including dyskinesias and other neurologic complications, in a new randomized, sham-controlled trial.
“Longer-term and larger trials are needed to determine the role of focused ultrasound subthalamotomy in the management of Parkinson’s disease and its effect as compared with other available treatments, including deep-brain stimulation,” the authors concluded.
The trial was published online Dec.24, 2020, in the New England Journal of Medicine.
An accompanying editorial concluded that the high rate of adverse events and the lack of ability to modulate treatment over time to treat prominent tremor “raise questions about the appropriate implementation of focused ultrasound–produced lesions for the treatment of Parkinson’s disease.”
A scalpel-free alternative to brain surgery
The study authors, led by Raul Martinez-Fernandez, MD, PhD, University Hospital HM Puerta del Sur, Mostoles, Spain, explained that, in severe cases of refractory motor manifestations such as tremor and motor complications, a neurosurgical approach using deep-brain stimulation of the subthalamic nucleus can be used. But to avoid craniotomy and electrode penetration, MRI-guided focused ultrasound for the ablation of deep-brain structures, including the subthalamic nucleus, is being investigated as a treatment for Parkinson’s disease.
Patients are potential candidates for ultrasound ablation if they have prominently asymmetric parkinsonism, if they are not considered to be clinically suitable candidates for surgery because of contraindications, or if they are reluctant to undergo a brain operation or to have an implanted device.
The current trial involved 40 patients with markedly asymmetric Parkinson’s disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery. They were randomly assigned in a 2:1 ratio to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure.
Results showed that the mean Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) motor score for the more affected side – which was the primary endpoint – decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points); and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points). The between-group difference was 8.1 points (P < .001).
The change from baseline in the MDS-UPDRS III score for the more affected side in patients who underwent active treatment varied, ranging from 5% to 95%; the changes were qualitatively more evident for reduction of tremor and rigidity than for bradykinesia.
Adverse events in the active-treatment group were the following:
- Dyskinesia in the off-medication state in six patients and in the on-medication state in six, which persisted in three and one, respectively, at 4 months.
- Weakness on the treated side in five patients, which persisted in two at 4 months.
- Speech disturbance in 15 patients, which persisted in 3 at 4 months.
- Facial weakness in three patients, which persisted in one at 4 months.
- in 13 patients, which persisted in two at 4 months.