Specific mode acupoint electrical stimulation combined with NGF for neurological recovery in ischemic stroke convalescence: A randomized controlled study
In brief
NGF improves stroke disability scores and adding SMES boosts cognitive recovery
In a multicenter trial of 324 patients with moderate ischemic stroke, daily NGF injections led to greater improvement in modified Rankin scores compared with placebo, while the combination of specific-mode acupoint electrical stimulation and NGF produced the largest gains in cognitive tests (MoCA and LOTCA). No serious safety issues were reported, but the added benefit was limited to cognition, leaving the overall functional advantage of SMES unclear.
- Journal
- BMC medicine (Q1)
- Published
- 20 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Mengyuan Dai, Zhaoxing Jia, Ziqi Xuan, Junhong Liu, Xuewen Wu, Yiqing Zhang, et al.
- PMID
- 42477731
- DOI
- 10.1186/s12916-026-05073-7
Why clinicians should know about it
- Picked for Complementary and Alternative Medicine (paper of the day, 22 July 2026): RCT of acupoint electrical stimulation + NGF for stroke
- Picked for Neurology (clinical) (paper of the day, 22 July 2026).
- Picked for Rehabilitation (paper of the day, 22 July 2026).
Abstract
BACKGROUND: Nerve growth factor (NGF) has neurorestorative potential after ischemic stroke, but its efficacy may be limited by the blood-brain barrier (BBB). Preclinical studies suggested that specific mode acupoint electrical stimulation (SMES) may transiently increase BBB permeability and facilitate neurotrophic factor delivery. This study evaluated the efficacy and safety of SMES combined with NGF in ischemic stroke and explored treatment-associated functional brain changes. METHODS: In this multicentre, randomized, placebo-controlled trial, adults aged 30-80 years with first-ever ischemic stroke, 14 days to 6 months after onset, modified Rankin Scale (mRS) score 3-4, and MMSE score < 27 were randomly assigned (1:1:1:1) to acupuncture + placebo, acupuncture + NGF, SMES + placebo, or SMES + NGF. NGF or placebo was administered by daily intramuscular injection for 28 days, followed by acupuncture or SMES at GV20 and GV26. The primary efficacy outcome was longitudinal change in mRS score. Secondary outcomes included the Modified Barthel Index, Fugl-Meyer Assessment, Tinetti Performance-Oriented Mobility Assessment, Montreal Cognitive Assessment, and Loewenstein Occupational Therapy Cognitive Assessment. Outcomes were assessed at baseline, week 2, and week 4, with mRS and MoCA further assessed during follow-up. Exploratory rs-fMRI and fNIRS assessments were performed at baseline and week 4. RESULTS: Among 324 randomized participants, 296 completed treatment and follow-up. Repeated-measures ANOVA showed significant time and group-by-time effects for mRS, indicating different recovery trajectories among groups. In factorial analysis, NGF had a significant main effect on mRS improvement (P = 0.001), whereas the SMES main effect and SMES-by-NGF interaction were not significant. Cognitive outcomes showed a clearer combined-treatment pattern: the SMES + NGF group had the greatest improvements in MoCA and LOTCA at week 4, and the SMES-by-NGF interaction for MoCA was significant at week 4 (P = 0.019) and during follow-up (P < 0.001). Exploratory neuroimaging analyses suggested treatment-associated functional brain changes. Six adverse events occurred, with no serious treatment-related adverse events. CONCLUSIONS: NGF-containing interventions were associated with improved neurological disability after ischemic stroke, while SMES combined with NGF showed additional benefits for cognitive recovery. SMES combined with NGF may represent a promising adjunctive strategy for post-stroke rehabilitation. TRIAL REGISTRATION: The protocol was registered in the Clinical Trials repository under NCT05231694.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.