Subtype Diagnosis of Sporadic Creutzfeldt–Jakob Disease with Diffusion Magnetic Resonance Imaging

Abstract

Objective Sporadic Creutzfeldt–Jakob disease (sCJD) comprises several subtypes as defined by genetic and prion protein characteristics, which are associated with distinct clinical and pathological phenotypes. To date, no clinical test can reliably diagnose the subtype. We established two procedures for the antemortem diagnosis of sCJD subtype using diffusion magnetic resonance imaging (MRI). Methods MRI of 1,458 patients referred to the National Prion Disease Pathology Surveillance Center were collected through its consultation service. One neuroradiologist blind to the diagnosis scored 12 brain regions and generated a lesion profile for each MRI scan. We selected 487 patients with autopsy‐confirmed diagnosis of “pure” sCJD subtype and at least one positive diffusion MRI examination. We designed and tested two data‐driven procedures for subtype diagnosis: the first procedure—prion subtype classification algorithm with MRI (PriSCA_MRI)—uses only MRI examinations; the second—PriSCA_MRI + Gen—includes knowledge of the prion protein codon 129 genotype, a major determinant of sCJD subtypes. Both procedures were tested on the first MRI and the last MRI follow‐up. Results PriSCA_MRI classified the 3 most prevalent subtypes with 82% accuracy. PriSCA_MRI + Gen raised the accuracy to 89% and identified all subtypes. Individually, the 2 most prevalent sCJD subtypes, MM1 and VV2, were diagnosed with sensitivities up to 95 and 97%, respectively. The performances of both procedures did not change in 168 patients with longitudinal MRI studies when the last examination was used. Interpretation This study provides the first practical algorithms for antemortem diagnosis of sCJD subtypes. MRI diagnosis of subtype is likely to be attainable at early disease stages to prognosticate clinical course and design future therapeutic trials. ANN NEUROL 2021;89:560–572

Two distinct conformers of PrPD type 1 of sporadic Creutzfeldt–Jakob disease with codon 129VV genotype faithfully propagate in vivo

“…The original classification of major sCJD subtypes based on histotype and PrP D characteristics has undergone recent revisions [2,11,12,27,32,43]. Sporadic CJDMM(MV)1 (a combination of -MM1 and -MV1, which share histotype and PrP D characteristics) as well as -MM2 (also referred to as MM2C) and -VV2, are seen as definitely distinct subtypes [5,18,19,32]. They are associated with PrP D variants that show distinct conformational and transmissible characteristics but have straightforward electrophoretic profiles of either PrP D type 1 or 2.…”

Sporadic Creutzfeldt–Jakob Disease Appears to Be Sporadic Fatal Insomnia: A Case Report and Review of the Literature

“… 14 Of note, parietal lobes were abnormal in 96% of patients with sCJDMM2C. 15 The frequency of PSWCs in patients with sCJDMM2C was 44.4%, and the CSF 14-3-3 protein was positive in 62.5% patients. 14 Pathological features of sCJDMM2C include large confluent vacuoles, cerebellar sparing, and PrP Sc perivacuolar deposition.…”

“… 5 Striatal and asymmetric lesions are frequently noted in sCJDMM1. 15 PSWCs were detected in 80% cases within 3 months of disease onset. 5 Elevated level of 14-3-3 protein is common in the CSF with 95% being sensitive.…”

Rarely fast progressive memory loss diagnosed as Creutzfeldt-Jakob disease: A case report

“…Caobelli et al [ 12 ] reported that DWI may be the most sensitive imaging technique for early diagnosis, and MRI in general is the most helpful test for suspected sCJD, as it has excellent specificity and sensitivity[ 13 ]. Repeat brain MRI revealed increased signal intensity in the cortex and head of the left caudate nucleus.…”