Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
Mult Scler Relat Disord. 2022 Jan;57:103432. doi: 10.1016/j.msard.2021.103432. Epub 2021 Nov 30.
Multiple sclerosis (MS) is the most common non-traumatic cause of disability in younger adults. MS can be presented with a wide range of symptoms such as cognitive impairment (CI). Oxidative stress (OXS) is a major basis of the pathogenesis of MS. There is a positive correlation between OXS factors and the progression of the disease in MS patients. There are limited studies regarding the role of OXS in MS-related CI. In this study, as an exploratory analysis, we assess the role of endogenous antioxidants and OXS factors in cognitive function, the severity of disability due to MS, and demographic findings in a sample of MS patients.
Adult (>18 years old) patients with a definite diagnosis of MS based on 2017 revised MacDonald criteria were included in this study. The neurophysiological assessment was conducted, using the validated Persian version of minimal assessment of cognitive function in multiple sclerosis (MACFIMS) battery, which is composed of seven different tests. Based on the structure of the battery, CI was defined as a failure in at least two different components of the MACFIMS battery. The patients were separated into two groups of CI and non-CI. Examined antioxidant factors included catalase Activity (CAT), Glutathione Peroxidase 1 (GPX1), Glutathione Peroxidase 2 (GPX2), Reduced Glutathione (GSH), Superoxide Dismutase (SOD), and serum total antioxidant capacity (TAC). Malondialdehyde (MDA) was also measured as an OXS marker.
71 patients were involved in this study. The type of MS was relapsing-remitting MS (RRMS) in 80.28% of the participants. Disease duration (P<0.01), type of MS (p<0.01), and EDSS score (p<0.01) were different between CI and non-CI groups, but there were not any significant differences in CAT (p = 0.80), GPX1 (p = 0.71), GPX2 (p = 0.41), GSH (p = 0.96), TAC (p = 0.13), SOD (p = 0.37), and MDA (p = 0.82). A significant difference between RRMS and progressive MS (PMS) patients in the levels of GPX1 (p = 0.01), GPX2 (p = 0.01), and SOD (p = 0.01) was observed. Also, we found higher circulatory levels of CAT (p = 0.02) and TAC (p<0.01) in male MS patients. We found significant correlations between aging and CAT (R = 0.28; p = 0.01), GPX1 (R = 0.36; p<0.01), GPX2 (R = 0.34; p<0.01), and SOD (R = 0.40; p<0.01). EDSS, the duration of the disease, relapse rate, and the number of impaired cognitive tasks were not correlated with any of investigated OXS or antioxidant factors (p>0.05). In terms of a detailed investigation of associations between MACFIMS battery components and levels of OXS and antioxidant factors, there were no significant relations in this regard (p>0.05). Based on the logistic regression multivariate analysis, only disease duration (p = 0.03) and GPX1 (p = 0.01) were independently associated with CI in MS patients in our sample.
The circulatory levels of GPX1, GPX2, and SOD are significantly different between RRMS and PMS patients. Neither endogenous antioxidants nor MDA, as an OXS biomarker, are associated with the cognitive function or level of physical disability in MS patients. Limitations of this study suggest a need for future studies in a larger sample of MS patients.
多发性硬化症(MS)是年轻成年人中最常见的非外伤性致残原因。MS 可表现出广泛的症状,如认知障碍(CI)。氧化应激(OXS)是 MS 发病机制的主要基础。MS 患者中 OXS 因素与疾病进展之间存在正相关关系。关于 OXS 在 MS 相关 CI 中的作用的研究有限。在这项研究中,作为一项探索性分析,我们评估了内源性抗氧化剂和 OXS 因素在认知功能、MS 患者残疾严重程度以及人口统计学发现方面的作用。
本研究纳入了根据 2017 年修订的 MacDonald 标准明确诊断为 MS 的成年(>18 岁)患者。使用经过验证的波斯语版多发性硬化症最小认知功能评估量表(MACFIMS)电池进行神经生理学评估,该电池由七个不同的测试组成。根据电池的结构,CI 定义为 MACFIMS 电池的至少两个不同组件中的失败。将患者分为 CI 和非 CI 两组。检查的抗氧化因素包括过氧化氢酶活性(CAT)、谷胱甘肽过氧化物酶 1(GPX1)、谷胱甘肽过氧化物酶 2(GPX2)、还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和血清总抗氧化能力(TAC)。还测量了丙二醛(MDA)作为 OXS 标志物。
本研究共有 71 名患者参与。参与者中 80.28%为复发缓解型 MS(RRMS)。CI 和非 CI 组之间在疾病持续时间(P<0.01)、MS 类型(p<0.01)和 EDSS 评分(p<0.01)方面存在差异,但 CAT(p=0.80)、GPX1(p=0.71)、GPX2(p=0.41)、GSH(p=0.96)、TAC(p=0.13)、SOD(p=0.37)和 MDA(p=0.82)之间无显著差异。我们观察到 RRMS 和进行性 MS(PMS)患者之间 GPX1(p=0.01)、GPX2(p=0.01)和 SOD(p=0.01)水平存在显著差异。此外,我们发现男性 MS 患者的 CAT(p=0.02)和 TAC(p<0.01)循环水平更高。我们发现 CAT(R=0.28;p=0.01)、GPX1(R=0.36;p<0.01)、GPX2(R=0.34;p<0.01)和 SOD(R=0.40;p<0.01)与年龄呈显著相关性。EDSS、疾病持续时间、复发率和受损认知任务数量与任何研究的 OXS 或抗氧化因素均无相关性(p>0.05)。在 MACFIMS 电池组件与 OXS 和抗氧化因素水平之间的关联的详细调查中,在这方面没有显著关系(p>0.05)。基于多元逻辑回归分析,只有疾病持续时间(p=0.03)和 GPX1(p=0.01)与我们样本中的 MS 患者的 CI 独立相关。
RRMS 和 PMS 患者之间 GPX1、GPX2 和 SOD 的循环水平存在显著差异。内源性抗氧化剂和 MDA 作为 OXS 生物标志物均与 MS 患者的认知功能或身体残疾程度无关。本研究的局限性表明需要在更大的 MS 患者样本中进行进一步研究。