Filippi Massimo, Rocca Maria Assunta
Neuroimaging Research Unit, Dept. of Neurology Scientific Institute and University Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
J Neurol. 2005 Nov;252 Suppl 5:v16-24. doi: 10.1007/s00415-005-5004-5.
The classical view of MS as a chronic inflammatory demyelinating disease leading to the formation of focal central nervous system (CNS) white matter (WM) lesions has been recently challenged by pathological studies and by the extensive application of modern MRI-based techniques. There is now overwhelming evidence supporting the following statements: MS causes widespread tissue damage in the normal-appearing white matter (NAWM) of the brain and spinal cord, whose extent and severity is more strictly associated to the clinical manifestations of the disease than the extent of focal pathology. Discrete, macroscopic lesions are just the tip of the iceberg of MS pathology. Grey matter (GM) damage is a consistent feature of all MS phenotypes, which is progressive from the start of the relapsing-remitting phase of the disease. As is the case for WM, GM damage is also a mixture of focal lesions and diffuse pathology. High-field strength MR scanners are improving our ability to image focal GM lesions and modern MR-based techniques are enabling us to quantify in vivo the extent and severity of GM pathology, which have been shown to correlate only moderately with the amount of WM changes. At least part of GM pathology in MS is not secondary to retrograde degeneration of fibers traversing WM lesions. The neurodegenerative component of the disease is not a late phenomenon and it is not completely driven by inflammatory demyelination. In fact, neurodegeneration occurs very early in the course of MS and the correlation between MRI measures of inflammation and neurodegeneration is weak in all disease phases. The interplay of inflammation and neurodegeneration is a complex and still poorly understood phenomenon. At least part of MS-related neurodegeneration is not directly driven by Wallerian degeneration. Functional cortical changes can be seen in virtually all MS patients and are likely to play a central role in the ability of the MS brain to respond to tissue injury and, hence, limit the functional consequences of structural damage. MS disability is not just the result of tissue destruction but rather a balance between tissue destruction, tissue repair and adaptive cortical reorganization. All of this calls for the concept of MS as a focal, inflammatory demyelinating, WM disease to be reexamined and to start viewing MS as a diffuse CNS disease with an important neurodegenerative component. This is central for identifying novel and effective treatment strategies.
将多发性硬化症（MS）视为一种导致局灶性中枢神经系统（CNS）白质（WM）病变形成的慢性炎症性脱髓鞘疾病的传统观点，最近受到了病理学研究以及基于现代磁共振成像（MRI）技术的广泛应用的挑战。现在有压倒性的证据支持以下观点：MS会在大脑和脊髓的正常外观白质（NAWM）中造成广泛的组织损伤，其范围和严重程度与疾病的临床表现的关联比局灶性病理改变的程度更为紧密。离散的宏观病变仅仅是MS病理学的冰山一角。灰质（GM）损伤是所有MS表型的一个一致特征，从疾病复发缓解期开始就呈进行性发展。与WM情况一样，GM损伤也是局灶性病变和弥漫性病理改变的混合。高场强MR扫描仪正在提高我们对局灶性GM病变成像的能力，基于现代MR的技术使我们能够在体内量化GM病理学的范围和严重程度，已表明其与WM变化量仅呈中度相关。MS中至少部分GM病理学并非继发于穿过WM病变的纤维的逆行性变性。该疾病的神经退行性成分并非晚期现象，也并非完全由炎症性脱髓鞘驱动。事实上，神经退行性变在MS病程中很早就会发生，并且在所有疾病阶段，炎症的MRI测量值与神经退行性变之间的相关性都很弱。炎症与神经退行性变之间的相互作用是一个复杂且仍知之甚少的现象。至少部分与MS相关的神经退行性变并非直接由华勒氏变性驱动。几乎所有MS患者都可见功能性皮质改变，并且这些改变可能在MS大脑对组织损伤作出反应的能力中发挥核心作用，从而限制结构损伤的功能后果。MS残疾不仅仅是组织破坏的结果，而是组织破坏、组织修复和适应性皮质重组之间的平衡。所有这些都要求重新审视将MS视为一种局灶性、炎症性脱髓鞘性WM疾病的概念，并开始将MS视为一种具有重要神经退行性成分的弥漫性CNS疾病。这对于确定新的有效治疗策略至关重要。
