Normal Appearing White Matter N-Acetylaspartate Changes Impact on Fatigue in Multiple Sclerosis

Vasilena Petrova, Latchesar Traykov
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Abstract

Background: Fatigue is one of the most frequent complaints presented by multiple sclerosis patients. Fatigue may be multifactorial. Proton magnetic resonance spectroscopy studies have shown significant reductions in N-acetylaspartate/creatine ratios in multiple brain regions among fatigued multiple sclerosis patients in comparison to non-fatigued multiple sclerosis patients, suggesting axonal loss as a contributing factor. Females are twice as likely to develop the disease. Aim: To evaluate gender variability in fatigue scores in relapsing-remitting multiple sclerosis patients. To explore potential gender differences in metabolite profiles of normal appearing white matter. To correlate metabolite changes distribution with fatigue severity and to evaluate the gender impact. Methods: We enrolled 50 relapsing-remitting multiple sclerosis patients on disease modifying treatment and 28 healthy controls. All participants underwent proton magnetic resonance spectroscopy of normal appearing white matter corresponding regions and fatigue severity evaluation. Results: We found higher fatigue scores in the multiple sclerosis group, due to greater severity in female subjects. We found a significant decrease of N-acetylaspartate/creatine ratio with increase in N-acetylaspartate, choline, and creatine levels in multiple sclerosis subjects. N-acetylaspartate and choline levels were significantly higher in the multiple sclerosis males. Female multiple sclerosis patients presented with lower N-acetylaspartate levels than healthy controls and greater increases in Fatigue Severity Scale score. Regression analysis revealed metabolite specific relationships between fatigue against metabolite variables. Conclusion: Proton magnetic resonance spectroscopy registered differences in metabolite profiles in normal appearing white matter male and female multiple sclerosis subjects. We might presume gender dependent specifiers in metabolite profiles in relapsing- remitting multiple sclerosis. They impact fatigue severity. N- acetyaspartate might be crucial contributor in central fatigue in multiple sclerosis. Bioenergetic role of N-acetylaspartate needs further collaborative research on genetics and electrical properties of neurons to reveal the underlying mechanism of fatigue and conductivity deterioration.
正常白质n -乙酰天冬氨酸变化对多发性硬化症患者疲劳的影响
背景:疲劳是多发性硬化症患者最常见的主诉之一。疲劳可能是多因素的。质子磁共振波谱研究显示,与非疲劳型多发性硬化症患者相比,疲劳型多发性硬化症患者多个脑区n-乙酰天冬氨酸/肌酸比值显著降低,提示轴突损失是一个促成因素。女性患这种疾病的可能性是男性的两倍。目的:评价复发缓解型多发性硬化症患者疲劳评分的性别差异。探讨正常白质代谢产物谱的潜在性别差异。将代谢物变化分布与疲劳严重程度相关联,并评估性别影响。方法:我们招募了50例接受疾病改善治疗的复发缓解型多发性硬化症患者和28名健康对照。所有参与者都进行了正常白质相应区域的质子磁共振波谱检查和疲劳严重程度评估。结果:我们发现多发性硬化症组的疲劳评分较高,因为女性受试者的严重程度更高。我们发现,在多发性硬化症患者中,n -乙酰天冬氨酸/肌酸比值随着n -乙酰天冬氨酸、胆碱和肌酸水平的增加而显著降低。n -乙酰天冬氨酸和胆碱水平在多发性硬化症男性中显著升高。女性多发性硬化症患者的n -乙酰天冬氨酸水平低于健康对照组,疲劳严重程度量表评分增加较大。回归分析揭示了疲劳与代谢物变量之间的代谢物特异性关系。结论:质子磁共振波谱记录了表现正常的男性和女性多发性硬化症患者白质代谢物谱的差异。我们可以假设在复发-缓解型多发性硬化症的代谢物谱中存在性别依赖的指示因子。它们影响疲劳的严重程度。N-乙酰天冬氨酸可能是多发性硬化症中枢性疲劳的重要诱因。n -乙酰天冬氨酸的生物能量作用需要进一步的遗传学和神经元电特性的合作研究,以揭示疲劳和电导率下降的潜在机制。
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