Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease

Abstract

Background: Making a clinical diagnosis of sporadic Creutzfeldt-Jakob disease relies on the evaluation of rapidly progressive dementia, ataxia, myoclonus, changes on the electroencephalogram, and other neurological signs. A definite diagnosis, however, is confined to cases that have been evaluated neuropathologically or by equivalent diagnostic techniques. This places a high priority on the establishment of reliable neuropathologic methods for the investigation and diagnosis of Creutzfeldt-Jakob disease. Objective: To evaluate existing morphological and laboratory diagnostic techniques to reach a consensus on the definition of "definite Creutzfeldt-Jakob disease." Methods: The existing morphological techniques, particularly immunohistochemistry, used in 4 laboratories—Germany, Great Britain, Japan, and the United States—are evaluated, and various laboratory diagnostic techniques are discussed. Results: Immunohistochemistry with antibodies against the prion protein combined with special tissue pretreatment regimens gives reliable diagnostic results and, for its applicability to formalin-fixed and paraffin-embedded tissue, is superior to other techniques that may be more sensitive but require fresh, unfixed brain tissue. Conclusions: Our experience suggests the following regimen for the diagnosis of suspected Creutzfeldt-Jakob disease: light microscopy of various brain regions, which in typical cases may lead to definite diagnosis. Immunohistochemistry with antibodies against the prion protein is preferable in all suspected cases of Creutzfeldt-Jakob disease and is mandatory whenever a routine histological workup does not yield definite results. Additional special techniques can be applied if required.