This study was undertaken to examine the transplacental transmission of phenytoin (PHT) and its possible adverse effects on the fetal growth. The animals used in this experiment were 8-week-old female mice of the ICR-JCL strain. When 50mg/kg of body weight of PHT was administered orally to mothers with chow, maternal serum levels of PHT were the lowest at noon and highest at midnight. The concentration of PHT in serum showed a close correlation with each dose increment, when blood was drown at a certain time. Serum levels of PHT in the fetus were about 80% of those in maternal serum on day 18 of gestation. The differences in serum levels of PHT between the fetuses and their mothers were attributed to the differences in levels of albumin-bound PHT, and the level of albumin- free PHT in the fetuses were almost same as that in their mothers.

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This study was undertaken to examine the transplacental transmission of phenytoin and its possible adverse effects on the fetal growth. When pregnant mice were fed with the chow containing various doses of PHT from 14 days before mating until the 18th day of gestation and then they were sacrificed, PHT concentrations in the fetal brain, liver, kidney and amniotic fluid increased steadily with each increment of mate rnal serum concentration and correlated well with maternal serum PHT. The abortion ratein the experimental groups increased steadily with each increment of PHT dosage. The body length, bodyweight, and contents of DNA and RNA in the brain of experimental groups were significantly lower than those in the controls. The incidence of cleft palate increased steadily in the experimental groups with each increment of PHT dosage.

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This study was undertaken to elucidate the effects of phenytoin given transplacentally on the neurofunctional and biochemical maturation of the offspring after birth. In the experimental group, a lag of 1 or 2 days in the disappearance of the primitive reflexes and also in the development and maturation of the acquired reflexes was recognized. The activity of 2', 3'-cyclic nucleotide 3'-phosphohydrolase in the brain of the experimental group was significantly lower than that in the control group at 1, 2 and 3 weeks of age. This result indicates that the inhibition of myelination in the brain stem and cerebrum may be one of the causes of delayed maturation of reflexes in the experimental group.

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Serial MRI and X-ray CT scans were performed on a one-year 7-month old girl with Reye-like syndrome.
X-ray CT scan revealed marked hemispheric brain edema in the acute stage and moderate ventricular dilatation with diffuse low density area and cortical atrophy in the chronic stage. MRI performed in the chronic stage showed marked progressive changes. Linear high intensity areas were demonstrated on T₂ weighted MRI performed 21 days after the onset. These high intensity areas increased gradually and 60 days after the onset these high intensity areas spread to the grey matter. These high intensity changes seemed to be correspond to cortical necrosis, and those in the white matter to gliosis or degeneration of myelin.

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In order to clarify the neural mechanisms that contribute to the age dependency of epileptic seizures in ADEE, we examined sleep structures in four patients before and after administration of haloperidol (HAL) or L-DOPA. Case 1 suffered from tuberous sclerosis and developed West syndrome at 5 months. At 2 years tonic seizures developed and HAL administration at 14 years caused reduction of seizures for one month. Case 2 suffered from neonatal seizures. At 8 years he developed Lennox syndrome and also showed the sleep-wake rhythm disturbance followed by an increase of epileptic seizures. At 14 years, HAL was administered in addition to anticonvulsants, and seizures decreased for 2 months. Case 3 was born with asphyxia and developed West syndrome at 10 months. At 8 years tonic spasms and tonic seizures started. The seizures disappeared for one month by the administration of HAL at 14 years. Case 4 suffered from tuberous sclerosis. She developed West syndrome and Lennox syndrome at 10 months and 5 years, respectively. The seizures were improved by administration of L-DOPA at 10 years of age.
Polysomnographical examination was performed before and after administration of HAL or L-DOPA. Body movements (BM) were classified into two types; gross movement (GM) involving the body trunk and lasting for more than two seconds, and twitch movement (TM) localized in one muscle on surface EMG recordings and lasting less than 0.5 second.
The frequency of TM of mentalis muscle during sleep in cases 1 and 3 was high, and it decreased to the control level by HAL administration. In contrast to this, the frequency of GM and TM was low in Case 4, and TM increased after L-DOPA. Our previous study revealed that in ADEE the frequency of BM was low during early childhood and paradoxically increased thereafter. The present study confirmed that a dopamine antagonist suppressed the paradoxical increase of TM in ADEE and decreased seizures. In contrast, the administration of HAL before this paradoxical increase rather enhanced the seizure activity while the administration of L-DOPA showed beneficial effects.

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Neuron-specific enolase (NSE) is expected as a marker in evaluating the prognosis of infections of central nervous system (CNS). Sequential examinations of NSE in cerebrospinal fluid (CSF) and serum were performed in eight children with rubella infection of CNS. Seven children developed acute encephalitis, and one developed acute cerebellar ataxia. NSE activities in CSF and serum from normalcontrol children were less than 9.1ng/ml and 12.4ng/ml, respectively. Seven patients recovered well, and NSE activities in CSF never increased more than 40ng/ml during the first five days of illness. However, in one patient, who sustained minor psychological problems such as hyperactivity, NSE in CSF increased upto 65ng/ml. In the convalescent state, NSE in CSF slightly increased up to 20ng/ml in many cases. On the other hand, NSE in serum never increased beyond the value of 20ng/ml in any cases.
NSE in CSF would be a useful marker in patients during the active stage of rubella infection of CNS for evaluating the degree of neuronal damage and also for prognosis.

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Clinical, neuropsychological and electroencephalographic studies were performed to investigate an atypical pervasive developmental disorder (APDD). Among 134 children with communication disorders 52 children, aged 1 year 10 months to 8 years and 10 months, were classified into APDD according to the classification of DSM-III. They showed autistic behavior and reaction, but did not show either total lack of responsiveness to other people or gross deficits of language development. Many children showed good prognosis. It was especially remarkable that 37 cases showed precocious word reading from 2-3 years of age. Although many children showed disorders of auditory closure function, auditory association function and visualmotor skills contrary to excellent skills of auditory sequential memory by neuropsychological studies. The patchy defects disappeared and IQ scores were markedly increased with age. The EEG showed normal development of the background activity in many children, and the incidence of seizure discharges was 34.6%(18cases). The children with a communication disorder who show both precocious word reading and good prognosis may constitute a clinical entity entirely separated from infantile autism or hyperlexia.
We propose that this peculiar type of communication disorder should be called as benign hyperlexia.

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To elucidate the relationship between cerebral blood flow and metabolism in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes), positron emission tomography (PET) was carried out in two patients who were diagnosed as having MELAS based on the clinical course, laboratory data and muscle biopsy findings. Using the HEADTOME-III, cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMR0₂), oxygen extraction fraction (OEF) and cerebral metabolic rate of glucose (CMRG1u) were measured quantitatively in 26 regions of interest located in the cerebellum, brainstem, thalamus, basal ganglia and cerebral cortices. The values obtained from young adult volunteers served as a control for the PET studies. Case 1 is a 13-year-old boy who has been showing physical and intellectual deterioration since he was 5 years old. He has had repeated headache, episodic vomiting and convulsive seizures for 3 years. He showed a short stature, generalized muscle wasting and weakness. Ragged-red fibers were confirmed upon biopsy of the quadriceps muscle. Case 2 is a 12-year-old boy who has been showing a normal physical and mental development until he experienced frequent attacks of homonymous hemianopia accompanied by headache, episodic vomiting and Jacksonian seizures. Low density areas appeared on CT alternatively in the territories of the posterior cerebral arteries but no occlusive lesion was detected on angiogram. Biopsy of the quadriceps muscle showed ragged-red fibers. In both cases, CBF was higher than the control values in the cerebral cortices, whereas CMRO₂ was markedly reduced in almost all regions; OEF was much lower than the control values in all regions. By contrast, CMRGlu was relatively preserved in the cerebral cortices. The reduced oxygen metabolism was considered to be primarily associated with breakdown of aerobic glycolysis due to the mitochondrial dysfunction. The relative luxury perfusion syndrome, a hyperemia out of proportion to the oxygen metabolism, might be related to vasodilation due to the lactic acidosis.

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A case of 5-year-5-month-old girl with diploid/tetraploid mosaicism was reported. Physical examination revealed shortness of stature and low weight for age, microcephaly, hypertelorism, low set ears, cleft palate, micrognathia, clinodactyly of and single crease on fifth digits, and equinovarus of right lower limb. Neurological examinations showed no abnormal sign except internal strabismus. Electroencephalography demonstrated sharp waves in the right temporal area, but no epileptic seizure had appeared. Gyral anomaly to be considered agylia and dilatation of lateral ventricle were shown in cranial CT examination. Agenesis of cerebeller vermis was suspected in that CT. Her mental development was assessed longitudinally by a developmental test for infants, and the result was discussed. The feature of her development were as follows, 1) Severe general retardation of mental development was seen. 2) Development of language, especially of speech was most severely retarded. 3) Though slowly, her mental development was still in progress. Intensive approaches were required to promote her mental development.

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The Fukuyama type congenital muscular dystrophy (F-CMD) has been generally recognized as a well delineated subgroup of progressive muscular dystrophy with uniform clinical and pathological features. But the pathogenesis is not yet clear. Two theories have been proposed autosomal recessive inheritance and intrauterine infection.
We experienced a female case of F-CMD, and tried serial brain CT scanning from thebirth to one year of age. Low density changes of white matter were not found at the first day of her life. But marked brain atrophy and low density changes of white matter were found after three months.
We propose that CT examination should be repeated from early stage to clarify the pathogenesis of F-CMD.

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We encountered a girl, 7 years and 3 months old, with nemaline myopathy suffering from severe respiratory insufficiency during sleep, which necessitated for her frequent emergency admissions to our hospital to receive rescue resuscitation by means of artificial respiration. When a negative pressure- controlled chest respirator, commercially available in the U. S., but not in our country, was used for this patient, favorable clinical effects were obtained, and no further emergency admission was necessary. The girl is at present under treatment at her home. The respirator of this type is quite useful for patients with neuromuscular diseases associated with chronic respiratory insufficiency.

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We reported a case of cystinuria with delayed psychomotor development. According to oral cystine and lysine loading studies in the patient and his parents, we estimated that he was the double heterozygote of type I-III. The relationship between cystinuria and delayed psychomotor development was unclear. The disturbance of active transport in placenta or brain may have caused the deficiency of essential amino acids and consequently delayed psychomotor development, because cystinuria has been known as an inheritable disorder of cystine and dibasic amino acids affecting the epithelial cells of the renal tubules and the gastrointestinal tract.

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[in Japanese]

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