Brain Stem Glucose Hypermetabolism in Amyotrophic Lateral Sclerosis/Frontotemporal Dementia and Shortened Survival: An 18F-FDG PET/MRI Study

J Nucl Med. 2022 May;63(5):777-784. doi: 10.2967/jnumed.121.262232. Epub 2021 Sep 9.


A few 18F-FDG PET/CT studies have revealed the presence of brain hypermetabolism in the brain stem and cervical spinal cord of patients within the amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) continuum. We aimed to investigate this finding through a hybrid PET/MRI system, allowing a more precise depiction of the spatial pattern of metabolic changes in the brain stem and cervical spinal cord. Methods: Twenty-eight patients with a diagnosis of ALS or a diagnosis of the behavioral variant of FTD plus motoneuron disease, as well as 13 control subjects, underwent 18F-FDG PET/MRI. Mean normalized 18F-FDG uptake in the midbrain/pons, medulla oblongata, and cervical spinal cord as defined on the individual's MRI scans were compared between groups. Furthermore, the associations between regional 18F-FDG uptake 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 (spinal-ALS and FTD-motor neuron disease subgroups) in comparison to controls. 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 brain stem might be due to neuroinflammation, one of the key steps in the pathogenic cascade that leads to neurodegeneration in ALS/FTD. 18F-FDG PET/MRI 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/MRI in this setting.

Keywords: FTD; PET; amyotrophic lateral sclerosis; brain stem; survival.

MeSH terms

  • Amyotrophic Lateral Sclerosis* / diagnostic imaging
  • Brain Stem
  • Fluorodeoxyglucose F18
  • Frontotemporal Dementia* / diagnostic imaging
  • Glucose
  • Humans
  • Magnetic Resonance Imaging
  • Positron Emission Tomography Computed Tomography
  • Prospective Studies
  • Tomography, X-Ray Computed


  • Fluorodeoxyglucose F18
  • Glucose