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Before the introduction of MRI diffusion-weighted images (DWI), the diagnosis of Creutzfeldt–Jakob disease (CJD) relied upon nonspecific findings including clinical symptoms, EEG abnormalities, and elevated levels of cerebrospinal fluid 14-3-3 protein. Subsequently, the use of DWI has improved diagnostic accuracy, but it sometimes remains difficult to differentiate CJD from encephalitis, epilepsy, and other dementing disorders. The revised diagnostic criteria include real-time quaking-induced conversion (RT-QuIC), detecting small amounts of CJD-specific prion protein, and clinically sensitive DWI. Combining these techniques has further improved diagnostic accuracy, enabling earlier diagnosis. Herein, the authors review the recent advances in diagnostic methods and revised diagnostic criteria for sporadic CJD. They also discuss other prion diseases, such as variant CJD and chronic wasting disease, where the emergence of new types is a concern. Despite improvements in diagnostic methods and criteria, some subtypes of prion disease are still difficult to diagnose, and even the diagnosis using the most innovative RT-QuIC test remains a challenge in terms of accuracy and standardization. However, these revised criteria can be adapted to the emergence of new types of prion diseases. It is essential to continue careful surveillance and update information on the latest prion disease phenotypes.

The advances in the early and accurate diagnosis of Creutzfeldt–Jakob disease and other prion diseases: where are we today?