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How to improve the clinical diagnosis of Creutzfeldt-Jakob disease
S Poser1, B Mollenhauer, A Kraubeta
1Department of Neurology, University of Göttingen, Germany.
Insights
This study on suspected Creutzfeldt-Jakob disease found many misdiagnoses. Cerebrospinal fluid (CSF) 14-3-3 protein testing improved diagnostic accuracy for prion diseases.
Area of Science:
- Neurology
- Neuroscience
- Pathology
Background:
- Creutzfeldt-Jakob disease (CJD) diagnosis can be challenging, with potential for misdiagnosis.
- Accurate differentiation of CJD from other rapidly progressive neurological disorders is crucial for patient management and research.
Purpose of the Study:
- To evaluate the diagnostic accuracy of suspected Creutzfeldt-Jakob disease cases in a prospective follow-up study.
- To identify alternative diagnoses in patients initially suspected of having CJD.
- To assess the utility of 14-3-3 protein in cerebrospinal fluid (CSF) for improving CJD diagnosis.
Main Methods:
- Prospective follow-up of 364 patients with suspected Creutzfeldt-Jakob disease.
- Clinical review, autopsy, and diagnostic testing including CSF 14-3-3 protein analysis, EEG, and MRI.
- Exclusion of genetic prion diseases identified by blood analysis.
Main Results:
- Of 358 evaluated patients, 193 were probable CJD, but autopsy revealed 5 misdiagnoses.
- Among possible CJD cases, 10 had other diagnoses; 2 initially classified otherwise were confirmed CJD post-mortem.
- CSF 14-3-3 protein showed better discrimination between CJD and other rapidly progressive dementias than EEG or MRI.
Conclusions:
- A significant proportion of suspected CJD cases are misdiagnosed, with conditions like Alzheimer's disease and Hashimoto encephalitis being common alternatives.
- Incorporating CSF 14-3-3 protein testing into diagnostic criteria enhances the accuracy and confidence in diagnosing Creutzfeldt-Jakob disease.
- This study highlights the importance of autopsy and advanced biomarkers in refining neurological disorder diagnoses.
Abstract:
This paper describes a prospective follow-up of 364 patients initially notified as suspected Creutzfeldt-Jakob disease to a Surveillance Unit in Göttingen, Germany. Six patients were diagnosed as having genetic prion disease by blood analysis and were excluded from the study. After examination and review of the remaining 358, 193 were classified as probable Creutzfeldt-Jakob disease. However, autopsy revealed that five of the 193 did not have Creutzfeldt-Jakob disease (four cases, Alzheimer's disease; one case, cerebral lymphoma). Of the 54 patients classified as possible Creutzfeldt-Jakob disease, 10 had another diagnosis made at autopsy. Two of the 111 cases originally classified as having other diseases were found to have Creutzfeldt-Jakob disease on autopsy. Autopsy evidence, together with follow-up of the patients still living and those who died without autopsy, revealed a broad range of other diagnoses. In the younger age groups, the commonest were chronic inflammatory diseases including Hashimoto encephalitis, whilst rapidly progressive Alzheimer's disease was most common in the older age groups. The presence of 14-3-3 protein in the CSF discriminated better between Creutzfeldt-Jakob disease and other rapidly progressive dementias than did the EEG pattern or the MRI. The inclusion of this CSF protein in the criteria of Masters and colleagues (Ann Neurol 1979; 5: 177-88) improves the accuracy and confidence in the clinical diagnosis of Creutzfeldt-Jakob disease.
