Multiple sclerosis is a systemic venous vasculopathy: A single unifying mechanism
Multiple sclerosis is a systemic venous vasculopathy: A single unifying mechanism
复制标题
DOI：
10.1016/j.mehy.2020.109645
复制
发表时间：
2020-07-01
影响因子：
4.7
通讯作者：
Dmytriw, Adam A.
中科院分区：
文献类型：
--
作者：
Kapadia, Anish;Dmytriw, Adam A.
多发性硬化（MS）是一种影响中枢神经系统（CNS）的潜在衰弱性疾病，临床特征为进行性神经功能恶化。它是脱髓鞘疾病中最常见的疾病，被认为是原发性自身免疫性损伤的结果。各种遗传和环境风险因素被认为是潜在的触发因素和/或诱发因素;然而，疾病的确切机制仍然难以捉摸。诊断和管理是基于临床表现，辅助影像学和生化评估。自19世纪以来，观察到MS病变的解剖学分布表现出特征性的脑室周围、静脉周围分布;脊髓和皮质病变也表现出这种静脉周围优势。静脉异常在病理学上表现为不规则的狭窄和扩张，伴有静脉壁和静脉周围浸润。活动性CNS病变的特征在于小静脉周围炎性浸润。伴随着血脑屏障的整体功能障碍，即使在正常出现的组织内，病理学上观察到低水平的炎症变化和组织损伤。虽然几种CNS抗原已被确定为潜在的候选抗原，包括髓磷脂相关抗原，但特异性致病性抗原仍然难以捉摸。脑脊液评价揭示了特征性寡克隆带，表明对各种CNS抗原的广泛炎症反应。已在MS患者血清中鉴定出抗内皮成分的抗体，其作用尚未明确阐明。新出现的证据表明，可能有一个更系统的炎症过程，预示着系统性临床前前驱症状。鉴于这种严重不一致的临床，解剖，免疫和病理结果，我们提出了一个统一的理论，特别是我们提出，MS是一种原发性自身免疫性血管病变，与中枢神经系统静脉结构的偏好。特征性CNS病变是由对通常特权的CNS抗原的暴露的炎症反应引起的继发表现。
Multiple sclerosis (MS) is a potentially debilitating disease affecting the central nervous system (CNS) clinically characterized by progressive neurological deterioration. It is the most common condition under the umbrella of demyelinating disease, thought to occur as a result of a primary autoimmune insult. Various genetic and environmental risk factors have been implicated as potential triggers and/or predisposing factors; however, the exact mechanism of disease remains elusive. Diagnosis and management are based on clinical presentation, with adjunct imaging and biochemical assessment. Since the 19th century anatomical distribution of lesions in MS have been observed to demonstrate a characteristic periventricular, perivenular distribution; spinal cord and cortical lesions also demonstrate this perivenous preponderance. Venous abnormalities have long been observed on pathology characterized by irregular narrowing and dilatation with associated venous wall and perivenous infiltrates. Active CNS lesions are characterized by perivenular inflammatory infiltrates. There is accompanying global dysfunction of the blood-brain barrier, even within normal appearing tissue, with low levels of inflammatory change and tissue injury seen at pathology. Although several CNS antigens have been identified as potential candidates, including myelin related antigens, a specific pathogenic antigen remains elusive. Evaluation of the cerebrospinal fluid reveals characteristic oligoclonal bands, indicating a broad inflammatory response against a variety of CNS antigens. Antibodies have been identified against endothelial elements in sera of patients with MS, their role is not yet clearly elucidated. Emerging evidence suggests there may be a more systemic inflammatory process, heralded by a systemic preclinical prodrome. In light of such seemingly-discrepant clinical, anatomic, immunologic and pathologic findings we propose a unifying theory; specifically we propose that MS is a primary autoimmune vasculopathy, with a predilection of CNS venous structures. Characteristic CNS lesions are a secondary manifestation resulting from an inflammatory response to the uncovering of usually privileged CNS antigens.