Highlights
- •Serum glutamate and nitric oxide are significantly higher in MS patients during relapse.
- •Serum glutamate and nitric oxide levels can predict occurrence of a relapse.
- •There is positive correlation between glutamate and nitric oxide in MS patients.
Abstract
Background
Despite multiple diagnostic tests, multiple sclerosis (MS) remains a clinical diagnosis
with supportive paraclinical evidence.
Objective
To measure glutamate and nitric oxide serum levels in MS patients during and in between
relapses to assess their potential role as biomarkers of disease activity and relapses.
Subjects and Methods
This cross sectional study was carried out on 70 MS patients and 40 age and sex matched
apparently healthy controls. MS patients were divided into 2 groups; group 1 that
included thirty MS patients without history of relapse within the last 3 months prior
to recruitment and group 2 that included forty MS patients with history of relapse
within the last 30 day prior to recruitment.
Results
Serum glutamate was significantly higher in group 2 (24.67 ± 9.58 μg/ml) compared
to group 1(12.5 ± 4.9 μg/ml) (P value < 0.0001) and apparently healthy controls (3.5 ± 1.3 μg/ml) (P value < 0.0001). Serum nitric oxide was significantly higher in group 2 (84.87 ± 29.6 nmol/μl)
than group 1 (41.99 ± 24.2 nmol/μl) (P value < 0.0001) and apparently healthy controls
(12.03 ± 3.59 nmol/μl) (P value < 0.0001). Cutoff values of 17.5 μg/ml for glutamate and 75.2 nmol/μl for nitric
oxide were found to predict occurrence of a relapse (sensitivity = 70% and 72.5% and
specificity= 90% and 93.3% respectively).
Conclusion
Serum glutamate and nitric oxide can be potential easily-accessible biomarkers of
disease activity and relapses in MS patients.
Keywords
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References
- Nitric oxide as an activity marker in multiple sclerosis.J. Neurol. 2003; 250: 588-592
- CSF and serum orosomucoid (α-1-acid glycoprotein) in patients with multiple sclerosis: a comparison among particular subgroups of MS patients.Clinica Chimica Acta. 2003; 334: 107-110
- Genetic variation influences glutamate concentrations in brains of patients with multiple sclerosis.Brain. 2010; 133: 2603-2611
- Nitric oxide neurotoxicity in neurodegenerative diseases.Front. Biosci. 2004; 9: 763-776
- Nitric oxide synthase expression and enzymatic activity in multiple sclerosis.Acta. Neurol. Scand. 2004; 109: 261-269
- Glutamate NMDA receptors in pathophysiology and pharmacotherapy of selected nervous system diseases.Adv. Hyg. Experim. Med./Poste. Higie. Medy. Doswiad. 2011; 65: 338-346
- The potential role of nitric oxide in multiple sclerosis.Mul. Scler. J. 1998; 4: 212-216
- Serum nitric oxide is increased in untreated multiple sclerosis patients.Mul. Scler. J. 2017; 23: 586-587
- Disease biomarkers in multiple sclerosis.Mol. Diagn. Ther. 2009; 13: 225-244
- Biomarkers of therapeutic response in multiple sclerosis: current status.Mol. Diagn. Ther. 2014; 18: 605-617
- Serum lactate and uric acid as biomarkers for disease activity and progression in multiple sclerosis.Egyp. J. Neur., Psy. Neuros. 2015; 52: 127-131
- Serum nitric oxide concentrations in patients with multiple sclerosis and patients with epilepsy.J. Neural. Transm. 2012; 119: 7-11
- Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).Neurology. 1983; 33: 1444
- Defining the clinical course of multiple sclerosis: the 2013 revisions.Neurology. 2014; 83: 278-286
- Nitric oxide from inflammatory‐activated glia synergizes with hypoxia to induce neuronal death.J. Neurosci. Res. 2005; 79: 208-215
- Predictors of attack severity and duration in multiple sclerosis: a prospective study.Open Neurol. J. 2011; 5: 75
- Serum nitric oxide metabolites in patients with multiple sclerosis.J. cli. neurosci. 2002; 9: 530-532
- Multiple sclerosis: Identification and clinical evaluation of novel CSF biomarkers.J. Proteomics. 2010; 73: 1117-1132
- Glutamate uptake by Oligodendrocytes Implications for excitotoxicity in multiple sclerosis.Neurology. 2003; 61: 1113-1120
- Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria.Ann. Neurol. 2011; 69: 292-302
- CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis.Neurology. 2004; 63: 1439-1445
- Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosis.Mul. Scler. J. 2008; 14: 59-66
- Excitatory amino acid induced oligodendrocyte cell death in vitro: receptor‐dependent and‐independent mechanisms.J. Neurochem. 2004; 90: 1173-1185
- Excitatory amino acids and multiple sclerosis: evidence from cerebrospinal fluid.Arch. Neurol. 2003; 60: 1082-1088
- Degenerative and inflammatory markers in the cerebrospinal fluid of multiple sclerosis patients with relapsing-remitting course of disease and after clinical isolated syndrome.Neurol. Res. 2011; 33: 415-420
- The role of nitric oxide in multiple sclerosis.The Lanc. Neurolog. 2002; 1: 232-241
- Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T.Brain. 2005; 128: 1016-1025
- Neurotransmitters in cerebrospinal fluid reflect pathological activity.Eur. J. Clin. Invest. 1997; 27: 1038-1043
- Increased concentrations of glutamate and glutamine in normal-appearing white matter of patients with multiple sclerosis and normal MR imaging brain scans.PLoS ONE. 2013; 8: e61817
- Changes in nitrite and nitrate (NO2−/NO3−) levels in cerebrospinal fluid of patients with multiple sclerosis.J. Neurol. Sci. 1997; 153: 32-34
Article info
Publication history
Published online: November 25, 2019
Accepted:
November 24,
2019
Received in revised form:
October 24,
2019
Received:
July 16,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
