Vagus Nerve Stimulation for Upper Limb Function: Significant Difference, but Clinically Important?

Introduction: Vagus Nerve Stimulation (VNS) paired with rehabilitation induces movement specific plasticity in rat motor cortex and improves forepaw function in a rat ischemic model compared to rehabilitation alone. A 20 subject first-in-human study in the UK indicated acceptable safety and feasibility of this approach in patients with arm weakness after stroke and showed a significant difference in favour of VNS paired with rehabilitation in the per-protocol analysis (Upper Extremity Fugl Meyer difference of 9.6 points for VNS vs. 3.0 Control; p = 0.038). We conducted a new, double-blind sham controlled study to further assess this technique. Methods: Subjects with chronic moderate to severe upper extremity hemiparesis secondary to ischemic stroke (Upper Extremity Fugl Meyer (UEFM) 20-50) were enrolled at four sites (3 US, 1 UK). After baseline assessments subjects were implanted with a vagus nerve stimulation device if all eligibility criteria were met. Following implantation, randomization was made to either paired VNS (1/2 second, 30 Hz., 0.8 mA, 100 uS stimulation with task-specific movement) or sham control (stimulation only on first 5 movements). All received the same intensive and task-specific rehabilitation and had 18 treatment sessions (2-hourly, 3 times a week for 6-weeks, approximately 50 repetitions per task and 300 to 400 repetition movements per session). Outcomes were assessed on the first and 30 th day following completion of the 6-week therapy course. Results: Sixteen patients (8 female) were implanted (8 VNS, 8 Control). Mean age (SD) was 63.2(6.9), with an average (SD) of 21.7 months (12.9) post stroke. One study related serious adverse event was reported (a wound infection that resolved with IV antibiotics). Blinded results (change in UEFM, WMFT, and UEFM responders for both groups) will be available and presented. Conclusions: A pivotal study of VNS paired with rehabilitation movements will be justified if preliminary results are confirmed.

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Transcutaneous Vagus Nerve Stimulation Combined with Robotic Rehabilitation Improves Upper Limb Function after Stroke

Neural Plasticity ◽

10.1155/2017/7876507 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

Fioravante Capone ◽

Sandra Miccinilli ◽

Giovanni Pellegrino ◽

Loredana Zollo ◽

Davide Simonetti ◽

...

Keyword(s):

Vagus Nerve ◽

Upper Limb ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Controlled Trial ◽

Chronic Stroke ◽

Robotic Rehabilitation ◽

Double Blind ◽

Upper Limb Function ◽

Transcutaneous Vagus Nerve Stimulation

The efficacy of standard rehabilitative therapy for improving upper limb functions after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) paired with rehabilitation is a promising approach, but the invasiveness of this technique limits its clinical application. Recently, a noninvasive method to stimulate vagus nerve has been developed. The aim of the present study was to explore whether noninvasive VNS combined with robotic rehabilitation can enhance upper limb functionality in chronic stroke. Safety and efficacy of this combination have been assessed within a proof-of-principle, double-blind, semirandomized, sham-controlled trial. Fourteen patients with either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted therapy associated with real or sham VNS, delivered for 10 working days. Efficacy was evaluated by change in upper extremity Fugl–Meyer score. After intervention, there were no adverse events and Fugl–Meyer scores were significantly better in the real group compared to the sham group. Our pilot study confirms that VNS is feasible in stroke patients and can produce a slight clinical improvement in association to robotic rehabilitation. Compared to traditional stimulation, noninvasive VNS seems to be safer and more tolerable. Further studies are needed to confirm the efficacy of this innovative approach.

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

The Lancet ◽

10.1016/s0140-6736(21)00475-x ◽

2021 ◽

Vol 397 (10284) ◽

pp. 1545-1553 ◽

Cited By ~ 1

Author(s):

Jesse Dawson ◽

Charles Y Liu ◽

Gerard E Francisco ◽

Steven C Cramer ◽

Steven L Wolf ◽

...

Keyword(s):

Ischaemic Stroke ◽

Vagus Nerve ◽

Motor Function ◽

Upper Limb ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation

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

Neurorehabilitation and Neural Repair ◽

10.1177/1545968320924361 ◽

2020 ◽

Vol 34 (7) ◽

pp. 609-615

Author(s):

Jesse Dawson ◽

Navzer D. Engineer ◽

Cecília N. Prudente ◽

David Pierce ◽

Gerard Francisco ◽

...

Keyword(s):

Ischemic Stroke ◽

Vagus Nerve ◽

Upper Limb ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Exercise Program ◽

Home Exercise ◽

Home Exercise Program

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.

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Vagus nerve stimulation for depression: efficacy and safety in a European study

Psychological Medicine ◽

10.1017/s0033291707001924 ◽

2008 ◽

Vol 38 (5) ◽

pp. 651-661 ◽

Cited By ~ 104

Author(s):

T. E. Schlaepfer ◽

C. Frick ◽

A. Zobel ◽

W. Maier ◽

I. Heuser ◽

...

Keyword(s):

Side Effects ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Rating Scale ◽

Response Rates ◽

European Study ◽

Multi Centre Study ◽

Significant Difference ◽

Remission Rates

BackgroundVagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression.MethodAn open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically.ResultsThe baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (⩾50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%).ConclusionsVNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.

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Effect of Acupuncture Transcutaneous Electrical Nerve Stimulation on Upper Limb Function in Stroke Patients

The Medical Journal of Cairo University ◽

10.21608/mjcu.2019.86329 ◽

2019 ◽

Vol 87 (12) ◽

pp. 5075-5082

Author(s):

MARAM A. MAHMOUD, M.Sc.; EMAN S. FAYEZ, Ph.D. ◽

MAGED M. ABDEL NASEER, M.D.; RANIA M. TAWFIK, Ph.D.

Keyword(s):

Upper Limb ◽

Nerve Stimulation ◽

Transcutaneous Electrical Nerve Stimulation ◽

Stroke Patients ◽

Limb Function ◽

Electrical Nerve Stimulation ◽

Upper Limb Function

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Effect of Immersive Virtual Reality-Based Bilateral Arm Training in Patients with Chronic Stroke

Brain Sciences ◽

10.3390/brainsci11081032 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1032

Author(s):

Yo-Han Song ◽

Hyun-Min Lee

Keyword(s):

Virtual Reality ◽

Upper Limb ◽

Chronic Stroke ◽

Limb Function ◽

Upper Limb Rehabilitation ◽

Upper Limb Function ◽

Artificial Environment ◽

Beta Power ◽

Significant Difference ◽

Bilateral Arm Training

Virtual reality (VR)-based therapies are widely used in stroke rehabilitation. Although various studies have used VR techniques for bilateral upper limb training, most have been only semi-immersive and have only been performed in an artificial environment. This study developed VR content and protocols based on activities of daily living to provide immersive VR-based bilateral arm training (VRBAT) for upper limb rehabilitation in stroke patients. Twelve patients with chronic stroke were randomized to a VRBAT group or a normal bilateral arm training (NBAT) group and attended 30-min training sessions five times a week for four weeks. At the end of the training, there was a significant difference in upper limb function in both groups (p < 0.05) and in the upper limb function sensory test for proprioception in the NBAT group (p < 0.05). There was no significant between-group difference in upper limb muscle activity after training. The relative alpha and beta power values for electroencephalographic measurements were significantly improved in both groups. These findings indicate that both VRBAT and NBAT are effective interventions for improving upper limb function and electroencephalographic activity in patients with chronic stroke.

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Vagus Nerve Stimulation as a Potential Adjuvant to Rehabilitation for Post-stroke Motor Speech Disorders

Frontiers in Neuroscience ◽

10.3389/fnins.2021.715928 ◽

2021 ◽

Vol 15 ◽

Author(s):

Robert A. Morrison ◽

Seth A. Hays ◽

Michael P. Kilgard

Keyword(s):

Synaptic Plasticity ◽

Vagus Nerve ◽

Upper Limb ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Speech Therapy ◽

Speech Disorders ◽

Motor Speech ◽

Motor Speech Disorders ◽

Post Stroke

Stroke often leaves lasting impairments affecting orofacial function. While speech therapy is able to enhance function after stroke, many patients see only modest improvements after treatment. This partial restoration of function after rehabilitation suggests that there is a need for further intervention. Rehabilitative strategies that augment the effects of traditional speech therapy hold promise to yield greater efficacy and reduce disability associated with motor speech disorders. Recent studies demonstrate that brief bursts of vagus nerve stimulation (VNS) can facilitate the benefits of rehabilitative interventions. VNS paired with upper limb rehabilitation enhances recovery of upper limb function in patients with chronic stroke. Animal studies reveal that these improvements are driven by VNS-dependent synaptic plasticity in motor networks. Moreover, preclinical evidence demonstrates that a similar strategy of pairing VNS can promote synaptic reorganization in orofacial networks. Building on these findings, we postulate that VNS-directed orofacial plasticity could target post-stroke motor speech disorders. Here, we outline the rationale for pairing VNS with traditional speech therapy to enhance recovery in the context of stroke of speech motor function. We also explore similar treatments that aim to enhance synaptic plasticity during speech therapy, and how VNS differs from these existing therapeutic strategies. Based on this evidence, we posit that VNS-paired speech therapy shows promise as a means of enhancing recovery after post-stroke motor speech disorders. Continued development is necessary to comprehensively establish and optimize this approach, which has the potential to increase quality of life for the many individuals suffering with these common impairments.

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