Multiple sclerosis

Abstract Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease affecting the central nervous system (CNS) of young adults in the western countries, leading, in the majority of the cases, to severe and irreversible clinical disability. Since its clinical introduction, conventional magnetic resonance imaging (cMRI — dual-echo and post-contrast T1-weighted scans) has greatly improved our ability to diagnose MS and to monitor its evolution, either natural or modified by treatment. CMRI-derived measures have indeed shown several advantages over clinical assessment, including their more objective nature and increased sensitivity to MS-related changes. Nevertheless, the magnitude of the relationship between cMRI measures of disease activity or burden and the clinical manifestations of the disease is weak (Fig. 11.1). This necessarily limits the role of cMRI for the understanding of MS pathophysiology and monitoring of experimental treatment. Several factors are likely to be responsible for this clinical/MRI discrepancy. First, dualecho imaging lacks specificity with regard to the heterogeneous pathological substrates of individual lesions and, as a consequence, does not allow an accurate quantification of tissue damage. Specifically, oedema, inflammation, demyelination, remyelination, gliosis, and axonal loss all lead to a similar appearance of hyperintensity on T2-weighted images. This is a major issue now that there is compelling evidence that: (a) inflammatory demyelination is not enough to explain ‘fixed’ neurological deficits in MS; (b) irreversible axonal damage does occur in inflamed MS lesions; and (c) axonal damage is the main contributor to the clinical manifestations of the disease and to its clinical worsening over time. Secondly, T2-weighted images do not delineate tissue damage occurring in the normal-appearing white matter (NAWM), which usually represents a large portion of the brain tissue from MS patients and which is known to be damaged in MS patients. Post-mortem studies have shown subtle changes in the NAWM from MS patients, which not only include diffuse astrocytic hyperplasia, patchy oedema, and perivascular cellular infiltration, but also axonal damage. Finally, dual-echo imaging does not provide an accurate picture of gray matter (GM) damage, which several pathological studies have shown to be prominent in MS and which is likely to be associated with some clinical manifestations of the disease, such as cognitive impairment and fatigue.