Microstructural and functional brain abnormalities in multiple sclerosis predicted by osteopontin and neurofilament light

2021 ◽  
pp. 102923
Author(s):  
Gergely Orsi ◽  
Tamas Cseh ◽  
Zsofia Hayden ◽  
Gabor Perlaki ◽  
Szilvia Anett Nagy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Abnormalities ◽  
Neurofilament Light ◽  
Functional Brain

scholarly journals Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis

2021 ◽  
Vol 14 ◽  
pp. 175628642110034
Author(s):  
Caspar B. Seitz ◽  
Falk Steffen ◽  
Muthuraman Muthuraman ◽  
Timo Uphaus ◽  
Julia Krämer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Neuritis ◽  
Previous History ◽  
Supervised Machine Learning ◽  
Support Vector ◽  
Retinal Layer ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Retinal Layers ◽  
History Of

Background: Serum neurofilament light chain (sNfL) and distinct intra-retinal layers are both promising biomarkers of neuro-axonal injury in multiple sclerosis (MS). We aimed to unravel the association of both markers in early MS, having identified that neurofilament has a distinct immunohistochemical expression pattern among intra-retinal layers. Methods: Three-dimensional (3D) spectral domain macular optical coherence tomography scans and sNfL levels were investigated in 156 early MS patients (female/male: 109/47, mean age: 33.3 ± 9.5 years, mean disease duration: 2.0 ± 3.3 years). Out of the whole cohort, 110 patients had no history of optic neuritis (NHON) and 46 patients had a previous history of optic neuritis (HON). In addition, a subgroup of patients ( n = 38) was studied longitudinally over 2 years. Support vector machine analysis was applied to test a regression model for significant changes. Results: In our cohort, HON patients had a thinner outer plexiform layer (OPL) volume compared to NHON patients ( B = −0.016, SE = 0.006, p = 0.013). Higher sNfL levels were significantly associated with thinner OPL volumes in HON patients ( B = −6.734, SE = 2.514, p = 0.011). This finding was corroborated in the longitudinal subanalysis by the association of higher sNfL levels with OPL atrophy ( B = 5.974, SE = 2.420, p = 0.019). sNfL levels were 75.7% accurate at predicting OPL volume in the supervised machine learning. Conclusions: In summary, sNfL levels were a good predictor of future outer retinal thinning in MS. Changes within the neurofilament-rich OPL could be considered as an additional retinal marker linked to MS neurodegeneration.

scholarly journals Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case–control studies

2019 ◽  
Vol 90 (9) ◽  
pp. 1059-1067 ◽  
Author(s):  
Sarah-Jane Martin ◽  
Sarah McGlasson ◽  
David Hunt ◽  
James Overell
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Light Chain ◽  
Meta Analysis ◽  
Grey Literature ◽  
Case Control ◽  
Disease Stage ◽  
Case Control Studies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

ObjectiveNeurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case–control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other.MethodsGuidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Electronic databases were searched for published and ‘grey’ literature, with 151 hits. Of 51 full articles screened, 20 were included in qualitative analysis, and 14 in meta-analysis.ResultsCSF NfL was higher in 746 pwMS than 435 (healthy and disease) controls, with a moderate effect size of 0.61 (p < 0.00001). Mean CSF NfL levels were significantly higher in 176 pwMS with relapsing disease than 92 with progressive disease (2124.8 ng/L, SD 3348.9 vs 1121.4 ng/L, SD 947.7, p = 0.0108). CSF NfL in 138 pwMS in relapse (irrespective of MS subtype) was double that seen in 268 pwMS in remission (3080.6 ng/L, SD 4715.9 vs 1541.7 ng/L, SD 2406.5, p < 0.0001).ConclusionsCSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease ‘activity’ rather than as a marker of disability or disease stage.

scholarly journals Natural Variation of Vitamin D and Neurofilament Light Chain in Relapsing-Remitting Multiple Sclerosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Egil Røsjø ◽  
Jonas C. Lindstrøm ◽  
Trygve Holmøy ◽  
Kjell-Morten Myhr ◽  
Kristin N. Varhaug ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Light Chain ◽  
Natural Variation ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

scholarly journals Structural and functional brain abnormalities in chronic low back pain: A systematic review☆

2015 ◽  
Vol 45 (2) ◽  
pp. 229-237 ◽  
Author(s):  
Jeroen Kregel ◽  
Mira Meeus ◽  
Anneleen Malfliet ◽  
Mieke Dolphens ◽  
Lieven Danneels ◽  
...  
Keyword(s):  
Systematic Review ◽  
Low Back Pain ◽  
Back Pain ◽  
Chronic Low Back Pain ◽  
Low Back ◽  
Brain Abnormalities ◽  
Functional Brain

scholarly journals Antibodies to neurofilament light as potential biomarkers in multiple sclerosis

2021 ◽  
Vol 3 (2) ◽  
pp. e000192
Author(s):  
Fabiola Puentes ◽  
Pascal Benkert ◽  
Sandra Amor ◽  
Jens Kuhle ◽  
Gavin Giovannoni
Keyword(s):  
Multiple Sclerosis ◽  
Immune Complexes ◽  
Quantitative Measure ◽  
Immune Reactivity ◽  
High Avidity ◽  
Disability Score ◽  
Neurofilament Light ◽  
Prospective Longitudinal Study ◽  
Baseline Serum ◽  
Prospective Longitudinal

Background and objectiveThe concentration of neurofilament light (NfL) protein in cerebrospinal fluid (CSF) and blood is widely considered as a quantitative measure of neuro-axonal injury. Immune reactivity to NfL released into extracellular fluids induces specific autoantibody response. We investigated the levels and avidity of antibodies to NfL in patients with multiple sclerosis (MS) treated with disease-modifying therapies (DMTs) and their correlation with disease worsening and NfL protein concentration.MethodsWe conducted a prospective longitudinal study in 246 patients with MS (125 DMT-treated and 121 untreated at baseline). Serum levels of NfL antibodies, antibody avidity and immune complexes were determined by ELISA. NfL protein was measured using the Simoa platform. Clinical variables were tested for their association with the measured parameters in multivariate generalised estimating equation models.ResultsMultivariate analysis showed that levels of NfL antibodies were higher in progressive MS compared with clinically isolated syndrome (CIS)/relapsing remitting multiple sclerosis (RRMS) (p=0.010). Anti-NfL levels drop with increasing disability score (Expanded Disability Status Scale (EDSS)) (p=0.002), although conversely, were significantly elevated in CIS/RRMS after a recent EDSS increase (p=0.012). Patients receiving DMTs showed decreased levels of anti-NfL (p=0.008), high-avidity antibodies (p=0.017) and immune-complexes compared with untreated CIS/RRMS. Patients with MS switching to natalizumab showed lower levels of anti-NfL but higher immune complexes compared with healthy controls (p=0.0071). A weak association was observed between the levels of NfL protein and NfL antibodies.ConclusionsThese results support the potential usefulness of quantifying antibody response to NfL as potential markers of progression and treatment response in MS and need to be considered when interpreting peripheral blood NfL levels.

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