苏格兰 65 岁以上人群中增强型克雅氏病监测的研究方案：一项针对银行储存的脑组织捐赠样本进行神经病理学筛查以寻找朊病毒病证据的观察性研究。

Study protocol for enhanced CJD surveillance in the 65+ years population group in Scotland: an observational neuropathological screening study of banked brain tissue donations for evidence of prion disease.

机构信息

Centre for Clinical Brain Sciences, National CJD Research & Surveillance Unit, Edinburgh, UK

Centre for Clinical Brain Sciences, National CJD Research & Surveillance Unit, Edinburgh, UK.

出版信息

BMJ Open. 2019 Oct 28;9(10):e033744. doi: 10.1136/bmjopen-2019-033744.

DOI:10.1136/bmjopen-2019-033744

PMID:31662408

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6830687/

Abstract

INTRODUCTION

Creutzfeldt-Jakob disease (CJD) is a human prion disease that occurs in sporadic, genetic and acquired forms. Variant CJD (vCJD) is an acquired form first identified in 1996 in the UK. To date, 178 cases of vCJD have been reported in the UK, most of which have been associated with dietary exposure to the bovine spongiform encephalopathy agent. Most vCJD cases have a young age of onset, with a median age at death of 28 years. In the UK, suspected cases of vCJD are reported to the UK National Creutzfeldt-Jakob Disease Research & Surveillance Unit (NCJDRSU). There is, however, a concern that the national surveillance system might be missing some cases of vCJD or other forms of human prion disease, particularly in the older population, perhaps because of atypical clinical presentation. This study aims to establish whether there is unrecognised prion disease in people aged 65 years and above in the Scottish population by screening banked brain tissue donated to the Edinburgh Brain Bank (EBB).

METHODS

Neuropathological screening of prospective and retrospective brain tissue samples is performed. This involves histopathological and immunohistochemical analysis and prion protein biochemical analysis. During the study, descriptive statistics are used to describe the study population, including the demographics and clinical, pathological and referral characteristics. Controlling for confounders, univariate and multivariate analyses will be used to compare select characteristics of newly identified suspect cases with previously confirmed cases referred to the NCJDRSU.

ETHICS AND DISSEMINATION

Brain tissue donations to EBB are made voluntarily by the relatives of patients, with consent for use in research. The EBB has ethical approval to provide tissue samples to research projects (REC reference 16/ES/0084). The findings of this study will be disseminated in meetings, conferences, workshops and as peer-reviewed publications.

TRIAL REGISTRATION NUMBERS

10/S1402/69 and 10/S1402/70.

摘要

简介

克雅氏病（CJD）是一种人类朊病毒病，可分为散发性、遗传性和获得性三种类型。变异型克雅氏病（vCJD）是一种获得性疾病，于 1996 年在英国首次发现。迄今为止，英国已报告了 178 例 vCJD 病例，其中大多数与食用感染牛海绵状脑病（BSE）因子的牛源性食品有关。大多数 vCJD 病例的发病年龄较轻，中位死亡年龄为 28 岁。在英国，疑似 vCJD 病例报告给英国国家克雅氏病研究与监测机构（NCJDRSU）。然而，人们担心国家监测系统可能会遗漏一些 vCJD 或其他形式的人类朊病毒病病例，特别是在老年人群中，这可能是因为临床表现不典型。本研究旨在通过对捐赠给爱丁堡大脑银行（EBB）的大脑组织进行筛查，确定苏格兰老年人群中是否存在未被识别的朊病毒病。

方法

对前瞻性和回顾性脑组织样本进行神经病理学筛查。这涉及组织病理学和免疫组织化学分析以及朊病毒蛋白的生化分析。在研究过程中，使用描述性统计来描述研究人群，包括人口统计学特征以及临床、病理和转诊特征。在控制混杂因素的情况下，将使用单变量和多变量分析来比较新发现的疑似病例与已向 NCJDRSU 转诊的确诊病例的某些特征。