Implantable neurostimulator for Parkinson’s disease shows sustained benefits

In the treatment of Parkinson’s disease (PD), the improvements observed following deep brain stimulation of the subthalamic nucleus using an implantable pulse generator system persisted over a 5-year period, according to long-term data from the INTREPID trial.

Deep brain stimulation was associated with a 51-percent improvement in motor function off medication at 1 year, with the mean Unified Parkinson’s Disease Rating Scale (UPDRS-III) motor score decreasing from a baseline of 42.8 to 21.1 points (p<0.001). At the 5-year follow-up, the mean UPDRS-III motor score slightly increased to 27.6 points, representing a 36-percent improvement from baseline (p<0.001). [JAMA Neurol 2025;doi:10.1001/jamaneurol.2025.3373]

A similar pattern of improvement was observed in activities of daily living (ADL) off medication, with the mean UPDRS-III ADL score dropping from 20.6 points at baseline to 12.4 points at year 1 and 16.4 points at year 5. These changes corresponded to a 41-percent and 22-percent improvement from baseline, respectively (p<0.001 for both).

Mean dyskinesia scores decreased by 75 percent at year 1 (from 4 to 1 point; p<0.001) and by 70 percent at year 5 (from 4 to 1.2 points; p<0.001). Finally, anti-parkinsonian medication use was reduced throughout the 5-year follow-up, with the average levodopa dose decreasing by 28 percent at year 1 and remaining stable by year 5 (28 percent; p<0.001).

“These findings support the long-term benefit of subthalamic nucleus deep brain stimulation to improve motor function, reduce motor fluctuations, lower anti-parkinsonian medication use, and treat dyskinesia in PD patients,” the investigators said.

“Analysis of UDPRS-III subcategories showed sustained improvement in tremor, rigidity, and bradykinesia. While tremor, rigidity, and dyskinesia remained well controlled, bradykinesia, gait, and other aspects of motor performance such as postural instability gradually worsened. This is not surprising as PD is a progressive neurodegenerative disorder and motor performance deteriorates with disease progression,” they explained.

Satisfaction with treatment was high, with 94 percent expressing satisfaction and 6 percent expressing dissatisfaction across the 5-year follow-up. This high level of patient satisfaction was reflected in the Clinical Global Impression of Change (CGIC) scale scores, where a high mean percentage of patients (87 percent), physicians (93 percent), and caregivers (82 percent) perceived significant and sustained improvements in a patient’s condition. Between 80 percent and 88 percent of these evaluators maintained a perception of patient improvement at the 5-year follow-up.

Quality of life, as measured by the Parkinson’s Disease Questionnaire-39 (PDQ-39) Summary Index, improved by 32 percent at year 1 (p<0.001) and then declined gradually over the subsequent years. By year 5, the improvement in quality of life was much smaller, settling at just 5 percent relative to baseline.

As for safety, a total of 1,136 adverse events (AEs) occurred in 182 patients, including 91 serious AEs reported in 98 patients, of which with 66 were related to the study intervention. The most common serious AE was infection, reported in nine patients. Ten patients died, but none of these deaths were related to the study intervention.

The investigators pointed out that while the degree of improvement in UPDRS-III scores may diminish over time, subthalamic nucleus deep brain stimulation continues to provide significant long-term motor benefits for PD patients.

“Deep brain stimulation not only enhances quality of life in the short term but also maintains its efficacy in managing motor symptoms and reduces the need for anti-parkinsonian medication and dyskinesia while improving ADLs over many years,” they said.

INTREPID was a 12-week double-blind sham-controlled study that involved 191 patients (mean age 60 years, 73 percent male) with a diagnosis of bilateral idiopathic PD, had more than 5 years of motor symptoms and at least 6 hours per day of poor motor function, had modified Hoehn and Yahr Scale scores >2, and had UPDRS-III score of at least 30 (medication-off state).

The patients received an implantable pulse generator system and were randomly assigned to undergo bilateral subthalamic nucleus deep brain stimulation or subtherapeutic stimulation for 12 weeks. After 12 weeks, all patients underwent active deep brain stimulation for up to 5 years. A total of 137 patients (72 percent) completed the 5-year follow-up.