Abstract
OBJECTIVE: Heightened awareness of Creutzfeldt-Jakob disease (CJD) among physicians and the lay public has led to its frequent consideration in the differential diagnosis of patients with rapidly progressive dementia (RPD). Our goal was to determine which treatable disorders are most commonly mistaken for CJD. METHODS: We performed a retrospective clinical and neuropathological review of prion-negative brain autopsy cases referred to the US National Prion Disease Pathology Surveillance Center at Case Western Reserve University from January 2006 through December 2009. RESULTS: Of 1,106 brain autopsies, 352 (32%) were negative for prion disease, 304 of which had adequate tissue for histopathological analysis. Alzheimer disease (n = 154) and vascular dementia (n = 36) were the 2 most frequent diagnoses. Seventy-one patients had potentially treatable diseases. Clinical findings included dementia (42 cases), pyramidal (n = 20), cerebellar (n = 14), or extrapyramidal (n = 12) signs, myoclonus (n = 12), visual disturbance (n = 9), and akinetic mutism (n = 5); a typical electroencephalogram occurred only once. Neuropathological diagnoses included immune-mediated disorders (n = 26), neoplasia (n = 25, most often lymphoma), infections (n = 14), and metabolic disorders (n = 6). INTERPRETATION: In patients with RPD, treatable disorders should be considered and excluded before diagnosing CJD. Misdiagnosed patients often did not fulfill World Health Organization criteria. RPD with positive 14-3-3 cerebrospinal fluid protein should not be regarded as sufficient for the diagnosis of CJD. Adherence to revised criteria for CJD, which include distinctive magnetic resonance imaging features of prion disease, is likely to improve diagnostic accuracy.