This article attempts to summarize the available literature concerned with the morphological and biochemicaleffects of growth hormone (GH) on brain development.
Review of experimental works is as follows. In early hypophysectomized rats, the mortality rate was very high during the immediate postoperative periods. The death may be attributed to the brain damage due to the increased intracranial pressure and the herniation of the brain stem into the foramen magnum caused by the postoperative deformity of the skull. There were marked differences in body weight, body length, weights of endocrine organs and osteogenesis betweenearly hypophysectomized and normal rats. Hypophysectomy also resulted in the vertical increase in the volume of diencephalon, the decrease of acetylcholinesterase activities in the somatosensory and ventral cortex, the decrease of cholinesterase activity in the hypothalamus, fall in the synthesis of RNA and protein of the brain, and lack of the large polysomes.
GH, when given to frog larvae, increased the cell number and the weight of brain. Similar findings were reported on the effect of maternal treatment of bovine GH on neonatal rat. These results indicated that this hormone enhanced mitosis and thereby increased tissue mass in the developing brain.
The review of clinical study reveals that the patients with pituitary dwarfism with high serum concentration of an immunoreactive but biologically inactive human GH showed low IQ's by Wechsler Intelligence test and below age norms by Bender Gestalt test. This suggested a recognizable pattern of organic impairment of central nervous system in the deficiency state of human GH.

View full abstract

An early-infantile epileptic syndrome is reported. This syndrome is characterized by its early onset (less than 3 months of age), frequent tonic spasms, suppression-burst on EEG, extremely poor response to treatment and grave outcome.
Out of 8 cases (5 boys and 3 girls) experienced thus far, 6 had thir onset before 1 month of age. Tonic spasms appeared in series in 4 cases, and were seen during awake and sleep period.
The underlying pathologies, known in 4 cases, were porencephaly (in 2), Aicardi syndrome (in one), and subacute diffuse encephalopathy (in one).
In all cases the EEG showed suppression-burst as a common denominator of this syndrome when awake or asleep, in addition to desynchronization during seizure.
It is worthy of mention that hypsarhythmia was observed in 5 patients during the follow up period, and the transition to the West's syndrome in 4 cases. In most cases the suppression-burst pattern disappeared after 3 months of age.
Follow up study of up to 3 years indicated the extreme ref actoriness to therapy; 4 are dead, and the remaining 4 have been suffering from severe mental and physical handicaps.
Supposed pathophysiology of this syndrome studied from the burst-burst intervals was also discussed.
In conclusion we would like to list this syndrome as the third specific, age-dependent childhood epileptic encephalopathy, to be entirely separated from the West's and the Lennox syndromes.

View full abstract

Peripheral nerve functions (MCV, SCV, M wave latency, T wave latency, continuotis evoked potential and post-tetanic action potential) were assessed in 34 patients on long-term diphenylhydantoin (DPH) therapy and were compared with those of a control group consisting of 22 subjects including 2 epileptic patients without DPH treat ment.
The results were as follows;
1) The MCV's were 47.6±9.3 m/sec in DPH group and 57.1±7.0 m/sec in the control group respectively. There was significant difference between two groups (t-test, P<0.05). The incidence of MCV below 2 standard deviations from the control mean was 32% in the DPH group, and none in the control group.
2) The SCV's were 45.2±10.9 m/sec in the DPH group and 56.7±7.0 m/sec in the control groups. There was significant difference between two groups (P<0.05). The incidence of individuals with SCV below 2 standard deviations from the control mean was 42% in the DPH group, whereas 5% in the control group.
3) For T wave latency, the correlation coefficient between T wave latency and the age was 0.6733 in the DPH group and 0.7460 in the control group. There was, however, no significant difference between the two groups.
4) M wave latency was delayed in the DPH group. There was a notistical significance bet ween the two groups (P<0.01).
5) The continuous evoked action potential and the post-tetanic action potential showed a waning phenomenon was in two patients of the DPH group and none in the control group.
6) Serum DPH determined concurrently ranged 13.8 to 0.3 r/ml. The factors affecting on MCV, SCV, T wave latency and M wave latency (serum DPH levels, duration of therapy, total dosage (g/kg) and gum hypertrophy) were evaluated. There were correlations between duration of theray and T wave latency (r=0.4923, p<0.01), and between total dosage and MCV (r=-0.3584, P<0.05). The patients with gum hypertrophy showed significantly lower without gum hypertrophy. There was no significant correlation between the serum level of DPH and MCV, SCV or T wave latency. There was no significant correlation between M wave latency and serum level, duration of therapy or total dosage.

View full abstract

In order to investigate the hydrodynamic changes of the CSF in diseases of children, cisternography by Yb¹⁶⁹ DTPA was carried out in 55 cases with neurological diseases including microcephaly, hydrocephalus ex vacuo, degenerative diseases and others.
The results obtained were as follows;
1) Early reflux into the lateral ventricles was recognized in cases with microcephales associated with agenesis of the corpus callosum, agenesis of the septum pellucidum and noncommunicating septum pellucidum cyst. In addition to the primary microcephaly due to developmental anomaly mentioned above, secondary microcephalies with periventricular calcifications also showed an early ventricular reflux.
2) In the diseases which showed the early reflux into the ventricles there was the dilatation of the lateral ventricles with over than 0.33 of Evans' ratio.
3) Cisternography showed an early reflux into the ventricles in Hunter disease and isotope in the synvian subarachnoid cistern at 24 hours and 48 hours without any progression to the convexity of the hemispheres in the disease of GM₁ gangliosidosis.

View full abstract

Cystinuria is a hereditary disorder due to a defect in the renal transport of dibasic amino acids consisting of cystine, lysine, arginine and ornithine. The disorder has been known to develop recurrent urolithiasis clinically. Recently the screening for aminoaciduria, however, revealed that most of the patients with cystinuria existed as “biochemical cystinuria” without manifestation of urinay calculi. Throughout our experience of screening for aminoaciduria, we had the impression that there might be a higher frequency of cystinuria among the mentally retarded children.
The present study was undertaken in order to elticidate this question. Cyanide-nitroprusside reaction was tested on the urine specimens from 4852 normal children and from 1325 mentally retarded children, in Osaka district. The specimens which gave a positive reaction was quantitatively analyzed for amino acids. Three cases of homozygotes (all four amino acids excreted in excess) and 12 heterozygotes (only lysine and cystine excreted in excess) were found in the mentally retarded group, whereas one case of homozygote and 9 cases of heterozygotes were found in the normal group. This indicates a significantly higher frequency of cystinuria in the mentally retarded children than in the normal children, not only in homozygotes but also in heterozygotes.
Oral loading test lysine (150 mg/kg) was performed in order to investigate intestinal absorption of lysine in these cases. It was found that the intestinal absorption rate in cystinuria with mental retardation was statistically lower than those who have normal mentality. Lysine is the only essential amino acid among four dibasic amino acids. The patient with cystinuria may be apt to fall in deficiency in lysine because of genetic handicap of its transport, particularly its poor absorption in the gut. A possibility was postulated that the deficiency in lysine during infancy may influence upon brain developement.

View full abstract

A case of 16-year-old male who had congenital blindness, severe mental and physical handicaps and polydipsia, was studied clinically and neuropathologically.
At autopsy, kidneys showed nephrosclerotic changes due to arteriosclerosis and agenesis of vermis were observed in the cerebellum.
Six cases of the congenital polycystic kidney syndrome associated with both congenital blind ness and agenesis of vermis have been reported by Dekaban et al., Heffner et al. and Koya et al. In this case, agenesis of vermis and congenital blindness were similarly recognized. It is inter esting, however, that the renal change was that of arteriosclerotic nephrosclerosis which was not described in the above-mentioned reported cases.
The present case was examined and discussed in connection with the vermic agenesis, and also regarding the renal lesion in relation to the congenital polycystic kidney syndrome observed in the reported cases.

View full abstract

An autopsy case of holoprosencephaly was reported. Her birth weight was 2800 g and head circumference, 31.5 cm. She had median cleftlip, ocular hypotelorism and flat nose. Then stridor appeared at 3 weeks of age and tonic convulsion of extremities at 9 weeks of age. On examination the knee and ankle reflexes were hyperactive. She had normal chromosomes. She died at 1 year 8 months of age.
The gross findings of the brain at necropsy were as follows. 1) Cerebral hemispheres were less developed than the other areas, especially in frontal and occipital lobes. 2) The interhemispheric fissure was interrupted anteriorly and the both lateral ventricles were in communication. 3) The primary sulci of hemispheres were present. 4) The anterrior circulation derived from 3 arterial trunks ; 1 anterior cerebral artery and 2 middle cerebral arteries. There was no abnormality in the vertebro-basilar system.
Considering from many other previous reports, we could devide the anterior circulation of holoprosencephaly into three types as below.
1) two anterior cerebral arteries and two middle cerebral arteries
2) one anterior cerebral artery and two middle cerebral arteries
3) two middle cerebral arteries alone

View full abstract

A case, aged 6, of intracranial tumor with a bruit over bilateral eyeballs and temporal regions was presented with an accompanying phonocardiogram. The bruit decreased when the ipsilateral carotid artery was compressed. Operation disclosed an ependymoblastoma in the left superficial central area. The bruit disappeared after subtotal excision (200 g). In this case, the intracranial bruit was caused by highly vascular character with three afferent vessels, the superficial location and multiple arteriovenous communication with red veins.
The literature pertinent to intracranial bruits, their significance and pathophysiology, was briefly reviewed, and the importance of cranial auscultation was stressed.

View full abstract

A case of 5-year-old girl, who began to walk at 11 months of age, with atypical Werdnig-Hoffmann disease was reported.
Astasia-like and generalized clonic seizures began at 3 years. At 4 years, she had difficulty going up and down stairs.
At 5 years and 8 months, Gowers' sign appeared.
The clinical and laboratory findings, such as generalized muscular atrophy, absence of tendon jerks, typical neurogenic pattern in EMG record and normal level of serum CPK, suggested that the patient's condition might belong to infantile spinal muscular atrophy.
Biopsy of left triceps brachii and quadriceps femoris was performed. Histology showed three large groups of muscle fibers; hypertrophic, intermediate, and atrophic.

View full abstract