title: Glutamate levels in cerebrospinal fluid in amyotrophic lateral sclerosis: a reappraisal using a new HPLC method with coulometric detection in a large cohort of patients.
abstract: Glutamate is involved in the degeneration of motor neurons in amyotrophic lateral sclerosis (ALS). However, the aetiology of ALS appears heterogeneous, leading to the possibility that patient subgroups with different pathophysiology may exist. The concentration of glutamate in cerebrospinal fluid (CSF) is measured using a new HPLC method with coulometric detection in a large cohort of ALS patients and controls: 377 ALS patients, 88 neurological patients and 18 normal controls. In ALS patients, and only in these subjects, the existence of two groups was observed, one with normal glutamate concentrations and one (40.8% of ALS patients) with high glutamate concentrations. High glutamate concentrations were correlated with a spinal onset of the disease, more impaired limb function and a higher rate of muscle deterioration. These results suggest that elevations of CSF glutamate concentrations could reflect the intensity of cell insult in the spinal cord. It remains to be determined if the group of patients with high CSF glutamate concentrations represents a specific subgroup of patients in terms of mechanism of disease, or only in terms of the spatial extent of motor neuron insult.
authors.affiliation: Service de Biochimie-Pharmacologie et d'Anesthésie, Hôpital de Versailles, Le Chesnay, France
authors.forename: Odile
authors.initials: O
authors.lastname: Spreux-Varoquaux
authors.forename: Gilbert
authors.initials: G
authors.lastname: Bensimon
authors.forename: Lucette
authors.initials: L
authors.lastname: Lacomblez
authors.forename: François
authors.initials: F
authors.lastname: Salachas
authors.forename: Pierre François
authors.initials: PF
authors.lastname: Pradat
authors.forename: Nadine
authors.initials: N
authors.lastname: Le Forestier
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Marouan
authors.forename: Michel
authors.initials: M
authors.lastname: Dib
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
mesh_terms: D000367:Age Factors; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015331:Cohort Studies; D003124:Colorimetry / Q000379:methods; D018450:Disease Progression; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010291:Paresis / Q000503:physiopathology; D012249:Rhombencephalon / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012737:Sex Factors; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018698:Glutamic Acid