Abstract
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. γ-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 μM)
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.
Keywords
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Article info
Publication history
Accepted:
November 8,
2000
Received in revised form:
November 1,
2000
Received:
September 1,
2000
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
