Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke Jan. 2016
Earlier research on this is here July, 2012;
and here Jan. 2013;
and here - Sept. 2013;
The latest here:
Pilot study shows significant long-term improvements significant
In the randomized, sham-controlled pilot trial, there were no significant differences between groups in change in Upper Extremity Fugl Meyer Assessment (FMA) scores after 6 weeks of stimulation plus rehabilitation (mean change 7.6 points for VNS and 5.3 points for controls, P=0.26), according to Jesse Dawson, MD, of the University of Glasgow.
But those scores diverged significantly 90 days after the stimulation and rehabilitation therapy was over (9.5 versus 3.8, P=0.05), Dawson reported during a press briefing at the International Stroke Conference.
"All in all, we feel this is promising," Dawson said. "I think we've shown that the technique is acceptably safe. Crucially, I think we have shown that we can deliver a partially home-based brain stimulation technique."
Dawson's group enrolled 17 ischemic stroke patients, mean age 60 and with an even gender divide, who had moderate-to-severe arm weakness as assessed by FMA scores of 20 to 50.
All of them received the device -- the intervention arm received stimulation plus rehabilitation, performed for 6 weeks in the clinic and with 30-minutes daily of home exercises. Controls received sham stimulation plus rehab, and were able to cross-over and receive stimulation after the study was complete.
The stimulation was delivered at 0.5 seconds of 0.8 milliamps (mA) per movement, with about 400 stimulations per session, and controls were given 0 mA. Dawson noted that to optimize blinding, they initially gave all participants some stimulation, as some evidence has suggested that some people feel the stimulation at first but it wears off.
"When we asked people which group they thought they were in, 33% were right. It should have been 50%, so we feel like our paradigm worked," he said.
Participants, therapists, and assessors were blinded through 90 days after the therapy was completed.
Overall, there were three serious adverse events: one infection, one shortness of breath and dysphagia due to intubation, and one vocal cord paralysis. The former two cases resolved, but the patient who had vocal cord paralysis is still recovering, the researchers said.
Philip Gorelick, MD, MPH, of Michigan State University in Grand Rapids said that while the "target benefit is the release of neuroplastic substances, there are going to be other effects because you're stimulating the vagal nerve."
Gorelick, , who was not involved in this study but is conducting related work with VNS, said the stimulation should be monitored to ensure that it's reaching the target area, particularly when patients are performing therapeutic exercises at home.
Other adverse events in the trial included typical surgical events such as bruising, pain, swelling, and scarring. There were no cardiac events, Dawson said.
In addition to missing the primary endpoint in the shorter term, but garnering improvements at 90 days, there was a significantly higher responder rate in the intervention group at that time point (88% versus 33%, P=0.05).
The responder rate was also higher immediately after therapy, but not significantly so (75% versus 33%).
There were also non-significant trends in the right direction for change in the Wolf Motor Function Test (WMFT) both in the short term (0.25 versus 0.13, P=0.26) and at 90 days (0.36 versus 0.04, P=0.07), they reported.
When sham stimulation patients were allowed to cross over, FMA scores improved significantly, by a mean of about 8 points (P=0.002), and there was a similar significant pattern for WMFT scores, Dawson said.
Between this study and earlier research, Dawson said there appears to be about a 9-point change in FMA scores, "which I think most people would regard as clinically important."
The 9-point change is relative to where patients started at baseline, he explained. For those who have extremely poor function, they might be able to regain some grasp function so they could pick up a plate. If they were able to grasp when they started the trial, they might be able to regain some fine motor function, he said.
Gorelick agreed that the change would likely be clinically significant, but he also called for quality-of-life data.
"When we a see jump like that, we think it's safe to conclude there is clinical significance, but additional information about quality-of-life and some other scales could be very helpful in cementing the benefit," he said.
He also said that functional MRI data, to illustrate the neuroplasticity remodeling that is supposed to taking place in the brain because of the stimulation, would be an important part of the picture.
A 120-patient study will begin in summer 2017. Asked if his group is considering changing the timing of the primary endpoint for the next trial, Dawson said they believe that, with a larger number of patients, they should be able to detect a benefit early on.
"We would like to show that there's an effect with just 6 weeks of therapy," he said, "but it does seem like an investment in longer treatment would be worth taking."
Dawson and co-authors disclosed relevant relationships with MicroTransponder.
- Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College