Fatigue stands among the most debilitating multiple sclerosis (MS) manifestations. Several pathophysiological mechanisms have been proposed at its origin. However, unmet needs still exist, and further investigations are required to better understand and manage this complaint. A new imaging modality—the phosphorous magnetic resonance spectroscopy (³¹P-MRS)—might help studying fatigue by allowing the measurement of energy metabolites of various cerebral regions. Therefore, this work aimed to explore the association between fatigue and brain energy status. Thirty MS patients with progressive disease forms completed the study. Their sociodemographic and clinical data including fatigue and disability scores [i.e., Fatigue Severity Scale (FSS) and Expanded Disability Status Scale (EDSS)] were collected. ³¹P-MRS spectra of (1) bilateral frontoparietal area and (2) centrum semiovale normal appearing white matter (NAWM) were obtained. Percentages of phosphocratine and β-adenosine triphosphate (β-ATP) were calculated. FSS scores were found to be directly correlated with the frontoparietal β-ATP % (p < 0.05). However, there were no significant correlations between FSS scores and NAWM energy metabolites or clinical data (i.e., age, EDSS scores or disease duration). These findings point toward the existence of a link between fatigue severity and the amount of cerebral ATP metabolites. Such a link might reflect either a high production or low utilization of ATP, both of which were paralleled with increased fatigue perception. While the former would be due to a redistribution of ion channels along demyelinated axons and subsequent changes in mitochondrial activity; the latter could be interpreted in the light of neuronal loss which would lead to a decrease in ATP utilization and accumulation of its metabolites.

疲劳是最使人虚弱的多发性硬化症 (MS) 表现之一。已经提出了几种病理生理机制。但是，未满足的需求仍然存在，需要进一步调查以更好地理解和管理此投诉。一种新的成像方式——磷磁共振波谱 ( ³¹ P-MRS)——可以通过测量大脑各个区域的能量代谢物来帮助研究疲劳。因此，这项工作旨在探索疲劳与脑能量状态之间的关联。30 名患有进展性疾病的 MS 患者完成了这项研究。收集了他们的社会人口学和临床数据，包括疲劳和残疾评分 [即疲劳严重程度量表 (FSS) 和扩展残疾状态量表 (EDSS)]。获得了（1）双侧额顶区和（2）半卵圆中心正常出现的白质（NAWM）的^31个P-MRS谱。计算了磷酸肌酸和 β-三磷酸腺苷 (β-ATP) 的百分比。发现 FSS 分数与额顶叶 β-ATP % ( p < 0.05)。然而，FSS 评分与 NAWM 能量代谢物或临床数据（即年龄、EDSS 评分或疾病持续时间）之间没有显着相关性。这些发现表明疲劳严重程度与大脑 ATP 代谢物的数量之间存在联系。这种联系可能反映了 ATP 的高产量或低利用率，这两者都伴随着疲劳感的增加。前者是由于离子通道沿脱髓鞘轴突的重新分布以及随后线粒体活性的变化；后者可以根据神经元损失来解释，这将导致 ATP 利用率和其代谢物积累的减少。