Kiyoshi Hosokawa

Depression Antedating the Onset of Parkinson's Disease

Abstract: Neurological and depressive symptoms in a subtype of Parkinsons disease (PD), in which a depressive state precedes the clinical manifestation of neurological symptoms, were examined on the basis of clinical observations for 3 years or more. PD, in which depression preceded, was different from PD with preceding neurological symptoms, in the severity of not only neurological but also depressive symptoms. These results suggest that PD in which depression precedes neurological symptoms is a specific subtype of PD. It was speculated that the differences in clinical symptoms might be due to a biological background, in particular the dopaminergic system.

Spike‐Wave Stupor

Five cases of spike‐wave stupor are presented. One case occurred in association with cerebrovascular disease and another in association with the Vogt‐Koyanagi syndrome. A third case had repeated episode of spike‐wave stupor as the only sign of a seizure disorder. A fourth case was characterized by behavior quite similar to catatonic schizophrenia and was so diagnosed. These atypical cases are contrasted with a case more typical of petit mal status as reported in the literature. Thus while spike‐wave stupor is usually superimposed on a chronic centrencephalic seizure disorder, it must be recognized as a syndrome that can arise from a variety of etiological mechanisms. Detailed clinical and EEG investigation is necessary for an understanding of the mechanisms involved in any individual case.

A Female Case with the Kleine‐Levin Syndrome and Its Physiopathologic Aspects

Abstract: A female case with the Kleine‐Levin syndrome (KLS), which first occurred at the age of 19, was discussed in relation to the following four characteristics: 1) a female case, 2) a loss of memory and the appearance of slow waves in the pathosis, 3) the abnormal pattern of growth hormone (GH) secretion during sleep in the pathosis, and 4) a prolonged latency between the peaks of III and V in the auditory brainstem response (ABR) in both the pathosis and nonpathosis. These characteristics may suggest that there is a slight disturbance of consciousness in the pathosis, and that there is a functional disturbance in the hypothalamus.

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.

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).

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.