Journal of Neuroimaging Vol 14 No 3(Supplement) July 2004

Introduction

Atrophy of the Brain andSpinal Cord in Multiple Sclerosis

Rohit Bakshi, MD

A B S T R A C T

The destructive nature of the multiple sclerosis disease processis of growing clinical and neuroscientific interest. Axonaltransection, neuronal loss, Wallerian degeneration, and chronicdemyelination likely contribute to macroscopic atrophy of thebrain and spinal cord in patients with the disease. Thisneurodegenerative process belies the traditional view of multiplesclerosis as an inflammatory demyelinating disease. Magneticresonance imaging is a key tool in the diagnosis and longitudinalmonitoring of central nervous system atrophy. This supplementto the Journal of Neuroimaging is devoted to brain and spinalcord atrophy in MS, with a focus on the role of magnetic reso-nance imaging. The authors and topics of the articles have beenchosen by the Guest Editor to provide a state-of-the-art reviewof this important field. An emphasis is placed on several keyissues pertaining to central nervous system atrophy in multiplesclerosis: pathogenesis, magnetic resonance imaging tech-niques for quantification, clinical relevance, and effects of dis-ease-modifying therapies.

Bakshi R.Introduction: atrophy of the brain

and spinal cord in multiple sclerosisJ Neuroimaging 2004;14:3S-4S.

DOI: 10.1177/1051228404266262

This supplement to the Journal of Neuroimaging is devotedto the topic of brain and spinal cord atrophy in patientswith multiple sclerosis (MS). Although traditionally

thought of as an inflammatory demyelinating disease ofthe white matter, a growing body of evidence hasrevealed that MS has a destructive pathogenesis. Axonaltransection, neuronal loss, Wallerian degeneration,chronic demyelination, and the resulting macroscopiccentral nervous system (CNS) atrophy are now regardedas integral components of MS. The neurodegenerativeprocess is widespread and appears to involve both whiteand gray matter. Atrophy begins early in the disease pro-cess, affects the majority of patients, is virtually continu-ous and progressive, and shows moderate associationswith clinical status and predictive value toward clinicalprogression. The measurement of atrophy using mag-netic resonance imaging (MRI) shows promise in provid-ing a clinically relevant surrogate marker of disease andin being able to partially resolve the “clinical-MRI para-dox” that has existed for conventional white matter lesionmeasurements.

During the past 6 years, major advances have occurredin our understanding of CNS atrophy in MS. Axonaltransection in the white matter and neuronal loss andapoptosis in the gray matter have been demonstrated intissue samples from patients with MS obtained at autopsy.A range of MRI techniques has been applied to the mea-surement of CNS atrophy in MS, including assessment ofwhole-brain, spinal cord, and regional volume loss. Theatrophy rate has been assessed in various subgroups ofpatients with MS and at various stages of the disease. Aconsensus is developing that atrophy occurs early in thedisease process, affects the majority of patients, and iscontinuous and progressive. Several cross-sectional andlongitudinal studies have correlated MRI measures ofatrophy with clinical status. The central theme emergingfrom these reports is that CNS atrophy is related to physi-cal disability, neuropsychological dysfunction, andimpaired quality of life. Furthermore, atrophy has moder-ate predictive value for subsequent development of clini-cal progression in patients with MS. MRI measures ofatrophy account for the unique variance in clinical mea-sures, after adjusting for the influence of white matter

Copyright © 2004 by the American Society of Neuroimaging 3S

From the Center for Neurological Imaging, Partners Mul-tiple Sclerosis Center, Department of Neurology,Brigham & Women’s Hospital, Harvard Medical School,Boston, Massachusetts.

Address correspondence to Dr Rohit Bakshi, Center forNeurological Imaging, Brigham & Women’s Hospital,Harvard Medical School, 221 Longwood Avenue RF396,Boston, MA 02115. E-mail: rbakshi@bwh.harvard.edu.

lesions. Unfortunately, disease-modifying therapies haveonly partial efficacy, at best, in limiting brain and spinalcord atrophy. This supplement to the Journal ofNeuroimaging reviews current concepts of CNS atrophy inMS and its assessment by MRI, while providingcomprehensive critical analyses of recent data.

The first article sets a backdrop for this supplement bydescribing immunologic and pathologic data and pre-senting hypotheses on the pathogenesis of CNS atrophy.Dr Minagar and colleagues review the complexity of thepathophysiology of MS; they describe such newly emerg-ing concepts as axonal transection, loss of trophic sup-port, apoptosis, and the role of dysimmunity and inflam-mation in tissue destruction.

The following 2 articles focus on the use of MRI as atool to quantify CNS atrophy. Dr Pelletier and colleaguesreview the techniques of measuring whole-brain atrophy,emphasizing the methodological challenges and lessonslearned. Dr Constantinescu and colleagues review thetechnical aspects of measurement of spinal cord atrophy.

The next 2 articles review the literature on the impor-tant topic of clinical relevance of CNS atrophy.Dr Zivandinov and I review the relationship betweenatrophy and physical disability, quality of life, and auto-

nomic function. Dr Benedict and colleagues assess theemerging literature on the correlation between brain atro-phy and neuropsychological dysfunction.

Next, Dr Meier and colleagues describe the relation-ship between atrophy and other MRI measures of diseaseactivity and disease burden, forming interesting hypothe-ses on disease pathophysiology. The final article byDr Rudick summarizes the evolving data on the effect ofdisease-modifying immunotherapies on the progressionof CNS atrophy.

Together, these articles are intended to present a state-of-the-art review of the field of CNS atrophy in MS and itspotential use in defining the pathogenesis of MS, provid-ing clinically relevant information for the monitoring ofpatients and serving as a robust surrogate outcome mea-sure in therapeutic trials. I am hopeful that this supple-ment may serve as a useful reference for both scientistsand practitioners interested in research into MS, theimaging of MS, and the clinical care of patients with MS.

Dr Bakshi is supported by grants from the National Institutes of Health(NIH-NINDS 1 K23 NS42379-01) and National Science Foundation(DBI-0234895). This journal supplement was supported by an unre-stricted educational grant from Biogen Idec, Inc. Dr Bakshi has receivedhonoraria and research support from Biogen Idec, Inc and Teva Neuro-science, Inc.

4S Journal of Neuroimaging Vol 14 No 3(Supplement) July 2004