Nikitina M A, Bragina E Yu, Ivanova S A, Boyko A S, Levchuk L A, Nazarenko M S, Alifirova V M
Siberian State Medical University, Tomsk, Russia.
Tomsk National Research Medical Center Russian Academy of Sciences, Tomsk, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(9):79-87. doi: 10.17116/jnevro202412409179.
To study the prevalence of chronic fatigue syndrome (CFS) and association of CFS with other clinical and neuropsychological manifestations of Parkinson's disease (PD) as well as with serum inflammatory markers and genetic polymorphisms.
The study included 533 patients with PD. All patients underwent clinical, neurological examination and neuropsychological testing using validated questionnaires: MoCA test, HADS, BDI-II, the Fatigue Severity Scale (FSS). Serum concentrations of inflammatory markers (slCAM-1, sVCAM-1, NCAM, CCL5, PAI-1 and MPO) were assessed in 144 patients using xMAP technology. A case-control study of (rs2107538) and (rs2227631) gene polymorphisms was performed in connection with PD development and in groups differing in the presence/absence of CFS in PD. In addition, the relationship of these polymorphisms with variability in the levels of the corresponding proteins in the blood serum of patients was studied. Genotyping of (rs2107538) and (rs2227631) polymorphisms was performed using real-time PCR with TaqMan probes.
CFS is common in 66.7% of patients in the PD group. In addition, non-motor symptoms (emotional-affective, cognitive, autonomic disorders and pain) were more common in patients with CFS. A strong correlation has been established between the severity of CFS assessed with FSS and serum concentrations of CCL5, sVCAM-1, NCAM and slCAM-1. In newly diagnosed patients with PD who were not taking antiparkinsonian drugs at the time of the study and had CFS, higher correlations were noted between inflammatory markers and the severity of CFS manifestations. When comparing the distribution of genotypes and alleles of CCL5 (rs2107538) and PAI-1 (rs2227631) polymorphisms, some differences were found between the groups of patients with PD and controls (<0.05). However, these polymorphisms did not affect the variability of serum protein levels CCL5 and PAI-1, respectively, nor did they affect the development of CFS in patients with PD.
CFS is common in PD, and patients with PD and CFS are characterized by elevated levels of serum markers CCL5, sVCAM-1, slCAM-1 and NCAM, suggesting the importance of the inflammatory component in the development of neurodegenerative disease. In addition, the clinical course of PD in patients with CFS is aggravated by other non-motor manifestations, including emotional-affective, cognitive, autonomic disorders and pain. These results highlight the potential contribution of an inflammatory component to the development of fatigue associated with PD, starting from the earliest clinical stages of the disease.
研究慢性疲劳综合征（CFS）的患病率，以及CFS与帕金森病（PD）的其他临床和神经心理学表现、血清炎症标志物及基因多态性之间的关联。
该研究纳入了533例PD患者。所有患者均接受了临床、神经学检查以及使用经过验证的问卷进行的神经心理学测试：蒙特利尔认知评估量表（MoCA）测试、医院焦虑抑郁量表（HADS）、贝克抑郁量表第二版（BDI-II）、疲劳严重程度量表（FSS）。采用xMAP技术对144例患者的血清炎症标志物（可溶性细胞间黏附分子-1（slCAM-1）、可溶性血管细胞黏附分子-1（sVCAM-1）、神经细胞黏附分子（NCAM）、趋化因子配体5（CCL5）、纤溶酶原激活物抑制剂-1（PAI-1）和髓过氧化物酶（MPO））浓度进行了评估。针对与PD发生以及PD中有无CFS的不同组患者，开展了CCL5基因（rs2107538）和PAI-1基因（rs2227631）多态性的病例对照研究。此外，还研究了这些多态性与患者血清中相应蛋白质水平变化的关系。使用带有TaqMan探针的实时聚合酶链反应对CCL5基因（rs2107538）和PAI-1基因（rs2227631）多态性进行基因分型。
PD组中66.7%的患者存在CFS。此外，CFS患者的非运动症状（情感、认知、自主神经功能障碍和疼痛）更为常见。通过FSS评估的CFS严重程度与CCL5、sVCAM-1、NCAM和slCAM-1的血清浓度之间建立了强相关性。在研究时未服用抗帕金森病药物且患有CFS的新诊断PD患者中，炎症标志物与CFS表现的严重程度之间的相关性更高。比较CCL5基因（rs2107538）和PAI-1基因（rs2227631）多态性的基因型和等位基因分布时，发现PD患者组与对照组之间存在一些差异（P<0.05）。然而，这些多态性分别未影响血清蛋白CCL5和PAI-1水平的变化，也未影响PD患者中CFS的发生。
CFS在PD中很常见，PD合并CFS的患者血清标志物CCL5、sVCAM-1、slCAM-1和NCAM水平升高，提示炎症成分在神经退行性疾病发生中的重要性。此外，CFS患者的PD临床病程因其他非运动表现而加重，包括情感、认知、自主神经功能障碍和疼痛。这些结果突出了炎症成分从疾病最早临床阶段开始对与PD相关疲劳发生的潜在作用。
