Skip to main content
Top
Published in: Journal of Neurology 11/2006

01-11-2006 | ORIGINAL COMMUNICATION

Localization of grey matter atrophy in early RRMS

A longitudinal study

Authors: Bertrand Audoin, MD, PhD, Gerard R. Davies, MD, PhD, Leonara Finisku, MD, Declan T. Chard, MD, PhD, Alan J. Thompson, MD, PhD, Prof. David H. Miller, MD, PhD

Published in: Journal of Neurology | Issue 11/2006

Login to get access

Abstract

Previous MR studies have established that grey matter (GM) atrophy occurs in multiple sclerosis (MS) from clinical onset. However, it is uncertain whether early GM atrophy is global or has certain local predilections: using Voxel-Based Morphometry this study aimed to address this question.
Twenty-one patients with early RRMS (mean age 36 years, mean disease duration from symptom onset 25.8 months) and 10 healthy control subjects (mean age 37 years) were studied. T1-weighted three-dimensional MRI images were acquired at baseline and two year follow-up, and analysed with statistical parametric mapping software (SPM2). Two-sample t-tests (p < 0.05 corrected for multiple comparisons at cluster level) were used to compare GM maps from all patients and controls on a voxel-by-voxel basis. At baseline, no GM region appears significantly atrophic in MS subjects compared with controls. However, during the follow-up period significantly greater atrophy occurred in both thalami and the right lateral prefrontal cortex of MS patients when compared with controls. By year two, cross-sectional group comparison revealed GM atrophy in the thalami of MS patients relative to controls. The rate of thalamic atrophy in MS subjects was correlated with changes in EDSS during the follow-up period.
This study suggests that early in the clinical course of RRMS, the thalamic atrophy is more consistently apparent than regional cortical atrophy.
Literature
1.
go back to reference Alexander G, Crutcher M (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13:166–171CrossRef Alexander G, Crutcher M (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13:166–171CrossRef
2.
go back to reference Amato MP, Bartolozzi ML, Zipoli V, Portaccio E, Mortilla M, Guidi L, Siracusa G, Sorbi S, Federico A, De Stefano N (2004) Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment. Neurology 63:89–93PubMed Amato MP, Bartolozzi ML, Zipoli V, Portaccio E, Mortilla M, Guidi L, Siracusa G, Sorbi S, Federico A, De Stefano N (2004) Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment. Neurology 63:89–93PubMed
3.
4.
go back to reference Audoin B, Ranjeva JP, My Van AD, Ibarrola D, Malikova I, Confort-Gouny S, Soulier E, Viout P, Ali-Cherif A, Pelletier J, Cozzone PJ (2004) Voxel-based analysis of MTR images: a method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis. J Magn Reson Imaging 20:765–771CrossRefPubMed Audoin B, Ranjeva JP, My Van AD, Ibarrola D, Malikova I, Confort-Gouny S, Soulier E, Viout P, Ali-Cherif A, Pelletier J, Cozzone PJ (2004) Voxel-based analysis of MTR images: a method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis. J Magn Reson Imaging 20:765–771CrossRefPubMed
5.
go back to reference Bakshi R, Benedict RH, Bermel RA, Caruthers SD, Puli SR, Tjoa CW, Fabiano AJ, Jacobs L (2002) T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study. Arch Neurol 59:62–68CrossRefPubMed Bakshi R, Benedict RH, Bermel RA, Caruthers SD, Puli SR, Tjoa CW, Fabiano AJ, Jacobs L (2002) T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study. Arch Neurol 59:62–68CrossRefPubMed
6.
go back to reference Benedict RH, Weinstock-Guttman B, Fishman I, Sharma J, Tjoa CW, Bakshi R (2004) Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Arch Neurol 61:226–230CrossRefPubMed Benedict RH, Weinstock-Guttman B, Fishman I, Sharma J, Tjoa CW, Bakshi R (2004) Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Arch Neurol 61:226–230CrossRefPubMed
7.
go back to reference Bo L, Vedeler CA, Nyland HI, Trapp BD, Mork SJ (2003) Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol 62:723–732PubMed Bo L, Vedeler CA, Nyland HI, Trapp BD, Mork SJ (2003) Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol 62:723–732PubMed
8.
go back to reference Brex PA, Jenkins R, Fox NC, Crum WR, O’Riordan JI, Plant GT, Miller DH (2000) Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology 54:1689–1691PubMed Brex PA, Jenkins R, Fox NC, Crum WR, O’Riordan JI, Plant GT, Miller DH (2000) Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology 54:1689–1691PubMed
9.
go back to reference Brownell B, JT Hughes JT (1962) The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry 25:315–320PubMedCrossRef Brownell B, JT Hughes JT (1962) The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry 25:315–320PubMedCrossRef
10.
go back to reference Chard DT, Brex PA, Ciccarelli O, Griffin CM, Parker GJ, Dalton C, Altmann DR, Thompson AJ, Miller DH (2003) The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study. J Neurol Neurosurg Psychiatry 74:1551–1554CrossRefPubMed Chard DT, Brex PA, Ciccarelli O, Griffin CM, Parker GJ, Dalton C, Altmann DR, Thompson AJ, Miller DH (2003) The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study. J Neurol Neurosurg Psychiatry 74:1551–1554CrossRefPubMed
11.
go back to reference Chard DT, Griffin CM, Parker GJ, Kapoor R, Thompson AJ, Miller DH (2002) Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain 125:327–337CrossRefPubMed Chard DT, Griffin CM, Parker GJ, Kapoor R, Thompson AJ, Miller DH (2002) Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain 125:327–337CrossRefPubMed
12.
go back to reference Chard DT, Griffin CM, Rashid W, Davies GR, Altmann DR, Kapoor R, Barker GJ, Thompson AJ, Miller DH (2004) Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis. Mult Scler 10:387–391PubMedCrossRef Chard DT, Griffin CM, Rashid W, Davies GR, Altmann DR, Kapoor R, Barker GJ, Thompson AJ, Miller DH (2004) Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis. Mult Scler 10:387–391PubMedCrossRef
13.
go back to reference Cifelli A, Arridge M, Jezzard P, Esiri MM, Palace J, Matthews PM (2002) Thalamic neurodegeneration in multiple sclerosis. Ann Neurol 52:650–653CrossRefPubMed Cifelli A, Arridge M, Jezzard P, Esiri MM, Palace J, Matthews PM (2002) Thalamic neurodegeneration in multiple sclerosis. Ann Neurol 52:650–653CrossRefPubMed
14.
go back to reference Dalton CM, Brex PA, Jenkins R, Fox NC, Miszkiel KA, Crum WR, O’Riordan JI, Plant GT, Thompson AJ, Miller DH (2002) Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis. J Neurol Neurosurg Psychiatry 73:141–147CrossRefPubMed Dalton CM, Brex PA, Jenkins R, Fox NC, Miszkiel KA, Crum WR, O’Riordan JI, Plant GT, Thompson AJ, Miller DH (2002) Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis. J Neurol Neurosurg Psychiatry 73:141–147CrossRefPubMed
15.
go back to reference Dalton CM, Chard DT, Davies GR, Miszkiel KA, Altmann DR, Fernando K, Plant GT, Thompson AJ, Miller DH (2004) Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain 127:1101–1107CrossRefPubMed Dalton CM, Chard DT, Davies GR, Miszkiel KA, Altmann DR, Fernando K, Plant GT, Thompson AJ, Miller DH (2004) Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain 127:1101–1107CrossRefPubMed
16.
go back to reference Davies GR, Altmann DR, Rashid W, Chard DT, Griffin CM, Barker GJ, Kapoor R, Thompson AJ, Miller DH (2005) Emergence of thalamic magnetization transfer ratio abnormality in early relapsing-remitting multiple sclerosis. Mult Scler 11:276–281CrossRefPubMed Davies GR, Altmann DR, Rashid W, Chard DT, Griffin CM, Barker GJ, Kapoor R, Thompson AJ, Miller DH (2005) Emergence of thalamic magnetization transfer ratio abnormality in early relapsing-remitting multiple sclerosis. Mult Scler 11:276–281CrossRefPubMed
17.
go back to reference De Stefano N, Matthews PM, Filippi M, Agosta F, De Luca M, Bartolozzi ML, Guidi L, Ghezzi A, Montanari E, Cifelli A, Federico A, Smith SM (2003) Evidence of early cortical atrophy in MS: relevance to white matter changes and disability. Neurology 60:1157–1162PubMed De Stefano N, Matthews PM, Filippi M, Agosta F, De Luca M, Bartolozzi ML, Guidi L, Ghezzi A, Montanari E, Cifelli A, Federico A, Smith SM (2003) Evidence of early cortical atrophy in MS: relevance to white matter changes and disability. Neurology 60:1157–1162PubMed
18.
go back to reference Fabiano AJ, Sharma J, Weinstock-Guttman B, Munschauer FE, 3rd, Benedict RH, Zivadinov R, Bakshi R (2003) Thalamic involvement in multiple sclerosis: a diffusion-weighted magnetic resonance imaging study. J Neuroimaging 13:307–314CrossRefPubMed Fabiano AJ, Sharma J, Weinstock-Guttman B, Munschauer FE, 3rd, Benedict RH, Zivadinov R, Bakshi R (2003) Thalamic involvement in multiple sclerosis: a diffusion-weighted magnetic resonance imaging study. J Neuroimaging 13:307–314CrossRefPubMed
19.
go back to reference Fischer JS, Rudick RA, Cutter GR, Reingold SC (1999) The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult Scler 5:244–250CrossRefPubMed Fischer JS, Rudick RA, Cutter GR, Reingold SC (1999) The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult Scler 5:244–250CrossRefPubMed
20.
go back to reference Fisher E, Rudick RA, Simon JH, Cutter G, Baier M, Lee JC, Miller D, Weinstock-Guttman B, Mass MK, Dougherty DS, Simonian NA (2002) Eight-year follow-up study of brain atrophy in patients with MS. Neurology 59:1412–1420PubMed Fisher E, Rudick RA, Simon JH, Cutter G, Baier M, Lee JC, Miller D, Weinstock-Guttman B, Mass MK, Dougherty DS, Simonian NA (2002) Eight-year follow-up study of brain atrophy in patients with MS. Neurology 59:1412–1420PubMed
21.
go back to reference Friston KJ, Holmes AP, Price CJ, Buchel C, Worsley KJ (1999) Multisubject fMRI studies and conjunction analyses. Neuroimage 10:385–396CrossRefPubMed Friston KJ, Holmes AP, Price CJ, Buchel C, Worsley KJ (1999) Multisubject fMRI studies and conjunction analyses. Neuroimage 10:385–396CrossRefPubMed
22.
go back to reference Grimaud J, Lai M, Thorpe J, Adeleine P, Wang L, Barker GJ, Plummer DL, Tofts PS, McDonald WI, Miller DH (1996) Quantification of MRI lesion load in multiple sclerosis: a comparison of three computer-assisted techniques. Magn Reson Imaging 14:495–505CrossRefPubMed Grimaud J, Lai M, Thorpe J, Adeleine P, Wang L, Barker GJ, Plummer DL, Tofts PS, McDonald WI, Miller DH (1996) Quantification of MRI lesion load in multiple sclerosis: a comparison of three computer-assisted techniques. Magn Reson Imaging 14:495–505CrossRefPubMed
23.
go back to reference Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T (1999) Cortical lesions in multiple sclerosis. Brain 122(Pt 1):17–26CrossRefPubMed Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T (1999) Cortical lesions in multiple sclerosis. Brain 122(Pt 1):17–26CrossRefPubMed
24.
go back to reference Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMed Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMed
25.
go back to reference Losseff NA, Wang L, Lai HM, Yoo DS, Gawne-Cain ML, McDonald WI, Miller DH, Thompson AJ (1996) Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain 119(Pt 6):2009–2019PubMed Losseff NA, Wang L, Lai HM, Yoo DS, Gawne-Cain ML, McDonald WI, Miller DH, Thompson AJ (1996) Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain 119(Pt 6):2009–2019PubMed
26.
go back to reference Luks TL, Goodkin DE, Nelson SJ, Majumdar S, Bacchetti P, Portnoy D, Sloan R (2000) A longitudinal study of ventricular volume in early relapsing-remitting multiple sclerosis. Mult Scler 6:332–337CrossRefPubMed Luks TL, Goodkin DE, Nelson SJ, Majumdar S, Bacchetti P, Portnoy D, Sloan R (2000) A longitudinal study of ventricular volume in early relapsing-remitting multiple sclerosis. Mult Scler 6:332–337CrossRefPubMed
27.
go back to reference Lumsden CE (1970) The neuropathology of multiple sclerosis. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, Volume 9. Amsterdam, pp 217–309 Lumsden CE (1970) The neuropathology of multiple sclerosis. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, Volume 9. Amsterdam, pp 217–309
28.
go back to reference Pagani E, Rocca MA, Gallo A, Rovaris M, Martinelli V, Comi G, Filippi M (2005) Regional brain atrophy evolves differently in patients with multiple sclerosis according to clinical phenotype. AJNR Am J Neuroradiol 26:341–346PubMed Pagani E, Rocca MA, Gallo A, Rovaris M, Martinelli V, Comi G, Filippi M (2005) Regional brain atrophy evolves differently in patients with multiple sclerosis according to clinical phenotype. AJNR Am J Neuroradiol 26:341–346PubMed
29.
go back to reference Peterson JW, Bo L, Mork S, Chang A, Trapp BD (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389–400CrossRefPubMed Peterson JW, Bo L, Mork S, Chang A, Trapp BD (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389–400CrossRefPubMed
30.
go back to reference Ranjeva JP, Audoin B, Duong MV, Ibarrola D, Confort-Gouny S, Malikova I, Soulier E, Viout P, Ali-Cherif A, Pelletier J, Cozzone P (2005) Local tissue damage assessed with statistical mapping analysis of brain magnetization transfer ratio: relationship with functional status of patients in the earliest stage of multiple sclerosis. AJNR Am J Neuroradiol 26:119–127PubMed Ranjeva JP, Audoin B, Duong MV, Ibarrola D, Confort-Gouny S, Malikova I, Soulier E, Viout P, Ali-Cherif A, Pelletier J, Cozzone P (2005) Local tissue damage assessed with statistical mapping analysis of brain magnetization transfer ratio: relationship with functional status of patients in the earliest stage of multiple sclerosis. AJNR Am J Neuroradiol 26:119–127PubMed
31.
go back to reference Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L (1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology 53:1698–1704PubMed Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L (1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology 53:1698–1704PubMed
32.
go back to reference Sailer M, Fischl B, Salat D, Tempelmann C, Schonfeld MA, Busa E, Bodammer N, Heinze HJ, Dale A (2003) Focal thinning of the cerebral cortex in multiple sclerosis. Brain 126:1734–1744CrossRefPubMed Sailer M, Fischl B, Salat D, Tempelmann C, Schonfeld MA, Busa E, Bodammer N, Heinze HJ, Dale A (2003) Focal thinning of the cerebral cortex in multiple sclerosis. Brain 126:1734–1744CrossRefPubMed
33.
go back to reference Simon JH, Jacobs LD, Campion MK, Rudick RA, Cookfair DL, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Simonian N, Lajaunie M, Miller DE, Wende K, Martens-Davidson A, Kinkel RP, Munschauer FE, 3rd, Brownscheidle CM (1999) A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology 53:139–148PubMed Simon JH, Jacobs LD, Campion MK, Rudick RA, Cookfair DL, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Simonian N, Lajaunie M, Miller DE, Wende K, Martens-Davidson A, Kinkel RP, Munschauer FE, 3rd, Brownscheidle CM (1999) A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology 53:139–148PubMed
34.
go back to reference Talairach J, Tournoux P (1988) Co-Planar Stereotaxic Atlas of the Human Brain. Thieme Medical Publishers, Inc., New York Talairach J, Tournoux P (1988) Co-Planar Stereotaxic Atlas of the Human Brain. Thieme Medical Publishers, Inc., New York
35.
go back to reference Tiberio M, Chard DT, Altmann DR, Davies G, Griffin CM, Rashid W, Sastre-Garriga J, Thompson AJ, Miller DH (2005) Gray and white matter volume changes in early RRMS: a 2-year longitudinal study. Neurology 64:1001–1007PubMed Tiberio M, Chard DT, Altmann DR, Davies G, Griffin CM, Rashid W, Sastre-Garriga J, Thompson AJ, Miller DH (2005) Gray and white matter volume changes in early RRMS: a 2-year longitudinal study. Neurology 64:1001–1007PubMed
36.
go back to reference Wylezinska M, Cifelli A, Jezzard P, Palace J, Alecci M, Matthews PM (2003) Thalamic neurodegeneration in relapsing-remitting multiple sclerosis. Neurology 60:1949–1954PubMed Wylezinska M, Cifelli A, Jezzard P, Palace J, Alecci M, Matthews PM (2003) Thalamic neurodegeneration in relapsing-remitting multiple sclerosis. Neurology 60:1949–1954PubMed
Metadata
Title
Localization of grey matter atrophy in early RRMS
A longitudinal study
Authors
Bertrand Audoin, MD, PhD
Gerard R. Davies, MD, PhD
Leonara Finisku, MD
Declan T. Chard, MD, PhD
Alan J. Thompson, MD, PhD
Prof. David H. Miller, MD, PhD
Publication date
01-11-2006
Publisher
Steinkopff-Verlag
Published in
Journal of Neurology / Issue 11/2006
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-006-0264-2

Other articles of this Issue 11/2006

Journal of Neurology 11/2006 Go to the issue