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Background: Dysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic subnuclei are not well documented. We aimed to address the multimodal structuro-metabolic pattern at the level of the thalamic nuclei in fatal familial insomnia patients, and investigated the clinical presentation of primary thalamic alterations. Materials and Methods: Five fatal familial insomnia patients and 10 healthy controls were enrolled in this study. All participants underwent neuropsychological assessments, polysomnography, electroencephalogram, and cerebrospinal fluid tests. MRI and fluorodeoxyglucose PET were acquired on a hybrid PET/MRI system. Structural and metabolic changes were compared using voxel-based morphometry analyses and standardized uptake value ratio analyses, focusing on thalamic subnuclei region of interest analyses. Correlation analysis was conducted between gray matter volume and metabolic decrease ratios, and clinical features. Results: The whole-brain analysis showed that gray matter volume decline was confined to the bilateral thalamus and right middle temporal pole in fatal familial insomnia patients, whereas hypometabolism was observed in the bilateral thalamus, basal ganglia, and widespread cortices, mainly in the forebrain. In the regions of interest analysis, gray matter volume and metabolism decreases were prominent in bilateral medial dorsal nuclei, anterior nuclei, and the pulvinar, which is consistent with neuropathological and clinical findings. A positive correlation was found between gray matter volume and metabolic decrease ratios. Conclusions: Our study revealed specific structuro-metabolic pattern of fatal familial insomnia that demonstrated the essential roles of medial dorsal nuclei, anterior nuclei, and pulvinar, which may be a potential biomarker in diagnosis. Also, primary thalamic subnuclei alterations may be correlated with insomnia, neuropsychiatric, and autonomic symptoms sparing primary cortical involvement.

BackgroundBehavioral variant frontotemporal dementia (bvFTD) is a clinically heterogeneous syndrome with high heredity. However, the frequencies of mutations associated with bvFTD have yet to be determined. The aim of the current study was to investigate the frequency of Chinese Han patients harboring genetic bvFTD variants.MethodsA total of 49 bvFTD patients selected from our frontotemporal lobar degeneration database, including 14 familial cases belonging to eight families and 35 sporadic cases were consecutively recruited from July 2014 to December 2019 at Xuanwu Hospital (Beijing, China). Whole-exome sequencing (WES) was performed and repeat-primed PCR was used to test samples for the C9orf72 hexanucleotide repeat expansion mutation. The frequency of genetic variants and the pathogenicity of the novel variants were analyzed.ResultsTen pathogenic or likely pathogenic variants were identified in 17 bvFTD patients, including C9orf72 repeat expansions, six previously reported mutations and three novel mutations (MAPT p. R5C, p. D54N, GRN p. P451L). Genetic mutations accounted for 27.9% (12/43) of total cases, 87.5% (7/8) of patients with familial bvFTD, and 14.3% (5/35) with sporadic bvFTD. Pathogenic variants mostly occurred in MAPT gene (20.9%, 9/43), followed by C9orf72 repeat expansions (2.3%, 1/43), GRN gene (2.3%, 1/43) and FUS gene (2.3%, 1/43).ConclusionThere was a high prevalence of genetic variants in Chinese bvFTD patients, highlighting the necessity of genetic testing for bvFTD.

ObjectiveThe 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).MethodsSeven 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).ResultsNeither 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.ConclusionChanges in integrity within multiple WM tracts can be detected during the preclinical stage of fCJD.

Posterior cortical atrophy (PCA) is widely considered as an atypical variant of Alzheimer disease and is characterized by a progressive decline in visual function. PCA has been investigated from the standpoints of brain structure and metabolism, but tau deposition and its relationship to disease severity still remain unclear. Here, we used a novel tau ligand, [18F]PI2620, to visualize tau deposition in a PCA patient. The results showed that high [18F]PI2620 uptake in posterior cortical regions was associated with clinical manifestations, morphologic changes in the brain observed by magnetic resonance imaging (MRI), and hypometabolism detected by [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET). This is the first report demonstrating a clinical anatomical correspondence between [18F]PI2620 PET results, clinical manifestations, MRI, and [18F]FDG PET findings in a Chinese patient with PCA. The results also support the utility of [18F]PI2620 for visualizing tau aggregation in PCA.