1. ¹Veterans Administration Medical Center, Syracuse, NY, USA
2. ²Department of Neurology, SUNY Upstate Medical University, Syracuse, NY, USA

Correspondence: Dr B Kalman, MD, PhD, Veterans Administration Medical Center and Department of Neurology, SUNY Upstate Medical University, 800 Irving Avenue, Research (151), Syracuse, NY 13210, USA. E-mail: kalmanb@upstate.edu

Received 12 March 2008; Revised 21 April 2008; Accepted 25 April 2008; Published online 2 June 2008.

Abstract

Neurodegeneration develops in association with inflammation and demyelination in multiple sclerosis. Available data suggest that the progressive neuroaxonal loss begins in the earliest stages of the disease and underlies the accumulation of clinical disability. The loss of neurons and their processes is driven by a complex molecular mechanism involving cellular and humoral immune histotoxicity, demyelination, reduced neurotrophic support, metabolic impairment, and altered intracellular processes. Here we survey available data concerning the role of autoreactive immunoglobulins in neurotoxicity. A better understanding of molecular pathways leading to immune-mediated neurodegeneration may have key importance in the successful treatment of the disease.