A New Role for Vagus Nerve Stimulation

A treatment approach that has been used to treat uncontrollable epilepsy for more than 20 years has now assumed a potentially important role in upper extremity recovery from stroke. According to a study recently published in The Lancet, vagus nerve stimulation (VNS), when paired with traditional rehabilitation therapies, is showing promise as a treatment option for patients who have long-term moderate-to-severe arm impairment following an ischemic stroke.

Dr. Michael O’Dell with vagal nerve stimulation device

“There have been relatively few proven treatments in stroke recovery,” says Michael W. O’Dell, MD, Professor of Clinical Rehabilitation Medicine, Department of Rehabilitation Medicine at Weill Cornell Medicine. “While constraint-induced movement therapy appears to be very effective, it is difficult to provide the intensive therapy that is needed because it requires a huge amount of time and effort on the part of the patient in terms of exercise. So we have few methods available, particularly in chronic stroke, that we can offer.”

Dr. O’Dell, in collaboration with neurosurgeon Theodore H. Schwartz, MD, Director of the Center for Epilepsy and Pituitary Surgery at NewYork-Presbyterian/Weill Cornell, participated in a pivotal, randomized, triple-blind, sham-controlled trial of VNS conducted in 19 stroke rehabilitation services in the United States and United Kingdom.

“The concept was originally tested in an animal model, which suggested that stimulation of the vagus nerve affects different neurotransmitter systems in the brain, particularly acetylcholine and norepinephrine and demonstrated that the release of these neuromodulators strengthens the neural connections during the rehabilitation exercises, making rehabilitation therapy more effective,” says Dr. O’Dell. “These experimental studies and initial data from a small pilot study reported in Stroke in 2018 suggested that if the vagus nerve is stimulated while someone is doing an exercise, it may improve the recovery of upper extremity weakness. The theory was that the patient still had to exercise, but vagus nerve stimulation could enhance the efficacy of that exercise. These findings paved the way for the larger multicenter trial.”

Combining Nerve Stimulation with Rehabilitation Therapy

Participants in the current trial had moderate-to-severe arm weakness and were at least nine months post ischemic stroke. All 108 patients were implanted with the Vivistim neurostimulation device – 53 were randomly assigned to the VNS group and underwent rehabilitation paired with active vagus nerve stimulation and 55 were assigned to the control group, which received rehabilitation paired with sham stimulation. The pacemaker-size device is implanted under the skin of the chest and is programmed to deliver pulses or stimulation at regular intervals.

With the Vivistim Paired VNS™ System, each time the vagus nerve is stimulated, it sends a signal to the brain, which triggers the release of neurotransmitters broadly across the brain, including the motor cortex, thus enabling neuroplasticity to increase motor function.
(Courtesy of MicroTransponder®)

On the first day after completion of in-clinic therapy, the mean Fugl-Meyer Assessment for upper extremity (FMA-UE) score increased in the VNS group by 5.0 points and in the control group by 2.4 points. Ninety days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 of the 53 patients (47 percent) in the VNS group versus 13 of 55 patients (24 percent) in the control group. In addition to the FMA, the Wolf Motor Function Test provided a basic measure of semi-functional activities in the arm, such as grasp and release, reaching to your mouth, and other practical aspects of daily living.

“It is extremely important to point out that the device is used in conjunction with fairly intense occupational therapy 90 minutes, three times a week for six weeks followed by a home exercise program,” says Dr. O’Dell. “The study found that those individuals who had the VNS device turned on had substantially higher scores on the Fugl-Meyer Assessment and Wolf Motor Function Test obtained in the days following the completion of the occupational therapy and at three months later. The study not only analyzed the average change in these measures, but also specific changes that were clinically significant. For the Fugl-Meyer Assessment, almost twice as many individuals had a major change on that score as the placebo group, and for the Wolf Motor Function, nearly three times the number of patients in the VNS group had an excellent response. This is a big deal because we have so few treatments for upper extremity recovery following a stroke and this approach may prove to fill that gap.”

Dr. O’Dell also notes that the paper published in The Lancet provides a substantial analysis of the risks related to both the surgical implantation procedure and to the device. “There were very few complications and none that we didn't expect from past experience with the device or surgical placement,” says Dr. O’Dell. “The procedure is quite safe with relatively few side effects. This is a very interesting and substantial advance in the treatment of upper extremity impairment after stroke. If you consider there are between seven and eight million people in the United States living with some residual sequella of stroke, the potential pool of folks who could benefit is rather enormous.”

On August 31, 2021, the Vivistim Paired VNS™ System was granted a Breakthrough Device Designation by the FDA and will be available in targeted United States markets in late 2021, expanding nationally by the end of 2022.