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耳迷走神经刺激减轻蛛网膜下腔出血中的炎症和血管痉挛:一项单机构随机对照试验。

Auricular vagus nerve stimulation for mitigation of inflammation and vasospasm in subarachnoid hemorrhage: a single-institution randomized controlled trial.

作者信息

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

机构信息

Departments of1Neurosurgery.

5Division of Neurotechnology, Washington University in St. Louis, Missouri; and.

出版信息

J Neurosurg. 2025 Jan 24;142(6):1720-1731. doi: 10.3171/2024.10.JNS241643. Print 2025 Jun 1.

Abstract

OBJECTIVE

Inflammation contributes to morbidity following subarachnoid hemorrhage (SAH). The authors of this study evaluate how applying noninvasive transauricular vagus nerve stimulation (taVNS) can target this deleterious inflammatory response following SAH and reduce the rate of radiographic vasospasm.

METHODS

In this prospective, triple-blinded, randomized controlled trial, 27 patients were randomized to taVNS or sham stimulation. Serial blood and CSF samples were collected every 3 days to quantify inflammatory markers. Radiographic cerebral vasospasm severity and functional outcomes (modified Rankin Scale scores) 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 in the sham-treated group (p < 0.001). In the taVNS group, tumor necrosis factor-α was significantly reduced in both plasma (days 7 and 10) and CSF (day 13); interleukin-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%). Patients treated with taVNS had significant improvement in modified Rankin Scale scores from admission to first follow-up (p = 0.014), unlike patients in the sham-treated group (p = 0.18). The taVNS group had a significantly lower rate of discharge to a skilled nursing facility or hospice (p = 0.04).

CONCLUSIONS

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

摘要

目的

炎症会导致蛛网膜下腔出血(SAH)后的发病情况。本研究的作者评估了应用非侵入性经耳迷走神经刺激(taVNS)如何针对SAH后的这种有害炎症反应,并降低影像学血管痉挛的发生率。

方法

在这项前瞻性、三盲、随机对照试验中,27名患者被随机分为taVNS组或假刺激组。每3天采集系列血液和脑脊液样本以量化炎症标志物。分析影像学脑血管痉挛严重程度和功能结局(改良Rankin量表评分)。

结果

未发生不良事件。影像学血管痉挛明显减轻(p = 0.018),系列血管管径测量显示,与假治疗组相比,其恢复正常的速度更快(p < 0.001)。在taVNS组,血浆(第7天和第10天)和脑脊液(第13天)中的肿瘤坏死因子-α均显著降低;白细胞介素-6在血浆(第4天)和脑脊液(第13天)中也显著降低(p < 0.05)。接受taVNS治疗的患者出院时(38.4%对21.4%)和首次随访时(76.9%对57.1%)的良好结局发生率更高。与假治疗组患者(p = 0.18)不同,接受taVNS治疗的患者从入院到首次随访时改良Rankin量表评分有显著改善(p = 0.014)。taVNS组转至专业护理机构或临终关怀机构的出院率显著更低(p = 0.04)。

结论

taVNS是一种非侵入性的神经和全身免疫调节方法。该试验支持以下发现:SAH后进行taVNS可减轻炎症反应,降低影像学血管痉挛,并可能改善功能和神经学结局。

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