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The relationship between the phenytoin pharmacokinetics, expressed by the mean of the Michaelis-Menten equation and the CYP2C19 genotype was investigated in 16 Japanese epileptic patients treated with phenytoin. Between genetically (S)-mephenytoin poor and extensive metabolizers, there were no differences in the Michaelis-Menten parameters. But divided into genotype groups, Vmax values were 3.9 +/- 0.4, 5.3 +/- 0.7, and 5.7 +/- 1.4 mg/kg/day for the patients with the m2 allele, with the m1 allele, and with neither the m1 or m2 allele, respectively. In the patients with the m2 allele of CYP2C19, the Vmax value was significantly lower than in those without the m2 allele. It is possible that the m2 allele of CYP2C19 may be one of the factors of slow phenytoin metabolism, and its frequency may underlie the ethnic difference in phenytoin metabolism between Japanese and white individuals.

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Quality of life (QOL) research in epilepsy is a relatively recent development, but the field has expanded rapidly over the past 10 to 15 years. This expansion has seen the development of many tools with which to measure QOL in specific psychosocial domains and treatment settings. However, to date the initial development of these tools has been in English. Tools are also necessary to assess the QOL of people with epilepsy in non-English-speaking countries. These tools can be produced in two ways: by developing original tools in the language spoken in the country of use, or by translating and validating tools originally published in English. The latter approach has the advantages of being more rapid and allowing cross-cultural comparisons. We have completed or are in the process of translating into Japanese and validating three QOL assessment tools: the Washington Psychosocial Seizure Inventory, the Side Effects and Life Satisfaction inventory, and the Quality of Life in Epilepsy questionnaire. In this article, the results of this process are reported and cross-cultural comparisons using some of these tools are made. In this way, some of the problems associated with translating and validating QOL assessment tools are illustrated, and differences and similarities in the psychosocial impact of epilepsy in different countries are highlighted.

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Phenytoin pharmacokinetics in 18 of 126 Japanese epileptic patients were investigated using the Michaelis-Menten equation. Five of these (4% of total) patients, who showed significantly high plasma concentrations of phenytoin even when administered a relatively low daily dose of phenytoin, were classified as slow metabolizers; 13 of these, who showed lower plasma concentrations, were classified as normal metabolizers. Comparison of slow and normal metabolizers revealed that the maximum rate of metabolism, Vmax, differed significantly between the two groups, the borderline Vmax value between the two groups being approximately 4.5-4.8 mg/kg/day. The mean Vmax value of slow metabolizers was calculated to be 70% that of normal metabolizers. It is possible that one means of phenotyping slow and normal phenytoin metabolizers is by analysis of phenytoin pharmacokinetics, with estimation of Vmax values.

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Quality of life (QOL) must be determined from the patients' subjective viewpoint. To determine QOL in epilepsy, it is necessary to use disease-specific scales. We introduced the Side Effects and Life Satisfaction (SEALS) scale to Japan and performed a comparative study on adult patients with epilepsy and normal subjects. The results for patients with epilepsy were determined by the number of prescribed antiepileptic drugs (AEDs), the total dosage, and the type of epilepsy. Problems in patients with epilepsy were expressed by vertically crossing lines. A horizontal line expressed the severity of disease, and a vertical line expressed the psychosocial functioning. Therefore we cannot separate the severity and QOL when considering the influence of epilepsy disorders on individual patients. These two components compose the biphasic dimensions of QOL and thus are analyzed coincidentally. The concepts of QOL and comprehensive management in epilepsy are closely related, but the fundamental viewpoints are located at opposite positions. The former is based on the physicians' viewpoints and the latter on the patients' viewpoints. Although ideally these two concepts should be in harmony, they are in reality frequently dissociated. In comprehensive management, the treating physician must vigorously consider the influence of therapy on the patients' QOL.

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No reports of the Washington Psychosocial Seizure Inventory (WPSI) have yet been presented from Asian countries in detail. We performed a multiinstitutional study of this test in 652 Japanese subjects. The mean value of the Lie Scale was high, and only one third of our subjects were under the limit of the original criterion; this has been the biggest obstacle to use of the validity scales of this test in Japan. The profile form of the clinical scales was very similar to those reported from other countries. According to the relation between clinical characteristics and the WPSI scales, seizure frequency showed the strongest influence. In a comparison of whole subjects, mean scores of the clinical scales in Japan remained at an intermediate value or lower. This result was obviously distorted by the high score of the Lie Scale. When comparison was restricted to cases with valid Lie Scale scores, the values of five clinical scales showed high levels. Therefore, Japanese patients among developed countries apparently showed relatively severe levels of problems. We conclude that the WPSI could be a useful examination in Japan to determine reliably the various psychosocial problems of epileptic persons, but use of the Lie Scale according to the original criterion is not practical. Modifications of the limitation may be needed.

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A 62-year-old woman, who frequently had numbness seizures in the right half of her body, is reported. Weakness and consciousness disturbance did not occur during the seizure, and an abnormal electroencephalogram was not observed during the seizure or between seizures. The seizure was completely inhibited by a single-blind administration of phenytoin. It also disappeared on administration of carbamazepine, suggesting that the numbness seizures in this patient were of an epileptic nature.

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The plasma levels of urea and ammonia were examined in patients with primary generalized epilepsy, patients with partial epilepsy and in the first-degree relatives of these subjects. The results show a significant decrease in plasma urea in both groups of patients and their first-degree relatives as compared to the non-epileptic controls. The plasma ammonia concentrations were significantly higher in both groups of patients and in the relatives of generalized epilepsy patients as compared to the controls. The observed changes in plasma urea and ammonia were found not to be due to the effect of anticonvulsant drugs. The data suggest that a metabolic defect in urea synthesis may constitute one of the genetic components in the multifactorial etiologies of primary generalized and partial epilepsies.

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Plasma levels of glutamic acid and leukocyte glutamate dehydrogenase (GDH) activity were determined in patients with primary generalized epilepsy, patients with partial epilepsy and in the first-degree relatives of these subjects. The results show a significant increase in plasma glutamic acid in both groups of patients and their relatives compared to non-epileptic controls. The leukocyte GDH activity in the patients and the relatives was not different from controls. The data support a genetic basis for plasma glutamic acid increase in both primary generalized and partial epilepsy and are compatible with the multifactorial mode of inheritance of these disorders. This is the first study showing a familial plasma glutamic acid increase in epilepsy in a Japanese population.

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