Ammonia-independent modifications of the background EEG signal and paradoxical enhancement of epileptic abnormalities in EEG after acute administration of valproate to epileptic patients

The effects on the background quantitative EEG (power spectral analysis) and concentration of valproate in plasma were studied after single-dose (14.3-33.3 mg/kg) oral administration in 12 epileptic patients with generalized nonconvulsive or partial seizures. An increase of the amplitude of the background EEG (diffuse and preponderant on anterior scalp areas) and a decrease of the 12.5-32.0 Hz relative power (limited to the posterior electrode deviations) were observed; the increase in the EEG total power was paralleled by a definite increment in incidence of epileptic phenomena in the EEG. Both effects proved unrelated to shifts in vigilance or changes in the concentration of ammonia or serum glucose in plasma and confirm previous observations from superimposable study designs. These findings are qualitatively opposite to those observed during long-term treatment at comparable doses and are suggested to reflect a direct CNS action of acute administration of valproate.

[1]  M. Fink.  EEG and human psychopharmacology , 1963 .

[2]  E. Banister,et al.  Exercise-Induced Hyperammonemia: Peripheral and Central Effects , 1990, International journal of sports medicine.

[3]  B. J. Winer.  Statistical Principles in Experimental Design , 1992 .

[4]  M. Fink.  EEG and psychopharmacology. , 1978, Electroencephalography and clinical neurophysiology. Supplement.

[5]  Turan M. Itil,et al.  Psychotropic drugs and the human EEG , 1974 .

[6]  A. Marini,et al.  Sodium Valproate‐induced hyperammonemia without clinical hepatic dysfunction , 1982, Neurology.

[7]  M. Trimble,et al.  Anticonvulsant serum levels: relationship to impairments of cognitive functioning. , 1983, Journal of neurology, neurosurgery, and psychiatry.

[8]  J. Mcreynolds,et al.  Valproic acid‐induced hyperammonemia in mentally retarded adults , 1984, Neurology.

[9]  H. Kupferberg.  Sodium-valproate , 1988, The Lancet.

[10]  Gerald E. Slater,et al.  Sodium Valproate Increases Potassium Conductance in Aplysia Neurons , 1978, Epilepsia.

[11]  Rudolf Nieuwenhuys,et al.  Chemoarchitecture of the Brain , 1985, Springer Berlin Heidelberg.

[12]  K. Koch,et al.  Beta-oxidation of valproic acid. I. Effects of fasting and glucose in humans. , 1989, Epilepsia.

[13]  [Electroencephalographic changes in epileptic child treated by Depakene]. , 1968, Revue neurologique.

[14]  Jarl Risberg,et al.  Observations on the functional significance of regional cerebral blood flow in “resting” normal subjects , 1980, Neuropsychologia.

[15]  R. Horton,et al.  Paradoxical enhancement of seizures in the gerbil after chronic treatment with sodium valproate , 1988, Neuropharmacology.

[16]  R. Allen,et al.  SECONDARY HYPERAMMONÆMIA: A POSSIBLE MECHANISM FOR VALPROATE ENCEPHALOPATHY , 1980, The Lancet.

[17]  W H Theodore,et al.  Effect of Valproate on Human Cerebral Glucose Metabolism , 1991, Epilepsia.

[18]  R. A. Davidoff,et al.  The presynaptic effects of valproic acid in the isolated frog spinal cord , 1981, Brain Research.

[19]  W. Sannita,et al.  Quantitative EEG effects and plasma concentration of sodium valproate: acute and long-term administration to epileptic patients. , 1989, Neuropsychobiology.

[20]  E. Speckmann,et al.  Effects of Valproate in a Model Nervous System (Buccal Ganglia of Helix Pomatia): I. Antiepileptic Actions , 1992, Epilepsia.

[21]  David John Adams,et al.  Sodium valproate in the treatment of intractable seizure disorders , 1978, Neurology.

[22]  P. Lomax,et al.  The Mongolian gerbil (Meriones unguiculatus) as a model for the study of the epilepsies: EEG records of seizures. , 1975, Electroencephalography and clinical neurophysiology.

[23]  Study of bioequivalence of magnesium and sodium valproates. , 1991, Journal of pharmaceutical and biomedical analysis.

[24]  R. Cohen,et al.  Reversible Valproic Acid‐Induced Dementia: A Case Report , 1986, Epilepsia.

[25]  D. Chadwick,et al.  Acute intoxication with sodium valproate , 1979, Annals of neurology.

[26]  EFFECT ON THE ELECTROENCEPHALOGRAM OF CHANGING THE BLOOD SUGAR LEVEL , 1943 .

[27]  Psychological Changes Associated with Induced Hyperammonemia , 1964, Science.

[28]  R. Schain,et al.  Effects of Phenobarbital on Seizure Activity in the Gerbil , 1978, Pediatric Research.

[29]  W. Raabe,et al.  Disinhibition in cat motor cortex by ammonia. , 1975, Journal of neurophysiology.

[30]  H. Hinrichs,et al.  International Pharmaco-EEG Group (IPEG) , 1987 .

[31]  H. Blume,et al.  Sodium di-n-propylacetate (valproate) action on single neurons in rat cerebral cortex and hippocampus , 1979, Brain Research.

[32]  C. Marescaux,et al.  Stuporous Episodes During Treatment with Sodium Valproate: Report of Seven Cases , 1982, Epilepsia.

[33]  G. Zaccara,et al.  Hyperammonemia and valproate-induced alterations of the state of consciousness. A report of 8 cases. , 1984, European neurology.

[34]  J. Sackellares,et al.  Stupor Following Administration of Valproic Acid to Patients Receiving Other Antiepileptic Drugs , 1979, Epilepsia.

[35]  M. Schiphorst,et al.  A kinetic determination of ammonia in plasma. , 1974, Clinica chimica acta; international journal of clinical chemistry.

[36]  L. Gram,et al.  Valproate: an updated review , 1985, Acta neurologica Scandinavica.