Electrophysiological investigations in adoptively transferred experimental autoimmune encephalomyelitis in the Lewis...

Lewis rats with experimental autoimmune encephalomyelitis transferred adoptively with myelin basic protein-specific T line cells (AT-EAE) were studied clinically, electrophysiologically, and histologically. Injection with 5 x 10(6) line cells induced EAE with a rapidly developing tetraplegia after a latent period of 4 days. Electrophysiological testing revealed a profound slowing of afferent conduction within the dorsal column of the spinal cord, and conduction abnormalities in the spinal roots. Injection with a lower cell dose of 1 x 10(6) T line cells caused only moderate clinical signs paralleled by milder conduction slowing and conduction failure. Light microscopy showed marked inflammation with infiltration of mononuclear cells and some demyelination throughout the spinal cord and roots. Inflammation and demyelination were dose dependent and the caudal parts of the spinal cord were more affected than the cranial parts. The peripheral nerves were free of electrophysiological and morphological alterations. Systemic treatment with 4-aminopyridine accelerated and partially restored conduction in the dorsal columns and roots, while increasing the body temperature had a detrimental effect, suggesting demyelination as a prominent pathophysiological mechanism. These findings show that in AT-EAE in Lewis rats the dysfunction of the central nervous system and of spinal roots is cell dose dependent, that the peripheral nervous system distal to the spinal roots is spared, and suggest that paranodal demyelination is an important pathogenic mechanism.