http://orcid.org/0000-0003-4048-3513
Dear Editor,
We read with great interest the recent publication by Trikamji et al.,Citation1 on the case of rapidly progressive dementia with elevated real-time quaking-induced conversion (RT-QUIC) and negative 14-3-3 and tau proteins. Although, conclusive diagnosis of the case was understandably difficult, a detailed clinical work-up such as rigorous differential diagnosis should have been conducted. As a rule, prion diseases should be considered, if the patient presents with rapidly progressive dementia. However, the study lacked the complete clinical work-up for rapidly progressive dementia. To confirm the clinical diagnosis for prion diseases, clinicians should employ not only MRI including diffusion-weighted images (DW-MRI) and cerebrospinal fluid (CSF) biomarkers, but also PRNP gene analysis. Currently, PRNP gene analysis is a standard step in the diagnostic work-up of prion diseases, including sporadic cases.
DW-MRI and a CSF work-up are useful for diagnosing prion diseases and/or distinguishing between prion and non-prion diseases. Particularly, the positive results of the RT-QUIC assay led to the suspicion of a prion disease. In the case of Trikamji et al, as the MRI findings or the results of 14-3-3 and tau proteins did not suggest the diagnosis of prion diseases, atypical or subclinical prion disease should be considered. Nevertheless, wide-ranged differential diagnoses excluding prion disease are also warranted in the case of rapidly progressive dementia without cortical hyper-intense areas on DW-MRI. MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (CJD)Citation2 or one of the familial prion diseases (e.g., fatal familial insomnia, or another type of genetic CJD) lack the typical cortical, basal ganglia or thalamic hyper-intensities detected by DW-MRI. Therefore, information from the PRNP gene analysis and/or other neuroradiological approaches (e.g., SPECT or PET) may be required to fortify the clinical diagnosis of atypical prion disease or other causes of dementia.
The RT-QUIC assay has been established as a method of the diagnosis of prion disease. The sensitivity and specificity of the RT-QUIC assay using a CSF sample were recently reported to be 85% and 99%, respectivelyCitation3; however, cases with false-positive results have been reported.Citation3,4,5 The study by Trikamji et al., did not include pathological information. Therefore, we wonder whether the RT-QUIC assay result was a true-positive finding or not. Presently, a positive RT-QUIC assay result is not sufficiently specific to diagnose atypical prion disease, and a postmortem diagnosis remains the gold standard.Citation6
DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
No potential conflicts of interest were disclosed.
REFERENCES
- Trikamji B, Hamilin C, Baldwin KJ. A rare case of rapid progressive dementia with elevated RT-QuIC and negative 14-3-3 and tau proteins. Prion. 2016;10:262–4. doi:10.1080/19336896.2016.1175698. PMID:27249661.
- Hayashi Y, Iwasaki Y, Yoshikura N, Asano T, Hatano T, Tatsumi S, Satoh K, Kimura A, Kitamoto T, Yoshida M, et al. Decreased regional cerebral blood flow in the bilateral thalami and medulla oblongata determined by an easy Z-score (eZIS) analysis of 99mTc-ECD-SPECT images in a case of MM2-thalamic-type sporadic Creutzfeldt-Jakob disease. J Neurol Sci. 2015;358:447–52. doi:10.1016/j.jns.2015.09.356. PMID:26421831.
- Cramm M, Schmitz M, Karch A, Mitrova E, Kuhn F, Schroeder B, Raeber A, Varges D, Kim YS, Satoh K, et al. Stability and reproducibility underscore utility of RT-QuIC for diagnosis of Creutzfeldt-Jakob disease. Mol Neurobiol. 2016;53:1896–904. doi:10.1007/s12035-015-9133-2. PMID:25823511.
- Hayashi Y, Iwasaki Y, Yoshikura N, Asano T, Mimuro M, Kimura A, Satoh K, Kitamoto T, Yoshida M, Inuzuka T. An autopsy-verified case of steroid-responsive encephalopathy with convulsion and a false-positive result from the real-time quaking-induced conversion assay. Prion. 2017;11:284–92. doi:10.1080/19336896.2017.1345416. PMID:28749249.
- Hayashi Y, Iwasaki Y, Takekoshi A, Yoshikura N, Asano T, Mimuro M, Kimura A, Satoh K, Kitamoto T, Yoshida M, et al. An autopsy-verified case of FTLD-TDP type A with upper motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease. Prion. 2016;10:492–501. doi:10.1080/19336896.2016.1243192. PMID:27929803.
- Hayashi Y, Inuzuka T. Reply to: Amyotrophic lateral sclerosis with frontotemporal dementia (ALS-FTD) syndrome as a phenotype of Creutzfeldt-Jakob disease (CJD)? A case report. J Neurol Sci. 2017;375:489. doi:10.1016/j.jns.2017.02.055. PMID:28258726.