Utilizing metabolomic profiling as a supportive diagnostic tool for radiologically isolated syndrome

Background: Radiologically Isolated Syndrome (RIS) characterized by abnormalities on MRI that do not manifest as clinical symptoms of Multiple Sclerosis (MS) but raise suspicion for MS. Considering that RIS often evolves into MS, various diagnostic criteria have been established, and each suggested biomarker warrants thorough consideration and discussion. In this study, metabolomic profiling of body fluids of patients who were being followed up with a pre-diagnosis of RIS or MS and had not yet received any treatment was conducted. The results were compared internally and with healthy controls to contribute to the early diagnosis of the disease.

Methods: In this study, the body fluids of 63 patients (30 RIS, 33 MS) and 30 healthy controls were used. From the patient group, samples of cerebrospinal fluid (CSF), serum, and urine; from the healthy group, blood and urine were collected. Metabolomic profiles of the body fluids were generated using Nuclear Magnetic Resonance spectroscopy (NMRS). Multivariate statistics were conducted on the NMRS intensity data using the MetaboAnalyst R package after auto-scaling and log-transformation.

Results: In CSF levels of lactate, creatine phosphate, and pyruvate; in serum, levels of hydroxyvalerate, xylitol, and agmatine; in urine threonine, creatine, cystine, 2-aminobutyrate, and ascorbic acid were found significantly higher in the MS group compared to RIS (p ≤ 0.05). In Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA), it was observed that there was not enough differentiation between these two groups. Enrichment Analysis was performed on the CSF results of the RIS group, it was highly consistent with MS disease (ratio=∼1.8).

Conclusion: Literature reveals various results in this regard; however, the findings here emphasize a new distinction. It's important not to expect a single biomarker to stand out in metabolomic profiling methods; instead, the patient's overall results should be collectively evaluated to conduct a comprehensive analysis. The collective findings of RIS patients being consistent with MS indicate the necessity of widespread adoption and utilization of NMRS technique and metabolomic profiling, especially for CSF, in MS diagnostic criteria. Furthermore, this study provides laboratory evidence suggesting that RIS patients constitute a subtype of MS.