Dyskinesia and motor impairment are two common symptoms of Parkinson’s disease, a neurodegenerative disorder that affects movement and can lead to significant disability.
Dyskinesia refers to the presence of abnormal, involuntary movements that are typically seen in patients with advanced Parkinson’s disease who have been treated with levodopa, a medication used to manage symptoms. Dyskinesia can be disabling and can significantly impact a patient’s quality of life.
Motor impairment refers to the difficulty that Parkinson’s disease patients experience in controlling their movements. This can manifest as tremors, rigidity, bradykinesia (slowness of movement), and postural instability. Motor impairment is a hallmark feature of Parkinson’s disease and is caused by the loss of dopamine-producing neurons in the brain.
Treatment options for dyskinesia and motor impairment in Parkinson’s disease include medications such as levodopa, as well as deep brain stimulation and focused ultrasound treatment, which have shown promise in reducing these symptoms. Rehabilitation therapies, such as physical and occupational therapy, can also be helpful in managing motor impairment and improving quality of life for patients with 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.
Original Research: Closed access.
“Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson’s Disease” by Vibhor Krishna et al. NEJM
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.)
Stereotactic surgery, and in particular deep brain stimulation, has been shown to reduce motor symptoms of Parkinson’s disease; however, it has been associated with a modest risk of intracranial bleeding and infection.
Focused ultrasound ablation (FUSA) is an incisionless procedure already investigated in several movement disorders and recently approved by the Food and Drug Administration for the treatment of refractory essential tremor and tremor-predominant Parkinson’s disease (PD).
Open-label studies investigated FUSA of globus pallidus in PD patients with motor fluctuations, reporting an improvement of motor function in these patients.
Our paper of the month presents the results of a prospective, double-blind, randomised, sham-controlled trial involving 16 centres and investigating the safety and efficacy of unilateral FUSA of the globus pallidus internus in patients with medication-refractory idiopathic PD.
After screening for eligibility, 69 patients underwent FUSA of the globus pallidus internus while 29 patients received the sham procedure. At three months, an improvement of at least three points in either of two clinical rating scales (MDS-UPDRS IIIa in the off-medication state; UDysRSb in the on-medication state) on the treated side was reported in the 69% and in the 32% of the patients who received FUSA or sham-procedure, respectively (p value = 0.003).
Moreover, the patients in the interventional group showed a significantly greater improvement on the MDS-UPDRS IV as well as on the MDS-UPDRS III than patients who underwent the sham procedure. After the three months blinded phase, the trial continued in an open-label phase in which the response to treatment with FUSA at 12 months was observed in 70% of the patients.
Regarding safety outcomes, the most common pallidotomy-related adverse events were mild or moderate in severity and included dysarthria, gait disorders, loss of taste, visual disturbance, and facial weakness. Procedure-related adverse events were mostly mild-moderate and resolved by 12 months, with the exception of one severe adverse event (nonfatal pulmonal embolism) that occurred within one week after treatment.
In conclusion, this randomised clinical trial showed that focused ultrasound ablation of globus pallidus internus was associated with improvement of motor function and reduction of dyskinesia in PD patients; however, it was associated with adverse events. Larger and longer trials are still needed in order to further investigate the efficacy and safety of this procedure in PD.