CSF levels of glutamine synthetase and GFAP to explore astrocytic damage in seronegative NMOSD

ObjectiveTo explore levels of astrocytopathy in neuromyelitis optica spectrum disorder (NMOSD) by measuring levels of the astrocytic enzyme glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), an established astrocytic biomarker known to be associated with disease activity in multiple sclerosis.MethodsCerebrospinal fluid concentrations of GS and GFAP were measured by ELISA in patients with NMOSD (n=39, 28 aquaporin-4 (AQP4)-Ab-seropositive, 3 double-Ab-seronegative, 4 myelin oligodendrocyte glycoprotein (MOG)-Ab-seropositive and 4 AQP4-Ab-seronegative with unknown MOG-Ab-serostatus), multiple sclerosis (MS) (n=69), optic neuritis (n=5) and non-neurological controls (n=37).ResultsGFAP and GS concentrations differed significantly across groups (both p<0.001), showing a similar pattern of elevation in patients with AQP4-Ab-seropositive NMOSD. GS and GFAP were significantly correlated, particularly in patients with AQP4-Ab-seropositive NMOSD (rs=0.70, p<0.001). Interestingly, GFAP levels in some patients with double-Ab-seronegative NMOSD were markedly increased.ConclusionsOur data indicate astrocytic injury occurs in some patients with double-Ab-seronegative NMOSD, which hints at the possible existence of yet undiscovered astrocytic autoimmune targets. We hypothesise that elevated GS and GFAP levels could identify those double-Ab-seronegative patients suitable to undergo in-depth autoimmune screening for astrocytic antibodies.

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Osteopontin concentrations are increased in cerebrospinal fluid during attacks of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510382247 ◽

2010 ◽

Vol 17 (1) ◽

pp. 32-42 ◽

Cited By ~ 48

Author(s):

Lars Börnsen ◽

Mohsen Khademi ◽

Tomas Olsson ◽

Per Soelberg Sørensen ◽

Finn Sellebjerg

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Disease Activity ◽

Cross Sectional Study ◽

Enzyme Linked Immunosorbent Assay ◽

Cross Sectional ◽

Blood Samples ◽

Relapsing Remitting ◽

Repeated Sampling ◽

Csf Levels

Background:The cytokine osteopontin (OPN) is a potential key player in the immunopathogenesis of multiple sclerosis (MS) and a candidate biomarker for disease activity. Objective:The objective of this study was to examine concentrations of OPN in the cerebrospinal fluid (CSF) across the clinical spectrum of MS. Methods:Our research consisted of a cross-sectional study of patients from two randomized, placebo-controlled trials. Concentrations of OPN and other blood and CSF markers were determined using an enzyme-linked immunosorbent assay (ELISA). Samples were obtained from untreated patients with exacerbation of clinically isolated syndrome (CIS) ( n = 25) and relapsing–remitting MS (RRMS) ( n = 41) of whom 48 participated in clinical trials, randomly allocated to treatment with placebo or methylprednisolone (MP) and undergoing repeated sampling after 3 weeks. Furthermore, we obtained CSF and blood samples from patients with primary progressive MS (PPMS, n = 9), secondary progressive MS (SPMS, n = 28) and other neurological disorders (OND, n = 44), and blood samples from 24 healthy subjects. Results:OPN concentrations were significantly increased in the CSF of patients with CIS ( p = 0.02) and RRMS ( p < 0.001) in exacerbation compared to patients with OND, and increased levels of OPN were associated with high values of other biomarkers of inflammation. At 3-week follow-up CSF OPN concentrations had decreased significantly from baseline regardless treatment with placebo or MP. Patients with PPMS had increased OPN levels in the CSF ( p = 0.004) and high CSF levels of OPN were associated with high degrees of disability. Conclusions:OPN concentration in the CSF is a dynamic indicator of disease activity in RRMS, presumably reflecting ongoing inflammation. Increased CSF OPN concentrations in PPMS may indicate ongoing inflammation even in these patients.

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Increased Levels of Endothelin-1 in Cerebrospinal Fluid Are a Marker of Poor Visual Recovery after Optic Neuritis in Multiple Sclerosis Patients

Disease Markers ◽

10.1155/2019/9320791 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Massimiliano Castellazzi ◽

Giuseppe Lamberti ◽

Maria Vittoria Resi ◽

Eleonora Baldi ◽

Luisa Maria Caniatti ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Optic Neuritis ◽

Prognostic Marker ◽

Cerebral Hypoperfusion ◽

Cross Sectional ◽

Endothelin 1 ◽

Csf Levels ◽

Vascular Hypoperfusion ◽

Multiple Sclerosis Patients

Background. Multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the central nervous system, typically features immune-mediated focal demyelination and secondary axonal degeneration. Cerebral hypoperfusion of the normal-appearing white matter (NAWM) has been reported in MS patients and may be mediated by elevated levels of endothelin-1 (ET-1), a most potent vasoconstrictive peptide released from reactive astrocytes in MS focal lesions. Optic neuritis (ON) is one of the most frequent manifestations of MS and also shows peripapillary vascular hypoperfusion in combination with disc swelling. Aims. We aimed to compare serum and cerebrospinal fluid (CSF) levels of ET-1 as a potential prognostic marker of MS-ON in two groups of patients differing for severity of MS-ON clinical presentation. Materials and Methods. A cross-sectional study to compare serum and CSF levels of ET-1 between patients with clinically aggressive MS-ON (A-MS-ON) and nonaggressive MS-ON (NA-MS-ON) according to conventional ophthalmological criteria, including optical coherence tomography. CSF and serum concentrations of ET-1 were measured using a commercially available ELISA method. Results. Sixteen patients consecutively referred to the Units of Neurology for visual disturbances attributable to MS were recruited, 11 (69%) patients with A-MS-ON and 5 (31%) with NA-MS-ON. Median CSF ET-1 levels and CSF/serum ET-1 quotient were significantly higher in patients with A-MS-ON (0.30 vs. 0.56 ng/ml) as compared to NA-MS-ON (0.16 vs. 0.16). Conclusions. Severity and failure in the recovery from ON in MS patients may depend from vascular hypoperfusion of the optic nerve induced by high intrathecally produced ET-1, a potential prognostic marker of ON recovery in MS. The detection of CSF ET-1 levels may allow identifying groups of ON patients potentially benefitting from treatment with ET-1 antagonists (e.g., bosentan).

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Evaluating Soluble EMMPRIN as a Marker of Disease Activity in Multiple Sclerosis: Studies of Serum and Cerebrospinal Fluid

PLoS ONE ◽

10.1371/journal.pone.0163802 ◽

2016 ◽

Vol 11 (10) ◽

pp. e0163802 ◽

Cited By ~ 1

Author(s):

Deepak K. Kaushik ◽

Heather Y. F. Yong ◽

Jennifer N. Hahn ◽

Claudia Silva ◽

Steven Casha ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Disease Activity

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Serum glial fibrillary acidic protein correlates with multiple sclerosis disease severity

Multiple Sclerosis Journal ◽

10.1177/1352458518819380 ◽

2018 ◽

Vol 26 (2) ◽

pp. 210-219 ◽

Cited By ~ 16

Author(s):

Heidi Högel ◽

Eero Rissanen ◽

Christian Barro ◽

Markus Matilainen ◽

Marjo Nylund ◽

...

Keyword(s):

Multiple Sclerosis ◽

Nervous System ◽

Glial Fibrillary Acidic Protein ◽

Disease Progression ◽

Disease Severity ◽

Single Molecule ◽

Progressive Disease ◽

Disease Duration ◽

Acidic Protein ◽

Csf Levels

Background: Cerebrospinal fluid (CSF) levels of two soluble biomarkers, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), have been shown to associate with multiple sclerosis (MS) disease progression. Now, both biomarkers can be detected reliably in serum, and importantly, their serum levels correlate well with their CSF levels. Objective: To evaluate the usability of serum GFAP measurement as a biomarker of progressive disease and disease severity in MS. Methods: Clinical course, Expanded Disability Status Scale (EDSS), disease duration, patient age and magnetic resonance imaging (MRI) parameters were reviewed in 79 MS patients in this cross-sectional hospital-based study. Serum samples were collected for measurement of GFAP and NfL concentrations using single molecule array (Simoa) assay. A cohort of healthy controls was evaluated for comparison. Results: Higher serum concentrations of both GFAP and NfL were associated with higher EDSS, older age, longer disease duration, progressive disease course and MRI pathology. Conclusion: Earlier studies have demonstrated that GFAP, unlike NfL, is not increased in association with acute focal inflammation-related nervous system damage. Our work suggests that GFAP serum level associates with disease progression in MS and could potentially serve as an easily measurable biomarker of central nervous system (CNS) pathology related to disease progression in MS.

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Cerebrospinal Fluid Biomarkers for Predicting Development of Multiple Sclerosis in Acute Optic Neuritis: A Population-Based Prospective Cohort Study

SSRN Electronic Journal ◽

10.2139/ssrn.3237723 ◽

2018 ◽

Author(s):

Mads N Olesen ◽

Kerstin Soelberg ◽

Birgit Debrabant ◽

Anne C Nilsson ◽

Soren T Lillevang ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Cohort Study ◽

Optic Neuritis ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Population Based ◽

Acute Optic Neuritis ◽

Cerebrospinal Fluid Biomarkers

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Multiple sclerosis and optic neuritis: CCR5 and CXCR3 expressing T cells are augmented in blood and cerebrospinal fluid

Journal of Neurology ◽

10.1007/s00415-002-0699-z ◽

2002 ◽

Vol 249 (6) ◽

pp. 723-729 ◽

Cited By ~ 49

Author(s):

Natalia Teleshova ◽

Mikhail Pashenkov ◽

Yu-Min Huang ◽

Mats Söderström ◽

Pia Kivisäkk ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Cerebrospinal Fluid ◽

Optic Neuritis

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Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/1352458505ms1187sr ◽

2005 ◽

Vol 11 (4) ◽

pp. 492-494 ◽

Cited By ~ 61

Author(s):

E T Lim ◽

T Berger ◽

M Reindl ◽

C M Dalton ◽

K Fernando ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Magnetic Resonance ◽

Optic Neuritis ◽

Myelin Basic Protein ◽

Basic Protein ◽

Myelin Oligodendrocyte Glycoprotein ◽

Clinically Isolated Syndrome ◽

Resonance Imaging

This study investigates whether the presence of serum and plasma anti-myelin oligodendrocyte glycoprotein (MOG) and anti-myelin basic protein (MBP) in patients presenting with a clinically isolated syndrome compatible with demyelination (CIS) predicts early conversion to multiple sclerosis (MS). Forty-seven patients with CIS (46 with optic neuritis) had anti-MOG and anti-MBP antibodies analysed at baseline, and clinical and magnetic resonance imaging assessments. There was no evidence that the MS status based on either the McDonald or Poser criteria relates to the antibody status.

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