Yutaka Fukushima

Potentiation of GABA by Midazolam and Its Therapeutic Effect against Status Epilepticus

Abstract: The anticonvulsive effect of midazolam was studied in rats and mice brains. Microiontophoretically applied midazolam (0.2M, pH 3.5) potentiated the GABA effect at the single neurone level, and inhibited neuronal firing in the rat cuneate neurones. Midazolam administered intraperitoneally (15 mg/kg) increased the primary afferent depolarization for at least two hours. Three mg/kg of midazolam slightly increased the glutamate decarboxylase activities in the mice cerebrum and the increase was statistically significant (p < 0.05). The authors reported a case of clinical application of midazolam: a status epilepticus was successfully treated with it, while intravenous diazepam of 30 mg failed to control the status.

Teratogenicity of Antiepileptic Drugs: Is the Prevention Possible?

Abstract: To assess the relative contribution of antiepileptic drugs (AEDs) toward the occurrence of congenital malformation, two prospective studies (previous and present) were compared. In the present subjects of 145 cases, the total daily dose of AEDs (drug score) in each case was decreased as much as possible, and polypharmacy was changed to monopharmacy before conception where it was possible. The incidence of malformations significantly decreased from 13.5% to 6.2% (p = 0.031) by the change in drug regimen. The drug score, number of AEDs, maternal age at delivery, seizure type, and etiology of epilepsy were statistically different between the two study groups. Even after the correction of the data by the last three factors, the difference in the incidence of malformation did not disappear, while it disappeared if data were corrected either by the drug score or number of AEDs. These results suggest that the possibility of prevention of AED related malformations is possible by an improvement in AED therapy.

Mono‐Unsaturated Metabolites of Valproic Acid in Epileptic Women and Their Neonates

The incidence of malformation was highest in patients receiving polypharmacy including valproic acid (VPA).l Nau and Loscher5 showed the teratogenicity of 2-propyl-4pentenoic acid (4-en), one of the mono-unsaturated metabolites of VPA, while fetal accumulation of VPA has been reported.2 These reports prompted us to study the influence of pregnancy and polypharmacy on the metabolism of VPA, the transplacental passage of the mono-unsaturated metabolites of VPA to the fetus and its elimination from the neonates.

Discussion on the ‘Problem of Driving License for People with Epilepsy’

Abstract: From the socio‐medical points of view, the problem of a driving license for people with epilepsy was discussed. It was concluded that not only seizure but also the presence of side‐effects of drugs and of personality change should be assessed to allow them the license. Finally, a medical guideline was proposed for the driving license for people with epilepsy.

A Study on Long‐Term Prognosis of Epilepsy

Of 631 epileptic patients examined in our seizure clinic in the period between January 1961 and December 1966, 97 (15.4%) have been treated until September 1976, when the long‐term prognosis was evaiuated. The “good prognosis (completely controlled)” were found in 59% of grand mal, in 55% of focal motor seizure, in 42% of psychomotor and in 33% of the mixed seizure in which more than two types of seizures were combined; in 49% (48 cases) on the average. Seventy‐nine percent of the cases of the mixed seizure were combined with psychomotor seizures. In the psycho‐motor and the mixed seizure groups, the presence of personality disorders tended to lead them to “poor prognosis” which meant that the seizures were not well controlled.

Various Hormonal Concentrations in Pregnant Epileptic Women and Their Offspring

The subjects comprised 3 I treated pregnant epileptic women (E Group), noncpileptic pregnant women (matched control: C Group), and the offspring of both groups. In the E Group, the mean duration of AED therapy was 1 1 years and 5 months. The average gestational weeks of the offspring in the E and C Groups were 40 weeks and 3 days, and 40 weeks and 1 day, respectively. Radioimmunoassay was used to determine the hormonal levels [growth hormone (GH), thyroxine (T4) , triiodothyronine (T3 ) , reverse-T3 (r-T3), thyrotropin (TSH) , human cholionic gonadotropin (hCG), estradiol (E2), progesterone and cortisol] in the sera. To detect the relationship between the effects of drug dosage and hormonal effects of AED, a drug scoring system was a d ~ p t e d . ~ Results

A Longitudinal Study on Epilepsy: With Special Reference to Recurrence of Seizure after Long Seizure-Free Period

Abstract: The clinical course was investigated of 137 epileptic patients who had been under continuous observation and therapy for the past 11 to 23 years. When a remission of epilepsy was defined as a seizure‐free period for three years and a relapse was defined as an occurrence of seizures after the remission, the remission rate was 45%, but 32% of the subjects had experienced the relapse. When the term of three years in the definition of remission and relapse was altered to five years, the rates of remission and relapse shifted to 36% and 20%, respectively. A relapse of seizure was found more often in grand mal of primary generalized epilepsy than other types of seizures. Especially, no relapse was observed in benign epilepsy of children with centro‐temporal EEG foci.