Effect of Gestational Exposure to Bisphenol A on Cell Proliferation and Differentiation in the Neonatal Rat Brain / 대한소아신경학회지

PURPOSE: Bisphenol A (BPA), a plasticizer, shows estrogenic activity at low concentrations in cells expressing estrogen receptors, and therefore, it is classified as an endocrine disruptor. Although many studies have focused on the toxicity of BPA to the reproductive and immune systems, relatively less attention has been given to the effect of BPA on the central nervous system. Therefore, the purpose of this study was to investigate the changes in cell proliferation and differentiation during infant brain development in BPA-exposed pregnant rats. METHODS: Two different doses of BPA were exposed to pregnant rats: (1) a low dose (0.01 mg/kg-bw/day) and (2) a high dose (1 mg/kg-bw/day). Infant brains were excised at days 3, 7, and 14 after birth, and tissues were processed for histological and biochemical analyses. RESULTS: Immunohistochemistry for proliferating cell nuclear antigen (PCNA) showed that although cells in the cerebral cortex at days 3 and 7 after birth were highly proliferating, the cells at day 14 divided less often. Immunopositive cells for glial fibrillary acidic protein (GFAP) were observed from days 7 to 14 in control tissues. Western blotting clearly showed that exposure to BPA in pregnant rats resulted in increased GFAP protein expression in the infant rat brain compared to the controls. CONCLUSION: Exposure to BPA during the gestational period might result in precocious neurogenesis in the infant rat brain.

Effect of Gestational Exposure to Bisphenol A on Neuronal Stem Cell Differentiation in the Neonatal Rat Hippocampus / 대한소아신경학회지

PURPOSE: Neurogenesis in neonatal period after birth occurs consequently through a series of neuronal stem/progenitor cell proliferation and differentiation. This stage is critical for determining of normal development and maturation of the brain throughout the life. Therefore, exposure to a certain physical or chemical factor(s) during pregnancy can result in serious damage in the developing brain. Bisphenol A (BPA), a plasticizer, is generally known as an endocrine disruptor exhibiting adverse effects when exposed to animals under experimental conditions. The purpose of this study was to investigate the changes in neuronal stem cell proliferation and differentiation during neonatal brain development in BPA-exposed pregnant rats. METHODS: After exposure of BPA to pregnant rats, infant brains were excised at days 3, 7, and 14 after birth, and tissues were processed for histological and biochemical analyses. RESULTS: Proliferating cell nuclear antigen (PCNA) immunostaining showed that whereas cells in the hippocampus at days 3 and 7 after birth were highly proliferating, the cells at day 14 divided less often. Immunohistochemical staining for nestin in the control group revealed that nestin-positive cells were only observed at day 3 after birth, but the immunoreactivity was not observed at day 14. In addition, glial fibrillary acidic protein (GFAP) immunoreactive cells were observed from days 7 to 14 in control tissues. However, in the BPA-exposed groups, 1) the number of PCNA-positive cells in the BPA-exposed groups at days 3 and 7 were higher than those of the control, 2) nestin-positive cells were observed at day 3 which is earlier than that of control, and 3) GFAP-positive cells were detected in the hippocampus tissue from day 3. Furthermore, western blotting showed that exposure to BPA in pregnant rats resulted in earlier expression of nestin in the neuronal rat brain compared to the controls. CONCLUSION: Taken together, it is assumed that precocious neurogenesis in the infant rat hippocampus might be due to BPA exposure during the gestational period. Further studies on adult brain perinatally exposed to BPA are needed to evaluate the pathological status of the hippocampus.

Expression of Intermediate Filament Proteins in Rat Brain after Cryoinjury / 대한소아신경학회지

PURPOSE: Traumatic brain injury is a multifaceted injury that involves direct mechanical damage, intraparenchymal and subarachnoid hemorrhage, breakdown of the blood-brain barrier, excitotoxicity, and ischemia. Even though much investigations were performed, acceptable mechanical informations were rare. The aim of this study was to reveal the expression pattern of intermediate filament proteins associated with gliotic scars in cerebral cortex of rats after cryoinjury. METHODS: A total of 18 male Sprague-Dawley rats weighing 300 g, 2 months old, were used throughout the experiments. To injure the brain, rats were anesthetized for surgery with 3.5% chloral hydrate(1 mL/100 g, intraperitoneally); the frontal bones were exposed by elevating the skin; and craniectomies were performed adjacent to the central suture, midway between lambda and bregma. A cryoinjury was then created by applying a cold probe(3-mm-diameter steel rod chilled in liquid nitrogen) to the left frontal cortex(ipsilateral cortex) for 1 min. Rats were sacrificed at 1, 4, 7 and 14 days postsurgery(n=3, per time point), and three rats were sacrificed as normal controls. Serial brain cryosections were made by cryostat. For immunohistochemistry, brain tissue sections were allowed to react with mouse anti-rat GFAP antibody(1:200), mouse anti-rat vimentin antibody(1: 200), and mouse anti-rat nestin antibody(1:200). RESULTS:Reactive astrocytes expressing GFAP, vimentin and nestin appeared for the first time at 6 hours after cryoinjury. Proliferation of GFAP and nestin positive cells started at 1 day after cryoinjury, reached its maximum on day 4, and returned to normal level after the 7th post-injured day. Proliferation of vimentin positive cells started at 1 day after cryoinjury, reached its maximum on day 4, and returned to normal level after the 14th post-injured day. Characteristic morphological changes in reactive astrocytes were seen at 4 days after cryoinjury. CONCLUSION: The above results suggest that GFAP, vimentin and nestin positive cells attend in the formation of gliotic scars.

Antigen Presenting Cells Appearing in Injured Rat Brain Detected by Immunohistochemistry Method / 대한소아신경학회지

PURPOSE: Traumatic brain injury is a multifaceted injury that involves direct mechanical damage, intraparenchymal and subarachnoid hemorrhage, breakdown of the blood- brain barrier, excitotoxicity, and ischemia. Despite the dozens of previous investigations, the information about its pathogenic mechanism is still limited. The aim of this study was to reveal the appearance of antigen presenting cells in the cerebral cortex of rats after cauterization. METHODS: A total of 18 male Sprague-Dawley rats weighing 300 g and 2 months old on the average were used throughout the experiment. The frontal bones were exposed by elevating the skin and craniectomies were performed adjacent to the central suture, midway between lambda and bregma. Cauterizing injury was then created by battery-operated small vessel cauterizers to the left frontal cortex. The rats were sacrificed on the 1st, 4th, 7th and 14th days after the surgery(n=3, each time), and three rats were sacrificed as normal controls. Serial brain cryosections were made by cryostat. For immunohistochemistry, brain tissue sections were allowed to react with mouse anti-rat MHC class II antibody(1:500) and mouse anti-rat ED2 antibody(1:200). Also, brain tissues were routinely stained by H-E, and then microscopic observation and cell counts were performed. RESULTS: 1) MHC class II positive dendritic cells were absent in normal cerebral cortex parenchyme, but were found 28 times more in number in injured rats on the 7th day after cauterization. 2) ED2 positive macrophages were absent in normal cerebral cortex parenchyme, and were found 16 times more in number in injured rats on the 7th day after cauterization. 3) The number of MHC class II positive dendritic cells were smaller in number than that of ED2 positive macrophages 6 hours and 1st day later after cauterization, but it was higher in number on the 4th, 7th and 14th days. 4) The number of MHC class II positive dendritic cells were higher in number than that of ED2 positive macrophages around blood vessels and peripheral regions in the injured brain. 5) MHC class II positive dendritic cells were usually aggregated. CONCLUSION: It can be suggested that the increase in number of two kinds of antigen- presenting cells affect cell-mediated immune responses and phagocytosis.

A Case of Child with Miller Fisher Syndrome Diagnosed by Anti-GQ1b Antibody from Mycoplasma Pneumoniae / 대한소아신경학회지

Miller Fisher syndrome, first reported by Miller Fisher in 1956, is characterized by a triad of external ophthalmoplegia, areflexia, and ataxia. Many features shared with Guillain-Barre syndrome; CSF usually shows elevated proteins and the syndrome is often is preceded by an infectious disorder. It is believed that the level of anti-GQ1b IgG antibody is elevated during an acute phase, increases and decreases rapidly during clinical recovery, that the level of anti-GQ1b IgG can be used as a diagnostic tool for Miller Fisher syndrome during an acute phase. We report an 8 year-old boy who showed typical clinical manifestations of Miller Fisher syndrome, with respiratory tract illness, associated with the seroconversion of Mycoplasma pneumoniae titers during the development of neurological symptom, with positive anti- GQ1b IgG.

A Study of Epileptiform Discharges in Children with Chronic Recurrent Headaches / 대한소아신경학회지

PURPOSE: This study was undertaken to determine the incidence and the meaning of epileptiform discharges accompanied by chronic recurrent headaches. METHODS: We selected 449 cases of children who visited Dong-A University Hospital because of recurrent headaches from January 1999 to July 2005. The headaches were classified by the criteria established by the International Headache Research Committee in 2004. The electroencephalography was performed in 336 cases and 36 cases who showed epileptiform discharges were selected. We studied the characteristics of epileptiform discharges, MRI findings and the relationship with epilepsy. RESULTS: The incidence of interictal epileptiform discharges(ILEDs) of the patients with chronic headaches was 10.7%, which was higher than that in a normal population. In the location of ILEDs, focal areas(9.2%) were more common than general areas(1.5%). The incidence of the ILEDs was different according to the types of headaches(P<0.01). The focal ILEDs were concentrated at the central temporal areas. The most common type of ILEDs was frequent epileptiform discharges(63.9%). For the wave forms of ILEDs, focal spike activities were 83.3%, and bursts of slow waves mixed with spikes were 13.9%. Among the 36 cases that showed the ILEDs, 2 cases were associated with epilepsy and another 2 with AV malformation on the MRI images. CONCLUSION: The ILEDs of the patients with chronic recurrent headaches mainly occurred in the central temporal areas as focal spike wave forms, which shows a benign course. Because a few cases can accompany epilepsy and brain abnormalities, close observation and follow-up tests are needed.

The Effect of Topiramate on Status Epilepticus-Induced Neurotoxicity in Immature Mouse Brain / 대한소아신경학회지

PURPOSE:This study was performed to elucidate that status epilepticus (SE) induces long- term neuronal damages in an immature brain and to evaluate that topiramate (TPM) has a protective effect. METHODS:We investigated the changes in a subtype expression of glutamate and gamma- amino butyric acid (GABA) receptors, and the structural integrity due to cell losses in the mouse pup hippocampus after SE using an immunoblot and confocal microscopy. RESULTS:SE induced significant cell losses with structural changes in the hippocampus 1 month later. SE up-regulated the glutamate receptor1 (GluR1) expression with an increased ratio of GluR1 to glutamate recptor2 (GluR2), leading to the formation of Ca2+ permeable alpha- amino-3-hydroxy-5-methyl-4-isoxazoleepropionic acid (AMPA) receptors for the enhanced neurotoxicity. TPM prevented the SE-induced GluR1 expression. The expression of GABAA receptors was highly increased 1 month after SE, whereas that of GABAB receptors was not changed. The TPM treatment attenuated SE-induced upregulation of GABAA receptors. SE induced significant cell losses and disruption of structural integrity in the hippocampus CA1 and CA3 regions, but the TPM treatment for 1 month in developing brains reduced the SE- induced hippocampal damage. CONCLUSION:TPM has a neuroprotective action, which might be mediated by the modulation of GluR1 and GABAA receptors.

A Case of Reversible Posterior Leukoencephalopathy Involving in the Spinal Cord with Pheochromocytoma / 대한소아신경학회지

Reversible posterior leukoencephalopathy with hypertension is characterized by an acute and severe rise in blood pressure with headache, altered mental status, cortical visual disturbance, seizure and transient edematous changes in neuroimaging. The most common abnormality in neuroimaging is presumed edema involving the cortical and subcortical white matter predominant in the posterior region of the cerebral hemisphere and rarely the cerebellum and the brain stem, but not in the spinal cord. We experienced a case of 10-year-old girl with hypertensive encephalopathy involving the brainstem and the spinal cord.

A Case of Acute Necrotizing Encephalopathy with a Thalamic Hemorrhage / 대한소아신경학회지

Acute necrotizing encephalopathy predominantly affects young children and infants living in Japan and Taiwan, and is characterised by acute encephalopathy with seizures and decreased level of consciousness. The Hallmark of the disease is diffuse and symmetrical CNS lesions of both thalami, brainstem tegmentum, cerebral periventricular white matter and cerebellar medula. The clinical, radiological and pathological features of this disease, a disease entity established recently, is proposed by Masashi Mizuguchi et al in 1995. The aetiology is unknown but infectious or parainfectious process seems likely. The diagnosis can be made without difficulty on the basis of the combination of a typical clinical figures and characteristic radiologic findings. There is no specific therapy or prevention. The prognosis was poor in the 1980s but has improved recently. We experienced a case of 6-month-old female infant with acute necrotizing encephalopathy and a thalamic hemorrhage. We report this case with a review of the related literatures.

A Case of Jarcho-Levin Syndrome with Intrathoracic Kidney / 소아과

In 1938, Jarcho and Levin initially described shortening of the trunk, prominent occiput, broad forehead, multiple vertebral defects and ribs anomaly, short neck, increased anteroposterior chest diameter, lordosis, kyphoscoliosis. After that, Jarcho-Levin syndrome is an eponym that has been used to describe a variety of clinical phenotypes. We examined a girl who was suspected as suffering from Jarcho-Levin syndrome because she had shortening of the trunk, multiple vertebral defects and ribs anomaly, short neck, increased anteroposterior chest diameter, lordosis, kyphoscoliosis. We report a case of Jarcho-Levin syndrome with intrathoracic kidney, and review related literature.

Febrile Seizure-induced Neuroexcitability in Immature Rat Hipocampus / 소아과

PURPOSE: To determine whether febrile seizure enhances neuroexcitability by altering synaptic transmission and whether febrile seizure-induced hyperexcitability leads to long-lasting neuronal death. METHODS: We investigated the expression of synaptic and postsynaptic proteins and the apoptosis of neuronal cells in rat pup hippocampus after hyperthermic seizure using immunoblotting and confocal microscopy. RESULTS: Hyperthermic seizure enhanced the long-term expressions of presynaptic proteins such as syntaxin, VAMP, SNAP-25 and nSec1, whereas that of NSF was decreased. The expressions of postsynaptic NMDA receptors 1, 2a and 2b were up-regulated. The expression of postsynaptic AMPA glutamate receptors 1 month after hyperthermic seizures altered by way of increasing the ratio of GluR1 to GluR2 and decreasing NSF-GluR2 interaction, which leads to the formation of Ca2+permeable AMPA receptors and enhanced toxicity. However, in spite of enhanced neuroexcitability, there was a transient increase of neuronal death in hipocampus one week after hyperthermic seizure, but returned to baseline one month later. CONCLUSION: These results demonstrate both presynaptic and postsynaptic forms of long-term enhancement of glutamate synaptic transmission after hyperthermic seizure and support the idea that early-life febrile seizure might have persistent effects on neuronal excitability in the hippocampus.

A Case of Infantile Spasm Associated with Acute Renal Failure and Kwashiorkor after Ketogenic Diet

The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of difficult-to-control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. In this situation, a ketogenic diet should be considered as an alternative therapy. However, less attention has been paid to associated adverse events in the ketogenic diet. We report a case of infantile spasm associated with acute renal failure, lipoid pneumonitis and kwashiorkor after ketogenic diet. A better understanding of this adverse event profile will allow the pediatric neurologist to have a true informed consent discussion with the care giver when considering initiation of the ketogenic diet.

Developmental Disorders

No abstract available.

A Case of Myotubular Myopathy

The term myotubular myopathy (MTM) implies a maturational arrest of fetal muscle during the myotubular stage of development at 8-15 weeks of gestation. Characteristic muscle histopathology consists of small hypotrophic muscle fibers with centrally placed nuclei and a surrounding clear area devoid of myofibrils. X-linked recessive inheritance is the most common trait. Autosomal recessive and autosomal dominant forms are less frequently reported. The clinical diagnostic criterion for X-linked MTM has relied on a positive family history and the demonstration of the presence of characteristic biopsy findings from affected male subjects. Additional features may include perinatal onset, severe hypotonia, respiratory failure, dysphagia, thin ribs, contractures of the hips or knees, puffy eyelids and ophthalmoplegia. The prognosis is often fatal, and most patients die within the first year of life from respiratory failure. The authors report a case of presumed X-linked MTM with severe hypotonia, muscle weakness and respiratory failure at birth.

Studies of the Change of Antibody Titers after Vaccination of Haemophilus Influenzae PRP-T Conjugate Vaccine

PURPOSE: This study was carried out to survey the serum anti-PRP titers after the completion of a primary series with 3 doses of the PRP-T conjugate vaccine(ACT-HIBTM), to evaluate the necessity of booster vaccination. METHODS: One hundred twenty healthy infants who went for consultations at Moon Hwa hospital between December 1999 to May 2001 were vaccinated at two, four and six months after birth. The serum antibody levels were measured at 7-8 months and 19-20 months of age by the "Farr" type of radioimmunological method at Aventis Pasteur International in France. RESULTS: The geometric mean of Anti-PRP titers were 24.6 microgram/mL at 7-8 months and then fell to 2.10 microgram/mL at 19-20 months. Minimum Anti-PRP titer was 0.75 microgram/mL at 7-8 months, and 0.1 microgram/mL at 19-20 months. Maximum Anti- PRP titer was 99.2 microgram/mL at 7-8 months, and 9.1 microgram/mL at 19-20 months. Subjects of Anti-PRP titers more than 0.15 microgram/mL were 100% at 7-8 months, and 97.0% at 19-20 months, and subjects of Anti-PRP titers more than 1.0 microgram/mL were 98.3% at 7-8 months, and 61.6% at 19-20 months. CONCLUSION: The Anti-PRP titers at 7-8 months were very high but rapidly decreased at 19-20 months of age, so the necessity of booster vaccination could be considered in Korean children.

Age-Related Changes of MHC Class II-immunoreactive Dendritic Cells in Rat Brain / 대한소아신경학회지

PURPOSE: Dendritic cells are antigen presenting cells(APC) that express class II major histocompatibility complex gene products on their surface. Recently, it was proved that dendritic cells activate antitumor immunity for intracranial germ cell tumor. The aim of the present study is to investigate the age-related changes of MHC class II-immunoreactive dendritic cells in the rat brain. METHODS: Male rats(Sprague-Dawley) were sacrificed at 1 month, 12 months and 24 months after birth. Brains were removed and sliced in rat brain matrix. Brain slices were cryosectioned coronally at interaural 5.70-6.70 mm. Brain tissue sections were immunohistochemically reacted with monoclonal MHC class II antibody. RESULTS: MHC class II-immunoreactive dendritic cells were observed in choroid plexuses and white matter(corpus callosum, cerebral peduncle and external capsule). The number of MHC class II-immunoreactive dendritic cells was slightly increased with age. As age increases, shapes of MHC class II-immunoreactive dendritic cells became more complex and aggregated together. CONCLUSION: As age increases, MHC class II-immunoreactive dendritic cells in choroid plexuses and white matter of the brain became not only more complex in shape, but also increased in number to improve immunity.

A Case of Neurocutaneous Giant Melanosis Associated with Dandy-Walker Syndrome / 대한소아신경학회지

Neurocutaneous melanosis is a rare congenital phacomatosis, characterized by the presence of multiple pigmented skin nevi at birth. Meningeal melanosis tending to become malignant and seizure. Dandy-Walker syndrome is a developmental disorder of brain characterized by cystic dilatation of the fourth ventricle and agenesis or hypoplasia of the cerebellar vermis. We studied a case of Dandy-Walker syndrome with neurocutaneous giant melanosis in a 3 years old boy.

Severe Epileptic Encephalopathies in Infant and Children / 대한소아신경학회지

No abstract available.

Changes of Total Leukocytes and Leukocyte Types in Cerebrospinal Fluid and Peripheral Blood According to the Time Interval of Collection of Spinal Fluid after Onset of Illness in Aseptic Meningitis / 대한소아신경학회지

PURPOSE: We performed this study to evaluate the changes of total leukocytes and leukocyte types in CSF and peripheral blood (PB) in the early course of aseptic meningitis. METHODS: One hundred and eighty-nine children with aseptic meningitis, who were admitted to the Pediatric Department of Dong-A University Hospital during the period from June 1996 to October 1997 were included. Patients were divided into 4 groups by 12-hour intervals according to the time between the onset of illness and initial diagnostic lumbar puncture. We analyzed clinical pictures, total leukocytes and leukocyte types in CSF and peripheral blood (PB) in each group. RESULTS: 1) There was no significant difference in average total leukocyte counts in CSF between each group, and all groups were considered to be acute stage of illness. 2) The PMNL proportion of CSF leukocytes was 57.0+/-31.6% in group I, 44.1+/-32.3% in group II, 39.4+/-33.1% in group III and 26.9+/-27.9% in group IV. The PMNL percentage was significantly higher in group I than group III and IV and the proportion of patients with a predominance of PMNL was higher in group I than group III and IV (p<0.05) 3) The proportion of neutrophils in PB was highest in group I (76.5+/-15.7%) and significantly higher in group I and II than group III and IV (p<0.05). 4) Significant correlations were found between the proportion of PMNL in CSF and PB of patients (r=0.62, p<0.001) CONCLUSION: The change from a predominance of PMNL to a predominance of mononucler leukocytes was occurred 12-24 hours after onset, and there was a strong correlation between the proportion of neutrophils in CSF and PB.

A Case of Acute Motor Axonal Type Guillain-Barr Syndrome with Anti-GM1 Antibody and Anti-GD1 Antibody / 대한소아신경학회지

Acute motor axonal Guillain-Barr syndrome is a paralytic disorder of abrupt onset, characterized electrophysiologically by near-normal terminal latencies, preserved nerve conduction velocity with low CAMP amplitude without a conduction block, and early appearing nerve inexcitability and by sparing sensory fibers. Most cases have antecedental infection with Campylobacter jejuni and have antibodies directed toward GM1 ganglioside-like epitopes. We have experienced a case of primary axonal type of Guillain-Barr syndrome in a 14-year-old female patient, who has symptoms of difficulty in swallowing and progressive flaccid paralysis associated with anti-GM1 antibody and anti-GD1 antibody.