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Multiple Sclerosis, Vol. 10, No. 2, 182-187 (2004)
DOI: 10.1191/1352458504ms996oa

Progressive change in primary progressive multiple sclerosis normal-appearing white matter: a serial diffusion magnetic resonance imaging study

Klaus Schmierer

Klinik für Neurologie, Charité, Humboldt-Universität Berlin, Germany, Department of Neuroinflammation, MS NMR Research Unit, Institute of Neurology, University College London, UK, k.schmierer{at}ion.ucl.ac.uk

Daniel R Altmann

Department of Neuroinflammation, MS NMR Research Unit, Institute of Neurology, University College London, UK, London School of Hygiene and Tropical Medicine, UK

Nadja Kassim

Klinik für Neurologie, Charité, Humboldt-Universität Berlin, Germany

Hagen Kitzler

Klinik für Neurologie, Charité, Humboldt-Universität Berlin, Germany

Christian M Kerskens

Klinik für Neurologie, Charité, Humboldt-Universität Berlin, Germany

Claudia A Doege

Klinik für Neurologie, Charité, Humboldt-Universität Berlin, Germany

Orhan Aktas

Institut für Neuroimmunologie, Charité, Humboldt-Universität Berlin, Germany

Jan D Lünemann

Institut für Neuroimmunologie, Charité, Humboldt-Universitä tBerlin, Germany

David H Miller

Department of Neuroinflammation, MS NMR Research Unit, Institute of Neurology, University College London, UK

Frauke Zipp

Institut für Neuroimmunologie, Charité, Humboldt-Universita

Arno Villringer

Klinik für Neurologie, Charité, Humboldt-Universität Berlin, Germany

In spite of marked disability, patients with primary progressive multiple sclerosis (PPMS) display smaller lesion volumes on conventional magnetic resonance imaging (MRI) compared with other forms of multiple sclerosis (MS). Hence, damage to the normal-appear ing brain tissue (NA BT) may play an important role in explaining the patho genesis of disability in PPMS. Diffusion-weighted MRI (DW-MRI) probes water diffusion in vivo that can be altered by patho logic changes. Using DW-MRI we investigated diffusion in the NA BT of 15 patients with PPMS over one year. The average apparent diffusion coefficient (A DC av) was measured in 10 regions of interest located in the normal- appearing thalamus and the normal-appearing white matter (NAWM). Six healthy subjects served as a reference. In contrast to healthy subjects, patients with PPMS showed an increment within 12 months of the A DC av in NAWM which was associated with an increase of the T2- and T1-lesion volumes. The A DC av in frontal NAWM was associated with disability as measured by the MS Functio nal C omposite Measure. Serial DW-MRI depicts progressive changes in the NAWM of patients with PPMS. O ur preliminary findings suggest that the processes causing structural damage in NAWM and lesions in patients with PPMS are partially linked and that changes of water diffusion in NAWM depicted by DW-MRI are clinically relevant.

Key Words: diffusion • MRI • multiple sclerosis • natural history • primary progressive course


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