Background 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. Main body 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. Conclusions 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.

中文翻译：

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在不可逆的脑组织损失开始之前检测多发性硬化症的神经退行性病变。

背景多发性硬化症（MS）是一种复杂的中枢神经系统慢性炎症和退行性疾病。加速脑容量减少，或也称为萎缩，目前正在成为受影响患者神经退行性变的流行成像标志物，但不幸的是，只能在可能已经发生不可逆组织损伤时才能可靠地解释。因此，基于脑萎缩的治疗决定时机可能被视为次优。主体 本叙述性评论侧重于具有在萎缩阶段之前检测 MS 受试者大脑中的神经退行性事件的潜力的替代技术。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，这是 MS 轴突变性的假定核心机制。其次，在整个疾病的临床谱中都观察到脑灌注不足，但它是否作为代谢活动降低的替代标志物，还是作为由内皮素-1 高表达介导的独立贡献过程存在，仍然是一个悬而未决的问题。第三，代谢和灌注改变都可能导致网络性能和结构连接水平的影响，分别可通过功能和扩散张量成像进行评估。第四，也是最后一点，神经丝的体液水平升高作为各种神经系统疾病中轴突损伤的生化镜像引起了人们的兴趣，MS 患者的早期升高似乎预示着未来的脑萎缩。结论 来自高级神经放射学和神经化学领域的最新发现为在萎缩之前证明 MS 患者的退行性脑病理学提供了有希望的前景。尽管关于所提出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探索上述措施之间关系的纵向和多模式研究铺平道路，可能会导致对早期疾病机制和治疗干预策略的新见解。