Effect of the treatment with methylprednisolone on the cerebrospinal fluid and serum levels of CCL2 and CXCL10 chemokines in patients with active multiple sclerosis

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.

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Increased levels of circulating ICAM-1 in serum and cerebrospinal fluid of patients with active multiple sclerosis. Correlation with TNF-α and blood-brain barrier damage

Journal of Neuroimmunology ◽

10.1016/0165-5728(93)90070-f ◽

1993 ◽

Vol 43 (1-2) ◽

pp. 15-21 ◽

Cited By ~ 129

Author(s):

M.K. Sharief ◽

M.A. Noori ◽

M. Ciardi ◽

A. Cirelli ◽

E.J. Thompson

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Blood Brain ◽

Tnf Α ◽

Blood Brain Barrier Damage ◽

Active Multiple Sclerosis

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25-Hydroxyvitamin D in cerebrospinal fluid during relapse and remission of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458509107008 ◽

2009 ◽

Vol 15 (11) ◽

pp. 1280-1285 ◽

Cited By ~ 58

Author(s):

Trygve Holmøy ◽

Stine Marit Moen ◽

Thomas A Gundersen ◽

Michael F Holick ◽

Enrico Fainardi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Mass Spectrometry ◽

Cerebrospinal Fluid ◽

Neurological Diseases ◽

Hypovitaminosis D ◽

Serum Levels ◽

Liquid Chromatography Mass Spectrometry ◽

Hydroxyvitamin D ◽

Relapsing Remitting ◽

25 Hydroxyvitamin D

Hypovitaminosis D may play a role in multiple sclerosis (MS), but little is known about intrathecal vitamin D. 25-Hydroxyvitamin D was measured in cerebrospinal fluid and sera from 36 patients with relapsing-remitting MS, 20 patients with other inflammatory neurological diseases and 18 patients with non-inflammatory neurological diseases with liquid chromatography-mass spectrometry. There were no significant differences in cerebrospinal fluid concentrations of 25-hydroxyvitamin D, but the cerebrospinal fluid:serum ratio was significantly lower in MS compared with other inflammatory neurological diseases (p=0.0012) and non-inflammatory neurological diseases (p=0.041) patients. The concentrations of 25-hydroxyvitamin D in cerebrospinal fluid and serum were positively correlated and their ratio was similar to that of albumin. Neither the concentrations of 25-hydroxyvitamin D in cerebrospinal fluid or serum nor their ratio were associated with the presence of relapses or gadolinium-enhanced lesions. These results do not support that 25-hydroxyvitamin D is actively transported to the cerebrospinal fluid, or that the cerebrospinal fluid or serum levels or their ratio exert a major impact on MS activity.

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Soluble CD146 in cerebrospinal fluid of active multiple sclerosis

Neuroscience ◽

10.1016/j.neuroscience.2013.01.020 ◽

2013 ◽

Vol 235 ◽

pp. 16-26 ◽

Cited By ~ 13

Author(s):

H. Duan ◽

Y. Luo ◽

H. Hao ◽

L. Feng ◽

Y. Zhang ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Soluble Cd146 ◽

Active Multiple Sclerosis

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Reduced intrathecal IgG synthesis in the cerebrospinal fluid from natalizumab-treated patients with active multiple sclerosis

Journal of the Neurological Sciences ◽

10.1016/j.jns.2013.07.1410 ◽

2013 ◽

Vol 333 ◽

pp. e389

Author(s):

A. Harrer ◽

G. Pilz ◽

P. Wipfler ◽

K. Oppermann ◽

B. Holl ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Igg Synthesis ◽

Intrathecal Igg Synthesis ◽

Active Multiple Sclerosis

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Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in cerebrospinal fluid protein nitrotyrosine and S-nitrosothiols and with changes in glutathione levels

Journal of Neuroscience Research ◽

10.1002/jnr.10408 ◽

2002 ◽

Vol 70 (4) ◽

pp. 580-587 ◽

Cited By ~ 99

Author(s):

Vittorio Calabrese ◽

Giovanni Scapagnini ◽

Agrippino Ravagna ◽

Rita Bella ◽

Roberta Foresti ◽

...

Keyword(s):

Nitric Oxide ◽

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Nitric Oxide Synthase ◽

Oxide Synthase ◽

Cerebrospinal Fluid Protein ◽

Active Multiple Sclerosis

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Blood and CSF Biomarker Dynamics in Multiple Sclerosis: Implications for Data Interpretation

Multiple Sclerosis International ◽

10.1155/2011/823176 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

M. J. Eikelenboom ◽

B. M. J. Uitdehaag ◽

A. Petzold

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Peripheral Nervous System ◽

Serum Levels ◽

Disability Progression ◽

Protein Biomarker ◽

The Central Nervous System ◽

Neuroaxonal Degeneration

Background. Disability in multiple sclerosis (MS) is related to neuroaxonal degeneration. A reliable blood biomarker for neuroaxonal degeneration is needed.Objectives. To explore the relationship between cerebrospinal fluid (CSF) and serum concentrations of a protein biomarker for neuroaxonal degeneration, the neurofilaments heavy chain (NfH).Methods. An exploratory cross-sectional (n=51) and longitudinal (n=34) study on cerebrospinal fluid (CSF) and serum NfH phosphoform levels in patients with MS. The expanded disability status scale (EDSS), CSF, and serum levels of NfH-SMI34 and NfH-SMI35 were quantified at baseline. Disability progression was assessed at 3-year followup.Results. At baseline, patients with primary progressive MS (PPMS, EDSS 6) and secondary progressive MS (SPMS, EDSS 6) were more disabled compared to patients with relapsing remitting MS (RRMS, EDSS 2,P<.0001). Serum and CSF NfH phosphoform levels were not correlated. Baseline serum levels of the NfH-SMI34 were significantly (P<.05) higher in patients with PPMS (2.05 ng/mL) compared to SPMS (0.03 ng/mL) and RRMS (1.56 ng/mL). In SPMS higher serum than CSF NfH-SMI34 levels predicted disability progression from baseline (ΔEDSS2,P<.05). In RRMS higher CSF than serum NfH-SMI35 levels predicted disability progression (ΔEDSS2,P<.05).Conclusion. Serum and CSF NfH-SMI34 and NfH-SMI35 levels did not correlate with each other in MS. The quantitative relationship of CSF and serum NfH levels suggests that neuroaxonal degeneration of the central nervous system is the likely cause for disability progression in RRMS. In more severely disabled patients with PP/SPMS, subtle pathology of the peripheral nervous system cannot be excluded as an alternative source for blood NfH levels. Therefore, the interpretation of blood protein biomarker data in diseases of the central nervous system (CNS) should consider the possibility that pathology of the peripheral nervous system (PNS) may influence the results.

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Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/135248506ms1274oa ◽

2006 ◽

Vol 12 (3) ◽

pp. 294-301 ◽

Cited By ~ 84

Author(s):

E Fainardi ◽

M Castellazzi ◽

T Bellini ◽

M C Manfrinato ◽

E Baldi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Matrix Metalloproteinase ◽

Disease Activity ◽

Neurological Disorders ◽

Serum Levels ◽

Matrix Metalloproteinase 9 ◽

Active Matrix ◽

Magnetic Resonance Imaging Mri ◽

Metalloproteinase 9

In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND ( P <0.05, <0.02 and <0.02, respectively), serum active MMP-9/TIMP-1 ratio was higher in MS ( P<0.01) and OIND ( P<0.02) than in NIND, and serum TIMP-1 concentrations were lower in MS than in NIND ( P<0.05). More importantly, serum active MMP-9 mean levels, serum active MMP-9/TIMP-1 ratio and intrathecal production of active MMP-9 were increased in MS patients with clinical ( P<0.001, <0.001 and <0.05, respectively) and MRI ( P<0.001, <0.001 and <0.02, respectively) disease activity, whereas CSF mean concentrations of active MMP-9 and CSF active MMP-9/TIMP-1 ratio were enhanced only in MS patients with MRI evidence of disease activity ( P<0.02 and <0.01, respectively). Altogether, these findings suggest that a shift in MMP-9/TIMP-1 balance towards proteolytic activity of MMP-9 could be relevant in MS immune dysregulation. In addition, our results indicate that CSF and serum levels of active MMP-9 may represent a potential surrogate biomarker for monitoring MS disease activity. In particular, serum active MMP-9/TIMP-1 ratio seems to be a very appropriate indicator of ongoing MS inflammation, since it is easily measurable.

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