Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Stroke: One-Year Follow-up

Abstract

Background. Vagus nerve stimulation (VNS) paired with rehabilitation may improve upper-limb impairment and function after ischemic stroke. Objective. To report 1-year safety, feasibility, adherence, and outcome data from a home exercise program paired with VNS using long-term follow-up data from a randomized double-blind study of rehabilitation therapy paired with Active VNS (n = 8) or Control VNS (n = 9). Methods. All people were implanted with a VNS device and underwent 6 weeks in clinic therapy with Control or Active VNS followed by home exercises through day 90. Thereafter, participants and investigators were unblinded. The Control VNS group then received 6 weeks in-clinic Active VNS (Cross-VNS group). All participants then performed an individualized home exercise program with self-administered Active VNS. Data from this phase are reported here. Outcome measures were Fugl-Meyer Assessment—Upper Extremity (FMA-UE), Wolf Motor Function Test (Functional and Time), Box and Block Test, Nine-Hole Peg Test, Stroke Impact Scale, and Motor Activity Log. Results. There were no VNS treatment–related serious adverse events during the long-term therapy. Two participants discontinued prior to receiving the full crossover VNS. On average, participants performed 200 ± 63 home therapy sessions, representing device use on 57.4% of home exercise days available for each participant. Pooled analysis revealed that 1 year after randomization, the FMA-UE score increased by 9.2 points (95% CI = 4.7 to 13.7; P = .001; n = 15). Other functional measures were also improved at 1 year. Conclusions. VNS combined with rehabilitation is feasible, with good long-term adherence, and may improve arm function after ischemic stroke.

Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial

“…There were low levels of missing data and all but two participants completed the study to day 90. While the long-term data from this study are not yet available, our earlier pilot study suggests that benefits of paired VNS therapy are maintained over time 43 .…”

“…We randomised participants at the time of VNS implant surgery to either rehabilitation paired with active VNS (VNS group) or rehabilitation paired with sham stimulation (Control group) on a 1:1 basis. Randomisation was done by ResearchPoint Global (USA) using SAS PROC PLAN, with stratification by region (US/UK), age (≤30, >30), and baseline FMA-UE score (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50). The randomisation allocation was sent via email to an unblinded clinical engineer at each site who tested and programmed the device with the appropriate stimulation settings for group assignment during implantation.…”

Targeting the Autonomic Nervous System for Risk Stratification, Outcome Prediction and Neuromodulation in Ischemic Stroke

“…Notably, the participants assigned to sham stimulation experienced a similar benefit when they crossed over to active VNS treatment [166]. Moreover, 73% of participants demonstrated a clinically meaningful improvement, attested by an increase of more than 10 points in Upper Limb Fugl-Meyer Score, after 1-year follow-up of VNS paired with rehabilitation [186]. Recently, also the tVNS has been the subject of some clinical studies in the context of ischemic stroke.…”

Efficacy and safety of manual acupuncture for the treatment of upper limb motor dysfunction after stroke: Protocol for a systematic review and meta-analysis

“…In line with China's 2015 diagnostic criteria for classifying cerebrovascular diseases, patients who had a first stroke confirmed using computed tomography or magnetic resonance imaging, a disease course longer than 1 month, but less than or equal to 6 months, and moderate to severe upper extremity and hand dysfunction that meet the standard criteria (Brunnstrom grade 2-4, Fugl Meyer Assessment [FMA] score < 20, improved Ashworth Spasm Scale score less than level 3 [13]) will be included, regardless of their sex and nationality. Exclusion criteria will include: 1) presence of other diseases resulting in serious cognitive or speech disorders 2) inability to understand and complete the therapist's instructions (Mini-Mental State Examination score < 21 points [14]) 3) history of drug or alcohol dependence 4) serious liver or kidney disease 5) other diseases that may affect brain structure and function; and 6) other mental disorders.…”