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MRI evidence of acute inflammation in leukocortical lesions of patients with early multiple sclerosis

  1. Sridar Narayanan, PhD
  1. From the Department of Neurology and Neurosurgery (J.M., D.A.R., K.N., D.L.A., S.N.), Montreal Neurological Hospital and Institute, McGill University, Canada; Cleveland Clinic (K.N.), OH; Rutgers-New Jersey Medical School (S.C., D.C.), Newark, NJ; and Case Western Reserve University (L.W.), Cleveland, OH. L.W. is currently with the University of Connecticut, School of Medicine, Farmington.
  1. Correspondence to Dr. Narayanan: sridar.narayanan{at}mcgill.ca
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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. (1)CIHR, MOP #84367, Researcher, 2015-2017

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. (1) Multiple Sclerosis Society of Canada Project/Grant #2296

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

Funding for travel or speaker honoraria:

  1. (1) Sanofi Genzyme, Speaker fee

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  1. NONE

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  1. NONE

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  1. NONE

Employment, Commercial Entity:

  1. NONE

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  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. (1) Biogen, (2) Sanofi Genzyme, (3) Novartis

Research Support, Government Entities:

  1. (1) NIH, R35N097303, Co-investigator, 2016-2024 (2) NIH, U01NS082329, Co-investigator, 2013-2018 (3) DOD, CDMRP MS150097, Co-investigator, 2017-2020

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. (1) National Multiple Sclerosis Society

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License fee payments, Technology or Inventions:

  1. (1) Software for gray matter atrophy, Biogen

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

Editorial Boards:

  1. (1) Neurology Reviews, Editorial Board, 1997-present

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  1. NONE

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  1. NONE

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  1. NONE

Consultancies:

  1. (1) Merck Serono -commercial

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  1. NONE

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  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. (1) Merck Serono (2) Bayer Healthcare

Research Support, Government Entities:

  1. NONE

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  1. NONE

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  1. NONE

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Funding for travel or speaker honoraria:

  1. I'm a full time paid employee of Fulcrum Therapeutics, which is not involved on any research related to this publication

Editorial Boards:

  1. NONE

Patents:

  1. I'm listed as an inventor on pending patent applications related to the use of drugs that block LINGO-1 to treat demyelination in multiple sclerosis.

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. I'm a full time paid employee of Fulcrum Therapeutics. This work is not related to my employment in Fulcrum Therapeutics.

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. I'm a full time paid employee of Fulcrum Therapeutics.

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. I own restricted stock units and stock as compensation for my full time employment at Biogen.

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. I own restricted stock units and stock as compensation for my full time employment at Biogen.

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

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Scientific Advisory Boards:

  1. Immunocellular Therapeutics: Data Monitoring Committee

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  1. NONE

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  1. NONE

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  1. NONE

Patents:

  1. NONE

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  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. Guerbet Group

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. Salary support from Bayer during the BECOME trial. Grant support from Bracco Diagnostics during the course of the trial, but unrelated to the trial.

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. University of Connecticut School of Medicine

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE

Scientific Advisory Boards:

  1. Adelphi, Acorda Therapeutics, Biogen, Genentech, Genzyme, Hoffman LaRoche, Medday, Novartis, Pfizer, Receptos, Roche, Sanofi-Aventis

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. Genzyme, travel support

Editorial Boards:

  1. NONE

Patents:

  1. Method of evaluating the efficacy of drug on brain nerve cells

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. Biogen, Novartis

Research Support, Government Entities:

  1. CIHR 15630 co-PI 2007 2012 CIHR 84360 co-PI 2007-2012 CIHR 84367 PI 2007-2012 CIHR 111169 coPI 2011-2014 CIHR 43871 co-PI 2010-2015 CIHR 377721 PI 2017-2020

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. International Progressive MS Alliance Multiple Sclerosis Research Foundation

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NeuroRx Research, 2002-2013

Legal Proceedings:

  1. NONE

Scientific Advisory Boards:

  1. NONE

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  1. NONE

Funding for travel or speaker honoraria:

  1. (1) Novartis Canada, speaker honorarium

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. (1) NeuroRx Research Inc.

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. (1) Canadian Institutes of Health Research, 84367, Co-Principal Investigator (P.I. Dr. Douglas L. Arnold), 2013-2018. (3) Canadian Institutes of Health Research, N/A, Co-investigator (P.I. Dr. Chawki Benkelfat), 2012-2017. (4) Canadian Institutes of Health Research, N/A, Co-investigator (P.I. Dr. Louis Collins), 2012-2015. (5) Canadian Institutes of Health Research, N/A, Co-investigator (P.I. Dr. Lisa Koski), 2012-2015.

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. (1) International Progressive MS Alliance (2) Multiple Sclerosis Society of Canada Scientific Research Foundation (3) Multiple Sclerosis Society of Canada

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

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  1. NONE

Legal Proceedings:

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Abstract

Objective: To identify gadolinium-enhancing lesions affecting the cortex of patients with early multiple sclerosis (MS) and to describe the frequency and evolution of these lesions.

Methods: We performed a retrospective, observational, longitudinal analysis of MRI scans collected as part of the Betaseron vs Copaxone in Multiple Sclerosis with Triple-Dose Gadolinium and 3T MRI Endpoints (BECOME) study. Seventy-five patients with early-stage MS were scanned monthly, over a period of 12–24 months, using 3T MRI after administration of triple-dose gadolinium. A total of 1,188 scans were included in the analysis. A total of 139 were selected using an image pipeline algorithm that integrated the image information from cortical gray matter masks and gadolinium-enhancing lesion masks. These scans were evaluated to identify gadolinium-enhancing lesions affecting the cortex.

Results: The total number of gadolinium-enhancing lesions was 2,044. The number of gadolinium-enhancing lesions affecting the cortex was 120 (6%), 95% of which were leukocortical. The number of patients who showed gadolinium-enhancing lesions affecting the cortex was 27 (36%). The number of gadolinium-enhancing lesions affecting the cortex at baseline was 25 (21%) and the number of new lesions that developed in follow-up scans was 49 (41%). The number of persistent lesions was 46 (38%).

Conclusions: The presence of enhancing lesions affecting the cortex and adjacent white matter, although transient and not frequent, suggests that at least some cortical lesions are related to blood–brain barrier disruption. Our data support the concept that there may be an acute inflammatory phase in the development of leukocortical MS lesions.

Clinicaltrials.gov identifier: NCT00176592.

  • Received September 15, 2016.
  • Accepted in final form May 22, 2017.
  1. Published online before print July 19, 2017, doi: 10.1212/WNL.0000000000004227 Neurology 10.1212/WNL.0000000000004227
  1. » Abstract
  2. Full Text (PDF)

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