Metabolic Changes Detected by 18F-FDG PET in the Preclinical Stage of Familial Creutzfeldt-Jakob Disease

Abstract

Background: Pathologic processes in Creutzfeldt-Jakob disease (CJD) are not fully understood. Familial CJD (fCJD) gives opportunities to discover pathologic changes in the preclinical stage. Objective: To investigate cerebral glucose metabolism in the preclinical stage via 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in fCJD. Methods: Seven asymptomatic carriers of G114V mutation and six family members without PRNP mutation from the same fCJD kindred were included, and were followed for 2 years. Ten symptomatic CJD patients were also recruited. All subjects underwent standardized clinical examinations and 18F-FDG PET scans. 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: No carriers developed any neurological symptoms during 2-year follow-up. Baseline analysis: carriers demonstrates decreased metabolism (p < 0.001) in left and right postcentral, left fusiform, left superior temporal, left lingual, left superior parietal, and left Heschl gyrus. Follow-up analysis shows metabolic decline (p < 0.001) in right inferior temporal, left supra-marginal and left postcentral lobe, and increased metabolism (p < 0.001) in left fusiform, left angular, left thalamus, left Heschl’s, right Rolandic operculum, and left superior parietal gyrus. CJD patients demonstrates decreased metabolism in right inferior triangularis frontal gyrus, right middle occipital gyrus, right putamen, right thalamus, and right middle temporal gyrus. Conclusion: Hypo-metabolism of parietal and temporal lobe can be detected by 18F-FDG PET in the preclinical stage of CJD. Subcortical area might compensate in the preclinical stage and decompensate in the symptomatic stage.

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

“…Asymptomatic family members ( n = 13) were recruited from the same kindred [the same participants were reported in our previous FDG-PET study ( Lu et al, 2020 )]. A detailed family tree was published in the report of the FDG-PET and is provided in Supplementary Figure 1 ( Lu et al, 2020 ). In this kindred, nine family members (four males and five females) have passed away due to CJD.…”

“…An FDG-PET study was previously conducted in the same participants included in this investigation. The FDG-PET study focused on gray matter alterations, and the results suggested hypometabolic changes in the parietal and temporal lobes in the preclinical stage of CJD ( Lu et al, 2020 ). Although there is limited evidence supporting WM changes in non-affected carriers, preclinical gray matter changes in the same participants could suggest the involvement of WM.…”

“…Asymptomatic participants were defined as those who did not report any neurological complaints and were normal on neurological examination. Detailed exclusion criteria are provided in our previous FDG-PET study ( Lu et al, 2020 ). Participants were divided into two groups: seven asymptomatic carriers of the PRNP V mutation and six non-carriers.…”

“…A pathological study including 26 patients with CJD applying DTI and post-mortem analysis demonstrated reduced MD and reactive astrocytic gliosis in WM, suggesting WM pathological involvement in symptomatic CJD ( Caverzasi et al, 2014b ); however, there has been little research investigating WM integrity in the preclinical stage of CJD, although gray matter involvement has been proven ( Lee et al, 2009 ). An FDG-PET study conducted by our research group revealed hypometabolism in the parietal and temporal lobes of the same individual with preclinical CJD ( Lu et al, 2020 ), suggesting that metabolic changes may occur at least 10 years before the estimated onset of clinical symptoms. Therefore, further observations of changes in WM in preclinical CJD are of great significance in studying CJD pathogenesis, as such changes may jointly contribute to disease onset, along with alterations in gray matter.…”

“…To investigate changes in WM, we conducted a prospective DTI study in asymptomatic carriers and non-carriers of the PRNP G114V mutation from the same fCJD kindred, which were the same individuals as those included in our previous FDG-PET study ( Lu et al, 2020 ). The purpose of the current study was to investigate the patterns of WM changes in the brains of individuals with preclinical CJD.…”