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ta-VNS for acute stroke

Efficacy and safety of transcutaneous auricular vagus nerve stimulation combined with conventional rehabilitation training in acute stroke patients: a randomized controlled trial conducted for 1 year involving 60 patients

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Year of Publication: 2022

Authors: Jia-Ni Li, Chen-Chen Xie, Chang-Qing Li, ..., Ling-Chuan Niu

Journal: Neural Regeneration Research

Citation: Neural Regen Res 17(8):1809-1813.

Link: https://pmc.ncbi.nlm.nih.gov/articles/PM...NRR-17-1809.pdf

PDF: https://pmc.ncbi.nlm.nih.gov/articles/PM...NRR-17-1809.pdf

Clinical Question

To investigate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (ta-VNS) combined with conventional rehabilitation training on the recovery of motor function, sensory function, and emotional responses in patients with acute ischemic or hemorrhagic stroke over a 1-year follow-up period.

Bottom Line

In patients with acute ischemic or hemorrhagic stroke, non-invasive transcutaneous auricular vagus nerve stimulation (ta-VNS) combined with conventional rehabilitation training was safe and significantly improved the recovery of motor and sensory functions, as well as emotional responses, compared to sham stimulation with rehabilitation. These benefits were observed starting from 2 weeks and were sustained for up to 1 year.

        Major Points
        This was a double-blind, randomized, sham-controlled trial involving 60 patients with acute stroke (both ischemic and hemorrhagic) within one month of symptom onset.
Patients were randomized 1:1 to receive either active ta-VNS or sham ta-VNS, with both groups also receiving conventional rehabilitation training.
The intervention consisted of 20-minute stimulation sessions five times per week for four weeks, immediately followed by a 30-minute rehabilitation session.
The ta-VNS group showed significantly greater improvements compared to the control group across all primary functional outcomes (Fugl-Meyer Assessment for Upper and Lower Extremity, Sensory function, and Wolf Motor Function Test) at all follow-up time points from 2 weeks to 1 year.
Patients in the ta-VNS group also reported significantly less anxiety and depression (HADS scale) and better quality of life (Stroke Impact Scale) compared to controls.
The treatment was safe and well-tolerated, with no major side effects reported and no significant changes in cardiovascular vital signs.

      

Design

Study Type: Two-group, pragmatic, double-blinded, randomized controlled trial

Randomization: 1

Blinding: Double-blind (participants, physical therapists, and researchers)

Enrollment Period: November 2018 to March 2020

Follow-up Duration: 1 year

Centers: 1

Countries: China

Sample Size: 60

Analysis: A per-protocol analysis was conducted. Outcomes were analyzed using a two-way analysis of variance followed by Šidák's post hoc multiple comparison test.

Inclusion Criteria

Age 18-80 years
History of first-time symptomatic ischemic or hemorrhagic stroke, demonstrated by imaging
Stroke had occurred within the previous month

Exclusion Criteria

Progressive decline in cardiac, pulmonary, liver, or kidney function
Apraxia
Resting heart rate <50 beats/min
Previous operation on the vagus nerve
Alcohol or drug abuse
Participation in other clinical experiments

Baseline Characteristics

Characteristic	Control	Active
Group	Control (n=30)	ta-VNS (n=30)
Age (yr), mean±SD	68.3±12.1	69.2±12.3
Male, n (%)	14 (47)	15 (50)
Type of stroke (ischemic/hemorrhagic), n	28/2	27/3
FMA-U, mean±SD	30.8±5.3	31.4±5.7
FMA-L, mean±SD	17.2±2.9	17.6±3.0

Arms

Field	Control	ta-VNS + Rehabilitation
Intervention	A 4-week course of conventional rehabilitation training (30-minute sessions, 5x/week) immediately preceded by a 20-minute session of sham ta-VNS, where electrodes were placed but no electrical current was delivered.	A 4-week course of conventional rehabilitation training (30-minute sessions, 5x/week) immediately preceded by a 20-minute session of active transcutaneous auricular vagus nerve stimulation (0.3-ms square pulses at 20 Hz for 30 seconds, repeated every 5 minutes).
Duration	4 weeks of treatment	4 weeks of treatment

Outcomes

Outcome	Type	Control	Intervention	P-value
The primary functional outcome was the improvement in motor and sensory functions, as evaluated by the Wolf Motor Function Test (WMFT) and Fugl-Meyer Assessment (FMA) scales at multiple time points up to 1 year.	Primary	Showed significant improvement from baseline but was significantly lower than the ta-VNS group at all follow-up points.	Showed significantly greater improvement on FMA-Upper limb, FMA-Lower limb, FMA-Sensory, and WMFT scores compared to the control group at all follow-up points (2 weeks, 1, 3, 6, and 12 months).	<0.05 for all comparisons at all follow-up time points
Activities of daily living (Stroke Impact Scale - SIS) and emotional state (Hospital Anxiety and Depression Scale - HADS).	Secondary	Showed improvement but was significantly worse than the ta-VNS group.	Had significantly lower scores for anxiety and depression (HADS) from month 1 onwards, and significantly higher SIS scores (better quality of life) from month 3 onwards, compared to the control group.	<0.05 for all comparisons from the specified time points onwards
Skin redness	Adverse	0	2 participants (resolved after adjusting current)

Criticisms

The study had a small sample size (60 patients).
The lack of an active stimulation control group means that placebo effects cannot be entirely ruled out.
The optimal parameters for electrical stimulation (timing, electrode placement, waveform) have not been identified and may have influenced the therapeutic effect.

Funding

Medical Scientific Research Project of Chongqing Municipal Health Commission of China; Chongqing General Hospital of China.

Based on: ta-VNS for acute stroke (Neural Regeneration Research, 2022)