In the previous study (Fukuyama et al: Neuropaediatrie 8: 224, 1977) 185 cases of infantile spasms during the period between May, 1968 and March, 1972 were analized clinically. In this report the authors evaluated the role of immunization as an etiological factor in infantile spasms in 199 cases seen at the Tokyo Women's Medical College between April 1972 and March 1977.
Twenty-two patients were selected who developed seizures of infantile spasms within 30 days after immunization. The causal relationship could be suspected most reasonably in the patients with (1) no apparent causal factors other than immunization, (2) normal psychomotor development prior to immunization, and (3) the onset of seizures within 48 hours of immunization with DPT vaccine, after 4 to 18 days with smallpox, polio or BCG vaccine. Two cases were found to satisfy the conditions described above, after oral polio vaccine and BCG inoculation respectively. These vaccines have been known to be least toxic neurologically.
The 1975 revision of the Japanese immunization law effected the changes that DPT vaccine should not be given to childern under two and smallpox vaccine to those under three years of age. But in spite of changes in the vaccination program, the age distribution of the onset of infantile spasms did not change at all.
It was concluded that there was no postitive evidence of causal relationship between immunization and infantile spasms.

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This repot is based on 30 cases with typical absence, which were followed for more than three to fifteen years at the Department of Pediatrics of Keio University from January 1963 to December 1975.
Typiaci absence was defined as follows: The attacks were characterized by a sudden and brief disturbance of consciousness lasting 5-20 seconds without aura and postparoxysmal symptoms, either with or without minor motor, automatic and automic components, accompanied by diffuse rhythmic 3 c/sec spike-wave discharges in EEG during the attacks. The termination of the attacks was abrupt and the attacks occurred frequently.
The cases with typical absence during the period of observation totalled forty-five, but there were 33%(15 cases) of drop-outs.
Of the 30 cases, 12 (40%) were male and 18 (60%) were female. The onset of the illness occurred mostly between the fourth and ninth years of life. Their ages at the time of this report varied from seven to 26 years.
Twenty-one (70%) were not preceded by other epileptic seizures, while 9 cases (30%) suffered grand mal of febrile convulsions prior to the onset to typical absence. Transformation of clinical seizures, mental outcome and electroencephalographic findings during the follow-up were studied.
The results were summarized as follows:
1) Of all 30 patients who had ceased to have attacks of typical absence at the follow-up study, 27 (90%) were seizure-free for more than two years, whereas other three cases were seizur-free for less than two yeasrs. Other epileptic seizures including grand mal were never seen at the time of follow-up.
2) Twenty-nine cases (97%) had normal I. Q. and only 1 case (3%) had mild retardation at the final examination.
3) Four types of the transformation of generalized spike--wave discharges during follow-up studies of the interictal EEG recordings in 30 cases were observed, i. e., (a) 3 c/sec spike-wave discharges subsequently disappeared (40%), (b) 3 c/sec spike-wave discharges were transformed into fast or irregular spike-wave paroxysms, afterward these patterns persisted or disappeared (47%), (c) 3 c/sec spike-wave discharges were still present (6.6%) and (d) fast or irregular spike-wave discharges persisted or disappeared (6.6%).
There was no significant difference in the mode of transformation of generalizedspikewave discharges, between male and female, between presence and absence of febrile convulsions or grand mal in past history, between early and late onset of typical absence, and between short and long duration of attack of typical absence.

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Twenty-seven patients with infantile spasms were investigated by brain CT for the assessment of the prognosis of infantile spasms. Fifteen cases were male and 12 female. The ages were between 4 months and 9 years. The duration of clinical observation was from 3 months to 9 years.
(1) Brain CT findings were classified into 6 image patterns.
Type 1: prominent cortical atrophy with slight ventricular dilatation (6 cases), Type 2: prominent ventricular dilatation with slight cortical atrophy (5 cases), Type 3: cortical atrophy and ventricular dilatation (7 cases), Type 4: subependymal high density spots (5 cases), Type 5: atrophy of cerebral hemisphere (2 cases), Type 6: no abnormal findings (2 cases).
(2) Relationship between the type of CT findings and mental retardation.
Average D. Q. of each type was as follows; Type 1: 70, Type 2: 34, Type 3: 24, Type 4: 55, Type 5: 70, Type 6: 90. D. Q. was relatively high in Type 1, 5 and 6, while it was low in Type 2, 3 and 4. No remarkable changes could be observed in each type after ACTH treatment.
(3) Relationship between the type of CT findings and convulsive seizures.
Attacks were well controlled in 5 out of 6 cases of Type 1 and all cases in Type 6, while those were controlled in only 2cases in Type 3 and 1 case in Type 2 and 4 respectively. In 4 out of 5 cases of Type 4 the attacks were transformed to Lennox- Gastaut type.
The prognosis of infnatile spasms concerning convulsive attacks and mental retardation was relatively good in the types with prominent cortical atrophy (Type 1) or no abnormal findings (Type 6), while it was poor in the types with prominent ventricular dilatation (Type 2) or the CT findings of cortical atrophy and ventricular dilatation (Type 3).
The present authors realized that the morphological findings of the brain obtained by CT-scan fairly made clear the prognosis of convulsive attack and mental retardation. CT-scan as well as EEG should be employed for the monitoring of epileptic patients, especially of infantile spasms.

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The necessity and effectiveness of anticonvulsant therapy for the prevention of febrile convulsions are controversial matters. However, the continuous prophylactic anticonvulsant therapy has been recommended by many recent studies, especially in children who are at an increased risk for developing neurologic sequelae and epilepsy.
Faerø et al. (1972) reported that consistent prevention of recurrences of febrile convulsions is provided by using phenobarbital (PB) only when the plasma levels are maintained above 16 μg/ml. It was also suggested that primidone (PRM) is effective for prophylaxis of a new attack (Wallace, 1975; Cavazzuti, 1975).
The present study aimed to assess the effectiveness of daily PRM for the prevention of febrile convulsions in relation to plasma levels of both PRM and PB derived from PRM.
A total of 50 children aged 1-6 years who had febrile convulsions more than twice was classified into two groups; 25 as “simple” febrile convulsions (group A), and another 25 as “epilepsy triggered by fever”(group B). All children in both groups were given PRM of 15-20 mg/kg daily in two divided doses and were followed for 9 to 21 months. The plasma concentrations of PRM and PB were determined 4 to 6 weeks after the initiation of therapy at first and thereafter every 6 months. All blood samples were drawn 2-4 hours after the morning dose.
Plasma levels of both PRM and PB in individual patients varied considerably and the majority of the patients (18 at the first and 14 at the second) had plasma PB levels clearly below the effective level (less than 16 μg/ml).
All of these 50 children had febrile episodes during the follow-up period. However, only 5 patients (4 in group A, and 1 in group B) had new convulsions. In the cases of recurrence, plasma PRM levels ranged from 6.2 to 17.4 μg/ml, while the PB levels were less than 10 μg/ml.
This study shows that the continuous therapy with PRM of ordinary dosage is effective for the prevention of febrile convulsion recurrences. The prophylactic effect seemed to be achieved by PRM itself, and not PB derived from PRM. However, an effective plasma level of PRM could not be established.
In the present series of PRM mono-therapy, the initial plasma level/dose ratios had a tendency to decrease in PRM and to increase in PB during subsequent 6 months; at the first determination, daily dosage, plasma PRM level, plasma PB level and plasma PB/PRM level ratio were 18.2 ± 2.0 mg/kg, 9.1 ± 3.1 μg/ml, 11.3 ± 4.3 μg/ml and 1.4 ± 0.6, while at the second, these were 17.0 ± 2.0 mg/kg, 7.6 ± 3.4 μg/ml, 11.6 ± 5.5 μg/ml and 1.8 ± 1.3, respectively. These changes may suggest that PRM induces its own metabolism (autoinduction).

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Percutaneous needle biopsy was carried out in 75 patients with various neurological and muscle diseases and its usefulness as a diagnostic procedure was evaluated. The subjects consisted of 34 cases with myopathies, 22 lower and 6 upper motor neuron diseases, and 13 unlocalized or miscellaneous diseases. The ages were from 2 months to 35 years. Seventyseven percent of the patients were less than six years of age. The material obtained was processed routinely for histological, histochemical and electron microscopical examinations.
The results were as follows:
1. The muscle volume obtained by needle biopsy was sufficient for studies in 64 cases (85%), insufficient in 8 (11%), while in 3 cases no samples were obtained.
2. Histological staining properties were excellent in all samples examined. In histochemical preparations, staining was judged as good in 61 cases, but poor in 11 with inappropriate freezing procedure.
3. In 33 cases, both the needle and open biopsies were carried out simultaneously, and the morphological findings of each specimen were compared. There were no significant differences between them histologically as well as histochemically. Electron microscopic examinations provided also an identical information each other in seven cases studied till now.
4. The authors recognized that the method of needle biopsy has many advantages over open biopsy as a routine diagnostic procedure of neuromuscular disorders in infants and young children, but a few disadvantages such as requirement of technical skillfulness and inappropriateness for the histogram construction were also noticed as well.

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The purpose of the present study was to investigate the following four points in connection with status convulsivus in childhood; 1) the prevalence of patients with status epilepticus among epileptic children; 2) clinical pictures of status convulsivus in the acute stage; 3) follow-up observation of children with a history of status epilepticus, and 4) the characteristics of patients with recurring status convulsivus as compared with those who experienced a single episode of status only.
The records of 348 epileptic patients under 15 years of age who visited our outpatient clinic for the first time during the period between October 1977 and September 1978, the records of 67 children hospitalized for an episode of status convulsivus between January 1975 and October 1978, and the records of 32 epileptic outpatients hospitalized before 1974 and followed up as outpatients were studied and applied to each of the four above-mentioned points.
The frequency of status epilepticus was 8% among epileptic children. There was no difference in the frequency of incidence between males and females. Patients with mental retardation, however, were found to have status epilepticus two to three times more frequently than those with normal intellects.
The major seizure types of status epilepticus in childhood were generalized tonic clonic convulsions and unilateral clonic convulsions. In 25% of the cases, status epilepticus was the first ictal manifestation. The major cause of status convulsivus was epilepsy, followed by encephalitis and encephalopathy in order of frequency. Cases in which the condition was caused by brain tumor were rare.
Diazepam is widely recognized as the drug of first choice for status convulsivus. In our experiences, the effective dose of diazepam was within the range of 0.3-0.5mg/kg. If the results are not sufficient at this dosage, it should be increased to 1mg/kg while watching the general condition of the patients. If there is any difficulty in controlling the condition in this manner, it may be worthwhile to investigate the cause of the status convulsivus, the seizure type and/or the basic disease of the patient.
Status convulsivus could be classified into three types according to the characteristics of the condition: Type A (continuous convulsion); Type B (frequent and repetitive convulsions), and Type C (continuous convulsion and frequent and repetitive convulsions).
Most of the patients fell into Type A. The age distribution did not differ for Types A and B. As a cause, epilepsy was dominant in each group. In the C Type, however, causes other than epilepsy were noted more frequently than in the A and B Types. There was no difference in the frequency of idiopathic and symptomatic epilepsy between the A and B Types. As a seizure type, unilateral clonic convulsion was dominant in the A Type and generalized clonic convuision and generalized tonic convulsion in the B Type.
The duration of the convulsion was within two hours for most of the A Type patients. This was longer, however, for about half of the patients of the B and C Types. The anticonvulsive effects of diazepam were better for the A Type and somewhat less noticeable among the patients with the B and C Types.
Factors affecting the prognosis of status convulsivus were its cause, duration, onset age, effectiveness of therapy during the acute stage and the type of the status.
The frequency of cases who suffered disability after status epilepticus was 56%(transient disability 43% and permanent disability 13%).
Pathologic backgrounds for repeating status were usually either hemispheric brain damage or diffuse corticocentrencephalic damage.

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Papillomas of the choroid plexus in infancy are relatively rare. Total of only 9 cases, including our two cases, have been reported up to May 1979 in Japan. In this paper, two surgical cases of papillomas in infancy were reported.
Case 1: A 4-month-old female had projectile vomiting, increasing drowsiness, enlarged head with bulging fontanel. Lumbar puncture revealed clear CSF under an increased pressure of 300 mm H2O. RI scintigram revealed a mass of dense uptake in the left posterior-parietal region. Ventriculogram with positive contrast medium demonstrated hydrocephalic condition with a mass of the trigonal part of the left lateral ventricle. Left carotid angiography revealed also marked hypertrophy of the anterior choroid artery and a vascular stain of the mass. A left parietal carniectomy was done. The tumor was exposed through a transcortical incision and removed completely. The histological diagnosis of the tumor was papilloma of the choroid plexus, benign. This case was reported in this magazine previously. Now the patient is doing all right 5 year after the surgery.
Case 2: An 8-month-old female had a tonic clonic generalized convulsion with sudden onset. The attacks occurred repeatedly for 5 days prior to admission. When she was admitted to our department, She was comatose with widely dilated and fixed pupils. Her arms and legs showed fragmentary decerebrate response following deep supraorbital pressure. The respiration lessened in depth and rate but continued to be slightly labored. The anterior fontanel was enlarged and bulged. Cricumference of her head was 49.7 cm. Lumbar puncture revealed bloody CSF. Left carotid angiography followed by ventricular drainage was performed. There was marked hypertrophy of the anterior choroid artery and a vascular stain in the plexus portion. Computed tomograshy demonstrated a high density area in the left parietal region and low density area in the temporal region which showed a porencephalic cyst. As an emergency operation the cyst was found to be a very dilated temporal horn of the left lateral ventricle with xanthochromic fluid. A large tumoro of the choroid plexus in the lateral ventricle was totally removed at the second, radical operation. Three weeks later, V-P shunt was performed because marked hydrocephalic condition was noted. The histological feature showed malignant papilloma of the choroid plexus with ill-defined papillary, tubular structure, pleomorphysm, nuclear atypicality, hyperchromatism, multinucleation and stromal invasion. At six months follow-up after surgery, the patient was mentally retarded and could not hold her head up by herself.

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Two siblings with congenital myopathy without specific cytoarchitectural features such as nemaline myopathy, central core disease, myotubular myopathy, etc. were subjected to clinical and histopathologic examinations. Their clinical symptoms included early onset of proximally dominant mucle wasting and weakness, noticeable contractures of joints since infancy, myopathic electromyogram and slightly elevated serum creatine phosphokinase, but without central nervous system manifestation and facial muscle involvement. Although a number of cases of congenital muscular dystrophy (CMD) associated with mental retardation and facial muscle involvement (Fukuyama type CMD) have been reported, patients of congenital myopathy lacking such peculiar symptoms seem to be rare in Japan.
Case 1 (8 year-old boy): He was born at full term pregnancy with an uneventful delivery. His developmental milestones were slightly delayed; he sat with assist of his arms at 7 months, and learned to walk using brace at 15 months of age when he was already noted to have remarkable waddling gait and lumbar lordosis. He developed acute encephalopathy of unknown etiology at the age of 5 years, then he failed to walk and stand without support. On physical examination, he had severe generalized muscle wasting and weakness, and contractures of joints involving spine, hip, hands, fingers and ankle joints.
The muscle biopsy was performed from the rectus femoris at 3 years of age. The formalin-fixed and paraffin-embedded specimen demonstrated mild variation in muscle fiber size in association with scattered several “opaque” fibers and focal phagocytosis.
Case 2 (6 year-old girl, sister of Case 1): Her muscle weakness and hypotonia were much more remarkable in comparison with those of her brother. She was hypotonic since birth with a marked delay in developmental milestones. She started to crawl or shuffle at the age of 11 months, but she did not obtain standing or walking ability at all.
The biopsied muscle from the rectus femoris was stained with H & E, modified Gomori's trichrome, and a battery of histochemical methods including PAS, oil red 0, menadione-linked alphaglycerophosphatase, NADH-TR, ATPase with preincubation at pH 9.4, 4.6 and 4.2, phosphorylase and nonspecific esterase. There was marked variation in fiber size with severe fibrous as well as adipose tissue replacement, representing advanced myopathic changes. No evidence of metabolic muscle disorders was recognized on histochemical examination. However, type 2 fiber predominance (95%) and areas of type 2 fiber grouping suggested the possibly coexisted neural influence on the basic myopathic process.

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Three male siblings were reported with hyperphenylalaninemia and moderate to severe progressive neurological illness. They were unresponsive to a low phenylalanine diet. Finally they were found to be deficient in dihydropteridine reductase in the cultured skin fibroblasts.
They were born of consanguineous parents (first cousins) and had similar clinical courses. Developmental delay and epileptic seizures were noticed between the ages of three months and two years. Urinary FeCl₃ reactions were negative and serum phenylalanine levels were between high normal and 15 mg/dl. Phenylalanine load tests showed high peaks and delay in return to preload levels of serum phenylalanine. Low phenylalanine diets were ineffective on their clinical courses. The eldest brother died at the age of ten years from bronchopheumonia, and the second and the third broteer are still alive but moderately neurologically retarded.
Dihydropteridine reductase in fibroblasts were below ten percent of the average normal values in the second and the third child. Excretion of Urinary biopterin-like compounds was within normal range in the third child. 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid were lower than normal range in the second and the third child. The multiple foci of calcification-deposit were found in the brain in autopsy material, on the skull X-ray film or on the CT scanning film in all siblings. This pathological finding may be significant in this particular disorder.

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Recently we treated two patients with transient neonatal myasthenia gravis. The serum samples of one patient and her mother were examined for anti-acetylcholine receptor (anti-AchR) antibody by radioimmunoassay system using anti-human IgG serum.
The infant, a 2500 gm male baby, was delivered at term from a 27-year-old primiparous myasthenic mother to whom had been prescribed ambenonium chloride for three years. He required immediate intubation because of poor respiratory effort and falling heart rate, but his myasthenic symptoms disappeared after the administration of neostigmine bromide. He was discharged on 27 days of life without any recurrence of symptoms and given no medicine. Anti-AchR antibody in his serum was not measured.
Another infant, a 2620 gm female baby, was delivered at term from a 30-year-old multiparous woman who had had generalized myasthenia gravis for seven years. The mother was successfully treated with ambenonium chloride. Her first delivery was uneventful, but the myasthenic symptoms of the mother relapsed immediately after delivery. Therefore, thymectomy was performed and she was given ambenonium chloride daily throughout second pregnancy. The patient appeared to be normal at birth. One day after birth, however, she was observed to be weak in sucking and developed respiratory difficulty. Edrophonium chloride test was positive and she was given oral neostigmine bromide with satisfactory control of symptoms. Medication was completely discontinued at 30 days without any recurrence of symptoms. She was discharged on 34 days of life and appeared perfectly normal, The anti-A chR antibody titer in baby's serum gradually fell from 2.19 pmoles/ml at 4 days to 0.73 pmole/ml at 15 days and 0.38 pmole/ml at 20 days concomitant with the amelioration of myasthenic symptoms. On the other hand, high titer of anti-AchR antibody (3.42 pmoles/ml) was detected in the serum of the mother at delivery.
These findings suggested that the nature of the disorder might be due to placental transmission of anti-AchR antibody.

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