Dataset Information

Neurofilament light chain serum levels correlate with 10-year MRI outcomes in multiple sclerosis.

ABSTRACT: Objective:To assess the value of annual serum neurofilament light (NfL) measures in predicting 10-year clinical and MRI outcomes in multiple sclerosis (MS). Methods:We identified patients in our center's Comprehensive Longitudinal Investigations in MS at Brigham and Women's Hospital (CLIMB) study enrolled within 5 years of disease onset, and with annual blood samples up to 10 years (n = 122). Serum NfL was measured using a single molecule array (SIMOA) assay. An automated pipeline quantified brain T2 hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) from year 10 high-resolution 3T MRI scans. Correlations between averaged annual NfL and 10-year clinical/MRI outcomes were assessed using Spearman's correlation, univariate, and multivariate linear regression models. Results:Averaged annual NfL values were negatively associated with year 10 BPF, which included averaged year 1-5 NfL values (unadjusted P < 0.01; adjusted analysis P < 0.01), and averaged values through year 10. Linear regression analyses of averaged annual NfL values showed multiple associations with T2LV, specifically averaged year 1-5 NfL (unadjusted P < 0.01; adjusted analysis P < 0.01). Approximately 15-20% of the BPF variance and T2LV could be predicted from early averaged annual NfL levels. Also, averaged annual NfL levels with fatigue score worsening between years 1 and 10 showed statistically significant associations. However, averaged NfL measurements were not associated with year 10 EDSS, SDMT or T25FW in this cohort. Interpretation:Serum NfL measured during the first few years after the clinical onset of MS contributed to the prediction of 10-year MRI brain lesion load and atrophy.

SUBMITTER: Chitnis T

PROVIDER: S-EPMC6292183 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neurofilament light chain serum levels correlate with 10-year MRI outcomes in multiple sclerosis.

Chitnis Tanuja T Gonzalez Cindy C Healy Brian C BC Saxena Shrishti S Rosso Mattia M Barro Christian C Michalak Zuzanna Z Paul Anu A Kivisakk Pia P Diaz-Cruz Camilo C Sattarnezhad Neda N Pierre Isabelle V IV Glanz Bonnie I BI Tomic Davorka D Kropshofer Harald H Häring Dieter D Leppert David D Kappos Ludwig L Bakshi Rohit R Weiner Howard L HL Kuhle Jens J

Annals of clinical and translational neurology 20181016 12

<h4>Objective</h4>To assess the value of annual serum neurofilament light (NfL) measures in predicting 10-year clinical and MRI outcomes in multiple sclerosis (MS).<h4>Methods</h4>We identified patients in our center's Comprehensive Longitudinal Investigations in MS at Brigham and Women's Hospital (CLIMB) study enrolled within 5 years of disease onset, and with annual blood samples up to 10 years (<i>n</i> = 122). Serum NfL was measured using a single molecule array (SIMOA) assay. An automated p ...[more]

PMID: 30564615

Similar Datasets

Project description:ImportanceUnrecognized demyelinating events often precede the clinical onset of multiple sclerosis (MS). Identification of these events at the time of occurrence would have implications for early diagnosis and the search of causal factors for the disease.ObjectiveTo assess whether serum neurofilament light chain (sNfL) levels are elevated before the clinical MS onset.Design, setting, and participantsNested case-control study among US military personnel who have serum samples stored in the US Department of Defense Serum Repository. Serum samples were collected from 2000 to 2011; sNfL assays and data analyses were performed from 2018 to 2019. We selected 60 case patients with MS who either had 2 samples collected before onset (mean follow-up, 6.3 years) or 1 sample collected before and 1 after onset (mean follow-up, 1.3 years), among 245 previously identified case patients. For each case, we randomly selected 1 of 2 previously identified control individuals matched by age, sex, race/ethnicity, and dates of sample collection. The sample size was chosen based on the available funding.ExposuresSerum NfL concentrations measured using an ultrasensitive single-molecule array assay (Simoa).Main outcomes and measurementsLog-transformed sNfL concentrations in case patients and control individuals compared using conditional logistic regression and linear mixed models.ResultsMean age at baseline was 27.5 years, and 92 of 120 participants (76.7%) were men. Serum NfL levels were higher in case patients with MS compared with their matched control individuals in samples drawn a median of 6 years (range, 4-10 years) before the clinical onset (median, 16.7 pg/mL; interquartile range [IQR], 12.6-23.1 pg/mL vs 15.2 pg/m; IQR, 10.3-19.9 pg/mL; P = .04). This difference increased with decreasing time to the case clinical onset (estimated coefficient for interaction with time = 0.063; P = .008). A within-person increase in presymptomatic sNfL levels was associated with higher MS risk (rate ratio for ≥5 pg/mL increase, 7.50; 95% CI, 1.72-32.80). The clinical onset was associated with a marked increase in sNfL levels (median, 25.0; IQR, 17.1-41.3 vs 45.1; IQR, 27.0-102.7 pg/mL for presymptomatic and postonset MS samples; P = .009).Conclusions and relevanceThe levels of sNfL were increased 6 years before the clinical MS onset, indicating that MS may have a prodromal phase lasting several years and that neuroaxonal damage occurs already during this phase.

Project description:Background: Ischemic stroke causes increased blood-brain barrier permeability and release of markers of axonal damage and inflammation. To investigate diagnostic and prognostic roles of neurofilament light chain (NF-L), we assessed levels of NF-L, S100B, interleukin-6 (IL-6), E-selectin, vascular endothelial growth factor-A (VEGF-A), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in patients with acute ischemic stroke or transient ischemic attack (TIA) and healthy controls. Methods: We studied neurofilament (NF) expression in 2 cases of human postmortem ischemic stroke, representing infarcts aged 3- to >7-days. In a prospective study, we measured plasma NF-L and inflammatory markers <8 h of symptom onset and at 72 h in acute ischemic stroke (n = 31), TIA (n = 9), and healthy controls (n = 29). We assessed whether NF-L, S100B, and IL-6 were associated with clinical severity on admission (Scandinavian Stroke Scale, SSS), diagnosis of ischemic stroke vs. TIA, and functional outcome at 3 months (modified Rankin Scale, mRS). Results: NF expression increased in ischemic neurons and in the infarcted brain parenchyma after stroke. Plasma NF-L levels were higher in stroke patients than in TIA patients and healthy controls, but IL-6 levels were similar. Higher acute NF-L levels were associated with lower SSS scores at admission and higher mRS scores at 3 months. No correlation was observed between NF-L and S100B, NF-L and IL-6, nor between S100B or IL-6 and SSS or mRS. Compared to controls, stroke patients had significantly higher VEGF-A and VCAM-1 at <8 h that remained elevated at 72 h, with significantly higher VEGF-A at <8 h; ICAM-1 was significantly increased at <8 h, while S100B and E-selectin were unchanged. Conclusions: Plasma NF-L levels, but not IL-6 and S100B, were significant predictors of clinical severity on admission and functional outcome at 3 months. Plasma NF-L is a promising biomarker of functional outcome after ischemic stroke.

Project description:ImportanceBlood sample-based biomarkers that are associated with clinically meaningful outcomes for patients with multiple sclerosis (MS) have not been developed.ObjectiveTo evaluate the potential of serum neurofilament light chain (sNFL) measurements as a biomarker of disease activity and progression in a longitudinal MS data set.Design, setting, and participantsSingle-center, ongoing, prospective observational cohort study of 607 patients with MS from the longitudinal EPIC (Expression, Proteomics, Imaging, Clinical) study at the University of California, San Francisco from July 1, 2004, through August 31, 2017. Clinical evaluations and sample collection were performed annually for 5 years, then at different time points for up to 12 years, with a median follow-up duration of 10 (interquartile range, 7-11) years. Serum NFL levels were measured using a sensitive single molecule array platform and compared with clinical and magnetic resonance imaging variables with the use of univariable and multivariable analyses.Main outcomes and measuresThe main outcomes were disability progression defined as clinically significant worsening on the Expanded Disability Status Scale (EDSS) score and brain fraction atrophy.ResultsMean (SD) age of the 607 study participants at study entry was 42.5 (9.8) years; 423 (69.7%) were women; and all participants were of non-Hispanic European descent. Of 3911 samples sequentially collected, 3904 passed quality control for quantification of sNFL. Baseline sNFL levels showed significant associations with EDSS score (β, 1.080; 95% CI, 1.047-1.114; P < .001), MS subtype (β, 1.478; 95% CI, 1.279-1.707; P < .001), and treatment status (β, 1.120; 95% CI, 1.007-1.245; P = .04). A significant interaction between EDSS worsening and change in levels of sNFL over time was found (β, 1.015; 95% CI, 1.007-1.023; P < .001). Baseline sNFL levels alone were associated with approximately 11.6% of the variance in brain fraction atrophy at year 10. In a multivariable analysis that considered sex, age, and disease duration, baseline sNFL levels were associated with 18.0% of the variance in brain fraction atrophy at year 10. After 5 years' follow-up, active treatment was associated with lower levels of sNFL, with high-potency treatments associated with the greater decreases in sNFL levels compared with platform therapies (high-potency vs untreated: β, 0.946; 95% CI, 0.915-0.976; P < .001; high-potency vs platform: β, 0.972; 95% CI, 0.948-0.998; P = .04).Conclusions and relevanceThis study found that statistically significant associations of sNFL with relevant clinical and neuroimaging outcomes in MS were confirmed and extended, supporting the potential of sNFL as an objective surrogate of ongoing MS disease activity. In this data set of patients with MS who received early treatment, the prognostic power of sNFL for relapse activity and long-term disability progression was limited. Further prospective studies are necessary to assess the assay's utility for decision-making in individual patients.

Dataset Information

Neurofilament light chain serum levels correlate with 10-year MRI outcomes in multiple sclerosis.

Publications

Neurofilament light chain serum levels correlate with 10-year MRI outcomes in multiple sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure