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 recessive disorder. Untreated patients suffer from a progressive encephalopathy with mental retardation, intractable epilepsy, and progressive neurological signs and symptoms. Lifelong supplementation with vitamin B6 is the treatment of choice. However, despite early treatment, many patients develop mental retardation.


OBJECTIVE
To assess the role of glutamate as an excitatory neurotransmitter and neurotoxin in pyridoxine-dependent epilepsy.


METHODS
We examined cerebrospinal fluid (CSF) levels of glutamate, gamma-aminobutyric acid, and pyridoxal-5'-phosphate in a patient with pyridoxine dependency while on and off vitamin B6 treatment.


RESULTS
Off vitamin B6 the glutamate level was two hundred times normal. An intermediate dose of vitamin B6 (5 mg/kg BW/day) caused normalization of the EEG and remission of the seizures, but the CSF glutamate concentration was still ten times normal. With a higher dose of pyridoxine (10 mg/kg BW/day) the CSF glutamic acid normalized.


CONCLUSIONS
The results indicate that control of epilepsy might not suffice as the therapeutic aim in treating of pyridoxine dependency. In view of the evidence for the role of excitatory amino acids in destruction of CNS nerve cells, the optimal treatment must counteract the raised levels of CSF glutamate and the dosage of vitamin B6 must be adjusted accordingly. The development of mental retardation might theoretically be prevented by adjusting the dose of vitamin B6 to achieve not only remission of epilepsy but also normalization of CSF glutamate.
Baumeister
F A
FA
Dr. v. Haunersches Kinderspital, Universität München, Germany.
Gsell
W
W
Shin
Y S
YS
Egger
J
J
D000324:Adrenocorticotropic Hormone / Q000627:therapeutic use; D004569:Electroencephalography; D004827:Epilepsy / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000235:genetics; D005808:Genes, Recessive; D005971:Glutamates / Q000134:cerebrospinal fluid* / Q000502:physiology; D018698:Glutamic Acid; D006257:Head / Q000033:anatomy & histology; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000517:prevention & control; D008297:Male; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid* / Q000502:physiology; D011732:Pyridoxal Phosphate / Q000134:cerebrospinal fluid; D011736:Pyridoxine / Q000378:metabolism / Q000627:therapeutic use*; D005680:gamma-Aminobutyric Acid / Q000134:cerebrospinal fluid
D005971:Glutamates; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011732:Pyridoxal Phosphate; D000324:Adrenocorticotropic Hormone; D011736:Pyridoxine