Multiple Sclerosis

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here for more information

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Simon, J H
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Simon, J H
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Multiple Sclerosis, Vol. 12, No. 6, 679-687 (2006)
DOI: 10.1177/1352458506070823
© 2006 SAGE Publications

Reviews

Brain atrophy in multiple sclerosis: what we know and would like to know

J H Simon

Department of Radiology, University of Colorado Health Science Center, Denver, CO, USA, jack.simon{at}uchsc.edu

Brain and spinal cord atrophy measures are becoming standard in multiple sclerosis (MS) clinical trials, yet we know little about the underlying mechanisms resulting in atrophy, or the factors accounting for variable rates of atrophy in individuals and across the MS phenotype. We do not understand, as yet, why apparently effective treatment does or does not affect atrophy. Some limitations of this measure may be accounted for by complex structural and temporal factors that become active at the initiation of injury, but are not immediately expressed. Additional limitations include differential effects related to the focal versus diffuse pathology in MS, and variable expression of the pathology underlying atrophy, depending on location in central nervous system (CNS) tissue.

Key Words: atrophy • brain • clinical trials • degeneration • MRI • multiple sclerosis • spinal cord

References

  • Miller DH, Barkhof F, Frank JA, Parker GJM, Thompson AJ. Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance [review] . Brain 2002; 125: 1676-1695 .[Abstract/Free Full Text]
  • Fisher E, Rudick RA, Simon JH, Cutter G, Baier M, Lee J-Cet al. Eight-year follow-up study of brain atrophy in patients with MS . Neurology 2002; 59: 1412-1420 .[Abstract/Free Full Text]
  • Simon JH. Brain and spinal cord atrophy in multiple sclerosis: role as a surrogate measure of disease progression . CNS Drugs 2001; 15: 427-436 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Pelletier D, Garrison K, Henry R. Measurement of whole-brain atrophy in multiple sclerosis . J Neuroimag 2004; 14: 11S-19S .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Lucchinetti CF, Bruck W, Rodriguez M, Lassmann H. Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis . Brain Pathol 1996; 6: 259-274 .[ISI][Medline] [Order article via Infotrieve]
  • Miller DH, Thompson AJ, Filippi M. Magnetic resonance studies of abnormalities in the normal appearing white matter and grey matter in multiple sclerosis . J Neurol 2003; 250: 1407-1419 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Perry VH, Anthony DC. Axon damage and repair in multiple sclerosis . Philos Trans R Soc Lond B Biol Sci 1999; 354: 1641-1647 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Bjartmar C, Trapp BD. Axonal degeneration and progressive neurologic disability in multiple sclerosis . Neurotox Res 2003; 5: 157-164 .[ISI][Medline] [Order article via Infotrieve]
  • Ganter P, Prince C, Esiri MM. Spinal cord axonal loss in multiple sclerosis: a post-mortem study . Neuropathol Appl Neurobiol 1999; 25: 459-467 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Lovas G, Szilagyi N, Majtenyi K, Palkovits M, Komoly S. Axonal changes in chronic demyelinated cervical spinal cord plaques . Brain 2000; 123: 308-317 .[Abstract/Free Full Text]
  • DeLuca GC, Ebers GC, Esiri MM. Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts . Brain 2004; 127: 1009-1018 .[Abstract/Free Full Text]
  • Bjartmar C, Kidd G, Mork S, Rudick R, Trapp BD. Neurological disability correlates with spinal cord axonal loss and reduced N -acetyl aspartate in chronic multiple sclerosis patients . Ann Neurol 2000; 48: 893-901 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Pelletier J, Suchet L, Witjas T, Habib M, Guttmann CR, Salamon Get al. A longitudinal study of callosal atrophy and interhemispheric dysfunction in relapsing-remitting multiple sclerosis . Arch Neurol 2001; 58: 105-111 .[Abstract/Free Full Text]
  • Ranjeva JP, Pelletier J, Confort-Gouny S, Ibarrola D, Audoin B, Le FYet al. MRI/MRS of corpus callosum in patients with clinically isolated syndrome suggestive of multiple sclerosis . Mult Scler 2003; 9: 554-565 .[Abstract/Free Full Text]
  • McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FDet al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis . Ann Neurol 2001; 50: 121-127 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Simon JH, Jacobs LD, Campion MK, Rudick RA, Cookfair DL, Herndon RMet al., and The Multiple Sclerosis Collaborative Research Group (MSCRG). A longitudinal study of brain atrophy in relapsing multiple sclerosis . Neurology 1999; 53: 139-148 .[Abstract/Free Full Text]
  • Evangelou N, Esiri MM, Smith S, Palace J, Matthews PM. Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis . Ann Neurol 2000; 47: 391-395 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Evangelou N, Konz D, Esiri MM, Smith S, Palace J, Matthews PM. Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis . Brain 2000; 123: 1845-1849 .[Abstract/Free Full Text]
  • Simon JH, Jacobs L, Kinkel RP. Transcallosal bands: a sign of neuronal tract degeneration in early MS? Neurology 2001; 57: 1888-1890 .[Abstract/Free Full Text]
  • Simon JH. Linear and regional measures of brain atrophy in multiple sclerosis. In Zivadinov R, Bakshi R eds. Brain and spinal cord atrophy in multiple sclerosis. Nova Science Publishers, Inc ., 2004.
  • Hickman SJ, Toosy AT, Jones SJ, Altmann DR, Miszkiel KA, MacManus DGet al. Serial magnetization transfer imaging in acute optic neuritis . Brain 2004; 127: 692-700 .[Abstract/Free Full Text]
  • Evangelou N, Konz D, Esiri MM, Smith S, Palace J, Matthews PM. Size-selective neuronal changes in the anterior optic pathways suggest a differential susceptibility to injury in multiple sclerosis . Brain 2001; 124: 1813-1820 .[Abstract/Free Full Text]
  • Coleman MP, Perry VH. Axon pathology in neurological disease: a neglected therapeutic target . Trends Neurosci 2002; 25: 532-537 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Griffin JW, George R, Lobato C, Tyor WR, Yan LC, Glass JD. Macrophage responses and myelin clearance during Wallerian degeneration: relevance to immune-mediated demyelination . J Neuroimmunol 1992; 40: 153-165 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Thomalla G, Glauche V, Koch MA, Beaulieu C, Weiller C, Rother J. Diffusion tensor imaging detects early Wallerian degeneration of the pyramidal tract after ischemic stroke . Neuroimage 2004; 22: 1767-1774 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Kuhn MJ, Mikulis DJ, Ayoub DM, Kosofsky BE, Davis KR, Taveras JM. Wallerian degeneration after cerebral infarction: evaluation with sequential MR imaging . Radiology 1989; 172: 179-182 .[Abstract/Free Full Text]
  • Buss A, Brook GA, Kakulas B, Martin D, Franzen R, Schoenen Jet al. Gradual loss of myelin and formation of an astrocytic scar during Wallerian degeneration in the human spinal cord . Brain 2004; 127: 34-44 .[Abstract/Free Full Text]
  • Becerra JL, Puckett WR, Hiester ED, Quencer RM, Marcillo AE, Post MJet al. MR-pathologic comparisons of Wallerian degeneration in spinal cord injury . AJNR Am J Neuroradiol 1995; 16: 125-133 .[Abstract]
  • Bjartmar C, Kinkel RP, Kidd G, Rudick RA, Trapp BD. Axonal loss in normal-appearing white matter in a patient with acute MS . Neurology 2001; 57: 1248-1252 .[Abstract/Free Full Text]
  • Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES. Multiple sclerosis: remyelination of nascent lesions . Ann Neurol 1993; 33: 137-151 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Raine CS, Wu E. Multiple sclerosis: remyelination in acute lesions . J Neuropathol Exp Neurol 1993; 52: 199-204 .[ISI][Medline] [Order article via Infotrieve]
  • Prineas JW, Connell F. Remyelination in multiple sclerosis . Ann Neurol 1979; 5: 22-31 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Cifelli A, Arridge M, Jezzard P, Esiri MM, Palace J, Matthews PM. Thalamic neurodegeneration in multiple sclerosis . Ann Neurol 2002; 52: 650-653 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Wylezinska M, Cifelli A, Jezzard P, Palace J, Alecci M, Matthews PM. Thalamic neurodegeneration in relapsing-remitting multiple sclerosis . Neurology 2003; 60: 1949-1954 .[Abstract/Free Full Text]
  • Bakshi R, Benedict RH, Bermel RA, Caruthers SD, Puli SR, Tjoa CWet al. T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study . Arch Neurol 2002; 59: 62-68 .[Abstract/Free Full Text]
  • De Stefano N, Matthews PM, Filippi M, Agosta F, De Luca M, Bartolozzi MLet al. Evidence of early cortical atrophy in MS: relevance to white matter changes and disability . Neurology 2003; 60: 1157-1162 .[Abstract/Free Full Text]
  • Quarantelli M, Ciarmiello A, Morra VB, Orefice G, Larobina M, Lanzillo Ret al. Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load . Neuroimage 2003; 18: 360-366 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Dalton CM, Chard DT, Davies GR, Miszkiel KA, Altmann DR, Fernando Ket al. Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes . Brain 2004; 127: 1101-1107 .[Abstract/Free Full Text]
  • Chard DT, Griffin CM, Rashid W, Davies GR, Altmann DR, Kapoor Ret al. Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis . Mult Scler 2004; 10: 387-391 .[Abstract/Free Full Text]
  • Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T. Cortical lesions in multiple sclerosis . Brain 1999; 122: 17-26 .[Abstract/Free Full Text]
  • Bo L, Vedeler CA, Nyland HI, Trapp BD, Mork SJ. Subpial demyelination in the cerebral cortex of multiple sclerosis patients . J Neuropathol Exp Neurol 2003; 62: 723-732 .[ISI][Medline] [Order article via Infotrieve]
  • Sailer M, Fischl B, Salat D, Tempelmann C, Schonfeld MA, Busa Eet al. Focal thinning of the cerebral cortex in multiple sclerosis . Brain 2003; 126: 1734-1744 .[Abstract/Free Full Text]
  • Peterson JW, Bo L, Mork S, Chang A, Trapp BD. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions . Ann Neurol 2001; 50: 389-400 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Thompson A. Overview of primary progressive multiple sclerosis (PPMS): similarities and differences from other forms of MS, diagnostic criteria, pros and cons of progressive diagnosis . Mult Scler 2004; 10: S2-S7 .[Abstract/Free Full Text]
  • Stevenson VL, Ingle GT, Miller DH, Thompson AJ. Magnetic resonance imaging predictors of disability in primary progressive multiple sclerosis: a 5-year study . Mult Scler 2004; 10: 398-401 .[Abstract/Free Full Text]
  • Filippi M, Bozzali M, Rovaris M, Gonen O, Kesavadas C, Ghezzi Aet al. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis . Brain 2003; 126: 433-437 .[Abstract/Free Full Text]
  • Lassmann H. Brain damage when multiple sclerosis is diagnosed clinically . Lancet 2003; 361: 1317-1318 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Dalton CM, Brex PA, Jenkins R, Fox NC, Miszkiel KA, Crum WRet al. Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis . J Neurol Neurosurg Psychiatry 2002; 73: 141-147 .[Abstract/Free Full Text]
  • Kinkel P, Kollman C, Glassman A, Fisher E, Simon J, O’Connor Pet al. The development of brain atrophy 5 years after a first clinical demyelinating event [abstract] . Neurology 2004; 62: A424-A424 .
  • The CHAMPS Study Group. MRI predictors of early conversion to clinically definite MS in the CHAMPS placebo group . Neurology 2002; 59: 998-1005 .[Abstract/Free Full Text]
  • Enzinger C, Ropele S, Smith S, Strasser-Fuchs S, Poltrum B, Schmidt Het al. Accelerated evolution of brain atrophy and ‘black holes’ in MS patients with APOE-epsilon 4 . Ann Neurol 2004; 55: 563-569 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Simon JH. From enhancing lesions to brain atrophy in relapsing MS . J Neuroimmunol 1999; 98: 7-15 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Rudick RA, Fisher E, Lee J-C, Simon JH, Jacobs LD, and the Multiple Sclerosis Collaborative Research Group. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS . Neurology 1999; 53: 1698-1704 .[Abstract/Free Full Text]
  • Fisher E, Rudick RA, Cutter G, Baier M, Miller D, Weinstock-Guttman Bet al. Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients . Mult Scler 2000; 6: 373-377 .[Abstract/Free Full Text]
  • Paolillo A, Piattella MC, Pantano P, Di Legge S, Caramia F, Russo Pet al. The relationship between inflammation and atrophy in clinically isolated syndromes suggestive of multiple sclerosis: a monthly MRI study after triple-dose gadolinium-DTPA . J Neurol 2004; 251: 432-439 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Chard DT, Griffin CM, Parker GJM, Kapoor R, Thompson AJ, Miller DH. Brain atrophy in clinically early relapsing-remitting multiple sclerosis . Brain 2002; 125: 327-337 .[Abstract/Free Full Text]
  • Leist TP, Gobbini MI, Frank JA, McFarland HF. Enhancing magnetic resonance imaging lesions and cerebral atrophy in patients with relapsing multiple sclerosis . Arch Neurol 2001; 58: 57-60 .[Abstract/Free Full Text]
  • Luks TL, Goodkin DE, Nelson SJ, Majumdar S, Bacchetti P, Portnoy Det al. A longitudinal study of ventricular volume in early relapsing-remitting multiple sclerosis . Mult Scler 2000; 6: 332-337 .[Abstract/Free Full Text]
  • Kalkers NF, Vrenken H, Uitdehaag BM, Polman CH, Barkhof F. Brain atrophy in multiple sclerosis: impact of lesions and of damage of whole brain tissue . Mult Scler 2002; 8: 410-414 .[Abstract/Free Full Text]
  • Coles AJ, Wing MG, Molyneux P, Paolillo A, Davie CM, Hale Get al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis . Ann Neurol 1999; 46: 296-304 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Jones CK, Riddehough A, Li DK, Zhao G, Paty DW, and the PRISIMS Study Group. MRI cerebral atrophy in relapsing-remitting MS: results from the PRISMS trial [abstract] . Neurology 2001; 56: 379-379 .
  • Filippi M, Rovaris M, Inglese M, Barkhof F, De Stefano N, Smith Set al. Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial . Lancet 2004; 364: 1489-1496 .[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Frank JA, Richert N, Bash C, Stone L, Calabresi PA, Lewis Bet al. Interferon b-1b slows progression of atrophy in RRMS: three-year follow-up in NAb+/and NAb = patients . Neurology 2004; 62: 719-725 .[Abstract/Free Full Text]
  • Molyneux PD, Kappos L, Polman C, Pozzilli C, Barkhof F, Filippi Met al. 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 2000; 123: 2256-2263 .[Abstract/Free Full Text]
  • Rudick RA. Impact of disease-modifying therapies on brain and spinal cord atrophy in multiple sclerosis . J Neuroimag 2004; 14: 54S-64S .[ISI][Medline] [Order article via Infotrieve]
  • Rovaris M, Comi G, Rocca MA, Wolinsky JS, Filippi M. Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications . Brain 2001; 124: 1803-1812 .[Abstract/Free Full Text]
  • Rovaris M, Filippi M. Treatment effects on MRI measures of central nervous system atrophy in multiple sclerosis. In Zivadinov R, Bakshi R eds. Brain and spinal cord atrophy in multiple sclerosis, Chapter XI. Nova Biomedical Books , 2004: 175-190.
  • Leary SM, Miller DH, Stevenson VL, Brex PA, Chard DT, Thompson AJ. Interferon ß-1a in primary progressive MS: an exploratory, randomized, controlled trial . Neurology 2003; 60: 44-51 .[Abstract/Free Full Text]
  • Filippi M, Rovaris M, Iannucci G, Mennea S, Sormani MP, Comi G. Whole brain volume changes in patients with progressive MS treated with cladribine . Neurology 2000; 55: 1714-1718 .[Abstract/Free Full Text]
  • Paolillo A, Coles AJ, Molyneux PD, Gawne-Cain M, MacManus D, Barker GJet al. Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H . Neurology 1999; 53: 751-757 .[Abstract/Free Full Text]
  • Zivadinov R, Rudick RA, De Masi R, Nasuelli D, Ukmar M, Pozzi-Mucelli RSet al. Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS . Neurology 2001; 57: 1239-1247 .[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Simon, J H
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Simon, J H
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?