GLUTAMATE IN PYRIDOXINE-DEPENDENT EPILEPSY - NEUROTOXIC GLUTAMATE CONCENTRATION IN THE CEREBROSPINAL-FLUID AND ITS NORMALIZATION BY PYRIDOXINE

Background. Pyridoxine-dependent epilepsy is a rare autosomal recessiv e disorder. Untreated patients suffer from a progressive encephalopath y with mental retardation, intractable epilepsy, and progressive neuro logical signs and symptoms. Lifelong supplementation with vitamin B-6 is the treatment of choice. However, despite early treatment, many pat ients develop mental retardation. Objectives. To assess the role of gl utamate as an excitatory neurotransmitter and neurotoxin in pyridoxine -dependent epilepsy. Methods. We examined cerebrospinal fluid (CSF) le vels of glutamate, gamma-aminobutyric acid, and pyridoxal-5'phosphate in a patient with pyridoxine dependency while on and off vitamin B-6 t reatment. Results. Off vitamin B-6 the glutamate level was two hundred times normal. An intermediate dose of vitamin B-6 (5 mg/kg BW/day) ca used normalization of the EEG and remission of the seizures, but the C SF glutamate concentration was still ten times normal. With a higher d ose of pyridoxine (10 mg/kg BW/day) the CSF glutamic acid normalized. Conclusions. The results indicate that control of epilepsy might not s uffice as the therapeutic aim in treating of pyridoxine dependency. In view of the evidence for the role of excitatory amino acids in destru ction of CNS nerve cells, the optimal treatment must counteract the ra ised levels of CSF glutamate and the dosage of vitamin B-6 must be adj usted accordingly. The development of mental retardation might theoret ically be prevented by adjusting the dose of vitamin B-6 to achieve no t only remission of epilepsy but also normalization of CSF glutamate.