Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosis

2008 ◽  
Vol 14 (1) ◽  
pp. 59-66 ◽  
Author(s):  
K. Rejdak ◽  
A. Petzold ◽  
Z. Stelmasiak ◽  
G. Giovannoni
Keyword(s):  
Nitric Oxide ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Nitrosative Stress ◽  
Study Groups ◽  
Relapsing Remitting ◽  
Specific Proteins ◽  
Nitric Oxide Metabolites ◽  
Nitrate And Nitrite

This study investigated the cerebrospinal fluid (CSF) levels of ferritin, S100B as biomarkers for glial activation and NfHSM135 — a biomarker of axonal damage — in relation to nitric oxide (NO) metabolites: nitrate and nitrite (NOx) during acute multiple sclerosis (MS) relapse. Thirty-four relapsing—remitting MS (RR-MS) patients during acute relapse and 12 controls were enrolled. Patients were assessed on Expanded Disability Status Scale (EDSS) and underwent lumbar puncture within two weeks following relapse. Twenty patients were available for further follow-up and were assessed on EDSS 6—8 weeks since the relapse onset. The CSF NOx ( P < 0.0001), NfHSM135 ( P = 0.01) and S100B ( P = 0.009) but not ferritin ( P > 0.05) were significantly raised in MS group. There was a significant correlation between CSF ferritin and S100B in RR-MS group ( P = 0.004). CSF NOx did not correlate with S100B and ferritin in study groups. RR-MS patients with detectable NfHSM135 levels had higher NOx compared with subjects having undetectable NfHSM135 ( P = 0.03). In the follow-up study, raised baseline levels of NOx ( P = 0.016) or NfHSM135 ( P = 0.04) inversely correlated with the clinical recovery grade expressed as relative EDSS change between baseline and follow-up. In conclusion, NO metabolites were increased and because of their correlation with a biomarker of axonal degeneration (neurofilaments) and a measure for clinical disability (EDSS), relapse-related nitrosative stress is likely to be relevant to the development of sustained disability in an individual patient. Multiple Sclerosis 2008; 14: 59—66. http://msj.sagepub.com

Cerebrospinal fluid and serum nitric oxide metabolites in patients with multiple sclerosis

1998 ◽  
Vol 4 (1) ◽  
pp. 27-30 ◽  
Author(s):  
G Giovannoni
Keyword(s):  
Nitric Oxide ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
Nitric Oxide Metabolites ◽  
Nitrate And Nitrite

Nitric oxide is hypothesised to play a role in the immunopathogenesis of multiple sclerosis. Raised cerebrospinal fluid and serum levels of the nitric oxide metabolites nitrate and nitrite have been described in patients with multiple sclerosis. Cerebrospinal fluid and serum nitrate and nitrite were measured in patients with multiple sclerosis, inflammatory and non-inflammatory neurological diseases, and correlated with the albumin quotient, an index of blood-brain-barrier dysfunction. Patients undergoing diagnostic lumbar and vene puncture were prospectively recruited, clinical data were obtained from the hospital records, and the CSF and serum nitrate and nitrite levels were measured by the nitrate reductase and Griess reaction methods. Nitrate and nitrite, were raised in the CSF and serum of patients with multiple sclerosis and other inflammatory neurological diseases compared to patients with non-inflammatory neurological disorders (median nitrate and nitrite: cerebrospinal fluid=10.3 μM vs 15.4 μMvs 6.6 μM, P50.001, and serum=49.0 μM vs 46.4 μM vs 38.8 μM, P=0.02, respectively). CSF nitrate and nitrite levels correlated with the albumin quotient (n=59, r=0.42, P50.001). This study provides further evidence for a role of nitric oxide in the immunopathogenesis of multiple sclerosis and supports a role for nitric oxide as a possible mediator of inflammatory blood-brain-barrier dysfunction.

Increased cerebrospinal fluid albumin and immunoglobulin A fractions forecast cortical atrophy and longitudinal functional deterioration in relapsing-remitting multiple sclerosis

2017 ◽  
Vol 25 (3) ◽  
pp. 338-343 ◽  
Author(s):  
Julia Kroth ◽  
Dumitru Ciolac ◽  
Vinzenz Fleischer ◽  
Nabin Koirala ◽  
Julia Krämer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Functional Disability ◽  
Immunoglobulin A ◽  
Cortical Atrophy ◽  
Disease Evolution ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: Currently, no unequivocal predictors of disease evolution exist in patients with multiple sclerosis (MS). Cortical atrophy measurements are, however, closely associated with cumulative disability. Objective: Here, we aim to forecast longitudinal magnetic resonance imaging (MRI)-driven cortical atrophy and clinical disability from cerebrospinal fluid (CSF) markers. Methods: We analyzed CSF fractions of albumin and immunoglobulins (Ig) A, G, and M and their CSF to serum quotients. Results: Widespread atrophy was highly associated with increased baseline CSF concentrations and quotients of albumin and IgA. Patients with increased CSFIgA and CSFIgM showed higher functional disability at follow-up. Conclusion: CSF markers of blood–brain barrier integrity and specific immune response forecast emerging gray matter pathology and disease progression in MS.

Nitric oxide metabolites and interleukin-6 in cerebrospinal fluid from multiple sclerosis patients

2002 ◽  
Vol 9 (4) ◽  
pp. 413-418 ◽  
Author(s):  
Dj. Miljkovic ◽  
J. Drulovic ◽  
V. Trajkovic ◽  
S. Mesaros ◽  
I. Dujmovic ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Interleukin 6 ◽  
Nitric Oxide Metabolites ◽  
Multiple Sclerosis Patients

Increased urinary nitric oxide metabolites in patients with multiple sclerosis correlates with early and relapsing disease

1999 ◽  
Vol 5 (5) ◽  
pp. 335-341 ◽  
Author(s):  
Gavin Giovannoni ◽  
N C Silver ◽  
J O'Riordan ◽  
R F Miller ◽  
S J.R. Heales ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Progressive Disease ◽  
Demyelinating Disease ◽  
Neuronal Loss ◽  
Clinical Relapse ◽  
Potential Mediator ◽  
Relapsing Remitting ◽  
Nitric Oxide Metabolites ◽  
Nitrate And Nitrite

Nitric oxide (•NO) has been implicated in the immunopathogenesis of MS as a potential mediator of neuronal loss. To investigate the role of .NO in the development of progressive disease we measured the .NO metabolites (nitrate and nitrite) and neopterin, in the urine of 129 patients with demyelinating disease (DD): 23 with clinically isolated syndromes compatible with demyelination and in 46 relapsing remitting (RR) and 60 patients with progressive MS. Eighty-nine of these 129 patients underwent Gd-enhanced MRI. In addition 58 normal control subjects (NC), 19 AIDS and 35 rheumatoid arthritis (RA) patients were studied. Patients with DD, AIDS and RA had significantly elevated urinary nitrate plus nitrite (nit: creat.urine) and neopterin (neopt: creat.urine) to creatinine ratios compared to NC subjects. (Median[25th-75th%] nit: creat.urine: NC=1183[962-1365] vs DD=1245[875-2403], AIDS=1686[1231-2531], and RA=1950[1214-2726] mmol/mol, P50.001 and median[25th-75th%] neopt: creat.urine: NC=99[76-151] vs DD=163[119-266], AIDS=972[653-1456], and RA=389[257-623] mmol/mol, P50.001). Patients with early DD and RR MS had significantly elevated nit: creat.urine compared to patients with progressive MS (nit: creat.urine: 1612[1020-2733] vs 1159[790-1641] mmol/mol, P=0.006). The nit: creat.urine and neopt: creat.urine did not correlate with clinical relapse or MRI activity. Excretion of .NO metabolites is increased in patients with early or relapsing-remitting disease. .NO appears to be a double-edged sword, mediating tissue damage and modulating complex immunological functions which may be protective in MS.

scholarly journals Cerebrospinal fluid growth-associated protein 43 in multiple sclerosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Åsa Sandelius ◽  
Sofia Sandgren ◽  
Markus Axelsson ◽  
Clas Malmeström ◽  
Lenka Novakova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Resonance Imaging ◽  
Secondary Progressive ◽  
Highly Active ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying

AbstractNeurodegeneration in multiple sclerosis (MS) correlates with disease progression and reparative processes may be triggered. Growth-associated protein 43 (GAP-43) exhibits induced expression during axonal growth and reduced expression during MS progression. We aimed to evaluate if GAP-43 can serve as a biomarker of regeneration in relapsing-remitting MS (RRMS) and whether disease-modifying therapies (DMTs) influence GAP-43 concentration in cerebrospinal fluid (CSF). GAP-43 was measured using an enzyme-linked immunosorbent assay in 105 MS patients (73 RRMS, 12 primary progressive MS, 20 secondary progressive MS) and 23 healthy controls (HCs). In 35 of the patients, lumbar puncture, clinical assessment, and magnetic resonance imaging was performed before initiation of therapeutic intervention, and at follow-up. CSF GAP-43 concentration was significantly lower in progressive MS compared with HCs (p = 0.004) and RRMS (p =  < 0.001) and correlated negatively with disability (p = 0.026). However, DMTs did not alter CSF GAP-43. Interestingly, in RRMS CSF GAP-43 levels were higher in patients with signs of active inflammatory disease than in patients in remission (p = 0.042). According to CSF GAP-43 concentrations, regeneration seems reduced in progressive MS, increased during disease activity in RRMS but is unaffected by treatment of highly active DMTs.

scholarly journals Adiponectin in Cerebrospinal Fluid from Patients Affected by Multiple Sclerosis Is Correlated with the Progression and Severity of Disease

2021 ◽  
Author(s):  
Elisabetta Signoriello ◽  
Marta Mallardo ◽  
Ersilia Nigro ◽  
Rita Polito ◽  
Sara Casertano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Severe Phenotype ◽  
Severity Of Disease ◽  
Total Adiponectin ◽  
Relapsing Remitting ◽  
Worse Prognosis ◽  
Age And Sex

AbstractAdiponectin exerts relevant actions in immunity and is modulated in several disorders, such as multiple sclerosis (MS). In this study, we characterized adiponectin expression and profiles in cerebrospinal fluid (CSF) from MS patients to investigate its potential relationship with the severity and progression of the disease. Total adiponectin in CSF was measured by ELISA in 66 unrelated CSF MS patients and compared with 24 age- and sex-matched controls. Adiponectin oligomer profiles were analysed by Western blotting and FPLC chromatography. Total CSF adiponectin was significantly increased in MS patients compared with controls (9.91 ng/mL vs 6.02 ng/mL) (p < 0.001). Interestingly, CSF adiponectin positively correlated with CSF IgG, and CSF/serum albumin directly correlated with CSF/serum adiponectin. Our data demonstrated that CSF adiponectin predicts a worse prognosis: patients with the progressive form of MS had higher levels compared with the relapsing remitting form; patients with higher EDSS at baseline and a higher MS severity score at 4.5-year follow-up had significantly elevated adiponectin levels with respect to patients with a less severe phenotype. Finally, the adiponectin oligomerization profile was altered in CSF from MS patients, with a significant increase in HMW and MMW. The correlation of CSF adiponectin with the severity and prognosis of MS disease confirmed the role of this adipokine in the inflammatory/immune processes of MS and suggested its use as a complementary tool to assess the severity, progression and prognosis of the disease. Further studies on larger MS cohorts are needed to clarify the contribution of adiponectin to the etiopathogenesis of MS.

Levels of nitric oxide metabolites in cerebrospinal fluid correlate with cognitive impairment in early stage multiple sclerosis

2017 ◽  
Vol 88 (10) ◽  
pp. 892-893 ◽  
Author(s):  
Kazumasa Okada ◽  
Masako Kobata ◽  
Yusuke Sennari ◽  
Yukio Iwanaka ◽  
Tomoyo Hashimoto ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Early Stage ◽  
Nitric Oxide Metabolites
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