NASHVILLE, TENN. – Patients with upper limbs affected by ischemic stroke who paired traditional rehabilitation exercises with pulsed vagus nerve stimulation boosted functional scores significantly higher than did those who performed exercises alone in a small, randomized pilot trial.
Taken together with the low rate of adverse events associated with device implantation, the study suggests that coupling the interventions is feasible and likely to be beneficial, Dr. Jesse Dawson of the University of Glasgow, Scotland, said at the International Stroke Conference, sponsored by the American Heart Association.
The vagus nerve stimulator (VNS) is typically used to suppress epileptiform discharges and circumvent seizures. The usual stimulation pattern is continuous cycles of 30 seconds on and 5 minutes off. In his randomized, controlled trial, Dr. Dawson set the device to deliver 0.5-second pulses that coincided with each repetition of a rehabilitative movement. When simulated, the nerve releases two proneuroplastic neurotransmitters, acetylcholine and norepinephrine, which then disperse over the cerebral cortex.
“Our theory was that if we timed these releases at specific periods during rehabilitation therapy, we might be able to drive neuroplasticity toward those specific tasks,” Dr. Dawson said at the conference. The technique has proved effective in both aged rats and rat stroke models, he added.
The trial comprised 20 patients who had experienced an ischemic stroke about 2 years prior. Each was left with residual dysfunction in an upper extremity; seven had a paretic limb. The mean Action Research Arm Test (ARAT) score was 33, and the mean upper extremity Fugl-Meyer score was 43, indicating moderate impairment.
Ten patients underwent VNS implantation. Nine completed the trial. One withdrew after 2 weeks because of a transient vocal cord palsy. This later resolved spontaneously.
Other adverse events related to the VNS were also transient. They included taste disturbance, chest pain, mild dysphagia, and nausea after a therapy session.
The 6-week intervention consisted of 18 sessions, each lasting 2 hours. In each, the rehabilitative movement was repeated 300-400 times.
In a per-protocol analysis, there was no significant difference in the upper extremity Fugl-Meyer score at the study’s end. However, when the patient who had withdrawn was excluded from the analysis, the results did become statistically significant. Patients in the dual-therapy group gained almost 10 points, compared with a 3-point gain in the exercise-only group. The ARAT scores were not different at study’s end.
In light of the positive initial results, a sham-controlled, randomized trial is in the works. The trial will randomize 20-25 patients to either the VNS-paired exercise or exercise-only interventions. All participants will receive the VNS device, but only the paired intervention group will receive actual stimuli.
Patricia Smith, Ph.D., the Doris E. Porter Professor in Physical Therapy at the University of Texas Southwestern, Dallas, is the lead investigator.
MicroTransponder, which makes the VNS unit, is sponsoring both the studies. Neither Dr. Dawson nor Dr. Smith have any financial ties to the company.
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