Skip to main content
Top
Published in: Journal of Neurology 9/2010

01-09-2010 | Original Communication

A longitudinal study of MRI-detected atrophy in secondary progressive multiple sclerosis

Authors: J. Furby, T. Hayton, D. Altmann, R. Brenner, J. Chataway, K. J. Smith, D. H. Miller, R. Kapoor

Published in: Journal of Neurology | Issue 9/2010

Login to get access

Abstract

MRI measures of tissue atrophy within the central nervous system may reflect the neurodegenerative process which underpins the progressive phase of multiple sclerosis (MS). There has been limited longitudinal investigation of MRI-detected atrophy in secondary progressive MS. This study includes 56 subjects with secondary progressive MS. Subjects were followed up for 2 years and MRI analysis was conducted at 12 month intervals using the following measures: (1) whole brain (WB) volume change; (2) grey and white matter (WM) volumes; (3) central brain volume; (4) upper cervical spinal cord (SC) area; (5) T2 lesion volumes. Clinical measures included the Expanded Disability Status Scale and the MS Functional Composite. All volumetric MRI measures were assessed for sensitivity, responsiveness, reliability and correlation with disability. The mean annual atrophy rate of WB was 0.59% per year and this was the most responsive atrophy measure assessed. Grey matter (GM) atrophy (−1.18% per year) was greater and more responsive than WM atrophy (0.12% per year). The SC demonstrated the highest atrophy rate at 1.63% per year. WB, GM and SC atrophy all correlated with change in the Multiple Sclerosis Functional Composite z score (r = 0.35, 0.42, 0.34), and GM atrophy was the only correlate of change in the 9 Hole Peg Test and Paced Auditory Serial Addition Test performance. None of the MRI measures correlated with Expanded Disability Status Score progression. Measures of WB, GM and SC atrophy all have attributes for use as surrogate markers in secondary progressive MS trials and improvement in the reliability of the GM and SC volume measurements may enhance these further.
Literature
1.
go back to reference Trapp BD, Petereson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in lesions of multiple sclerosis. N Eng J Med 338:278–285CrossRef Trapp BD, Petereson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in lesions of multiple sclerosis. N Eng J Med 338:278–285CrossRef
2.
go back to reference Bjartmar C, Kidd G, Mork S, Rudick R, Trapp BD (2000) Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 48:893–901CrossRefPubMed Bjartmar C, Kidd G, Mork S, Rudick R, Trapp BD (2000) Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 48:893–901CrossRefPubMed
3.
go back to reference Losseff NA, Wang L, Lau HM, Yoo DS, Gawne-Cain ML, McDonald WI et al (1996) Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain 119:2009–2019CrossRefPubMed Losseff NA, Wang L, Lau HM, Yoo DS, Gawne-Cain ML, McDonald WI et al (1996) Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain 119:2009–2019CrossRefPubMed
4.
go back to reference Losseff NA, Webb SL, O’Riordan JI, Page R, Wang L, Barker GJ et al (1996) Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. Brain 119:701–708CrossRefPubMed Losseff NA, Webb SL, O’Riordan JI, Page R, Wang L, Barker GJ et al (1996) Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. Brain 119:701–708CrossRefPubMed
5.
go back to reference Fisher E, Rudick RA, Simon JH, Cutter G, Baier M, Lee JC et al (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 et al (2002) Eight-year follow-up study of brain atrophy in patients with MS. Neurology 59:1412–1420PubMed
6.
go back to reference Lin X, Tench CR, Turner B, Blumhardt LD, Constantinescu CS (2003) Spinal cord atrophy and disability in multiple sclerosis over 4 years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon beta-1a treatment trial. J Neurol Neurosurg Psychiatry 74:1014–1015CrossRef Lin X, Tench CR, Turner B, Blumhardt LD, Constantinescu CS (2003) Spinal cord atrophy and disability in multiple sclerosis over 4 years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon beta-1a treatment trial. J Neurol Neurosurg Psychiatry 74:1014–1015CrossRef
7.
go back to reference Truyen L, van Waesberghe JH, van Walderveen MA, van Oosten BW, Polman CH et al (1996) Accumulation of hypointense (black holes) on T1 spin-echo MRI correlates with disease progression in multiple sclerosis. Neurology 47:1469–1476PubMed Truyen L, van Waesberghe JH, van Walderveen MA, van Oosten BW, Polman CH et al (1996) Accumulation of hypointense (black holes) on T1 spin-echo MRI correlates with disease progression in multiple sclerosis. Neurology 47:1469–1476PubMed
8.
go back to reference De Stefano N, Matthews PM, Fu L, Narayanan S, Stanley J, Francis GS et al (1998) Axonal damage correlates with disability in patients with relapsing remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121:1469–1477CrossRefPubMed De Stefano N, Matthews PM, Fu L, Narayanan S, Stanley J, Francis GS et al (1998) Axonal damage correlates with disability in patients with relapsing remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121:1469–1477CrossRefPubMed
9.
go back to reference Fox NC, Jenkins R, Leary SM, Stevenson VL, Losseff NA, Cum WR et al (2000) Progressive cerebral atrophy in MS: a serial study using registered volumetric MRI. Neurology 54:807–812PubMed Fox NC, Jenkins R, Leary SM, Stevenson VL, Losseff NA, Cum WR et al (2000) Progressive cerebral atrophy in MS: a serial study using registered volumetric MRI. Neurology 54:807–812PubMed
10.
go back to reference Smith SM, Zhang Y, Jenkinson M, Chen J, Matthews PM, Frederico A et al (2002) Accurate, robust and automated longitudinal and cross-sectional brain change analysis. Neuroimage 17:479–489CrossRefPubMed Smith SM, Zhang Y, Jenkinson M, Chen J, Matthews PM, Frederico A et al (2002) Accurate, robust and automated longitudinal and cross-sectional brain change analysis. Neuroimage 17:479–489CrossRefPubMed
11.
go back to reference Anderson VM, Fox NC, Miller DH (2006) Magnetic resonance imaging measures of brain atrophy in multiple sclerosis. J Magn Reson Imaging 23:605–618CrossRefPubMed Anderson VM, Fox NC, Miller DH (2006) Magnetic resonance imaging measures of brain atrophy in multiple sclerosis. J Magn Reson Imaging 23:605–618CrossRefPubMed
12.
go back to reference Rudick RA, Fisher E, Lee J, Simon J, Jacobs L, The Multiple Sclerosis Collaborative Research Group (1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Neurology 53:1698–1704PubMed Rudick RA, Fisher E, Lee J, Simon J, Jacobs L, The Multiple Sclerosis Collaborative Research Group (1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Neurology 53:1698–1704PubMed
13.
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
14.
go back to reference Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M et al (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705–2712CrossRefPubMed Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M et al (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705–2712CrossRefPubMed
15.
go back to reference Vrenken H, Barkhof F, Uitdehaag BM, Castelijns JA, Polman CH et al (2005) MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter. Magn Reson Med 53:256–266CrossRefPubMed Vrenken H, Barkhof F, Uitdehaag BM, Castelijns JA, Polman CH et al (2005) MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter. Magn Reson Med 53:256–266CrossRefPubMed
16.
go back to reference Hoogervorst EL, Kalkers NF, Cutter GR, Uitdehaag BM, Polman CH (2004) The patients perception of a reliable change in the multiple sclerosis functional composite. Multiple Scler 10:55–60CrossRef Hoogervorst EL, Kalkers NF, Cutter GR, Uitdehaag BM, Polman CH (2004) The patients perception of a reliable change in the multiple sclerosis functional composite. Multiple Scler 10:55–60CrossRef
17.
go back to reference Ashburner J, Friston K (1997) Multimodal image coregistration and partitioning—a unified framework. Neuroimage 6:209–217CrossRefPubMed Ashburner J, Friston K (1997) Multimodal image coregistration and partitioning—a unified framework. Neuroimage 6:209–217CrossRefPubMed
18.
go back to reference Studholme C, Hill DLG, Hawkes DJ (1999) An overlap invariant entropy measure of 3D medical image alignment. Pattern Recognit 32:71–86CrossRef Studholme C, Hill DLG, Hawkes DJ (1999) An overlap invariant entropy measure of 3D medical image alignment. Pattern Recognit 32:71–86CrossRef
19.
go back to reference Freeborough PA, Fox NC, Kitney RI (1997) Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans. Comput Methods Programs Biomed 53:15–25CrossRefPubMed Freeborough PA, Fox NC, Kitney RI (1997) Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans. Comput Methods Programs Biomed 53:15–25CrossRefPubMed
20.
go back to reference Cutter GR, Baier ML, Rudick RA, Cookfair DL, Fischer JS, Petkau J et al (1999) Development of the multiple sclerosis functional composite as a clinical trial outcome measure. Brain 122:871–882CrossRefPubMed Cutter GR, Baier ML, Rudick RA, Cookfair DL, Fischer JS, Petkau J et al (1999) Development of the multiple sclerosis functional composite as a clinical trial outcome measure. Brain 122:871–882CrossRefPubMed
21.
go back to reference De Luca GC, Williams K, Evangelou N, Ebers GC, Esiri MM (2006) The contribution of demyelination to axonal loss in multiple sclerosis. Brain 129:1507–1516CrossRef De Luca GC, Williams K, Evangelou N, Ebers GC, Esiri MM (2006) The contribution of demyelination to axonal loss in multiple sclerosis. Brain 129:1507–1516CrossRef
22.
go back to reference De Luca GC, Ebers GC, Esiri MM (2004) Axonal loss in multiple sclerosis: a pathological survey of the sensory and corticospinal tracts. Brain 127:1009–1018CrossRef De Luca GC, Ebers GC, Esiri MM (2004) Axonal loss in multiple sclerosis: a pathological survey of the sensory and corticospinal tracts. Brain 127:1009–1018CrossRef
23.
go back to reference Fisher E, Lee JC, Nakamura K, Rudick RA (2008) Gray matter atrophy in multiple sclerosis. Ann Neurol 64:255–265CrossRefPubMed Fisher E, Lee JC, Nakamura K, Rudick RA (2008) Gray matter atrophy in multiple sclerosis. Ann Neurol 64:255–265CrossRefPubMed
24.
go back to reference Dalton CM, Miszkiel KA, O’Connor PW, Plant GT, Rice GP, Miller DH (2006) Ventricular enlargement in MS: one-year change at various stages of disease. Neurology 66:693–698CrossRefPubMed Dalton CM, Miszkiel KA, O’Connor PW, Plant GT, Rice GP, Miller DH (2006) Ventricular enlargement in MS: one-year change at various stages of disease. Neurology 66:693–698CrossRefPubMed
25.
go back to reference Lin X, Blumhardt LD, Constantinescu CS (2003) The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three dimensional study. Acta Neurol Scand 108:401–406CrossRefPubMed Lin X, Blumhardt LD, Constantinescu CS (2003) The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three dimensional study. Acta Neurol Scand 108:401–406CrossRefPubMed
26.
go back to reference Kalkers NF, Ameziane N, Bot JC, Minneboo A, Polman CH, Barkhof F (2002) Longitudinal brain volume measurement in multiple sclerosis: rate of brain atrophy is independent of disease subtype. Arch Neurol 59:1572–1576CrossRefPubMed Kalkers NF, Ameziane N, Bot JC, Minneboo A, Polman CH, Barkhof F (2002) Longitudinal brain volume measurement in multiple sclerosis: rate of brain atrophy is independent of disease subtype. Arch Neurol 59:1572–1576CrossRefPubMed
27.
go back to reference Altmann DR, Jasperse B, Barkhof F, Beckmann K, Filippi M, Kappos LD (2009) Sample sizes for brain atrophy outcomes in trials for secondary progressive multiple sclerosis. Neurology 72:595–601CrossRefPubMed Altmann DR, Jasperse B, Barkhof F, Beckmann K, Filippi M, Kappos LD (2009) Sample sizes for brain atrophy outcomes in trials for secondary progressive multiple sclerosis. Neurology 72:595–601CrossRefPubMed
28.
go back to reference Sanfilipo MP, Benedict RHB, Sharma J, Weinstock-Guttman B, Bakshi R (2005) The relationship between whole brain volume and disability in multiple sclerosis: a comparison of normalized gray vs. white matter with misclassification correction. Neuroimage 26:1068–1077CrossRefPubMed Sanfilipo MP, Benedict RHB, Sharma J, Weinstock-Guttman B, Bakshi R (2005) The relationship between whole brain volume and disability in multiple sclerosis: a comparison of normalized gray vs. white matter with misclassification correction. Neuroimage 26:1068–1077CrossRefPubMed
29.
go back to reference Ramio-Torrenta L, Sastre Garriga Jingle GT et al (2006) Abnormalities in normal appearing tissues in early primary progressive multiple sclerosis and their relation to disability: a tissue specific magnetisation transfer study. J Neurol Neurosurg Psychiatry 77:40–45CrossRefPubMed Ramio-Torrenta L, Sastre Garriga Jingle GT et al (2006) Abnormalities in normal appearing tissues in early primary progressive multiple sclerosis and their relation to disability: a tissue specific magnetisation transfer study. J Neurol Neurosurg Psychiatry 77:40–45CrossRefPubMed
30.
go back to reference Horakova D, Cox JL, Havradova E, Hussein S, Dolezal O, Cookfair D et al (2008) Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years. A case control study. J Neurol Neurosurg Psychiatry 79:407–414CrossRefPubMed Horakova D, Cox JL, Havradova E, Hussein S, Dolezal O, Cookfair D et al (2008) Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years. A case control study. J Neurol Neurosurg Psychiatry 79:407–414CrossRefPubMed
31.
go back to reference Sastre-Garriga J, Ingle GT, Chard DT, Cercignani M, Ramio-Torrenta L, Miller DH, Thompson AJ (2005) Grey and white matter volume changes in early primary progressive multiple sclerosis: a longitudinal study. Brain 128:1454–1460CrossRefPubMed Sastre-Garriga J, Ingle GT, Chard DT, Cercignani M, Ramio-Torrenta L, Miller DH, Thompson AJ (2005) Grey and white matter volume changes in early primary progressive multiple sclerosis: a longitudinal study. Brain 128:1454–1460CrossRefPubMed
32.
go back to reference Dalton CM, Chard DT, Davies GR, Miszkiel KA, Altmann DR, Fernando K et al (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 et al (2004) Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain 127:1101–1107CrossRefPubMed
33.
go back to reference Chard DT, Parker GJM, Griffin C, Thompson AJ, Miller DH (2002) The reproducibility and sensitivity of brain tissue volume measurements derived from an SPM-based segmentation methodology. J Magn Reson Imaging 15:259–267CrossRefPubMed Chard DT, Parker GJM, Griffin C, Thompson AJ, Miller DH (2002) The reproducibility and sensitivity of brain tissue volume measurements derived from an SPM-based segmentation methodology. J Magn Reson Imaging 15:259–267CrossRefPubMed
34.
go back to reference Fisniku L, Chard DT, Jackson JS, Anderson VM, Altmann DR, Miskiel KA et al (2008) Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol 64:247–254CrossRefPubMed Fisniku L, Chard DT, Jackson JS, Anderson VM, Altmann DR, Miskiel KA et al (2008) Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol 64:247–254CrossRefPubMed
35.
go back to reference Furby J, Hayton T, Anderson V, Altmann D, Brenner R, Chataway J et al (2008) Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis. Multiple Scler 14:1068–1075CrossRef Furby J, Hayton T, Anderson V, Altmann D, Brenner R, Chataway J et al (2008) Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis. Multiple Scler 14:1068–1075CrossRef
36.
go back to reference Rudick RA, Lee J, Nakamura K, Fisher E (2009) Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS. J Neurol Sci 282:106–111CrossRefPubMed Rudick RA, Lee J, Nakamura K, Fisher E (2009) Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS. J Neurol Sci 282:106–111CrossRefPubMed
37.
go back to reference Tiberio M, Chard DT, Altmann DR, Davies G, Griffin CM, Rashid W et al (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 et al (2005) Gray and white matter volume changes in early RRMS: a 2-year longitudinal study. Neurology 64:1001–1007PubMed
38.
go back to reference Valsasina P, Benedetti B, Rovaris M, Sormani MP, Comi G, Filippi M (2005) Evidence for progressive gray matter loss in patients with relapsing-remitting MS. Neurology 65:1125–1128CrossRef Valsasina P, Benedetti B, Rovaris M, Sormani MP, Comi G, Filippi M (2005) Evidence for progressive gray matter loss in patients with relapsing-remitting MS. Neurology 65:1125–1128CrossRef
39.
go back to reference Molyneux PD, Kappos L, Polman C, Pozzilli C, Barkhof F, Filippi M (2000) The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study Group on Interferon beta-1b in secondary progressive multiple sclerosis. Brain 123:2256–2263CrossRefPubMed Molyneux PD, Kappos L, Polman C, Pozzilli C, Barkhof F, Filippi M (2000) The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study Group on Interferon beta-1b in secondary progressive multiple sclerosis. Brain 123:2256–2263CrossRefPubMed
40.
go back to reference CAMMS223 Trial Investigators (2008) Alemtuzumab vs Interferon Beta-1a in early multiple sclerosis. N Eng J Med 359:1786–1801CrossRef CAMMS223 Trial Investigators (2008) Alemtuzumab vs Interferon Beta-1a in early multiple sclerosis. N Eng J Med 359:1786–1801CrossRef
41.
go back to reference Stevenson VL, Leary SM, Losseff NA, Parker GJ, Barker GJ, Husmani Y et al (1998) Spinal cord atrophy and disability in MS: a longitudinal study. Neurology 51:234–238PubMed Stevenson VL, Leary SM, Losseff NA, Parker GJ, Barker GJ, Husmani Y et al (1998) Spinal cord atrophy and disability in MS: a longitudinal study. Neurology 51:234–238PubMed
42.
go back to reference Stevenson VL, Miller DH, Leary SM, Rovaris M, Barkhof F, Brochet B et al (2000) One year follow-up study of primary and transitional progressive MS. J Neurol Neurosurg Psychiatry 68:713–718CrossRefPubMed Stevenson VL, Miller DH, Leary SM, Rovaris M, Barkhof F, Brochet B et al (2000) One year follow-up study of primary and transitional progressive MS. J Neurol Neurosurg Psychiatry 68:713–718CrossRefPubMed
43.
go back to reference Hobart J, Kalkers N, Barkhof F, Uitdehaag B, Polman C, Thompson A (2004) Outcome measures for multiple sclerosis clinical trials: relative measurement precision of the expanded disability status scale and multiple sclerosis functional composite. Multiple Scler 10:41–46CrossRef Hobart J, Kalkers N, Barkhof F, Uitdehaag B, Polman C, Thompson A (2004) Outcome measures for multiple sclerosis clinical trials: relative measurement precision of the expanded disability status scale and multiple sclerosis functional composite. Multiple Scler 10:41–46CrossRef
Metadata
Title
A longitudinal study of MRI-detected atrophy in secondary progressive multiple sclerosis
Authors
J. Furby
T. Hayton
D. Altmann
R. Brenner
J. Chataway
K. J. Smith
D. H. Miller
R. Kapoor
Publication date
01-09-2010
Publisher
Springer-Verlag
Published in
Journal of Neurology / Issue 9/2010
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-010-5563-y

Other articles of this Issue 9/2010

Journal of Neurology 9/2010 Go to the issue

Medical Progress in the Journal of Neurology

Advances in multiple sclerosis research in 2009