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Brain metabolic changes across King's stages in amyotrophic lateral sclerosis: a 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography study.

Authors
  • Canosa, Antonio1, 2
  • Calvo, Andrea3, 4, 5
  • Moglia, Cristina3, 4
  • Manera, Umberto3
  • Vasta, Rosario3
  • Di Pede, Francesca3
  • Cabras, Sara3
  • Nardo, Davide6
  • Arena, Vincenzo7
  • Grassano, Maurizio3
  • D'Ovidio, Fabrizio3
  • Van Laere, Koen8, 9
  • Van Damme, Philip10, 11, 12
  • Pagani, Marco13, 14
  • Chiò, Adriano3, 4, 5, 13
  • 1 ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Via Cherasco 15, 10126, Turin, Italy. [email protected] , (Italy)
  • 2 Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy. [email protected] , (Italy)
  • 3 ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Via Cherasco 15, 10126, Turin, Italy. , (Italy)
  • 4 Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy. , (Italy)
  • 5 Neuroscience Institute of Turin (NIT), Turin, Italy. , (Italy)
  • 6 MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
  • 7 Positron Emission Tomography Centre AFFIDEA-IRMET S.p.A, Turin, Italy. , (Italy)
  • 8 Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven - University of Leuven, Leuven, Belgium. , (Belgium)
  • 9 Division of Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium. , (Belgium)
  • 10 Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute (LBI), KU Leuven - University of Leuven, Leuven, Belgium. , (Belgium)
  • 11 VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium. , (Belgium)
  • 12 Department of Neurology, University Hospitals Leuven, Leuven, Belgium. , (Belgium)
  • 13 Institute of Cognitive Sciences and Technologies, C.N.R., Rome, Italy. , (Italy)
  • 14 Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden. , (Sweden)
Type
Published Article
Journal
European Journal of Nuclear Medicine
Publisher
Springer-Verlag
Publication Date
Apr 01, 2021
Volume
48
Issue
4
Pages
1124–1133
Identifiers
DOI: 10.1007/s00259-020-05053-w
PMID: 33029654
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To assess the brain metabolic correlates of the different regional extent of ALS, evaluated with the King's staging system, using brain 18F-2-fluoro-2-deoxy-D-glucose-PET (18F-FDG-PET). Three hundred ninety ALS cases with King's stages 1, 2, and 3 (n = 390), i.e., involvement of 1, 2, and 3 body regions respectively, underwent brain 18F-FDG-PET at diagnosis. King's stage at PET was derived from ALSFRS-R and was regressed out against whole-brain metabolism in the whole sample. The full factorial design confirmed the hypothesis that differences among groups (King's 1, King's 2, King's 3, and 40 healthy controls (HC)) existed overall. Comparisons among stages and between each group and HC were performed. We included age at PET and sex as covariates. Brain metabolism was inversely correlated with stage in medial frontal gyrus bilaterally, and right precentral and postcentral gyri. The full factorial design resulted in a significant main effect of groups. There was no significant difference between stages 1 and 2. Comparing stage 3 to stage 1+2, a significant relative hypometabolism was highlighted in the former in the left precentral and medial frontal gyri, and in the right medial frontal, postcentral, precentral, and middle frontal gyri. The comparisons between each group and HC showed the extension of frontal metabolic changes from stage 1 to stage 3, with the larger metabolic gap between stages 2 and 3. Our findings support the hypothesis that in ALS, the propagation of neurodegeneration follows a corticofugal, regional ordered pattern, extending from the motor cortex to posterior and anterior regions.

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