Focused Ultrasound Improves Motor Control In Parkinson's But With More Side Effects

Doctors in Spain and the United States say they have successfully treated cases of Parkinson's disease by destroying portions of the brain with focused ultrasound.

The technique was done on 27 volunteers with asymmetric signs, which allowed them to perform the subthalamotomy on just one side of the brain.

The result was an improvement from 19.9 to 9.9 on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, which ranges from 0 to 44, on the affected side after four months. There was little change in 13 patients randomly assigned to receive a fake procedure, with an 8.1-point between-group difference (P<0.001).

The hope is that "some Parkinson's disease patients may not need surgery to get their motor problems improved and we envisage applying this approach earlier in disease evolution," senior author Dr. Jose Obeso of University Hospital HM Puerta del Sur, in Mostoles, Spain, told Reuters Health by email.

But concern remains because of side effects.

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"A focused ultrasound-produced lesion in one hemisphere reduced the motor features of parkinsonism on the opposite side of the body by 50%, as compared with essentially no improvement in a group of patients who underwent a sham procedure. However, in this small trial, the group of patients who underwent focused ultrasound had almost 5 times as many adverse events as those who underwent the sham procedure," write Drs. Joel Perlmutter and Mwiza Ushe of Washington University School of Medicine in St. Louis, Missouri, in an editorial in the New England Journal of Medicine, where the study appears.

Six patients receiving ultrasound developed dyskinesia in the off-medication state two months later. The problem had faded in three of them by the four-month mark and was gone in all six after one year. Dyskinesia in the on-medication state developed in six and persisted for at least a year in two.

Weakness on the affected side was seen in five patients 24 hours after treatment. It disappeared in three patients but the other two still had it at the one-year mark in the form of hand clumsiness and asymmetric stride.

Speech disturbance and gait disturbance were other side effects that were common - seen at some point in 56% and 48%, respectively, of patients in the active-treatment group. They persisted at the 12-month mark in only one patient each.

None of those problems appeared in the 13 patients who underwent the sham procedure.

Dizziness, head discomfort and head tilting were at least three times more common in the ultrasound group than in the sham group.

"These adverse events in a group of relatively young patients 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," write Drs. Perlmutter and Ushe.

Although Dr. Obeso acknowledged that "further refinement of the technique is needed for wider applicability," he expressed strong support for its promise.

He said when he was involved in early research on deep-brain stimulation for Parkinson's "the initial results were far less favorable in terms of benefit versus risk and the major demands and labor needed for the surgery and follow-up. Today it is standard procedure in hundreds of places around the world."

Dr. Obeso said such side effects were expected "and we are not specially dissatisfied with that. Most were not severe and, by and large, transient. If one is too cautious with a lesioning technique, adverse effects are reduced but the benefit is not good at all, and the treatment has no benefit. Moreover, as the technique and technology improve, the benefit/risk ratio will surely get better."

Insightec, which makes the ultrasound device, financed and helped organize the study.

Focused ultrasound subthalamotomy offers a potential alternative to deep-brain stimulation of the subthalamic nucleus, avoiding craniotomy and electrode insertion. The technique is approved in the U.S. for essential and parkinsonian tremors.

All of the volunteers in the new study had highly asymmetric motor signs that were not well controlled with dopaminergic medication. All continued to receive medical therapy.

Twelve of the 13 patients who were assigned to sham treatment ultimately decided to receive the actual therapy after four months when unblinding revealed they had been in the control group.

There has been no head-to-head comparison with deep-brain stimulation, which is usually done on both sides of the brain. "What we know is that the impact of subthalamotomy against the main motor features of Parkinson's disease is quite similar, and certainly not inferior to deep-brain stimulation for the body side treated," said Dr. Obeso.

All but one of the patients who received ultrasound correctly discerned that they were in the active-treatment group; 11 of the 13 in the control group correctly guess that they had received the sham therapy.

"Investigators who were intended to be unaware of the trial-group assignments identified the actual assignment in all the patients," the researchers said.

Dr. Obeso said the reason is that the "treatment is highly efficacious! This happens with every treatment which provides high improvement. Deep-brain stimulation is the same."

—Gene Emery

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