Kirk J, Zhou A L
Queens University School of Clinical Medicine (Neuropathology), Institute of Pathology, Belfast, UK.
Mult Scler. 1996 Feb;1(4):242-52.
Although viral infections are often invoked as environmental factors in the aetiology and pathogenesis of multiple sclerosis (MS) it is only recently that a specific, indirect, cytokine-mediated mechanism for triggering of relapses during viral infections has been demonstrated. It is not yet clear however whether this indirect mechanism can account for all reported viral associations with the aetiopathogenesis of MS. A direct causal role of central nervous system (CNS) viral infection in MS has largely been discounted following repeated failures to demonstrate virus within the oligodendrocyte-myelin unit. In the light of increasing evidence of blood-brain barrier (BBB) dysfunction in MS and to further explore the issue of possible viral involvement in MS, an ultrastructural search for viruses was undertaken in the CNS microvasculature, in autopsy and biopsy tissue from human CNS primary demyelinating diseases, including MS (20 cases), idiopathic monophasic CNS demyelinating disease (Mdemy, four cases) and metabolic or immunopathological demyelinating disease (two cases). For comparison, tissues from CNS viral disease in which demyelination is a major feature (nine cases) were examined in the same way. Control CNS tissues (nine cases) from a range of other neurological and non-neurological diseases were also examined. Outside the MS and Mdemy groups, morphological evidence of virus associations with the BBB were found only in the acute and subacute viral encephalitides (three cases subacute sclerosing panencephalitis, one case of Herpes encephalitis) and in one case of disseminated Cytomegalovirus infection. In a small proportion of MS and Mdemy cases, particles resembling either adenovirus (one case of MS) or paramyxovirus (one case of MS, one case of Mdemy) were found in the vicinity of microvessels. In each case a different cell type or extracellular compartment was involved and an exact correlation between the virus particles and the demyelinating lesions could not be demonstrated. Furthermore, corroborative clinical or laboratory evidence of current CNS infection in these primary demyelinating disease cases was available only from the single positive Mdemy case and not from the two cases of MS. This and other previously published evidence from MS (which implicated a Coronavirus) and other diseases highlights the potential vulnerability to viral infection of cells associated with the BBB. Furthermore it is concluded that the detection rate of such infections in pathological tissue could underestimate their true frequency. A possible role of transient virus-BBB interactions in triggering focal inflammation, BBB breakdown and demyelination in some cases of MS and parainfectious demyelinating disease cannot be discounted.
尽管病毒感染常被认为是多发性硬化症（MS）病因和发病机制中的环境因素，但直到最近才证实了一种特定的、间接的、细胞因子介导的病毒感染期间触发复发的机制。然而，目前尚不清楚这种间接机制是否能解释所有报道的与MS病因发病机制相关的病毒关联。由于多次未能在少突胶质细胞 - 髓鞘单位内检测到病毒，中枢神经系统（CNS）病毒感染在MS中的直接因果作用在很大程度上已被否定。鉴于MS中血脑屏障（BBB）功能障碍的证据越来越多，并且为了进一步探讨病毒可能参与MS的问题，我们对包括MS（20例）、特发性单相CNS脱髓鞘疾病（Mdemy，4例）和代谢或免疫病理脱髓鞘疾病（2例）在内的人类CNS原发性脱髓鞘疾病的尸检和活检组织中的CNS微血管进行了病毒的超微结构搜索。作为对照，以同样的方式检查了以脱髓鞘为主要特征的CNS病毒疾病的组织（9例）。还检查了一系列其他神经和非神经疾病的对照CNS组织（9例）。在MS和Mdemy组之外，仅在急性和亚急性病毒性脑炎（3例亚急性硬化性全脑炎，1例疱疹性脑炎）以及1例播散性巨细胞病毒感染中发现了病毒与血脑屏障相关的形态学证据。在一小部分MS和Mdemy病例中，在微血管附近发现了类似腺病毒（1例MS）或副粘病毒（1例MS，1例Mdemy）的颗粒。在每种情况下，涉及的细胞类型或细胞外区室都不同，并且无法证明病毒颗粒与脱髓鞘病变之间存在确切的相关性。此外，这些原发性脱髓鞘疾病病例中当前CNS感染的确证临床或实验室证据仅来自单一阳性的Mdemy病例，而不是来自2例MS病例。这以及先前发表的来自MS（涉及冠状病毒）和其他疾病的其他证据凸显了与血脑屏障相关的细胞对病毒感染的潜在易感性。此外，可以得出结论，在病理组织中此类感染的检出率可能低估了它们的实际发生率。短暂的病毒 - 血脑屏障相互作用在某些MS和感染后脱髓鞘疾病病例中触发局灶性炎症、血脑屏障破坏和脱髓鞘的可能作用不能被忽视。
