Plasma neurofilament light chain levels are predictors of disease activity in multiple sclerosis as measured by four-domain NEDA status, including brain volume loss

Szilasiová, Jarmila; Mikula, Pavol; Rosenberger, Jaroslav; Fedičová, Miriam; Gdovinová, Zuzana; Urban, Peter; Frigová, Lýdia

doi:10.1177/1352458521998039

Cited by 10 publications

(10 citation statements)

References 24 publications

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“…However, baseline sNfL levels were not associated with either brain volume or cervical cord area loss at baseline, or with brain volume or cervical cord area changes during follow-up. These data contrast with the numerous studies showing significant correlations between blood and CSF sNfL levels and brain volume loss in patients with relapsing MS,11 15–18 22 27–31 although data in patients with progressive MS are scarce 3. Noteworthy, when sNfL determinations across all time points were plotted together, sNfL levels significantly correlated with EDSS and with all radiological parameters except for the MUCCA.…”

Section: Discussioncontrasting

confidence: 81%

Serum neurofilament light chain levels predict long-term disability progression in patients with progressive multiple sclerosis

Comabella

Sastre‐Garriga

Carbonell‐Mirabent

et al. 2022

J Neurol Neurosurg Psychiatry

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ObjectiveThere is a lack of sensitive and specific biomarkers for use in progressive multiple sclerosis (MS). The study aimed to assess the potential of serum neurofilament light chain (sNfL) levels as biomarker of disability progression in patients with progressive MS.MethodsWe performed a prospective observational cohort study in 51 patients with progressive MS who participated in a 2-year phase II single-centre, randomised, double-blind, placebo-controlled trial of interferon-beta. Mean (SD) follow-up duration was 13.9 (6.2) years. Levels of sNfL were measured using a single molecule array immunoassay at baseline, 1, 2 and 6 years. Univariable and multivariable analyses were carried out to evaluate associations between sNfL levels and disability progression at short term (2 years), medium term (6 years) and long term (at the time of the last follow-up).ResultsA sNfL cut-off value of 10.2 pg/mL at baseline discriminated between long-term progressors and non-progressors with a 75% sensitivity and 67% specificity (adjusted OR 7.8; 95% CI 1.8 to 46.4; p=0.01). Similar performance to discriminate between long-term progressors and non-progressors was observed using age/body mass index-adjusted sNfL Z-scores derived from a normative database of healthy controls. A cut-off increase of 5.1 pg/mL in sNfL levels between baseline and 6 years also discriminated between long-term progressors and non-progressors with a 71% sensitivity and 86% specificity (adjusted OR 49.4; 95% CI 4.4 to 2×103; p=0.008).ConclusionssNfL can be considered a prognostic biomarker of future long-term disability progression in patients with progressive MS. These data expand the little knowledge existing on the role of sNfL as long-term prognostic biomarker in patients with progressive MS.

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Section: Discussioncontrasting

confidence: 81%

Serum neurofilament light chain levels predict long-term disability progression in patients with progressive multiple sclerosis

Comabella

Sastre‐Garriga

Carbonell‐Mirabent

et al. 2022

J Neurol Neurosurg Psychiatry

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“…Current research is focused on identifying reliable, sensitive and easily available laboratory and neuroimaging biomarkers of disease activity in treated MS patients that would reflect the effect of a given long-term treatment [22,23]. Given that OCT is an easily accessible, non-invasive and objective method, regular OCT examination could be an alternative to annual brain MRI in multiple sclerosis patients monitored in routine practice, especially in clinically stable patients.…”

Section: Discussionmentioning

confidence: 99%

Associations of optical coherence tomography with disability and brain MRI volumetry in patients with multiple sclerosis

Skirková

Mikula

Maretta

et al. 2022

Neurol Neurochir Pol.

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Aim of the study. To investigate in a cross-sectional study the correlations of optical coherence tomography (OCT) with clinical and magnetic resonance imaging (MRI) parameters in multiple sclerosis (MS) patients. Material and methods.OCT parameters include the peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell complex (GCC). Brain magnetic resonance volumetry (T2-and T1-lesions volume, whole brain volume and grey matter volume) was evaluated using the Icobrain program. Clinical data was compared according to the history of optic neuritis (HON). Correlations were determined between OCT parameters and demographic (age, gender), clinical (disease duration, Expanded Disability Status Scale score [EDSS]), and MRI data.Results. Out of 83 recruited people with MS, 27 had HON. The mean age of 75 patients with non-ON eyes was 42.08 ± 10.36 years, and 70.67% of the sample were females. Significant correlations were found between pRNFL and disability, along with several brain MRI-volumetry variables (Fluid-attenuated Inversion Recovery lesions volume [FLAIR]; T1-hypointense lesions volume; T1-lesions volume change; T1-volume lesions enlarging; whole brain volume; whole brain volume normative percentile; and volume of periventricular lesions). Multivariable linear regression analysis showed that age, pRNFL and GCC were significantly associated with T1-hypointense lesions volume change (the model explained 24% of the overall variance of the dependent variable).Conclusions. The pRFNL value correlates with disability and brain MRI-volumetric parameters in MS patients, serving as a useful neurodegeneration and inflammation surrogate marker.

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“…In addition, high sNfL in patients with EDA-3 was associated with accelerated global and regional brain volume loss during the preceding as well as the following year, which supports the predictive role of sNfL on development of brain atrophy. 14,16,17,20…”

Section: Discussionmentioning

confidence: 99%

“…9 –19 However, the practical value of sNfL as a monitoring tool for clinical practice has been less studied. 13 –20…”

Section: Introductionmentioning

confidence: 99%

Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis

et al. 2021

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Background: The added value of neurofilament light chain levels in serum (sNfL) to the concept of no evidence of disease activity-3 (NEDA-3) has not yet been investigated in detail. Objective: To assess whether combination of sNfL with NEDA-3 status improves identification of patients at higher risk of disease activity during the following year. Methods: We analyzed 369 blood samples from 155 early relapsing-remitting MS patients on interferon beta-1a. We compared disease activity, including the rate of brain volume loss in subgroups defined by NEDA-3 status and high or low sNfL (> 90th or < 90th percentile). Results: In patients with disease activity (EDA-3), those with higher sNFL had higher odds of EDA-3 in the following year than those with low sNFL (86.5% vs 57.9%; OR = 4.25, 95% CI: [2.02, 8.95]; p = 0.0001) and greater whole brain volume loss during the following year (β = −0.36%; 95% CI = [−0.60, −0.13]; p = 0.002). Accordingly, NEDA-3 patients with high sNfL showed numerically higher disease activity (EDA-3) in the following year compared with those with low sNfL (57.1% vs 31.1%). Conclusion: sNfL improves the ability to identify patients at higher risk of future disease activity, beyond their NEDA-3 status. Measurement of sNfL may assist clinicians in decision-making by providing more sensitive prognostic information.

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Plasma neurofilament light chain levels are predictors of disease activity in multiple sclerosis as measured by four-domain NEDA status, including brain volume loss

Cited by 10 publications

References 24 publications

Serum neurofilament light chain levels predict long-term disability progression in patients with progressive multiple sclerosis

Serum neurofilament light chain levels predict long-term disability progression in patients with progressive multiple sclerosis

Associations of optical coherence tomography with disability and brain MRI volumetry in patients with multiple sclerosis

Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis

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