KYNURENINE PATHWAY METABOLITES IN CEREBROSPINAL-FLUID AND SERUM IN COMPLEX PARTIAL SEIZURES

The kynurenine pathway metabolites, quinolinic acid (QUIN) and L-kynur enine are convulsants, whereas kynurenic acid (KYNA) is an antagonist of excitatory amino acid receptors. Imbalances in the concentrations o f these metabolites have been implicated in the etiology of human seiz ure disorders. In the present study, L-kynurenine and QUIN concentrati ons in both cerebrospinal fluid (CSF) and serum were reduced in patien ts with intractable complex partial seizures (CPS) in both the postict al period (15-75 min after a seizure) and the interictal period (absen ce of seizure for >24 h) as compared with neurologically normal contro l subjects. Linear regression analyses and analysis of covariance show ed that the reductions in serum QUIN and L-kynurenine were correlated to blood antiepileptic medication. L-Tryptophan (L-TRP) levels also te nded to be lower in both CSF and serum of the seizure patients. CSF KY NA and serum 3-hydroxykynurenine concentrations were not affected in s eizure patients, whereas serum levels of KYNA were reduced. 3-Hydroxyk ynurenine was not detected in the CSF of either control or seizure pat ients. The results do not support a role for a generalized reduction i n KYNA concentrations or an increased ratio of QUIN:KYNA, or increases in CSF L-kynurenine in initiation and maintenance of intractable CPS humans.