Personalized Brain Stimulation Improves Parkinson’s Motor Symptoms

Adaptive deep-brain stimulation (DBS) that used personalized neural signals was feasible and improved motor symptoms in Parkinson’s disease, a cross-over pilot study of four patients showed.

Adaptive DBS reduced the duration of motor symptoms by about 50% relative to conventional DBS, reported Carina Oehrn, MD, PhD, of the University of California San Francisco, and co-authors.

Compared with conventional DBS, Parkinson’s patients with adaptive DBS reported improvement in the percentage of awake time experiencing their most bothersome symptom (β = -16.30%, P<10^-3) without worsening the percentage of time with the opposite symptom (β = -2.50%, P=0.26), the researchers wrote in Nature Medicine. The most bothersome symptoms included involuntary movements or difficulty initiating movement.

The effects on most bothersome and opposite symptoms were stable over time, Oehrn and colleagues said. Adaptive DBS also improved patient-reported quality of life.

Conventional DBS typically is delivered with constant stimulation parameters and is not responsive to a patient’s activity or symptoms, the authors noted. The adaptive approach used in this study, however, was designed to sense Parkinson’s symptoms before they occurred and calibrate the amount of stimulation needed to prevent them.

“This study marks a big step forward towards developing a DBS system that adapts to what the individual patient needs at a given time,” observed Megan Frankowski, PhD, of the NIH’s BRAIN Initiative, which helped fund the project.

“By helping to control residual symptoms while not exacerbating others, adaptive DBS has the potential to improve the quality of life for some people living with Parkinson’s disease,” Frankowski said in a press release.

The blinded, randomized cross-over trial aimed to identify neural correlates of specific motor signs in Parkinson’s disease and the feasibility of using these signals to drive adaptive DBS.

The researchers recruited male Parkinson’s patients from a population undergoing DBS implantation for motor symptoms. From a group of 17 patients clinically optimized on continuous DBS, the researchers identified four patients meeting criteria for an intensive study of adaptive DBS, based on persistence of their bothersome motor fluctuations and their willingness to participate.

Through continuous recordings that included wrist-worn monitors reporting bradykinesia and dyskinesia scores in 2-minute intervals, the researchers identified signals in the subthalamic nucleus and motor cortex that were reliable biomarkers of Parkinson’s motor symptoms in these four patients. They used these signals to personalize adaptive DBS for these patients during their daily routines.

Each patient received adaptive DBS and continuous DBS in a cross-over design so effects could be compared. Stimulation conditions were applied in multiple 2- to 7-day blocks at home, for 1 month per condition. Participant ages ranged from 47 to 68, and disease duration spanned from 10 to 15 years.

The findings are early, and the sample size is small, but the study provides a foundation for larger clinical trials to evaluate personalized adaptive neurostimulation in Parkinson’s and other neurologic disorders, the researchers said. The widespread scalability of adaptive DBS will depend on further automating the sensing and stimulation algorithm, including ways to modify it based on data from wearables or patient-reported problems.

“One of the big issues facing DBS, even in approved indications like Parkinson’s, is access, both for patients in terms of where they can get it and also the physicians who need special training to program these devices,” Frankowski noted. “If there were a way for a system to find the most optimal settings at the press of a button, that would really increase the availability of this treatment for more people.”

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