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[Preprint]. 2024 May 1:2024.04.29.24306598. [Version 1] doi: 10.1101/2024.04.29.24306598

Auricular Vagus Nerve Stimulation Mitigates Inflammation and Vasospasm in Subarachnoid Hemorrhage: A Randomized Trial

Anna L Huguenard, Gansheng Tan, Dennis J Rivet, Feng Gao, Gabrielle W Johnson, Markus Adamek, Andrew T Coxon, Terrance T Kummer, Joshua W Osbun, Ananth K Vellimana, David D Limbrick, Gregory J Zipfel, Peter Brunner, Eric C Leuthardt
PMCID: PMC11092685  PMID: 38746275

Abstract

Background

Inflammation contributes to morbidity following subarachnoid hemorrhage (SAH). Transauricular vagus nerve stimulation (taVNS) offers a noninvasive approach to target the inflammatory response following SAH.

Methods

In this prospective, triple-blinded, randomized, controlled trial, twenty-seven patients were randomized to taVNS or sham stimulation. Blood and cerebrospinal fluid (CSF) were collected to quantify inflammatory markers. Cerebral vasospasm severity and functional outcomes (modified Rankin Scale, mRS) were analyzed.

Results

No adverse events occurred. Radiographic vasospasm was significantly reduced (p = 0.018), with serial vessel caliber measurements demonstrating a more rapid return to normal than sham (p < 0.001). In the taVNS group, TNF-α was significantly reduced in both plasma (days 7 and 10) and CSF (day 13); IL-6 was also significantly reduced in plasma (day 4) and CSF (day 13) (p < 0.05). Patients receiving taVNS had higher rates of favorable outcomes at discharge (38.4% vs 21.4%) and first follow-up (76.9% vs 57.1%), with significant improvement from admission to first follow-up (p = 0.014), unlike the sham group (p = 0.18). The taVNS group had a significantly lower rate of discharge to skilled nursing facility or hospice (p = 0.04).

Conclusion

taVNS is a non-invasive method of neuro- and systemic immunomodulation. This trial supports that taVNS following SAH can mitigate the inflammatory response, reduce radiographic vasospasm, and potentially improve functional and neurological outcomes.

Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04557618

Full Text

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