[Importance of measuring blood level of lamotrigine for optimum dosing schedule].

OBJECTIVE: It is sometime difficult to achieve effective blood levels of lamotrigine (LTG) by the methods of administration presented in the product labeling (PL). We highlighted the importance of measuring LTG blood levels, and proposed a method of adjusting the optimum dosage of LTG based on the pharmacokinetic interaction. METHOD: Four types of maintenance dose of LTG were determined whether LTG was administrated in combination with valproate sodium and/or enzyme-inducing antiepileptic drugs or with agents except for them. This method is compared with the method presented in the PL. We exhibited the clinical course of three patients who took LTG according to our method since the blood levels were not elevated enough by the method shown in the PL. RESULTS: The maintenance dosage described in the PL was lower than that in our methods. The blood levels in these three patients were increased enough to be effective after the therapy by our method. CONCLUSIONS: Measuring the LTG blood level is important to create an optimum dosing schedule. Since the maintenance doses of LTG presented in PL may be inappropriate, they should be adequately adjusted by reference to the LTG blood level.

[Characteristics of women with epilepsy who developed polycystic ovary syndrome owing to the therapy with valproate sodium].

OBJECTIVE: The purpose of this study was to assess the characteristics of women with epilepsy who developed polycystic ovary syndrome (PCOS) owing to therapy with valproate sodium (VPA). METHODS: Our study comprised 77 patients on therapy with VPA--20 patients with PCOS and 57 without PCOS (control group). We assessed their epilepsy type, status of seizure control, and mental and physical statuses as well as the starting age, administration period, total dosage, and the highest value of blood concentration of VPA. RESULTS: As compared with the control group, the PCOS group showed significantly high rates of association with mental retardation, severe physical disabilities, and poor seizure control, and symptomatic generalized epilepsy. However, the starting age, administration period, total dosage, and the highest value of blood concentration of VPA were not significantly different between the 2 groups. Nineteen of the 20 patients with PCOS had characteristically high androstenedione levels. CONCLUSIONS: Our study demonstrated that refractory symptomatic generalized epilepsy, polypharmacy including VPA and severe motor and intellectual disabilities are risk factors of developing PCOS.

Clinical and radiological features of Japanese patients with a severe phenotype due to CASK mutations.

Heterozygous loss of function mutations of CASK at Xp11.4 in females cause severe intellectual disability (ID) and microcephaly with pontine and cerebellar hypoplasia (MICPCH). However, the longitudinal clinical and radiological course of affected patients, including patterns of postnatal growth, has not been described. Neurodevelopmental and imaging information was retrospectively accrued for 16 Japanese (15 female and 1 male) patients with ID and MICPCH associated with CASK mutations. All records were analyzed; patient age ranged from 2 to 16 years at the time of the most recent examinations. The growth pattern, neurological development, neurological signs/symptoms, and facial features were similar in the 15 female patients. Their head circumference at birth was within the normal range in about half, and their height and weight were frequently normal. This was followed by early development of severe microcephaly and postnatal growth retardation. The patients acquired head control almost normally between 3 and 6 months, followed by motor delay. More than half of the female patients had epilepsy. Their MRIs showed microcephaly, brainstem, and cerebellar hypoplasia in early infancy, and a normal or large appearing corpus callosum. The male patient showed a more severe clinical phenotype. These uniform clinical and radiological features should facilitate an early diagnosis and be useful for medical care of females with ID and MICPCH associated with CASK mutations.

[Short-term and long-term efficacy of topiramate in refractory generalized epilepsy of children].

Topiramate (TPM) was administered to 25 children with intractable generalized epilepsy. A > or =50% decrease in seizure frequency was observed in 56% and 45% of children at two months and one year after initiation of TPM therapy, respectively. However, efficacy of TPM for Lennox-Gastaut syndrome was low. TPM therapy was discontinued in five of 25 children at 3-5.5 months due to lack of efficacy or aggravation of seizures. No serious adverse effects were observed during TPM therapy. The present study revealed that TPM has clinical efficacy in the treatment of children with intractable generalized epilepsy.