Implementing Paired VNS with Rehab to Improve Motor Function for Chronic Stroke Patients with Moderate to Severe Upper Extremity Impairment: The Clinical Studies

This blog is part 2 of a 3-part series transcription from a recorded webinar with Dr. Gerard Francisco of TIRR Memorial Hermann and Isha Vora, MS, OT R/L of MGH Institute of Health Professions. This webinar highlights how Paired VNS™ Therapy can help improve motor function for chronic stroke patients who have moderate to severe upper extremity impairments.

To read part 1 of this webinar transcription about chronic stroke and VNS therapy, click here.

Summary of the Preclinical and Clinical Studies:

The stimulation parameters were established and reported over a decade ago. The stroke animal models, which gave a lot of support to translating this into humans, invariably showed improvement. The mechanism of action is believed to be the vagus nerve stimulation (VNS) triggered neuromodulatory input to the motor cortex, the one that drives plasticity. It is important to time lock the motor task with the VNS trigger.

VNS has an interesting history–in addition to its use in depression and epilepsy, it has also been thought of as potential therapy for tinnitus. As well, there were other models in treating people with post-traumatic stress disorder, autism, and people with spinal cord and traumatic brain injuries.

The first feasibility trial in stroke was published by Jesse Dawson in 2016–there were 20 subjects, and this study showed the efficacy and the feasibility of VNS for chronic stroke. This was followed by a pilot study with 17 subjects that was done here in the United States and the UK. Dr. Teresa Kimberley participated and collaborated with the group from the UK for this pilot trial. This trial supported and justified the pivotal trial that was initiated in 2017 and published in The Lancet in 2021. This pivotal trial showed significant improvement and supported the safety of this device, leading to the FDA approval of VNS as a class III device in August 2021.

In both animal studies and human studies, it has consistently shown that there is at least  two to three times improvement in impairment and function when VNS is paired with therapy as opposed to intensive rehab alone.¹ The various rat models that were studied previously, studied with experimentally induced ischemic stroke, chronic stroke, and hemorrhagic stroke. In ischemic stroke with the older rats, all showed a significant improvement. When translated to humans, the stroke feasibility pilot and pivotal studies all show consistent improvement, often in the same range of magnitude when the primary outcome measures of the Fugl-Meyer Assessment for the upper limb and the Wolf Motor Function Test were used.

This is the most important finding in our pivotal study that was published in The Lancet. This was a randomized placebo-controlled triple-blinded study and there were 108 implanted patients. All patients were implanted with Vivistim and randomized to either receive intensive rehabilitation right away, or placed in the control group which had the device, but the VNS was not turned on. There was a sham stimulation that was paired with the same type of task-specific intensive therapy. The groups then received six weeks of in-clinic therapy under the supervision of a skilled therapist which was followed by home therapy.

After six weeks, the control subjects were crossed over to now receive the same treatment protocol that the active group received during the first phase of the study, and this is what we found:

• There was both statistically and clinically significant improvement in impairments and function as measured by the Fugl-Meyer upper extremity scale and the Wolf Motor Function Test.
• The crossover group that initially only received the sham stimulation, when they were crossed over to receive the real stimulation along with the therapy, showed a similar improvement. This shows that even when done in a delayed manner, if the right therapy and the pairing of the VNS with the therapy is performed, significant changes can be seen.
• The secondary measure of the Wolf Motor Function Test also showed significant improvement and it mirrored the Fugl-Meyer improvement as well.
• About twice as many VNS group subjects reached clinically significant improvement in function over the control group, which for the study we defined as a change in the Fugl-Meyer score of at least six. ²

This is the long-term pilot data from our initial study. We had 17 participants and were fortunate that none of them dropped out of the study due to complications, tolerance, or lack of efficacy, so we were able to follow most of these subjects. An N of 17 seems like it is a small number, however in newer rehabilitation literature, it is rare to find a study that will report findings beyond 12 months.

What we found in this long-term follow-up study was that there were significant effects of paired VNS therapy at 1 year that were maintained at years 2 and 3 with further improvements in both impairment and function observed. The participants completed at home therapy at an average of 2.2 hours per week, and in some cases several times a day over 3 years. This graph above is a pictorial representation of the Fugl- Meyer assessment upper limb scale at baseline at years 1, 2, and 3. It shows promise not only as a short-term therapy for chronic stroke survivors but as well as for those who continue using the VNS with therapy 2-3 years after the initial implantation.³

To learn more about Vivistim’s unique Paired VNS Therapy and how it can help improve motor development after a stroke, contact us and we will connect you with a Vivistim representative. We also encourage you to explore the other pages of vivistim.com to find additional information and resources.

Additional Resources:

Watch the Full Webinar

Vivistim Safety Information

The Lancet Publication

Contact Us

^{1. Dawson J et al, The Lancet, 2021}

^{2. Dawson et al. Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial. Lancet. 2021; 397 1545–1553.}

^{3. Francisco G, Engineer N, Dawson J, et al. Vagus Nerve Stimulation Paired with Upper-Limb Rehabilitation After Stroke: Two- and Three-Year Follow-up from the Pilot Study. Archives of Physical Medicine and Rehabilitation. 2023 In Press.}

^{The MicroTransponder® Vivistim® Paired VNS™ System is intended to be used to stimulate the vagus nerve during rehabilitation therapy in order to reduce upper extremity motor deficits and improve motor function in chronic ischemic stroke patients with moderate to severe arm impairment.  Do not use if you have had a bilateral or left cervical vagotomy.  Risks may include, but are not limited to pain after surgery, hoarseness, bruising, swelling, coughing and throat irritation. Infection leading to explant is a risk associated with any device surgery.  For full safety information, please see www.vivistim.com/safety.  Individual results may vary.}  

^{©2024 MicroTransponder Inc. All rights reserved.  Vivistim, Vivistim Therapy and Paired VNS are trademarks of MicroTransponder Inc.} 

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