Cerebrospinal fluid lipocalin 2 in patients with clinically isolated syndromes and early multiple sclerosis

2016 ◽  
Vol 22 (12) ◽  
pp. 1560-1568 ◽  
Author(s):  
M Khalil ◽  
A Renner ◽  
C Langkammer ◽  
C Enzinger ◽  
S Ropele ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Basal Ganglia ◽  
Iron Accumulation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lipocalin 2 ◽  
Brain Iron ◽  
Disease Evolution ◽  
Cortical Grey Matter

Background: Lipocalin 2 (LCN2) may be involved in the immunopathogenesis of multiple sclerosis (MS) and might further impact on iron homoeostasis. Brain iron accumulates in MS; however, the association to iron-related proteins is still unsolved. Objective: To investigate cerebrospinal fluid (CSF) and serum LCN2, transferrin (Trf) and ferritin in early MS in relation to disease evolution and longitudinal brain iron accumulation. Methods: We analysed CSF and serum LCN2 by enzyme-linked immunosorbent assay (ELISA) and Trf and ferritin by nephelometry in 55 patients (45 clinically isolated syndrome (CIS), 10 MS, median clinical follow-up 4.8 years) and 63 controls. In patients, we assessed sub-cortical grey matter iron by 3T magnetic resonance imaging (MRI) R2* relaxometry (median imaging follow-up 2.2 years). Results: Compared to controls serum ( p < 0.01), CSF ( p < 0.001) LCN2 and CSF Trf ( p < 0.001) levels were reduced in the patients. CSF LCN2 correlated with CSF Trf ( r = 0.5, p < 0.001). In clinically stable patients, CSF LCN2 levels correlated with basal ganglia iron accumulation ( r = 0.5, p < 0.05). In CIS, higher CSF LCN2 levels were associated with conversion to clinically definite MS ( p < 0.05). Conclusion: We demonstrate altered LCN2 regulation in early MS and provide first evidence for this to be possibly linked to both clinical MS activity and iron accumulation in the basal ganglia.

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.

Quantitative assessment of brain iron by R2* relaxometry in patients with clinically isolated syndrome and relapsing–remitting multiple sclerosis

2009 ◽  
Vol 15 (9) ◽  
pp. 1048-1054 ◽  
Author(s):  
M Khalil ◽  
C Enzinger ◽  
C Langkammer ◽  
M Tscherner ◽  
M Wallner-Blazek ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Basal Ganglia ◽  
Quantitative Assessment ◽  
Disease Duration ◽  
Clinically Isolated Syndrome ◽  
Iron Accumulation ◽  
Iron Deposition ◽  
Relaxation Rates ◽  
Brain Iron ◽  
Relapsing Remitting

Background Increased iron deposition has been implicated in the pathophysiology of multiple sclerosis (MS), based on visual analysis of signal reduction on T2-weighted images. R2* relaxometry allows to assess brain iron accumulation quantitatively. Objective To investigate regional brain iron deposition in patients with a clinically isolated syndrome (CIS) or relapsing–remitting MS (RRMS) and its associations with demographical, clinical, and conventional magnetic resonance imaging (MRI) parameters. Methods We studied 69 patients (CIS, n = 32; RRMS, n = 37) with 3T MRI and analyzed regional R2* relaxation rates and their correlations with age, disease duration, disability, T2 lesion load, and normalized brain volumes. Results Basal ganglia R2* relaxation rates increased in parallel with age ( r = 0.3–0.6; P < 0.01) and were significantly higher in RRMS than in CIS ( P < 0.05). Using multivariate linear regression analysis, the rate of putaminal iron deposition was independently predicted by the patients’ age, disease duration, and gray matter atrophy. Conclusions Quantitative assessment by R2* relaxometry suggests increased iron deposition in the basal ganglia of MS patients, which is associated with disease duration and brain atrophy. This technique together with long-term follow-up thus appears suited to clarify whether regional iron accumulation contributes to MS morbidity or merely reflects an epiphenomenon.

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.

Torticollis as an Initial Manifestation of a Seronegative Demyelinating Disorder in a Child: A Case Report

2021 ◽  
Author(s):  
Sandesh Kini ◽  
Yellanthoor Ramesh Bhat ◽  
Lakshmikanth Halegubbi Karegowda
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Case Report ◽  
Demyelinating Disease ◽  
Oligoclonal Bands ◽  
Initial Manifestation ◽  
Demyelinating Disorder ◽  
The Brain

AbstractTorticollis refers to a condition in which the head is persistently tilted to one side, sometimes associated with pain. Torticollis in a child can be congenital or acquired. Torticollis as an initial manifestation of an underlying demyelinating syndrome is quite rare in children. Here, we report a 7-year-old girl who presented with persistent torticollis. Neuroimaging of the brain revealed features of a demyelinating disease. Further studies did not show any evidence of multiple sclerosis. Cerebrospinal fluid was negative for antiaquaporin-4 antibodies, antimyelin oligodendrocyte glycoprotein antibodies, and oligoclonal bands. A seronegative demyelinating disorder was considered. She was treated with pulsed methylprednisolone therapy. She responded well to steroids with no progression of illness during follow-up. Torticollis was partially improved.

Epstein-Barr virus-specific antibody response in cerebrospinal fluid and serum of patients with multiple sclerosis

2010 ◽  
Vol 16 (7) ◽  
pp. 883-887 ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Carmine Tamborino ◽  
Alice Cani ◽  
Elena Negri ◽  
Eleonora Baldi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disorders ◽  
Epstein Barr Virus ◽  
Serum Levels ◽  
Nuclear Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Barr Virus ◽  
Epstein Barr ◽  
Multiple Sclerosis Patients

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.

Cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis

2015 ◽  
Vol 21 (14) ◽  
pp. 1761-1770 ◽  
Author(s):  
S Modvig ◽  
M Degn ◽  
H Roed ◽  
TL Sørensen ◽  
HBW Larsson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Optic Neuritis ◽  
Light Chain ◽  
Oligoclonal Bands ◽  
Enzyme Linked Immunosorbent Assay ◽  
Csf Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Background: Cerebrospinal fluid (CSF) biomarkers have been suggested to predict multiple sclerosis (MS) after clinically isolated syndromes, but studies investigating long-term prognosis are needed. Objective: To assess the predictive ability of CSF biomarkers with regard to MS development and long-term disability after optic neuritis (ON). Methods: Eighty-six patients with ON as a first demyelinating event were included retrospectively. Magnetic resonance imaging (MRI), CSF leukocytes, immunoglobulin G index and oligoclonal bands were registered. CSF levels of chitinase-3-like-1, osteopontin, neurofilament light-chain, myelin basic protein, CCL2, CXCL10, CXCL13 and matrix metalloproteinase-9 were measured by enzyme-linked immunosorbent assay. Patients were followed up after 13.6 (range 9.6–19.4) years and 81.4% were examined, including Expanded Disability Status Scale and MS functional composite evaluation. 18.6% were interviewed by phone. Cox regression, multiple regression and Spearman correlation analyses were used. Results: Forty-six (53.5%) developed clinically definite MS (CDMS) during follow-up. In a multivariate model MRI ( p=0.0001), chitinase 3-like 1 ( p=0.0033) and age ( p=0.0194) combined predicted CDMS best. Neurofilament light-chain predicted long-term disability by the multiple sclerosis severity scale ( p=0.0111) and nine-hole-peg-test ( p=0.0202). Chitinase-3-like-1 predicted long-term cognitive impairment by the paced auditory serial addition test ( p=0.0150). Conclusion: Neurofilament light-chain and chitinase-3-like-1 were significant predictors of long-term physical and cognitive disability. Furthermore, chitinase-3-like-1 predicted CDMS development. Thus, these molecules hold promise as clinically valuable biomarkers after ON as a first demyelinating event.

Prognostic value of cerebrospinal fluid IgA and IgG in multiple sclerosis

2004 ◽  
Vol 10 (4) ◽  
pp. 469-471 ◽  
Author(s):  
Magnus Vrethem ◽  
Ingrid Fernlund ◽  
Jan Ernerudh ◽  
Sten Öhman
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Experimental Design ◽  
Prognostic Value ◽  
Walking Distance ◽  
Iga Antibodies ◽  
A Prospective Study ◽  
Myelin Degradation ◽  
Walking Aid

IgA antibodies do not activate complement and may compete with and protect against myelin degradation caused by IgM and IgG in multiple sclerosis (MS). We retrospectively evaluated cerebrospinal fluid (CSF) IgA and IgG (as indices and extended indices) from 1980 to 1988 in 68 patients with definitive MS. Sixty-one of them had survived since the time of sampling (11- 19 years). IgA Extended Index was significantly higher for surviving patients (median 0.65) than for the dead patients (median 0.33). CSF IgA or IgG indices did not correlate with disability, walking distance, or time from onset of symptoms to the need of walking aid. The retrospective experimental design allowed an unusually long follow-up time, but it also had the disadvantages of such a study. Thus the results warrant a prospective study to verify the prognostic vale of CSF IgA in MS.

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

2010 ◽  
Vol 17 (1) ◽  
pp. 32-42 ◽  
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.

Variability in longitudinal cerebrospinal fluid tau and phosphorylated tau measurements

2008 ◽  
Vol 46 (9) ◽  
Author(s):  
Nicolaas A. Verwey ◽  
Femke H. Bouwman ◽  
Wiesje M. van der Flier ◽  
Rob Veerhuis ◽  
Philip Scheltens ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Setting ◽  
Neurological Disorders ◽  
Enzyme Linked Immunosorbent Assay ◽  
Phosphorylated Tau ◽  
Memory Clinic ◽  
Duration Of Storage ◽  
Csf Levels ◽  
Lower Variability

Abstract: The influence of assay variation and duration of storage on changes in cerebrospinal fluid (CSF) levels of tau and phosphorylated (P)-tau with time was evaluated in 112 patients with various neurological disorders.: These patients (aged 66±9 years, 52% male), referred to our memory clinic, underwent two spinal taps (mean interval 19 months) and the baseline samples were assayed twice in a sandwich enzyme-linked immunosorbent assay (ELISA): once after the first spinal tap (A1) and once in a separately stored aliquot (A2) simultaneous with the follow-up sample (B).: Coefficients of variances (CVs) of tau and P-tau levels determined in repeated spinal taps (ΔB–A2) measured in one assay (10.9% and 7.6%) were lower (p<0.01) than the CVs observed in two different (ΔB–A1) assays (16.5% and 11.7%). The CVs of tau and P-tau measurement of one CSF sample repeated on two occasions (ΔA1–A2) were 12.3% and 8.6%. A difference in mean P-tau level was found if the same CSF samples were repeatedly measured in two different ELISAs (A1–A2).: Longitudinal CSF tau and P-tau are best measured in one assay resulting in a lower variability compared to measurement in two different assays. The within person variability in levels of these markers currently limits the use of these ELISAs in a longitudinal clinical setting.Clin Chem Lab Med 2008;46:1300–4.

scholarly journals Analysis of cerebrospinal fluid and cerebrospinal fluid cells from patients with multiple sclerosis for detection of JC virus DNA

2009 ◽  
Vol 15 (1) ◽  
pp. 28-35 ◽  
Author(s):  
E Iacobaeus ◽  
C Ryschkewitsch ◽  
M Gravell ◽  
M Khademi ◽  
E Wallstrom ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Copy Number ◽  
Jc Virus ◽  
Neurological Diseases ◽  
Csf Cells ◽  
Increased Risk ◽  
Low Copy Number ◽  
Patient At Risk

Objective 1) To determine whether JC virus (JCV) DNA was present in the cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) in comparison with controls and 2) to find out if our clinical material, based on presence of JCV DNA, included any patient at risk for progressive multifocal leukoencephalopathy (PML). Methods The prevalence of JCV DNA was analyzed in CSF and plasma from 217 patients with MS, 86 patients with clinically isolated syndrome (CIS), and 212 patients with other neurological diseases (OND). In addition, we analyzed CSF cells, the first report of JCV DNA in CSF cells in a single sample, and peripheral blood cells in a subgroup of MS ( n = 49), CIS ( n = 14) and OND ( n = 53). Results A low copy number of JCV DNA was detected in one MS cell free CSF sample and in one MS CSF cell samples. None of these had any signs of PML or developed this disease during follow-up. In addition, two OND plasma samples were JCV DNA positive, whereas all the other samples had no detectable virus. Conclusion A low copy number of JCV DNA may occasionally be observed both in MS and other diseases and may occur as part of the normal biology of JC virus in humans. This study does not support the hypothesis that patients with MS would be at increased risk to develop PML, and consequently screening of CSF as a measurable risk for PML is not useful.

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