Ma Jia-Yin, Wu Jia-Jia, Zhu Yi, Zheng Mou-Xiong, Hua Xu-Yun, Xu Jian-Guang
Center of Rehabilitation Medicine, Yueyang Hospital of integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Center of Rehabilitation Medicine, Yueyang Hospital of integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China.
Brain Res Bull. 2025 Jan;220:111158. doi: 10.1016/j.brainresbull.2024.111158. Epub 2024 Dec 13.
Autonomic dysfunction is a well-recognized complication associated with post-COVID-19 syndrome (PCS). ANS maladaptation could underlie a potential pathogenetic mechanism of PCS, contributing to PCS symptoms. However, there remains an ongoing debate regarding whether autonomic and neuropathic symptoms observed in PCS patients are indicative of central or peripheral ANS pathology. The purpose of this study is to investigate both the central and peripheral nervous systems of ANS in patients with PCS.
We evaluated the integrity of the peripheral ANS using sympathetic skin response (SSR) and examined the central ANS using functional near-infrared spectroscopy (fNIRS) covering the fronto-parietal cortex in PCS patients (n = 7) and matched healthy controls (n = 7). Functional connectivity, topological parameters of fNIRS brain network were analyzed. To compare the SSR and fNIRS parameters between patients and age-matched healthy controls, Mann-Whitney U tests were performed for each parameter separately. The AUC of each topological metric of fNIRS network was utilized as a statistical scalar for comparison. To characterize the correlation between SSR and significantly different topological metrics of fNIRS network, Spearman correlation analysis was performed.
The latencies of palmar SSR were significantly prolonged in the patients with PCS than the controls (p < 0.05). 34 functional connections showed a significant increase (p < 0.05, uncorrected). Regional nodal properties revealed that the fronto-parietal networks of PCS patients had a higher degree in primary somatosensory cortex (S1) (p < 0.001, corrected) and motor cortex, a lower node efficiency in dorsolateral prefrontal cortex (DLPFC), and a higher efficiency in S1 (p < 0.05, uncorrected). Latencies of palmar SSR were significantly positively correlated with zFC within sensorimotor cortex, and node efficiency/degree of S1 (p < 0.01). Amplitudes of palmar and plantar SSR were significantly positively correlated with node efficiency of DLPFC (p < 0.05).
Our findings suggest that there were alternations in both central and peripheral parts of ANS in PCS patients. These preliminary results indicate that PCS may lead to changes in both the peripheral and central aspects of ANS, which would help to extend the understanding of the role of the ANS in PCS, offering new perspectives on evaluation and treatment.
This study has been registered with the Chinese Clinical Trial Registration Center (registration number: ChiCTR2200064342; registration date:2022/10/3).
自主神经功能障碍是新冠后综合征（PCS）一种公认的并发症。自主神经系统（ANS）适应不良可能是PCS潜在的发病机制，导致PCS症状。然而，关于PCS患者中观察到的自主神经和神经病变症状是否表明中枢或外周ANS病理，仍存在持续的争论。本研究的目的是调查PCS患者ANS的中枢和外周神经系统。
我们使用交感皮肤反应（SSR）评估外周ANS的完整性，并使用功能近红外光谱（fNIRS）检查中枢ANS，该光谱覆盖了PCS患者（n = 7）和匹配的健康对照者（n = 7）的额顶叶皮层。分析了fNIRS脑网络的功能连接性、拓扑参数。为了比较患者和年龄匹配的健康对照者之间的SSR和fNIRS参数，对每个参数分别进行曼-惠特尼U检验。fNIRS网络每个拓扑指标的曲线下面积（AUC）用作统计标量进行比较。为了表征SSR与fNIRS网络显著不同的拓扑指标之间的相关性，进行了斯皮尔曼相关性分析。
PCS患者手掌SSR的潜伏期比对照组显著延长（p < 0.05）。34个功能连接显示显著增加（p < 0.05，未校正）。区域节点属性显示，PCS患者的额顶叶网络在初级体感皮层（S1）（p < 0.001，校正）和运动皮层具有更高的度，在背外侧前额叶皮层（DLPFC）具有更低的节点效率，而在S1具有更高的效率（p < 0.05，未校正）。手掌SSR的潜伏期与感觉运动皮层内的zFC以及S1的节点效率/度显著正相关（p < 0.01）。手掌和足底SSR的振幅与DLPFC的节点效率显著正相关（p < 0.05）。
我们的研究结果表明，PCS患者ANS的中枢和外周部分均存在改变。这些初步结果表明，PCS可能导致ANS外周和中枢方面的变化，这将有助于扩展对ANS在PCS中作用的理解，为评估和治疗提供新的视角。
本研究已在中国临床试验注册中心注册（注册号：ChiCTR2200064342；注册日期：2022/10/3）。
