Cerebrospinal Fluid γ‐Aminobutyric Acid Levels in Children with Different Types of Epilepsy: Effect of Anticonvulsant Treatment

Abstract

The mean gamma-aminobutyric acid (GABA) level in lumbar CSF of 31 children with epilepsy was not significantly different from that of 41 age-matched controls. However, when the epileptic children were subdivided into untreated patients and patients treated with antiepileptic drugs, the medication-free subgroup had a significantly lower mean CSF GABA level than nonepileptic children. Patients controlled by anticonvulsant therapy had significantly higher CSF GABA levels than untreated epileptic patients. A more detailed analysis of the children taking antiepileptic medication indicated that the only drug that significantly increased GABA in CSF was valproic acid. Analysis of CSF data with respect to the seizure type of the patients showed that, compared with controls, significantly reduced average GABA levels were present in children with infantile spasms (mostly untreated) and unmedicated generalized tonic-clonic seizures, whereas treated children with generalized tonic-clonic seizures and patients with partial epilepsy (mostly treated) did not significantly differ from controls. The data provide further evidence that impairment of the central GABA system may be involved in human epilepsy.

GABAergic mechanisms in the pathogenesis and treatment of epilepsy.

“…Comparison of tissue from the epileptogenic zone (determined electrographically) with non-epileptogenic tissue showed a decrease in glutamic acid decarboxylase activity in a proportion, but not all, of a group of 27 patients undergoing focal resection (Lloyd et al, 1985). However, Babb (1986) Studies of the GABA content in lumbar CSF have shown a significant reduction in patients with a wide range of epileptic syndromes compared with non-neurological controls, both for adults (Manyam et al, 1980;Wood et al, 1979) and for children Loscher & Siemes, 1985). These data support the concept that diminished GABAergic inhibition contributes to seizure susceptibility.…”

Disorders of glutamate metabolism

“…isoniazid treatment, lend credence to this theory. However, low GABA has been detected in other, nonpyridoxine dependent seizure disorders [Rating et al, 1983;Loscher and Siemes, 1985]. In one patient, transient resolution of seizure activity occurred with intravenous GABA administration [Kurlemann et al, 1987].…”

Inhibitory and excitatory amino acids in cerebrospinal fluid of chronic epileptic patients

“…Sodium valproate has been found to elevate levels of GABA in the brain (Patsalos and Lascelles, 1981) and CSF (L6scher and Siemes, 1985). We did not observe any difference in the CSF levels of FGABA, TGABA, or HC between epileptic patients with or without valproate in their medication.…”

“…Lloyd et al (1986) suggested that GABAergic defect is present in about 50-60% of the patients with drug-resistant epilepsy of focal onset. Furthermore, the CSF levels of GABA that reflect GABA concentration in the brain (Grove et al, 1983) are found to be low in children with febrile seizures (L6scher et al, 1981), infantile spasms (L6scher and Siemes, 1985) and also in focal epilepsy of adults (Wood et al, 1979). In some studies GABA levels have also been found to be normal (Schmidt and L6scher, 1981;Knight et al, 1985;Crawford and Chadwick, 1987).…”

“…Levels of GABA in the cerebrospinal fluid (CSF) of dogs are correlated with the seizure threshold for pentylenetetrazol-induced convulsions (L6scher, 1982). Furthermore, previous findings suggest that the levels of some amino acids (such as GABA, glutamate, aspartate, taurine, and glycine) in epileptic brain tissue (Van Gelder et al, 1972;Perry and Hansen, 1981 ;Lloyd et al, 1986;Nadi et al, 1987), CSF (Mutani et al, 1974;Pozdeev and II'in, 1978;Wood et al, 1979;Manyam et al, 1980;Honda, 1984;L6scher and Siemes, 1985;Pozdeev, 1985) or plasma (Van Gelder et al, 1980;Janjua et al, 1982) may be abnormal at the interictal stage. Although the studies have to some extent been contradictory, the promising results achieved in the treatment of epilepsy by drugs that affect the neurotransmission mediated by amino acids, especially the GABA mimetic drugs, emphasize that these compounds are involved in the pathophysiology of lowered threshold for seizures .…”