Can Progression of Parkinson Disease Be Slowed?

Deep brain stimulation (DBS) implanted in early stage Parkinson disease (PD) was found to decrease the risk of disease progression and lessen the need for multiple, simultaneous prescription drugs, according to study findings published in Neurology.

PD serves as the fastest growing neurological disorder worldwide, with as many as 60,000 US cases diagnosed each year. Innovations within the treatment of PD have led to better, noninvasive outcomes for common symptoms such as tremor and OFF periods. However, as the disease progresses, these therapies may not prove as effective and can contribute to significant economic burden for both patients and caregivers.

When it comes to managing PD, senior author David Charles, MD, professor and vice chair of neurology at Vanderbilt University Medical Center (VUMC), noted the “relentless” nature of the disease, which currently has no therapies approved to slow its progression.

Charles and fellow VUMC colleagues sought to examine the potential of DBS surgery, a procedure that implants a pair of ultra-thin electrodes deep into the brain to deliver electric pulses to a small cluster of neurons in the subthalamic nucleus (STN). Often compared with a heart pacemaker, the electric pulses from the DBS are supplied by a battery implanted under the skin.

Researchers recruited 30 patients with early-stage PD, defined as within 4 years of disease onset, for a pilot study from 2006 to 2009. In this prospective, single-blind clinical trial, all participants received optimal drug therapy (ODT), with half randomly selected to receive DBS. Of those who completed the 2-year trial, 28 patients participated in an additional observational follow-up study that included annual outpatient visits through 5 years.

After the 5-year follow-up, the study found that those with early-stage PD who received early DBS with ODT had a more than 5 times lesser odds of of experiencing worsening of their rest tremor compared with those given only ODT (odds ratio [OR] = 0.21; 95% CI, 0.09-0.45; P <.001).

“With this pilot study, we've shown that if DBS is implanted early it's likely to decrease the risk of progression, and if this is borne out in our larger study it would be a landmark achievement in the field of Parkinson disease," said Charles.

Moreover, those given early DBS with ODT also required lower levodopa equivalent daily doses (β = —240mg; 95%CI: –471 to –8; P = .04) and were less likely to require polypharmacy at 5 years compared with those given solely ODT (OR = 0.06; 95% CI, 0.09-0.45; P <.001).

"Patients who were randomized to receive early optimal drug therapy had 15-fold greater odds of needing multiple types of Parkinson disease medications," expanded lead study author Mallory Hacker, PhD, MSCI, assistant professor of neurology at VUMC.

Notably, those with ODT were also more than twice as likely to have worse motor symptoms than patients who received early DBS with ODT, but this fell short of statistical significance.

Based on these study findings, the FDA approved VUMC to lead a subsequent 130-patient, multisite, double-blinded, randomized clinical trial of DBS for early-stage PD. While promising, Charles highlighted that patients and physicians should not change clinical practice yet.

"What this pilot study is most clearly telling us is that the new FDA-approved phase 3 study must be done to definitively determine whether DBS slows the progress of Parkinson's disease when implanted in the very earliest stages," said Charles.

Reference

Hacker ML, Turchan M, Heusinkveld LE, et al. Deep brain stimulation in early-stage Parkinson disease: five year outcomes. Neurol. Published online June 29, 2020. doi:10.1212/WNL.0000000000009946