Minagar Alireza, Toledo Eduardo Gonzalez, Alexander J Steven, Kelley Roger E
Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
J Neuroimaging. 2004 Jul;14(3 Suppl):5S-10S. doi: 10.1177/1051228404266263.
For more than a century, multiple sclerosis was viewed as a disease process characterized by oligodendrocyte and myelin loss, and research into the pathogenesis of multiple sclerosis was mainly focused on the mechanisms of inflammation. However, with development of more sophisticated neuroimaging and molecular biology techniques, attention has shifted to new aspects of pathogenesis of multiple sclerosis: axonal loss and neurodegeneration. Evidence is increasing that tissue destruction, primarily axonal loss and neurodegeneration, is a key element in the pathogenesis of multiple sclerosis. In addition, it is now known that brain and spinal cord atrophy begins early in the disease process of multiple sclerosis and advances relentlessly throughout the course of the disease. Cumulative data suggest that axonal loss is the major determinant of progressive neurologic disability in patients with multiple sclerosis. Magnetic resonance imaging and magnetic resonance spectroscopy in patients with multiple sclerosis for < 5 years indicate brain atrophy and loss of axonal integrity. Neurodegeneration and axonal loss in patients with multiple sclerosis are initially accompanied by a local response from oligodendrocyte progenitor cells and some remyelination. However, these repair mechanisms eventually fail, and patients typically develop generalized brain atrophy, cognitive decline, and permanent disability. Although the exact mechanisms underlying central nervous system atrophy in patients with multiple sclerosis are largely unknown, evidence exists that atrophy may represent an epiphenomenon related to the effects of dynamic inflammation within the central nervous system, including demyelination, axonal injury, neuronal loss, Wallerian degeneration, and possibly iron deposition. This article summarizes the potential mechanisms involved in central nervous system atrophy in patients with multiple sclerosis.
一个多世纪以来，多发性硬化症一直被视为一种以少突胶质细胞和髓鞘丢失为特征的疾病过程，对多发性硬化症发病机制的研究主要集中在炎症机制上。然而，随着更先进的神经影像学和分子生物学技术的发展，人们的注意力已转向多发性硬化症发病机制的新方面：轴突丢失和神经退行性变。越来越多的证据表明，组织破坏，主要是轴突丢失和神经退行性变，是多发性硬化症发病机制中的关键因素。此外，现在已知脑和脊髓萎缩在多发性硬化症病程早期就已开始，并在整个疾病过程中持续进展。累积数据表明，轴突丢失是多发性硬化症患者进行性神经功能残疾的主要决定因素。对病程小于5年的多发性硬化症患者进行磁共振成像和磁共振波谱分析显示存在脑萎缩和轴突完整性丧失。多发性硬化症患者的神经退行性变和轴突丢失最初伴有少突胶质细胞前体细胞的局部反应和一些髓鞘再生。然而，这些修复机制最终会失效，患者通常会出现广泛性脑萎缩、认知衰退和永久性残疾。尽管多发性硬化症患者中枢神经系统萎缩的确切机制在很大程度上尚不清楚，但有证据表明萎缩可能是一种与中枢神经系统内动态炎症效应相关的附带现象，包括脱髓鞘、轴突损伤、神经元丢失、华勒氏变性以及可能的铁沉积。本文总结了多发性硬化症患者中枢神经系统萎缩所涉及的潜在机制。
