Biological indicators of the neurodegenerative phase of multiple sclerosis.

The recent re-discovery of axonal damage in multiple sclerosis has led to a renewed interest in neurodegenerative mechanisms of the disease. Transected or injured axons release several molecules from their proximal extremity into the intercellular space. Although these molecules can be measured, however, a biological marker of axonal and neuronal degeneration is still lacking. Cytoskeleton structural proteins like actin, tubulin, L-neurofilaments and tau protein, axon-specific antibodies, other neuronal or glial proteins like S-100, 14-3-3 and glial fibrillary acid protein, neuronal specific enolase, and nitric oxide and its metabolites are some of the putative markers that deserve further investigation and validation. At present, none of them fulfils the criteria of applicability in clinical practice, and the levels of N-acetylaspartate determined by magnetic resonance spectroscopy remain the most reliable measure of axonal damage.