Vagus Nerve stimulation paired with Rehabilitation Improves Upper Limb Recovery after Chronic Ischemic Stroke.

Research Report
Population: Adult

Teresa J Kimberley, PhD, PT, Associate Professor, University of MN

Patricia Smith, PT, PhD, NCS, Professor, UT Southwestern Medical Center, School of Health Professions, Department of Physical Therapy

Nuray Yozbatiran, PT, PhD, Assistant Professor, UT Health Science Center at Houston, TIRR Memorial Hermann

Jesse Dawson, MD, Honarary consultant, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow

Navzer Engineer, MD, Chief Scientific Officer, MicroTransponder, Inc

Keywords: Prevention

Purpose/hypothesis: Vagus nerve stimulation (VNS) paired with rehabilitation induces movement specific plasticity in rat motor cortex. We demonstrated that VNS paired with rehabilitative training can significantly improve recovery of forelimb function compared to rehabilitative training alone in a rat model of cortical ischemic stroke. These effects may be mediated via activation of nucleus basalis and locus ceruleus neurons and subsequent acetylcholine and norepinephrine release. We hypothesize that short bursts of VNS paired with rehabilitation will facilitate motor recovery after stroke in humans. We conducted a proof-of-concept randomized, controlled pilot study assessing VNS paired with rehabilitation for the upper-limb function in a chronic stroke population.

Subjects: 20 subjects with chronic stroke (>6m) with moderate to severe upper-limb impairment completed an initial trial in the UK.

Methods: Subjects were randomized to either VNS plus rehabilitation vs. rehabilitation alone. Nine subjects were randomized to VNS plus rehabilitation and 11 to rehabilitation only. Rehabilitation consisted of 3 two-hour sessions/week for 6-weeks in both groups. During each session, participants performed ~400 tasks that were goal-oriented, repetitive, and progressive. In the VNS group, each movement trial was paired with a 0.5s burst of VNS. The primary endpoint was safety and feasibility and secondary endpoints included change in measures of upper-limb function (Upper Limb Fugl Meyer (UEFM) score, ARAT score, etc). Endpoints were assigned by independent observers.

Results: The VNS group had greater infarct volume at enrollment (85170 vs. 7206 mm3) and more cortico-spinal tract (CST) disruption (CST FA ratio 0.75 vs 0.85). There were no serious adverse events related to VNS implantation or therapy, although one patient in the VNS group suffered transient vocal cord palsy after implantation. All patients completed the therapy protocol. In the full analysis set, the increase in UEFM scores was significantly greater in the VNS treated group (9.6 vs 3.0, between group difference 6.5 points, p=0.038). 75% of VNS treated patients achieved a clinically meaningful response measured by the UEFM score. There were no other significant effects.

Conclusion: Since VNS paired with rehabilitation appears promising and feasible in adults with chronic stroke, a further study of this technique is now underway in the US and UK. In this study all subjects will be implanted with the VNS device, with ½ of subjects randomized to treatment VNS and ½ of subjects randomized to control VNS for the 10-week blinded portion of the study. Control subjects will receive treatment VNS after the randomized, blinded portion of the study. Outcomes measures will be the same include UEFM, Wolf Motor Function Test (WMFT), Box and Block, 9 hole peg test. Enrollment is projected to conclude in fall 2015, with full results from the randomized portion available in Spring 2016.

Clinical Relevance: VNS may be one form of neuromodulation that can be paired with rehabilitation to achieve greater clinical benefit than currently available treatments.

Kimberley, Teresa J, PhD, PT; Smith, Patricia , PT, PhD, NCS; Yozbatiran, Nuray , PT, PhD; Dawson, Jesse , MD; Engineer, Navzer , MD. Vagus Nerve stimulation paired with Rehabilitation Improves Upper Limb Recovery after Chronic Ischemic Stroke.. Poster Presentation. IV STEP Conference, American Physical Therapy Association, Columbus, OH, July 17, 2016. Online.