We investigated clinical and electroencephalographic data on 12 children with agenesis of corpus callosum. Seven patients had associated malformations of the central nervous system, including microcephalus, hypoplasia of cerebellum, and arachnoid cyst. Nine patients had extraneural anomalies, including unilateral microphthalmia, blephalophimosis, malformed auricles, low set ear, clenched fingers, nail hypoplasia, PDA, PS, and hypogonadism. Eleven patients had psychomotor retardation, D. Q. or I. Q. below 50 in 10 patients. Eight patients had epilepsy; generalized tonic-clonic seizures in 7 and focal motor seizure in one. EEG showed asymmetry in the basic activity or the background activity in 8 patients. Asymmetry of humps, spindles, and K-complexes was also noticed in 5, 9, and 2 cases, respectively. Five patients had asynchronous sleep spindles.

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Rett syndrome is a disorder of characteristic motor, mental and psychological symptoms.
It was initially described by A. Rett in 1966 as cerebral atrophy associated with hyperammonemia. However, it was only recent that this disease has arisen great interest. Hyperammonemia has been denied by Rett himself and the pathophysiology and etiology remain unknown. We have clarified that the characteristic symptoms of Rett syndrome occur sequentially at certain ages reflecting the background pathophysiology, and that it is important for the diagnosis.
This paper describes the detailed clinical characteristics of five personal cases of Rett syndrome and discuss the pathophysiology based on the clinical characteristics.
The ages of the five female patients ranged from 3 years 4 months to 12 years 5 months. The follow-up periods were from 4 months to 9 years 5 months with mean of 4 years 9 months.
A detailed clinical course and neurological findings on two cases, and summary of all 5 cases were presented.
Family history and pre-and perinatal history of all the patients revealed to be non-consistent.
Initial chief complaints were psychomotor retardation and regression accompanied by stereotyped movement of hands.
Delay in motor milestones showed some variability, but delay was more prominent from rolling-over and regression was observed in early childhood. The gait was characterized by interlimb discoordination which simulated akinesia of Parkinson disease.
Autistic behaviour observed from early infancy was soon overlayed by profound mental deficiency.
The characteristic stereotyped movements of hands developed between 8 months and 2 years 6 months of age with mean of 1 year 8 months.
Convulsion occurred in 4, and intermittent hyperventilation and tremulous movements were observed in 3 and 2 out of 5 respectively.
Abnormal muscle tone, initially hypotonic and later rigidospastic with increased deep tendon reflex, pes equinovarus or pes valgus, thumb adduction, and claw toes and hands were observed.
Head circumference at birth was normal in 4 and subnormal in 1 and became progressively microcephalic.
Laboratory examinations revealed to be non-contributory.
It is stressed again that these symptoms occur in sequence at certain ages.
The pathophysiology is speculated that the specific neuronal system of CNS is involved and the main primary localization of the dysfunction is thought to be in the subcortical system. The subcortical system has nearly matured by early childhood and manifest the characteristic symptoms when it is lesioned.
In our previous work, we speculated the primary lesion of Rett syndrome is the locus ceruleus and raphe nuclei in the midbrain and brainstem.
These nuclei are known to mature early and influence spatially and temporally the higher central nervous system.
Detailed clinical evaluations presented in this paper give further support for this hypothesis.

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We presented clinical and neuropathological findings of 3 cases of congenital myotonic dystrophy and reviewed the autopsied cases in the literature. Our cases had typical signs of congenital myotonic dystrophy, which consisted of severe asphyxia, hypotonia, facial weakness, maternal hydramnios and reduced fetal movement. All cases which died in the early neonatal period were complicated by perinatal brain damage of hemorrhage and necrosis.
Pathology of 16 cases in literatures, containing 3 cases of our own, showed a maturational delay in the skeletal muscles and diaphragms, and dysplastic changes in several other organs. There were, however, no dysgenesis in the central nervous system, but perinatal brain damages in 12 of 16 cases.
The perinatal brain damage may be one of the causative factors for mental retardation which is more severe in congenital myotonic dystrophy than in the adult type, although genetic and maternal factors are also important for pathogenesis of congenital myotonic distrophy.

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Diagnosis of the Cockayne syndrome (CS) has been dependent mainly on clinical features such as dwarfism, mental retardation, microcephaly, ataxia, retinal pigmentation, deafness, progeroid feature and intracranial calcification. Our four cases showed almost all these clinical manifestations although a typical CS face was not observed in case 1.
For the analysis of cytological features, we examined the UV or X-ray sensitivity by colony forming ability, unscheduled DNA synthesis (UDS), repair replication and total cellular DNA or RNA synthesis after UV irradiation in these four cases. All fibroblasts derived from these four cases showed remarkable hypersensitivities to UV. With regard to X-ray, the fibroblast strain from case 3 had the intermediate sensitivity between that of X-ray sensitive ataxia-telangiectasia cells and those of normal cells and other three CS strains. This result suggests that there are broad spectra of X-ray sensitivity in CS cell strains.
All CS cells showed normal UDS and repair replication after UV irradiation. Total cellular DNA and RNA syntheses were depressed 6 hours after UV irradiation in all CS cell strains compared with normal cells. The depressed syntheses in these CS cells recovered and became indistinguishable from those in normal cells 24 hours after UV irradiation.
Further investigation is necessary to clarify the relationship between the inhibition of DNA and RNA syntheses after UV irradiation and various neurological manifestations in CS.

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We studied anticonvulsant and prophylactic effects of flunarizine on amygdaloid kindling in sucklings (18 days old) and adults (older than 3 months) of male Wistar rats. (1) Anticonvulsant effects; When a low dose (20 mg/kg) was injected (i. p.), duration of after-discharges (ADs) after 30 minutes decreased by 25% only in the sucklings. With a high dose (80 mg/kg), AD duration was strikingly reduced in both sucklings and adults, and the decrease was 50% and 74% when examined 30 minutes after the injection. The same decrease was also observed 24 hours later in the former group. There was no change in the amplitude of AD. The changes in the kindling stages were not consistent. (2) Prophylactic effects; We gave a high dose of flunarizine to compare the number of conditioning stimulations which induced the kindling seizure, stage 4. Both sucklings and adults, even with this high dose, developed the seizure, stage 4 without any apparent difference from those of control rats not given flunarizine.
The antiepileptic profile of flunarizine seemed to resemble closely that of phenytoin.

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A one-month-old girl was admitted with sucking difficulty and hypothermia. She was spontaneously born at 36 weeks of gestation and had fever on 15 and 16 days after birth. Muscle hypotonus, hyperactive deep tendon reflexes and decrease of primitive reflexes were noticed on admission. Hepatosplenomegaly and dermal vesicles were not found. Convulsions continued for about one month after the admission.
Peculiar calcifications in white matter and periventricular areas were always detected by serial findings of brain CT scan. Multicystic encephalomalacia was shown by brain echogram. EEG disclosed flat rhythms.
Antibodies to herpes simplex virus, probably type 2, and echovirus, type 22, were presented in high titers in bloods and CSFs. Echovirus was cultured from throat swab. Herpes simplex virus was not cultured from either blood of CSF.
HSV encephalitis without ecovirus encephalitis was considered from the results of virus antibody titers in bloods and CSFs.
Microcephalus and cerebral palsy developed subsequently. Anti-viral drugs were not used.

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The Joubert syndrome is a rare syndrome recognized by Joubert et al. in 1969. Two further cases of that syndrome are described in this paper. Both had episodic panting tachypnea and abnormal eye movements (horizontal nystagmus, jerking and floating eye movement) in their periods, and subsequently developed mental retardation, ataxia, and blindness. Agenesis of the vermis was confirmed by computed tomograph (CT) of the brain and by metrizamide CT cisternography. One patients had also polycystic kidneys, and abnormal renal function was found at one year of age. In the other case, the parents were related.
Early recognition of this syndrome is important in view of the prognosis and for genetic counselling.

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We reported a 3-month-old male with recurrent vomiting, lethargic tendency and poor body weight gain. There was neither consanguinity nor family history of any metabolic disorders. On admission remarkable metabolic acidosis was noticed in blood gas examination with the association of nonketotic dicarboxylic aciduria. Serum and muscle carnitine levels were significantly low (60% and 10% of the control mean, respectively), suggesting that the patient had a systemic carnitine deficiency. Quadriceps mucle histochemistry revealed a slight increase of intrafiber lipid droplets and a marked accumulation of glycogen in the subsarcolemmal region. An in vitro study of anaerobic glycolysis showed a block after glucose-l-phosphate and before glucose-6-phosphate. Direct measurement of individual glycolytic enzymes in the muscle of the patient demonstrated a marked decrease of phosphoglucomutase (PGM) activity (13% of the control mean). The coincidental association of two rare conditions such as PGM deficiency and systemic carnitine deficiency is unlikely. The specific enzyme deficiency of PGM in this patient suggests that the block in an anaerobic glycolysis is the primary abnormality. Therefore carnitine deficiency is regarded as the secondary condition. PGM deficiency should be added as a newly recognized cause of the secondary carnitine deficiency syndrome.

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A case of infantile spasms associated with unilateral gangliocytoma in the right parietal motor area was described. A 7-month-old boy with normal prenatal, perinatal and early postnatal course developed infantile spasms consisting of sudden flexion of the neck and trunk and forward flexion of the arms. Focal signs were not present. The head size was normal. There was no depigmentation of skin. Fundoscopic tests were negative. The electroencephalogram showed a hypsarhythmic pattern. Routine laboratory tests were normal including CT scan.
At 11 months the seizures became more intractable despite treatment with administration various anticonvulsants, ACTH, γ-globlin and DN-1417. Mild paresis of the left foot and developmental delay were found. A CT scanning revealed a large high density area in the right parietal area. A gangliocytoma was removed partially at 2 years of age. His seizures and paresis were improved mildly.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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