scholarly journals Tetravalent Influenza Vaccine Is Not Associated With Neuroaxonal Damage in Multiple Sclerosis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Tobias Moser ◽  
Michael Seiberl ◽  
Julia Feige ◽  
Lara Bieler ◽  
Richard F. Radlberger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Influenza Vaccine ◽  
Fold Increase ◽  
Dimethyl Fumarate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Humoral Immune ◽  
Antibody Titers ◽  
Disease Reactivation ◽  
Multiple Sclerosis Patients

BackgroundEfficacy of vaccines and disease activity linked to immunization are major concerns among people with multiple sclerosis (pwMS).ObjectiveTo assess antibody responses to seasonal influenza antigens and vaccine-associated neuroaxonal damage utilizing serum neurofilament light chain (sNfL) in pwMS receiving dimethyl fumarate (DMF).MethodsIn this prospective study, the 2020/2021 seasonal tetravalent influenza vaccine was administered to 20 pwMS treated with DMF and 15 healthy controls (HCs). The primary endpoints were responder rate of strain-specific antibody production (seroconversion or significant (4-fold) increase in influenza-antibody titers for ≥2/4 strains) at 30 days post-vaccination and changes in sNfL levels.ResultsAll patients treated with DMF fulfilled the responder criteria for immunization compared with 53% of the controls. However, higher proportions of HCs already had influenza-antibody titers ≥1:40 at baseline (53% vs. 41%, p = 0.174). sNfL levels were comparable among both groups at baseline and did not increase 34 days after vaccination. In addition, no clinical or radiological disease reactivation was found.ConclusionDMF-treated patients mount an adequate humoral immune response to influenza vaccines. Within the limits of the small cohort investigated, our data suggest that influenza immunization is not associated with clinical or subclinical disease reactivation.

Establishment of neurofilament light chain Simoa assay in cerebrospinal fluid and blood

Bioanalysis ◽  
2019 ◽  
Vol 11 (15) ◽  
pp. 1405-1418 ◽  
Author(s):  
Robert Hendricks ◽  
Dana Baker ◽  
Jochen Brumm ◽  
Teresa Davancaze ◽  
Chris Harp ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Conversion Factor ◽  
Plasma Samples ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Highly Sensitive ◽  
Csf Biomarker ◽  
Multiple Sclerosis Patients ◽  
Elisa Data

Background: Neurofilament light (NfL) chain is an established cerebrospinal fluid (CSF) biomarker for neuroaxonal injury. The highly sensitive Quanterix Simoa™ platform is evaluated for NfL measurement in both CSF and blood. There is a need to link historical ELISA data that use bovine NfL to that of Simoa using a recombinant human (rhuman) NfL standard. Results/Methodology: The Simoa NF-light® Advantage Kit was validated for CSF and qualified for serum and plasma, using both rhuman and bovine NfL calibrators. Matched CSF, serum and plasma samples from 112 multiple sclerosis patients were analyzed using both calibrators. Conclusion: In multiple sclerosis, there is a good correlation between blood and CSF NfL levels. A conversion factor of approximately 5:1 was established between bovine and rhuman NfL calibrators.

Neurofilament Light Chain Levels Are Associated with Disease Activity Determined by No Evident Disease Activity in Multiple Sclerosis Patients

2021 ◽  
pp. 1-8
Author(s):  
Jarmila Szilasiová ◽  
Jaroslav Rosenberger ◽  
Miriam Fedičová ◽  
Pavol Mikula ◽  
Peter Urban ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Disease Activity ◽  
Sensitivity And Specificity ◽  
Light Chain ◽  
Operating Characteristics ◽  
Disability Score ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Multiple Sclerosis Patients

<b><i>Introduction:</i></b> There is a need for blood biomarkers of disease activity in multiple sclerosis (MS). The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept three-domain no evident disease activity (NEDA-3). <b><i>Methods:</i></b> Levels of pNfL (SIMOA) were examined in 159 MS patients and analyzed in relationship to NEDA-3 status (absence of relapse, disability score worsening, and brain magnetic resonance activity) during the last 12 months. The accuracy of the proposed model was evaluated by calculating the area under the receiver operating characteristics (ROC) curve. From the pNfL cutoff, we evaluated the NEDA-NfL status (no relapse, no Expanded Disability Status Scale [EDSS] worsening, and pNfL below the cutoff value). <b><i>Results:</i></b> Levels of pNfL were significantly higher in MS patients than in healthy controls (<i>p</i> &#x3c;  0.001). From a total of 159 patients, 80 (50.3%) achieved NEDA-3 status, while 79 (49.7%) patients showed evident disease activity (EDA) status. pNfL were significantly lower in the NEDA-3 group than in the EDA group (pNfL mean 7.06 pg/mL [standard deviation (SD) 2.37] vs. pNfL mean 13.04 pg/mL [SD 7.07]) (<i>p</i> &#x3c; 0.001). ROC analysis showed that pNfL predicts NEDA-3 status (sensitivity and specificity were 80.5 and 72.7%, respectively, <i>p</i> &#x3c; 0.001), and NEDA-NfL predicts NEDA-3 status (sensitivity and specificity were 97.1 and 82.9%, respectively, <i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA status in patients with MS and could be an alternative to brain magnetic resonance investigation.

scholarly journals Real-world effectiveness of dimethyl fumarate versus fingolimod in a cohort of patients with multiple sclerosis using standardized, quantitative outcome metrics

2022 ◽  
Vol 8 (1) ◽  
pp. 205521732110698
Author(s):  
Carrie M Hersh ◽  
Arman Altincatal ◽  
Nicholas Belviso ◽  
Shivani Kapadia ◽  
Carl de Moor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sensitivity Analysis ◽  
Real World ◽  
Dimethyl Fumarate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Brain Volume Loss ◽  
Disability Status ◽  
Magnetic Resonance Imaging Mri

Background Prior studies suggest comparable effectiveness of dimethyl fumarate (DMF) and fingolimod (FTY) in multiple sclerosis (MS) using relapse, Expanded Disability Status Score (EDSS), and magnetic resonance imaging (MRI) lesion metrics. Objective Compare the real-world effectiveness of DMF versus FTY using quantitative, validated neuroperformance tests, MRI, and serum neurofilament light chain (sNfL) outcomes while controlling for between-group differences. Methods Patients were eligible if on DMF or FTY when first enrolled in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network and had ≥1-year follow-up in MS PATHS. Sensitivity analysis included a subgroup who started DMF/FTY ≤2 years from enrolment. After propensity score weighting, differences in means and in mean 1-year change of neuroperformance and MRI outcomes were compared. sNfL levels were assessed. This was a non-randomized comparison. Results In the overall cohort, no significant differences were observed between DMF ( n = 702) and FTY ( n = 600) in neuroperformance or MRI outcomes including brain volume loss; mean time (SD) since treatment initiation was 1.98 (0.68) years for DMF and 2.02 (0.75) years for FTY. A sensitivity analysis controlling for DMF and FTY treatment duration yielded similar results. Conclusion In this study, DMF and FTY demonstrated similar effects on physical and cognitive neuroperformance and MRI outcomes. Direct comparisons to other fumarates and S1P receptor modulators were not conducted.

scholarly journals Brain disconnectome mapping and serum neurofilament light levels in multiple sclerosis

2021 ◽  
Author(s):  
Henning H. Rise ◽  
Synne Brune ◽  
Claudia Chien ◽  
Tone Berge ◽  
Steffan D. Bos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Single Molecule ◽  
Brain Network ◽  
Axonal Damage ◽  
Base Line ◽  
Lesion Volume ◽  
Neurofilament Light Chain ◽  
Random Factor ◽  
Neurofilament Light ◽  
Multiple Sclerosis Patients

AbstractThe pathophysiological mechanisms for classical plaque characteristics and their predictive value for clinical course and outcome in multiple sclerosis is unclear. Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative brain network aberrations and levels of serum neurofilament light chain (sNfL) as a neuroaxonal injury biomarker.Multiple sclerosis patients (n = 328, mean age 42.9 years, 71 % female) were prospectively enrolled at four European multiple sclerosis centres, and reassessed after two years (n = 280). Post-processing of 3 Tesla (3T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient’s white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient and centre as a random factor, sNfL, age, sex, timepoint for visit, diagnosis, and treatment as fixed factors were run.Robust LMM revealed significant associations between higher levels of GD and increased sNfL (t = 2.30, β = 0.03, p = 0.02), age (t = 5.01, β = 0.32, p < 5.5 × 10−7), and diagnosis progressive multiple sclerosis (PMS); t = 1.97, β = 1.06, p = 0.05), but not for sex (t = 0.78, p = 0.43), treatments (effective; t = 0.85, p = 0.39, highly-effective; t = 0.86, p = 0.39) or sNfL change between base line and two-year follow up (t = −1.65, p = 0.10). Voxel-wise analyses revealed distributed associations in cerebellar and brainstem regions.In our prospective multi-site multiple sclerosis cohort, rLMMs demonstrated that the extent of global brain disconnectivity is sensitive to a systemic biomarker of axonal damage, sNfL, in patients with multiple sclerosis. These findings provide a neuropathological correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and clinical relevance in patients with brain disorders.

Neurofilament light chain levels in pregnant multiple sclerosis patients: a prospective cohort study

2019 ◽  
Vol 26 (9) ◽  
pp. 1200-1204 ◽  
Author(s):  
J. P. Cuello ◽  
M. L. Martínez Ginés ◽  
J. Kuhle ◽  
J. M. García Domínguez ◽  
A. Lozano Ros ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Light Chain ◽  
Prospective Cohort ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Multiple Sclerosis Patients

Longitudinal serum neurofilament light chain (sNfL) concentration relates to cognitive function in multiple sclerosis patients

2020 ◽  
Vol 267 (8) ◽  
pp. 2245-2251 ◽  
Author(s):  
Flavia Mattioli ◽  
F. Bellomi ◽  
C. Stampatori ◽  
S. Mariotto ◽  
S. Ferrari ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Function ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Multiple Sclerosis Patients

scholarly journals Longitudinal Serum Neurofilament Levels of Multiple Sclerosis Patients Before and After Treatment with First-Line Immunomodulatory Therapies

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 312
Author(s):  
André Huss ◽  
Makbule Senel ◽  
Ahmed Abdelhak ◽  
Benjamin Mayer ◽  
Jan Kassubek ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Diseases ◽  
Therapy Response ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Time Points ◽  
Longitudinal Measurement ◽  
Before And After ◽  
Multiple Sclerosis Patients

Serum neurofilament light chain (NfL) has been shown to correlate with neuroaxonal damage in multiple sclerosis (MS) and various other neurological diseases. While serum NfL is now regularly reported in clinical approval studies, there is a lack of longitudinal data from patients treated with established basic immunotherapies outside of study conditions. In total, 34 patients with early relapsing-remitting MS (RRMS) were included. The follow-up period was 24 months with regular follow-up visits after 3, 6, 9, 12 and 18 months. Therapy with glatiramer acetate was initiated in 20 patients and with interferon-beta in 12 patients. The disease course was monitored by the events of relapses, Expanded Disability Status Scale (EDSS) score and MRI parameters. Overall, serum NfL levels were higher at time points with a current relapse event than at time points without relapse (12.8 pg/mL vs. 9.7 pg/mL, p = 0.011). At follow-up, relapse-free patients showed significantly reduced serum NfL levels starting from 9 months compared to baseline (p < 0.05) and reduced levels after 12 months compared to baseline (p = 0.013) in patients without EDSS progression for 12 months. In this explorative observational study, our data suggest that the longitudinal measurement of serum NfL may be useful in addition to MRI to monitor disease activity and therapy response.

scholarly journals Blood neurofilament light levels segregate treatment effects in multiple sclerosis

Neurology ◽  
2020 ◽  
Vol 94 (11) ◽  
pp. e1201-e1212 ◽  
Author(s):  
Bénédicte Delcoigne ◽  
Ali Manouchehrinia ◽  
Christian Barro ◽  
Pascal Benkert ◽  
Zuzanna Michalak ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Test Performance ◽  
Dimethyl Fumarate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Light Levels ◽  
Age Related ◽  
Relapsing Remitting ◽  
Baseline Factors ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo determine factors (including the role of specific disease modulatory treatments [DMTs]) associated with (1) baseline, (2) on-treatment, and (3) change (from treatment start to on-treatment assessment) in plasma neurofilament light chain (pNfL) concentrations in relapsing-remitting multiple sclerosis (RRMS).MethodsData including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with RRMS starting novel DMTs were analyzed using linear regressions to model pNfL and changes in pNfL concentrations as a function of clinical variables and DMTs (alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, rituximab, and teriflunomide).ResultsThe baseline pNfL concentration was positively associated with relapse rate, Expanded Disability Status Scale score, Age-Related MS Severity Score, and MS Impact Score (MSIS-29), and negatively associated with Symbol Digit Modalities Test performance and the number of previously used DMTs. All analyses, which used inverse propensity score weighting to correct for differences in baseline factors at DMT start, highlighted that both the reduction in pNfL concentration from baseline to on-treatment measurement and the on-treatment pNfL level differed across DMTs. Patients starting alemtuzumab displayed the highest reduction in pNfL concentration and lowest on-treatment pNfL concentrations, while those starting teriflunomide had the smallest decrease and highest on-treatment levels, but also starting from lower values. Both on-treatment pNfL and decrease in pNfL concentrations were highly dependent on baseline concentrations.ConclusionChoice of DMT in RRMS is significantly associated with degree of reduction in pNfL, which supports a role for pNfL as a drug response marker.

scholarly journals Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paulette Esperanza Walo-Delgado ◽  
Susana Sainz de la Maza ◽  
Noelia Villarrubia ◽  
Enric Monreal ◽  
Silvia Medina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
T Lymphocytes ◽  
Disease Activity ◽  
Single Molecule ◽  
Dimethyl Fumarate ◽  
Memory B Cells ◽  
Response To Treatment ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

AbstractSerum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing–remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Blood lymphocyte subsets were measured at baseline and at 6 months by flow cytometry. Patients were followed a year and classified as NEDA (no evidence of disease activity) or ODA (ongoing disease activity). NEDA patients had lower sNfL levels at baseline (p = 0.0001), and after three (p = 0.004) and six (p = 0.03) months of DMF treatment. Consequently, low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82–15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p < 0.0001). This shows that low baseline sNfL values identify MS patients with higher probability of optimal response to DMF and of a reduction in effector immune cells.

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