Low brain GABA level is associated with poor seizure control

Low gamma‐aminobutyric acid (GABA) concentrations in the cerebrospinal fluid are seen in a variety of epileptic syndromes. Low GABA levels outside of the epileptic focus may facilitate spread of discharges beyond the focus. In vivo measurements of GABA were made by 1H spectroscopy using a 2.1‐T magnetic resonance imager‐spectrometer and an 8‐cm surface coil to measure a 14‐cm3 volume in the occipital lobe. Patients with complex partial seizures had lower GABA levels (1.03 mmol/kg of brain; 95% confidence interval [CI], 0.95−1.12; n = 28; p < 0.02) than did subjects without epilepsy (1.18; 95% CI, 1.13−1.24; n = 19). There was a significant association between low GABA levels and recent seizures (correlation coefficient of 0.548, p < 0.01, df of 32). Conversely, patients with well‐controlled seizures had higher brain GABA levels than did patients with recent seizures. Patients with seizures within a day of the measurement had lower GABA levels (0.92 mmol/kg; 95% CI, 0.78−1.06; n = 7) than did patients who were seizure free for 5 years or longer (1.28; 95% CI, 1.09−1.47; n = 4). Poor seizure control is associated with low brain GABA levels.

[1]  M. During,et al.  Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain , 1993, The Lancet.

[2]  R. Mattson,et al.  Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[3]  W. Löscher,et al.  Strategies in antiepileptic drug development: is rational drug design superior to random screening and structural variation? , 1994, Epilepsy Research.

[4]  E. Roberts Failure of GABAergic inhibition: a key to local and global seizures. , 1986, Advances in neurology.

[5]  Graeme D. Jackson,et al.  Magnetic Resonance in Epilepsy , 1994 .

[6]  N. Fountain,et al.  Pathophysiology of Status Epilepticus , 1995, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[7]  R. Mattson,et al.  Initial Observations on Effect of Vigabatrin on In Vivo 1H Spectroscopic Measurements of γ‐Aminobutyric Acid, Glutamate, and Glutamine in Human Brain , 1995, Epilepsia.

[8]  B. Meldrum,et al.  GABAergic mechanisms in the pathogenesis and treatment of epilepsy. , 1989, British journal of clinical pharmacology.

[9]  O. Petroff,et al.  Symbiosis between in vivo and in vitro NMR spectroscopy: the creatine, N-acetylaspartate, glutamate, and GABA content of the epileptic human brain. , 1995, Magnetic resonance imaging.

[10]  N. Lambert,et al.  The mechanism of biphasic GABA responses , 1995, Science.

[11]  C. V. van Donselaar,et al.  Value of the electroencephalogram in adult patients with untreated idiopathic first seizures. , 1992, Archives of neurology.

[12]  K. Behar,et al.  Measurement of GABA following GABA‐transaminase inhibition by gabaculine: A 1H and 31P NMR spectroscopic study of rat brain in vivo , 1994, Magnetic resonance in medicine.

[13]  R G Shulman,et al.  Homonuclear 1H double-resonance difference spectroscopy of the rat brain in vivo. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Alger,et al.  High‐field proton magnetic resonance spectroscopy of human cerebrum obtained during surgery for epilepsy , 1989, Neurology.

[15]  R. Mattson,et al.  The effect of gabapentin on brain gamma‐aminobutyric acid in patients with epilepsy , 1996, Annals of neurology.

[16]  A. Draguhn,et al.  Strategies for the Development of Drugs for Pharmacoresistant Epilepsies , 1994, Epilepsia.

[17]  R. Mattson,et al.  Vigabatrin: Effects on Human Brain GABA Levels by Nuclear Magnetic Resonance Spectroscopy , 1994, Epilepsia.

[18]  R. D'Hooge,et al.  Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants , 1992, Epilepsy Research.

[19]  R. Post,et al.  Low cerebrospinal fluid γ‐aminobutyric acid content in seizure patients , 1979, Neurology.

[20]  K. Behar,et al.  Analysis of macromolecule resonances in 1H NMR spectra of human brain , 1994, Magnetic resonance in medicine.

[21]  Dennis D. Spencer,et al.  Hippocampal GABA transporter function in temporal-lobe epilepsy , 1995, Nature.

[22]  M. Palfreyman,et al.  The relationship between GABA concentrations in brain and cerebrospinal fluid , 1979, Brain Research.