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

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2025-02-20 DOI:10.1002/ana.27201

Antonio Canosa MD, PhD, Umberto Manera MD, PhD, Rosario Vasta MD, PhD, Grazia Zocco MD, Francesca Di Pede MD, Sara Cabras MD, Filippo De Mattei MD, Francesca Palumbo MD, Barbara Iazzolino PsyD, PhD, Emilio Minerva MD, Luca Sbaiz MSc, Maura Brunetti MSc, Salvatore Gallone MD, Maurizio Grassano MD, PhD, Enrico Matteoni MD, Giulia Polverari MD, Giuseppe Fuda MSc, Federico Casale MSc, PhD, Paolina Salamone MSc, PhD, Giovanni De Marco MSc, PhD, Giulia Marchese MSc, Cristina Moglia MD, PhD, Andrea Calvo MD, PhD, Marco Pagani MD, PhD, Adriano Chiò MD

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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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FUS-ALS的脑代谢特征：2-[18F]FDG-PET研究。

目的：采用2-[氟-18]氟-2-脱氧-d -葡萄糖正电子发射断层扫描（2-[18F]FDG-PET），比较融合型肌萎缩性侧索硬化症（FUS-ALS）与散发性肌萎缩性侧索硬化症（sALS）的脑代谢特征。方法：采用MATLAB实现的SPM12双样本t检验模型，对2009年至2019年在意大利都灵ALS中心诊断时接受脑2-[18F]FDG-PET治疗的12例FUS-ALS患者与40例健康对照（HC）和48例ALS患者进行比较。在病例和HC之间的比较中，我们将PET时的年龄和性别作为协变量。由于FUS-ALS通常在脊柱区域显示早期发病，在FUS-ALS和sALS之间的比较中，我们在第二步中单独纳入了以下协变量，以评估最终代谢差异的决定因素：PET时的年龄、性别和发病（脊柱/球）。结果：与FUS-ALS患者相比，sALS患者双侧额颞枕皮质和右侧脑岛代谢明显降低。经年龄调整后，双侧中央前回和右侧颞中下回仍存在相对低代谢。与HC相比，FUS患者在桥球区、右侧小脑扁桃体、齿状核和小舌表现出明显的相对高代谢，而sALS患者在双侧额叶和枕叶皮层以及左侧颞叶和顶叶区表现出相对低代谢。解释：与sALS患者相比，FUS-ALS患者表现出相对保存的运动皮质代谢，可能反映了其表型中较低运动神经元损伤的患病率。在临床试验中，2-[18F]FDG-PET作为追踪疾病传播的生物标志物的可能作用还需要前瞻性研究。Ann neurol 2025。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.