CSF and Plasma Amino Acid Levels in Motor Neuron Disease: Elevation of CSF Glutamate in a Subset of Patients

Abstract

Fasting plasma and/or CSF amino acid levels have been measured in a group of 37 patients with motor neurone disease (MND) and in 35 neurological control patients undergoing lumbar puncture prior to myelography. There were no significant differences in the plasma levels of 22 amino acids between the two groups. In CSF, there was a significant elevation of the glutamate level in the MND patients (P=0.008). However, the MND group were heterogeneous with regard to CSF glutamate: 19/31 (61%) had levels within the normal range; eight (26%) had levels more than twice the upper limit of normal (≥10 μmol/l) and five (16%) had levels more than seven times normal (≥30 μmol/l). In a subset of seven MND patients there was a significant inverse correlation (r_s=−0.775,P<0.03) between CSF glutamate levels in life and the density of pre-synaptic glutamate re-uptake sites in the lumbar spinal cord measured in a post-mortem autoradiographic study. A possible interpretation of these findings is that an abnormality of glutamate transport may underlie the increase in CSF glutamate. The identification of a subgroup of MND patients with high CSF glutamate levels may be important in evaluating the clinical response to anti-glutamate therapeutic agents.