Van Schependom Jeroen, Guldolf Kaat, D'hooghe Marie Béatrice, Nagels Guy, D'haeseleer Miguel
1Neurology Department, Universitair Ziekenhuis Brussel; Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussel, Belgium.
2Radiology Department Universitair Ziekenhuis Brussel, Brussels, Belgium.
Transl Neurodegener. 2019 Dec 9;8:37. doi: 10.1186/s40035-019-0178-4. eCollection 2019.
Multiple sclerosis (MS) is a complex chronic inflammatory and degenerative disorder of the central nervous system. Accelerated brain volume loss, or also termed atrophy, is currently emerging as a popular imaging marker of neurodegeneration in affected patients, but, unfortunately, can only be reliably interpreted at the time when irreversible tissue damage likely has already occurred. Timing of treatment decisions based on brain atrophy may therefore be viewed as suboptimal.
This Narrative Review focuses on alternative techniques with the potential of detecting neurodegenerative events in the brain of subjects with MS prior to the atrophic stage. First, metabolic and molecular imaging provide the opportunity to identify early subcellular changes associated with energy dysfunction, which is an assumed core mechanism of axonal degeneration in MS. Second, cerebral hypoperfusion has been observed throughout the entire clinical spectrum of the disorder but it remains an open question whether this serves as an alternative marker of reduced metabolic activity, or exists as an independent contributing process, mediated by endothelin-1 hyperexpression. Third, both metabolic and perfusion alterations may lead to repercussions at the level of network performance and structural connectivity, respectively assessable by functional and diffusion tensor imaging. Fourth and finally, elevated body fluid levels of neurofilaments are gaining interest as a biochemical mirror of axonal damage in a wide range of neurological conditions, with early rises in patients with MS appearing to be predictive of future brain atrophy.
Recent findings from the fields of advanced neuroradiology and neurochemistry provide the promising prospect of demonstrating degenerative brain pathology in patients with MS before atrophy has installed. Although the overall level of evidence on the presented topic is still preliminary, this Review may pave the way for further longitudinal and multimodal studies exploring the relationships between the abovementioned measures, possibly leading to novel insights in early disease mechanisms and therapeutic intervention strategies.
多发性硬化症（MS）是一种中枢神经系统的复杂慢性炎症性和退行性疾病。脑容量加速丢失，或也称为萎缩，目前正成为受影响患者神经退行性变的一种常见影像学标志物，但不幸的是，只有在可能已经发生不可逆组织损伤时才能可靠地解读。因此，基于脑萎缩做出治疗决策的时机可能被认为是次优的。
本叙述性综述重点关注在萎缩阶段之前检测MS患者大脑中神经退行性事件的替代技术。首先，代谢和分子成像提供了识别与能量功能障碍相关的早期亚细胞变化的机会，能量功能障碍被认为是MS轴突变性的核心机制。其次，在该疾病的整个临床谱中都观察到了脑灌注不足，但这是作为代谢活性降低的替代标志物，还是作为由内皮素-1过度表达介导的独立促成过程存在，仍是一个悬而未决的问题。第三，代谢和灌注改变可能分别导致网络性能和结构连通性水平的影响，可通过功能和扩散张量成像进行评估。第四也是最后一点，神经丝体液水平升高作为多种神经系统疾病中轴突损伤的生化反映正受到关注，MS患者早期升高似乎可预测未来脑萎缩。
先进神经放射学和神经化学领域的最新发现为在萎缩出现之前在MS患者中证明脑退行性病变提供了有希望的前景。尽管关于本主题的总体证据水平仍处于初步阶段，但本综述可能为进一步的纵向和多模态研究铺平道路，探索上述措施之间的关系，可能会在早期疾病机制和治疗干预策略方面带来新的见解。
