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

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
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.

Disappearance of cerebrospinal fluid oligoclonal bands after natalizumab treatment of multiple sclerosis patients

2011 ◽  
Vol 18 (7) ◽  
pp. 1038-1041 ◽  
Author(s):  
Felipe von Glehn ◽  
Alessandro S Farias ◽  
Augusto C Penalva de Oliveira ◽  
Alfredo Damasceno ◽  
Ana Leda F Longhini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Oligoclonal Bands ◽  
Natalizumab Treatment ◽  
The Central Nervous System ◽  
Immunologic Abnormality ◽  
Csf Oligoclonal Bands ◽  
Multiple Sclerosis Patients

Intrathecal immunoglobulin synthesis in an oligoclonal pattern is the most common immunologic abnormality detected in MS patients. Various treatments, such as immunomodulators and immunosuppressors, have not been found to modify it. Natalizumab hinders migration of encephalitogenic T-cells into the central nervous system (CNS), reducing inflammatory response. Its impact on CSF oligoclonal bands (OCBs) has not been demonstrated. This report describes its effect in four out of six patients with multiple sclerosis after a mean of 10 infusions: the CSF was negative for OCBs at the second lumbar puncture. In conclusion, natalizumab treatment can reduce CSF OCBs to undetectable levels, although the clinical significance of this observation is not yet known.

Multiple Sclerosis: Monitoring Disease Activity and Progression

2017 ◽  
Author(s):  
Pavan Bhargava ◽  
Shiv Saidha
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Disease Activity ◽  
Cerebrospinal Fluid Biomarkers ◽  
The Central Nervous System ◽  
Degenerative Disorder ◽  
Clinical Measures ◽  
Assessment Strategies

Multiple sclerosis is a chronic inflammatory and degenerative disorder of the central nervous system. Measuring disease activity and progression are an integral part of the management of the disorder. A number of different approaches, including clinical measures, imaging metrics, and blood/cerebrospinal fluid biomarkers have been investigated for their utility in monitoring disease activity and progression. Each of these different approaches has certain advantages, as well as limitations, and this chapter provides an overview of these different assessment strategies.

Chlamydia pneumoniae in the cerebrospinal fluid of patients with multiple sclerosis and neurological controls

2001 ◽  
Vol 7 (6) ◽  
pp. 371-374 ◽  
Author(s):  
S Sotgiu ◽  
A Piana ◽  
M Pugliatti ◽  
A Sotgiu ◽  
G A Deiana ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Chlamydia Pneumoniae ◽  
Immunofluorescence Microscopy ◽  
Antibody Detection ◽  
Common Event ◽  
Neurological Patients ◽  
The Central Nervous System

Chlamydia pneumoniae infection is a common event in neurological patients and recovery of C. pneumoniae DNA in the cerebrospinal fluids (CSF) of multiple sclerosis (MS) patients could represent an epiphenomenon. We assessed the relevance of C. pneumoniae infection in 62 CSF samples from 32 MS patients and 30 neurological controls by means of PCR, immunofluorescence microscopy, enzyme-linked fluorescence and antibody detection. Multiple sclerosis (9.3%) and neurological controls (13.3) had similar percentage of anti-C. pneumoniae antibodies. However, C. pneumoniae DNA was only detectable in MS patients' CSF (9.3%). Our data support the hypothesis that C. pneumoniae persistence in some MS patients may be the result of an impaired clearance within the central nervous system.

scholarly journals Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis

Metabolomics ◽  
2011 ◽  
Vol 8 (2) ◽  
pp. 253-263 ◽  
Author(s):  
Marek J. Noga ◽  
Adrie Dane ◽  
Shanna Shi ◽  
Amos Attali ◽  
Hans van Aken ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Rat Model ◽  
The Central Nervous System ◽  
System Metabolism

scholarly journals Differential Gene Expression Patterns in Blood and Cerebrospinal Fluid of Multiple Sclerosis and Neuro-Behçet Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Olfa Maghrebi ◽  
Mariem Hanachi ◽  
Khadija Bahrini ◽  
Mariem Kchaou ◽  
Cyrine Jeridi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Neurological Disorders ◽  
Expression Patterns ◽  
Behçet Disease ◽  
Behcet Disease ◽  
The Central Nervous System

Inflammatory demyelinating disorders of the central nervous system are debilitating conditions of the young adult, here we focus on multiple sclerosis (MS) and neuro-Behçet disease (NBD). MS is an autoimmune disorder of the central nervous system. NBD, a neurological manifestation of an idiopathic chronic relapsing multisystem inflammatory disease, the behçet disease. The diagnosis of MS and NBD relies on clinical symptoms, magnetic resonance imaging and laboratory tests. At first onset, clinical and imaging similarities between the two disorders may occur, making differential diagnosis challenging and delaying appropriate management. Aiming to identify additional discriminating biomarker patterns, we measured and compared gene expression of a broad panel of selected genes in blood and cerebrospinal fluid (CSF) cells of patients suffering from NBD, MS and non inflammatory neurological disorders (NIND). To reach this aim, bivariate and multivariate analysis were applied. The Principal Analysis Component (PCA) highlighted distinct profiles between NBD, MS, and controls. Transcription factors foxp3 in the blood along with IL-4, IL-10, and IL-17 expressions were the parameters that are the main contributor to the segregation between MS and NBD clustering. Moreover, parameters related to cellular activation and inflammatory cytokines within the CSF clearly differentiate between the two inflammatory diseases and the controls. We proceeded to ROC analysis in order to identify the most distinctive parameters between both inflammatory neurological disorders. The latter analysis suggested that IL-17, CD73 in the blood as well as IL-1β and IL-10 in the CSF were the most discriminating parameters between MS and NBD. We conclude that combined multi-dimensional analysis in blood and CSF suggests distinct mechanisms governing the pathophysiology of these two neuro-inflammatory disorders.

Relapse of multiple sclerosis in a patient retaining CCR7-expressing T cells in CSF under fingolimod therapy

2013 ◽  
Vol 19 (9) ◽  
pp. 1230-1233 ◽  
Author(s):  
Akiko Yokoseki ◽  
Etsuji Saji ◽  
Musashi Arakawa ◽  
Mariko Hokari ◽  
Takanobu Ishiguro ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Ccr7 Expression ◽  
Blood Lymphocytes ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System ◽  
Secondary Lymphoid Organs

Fingolimod acts as a functional antagonist of the sphingosine-1-phosphate receptor, and it traps lymphocytes in secondary lymphoid organs and precludes their migration into the central nervous system. We report the case of a patient who suffered a relatively severe relapse of multiple sclerosis (MS) during the initial 3 months of fingolimod therapy, with retention of CCR7 expression on CD4+ T cells in the cerebrospinal fluid (CSF) despite decreased numbers of lymphocytes and decreased expression of CCR7 on CD4+ T cells in the blood. These data suggest that fingolimod may cause differential effects on the CSF and blood lymphocytes of patients with MS during the initial months of therapy.

scholarly journals Diagnostic significance of intrathecally synthesized immunoglobulins against neurotropic viruses (MRZ-reaction) in diagnosis of multiple sclerosis

2020 ◽  
Vol 9 (5-6) ◽  
pp. 703-712
Author(s):  
A. N. Moshnikova ◽  
V. K. Maksimchuk ◽  
S. V. Lapin ◽  
V. D. Nazarov ◽  
E. A. Surkova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Light Chains ◽  
Mrz Reaction ◽  
Neurotropic Viruses ◽  
Autoimmune Inflammation ◽  
The Central Nervous System ◽  
Oligoclonal Igg

Multiple sclerosis is chronic demyelinating disease of the central nervous system with autoimmune inflammation and accretive neurodegeneration. One of the characteristics of autoimmune inflammation in multiple sclerosis is a polyspecific intrathecal humoral immune response against neurotropic viruses (Measles, Rubella and varicella Zoster) called MRZ-reaction. This immune response is based on polyclonal activation of mature B lymphocytes in the central nervous system and intrathecal synthesis of antibodies to anamnestic antigens unrelated to viral replication in the central nervous system as well as serum antibody release. Immunoglobulins produced against neurotropic viruses are an integral part of the oligoclonal antibody pool in the cerebrospinal fluid. Because immunoglobulins can penetrate the blood brain barrier, not only serum and cerebrospinal fluid specific antibody indices are calculated, but also blood-brain barrier antibody permeability (Qalbumin, QIgG) are taken into account to assess their intrathecal synthesis. The aim of the study was to assess the informative value of the intrathecal antibodies against neurotropic viruses (MRZ-reaction) in multiple sclerosis. There were enrolled 60 patients divided into 2 groups: group 1 — 35 patients diagnosed with multiple sclerosis, group 2 — 25 patients with inflammatory and non-inflammatory disоrders of the central nervous system. Paired cerebrospinal fluid and serum samples were collected from all patients to measure level of oligoclonal IgG, immunoglobulin free kappa and lambda light chains, IgG index and specific antibodies indices, followed by assessing magnitude of MRZ-reaction. We found that the MRZ-reaction was the most specific test to diagnose multiple sclerosis. Intrathecally produced antibodies against neurotropic viruses were detected in 3 of 35 multiple sclerosis patients with lacking oligoclonal IgG antibodies. In addition, a relationship between MRZ-reaction and degree of EDSS disability was found in MS patients: peak EDSS score was reported in patients with intrathecally synthesized antibodies against 3 viral agents, whereas the minimum EDSS score — among MRZ-negative patients. Thus, assessing MRZ-reaction seems rational for confirming MS diagnosis in case of other negative laboratory tests (oligoclonal immunoglobulins and free kappa/lambda light chains in cerebrospinal fluid) allowing to improves diagnostic accuracy and evaluation of MS severity.

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