Summary: Focused ultrasound treatments help to improve motor symptoms associated with Parkinson’s disease and dyskinesia.
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.
About this Parkinson’s disease research news
Author: Mark Derewicz Source: UNC Contact: Mark Derewicz – UNC Image: The image is in the public domain
Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson’s Disease
Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson’s disease in open-label studies.
We randomly assigned, in a 3:1 ratio, patients with Parkinson’s disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months.
Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P=0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness.
Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson’s disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485. opens in new tab.)