Revised criteria for Creutzfeldt-Jakob disease improve diagnosis

Revisions to diagnostic criteria for sporadic Creutzfeldt-Jakob disease have led to greater accuracy in both clinical care and surveillance, according to a European study published in JAMA Network Open.

“Accurate diagnosis is essential to exclude potentially reversible conditions that can mimic sCJD [sporadic Creutzfeldt-Jakob disease], which can facilitate appropriate supportive care and prompt public health actions to reduce transmission, as well as support the recruitment to clinical trials,” Neil Watson, MD, of the National CJD Research & Surveillance Unit and Centre for Clinical Brain Sciences at the University of Edinburgh in Scotland, and colleagues wrote.

Researchers sought to evaluate the accuracy of the 2017 International CJD Surveillance Network diagnostic criteria through the retrospective diagnosis of autopsy-confirmed cases of sCJD. They collected data through a 3-year clinicopathological series, from January 2017 to December 2019, using 501 cases of autopsy-confirmed sCJD and 146 cases of alternative neuropathological diagnoses from national surveillance centers in the United Kingdom, France, Germany and Italy. Researchers measured sensitivity and specificity of the revised criteria and diagnostic investigations and performed secondary analyses to assess sCJD subgroups by genotype, pathological classification, disease duration and age.

Results showed that participants from the sCJD cases cohort were younger than the alternative diagnosis cohort (mean age, 68.8 years vs. 72.8 years; P<.001) and had a longer median duration of the disease (118 days vs. 85 days; P=.002).

Among 223 sCJD cases and 52 alternative cases with a full panel of investigations, sensitivity of revised criteria (97.8%; 95% CI, 94.9-99.3) was increased compared with prior criteria (76.2%; 95% CI, 70.1-81.7) while specificity was unchanged (67.3%; 95% CI, 52.9-79.7 vs. 69.2%; 95% CI, 54.9-81.3). Data also revealed varied sensitivity with genetic and pathological features, disease duration and age.

“A major benefit of rapid and accurate in-life diagnosis is the potential for recruitment to therapeutic trials; challenges to recruitment include short survival, diagnostic latency and rarity of CJD,” Watson and colleagues wrote. “Our results demonstrate that the diagnosis can be made with high confidence during life.”