Neurofilament light chain serum levels correlate with 10‐year MRI outcomes in multiple sclerosis
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...
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| Vydáno v: | Annals of clinical and translational neurology Ročník 5; číslo 12; s. 1478 - 1491 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
John Wiley & Sons, Inc
01.12.2018
John Wiley and Sons Inc |
| Témata: | |
| ISSN: | 2328-9503, 2328-9503 |
| On-line přístup: | Získat plný text |
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| 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. |
|---|---|
| AbstractList | To assess the value of annual serum neurofilament light (NfL) measures in predicting 10-year clinical and MRI outcomes in multiple sclerosis (MS).
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 (
= 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.
Averaged annual NfL values were negatively associated with year 10 BPF, which included averaged year 1-5 NfL values (unadjusted
< 0.01; adjusted analysis
< 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
< 0.01; adjusted analysis
< 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.
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. ObjectiveTo assess the value of annual serum neurofilament light (NfL) measures in predicting 10‐year clinical and MRI outcomes in multiple sclerosis (MS).MethodsWe 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.ResultsAveraged 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.InterpretationSerum 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. To assess the value of annual serum neurofilament light (NfL) measures in predicting 10-year clinical and MRI outcomes in multiple sclerosis (MS).OBJECTIVETo assess the value of annual serum neurofilament light (NfL) measures in predicting 10-year clinical and MRI outcomes in multiple sclerosis (MS).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.METHODSWe 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.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.RESULTSAveraged 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.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.INTERPRETATIONSerum 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. 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. |
| Author | Rosso, Mattia Glanz, Bonnie I. Michalak, Zuzanna Bakshi, Rohit Sattarnezhad, Neda Tomic, Davorka Chitnis, Tanuja Kuhle, Jens Kropshofer, Harald Gonzalez, Cindy Häring, Dieter Kappos, Ludwig Diaz‐Cruz, Camilo Kivisakk, Pia Pierre, Isabelle V. Barro, Christian Leppert, David Weiner, Howard L. Healy, Brian C. Saxena, Shrishti Paul, Anu |
| AuthorAffiliation | 1 Department of Neurology Partners Multiple Sclerosis Center Brigham and Women's Hospital Boston Massachusetts 4 Massachusetts General Hospital Biostatistics Center Boston Massachusetts 2 Harvard Medical School Boston Massachusetts 02115 3 Ann Romney Center for Neurologic Disease Harvard Medical School Boston Massachusetts 02115 5 Departments of Medicine, Biomedicine and Clinical Research Neurologic Clinic and Policlinic University Hospital Basel University of Basel Basel Switzerland 6 Novartis Neuroscience Development Unit Basel Switzerland |
| AuthorAffiliation_xml | – name: 4 Massachusetts General Hospital Biostatistics Center Boston Massachusetts – name: 2 Harvard Medical School Boston Massachusetts 02115 – name: 6 Novartis Neuroscience Development Unit Basel Switzerland – name: 3 Ann Romney Center for Neurologic Disease Harvard Medical School Boston Massachusetts 02115 – name: 1 Department of Neurology Partners Multiple Sclerosis Center Brigham and Women's Hospital Boston Massachusetts – name: 5 Departments of Medicine, Biomedicine and Clinical Research Neurologic Clinic and Policlinic University Hospital Basel University of Basel Basel Switzerland |
| Author_xml | – sequence: 1 givenname: Tanuja surname: Chitnis fullname: Chitnis, Tanuja email: tchitnis@rics.bwh.harvard.edu organization: Harvard Medical School – sequence: 2 givenname: Cindy surname: Gonzalez fullname: Gonzalez, Cindy organization: Harvard Medical School – sequence: 3 givenname: Brian C. surname: Healy fullname: Healy, Brian C. organization: Massachusetts General Hospital Biostatistics Center – sequence: 4 givenname: Shrishti surname: Saxena fullname: Saxena, Shrishti organization: Harvard Medical School – sequence: 5 givenname: Mattia surname: Rosso fullname: Rosso, Mattia organization: Harvard Medical School – sequence: 6 givenname: Christian surname: Barro fullname: Barro, Christian organization: University of Basel – sequence: 7 givenname: Zuzanna surname: Michalak fullname: Michalak, Zuzanna organization: University of Basel – sequence: 8 givenname: Anu surname: Paul fullname: Paul, Anu organization: Harvard Medical School – sequence: 9 givenname: Pia surname: Kivisakk fullname: Kivisakk, Pia organization: Harvard Medical School – sequence: 10 givenname: Camilo surname: Diaz‐Cruz fullname: Diaz‐Cruz, Camilo organization: Harvard Medical School – sequence: 11 givenname: Neda surname: Sattarnezhad fullname: Sattarnezhad, Neda organization: Harvard Medical School – sequence: 12 givenname: Isabelle V. surname: Pierre fullname: Pierre, Isabelle V. organization: Harvard Medical School – sequence: 13 givenname: Bonnie I. surname: Glanz fullname: Glanz, Bonnie I. organization: Harvard Medical School – sequence: 14 givenname: Davorka surname: Tomic fullname: Tomic, Davorka organization: Neuroscience Development Unit – sequence: 15 givenname: Harald surname: Kropshofer fullname: Kropshofer, Harald organization: Neuroscience Development Unit – sequence: 16 givenname: Dieter surname: Häring fullname: Häring, Dieter organization: Neuroscience Development Unit – sequence: 17 givenname: David surname: Leppert fullname: Leppert, David organization: Neuroscience Development Unit – sequence: 18 givenname: Ludwig surname: Kappos fullname: Kappos, Ludwig organization: University of Basel – sequence: 19 givenname: Rohit orcidid: 0000-0001-8601-5534 surname: Bakshi fullname: Bakshi, Rohit organization: Harvard Medical School – sequence: 20 givenname: Howard L. surname: Weiner fullname: Weiner, Howard L. organization: Harvard Medical School – sequence: 21 givenname: Jens surname: Kuhle fullname: Kuhle, Jens organization: University of Basel |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30564615$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | 2018 The Authors. published by Wiley Periodicals, Inc on behalf of American Neurological Association. 2018. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 This study was funded in part by Novartis, the Swiss National Research Foundation (320030_160221) and the U.S. Department of Defense (MS170140). The National MS Society has provided funding for the CLIMB and SUMMIT cohort studies. We thank Merck Serono and the Nancy Davis Center Without Walls for their support of the CLIMB study. |
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To assess the value of annual serum neurofilament light (NfL) measures in predicting 10‐year clinical and MRI outcomes in multiple sclerosis (MS).... To assess the value of annual serum neurofilament light (NfL) measures in predicting 10-year clinical and MRI outcomes in multiple sclerosis (MS). We... ObjectiveTo assess the value of annual serum neurofilament light (NfL) measures in predicting 10‐year clinical and MRI outcomes in multiple sclerosis... To assess the value of annual serum neurofilament light (NfL) measures in predicting 10-year clinical and MRI outcomes in multiple sclerosis (MS).OBJECTIVETo... |
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| Title | Neurofilament light chain serum levels correlate with 10‐year MRI outcomes in multiple sclerosis |
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