Visualization of central European tick-borne encephalitis infection in fatal human cases
Visualization of central European tick-borne encephalitis infection in fatal human cases
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DOI：
10.1093/jnen/64.6.506
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发表时间：
2005-06-01
影响因子：
3.2
通讯作者：
Budka, H
中科院分区：
文献类型：
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作者：
Gelpi, E;Preusser, M;Budka, H
中欧蜱传脑炎（TBE）是由一种由蓖麻蜱传播的黄病毒引起的。在严重感染时，TBE表现为（髓）脑膜脑炎，死亡率相当高。特征性的神经病理改变表现为脊髓、脑干和小脑的多结节到斑片状脊髓灰质炎。病毒感染的免疫组织化学可视化尚未实现。我们用免疫组织化学方法分析了28例临床诊断为TBE并经神经病理证实为脑脊髓炎（脑膜）的病例中病毒抗原的分布及其与神经病理改变、血清学数据和病程的相关性。在20个大脑中（包括10个血清阳性），可以检测到病毒抗原。这些病例的特点是临床持续时间相对较短，从4天到35天不等。免疫反应性在浦肯野细胞核周和突起以及齿状核、下橄榄和前角的大神经元中最为突出。此外，在其他脑干核、同皮层和基底神经节的神经元中检测到免疫反应性。严重的炎症变化与病毒抗原的存在呈负相关。一些细胞毒性T细胞直接接触蜱传脑炎病毒（TBEV）感染的神经元。我们的结论是：1)TBE病毒抗原在死亡病例的大脑中免疫组织化学检测到，自然临床病程相对较短；2) be病毒嗜神经性优先作用于前角、延髓、脑桥、齿状核、浦肯野细胞和纹状体等大神经元；3)炎症变化与病毒抗原分布的地形相关性较差；4)免疫机制可能导致TBE患者神经细胞的破坏。
Central European tick-borne encephalitis (TBE) is caused by a flavivirus vectored by the Ixodes ricinus tick. In severe infections, TBE presents as (myelo)meningoencephalitis with considerable mortality. Characteristic neuropathologic changes feature a multinodular to patchy polioenceptialomyelitis accentuated in spinal cord, brainstem, and cerebellum. Visualization of viral infection by immuno-histochemistry has not yet been achieved. We analyzed immunohistochemically the distribution of viral antigens and its correlation with neuropathologic changes, serological data, and disease duration in 28 brains of cases with a clinical diagnosis of TBE and neuropathologically confirmed (meningo)encephalomyelitis. In 20 brains (including 10 seropositives), viral antigens were detectable. These cases were characterized by relatively short clinical duration ranging from 4 to 35 days. Immunoreactivity was most prominent in perikarya and processes of Purkinje cells and large neurons of dentate nucleus, inferior olives, and anterior horns. In addition, immunoreactivity was detected in neurons of other brainstem nuclei, isocortex, and basal ganglia. There was an inverse topographical association of severe inflammatory changes with presence of viral antigens. Some cytotoxic T cells were in direct contact with tick-borne encephalitis virus (TBEV)-infected neurons. We conclude that 1) TBE viral antigens are immunohistochemically detectable in brains of fatal cases with relatively short natural clinical course; 2) TBE virus neurotropism preferentially targets large neurons of anterior horns, medulla oblongata, pons, dentate nucleus, Purkinje cells, and striatum; 3) topographical correlation between inflammatory changes and distribution of viral antigens is poor; and 4) immunologic mechanisms may contribute to nerve cell destruction in human TBE.