Gray matter atrophy and disability progression in patients with early relapsing–remitting multiple sclerosis A 5-year longitudinal study

We assessed the relationship between gray matter (GM) and white matter (WM) atrophy and clinical status in early relapsing-remitting multiple sclerosis (MS) patients over 5 years. A group of 181 patients who participated in the ASA (Avonex-Steroid-Azathioprine) study and had complete clinical and MRI assessments over 2 and 5 years was investigated. One hundred seventy (170) patients completed the 12-month follow-up, 147 the 24-month, 98 the 36-month, 65 the 48-month and 47 the 60-month. Changes in GM (GMV), WM (WMV) and peripheral GM (PGV) volumes, whole brain volume (percentage brain volume change PBVC), lateral ventricle volume (LVV), third ventricle width (3VW) and T2-lesion volume (T2-LV) were measured. Patients were assigned according to their clinical status to one of two groups: the Stable group, and the Reached Confirmed Sustained Progression (RCSP) group (24-week interval). At 0-6 months PBVC and GMV, at 0-12 months PBVC, GMV and T2-LV, at 0-24 months PBVC and GMV, at 0-36 months PBVC, GMV and T2-LV, and at 0-48 PBVC predicted the differences between the RCSP and Stable groups. PBVC and LVV showed the strongest ability to differentiate patients who presented 0 or >or=3 relapses in the Stable group. Decline in PBVC and GMV were predictive markers of disability deterioration. Correlation of T2-LV with clinical status was weaker and decreased over time. Higher number of relapses was associated with faster decline in whole brain volume.

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

[2]  Stephen M. Smith,et al.  Accurate, Robust, and Automated Longitudinal and Cross-Sectional Brain Change Analysis , 2002, NeuroImage.

[3]  A. Thompson,et al.  The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up. , 1998, Brain : a journal of neurology.

[4]  Stephen M. Smith,et al.  Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm , 2001, IEEE Transactions on Medical Imaging.

[5]  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.

[6]  G Cutter,et al.  Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients. , 2000, Multiple sclerosis.

[7]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[8]  M Rovaris,et al.  Evidence for progressive gray matter loss in patients with relapsing-remitting MS , 2005, Neurology.

[9]  J A Frank,et al.  MRI T2 lesion burden in multiple sclerosis , 2006, Neurology.

[10]  Rohit Bakshi,et al.  Imaging of multiple sclerosis: Role in neurotherapeutics , 2005, NeuroRX.

[11]  F. Barkhof The clinico‐radiological paradox in multiple sclerosis revisited , 2002, Current opinion in neurology.

[12]  F. Lublin,et al.  Effect of relapses on development of residual deficit in multiple sclerosis , 2003, Neurology.

[13]  R. Rudick,et al.  Gray matter atrophy in multiple sclerosis: A longitudinal study , 2008, Annals of neurology.

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

[15]  Mara Cercignani,et al.  Grey and white matter volume changes in early primary progressive multiple sclerosis: a longitudinal study. , 2005, Brain : a journal of neurology.

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

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

[18]  O. Kantarci,et al.  Gray Matter Atrophy Is Related to Long-Term Disability in Multiple Sclerosis , 2009 .

[19]  R. Bergamaschi Prognosis of multiple sclerosis: clinical factors predicting the late evolution for an early treatment decision , 2006, Expert review of neurotherapeutics.

[20]  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.

[21]  J. L. Cox,et al.  Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years: a case–control study , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[22]  Alan J. Thompson,et al.  Grey and white matter atrophy in early clinical stages of primary progressive multiple sclerosis , 2004, NeuroImage.

[23]  J. Parisi,et al.  Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination , 2000, Annals of neurology.

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

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

[26]  R. Rudick,et al.  Significance of T2 lesions in multiple sclerosis: A 13‐year longitudinal study , 2006, Annals of neurology.

[27]  D. Louis Collins,et al.  Relating neocortical pathology to disability progression in multiple sclerosis using MRI , 2004, NeuroImage.

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

[29]  À. Rovira,et al.  Baseline MRI predicts future attacks and disability in clinically isolated syndromes , 2006, Neurology.

[30]  Frederik Barkhof,et al.  Grey matter pathology in multiple sclerosis , 2008, The Lancet Neurology.

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

[32]  J. Kurtzke Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[33]  R. Zivadinov Can imaging techniques measure neuroprotection and remyelination in multiple sclerosis? , 2007, Neurology.

[34]  J. Babb,et al.  Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis. , 2002, AJNR. American journal of neuroradiology.

[35]  A J Thompson,et al.  Brain atrophy in clinically early relapsing-remitting multiple sclerosis. , 2002, Brain : a journal of neurology.

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

[37]  A. Thompson,et al.  Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. , 2008, Brain : a journal of neurology.

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

[39]  Rohit Bakshi,et al.  Role of MRI in multiple sclerosis I: inflammation and lesions. , 2004, Frontiers in bioscience : a journal and virtual library.

[40]  R. Rudick,et al.  Axonal transection in the lesions of multiple sclerosis. , 1998, The New England journal of medicine.

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

[42]  G. Plant,et al.  Ventricular enlargement in MS , 2006, Neurology.

[43]  Robert Zivadinov,et al.  Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. , 2006, Archives of neurology.

[44]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[45]  S. Vukusic,et al.  Accumulation of irreversible disability in multiple sclerosis: From epidemiology to treatment , 2006, Clinical Neurology and Neurosurgery.

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

[47]  S. Reingold,et al.  Defining the clinical course of multiple sclerosis , 1996, Neurology.

[48]  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.

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

[50]  Hans Lassmann,et al.  Cortical demyelination and diffuse white matter injury in multiple sclerosis. , 2005, Brain : a journal of neurology.

[51]  H. Waldmann,et al.  The window of therapeutic opportunity in multiple sclerosis , 2005, Journal of Neurology.