Cells (Mar 2023)

Differences in Cerebral Glucose Metabolism in ALS Patients with and without <i>C9orf72</i> and <i>SOD1</i> Mutations

  • Joke De Vocht,
  • Donatienne Van Weehaeghe,
  • Fouke Ombelet,
  • Pegah Masrori,
  • Nikita Lamaire,
  • Martijn Devrome,
  • Hilde Van Esch,
  • Mathieu Moisse,
  • Michel Koole,
  • Patrick Dupont,
  • Koen Van Laere,
  • Philip Van Damme

DOI
https://doi.org/10.3390/cells12060933
Journal volume & issue
Vol. 12, no. 6
p. 933

Abstract

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Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons. In 10% of patients, the disorder runs in the family. Our aim was to study the impact of ALS-causing gene mutations on cerebral glucose metabolism. Between October 2010 and October 2022, 538 patients underwent genetic testing for mutations with strong evidence of causality for ALS and 18F-2-fluoro-2-deoxy-D-glucose-PET (FDG PET), at University Hospitals Leuven. We identified 48 C9orf72-ALS and 22 SOD1-ALS patients. After propensity score matching, two cohorts of 48 and 21 matched sporadic ALS patients, as well as 20 healthy controls were included. FDG PET images were assessed using a voxel-based and volume-of-interest approach. We observed widespread frontotemporal involvement in all ALS groups, in comparison to healthy controls. The degree of relative glucose metabolism in SOD1-ALS in motor and extra-motor regions did not differ significantly from matched sporadic ALS patients. In C9orf72-ALS, we found more pronounced hypometabolism in the peri-rolandic region and thalamus, and hypermetabolism in the medulla extending to the pons, in comparison to matched sporadic ALS patients. Our study revealed C9orf72-dependent differences in glucose metabolism in the peri-rolandic region, thalamus, and brainstem (i.e., medulla, extending to the pons) in relation to matched sporadic ALS patients.

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