Long-term DBS Linked to Less Psychosis, Falls in Parkinson's

Pauline Anderson

June 21, 2018

LISBON, Portugal — Patients with Parkinson's disease (PD) have less risk for psychosis and falls 10 years after undergoing deep-brain stimulation (DBS) compared with controls not receiving this intervention, a new study has found.

However, DBS had no benefit in terms of survival, development of dementia, or placement in a nursing home, the researchers report.

"We found that the risk of falls and psychosis was reduced after DBS," which has not been shown before, said Philipp Mahlknecht, resident, Department of Neurology, Innsbruck Medical University, Austria.

"We think that DBS would be beneficial in terms of these outcomes, in addition to what has already been shown in terms of motor outcomes," said Mahlknecht. "We don't actually think DBS is disease-modifying, but may modify the disease course."

The study was presented at the Congress of the European Academy of Neurology (EAN) 2018.

Proven Effective

Subthalamic DBS (STN-DBS) has been used for more than 20 years in PD. Previous randomized controlled trials showed various levels of improvement following this intervention in terms of motor symptoms, off time, dyskinesia severity, levodopa equivalent dose, and quality of life. For this reason, professional groups have determined that STN-DBS is effective for severe motor fluctuations and/or dyskinesia.

There have also been longer-term studies, but for the key disability milestones of psychosis, falls, dementia, nursing home placement, and death, all such studies to date have been uncontrolled, Mahlknecht told congress delegates. "So it remains unclear whether DBS can actually reduce the frequency of these important outcomes."

The new study included 53 patients with PD who underwent STN-DBS at Mahlknecht's center from 1999 to 2007. Most were male, and the mean age was 62.8 years. The study also included 52 control patients who did not undergo DBS and were followed in a registry study that was performed in 2003-2004.

The two groups were similar in terms of age, sex, disease duration, and number of comorbidities.

The levodopa equivalent dose was significantly higher in the DBS group (1.550 mg at baseline compared with 780 mg in controls) but dropped significantly to 566 mg 2 to 4 months after the DBS surgery.

The total number of medications was slightly higher in the stimulation group (5 vs 4.5), but this difference was not statistically significant.

Over time, 25% of the DBS patients and 52% of control patients developed hallucinations or delusions (hazard ratio [HR] for stimulated vs control group, 0.43; 95% confidence interval [CI], 0.19 - 0.98; P = .044).

Close to three quarters of patients in both groups had recurrent falls, but the number was significantly lower in the treatment group (HR, 0.62; 95% CI, 0.39 - 0.99; P = .048).

About a third of patients — 38% in the treatment and 33% in the control group — developed dementia, but there was no significant between-group difference in risk (HR, 1.19; P = .64).

In the DBS group, 23% of patients needed to enter a nursing home, as did 27% in the control group, with a nonsignificant difference between the groups (HR, 0.68; P = .21).

Forty-seven percent of stimulated patients and 42% of controls died, but, again, there was no statistical difference here (HR, 1.23; P = .49).

The researchers also looked at the progression on the Hoehn and Yahr scale. In the stimulation group, the score at baseline (2.3) dropped slightly at 2 to 4 months, but then picked up to 3.3 at the last follow-up, for an incremental increase of 1 point. In controls, the score went from 2.0 to 3.5 at the last follow-up, representing an incremental increase of 1.5 points.

Some session attendees wondered about selection bias. Mahlknecht noted that the researchers made every effort to "balance out" the two groups, but he also stressed that because it was a retrospective study,  these new results "must be taken with a grain of caution."  

One delegate wondered whether there was a correlation between the levodopa reduction after surgery and clinical outcome. Mahlknecht said he has not yet analyzed all the data; however, the reduction in psychosis among treated patients was "striking," he added. "Of course, one obvious thing you think about is maybe the levodopa dose is responsible for that effect."

One of the session chairs, Patricia Canhao, MD, PhD, Faculty of Medicine, University of Lisbon, Portugal, wondered whether the researchers expected DBS patients to have a positive outcome and whether the control group used in the study "was appropriate to show that."

Mahlknecht reiterated that "we think we have two well-balanced groups."

He noted that animal studies suggest that DBS may be neuroprotective but that this has not been found in humans.

The investigators have disclosed no relevant financial relationships.

Congress of the European Academy of Neurology (EAN) 2018. Oral session TCLIN05. Presented June 18, 2018.

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