Objective To clinically diagnose MM2-cortical (MM2C) and MM2-thalamic (MM2T)-type sporadic Creutzfeldt-Jakob disease (sCJD) at early stage with high sensitivity and specificity.
Methods We reviewed the results of Creutzfeldt-Jakob disease Surveillance Study in Japan between April 1999 and September 2019, which included 254 patients with pathologically confirmed prion diseases, including 9 with MM2C-type sCJD (MM2C-sCJD) and 10 with MM2T-type sCJD (MM2T-sCJD), and 607 with non-prion diseases.
Results According to the conventional criteria of sCJD, 4 of 9 patients with MM2C- and 7 of 10 patients with MM2T-sCJD could not be diagnosed with probable sCJD until their death. Compared with other types of sCJD, patients with MM2C-sCJD showed slower progression of the disease and cortical distribution of hyperintensity lesions on diffusion-weighted images of brain MRI. Patients with MM2T-sCJD also showed relatively slow progression and negative results for most of currently established investigations for diagnosis of sCJD. To clinically diagnose MM2C-sCJD, we propose the new criteria; diagnostic sensitivity and specificity to distinguish ‘probable’ MM2C-sCJD from other subtypes of sCJD, genetic or acquired prion diseases and non-prion disease controls were 77.8% and 98.5%, respectively. As for MM2T-sCJD, clinical and laboratory features are not characterised enough to develop its diagnostic criteria.
Conclusions MM2C-sCJD can be diagnosed at earlier stage using the new criteria with high sensitivity and specificity, although it is still difficult to diagnose MM2T-sCJD clinically.
Statistics from Altmetric.com
Contributors Study concept and design: TH and MY. Acquisition, analysis or interpretation of data: TH, NS, RA, NY, KSak, MT, SM, YI, KSat, HMu, MH, TT, HMi and MY. Drafting of the manuscript: TH and MY. Critical revision of the manuscript for important intellectual content: TH, NS, RA, NY, KSak, MT, SM, YI, KSat, HMu, MH, TT, HMi and MY.
Funding TH, NS, RA, MT, YI, MH, HMi and MY are supported by a grant-in-aid from the Research Committee of Prion Disease and Slow Virus Infection, the Ministry of Health, Labour and Welfare of Japan. NS, YN, SM, KSat, HMu, MH, TT, HMi and MY are supported by a grant-in-aid from the Research Committee of Surveillance and Infection Control of Prion Disease, the Ministry of Health, Labour and Welfare of Japan.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This study was conducted with the approval of the institutional ethics committees at Kanazawa University (no. 648), Tokyo Medical and Dental University (no. 952), and National Center of Neurology and Psychiatry (no. A2014-014). The prospective nationwide surveillance data of the CJD Surveillance Committee in Japan between April 1999 and September 2019 were used.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author, upon reasonable request.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.