Abstract
The present article reviews the currently ongoing scientific debate on the specific characteristics of primary progressive multiple sclerosis. The most important observations come from the studies using magnetic resonance imaging showing involvement of the normal-appearing brain tissue and also from the clinical and magnetic-resonance-imaging descriptions in longitudinal studies. Progress in the diagnosis of primary progressive multiple sclerosis has been made. Long- and short-term natural history are now better known, which will allow the designing of clinical trials in the near future. Magnetic-resonance-imaging studies have demonstrated damage of the normal-appearing brain tissue, which may explain in part the apparent clinical and radiological paradox, common to all clinical forms of multiple sclerosis but perhaps more evident in the primary progressive form. Preliminary results from exploratory trials seem to indicate that these patients should no longer be excluded from therapeutic trials.
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