High or increasing serum NfL is predictive of impending multiple sclerosis relapses

Thebault, Simon; Reaume, Michael; Marrie, Ruth Ann; Marriott, James; Furlan, Roberto; Laroni, Alice; Uccelli, Antonio; Booth, Ronald A.; Freedman, Mark S.

doi:10.1016/j.msard.2022.103535

Cited by 28 publications

(21 citation statements)

References 23 publications

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“…In the short term, elevation of NfL blood levels above the 80th percentile of measured samples correlates with worsening disability within 1 year, as measured by the Expanded Disability Status Scale (EDSS) score. This elevation is also predictive of the occurrence of relapses and progression of brain atrophy in the short term (Disanto et al, 2017 ; Barro et al, 2018 ; Calabresi et al, 2021a ; Thebault et al, 2022 ). In the long term, elevated blood NfL levels seem to be predictive of increased brain atrophy at 5 or even 10 years (Kuhle et al, 2017 ; Barro et al, 2018 ; Chitnis et al, 2018 ; Cantó et al, 2019 ; Jakimovski et al, 2019 ; Srpova et al, 2021 ).…”

Section: Nfl and Neurodegenerative Diseasesmentioning

confidence: 99%

Neurofilaments contribution in clinic: state of the art

Delaby

Bousiges²,

Bouvier

et al. 2022

Front. Aging Neurosci.

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Neurological biomarkers are particularly valuable to clinicians as they can be used for diagnosis, prognosis, or response to treatment. This field of neurology has evolved considerably in recent years with the improvement of analytical methods, allowing the detection of biomarkers not only in cerebrospinal fluid (CSF) but also in less invasive fluids like blood. These advances greatly facilitate the repeated quantification of biomarkers, including at asymptomatic stages of the disease. Among the various informative biomarkers of neurological disorders, neurofilaments (NfL) have proven to be of particular interest in many contexts, such as neurodegenerative diseases, traumatic brain injury, multiple sclerosis, stroke, and cancer. Here we discuss these different pathologies and the potential value of NfL assay in the management of these patients, both for diagnosis and prognosis. We also describe the added value of NfL compared to other biomarkers currently used to monitor the diseases described in this review.

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Section: Nfl and Neurodegenerative Diseasesmentioning

confidence: 99%

Neurofilaments contribution in clinic: state of the art

Delaby

Bousiges²,

Bouvier

et al. 2022

Front. Aging Neurosci.

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“…6 ), a person with MS having 2 alleles for rs12722559 and ≥ 1 allele for rs4808760 has a faster rate of disability accrual (expected time of transitioning is ~ 33 days), compared to some one having ≤ 1 allele for rs10271373 and > 1 allele for rs12434551 (expected time of transitioning is 270 days). Further, incorporating recently established clinical biomarkers such as brain MRI T2L load, baseline blood CSF parameters 18 , 19 and NFL 18 , 20 ; and disease modifiable risk factors such as VitD treatments and type of DMT use 7 – 10 , will enhance the clinical utility of these decision rules. Additionally, combining the effects of the 28 variants into a standard polygenic risk score (PRS) may further improve the predictive accuracy of the derived ensembles.…”

Section: Discussionmentioning

confidence: 99%

Ensemble machine learning identifies genetic loci associated with future worsening of disability in people with multiple sclerosis

Fuh-Ngwa

Zhou

Melton

et al. 2022

Sci Rep

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Limited studies have been conducted to identify and validate multiple sclerosis (MS) genetic loci associated with disability progression. We aimed to identify MS genetic loci associated with worsening of disability over time, and to develop and validate ensemble genetic learning model(s) to identify people with MS (PwMS) at risk of future worsening. We examined associations of 208 previously established MS genetic loci with the risk of worsening of disability; we learned ensemble genetic decision rules and validated the predictions in an external dataset. We found 7 genetic loci (rs7731626: HR 0.92, P = 2.4 × 10–5; rs12211604: HR 1.16, P = 3.2 × 10–7; rs55858457: HR 0.93, P = 3.7 × 10–7; rs10271373: HR 0.90, P = 1.1 × 10–7; rs11256593: HR 1.13, P = 5.1 × 10–57; rs12588969: HR = 1.10, P = 2.1 × 10–10; rs1465697: HR 1.09, P = 1.7 × 10–128) associated with risk worsening of disability; most of which were located near or tagged to 13 genomic regions enriched in peptide hormones and steroids biosynthesis pathways by positional and eQTL mapping. The derived ensembles produced a set of genetic decision rules that can be translated to provide additional prognostic values to existing clinical predictions, with the additional benefit of incorporating relevant genetic information into clinical decision making for PwMS. The present study extends our knowledge of MS progression genetics and provides the basis of future studies regarding the functional significance of the identified loci.

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“…On the other hand, NF-H is considered as a marker of neurodegeneration since it highly corresponds with the axonal damage in the course of disease progression [13]. Elevated sNfL levels are prognostic short-and long-term markers, including recurrence, progression of disability, development of MRI lesions, and loss of brain volume [17].…”

Section: Neurofilamentsmentioning

confidence: 99%

Biomarkers in Multiple Sclerosis

Ignatova¹

2024

Multiple Sclerosis - Genetics, Disease Mechanisms and Clinical Developments

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Clinical, biological, and radiological evidence are currently needed to diagnose MS, but lack of preclinical biomarkers hinders the earliest possible diagnosis and treatment. Conventional biomarkers target immunity, blood-brain barrier disruption, demyelination, and neuronal and axonal damage, as well as mitochondrial activity. An increase of specific brain metabolites with 30–40% is registered before detection of MRI lesions in MS. Potential lipid biomarkers are fatty acids, phospholipids, and oxysterols. The role of proteoforms in the pathogenesis of MS was confirmed. Serum neurofilament light chains (sNfL) are currently being studied as a readily available biomarker for prognosis and response to treatment in MS. The sNfL levels reflect ongoing neuroaxonal damage caused by inflammation, and the sNfL levels predict disease activity over the next few years. The retinal nerve fiber layer (RNFL) thinning is reliable as a biomarker of disability worsening. The neutrophil-to-lymphocyte ratio and CRP are also MS biomarkers. The development of rationally targeted therapeutic agents that allow preventive treatment to stop the disease is also delayed without definite biomarkers.

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High or increasing serum NfL is predictive of impending multiple sclerosis relapses

Cited by 28 publications

References 23 publications

Neurofilaments contribution in clinic: state of the art

Neurofilaments contribution in clinic: state of the art

Ensemble machine learning identifies genetic loci associated with future worsening of disability in people with multiple sclerosis

Biomarkers in Multiple Sclerosis

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