Yoo, Sang Soo;Rhee, Min Hee;Lee, Jeongho;Lee, Dong Hwan
Journal of The Korean Society of Inherited Metabolic disease
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v.13
no.2
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pp.98-103
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2013
Purpose: MAT-I/III deficiency by MAT1A gene mutation causes isolated hypermethioninemia, which is considered to be a clinically benign disease. But in some patients, mental retardation, developmental delay, myelination disorder may be shown. This study was performed to find out the clinical manifestations and genetic characteristics of patients with isolated hypermethioninemia. Methods: Clinical, biochemical and genetic analysis were done to 10 patients with isolated hypermethioninemia who were referred to department of pediatrics, Soonchunhyang University Hospital from March 1999 to March 2012. Results: At first visit, all patients' mean plasma methionine level was 5.5 mg/dL (2.1-14.6) and there were no increase of amino acid levels including homocystine in all patients. Serum homocysteine level was evaluated in seven patients who visited after year 2003, and ranged from 4.96 to $11.15{\mu}mol/L$ (normal < $25{\mu}mol/L$). Methionine restricted diet was started to all patients. Nine patients who managed regularly showed normal development, but one patient whose initial plasma methionine level was 14.6 mg/dL showed language delay at 1 year of age and was diagnosed as mild mental retardation (IQ=66) at 6 years of age. Genetic analysis was done to eight patients, R264H mutation was identified in seven patients. Also, both R299C and R356Q mutation were identified in one patient. Conclusion: Clinical findings in patients with isolated hypermethioninemia were generally good, but one patient showed mental retardation and language difficulty. R264H mutation which usually inherits as an autosomal dominant trait was most frequently found in our patients, and R299C/R356Q mutation were also identified.
Purpose : The development of the corpus callosum occupies the entire period of cerebral formation. The myelination pattern on magnetic resonance imaging (MRI) is very useful to evaluate neurologic development and to predict neurologic outcome in high risk infants. The thickness of the corpus callosum is believed to depend on the myelination process. It is possible to calculate the length and thickness of the corpus callosum on MRI. Thus, we can quantitatively evaluate the development of the corpus callosum. We investigated the clinical significance of measuring various portions of the corpus callosum in neonate with neurologic disorders such as hypoxic brain damage and seizure disorder. Methods : Forty-two neonates were evaluated by brain MRI. We measured the size of the genu, body, transitional zone, splenium, and length of the corpus callosum. Each measurement was divided by the total length of the corpus callosum to obtain its corrected size. The ratio of corpus callosal length and the anteroposterior diameter of the brain was also measured. Results : There was no statistical significance in the sample size of each part of the corpus callosum. However, the corrected size or the ratio of body of the corpus callosum correlated with periventricular leukomalacia and hypoxic ischemic encephalopathy. Conclusion : The abnormal size of the corpus callosum showed a good correlation with periventricular leukomalacia and hypoxic ischemic encephalopathy in neonates. We can predict clinical neurological problems by estimation of the corpus callosum in the neonatal period.
Myelin-associated glycoprotein (MAG) has been known to have a crucial role to the formation of myelin sheath during initial stage of myelination. In the present study, we investigated the aging-related expressional changes of MAG in the rat cerebrum. MAG expression was markedly decreased in cerebral cortex by aging. In the adult rat cerebrum, MAG-positive rolls were process-bearing cells with large nucleus, and extensively distributed. However, in the aged rat brain, MAG-positive cells showed small and round morphology with little cytoplasm and few processes. MAG was co-expressed with galatocerebroside, but not with Iba-1, or GFAP. These results suggest that the expressional change of MAG-positive cells is associated with degeneration of oligodendrocyte-myelin system by aging, and that MAG is likely to be a reliable marker for the mature oligodendrocytes in the aged rat brain.
A peripheral nerve when approximation of the ends imparts tension at the anastomosis and with a relatively long segment defect after excision of neuroma and neurofibroma cannnot be repaired by early primary suture. The one of the optimistic reconstruction method of severed peripheral nerves is to restore tension-free continuity at the repair site putting an autogenous nerve graft into the neural gap despite of ancipating motor or sensory deficit of the donor nerve area. To overcome the deficit of the autogenous nerve graft, several other conduits supplying a metabolically active environment which is able to support axon regeneration and progression, providing protection against scar invasion, and guiding the regrowing axons to the distal stump of the nerve have been studied. An author have used ipsilateral femoral vein, ipsilateral femoral vein filled with fresh thigh muscle, and autogenous sciatic nerve for the sciatic nerve defect of around 10 mm in length to observe the regeneration pattern in rat by light and electron microscopy. The results were as follows. 1. Light microscopically regeneration pattern of nerve fibers in the autogenous graft group was more abundant than vein graft and vein filled with muscle group. 2. On ultrastructural findings, the proxial end of the graft in various groups showed similar regenerating features of the axons, myelin sheaths, and Schwann cells. The fascicular arrangement of the myelinated and unmyelinated fibers was same regardless of the type of conduits. There were more or less increasing tendency in the number and the diameter of myelinated fibers correlated with the regeneration time. 3. In the middle of the graft, myelinated nerve fibers of vein filled with muscle group were more in number and myelin sheath was thinner than in the venous graft, but the number of regenerating axons in autogenous nerve graft was superior to that in both groups of the graft. The amount of collagen fibrils and amorphous materials in the endoneurial space was increased to elapsed time. 4. There was no difference in regenerating patterns of the nerve fibers of distal end of the graft. The size and shape of the myelinated nerve fbers were more different than that of proximal and middle portion of the graft. From the above results, the degree of myelination and regenerating activity in autogenous nerve is more effective and active in other types of the graft and there were no morphological differences in either ends of the graft regardless of regeneration time.
Adequate vascularization is pivotally essential for a successful nerve graft. Theoretically, the immediate vascularization will inhibit fibroblast infiltration and stimulate nerve cell regeneration. In this study, histomorphological and electrophysiological studies were performed to determine if vascularized grafts are functionally superior. In rat model, a 4cm segment of the sciatic nerve was obtained and placed as a non vascularized graft on one side, and as a vascularized graft connected to the inferior gluteal vessels on the opposite side. To determine the compound action potential of the gastrocnemius muscle, electromyography was done after 2, 3 and 4 months. Histomorphologically, the distribution of myelinated nerve fibers and Schwann cell were evaluated after toluidine blue staining, The following resutls were obtained: 1. The electrophysiological studies showed no difference between the nonvascularized and vascularized grafts. 2. Two and three months after grafting, myelinated nerve fibers were more abundant in the vascularized proximal, middle and distal areas in all nerve fibers of varying diameters. 3. In the post-nonvascularized graft 2-month group, a few myelinated nerve fibers were present in the proximal and middle areas, but none distally. In the post-vascularized graft 2 month group, myelinated nerve fibers ranging $2-8{\mu}m$ were present in all three areas. 4. In the post-nonvascularized graft 3 month group, a few myelinated nerve fibers ranging in $2-6{\mu}m$ were present in all three areas, but in the post-vascularized graft 3 month group, many myelinated nerve fibers ranging in $2-10{\mu}m$ were present in all three areas. 5. In the post-graft 4-month group, more myelinated nerve fibers were present in all three areas of the vascularized grafts. However, nerve fibers of less than $2{\mu}m$ in diameter were more abundant in the non vascularized grafts. 6. Schwann cells were more abundant in the proximal, middle and distal areas of the post-vascularized 2, 3 and 4-month grafts. Based on these findings, the immediate restoration of circulation in vascularized nerve grafts allows for the increased number of surviving Schwann cells, rapid healing of the axon and myelin sheath changes which occur during Wallerian degeneration, and thus is able to stimulate a morphologically optimal regeneration.
Kim, Yoon-Myung;Choi, In-Hee;Kim, Jun Suk;Kim, Ja Hye;Cho, Ja Hyang;Lee, Beom Hee;Kim, Gu-Hwan;Choi, Jin-Ho;Seo, Eul-Ju;Yoo, Han-Wook
Clinical and Experimental Pediatrics
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v.59
no.sup1
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pp.25-28
/
2016
Phelan-McDermid syndrome is a rare genetic disorder caused by the terminal or interstitial deletion of the chromosome 22q13.3. Patients with this syndrome usually have global developmental delay, hypotonia, and speech delays. Several putative genes such as the SHANK3, RAB, RABL2B, and IB2 are responsible for the neurological features. This study describes the clinical features and outcomes of Korean patients with Phelan-McDermid syndrome. Two patients showing global developmental delay, hypotonia, and speech delay were diagnosed with Phelan-McDermid syndrome via chromosome analysis, fluorescent in situ hybridization, and multiplex ligation-dependent probe amplification analysis. Brain magnetic resonance imaging of Patients 1 and 2 showed delayed myelination and severe communicating hydrocephalus, respectively. Electroencephalography in patient 2 showed high amplitude spike discharges from the left frontotemporoparietal area, but neither patient developed seizures. Kidney ultrasonography of both the patients revealed multicystic kidney disease and pelviectasis, respectively. Patient 2 experienced recurrent respiratory infections, and chest computed tomography findings demonstrated laryngotracheomalacia and bronchial narrowing. He subsequently died because of heart failure after a ventriculoperitoneal shunt operation at 5 months of age. Patient 1, who is currently 20 months old, has been undergoing rehabilitation therapy. However, global developmental delay was noted, as determines using the Korean Infant and Child Development test, the Denver developmental test, and the Bayley developmental test. This report describes the clinical features, outcomes, and molecular genetic characteristics of two Korean patients with Phelan-McDermid syndrome.
Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain sensation in some way protects body from imminent threat or injury. Peripheral sensory nerves innervated to peripheral tissues initially respond to multiple forms of noxious or strong stimuli, such as heat, mechanical and chemical stimuli. In response to these stimuli, electrical signals for conducting the nociceptive neural signals through axons are generated. These action potentials are then conveyed to specific areas in the spinal cord and in the brain. Sensory afferent fibers are heterogeneous in many aspects. For example, sensory nerves are classified as $A{\alpha}$, $-{\beta}$, $-{\delta}$ and C-fibers according to their diameter and degree of myelination. It is widely accepted that small sensory fibers tend to respond to vigorous or noxious stimuli and related to nociception. Thus these fibers are specifically called nociceptors. Most of nociceptors respond to noxious mechanical stimuli and heat. In addition, these sensory fibers also respond to chemical stimuli [Davis et al. (1993)] such as capsaicin. Thus, nociceptors are considered polymodal. Recent advance in research on ion channels in sensory neurons reveals molecular mechanisms underlying how various types of stimuli can be transduced to neural signals transmitted to the brain for pain perception. In particular, electrophysiological studies on ion channels characterize biophysical properties of ion channels in sensory neurons. Furthermore, molecular biology leads to identification of genetic structures as well as molecular properties of ion channels in sensory neurons. These ion channels are expressed in axon terminals as well as in cell soma. When these channels are activated, inward currents or outward currents are generated, which will lead to depolarization or hyperpolarization of the membrane causing increased or decreased excitability of sensory neurons. In order to depolarize the membrane of nerve terminals, either inward currents should be generated or outward currents should be inhibited. So far, many cationic channels that are responsible for the excitation of sensory neurons are introduced recently. Activation of these channels in sensory neurons is evidently critical to the generation of nociceptive signals. The main channels responsible for inward membrane currents in nociceptors are voltage-activated sodium and calcium channels, while outward current is carried mainly by potassium ions. In addition, activation of non-selective cation channels is also responsible for the excitation of sensory neurons. Thus, excitability of neurons can be controlled by regulating expression or by modulating activity of these channels.
Objectives: The purpose of this study was to research learning based on brain science and the learning methodology of Korean Medicine according to disparity of age. Through this, the study aimed to provide a guideline to related Korean Medicine treatments as well as the common nurturing/educational institutions. Methods: All journals and dissertations on brain science based learning methods studied in Korea to date that could be found in the National Assembly Library and the RISS were implemented in the analysis. The terminology used for search was as follows: 1st search, 'Brain'; 2nd search, 'Learning', 'Education'; 3rd search, 'Baby, 'Infant', 'Child'. For the learning methodology of Korean Medicine according to disparity of age, the related contents were extracted from Donguibogam and Liuyi, Sasang constitutional medicine. Results: A total of 30 studies, were collected as data. In the baby stage, the development and myelination of brain neurons are accelerated by experience and learning, highly influenced by social, cognitive and emotional movement. In infancy, the frontal lobe actively develops, so education for development of the prefrontal cortex is suggested. The brain of the infant at this stage can be developed by arts and physical education. In the child stage, the parietal and temporal lobe develop actively. Thus, programs to stimulate brain activity including brain respiration would be helpful in enhancing learning ability, concentration, etc. As evidence for learning and nurturing methodology according to disparity of age from Korean Medicine prospective, the following are listed: Location and time for sexual intercourse before pregnancy, stabilization during pregnancy, baby nurturing methods for nurturing from Donguibogam. Also Liuyi and Sasanag constitutional medicine can be the learning methodology according to disparity of age. And there are acupuncture points on each head section according to age in Donguibogam. Conclusions: Studies on 'brain-science based learning' are continuously being conducted. Based on these studies, diverse new brain-science based learning will be developed in the future. There is also a need to develop the learning methodology of Korean Medicine according to disparity of age in a more systematic and diverse way.
Purpose: The aim of this study was to investigate the effect of perinatal risk factors on brain maturation and the relationship of brain maturation and neurodevelopmental outcomes with brain maturation scoring system in brain MRI. Methods: ELBWI infants born at the Seoul National University Children's Hospital from January 2006 to December 2010 were included. A retrospective analysis was performed with their medical record and brain MR images acquired at near full term. We read brain MRI and measured maturity with total maturation score (TMS). TMS is a previously developed anatomic scoring system to assess brain maturity. The total maturation score was used to evaluate the four parameters of maturity: (1) myelination, (2) cortical infolding, (3) involution of glial cell migration bands, and (4) presence of germinal matrix tissue. Results: Images from 124 infants were evaluated. Their mean gestational age at birth was 27.1${\pm}$2.1 weeks, and mean birth weight was 781.5${\pm}$143.9 g. The mean TMS was 10.8${\pm}$2.0. TMS was significantly related to the postmenstrual age (PMA) of the infant, increasing with advancing postmenstrual age (P<0.001). TMS showed no significance with neurodevelopmental delay, and with brain injury, respectively. Conclusion: TMS was developed for evaluating brain maturation in conventional brain MRI. The results of this study suggest that TMS was not useful for predicting neurodevelopmental delay, but further studies are needed to make standard score for each PMA and to re-evaluate the relationship between brain maturation and neurodevelopmental delay.
Mathematical ability is important for academic achievement and technological renovations in the STEM disciplines. This study concentrated on the relationship between neural basis of mathematical cognition and its mechanisms. These cognitive functions include domain specific abilities such as numerical skills and visuospatial abilities, as well as domain general abilities which include language, long term memory, and working memory capacity. Individuals can perform higher cognitive functions such as abstract thinking and reasoning based on these basic cognitive functions. The next topic covered in this study is about individual differences in mathematical abilities. Neural efficiency theory was incorporated in this study to view mathematical talent. According to the theory, a person with mathematical talent uses his or her brain more efficiently than the effortful endeavour of the average human being. Mathematically gifted students show different brain activities when compared to average students. Interhemispheric and intrahemispheric connectivities are enhanced in those students, particularly in the right brain along fronto-parietal longitudinal fasciculus. The third topic deals with growth and development in mathematical capacity. As individuals mature, practice mathematical skills, and gain knowledge, such changes are reflected in cortical activation, which include changes in the activation level, redistribution, and reorganization in the supporting cortex. Among these, reorganization can be related to neural plasticity. Neural plasticity was observed in professional mathematicians and children with mathematical learning disabilities. Last topic is about mathematical creativity viewed from Neural Darwinism. When the brain is faced with a novel problem, it needs to collect all of the necessary concepts(knowledge) from long term memory, make multitudes of connections, and test which ones have the highest probability in helping solve the unusual problem. Having followed the above brain modifying steps, once the brain finally finds the correct response to the novel problem, the final response comes as a form of inspiration. For a novice, the first step of acquisition of knowledge structure is the most important. However, as expertise increases, the latter two stages of making connections and selection become more important.
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