Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Can J Neurol Sci. 2010 Sep;37 Suppl 2:S16-23. doi: 10.1017/s0317167100022393.
Multiple sclerosis (MS) is traditionally considered an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) with much knowledge available to support this view. However, this characterization implies that the primary event is an aberrant immune response directed at CNS antigens, promoting inflammation and later driving progressive axo-glial degeneration. Trials with potent anti-inflammatory agents and detailed neuropathological studies raise questions about this sequence of events. This hypothetical paper argues that MS may be primarily a "cytodegenerative" disease, possibly first involving the oligodendrocyte/myelin unit. Liberation of autoantigens secondarily recruits an immune response, the force of which heavily depends on the host's immune predisposition. Thus, the spectrum of MS from highly aggressive Marburg type, to primary progressive disease with little inflammatory burden, is governed by a "convolution" between the underlying cytodegeneration and the host's immune predilection. Clinical heterogeneity may be a reflection of a variable immune response, whereas in reality, the "real MS" may be a homogeneous degenerative process analogous to well known primary neurodegenerative diseases.
多发性硬化症（MS）传统上被认为是一种中枢神经系统（CNS）的自身免疫性炎症脱髓鞘疾病，有大量知识支持这一观点。然而，这种特征表明主要事件是针对 CNS 抗原的异常免疫反应，促进炎症，随后导致进行性轴突-胶质退化。具有强大抗炎作用的试验药物和详细的神经病理学研究对这一系列事件提出了质疑。这篇假设性论文认为，MS 可能主要是一种“细胞退行性”疾病，可能首先涉及少突胶质细胞/髓鞘单位。自身抗原的释放随后招募免疫反应，其强度在很大程度上取决于宿主的免疫倾向。因此，从高度侵袭性的马尔堡型到炎症负担较小的原发性进行性疾病，MS 的谱受到潜在细胞退行性变和宿主免疫倾向之间的“卷积”的控制。临床异质性可能反映了免疫反应的变化，而实际上，“真正的 MS”可能是一种类似于众所周知的原发性神经退行性疾病的同质退行性过程。
