Chen et al. 2024, multisite skin biopsies versus CSF for prion seeding activity (JAMA Neurology)

A diagnostic study from Xuanwu Hospital in Beijing with the China CDC prion laboratory that compared skin biopsies from several body sites with paired cerebrospinal fluid, both tested by RT-QuIC, in people with suspected prion disease in China. A single skin site performed about as well as CSF, while combining two or more sites, and testing at several dilutions, gave higher sensitivity than CSF. The headline claim of superiority rests on the combined-site analysis, not on a single biopsy.

Key facts

  • Citation verified: Chen ZY, Shi Q, Xiao K and 16 co-authors, JAMA Neurology 2024;81(12):1263-1273, DOI 10.1001/jamaneurol.2024.3458, PMID 39401015, with 19 authors in total.
  • First author and most authors are from the Department of Neurology at Xuanwu Hospital; the senior and last author, Xiao-Ping Dong, and several co-authors are at the China CDC National Institute for Viral Disease Control and Prevention. Corresponding authors are Li-Yong Wu (Xuanwu) and Xiao-Ping Dong (China CDC).
  • The exploratory cohort was single-centre at Xuanwu and included 101 patients with prion disease and 23 without, of whom 94 with prion disease had paired CSF.
  • At the lowest tested skin dilution, single-site positivity ranged from 69.2 to 79.6 percent, comparable to CSF at 75.5 percent (71 of 94); testing three dilutions lifted every site above 80 percent.
  • Pairing near-ear, inner thigh and lower back sites gave over 92 percent positivity (93 of 101), significantly higher than CSF (P = .002); all sites at three dilutions gave 95.0 percent (96 of 101).
  • In the confirmatory multicentre cohort of 43 prion disease patients from four Chinese hospitals, one skin biopsy was positive in 79.1 percent (34 of 43) against 72.1 percent (31 of 43) for CSF, a difference that was not statistically significant (P = .45).
  • The authors suggest testing two or more skin sites may help people with negative CSF or those who cannot or will not have a lumbar puncture.
  • Stated limitations: sporadic CJD cases clinically diagnosed without pathology confirmation, subtype assigned by clinical criteria, uneven site sampling because the upper arm site was dropped after low positivity, and undiluted CSF.
  • Funding came from Capital's Funds for Health Improvement and Research, the National Natural Science Foundation of China, the Beijing Postdoctoral Research Foundation and Nanchang University hospital funds; no conflicts were declared.
  • Metadata quirks: the abstract prints a confirmatory end date of "June 31, 2024", which is not a real date, and refers to three skin sites while naming four.

Timeline

  1. 2021Exploratory cohort enrolment begins at Xuanwu Hospital (ran to 2023-12).
  2. 2023Confirmatory multicentre enrolment begins (ran to mid 2024).
  3. 2024Manuscript accepted.
  4. 2024Published online.
  5. 2024Print issue, volume 81 issue 12.

Last checked 1 November 2026

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