| Abstract: | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a wide range of survival times. We aimed to explore prognostic factors related to short survival based on clinical features and plasma metabolic signatures using surface‐enhanced Raman spectroscopy (SERS). One hundred and thirty‐eight sporadic ALS cases were enrolled serially, including 62 for the short‐duration group (≤3 years) and 76 for the long‐duration group (>3 years). Multivariate analysis showed that an older age of onset (>60 years; odds ratio OR] = 3.98, 95% CI: 1.09‐14.53), lower body mass index (BMI) (<18.5; OR = 6.80, 95% CI: 1.36‐33.92), and lower ALSFRS‐R score (<35; OR = 6.03, 95% CI: 1.42‐25.63) were associated with higher odds of tracheotomy or death, while a higher uric acid (UA) level showed a protective effect (>356.36 μmol/L; OR = 0.19, 95% CI: 0.05‐0.73). SERS analysis showed significant differences between the two groups, and pathway analysis highlighted five main metabolic pathways, including metabolisms of glutathione, pyrimidine, phenylalanine, galactose, and phenylalanine‐tyrosine‐tryptophan biosynthesis. In conclusion, age of onset, BMI, ALSFRS‐R score and UA, together with dysregulation of glucose, amino acid, nucleic acid, and antioxidant metabolism contributed to disease progression, and are therefore potential therapeutic targets for ALS. |
