Introduction Sporadic CJD (sCJD) is universally fatal. While median survival is 5 months, there is consider- able heterogeneity with some surviving weeks while others survive several months or years. We sought to evaluate characteristics influencing disease duration, and the performance of latest diagnostic criteria incorporating cortical ribboning on MRI brain and the RT-QuIC assay.

Methods 501 autopsy-confirmed cases from surveillance centres in the UK, France, Germany and Italy were stratified into short (<75 days), typical (75-222 days) and long (>222 days) survival groups. We evaluated clinical features, investigation results, and diagnostic criteria classification.

Results Short survival was associated with male sex (p=0.02) and older age (p=0.004). Prion protein gene codon 129 polymorphism status greatly influenced duration (p=<0.001, with longest survival in methionine- valine heterozygotes). Extrapyramidal features were most frequent in long survivors (p=0.04). EEG and 14-3-3 were most sensitive with short survival (p<0.001), RT-QuIC with typical survival (p=0.03) and MRI sen- sitivity did not vary (p=0.4). Previous diagnostic criteria lacked sensitivity in long survivors (p=0.001) while updated criteria were equivalent between groups (p=0.19): sensitivity for long survivors increased 27.7%.

Conclusions This study demonstrates important factors influencing survival and associated phenotypes. The latest diagnostic criteria for sCJD have significantly enhanced diagnosis in long survivors.