Two preparations of Phenytoin PHT, PHT Na (mean particle size 260μ) and free PHT (mean particle size 24μ) were administered to nineteen epileptic patients.
Serum levels of PHT were measured gaschromatographically by the Solow method.
In fifteen patients, free PHT was given orally for a twoweekperiod and then PHT Na of the same dose was given for another twoperiod after an interval of two weeks without medication. The mean values of the serum levels on 9th, 11th and 13th day of each respective period were calculated, and then compared in each patient.
In one patient, PHT Na was initially administered for a week and then, the preparation were changed to free PHT. In this case, the mean values of the serum levels obtained on 5th, 6th and 7th days, 10th, 14th and 21th days after the initial administration were compared.
In three other patients already on free PHT, PHT Na was started after PHT serum levels were measured three times.In these cases, serum levels of PHT were measured at least five days after PHT Na administration was started.
A significant increase in the serum levels of PHT following PHT Na administration was found in only two out of nineteen cases. However, four cases showed a significant decrease of PHT serum levels.
These data suggest that the sodium salt of PHT is not superior in bioavailability than the free PHT.
This result is differnt from those in the previous reports. This fact may be attributed to the particle size of PHT Na which is larger than the size of PHT Na reported in the foreign literature.

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In order to elucidate the mechanism of brain damage caused by neonatal asphyxia in human being, we studied protein metabolism of rat brain in hypoxia at the neonatal asphyxia.
The rats were devided into the following three groups.
Group A matureasphyxiated rats and mature-control rats. The caesarean section was carried out immediately after the first baby was delivered by natural birth, and the uterus containing fetuses was isolated from the mother, and fetuses were left in the uterus for a certain period under the asphyxic condition without suppling oxygen at room temprature. Then the fetuses were removed from the uterus to be respired.Non treated rats were called the maturecontrol rats.
Group B prematureasphyxiated rats and prematurecontrol rats. The section was carried out at 3-6 hours before the expected time of natural birth, and uterus was isolated from the mother. Half of the fetuses were left in the uterus under the asphyxic condition for 10min, then they were removed from the uterus to be respired. The other half were removed from the uterus as soon as possible so as to respire immediately. The latter group was called the premature-control rats.
Group C lowprotein asphyxiated rats and lowprotein control rats. Pregnant rats were fed by 9% protein diet, then they were treated in the same way as in group A for asphyxiation. Non treated Iow protein rats were called the low-protein control rats.
1) The rates of C14-leucine incorporation into the proteins of the brain were measured with 3day-old rats. The rate in the group A did not change even when asphyxic condition was pro-longed up to 30min, but the ones in groups B and C were significantly lowered. In fact, the average half life of the proteins in group B was found to be prolonged remarkably, when C¹⁴-leucine and C¹⁴-lysine were applied.
2) In order to study whether the observed impairment of protein metabolism was due to the reduced energy reserve, the concentrations of ATP in the brain were measured. In groups A and B, there was found no significant difference in the ATP levels between control and asphyxiated group when measured at 16 min and 3 hours after birth. On the other hand, the level was significantly lowered in the asphyxiated rats in group C when measured at 16 min after birth.However, this difference was minimizid by restoring the ATP level in the asphyxiated rats, when measured at 3 hours after birth.
3) In control experiment it was found that the ATP level in group C was significantly lower than that in group A when measured at 3 hours after birth. There is a general agreement that immature animals have high resistance to anoxia, which was confirmed also in the group A experiment of this study.However, the animals born prematurely or malnoulished during the fetal period were more vulnerable to neonatal asphyxia in view of protein metabolism.

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Cerebral angiography is an essential diagnostic procedure in the evaluation of various intracranial vascular diseases. However, catheter cerebral angiographies for neonates and infants are usually neglected because of the technical difficulties and possible occurrence of side effects. In the past two years, selective cerebral angiography via femoral artery catheterization has been performed on 51 cases of neonates and infants with body weight under 10kg in our service. Under general anesthesia, small skin incision was made at the right inguinal region and the right femoral artery was dissected out. Then the catheter was introduced into the exposed femoral artery after systemic heparinization. The dosage of heparin was decided according to the body weight of the patients. Average dosage was approximately 1/mg/kg bodyweight. Polyethylene catheters (Becton Dickinson, Formocath 7620-736) were used, and the tip of the catheter was slightly curved as just like“J”or“S”shape. Under image fluoroscopy, the tip of the catheter was guided through the arch of the aorta and the brachiocephalic artery, then into the right com-mon carotid artery. Three to 5ml of 60 percent Conray was then injected by the auto-injector (Toshiba CIJ-I) with 2-4kg/cm pressure. Successively the top of the catheter was inserted into the left common carotid artery and the left vertebral artery.
After the procedure, Z-suture of the extima at the site of the insertion of the femoral artery was carried out with a nylon yarn (8-0) and thus hemostasis after the withdrawal of the catheter was made. In such a way satisfactory 3 vessel studies were perfomed on 24 cases. Furthermore, we obtained successful results in 43 cases out of 46 cases (93%) when angiography of the vertebral artery was intended. No neurological deficit resulted from the angiographic studies nor were there serious local complications from the femoral artery punctures. In one boy, 11 months old, transitory cardiac arrest for about 1 minute occurred after the left vertebral angiography. This episode was transient and the patient recovered completely. It can be concluded that tansfemoral catheter cerebral angiography is a choice of method in the neonates and infants.

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Age-dependent epilepsy in infancy is composed of infantile spasms and earlyinfantile epileptic encephalopathy with suppression-brust (E. I. E. E.). In this study, occurrence time and analysis of clinical seizures of this epilepsy during sleep and wakefulness were examined electrophysiologically by means of overnight sleep polygraphy. Two cases of infantile spasms (Case 1, Case 2) and one case of E. I. E. E. were studied. The polygraphic recordings were performed on each subject on the first night. The second overnight sleep polygraphy was conducted when the clinical seizures in Case 2 and the case of E. I. E. E. increased.
The clinical seizures in the cases of infantile spasms occurred shortly after awakening. In Case 1, the same EEG findings and eye movements as in the clinical seizures were observed during REM sleep without any apparent clinical seizures. The clinical seizures in the case of E. I. E. E. occurred more frequently during NREM sleep than during wakefulness and REM sleep. After the ceasing of clinical seizures, the state transfered mostly to REM sleep or wakefulness. The ictal EEG in the cases of infantile spasms showed hypersynchronous activities. The ictal EEG in the case of E. I. E. E. exhibited synchronous bursts of high voltage slow waves mixed with spikes, and the EEG before and after clinical seizures showed flattening of the trace.
In the next place, the series of spasms in each subject were examind and the results were as follows: the duration of the spasm in the cases of infantile spasms was about 1 second and the interval between the spasms was 3 to 10 seconds. Usually the duration of spasm in the series became longer gradually and then reached a constant level, and became shorter gradually towards the end. But in a few series of spasms in case 2, the duration of spasm was the longest at first and became shorter gradually towards the end. In most series of spasms, the interval between spasms became shorter when the duration of spasm became longer and it became longer when the duration of spasm became shorter. The mean duration of spasm in the case of E. I. E. E. was 5 to 7 seconds and mean interval between spasms was about 20 seconds. In the case of E. I. E. E., the duration of spasms in the series had no constant trend but the interval between spasms became shorter towards the end. In addition, the duration of spasm and the interval between spasms in the case of E. I. E. E. were more irregular than those in the cases of infantile spasms.

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Myelography, ventriculography and CT cisternography with metrizamide was performed in thirty-two children, aged nine days to seven years, at fourty-six occasions. Twenty-one patients were less than twelve months of age.
The lumbar and cervical myelography was performed in fourteen children for evaluation of spinal disorders. Metrizamide was injected by lumbar puncture in different concentrations (114-197 mgI/ml, 3-8 ml) depending upon the body weight of the children and site of interest. The higher concentrations were preferred for examination of the cervical myelography.
Ventriculography was done in six children. The needle was introduced into the lateral ventricle through the lateral angle of the anterior fontanel. A small amount of high concentration metrizamide (114-197 mgI/ml, 2-8 ml) was used. During TV fluoroscopy, the contrast medium was injected. The third ventricle, aqueduct and fourth ventricle were opacified selectively.
CT cisternography was carried out in twentythree children. Metrizamide was injected via lumbar route (98-197 mgI/ml, 3-9 ml). Computed tomography was performed after 1, 3, 6 and 24 hours (48 hours, if necessary) for evaluation of cerebrospinal fluid dynamics.
Adverse reactions were mild and transient (3 patients with headache, 4 with vomiting and 5 with fever). Neither significant alterations occurred in the vital signs, nor severe complications were encountered in this series. In eleven cases cerebrospinal fluid analysis was done before and after the study. A mild increase of cerebrospinal fluid white cell counts and protein content was noted in five cases.
Metrizamide is well suited for radiological contrast study of cerebrospinal fluid spaces in children.

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A 13-year-old girl of idiopathic polyneuritis with ophthalmoplegia, ataxia, and areflexia (Fisher's syndrome) was reported. Nine days be-fore admission, the patient had a two-day history of mild fever, sore throat, and nasal discharge. Two days prior to admission, she noted double vision, dysarthria, unsteadiness on walking, and numbness of both hands and feet. On admission, she was husky and flushed, and showed, bilateral ptosis. Neurological examination revealed a symmetrical external ophthalmoplegia. The eyes were immobile, and only medial movement was preserved. There was impaired vibration sense of extremities, but little motor wakness. Ataxia seemes to be of a cerebellar type, because dysmetry and adiadochokinesis were also noted. Deep tendon reflexes were absent. The optic disc was normal, and visual activity was not impai-red. Mental status was normal.
The albuminocytologic dissociation in the cer-ebrospinal fluid was first noted on the 18th day after onset, and continued until the 74th day. EMG showed a neurogenic pattern in the muscles of lower extremities, but nerve conduction velocity was normal.
Difficulties in swallowing necessitated infusion and tube feeding for 35 days. She was treated with prednisone 40mg per day starting on the second hospital day. On the 35 th day, truncal ataxia and dysarthria disappeared. On the 43 rd day, there was no sensory paresis. Mild abducens nerve palsy and areflexia were persistent until the 100 th day, but after then, both were gradually improved to complete recovery. No relapse has been noted for more than 2 years.
The review of 60 cases of Fisher's syndrome in the literature revealed there are 22 cases under 15 years of age. As the differential diagnosis, Guil-lain-Barre syndrome, brain stem encephalitis, and acute cerebellar ataxia should be listed, all of which more or less resemble Fisher's syndrome with regard to pathogenesis and prognosis. Fisher's syndrome can be considered clinical entity characterized by total external ophthalmoplegia (45/57), severe ataxia (60/60), areflexia (60/60), and rare relapses (2/60). It is not a common disease, but a relatively high incidence in children should be stressed.

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A case of 3year-old boy with recurrent polyneuropathy was described. The initial attack disappeared about three months after the onset of the symptoms with corticosteroid treatment. However, he had weakness and gait disturbance two months after the discontinuation of the treat-ment.
Sural nerve biopsy performed before the readministration of corticosteroid revealed the loss of large myelinated fibers, the neuronal fibrosis, the appearance of macrophages, and the initial stage of onion-bulb formation.
Since one week after the readministration of corticosteroid, he was able to walk with support and his other neurological symtoms disappeared gradually. The corticosteroid was discontinuated five months later. Thereafter he has had no neurological symtoms till now.

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A case of hypoglycemia associated with ketosis and overt CNS abnormalities was reported and the significance of such association was discussed with regard to the pathogenesis of hypoglycemia. A boy aged 4 years and 1 month on admission showed severe psychomotor retardation, epilepsy, large and long head, multiple minor anomalies, generalized hypotonia, hyperelasticity of joints and skin, horizontal nystagmus and radiologically enlarged cavum septi pellucidi. He suffered from several attacks of fasting ketotic hypoglycemia in the past and was also reported to have had a transient hypoglycemia in the neonatal period. A significant drop of blood sugar, ketonuria and characteristic clinical signs and symptoms of hypoglycemia were provocated by ketogenic diet loading test as described by Colle and Ulstrom. There was no response of blood sugar to glucagon administration after 19.5 hours of the provocative diet.
The findings described above can satisfy the conventional diagnostic criteria of “ketotic hypoglycemia” reasonably well.However, there were some additional clinical and biochemical features in this patient.He had profound psychomotor retardation and multiple congenital anomalies including brain midline anomalies, and meticulous endocrinological loading tests such as insulin loading test, glucagonpropranolol test, arginine test, l-DOPA test, metyrapone test revealed hyporesponsiveness of pituitary gland to secrete growth hormone and ACTH.The authors concluded that in this case the cerebral impairment of prenatal origin contributed to the neonatal hypoglycemia and the later recurrence of episodes of hypoglycemia associated with ketosis through the hypothalamopituitary dysfunction under some stressful conditions.

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We have described a 6-year 7 month-old girl with hyperammonemia due to ornithine transcabamylase (OTC) deficiency accompanied by decreased activity of carbamyl phosphate synthetase (CPS).
Her illness was characterized by reccurent episodes of vomiting and irritability at night since 4 years and 11 months of age. Hyperammonemia, orotic aciduria and high serum glutamine level were observed. The enzyme assays of the biopsied liver tissue revealed that the activities of OTC and CPS wrer markedly deficient (OTC and CPS are 2.5% and 5% of the control values, respectively), but kinetic and physical properties of OTC were normal.
The combined deficiency of OTC and CPS is very rare and this report may be useful for the several problems of OTC deficiency. Treatment with oral amino acids and low protein diet according to protein score and adequate caloric intake has been successful for the control of clinical symptoms and hyperammonemia in this case.
The patient is 7 years old at present and has apparently normal psychomotor development.
The mother showed heterozygous carrier according to the ammonia loading test.

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A one-year and two month old boy with infantile spasms was treated with 0.5mg/day of adrenocorticotropic hormone (ACTH) for twenty nine days. A seven-month old girl of tuberous sclerosis with infantile spasms was treated with 0.25 mg/day of ACTH for fourteen days. Electroencephalographic and computed tomographic examinations were carried out before, during and after the treatment.
The abnormal pattern of electroencephalogram was markedly corrected, while remarkable cerebral atrophy was observed immediately after the completion of the therapy.
Cerebral atrophy was slightly recovered after one or two months. It is suspected that adrenocorticotropic hormone affected the recovery of electroencephalography but caused the atrophy of infant's cerebrum.

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