Vagus Nerve Stimulation in Intracerebral and Subarachnoid Haemorrhage: A Systematic Review, Narrative Synthesis and Exploratory Meta-Analysis
- 1Sheffield Institute for Translational Neurology, University of Sheffield
Abstract
Background/ObjectivesHaemorrhagic stroke, comprising intracerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH), accounts for a disproportionate share of stroke mortality and disability, and its incidence rises steeply with age. Secondary injury processes, including neuroinflammation, cerebral oedema, autonomic dysfunction and vasospasm, are potentially modifiable. Vagus nerve stimulation (VNS) engages several of these pathways, but its therapeutic role remains uncertain. We reviewed the preclinical and clinical evidence for VNS in haemorrhagic stroke.
MethodsPubMed and MEDLINE were searched from inception to 1 June 2026 for preclinical studies and randomised clinical trials of VNS in ICH or SAH. Evidence was synthesised narratively; quality was assessed using SYRCLE and PEDro. Comparable binary functional outcomes (modified Rankin Scale [mRS] 0-2) were pooled using a random-effects inverse-variance model.
ResultsNine reports were included: four preclinical (179 animals) and five clinical (166 participants representing four independent cohorts). Preclinical studies reported reduced inflammatory signalling, smaller haematoma volume, lower aneurysm rupture rates, improved survival and enhanced motor recovery, with attenuated effects in severe injury models. Clinically, non-invasive VNS was feasible and well tolerated, with signals of reduced tumour necrosis factor alpha and interleukin-6, less radiographic vasospasm and delayed cerebral ischaemia, and increased parasympathetic activity. Pooled favourable functional outcome favoured VNS but was not statistically significant (odds ratio [OR] 1.82, 95% confidence interval [CI] 0.68-4.86; p = 0.24; I{superscript 2} = 0%). Excluding major haemorrhage yielded OR 2.85 (95% CI 0.97- 8.36; p = 0.06).
ConclusionsVNS is biologically active and feasible after haemorrhagic stroke but remains unproven. Adequately powered, severity-stratified multicentre trials with standardised stimulation protocols and age-appropriate outcomes are required.
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BibTeX
@misc{tupper2026vagus,
title = {{Vagus Nerve Stimulation in Intracerebral and Subarachnoid Haemorrhage: A Systematic Review, Narrative Synthesis and Exploratory Meta-Analysis}},
author = {M. Tupper and M. Myers and S. Baig and M. Aziz and J. Balami and L. Su and A. Majid and A. N. Ali},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.26362993},
url = {https://www.medrxiv.org/content/10.64898/2026.09.14.26362993v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Vagus Nerve Stimulation in Intracerebral and Subarachnoid Haemorrhage: A Systematic Review, Narrative Synthesis and Exploratory Meta-Analysis
AU - M. Tupper
AU - M. Myers
AU - S. Baig
AU - M. Aziz
AU - J. Balami
AU - L. Su
AU - A. Majid
AU - A. N. Ali
PY - 2026
DA - 2026/09/14
PB - medRxiv
DO - 10.64898/2026.09.14.26362993
UR - https://www.medrxiv.org/content/10.64898/2026.09.14.26362993v1
AB - Background/ObjectivesHaemorrhagic stroke, comprising intracerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH), accounts for a disproportionate share of stroke mortality and disability, and its incidence rises steeply with age. Secondary injury processes, including neuroinflammation, cerebral oedema, autonomic dysfunction and vasospasm, are potentially modifiable. Vagus nerve stimulation (VNS) engages several of these pathways, but its therapeutic role remains uncertain. We reviewed the preclinical and clinical evidence for VNS in haemorrhagic stroke. MethodsPubMed and MEDLINE were searched from inception to 1 June 2026 for preclinical studies and randomised clinical trials of VNS in ICH or SAH. Evidence was synthesised narratively; quality was assessed using SYRCLE and PEDro. Comparable binary functional outcomes (modified Rankin Scale [mRS] 0-2) were pooled using a random-effects inverse-variance model. ResultsNine reports were included: four preclinical (179 animals) and five clinical (166 participants representing four independent cohorts). Preclinical studies reported reduced inflammatory signalling, smaller haematoma volume, lower aneurysm rupture rates, improved survival and enhanced motor recovery, with attenuated effects in severe injury models. Clinically, non-invasive VNS was feasible and well tolerated, with signals of reduced tumour necrosis factor alpha and interleukin-6, less radiographic vasospasm and delayed cerebral ischaemia, and increased parasympathetic activity. Pooled favourable functional outcome favoured VNS but was not statistically significant (odds ratio [OR] 1.82, 95% confidence interval [CI] 0.68-4.86; p = 0.24; I{superscript 2} = 0%). Excluding major haemorrhage yielded OR 2.85 (95% CI 0.97- 8.36; p = 0.06). ConclusionsVNS is biologically active and feasible after haemorrhagic stroke but remains unproven. Adequately powered, severity-stratified multicentre trials with standardised stimulation protocols and age-appropriate outcomes are required.
ER -