Toshiaki Kugoh

Blood ammonia level during valproic acid therapy

Abstract: We determined the blood ammonia level of epileptic patients in relation to valproic acid (VPA) therapy. A total determination of 256 specimens obtained from 174 cases were analyzed. The materials were assigned to the following three treatment groups: (a) VPA‐monotherapy, (b) VPA‐polytherapy and (c) non‐administration of VPA. The distribution ranges of the blood ammonia level (μg/dl) were 40.5, 56.6 and 40.7 in mean, respectively. The VPA‐polytherapy group showed a significantly higher level compared with the other two groups. On the other hand, the latter two groups showed no difference. There was a positive relationship between the blood ammonia and VPA serum levels with statistical significance. In conclusion, a critical factor causing hyperammonemia seemed to be the multiple use of antiepileptic drugs including VPA.

GABA Levels in Cerebrospinal Fluid of Patients with Epilepsy

Abstract: The lumbar cerebrospinal fluid (CSF) γ‐aminobutyric acid (GABA) levels were measured in 27 patients with epilepsy, another three epileptic patients with status epilepticus and three epileptic patients with chronic cerebellar ataxia. The mean lumbar CSF GABA levels of the 27 patients with epilepsy were not significantly different from those of normal controls. Six of these 27 patients who had daily partial complex and partial motor seizures showed significantly low CSF GABA levels as did the six other patients, three each with status epilepticus and chronic cerebellar ataxia. These findings suggest that some epileptic patients have impaired brain GABAergic neurons.

A trial of discontinuation of barbiturates in patients with secondary generalized epilepsy.

Abstract: The vast majority of patients with secondary generalized epilepsy (SGE) were under polytherapy including barbiturates. We were able to completely withdraw barbiturates in 17 cases with a refractory course of SGE.

Simplification of antiepileptic pharmacotherapy: from the viewpoint of rational management for epilepsy

Abstract: Rational management for epilepsy was investigated mainly from the viewpoint of antiepileptic pharmacotherapy. At first, diagnoses were reviewed by the ILAE classification for epilepsies and epileptic syndromes in 603 patients who visited a newly‐established outpatient clinic for epilepsy and problems concerning the diagnosis of epilepsy were pointed out. Then, habitual pharmacotherapy in the past was assessed critically in cases where details of treatment before hospital attendance could be known. Further, the results of prospectively conducted simplification of pharmacotherapy where the appropriate choice of drugs and dosage were taken into account were reported. Furthermore, questions about the conventional criteria for drug effect evaluation were described and new criteria through which the influence on the daily life was also evaluated were presented. Finally, from the standpoint of comprehensive treatment, the system of rational management was discussed,

Kindling: Bilateral Interhemispheric Synchrony and Amygdaloid Kindling in Congenitally Acallosal and Corpus Callosum Bisected Mice

It is generally recognized that the corpus callosum (CC) has an important role to play in the development of kindled seizures. The first purpose of this study is to examine the role of CC in bilateral interhemispheric synchrony on cortical EEG of the normal, congenitally acallosal and artificial CC bisected mice. Moreover, we examined the role of CC in an amygdaloid kindling model. The congenital absence of CC was found to occur in some mice of the ddN strain in our laboratories.’

A Trial of Once‐Daily Administration of KW6066N for Patients with Benign Rolandic and Primary Generalized Epilepsy

KW6066N is a preparation of valproic acid (VPA) being intended to prolong the biological half-life by delaying the absorption velocity. The use of this preparation may enable to reduce the frequency of drug intake because the daily fluctuation of serum level in a steady state becomes theoretically small. In this study, we tested the once-daily administration of this drug in patients with benign rolandic epilepsy (BRE) and primary generalized epilepsy (PGE).

Pharmacodynamic Factors in the Occurrence of Psychiatric Symptoms among Patients with Epilepsy

Abstract: The frequency of the cases which showed the toxic levels and the relationship between the serum levels and mental symptoms were discussed on the basis of determination of the serum antiepileptic drugs. This was aimed at recognizing the effects of drug therapy in the appearance of some psychiatric symptoms in patients with epilepsy. The serum levels of folate and vitamin B12 were measured simultaneously to examine the relationship with some mental change. The direct cause‐and‐effect relationship could not be demonstrated between the serum levels and the mental symptoms.

Pharmacokinetic Analysis of a New Slow-Release Preparation of Valproic Acid (KW6066N)

The subjects were 10 healthy male volunteers aged 22.1 (mean) and weighing 64.8 kg (mean), of whom a health-check revealed no abnormalities. The study schedule was explained in detail and informed written consents were obtained. The subjects were divided randomly into two groups comprising five persons each. Each of them was given the slow-release and normal tablets both containing 200 mg sodium valproate at 9:OO a.m. (mean dose amount: 15.4 mg/kg) in a cross-over manner. The blood was sampled at 0, 2, 4, 6, 8, 10, 24 and 30 hr. after ingestion in the first group and at 0, 116, 216, 316, 1, 2, 3, 6, 10, 24 and 30 hr. in the other, taking into consideration of their pharmaceutical characteristics. Sera obtained were subjected in part for ultrafiltration to monitor the free levels. The drug level was determined using a gaschromatography and, with these values, the pharmacokinetic parameters as one compartment open model were calculated using a microcomputer program.

Level Dose Ratio and the Threshold of Intoxication Level by Dosages of Three Different Phenytoin Preparations

The subjects used were adult patients aged 15 or over, from whom 1,014 samples were obtained to determine the PHT serum concentration. The drugs used were confined to a 100 mg tablet (64 samples), fine powder (456 samples) and 20% parvule (494 samples) which are marketed by the same pharmaceutical company. Those samples obtained from patients with complications such as impaired hepatic and/or renal function were excluded. The blood was sampled under a steady state within 12 hours following the final dosage after the regularity of drug intake was confirmed. The serum level was determined according to the enzyme immunoassay or HPLC method.

A Variety of Clinical Symptoms in Children with Rolandic Discharges

Up to now functional partial epilepsy (FPE) has been regarded as a syndrome which focuses on the centro-temporal or occipital regions. There is no agreement about the fields involved in FPE. One cause seems to be the marked migration of electroencephalographic focuses and various changes in ictal symptoms. Here particularly atypical symptoms are analyzed and discussed in cases with rolandic discharges (RD) on EEG. Subjects and Methods