• Clinical and Experimental Pediatrics
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• v.61 no.5
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• pp.150-155
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• 2018

Purpose: Infantile spasms, also known as West syndrome, is an age-specific epileptic seizure. Most patients with this condition also exhibit delayed development. This study aimed to determine the effect of long-term prenatal stress on susceptibility to infantile spasms. Methods: We subjected pregnant rats to acute or chronic immobilization stress. Resulting offspring received N-methyl-D-aspartic acid (15 mg/kg, intraperitoneally) on postnatal day 15, and their behaviors were observed 75 minutes after injection. The expression of KCC2 and GAD67 was also determined using immunohistochemistry. Results: Exposure to long-term prenatal stress increased the frequency of spasms and decreased the latency to onset of spasms compared with offspring exposed to short-term prenatal stress. Expression of KCC2 and GAD67 also decreased in the group exposed to long-term prenatal stress compared with the group exposed to short-term prenatal stress. Conclusion: Our study suggests that exposure to long-term prenatal stress results in increased susceptibility to seizures.

• The Journal of Korean Medicine
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• v.36 no.2
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• pp.50-55
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• 2015

Infants with tuberous sclerosis complex (TSC) have a higher chance of experiencing seizures before the age of 1 year; in particular, they commonly accompany infantile spasms. In cases where infantile spasms resulting from TSC are drug-resistant, more severe neuro-developmental and cognitive impairments occur. This particular case dealt with an infant with TSC who continued to experience partial seizures and infantile spasms despite using two different kinds of antiepileptic drugs (AEDs). His spasms ceased on the seventh day of taking modified Yukmijihwang-tang (YMJ), at which point he stopped the use of all AEDs. He became seizure-free after a month of the treatment and modified hypsarrythmia was found to have been resolved in the electroencephalogram test. Until now, the infant has been taking YMJ for 16 months and is maintaining the seizure-free state without side effects. Moreover, his developmental status is continually improving, with a significant progress in language and cognitive-adaptive abilities. Such results suggest that YMJ can serve as an alternative treatment option for refractory epilepsy.

• Journal of Genetic Medicine
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• v.18 no.1
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• pp.55-59
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• 2021

West syndrome (WS) presenting with infantile spasms, developmental delay, and hypsarrhythmia has genetic etiology in some patients. Movement disorders or visual impairment that share genetic underpinnings with infantile spasms can provide diagnostic clues for specific genetic mutations. Mutations of the GRIN1 gene encoding the glutamate receptor inotropic N-methyl-D-aspartate subunit can result in WS with hyperkinetic movements, cortical visual impairment, autistic features, and bilateral polymicrogyria. An 11-month-old boy with WS showed hyperkinetic movements and visual impairment. Brain magnetic resonance imaging and metabolic investigations revealed no abnormalities. Whole-exome sequencing revealed a novel likely pathogenic variant (c.1561_1563del; p.Asn521del) of GRIN1 (NM_007327.3). The proband was treated with vigabatrin and became seizure-free within one week. Notably, the cortical blindness improved within 3 months and the hyperkinetic movements resolved one year after the proband became seizure-free. To the best of our knowledge, this is the first report of GRIN1 encephalopathy in Koreans.

• Clinical and Experimental Pediatrics
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• v.52 no.7
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• pp.804-810
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• 2009

Purpose : We investigated whether ictal single-photon emission computed tomography (SPECT) with prolonged injection of technetium-99m (99mTc) ethyl cysteinate dimer during repeated spasms can localize the epileptogenic foci in children with infantile spasms. Methods : Fourteen children with infantile spasms (11 boys, 3 girls; mean age, $2.2{\pm}1.3$ years) were examined. When a cluster of spasms was detected during video electroencephalography (EEG) monitoring, $^{99m}Tc$ ethyl cysteinate dimer was slowly and continuously injected for 2 minutes to determine the presence of ictal SPECT. For 7 children, the ictal and interictal SPECT images were visually analyzed, while for the remaining 7 children, the SPECT images were analyzed using the subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM) technique. Subsequently, we analyzed the association between the ictal SPECT findings and those of other diagnostic modalities such as EEG, MRI, and positron emission tomography (PET). Results : Increase in cerebral blood flow on ictal SPECT involved the epileptogenic foci in 10 cases6 cases analyzed by visual assessment and 4 analyzed by the SISCOM technique. The ictal SPECT and video-EEG findings showed moderate agreement (Kappa=0.57; 95% confidence interval, 0.18-0.96). Conclusion : Ictal SPECT with prolonged injection of a tracer could provide supplementary information to localize the epileptogenic foci in infantile spasms.

• The Journal of Pediatrics of Korean Medicine
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• v.28 no.1
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• pp.61-70
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• 2014

Objectives The purpose of this study is to report three cases of epileptic children who were treated by oriental medicine. Methods Three epileptic children were treated by Gwakhyangjeonggi-san and Kuibiondam-tang. Two children had took combination therapy; anti-epilepsy drugs and oriental medicines and the other one took only oriental medicines. We measured frequency and intensity of seizure, and observed general conditions. Results The oriental medicine treatment is not only reducing seizures, but also improving general condition like digestion, constipation and reducing frequency of common cold and symptom of rhinitis. Conclusions Epilepsy in childhood is induced by various factor like Fung (風), Dam (痰), Sik (食), Kyung (驚). We administrated oriental medicine and prevented seizures.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.29-31
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• 2016

Glucose transport 1 (GLUT-1) deficiency is a rare syndrome caused by mutations in the glucose transporter 1 gene (SLC2A1) and is characterized by early-onset intractable epilepsy, delayed development, and movement disorder. De novo mutations and several hot spots in N34, G91, R126, R153, and R333 of exons 2, 3, 4, and 8 of SLC2A1 are associated with this condition. Seizures, one of the main clinical features of GLUT-1 deficiency, usually develop during infancy. Most patients experience brief and subtle myoclonic jerk and focal seizures that evolve into a mixture of different types of seizures, such as generalized tonic-clonic, absence, myoclonic, and complex partial seizures. Here, we describe the case of a patient with GLUT-1 deficiency who developed infantile spasms and showed delayed development at 6 months of age. She had intractable epilepsy despite receiving aggressive antiepileptic drug therapy, and underwent a metabolic workup. Cerebrospinal fluid (CSF) examination showed CSF-glucose-to-blood-glucose ratio of 0.38, with a normal lactate level. Bidirectional sequencing of SLC2A1 identified a missense mutation (c.1198C>T) at codon 400 (p.Arg400Cys) of exon 9.

• Clinical and Experimental Pediatrics
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• v.54 no.6
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• pp.241-245
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• 2011

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder that results from mutations in the TSC1 or TSC2 genes, and is associated with hamartomas in several organs, including subependymal giant cell tumors. The neurological manifestations of TSC are particularly challenging and include infantile spasms, intractable epilepsy, cognitive disabilities, and autism. The TSC1- and TSC2-encoded proteins modulate cell function via the mammalian target of rapamycin (mTOR) signaling cascade, and are key factors in the regulation of cell growth and proliferation. The mTOR pathway provides an intersection for an intricate network of protein cascades that respond to cellular nutrition, energy levels, and growth factor stimulation. In the brain, TSC1 and TSC2 have been implicated in cell body size, dendritic arborization, axonal outgrowth and targeting, neuronal migration, cortical lamination, and spine formation. The mTOR pathway represents a logical candidate for drug targeting, because mTOR regulates multiple cellular functions that may contribute to epileptogenesis, including protein synthesis, cell growth and proliferation, and synaptic plasticity. Antagonism of the mTOR pathway with rapamycin and related compounds may provide new therapeutic options for TSC patients.

• Journal of Interdisciplinary Genomics
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• v.3 no.1
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• pp.13-20
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• 2021

Developmental and epileptic encephalopathies are the most devastating early-onset epilepsies, characterized by early-onset seizures that are often intractable, electroencephalographic abnormalities, developmental delay or regression, and various comorbidities. A large number of underlying genetic variants of developmental and epileptic encephalopathies have been identified over the past few decades. However, the most thorough sequencing studies leave 60-65% of patients without a molecular diagnosis. This review explores the genetic basis of developmental and epileptic encephalopathies that start within the first year of life, including Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, infantile spasms, and Dravet syndrome. The purpose of this review is to give an overview and encourage the clinicians to start considering genetic testing as an important investigation along with electroencephalogram for better understanding and management of developmental and epileptic encephalopathies.

• Clinical and Experimental Pediatrics
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• v.53 no.1
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• pp.80-84
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• 2010

Purpose : The aims of this study were to investigate the long-term outcomes in children with infantile spasms (IS) and to identify the prognostic factors influencing their neurodevelopment. Methods : We retrospectively evaluated seventy two children over five years old who were treated for IS at Asan Medical Center, Seoul, Korea, between 1994 and 2007. Forty-three children were contacted by telephone or medical follow-up to assess their current neurodevelopmental status. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence interval (95% CIs) of risk factors for unfavorable outcomes.Results : The mean follow-up duration for these 43 children was $7.2{\pm}1.5$ years (range, 4.5 to 13.0 years). Of these, 13 (30.2%) had cryptogenic and 30 (69.8%) had symptomatic IS. Eleven (25.6%) children were initially treated with adrenocorticotrophic hormone (ACTH) therapy, with a mean treatment lag of $1.3{\pm}1.9$ months (range; 0.1 to 7.0 months). Eighteen (41.8%) children clinically responded to initial treatment, as shown by EEG response. Overall, 22 (51.2%) children had at least moderate neurodevelopmental disorders and 2 (4.8%) died. In univariate analysis, etiology (symptomatic) and poor electroclinical response to initial treatment were related to long-term unfavorable outcomes. In multivariate analysis, response to primary treatment was the sole significant independent risk factor with a high OR. Conclusion : Overall prognosis of children with IS was poor. Electroclinical non-responsiveness to initial treatment was related to unfavorable long-term outcomes, indicating that initial control of seizures may be important in reducing the likelihood of poor neurodevelopment.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.2
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• pp.62-67
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• 2018

Hunter syndrome, also known as mucopolysaccharidosis Type II (MPS II), is one of the lysosomal storage diseases caused by a lack of the enzyme iduronate 2-sulfatase (I2S). Lack of the I2S enzyme activity leads to accumulation of the glycosaminoglycans (GAG), causing dysfunction of multiple organs and systems. MPS II is an X-linked recessive disease due to mutation of IDS gene located on long arm of the X chromosome (Xq28). To date, more than 350 mutations of IDS gene have been identified in Hunter syndrome. Phenotypes of MPS II are classified as either severe or attenuated depending on the degree of cognitive impairment. Because the phenotype of MPS II is related to the type of mutation, identifying mutations is useful in predicting prognosis. We recently had a case of MPS II diagnosed by exome sequencing in a 7 month old boy with infantile spasm uncontrolled by AED. He was diagnosed with hearing loss at 2 months of age, and he took vigabatrin and prednisolone to control infantile spasms diagnosed at 3 months of age. At 6 months of age, whole exome sequencing was performed to evaluate the infantile spasm and hearing loss in this patient, and the mutation c.851C>T (p.Pro284Leu) inherited from hemizygous mother was revealed. The results of urine Cetylpyridinium Chloride (CPC) precipitation test, which were negative until 8 months of age, were positive from 9 months of age. We report a case of MPS II diagnosed by exome sequencing and treated through enzyme replacement therapy from 9 months after birth.