A peer-reviewed article co-authored by affiliated physician Gerard E. Francisco, MD, chief medical officer at TIRR Memorial Hermann and professor and Wulfe Family Chair in Physical Medicine and Rehabilitation at McGovern Medical School at UTHealth Houston, described a highly promising treatment addressing post-stroke upper-limb weakness. Results of the clinical trial were published in The Lancet in April 2021.1
The international, multicenter study conducted at institutions across the United States and the United Kingdom investigated the effect of vagus nerve stimulation (VNS) combined with intensive upper-limb therapy on recovery of arm mobility after ischemic stroke. The pivotal study was conducted following two earlier pilot studies that demonstrated the safety and potential efficacy of VNS. In the current study, about half of the patients treated with combined VNS and therapy showed significant improvement in arm movement, compared with only about a quarter of those who received only sham stimulation with intensive therapy.
All 108 study participants had an ischemic stroke between 9 months and 10 years prior to beginning the study protocol and were implanted with the Vivistim® Paired VNS™ System designed by MicroTransponder™, Inc., of Austin, Texas. They were then randomized to one of two groups: Half of the participants received VNS during intensive upper-limb therapy under the supervision of a therapist, while the other half had the implanted device deactivated so that they did not receive actual stimulation during the same therapy program. The supervising therapist activated the device, and delivery of the electrical pulse was timed to coincide with the upper-limb exercises. Stimulation of the vagus nerve was delivered through a minimal electrical current from a cuff wrapped around the nerve. Participants were not informed of the group to which they had been assigned. In-clinic therapy under therapist supervision was provided 3 times a week for 6 weeks, after which the participants performed a prescribed daily home exercise program for 3 months. While performing the home exercises, the participants activated the VNS themselves.
At the end of the first day after completing the 6-week in-clinic therapy, and again 90 days afterward, the participants were reevaluated using the Fugl-Meyer Assessment-Upper Limb (FMA-UL), a widely used research and clinical assessment tool. At the beginning of the study, participants’ FMA-UL scores ranged from 20 to 50 out of 66 (the higher the score, the less impairment exists). Following in-clinic therapy, those who received combined VNS and intensive upper-limb therapy improved their FMA-UL scores by about five points, while those who performed the intensive upper-limb therapy without concomitant VNS improved only by 2.4 points. Ninety days later, the VNS plus therapy group’s mean FMA-UL scores improved by 5.8 points, while the therapy-only group improved by a mere average of 2.8 points. Quality of life also improved more for those who received both VNS and therapy.
The study also did not result in any unexpected or serious adverse events associated with VNS. “Maximizing recovery and optimizing functional use of the weak limb after a stroke has been a holy grail in rehabilitation,” says Dr. Francisco, who directs the NeuroRecovery Research Center at TIRR Memorial Hermann. “We are fortunate to have participated in this landmark trial that investigated the potential of VNS to increase the ability of some people with post-stroke weakness to use the affected arm and hand once again. VNS may be helping the brain ‘rewire’ as it recovers from a stroke.”
The study was funded by MicroTransponder™.
1Dawson J, Liu CY, Francisco GE, Cramer SC, Wolf SL, Dixit A, Alexander J, Ali R, Brown BL, Feng W, DeMark L, Hochberg LR, Kautz SA, Majid A, O’Dell MW, Pierce D, Prudente CN, Redgrave J, Turner DL, Engineer ND, Kimberley TJ. Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal device trial. The Lancet. 2021 Apr 24;397(10284):1545-1553.
