• Clinical and Experimental Pediatrics
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• v.60 no.1
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• pp.1-9
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• 2017

Malformations of cortical development are rare congenital anomalies of the cerebral cortex, wherein patients present with intractable epilepsy and various degrees of developmental delay. Cases show a spectrum of anomalous cortical formations with diverse anatomic and morphological abnormalities, a variety of genetic causes, and different clinical presentations. Brain magnetic resonance imaging has been of great help in determining the exact morphologies of cortical malformations. The hypothetical mechanisms of malformation include interruptions during the formation of cerebral cortex in the form of viral infection, genetic causes, and vascular events. Recent remarkable developments in genetic analysis methods have improved our understanding of these pathological mechanisms. The present review will discuss normal cortical development, the current proposed malformation classifications, and the diagnostic approach for malformations of cortical development.

• Journal of Genetic Medicine
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• v.12 no.1
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• pp.12-18
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• 2015

Malformations of cortical development (MCD) cover a broad spectrum of developmental disorders which cause the various clinical manifestations including epilepsy, developmental delay, and intellectual disability. MCD have been clinically classified based on the disruption of developmental processes such as proliferation, migration, and organization. Molecular genetic studies of MCD have improved our understanding of these disorders at a molecular level beyond the clinical classification. These recent advances are resulted from the development of massive parallel sequencing technology, also known as next-generation sequencing (NGS), which has allowed researchers to uncover novel molecular genetic pathways associated with inherited or de novo mutations. Although an increasing number of disease-related genes or genetic variations have been identified, genotype-phenotype correlation is hampered when the biological or pathological functions of identified genetic variations are not fully understood. To elucidate the causality of genetic variations, in vivo disease models that reflect these variations are required. In the current review, we review the use of NGS technology to identify genes involved in MCD, and discuss how the functions of these identified genes can be validated through in vivo disease modeling.

• Journal of Korean Neurosurgical Society
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• v.62 no.3
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• pp.265-271
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• 2019

The expansion and folding of the cerebral cortex occur during brain development and are critical factors that influence cognitive ability and sensorimotor skills. The disruption of cortical growth and folding may cause neurological disorders, resulting in severe intellectual disability and intractable epilepsy in humans. Therefore, understanding the mechanism that regulates cortical growth and folding will be crucial in deciphering the key steps of brain development and finding new therapeutic targets for the congenital anomalies of the cerebral cortex. This review will start with a brief introduction describing the anatomy of the brain cortex, followed by a description of our understanding of the proliferation, differentiation, and migration of neural progenitors and important genes and molecules that are involved in these processes. Finally, various types of disorders that develop due to malformation of the cerebral cortex will be discussed.

• Journal of Korean Neurosurgical Society
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• v.62 no.3
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• pp.321-327
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• 2019

Focal cortical dysplasia (FCD) is the major cause of intractable focal epilepsy in childhood leading to epilepsy surgery. The overall seizure freedom after surgery ranges between 50-75% at 2 years after surgery and the long-term seizure freedom remain relatively stable. Seizure outcome after surgery depends on a various factors such as pathologic etiologies, extent of lesion, and types of surgery. Therefore, seizure outcome after surgery for FCD should be analyzed carefully considering cohorts' characteristics. Studies of pediatric epilepsy surgery emphasize the early surgical intervention for a better cognition. Early surgical intervention and cessation of seizure activity are important for children with intractable epilepsy. However, there are limited data on the cognitive outcome after surgery in pediatric FCD, requiring further investigation. This paper reviews the seizure and cognitive outcomes of epilepsy surgery for FCD in children. Several prognostic factors influencing seizure outcome after surgery will be discussed in detail.

• The Korean Journal of Nuclear Medicine
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• v.35 no.1
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• pp.23-32
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• 2001

Purpose: Cortical dysplasia (CD) designates a diverse group of malformations resulting from one or more abnormalities in the development of the cerebral cortex. We investigated the findings of interictal SPECT and the diagnostic usefulness of interical and ictal SFECT according to pathological grading (PG) in comparison with MRI. Materials and Methods: This study included 16 patients (M:F=9:7, age: $19.9{\pm}11.8$ yrs) with pathologically proven CD. Tc-99m ECD SPECT was performed in all patients: interictal 11, interictal and ictal 3, ictal 2. MRI were obtained in all patients and image analysis was done blindly as to the result of SPECT. Pathologic findings of CD were classified into grade 1 G1, dyslamination), grade 2 (G2, dysplastic neurons) and grade 3 (G3, balloon cells). We compared SFECT with MRI in lesions-to-lesions and analyzed the result according to PG. Results: In SFECT and MRI. 38 and 27 lesions were visually recognized. In 14 interictal SPECT, variable findings in 35 lesions were demonstrated: 25 were hypoperfusion, 7 hyperperfusion, 2 heterotopic perfusion in the white matter. By comparison between two studios, missed lesions were founded: SPECT were 1 lesion, MRI 12. Review of missed 12 lesions of MRI were followed according to PG: G1 patients were 16.7% (4/19), G2 40.0% (6/15), and G3 50% (2/4). Conclusion: Interictal SFECT in CD showed variable findings such as hypoperfusion, hyperperfusion or heterotopic perfusion. However, for detection of missed CD on MRI, SFECT may help to detect a functional abnormality of the lesion with high PG.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.48-54
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• 2017

Purpose: Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal-recessive disorder characterized by early-onset hypotonia associated with brain malformations in dystroglycanopathy. Although the wide spectrum of congenital muscular dystrophies causes difficulty in diagnosis, correlating the genotype with the clinical phenotype can help diagnose FCMD. Here, we evaluated the correlation of targeted molecular genetic analysis of FKTN gene mutation with the FCMD phenotype. Methods: This study was conducted retrospectively with 9 subjects. Inclusion criteria included clinical symptoms characterized by early-onset hypotonia with magnetic resonance imaging (MRI) featuring brain malformations. FKTN gene-alteration analysis was performed using various FKTN gene-analysis methods, including sequencing. Results: Among the 9 subjects studied, 4 (44.4%) were male and 5 (55.6%) were female. The median age of onset of the first symptom was 3.1 months. The first symptom was a delayed milestone in 6 cases (66.7%). All 9 subjects (100%) presented with early-onset hypotonia and global delayed development. All subjects presented with cortical malformation in their brain MRIs. Of the 9 subjects, 6 subjects had previously undergone muscle biopsy and 4 cases (4/6; 66.7%) showed dystrophic or myopathic features. Pathogenic mutations causing FCMD were identified in 3 cases. Conclusions: In this study, all 3 subjects with FKTN mutations showed important MRI findings (pachygyria and cerebellar dysplasia). These data suggest that patients with characteristic phenotypes who show pachygyria and cerebellar abnormalities in brain MRIs may have a high probability of being diagnosed with FCMD.

• Clinical and Experimental Pediatrics
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• v.46 no.12
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• pp.1253-1259
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• 2003

Backgroud : Seizures in the neonate are relatively common and their clinical features are different from those in children and adults. The study aimed to provide the clinical profiles of neonatal seizure in our hospital. Methods : A total of 41 newborns with seizures were enrolled in this study over a period of three years. They were evaluated with special reference to risk factors, neurologic examinations, laboratory data, neuroimaging studies, EEG findings, seizure types, response to treatment, and prognosis, etc. Results : The average age at onset of seizures was $6.1{\pm}4.6days$ and the majority of patients(42%) had multifocal clonic seizure and 24% had subtle seizure. Factors that are known to increase risk of neonatal seizures include abnormal delivery history, birth asphyxia, and electrolyte imbalance, etc. However, they remain obscure in about 20% of cases. More than 50 percent showed abnormal lesions on neuroimaging studies such as brain hemorrhage, periventricular leukomalacia, brain infarction, cortical dysplasia, hydrocephalus, etc. and 17 out of 32 patients showed abnormal electroencephalographic patterns. Phenobarbital was tried as a first line antiepileptic drug and phenytoin was added if it failed to control seizures. The treatments were terminated in the majority of patients during the hospital stay. The overall prognosis was relatively good except for those with abnormal EEG background or congenital central nervous system malformations. Conclusion : Neonatal seizures may permanently disrupt brain development. Better understanding of their clinical profiles and appropriate management may lead to a reduction in neurological disability in later childhood.