s disease who had motor signs not fully controlled by medication or who were ineligible for DBS surgery. In total, 27 patients (mean age 56.6, 59% men) had focused ultrasound subthalamotomy on the side opposite their main motor signs and 13 had a sham procedure (mean age 58.1, 77% men).

At 4 months, mean MDS-UPDRS motor scores for the more affected side decreased from 19.9 at baseline to 9.9 in the treated group (least-squares mean difference 9.8 points, 95% CI 8.6-11.1) and from 18.7 to 17.1 in the sham group (least-squares mean difference 1.7 points, 95% CI 0.0-3.5).

“Side effects such as dysarthria may limit application to focused ultrasound-produced lesions in one hemisphere because the frequency of dysarthria is likely to be greater with procedures that are conducted in both hemispheres,” Perlmutter and Ushe wrote. But “limiting the treatment to one side of the brain by ultrasound-produced lesioning constrains the application, since most patients with Parkinson’s disease have progression of symptoms on both sides of the body,” they added.

The trial had several limitations, including its small sample size, the researchers noted. Almost all patients were enrolled at one of the two trial sites, making it in effect a single-center trial. In addition, both patients and assessors correctly guessed trial group assignments, erasing the intended effect of blinding.