Clinical Data

Vivistim Therapy is Proven Effective Across Multiple Studies

Vivistim Therapy is Proven Effective Across Multiple Studies

VNS-REHAB Pivotal Study, triple-blind RCT

The Lancet | 2021
  • Significant improvements in impairment and function compared with intense rehabilitation alone.2
  • Crossover group matched VNS group outcomes once VNS was enabled.
Neurorehabilitation and Neural Repair | 2023
  • The effects of Paired VNS were consistent across subgroups, including age, severity, and time post stroke.5
Stroke | 2025
  • Individuals treated with Paired VNS maintained long-term improvements in impairment, activity, participation, and quality of life at one-year.
  • Paired VNS is an FDA-approved, valuable treatment option providing long-term benefits for individuals with chronic upper extremity limitations after stroke.

Paired Vagus Nerve Stimulation for Stroke Bibliography

The following bibliography is a list of peer-reviewed publications related to the clinical use of Paired VNS for the treatment of chronic stroke and its mechanisms of action. This bibliography is not intended to be a comprehensive list of every publication on the subject. This list does not include applications for Paired VNS that have been studied outside of stroke except where mechanism of action may overlap. The bibliography was compiled through PubMed and provides links to the journal articles referenced. Book chapters, abstracts, and posters are not included.

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.

Clinical Studies

  1. Roy JM, Musmar B, Ritz C, et al. (July 2025) Vagus Nerve Stimulation Paired with Rehabilitation for Post-Stroke Recovery: A Single Center Experience of Patient Satisfaction and Outcomes. Clin Neurol Neurosurg, 3(257):109043. doi:10.1016/j.clineuro.2025.109043
  2. Khan I, Shakir M, Vijayanarasimhan V, et al. (June 2025) Implantable Vagus Nerve Stimulator-Paired Neurorehabilitation for Upper Limb Function After Ischemic Stroke: Evidence from a Systematic Review and Meta-Analysis with Best Practice Recommendations. Neurosurgery, online ahead of print. doi:10.1227/neu.0000000000003545
  3. Kimberly TJ, Cramer SC, Wolf SL, et al. (May 2025) Long-Term Outcomes of Vagus Nerve Stimulation Paired with Upper Extremity Rehabilitation After Stroke. Stroke, online ahead of print. org/10.1161/STROKEAHA.124.050479
  4. Vora I, Gochyyev P, Engineer N, Wolf SL, Kimberley TJ. (May 2024) Distal Versus Proximal Arm Improvement After Paired Vagus Nerve Stimulation Therapy After Chronic Stroke. Arch Phys Med Rehabil, 28:S0003-9993(24)01014-1. doi: 10.1016/j.apmr.2024.05.018.
  5. Cummins DD, Kalagara R, Downes MH, et al. (March 2024) Vagus nerve stimulation for enhanced stroke recovery after intracerebral hemorrhage: illustrative case. J Neurosurg Case Lessons. 11;7(11): CASE23676 doi: 10.3171/CASE23676
  6. Malakouti N, Serruya MD, Cramer SC, et al. (Feb 2024) Making Sense of Vagus Nerve Stimulation for Stroke. Stroke, 55(2), 519-522. doi: 10.1161/STROKEAHA.123.044576
  7. Kimberley TK, Prudente CN, Engineer ND, et al. (September 2023) Vagus Nerve Stimulation Paired with Mobility Training in Chronic Ischemic Stroke: A Case Report. Phys Ther, in press.
    doi: 10.1093/ptj/pzad097
  8. Dawson J, Engineer ND, Cramer SC, et al. (June 2023) Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial. Neurorehabilitation and Neural Repair, 37(6) 367-373. doi: 10.1177/15459683221129274
  9. Francisco GE, Engineer N, Dawson J, et al. (March 2023) Vagus Nerve Stimulation Paired with Upper-Limb Rehabilitation After Stroke: Two- and Three-Year Follow-up from the Pilot Study.  Arch Phys Med Rehabil, 104(8), 1180-1187. doi.org/10.1016/j.apmr.2023.02.012
  10. Liu CY, Russin J, Adelson DP, et al. (September 2022). Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial. Journal of Clinical Neuroscience 105, 122–128. https://doi.org/10.1016/j.jocn.2022.09.013
  11. Dawson J, Liu CY, Francisco GE, et al. (April 2021). Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial. Lancet, 397(10284), 1545–1553. https://doi.org/10.1016/S0140-6736(21)00475-X 
  12. Dawson J, Engineer ND, Prudente CN, et al. (June 2020). Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Stroke: One-Year Follow-up. Neurorehabilitation and Neural Repair, 34(7), 609–615. https://doi.org/10.1177/1545968320924361
  13. Dickie DA, Kimberley TJ, Pierce D, et al. (November 2019). An Exploratory Study of Predictors of Response to Vagus Nerve Stimulation Paired with Upper-Limb Rehabilitation After Ischemic Stroke. Scientific Reports, 9(1), 15902. https://doi.org/10.1038/s41598-019-52092-x
  14. Kimberley TJ, Prudente CN, Engineer ND, et al. (June 2019). Study protocol for a pivotal randomised study assessing vagus nerve stimulation during rehabilitation for improved upper limb motor function after stroke. European Stroke Journal, 4(4), 363–377. https://doi.org/10.1177/2396987319855306
  15. Kimberley TJ and Dawson J. (January 2019). Response by Kimberley and Dawson Regarding Article, “Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke: A Blinded Randomized Pilot Study”. Stroke, 50(2), e38. https://doi.org/10.1161/STROKEAHA.118.024405
  16. Kumaria A and Tolias CM. (January 2019). Letter by Kumaria and Tolias Regarding Article, “Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke: A Blinded Randomized Pilot Study”. Stroke, 50(2), e37. https://doi.org/10.1161/STROKEAHA.118.024182
  17. Kimberley TJ, Pierce D, Prudente CN, et al. (September 2018). Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke. Stroke, 49(11), 2789–2792. https://doi.org/10.1161/STROKEAHA.118.022279
  18. Kilgard MP, Rennaker RL, Alexander J, and Dawson J. (March 2018). Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient. NeuroRehabilitation, 42(2), 159–165. https://doi.org/10.3233/NRE-172273
  19. Dawson J, Pierce D, Dixit A, et al. (January 2016). Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke. Stroke, 47(1), 143–150. https://doi.org/10.1161/STROKEAHA.115.010477

 

Review Articles

  1. Dawson J, and Abdul-Rahim AH. (April 2022). Paired vagus nerve stimulation for treatment of upper extremity impairment after stroke. International Journal of Stroke: Official Journal of the International Stroke Society, 17(10), 1061-1066. https://doi.org/10.1177/17474930221094684
  2. Morrison RA, Hays SA, and Kilgard MP. (August 2021). Vagus Nerve Stimulation as a Potential Adjuvant to Rehabilitation for Post-stroke Motor Speech Disorders. Frontiers in Neuroscience, 15, 715928. https://doi.org/10.3389/fnins.2021.715928
  3. Engineer ND, Kimberley TJ, Prudente CN, et al. (March 2019). Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke. Frontiers in Neuroscience, 13, 280. https://doi.org/10.3389/fnins.2019.00280
  4. Hays SA. (January 2016). Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation. Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics, 13(2), 382–394. https://doi.org/10.1007/s13311-015-0417-z

 

Pre-Clinical Publications / MOA

  1. Bowles S, Hickman J, Peng X, et al. (September 2022). Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement. Neuron, S0896-6273(22)00555-4. https://doi.org/10.1016/j.neuron.2022.06.017 
  2. Rodenkirch C, Carmel JB, and Wang Q. (July 2022). Rapid Effects of Vagus Nerve Stimulation on Sensory Processing Through Activation of Neuromodulatory Systems. Frontiers in Neuroscience, 16, 922424. https://doi.org/10.3389/fnins.2022.922424
  3. Morrison RA, Abe ST, Danaphongse T, et al. (February 2022). Common Cholinergic, Noradrenergic, and Serotonergic Drugs Do Not Block VNS-Mediated Plasticity. Frontiers in Neuroscience, 16, 849291. https://doi.org/10.3389/fnins.2022.849291
  4. Tseng CT, Gaulding SJ, Dancel C, and Thorn CA. (November 2021). Local activation of α2 adrenergic receptors is required for vagus nerve stimulation induced motor cortical plasticity. Scientific Reports, 11(1), 21645. https://doi.org/10.1038/s41598-021-00976-2
  5. Kunii N, Koizumi T, Kawai K, Shimada S, and Saito N. (August 2021). Vagus Nerve Stimulation Amplifies Task-Induced Cerebral Blood Flow Increase. Frontiers in Human Neuroscience, 15, 726087. https://doi.org/10.3389/fnhum.2021.726087
  6. Brougher J, Sanchez CA, Aziz US, et al. (August 2021). Vagus Nerve Stimulation Induced Motor Map Plasticity Does Not Require Cortical Dopamine. Frontiers in Neuroscience, 15, 693140. https://doi.org/10.3389/fnins.2021.693140
  7. Pruitt DT, Danaphongse TT, Lutchman M, et al. (June 2021). Optimizing Dosing of Vagus Nerve Stimulation for Stroke Recovery. Translational Stroke Research, 12(1), 65–71. https://doi.org/10.1007/s12975-020-00829-6
  8. Morrison RA, Danaphongse TT, Abe ST, et al. (April 2021). High intensity VNS disrupts VNS-mediated plasticity in motor cortex. Brain Research, 1756, 147332. https://doi.org/10.1016/j.brainres.2021.147332
  9. Darrow MJ, Mian TM, Torres M, et al. (January 2021). The tactile experience paired with vagus nerve stimulation determines the degree of sensory recovery after chronic nerve damage. Behavioural Brain Research, 396, 112910. https://doi.org/10.1016/j.bbr.2020.112910
  10. Morrison RA, Danaphongse TT, Pruitt DT, et al. (August 2020). A limited range of vagus nerve stimulation intensities produce motor cortex reorganization when delivered during training. Behavioural Brain Research, 391, 112705. https://doi.org/10.1016/j.bbr.2020.112705
  11. Darrow MJ, Torres M, Sosa MJ, et al. (January 2020). Vagus Nerve Stimulation Paired with Rehabilitative Training Enhances Motor Recovery After Bilateral Spinal Cord Injury to Cervical Forelimb Motor Pools. Neurorehabilitation and Neural Repair, 34(3), 200–209. https://doi.org/10.1177/1545968319895480
  12. Darrow MJ, Mian TM, Torres M, et al. (January 2020). Restoration of Somatosensory Function by Pairing Vagus Nerve Stimulation with Tactile Rehabilitation. Annals of Neurology, 87(2), 194–205. https://doi.org/10.1002/ana.25664
  13. Hulsey DR, Shedd CM, Sarker SF, et al. (October 2019). Norepinephrine and serotonin are required for vagus nerve stimulation directed cortical plasticity. Experimental Neurology, 320, 112975. https://doi.org/10.1016/j.expneurol.2019.112975
  14. Morrison RA, Hulsey DR, Adcock KS, et al. (March 2019). Vagus nerve stimulation intensity influences motor cortex plasticity. Brain Stimulation, 12(2), 256–262. https://doi.org/10.1016/j.brs.2018.10.017 
  15. Meyers EC, Solorzano BR, James J, et al. (January 2018). Vagus Nerve Stimulation Enhances Stable Plasticity and Generalization of Stroke Recovery. Stroke, 49(3), 710–717. https://doi.org/10.1161/STROKEAHA.117.019202
  16. Hays SA, Ruiz A, Bethea T, et al. (July 2016). Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats. Neurobiology of Aging, 43, 111–118. https://doi.org/10.1016/j.neurobiolaging.2016.03.030
  17. Pruitt DT, Schmid AN, Kim LJ, et al. (April 2016). Vagus Nerve Stimulation Delivered with Motor Training Enhances Recovery of Function after Traumatic Brain Injury. Journal of Neurotrauma, 33(9), 871–879. https://doi.org/10.1089/neu.2015.3972
  18. Hulsey DR, Hays SA, Khodaparast N, et al. (March 2016). Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation. Brain Stimulation, 9(2), 174–181. https://doi.org/10.1016/j.brs.2015.12.007
  19. Khodaparast N, Kilgard MP, Casavant R, et al. (January 2016). Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats. Neurorehabilitation and Neural Repair, 30(7), 676–684. https://doi.org/10.1177/1545968315616494
  20. Hays SA, Khodaparast N, Hulsey DR, et al. (August 2014). Vagus nerve stimulation during rehabilitative training improves functional recovery after intracerebral hemorrhage. Stroke, 45(10), 3097–3100. https://doi.org/10.1161/STROKEAHA.114.006654
  21. Hays SA, Khodaparast N, Ruiz A, et al. (June 2014). The timing and amount of vagus nerve stimulation during rehabilitative training affect poststroke recovery of forelimb strength. Neuroreport, 25(9), 676–682. https://doi.org/10.1097/WNR.0000000000000154
  22. Khodaparast, N., Hays, S. A., Sloan, A. M., Fayyaz, T., Hulsey, D. R., Rennaker, R. L., 2nd, & Kilgard, M. P. (February 2014). Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke. Neurorehabilitation and Neural Repair, 28(7), 698–706. https://doi.org/10.1177/1545968314521006
  23. Khodaparast, N., Hays, S. A., Sloan, A. M., Hulsey, D. R., Ruiz, A., Pantoja, M., Rennaker, R. L., 2nd, & Kilgard, M. P. (December 2013). Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke. Neurobiology of Disease, 60, 80–88. https://doi.org/10.1016/j.nbd.2013.08.002
  24. Hays, S. A., Rennaker, R. L., & Kilgard, M. P. (2013). Targeting plasticity with vagus nerve stimulation to treat neurological disease. Progress in Brain Research, 207, 275–299. https://doi.org/10.1016/B978-0-444-63327-9.00010-2
  25. Porter, B. A., Khodaparast, N., Fayyaz, T., Cheung, R. J., Ahmed, S. S., Vrana, W. A., Rennaker, R. L., 2nd, & Kilgard, M. P. (October 2012). Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex. Cerebral Cortex, 22(10), 2365–2374. https://doi.org/10.1093/cercor/bhr316
  26. Engineer, N. D., Riley, J. R., Seale, J. D., Vrana, W. A., Shetake, J. A., Sudanagunta, S. P., Borland, M. S., & Kilgard, M. P. (January 2011). Reversing pathological neural activity using targeted plasticity. Nature, 470(7332), 101–104. https://doi.org/10.1038/nature09656 

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