scholarly journals Long-term prognostic value of longitudinal measurements of blood neurofilament levels

2020 ◽  
Vol 7 (5) ◽  
pp. e856 ◽  
Author(s):  
Dieter A. Häring ◽  
Harald Kropshofer ◽  
Ludwig Kappos ◽  
Jeffrey A. Cohen ◽  
Anuja Shah ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Light Chain ◽  
Prognostic Value ◽  
Long Term Outcomes ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Longitudinal Measurements ◽  
Relapsing Remitting ◽  
Edss Score

ObjectiveTo assess the long-term prognostic value of an integral of longitudinal measurements of plasma neurofilament light chain levels (NfLlong) over 12 and 24 months vs single neurofilament light chain (NfL) measurements in patients with relapsing-remitting MS (RRMS) and its additional value when combined with clinical and MRI measures.MethodsThis analysis included continuously fingolimod-treated patients with RRMS from the 24-month FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS)/12-month Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing–Remitting Multiple Sclerosis (TRANSFORMS) phase 3 trials and their long-term extension, LONGTERMS. Patients were classified into high (≥30 pg/mL, n = 110) and low (<30 pg/mL, n = 164) NfL categories based on the baseline (BL) NfL value or the geometric mean NfLlong calculated over 12 and 24 months to predict disability-related outcomes and brain volume loss (BVL). The additional prognostic value of NfL was quantified using the area under the receiver operating characteristic (ROC) curve.ResultsA single high (vs low) NfL measure at BL was prognostic of a higher risk of reaching Expanded Disability Status Scale (EDSS) score ≥4 earlier (hazard ratio [HR] = 2.19; 95% CI = 1.21–3.97) and higher BVL over 120 months (difference: −1.12%; 95% CI = −2.07 to −0.17). When NfLlong was measured over 24 months, high NfL was associated with a higher risk of reaching EDSS score ≥4 (HR = 7.91; 95% CI = 2.99–20.92), accelerated 6-month confirmed disability worsening (HR = 3.14; 95% CI = 1.38–7.11), and 20% worsening in the Timed 25-Foot Walk Test (HR = 3.05; 95% CI = 1.38–6.70). Area under the ROC curve was consistently highest in models combining NfL with clinical and MRI measures.ConclusionsNfLlong had a higher prognostic value than single NfL assessments on long-term outcomes in RRMS. Combining it with clinical and MRI measures increased sensitivity and specificity to predict long-term disease outcomes.Classification of evidenceThis study provides Class I evidence that NfLlong was more strongly associated with long-term outcomes than single NfL assessments in patients with RRMS.

Cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis

2015 ◽  
Vol 21 (14) ◽  
pp. 1761-1770 ◽  
Author(s):  
S Modvig ◽  
M Degn ◽  
H Roed ◽  
TL Sørensen ◽  
HBW Larsson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Optic Neuritis ◽  
Light Chain ◽  
Oligoclonal Bands ◽  
Enzyme Linked Immunosorbent Assay ◽  
Csf Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Background: Cerebrospinal fluid (CSF) biomarkers have been suggested to predict multiple sclerosis (MS) after clinically isolated syndromes, but studies investigating long-term prognosis are needed. Objective: To assess the predictive ability of CSF biomarkers with regard to MS development and long-term disability after optic neuritis (ON). Methods: Eighty-six patients with ON as a first demyelinating event were included retrospectively. Magnetic resonance imaging (MRI), CSF leukocytes, immunoglobulin G index and oligoclonal bands were registered. CSF levels of chitinase-3-like-1, osteopontin, neurofilament light-chain, myelin basic protein, CCL2, CXCL10, CXCL13 and matrix metalloproteinase-9 were measured by enzyme-linked immunosorbent assay. Patients were followed up after 13.6 (range 9.6–19.4) years and 81.4% were examined, including Expanded Disability Status Scale and MS functional composite evaluation. 18.6% were interviewed by phone. Cox regression, multiple regression and Spearman correlation analyses were used. Results: Forty-six (53.5%) developed clinically definite MS (CDMS) during follow-up. In a multivariate model MRI ( p=0.0001), chitinase 3-like 1 ( p=0.0033) and age ( p=0.0194) combined predicted CDMS best. Neurofilament light-chain predicted long-term disability by the multiple sclerosis severity scale ( p=0.0111) and nine-hole-peg-test ( p=0.0202). Chitinase-3-like-1 predicted long-term cognitive impairment by the paced auditory serial addition test ( p=0.0150). Conclusion: Neurofilament light-chain and chitinase-3-like-1 were significant predictors of long-term physical and cognitive disability. Furthermore, chitinase-3-like-1 predicted CDMS development. Thus, these molecules hold promise as clinically valuable biomarkers after ON as a first demyelinating event.

Prognostic value of cerebrospinal fluid neurofilament light chain and chitinase-3-like-1 in newly diagnosed patients with multiple sclerosis

2018 ◽  
Vol 25 (11) ◽  
pp. 1444-1451 ◽  
Author(s):  
Finn Sellebjerg ◽  
Lydia Royen ◽  
Per Soelberg Sørensen ◽  
Annette Bang Oturai ◽  
Poul Erik Hyldgaard Jensen
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Light Chain ◽  
Prognostic Value ◽  
Multivariable Analysis ◽  
Newly Diagnosed ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Relapse Risk ◽  
Relapsing Remitting Multiple Sclerosis

Background: Neurofilament light chain (NFL) and chitinase-3-like-1 (CHI3L1) concentrations in cerebrospinal fluid (CSF) may have prognostic value in clinically isolated syndromes (CIS) and relapsing–remitting multiple sclerosis (RRMS). Objectives: To compare the prognostic value of CSF concentrations of NFL and CHI3L1 in newly diagnosed CIS and RRMS patients. Methods: NFL and CHI3L1 were measured in CSF in 177 newly diagnosed patients with CIS or RRMS who were followed clinically for a mean of 5.7 years. Results: At baseline CSF concentrations of NFL correlated with CSF concentrations of CHI3L1, relapses in the previous year, time from last relapse, and the Expanded Disability Status Scale (EDSS) score. CSF concentrations of NFL and CHI3L1 were both associated with increased relapse risk during the first 2 years in univariate analyses, but only the CSF concentration of NFL was independently associated with relapse risk in a multivariable analysis. There was no relationship between CSF concentrations of NFL or CHI3L1 and risk of conversion to secondary progressive MS or development of disability. Conclusion: CSF concentrations of NFL are associated with 2-year relapse risk but not with disease progression or clinical worsening in newly diagnosed CIS and RRMS patients. This may be due to confounding by the effect of disease-modifying therapies.

scholarly journals Blood neurofilament light chain as a biomarker of MS disease activity and treatment response

Neurology ◽  
2019 ◽  
Vol 92 (10) ◽  
pp. e1007-e1015 ◽  
Author(s):  
Jens Kuhle ◽  
Harald Kropshofer ◽  
Dieter A. Haering ◽  
Uma Kundu ◽  
Rolf Meinert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Response ◽  
Light Chain ◽  
Healthy Controls ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo assess the value of blood neurofilament light chain (NfL) as a biomarker of recent, ongoing, and future disease activity and tissue damage and its utility to monitor treatment response in relapsing-remitting multiple sclerosis.MethodsWe measured NfL in blood samples from 589 patients with relapsing-remitting multiple sclerosis (from phase 3 studies of fingolimod vs placebo, FREEDOMS and interferon [IFN]-β-1a, TRANSFORMS) and 35 healthy controls and compared NfL levels with clinical and MRI-related outcomes.ResultsAt baseline, NfL levels (pg/mL) were higher in patients than in healthy controls (30.5 and 27.0 vs 16.9, p = 0.0001) and correlated with T2 lesion load and number of gadolinium-enhancing T1 lesions (p < 0.0001, both). Baseline NfL levels, treatment, and number of new or enlarging T2 lesions during the studies predicted NfL levels at the end of study (all p < 0.01). High vs low baseline NfL levels were associated (estimate [95% confidence interval]) with an increased number of new or enlarging T2 lesions (ratio of mean: 2.64 [1.51–4.60]; p = 0.0006), relapses (rate ratio: 2.53 [1.67–3.83]; p < 0.0001), brain volume loss (difference in means: −0.78% [−1.02 to −0.54]; p < 0.0001), and risk of confirmed disability worsening (hazard ratio: 1.94 [0.97–3.87]; p = 0.0605). Fingolimod significantly reduced NfL levels already at 6 months (vs placebo 0.73 [0.656–0.813] and IFN 0.789 [0.704–0.884]), which was sustained until the end of the studies (vs placebo 0.628 [0.552–0.714] and IFN 0.794 [0.705–0.894]; p < 0.001, both studies at all assessments).ConclusionsBlood NfL levels are associated with clinical and MRI-related measures of disease activity and neuroaxonal damage and have prognostic value. Our results support the utility of blood NfL as an easily accessible biomarker of disease evolution and treatment response.

scholarly journals Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Simon Thebault ◽  
Mohammad Abdoli ◽  
Seyed-Mohammad Fereshtehnejad ◽  
Daniel Tessier ◽  
Vincent Tabard-Cossa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcomes ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Neurofilament light levels are associated with long-term outcomes in multiple sclerosis

2019 ◽  
Vol 26 (13) ◽  
pp. 1691-1699 ◽  
Author(s):  
Jens Kuhle ◽  
Tatiana Plavina ◽  
Christian Barro ◽  
Giulio Disanto ◽  
Dipen Sangurdekar ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcomes ◽  
Single Molecule ◽  
Long Term Outcomes ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Lower Tertile ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal

Background: Neurofilament light chain (NfL) is a promising marker of disease activity/treatment response in multiple sclerosis (MS), although its predictive value for long-term clinical outcomes remains unclear. Objective: We measured NfL from a phase 3 trial in relapsing-remitting MS and investigated its association with outcomes after 8 and 15 years. Methods: NfL concentrations were measured by single molecule array assay in cerebrospinal fluid (CSF) from MS patients ( n = 235) in a 2-year randomized clinical trial (RCT) of intramuscular interferon β-1a, and in serum ( n = 164) from the extension study. Results: Year 2 CSF and Year 3 serum NfL were associated with brain parenchymal fraction (BPF) change over 8 years ( p < 0.0001, r = −0.46; p < 0.05. r = −0.36, respectively) and were predictive of reaching Expanded Disability Status Scale (EDSS) ⩾ 6.0 at Year 8 (odds ratio (OR) (upper vs lower tertile) = 3.4; 95% confidence interval (CI) = 1.2–9.9, p < 0.05; OR = 11.0, 95% CI = 2.0–114.6; p < 0.01, respectively). Serum NfL concentration (Year 4) was predictive of reaching EDSS score ⩾6.0 at 15 years (OR (upper vs lower tertile) = 4.9; 95% CI = 1.4–20.4; p < 0.05). NfL concentrations were complementary to 2-year BPF change in predicting long-term outcomes. Conclusion: Serum and CSF NfL concentrations were associated with long-term clinical outcomes in MS patients and are promising biomarkers for disease severity stratification supporting treatment decisions.

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