Brain, Vol. 124, No. 12, 2540-2549,
December 2001
© 2001 Oxford University Press
In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis
1 Neuroimaging Research Unit and 2 Clinical Trials Unit, Department of Neuroscience, Scientific Institute and University Ospedale San Raffaele, 3 Department of Neurology, Scientific Institute Don Gnocchi, University of Milan, Milan, 4 Multiple Sclerosis Center, Ospedale di Fidenza, Fidenza, 5 Department of Neurology, Ospedale di Orbassano, Orbassano, 6 Department of Neurological Sciences, Scientific Institute C. Mondino, University of Pavia, Pavia, 7 Department of Neurology, Spedali Civili, University of Brescia, Brescia, 8 Department of Neurological Sciences, University of Genoa, Genoa 9 Multiple Sclerosis Center, Ospedale di Gallarate, Gallarate, Italy
Correspondence to:
Dr Massimo Filippi, Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute and University Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italyfilippi.massimo{at}hsr.it
In patients with primary progressive (PP) multiple sclerosis, brain MRI lesion activity and burden are low, despite the presence of severe neurological impairment. On the contrary, the degree of cord atrophy and diffuse tissue damage in the brain and cervical cord have been found to be associated with clinical disability. Against this background, this study aimed at providing an in vivoindirect assessment of brain and cervical cord pathology in a large cohort of PP multiple sclerosis patients, using conventional MRI and magnetization transfer imaging (MTI). Ninety-one PP multiple sclerosis patients, 36 secondary progressive (SP) multiple sclerosis patients and 30 healthy controls underwent brain and cervical cord MRI scans, using dual echo (brain) or fast short-tau inversion recovery (cervical cord) MTI and T1-weighted sequences. For the brain, T2 hyperintense and T1 hypointense lesion volumes were calculated and the volume of the whole of the brain tissue measured. For the cervical cord, the number and burden of lesions and the cross-sectional area were assessed. MTI scans were post-processed and analysed to obtain magnetization transfer ratio (MTR) histograms from the whole of the brain and cervical cord tissue and from the normal-appearing brain tissue in isolation. In PP multiple sclerosis patients, brain, normal-appearing brain tissue and cervical cord MTR histogram-derived metrics revealed the presence of diffuse tissue damage whose characteristics did not significantly differ from those of SP multiple sclerosis patients, even though SP multiple sclerosis patients had higher MRI-visible lesion burdens. None of the correlations between MRI or MTI measures obtained from the brain and the cord were significant. PP multiple sclerosis patients' disability was significantly, albeit weakly associated with a composite MR model including measures of loss and intrinsic damage of cervical cord tissue. Our data indicate the presence of a diffuse tissue damage undetectable by conventional MRI in PP multiple sclerosis patients, whose extent seems to match that of SP multiple sclerosis patients with similar levels of disability. They also suggest that the severity of multiple sclerosis pathology in the cervical cord is one of the factors contributing to neurological impairment in PP multiple sclerosis.
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