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. 2025 Jun;97(6):1134-1143.
doi: 10.1002/ana.27201. Epub 2025 Feb 20.

Brain Metabolic Features of FUS-ALS: A 2-[18F]FDG-PET Study

Antonio Canosa  1   2   3 , Umberto Manera  1   2 , Rosario Vasta  1 , Grazia Zocco  1 , Francesca Di Pede  1 , Sara Cabras  1   4 , Filippo De Mattei  1 , Francesca Palumbo  1 , Barbara Iazzolino  1 , Emilio Minerva  1 , Luca Sbaiz  5 , Maura Brunetti  5 , Salvatore Gallone  2 , Maurizio Grassano  1 , Enrico Matteoni  1 , Giulia Polverari  6 , Giuseppe Fuda  1 , Federico Casale  1 , Paolina Salamone  1 , Giovanni De Marco  1 , Giulia Marchese  1 , Cristina Moglia  1   2 , Andrea Calvo  1   2   7 , Marco Pagani #  3   8 , Adriano Chiò #  1   2   3   7
Affiliations

Brain Metabolic Features of FUS-ALS: A 2-[18F]FDG-PET Study

Antonio Canosa et al. Ann Neurol. 2025 Jun.

Abstract

Objective: We aimed at evaluating the brain metabolic features of fused in sarcoma amyotrophic lateral sclerosis (FUS-ALS) compared with sporadic ALS (sALS), using 2-[fluorine-18] fluoro-2-deoxy-D-glucose positron emission tomography (2-[18F]FDG-PET).

Methods: We employed the 2-sample t-test model of SPM12, implemented in MATLAB, to compare 12 FUS-ALS cases with 40 healthy controls (HC) and 48 sALS, randomly collected from the series of patients who underwent brain 2-[18F]FDG-PET at the ALS Center of Turin (Italy) at diagnosis from 2009 to 2019. In the comparisons between cases and HC, we included age at PET and sex as covariates. Because FUS-ALS usually shows early onset in spinal regions, in the comparison between FUS-ALS and sALS, we included singularly the following covariates in a second step, to evaluate the determinants of eventual metabolic differences: age at PET, sex, and onset (spinal/bulbar).

Results: sALS patients showed significant relative hypometabolism in bilateral fronto-temporo-occipital cortex and right insula as compared with FUS-ALS. After adjusting for age, the relative hypometabolism remained in the bilateral precentral gyrus and in the right middle and inferior temporal gyrus. As compared with HC, FUS patients displayed a significant relative hypermetabolism in the pontobulbar region and right cerebellar tonsil, dentate nucleus, and uvula, while sALS showed relative hypometabolism in bilateral frontal and occipital cortices and in left temporal and parietal regions.

Interpretation: Patients with FUS-ALS show relative preservation of motor cortex metabolism compared with those with sALS, possibly reflecting the prevalence of lower motor neuron impairment in their phenotype. Prospective studies are necessary to investigate the possible role of 2-[18F]FDG-PET as a biomarker to track disease spreading in clinical trials. ANN NEUROL 2025;97:1134-1143.

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Conflict of interest statement

Nothing relevant to the current research.

Figures

FIGURE 1
FIGURE 1
The regions showing a statistically significant relative hypometabolism in sALS patients as compared to FUS‐ALS subjects are marked in blue and are reported on axial sections of a brain MRI template and on the brain surface of a glass brain rendering (bottom right).
FIGURE 2
FIGURE 2
The regions showing a statistically significant relative hypometabolism in sALS patients as compared to FUS‐ALS subjects after adjusting for age at PET are marked in red and are reported on axial sections of a brain MRI template and on the brain surface of a glass brain rendering (bottom right).
FIGURE 3
FIGURE 3
The regions showing a statistically significant relative hypermetabolism in FUS‐ALS patients as compared to HC after adjusting for age at PET and sex are marked in red and are reported on axial sections of a brain Magnetic Resonance Imaging template and on the brain surface of a glass brain rendering (bottom right).
See this image and copyright information in PMC

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