Moore Sarah Jo, Simmons Marion, Chaplin Melanie, Spiropoulos John
Department of Pathology, VLA-Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK.
Acta Neuropathol. 2008 Nov;116(5):547-59. doi: 10.1007/s00401-008-0433-8. Epub 2008 Sep 17.
Scrapie belongs to a group of diseases known as the transmissible spongiform encephalopathies or prion diseases. Two different categories of naturally occurring scrapie have been identified: classical scrapie, which was first recorded around 1750, and atypical scrapie or 'Nor-98', which was first identified in Norway in 1998. The molecular characteristics of atypical scrapie have been well defined, but detailed descriptions of the neuropathological phenotype are rare since the majority of cases have been detected through active surveillance programmes where only brainstem and cerebellum are collected for statutory diagnosis. In order to characterise the neuropathology of naturally occurring atypical scrapie in sheep, we examined multiple brain levels from 15 whole brains from field cases of atypical scrapie, both clinical suspects and fallen stock, collected in Great Britain between 2004 and 2006. We found that the distribution of disease-associated prion protein (PrP(Sc)) and vacuolation in atypical scrapie cases are very different to both classical scrapie and experimental bovine spongiform encephalopathy in sheep. Immunolabelling for PrP(Sc) is mild and restricted at the obex and more intense and widespread rostrally, particularly in the cerebellum, substantia nigra, thalamus and basal nuclei. Intracellular immunolabelling types are not seen, but distinctive white matter immunolabelling is widespread. Vacuolation associated with PrP(Sc) deposits was not observed in the brainstem neuroanatomical areas commonly affected in classical scrapie and bovine spongiform encephalopathy, but was instead most prominent in the cerebellar cortex and neocortex. This is the largest comprehensive descriptive study of atypical scrapie pathology to date, and provides baseline data against which other natural or experimental cases can be compared. It also reinforces the current recommendation to collect cerebellum in addition to brainstem to enable confident confirmation of this distinct disease phenotype within surveillance programmes.
羊瘙痒症属于一类被称为传染性海绵状脑病或朊病毒病的疾病。已鉴定出两种不同类型的自然发生的羊瘙痒症：经典型羊瘙痒症，最早于1750年左右有记录；非典型羊瘙痒症或“Nor-98”，1998年在挪威首次发现。非典型羊瘙痒症的分子特征已得到明确界定，但神经病理学表型的详细描述却很少，因为大多数病例是通过主动监测计划检测到的，在该计划中，仅采集脑干和小脑用于法定诊断。为了描述自然发生的绵羊非典型羊瘙痒症的神经病理学特征，我们检查了2004年至2006年在英国收集的15例非典型羊瘙痒症野外病例（包括临床疑似病例和死亡动物）的全脑多个脑区。我们发现，非典型羊瘙痒症病例中与疾病相关的朊病毒蛋白（PrP(Sc)）分布和空泡化与经典型羊瘙痒症以及绵羊实验性牛海绵状脑病均有很大不同。PrP(Sc)的免疫标记在延髓轻度且局限，在延髓上方更强烈且广泛，尤其是在小脑、黑质、丘脑和基底核。未观察到细胞内免疫标记类型，但独特的白质免疫标记广泛存在。与PrP(Sc)沉积相关的空泡化在经典型羊瘙痒症和牛海绵状脑病中常见的脑干神经解剖区域未观察到，而是在小脑皮质和新皮质中最为明显。这是迄今为止对非典型羊瘙痒症病理学最大规模的综合描述性研究，并提供了可用于与其他自然或实验病例进行比较的基线数据。它还强化了当前的建议，即在监测计划中除了采集脑干外还应采集小脑，以便可靠地确认这种独特的疾病表型。
