CONFERENCE UPDATE: AAN 2021
Vagus nerve stimulations paired with upper extremity rehabilitation as a potential treatment for post-ischemic stroke patients
Approximately 80% of people with acute stroke have upper limb motor impairment and 50-60% of these survivors still have persistent impaired upper limb function 6 months later.1,2 As persistent arm impairment is linked with poorer quality-of-life and reduced wellbeing, the identification of new treatments to improve upper limb function after stroke is thus a research priority for both stroke survivors and their caregivers.3,4
To enhance the reorganization potential of the brain following stroke, one potential method is to utilize the cholinergic and monoaminergic modulation of motor cortex neurons which can be achieved by vagus nerve stimulation (VNS).5 Evidence from rodent models suggested that VNS paired with rehabilitation can improve forelimb function after experimental stroke and enhance task-specific plasticity.5 Prof. Jesse Dawson, Professor at the University of Glasgow, United Kingdom, and his colleagues thereby conducted the VNS-REHAB trial to determine whether VNS paired with rehabilitation is a safe and effective treatment for improving the arm function in patients after stroke.
In the study, 108 patients with moderate-to-severe arm weakness at least 9 months after ischemic stroke were randomized 1:1 to receive either rehabilitation paired with active VNS (n=53) or rehabilitation paired with sham stimulation (n=55) (control group).5 Participants were implanted with a fully enclosed VNS device and underwent 6 weeks of in-clinical rehabilitation followed by home-based rehabilitation.5 The VNS group received 0.8mA, 100μs, 30Hz stimulation pulses, lasting 0.5 seconds.5 The control group received 0mA pulses.5 The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score on the first day after the completion of in-clinic therapy.5 FMA-UE response rates were also assessed at 90 days after in-clinic therapy as the secondary endpoint.5 After the completion of the blinded follow-up phase, Prof. Dawson noted that the control group further received paired VNS at post-90 days.
Prof. Dawson highlighted that “VNS-REHAB is the first multicenter trial with adequate statistical power to compare active VNS plus rehabilitation against sham stimulation plus rehabilitation and showed significant improvement for all primary and secondary endpoints.” On the first day after the completion of in-clinic therapy, the mean FMA-UE score increased by 5.0 points in the VNS group versus 2.4 points in the control group (between group difference=2.6 points; 95% CI: 1.0-4.2, p=0.0014).5 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved by 47% of patients in the VNS group versus 24% of patients in the control group (between group difference=24%; 95% CI: 6-41, p=0.0098).5 Furthermore, a post-hoc outcome measure of Wolf Motor Function Test (WMFT) response rate on day 90 also demonstrated a similar rate of clinically meaningful response (between group difference=0.30; 95% CI: 0.16-0.43, p<0.0001).5
When the control group crossed over to active VNS, Prof. Dawson remarked that the improvement in arm function matched that of the treatment group in the main study. The FMA and WMFT response rates were 44% different from baseline. Adverse events with the use of VNS were also observed at expected and low rates. Prof. Dawson thereby concluded that “VNS combined with rehabilitation is an acceptable safe and effective intervention for improving the upper limb impairment and function in people with moderate to severe arm weakness at least 9 months after ischemic stroke.”
Greater cardiovascular benefits with aggressive LDL-C reduction in patients with prior ischemic stroke
The recent 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the Management of Dyslipidemias have set a target low-density lipoprotein (LDL)-C goal of <55mg/dL for very high-risk patients requiring secondary prevention.1