We examined the genetic factors that cause congenital malformations and diseases in the offspring of pregnant women with epilepsy. The subjects were 177 offspring of epileptic patients who had been treated in the Department of Neuropsychiatry in Fukushima Medical University Hospital between July 1971 and February 2015. We found congenital malformations and diseases in 25 offspring. There were 12 malformation cases: 4 cleft lip and cleft palate cases, 3 congenital heart defect cases, 1 case of both cleft palate and congenital heart defect, 1 iridocoloboma, 1 hemirenal dysplasia, 1 arachnoid cyst, and 1 syndactylia. The medical situation of those pregnant women is usually monotherapy and the average dose of each antiepileptic drug (AED) is less than other reported cases. There is a possibility that side-effects are down on the appearance of malformation because of low AED dose. AEDs during pregnancy were not used in the arachnoid cyst and syndactylia cases. In 7 of the 12 malformation cases (58.3%), we found the same congenital malformations in first- to third-degree relatives. Moreover, the hemirenal dysplasia case and syndactylia case both had genetic factors of epilepsy with autosomal dominant inheritance in three generations. It is noteworthy that in the iridocoloboma case the husband of epileptic pregnant woman had the same malformation, and in the case of arachnoid cyst the pregnant woman with epilepsy also had the same malformation. The number of congenital malformations was only 3 in 168 cases (1.8%) with no genetic factors of epilepsy and congenital malformation. Disease cases: 10 epilepsy and/or febrile seizure cases, 1 case of sudden death within 6 months after birth, and a case each of autism, Down syndrome, and strabismus. In the strabismus case, we found the same disease in the husband of epileptic woman. There were genetic factors and chromosomal anomalies in 18 of the 25 cases with malformations and diseases including epilepsy (72%). This study showed that the occurrence of congenital malformations even without AEDs, and a high influence of genetic factors on the incidence of congenital malformations and diseases including epilepsy. Thus, the genetic factors should be taken into consideration for the offspring of pregnant epileptic women. Furthermore, considering that the incidence of congenital malformations is low in cases with no genetic factors, we should not fear the influence of medication. We should follow the fundamental rules that to use of monotherapy, proper quantities, and requisite minimum for the medical treatment of epilepsy.

View full abstract

Since 2001, Japan participated in the European Registry of Antiepileptic Drugs and Pregnancy (EURAP), a prospective observational study launched in Europe in 1999 by a consortium of independent research groups, and later extended to several other nations worldwide, with an aim to collect data on the risk of antiepileptic drugs (AED) during pregnancy. We report here the current data of the Japanese registry to EURAP. Two hundred and eighty-four pregnancies were enrolled. Generalized epilepsy in the mother accounted for 29.6% and partial epilepsy 64.8%. Folic acid was taken in 81.1%. Exposed to AED monotherapy was 65.2% and polytherapy 34.4%. CBZ (34.5%), VPA (33.3%), PHT (18.9%), PB (18.9%), LTG (11.6%), CZP (8.4%), ZNS (6.0%), CLB (5.2%) and LEV (4.8%) were the drugs mainly prescribed. There were 4.0% incidence of spontaneous abortions, 2.4% incidence of induced abortions and 3.7% incidence of major foetal malformations. The Japanese registry to EURAP will continue to collect data and welcome new referrals.

View full abstract

High frequency oscillations (HFOs) have been recently proposed as a potential new biomarker for locating epileptic foci. In addition, rhythmic spikes and post-spike slow waves (PSS) activity is associated with focal cortical dysplasia (FCD). Here, we report relationships between rhythmic spikes and PSS activity and scalp HFOs in three patients with epilepsy showing rhythmic spikes and PSS on scalp EEG. Two of three patients showed scalp HFOs, however, one patient did not. The scalp HFOs were observed on rhythmic spikes and PSS and, in one patient, were recorded even on slow waves. Electrodes with scalp HFO covered the almost same areas as FCD lesion on MRI. All patients underwent focus resection and postsurgical neuropathological diagnosis revealed FCD type II. Previous reports suggested that rhythmic spikes are associated with FCD type II. Our findings indicate that scalp HFOs spatiotemporally correspond to rhythmic spikes on scalp EEG, which suggests a relationship with FCD type II. We discuss scalp rhythmic spikes and scalp HFO in a typical scalp EEG setting.

View full abstract

[in Japanese]

View full abstract