HOUSTON—Compared with intensive physical therapy alone, vagus nerve stimulation (VNS) plus intensive physical therapy may improve upper-limb motor function in the long term among people with ischemic stroke, according to data described at the International Stroke Conference 2017. The current results are consistent with those of a previous study, and a larger pivotal study of the treatment is scheduled to begin this summer.
Jesse Dawson, MD
Research in animal models of stroke indicates that VNS in addition to physical therapy promotes task-specific neuroplasticity and increases recovery. In a study of 20 patients, Dr. Dawson and colleagues found that the combination of neurostimulation and physical therapy was safe and feasible. They also observed functional improvement in patients who received VNS plus physical therapy, compared with controls.
A Blinded Trial of VNS
To further assess the combination of VNS and physical therapy, Dr. Dawson and colleagues performed a blinded, randomized clinical trial. They enrolled participants with chronic moderate-to-severe upper-limb hemiparesis after ischemic stroke. Stroke had occurred between four months and five years before study enrollment. All participants received implantation with a VNS device and were randomized to VNS (0.8 mA) plus rehabilitation or control VNS (0.0 mA) plus rehabilitation.
All participants underwent six weeks of intensive and task-specific rehabilitation that included three two-hour sessions per week. A half second of stimulation was given with each movement in the active group. After six weeks of in-clinic therapy, participants did not receive a specific therapy for 30 days. Participants began exercising at home at day 30 of the follow-up period. This exercise included 30 min/day of self-administered VNS or sham stimulation.
Blinded assessors evaluated participants’ outcomes on days 1, 30, and 90 after completion of the six-week in-clinic rehabilitation period. Therapists and participants also remained blinded to therapy assignment throughout the study. The primary efficacy outcome was change in Upper Extremity Fugl-Meyer score. An increase of at least 6 points from baseline was considered clinically meaningful.
At the end of the main phase of the study, the controls received active VNS during six weeks of in-clinic therapy.
Significant Difference at 90 Days
In all, 17 patients were implanted and randomized. Eight patients received VNS, and nine patients received sham stimulation. At baseline, participants’ mean age was 60, and mean time since stroke onset was 1.5 years. The average Upper Extremity Fugl-Meyer score was 29.5 in the VNS group and 36.4 in the control group. Right-sided stroke predominated in the active group.
The investigators recorded three adverse events related to surgery; all occurred in the control group. One patient had an infection that was resolved, a second patient had dysphagia and shortness of breath that were resolved, and a third patient had vocal cord paralysis that later improved. Stimulation was not associated with any adverse events.
At day 1 after therapy, mean change in Upper Extremity Fugl-Meyer score was 2.3 points higher in the active group (ie, improvement of 7.6 points vs 5.3 points), but the difference was not statistically significant. The responder rate was 75% in the VNS group, compared with 33% in controls, but this difference also was not statistically significant. At day 90 after therapy, mean change in Upper Extremity Fugl-Meyer score was 9.5 in the active group and 3.8 in controls, and the difference was statistically significant. The responder rate at day 90 was 88% in the active group and 33% among controls, and this difference also was statistically significant. Controls who crossed over to receive six weeks of VNS therapy after the main phase of the study had improvements comparable to those of patients initially assigned to the active group.
Quality-of-Life Data Would Be Informative
“We have shown that we can deliver a partly home-based brain stimulation technique that appears to have promise,” said Dr. Dawson. The upcoming phase III pivotal trial of the technique will include 120 patients.
The study results are “spectacular,” said Philip B. Gorelick, MD, MPH, Medical Director of the Hauenstein Neuroscience Center at Saint Mary’s Health Care in Grand Rapids, Michigan. The fact that therapy does not need to begin immediately after stroke is especially promising, he added. Dr. Gorelick did not participate in the research.
Neurologists need to understand the way the brain reorganizes itself during therapy, and fMRI data for the patients would be informative, Dr. Gorelick continued. Furthermore, data about the technique’s effect on quality of life could provide a more complete picture of the benefits that it provides. “Obviously, the study is exploratory, but this creates a lot of hope.”
The trial was funded by MicroTransponder, the company that manufactures the VNS device.
—Erik Greb
Suggested Reading
Dawson J, Pierce D, Dixit A, et al. Safety, feasibility, and efficacy of vagus nerve stimulation paired with upper-limb rehabilitation after ischemic stroke. Stroke. 2016;47(1):143-150.
Langhorne P, Coupar F, Pollock A. Motor recovery after stroke: a systematic review. Lancet Neurol. 2009; 8(8):741-754.