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Updated: Jun 3, 2025
Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
Utilizing metabolomic profiling as a supportive diagnostic tool for radiologically isolated syndrome
Güllü Tarhan1, Saime Füsun Domaç1, Şahabettin Selek2
1Erenköy Mental and Nervous Diseases Hospital, Neurology, Turkey.
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.
Insights
Metabolomic profiling reveals distinct differences in body fluid biomarkers between Radiologically Isolated Syndrome (RIS) and Multiple Sclerosis (MS) patients. These findings support using Nuclear Magnetic Resonance spectroscopy for early MS diagnosis and suggest RIS may be a subtype of MS.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Diagnostics
Background:
- Radiologically Isolated Syndrome (RIS) presents MRI abnormalities suggestive of Multiple Sclerosis (MS) without clinical symptoms.
- Early diagnosis and understanding of RIS progression to MS are critical.
- Biomarker discovery is essential for differentiating RIS and predicting MS development.
Purpose of the Study:
- To investigate metabolomic profiles of body fluids in patients with pre-diagnosis of RIS or MS.
- To identify potential biomarkers for early diagnosis and differentiation between RIS and MS.
- To compare metabolomic data between RIS, MS, and healthy controls.
Main Methods:
- Collected cerebrospinal fluid (CSF), serum, and urine from 63 patients (30 RIS, 33 MS) and urine/blood from 30 healthy controls.
- Utilized Nuclear Magnetic Resonance spectroscopy (NMRS) for metabolomic profiling of body fluids.
- Applied multivariate statistical analyses including Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) using MetaboAnalyst R.
Main Results:
- Significant differences in CSF, serum, and urine metabolite levels were observed between MS and RIS groups (p ≤ 0.05).
- Specific elevated metabolites in MS patients included lactate, creatine phosphate, pyruvate (CSF), hydroxyvalerate, xylitol, agmatine (serum), and threonine, creatine, cystine, 2-aminobutyrate, ascorbic acid (urine).
- Enrichment analysis of RIS CSF samples showed high consistency with MS disease patterns, though PCA and PLS-DA showed limited differentiation between RIS and MS groups.
Conclusions:
- Metabolomic profiling, particularly of CSF using NMRS, shows promise for distinguishing RIS from MS.
- Collective evaluation of multiple biomarkers is more effective than relying on single markers for diagnosis.
- Findings suggest RIS patients may represent a distinct subtype of MS, warranting further investigation and potential integration into diagnostic criteria.
