Abstract
摘要:普利昂蛋白為庫賈氏病致病原,其在生物體內所扮演的角色功能並不明確,但經過異常折疊(misfolding)之後,變成具傳染性的變異普利昂蛋白(PrPsc)。我國自1996年開始庫賈氏病之監測作業,並於2007年將其公告為第四類法定傳染病,國內迄今已累計逾400名病例,惟因本國民情,病例死亡後接受解剖確診者極少,因此擬藉由本計畫之施行,探討我國人類庫賈氏病之發生、臨床病程及流行病學相關因子。本計劃屬三年期之計畫,計畫全程目標在於探討我國庫賈氏病之發生、臨床病程及流行病學相關因子分析研究,並藉由比對健保資料庫探討防疫制度之完整性。第一年計畫已經完成了邀請國際學者前來演講交流,組成跨領域團隊,從疾病管制署的通報資料庫與健保資料庫多面向的檢視我國庫賈氏病之發生率及臨床病程。本計劃自1999年起所通報的個案中整理出資料比較完整的315位庫賈氏病患的資料進行分析。已經分析歸納出包括平均發病年齡、發病高峰年齡、性別分布、症狀出現後平均診斷時間、診斷後平均存活時間、常見之前驅症狀、發病病徵、臨床病程。腦波具典型週期性尖銳組合波的百分比、典型腦波出現時間、腦波檢驗之敏感度、腦部磁振造影典型皮質緞帶徵象最常見部位、核磁共振的敏感度、腦部核磁共振出現特異病徵的平均時間。並由健保資料庫中依性別、年齡計算出年度發生率,與10年存活狀況。生物標記進行了前導研究,並將量測結果與Western Blot 14-3-3的結果做初步比較。第一年計畫之各項預定目標大致都已達標,詳見第一年計畫之報告。第二年計畫之主要目標為進行流行病學相關因子分析研究,訂定診斷工作標準流程並推廣之,並追蹤存活超過兩年個案。首先針對疾病管制署的通報資料庫進行庫賈氏病之流行病學相關因子分析,並與健保資料庫作對照,比對兩個資料庫庫賈氏病的個案年度發生及通報數的落差,以探討目前通報系統的工作流程是否有可能遺漏之處。這一部分因為牽涉到健保資料庫在法規上禁止在使用資料庫時溯及個人,將利用庫賈氏病罕病特性(發生率小於或等於百萬分之一),交叉比對地區、通報醫院、住院日期、性別、出生年月(年齡)。至於庫賈氏病相關因子與預後分析,將利用人口學資料、臨床症狀、共病為獨立變項,診斷分類及預後(存活年數、如,低於或超過兩年之個案)為因變項,進行邏輯回歸分析。另一項重要工作為訂定我國通報庫賈氏病之診斷標準工作流程。首先訂定一套暫定的標準工作流程,並與專科醫學學會(台灣臨床失智症學會、老年精神醫學會、神經學學會)合辦繼續教育課程。對象以診斷、照顧庫賈氏病之醫師為授課主體。課程收集與會者的意見之後,召開專家諮詢會議與各相關領域專家集思廣益,訂定我國通報庫賈氏病前之診斷工作標準流程,確立必要的臨床資料、實驗室檢查的項目,以及治療照護的原則,並將最後資料提供各相關專科醫學會參考。訂定長期存活個案的追蹤調查的方法,在第一年計畫中根據統計分析資料我們發現已有死亡通報的278位個案中,存活兩年以上的有71位。進一步會依診斷程度區分成極可能、可能、和陽性案例,並分析已有死亡通報者的人口學資料、臨床症狀、共病、腦波、腦部磁振影像是否有所差異。最後再去追蹤尚存活個案之現況,以探討長期存活的的最可能原因。第二年的計畫預計會在年中之前完成1篇期刊投稿,目前預定會將第一年的疾病管制署的通報資料庫的臨床整理分析結果投稿至國際期刊。至於新生物標記預期發展完成,開始接受臨床檢驗。第三年計畫 主要目標修訂病例調查表,辦理1場國際研討會,追蹤存活超過兩年庫賈氏病患者並分析其原因。整理新發展生物標記的結果,計畫結束前完成2篇國際期刊投稿。修訂病例調查表持續追蹤存活超過2年庫賈氏病個案之追蹤及調查,並進行相關分析整理新發展生物標記的結果辦理1場國際研討會完成2篇期刊投稿
Abstract: Prion is the pathogen of Creutzfeldt-Jakob disease (CJD). After mis-folding, the non-infectious cellular prion protein(PrPcPc)is converted into pathogenic prion protein. Taiwan started to monitor Creutzfeldt-Jakob disease since 1996. We have accumulated more than 400 cases. In the first year of this 3-year project, we collected and analyzed 315 cases registered since 1999 whose records are more comprehensive. We obtained average age onset, gender distribution, survival after diagnosis, most common prodromes, onset symptoms and signs and clinical manifestation during the course. We also obtained percentage of having EEG pathognomic sings of periodic sharp wave complexes (PSWC) and the timing of seeing these PSWC; most frequent brain regions for MRI cortical ribbon signs or hyperintensities. We computed from National Health Insurance database (NHIDB) for age and gender specific occurrences. We completed a pilot study of biomarkers. We measured about 30 CSF samples for their total Tau, p-Tau, Aβ40, 42, and α-synuclein and compared to the results from Western Blot 14-3-3. Basically we have achieved every expected goal of the first year project. In the second year of the project, our major goal is to investigate the epidemiological association factors of CJD in terms of prevalence and prognosis. We will also formulate a standard operating procedure (SOP) for diagnosis and will follow up those have lived longer than two years. In the first place, logistic regression using the demographic, clinical information, EEG and MRI findings as independent variables and using diagnosis categories such as possible, probable and positive (genetic) group, survival duration (shorter or longer than two years) as dependent variables to do logistic regression to find out possible association factor. We will also carefully examine the discrepancy between the CDC registration database and NHI database for to explore any possible pitfalls of our CDC registration system. We will have two separate educational conferences with the cooperation of professional societies. After the educational conferences, we will collect feedback from the participants and will hold multi-disciplinary meeting with experts of different professions to formulate SOP of CJD diagnosis. We will establish a protocol for follow up the long CJD survivors (longer than two year) and explore the possible reason accounting for. By middle of the second year, we will submit a manuscript to international journal with the content of our analysis our CDC-registration database. As for the newly developed biomarkers we plan to take order for clinical examination.
Keyword(s)
普利昂蛋白
庫賈氏病
腦波
腦部磁振造影
生物標記
健保資料庫
診斷工作標準流程
Prion
Creutzfeldt-Jakob disease
EEG
MRI
Biomarker
National Health Insurance Data Base
Standard Operating Procedure