Contributions
Abstract: P866
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Multiple sclerosis (MS) is a heterogeneous disease with nearly unpredictable disease course. Compelling evidence points to the autoimmune mechanisms affecting the central nervous system (CNS) but the underpinning pathomechanism of ongoing degradation of CNS is still matter of debate. At this time, immunomodulatory agents are reported to reduce disease burden. Studies that have analysed early treatment in patients highly likely to have MS report significant benefits in delaying further changes on MRI and further attacks. An early recognition of the inflammatory process enables patients to begin treatment with an immunomodulatory agent, but also may increase rate of false positive MS cases.
The aim of our study was to evaluate several metabolites and test their ability to correctly classified individuals as disease-free or as individuals with multiple sclerosis.
Method: A total of 23 metabolites have been quantitated for CSF samples using 7T BioSpec 70/20 USR - MRS/MRI from 29 control patients, 17 CIS patients (according to McDonald criteria from 2010), 29 patients with definite MS, and 11 patients with demyelinating lesions of the brain not fulfilling criteria for CIS or MS. All participants were included, prior to any MS treatment. The set of tested variables included also age, disease duration, and EDSS.
Results: Cerebrospinal fluid glutamine was the only metabolite capable of distinguishing between CIS or MS and other demyelinations or controls. Moreover, increased glutamine concentrations correlated with EDSS in definite MS.
Other metabolites detected in CIS and MS were histidin, creatin, aceton and pyruvate which all showed increased concentrations, and acetate, which showed decreased concentrations. In both CIS and MS pyruvate and acetate correlated with disease duration.
Conclusion: Our findings point at a nitric catabolic state in MS. Glutamine, involved in glutamate cycle, represents a storage form of waste nitrogen. As such, glutamine was long thought to be harmless to the brain. Recent evidence suggests that excess glutamine is neurotoxic.
Acetate is a metabolite of N-acetylaspartate but is also involved, as acetyl-CoA, in lipid metabolism. Pyruvate is converted to acetyl-CoA and with acetate are essential in cell respiration. Changes of their concentrations show mitochondrial deficit. Histidin is one of essential aminoacids, its increased levels can signalise degeneration of brain proteins.
Disclosure: The study was supported by grants VEGA 01/0287/16. The authors have nothing to disclose.
Abstract: P866
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Multiple sclerosis (MS) is a heterogeneous disease with nearly unpredictable disease course. Compelling evidence points to the autoimmune mechanisms affecting the central nervous system (CNS) but the underpinning pathomechanism of ongoing degradation of CNS is still matter of debate. At this time, immunomodulatory agents are reported to reduce disease burden. Studies that have analysed early treatment in patients highly likely to have MS report significant benefits in delaying further changes on MRI and further attacks. An early recognition of the inflammatory process enables patients to begin treatment with an immunomodulatory agent, but also may increase rate of false positive MS cases.
The aim of our study was to evaluate several metabolites and test their ability to correctly classified individuals as disease-free or as individuals with multiple sclerosis.
Method: A total of 23 metabolites have been quantitated for CSF samples using 7T BioSpec 70/20 USR - MRS/MRI from 29 control patients, 17 CIS patients (according to McDonald criteria from 2010), 29 patients with definite MS, and 11 patients with demyelinating lesions of the brain not fulfilling criteria for CIS or MS. All participants were included, prior to any MS treatment. The set of tested variables included also age, disease duration, and EDSS.
Results: Cerebrospinal fluid glutamine was the only metabolite capable of distinguishing between CIS or MS and other demyelinations or controls. Moreover, increased glutamine concentrations correlated with EDSS in definite MS.
Other metabolites detected in CIS and MS were histidin, creatin, aceton and pyruvate which all showed increased concentrations, and acetate, which showed decreased concentrations. In both CIS and MS pyruvate and acetate correlated with disease duration.
Conclusion: Our findings point at a nitric catabolic state in MS. Glutamine, involved in glutamate cycle, represents a storage form of waste nitrogen. As such, glutamine was long thought to be harmless to the brain. Recent evidence suggests that excess glutamine is neurotoxic.
Acetate is a metabolite of N-acetylaspartate but is also involved, as acetyl-CoA, in lipid metabolism. Pyruvate is converted to acetyl-CoA and with acetate are essential in cell respiration. Changes of their concentrations show mitochondrial deficit. Histidin is one of essential aminoacids, its increased levels can signalise degeneration of brain proteins.
Disclosure: The study was supported by grants VEGA 01/0287/16. The authors have nothing to disclose.