Clinical and differential diagnosis of Creutzfeldt-Jakob disease

Until recently, the clinical diagnosis of CJD relied mainly on three criteria. These include patient history (rapidly progressive dementia), neurological findings (ataxia, pyramidal/extrapyramidal signs, myoclonus, akinetic mutism) and typical electroencephalographic (EEG) findings. These criteria are fulfilled in typical cases. The occurrence or increase of certain proteins in cerebrospinal fluid (CSF; 14-3-3, neuron-specific enolase) now provide important adjuncts in recognizing variant forms. Although these proteins can be detected in other neurological diseases accompanied with substantial brain damage such as encephalitis, they are also characterized by their high sensitivity and specificity with regard to other dementing processes (Alzheimer and vascular dementia). The increase in the number of positive cases during the last years in Germany reflects an improved case ascertainment rather than the appearance of the variant CJD (vCJD). Although several recent cases with a long duration of the disease were actually recognized, they did not reveal the typical florid plaques at autopsy. They were revealed as a rare variant of sporadic CJD, which is characterized by homocygosity for valine at codon 129 and PrP(Sc) type 1. This variant is positive for the 14-3-3 protein in CSF. Further subtypes described by Parchi et al. can also be characterized by a certain pattern of clinical symptomatology, EEG- and 14-3-3-findings. In addition, differential diagnosis revealed some treatable dementias among the most common diseases (Alzheimer and vascular dementia) such as herpes encephalitis, multiple sclerosis and Hashimoto encephalitis, particularly in the younger age group.