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. 2021 May 19:13:655667.
doi: 10.3389/fnagi.2021.655667. eCollection 2021.

White Matter Integrity Involvement in the Preclinical Stage of Familial Creutzfeldt-Jakob Disease: A Diffusion Tensor Imaging Study

Donglai Jing  1   2 , Yaojing Chen  3 , Kexin Xie  1 , Yue Cui  1 , Chunlei Cui  4 , Li Liu  1 , Hui Lu  1 , Jing Ye  1 , Ran Gao  1 , Lin Wang  1 , Zhigang Liang  4 , Zhanjun Zhang  3 , Liyong Wu  1
Affiliations

White Matter Integrity Involvement in the Preclinical Stage of Familial Creutzfeldt-Jakob Disease: A Diffusion Tensor Imaging Study

Donglai Jing et al. Front Aging Neurosci. .

Abstract

Objective: The objective of the study was to explore patterns of white matter (WM) alteration in preclinical stage familial Creutzfeldt-Jakob disease (fCJD) using diffusion tensor imaging (DTI).

Methods: Seven asymptomatic carriers of the PRNP G114V mutation and six non-carriers were recruited from the same fCJD kindred and follow-up obtained from all asymptomatic carriers and two non-carriers 2 years later. Overlapping WM patterns were also explored in asymptomatic carriers and symptomatic CJD patients. All participants underwent clinical and neuropsychological assessments and DTI at baseline and follow-up. DTI data were subjected to whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) in WM using tract-based spatial statistics. Three comparisons were conducted: baseline carriers against non-carriers (baseline analysis), changes after 2 years in carriers (follow-up analysis), and differences between patients with symptomatic CJD and healthy controls (CJD patient analysis).

Results: Neither carriers nor non-carriers developed any neurological symptoms during 2 years of follow-up. Baseline analysis showed no differences between the carrier and non-carrier groups in MD and FA. Follow-up analysis showed significantly increased MD in multiple WM tracts, among which increased MD in the bilateral superior longitudinal fasciculus, bilateral anterior thalamic radiation, bilateral cingulate gyrus, and left uncinate fasciculus overlapped the patterns observed in patients with symptomatic CJD.

Conclusion: Changes in integrity within multiple WM tracts can be detected during the preclinical stage of fCJD.

Keywords: Creutzfeldt–Jakob disease; diffusion tensor imaging; preclinical stage; tract-based spatial statistics; white matter.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Tract-based spatial statistics (TBSS) analysis of asymptomatic carriers at baseline compared with follow-up. Increased mean diffusivity (MD) was detected by TBSS analysis in asymptomatic prion protein gene (PRNP) G114V mutation carriers at follow-up relative to baseline [family-wise error (FWE) correction, P < 0.05]. Significant areas of increased MD (red code) in asymptomatic carriers at follow-up relative to baseline are shown with the skeleton (green code).
FIGURE 2
FIGURE 2
TBSS analysis of symptomatic patients with Creutzfeldt–Jacob disease (CJD) compared with healthy controls. Increased MD was detected in patients with CJD compared with healthy controls (FWE correction, P < 0.05). Significant areas of increased MD (red code) in patients with CJD versus healthy controls are shown with the skeleton (green).
FIGURE 3
FIGURE 3
Overlapping patterns of increased MD were found between asymptomatic carriers and patients with CJD. Overlapping areas of increased MD (red code), significant areas of increase MD (blue code) in asymptomatic carriers at follow-up relative to baseline, and significant areas of increased MD (yellow code) in CJD patients versus healthy controls are shown with the skeleton (green code).
FIGURE 4
FIGURE 4
Detailed MD changes (FWE correction, P < 0.05) in overlapping white matter (WM) tracts between asymptomatic carriers and patients with CJD are shown. Overlapping patterns were detected in the bilateral superior longitudinal fasciculus, bilateral thalamic radiation, bilateral cingulate gyrus, and left uncinate fasciculus.
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