BACKGROUND / AIMS
Sporadic CJD is a rare but universally fatal neurodegenerative disease of unknown aetiology that
occurs worldwide. This study aims to characterise UK sCJD cases between 1993 and 2004 looking for
evidence of change over time. Transmission of cattle BSE to humans, with subsequent development of
variant CJD, has raised concerns that other novel phenotypes of human prion disease may develop with
potentially major public health implications. This study addresses this by reviewing suspect sCJD
patients referred before and after the identification of vCJD, by evaluating the phenotype of young
onset compared to older onset sCJD and by comparing UK cases with the sCJD databases in France
and other predominantly European countries with lower BSE exposure.
This study also aims to review the WHO sCJD diagnostic criteria and hence explore the differential
diagnosis of sCJD in the UK.
All suspected sCJD cases referred to the NCJDSU between 1993 and 2004 were evaluated by
retrospective case note review using the NCJDSU archives. A more detailed analysis of clinical
phenotype was performed on patients referred in 1993, 1994, 2003 and 2004, all cases with a negative
14-3-3 result and all patients aged 50 or less at disease onset. MRI, CSF, EEG and pathology results
were analysed. UK data were compared with European sCJD data extracted from the EUROCJD
database. Suspect sCJD cases that ultimately received an alternative, non CJD diagnosis were
reviewed, and the WHO sCJD criteria were evaluated.
RESULTS AND CONCLUSIONS
There is no evidence to support emergence of a novel, BSE related phenotype of human prion disease.
The sCJD demographic data and clinical phenotype are reassuringly similar between 1993/4 and
2003/4, between young and older onset cases and between UK and other European cases. The small
number of changes that have been observed can largely be attributed to alterations in data collection
and investigation use, plus improved case ascertainment. There is a suggestion that the proportion of
PRNP MM cases is decreasing in the UK and France, most likely related to improved identification of
atypical presentations. However, continued close observation of PRNP trends is important.
The current WHO diagnostic criteria for sCJD are a useful tool, both for research purposes and
clinicians in daily practise. Incorporation of CSF 14-3-3 into the Probable sCJD classification has
resulted in improved sensitivity of 72% but at the expense of moderate reduction in specificity to 79%.
The positive predictive value remains high of 89%. Currently there is insufficient evidence to support
inclusion of MRI in the diagnostic criteria.
The differential diagnosis of sCJD is wide but Alzheimer's disease is the condition most commonly
mistaken for sCJD. However, a significant minority of individuals initially suspected of having CJD
never receive a diagnosis, sometimes even after neuropathological studies. Accurate disease
surveillance remains a priority, not only to ensure that atypical sCJD presentations are not
misdiagnosed, but also to assess putative risk factors for developing sCJD and to identify any novel
CJD phenotypes that may emerge in the future.