White Matter Integrity Involvement in Preclinical Stage of Familial Creutzfeldt-Jakob Disease: A Diffusion Tensor Imaging Study
Background : To explore the patterns of white matter (WM) alterations using diffusion tensor imaging (DTI) in the preclinical stage of familial Creutzfeldt-Jakob disease (fCJD) . Methods: 7 asymptomatic carriers of PRNP G114V mutation and 6 non-carriers from the same fCJD kindred were recruited at baseline. Follow-up was obtained in 7 asymptomatic carriers and 2 non-carriers 2 years later. We also included 10 symptomatic CJD patients and 10 age-and gender-matched healthy controls out of the
... rols out of the kindred to observe the overlapping patterns of WM between asymptomatic carriers and symptomatic CJD patients. All subjects received clinical, neuropsychological assessments, electroencephalogram (EEG) tests, and DTI at baseline and follow-up. Tract-based spatial statistics (TBSS) was used in DTI study for whole-brain voxel wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) in WM. Results were compared in three groups: baseline carriers against non-carriers (baseline analysis), changes after 2 years in carriers (follow-up analysis), and differences between symptomatic CJD patients and healthy controls (CJD patients analysis). Results: Neither the carriers nor the non-carriers develop any neurological symptoms during 2 years follow-up. Baseline analysis showed no group differences between carriers and non-carriers in MD and FA. Follow-up analysis showed significant increased MD in left inferior fronto-occipital fasciculus, left uncinate fasciculus, bilateral superior longitudinal fasciculus, and bilateral corticospinal tract (p < 0.05), among which increased MD in bilateral superior longitudinal fasciculus and right corticospinal tract overlaps the pattern of CJD patients. Conclusion: Integrity involvement within multiple WM tracts could be detected in preclinical stage of fCJD.