Kyu-Chang Wang

Seoul National University Hospital, Sŏul, Seoul, South Korea

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Publications (208)513.47 Total impact

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    ABSTRACT: Moyamoya disease (MMD) is a common cause of childhood stroke, in which the abnormal function of the endothelial colony-forming cell (ECFC) plays a key role in the pathogenesis of the disease. This study was designed to identify genes involved in MMD pathogenesis using gene expression profiling and to understand the defective function of MMD ECFCs. We compared gene expression profiles of ECFCs isolated from patients with MMD and normal controls. Among the differentially expressed genes, we selected a gene with the most downregulated expression, retinaldehyde dehydrogenase 2 (RALDH2). The activity of RALDH2 in MMD ECFCs was assessed by in vitro tube formation assay and in vivo Matrigel plug assay in the presence of all-trans retinoic acid. The transcriptional control of RALDH2 was tested using ChIP assays on acetyl-histone H3. Through the gene expression profiling of 7 MMD ECFCs, we were able to identify 537 differentially expressed genes. Notably, the expression of RALDH2 was markedly suppressed in MMD ECFCs. MMD ECFCs inefficiently formed capillary tubes in vitro and capillaries in vivo, a defect restored by all-trans retinoic acid treatment. Knockdown of RALDH2 mRNA in normal ECFCs also induced decreased activity of capillary formation in vitro. The decreased level of RALDH2 mRNA in MMD ECFCs was attributed to defective acetyl-histone H3 binding to the promoter region. From these results, we conclude that the expression of RALDH2 was epigenetically suppressed in ECFCs from patients with MMD, which may play a key role in their functional impairment. © 2015 American Heart Association, Inc.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2015; DOI:10.1161/ATVBAHA.115.305363 · 5.53 Impact Factor
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    ABSTRACT: Primary melanocytic lesions of the central nervous system originate from leptomeningeal melanocytes, with a spectrum ranging from well-differentiated benign meningeal melanocytomas to malignant melanomas. Atypical melanocytomas are borderline tumors, which have clinical and pathological characteristics between benign melanocytomas and malignant melanomas. Melanocytomas are rare in children and infrequently arise from the cavernous sinus. Approximately five patients with such an origin site have been reported. We report a 15-year-old girl with an atypical melanocytoma arising from the cavernous sinus. She underwent partial resection of the tumor and postoperative gamma knife surgery (GKS). She is stable 39 months after surgery. We discuss the first pediatric case with an intracranial atypical melanocytoma arising from the cavernous sinus.
    Child s Nervous System 05/2015; DOI:10.1007/s00381-015-2741-3 · 1.16 Impact Factor
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    ABSTRACT: The location of a brain tumor is a fundamental characteristic, because various brain tumors develop in relatively specific locations. An atypical teratoid/rhabdoid tumor (AT/RT) is a highly age-specific tumor that occurs in infants and young children. However, AT/RTs develop in a variety of locations in the brain. This study aimed at uncovering the tumor location pattern of AT/RTs to enhance diagnoses. Neuroimages from 27 patients with a pathologically proven AT/RT were reviewed, and the specific tumor locations were described and categorized. The association of imaging characteristics and tumor location was analyzed. The posterior fossa was the most frequent locations accounting for 19 patients (70 %), followed by the diencephalon (four patients; 15 %), cerebrum (three patients; 11 %), and midbrain (one patient; 4 %). In the posterior fossa, the superior medullary velum (SMV) and cerebellopontine angle (CPA) areas were the most common sites (eight patients each) and three patients had a tumor in the inferior medullary velum (IMV) region. AT/RTs in the SMV area had a significantly higher chance of no/minimal enhancement compared with tumors in other locations (P = 0.001) and a lower likelihood of leptomeningeal tumor seeding at presentation (P = 0.053). The location spectrum of AT/RT follows a specific pattern, and some of the locations are linked with intriguing clinical characteristics. This information may not only help make correct preoperative diagnosis but also occasionally aid in postoperative pathological diagnosis.
    Child s Nervous System 05/2015; DOI:10.1007/s00381-015-2739-x · 1.16 Impact Factor
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    ABSTRACT: Congenital dermal sinus (CDS) is a type of occult spinal dysraphism characterized by a midline skin dimple. A 12-month-old girl presented with fever and ascending quadriparesis. She had a midline skin dimple in the upper sacral area that had been discovered in her neonatal period. Imaging studies revealed a holocord intramedullary abscess and CDS. Overlooking CDS or misdiagnosing it as benign sacrococcygeal dimple may lead to catastrophic infection and cause serious neurological deficits. Therefore, further imaging work-up or consultation with a pediatric neurosurgeon is recommended following discovery of any atypical-looking dimples in the midline.
    Journal of Korean Neurosurgical Society 03/2015; 57(3):225-8. DOI:10.3340/jkns.2015.57.3.225 · 0.52 Impact Factor
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    ABSTRACT: Purpose Langerhans cell histiocytosis (LCH) arising from the skull base is a rare acute optic neuropathy cause. We describe a clinical approach for the purpose of optic nerve decompression and simultaneous lesion excision. This is the first case of visual improvement following decompression operation via endoscopic endonasal approach for acute optic neuropathy that is produced by LCH. Methods An 11-year-old boy presented with a 2-week history of visual deterioration. Radiological evidence of compressive optic neuropathy by an expansile soft tissue mass around the optic canal was observed. The patient underwent an endoscopic endonasal optic nerve decompression and subtotal tumor removal. Results His visual impairment improved dramatically after the operation. Conclusions Acute optic neuropathy can be elicited by LCH arising in the sphenoid-ethmoid bone. Early decompression is the key to vision salvage. An endoscopic endonasal approach may be a good therapeutic option in this situation.
    Child s Nervous System 01/2015; 31(4). DOI:10.1007/s00381-014-2610-5 · 1.16 Impact Factor
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    ABSTRACT: TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%¿±¿8.7%, respectively (p¿<¿0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%¿±¿2% vs. 57.4%¿±¿1.8% (p¿<¿0.01)). In contrast, ß-catenin mutation sensitized TP53 mutant cells to radiation (p¿<¿0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%¿±¿1.5% in lithium treated cells vs. 56.6¿±¿3% (p¿<¿0.01)) accompanied by increased number of ¿H2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%¿±¿8% for lithium treated cells vs. 27%¿±¿3% for untreated controls (p¿=¿0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
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    ABSTRACT: Purpose Cranial distraction osteogenesis (DO) has many advantages for correcting skull deformities: Thus, DO is extensively used for the treatment of skull deformities. However, diverse, unexpected complications are associated with this procedure. In this study, we present the surgical outcomes and complications of DO. Moreover, we propose a modified protocol for DO to reduce complications. Methods This is a retrospective study on managed patients that underwent DO between March 2008 and May 2013. Their clinical courses were reviewed. Distraction protocols were individually inspected, and the final surgical outcomes, including complications, were evaluated. Results During the study period, a total of ten patients (seven boys and three girls) were treated at our institute. The median distraction period was 20.5 days (ranging from 17 to 50 days). The range of total distraction length was 19–22 mm. The median consolidation period was 96 days (ranging from 0 to 343 days). All patients achieved the goals of distraction. At follow-up evaluations, all patients, except one, showed good surgical outcomes in both head shape and neurologic symptoms. There were six patients with wound complications during the treatment period. Among them, the distractors were removed early in three patients. Interestingly, even these three patients, without a sufficient consolidation period, showed good outcomes. Conclusions Although DO has many merits for correcting skull deformities, it frequently causes severe wound complications. To reduce these complications, we propose a modified protocol with a minimal or even no consolidation period.
    Child s Nervous System 12/2014; 31(5). DOI:10.1007/s00381-014-2607-0 · 1.16 Impact Factor
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    ABSTRACT: Atypical teratoid/rhabdoid tumors (AT/RT) are among the most malignant pediatric brain tumors. Cells from brain tumors with high aldehyde dehydrogenase (ALDH) activity have a number of characteristics that are similar to brain tumor initiating cells (BTICs). This study aimed to evaluate the therapeutic potential of ALDH inhibition using disulfiram (DSF) against BTICs from AT/RT.
    Neuro-Oncology 11/2014; 17(6). DOI:10.1093/neuonc/nou305 · 5.29 Impact Factor
  • Kyu-Chang Wang
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    ABSTRACT: Thank you, Dachling, for the introduction. It is my great honor to be introduced by Dr. Pang.Prologue: Do you know this man?Do you know the man in Fig. 1?Fig. 1Mr. Ki-Moon Ban, the current secretary general of the United Nations (from the webpage of the United Nations, http://www.un.org/)Yes, he is Mr. Ki-Moon Ban who was born in 1944 in Korea before its liberation from Japan. At the age of 17, he had an opportunity to visit San Francisco as a winner of an English essay contest sponsored by the Red Cross. There, he met President John F. Kennedy and dreamed of being a diplomat. He, then, entered Seoul National University, majoring in international relations, and earned a master’s degree from the John F. Kennedy School of Government at Harvard University. In 2007, he became the secretary general of the United Nations (UN). He is now in his second term [1].Do you know the man in Fig. 2?Fig. 2Dr. Jong-Wook Lee, a former director general of the World Health Organization (courtesy of Jun-Woo ...
    Child s Nervous System 11/2014; 30(11). DOI:10.1007/s00381-014-2448-x · 1.16 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):3107-3107. DOI:10.1158/1538-7445.AM2014-3107 · 9.28 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):5513-5513. DOI:10.1158/1538-7445.AM2014-5513 · 9.28 Impact Factor
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    ABSTRACT: Approximately 30 % of patients with moyamoya disease (MMD) have presented with involvement of the posterior circulation, mainly the posterior cerebral artery (PCA). Diagnosis of delayed progression of PCA stenosis in MMD may be difficult due to the diversity in clinical features. The goal of this study was to evaluate pediatric MMD patients with delayed PCA involvement after completion of revascularization of the anterior circulation. Forty-one pediatric MMD patients who underwent revascularization of the PCA territory due to delayed posterior circulation insufficiency MMD from 2006 to 2011 were retrospectively reviewed. The average interval between the initial operation and the occipital artery (OA) procedure was 5.0 years. Common symptoms were headaches and transient visual symptoms. The decision to operate was made based on a combination of diagnostic tools. The results obtained with perfusion MRI, SPECT, MR angiography, and EEG supported posterior circulation insufficiency in 78, 41, 73, and 71 % of patients, respectively. Encephaloduroarteriosynangiosis (EDAS) using the OA was performed in 15 patients, and 26 patients received multiple burr hole trephination of the occipital area. All patients showed clinical improvement. Clinicians should be aware of the possibility of delayed involvement of the PCA in pediatric MMD patients. The clinical decision regarding treatment should be based on a combination of symptomatology and the results obtained with various tools to assess whether the blood flow in the PCA territory is insufficient. Surgical treatment using indirect revascularization appears to be effective for patients with delayed PCA involvement.
    Journal of Neurology 09/2014; DOI:10.1007/s00415-014-7484-7 · 3.84 Impact Factor
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    ABSTRACT: Stem cell-based treatment of traumatic brain injury has been limited in its capacity to bring about complete functional recovery, because of the poor survival rate of the implanted stem cells. It is known that biocompatible biomaterials play a critical role in enhancing survival and proliferation of transplanted stem cells via provision of mechanical support. In this study, we noninvasively monitored in vivo behavior of implanted neural stem cells embedded within poly-l-lactic acid (PLLA) scaffold, and showed that they survived over prolonged periods in corticectomized rat model. Corticectomized rat models were established by motor-cortex ablation of the rat. F3 cells expressing enhanced firefly luciferase (F3-effLuc) were established through retroviral infection. The F3-effLuc within PLLA was monitored using IVIS-100 imaging system 7 days after corticectomized surgery. F3-effLuc within PLLA robustly adhered, and gradually increased luciferase signals of F3-effLuc within PLLA were detected in a day dependent manner. The implantation of F3-effLuc cells/PLLA complex into corticectomized rats showed longer-lasting luciferase activity than F3-effLuc cells alone. The bioluminescence signals from the PLLA-encapsulated cells were maintained for 14 days, compared with 8 days for the non-encapsulated cells. Immunostaining results revealed expression of the early neuronal marker, Tuj-1, in PLLA-F3-effLuc cells in the motor-cortex-ablated area. We observed noninvasively that the mechanical support by PLLA scaffold increased the survival of implanted neural stem cells in the corticectomized rat. The image-guided approach easily proved that scaffolds could provide supportive effect to implanted cells, increasing their viability in terms of enhancing therapeutic efficacy of stem-cell therapy.
    PLoS ONE 09/2014; 9(9):e105129. DOI:10.1371/journal.pone.0105129 · 3.53 Impact Factor
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    ABSTRACT: The indication of surgical treatment for intracranial arachnoid cysts (ACs) is a controversial issue. In this study, we reviewed surgical outcomes of intracranial ACs that were treated with endoscopic fenestration or microscopic fenestration, which are currently standard practices for surgical treatment of AC. In addition, we also evaluated the validity of current surgical indications. We analyzed pediatric patients under 18 years of age who underwent surgical management for intracranial AC between January 2000 and December 2011. Patients with a follow-up period of less than 1 year were excluded. A total of 75 patients were enrolled in this study. These patients were assessed by subjective symptoms and by a clinician's objective evaluation. The radiological assessment of AC after surgery was also evaluated. The median age of patients at the initial operation was 5 years. The median follow-up period was 38 months. The goal of surgery was achieved in 28 % (21/75) of patients. The radiological alteration of AC after initial fenestration surgery was diverse. The results of the clinical and radiological assessments did not always coincide. A total of 35 complications occurred in 28 patients. Subdural fluid collection was the most common unexpected radiological complication. Our study showed that the fenestration procedure for AC produced unsatisfactory clinical improvements compared to the relatively high complication rate. Therefore, surgical treatment for AC should be strictly limited to patients who have symptoms directly related to AC.
    Child s Nervous System 08/2014; 31(1). DOI:10.1007/s00381-014-2525-1 · 1.16 Impact Factor
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    ABSTRACT: Object Ventriculoperitoneal (VP) shunt surgery is the most common treatment for hydrocephalus. In certain situations, uncommon complications can occur after shunting procedures. The authors undertook this study to analyze the clinical characteristics of pediatric patients who developed multifocal intraparenchymal hemorrhages (MIPHs) as a complication of shunt surgery. The authors also analyzed the risk factors for MIPH in a large cohort of patients with hydrocephalus. Methods This study included all pediatric patients (age < 18 years) who underwent VP shunt surgery at the authors' institution between January 2001 and December 2012. During this period, 507 VP shunt operations were performed in 330 patients. Four of these patients were subsequently diagnosed as having MIPH. The authors analyzed the clinical characteristics of these patients in comparison with those of the entire group of shunt-treated patients. Results The incidence of MIPH was 1.2% (4 of 330 cases) for all pediatric patients who underwent VP shunt placement but 2.9% (4 of 140 cases) for infants less than 1 year old. When the analysis was limited to patients whose corrected age was less than 3 months, the incidence was 5.3% (4 of 76 cases). Of the 4 patients with MIPH, 2 were male and 2 were female. Their median age at surgery was 54 days (range 25-127 days), and in all 4 cases, the patients' corrected age was less than 1 month. Three patients were preterm infants, whereas one patient was full-term. None of these patients had a prior history of intracranial surgery (including CSF diversion procedures). All showed severe hydrocephalus during the preoperative period. Their clinical courses as patients with MIPH were comparatively favorable, despite the radiological findings. Conclusions MIPH is a rare but not negligible complication of VP shunt surgery. This complication might be a unique phenomenon in infants, especially young, preterm infants with severe hydrocephalus. Moreover, the absence of previous intracranial procedures might be one of the risk factors for this complication. The rapid alteration of brain conditions in the setting of immaturity might cause MIPH. To prevent this complication, the authors recommend that pressure settings of programmable valves should be gradually adapted to the target pressure.
    Journal of Neurosurgery Pediatrics 07/2014; 14(4):1-7. DOI:10.3171/2014.6.PEDS13635 · 1.37 Impact Factor
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    ABSTRACT: Brainstem glioma is a highly devastating disease, and any mass-like lesion in the brainstem can raise suspicion of this diagnosis. However, other inflammatory, demyelinating, or degenerative diseases can mimic brainstem glioma in clinical presentation and imaging features. Therefore, diagnosis based solely on imaging is often insufficient for brainstem lesions and may lead to incorrect diagnosis and treatment. This case report is the first description of central nervous system aquaporin-4 (AQP4) autoimmunity confined mainly to the brainstem. It demonstrates the wide spectrum of neuroinflammatory diseases in children and highlights the utility of surgical biopsy for suspicious brainstem lesions with atypical imaging features for glioma.
    Journal of Neurosurgery Pediatrics 07/2014; DOI:10.3171/2014.6.PEDS13674 · 1.37 Impact Factor
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    ABSTRACT: Patient: Female, 14 monthsFinal Diagnosis: Slit ventricle syndromeSymptoms: Hydrocephalus • lethargy and seizure • vomitingMedication: —Clinical Procedure: —Specialty: Pediatrics and NeonatologyObjective:Challenging differential diagnosisBackground:Shunt surgery is a common solution for hydrocephalus in infancy. Slit ventricle syndrome and secondary craniosynostosis are late-onset complications after shunt placement; these 2 conditions occasionally occur together.Case Report:We report a case of early-onset secondary craniosynostosis with slit ventricle syndrome after shunt surgery in an infant, which led to a catastrophic increase in intracranial pressure (ICP). A 4-month-old girl with a Dandy-Walker malformation underwent a ventriculoperitoneal shunt procedure. Her head circumference (HC) gradually decreased to approximately the 5th percentile for her age group after shunt surgery. Seven months later, she developed increased ICP symptoms and underwent a shunt revision with a diagnosis of shunt malfunction. Her symptoms were temporarily relieved, but she repeatedly visited the emergency room (ER) for the same symptoms and finally collapsed, with an abrupt increase in ICP, 3 months later. Further evaluation revealed the emergence of sagittal synostosis at 7 months after initial shunt surgery. After reviewing all clinical data, slit ventricle syndrome combined with secondary craniosynostosis was diagnosed. Emergent cranial expansion surgery with shunt revision was performed, and the increased ICP signs subsided in the following days.Conclusions:Clinical suspicion and long-term HC monitoring are important in the diagnosis of slit ventricle syndrome and secondary craniosynostosis after shunt surgery, even in infants and young children.
    06/2014; 15:246-53. DOI:10.12659/AJCR.890590
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    ABSTRACT: Object Neurofibromatosis Type 2 (NF2) is an autosomal-dominant inherited disease, characterized by multiple neoplasia syndromes, including meningioma, schwannoma, glioma, and ependymoma. In this report, the authors present their clinical experience with pediatric NF2 patients. In particular, they focused on the clinical course of vestibular schwannoma (VS), including the natural growth rate, tumor control, and functional hearing outcomes. Methods From May 1988 to June 2012, the authors recruited patients who were younger than 18 years and fulfilled the Manchester criteria. In total, 25 patients were enrolled in this study. The authors analyzed the clinical course of these patients. In addition, they measured the natural growth rate of VS before any treatment in these children with NF2. Then, they evaluated the tumor control rate and functional hearing outcomes after the treatment of VS. Results The mean age at the onset of NF2-related symptoms was 9.9 ± 4.5 years (mean ± SD, range 1-17 years). The mean age at the diagnosis of NF2 was 12.9 ± 2.9 years (range 5-17 years). The mean follow-up period was 89.3 months (range 12-311 months). As initial manifestations, nonvestibular symptoms were frequently observed in pediatric patients with NF2. The mean natural growth rate of VS was 0.33 ± 0.41 cm(3)/year (range 0-1.35 cm(3)/year). The tumor control rate of VS was 35.3% at 3 years after Gamma Knife surgery (GKS). The actuarial rate of useful hearing preservation was 67% in the 1st year and 53% in the 5th year after GKS. Conclusions Clinical manifestations in children with NF2 were highly variable, compared with their adult counterparts. The natural growth rate of VS in children is slow, and this oncological feature may explain the diverse clinical manifestations besides vestibular symptoms in children with NF2. The treatment outcome of GKS for VS in children with NF2 was not favorable compared with previous reports of affected adults.
    Journal of Neurosurgery Pediatrics 04/2014; 13(6). DOI:10.3171/2014.3.PEDS13455 · 1.37 Impact Factor
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    ABSTRACT: Cortical dysplasia (CD) is a common cause of epilepsy in children and is characterized by focal regions of malformed cerebral cortex. The pathogenesis and epileptogenesis of CD have not been fully elucidated, and in particular, the potential role of epigenetics has not been examined. miRNA microarray was performed on surgical specimens from CD (n = 8) and normal control (n = 2) children. A total of 10 differentially expressed miRNAs (DEmiRs) that were up-regulated in CD were identified including hsa-miR-21 and hsa-miR-155. The microarray results were validated using quantitative real-time PCR. After searching for the putative target genes of the DEmiRs, their biological significance was further evaluated by exploring the pathways in which the genes were enriched. The mammalian target of rapamycin (mTOR) signaling pathway was the most significantly associated, and the pathway of lissencephaly gene in neuronal migration and development was also noted. This study suggests a possible role for miRNAs in the pathogenesis of CD, especially in relation to the mTOR signaling pathway. Future studies on the epigenetic mechanisms underlying CD pathogenesis and epileptogenesis are needed.
    Epilepsy research 03/2014; DOI:10.1016/j.eplepsyres.2014.01.005 · 2.19 Impact Factor
  • Ji Yeoun Lee, Kyu-Chang Wang
    Child s Nervous System 02/2014; 30(4). DOI:10.1007/s00381-014-2381-z · 1.16 Impact Factor

Publication Stats

2k Citations
513.47 Total Impact Points

Institutions

  • 1995–2015
    • Seoul National University Hospital
      • • Department of Neurosurgery
      • • Department of Pediatric Neurosurgery
      • • Department of Radiology
      Sŏul, Seoul, South Korea
  • 2002–2014
    • Seoul National University
      • • Law Research Institute
      • • Department of Neurosurgery
      Sŏul, Seoul, South Korea
  • 2006–2013
    • Jeju National University
      Tse-tsiu, Jeju, South Korea
    • Konkuk University Medical Center
      • Department of Neurosurgery
      Changnyeong, South Gyeongsang, South Korea
  • 2010–2012
    • Kangwon National University
      • Department of Neurosurgery
      Syunsen, Gangwon, South Korea
    • Seoul National University Bundang Hospital
      • Department of Neurosurgery
      Seoul, Seoul, South Korea
  • 2005
    • Konkuk University
      Sŏul, Seoul, South Korea
    • Kangwon National University Hospital
      Shunsen, Gangwon, South Korea