@article{6cc59868ede44a859f82295aa4c01c94,
title = "Nonlesional diffusely abnormal appearing white matter in clinically isolated syndrome: Prevalence, association with clinical and MRI features, and risk for conversion to multiple sclerosis",
abstract = "Background and Purpose: While diffusely abnormal white matter (DAWM) is a nonlesional MRI abnormality identified in ∼25% of patients with multiple sclerosis (MS), it has yet to be investigated in patients at an earlier disease stage, namely clinically isolated syndrome (CIS). The goals of this study were to (1) determine the prevalence of DAWM in patients with a CIS suggestive of MS, (2) evaluate the association between DAWM and demographic, clinical, and MRI features, and (3) evaluate the prognostic significance of DAWM on conversion from CIS to MS. Methods: One hundred and forty-two CIS participants were categorized into DAWM and non-DAWM groups at baseline and followed for up to 24 months or until MS diagnosis. The primary outcome was conversion to MS (2005 McDonald criteria) within 6 months. Results: DAWM was present in 27.5% of participants, and was positively associated with brainstem symptom onset, receiving corticosteroids, dissemination in space, and T2 lesion volume. DAWM was associated with an increased risk of conversion to MS over 6 months after adjustment for age and disability (hazard ratio [HR] = 2.24, p = 0.004). This association remained at a trend-level after adjustment for high-risk imaging features (HR = 1.68, p = 0.10). Conclusions: DAWM is present in a similar proportion of patients with CIS and clinically definite MS, and it is associated with increased risk of conversion to MS over 6 months.",
keywords = "clinically isolated syndrome, diffusely abnormal white matter, magnetic resonance imaging, multiple sclerosis",
author = "Holmes, {R. Davis} and Vavasour, {Irene M.} and Jamie Greenfield and Guojun Zhao and Lee, {Jimmy S.} and Moore, {G. R.Wayne} and Roger Tam and Metz, {Luanne M.} and Anthony Trablousee and Li, {David K.B.} and Cornelia Laule",
note = "Funding Information: RDH, IMV, JG, GZ, JSL, and LMM have nothing to disclose. GRWM has received funding support from the Multiple Sclerosis Society of Canada and the International Collaboration on Repair Discoveries. RT has received grant funding from NSERC, Multiple Sclerosis Society of Canada, and Mitacs, and research support as part of sponsored clinical studies from Novartis, Roche, and Sanofi Genzyme. AT has received research funding from Multiple Sclerosis Society of Canada, Roche, and Sanofi Genzyme; received honoraria or travel support from Consortium of Multiple Sclerosis Centers, Biogen, Teva, Roche, Merck/EMD Serono, and Sanofi Genzyme. DKBL has received research funding from the Multiple Sclerosis Society of Canada. He is Emeritus Director of the UBC MS/MRI Research Group, which has been contracted to perform central analysis of MRI scans for therapeutic trials with Roche and Sanofi‐Genzyme. The UBC MS/MRI Research Group has also received grant support for investigator‐initiated studies from Genzyme, Novartis, and Roche. He has been a consultant to Vertex Pharmaceuticals and Genzyme, served on the Scientific Advisory Board for Celgene and the PML‐MS Steering Committee for Biogen. He has given lectures, supported by nonrestricted education grants from Academy of Health Care Learning, Consortium of Multiple Sclerosis Centers, and Sanofi‐Genzyme. CL has research support from Natural Sciences and Engineering Research Council of Canada, the Multiple Sclerosis Society of Canada, and the International Collaboration on Repair Discoveries. Funding Information: RDH, IMV, JG, GZ, JSL, and LMM have nothing to disclose. GRWM has received funding support from the Multiple Sclerosis Society of Canada and the International Collaboration on Repair Discoveries. RT has received grant funding from NSERC, Multiple Sclerosis Society of Canada, and Mitacs, and research support as part of sponsored clinical studies from Novartis, Roche, and Sanofi Genzyme. AT has received research funding from Multiple Sclerosis Society of Canada, Roche, and Sanofi Genzyme; received honoraria or travel support from Consortium of Multiple Sclerosis Centers, Biogen, Teva, Roche, Merck/EMD Serono, and Sanofi Genzyme. DKBL has received research funding from the Multiple Sclerosis Society of Canada. He is Emeritus Director of the UBC MS/MRI Research Group, which has been contracted to perform central analysis of MRI scans for therapeutic trials with Roche and Sanofi-Genzyme. The UBC MS/MRI Research Group has also received grant support for investigator-initiated studies from Genzyme, Novartis, and Roche. He has been a consultant to Vertex Pharmaceuticals and Genzyme, served on the Scientific Advisory Board for Celgene and the PML-MS Steering Committee for Biogen. He has given lectures, supported by nonrestricted education grants from Academy of Health Care Learning, Consortium of Multiple Sclerosis Centers, and Sanofi-Genzyme. CL has research support from Natural Sciences and Engineering Research Council of Canada, the Multiple Sclerosis Society of Canada, and the International Collaboration on Repair Discoveries. Publisher Copyright: {\textcopyright} 2021 American Society of Neuroimaging",
year = "2021",
month = sep,
day = "1",
doi = "10.1111/jon.12900",
language = "English (US)",
volume = "31",
pages = "981--994",
journal = "Journal of Neuroimaging",
issn = "1051-2284",
publisher = "Wiley-Blackwell",
number = "5",
}