Masakazu Seino

Multi-institutional study on the teratogenicity and fetal toxicity of antiepileptic drugs: a report of a collaborative study group in Japan.

Summary: A multi‐institutional collaborative study was conducted concerning the course of pregnancy and delivery and the incidence of abnormal infants delivered of epileptic women. Of 657 women receiving antiepileptic drugs, 73% delivered live infants, 14% had miscarriage or stillbirth, and 13% underwent induced abortion. In contrast to the above findings, 80% of 162 patients not receiving antiepileptic drugs delivered live infants and 4% had miscarriage or stillbirth. The latter outcome was significantly increased in the medicated patients. In this series, 63 (9.9%) of 638 live births were malformed, 55 (11.5%) being from medicated mothers and 3 (2.3%) from nonmedicated mothers. The incidence of fetal malformation in medicated mothers was thus five times as high as that in nonmedicated mothers. Cleft lip and/or palate and malformations involving the cardiovascular system were found frequently in the infants from medicated mothers. General background factors that might exert teratogenic effects on pregnant patients with epilepsy were studied, and the potential toxicity of antiepileptic drugs to the fetus was also analyzed. In this regard, consideration should be given to whether the patient has partial epileptic seizures, whether the patient herself exhibits any malformation, or whether her previous pregnancy resulted in an abnormal outcome. The incidence of fetal malformation was the highest (12.7%) in the medicated patients who had epileptic seizures during the pregnancy. It is presumed on the basis of the results of analysis of the data that a combination of more than three drugs and a daily dose greater than a certain minimal level is likely to produce malformed infants.

Antiepileptic effects of topiramate on amygdaloid kindling in rats.

We examined the antiepileptic properties of topiramate (TPM) in amygdaloid (AM) kindling in rats. Electrodes were implanted into the left AM of adult male Wistar rats. The animals were kindled at the after-discharge (AD) threshold. After the completion of kindling, the generalized seizure triggering threshold was determined. The drugs were administered intraperitoneally in animals which showed stable generalized convulsions at near-threshold stimulation. Intraperitoneal administration of TPM at doses of 25 mg/kg or more produced an anticonvulsive effect, but did not readily suppress limbic seizures. Complete suppression of AD was observed in only 3/8 rats at the highest dose of 200 mg/kg, which was not statistically significant. On the other hand, TPM at 100 and 200 mg/kg significantly delayed AM kindling. Thus, TPM showed modest therapeutic properties of conventional antiepileptic drugs in kindling model, those of TPM more closely resemble those of phenobarbital and the benzodiazepines than those of phenytoin and carbamazepine.

Recommendation of Early Surgery from the Viewpoint of Daily Quality of Life

Summary: We surveyed pre‐ and postoperative levels of satisfaction with a range of the daily quality‐of‐life (QOL) domains in 132 sets of epilepsy surgery patients and their families. All patients underwent resective surgery for temporal lobe epilepsy and were monitored for >2 years. Patient and family assessments showed patients’ overall QOL markedly improves after surgery, depending on freedom from seizures. However, factors such as social contacts, family relations, or financial status improved little. Some families and patients were not satisfied with the postsurgical status, despite freedom from seizures. Patients who had surgery at a later age were not so satisfied with their postsurgical status as were patients who had surgery at a younger age, particularly on the QOL domains of role activities, memory function, leisure activities, or emotional well‐being. This lower satisfaction level in older patients likely results from a variety of problems affecting patients during the long‐lasting epileptic process; social handicaps, psychologic conflicts, and deterioration of cognitive/behavioral functions. Based on each case, we recommend that investigations start at an early stage of the illness, so that surgical intervention may be considered as early as possible.

Clinicoelectrographic Concordance Between Monozygotic Twins with Severe Myoclonic Epilepsy in Infancy

Summary: Clinical features of a pair of monozygotic male twins, both with severe myoclonic epilepsy in infancy (SME), are described. They were almost completely concordant with respect to seizure onset, clinical seizure symptomatology, interictal, and ictal EEG expressions and seizure prognosis. The existence of such twins suggests the possibility that a genetic factor is determinant in the etiology of this particular epileptic syndrome.

Effects of Clobazam and Its Active Metabolite on GABA-Activated Currents in Rat Cerebral Neurons in Culture

Summary: Purpose: The antiepileptic effects of clobazam, a 1,5‐benzodiazepine, have been well documented in animal experiments and clinical trials. However, the drugs mechanisms of antiepileptic actions are still undetermined. The purpose of this study was to learn how clobazam and its active metabolite modulate γ‐aminobutyric acid (GABA)‐activated currents in rat cerebral neurons in culture.

Wavelength Dependence of Photoparoxysmal Responses in Photosensitive Patients with Epilepsy

Purpose: We tried to specify the relation between the photoparoxysmal response (PPR) and the wavelength spectra of flashing light in various photosensitive epileptic syndromes in the physiologic state.

Long‐Term Course of Childhood Epilepsy with Intractable Grand Mal Seizures

Abstract: Twenty‐nine children with childhood epilepsy characterized by frequent grand mal (generalized tonic‐clonic) seizures in spite of maximal doses of antiepileptic drugs and by an early onset of seizures (before 1:year of age) were followed up for more than 5:years. The children were divided into 3:groups: severe myoclonic epilepsy in infancy (SME), no SME, and intractable childhood epilepsy with generalized tonic‐clonic seizures (GTC). In all the 3:groups, the grand mal seizures persisted, whereas the other types of seizures tended to disappear as the patients aged, and the prognosis for mental development was poor. In the majority of cases in all the 3:groups, the waking grand mal seizures altered to sleep grand mal seizures with aging. Two pairs of monozygotic twins with SME suggested that genetic factors play a role in this epileptic syndrome. Intractable childhood epilepsy with GTC is distinguished by the absence of other types of generalized seizures. It cannot be regarded as an epileptic syndrome, but its pathogenesis and treatment require further studies.

Risks of occurrence of psychoses in relation to the types of epilepsies and epileptic seizures.

Abstract: The possible existence of the risks of occurrence of psychoses was examined in relation to the types of epilepsies and epileptic seizures. This study consisted of two investigations: 1) A study of 879 epileptic patients was conducted in which the incidence of psychoses in the different types of epilepsies was surveyed; the result was that the incidence in temporal lobe epilepsy was the highest, being relatively higher than that of other (non‐temporal lobe) partial epilepsies but not significantly different from that of generalized epilepsies. 2) A comparative study was carried out on 96 patients with temporal lobe epilepsy in which 48 were psychotic and another 48 were non‐psychotic which served as a control group. The differences of seizure symptomatology between the two groups were compared. The results were that the psychotic group was found to exhibit at a significantly higher rate generalized tonic‐clonic convulsion and compound seizure manifestations in comparison with the non‐psychotic group. The results appear to support the fact that generalizing mechanisms of temporal lobe epileptic manifestations are closely related to a physiopathogenic factor influencing psychoses.

Wavelength specificity of photoparoxysmal responses in idiopathic generalized epilepsy

Summary: Using optic filters, we analyzed the wavelength specificity of photoparoxysmal responses (PPR) in photosensitive patients with idiopathic generalized epilepsy (ICE). We specified the wavelength spectrum ∼700 nm (660–720 nm) as the only visible spectrum essential for eliciting PPR in some normal trichromat IGE patients and showed that any flashing lights containing this essential wavelength spectrum could elicit PPR independent of the number of stimulated cones. Absorption of the wavelength spectrum ‐700 nm by optic filters eliminated PPR in normal trichromat ICE patients. In an IGE patient with deuteranomaly, intermittent flashing lights containing a part of the wavelength spectrum from 580 to 700 nm elicited PPR. These data suggest a new interpretation of wavelength specificity of PPR: Flashing lights containing the wavelength spectrum that does not produce antagonistic cone interactions at the level of retinal ganglion cells can elicit PPR in some photosensitive ICE patients.

A Prospective WISC‐R Study in Children with Epilepsy

A prospective intraindividual study of WISC-R testing in the 45 children with epilepsy revealed that: 1) antiepileptic drugs, phenobarbital in particular, resulted in a detrimental effect on the WISC-R scores, 2) of the WISC-R subtests, vocabulary tasks of the verbal test were the most susceptible indicators in children whose FSIQ scores either improved or deteriorated, and 3) in children whose antiepileptic drug dosage remained unchanged while the seizure frequency remained unchanged, both the VIQ and PIQ scores decreased. It was evident that either recurrent seizures or inappropriate medication may exert a detrimental effect on intelligence as expressed by the WISC-R testing. In addition, the possibility that the underlying cerebral pathology associated with the etiology of epilepsy may play a role in a progressive intellectual deterioration was suggested.