• BMB Reports
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• v.49 no.5
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• pp.255-262
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• 2016

The disease known as cerebral cavernous malformations mostly occurs in the central nervous system, and their typical histological presentations are multiple lumen formation and vascular leakage at the brain capillary level, resulting in disruption of the blood-brain barrier. These abnormalities result in severe neurological symptoms such as seizures, focal neurological deficits and hemorrhagic strokes. CCM research has identified 'loss of function' mutations of three ccm genes responsible for the disease and also complex regulation of multiple signaling pathways including the WNT/β-catenin pathway, TGF-β and Notch signaling by the ccm genes. Although CCM research is a relatively new and small scientific field, as CCM research has the potential to regulate systemic blood vessel permeability and angiogenesis including that of the blood-brain barrier, this field is growing rapidly. In this review, I will provide a brief overview of CCM pathogenesis and function of ccm genes based on recent progress in CCM research.

• Journal of Korean Neurosurgical Society
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• v.67 no.3
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• pp.299-307
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• 2024

Cerebral cavernous malformation (CCM) is a vascular anomaly commonly found in children and young adults. Common clinical presentations of pediatric patients with CCMs include headache, focal neurological deficits, and seizures. Approximately 40% of pediatric patients are asymptomatic. Understanding the natural history of CCM is crucial and hemorrhagic rates are higher in patients with an initial hemorrhagic presentation, whereas it is low in asymptomatic patients. There is a phenomenon known as temporal clustering in which a higher frequency of symptomatic hemorrhages occurs within a few years following the initial hemorrhagic event. Surgical resection remains the mainstay of treatment for pediatric CCMs. Excision of a hemosiderin-laden rim is controversial regarding its impact on epilepsy outcomes. Stereotactic radiosurgery is an alternative treatment, especially for deep-seated CCMs, but its true efficacy needs to be verified in a clinical trial.

• Journal of Korean Neurosurgical Society
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• v.55 no.2
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• pp.89-91
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• 2014

Chronic encapsulated intracerebral hematoma (CEIH) is a rare cerebrovascular disease that behaves as a slowly expanding lesion with a gradual onset. It is well established that CEIH is associated with arteriovenous malformations; however, CEIH associated with cavernous malformation (CM) is extremely rare. We herein report a case of CEIH associated with CM, and discuss its pathogenesis. A 12-year-old female was admitted to our hospital because of a one week history of progressive headache and nausea. Brain computed tomography scan and magnetic resonance imaging showed an intracerebral hematoma surrounded by edema in the right frontal lobe. One week later, her headache and nausea worsened, and a brain computed tomography scan revealed the enlargement of hematoma. A right frontal craniotomy was performed. The capsule, mass, and hematoma were totally removed. Histological examination confirmed the diagnosis of CEIH associated with CM. Immunohistochemical analysis revealed increased expression of vascular endothelial growth factor (VEGF) and the VEGF receptor-1 in the endothelium and fibroblasts. Our findings suggest that the activated VEGF pathway might have positively contributed to development of CEIH in the present patient.

• 대한두경부종양학회:학술대회논문집
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• 2001.11a
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• pp.271-271
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• 2001

• Journal of Korean Neurosurgical Society
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• v.38 no.1
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• pp.74-76
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• 2005

Cavernous angiomas represent 5 to 12% of spinal vascular malformations and usually are located at the vertebral body level with possible extension into the extradural space. The intradural intramedullary cavernous angioma occurs in about 3% of cases, whereas extramedullary localization is extremely rare. We report a case of intradural extramedullary cavernous angioma in which the patient presented with low back pain and both leg pain. The magnetic resonance imaging study showed intraspinal mass lesion at L1-2. It was removed totally through laminectomy of L1-2 and confirmed as cavernous angioma. The postoperative course was uneventful without any neurologic deficit. We report this unusual spinal malformation.

• Clinical and Experimental Pediatrics
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• v.59 no.6
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• pp.280-284
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• 2016

Cerebral cavernous malformation (CCM) is a vascular malformation characterized by abnormally enlarged capillary cavities without any intervening neural tissue. We report 2 cases of familial CCMs diagnosed with the CCM1 mutation by using a genetic assay. A 5-year-old boy presented with headache, vomiting, and seizure-like movements. Brain magnetic resonance imaging (MRI) revealed multiple CCM lesions in the cerebral hemispheres. Subsequent mutation analysis of his father and other family members revealed c.940_943 del (p.Val314 Asn315delinsThrfsX3) mutations of the CCM1 gene. A 10-month-old boy who presented with seizure-like movements was reported to have had no perinatal event. His aunt was diagnosed with cerebral angioma. Brain and spine MRI revealed multiple angiomas in the cerebral hemisphere and thoracic spinal cord. Mutation analysis of his father was normal, although that of the patient and his mother revealed c.535C>T (p.Arg179X) mutations of the CCM1 gene. Based on these studies, we suggest that when a child with a familial history of CCMs exhibits neurological symptoms, the physician should suspect familial CCMs and consider brain imaging or a genetic assay.

• Journal of Chest Surgery
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• v.15 no.2
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• pp.183-187
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• 1982

Pulmonary arteriovenous fistula is a congenital vascular malformation In the lung, various synonyms including Pulmonary cavernous vascular malformation, Pulmonary arteriovenous aneurysm, Cavernous hemangioma of the lung0 Pulmonary telangiectasia, Pulmonary hamartoma, etc. The pathogenesis of its symptoms is that unoxygenated, desaturated arterial blood enters into the pulmonary venous system directly. Recently we have experienced one case of the pulmonary arteriovenous fistula which was diagnosed as the pulmonary cystic lesion of the lung preoperatively in 20 years old, 61 kg, male patient. Operation was revealed well circumscribed cystic lesion filled with blood, subpleural and anterior mediobasal location, and bright red colored aspirates on two times needle aspirations. Microscopic finding shows ill circumscribed vascular lesion composed of varying sized blood vessels with irregular thickening of wall and final pathological diagnosis is Pulmonary Arteriovenous Fistula. Basal segmentectomy was done and the patient shows good postoperative course.

• Journal of Korean Neurosurgical Society
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• v.43 no.4
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• pp.198-200
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• 2008

Giant cavernous malformations (GCMs) occur very rarely and little has been reported about their clinical characteristics. The authors present a case of a 20-year-old woman with a GCM. She was referred due to two episodes of generalized seizure. Computed tomography and magnetic resonance image demonstrated a heterogeneous multi-cystic lesion of $7\times5\times5$ cm size in the left frontal lobe and basal ganglia, and enhancing vascular structure abutting medial portion of the mass. These fingings suggested a diagnosis of GCM accompanying venous angioma. After left frontal craniotomy, transcortical approach was done. Total removal was accomplished and the postoperative course was uneventful. GCMs do not seem differ clinically, surgically or histopathologically from small cavernous angiomas, but imaging appearance of GCMs may be variable. The clinical, radiological feature and management of GCMs are described based on pertinent literature review.

• Toxicological Research
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• v.21 no.2
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• pp.135-140
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• 2005

Although the pathogenesis of cerebral cavernous malformation (CCM) is unknown, a familial predisposition has been recognized, with up to $55\%$ of patients having an affected relatives. Genetic linkage studies have recently mapped a gene causing CCM to a segment of the long arm of chromosome 7 (7q). We report herein a genetic linkage analysis conducted on a Korean three generation family with CCM. It's first report in Korean family. A Korean family in which one member had undergone surgery for ubtracerebrak hematoma (ICH) and confirmed the CCM, was evaluated. They were examined clinically (n=18) and by magnetic resonance (MR) imaging (n=10). Polymorphic markers (D7S1813, D7S1789) spanning the CCM1 locus on 7q were genotyped by the polymerase chain reaction and analysis of linkage was performed in this family (n=17). Six had multiple lesions on brain MR image, one of them being symptomatic, and five were asymptomatic. Seven remaining members were asymptomatic and refused MR image study. One had died of ICH from presumed CCM. Analysis of the pedigree was consistent with an autosomal dominant pattern of inheritance. All affected patients were linked to CCM1. Linkage to CCM1 can account for inheritance of CCM in this family. They had some striking features with a low clinical penetrance and the presence of multiple lesions. These findings have implications for genetic testing of this disorder and represent an important step toward identification of the gene responsible for the pathogenesis of this disease.

• Journal of Korean Neurosurgical Society
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• v.56 no.3
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• pp.237-242
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• 2014

Objective : The purpose of this study was to investigate the clinical features and outcomes of pediatric cavernous malformation (CM) in the central nervous system. Methods : Twenty-nine pediatric patients with supratentorial CM underwent microsurgical excision. In selected cases, transparent tubular retractor system (TTRS) was used to reduce retraction injury and intraoperative neuromonitoring (IONM) was held to preserve functioning cortex. Patients' demographics and symptoms were reviewed and surgical outcomes were discussed. Results : The main initial clinical manifestations included the following : seizures (n=13, 45%), headache (n=7, 24%), focal neurological deficits (n=3, 10%), and an incidental finding (n=6, 21%). Overt hemorrhage was detected in 7 patients (24%). There were 19 children (66%) with a single CM and 10 (34%) children with multiple CMs. In 7 cases with deep-seated CM, we used a TTRS to minimize retraction. In 9 cases which location of CM was at eloquent area, IONM was taken during surgery. There was no major morbidity or mortality after surgery. In the 29 operated children, the overall long-term results were satisfactory : 25 (86%) patients had no signs or symptoms associated with CMs, 3 had controllable seizures, and 1 had mild weakness. Conclusion : With the assistance of neuronavigation systems, intraoperative neuromonitoring, and TTRS, CMs could be targeted more accurately and excised more safely. Based on the satisfactory seizure outcome achieved, complete microsurgical excision in children is recommended for CMs presenting with seizures but removal of hemosiderin-stained areas seems to be unnecessary.