Axonal loss results in spinal-cord atrophy, electrophysiological abnormalities and neurological deficits following demyelination in a chronic inflammatory model of multiple sclerosis

Recent pathological studies have re-emphasized that axonal injury is presen t in patients with multiple sclerosis, the most common demyelinating diseas e of the CNS in humans, However, the temporal profile of demyelination and axonal-loss in multiple sclerosis patients and their independent contributi ons to clinical and electrophysiological abnormalities are not completely u nderstood. In this study, we used the Theiler's murine encephalomyelitis vi rus model of progressive CNS inflammatory demyelination to demonstrate mar demyelination in the spinal cord is followed by a loss of medium to large m yelinated fibres, By measuring spinal cord areas, motor-evoked potentials, and motor coordination and balance, we determined that axonal loss followin g,demyelination was associated with electro-physiological abnormalities and correlated strongly with reduced motor coordination and spinal cord atroph y, These findings demonstrate that axonal loss can follow primary, immune-m ediated demyelination in the CNS and that the severity of axonal loss corre lates almost perfectly with the degree of spinal cord atrophy and neurologi cal deficits.