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Determination of soluble ICAM-1 and TNFaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis
Alves-Leon Soniza Vieira,Batista Elizabeth,Papais-Alvarenga Regina,Quírico-Santos Thereza
Arquivos de Neuro-Psiquiatria , 2001,
Abstract: Cytokines and adhesion molecules have been implicated in the pathogenesis of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. In this study we analyzed intrathecal (CSF) and serum levels of soluble intercellular adhesion molecule (ICAM-1) and TNFalphaR (60kD) from 20 patients with clinically definite MS during acute relapse or stable disease. Comparing to control groups of healthy individuals and patients with intervertebral herniated disc, MS patients showed increased levels (p< 0.001) of sICAM-1 and TNFalphaR in both serum and CSF samples. Regardless stage of disease there was no significant difference in the levels of sICAM-1 during acute relapse (657±124.9 ng/ml) or remission (627±36.2 ng/ml). A steady increase of TNFalphaR (60kD) in both serum and CSF, indicate the existence of a continuous inflammatory process within the brain tissue of MS patients despite absence of clinical signs of disease activity.
Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis  [PDF]
Marcel P. Stoop,Vaibhav Singh,Lennard J. Dekker,Mark K. Titulaer,Christoph Stingl,Peter C. Burgers,Peter A. E. Sillevis Smitt,Rogier Q. Hintzen,Theo M. Luider
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012442
Abstract: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85–90%) and primary progressive (PP) MScl (10–15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF proteins.
Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis
Moreira, M.A.;Souza, A.L.S.;Lana-Peixoto, M.A.;Teixeira, M.M.;Teixeira, A.L.;
Brazilian Journal of Medical and Biological Research , 2006, DOI: 10.1590/S0100-879X2006000400003
Abstract: multiple sclerosis (ms) is a chronic inflammatory demyelinating disease of the human central nervous system. although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. they are divided into subfamilies on the basis of the location of conserved cysteine residues. we determined the levels of some cc and cxc chemokines in the cerebrospinal fluid (csf) of 23 relapsing-remitting ms patients under interferon-?-1a therapy and 16 control subjects using elisa. ms patients were categorized as having active or stable disease. cxcl10 was significantly increased in the csf of active ms patients (mean ± sem, 369.5 ± 69.3 pg/ml) when compared with controls (178.5 ± 29.1 pg/ml, p < 0.05). csf levels of ccl2 were significantly lower in active ms (144.7 ± 14.4 pg/ml) than in controls (237.1 ± 16.4 pg/ml, p < 0.01). there was no difference in the concentration of ccl2 and cxcl10 between patients with stable ms and controls. ccl5 was not detectable in the csf of most patients or controls. the qualitative and quantitative differences of chemokines in csf during relapses of ms suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.
Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis  [cached]
Moreira M.A.,Souza A.L.S.,Lana-Peixoto M.A.,Teixeira M.M.
Brazilian Journal of Medical and Biological Research , 2006,
Abstract: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon- -1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean ± SEM, 369.5 ± 69.3 pg/mL) when compared with controls (178.5 ± 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 ± 14.4 pg/mL) than in controls (237.1 ± 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.
Quantitative Detection of Epstein-Barr Virus DNA in Cerebrospinal Fluid and Blood Samples of Patients with Relapsing-Remitting Multiple Sclerosis  [PDF]
Clementina E. Cocuzza, Fabrizio Piazza, Rosario Musumeci, Davide Oggioni, Simona Andreoni, Margherita Gardinetti, Letizia Fusco, Maura Frigo, Paola Banfi, Maria R. Rottoli, Paolo Confalonieri, Monica Rezzonico, Maria T. Ferrò, Guido Cavaletti, The EBV-MS Italian Study Group is formed, in addition to the cited, by the following persons:
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0094497
Abstract: The presence of Epstein-Barr Virus (EBV) DNA in cerebrospinal fluid (CSF) and peripheral blood (PB) samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS) and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish latent from lytic EBV infection. EBV DNA was detected in 5.5% and 18.2% of cell-free and cell-associated CSF fractions of patients with RRMS as compared to 7.8% and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC) positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No significant difference in median EBV viral loads of positive samples was found between RRMS and control patients in all tested samples. Absence of statistically significant differences in EBV positivity rates between RRMS and control patients, despite the use of highly sensitive standardized methods, points to the lack of association between EBV and MS disease activity.
Characteristic Cerebrospinal Fluid Cytokine/Chemokine Profiles in Neuromyelitis Optica, Relapsing Remitting or Primary Progressive Multiple Sclerosis  [PDF]
Takuya Matsushita, Takahisa Tateishi, Noriko Isobe, Tomomi Yonekawa, Ryo Yamasaki, Dai Matsuse, Hiroyuki Murai, Jun-ichi Kira
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0061835
Abstract: Background Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO), relapsing remitting multiple sclerosis (RRMS), and primary progressive MS (PPMS), and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis. Methods/Principal Findings We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND) by multiplexed fluorescent bead-based immunoassay. Interleukin (IL)-17A, IL-6, CXCL8 and CXCL10 levels were significantly higher in NMO patients than in OND and RRMS patients at relapse, while granulocyte-colony stimulating factor (G-CSF) and CCL4 levels were significantly higher in NMO patients than in OND patients. In NMO patients, IL-6 and CXCL8 levels were positively correlated with disability and CSF protein concentration while IL-6, CXCL8, G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-γ were positively correlated with CSF neutrophil counts at the time of sample collection. In RRMS patients, IL-6 levels were significantly higher than in OND patients at the relapse phase while CSF cell counts were negatively correlated with the levels of CCL2. Correlation coefficients of cytokines/chemokines in the relapse phase were significantly different in three combinations, IL-6 and GM-CSF, G-CSF and GM-CSF, and GM-CSF and IFN-γ, between RRMS and NMO/NMOSD patients. In PPMS patients, CCL4 and CXCL10 levels were significantly higher than in OND patients. Conclusions Our findings suggest distinct cytokine/chemokine alterations in CSF exist among NMO, RRMS and PPMS. In NMO, over-expression of a cluster of Th17- and Th1-related proinflammatory cytokines/chemokines is characteristic, while in PPMS, increased CCL4 and CXCL10 levels may reflect on-going low grade T cell and macrophage/microglia inflammation in the central nervous system. In RRMS, only a mild elevation of proinflammatory cytokines/chemokines was detectable at relapse.
Remitting - Relapsing Polyneuropathy In Juvenile Metachromatic Leukodystrophy
Taly AB,Santosh V,Balamurugan N,Arunodaya GR
Annals of Indian Academy of Neurology , 2004,
Abstract: A five-year-old girl manifested with acute relapsing polyradiculo-neuropathy. Elevated cerebrospinal fluid proteins, electro-physiological evidence of conduction block and remitting course suggested possible acquired demyelinating radiculoneuropathy. However, intellectual deterioration during follow up, evidence of extensive, symmetrical and periventricular demyelination on MRI of brain and metachromatic on sural nerve biopsy led to the diagnosis of metachromatic leukodystrophy (MLD). Inherited neuropathies such as MLD may occasionally present atypically in the early stages. Recognition of this variation has considerable therapeutic and prognostic significance.
Cognitive profile of patients with relapsing remitting multiple sclerosis
ANDRADE, VIVIAN M.;BUENO, ORLANDO F.A.;OLIEVIRA, MARIA GABRIELA M.;OLIVEIRA, ACARY S.B.;OLIVEIRA, ENEDINA M.L.;MIRANDA, M?NICA C.;
Arquivos de Neuro-Psiquiatria , 1999, DOI: 10.1590/S0004-282X1999000500007
Abstract: multiple sclerosis (ms) is a common disease in western countries of temperate/cold climate, but in tropical countries an increasing number of cases have been diagnosticated. moved by the lack of information about cognitive dysfunction of brazilian ms patients, the present study attempted to describe features of neuropsychological alterations in patients with relapsing remitting ms living in the city of s?o paulo. they were compared to healthy volunteers, matched for age and education. in the absence of global intellectual deterioration, the patients had a deficit: a) in learning and verbal long-term memory tasks and in visual long-term memory of complex figure; b) in timed tasks, accounted for by a slowness of mental processes; c) in tasks with a motor component. tendency to depression was observed; anxiety levels were normal.
Cognitive profile of patients with relapsing remitting multiple sclerosis
ANDRADE VIVIAN M.,BUENO ORLANDO F.A.,OLIEVIRA MARIA GABRIELA M.,OLIVEIRA ACARY S.B.
Arquivos de Neuro-Psiquiatria , 1999,
Abstract: Multiple sclerosis (MS) is a common disease in Western countries of temperate/cold climate, but in tropical countries an increasing number of cases have been diagnosticated. Moved by the lack of information about cognitive dysfunction of Brazilian MS patients, the present study attempted to describe features of neuropsychological alterations in patients with relapsing remitting MS living in the city of S o Paulo. They were compared to healthy volunteers, matched for age and education. In the absence of global intellectual deterioration, the patients had a deficit: a) in learning and verbal long-term memory tasks and in visual long-term memory of complex figure; b) in timed tasks, accounted for by a slowness of mental processes; c) in tasks with a motor component. Tendency to depression was observed; anxiety levels were normal.
Cognitive Impairment In Relapsing Remitting Multiple Sclerosis Patients  [PDF]
Tuncer N,Midi I,Feyzioglu A
Journal of Neurological Sciences , 2012,
Abstract: The purpose of this study is to evaluate the cognitive functions in cases with relapsing remitting MS during the period in which the physical disability is seen in a lower level, as well as to examine the level and predominant domain of cognitive loss while relating it with the duration of the disease, degree of disability, and number of the episodes.Materials and Methods: Twenty five (25) patients with relapsing remitting MS were included in the study.Neuropsychological test battery which is used for the assessment of cognitive functions included tests for verbal and visual memory, simple attention and sustained attention, executive functions, visuospatial ability and language. The results were compared with 17 healthy controls matched for age, gender and education level.Results: When the patient and control groups were compared, a significant impairment was observed in MS patients on short and long time free recall and clue recall, recognition processes, recent memory and free recall processes, attention and ability to maintain attention, verbal fluency and categoric fluency during memory tests, while impairment was detected in frontal functions such as difficulty in response inhibition, perseverations in Luria drawings.Conclusion: Cognitive impairment affects the quality of life independent from disability scores, and highly informative during follow-ups as it indicates the progression of the disease. Therefore, cognitive assessment should be included in routine follow-ups. Further studies are warranted to improve the definition of the limits of cognitive impairment, to highlight the physiopathogenic mechanisms and to develop treatment principles in MS
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