Excitatory amino acids and multiple sclerosis: evidence from cerebrospinal fluid.

Abstract

Recent evidence suggests an altered glutamate homeostasis in the brain of patients with multiple sclerosis (MS), as seen in experimental models of MS. To test whether the excitotoxic insult contributes to the pathological process in MS by measuring glutamate and aspartate levels in the cerebrospinal fluid of MS patients and control individuals. Twenty-five patients with the relapsing-remitting form of MS during a stable clinical phase, 30 patients with relapsing-remitting MS during relapse, and 25 patients with the secondary progressive form of MS were included in the study. Data were compared with those of 20 age-matched control subjects without diseases of the central and peripheral nervous systems. Glutamate and aspartate levels in the cerebrospinal fluid were measured by high-performance liquid chromatography. Cerebrospinal fluid glutamate levels were significantly higher in patients assessed during relapse compared with those of the patients with relapsing-remitting MS examined during the stable clinical phase and the controls (P<.001). The levels of glutamate detected in patients with relapsing-remitting MS during the stable phase who had active lesions were significantly higher than in those without neuroradiological evidence of disease activity (P<.001). Significantly higher levels of glutamate were found in patients with secondary progressive MS with an increase of 1 or more points on the Expanded Disability Status Scale score compared with stable patients with secondary progressive MS and control subjects (P<.001). Neurotoxic events occur in MS patients, and they can be responsible for oligodendrocyte and neuronal cell death in patients with this demyelinating disease. The manipulation of glutamate-altered homeostasis or antagonizing glutamate receptor-mediated excitotoxicity may have therapeutic implications in MS patients.