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Cerebrospinal fluid metabolomics in West Syndrome: central role of the serine metabolic pathway
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Edité par CCSD ; Arkansas State University -
International audience. Purpose: West Syndrome (WS) is a rare epileptic condition which specifically affects young infants, with a potentially severe outcome. Its pathophysiology remains unclear, which hinders progress in developing targeted medications. Here, we sought to determine whether WS patients have a specific cerebrospinal fluid (CSF) metabolic profile which could help to characterize the alterations involved.Method: CSF samples were collected during the 2010-2016 period from WS patients (n=9). The control group (n=9) included normally developing and seizure-free children who underwent a lumbar puncture (LP). Targeted and untargeted CSF metabolomics analyses were performed by Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-HRMS). The metabolic patterns were analyzed by multivariate analysis based on multiple machine-learning methods (i.e. biosigner algorithm including the use of training, test sets and bootstraps) and univariate statistical analysis.Results: Biosigner strategy revealed a significant model discriminating WS and controls from 2 metabolites including serine. The model correctly predicted diagnosis for 83% of subjects. Serine levels were also statistically different between the two groups by univariate analysis (p=0.0023).Conclusion: This is the first metabolomics study in WS. Our results suggest a pivotal need of serine in this disorder. The symptoms observed in WS are consistent with alterations of the serine metabolism pathway. We provide new data concerning this severe epileptic syndrome and highlight the potential value of metabolomics studies in pediatric neurological disorders, even when patients are scarce
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