Measurement of Brain and Spinal Cord Atrophy by Magnetic Resonance Imaging as a Tool to Monitor Multiple Sclerosis

Evaluation of brain and spinal cord atrophy by magnetic resonance imaging (MRI) has become an increasingly important component of understanding the multiple sclerosis (MS) disease process. These destructive aspects of the disease develop early in the disease course. A growing body of data links brain and spinal cord atrophy to clinical impairment more closely than can be linked with conventional measures of overt lesions. Thus, irreversible tissue damage may be a key factor leading to disease progression. In this review, the authors present the proposed mechanisms leading to central nervous system (CNS) atrophy. They describe the available MRI‐based techniques to measure regional and global atrophy of the brain and spinal cord. They compare the rate of atrophy among MS phenotypes and summarize the emerging data linking atrophy to neurological and neuropsychological impairment. Finally, they discuss the effect of disease‐modifying immunotherapies on the rate of CNS atrophy in patients with MS. Future research to clarify the etiology and pathophysiology of brain and spinal cord atrophy should provide new targets for therapeutic development.

[1]  Rohit Bakshi,et al.  Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis , 2006, Neurology.

[2]  Rohit Bakshi,et al.  The measurement and clinical relevance of brain atrophy in multiple sclerosis , 2006, The Lancet Neurology.

[3]  Robert Zivadinov,et al.  Clinical–Magnetic Resonance Imaging Correlations in Multiple Sclerosis , 2005, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[4]  D. Auer,et al.  Spinal Cord Imaging in Multiple Sclerosis , 2005, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[5]  Rohit Bakshi,et al.  Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity. , 2005, Archives of neurology.

[6]  Rohit Bakshi,et al.  Regional lobar atrophy predicts memory impairment in multiple sclerosis. , 2005, AJNR. American journal of neuroradiology.

[7]  G Tedeschi,et al.  Brain atrophy and lesion load in a large population of patients with multiple sclerosis , 2005, Neurology.

[8]  Rohit Bakshi,et al.  The relationship between whole brain volume and disability in multiple sclerosis: A comparison of normalized gray vs. white matter with misclassification correction , 2005, NeuroImage.

[9]  Elizabeth Fisher,et al.  Brain atrophy and magnetization transfer ratio following methylprednisolone in multiple sclerosis: short-term changes and long-term implications , 2005, Multiple sclerosis.

[10]  A J Thompson,et al.  Gray and white matter volume changes in early RRMS , 2005, Neurology.

[11]  E. Radue,et al.  Rate of brain atrophy in relapsing MS decreases during treatment with IFNβ-1a , 2005, Neurology.

[12]  Robert Zivadinov,et al.  Reproducibility and Accuracy of Quantitative Magnetic Resonance Imaging Techniques of Whole‐Brain Atrophy Measurement in Multiple Sclerosis , 2005, Journal of Neuroimaging.

[13]  G. Comi,et al.  Imaging spinal cord damage in multiple sclerosis. , 2005, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[14]  H. Peitgen,et al.  Sensitivity and reproducibility of a new fast 3D segmentation technique for clinical MR-based brain volumetry in multiple sclerosis , 2004, Neuroradiology.

[15]  Marco Rovaris,et 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 , 2004, The Lancet.

[16]  Rohit Bakshi,et al.  Correction for intracranial volume in analysis of whole brain atrophy in multiple sclerosis: the proportion vs. residual method , 2004, NeuroImage.

[17]  Xingchang Wei,et al.  Has your patient's multiple sclerosis lesion burden or brain atrophy actually changed? , 2004, Multiple sclerosis.

[18]  N. De Stefano,et al.  Neocortical volume decrease in relapsing–remitting MS patients with mild cognitive impairment , 2004, Neurology.

[19]  Rohit Bakshi,et al.  Central Nervous System Atrophy and Clinical Status in Multiple Sclerosis , 2004, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[20]  A. Minagar,et al.  Pathogenesis of Brain and Spinal Cord Atrophy in Multiple Sclerosis , 2004, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[21]  R. Henry,et al.  Measurement of Whole‐Brain Atrophy in Multiple Sclerosis , 2004, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[22]  R. Rudick,et al.  Impact of Disease‐Modifying Therapies on Brain and Spinal Cord Atrophy in Multiple Sclerosis , 2004, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[23]  Charles R G Guttmann,et al.  Magnetic Resonance Imaging Surrogates of Multiple Sclerosis Pathology and Their Relationship to Central Nervous System Atrophy , 2004, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[24]  Rohit Bakshi,et al.  Correlating Brain Atrophy With Cognitive Dysfunction, Mood Disturbances, and Personality Disorder in Multiple Sclerosis , 2004, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[25]  C. Tench,et al.  Measurement of Spinal Cord Atrophy in Multiple Sclerosis , 2004, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[26]  R. Bakshi,et al.  Whole-brain atrophy in multiple sclerosis measured by automated versus semiautomated MR imaging segmentation. , 2004, AJNR. American journal of neuroradiology.

[27]  David H. Miller,et al.  Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. , 2004, Brain : a journal of neurology.

[28]  M Rovaris,et al.  Measurement error of two different techniques for brain atrophy assessment in multiple sclerosis , 2004, Neurology.

[29]  P. Calabresi,et al.  Interferon-&bgr;-1b slows progression of atrophy in RRMS: Three-year follow-up in NAb− and NAb+ patients , 2004, Neurology.

[30]  R. Grossman,et al.  Neuronal cell injury precedes brain atrophy in multiple sclerosis , 2004, Neurology.

[31]  Rohit Bakshi,et al.  Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. , 2004, Archives of neurology.

[32]  Serial MRI in multiple sclerosis: a prospective pilot study of lesion load, whole brain volume and thalamic atrophy , 2004, Journal of Clinical Neuroscience.

[33]  M. A. Horsfield,et al.  Whole-brain atrophy in multiple sclerosis measured by two segmentation processes from various MRI sequences , 2003, Journal of the Neurological Sciences.

[34]  L. Blumhardt,et al.  The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three‐dimensional MRI study , 2003, Acta neurologica Scandinavica.

[35]  A J Thompson,et al.  The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study , 2003, Journal of neurology, neurosurgery, and psychiatry.

[36]  A. Thompson,et al.  Primary progressive multiple sclerosis: a 5-year clinical and MR study. , 2003, Brain : a journal of neurology.

[37]  Rohit Bakshi,et al.  Thalamic Involvement in Multiple Sclerosis: A Diffusion‐Weighted Magnetic Resonance Imaging Study , 2003, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[38]  Olivier Coulon,et al.  Application of a B‐spline active surface technique to the measurement of cervical cord volume in multiple sclerosis from three‐dimensional MR images , 2003, Journal of magnetic resonance imaging : JMRI.

[39]  A. Dale,et al.  Focal thinning of the cerebral cortex in multiple sclerosis. , 2003, Brain : a journal of neurology.

[40]  C. Tench,et al.  Spinal cord atrophy and disability in multiple sclerosis over four years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon β-1a (Rebif) treatment trial , 2003, Journal of neurology, neurosurgery, and psychiatry.

[41]  P. Jezzard,et al.  Thalamic neurodegeneration in relapsing-remitting multiple sclerosis , 2003, Neurology.

[42]  Zhengrong Liang,et al.  Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients , 2003, Neurology.

[43]  Rohit Bakshi,et al.  A semiautomated measure of whole-brain atrophy in multiple sclerosis , 2003, Journal of the Neurological Sciences.

[44]  P. M. Matthews,et al.  Evidence of early cortical atrophy in MS , 2003, Neurology.

[45]  Rohit Bakshi,et al.  Selective caudate atrophy in multiple sclerosis: a 3D MRI parcellation study , 2003, Neuroreport.

[46]  Paul S. Morgan,et al.  Magnetic resonance imaging of the cervical spinal cord in multiple sclerosis , 2003, Journal of Neurology.

[47]  N. Roberts,et al.  C erebral atrophy and disability in relapsing-remitting and secondary progressive multiple sclerosis over four years , 2003, Multiple sclerosis.

[48]  Bruno Alfano,et al.  Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load , 2003, NeuroImage.

[49]  Cris S Constantinescu,et al.  Magnetic resonance imaging of the cervical spinal cord in multiple sclerosis--a quantitative T1 relaxation time mapping approach. , 2003, Journal of neurology.

[50]  J H Simon,et al.  Eight-year follow-up study of brain atrophy in patients with MS , 2002, Neurology.

[51]  P. Matthews,et al.  Thalamic neurodegeneration in multiple sclerosis , 2002, Annals of neurology.

[52]  R. Zivadinov,et al.  Is Gadolinium Enhancement Predictive of the Development of Brain Atrophy in Multiple Sclerosis? A Review of the Literature , 2002, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[53]  C H Polman,et al.  Cerebral volume changes in multiple sclerosis patients treated with high-dose intravenous methylprednisolone , 2002, Multiple sclerosis.

[54]  F. Barkhof,et al.  Longitudinal brain volume measurement in multiple sclerosis: rate of brain atrophy is independent of the disease subtype. , 2002, Archives of neurology.

[55]  David H. Miller,et al.  Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. , 2002, Brain : a journal of neurology.

[56]  Nick C Fox,et al.  Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis , 2002, Journal of neurology, neurosurgery, and psychiatry.

[57]  Giuseppe Iannucci,et al.  MR correlates of cerebral atrophy in patients with multiple sclerosis , 2002, Journal of Neurology.

[58]  C. Pozzilli,et al.  MRI brain volume changes in relapsing-remitting multiple sclerosis patients treated with interferon beta-1a , 2002, Multiple sclerosis.

[59]  Rohit Bakshi,et al.  Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis. , 2002, Archives of neurology.

[60]  R. Bakshi,et al.  T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study. , 2002, Archives of neurology.

[61]  R. Rudick,et al.  Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS , 2001, Neurology.

[62]  B. Trapp,et al.  Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions , 2001, Annals of neurology.

[63]  M Rovaris,et al.  Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications. , 2001, Brain : a journal of neurology.

[64]  L G Nyúl,et al.  Relapsing-remitting Multiple Sclerosis: Fractional Volumetric Analysis of Gray Matter and White Matter , 2000 .

[65]  G Cazzato,et al.  A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis , 2001, Journal of neurology, neurosurgery, and psychiatry.

[66]  P. Matthews,et al.  Normalized Accurate Measurement of Longitudinal Brain Change , 2001, Journal of computer assisted tomography.

[67]  R Bakshi,et al.  Regional Brain Atrophy Is Associated With Physical Disability in Multiple Sclerosis: Semiquantitative Magnetic Resonance Imaging and Relationship to Clinical Findings , 2001, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[68]  A. Thompson,et al.  Measurement of spinal cord area in clinically isolated syndromes suggestive of multiple sclerosis , 2001, Journal of neurology, neurosurgery, and psychiatry.

[69]  R. Bakshi,et al.  Gray matter T2 hypointensity is related to plaques and atrophy in the brains of multiple sclerosis patients , 2001, Journal of the Neurological Sciences.

[70]  Ponnada A Narayana,et al.  United States open-label glatiramer acetate extension trial for relapsing multiple sclerosis: MRI and clinical correlates , 2001 .

[71]  M Rovaris,et al.  Intra-observer, inter-observer and inter-scanner variations in brain MRI volume measurements in multiple sclerosis , 2001, Multiple sclerosis.

[72]  M. Gobbini,et al.  Enhancing magnetic resonance imaging lesions and cerebral atrophy in patients with relapsing multiple sclerosis. , 2001, Archives of neurology.

[73]  M Rovaris,et al.  Whole brain volume changes in patients with progressive MS treated with cladribine , 2000, Neurology.

[74]  J. Duda,et al.  Brain atrophy in relapsing multiple sclerosis: relationship to relapses, EDSS, and treatment with interferon β-1a , 2000, Multiple sclerosis.

[75]  R. Rudick,et al.  Neurological disability correlates with spinal cord axonal loss and reduced N‐acetyl aspartate in chronic multiple sclerosis patients , 2000, Annals of neurology.

[76]  G J Barker,et 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. , 2000, Brain : a journal of neurology.

[77]  H. Adams,et al.  Progressive cerebral atrophy in MS: A serial study using registered, volumetric MRI , 2000, Neurology.

[78]  L D Blumhardt,et al.  Short‐term ventricular volume changes on serial MRI in multiple sclerosis , 2000, Acta neurologica Scandinavica.

[79]  J. Udupa,et al.  The effect of gadolinium-enhancing lesions on whole brain atrophy in relapsing-remitting MS , 2000, Neurology.

[80]  A. Thompson,et al.  One year follow up study of primary and transitional progressive multiple sclerosis , 2000, Journal of neurology, neurosurgery, and psychiatry.

[81]  Nick C Fox,et al.  Detection of ventricular enlargement in patients at the earliest clinical stage of MS , 2000, Neurology.

[82]  F. Barkhof,et al.  Magnetization Transfer Ratio of the Spinal Cord in Multiple Sclerosis: Relationship to Atrophy and Neurologic Disability , 2000, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[83]  Caterina Mainero,et al.  Brain atrophy in relapsing-remitting multiple sclerosis: relationship with ‘black holes’, disease duration and clinical disability , 2000, Journal of the Neurological Sciences.

[84]  R. Kinkel,et al.  A Wallerian degeneration pattern in patients at risk for MS , 2000, Neurology.

[85]  J K Udupa,et al.  Brain atrophy in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis: longitudinal quantitative analysis. , 2000, Radiology.

[86]  J K Udupa,et al.  Glatiramer acetate (Copaxone) treatment in relapsing–remitting MS , 2000, Neurology.

[87]  M. Rovaris,et al.  Quantitative brain volumetric analysis from patients with multiple sclerosis: a follow-up study , 1999, Journal of the Neurological Sciences.

[88]  R. Rudick,et al.  Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS , 1999, Neurology.

[89]  Frederik Barkhof,et al.  MRI in multiple sclerosis: correlation with expanded disability status scale (EDSS) , 1999, Multiple sclerosis.

[90]  R. Herndon,et al.  A longitudinal study of brain atrophy in relapsing multiple sclerosis , 1999, Neurology.

[91]  P. Dastidar,et al.  Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis , 1999, Journal of the Neurological Sciences.

[92]  L D Blumhardt,et al.  Three dimensional MRI estimates of brain and spinal cord atrophy in multiple sclerosis , 1999, Journal of neurology, neurosurgery, and psychiatry.

[93]  W R Kinkel,et al.  High‐Resolution Fluorodeoxyglucose Positron Emission Tomography Shows Both Global and Regional Cerebral Hypometabolism in Multiple Sclerosis , 1998, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[94]  G. Barker,et al.  Spinal cord atrophy and disability in MS , 1998, Neurology.

[95]  F. Barkhof,et al.  Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis , 1998, Neurology.

[96]  N. Losseff,et al.  Measures of brain and spinal cord atrophy in multiple sclerosis. , 1998, Journal of neurology, neurosurgery, and psychiatry.

[97]  F. Barkhof,et al.  Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms. , 1998, Brain : a journal of neurology.

[98]  ichard,et al.  AXONAL TRANSECTION IN THE LESIONS OF MULTIPLE SCLEROSIS , 1998 .

[99]  R Kikinis,et al.  Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis. , 1997, Archives of neurology.

[100]  A J Thompson,et al.  Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. , 1996, Brain : a journal of neurology.

[101]  A. Thompson,et al.  Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. , 1996, Brain : a journal of neurology.

[102]  G. Barker,et al.  MRI dynamics of brain and spinal cord in progressive multiple sclerosis. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[103]  Dewey Odhner,et al.  3DVIEWNIX: an open, transportable, multidimensional, multimodality, multiparametric imaging software system , 1994, Medical Imaging.

[104]  A. Thompson,et al.  Spinal cord MRI using multi‐array coils and fast spin echo , 1993, Neurology.

[105]  J Winter,et al.  Steroids and Apparent Cerebral Atrophy on Computed Tomography Scans , 1978, Journal of computer assisted tomography.

[106]  T. Naidich,et al.  The Normal Contrast‐Enhanced Computed Axial Tomogram of the Brain , 1977, Journal of computer assisted tomography.