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ESOC 2021 | Vagus Nerve Stimulation improves motor recovery following ischemic stroke

Vagus Nerve Stimulation (VNS) prompts the release of plasticity-inducing neuromodulators. Seth Hays, PhD, The University of Texas at Dallas, Dallas, TX, explains that delivering VNS during rehabilitation may therefore strengthen the neuronal connections driving the movement, and potentially enhance recovery in patients following stroke. Dr Hays discusses the results of pre-clinical studies that aimed to investigate VNS efficacy for the promotion of motor recovery in a rat model of stroke. Prior to inducing a stroke, rats were trained to perform a forelimb task. Following stroke, rats underwent rehabilitation, with half the animals additionally receiving VNS. VNS-treated animals showed significantly better recovery than those receiving rehabilitation only. More importantly, the effects of VNS were retained after treatment was stopped – with longer-lasting effects following prolonged treatment. Dr Hays also talks on VNS-REHAB, a phase III, pivotal clinical study (NCT03131960), which reported enhanced recovery following VNS in patients with moderate-to-severe arm impairment after ischemic stroke, compared to rehabilitation alone. This interview took place at the European Stroke Organisation Conference (ESOC), 2021.

Transcript (edited for clarity)

The concept behind this is that when you stimulate the vagus nerve, you get release of neuromodulators. Neuromodulators are associated with plasticity or changes in the brain. And so the way we use vagus nerve stimulation, others have used this as well, is to deliver the stimulation when a patient is doing rehab. The idea is that when a patient is moving their arm or something during rehab, there are neurons that are activated that are driving the movement of their arm and those are the ones that we want to strengthen...

The concept behind this is that when you stimulate the vagus nerve, you get release of neuromodulators. Neuromodulators are associated with plasticity or changes in the brain. And so the way we use vagus nerve stimulation, others have used this as well, is to deliver the stimulation when a patient is doing rehab. The idea is that when a patient is moving their arm or something during rehab, there are neurons that are activated that are driving the movement of their arm and those are the ones that we want to strengthen. Same concept that’s behind conventional rehab. If you stimulate the vagus nerve and release those neuromodulators when the patient’s moving their arm, the idea is that it’s going to strengthen those connections and that may lead to better recovery.

Where we are on this as a field is that we’ve been working on development of this and this was actually my main role in this was working on the preclinical development or the animal model testing of this. And so that’s been going on for about eight years now and that has actually just come to completion with a group led by Jesse Dawson who finished up a trial that was published recently in The Lancet describing, it was a Phase III pivotal study showing that pairing vagus nerve stimulation or VNS with rehabilitation in individuals with chronic stroke, significantly enhances recovery. Actually just a few days ago, they received FDA approval to use that strategy in stroke patients.

The experimental evidence basically follows a pretty consistent model. What we did was we trained rats to perform some sort of skilled pulling task, like they had to reach out and grab something and then they had to pull on it and they had to pull with a particular force. We trained them on this task and then we would induce a model of stroke, which basically restricted blood flow to the cortex and caused impairments that are consistent with what stroke patient sees. So like loss of motor control and weakness. Then what we did is we train those rats on that same task for an additional several weeks so they got intensive test specific rehabilitation. And what we saw was that half the animals did just the training and half the animals got a short half second burst of vagus nerve stimulation when they were moving their arm during the therapy.

And what we saw was that in animals who did just the training without the stimulation, they showed a significant benefit but they were still significantly impaired from where they were before the injury. This is consistent with the notion that if you get intensive task specific rehab, you’ll get some benefits but of course, most people still have lingering deficits even after that. But what we saw was that in the rats that got this closed loop short burst of VNS paired with arm movements is that they recovered significantly better. They were indistinguishable from their pre-therapy levels. They were to the extent that we could tell when rats were fully recovered. And one other important finding from that was that even after we stopped the therapy, they retained these benefits for, in many of the studies one week but when we tested longer than that, we also saw that they retained the benefits for six weeks.

And so that’s important, not only for the fact that, of course we want patients to make recoveries that are lasting but also because this is sort of consistent with the notion that what we’re doing is enhancing plasticity or changes in these brain networks and we would expect that to be long lasting.

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