Brain stimulation tops medications for Parkinson's; Serious adverse events occurred in 40%.

CHICAGO -- Preliminary data from two trials suggest that deep brain stimulation may be superior to the best medical therapy in Parkinson's disease, and that stimulating specific targets may lead to different cognitive and mood outcomes.

Complete data on 230 of 255 patients with idiopathic Parkinson's disease showed that motor functioning at 6 months, based on blinded ratings, improved 35.6% over baseline with deep brain stimulation (DBS), but only 4.5% with the best medical therapy (BMT), Frances M. Weaver, Ph.D., co-principal investigator, reported in a poster at the 12th International Congress of Parkinson's Disease and Movement Disorders.

Time without troublesome dyskinesia increased by 5.1 hours with DBS, compared with no change with BMT. The 111 DBS patients experienced significant improvement in all aspects of the Parkinson's Disease Questionnaire-39, except for social support, compared with the 119 BMT patients who had little change.

These gains must be weighed against the greater risk of serious adverse events after DBS, Dr. Weaver reported on behalf of the Veterans Affairs/National Institute of Neurological Disorders and Stroke (VA/NINDS-01) Study Group. At least one serious adverse event was experienced by 40% of DBS patients and 11% of BMT patients.

The Deep Brain Stimulation vs. Best Medical Therapy trial included patients aged 22 years or older (mean age 63 years) with Hoehn and Yahr stage 2 or greater idiopathic Parkinson's disease responsive to L-dopa, but with persistent motor complications. BMT patients received optimized medical therapy, and DBS patients were further randomized to bilateral stimulation of the subthalamic nucleus (STN) or globus pallidus interna (GPi).

The BMT arm was discontinued early as there was sufficient power to compare the primary outcome with the first 255 patients. Most BMT patients proceeded to surgical treatment, Dr. Weaver, of Hines (Ill.) Veterans Affairs Hospital, said in an interview. Results of the DBS target (STN vs. GPi) portion of the trial are expected in 2009.

Results from the prospective, randomized COMPARE (Comparison of Best Medical Therapy and Deep Brain Stimulation of Subthalamic Nucleus and Globus Pallidus for the Treatment of Parkinson's Disease) trial will not end the controversy over which surgical target is best, but will provide the first level 1 evidence that may allow physicians to tailor DBS to the patient's symptoms, said Dr. Michael S. Okun, co-principal investigator.

"We should stop thinking of these comparisons as yes-or-no phenomena, but start to think of where one target might be better than another and match our patients up so they can achieve optimal benefit," he said.

Six-month data on 45 of 52 patients (mean age 61 years) showed no significant difference between 22 STN and 23 GPi patients in seven of the eight subscales of the visual analog mood scale (VAMS), the primary outcome of the study. There was a significant difference between groups on the VAMS anger subscale; the mean change in anger scores was significantly larger with STN than with GPi (5.4 vs. -0.2). Both groups reported significant improvements in VAMS scores on the tension and tiredness subscales, but the difference between groups was not significant.

Significant worsening of verbal fluency was seen in the STN group, but not in the GPi group (-5.6 vs. 0.4). This was true whether the stimulator was on or off. The pattern of deterioration in the STN group may represent a surgical or lesional effect rather than a stimulation-induced effect, said Dr. Okun, codirector of the Movement Disorders Center, University of Florida, Gainesville, and national medical director for the National Parkinson's Foundation.

Both groups reported being significantly less happy, less energetic, and more confused when stimulation was delivered ventrally or one contact below the optimal stimulation site.

No significant difference was found in motor improvement between the STN and GPi groups (mean 29.9% vs. 26.6%), while medication reduction trended in favor of STN; however, the study was not powered for these outcomes.

There were 95 surgical adverse events with STN vs. 67 with GPi. There was one death because of pneumonia in the STN group, said Dr. Okun, who has received speaking and consulting fees from the National Parkinson's Foundation and Medtronic Inc.

Full results of the COMPARE trial, which was funded by the National Institute of Neurological Disorders and Stroke and the University of Florida, are expected in the fall of 2008.

Additional level 1 evidence on DBS is expected later this year from the double-blind, prospective Deep Brain Stimulation for Parkinson's Disease trial comparing unilateral STN with GPi in 121 patients. Preliminary analysis of motor scores at 6 months revealed no significant difference between STN and GPi, the principal investigator, Dr. Jerrold Vitek of the Cleveland Clinic Foundation, said in an interview. Formal analyses will address neuropsychological and psychiatric functioning, quality of life, and other secondary variables.

Patients were randomized based on motor symptom symmetry to determine if this factor can be used to decide whether patients require bilateral surgery or whether some may do well with unilateral stimulation, he said.

BY PATRICE WENDLING

Chicago Bureau