CSF glutamate/GABA concentrations in pyridoxine-dependent seizures: etiology of pyridoxine-dependent seizures and the mechanisms of pyridoxine actionin seizure control

Citation
T. Goto et al., CSF glutamate/GABA concentrations in pyridoxine-dependent seizures: etiology of pyridoxine-dependent seizures and the mechanisms of pyridoxine actionin seizure control, BRAIN DEVEL, 23(1), 2001, pp. 24-29
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurology,"Neurosciences & Behavoir
Journal title
BRAIN & DEVELOPMENT
ISSN journal
0387-7604 → ACNP
Volume
23
Issue
1
Year of publication
2001
Pages
24 - 29
Database
ISI
SICI code
0387-7604(200103)23:1<24:CGCIPS>2.0.ZU;2-J
Abstract
Several lines of evidence suggest that the binding affinity of glutamate de carboxylase (GAD) to the active form of pyridoxine is low in cases of pyrid oxine-dependent seizures (PDS) and that a quantitative imbalance between ex citatory (i.e. glutamate) and inhibitory (i.e. gamma -aminobutyric acid, GA BA) neurotransmitters could cause refractory seizures. However, inconsisten t findings with GAD insufficiency have been reported in PDS. We report a ca se of PDS that is not accompanied by an elevated cerebrospinal fluid (CSF) glutamate concentration. Intravenous pyridoxine phosphate terminated genera lized seizures which were otherwise refractory to conventional anti-epilept ic 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 da y). The electroencephalogram (EEG) normalized approximately 8 months after pyridoxine was started. The patient is gradually acquiring developmental mi lestones during the 15 months follow-up period. The CSF glutamate and GABA concentrations were determined on three separate occasions: (1) during stat us epilepticus; (2) during a seizure-free period with administration of pyr idoxine and PB; and (3) 6 days after suspension of pyridoxine and PB and im mediately before a convulsion. The CSF glutamate level was below the sensit ivity of detection (<1.0 <mu>M) on each of the three occasions; the CSF GAB A level was within the normal range or moderately elevated. The CSF and ser um concentrations of vitamin B-6-related substances, before pyridoxine supp lementation, 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. (C) 2001 Elsevier Science B.V. All rights re served.