scholarly journals Neurofilament light chain in the assessment of patients with multiple sclerosis

2019 ◽  
Vol 77 (6) ◽  
pp. 436-441 ◽  
Author(s):  
Renan Barros DOMINGUES ◽  
Gustavo Bruniera Peres FERNANDES ◽  
Fernando Brunale Vilela de Moura LEITE ◽  
Carlos SENNE
Keyword(s):  
Multiple Sclerosis ◽  
Axonal Degeneration ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Resonance Imaging ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
The Central Nervous System ◽  
New Biomarkers ◽  
Therapeutic Decision Making

ABSTRACT Multiple sclerosis (MS) is an autoimmune, inflammatory, and degenerative disease of the central nervous system. Axonal degeneration is triggered by inflammation and is the pathological substrate of progressive disability in patients with MS. Therapeutic interventions can reduce inflammatory activity, thus delaying neurodegeneration and the progression of disability. Disease activity and neurodegeneration are assessed mainly through clinical evaluation and magnetic resonance imaging. These measures lack sensitivity and accuracy, so new biomarkers are necessary. Several markers have been studied and to date the most promising is neurofilament light (NfL), a component of the axonal cytoskeleton, which is released into cerebrospinal fluid (CSF) following axonal damage. In the present study, we review the current knowledge about CSF NfL determination in MS, clinically isolated syndrome, and radiologically isolated syndrome, and critically discuss how CSF NfL measurement may contribute to therapeutic decision-making in these patients.

scholarly journals Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis

Science ◽  
2022 ◽  
Author(s):  
Kjetil Bjornevik ◽  
Marianna Cortese ◽  
Brian C. Healy ◽  
Jens Kuhle ◽  
Michael J. Mina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Epstein Barr Virus ◽  
Demyelinating Disease ◽  
Serum Levels ◽  
Unknown Etiology ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Barr Virus ◽  
The Central Nervous System ◽  
Epstein Barr

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service. Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.

Multiple sclerosis

2015 ◽  
Author(s):  
Alasdair Coles ◽  
Alastair Compston
Keyword(s):  
Multiple Sclerosis ◽  
Axonal Degeneration ◽  
Interferon Beta ◽  
Inflammatory Disorder ◽  
Resonance Imaging ◽  
Complex Interplay ◽  
Inflammatory Lesions ◽  
History Of ◽  
The Central Nervous System ◽  
Made In

The papers in this chapter illustrate the picture that has emerged of multiple sclerosis as an inflammatory disorder of the central nervous system, caused by a complex interplay of multiple genetic susceptibility alleles and unknown environmental triggers. Multiple sclerosis is a disease in which there is first demyelination of nerves, followed by axonal degeneration. Demyelination is caused by inflammation, as shown by the synthesis of immunoglobulins within the CNS, and magnetic resonance imaging has shown that only the minority of inflammatory lesions cause symptoms. All of these discoveries were made in the twentieth century, which ended with the first demonstration that a treatment—interferon-beta—could influence the natural history of the disease.

scholarly journals The Evolution of Neurofilament Light Chain in Multiple Sclerosis

2021 ◽  
Vol 15 ◽  
Author(s):  
Carolina Ferreira-Atuesta ◽  
Saúl Reyes ◽  
Gavin Giovanonni ◽  
Sharmilee Gnanapavan
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Light Chain ◽  
Extracellular Fluid ◽  
Treatment Decisions ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Diagnosis And Prognosis ◽  
The Central Nervous System ◽  
Individualized Management

Multiple sclerosis (MS) is an autoimmune, inflammatory neurodegenerative disease of the central nervous system characterized by demyelination and axonal damage. Diagnosis and prognosis are mainly assessed through clinical examination and neuroimaging. However, more sensitive biomarkers are needed to measure disease activity and guide treatment decisions in MS. Prompt and individualized management can reduce inflammatory activity and delay disease progression. Neurofilament Light chain (NfL), a neuron-specific cytoskeletal protein that is released into the extracellular fluid following axonal injury, has been identified as a biomarker of disease activity in MS. Measurement of NfL levels can capture the extent of neuroaxonal damage, especially in early stages of the disease. A growing body of evidence has shown that NfL in cerebrospinal fluid (CSF) and serum can be used as reliable indicators of prognosis and treatment response. More recently, NfL has been shown to facilitate individualized treatment decisions for individuals with MS. In this review, we discuss the characteristics that make NfL a highly informative biomarker and depict the available technologies used for its measurement. We further discuss the growing role of serum and CSF NfL in MS research and clinical settings. Finally, we address some of the current topics of debate regarding the use of NfL in clinical practice and examine the possible directions that this biomarker may take in the future.

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.

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