Role of magnetic resonance imaging, cerebrospinal fluid, and electroencephalogram in diagnosis of sporadic Creutzfeldt-Jakob disease

Abstract

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive dementia (RPD) that can be difficult to identify antemortem, with definitive diagnosis requiring tissue confirmation. We describe the clinical, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and electroencephalogram (EEG) measures of a small cohort of 30 patients evaluated for RPD. Clinical and diagnostic measures were cross-sectionally obtained from 17 sCJD patients (15 definite, two probable), 13 non-prion rapidly progressive dementia patients (npRPD), and 18 unimpaired controls. In a subset of patients (nine sCJD and nine npRPD) diffusion tensor imaging (DTI) measures [fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)] were also obtained for the caudate, corpus callosum, posterior limb of the internal capsule, pulvinar, precuneus, and frontal lobe. Differences among groups were assessed by an analysis of variance. Compared to npRPD individuals, sCJD patients had cerebellar dysfunction, significantly higher CSF tau, "positive" CSF 14-3-3, and hyperintensities on diffusion-weighted imaging (DWI) that met previously established imaging criteria for sCJD. EEG changes were similar for the two groups. In addition, sCJD patients had significant decreases in DTI measures (MD, AD, RD but not FA) within the caudate and pulvinar compared to either npRPD patients or unimpaired controls. Our results confirm that CSF abnormalities and MRI (especially DWI) can assist in distinguishing sCJD patients from npRPD patients. Future longitudinal studies using multiple measures (including CSF and MRI) are needed for evaluating pathological changes seen in sCJD patients.

Figure 1. Classification of patients

Diagram for classification of subjects as sporadic Creutzfeldt-Jakob disease (sCJD), non-prion rapidly progressive dementia (npRPD), or unimpaired control. * = 15 of 17 sCJD patients and 4 of 13 RPD controls had tissue confirmation of their diagnoses

Figure 2. Regions of interest for diffusion imaging analysis

Representative placement of six ROIs on diffusion images of a definite sCJD patient.

Figure 3. Diffusion weighted imaging (DWI) measurements with ROIs for patients

Fractional anisotropy (FA; panel A), mean diffusivity (MD; panel B), axial diffusivity (AD; panel C), and radial diffusivity (RD; panel D) values for the 6 ROIs in sCJD, npRPD, and unimpaired control subjects. sCJD patients had significant reductions in MD (primarily due to changes in both AD and RD) in the caudate and pulvinar compared to npRPD and unimpaired controls. No significant changes in FA were seen for the ROIs among the three groups. *= p < 0.05.