Predicting disability progression and cognitive worsening in multiple sclerosis using patterns of grey matter volumes.
Journal
Journal of neurology, neurosurgery, and psychiatry
ISSN: 1468-330X
Titre abrégé: J Neurol Neurosurg Psychiatry
Pays: England
ID NLM: 2985191R
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
12
11
2020
revised:
18
03
2021
accepted:
20
03
2021
pubmed:
22
4
2021
medline:
6
1
2022
entrez:
21
4
2021
Statut:
ppublish
Résumé
In multiple sclerosis (MS), MRI measures at the whole brain or regional level are only modestly associated with disability, while network-based measures are emerging as promising prognostic markers. We sought to demonstrate whether data-driven patterns of covarying regional grey matter (GM) volumes predict future disability in secondary progressive MS (SPMS). We used cross-sectional structural MRI, and baseline and longitudinal data of Expanded Disability Status Scale, Nine-Hole Peg Test (9HPT) and Symbol Digit Modalities Test (SDMT), from a clinical trial in 988 people with SPMS. We processed T1-weighted scans to obtain GM probability maps and applied spatial independent component analysis (ICA). We repeated ICA on 400 healthy controls. We used survival models to determine whether baseline patterns of covarying GM volume measures predict cognitive and motor worsening. We identified 15 patterns of regionally covarying GM features. Compared with whole brain GM, deep GM and lesion volumes, some ICA components correlated more closely with clinical outcomes. A mainly basal ganglia component had the highest correlations at baseline with the SDMT and was associated with cognitive worsening (HR=1.29, 95% CI 1.09 to 1.52, p<0.005). Two ICA components were associated with 9HPT worsening (HR=1.30, 95% CI 1.06 to 1.60, p<0.01 and HR=1.21, 95% CI 1.01 to 1.45, p<0.05). ICA measures could better predict SDMT and 9HPT worsening (C-index=0.69-0.71) compared with models including only whole and regional MRI measures (C-index=0.65-0.69, p value for all comparison <0.05). The disability progression was better predicted by some of the covarying GM regions patterns, than by single regional or whole-brain measures. ICA, which may represent structural brain networks, can be applied to clinical trials and may play a role in stratifying participants who have the most potential to show a treatment effect.
Identifiants
pubmed: 33879535
pii: jnnp-2020-325610
doi: 10.1136/jnnp-2020-325610
pmc: PMC8372398
doi:
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
995-1006Subventions
Organisme : Medical Research Council
ID : MR/S026088/1
Pays : United Kingdom
Organisme : Department of Health
ID : RP-2017-08-ST2-004
Pays : United Kingdom
Informations de copyright
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
Nat Rev Dis Primers. 2018 Nov 8;4(1):43
pubmed: 30410033
Curr Opin Neurol. 2002 Jun;15(3):239-45
pubmed: 12045719
Neuroimage. 2005 Mar;25(1):193-205
pubmed: 15734355
Mult Scler. 2011 Sep;17(9):1098-106
pubmed: 21586487
Neural Netw. 2000 May-Jun;13(4-5):411-30
pubmed: 10946390
Neuroimage Clin. 2016 Jun 14;12:123-31
pubmed: 27408797
Ther Adv Neurol Disord. 2019 Apr 24;12:1756286419838673
pubmed: 31040880
Clin Neuropsychol. 2014;28(2):281-99
pubmed: 24438521
Brain. 2016 Jan;139(Pt 1):115-26
pubmed: 26637488
J Magn Reson Imaging. 2019 May;49(5):1312-1321
pubmed: 30597656
Neuroimage. 2006 Feb 1;29(3):859-67
pubmed: 16203159
Lancet. 2018 Mar 31;391(10127):1263-1273
pubmed: 29576505
Ann Neurol. 2018 Feb;83(2):223-234
pubmed: 29328531
Childs Nerv Syst. 2002 Aug;18(8):386-404
pubmed: 12192499
Neuroimage. 2000 Jun;11(6 Pt 1):805-21
pubmed: 10860804
Brain. 2020 Feb 1;143(2):635-649
pubmed: 32040564
Nat Rev Neurol. 2018 Feb;14(2):75-93
pubmed: 29326424
Brain Struct Funct. 2019 Dec;224(9):3031-3044
pubmed: 31701266
Brain. 2016 Jan;139(Pt 1):7-10
pubmed: 26747854
Nat Rev Neurol. 2010 Jan;6(1):15-28
pubmed: 20057496
Stat Med. 2011 May 10;30(10):1105-17
pubmed: 21484848
J Neurol. 2012 Jan;259(1):139-46
pubmed: 21720932
Mult Scler Int. 2013;2013:627870
pubmed: 23878736
Mult Scler. 2017 Apr;23(5):721-733
pubmed: 28206827
Nat Rev Neurosci. 2015 Mar;16(3):147-58
pubmed: 25697158
J Int Neuropsychol Soc. 2010 Jan;16(1):6-16
pubmed: 19796441
Mult Scler. 2010 Sep;16(9):1117-25
pubmed: 20813778
Neurology. 2010 Jun 8;74(23):1868-76
pubmed: 20530323
Front Hum Neurosci. 2018 Nov 27;12:478
pubmed: 30542275
Brain. 2018 Jun 1;141(6):1665-1677
pubmed: 29741648
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13040-5
pubmed: 19620724
F1000Res. 2019 Jan 30;8:
pubmed: 30755797
Neuroimage. 2016 Oct 1;139:376-384
pubmed: 27377222
Ann Neurol. 2013 Dec;74(6):848-61
pubmed: 23868451
J Neuroimaging. 2005;15(4 Suppl):10S-21S
pubmed: 16385015
Front Neurosci. 2012 Dec 05;6:171
pubmed: 23227001
IEEE Trans Med Imaging. 2010 Jun;29(6):1310-20
pubmed: 20378467
Mult Scler. 2015 Jun;21(7):875-84
pubmed: 25139943
Ann Neurol. 2008 Sep;64(3):255-65
pubmed: 18661561
Lancet. 2016 Mar 12;387(10023):1075-1084
pubmed: 26827074
Cold Spring Harb Perspect Med. 2018 Mar 1;8(3):
pubmed: 29358320
Front Neuroinform. 2013 Dec 23;7:39
pubmed: 24409140
J Neurosci. 2019 Jan 2;39(1):3-14
pubmed: 30389839
Lancet Neurol. 2018 May;17(5):405-415
pubmed: 29545067
AJNR Am J Neuroradiol. 2005 Feb;26(2):341-6
pubmed: 15709132
J Neurol. 2020 May;267(5):1536-1546
pubmed: 32040710
Lancet Neurol. 2009 Mar;8(3):280-91
pubmed: 19233038
N Engl J Med. 2017 Jan 19;376(3):209-220
pubmed: 28002688
Neuroimage Clin. 2017 Nov 05;17:444-451
pubmed: 29159057
IEEE Trans Med Imaging. 2015 Sep;34(9):1976-88
pubmed: 25879909
Eur J Neurol. 2019 Jun;26(6):893-902
pubmed: 30629788
Mult Scler. 2020 Apr;26(4):442-456
pubmed: 30799709
Curr Psychiatry Rep. 2019 Aug 13;21(9):87
pubmed: 31410661
Front Neurol. 2021 Jan 14;11:621010
pubmed: 33519702
AJNR Am J Neuroradiol. 2019 Jan;40(1):107-108
pubmed: 30591510
Ann Neurol. 2007 Jan;61(1):14-24
pubmed: 17262850
Neurology. 2015 Sep 29;85(13):1115-22
pubmed: 26320199
Brain. 2019 Jul 1;142(7):1858-1875
pubmed: 31209474