Axonal degeneration in the pathogenesis of multiple sclerosis

Axonal degeneration plays an important role in the accumulation of disabili ty in patients with multiple sclerosis (MS). Pathological studies have demo nstrated axonal damage, particularly in areas of acute inflammation and dem yelination, and in chronic lesions. Axonal loss and its progression, which is associated with neurological disability, has also been demonstrated by m agnetic resonance imaging (MRI) studies. The mechanisms of axonal loss are uncertain, but may involve axonal degeneration secondary to demyelination, or damage to the axonal cytoskeleton. Inflammatory mediators, including cyt okines and proteolytic enzymes may contribute to axonal damage, as may nitr ic oxide. Axonal destruction may also be due to immune attack directed at a xonal components. The realisation that axonal degeneration is a fundamental component of MS that may occur early in the disease course should alter th e approach to management and open avenues to a more targeted immunotherapy aimed at reducing the progression of disability. (C) 1999 Elsevier Science B.V. All rights reserved.