Abstract T P108: A Novel Means of Augmenting Motor Recovery After Ischemic Stroke; Vagus Nerve Stimulation (VNS) Paired with Intensive Upper Limb Rehabilitation
Introduction: Chronic upper limb impairment is a major predictor of poor functional outcome after stroke. We have developed a rehabilitation intervention to address this isuue. It pairs VNS with intensive upper limb training. Our hypothesis is that short bursts of VNS, specifically timed during therapy, will drive cortical plasticity and improve clinical outcomes via timely release of neuromodulators such as acetylcholine and norepinephrine.
Methods: Our research includes preclinical and clinical studies. In pre-clinical studies VNS was paired with different types of motor training in a rat Endothelin-1 model of ischemic stroke (n=15). All studies included a sham and intensive therapy control arm (n=17). We also explored the effect of VNS timing through randomizing its timing (n=2 rats). A randomized, controlled clinical trial with blinded endpoint assessment is underway. Twenty patients, at least 6 months after ischaemic stroke with chronic arm impairment will be recruited (10 VNS device plus rehabilitation and 10 rehabilitation only). All participants receive upper limb rehabilitation 3 days a week for six weeks (90-120 minutes per session). The primary endpoint is safety and feasibility and secondary endpoints include measures of upper limb function (such as ARAT, Fugl Meyer score).
Results: Our animal results demonstrated that VNS resulted in rapid recovery of motor deficits after stroke in rats. This recovery persisted several weeks after the end of therapy. The non-VNS group showed only partial recovery despite the same intensive training. Improvement in motor performance does not appear to depend on precise timing of VNS within a therapy task.
Clinical Study: Updated interim safety and observational data will be presented. To date (August 2013) 8 subjects are enrolled (4 have received VNS paired therapy and 4 controls). There have been no serious adverse events related to therapy and all participants have adhered to the intensive therapy protocol.
Conclusions: In the ischemic preclinical models of stroke, VNS paired with physical therapy significantly improved outcomes compared to therapy alone. VNS also appears feasible and safe in adults at least 6 months after stroke and further clinical study of its effect on arm function is warranted.
Author Disclosures: J. Dawson: Research Grant; Significant; Research grant from Microtransponder inc. D. Pierce: Employment; Significant; Employed by Microtransponder Inc. M. Kilgard: Consultant/Advisory Board; Significant; Consultant to Microtransponder. M. Walters: None. B. Tarver: Employment; Significant; Employed by Microtransponder. N. Engineer: Employment; Significant; employed by microtransponder inc.
- © 2014 by American Heart Association, Inc.