Brainstem glucose hypermetabolism in ALS/FTD and shorten survival: a 18F-FDG PET/MR study

Introduction: A few 18F-FDG (FDG) PET-CT studies revealed the presence of brain hypermetabolism in the brainstem and cervical spinal cord of patients within the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia (ALS/FTD) spectrum. We aim to investigate this finding through a hybrid PET-MR system, allowing a more precise spatial pattern of metabolic changes in the brainstem and cervical spinal cord. Methods: Twenty-eight patients with a diagnosis of ALS or behavioural variant FTD plus motoneuron disease and 13 healthy subjects underwent 18F-FDG PET-MR study. Mean normalized FDG uptake values in the midbrain/pons, medulla oblongata, and cervical spinal cord defined on individual's MR scans were compared between groups. Furthermore, the associations between regional FDG uptake values and clinical and demographic characteristics, including gene mutation, type of onset (bulbar, spinal, dementia), and clinical characteristics were investigated. Results: A significant (P < 0.005) increment in glucose metabolism in the midbrain/pons and medulla oblongata was found in ALS/FTD patients in comparison to controls, independent from the type of disease onset. No relevant associations between clinical and metabolic features were reported, although medulla oblongata hypermetabolism was associated with shortened survival (P < 0.001). Conclusion: Increased glucose metabolism in the brainstem might be due to the local activation of astrocytes. FDG PET/MR could be a valuable tool to assess glial changes in the ALS/FTD spectrum and could serve as a prognostic biomarker. Large prospective initiatives would likely shed more light on the promising application of PET/MR in this setting.