Multisite Skin Biopsies vs Cerebrospinal Fluid for Prion Seeding Activity in the Diagnosis of Prion Diseases

作者：Zhongyun Chen, Qi Shi, Kang Xiao, Yu Kong, Dong-Lin Liang, Yihao Wang, Rong Min, Jing Zhang, Zhen Wang, Hong Ye, Ran Gao, Min Chu, Haitian Nan, Deming Jiang, Junjie Li, Lin Wang, Wen‐Quan Zou, Liyong Wu, Xiaoping Dong · 发表于：JAMA Neurology · 年份：2024 · DOI：10.1001/jamaneurol.2024.3458 · 被引用次数：11 · 研究领域：Prion Diseases and Protein Misfolding、Polyomavirus and related diseases、Cerebrospinal fluid and hydrocephalus

Importance: Recent studies have revealed that autopsy skin samples from cadavers with prion diseases (PRDs) exhibited a positive prion seeding activity similar to cerebrospinal fluid (CSF). It is worthwhile to validate the findings with a large number of biopsy skin samples and compare the clinical value of prion seeding activity between skin biopsies and concurrent CSF specimens. Objective: To compare the prion seeding activity of skin biopsies and CSF samples and to determine the effectiveness of combination of the skin biopsies from multiple sites and numerous dilutions on the diagnosis for various types of PRDs. Design, Setting, and Participants: In the exploratory cohort, patients were enrolled from September 15, 2021, to December 15, 2023, and were followed up every 3 months until April 2024. The confirmatory cohort enrolled patients from December 16, 2023, to June 31, 2024. The exploratory cohort was conducted at a single center, the neurology department at Xuanwu Hospital. The confirmatory cohort was a multicenter study involving 4 hospitals in China. Participants included those diagnosed with probable sporadic Creutzfeldt-Jakob disease or genetically confirmed PRDs. Patients with uncertain diagnoses or those lost to follow-up were excluded. All patients with PRDs underwent skin sampling at 3 sites (the near-ear area, upper arm, lower back, and inner thigh), and a portion of them had CSF samples taken simultaneously. In the confirmatory cohort, a single skin biopsy si...