ArticleEuropean journal of nuclear medicine and molecular imaging2026
Cerebral metabolic patterns on
Article in European journal of nuclear medicine and molecular imaging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons. However, the neurobiological basis of disease heterogeneity and its prognostic relevance remain incompletely understood.
methodsIn this prospective study, 127 patients with ALS and 128 age- and sex-matched healthy controls underwent brain fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Clinical assessments included standardized evaluations of motor function, cognition, anxiety, and depression. Associations between regional cerebral metabolism and clinical variables were examined using linear regression, whereas survival outcomes were evaluated with Cox proportional hazards models. Whole-exome sequencing was performed to assess genetic mutation status and mutation burden, and a neuroimaging-transcriptomic association analysis was conducted to link regional metabolic alterations with spatial gene expression patterns.
resultsCompared with the healthy controls, patients with ALS exhibited a distinctive cerebral metabolic pattern characterized by coexisting hypometabolism and hypermetabolism within the fronto-striatal-limbic network. Significant hypometabolism was observed in the visual pathways, temporal lobes, and cerebellum (all p < 0.05). Hypermetabolism within the fronto-striatal-limbic circuit was associated with better motor and cognitive performance, and lower levels of anxiety and depression (all p < 0.05). Multivariate Cox regression identified hypermetabolism in the right inferior frontal gyrus (opercular part), cognitive impairment, and disease progression rate as independent predictors of survival (all p < 0.05). In addition, genetic mutation status and mutation burden were significantly associated with region-specific metabolic alterations, and neuroimaging-transcriptomic analysis revealed distinct transcriptional signatures underlying hypermetabolic and hypometabolic brain regions.
conclusionCerebral metabolic abnormalities in patients with ALS reflected a complex interplay between compensatory and degenerative processes, which were closely linked to clinical symptoms and prognosis. Integrating FDG-PET metabolic profiles with genetic and transcriptional information may improve understanding of disease heterogeneity and support personalized prognostic assessment for patients with ALS. CLINICAL
trial registrationClinical trial number: not applicable.
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