Post-mortem magnetic resonance imaging in patients with suspected prion disease: Pathological confirmation, sensitivity, specificity and observer reliability. A national registry.

Lorna M. Gibson,Jonathan Best,Donald A. Collie,Richard Knight,James W. Ironside,Robin Sellar,David Summers,Joanna M. Wardlaw,Francesca M. Chappell,Luisa Gregori

doi:10.1371/journal.pone.0201434

Abstract

The relationship between magnetic resonance imaging (MRI) and clinical variables in patients suspected to have Creutzfeldt-Jakob Disease (CJD) is uncertain. We aimed to determine which MRI features of CJD (positive or negative), previously described in vivo, accurately identify CJD, are most reliably detected, vary with disease duration, and whether combined clinical and imaging features increase diagnostic accuracy for CJD. Prospective patients suspected of having CJD were referred to the National CJD Research and Surveillance Unit between 1994–2004; post-mortem, brains were sent for MRI and histopathology. Two neuroradiologists independently assessed MRI for atrophy, white matter hyperintensities, and caudate, lentiform and pulvinar signals, blind to histopathological diagnosis and clinical details. We examined differences in variable frequencies using Fisher’s exact tests, and associations between variables and CJD in logistic regression models. Amongst 200 cases, 118 (59%) with a histopathological diagnosis of CJD and 82 (41%) with histopathological diagnoses other than CJD, a logistic regression model including age, disease duration at death, atrophy, white matter hyperintensities, bright or possibly bright caudate, and present pulvinar sign correctly classified 81% of cases as CJD versus not CJD. Pulvinar sign alone was not independently associated with an increased likelihood of histopathologically-confirmed CJD (of any subtype) or sporadic CJD after adjustment for age at death, disease duration, atrophy, white matter hyperintensities or caudate signal; despite the large sample, data sparsity precluded investigation of the association of pulvinar sign with variant CJD. No imaging feature varied significantly with disease duration. Of the positive CJD signs, neuroradiologists most frequently agreed on the presence or absence of atrophy (agreements in 169/200 cases [84.5%]). Combining patient age, and disease duration, with absence of atrophy and white matter hyperintensities and presence of increased caudate signal and pulvinar sign predicts CJD with good accuracy. Autopsy remains essential.

Highlights

Creutzfeldt-Jakob disease (CJD) is a fatal neurological disease characterised by a post-translational conformational change in the prion protein
Patients with CJD were significantly younger at death than patients without CJD (mean age 54 vs 62 [SD 22] years, p = 0.004) and had significantly longer disease duration
We found that brain atrophy and white matter hyperintensities are less frequently present in patients with CJD, and the presence of bright caudate increases the likelihood of a final diagnosis of CJD, in this large dataset

Summary

Introduction

Creutzfeldt-Jakob disease (CJD) is a fatal neurological disease characterised by a post-translational conformational change in the prion protein. It most often occurs sporadically (sCJD), can be genetic, but importantly sometimes is iatrogenic (iCJD) or acquired by zoonotic infection (variant CJD [vCJD]) arising from dietary contamination with bovine spongiform encephalopathy[1]. Various brain MRI features have been described in patients with CJD. Most notably these include increased signal in the caudate and lentiform nucleus in sCJD and, in vCJD, increased signal in the posterior third of the thalamus compared to other basal ganglia (named the pulvinar sign)[2]. Some variation in reported imaging findings may reflect the point in the disease course at which the patient was imaged, as it is often difficult to undertake MRI in patients with advanced forms of neurodegenerative diseases

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