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.