Researchers at the UNC School of Medicine led the pivotal multicenter, double-blinded, randomized clinical trial to show that unilateral focused ultrasound ablation reduced dyskinesia and motor impairment in patients with Parkinson’s disease. Vibhor Krishna, MD, co-led the study.
CHAPEL HILL, NC – In a study published in the New England Journal of Medicine co-authored by Vibhor Krishna, MD, associate professor of neurosurgery at the UNC School of Medicine, researchers show that a new focused ultrasound treatment improved dyskinesia and motor impairment in patients with Parkinson’s disease.
Parkinson’s disease is a common neurological disorder characterized by the loss of dopamine neurons in the brain. Patients with Parkinson’s disease can be effectively treated with medications such as levodopa. However, some patients develop dyskinesia – involuntary movements – and motor impairment. Dyskinesia is an involuntary movement of any region of the body that can occur with long-term use of levodopa. At the same time, motor impairment is characterized by the return of debilitating Parkinsonian symptoms as medication effectiveness declines.
“Focused ultrasound is an exciting new treatment for patients with certain neurological disorders,” said Krishna, who also is vice chair of inpatient operations in the UNC Department of Neurosurgery. “The procedure is incisionless, eliminating the risks associated with surgery. Using focused ultrasound, we can target a specific area of the brain and safely ablate the diseased tissue.”
Patients who receive focused ultrasound treatment can go home the same day after surgery. This treatment was FDA-approved for patients with essential tremor in 2016, and now this pivotal trial has led to FDA-approval of focused ultrasound ablation to treat dyskinesia and motor impairment in Parkinson’ disease.
“Almost twice as many patients achieved improved motor function or reduced dyskinesia in the focused ultrasound group than those who underwent a sham procedure,” Krishna said. “In addition, we observed that 75% of patients in the focused ultrasound group maintained their results for up to one year after the treatment.”
For this pivotal trial, the researchers randomly assigned 94 Parkinson’s disease patients with dyskinesias or motor impairment to undergo either focused ultrasound ablation or a “sham” procedure. The primary outcome was a response to therapy at three months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale, part III (off medication state), or in the score on the Unified Dyskinesia Rating Scale (on medication state). Secondary outcomes included changes from baseline to month three in the scores on various parts of the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale.
Sixty-nine patients were assigned to undergo ultrasound ablation, and 25 underwent the sham (control) procedure. In the focused ultrasound group, 65 patients completed the primary-outcome assessment, while 22 in the control group completed the study. In the focused ultrasound group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group.
The adverse effects related to ablation of the globus pallidus were infrequent and included speech difficulty, visual disturbance, and gait difficulty – in one patient each. There was one serious adverse event documented one week after the treatment in one patient.
“Our research aims to optimize focused ultrasound treatment to minimize risks and maximize improvements,” Krishna said. “We observed that clinical outcomes after focused ultrasound ablation can be site-specific. Specifically, we observed two distinct hotspots in the globus pallidus that correlated with improvements in dyskinesia and motor impairment respectively. In the future, we aim to investigate whether these findings can lead to a personalized approach to treating Parkinson’s disease with focused ultrasound.”
The study’s sponsor and device manufacturer, INSIGHTEC, Inc., provided trial oversight for regulatory processes.
Dr. Krishna, whose expertise is in functional neurosurgery and neuromodulation, leads an NIH-funded translational neuroimaging research program with a goal to improve patient outcomes. You can learn more about Dr. Krishna’s research by watching this video and at the Krishna Lab website.
UNC School of Medicine contact: Mark Derewicz