Bilateral transcutaneous auricular nerve stimulation promotes motor function recovery after stroke: A randomized controlled trial.

Background: Vagus nerve stimulation (VNS) has emerged as a promising adjunctive approach for stroke rehabilitation. However, current clinical applications are predominantly limited to invasive VNS implantation or unilateral transcutaneous auricular nerve stimulation (taNS), often characterized by small sample sizes and a primary focus on upper limb motor recovery. Although emerging evidence suggests that bilateral taNS (BtaNS) may confer superior neuromodulatory effects compared with conventional left-sided unilateral taNS (LtaNS), its efficacy and safety profile for comprehensive post-stroke limb motor rehabilitation remain largely unexplored. Objectives: To evaluate the efficacy and safety of BtaNS combined with routine rehabilitation in promoting motor recovery in post-stroke patients with hemiplegia. Design: A prospective, double-blinded, three-arm randomized controlled trial. Methods: Patients with subacute or chronic stroke were recruited from the Department of Rehabilitation Medicine at the First Affiliated Hospital of Nanchang University between January 2025 and December 2025. Participants were randomly assigned to one of three groups: BtaNS, LtaNS, or a control group. All patients received routine rehabilitation therapy targeting both upper and lower limb motor function. Additionally, patients in the taNS groups received either LtaNS or BtaNS (stimulation parameters: 20 Hz frequency, 300 µs pulse width, intensity individually adjusted within a range of 0.5-1.0 mA) for 30 minutes twice daily, six days per week, over a four-week period. The primary outcome measures included the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Fugl-Meyer Assessment for Lower Extremities (FMA-LE) and the Wolf Motor Function Test (WMFT). Secondary outcomes encompassed the Berg Balance Scale (BBS), the Modified Barthel Index (MBI), and low-frequency oscillations measured via functional near-infrared spectroscopy (fNIRS). Adverse events were monitored to assess safety throughout the treatment period. Results: A total of 111 patients were enrolled in this study, of whom 5 withdrew and 4 were lost to follow-up, resulting in 102 participants completing the trial (34 per group). Compared with the control group, both the LtaNS and BtaNS groups exhibited significantly greater improvements in the FMA-UE, FMA-LE, and WMFT scores at all post-intervention assessment time points. Moreover, the BtaNS group demonstrated superior motor recovery relative to the LtaNS group. In addition, BtaNS was associated with significantly greater improvements in BBS and MBI scores at 4 weeks post-intervention and at follow-up compared with both the LtaNS and control groups. Subgroup analyses indicated that patients with a shorter time since stroke onset and those diagnosed with hemorrhagic stroke exhibited more pronounced improvements. No serious adverse events occurred; only mild, transient skin irritation was observed. Conclusion: BtaNS is a safe and well-tolerated intervention that demonstrates superior efficacy compared to LtaNS in enhancing motor recovery, balance, and independence in activities of daily living following stroke. The underlying mechanism may be associated with increased bilateral cortical engagement. Registration: This study was registered at Chinese Clinical Trial Registry: ChiCTR2400093825.