Degeneration of gray and white matter differs between hypometabolic and hypermetabolic brain regions in a patient with ALS-FTD: a longitudinal MRI - PET multimodal study.

[18F]-fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET) imaging and magnetic resonance imaging (MRI) of brain in ALS patients with frontotemporal lobe dementia (ALS-FTD) reveal hypometabolism and hypermetabolism, as well as gray matter (GM) and white matter (WM) abnormalities in different brain regions, respectively. Hypometabolism arising from neuronal dysfunction or loss is the most recognized pathophysiologic change in neurodegeneration, whereas mechanisms underlying hypermetabolism remain unclear. We hypothesize that hypometabolic and hypermetabolic brain regions in ALS-FTD represent differential degeneration of GM and WM structures, as revealed by co-registered MRI in a two time-point longitudinal multimodal study. Methods: A 69-year-old female with ALS-FTD underwent 18F-FDG PET, diffusion tensor imaging (DTI), and T1-weighted MRI at baseline (15 months after symptom onset), and 20.4 months later. Cerebral glucose metabolism rate, cortical thickness, cortical area, and WM network changes were measured longitudinally. Results and conclusion: The patient had symptoms and signs of bulbar-onset upper motor neuron (UMN)-predominant ALS with language and behavioral dysfunction. Evaluation at baseline showed bulbar dysfunction, and impaired language and executive function. At follow-up, worsened bulbar and other motor functions, and prominent FTD both reflected significant progression. Cortical thickness and surface area showed differential involvement in the hypometabolic and hypermetabolic regions. WM connections from frontal regions to other brain regions were completely absent by graph theory-based network analysis when compared to temporal regions indicating prominent frontal lobe degeneration. Structural neuroimaging reveals different patterns of GM and WM involvement in the hypometabolic and hypermetabolic brain regions in a patient with ALS-FTD.