Arch Neurol. 2003 Aug;60(8):1082-8
Sarchielli P, Greco L, Floridi A, Floridi A, Gallai V.
Neuroscience Department, Institute of Clinical and Applied Biochemistry,
Policlinico Monteluce, University of Perugia, Via E Dal Pozzo, 06126 Perugia,
Italy.
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 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).
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.