Oligoclonal bands and cerebrospinal fluid markers in multiple sclerosis: associations with disease course and progression

2012 ◽  
Vol 19 (5) ◽  
pp. 577-584 ◽  
Author(s):  
Pedro Lourenco ◽  
Afsaneh Shirani ◽  
Jameelah Saeedi ◽  
Joel Oger ◽  
William E Schreiber ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Disease Progression ◽  
Oligoclonal Bands ◽  
Disease Course ◽  
Disability Progression ◽  
Protein Levels ◽  
Clinical Presentations ◽  
Disability Status ◽  
Work Up

Background: The use of oligoclonal bands (OCBs) and cerebrospinal fluid (CSF) parameters are established in the diagnosis of MS, but poorly as markers of disease. Objective: To investigate the role of OCBs in disease course and progression. Methods: CSF data for 1120 patients with MS were analyzed for associations between OCBs and CSF parameters and clinical data (disease course [relapsing-onset MS (ROMS) vs primary-progressive MS (PPMS)]), disability progression (proportion reaching Expanded Disability Status Scale 6 within 10 years of onset and progression index) and ethnicity. Results: Of patients with MS, 72.5% had detectable OCBs. For patients with detectable OCBs, 84.6% had ROMS and 15.4% PPMS versus 89.7% and 10.3%, respectively for those without detectable OCBs ( p=0.04). Total CSF IgG and protein levels were higher in PPMS compared with ROMS ( p<0.001). Disease progression appeared independent of OCB status. Patients with CSF (vs without) data were more likely to be male, older at onset, have PPMS and lack optic neuropathy at onset ( p<0.001). Conclusions: OCB positivity and elevated total CSF IgG and protein were moderately associated with a PPMS disease course, but not disease progression. Patients with atypical clinical presentations were more likely to have had CSF work-up, suggesting a testing bias.

scholarly journals Does CSF pleocytosis have a predictive value for disease course in MS?

2019 ◽  
Vol 6 (5) ◽  
pp. e584 ◽  
Author(s):  
Itay Lotan ◽  
Felix Benninger ◽  
Rom Mendel ◽  
Mark A. Hellmann ◽  
Israel Steiner
Keyword(s):  
Clinical Course ◽  
Medical Center ◽  
Oligoclonal Bands ◽  
Disease Course ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Csf Pleocytosis ◽  
Csf Oligoclonal Bands ◽  
Rabin Medical

ObjectiveMS is a demyelinating CNS disorder with a spectrum of clinical patterns regarding course and prognosis. Although several prognostic factors are considered in the initial evaluation of patients, biological markers defining the disease course and guiding treatments are currently lacking. It is unknown whether patients with CSF pleocytosis differ in regard to symptoms, disease course, and prognosis from those without. The aim of this study was to evaluate whether CSF pleocytosis during the initial presentation has an impact on the clinical course and progression of MS.MethodsWe retrospectively evaluated patients attending the MS Clinic at Rabin Medical Center between January 1999 and January 2016 who underwent lumbar puncture (LP) at disease presentation, considering CSF cell count, clinical diagnosis (clinically isolated syndrome [CIS] and relapsing-remitting MS [RRMS]), annualized relapse rate (ARR), paraclinical findings (imaging, CSF oligoclonal bands, and evoked potentials), and disease progression, expressed by the Expanded Disability Status Scale (EDSS).ResultsOne hundred fourteen patients (72 females) underwent LP at disease presentation (RRMS: n = 100, CIS: n = 14). Age at diagnosis was 32.4 ± 12.2 years, and the follow-up time was 9.4 ± 3.8 years. Forty-six patients showed a pleocytic CSF (≥5 cells per μL). Compared with patients with <4 cells per μL, patients with pleocytosis had a higher ARR (0.60 ± 0.09 vs 0.48 ± 0.04; p = 0.0267) and a steeper increase (slope) in the EDSS score throughout the follow-up period (correlation coefficient: r2 = 0.04; p = 0.0251).ConclusionsCSF pleocytosis may be considered a biological unfavorable predictive factor regarding disease course and progression in MS.

Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course

2010 ◽  
Vol 17 (3) ◽  
pp. 335-343 ◽  
Author(s):  
Mohsen Khademi ◽  
Ingrid Kockum ◽  
Magnus L Andersson ◽  
Ellen Iacobaeus ◽  
Lou Brundin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Bacterial Infections ◽  
Neurological Diseases ◽  
Activity Levels ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Diagnostic Work ◽  
In Cis ◽  
Work Up

Background: Levels of CXCL13, a potent B-cell chemoattractant, are elevated in the cerebrospinal fluid (CSF) during multiple sclerosis (MS) and are associated with markers of MS activity. Levels decrease upon effective treatments. Objective: Here we validate the potential role of CSF CXCL13 as a biomarker for aspects of MS in a large amount of clinical material, the majority collected at early diagnostic work-up. Methods: CXCL13 was measured by ELISA in 837 subjects: relapsing–remitting MS (RRMS; n = 323), secondary progressive MS (SPMS; n = 40), primary progressive MS (PPMS; n = 24), clinically isolated syndrome (CIS; n = 79), other neurological diseases (ONDs; n = 181), ONDs with signs of inflammation or viral/bacterial infections (iONDs; n = 176) and healthy controls ( n = 14). Results: Subjects with viral/bacterial infections had extremely high CXCL13 levels compared to all included groups ( p < 0.0001). CXCL13 was otherwise significantly higher in MS compared to the remaining controls ( p < 0.0001), and CIS ( p < 0.01). A significant and positive correlation between CXCL13 and relapse rate, the results obtained for the Expanded Disability Status Scale (EDSS) and the number of lesions detected by MRI was demonstrated. CXCL13 was increased in CIS conversion to clinically definite MS ( p < 0.001). Oligoclonal immunoglobulin band (OCB)-positive CIS or MS had significantly increased CXCL13 levels compared to OCB-negative CIS or MS ( p < 0.001 and p < 0.0001, respectively). Conclusion: CXCL13 was associated with disease exacerbations and unfavourable prognosis in RRMS. Increased CXCL13 was not specific for MS since subjects with viral/bacterial infections exhibited even higher levels. High levels predicted CIS conversion to MS. We suggest that measurement of CSF CXCL13 can be part of the armamentarium in the diagnostic and prognostic work-up in MS and be of help in future treatment decisions.

Role of cerebrospinal fluid tau protein levels as a biomarker of brain injury in Pediatric Status Epilepticus

2021 ◽  
pp. 1-13
Author(s):  
Shivanjali Sood ◽  
Chandrika Azad ◽  
Jasbinder Kaur ◽  
Pankaj Kumar ◽  
Vishal Guglani ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Status Epilepticus ◽  
Brain Injury ◽  
Tau Protein ◽  
Protein Levels

Absence of cerebrospinal fluid oligoclonal bands is associated with delayed disability progression in relapsing-remitting MS patients treated with interferon-β

2006 ◽  
Vol 244 (1-2) ◽  
pp. 97-102 ◽  
Author(s):  
Pasquale Annunziata ◽  
Antonio Giorgio ◽  
Lorenzo De Santi ◽  
Valentina Zipoli ◽  
Emilio Portaccio ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Oligoclonal Bands ◽  
Interferon Β ◽  
Disability Progression ◽  
Relapsing Remitting

Methylation of HAI-2/SPINT2 in Bone Marrow Mesenchymal Stromal Cells of MDS and AML Patients Affects Hematopoietic Stem Cell Survival and Adhesion

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2847-2847
Author(s):  
Fernanda Marconi Roversi ◽  
Nathalia Moreno Cury ◽  
Matheus Rodrigues Lopes ◽  
Fernando Vieira Pericole ◽  
Marisa Claudia Alvarez Prax ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Adhesion ◽  
High Risk ◽  
Tumor Microenvironment ◽  
Disease Progression ◽  
Stromal Cell ◽  
Low Risk ◽  
Hematopoietic Stem ◽  
Protein Levels

Abstract In recent years, the role of tumor microenvironment in neoplasm initiation and malignant evolution has been increasingly recognized. However, the bone marrow mesenchymal stem/stromal cell (BMMSC) contribution to disease progression remains poorly explored. We had previously performed a microarray analysis of myelodysplastic syndrome (MDS) patient-derived BMMSC (MDS-BMMSC) and found an underexpression of HAI-2/SPINT2, an endogenous inhibitor of the hepatocyte growth factor (HGF) activator. This gene has been described as methylated in various cancer types and has been associated with disease progression. Despite of being related to the pathogenesis of several neoplasms, the role of HAI-2/SPINT2 has not yet been fully elucidated in hematological diseases, such as MDS and acute myeloid leukemia (AML). Thus, the aim of this study was to evaluate HAI-2/SPINT2 expression in derived BMMSC and total bone marrow (BM) of healthy donors (HD), MDS and AML patients as well as in BMMSC treated with 5-Azacitidine (Aza), a DNA methyltransferase (DNMT) inhibitor. To achieve this, we collected BM hematopoietic cells and plastic-adherent BMMSC from aspirates of HD, MDS and AML patients. BMMSC were expanded to passage 4 and defined as CD73+/CD90+/CD105+/CD45-/CD34-/CD31-/HLA-DR-. A total of 29 HD and 121 patients at diagnosis (MDS=72 [low-risk=46, high-risk=26], AML with myelodysplastic related changes (AML-MRC)=17 and de novo AML=32) were included. HAI-2/SPINT2 mRNA was significantly decreased in MDS- (0.34[0.01-2.06];P <.01) compared to HD-BMMSC (0.89[0.46-1.59]). When patients were stratified according to WHO classification, HAI-2/SPINT2 expression was lower in both low-risk (0.31[0.01-1.33]) and high-risk (0.43[0.01-2.06]) MDS-BMMSC. Similar results were found in total BM: HAI-2/SPINT2 transcripts were significantly decreased in MDS (0.41[0.01-2.53];P <.01), AML-MRC (0.38[0.014-0.84];P <.01) and AML patients (0.33[0.01-2.07];P <.001) compared to HD (0.91[0.19-4.79]). To investigate whether this loss of expression was due to HAI-2/SPINT2 methylation, BMMSC were treated with Aza (1µM or IC50 value) for 48h. In MDS- and AML-BMMSC, Aza treatment resulted in a pronounced upregulation of HAI-2/SPINT2 mRNA and protein levels. Moreover, Aza treatment of HD-BMMSC did not improve the HAI-2/SPINT2 mRNA and protein levels as much as the observed in MDS- and AML-BMMSC. To better understand the role of HAI-2/SPINT2 downregulation in BMMSC physiology, its expression was inhibited in a BM stromal cell line (HS5). As previously reported, HAI-2/SPINT2 silencing resulted in an increased secretion of HGF, known to be overexpressed in plasma of MDS patients and considered a prognostic factor in MDS and AML patients (Matsuda et al., Leukemia, 2004). Moreover, after co-culture, HAI-2/SPINT2 knockdown improved survival of blasts isolated from AML-MRC and AML patients. We also observed an increased adhesion of CD34+ hematopoietic stem cells (HSC) to HAI-2/SPINT2 silenced HS5 cells. This prompted us to analyze the expression of cell adhesion molecules in MDS- and AML-BMMSC. We observed a significant augment in the expression of CD49b and CD49d integrins in MDS- and AML-compared to HD-BMMSC. Taken together, SPINT2 inhibition improves HGF secretion, consequently with alteration in molecule receptor adhesion, resulting in an increased expression of integrins (CD49b and CD49d) responsible for cell-to-cell adhesion. Thus, reactivation of HAI-2/SPINT2 levels after Aza treatment indicates that this gene is probably epigenetically silenced by methylation in MDS and AML, and is possibly a tumor suppressor gene. Interestingly, nowadays, epigenetic therapy by Aza is the first-line treatment for MDS patients, and induces prolonged survival and delayed AML evolution. Likewise, our results suggest that HAI-2/SPINT2 may play a role in deregulation of HGF cytokine secretion with consequently alteration in HSC adhesion and growth/survival. Tumor microenvironment niche is currently known to play a critical role in cancer initiation and progression, thus HAI-2/SPINT2 may contributes to functional and morphological abnormalities of microenvironment niche and with the stem/progenitor cancer cell progression. Hence, downregulation in HAI-2/SPINT2 gene expression, due to methylation in MDS- and AML-BMMSC, provides novel insights into the pathogenic role of the leukemic bone marrow microenvironment. Disclosures No relevant conflicts of interest to declare.

scholarly journals Discoidin Domain Receptor 1 is a therapeutic target for neurodegenerative diseases

2020 ◽  
Vol 29 (17) ◽  
pp. 2882-2898 ◽  
Author(s):  
Alan J Fowler ◽  
Michaeline Hebron ◽  
Kaluvu Balaraman ◽  
Wangke Shi ◽  
Alexander A Missner ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Therapeutic Target ◽  
Lewy Body Dementia ◽  
Protein Levels ◽  
Discoidin Domain Receptors ◽  
Discoidin Domain Receptor 1 ◽  
Complete Deletion

Abstract The role of Discoidin Domain Receptors (DDRs) is poorly understood in neurodegeneration. DDRs are upregulated in Alzheimer’s and Parkinson’s disease (PD), and DDRs knockdown reduces neurotoxic protein levels. Here we show that potent and preferential DDR1 inhibitors reduce neurotoxic protein levels in vitro and in vivo. Partial or complete deletion or inhibition of DDR1 in a mouse model challenged with α-synuclein increases autophagy and reduces inflammation and neurotoxic proteins. Significant changes of cerebrospinal fluid microRNAs that control inflammation, neuronal injury, autophagy and vesicular transport genes are observed in PD with and without dementia and Lewy body dementia, but these changes are attenuated or reversed after treatment with the DDR1 inhibitor, nilotinib. Collectively, these data demonstrate that DDR1 regulates autophagy and reduces neurotoxic proteins and inflammation and is a therapeutic target in neurodegeneration.

scholarly journals Diagnostic and Prognostic Role of Blood and Cerebrospinal Fluid and Blood Neurofilaments in Amyotrophic Lateral Sclerosis: A Review of the Literature

2019 ◽  
Vol 20 (17) ◽  
pp. 4152 ◽  
Author(s):  
Delia Gagliardi ◽  
Megi Meneri ◽  
Domenica Saccomanno ◽  
Nereo Bresolin ◽  
Giacomo Pietro Comi ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Progression ◽  
Neurodegenerative Disorder ◽  
Diagnostic Delay ◽  
Cytoskeletal Proteins ◽  
Pharmacological Intervention ◽  
Prognostic Role ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting upper and lower motor neurons (MNs) that still lacks an efficacious therapy. The failure of recent therapeutic trials in ALS, other than depending on the poor knowledge of pathogenic mechanisms responsible for MNs loss, is largely due to diagnostic delay and the lack of reliable biomarkers for diagnosis, prognosis and response to pharmacologic intervention. Neurofilaments (Nfs) are neuron-specific cytoskeletal proteins, whose levels increased in biological fluids proportionally to the degree of axonal damage, both in normal and in pathologic conditions, representing potential biomarkers in various neurological disorders, such as motor neuron disorder (MND). Growing evidence has shown that phosphorylated neurofilaments heavy chain (p-NfH) and neurofilaments light chain (NfL) are increased in blood and cerebrospinal fluid (CSF) of ALS patients compared to healthy and neurological controls and are found to correlate with disease progression. In this review, we reported the most relevant studies investigating the diagnostic and prognostic role of Nfs in ALS. Given their reliability and reproducibility, we consider Nfs as promising and useful biomarkers in diagnosis of MND, early patient identification for inclusion in clinical trials, prediction of disease progression, and response to pharmacological intervention, and we suggest the validation of their measurement in clinical activity.

scholarly journals Serum Neurofilament Light Chain Levels and Myelin Oligodendrocyte Glycoprotein Antibodies in Pediatric Acquired Demyelinating Syndromes

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Simone ◽  
Claudia Palazzo ◽  
Mariangela Mastrapasqua ◽  
Luca Bollo ◽  
Francesco Pompamea ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Light Chain ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Oligoclonal Bands ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Significant Difference ◽  
The Relationship

Introduction: The relationship between serum neurofilament light chain (sNfL) and myelin oligodendrocyte glycoprotein antibody (MOG-Ab) status has not been yet investigated in children with the acquired demyelinating syndrome (ADS).Objective and Methods: The sNfL levels and MOG-Abs were measured by ultrasensitive single-molecule array and cell-based assay in a cohort of 37 children with ADS and negativity for serum anti-aquaporin 4 (AQP4) antibodies. The sNfL levels were compared in MOG-Ab+/MOG-Ab– and in two subgroups MOG-Ab+ with/without encephalopathy.Results: About 40% ADS resulted in MOG-Ab+. MOG-Ab+ were younger at sampling (median = 9.8; range = 2.17–17.5 vs. 14.7/9–17; p = 0.002) with lower frequency of cerebrospinal fluid oligoclonal bands positivity (27% vs. 70%; p = 0.013) compared to MOG-Ab–. About 53% of MOG-Ab+ presented encephalopathy at onset, 1/22 of MOG-Ab– (p = 0.0006). Higher sNfL levels (p = 0.0001) were found in MOG-Ab+ (median/range = 11.11/6.8–1,129) and MOG-Ab– (median/range = 11.6/4.3–788) compared to age-matched controls (median/range = 2.98/1–4.53), without significant difference. MOG-Ab+ with encephalopathy resulted significantly younger at sampling (median/range: 4.5/2.17–11.17 vs. 14.16/9.8–17.5; p = 0.004), had higher sNfL levels (median/range:75.24/9.1–1,129 vs. 10.22/6.83–50.53; p = 0.04), and showed a trend for higher MOG-Ab titer (0.28/0.04–0.69 vs. 0.05/0.04–0.28; p = 0.1) in comparison to those without encephalopathy.Discussion: We confirmed high sNfL levels in pediatric ADS independently from the MOG-Ab status. Encephalopathy at onset is associated more frequently with MOG Ab+ children with higher sNfL levels and MOG titer. These findings suggest a role of acute demyelination in association with axonal damage in the pathogenesis of encephalopathy in pediatric ADS.

Primary progressive versus relapsing-onset multiple sclerosis: presence and prognostic value of cerebrospinal fluid oligoclonal IgM

2010 ◽  
Vol 17 (3) ◽  
pp. 303-311 ◽  
Author(s):  
Patrizia Sola ◽  
Jessica Mandrioli ◽  
Anna M Simone ◽  
Diana Ferraro ◽  
Roberta Bedin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Prognostic Value ◽  
Age At Onset ◽  
Disease Course ◽  
Expanded Disability Status Scale ◽  
Biological Factors ◽  
Primary Progressive ◽  
Disability Status ◽  
The Impact

Background: There is increasing evidence on cerebrospinal fluid (CSF) oligoclonal IgM (OCIgM) predicting a more aggressive disease course in relapsing–remitting Multiple Sclerosis (MS), while there is a scarcity of data for primary progressive MS (PPMS). Objective: Our aim was to investigate the presence and possible prognostic value of CSF OCIgM in a group of PPMS and in a group of relapsing-onset MS patients. The possible prognostic role of other clinical and biological factors was also evaluated. Methods: We calculated the impact of single clinical and biological factors, including CSF OCIgM at onset, on the probability of reaching an Expanded Disability Status Scale of 3 and 4 in 45 PPMS and 104 relapsing-onset MS patients. Results: CSF OCIgM were found in only 13% of PPMS patients and did not influence the time taken to reach an Expanded Disability Status Scale of 3 and 4. Conversely, they were present in 46% of relapsing-onset MS patients and increased the risk of reaching an Expanded Disability Status Scale of 4. Clinical factors with a negative prognostic value in PPMS were age at onset <30 years and onset with pyramidal symptoms, while onset with sensory symptoms in relapsing-onset MS predicted a more favourable course. Conclusion: This study confirms that, in relapsing-onset MS patients, the presence of CSF OCIgM at onset predicts a worse disease course. In the cohort of PPMS patients, however, CSF OCIgM were rare, suggesting that heterogeneous pathogenetic mechanisms may be involved in the different MS forms.

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