Identification of Biomarkers of Drug-resistant Epilepsy Using a Metabolomic Approach: A Multicenter Validation Study
Abstract number :
3.211
Submission category :
2. Translational Research / 2C. Biomarkers
Year :
2024
Submission ID :
1104
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Monica Puligheddu, MD, PhD – University of Cagliari
Davide Fonti, MD – PO Sirai, ASL Carbonia
Federica Murgia, PhD – University of Cagliari
Sara Casciato, MD, PhD – San Camillo Forlanini Hospital
Patrizia Pulitano, MD, PhD – AOU Policlinico Umberto I
Antonella Muroni, MD, PhD – AOU Cagliari
Lorenzo Polizzi, MD – AOU Cagliari
Roberta Coa, MD, PhD – AOU Cagliari
Oriano Mecarelli, MD, PhD – AOU Policlinico Umberto I
Giancarlo Di Gennaro, MD, PhD – I.R.C.C.S. Neuromed
Luigi Atzori, MD, PhD – University of Cagliari
Rationale: Currently, no biomarkers of drug-resistant (FR) epilepsy are available in clinical practice. The study aimed to validate some previously patented molecules in a larger cohort of people with epilepsy (PwE).
Methods: A rigorous and comprehensive approach was taken in this study. Serum samples were collected from 103 drug-sensitive PcE (R), 126 FR PcE, and 115 healthy controls (CS) at three different adult epilepsy centers (AOU-Cagliari, Policlinico Umberto I Rome, Neuromed of Pozzilli). These samples were then processed at the esteemed Clinical Metabolomics Laboratory of the University of Cagliari using spectrometry coupled with gas chromatography. The following molecules were quantified: 3-hydroxybutyrate, acetoacetate, choline, citrate, glucose, glutamate, lactate, scyllo-inositol, alanine. The data were meticulously processed using multivariate and univariate statistical techniques, ensuring the validity and reliability of our results.
Results: In the comparison between CS and R, the concentrations of alanine and citrate (decreased in R) and 3-OH butyrate (increased in R) were significantly different. In comparing CS and FR, the concentrations of lactic acid, glutamate, acetate, and choline (increased in FR) and Scylla-inositol and citrate (decreased in FR) were significantly different. In comparing R and FR, the concentrations of lactic acid, acetate, and choline (increased in FR) and citrate (decreased in FR) were significantly different. Comparisons between controls and PcE (R+FR) highlighted significant differences for metabolites lactic acid, choline, acetate, glutamic acid increased in the PcE group and scyllo-inositol and citrate decreased in the same group.
Conclusions: The results of this study, conducted on a population of over 200 PcE from different Italian centers, are significant. They demonstrate that a limited number of metabolites present in peripheral blood can effectively classify FR patients. This finding holds immense potential for the development of a device for early recognition of this condition, thereby emphasizing the importance of our research in the field of epilepsy and neurology.
Funding: MIUR, Proof of Concept, D.D. del 2 marzo 2018 n. 467 POC01_00094
Translational Research