by Summary: Focused ultrasound treatments help improve motor symptoms associated with Parkinson’s disease and dyskinesia.
Source: UNC
In a study published in the New England Journal of Medicine Co-author 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 part 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 the effectiveness of the drugs decreases.
“Focused ultrasound is an exciting new treatment for patients with certain neurological disorders,” said Krishna, who is also vice chair for inpatient surgeries at UNC’s Department of Neurosurgery.
“The procedure is seamless, eliminating the risks associated with surgery. With 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 approved by the FDA in 2016 for patients with essential tremor, and now this pivotal study has led to FDA approval of focused ultrasound ablation for the treatment of dyskinesia and motor impairment in Parkinson’s disease.
“Almost twice as many patients in the focused ultrasound group achieved improved motor function or reduced dyskinesia 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 up to one year after treatment.”
For this pivotal study, researchers randomly assigned 94 Parkinson’s disease patients with dyskinesia or motor impairment to 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 in either the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale, Part III (medication-free status) score or the Score on the Unified Dyskinesia Rating Scale (by medication status).
Secondary outcomes included changes from baseline through month three in scores on different parts of the Movement Disorders Society – Unified Parkinson’s Disease Rating Scale.
Sixty-nine patients were assigned to 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%) responded compared to 7 (32%) in the control group.
Adverse events associated with globus pallidus ablation were rare and included speech difficulties, visual disturbances, and gait difficulties—in one patient each. A serious adverse event was documented in one patient one week after treatment.
“Our research aims to optimize focused ultrasound treatment to minimize risks and maximize improvements,” Krishna said.
“We have observed that clinical outcomes after focused ultrasound ablation can be site specific. Specifically, we observed two distinct globus pallidus hotspots that correlated with improvements in dyskinesia and motor impairment, respectively. Going forward, we want to investigate whether these findings can lead to a personalized approach to treating Parkinson’s disease using focused ultrasound.”
The study’s sponsor and device manufacturer, INSIGHTEC, Inc., has provided study oversight for regulatory procedures.
About this news from Parkinson’s research
Author: Markus Derewicz
Source: UNC
Contact: Mark Derewicz – UNZ
Picture: The image is in the public domain
Original research: Closed access.
“Attempting Globus Pallidus Focused Ultrasound Ablation in Parkinson’s Disease” by Vibhor Krishna et al. NEJM
Abstract
Study of focused ultrasound ablation of globus pallidus in Parkinson’s disease
BACKGROUND
Unilateral focused ultrasound ablation of the inner segment of the globus pallidus has reduced motor symptoms in Parkinson’s disease in open studies.
METHODS
We randomized patients with Parkinson’s disease and dyskinesia or motor fluctuations and motor impairment in the off-medication state in a 3:1 ratio to either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary endpoint was a response at 3 months, defined as a decrease of at least 3 points from baseline in either the Movement Disorders Society – Unified Parkinson’s Disease Rating Scale, Part III (MDS-UPDRS III) score for the treated side in the unmedicated state or the Unified Dyskinesia Rating Scale (UDysRS) score in the medicated state. Secondary outcomes included changes from baseline to month 3 in the outcomes of various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted up to 12 months.
RESULTS
Of 94 patients, 69 were assigned to ultrasound ablation (active treatment) and 25 to sham (control); 65 patients and 22 patients completed the primary outcome assessment. In the actively treated group, 45 patients (69%) responded compared to 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 demonstrated response, 19 met only the MDS-UPDRS III criterion, 8 met only the UDysRS criterion, and 18 met both criteria. The results for the secondary endpoints were generally in the same direction as those for the primary endpoint. Of the 39 patients in the active treatment group who had responded at 3 months and who were evaluated at 12 months, 30 remained responsive to treatment. Pallidotomy-related adverse events in the active treatment group included dysarthria, gait disturbances, taste loss, visual disturbances, and facial weakness.
CONCLUSIONS
Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients with improved motor function or reduced dyskinesia over 3 months than a sham procedure, but was associated with adverse events. Longer and larger studies are needed to determine the effect and safety of this technique in people with Parkinson’s disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485. opens in new tab.)
