Parkinson’s motor symptoms are improved by focused ultrasound

Focused ultrasound on one cerebral 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 few falsely controlled studies showed.

In a selected group of patients with markedly asymmetric Parkinson’s signs, focused ultrasound subthalamotomy led to a significant improvement in motor scores (MDS-UPDRS III), the combined Parkinson’s scale for movement disorders (MDS-UPDRS III) within 4 months treatment group difference of 8.1 points (95% CI 6.0-10.3, Str<0.001), reported by Dr. Raul Martinez-Fernandez of the University of San Pablo in Mostoles in Spain and co-authors.

“This randomized, false-controlled study showed that focused ultrasound subthalamotomy performed on a single hemisphere improved the motor characteristics of Parkinson’s disease on the affected side after 4 months,” they wrote in New England Journal of Medicine.

“Adverse events such as dyskinesia, motor weakness, and gait and speech disorders were common and lasted in several patients,” Martinez-Fernandez and colleagues noted. “These results are similar to those in an uncontrolled series of stereotactic radiofrequency subthalamotomies for the treatment of Parkinson’s disease.”

Changes from baseline MDS-UPDRS scores on the motorized side varied, ranging from 5% to 95%, and were more apparent for shivering and stiffness reduction than bradykinesia.

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

• Dyskinesia at treatment in six patients and treatment in six patients, lasting for three and one patient, respectively, after 4 months
• Weakness on the treated side in five patients, which lasted in two patients after 4 months
• Speech disorder in 15 patients, which lasted in three patients in 4 months
• Facial weakness in three patients, which lasted in one patient after 4 months
• Gait disorder in 13 patients, which lasted in two patients after 4 months

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

Deep-brain stimulation (DBS) for the treatment of Parkinson’s disease has mostly targeted the subthalamic nucleus or the inner segment of the globe pallidus, but some patients are cautious about DBS surgery and hardware, noted Dr. Joel Perlmutter and Mwiza Ushe, dr. Med. University of Washington at St. Louis, in the accompanying editorial. Focused ultrasound, which is approved for the treatment of incurable essential tremor, “has the advantage of creating lesions without the need for a craniotomy,” they noted.

But in this small study, patients who focused on ultrasound subthalamotomy had nearly five times more adverse events than those who had a sham procedure, Perlmutter and Ushe noted.

“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 application of focused ultrasound-produced lesions to treat Parkinson’s disease,” they wrote.

The study included 40 adults with highly asymmetric Parkinson’s disease who had motor signs that were not fully controlled by medication or who were not eligible for DBS surgery. A total of 27 patients (mean age 56.6, 59% of men) had focused ultrasound subthalamotomy on the side as opposed to their main motor signs, and 13 had a false procedure (mean age 58.1, 77% of men).

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

“Side effects such as dysarthria may limit application to focused ultrasound-produced lesions in a single hemisphere because the incidence of dysarthria is likely to be higher with procedures performed on both hemispheres,” Perlmutter and Ushe wrote. But “limiting treatment to one side of the brain with an ultrasound-produced lesion limits application, as most Parkinson’s patients have a progression of symptoms on both sides of the body,” they added.

The study had several limitations, including a small sample, the researchers noted. Almost all patients were enrolled in one of two study sites, which actually did the study at one center. In addition, both patients and evaluators correctly hit the assignments of the trial groups, erasing the desired blinding effect.