Kynurenine pathway metabolites in cerebrospinal fluid and serum in complex partial seizures.
The kynurenine pathway metabolites, quinolinic acid (QUIN) and L-kynurenine are convulsants, whereas kynurenic acid (KYNA) is an antagonist of excitatory amino acid receptors. Imbalances in the concentrations of these metabolites have been implicated in the etiology of human seizure disorders. In the present study, L-kynurenine and QUIN concentrations in both cerebrospinal fluid (CSF) and serum were reduced in patients with intractable complex partial seizures (CPS) in both the postictal period (15-75 min after a seizure) and the interictal period (absence of seizure for > 24 h) as compared with neurologically normal control subjects. Linear regression analyses and analysis of covariance showed that the reductions in serum QUIN and L-kynurenine were correlated to blood antiepileptic medication. L-Tryptophan (L-TRP) levels also tended to be lower in both CSF and serum of the seizure patients. CSF KYNA and serum 3-hydroxykynurenine concentrations were not affected in seizure patients, whereas serum levels of KYNA were reduced. 3-Hydroxykynurenine was not detected in the CSF of either control or seizure patients. The results do not support a role for a generalized reduction in KYNA concentrations or an increased ratio of QUIN:KYNA, or increases in CSF L-kynurenine in initiation and maintenance of intractable CPS humans.
Heyes
M P
MP
Section on Analytical Biochemistry, NIMH, Bethesda, MD 20892.
Saito
K
K
Devinsky
O
O
Nadi
N S
NS
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use; D001921:Brain / Q000201:enzymology; D004569:Electroencephalography; D017029:Epilepsy, Complex Partial / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006801:Humans; D007736:Kynurenic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D007737:Kynurenine / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008875:Middle Aged; D017378:Quinolinic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D012044:Regression Analysis; D014364:Tryptophan / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000378:metabolism
D000927:Anticonvulsants; C005045:3-hydroxykynurenine; D007737:Kynurenine; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D017378:Quinolinic Acid; D007736:Kynurenic Acid