Prion Diseases.
Prion Diseases.
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DOI：
10.1212/con.0000000000000251
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Geschwind MD
中科院分区：
文献类型：
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作者：
Geschwind MD
本文介绍了人类朊病毒病的临床方面的最新进展，包括其介绍的广泛范围。朊病毒病是一组由称为朊病毒的异常形状蛋白质引起的疾病，以散发性（雅各布-克罗伊茨费尔特病），遗传性（遗传性雅各布-克罗伊茨费尔特病，Gerstmann-Sträussler-Scheinker综合征和致命的家族性失眠症）和获得性（库鲁病，变异型雅各布-克罗伊茨费尔特病和医源性雅各布-克罗伊茨费尔特病）形式发生。本文介绍了人类朊病毒病的临床特征和诊断方法的最新信息。基于扩增朊病毒以检测它们的新的死前潜在诊断测试显示出非常高的特异性。对人类朊病毒疾病可能表现的多样性的理解继续发展，一些遗传形式在几十年中进展缓慢，从自主神经功能障碍和神经病开始，发展到具有朊病毒病和tau蛋白病联合病理学的额叶执行痴呆。不幸的是，迄今为止，所有人类朊病毒疾病的临床试验都未能显示出生存益处。最近发现了朊病毒蛋白基因中一种非常罕见的多态性，这种多态性似乎可以预防朊病毒疾病;这一发现，除了提供对神经退行性疾病的朊病毒样机制的更好理解外，还可能导致潜在的治疗方法。散发性Jakob-Creutzfeldt病是人类朊病毒病的最常见形式。由朊病毒相关蛋白基因（PRNP）突变引起的遗传性朊病毒疾病根据突变、临床表型和神经病理学特征进行分类，并且由于其不同的表现而难以诊断。也许与神经传染病的连续性问题最相关的是，获得性朊病毒疾病是由意外传播给人类引起的，但幸运的是，它们是最不常见的形式，并且随着对传播风险的认识导致采取措施预防此类事件的发生而变得越来越罕见。
This article presents an update on the clinical aspects of human prion disease, including the wide spectrum of their presentations. Prion diseases, a group of disorders caused by abnormally shaped proteins called prions, occur in sporadic (Jakob-Creutzfeldt disease), genetic (genetic Jakob-Creutzfeldt disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia), and acquired (kuru, variant Jakob-Creutzfeldt disease, and iatrogenic Jakob-Creutzfeldt disease) forms. This article presents updated information on the clinical features and diagnostic methods for human prion diseases. New antemortem potential diagnostic tests based on amplifying prions in order to detect them are showing very high specificity. Understanding of the diversity of possible presentations of human prion diseases continues to evolve, with some genetic forms progressing slowly over decades, beginning with dysautonomia and neuropathy and progressing to a frontal-executive dementia with pathology of combined prionopathy and tauopathy. Unfortunately, to date, all human prion disease clinical trials have failed to show survival benefit. A very rare polymorphism in the prion protein gene recently has been identified that appears to protect against prion disease; this finding, in addition to providing greater understanding of the prionlike mechanisms of neurodegenerative disorders, might lead to potential treatments. Sporadic Jakob-Creutzfeldt disease is the most common form of human prion disease. Genetic prion diseases, resulting from mutations in the prion-related protein gene (PRNP), are classified based on the mutation, clinical phenotype, and neuropathologic features and can be difficult to diagnose because of their varied presentations. Perhaps most relevant to this Continuum issue on neuroinfectious diseases, acquired prion diseases are caused by accidental transmission to humans, but fortunately, they are the least common form and are becoming rarer as awareness of transmission risk has led to implementation of measures to prevent such occurrences.