Neurodegeneration and clinical relevance for early treatment in multiple sclerosis

The treatment of MS with immunomodulatory agents such as interferon beta and glatiramer acetate, early in the disease course, is increasingly recognized as benefiting patient outcome. MS is a chronic inflammatory disease of the central nervous system with morphological hallmarks of inflammation, demyelination, axonal loss and gliosis. While inflammation and demyelination induce neurological deficit, which is at least partly reversible, axonal loss beyond the threshold of compensation is always accompanied by irreversible clinical disease progression. These neuropathological findings suggest that, in addition to reducing the impact of inflammation, the ability to prevent axonal degeneration is a vital component of MS treatment. Approved immunomodulatory therapies shift immunological status from a pro-inflammatory response toward more beneficial anti-inflammatory conditions. Clinical studies also suggest that beta interferon helps to prevent, and may at least partially reverse, axonal injury. Future work in this area will be aided by using magnetic resonance imaging (MRI) to follow hypointense lesions and quantification of N-acetyl aspartate by MR spectroscopy, both of which are potential markers of structural damage. The urgent need to identify definitive markers of neuroprotection in humans remains. Such markers explain more about the underlying mechanisms of early MS pathophysiology.