Myelinating Proteins in MS Are Linked to Volumetric Brain MRI Changes

Staley A. Brod; John A. Lincoln; Flavia Nelson

doi:10.1111/jon.12605

Myelinating Proteins in MS Are Linked to Volumetric Brain MRI Changes

Staley A. Brod, John A. Lincoln, Flavia Nelson

Neurology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

BACKGROUND AND PURPOSE: There is evidence of a relationship between promyelinating proteins and clinical multiple sclerosis (MS) activity during clinical relapse or recovery from clinical relapses. We examined the linkage between promyelinating biomarkers and volumetric changes in MS subjects during serial magnetic resonance imaging (MRI). METHODS: We enrolled 13 MS subjects with active brain MRI scans not on disease modifying therapies. Subjects underwent baseline MRI, serum, and cerebrospinal fluid (CSF) sampling. Qualitative changes, new/resolving gadolinium, new/enlarging/diminishing T2 and T1 hypointense lesions, were compared to baseline in subsequent MRI scans, and volumetric analysis was calculated. Analysis of biomarkers on serial CSF samples was performed only in subjects with qualitative (and quantitative) changes on MRI. The study was performed at a MS Center of Excellence academic medical center. RESULTS: There was increased CSF neural cell adhesion molecule (N-CAM) during increased qualitative T1 activity. A positive correlation between CSF and serum N-CAM and T1 lesion volume was observed. A negative correlation between serum brain-derived neurotrophic factor (BDNF) and BPH (T1 vol/T2 vol + T1 vol) was observed. CONCLUSIONS: Increased N-CAM levels may be related to repair or remyelination following injury to the brain as shown by increased T1 volumes. Our data suggest an early kind of blood signaling that induces release of peripheral BDNF levels.

Original language	English (US)
Pages (from-to)	400-405
Number of pages	6
Journal	Journal of Neuroimaging
Volume	29
Issue number	3
DOIs	https://doi.org/10.1111/jon.12605
State	Published - May 1 2019

Bibliographical note

Funding Information:
Acknowledgment and Disclosure: The study was supported by Independent Medical Grant from EMD Serono and Pfizer. The content is solely the responsibility of the authors and does not necessarily represent the official views of EMD Serono and Pfizer. None of the investigators have financial interest in the outcome of the study. SAB: Consulting agreements or speaker for Acorda, Avanir, Bayer HealthCare, EMD Serono, Genzyme, Pfizer, Mallinckrodt, Teva Neurosciences, and research or contractual support from the Clayton Foundation for Research, EMD Serono, Pfizer, Genzyme, and Questcor. JL: Consulting or speaker for Biogen Idec, Genentech, Sanofi-Genzyme, and research support from the National Institutes of Health and McGovern Medical School, UTHealth. FN: Consulting or speaker for Bayer HealthCare, Biogen Idec, EMD Serono, National MS Society, MS Association of America, Novartis, Sanofi, Teva Neurosciences, and the University of Massachusetts Medical School and research or contractual support from the National Institutes of Health, Novartis, and Sanofi-Aventis.

Funding Information:
and Disclosure: The study was supported by Independent Medical Grant from EMD Serono and Pfizer. The content is solely the responsibility of the authors and does not necessarily represent the official views of EMD Serono and Pfizer.

Publisher Copyright:
© 2019 by the American Society of Neuroimaging

Keywords

BDNF
CSF
N-CAM
T1 volume
blood

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title = "Myelinating Proteins in MS Are Linked to Volumetric Brain MRI Changes",

abstract = "BACKGROUND AND PURPOSE: There is evidence of a relationship between promyelinating proteins and clinical multiple sclerosis (MS) activity during clinical relapse or recovery from clinical relapses. We examined the linkage between promyelinating biomarkers and volumetric changes in MS subjects during serial magnetic resonance imaging (MRI). METHODS: We enrolled 13 MS subjects with active brain MRI scans not on disease modifying therapies. Subjects underwent baseline MRI, serum, and cerebrospinal fluid (CSF) sampling. Qualitative changes, new/resolving gadolinium, new/enlarging/diminishing T2 and T1 hypointense lesions, were compared to baseline in subsequent MRI scans, and volumetric analysis was calculated. Analysis of biomarkers on serial CSF samples was performed only in subjects with qualitative (and quantitative) changes on MRI. The study was performed at a MS Center of Excellence academic medical center. RESULTS: There was increased CSF neural cell adhesion molecule (N-CAM) during increased qualitative T1 activity. A positive correlation between CSF and serum N-CAM and T1 lesion volume was observed. A negative correlation between serum brain-derived neurotrophic factor (BDNF) and BPH (T1 vol/T2 vol + T1 vol) was observed. CONCLUSIONS: Increased N-CAM levels may be related to repair or remyelination following injury to the brain as shown by increased T1 volumes. Our data suggest an early kind of blood signaling that induces release of peripheral BDNF levels.",

keywords = "BDNF, CSF, N-CAM, T1 volume, blood",

author = "Brod, {Staley A.} and Lincoln, {John A.} and Flavia Nelson",

note = "Funding Information: Acknowledgment and Disclosure: The study was supported by Independent Medical Grant from EMD Serono and Pfizer. The content is solely the responsibility of the authors and does not necessarily represent the official views of EMD Serono and Pfizer. None of the investigators have financial interest in the outcome of the study. SAB: Consulting agreements or speaker for Acorda, Avanir, Bayer HealthCare, EMD Serono, Genzyme, Pfizer, Mallinckrodt, Teva Neurosciences, and research or contractual support from the Clayton Foundation for Research, EMD Serono, Pfizer, Genzyme, and Questcor. JL: Consulting or speaker for Biogen Idec, Genentech, Sanofi-Genzyme, and research support from the National Institutes of Health and McGovern Medical School, UTHealth. FN: Consulting or speaker for Bayer HealthCare, Biogen Idec, EMD Serono, National MS Society, MS Association of America, Novartis, Sanofi, Teva Neurosciences, and the University of Massachusetts Medical School and research or contractual support from the National Institutes of Health, Novartis, and Sanofi-Aventis. Funding Information: and Disclosure: The study was supported by Independent Medical Grant from EMD Serono and Pfizer. The content is solely the responsibility of the authors and does not necessarily represent the official views of EMD Serono and Pfizer. Publisher Copyright: {\textcopyright} 2019 by the American Society of Neuroimaging",

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AU - Brod, Staley A.

AU - Lincoln, John A.

AU - Nelson, Flavia

N1 - Funding Information: Acknowledgment and Disclosure: The study was supported by Independent Medical Grant from EMD Serono and Pfizer. The content is solely the responsibility of the authors and does not necessarily represent the official views of EMD Serono and Pfizer. None of the investigators have financial interest in the outcome of the study. SAB: Consulting agreements or speaker for Acorda, Avanir, Bayer HealthCare, EMD Serono, Genzyme, Pfizer, Mallinckrodt, Teva Neurosciences, and research or contractual support from the Clayton Foundation for Research, EMD Serono, Pfizer, Genzyme, and Questcor. JL: Consulting or speaker for Biogen Idec, Genentech, Sanofi-Genzyme, and research support from the National Institutes of Health and McGovern Medical School, UTHealth. FN: Consulting or speaker for Bayer HealthCare, Biogen Idec, EMD Serono, National MS Society, MS Association of America, Novartis, Sanofi, Teva Neurosciences, and the University of Massachusetts Medical School and research or contractual support from the National Institutes of Health, Novartis, and Sanofi-Aventis. Funding Information: and Disclosure: The study was supported by Independent Medical Grant from EMD Serono and Pfizer. The content is solely the responsibility of the authors and does not necessarily represent the official views of EMD Serono and Pfizer. Publisher Copyright: © 2019 by the American Society of Neuroimaging

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N2 - BACKGROUND AND PURPOSE: There is evidence of a relationship between promyelinating proteins and clinical multiple sclerosis (MS) activity during clinical relapse or recovery from clinical relapses. We examined the linkage between promyelinating biomarkers and volumetric changes in MS subjects during serial magnetic resonance imaging (MRI). METHODS: We enrolled 13 MS subjects with active brain MRI scans not on disease modifying therapies. Subjects underwent baseline MRI, serum, and cerebrospinal fluid (CSF) sampling. Qualitative changes, new/resolving gadolinium, new/enlarging/diminishing T2 and T1 hypointense lesions, were compared to baseline in subsequent MRI scans, and volumetric analysis was calculated. Analysis of biomarkers on serial CSF samples was performed only in subjects with qualitative (and quantitative) changes on MRI. The study was performed at a MS Center of Excellence academic medical center. RESULTS: There was increased CSF neural cell adhesion molecule (N-CAM) during increased qualitative T1 activity. A positive correlation between CSF and serum N-CAM and T1 lesion volume was observed. A negative correlation between serum brain-derived neurotrophic factor (BDNF) and BPH (T1 vol/T2 vol + T1 vol) was observed. CONCLUSIONS: Increased N-CAM levels may be related to repair or remyelination following injury to the brain as shown by increased T1 volumes. Our data suggest an early kind of blood signaling that induces release of peripheral BDNF levels.

AB - BACKGROUND AND PURPOSE: There is evidence of a relationship between promyelinating proteins and clinical multiple sclerosis (MS) activity during clinical relapse or recovery from clinical relapses. We examined the linkage between promyelinating biomarkers and volumetric changes in MS subjects during serial magnetic resonance imaging (MRI). METHODS: We enrolled 13 MS subjects with active brain MRI scans not on disease modifying therapies. Subjects underwent baseline MRI, serum, and cerebrospinal fluid (CSF) sampling. Qualitative changes, new/resolving gadolinium, new/enlarging/diminishing T2 and T1 hypointense lesions, were compared to baseline in subsequent MRI scans, and volumetric analysis was calculated. Analysis of biomarkers on serial CSF samples was performed only in subjects with qualitative (and quantitative) changes on MRI. The study was performed at a MS Center of Excellence academic medical center. RESULTS: There was increased CSF neural cell adhesion molecule (N-CAM) during increased qualitative T1 activity. A positive correlation between CSF and serum N-CAM and T1 lesion volume was observed. A negative correlation between serum brain-derived neurotrophic factor (BDNF) and BPH (T1 vol/T2 vol + T1 vol) was observed. CONCLUSIONS: Increased N-CAM levels may be related to repair or remyelination following injury to the brain as shown by increased T1 volumes. Our data suggest an early kind of blood signaling that induces release of peripheral BDNF levels.

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Myelinating Proteins in MS Are Linked to Volumetric Brain MRI Changes

Abstract

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