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

• Published in: Brain & development (Tokyo. 1979) 2001-03, Vol.23 (1), p.24-29
• Main Authors: GOTO, Tomohide, MATSUO, Nobutake, TAKAHASHI, Takao
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; gamma-Aminobutyric Acid - blood; gamma-Aminobutyric Acid - cerebrospinal fluid; Glutamate Decarboxylase - deficiency; Glutamic Acid - blood; Glutamic Acid - cerebrospinal fluid; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Infant; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Pyridoxine - metabolism; Pyridoxine - pharmacokinetics; Seizures - cerebrospinal fluid; Seizures - drug therapy; Seizures - etiology; Seizures - physiopathology
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/S0387-7604(00)00193-5

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 (