Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central 
nervous system (CNS). Most patients undergo an initial relapsing-remitting 
(RR-MS) course that transforms into a relentless neurodegenerative disorder, 
termed secondary progressive (SP)-MS. Reversible inflammation and demyelination 
account readily for the pattern of RR-MS but provide an unsatisfactory 
explanation for irrevocable decline in SP-MS. Axon loss is thought to be 
responsible for progressive, non-remitting neurological disability during SP-MS. 
There is considerable potential for neuroprotective therapies in MS, but their 
application awaits animal models in which axonal loss correlates with permanent 
neurological disability. In this report, we describe quantitative 
immunohistochemical methods that correlate inflammation and axonal loss with 
neurological disability in chronic-relapsing experimental autoimmune 
encephalomyelitis (EAE). At first attack, CNS inflammation, but not axon loss, 
correlated with the degree of neurological disability. In contrast, fixed 
neurological impairment in chronic EAE correlated with axon loss that, in turn, 
correlated with the number of symptomatic attacks. As proposed for MS, these 
observations imply a causal relationship between inflammation, axon loss, and 
irreversible neurological disability. This chronic-relapsing EAE model provides 
an excellent platform for 2 critical objectives: investigating mechanisms of 
axon loss and evaluating efficacy of neuroprotective therapies.