Lancet neurology
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Traditionally, multiple sclerosis has been categorised by distinct clinical descriptors-relapsing-remitting, secondary progressive, and primary progressive-for patient care, research, and regulatory approval of medications. Accumulating evidence suggests that the clinical course of multiple sclerosis is better considered as a continuum, with contributions from concurrent pathophysiological processes that vary across individuals and over time. ⋯ These observations encourage a new consideration of the course of multiple sclerosis as a spectrum defined by the relative contributions of overlapping pathological and reparative or compensatory processes. New understanding of key mechanisms underlying progression and measures to quantify progressive pathology will potentially have important and beneficial implications for clinical care, treatment targets, and regulatory decision-making.
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The factor that is most relevant and strongly associated with the clinical course of multiple sclerosis is chronological age. Very young patients exclusively have relapsing remitting disease, whereas those with later onset disease face a more rapid development of permanent disability. For people with progressive multiple sclerosis, the poor response to current disease modifying therapies might be related to ageing in the immune system and CNS. ⋯ Both somatic and reproductive ageing processes might contribute to development of progressive multiple sclerosis. Understanding the role of ageing in immune and neural cell function in patients with multiple sclerosis might be key to halting non-relapse-related progression. The growing literature on potential therapies that target senescent cells and ageing processes might provide effective strategies for remyelination and neuroprotection.