scholarly journals Decreased Cerebrospinal Fluid Antioxidative Capacity Is Related to Disease Severity and Progression in Early Multiple Sclerosis

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1264
Author(s):  
Margarete M. Voortman ◽  
Anna Damulina ◽  
Lukas Pirpamer ◽  
Daniela Pinter ◽  
Alexander Pichler ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity ◽  
Neuronal Damage ◽  
Brain Mri ◽  
Time Interval ◽  
Antioxidative Capacity ◽  
Subclinical Disease ◽  
Relapsing Remitting

Background: Oxidative stress-induced neuronal damage in multiple sclerosis (MS) results from an imbalance between toxic free radicals and counteracting antioxidants, i.e., antioxidative capacity (AOC). The relation of AOC to outcome measures in MS still remains inconclusive. We aimed to compare AOC in cerebrospinal fluid (CSF) and serum between early MS and controls and assess its correlation with clinical/radiological measures. Methods: We determined AOC (ability of CSF and serum of patients to inhibit 2,2′-azobis(2-amidinopropane) dihydrochloride-induced oxidation of dihydrorhodamine) in clinically isolated syndrome (CIS)/early relapsing-remitting MS (RRMS) (n = 55/11) and non-inflammatory neurological controls (n = 67). MS patients underwent clinical follow-up (median, 4.5; IQR, 5.2 years) and brain MRI at 3 T (baseline/follow-up n = 47/34; median time interval, 3.5; IQR, 2.1 years) to determine subclinical disease activity. Results: CSF AOC was differently regulated among CIS, RRMS and controls (p = 0.031) and lower in RRMS vs. CIS (p = 0.020). Lower CSF AOC correlated with physical disability (r = −0.365, p = 0.004) and risk for future relapses (exp(β) = 0.929, p = 0.033). No correlations with MRI metrics were found. Conclusion: Decreased CSF AOC was associated with increased disability and clinical disease activity in MS. While our finding cannot prove causation, they should prompt further investigations into the role of AOC in the evolution of MS.

Anti-myelin antibodies predict the clinical outcome after a first episode suggestive of MS

2007 ◽  
Vol 13 (9) ◽  
pp. 1086-1094 ◽  
Author(s):  
V. Tomassini ◽  
L. De Giglio ◽  
M. Reindl ◽  
P. Russo ◽  
I. Pestalozza ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Mri ◽  
First Episode ◽  
Time Interval ◽  
Serum Samples ◽  
Double Positive ◽  
Baseline Serum ◽  
Patients At Risk ◽  
In Cis

The aim of this study was to test the contribution of anti-myelin antibodies in predicting conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) when considering either Poser's or McDonald's diagnostic criteria. Fifty-one patients with CIS and abnormal brain MRI were imaged monthly for six months and then at 12, 18, 24, 36 months. At baseline serum samples testing antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) and myelin basic protein (anti-MBP) were collected. During the 36-month follow-up, 26 (51%) patients developed a relapse thus becoming clinically definite MS (CDMS) according to Poser's criteria; 46 (90.2%) patients converted to MS according to McDonald's criteria. Out of 51 patients, 28 (54.9%) had either double or single positivity for anti-myelin antibodies. Antibody status significantly predicted MS according to Poser's criteria ( P = 0.004), but did not according to the McDonald's criteria. When compared to antibody negative patients, the risk of developing a relapse was 8.9 (95% CI: 2.7—29.8; P < 0.001) for anti-MBP positive (anti-MBP+) patients and 1.5 (95% CI: 0.4—5.4; P = 0.564) for those anti-MOG positive (anti-MOG+); double positive patients (ie, anti-MBP+/anti-MOG+) had a risk of relapse's occurrence equal to 3.4 (95% CI: 1.1—10.2; P = 0.031). Also, the antibody status predicted the median time span from CIS to CDMS, that was of 36 months in the anti-MOG-/anti-MBP- group, 33 months in the anti-MOG+/anti-MBP- group, 24 months in the anti-MOG+/anti-MBP+ group and 12 months in the anti-MOG-/anti-MBP+ patients ( P = 0.003 by ANOVA). Our data support the prognostic value of anti-myelin antibodies in CIS patients at risk of CDMS, with positive patients showing shorter time interval to relapse occurrence than negative patients. Multiple Sclerosis 2007; 13: 1086—1094. http://msj.sagepub.com

scholarly journals Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

Neurology ◽  
2017 ◽  
Vol 88 (6) ◽  
pp. 525-532 ◽  
Author(s):  
Julia Button ◽  
Omar Al-Louzi ◽  
Andrew Lang ◽  
Pavan Bhargava ◽  
Scott D. Newsome ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
First Year ◽  
Time Interval ◽  
Inclusion Criteria ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Retinal Atrophy ◽  
Disease Modifying ◽  
Relapsing Remitting Multiple Sclerosis

Objective:To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT).Methods:A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up. Combined thickness of the ganglion cell + inner plexiform (GCIP) and other retinal layers was computed utilizing automated macular segmentation. Retinal thickness changes were analyzed using mixed-effects linear regression.Results:The effects of glatiramer acetate (GA; n = 48), natalizumab (NAT; n = 46), and interferon-β-1a subcutaneously (IFNSC; n = 35) and intramuscularly (IFNIM; n = 28) were assessed. Baseline analyses revealed no significant differences between groups in terms of age, sex, optic neuritis history, or follow-up duration. During follow-up, relative to NAT-treated patients, IFNSC- and GA-treated patients exhibited 0.37 μm/y (p < 0.001) and 0.14 μm/y (p = 0.035) faster rates of GCIP thinning, respectively, adjusting for the interval between initiation of DMT and OCT monitoring (gap time), age, sex, relapses, and disease duration. In the IFNSC group, GCIP thinning was 1.53 μm/y faster during the first year of therapy vs during the time interval afterwards (p < 0.001).Conclusions:Rates of GCIP atrophy in patients with RRMS vary according to DMT utilization. Our findings support OCT for monitoring neurodegenerative treatment effects in the retina, an easily accessible tissue, and as a practical outcome measure in RRMS clinical trials.

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.

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.

scholarly journals Safety and Efficacy of Eculizumab Therapy in Multiple Sclerosis: A Case Series

2021 ◽  
Vol 11 (10) ◽  
pp. 1341
Author(s):  
Marco Allinovi ◽  
Angelo Bellinvia ◽  
Francesco Pesce ◽  
Sabrina Milan Manani ◽  
Lorenzo Razzolini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Case Series ◽  
Multicentric Study ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Before And After ◽  
System Activation ◽  
Ms Pathogenesis

(1) Background: Complement system activation has been proposed as one of the different factors that contribute to Multiple Sclerosis (MS) pathogenesis. In this study, we aimed to describe the potential effects of eculizumab, an anticomplement therapy, on MS disease activity in a cohort of relapsing–remitting (RR) MS patients who discontinued IFN-β therapy due to IFN-β-related thrombotic microangiopathy (TMA) onset. (2) Methods: In this retrospective observational multicentric study, we searched for all patients with MS treated by eculizumab with a survey of several nephrological and neurological centers (over 45 centers). (3) Results: Nine patients were included. The mean follow-up time under eculizumab was 3.72 ± 2.58 years. There were no significant differences in disease activity (EDSS, relapses, new T2, and/or Gd-enhancing lesions at MRI) considering the two years before and after eculizumab therapy. No adverse events potentially related to eculizumab therapy were reported during follow-up. (4) Conclusions: In this preliminary study, we described a good safety profile for eculizumab therapy in MS. However, the available data are not sufficient to make firm conclusions about the possible efficacy of eculizumab as a disease-modifying therapy for MS patients.

Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012752
Author(s):  
Claire Bridel ◽  
Cyra E Leurs ◽  
Zoë YGJ van Lierop ◽  
Zoé LE van Kempen ◽  
Iris Dekker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Inflammatory Disease ◽  
Medical Center ◽  
Neurofilament Light ◽  
Longitudinal Dynamics ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveThe objective of this study was to investigate the potential of serum neurofilament light (NfL) to reflect or predict progression mostly independent of acute inflammatory disease activity in patients with relapsing remitting multiple sclerosis (RRMS) treated with natalizumab.MethodsPatients were selected from a prospective observational cohort study initiated in 2006 at the VU University Medical Center Amsterdam, The Netherlands, including patients with RRMS treated with natalizumab. Selection criteria included an age of 18 years or older and a minimum follow-up of 3 years from natalizumab initiation. Clinical and MRI assessments were performedon a yearly basis, and serum NfL was measured at 5 time-points during the follow-up, including on the day of natalizumab initiation (baseline), 3 months, 1 year and 2 years after natalizumab initiation, and on last follow-up visit. Using general linear regression models, we compared the longitudinal dynamics of NfL between patients with and without confirmed EDSS progression between year 1 visit and last follow-up, and between individuals with and without EDSS+ progression, a composite endpoint including the EDSS, 9 hole peg test and timed 25 foot-walk.ResultsEighty-nine natalizumab-treated patients with RRMS were included. Median follow-up time was 5.2 years (IQR 4.3-6.7, range 3.0-11.0) after natalizumab initiation, mean age at time of natalizumab initiation was 36.9 (SD: 8.5), and median disease duration was 7.4 years (IQR 3.8-12.1). Between year 1 and the last follow-up, 28/89 (31.5%) individuals showed confirmed EDSS progression. Data for the EDSS+ endpoint was available for 73 out of the 89 patients and 35/73 (47.9%) showed confirmed EDSS+ progression.We observed a significant reduction in NfL levels 3 months after natalizumab initiation, which reached its nadir of close to 50% of baseline levels 1 year after treatment initiation. We found no difference in the longitudinal dynamics of NfL in progressors versus non-progressors. NfL levels at baseline and 1 year after natalizumab initiation did not predict progression at last follow-up.DiscussionIn our cohort of natalizumab-treated patients with RRMS, NfL fails to capture or predict progression that occurs largely independently of clinical or radiological signs of acute focal inflammatory disease activity. Additional biomarkers may thus be needed to monitor progression in these patients.Classification of EvidenceThis study provides Class II evidence that serum NfL levels are not associated with disease progression in natalizumab-treated patients with RRMS.

Efficacy of rituximab in refractory RRMS

2018 ◽  
Vol 25 (6) ◽  
pp. 828-836 ◽  
Author(s):  
Pierre Durozard ◽  
Adil Maarouf ◽  
Clémence Boutiere ◽  
Aurelie Ruet ◽  
Bruno Brochet ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Rescue Therapy ◽  
Outcome Data ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Retrospective Multicenter Study

Objective: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT). Methods: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts. Results: A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5–6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab ( p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4–18.4) months after rituximab ( p < 0.0001). Conclusion: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.

scholarly journals The Neutrophil-to-Lymphocyte Ratio is Related to Disease Activity in Relapsing Remitting Multiple Sclerosis

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1114 ◽  
Author(s):  
D’Amico ◽  
Zanghì ◽  
Romano ◽  
Sciandra ◽  
Palumbo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Large Scale ◽  
Total Sample ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

: Background: The role of the neutrophil-to-lymphocyte ratio (NLR) of peripheral blood has been investigated in relation to several autoimmune diseases. Limited studies have addressed the significance of the NLR in terms of being a marker of disease activity in multiple sclerosis (MS). Methods: This is a retrospective study in relapsing–remitting MS patients (RRMS) admitted to the tertiary MS center of Catania, Italy during the period of 1 January to 31 December 2018. The aim of the present study was to investigate the significance of the NLR in reflecting the disease activity in a cohort of early diagnosed RRMS patients. Results: Among a total sample of 132 patients diagnosed with RRMS, 84 were enrolled in the present study. In the association analysis, a relation between the NLR value and disease activity at onset was found (V-Cramer 0.271, p = 0.013). In the logistic regression model, the variable NLR (p = 0.03 ExpB 3.5, CI 95% 1.089–11.4) was related to disease activity at onset. Conclusion: An elevated NLR is associated with disease activity at onset in RRMS patients. More large-scale studies with a longer follow-up are needed.

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