Excitatory amino acids and multiple sclerosis - Evidence from cerebrospinal fluid

Background: Recent evidence suggests an altered glutamate homeostasis in the brain of patients with multiple sclerosis (MS), as seen in experimental models of MS. Objective: 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. Participants: 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. Methods: Glutamate and aspartate levels in the cerebrospinal fluid were measured by high-performance liquid chromatography. Results: 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 neuro radiological evidence of disease activity (P < .001). Significantly higher levels of glutamate were found in patients with secondary progressive MS with an increase of I or more points on the Expanded Disability Status Scale score compared with stable patients with secondary progressive MS and control subjects (P < .001). Conclusions: 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.