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

## TL;DR

This study uses brain scans to compare metabolic patterns in people with FUS-ALS and sporadic ALS, finding differences in brain activity that could help track disease progression.

## Contribution

The study identifies distinct brain metabolic profiles in FUS-ALS compared to sALS, suggesting potential biomarkers for disease tracking.

## Key findings

- FUS-ALS patients showed relative hypermetabolism in pontobulbar and cerebellar regions compared to healthy controls.
- sALS patients exhibited significant hypometabolism in fronto-temporo-occipital cortex and insula compared to FUS-ALS.
- FUS-ALS patients had preserved motor cortex metabolism compared to sALS, possibly due to lower motor neuron involvement.

## Abstract

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).

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).

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.

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