Karmon Yuval, Ramanathan Murali, Minagar Alireza, Zivadinov Robert, Weinstock-Guttman Bianca
The Jacobs Neurological Institute, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY, USA.
Neurol Res. 2012 Oct;34(8):754-60. doi: 10.1179/1743132812Y.0000000077.
This article reviews vascular risk factors with specific emphasis on lipid abnormalities reported to be associated with multiple sclerosis (MS).
The current paradigm of MS, supported only partially by MS lesion histopathology and its animal model (experimental allergic encephalomyelitis) considers MS to be a predominantly autoimmune disease. Until recently, most of the known risk factors for MS were interpreted in the context of the autoimmune theory, which still fails to explain why genetically close populations exposed to similar pathogens and/or environmental risk factors have different incidences of MS. Therapies which partially modulate the inflammatory arm of MS pathogenesis, fail to achieve similar benefits in later disease stages, when less inflammatory lesions and more neurodegeneration are present. Several studies have reported an increased cardiovascular morbidity in MS patients and that vascular comorbidity at any time during the disease course also increased the risk of progressive disability. A condition named chronic cerebrospinal venous insufficiency provided a different perspective, on the possible association of MS with the abnormalities of the venous system. Our recent findings revealed increased prevalence of chronic cerebrospinal venous insufficiency associated with MS disease progression as well as with other neurologic disorders. On the other hand, recently emerging evidence indicates that there is an association between lipoproteins and cholesterol metabolism and MS disease progression. Expanded disability status scale worsening was associated with higher baseline low-density lipoprotein and total cholesterol, and higher serum high-density lipoprotein levels were associated with lower contrast-enhancing T1-weigthed lesion volume. It is thought that apolipoprotein A-1 and paraoxonase anti-oxidant enzyme are associated with high-density lipoprotein and contribute to its anti-oxidant and anti-inflammatory properties. A significant inter-dependence was also recently demonstrated between vitamin D, one of the best known environmental risk factors for MS and MS disease progression and the serum lipid profile. Future work in this direction is required in order to better elucidate the role of lipid metabolism and vascular pathology in pathogenesis of MS.
本文回顾血管危险因素，特别强调据报道与多发性硬化症（MS）相关的脂质异常。
MS的当前范式仅部分得到MS病变组织病理学及其动物模型（实验性变应性脑脊髓炎）的支持，该范式认为MS主要是一种自身免疫性疾病。直到最近，大多数已知的MS危险因素都是在自身免疫理论的背景下进行解释的，但该理论仍无法解释为什么基因相近、暴露于相似病原体和/或环境危险因素的人群MS发病率不同。部分调节MS发病机制炎症环节的疗法，在疾病后期（此时炎症性病变较少而神经退行性变较多）未能取得类似的疗效。多项研究报告称MS患者心血管疾病发病率增加，且疾病过程中任何时候的血管合并症也会增加进展性残疾的风险。一种名为慢性脑脊髓静脉功能不全的病症为MS与静脉系统异常之间的可能关联提供了不同的视角。我们最近的研究结果显示，与MS疾病进展以及其他神经系统疾病相关的慢性脑脊髓静脉功能不全患病率增加。另一方面，最近出现的证据表明脂蛋白和胆固醇代谢与MS疾病进展之间存在关联。扩展残疾状态量表恶化与更高的基线低密度脂蛋白和总胆固醇相关，而更高的血清高密度脂蛋白水平与更低的对比增强T1加权病变体积相关。据认为，载脂蛋白A-1和对氧磷酶抗氧化酶与高密度脂蛋白相关，并有助于其抗氧化和抗炎特性。最近还证明，MS最知名的环境危险因素之一维生素D与MS疾病进展以及血清脂质谱之间存在显著的相互依存关系。为了更好地阐明脂质代谢和血管病理在MS发病机制中的作用，需要在这个方向上开展进一步的研究。
