Masataka Arima

Cerebro-Oculo-Hepato-Renal Syndrome (Arima's Syndrome): A Distinct Clinocopathological Entity

Three children with Lebers congenital amaurosis, agenesis of the cerebellar vermis, and infantile polycystic kidneys are described. The common clinical findings of three unrelated patients (two boys and one girl) included severe visual impairment from early infancy, profound psychomotor retardation, hypotonia, nystagmus, characteristic facial appearance with blepharoptosis, and progressive chronic renal insufficiency. The two boys died of uremia at ages 13 and 12 years. The common pathological findings in these two patients consisted of minor disproportions of cerebral lobes, almost total aplasia of the cerebellar vermis, micropolygyria of the dentate nuclei, malformations of the brain stem (including pachygyria of the inferior olivary nuclei and partial absence and anomalous position of the pyramidal tracts), and infantile polycystic kidneys; there was fatty liver in one case and hepatic fibrosis in the other. The clinicopathological findings of our two patients were entirely compatible with those of patients previously reported by Arima and other Japanese authors. Therefore, these patients seem to comprise a distinct clinicopathological entity, cerebro-oculo-hepato-renal syndrome (Arimas syndrome), different from other syndromes with retinal, cerebellar, and renal abnormalities. (J Child Neurol 1986;1:338-346)

MRI and CT findings in Krabbe disease

The progression and characteristics of magnetic resonance imaging (MRI) and computed tomographic (CT) findings in 3 patients with infantile Krabbe disease (i.e., globoid cell leukodystrophy or galactocerebroside beta-galactosidase deficiency) are reported. We obtained initial CT and MRI studies when patients demonstrated hyperirritability and hypertonicity. The following results facilitated early diagnoses: increased density in the thalami, corona radiata, and cerebellar cortex on CT and plaque-like, high signal intensity in the periventricular region and cerebellar white matter on MRI T2-weighted images. After severe motor and mental deterioration and spasticity had developed, progressive brain atrophy, low density in the white matter, and calcification-like, symmetric, punctate high-density areas in the corona radiata were evident on CT and high signal intensity in T2-weighted images and low signal intensity in T1-weighted images in the white matter were present on MRI. In particular, linear patterns were observed in the centrum semiovale on MRI.

Clinical effects of MND-19 (Inosiplex) on subacute sclerosing panencephalitis: — A multi-institutional collaborative study—

A total of 151 cases of subacute sclerosing panencephalitis (SSPE), comprising 89 cases treated with MND-19 (Inosiplex) and 62 untreated cases, were retrospectively investigated as to background characteristics, survival rate and clinical course in order to compare the findings in the 2 groups of cases. The survival rate for the cases treated with MND-19 (MND-19-treated group) was significantly higher than that for the untreated cases (control group), which was also true on stratified analysis or on smoothing of the background factors by means of Coxs multiple regression model. Investigation of the clinical course revealed that progression through the disease stages was significantly slow in the MND-19-treated group, compared with in the control group. Global rating of the clinical course showed that a prolonged remission was obtained in more MND-19-treated cases than control cases. The measles virus antibody titer was in no way affected in the former group. Side effects of MND-19 were observed in 17 of the 89 treated cases (19.1%).

Caffeine and its dimethylxanthines and fetal cerebral development in rat

The relationship between the distribution and pharmacokinetic behavior of caffeine and its dimethylxanthines in pregnant rats and fetuses and fetal cerebral development was compared in four groups with different modes of oral caffeine ingestion by the mothers. During the premating period and pregnancy, female Wistar rats were divided into 0.04% caffeine (C) and water (W) groups, respectively. When the groups are expressed as W or C before mating-W or C during pregnancy, the fetal body weight was low in the three caffeine-treated groups (W-C, C-W and C-C) and the fetal cerebral weight was the lowest in the W-C group. The mean concentration of caffeine or metabolites in maternal plasma, maternal liver, placenta and fetal cerebrum on gestational day (g d) 21 was increased in the W-C group compared to in the C-C group. The concentration of caffeine in fetal cerebrum was increased but that of metabolites was not, compared to the concentration of caffeine or metabolites in the placenta. Radioactivity in fetal cerebrum after intraperitoneal injection of 14C-caffeine was higher in the W-C group than in the other three groups. After intravenous injection of caffeine the apparent volume of distribution of caffeine in maternal plasma was markedly decreased in the W-C group, and the plasma molar concentration ratio of theophylline to caffeine was significantly increased in both the W-C and C-C groups. The adverse effect of maternal caffeine ingestion on the fetal cerebrum may be associated with the decreased apparent volume of distribution of caffeine in maternal plasma and the high caffeine content of fetal cerebrum.

Experimental studies on the influence of male alcoholism on fetal development

To study the effect of paternal chronic ethanol consumption on fetal development, an experimental rat model was established and compared to the fetal alcohol syndrome. Male and female Wistar rats were divided into 30% ethanol (E) and control groups. Before mating and during pregnancy the ethanol group and control group received E and water, respectively. Pregnancies were terminated on gestational day 21. The body weight, liver weight, blood glucose, serum insulin and cerebral CNPase activity were decreased in alcoholic males. The adverse effect of maternal chronic ethanol on fetal development was shown clearly and was not related to paternal ethanol. The adverse effect of paternal alcoholism on the fetus was shown in decreased litter size, or decreased body weight, cerebral weight and cerebral DNA, RNA and leucine incorporation into protein without a decrease in the litter size. The former finding was observed in the fetuses of aged male and female rats and latter in the fetuses of young female rats. In conclusion, both observations in our study indicate the adverse effect of paternal alcoholism on the fetal development.

Adverse effect of maternal caffeine ingestion on fetal cerebrum in rat

This study was undertaken to determine whether maternal caffeine ingestion is or is not a risk factor in fetal cerebral development using experimental rat models. Pregnant rats of the Wistar strain were given 0.04% caffeine in drinking water before and/or during pregnancy for various numbers of days. Control rats received water for the same periods. There was no reduction of maternal body weight, fetal body weight or fetal total brain weight. Low fetal cerebral weight and placental weight were observed when dams were given caffeine before mating for long times and/or throughout pregnancy. DNA, RNA and protein contents per cerebrum were also reduced in fetuses from dams given caffeine throughout pregnancy or for the last 6 gestational days. Cerebral DNA and protein contents as expressed per wet weight were higher and significantly lower respectively in the fetuses from dams given caffeine throughout pregnancy when compared to controls. Activity of thymidine kinase was not significantly decreased in caffeine-treated fetuses. There was a positive correlation between maternal serum and fetal cerebral caffeine levels. Additionally a negative correlation between maternal caffeine levels and fetal survival rates which decreased in litters from dams given caffeine throughout pregnancy was demonstrated. Our rat model indicates maternal caffeine ingestion during pregnancy is associated with reduction of fetal cerebral weight and protein content without reduction of body weight.

Cockayne syndrome with delayed recovery of RNA synthesis after ultraviolet irradiation but normal ultraviolet survival

ABSTRACT: We report a girl with Cockayne syndrome (CS) with atypical cellular features. We studied the ultraviolet (UV)-sensitivity of cultured fibroblast cells derived from this case and male CS siblings as positive controls. Cells from this female with CS displayed normal unscheduled DNA synthesis and repair replication capacity. However, the cells also displayed a less depressed level of RNA synthesis after UV irradiation, compared to control CS cells, and showed normal UV survival. This CS case with early onset of abnormalities had more serious clinical manifestations than the control CS siblings. These cytological results suggest that there is considerable clinical and cellular heterogeneity in CS and that cellular sensitivity to UV might not be as essential for the diagnosis of CS as previously thought.

Hypoglycemia in the fetal alcohol syndrome in rat

As a treatable cause of central nervous system dysfunctions in the fetal alcohol syndrome, ethanol-induced hypoglycemia was studied in experimental rat models. Female Wistar rats were divided into ethanol and control groups. Before mating and during pregnancy, the ethanol group received 30% ethanol (E), or E with 20% sucrose (S) or 20% glucose (G), and the control group received water (W), or W with S or G. Pregnancies were terminated on gestational day (gd) 15, 18, and 21 by cesarean section or by spontaneous delivery. Dams and offspring were weighed and examined for several biochemical factors. Maternal blood glucose levels were higher on gd 15, but significantly lower on gd 18 and 21 in the ethanol group than in the control group. The fetal blood glucose levels were correlated with maternal blood glucose levels on gd 21. Maternal serum insulin levels were lower on gd 15 and 18 in the ethanol group than in the control group. The body and cerebral weights were significantly lower on gd 15, 18, 21 and postnatal day 1 in the ethanol offspring than in the controls. Administration of S or G with E during pregnancy resulted in no better effects on fetal biochemical development and blood glucose levels than administration of E alone. In this work we demonstrated hypoglycemia only in the late gestational and perinatal periods in experimental rat models, which may cause the high perinatal mortality and growth retardation in the fetal alcohol syndrome.

Abnormal cortical excitability in Rett syndrome

Visual and somatosensory evoked potentials (VEPs and SEPs) were studied in 9 patients with Rett syndrome and compared with those in 6 patients with photosensitive progressive myoclonus epilepsy (PPME). In Rett syndrome, a giant III-IV amplitude of VEPs was present in 8 patients, although none exhibited giant II-III amplitudes. Four of 6 patients with Rett syndrome who demonstrated giant SEPs did not have a C reflex. Conversely, the patients with PPME demonstrated giant II-III and III-IV amplitudes in VEPs, and giant SEPs with concurrent positive C reflexes. It is concluded that the mechanism of altered cortical excitability in Rett syndrome is different from that in PPME.

Prevention possibility for brain dysfunction in rat with the fetal alcohol syndrome--low-zinc-status and hypoglycemia.

As a treatable cause of CNS dysfunctions in the fetal alcohol syndrome (FAS), low-zinc-status in addition to hypoglycemia has been investigated in experimental rat models. During the premating period female rats of an ethanol group and a control group received 30% ethanol (E) and water (W), respectively. During pregnancy, some of both groups received zinc or nicotinamide-adenine dinucleotide (NAD) or nicotinamide throughout pregnancy and glucose for gestational day (gd) 15 to 19 with E or W. Independent of maternal blood glucose levels, maternal insulin levels were lower on gd 15 and 18 in the ethanol group than in the control one. A decrease in the activity of carbonic anhydrase in the hippocampal area on postnatal day (pd) 1 was observed in the ethanol group. Administration of zinc with E resulted in a better effect on fetal total body weight and on preventing resorption, mean fetal body weight and protein content in the cerebrum than administration of E alone. Administration of glucose only in the late gestational period resulted in a better effect on fetal cerebral weight than administration of E alone, with a decrease in the litter size. Administration of zinc with E during pregnancy resulted in higher maternal serum zinc levels, without an increase in fetal cerebral zinc content, than administration without zinc with E. There was a positive correlation between fetal body ethanol levels and maternal blood ethanol levels, and a negative correlation between fetal body ethanol levels and fetal total body weight. The beneficial effect of supplementary zinc on fetal growth may possibly help preventing the CNS dysfunctions of FAS, but it is important that the effect was not good compared to the control without E.