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 present in patients with multiple sclerosis, the most common demyelinating disease of the CNS in humans. However, the temporal profile of demyelination and axonal loss in multiple sclerosis patients and their independent contributions to clinical and electrophysiological abnormalities are not completely understood. In this study, we used the Theiler's murine encephalomyelitis virus model of progressive CNS inflammatory demyelination to demonstrate that demyelination in the spinal cord is followed by a loss of medium to large myelinated fibres. By measuring spinal cord areas, motor-evoked potentials, and motor coordination and balance, we determined that axonal loss following demyelination was associated with electrophysiological abnormalities and correlated strongly with reduced motor coordination and spinal cord atrophy. These findings demonstrate that axonal loss can follow primary, immune-mediated demyelination in the CNS and that the severity of axonal loss correlates almost perfectly with the degree of spinal cord atrophy and neurological deficits.