Motor evoked potentials in a mouse model of chronic multiple sclerosis.
We tested cortical motor evoked potentials (cMEPs) as a quantitative marker for in vivo monitoring of corticospinal tract damage in a murine multiple sclerosis model (experimental autoimmune encephalomyelitis, EAE). The cMEPs, previously standardized in naive C57BL/6 developing and adult mice, were studied longitudinally in adult EAE mice. Central conduction times (CCTs) increased significantly shortly before the earliest clinical signs developed (10 days postimmunization, dpi), with peak delay in acute EAE (20-40 dpi). In clinically stable disease (80 dpi), CCTs did not increase further, but cMEP amplitude declined progressively, with complete loss in >80% of mice at 120 dpi. Increase in CCT correlated with presence of inflammatory infiltrates and demyelination in acute EAE, whereas small or absent cMEPs were associated with continuing axonal damage in clinically-stabilized disease and beyond (>80 dpi). These results demonstrate that cMEPs are a useful method for monitoring corticospinal tract function in chronic-progressive EAE, and provide insight into the pathological substrate of the condition.
Amadio
Stefano
S
Department of Neurology and Clinical Neurophysiology, San Raffaele Scientific Institute, Università Vita e Salute, Milan, Italy.
Pluchino
Stefano
S
Brini
Elena
E
Morana
Paolo
P
Guerriero
Roberta
R
Martinelli Boneschi
Filippo
F
Comi
Giancarlo
G
Zaratin
Paola
P
Muzio
Valeria
V
del Carro
Ubaldo
U
D000818:Animals; D002490:Central Nervous System / Q000503:physiopathology; D002908:Chronic Disease; D020278:Demyelinating Autoimmune Diseases, CNS / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004558:Electric Stimulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology*; D019054:Evoked Potentials, Motor; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009410:Nerve Degeneration; D009431:Neural Conduction; D011712:Pyramidal Tracts / Q000503:physiopathology; D013997:Time Factors