npj Parkinson's Disease:无创迷走神经刺激可改善帕金森病步态冻结患者的临床和分子生物标志物

2021-05-29 MedSci原创 MedSci原创

该研究为nVNS治疗帕金森病运动和非运动症状的有效性和安全性提供了初步证据。

非侵入性迷走神经刺激(nVNS)是一种公认的用于治疗癫痫、偏头痛和丛集性头痛的神经刺激疗法。最近,研究发现迷走神经刺激有助于改善PD大鼠模型的运动能力。此外,两项独立的初步研究发现,单次应用颈椎nVNS 后PD患者的步态得到改善。越来越多的证据表明,迷走神经刺激可降低氧化应激,下调炎症细胞因子和增强抗氧化机制,这表明迷走神经刺激可能是多种炎症相关疾病的潜在治疗手段。虽然,VNS在帕金森病中发挥作用的机制很大程度上尚不清楚,鉴于炎症蛋白的表达通常需要数小时,抗炎作用不太可能解释对nVNS的即时治疗反应。在试点研究中,单次应用nVNS后观察到的立即改善更可能是由于中枢神经回路的间接激活,包括蓝斑去甲肾上腺素能投射,蓝斑是与步态冻结的发病机制有关的大脑区域,而不是通过调节神经炎症。尽管nVNS在帕金森病的初步研究中有很好的结果,但慢性刺激是否会带来持续的益处以及确切的益处是什么还不清楚。

Mondal, B等组织了一项随机、双盲、假对照交叉试验,探讨了nVNS在帕金森病(PD)患者步态和其他运动症状治疗中的作用。研究结构发表在npj Parkinsons Dis杂志

在一组患者中,他们测量了实验干预前后血清中选定的神经营养因子水平和炎症和氧化应激标志物。33例伴有步态冻结的PD患者被随机分为nVNS组和假刺激组。基线评估后,患者根据指示在家里使用nVNS/sham装置(electroCore, Inc.)进行为期一个月的每天6次,每次2分钟刺激(共计12分钟/天)。然后对患者进行重新评估。在一个月的洗脱期后,同样的患者被分配到替代治疗组,并遵循同样的过程。

与假刺激组相比,nVNS在关键步态参数方面有显著改善,包括行走速度、站立时间和步长

同样,nVNS刺激后整体运动功能(MDS-UPDRS III)也有显著改善。

nVNS治疗后血清肿瘤坏死因子(TNF)-α和谷胱甘肽水平显著降低,脑源性神经营养因子(BDNF)水平显著升高(p<0.05)

该研究为nVNS治疗帕金森病运动和非运动症状的有效性和安全性提供了初步证据。未来关于nVNS治疗帕金森病的研究不仅应该确认其可重复性,还应该关注优化治疗参数,首先确定nVNS的治疗效果(和潜在的神经保护作用)在出现显著运动症状之前持续多久。

原文出处

Mondal, B., Choudhury, S., Banerjee, R. et al. Non-invasive vagus nerve stimulation improves clinical and molecular biomarkers of Parkinson’s disease in patients with freezing of gait. npj Parkinsons Dis. 7, 46 (2021). https://doi.org/10.1038/s41531-021-00190-x

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