Fetal malformations associated with the use of methylphenobarbital and carbamazepine during pregnancy. Two case reports and review of the literature.

The use of antiepileptic drugs (AEDs) during pregnancy has been associated with an increased risk of major and minor fetal malformations. This paper describes 2 infants with malformations born to epileptic mothers who used AEDs throughout pregnancy. In the first case, the AED used for seizure control was methylphenobarbital, while in the second case the patient had been prescribed carbamazepine. We noted major and minor congenital malformations in both infants exposed in utero to these anticonvulsant drugs. Pregnant women still experience poor obstetrical care because they report to tertiary centers at the end of their pregnancy or when in labor, making it difficult to provide proper medical care for both the infant and the mother.

[Intoxication due to replacement of the precursor methylphenobarbital by phenobarbital]. / Intoxicatie door het vervangen van de precursor methylfenobarbital door fenobarbital.

An 80-year-old woman with a history of familial primary generalised epilepsy presented to the outpatient clinic with complaints of dizziness, confusion, dullness and feeling of'being worthless'. It turned out that she had been using medication for some time in which the chemical nature of the pharmacologically active ingredient had been changed: methylphenobarbital 60 mg t.i.d. had been replaced by phenobarbital 60 mg t.i.d. The resultant phenobarbital concentration was much higher than the concentration to which she was accustomed. At the same dosage, phenobarbital is more active than methylphenobarbital. When one compound ofa pharmacologically active substance is replaced by a different compound, the dosage should be corrected for both the chemical structure, such as the molecular weight, and the pharmacokinetic properties such as absorption, metabolism and biological availability.

Behavior disturbance, phenobarbital, and febrile seizures.

Of 109 children treated daily with phenobarbital following the first fibrile convulsion, 42% developed a behavior disorder, usually hyperactivity. Daily phenobarbital therapy was prematurely discontinued in 54% of the children with behavior abnormality (20% of those treated). The behavior disturbance usually appeared within several months, was no correlated with high blood barbiturate levels, disappeared in 73%, and improved in all children when barbiturate therapy was discontinued. No characteristics of the child, the initial febrile seizure, or recurrence of febrile seizures were significantly correlated with the occurrence of the behavior disorder except for behavioral abnormality preceding the initial febrile convulsion. Eighteen percent of the children who received no phenobarbital developed behavior disorder, most often hyperactivity. The behavior disturbance spontaneously disappeared in 52%. Among these children not given phenobarbital, the group with normal behavior had a greater frequency of family history of seizures, especially febrile convulsions, and a lower frequency of preseizure behavior disturbance; abnormalities of pregnancy, labor, delivery, and neonatal period; delayed milestones; long seizures; abnormal results of neurological examination; abnormal EEG; and recurrent febrile seizures.

Treatable aspects of the dementia syndrome.

With attentive medical management, the elderly demented patient can live in greater comfort, dignity and independence. Errors in supervision can result in a drug intoxication, misdiagnoses, and personal neglect. Many of the elderly have a chronic dementing illness, and disability often is accelerated by complications. However, some of these complications are treatable. Case histories are presented to illustrate pitfalls in the care of such patients.

A randomized, double-blind, crossover study of phenobarbital and mephobarbital.

Some pediatric neurologists maintain that mephobarbital (Mebaral) causes fewer behavioral side effects than phenobarbital. Because this hypothesis has not been previously tested, we conducted a prospective, double-blind, randomized, crossover study of these two anticonvulsants. Both drugs were equally effective in reducing the frequency of seizure, although serum phenobarbital levels were significantly higher when the patients were taking phenobarbital compared to mephobarbital. As measured by the Abbott Parent Questionnaire, there was no significant deterioration of behavior with either phenobarbital or mephobarbital, regardless of which drug was administered first.

Ependymoblastoma associated with prenatal exposure to diphenylhydantoin and methylphenobarbitone.

Ependymoblastoma developed in a 28-month-old girl whose epileptic mother took diphenylhydantoin and methylphenobarbitone throughout pregnancy. The child was also shown to be a genetic carrier for ornithine transcarbamylase deficiency, an x-linked inborn error of urea cycle metabolism. The possibility of transplacental carcinogenesis should be considered, as other juvenile embryonic tumors such as neuroblastoma, melanotic neuroectodermal tumor, and mesenchymoma have been reported in offspring after diphenylhydantoin use by the mother during pregnancy.

Anticonvulsant medications: an iatrogenic cause of tic disorders.

A review of the relationship between anticonvulsant medications and tics is presented. Data on 5 patients in whom anticonvulsants, either caused tics or exacerbated existing tic disorders is discussed. Discontinuation of the medication resulted in a decrease in the frequency of tickings in all patients. The effects of anticonvulsants on the reticular system are discussed. It is felt that it may be important for clinicians to consider carefully the use of barbiturate anticonvulsants, especially phenobarbital, in children with tics or a family history of tics. Tic disorders caused or exacerbated by exposure to anticonvulsant medications appear to be more common than previously reported, and in some patients the tics may not remit with discontinuation of the medication.

[A barbiturate derivative-induced depressive syndrome in a 9-year-old boy with complex focal seizures and secondary generalization--a case report]. / Ein durch Barbituratabkömmlinge induziertes depressives Syndrom bei einem 9jährigen Jungen mit komplexen fokalen Anfällen und sekundärer Generalisierung - ein Fallbericht.

The mental side-effects of long-term anticonvulsant medication are still not widely enough known. The paper describes the case of a depressive syndrome induced in a nine-year-old boy, with complex localised attacks and secondary generalisation, which completely receded on treatment with Convulsofin.