Background

Cerebral metabolic rate of oxygen (CMRO₂), a measure of global oxygen metabolism, reflects resting cellular activity. The mechanisms underlying fatigue and cognitive dysfunction in multiple sclerosis (MS) remain unknown. If fatigue indeed reflects ongoing autoimmune activity and cortical reorganization, and cognitive decline is the result of gray matter atrophy and white matter degeneration, we postulate that changes in CMRO₂ should reflect disease activity and predict these symptoms.

Objective

We sought to utilize T₂-Relaxation-Under-Spin-Tagging (TRUST) and phase-contrast (PC) MRI to measure global CMRO₂ to understand its relationships to white matter microstructure, fatigue and cognitive dysfunction.

Methods

We measured venous oxygenation (TRUST) and cerebral blood flow (PC-MRI) in superior sagittal sinus to calculate global CMRO₂ and diffusion tensor imaging (DTI) to evaluate white matter microstructure in healthy controls (HC) and MS patients. Participants underwent neuropsychological examinations including Modified Fatigue Impact Scale (MFIS) and Symbol-Digit-Modalities Test (SDMT).

Results

We observed lower CMRO₂ in MS patients compared to HC. After controlling for demographic and disease characteristics (i.e., age, education, disability, lesion volume), CMRO₂ predicted increased fatigue (MFIS) and reduced cognitive performance (SDMT) in MS patients. Finally, MS patients with higher CMRO₂ have reduced FA in normal-appearing white-matter.

Conclusion

Altogether, these results suggest that increased CMRO₂ reflects ongoing demyelination and autoimmune activity which plays an important role in both fatigue and cognitive dysfunction.

中文翻译：

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基线脑代谢预测多发性硬化症患者的疲劳和认知。

背景

脑氧代谢率（CMRO ₂）是衡量整体氧代谢的指标，反映了静止的细胞活动。在多发性硬化症（MS）中疲劳和认知功能障碍的潜在机制仍然未知。如果疲劳确实反映了持续的自身免疫活性和皮质重组，而认知能力下降是灰质萎缩和白质变性的结果，则我们假设CMRO _2的变化应反映疾病活动并预测这些症状。

目的

我们试图利用T _2-放松下旋转标记（TRUST）和相衬（PC）MRI来测量整体CMRO _2，以了解其与白质微结构，疲劳和认知功能障碍的关系。

方法

我们测量了上矢状窦的静脉氧合（TRUST）和脑血流量（PC-MRI），以计算整体CMRO ₂和弥散张量成像（DTI），以评估健康对照（HC）和MS患者的白质微观结构。参加者接受了神经心理学检查，包括改良的疲劳影响量表（MFIS）和符号数字方式测试（SDMT）。

结果

我们观察到MS患者的CMRO ₂低于HC。在控制了人口统计学和疾病特征（即年龄，教育程度，残疾程度，病灶数量）之后，CMRO ₂预测MS患者的疲劳（MFIS）增加和认知能力（SDMT）降低。最后，具有较高CMRO _2的MS患者在正常出现的白色物质中的FA降低。

结论

总之，这些结果表明，CMRO _2的增加反映了持续的脱髓鞘和自身免疫活性，这在疲劳和认知功能障碍中都起着重要作用。