title: Spinal cord gray matter atrophy correlates with multiple sclerosis disability.
abstract: OBJECTIVE
  In multiple sclerosis (MS), cerebral gray matter (GM) atrophy correlates more strongly than white matter (WM) atrophy with disability. The corresponding relationships in the spinal cord (SC) are unknown due to technical limitations in assessing SC GM atrophy. Using phase-sensitive inversion recovery (PSIR) magnetic resonance imaging, we determined the association of the SC GM and SC WM areas with MS disability and disease type.
  
  
  METHODS
  A total of 113 MS patients and 20 healthy controls were examined at 3T with a PSIR sequence acquired at the C2/C3 disk level. Two independent, clinically masked readers measured the cord WM and GM areas. Correlations between cord areas and Expanded Disability Status Score (EDSS) were determined. Differences in areas between groups were assessed with age and sex as covariates.
  
  
  RESULTS
  Relapsing MS (RMS) patients showed smaller SC GM areas than age- and sex-matched controls (p = 0.008) without significant differences in SC WM areas. Progressive MS patients showed smaller SC GM and SC WM areas compared to RMS patients (all p ≤ 0.004). SC GM, SC WM, and whole cord areas inversely correlated with EDSS (rho: -0.60, -0.32, -0.42, respectively; all p ≤ 0.001). The SC GM area was the strongest correlate of disability in multivariate models including brain GM and WM volumes, fluid-attenuated inversion recovery lesion load, T1 lesion load, SC WM area, number of SC T2 lesions, age, sex, and disease duration. Brain and spinal GM independently contributed to EDSS.
  
  
  CONCLUSIONS
  SC GM atrophy is detectable in vivo in the absence of WM atrophy in RMS. It is more pronounced in progressive MS than RMS and contributes more to patient disability than SC WM or brain GM atrophy.
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA; Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Regina
authors.initials: R
authors.lastname: Schlaeger
authors.forename: Nico
authors.initials: N
authors.lastname: Papinutto
authors.forename: Valentina
authors.initials: V
authors.lastname: Panara
authors.forename: Carolyn
authors.initials: C
authors.lastname: Bevan
authors.forename: Iryna V
authors.initials: IV
authors.lastname: Lobach
authors.forename: Monica
authors.initials: M
authors.lastname: Bucci
authors.forename: Eduardo
authors.initials: E
authors.lastname: Caverzasi
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gelfand
authors.forename: Ari J
authors.initials: AJ
authors.lastname: Green
authors.forename: Kesshi M
authors.initials: KM
authors.lastname: Jordan
authors.forename: William A
authors.initials: WA
authors.lastname: Stern
authors.forename: H-Christian
authors.initials: HC
authors.lastname: von Büdingen
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
authors.forename: Alyssa H
authors.initials: AH
authors.lastname: Zhu
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Goodin
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.forename: Roland G
authors.initials: RG
authors.lastname: Henry
mesh_terms: D000368:Aged; D001284:Atrophy / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D006233:Persons with Disabilities; D005260:Female; D066128:Gray Matter; D006801:Humans; D007091:Image Processing, Computer-Assisted; D018868:Insurance, Disability; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000473:pathology*; D012372:ROC Curve; D013116:Spinal Cord / Q000473:pathology*
references.citation: Microsc Acta. 1982 May;86(1):13-24
references.pmid: 7048029
references.citation: J Neurol Neurosurg Psychiatry. 2009 Feb;80(2):182-7
references.pmid: 18829630
references.citation: Spine (Phila Pa 1976). 1996 Jun 1;21(11):1285-90
references.pmid: 8725917
references.citation: Ann Neurol. 2000 Dec;48(6):893-901
references.pmid: 11117546
references.citation: Cell Tissue Bank. 2008 Sep;9(3):195-203
references.pmid: 18548334
references.citation: Arch Neurol. 2005 Dec;62(12):1859-62
references.pmid: 16344343
references.citation: Lancet Neurol. 2012 Dec;11(12):1082-92
references.pmid: 23153407
references.citation: Neurology. 2005 Jul 26;65(2):280-5
references.pmid: 16043800
references.citation: Neurology. 2003 Apr 8;60(7):1157-62
references.pmid: 12682324
references.citation: Ann Neurol. 2001 Sep;50(3):389-400
references.pmid: 11558796
references.citation: Mult Scler. 2011 Sep;17(9):1098-106
references.pmid: 21586487
references.citation: J Neuropathol Exp Neurol. 2003 Jul;62(7):723-32
references.pmid: 12901699
references.citation: Neuroimage. 2004 Nov;23(3):1168-75
references.pmid: 15528116
references.citation: Neuroimage. 2012 Nov 15;63(3):1054-9
references.pmid: 22850571
references.citation: Mult Scler. 2008 Sep;14(8):1068-75
references.pmid: 18632782
references.citation: Mult Scler. 2014 Jan;20(1):72-80
references.pmid: 23812283
references.citation: J Magn Reson Imaging. 2014 Mar;39(3):617-23
references.pmid: 23633384
references.citation: Mult Scler Relat Disord. 2013 Apr;2(2):103-8
references.pmid: 25877631
references.citation: Brain. 2002 Aug;125(Pt 8):1676-95
references.pmid: 12135961
references.citation: Neurology. 1996 Apr;46(4):907-11
references.pmid: 8780061
references.citation: Ann Neurol. 2011 Mar;69(3):445-54
references.pmid: 21446020
references.citation: Radiology. 2005 Dec;237(3):854-60
references.pmid: 16304107
references.citation: MAGMA. 2014 Jun;27(3):257-67
references.pmid: 24052240
references.citation: Ann Neurol. 2011 Feb;69(2):292-302
references.pmid: 21387374
references.citation: J Neurol Neurosurg Psychiatry. 2011 Apr;82(4):471-2
references.pmid: 20710012
references.citation: Neurology. 2011 Jul 19;77(3):257-63
references.pmid: 21613600
references.citation: Neurology. 1983 Nov;33(11):1444-52
references.pmid: 6685237
references.citation: Mult Scler. 1999 Aug;5(4):244-50
references.pmid: 10467383
references.citation: Neurology. 2004 Jul 13;63(1):89-93
references.pmid: 15249616
references.citation: Neurology. 2006 Sep 26;67(6):960-7
references.pmid: 17000961
references.citation: Brain. 2004 May;127(Pt 5):1101-7
references.pmid: 14998914
references.citation: Ann Neurol. 2008 Sep;64(3):247-54
references.pmid: 18570297
references.citation: Brain. 2005 Nov;128(Pt 11):2705-12
references.pmid: 16230320
references.citation: Ann Neurol. 2008 Sep;64(3):255-65
references.pmid: 18661561
references.citation: Brain Pathol. 2009 Oct;19(4):642-9
references.pmid: 19170682
references.citation: Neuroimage. 2008 Aug 1;42(1):315-22
references.pmid: 18501636
references.citation: Hum Brain Mapp. 2011 Oct;32(10):1535-43
references.pmid: 20740643
references.citation: J Neurol Neurosurg Psychiatry. 2006 Sep;77(9):1036-9
references.pmid: 16793860
references.citation: Biostatistics. 2009 Jan;10(1):172-86
references.pmid: 18714084
references.citation: Magn Reson Med. 2002 Feb;47(2):372-83
references.pmid: 11810682
references.citation: Eur J Radiol. 2008 Jan;65(1):29-35
references.pmid: 18162353
references.citation: Radiology. 2013 Nov;269(2):542-52
references.pmid: 23737540
references.citation: Brain. 2005 Jan;128(Pt 1):29-34
references.pmid: 15548559
references.citation: Brain. 1996 Jun;119 ( Pt 3):701-8
references.pmid: 8673483
references.citation: Neurology. 2005 Mar 22;64(6):1001-7
references.pmid: 15781816
references.citation: Neuroimage. 2010 Apr 1;50(2):446-55
references.pmid: 20060481
references.citation: Neurology. 2011 Jun 14;76(24):2096-102
references.pmid: 21670439