Defining the phenotypic spectrum of sporadic Creutzfeldt–Jakob disease MV2K: the kuru plaque type.

The article focuses on the comprehensive clinical, histopathological, and molecular characterization of the MV2K subtype of sporadic Creutzfeldt–Jakob disease (sCJD), defined by heterozygosity at codon 129 (methionine/valine) of the prion protein gene and type 2 misfolded prion protein with kuru plaques. Analyzing 126 patients, the study found that MV2K exhibits a longer disease duration and a distinct clinical presentation marked by early cerebellar symptoms combined with cognitive decline, often complicating early diagnosis. Diagnostic evaluations revealed high sensitivity for cerebrospinal fluid (CSF) prion real-time quaking-induced conversion (RT-QuIC) assay and brain diffusion-weighted MRI, whereas CSF 14-3-3 protein and EEG showed lower sensitivity. Neuropathologically, MV2K is characterized by region-dependent prion protein fragment profiles and abundant cerebellar kuru plaques, correlating with disease duration and clinical phenotype. The findings support that MV2K, the most common atypical sCJD subtype, can be accurately diagnosed in living patients through combined clinical assessment, codon 129 genotyping, CSF RT-QuIC, and MRI, despite its atypical features and diagnostic challenges.