Several lines of evidence suggest that the binding affinity of
glutamate decarboxylase (GAD) to the active form of
pyridoxine is low in cases of
pyridoxine-dependent seizures (PDS) and that a quantitative imbalance between excitatory (i.e.
glutamate) and inhibitory (i.e.
gamma-aminobutyric acid,
GABA)
neurotransmitters could cause refractory
seizures. However, inconsistent findings with GAD insufficiency have been reported in PDS. We report a case of PDS that is not accompanied by an elevated cerebrospinal fluid (CSF)
glutamate concentration. Intravenous
pyridoxine phosphate terminated
generalized seizures which were otherwise refractory to conventional anti-epileptic medicines. No seizure occurred once oral
pyridoxine (13.5 mg/kg per day) was started in combination with
phenobarbital sodium (PB, 3.7 mg/kg per day). The electroencephalogram (EEG) normalized approximately 8 months after
pyridoxine was started. The patient is gradually acquiring developmental milestones during the 15 months follow-up period. The CSF
glutamate and
GABA concentrations were determined on three separate occasions: (1) during
status epilepticus; (2) during a seizure-free period with administration of
pyridoxine and PB; and (3) 6 days after
suspension of
pyridoxine and PB and immediately before a convulsion. The CSF
glutamate level was below the sensitivity of detection (<1.0 microM) on each of the three occasions; the CSF
GABA level was within the normal range or moderately elevated. The CSF and serum concentrations of
vitamin B6-related substances, before
pyridoxine supplementation, were within the normal range. We suggest that (1) PDS is not a discrete disease of single etiology in that insufficient activation of GAD may not account for seizure susceptibility in all cases and (2) mechanism(s) of anti-convulsive effect of
pyridoxine, at least in some cases, may be independent of GAD activation.