Cerebral cavernous malformations are a rare and congenital vascular malformation that can present as a challenge in neurosurgical management. The term “giant cerebral cavernous malformations” still does not have a c...Cerebral cavernous malformations are a rare and congenital vascular malformation that can present as a challenge in neurosurgical management. The term “giant cerebral cavernous malformations” still does not have a clear definition in the literature, with a wide variety of results. It is known, however, that there is an association between the size of the cavernoma and postoperative sequelae, especially in those with a size greater than 3 cm in its largest diameter. We present a case report of resection of a giant brain cavernoma measuring approximately 8 cm in its largest diameter, emphasizing on clinical presentation, diagnoses and postoperative evolution. Additionally, we performed a comprehensive review of the existing literature on the subject, addressing the epidemiology, pathophysiology, diagnostic methods, treatment options, and prognosis associated with this condition.展开更多
Cases of low-grade cerebral arteriovenous malformations(c AVMs)showing dynamic changes and large areas of brain edema on short-term MRI follow-up have rarely been reported.This report describes an incidentally discove...Cases of low-grade cerebral arteriovenous malformations(c AVMs)showing dynamic changes and large areas of brain edema on short-term MRI follow-up have rarely been reported.This report describes an incidentally discovered and initially misdiagnosed c AVM in a patient with malignancies.The presence of abnormal signals surrounded by large areas of brain edema combined with tortuous or dilated vessels indicates the possibility of an AVM,especially in young people.展开更多
Cerebral cavemous malformation (CCM) is a frequently occurring disease in Latin American populations, but little is known about the prevalence in China. This study enrolled one Chinese family with CCM, comprising 16...Cerebral cavemous malformation (CCM) is a frequently occurring disease in Latin American populations, but little is known about the prevalence in China. This study enrolled one Chinese family with CCM, comprising 16 members; four were diagnosed with CCM which corresponded with autosomal incomplete dominance inheritance. The main clinical manifestations included headache, focal neural dysfunction, and cerebral hemorrhage. The lesions were a mixture of hyperintensity and hypointensity signals on TlWl and T2Wl, with a black hypointensity ring on T2Wl. CCM cranial magnetic resonance imaging T2Wl revealed an iron ring as a result of hemosiderin deposition. Pathological findings of CCM revealed tightly packed and variably thickened vascular channels lacking smooth muscle or elastic tissue. Intralesional hyalinosis, calcification, or bleeding of different phases and perilesional glial hyperplasia were observed, as well as hemosiderin deposition within or around the lesions. These features of this family were consistent with specific genetic, imaging and pathological features of familial CCM. Pathological characteristics reveal repeated hemorrhage, as well as intralesional and perilesional hemosiderin deposition.展开更多
BACKGROUND: In the process of vascularization, vascular endothelial growth factor (VEGF), angiopoietin-2 and Tie2 are involved in the migration, differentiation and proliferation of vascular endothelial cells, and ...BACKGROUND: In the process of vascularization, vascular endothelial growth factor (VEGF), angiopoietin-2 and Tie2 are involved in the migration, differentiation and proliferation of vascular endothelial cells, and stimulate the rapid angiogenesis; Tiel and angiopoietin-1 play important roles in facilitating the formation of vascular lumen and maintaining the integrity of vascular wall. Thus the distributions and expressions may be associated with the occurrence of cerebral arteriovenous malformation. OBJECTIVE: To observe the biological effects of angiogenic factors in the occurrence and development of cerebral arteriovenous malformation. DESIGN: An observational comparative experiment. SETTINGS: Department of Neurosurgery, General Hospital of Shenyang Military Area Command of Chinese PLA; Department of Neurosurgery, General Hospital of Tianjin Medical University. PARTICIPANTS: Fresh samples of complete cerebral arteriovenous malformations resected in 47 patients were collected from the Department of Neurosurgery, General Hospital of Tianjin Medical University from August 1999 to May 2001, including 22 males and 25 females, the mean age was 34.5 years. Informed consents were obtained from all the patients or their relatives. The initial symptom was hemorrhage in 28 cases. All the patients were classified according to the clinical imaging data and Spetzler-Martin grading standard, including 11 cases of grade Ⅰ, 17 cases of grade Ⅱ, 11 cases of grade Ⅲ, and 8 cases of grade Ⅳ - Ⅴ. Normal brain tissues resected by decompression due to trauma were taken from 8 patients as controls, including 5 males and 3 females, aging 12 - 65 years. METHODS: ① The expressions of VEGF, Tie receptors, angiopoietin-1, angiopoietin-2, proto-oncogene c-myc and proliferating cell nuclear antigen(PCNA) in the samples of cerebral arteriovenous malformation were detected with immunohistochemical method. Under light microscope, the positively stained rat-anti-human factor Ⅷ-related antigens (specific marker of vascular endothelial cells) were counted, then the immuno-positive cells of the other antibodies in the visual field of neighboring section which was in "mirror" relation were counted, and the percentage of the latter to the former was considered as the labeling index of positive cells. The immunostaining intensity was classified negative ( - ): no positive cells; positive (+): number of positive cells 〈 20%; moderately positive (++): number of positive cells 20% - 50%; strongly positive (+++): number of positive cells 〉 50%. ② The differences of the enumeration data were compared with chi-squam test, and the correlation were analyzed with the linear correlation analysis. MAIN OUTCOME MEASURES: Expressions and distributions of VEGF, Tie 1 and Tie2 receptors, angiopoietin-1, angiopoietin-2, PCNA and c-myc in the samples of cerebral arteriovenons malformation and normal brain tissue. RESULTS: ① Expressions of angiogenic factors in the control group and cerebral arteriovenons malformation groups of each grade: The positive rates of VEGF, Tie2, angiopoietin-2, c-myc and PCNA expressions in the control group were significantly different from those in the cerebral arteriovenous malformation groups of each grade ( x^2=21.09 - 34.23, P 〈 0.05), whereas the positive rates of Tiel and angiopoietin-1 expressions were close ( x^2=3.43 - 3.869, P 〉 0.05). ② Expressions of angiogenic factors in hemorrhage group and non-hemorrhage group: The expressions of VEGF, angiopoietin-2 and PCNA in the hemorrhage group were significantly lower than those in the non-hemorrhage group ( x^2= 16.22 - 26.56, P 〈 0.05). There ware no obvious differences in the expressions of Tiel and angiopoietin-1 expressions between the hemorrhage group and non-hemorrhage group ( x^2=3.22 - 3.78, P 〉 0.05).The VEGF was positively correlated with the expressions of c-myc and PCNA (r = 0.728, 0.916, P 〈 0.05). CONCLUSION: ①The expressions of angiogenic factors and related receptors may be involved in the process of cerebral arteriovenous malformation, and had important correlation the its clinical grading. ② Angiogenic factors may induce the expression of endothelial cell c-myc in cerebral arteriovenous malformation, and then interfere the cell proliferation and apoptosis.展开更多
Background In the past 5 years, new treatment materials and techniques offering a different concept in endovascular treatment have been described for cerebral arteriovenous malformations (CAVMs). The aim of this stu...Background In the past 5 years, new treatment materials and techniques offering a different concept in endovascular treatment have been described for cerebral arteriovenous malformations (CAVMs). The aim of this study was to assess the endovascular treatment of CAVMs by using a liquid embolic material, Onyx ( Micro Therapeutics. Inc. , Irvine, CA, USA). Methods From September 2003 to September 2004, Onyx was used to treat 22 patients with CAVMs. Ten AVMS were located in functional areas, 8 in deep cerebral areas, and 4 in the cerebellar hemisphere. The size of CAVMs was about 3 cm in diameter in 5 patients, 3 -6 cm in 11, and more than 6 cm in 6. Results In the 22 patients, Onyx embolization was successful. Nidus occlusion was complete in 3 patients, 〉 90% in 8, 〉 80% and 〈 90% in 6, and 〉 50% and 〈 80% in 5. Complications included transient neurological deficits in 2 patients, and adherence of microcatheter to the site of injection in 2. Conclusions Being non-adhesiveness, Onyx is a safe and satisfactory embolic material in the treatment of CAVMs. But its long-term efficacy awaits further follow-up.展开更多
Background: Cerebral arteriovenous malformation (cAVM) is a type of vascular malformation associated with vascular remodeling, hemodynamic imbalance, and inflammation. We detected four angioarchitecture-related cyt...Background: Cerebral arteriovenous malformation (cAVM) is a type of vascular malformation associated with vascular remodeling, hemodynamic imbalance, and inflammation. We detected four angioarchitecture-related cytokines to make a better understanding of the potential aberrant signaling in the pathogenesis of cAVM and found useful proteins in predicting the risk of cerebral hemorrhage. Methods: lmmunohistochemical analysis was conducted on specimens from twenty patients with cAVM diagnosed via magnetic resonance imaging and digital subtraction angiography and twenty primary epilepsy controls using antibodies against vascular endothelial growth factor receptor-2 (VEGFR-2), matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule (VCAM- 1 ), and endothelial nitric oxide synthase (eNOS). Western blotting and real-time fluorescent quantitative polymerase chain reaction (PCR) were performed to determine protein and mRNA expression levels. Student's t-test was used for statistical analysis. Results: VEGFR-2, MMP-9, VCAM-1, and eNOS expression levels increased in patients with cAVM compared with those in normal cerebral vascular tissue, as determined by immunohistochemical analysis. In addition, Western blotting and real-time PCR showed that the protein and mRNA expression levels ofVEGFR-2, MMP-9, VCAM-1, and eNOS were higher in the cAVM group than in the control group, all the differences mentioned were statistically significant (P 〈 0,05). Conclusions: VEGFR-2, MMP-9, VCAM-1, and eNOS are upregulated in patients with cAVM and might play important roles in angiogenesis, vascular remodeling, and migration in patients with cAVM. MMP-9, VEGFR-2, VCAM-1, and eNOS might be potential excellent group proteins in predicting the risk of cerebral hemorrhage at arteriovenous malformation.展开更多
Background Stereotactic radiosurgery is an altemative to resection of intracranial cerebral arteriovenous malformations (AVMs), while it will fail in some cases. This study aimed to evaluate the changes after stereo...Background Stereotactic radiosurgery is an altemative to resection of intracranial cerebral arteriovenous malformations (AVMs), while it will fail in some cases. This study aimed to evaluate the changes after stereotactic radiosurgery for AVMs.Methods Nineteen cases with cerebral AVMs had failure after stereotactic radiosurgery therapy. The symptoms and angiography were assessed. All patients underwent microsurgery. Pathologic examination was performed for all cases and electron microscopic examination was carried out in 6 patients.Results Seven cases had hemorrhage from 12 to 98 months after stereotactic radiosurgery, 5 had headache, 4 had refractory encephalon edema, 2 had epilepsy as a new symptom and 1 had a pressure cyst 5 years after radiosurgery. Angiography in 18 cases, 8-98 months after radiation therapy, demonstrated no significant changes in 5 cases, slight reduction in 9, near complete obliteration in 1 and complete obliteration in 3. An abnormal vessel was found on pathologic examination in 17 cases, even one case had obliterated in angiography. Electron microscopy examination showed vessel wall weakness, but the vessels remained open and blood circulated. One case died because of a moribund state before surgery. The other 18 cases had no new neurological deficiencies, seizure control and no hemorrhage occurred after microsurgery at an average follow-up of 3 years.Conclusion Stereotactic radiotherapy for AVMs should have a long period follow-up. If serious complications occur, microsurgery can be performed as salvage treatment.展开更多
Glioma is the most malignant tumor in the brain, the origin of glioma is still unknown. Recently some papers indicated that glioma may be developed from cerebral cavernous malformation (CCM). We describe a man with ...Glioma is the most malignant tumor in the brain, the origin of glioma is still unknown. Recently some papers indicated that glioma may be developed from cerebral cavernous malformation (CCM). We describe a man with a right temporal lobe CCM, after gamma-knife radiotherapy, the patient developed a low-grade astrocytoma in the area of the preexistent CCM. This case, together with other reports, may indicated an oncogenetic properties of CCM, and we proposed that CCM may be a pre-glioma lesion.展开更多
INTRODUCTIOIN Cerebral cavernous malformation (CCM), also known as cavernous angioma, is a type of vascular malformation in the central nervous system. To date, rare cases of CCM and seizure have been reported in pr...INTRODUCTIOIN Cerebral cavernous malformation (CCM), also known as cavernous angioma, is a type of vascular malformation in the central nervous system. To date, rare cases of CCM and seizure have been reported in pregnancies, Nowadays,展开更多
OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine(TCM)for promoting blood circulation and removing blood stasis,as exemplified by cryptotanshinone and salvianol...OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine(TCM)for promoting blood circulation and removing blood stasis,as exemplified by cryptotanshinone and salvianolic acid B,exerted striking effects on modulating angiogenesis and vascular permeability,which suggests that they may be effective in treating vascular leak-driven diseases(e.g.tumor,cerebral cavernous malformation and diabetic retinopathy).However,the lack of reliable and advanced technologies and models sets up difficult hurdles for better understanding the role of TCM for promoting blood circulation and removing blood stasis.To this end,this study is to outline numerous cutting-edge platforms that can be utilized for exploring the function of TCM for promoting blood circulation and removing blood stasis in vascular leak-driven diseases.METHODS Two-photon laser scanning fluorescence microscopy was used to observe the interactions between neutrophils and blood vessels in a real-time manner.Dynamic flow system was employed to mimic the in vivo behaviors of neutrophils.RIP1-Tag5 spontaneous pancreatic cancer model was used to study the function of tumor blood vessels.CCM2ECKO(deletion of CCM2 in endothelial cells)mice were employed to establish the cerebral cavernous malformation(CCM)animal model.Micro-computed tomography(micro-CT)was utilized to assess the CCM lesion.Müller cell-knockout mouse model was used to study the progression of diabetic retinopathy.Vascular permeability in this model was assessed by fluorescein angiography.RESULTS The interactions between neutrophils and endothelial cells involve a series of complicated processes,including rolling,adhesion,intraluminal crawling and transmigration,which were all monitored in vivo by two-photon laser scanning fluorescence microscopy in a real-time manner.Dynamic flow system was capable of recapitulating the biological behaviors of neutrophils in vitro.Tumor vascular function in particular vascular perfusion could be assessed in the RIP1-Tag5 spontaneous pancreatic cancer model.In terms of CCM studies,specific deletion of CCM2 in endothelial cells resulted in the initiation of CCM lesion.The size and number of CCM lesions could be visualized and quantified by micro-CT.Furthermore,the Müller cell-knockout mouse model was able to precisely reflect the clinical symptoms of diabetic retinopathy.Vascular leak could be monitored at different time points using fluorescein angiography.CONCLUSION An array of high technologies and animal models can be used in investigating the occurrence and progression of multiple vascular leak-driven diseases.The pre-clinical and clinical studies of TCM for promoting blood circulation and removing blood stasis provide fundamental support for the application of the above-mentioned platforms,with the purpose of uncovering the scientific basis of TCM for promoting blood circulation and removing blood stasis.展开更多
Glioblastomas are highly malignant and invasive brain tumors. Cerebral cavernous malformations(CCMs) are vascular diseases of congenital and occult vascular dysplasia, which may arise sporadically or may be inherited ...Glioblastomas are highly malignant and invasive brain tumors. Cerebral cavernous malformations(CCMs) are vascular diseases of congenital and occult vascular dysplasia, which may arise sporadically or may be inherited due to autosomal dominant condition. To the best of our knowledge, cases of glioblastoma in the cerebral hemisphere mimicking cavernous malformation have not been reported in the literature. We reported a case of glioblastoma mimicking CCM. The patient was admitted at our hospital in July 2015 due to a 9-day history of intermittent dizziness. The present study reports a case of a glioblastoma on the right temporal lobe mimicking CCM, which was confirmed by postoperative pathology. The diagnosis of glioblastoma was not determined even during surgery, and the lesion was totally resected with no complications. During the surgical procedure, the lesion was very similar to a CCM. In conclusion, it is difficult to distinguish between glioblastoma and CCM. Therefore, when a lesion is present with hemorrhage and the imaging features are very similar to a vascular disease, a tumor must be considered in the differential diagnosis.展开更多
Background:Cerebral cavernous malformations(CCMs),a major neurosurgical condition,characterized by abnormally dilated intracranial capillaries,result in increased susceptibility to stroke.KRIT1(CCM1),MGC4607(CCM2),and...Background:Cerebral cavernous malformations(CCMs),a major neurosurgical condition,characterized by abnormally dilated intracranial capillaries,result in increased susceptibility to stroke.KRIT1(CCM1),MGC4607(CCM2),and PDCD10(CCM3)have been identified as causes of CCMs in which at least one of them is disrupted in most familial cases.Our goal is to identify potential biomarkers and genetic modifiers of CCMs,using a global comparative omics approach across several in vitro studies and multiple in vivo animal models.We hypothesize that through analysis of the CSC utilizing various omics,we can identify potential biomarkers and genetic modifiers,by systemically evaluating effectors and binding partners of the CSC as well as second layer interactors.Methods:We utilize a comparative omics approach analyzing multiple CCMs deficient animal models across nine independent studies at the genomic,transcriptomic,and proteomic levels to dissect alterations in various signaling cascades.Results:Our analysis revealed a large set of genes that were validated across multiple independent studies,suggesting an important role for these identified genes in CCM pathogenesis.Conclusion:This is currently one of the largest comparative omics analysis of CCM deficiencies across multiple models,allowing us to investigate global alterations among multiple signaling cascades involved in both angiogenic and non-angiogenic events and to also identify potential biomarker candidates of CCMs,which can be used for new therapeutic strategies.展开更多
文摘Cerebral cavernous malformations are a rare and congenital vascular malformation that can present as a challenge in neurosurgical management. The term “giant cerebral cavernous malformations” still does not have a clear definition in the literature, with a wide variety of results. It is known, however, that there is an association between the size of the cavernoma and postoperative sequelae, especially in those with a size greater than 3 cm in its largest diameter. We present a case report of resection of a giant brain cavernoma measuring approximately 8 cm in its largest diameter, emphasizing on clinical presentation, diagnoses and postoperative evolution. Additionally, we performed a comprehensive review of the existing literature on the subject, addressing the epidemiology, pathophysiology, diagnostic methods, treatment options, and prognosis associated with this condition.
文摘Cases of low-grade cerebral arteriovenous malformations(c AVMs)showing dynamic changes and large areas of brain edema on short-term MRI follow-up have rarely been reported.This report describes an incidentally discovered and initially misdiagnosed c AVM in a patient with malignancies.The presence of abnormal signals surrounded by large areas of brain edema combined with tortuous or dilated vessels indicates the possibility of an AVM,especially in young people.
基金the Medical Health Science and Tech-nology General Program of Guangzhou,No. 2009-YB-042
文摘Cerebral cavemous malformation (CCM) is a frequently occurring disease in Latin American populations, but little is known about the prevalence in China. This study enrolled one Chinese family with CCM, comprising 16 members; four were diagnosed with CCM which corresponded with autosomal incomplete dominance inheritance. The main clinical manifestations included headache, focal neural dysfunction, and cerebral hemorrhage. The lesions were a mixture of hyperintensity and hypointensity signals on TlWl and T2Wl, with a black hypointensity ring on T2Wl. CCM cranial magnetic resonance imaging T2Wl revealed an iron ring as a result of hemosiderin deposition. Pathological findings of CCM revealed tightly packed and variably thickened vascular channels lacking smooth muscle or elastic tissue. Intralesional hyalinosis, calcification, or bleeding of different phases and perilesional glial hyperplasia were observed, as well as hemosiderin deposition within or around the lesions. These features of this family were consistent with specific genetic, imaging and pathological features of familial CCM. Pathological characteristics reveal repeated hemorrhage, as well as intralesional and perilesional hemosiderin deposition.
文摘BACKGROUND: In the process of vascularization, vascular endothelial growth factor (VEGF), angiopoietin-2 and Tie2 are involved in the migration, differentiation and proliferation of vascular endothelial cells, and stimulate the rapid angiogenesis; Tiel and angiopoietin-1 play important roles in facilitating the formation of vascular lumen and maintaining the integrity of vascular wall. Thus the distributions and expressions may be associated with the occurrence of cerebral arteriovenous malformation. OBJECTIVE: To observe the biological effects of angiogenic factors in the occurrence and development of cerebral arteriovenous malformation. DESIGN: An observational comparative experiment. SETTINGS: Department of Neurosurgery, General Hospital of Shenyang Military Area Command of Chinese PLA; Department of Neurosurgery, General Hospital of Tianjin Medical University. PARTICIPANTS: Fresh samples of complete cerebral arteriovenous malformations resected in 47 patients were collected from the Department of Neurosurgery, General Hospital of Tianjin Medical University from August 1999 to May 2001, including 22 males and 25 females, the mean age was 34.5 years. Informed consents were obtained from all the patients or their relatives. The initial symptom was hemorrhage in 28 cases. All the patients were classified according to the clinical imaging data and Spetzler-Martin grading standard, including 11 cases of grade Ⅰ, 17 cases of grade Ⅱ, 11 cases of grade Ⅲ, and 8 cases of grade Ⅳ - Ⅴ. Normal brain tissues resected by decompression due to trauma were taken from 8 patients as controls, including 5 males and 3 females, aging 12 - 65 years. METHODS: ① The expressions of VEGF, Tie receptors, angiopoietin-1, angiopoietin-2, proto-oncogene c-myc and proliferating cell nuclear antigen(PCNA) in the samples of cerebral arteriovenous malformation were detected with immunohistochemical method. Under light microscope, the positively stained rat-anti-human factor Ⅷ-related antigens (specific marker of vascular endothelial cells) were counted, then the immuno-positive cells of the other antibodies in the visual field of neighboring section which was in "mirror" relation were counted, and the percentage of the latter to the former was considered as the labeling index of positive cells. The immunostaining intensity was classified negative ( - ): no positive cells; positive (+): number of positive cells 〈 20%; moderately positive (++): number of positive cells 20% - 50%; strongly positive (+++): number of positive cells 〉 50%. ② The differences of the enumeration data were compared with chi-squam test, and the correlation were analyzed with the linear correlation analysis. MAIN OUTCOME MEASURES: Expressions and distributions of VEGF, Tie 1 and Tie2 receptors, angiopoietin-1, angiopoietin-2, PCNA and c-myc in the samples of cerebral arteriovenons malformation and normal brain tissue. RESULTS: ① Expressions of angiogenic factors in the control group and cerebral arteriovenons malformation groups of each grade: The positive rates of VEGF, Tie2, angiopoietin-2, c-myc and PCNA expressions in the control group were significantly different from those in the cerebral arteriovenous malformation groups of each grade ( x^2=21.09 - 34.23, P 〈 0.05), whereas the positive rates of Tiel and angiopoietin-1 expressions were close ( x^2=3.43 - 3.869, P 〉 0.05). ② Expressions of angiogenic factors in hemorrhage group and non-hemorrhage group: The expressions of VEGF, angiopoietin-2 and PCNA in the hemorrhage group were significantly lower than those in the non-hemorrhage group ( x^2= 16.22 - 26.56, P 〈 0.05). There ware no obvious differences in the expressions of Tiel and angiopoietin-1 expressions between the hemorrhage group and non-hemorrhage group ( x^2=3.22 - 3.78, P 〉 0.05).The VEGF was positively correlated with the expressions of c-myc and PCNA (r = 0.728, 0.916, P 〈 0.05). CONCLUSION: ①The expressions of angiogenic factors and related receptors may be involved in the process of cerebral arteriovenous malformation, and had important correlation the its clinical grading. ② Angiogenic factors may induce the expression of endothelial cell c-myc in cerebral arteriovenous malformation, and then interfere the cell proliferation and apoptosis.
文摘Background In the past 5 years, new treatment materials and techniques offering a different concept in endovascular treatment have been described for cerebral arteriovenous malformations (CAVMs). The aim of this study was to assess the endovascular treatment of CAVMs by using a liquid embolic material, Onyx ( Micro Therapeutics. Inc. , Irvine, CA, USA). Methods From September 2003 to September 2004, Onyx was used to treat 22 patients with CAVMs. Ten AVMS were located in functional areas, 8 in deep cerebral areas, and 4 in the cerebellar hemisphere. The size of CAVMs was about 3 cm in diameter in 5 patients, 3 -6 cm in 11, and more than 6 cm in 6. Results In the 22 patients, Onyx embolization was successful. Nidus occlusion was complete in 3 patients, 〉 90% in 8, 〉 80% and 〈 90% in 6, and 〉 50% and 〈 80% in 5. Complications included transient neurological deficits in 2 patients, and adherence of microcatheter to the site of injection in 2. Conclusions Being non-adhesiveness, Onyx is a safe and satisfactory embolic material in the treatment of CAVMs. But its long-term efficacy awaits further follow-up.
文摘Background: Cerebral arteriovenous malformation (cAVM) is a type of vascular malformation associated with vascular remodeling, hemodynamic imbalance, and inflammation. We detected four angioarchitecture-related cytokines to make a better understanding of the potential aberrant signaling in the pathogenesis of cAVM and found useful proteins in predicting the risk of cerebral hemorrhage. Methods: lmmunohistochemical analysis was conducted on specimens from twenty patients with cAVM diagnosed via magnetic resonance imaging and digital subtraction angiography and twenty primary epilepsy controls using antibodies against vascular endothelial growth factor receptor-2 (VEGFR-2), matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule (VCAM- 1 ), and endothelial nitric oxide synthase (eNOS). Western blotting and real-time fluorescent quantitative polymerase chain reaction (PCR) were performed to determine protein and mRNA expression levels. Student's t-test was used for statistical analysis. Results: VEGFR-2, MMP-9, VCAM-1, and eNOS expression levels increased in patients with cAVM compared with those in normal cerebral vascular tissue, as determined by immunohistochemical analysis. In addition, Western blotting and real-time PCR showed that the protein and mRNA expression levels ofVEGFR-2, MMP-9, VCAM-1, and eNOS were higher in the cAVM group than in the control group, all the differences mentioned were statistically significant (P 〈 0,05). Conclusions: VEGFR-2, MMP-9, VCAM-1, and eNOS are upregulated in patients with cAVM and might play important roles in angiogenesis, vascular remodeling, and migration in patients with cAVM. MMP-9, VEGFR-2, VCAM-1, and eNOS might be potential excellent group proteins in predicting the risk of cerebral hemorrhage at arteriovenous malformation.
文摘Background Stereotactic radiosurgery is an altemative to resection of intracranial cerebral arteriovenous malformations (AVMs), while it will fail in some cases. This study aimed to evaluate the changes after stereotactic radiosurgery for AVMs.Methods Nineteen cases with cerebral AVMs had failure after stereotactic radiosurgery therapy. The symptoms and angiography were assessed. All patients underwent microsurgery. Pathologic examination was performed for all cases and electron microscopic examination was carried out in 6 patients.Results Seven cases had hemorrhage from 12 to 98 months after stereotactic radiosurgery, 5 had headache, 4 had refractory encephalon edema, 2 had epilepsy as a new symptom and 1 had a pressure cyst 5 years after radiosurgery. Angiography in 18 cases, 8-98 months after radiation therapy, demonstrated no significant changes in 5 cases, slight reduction in 9, near complete obliteration in 1 and complete obliteration in 3. An abnormal vessel was found on pathologic examination in 17 cases, even one case had obliterated in angiography. Electron microscopy examination showed vessel wall weakness, but the vessels remained open and blood circulated. One case died because of a moribund state before surgery. The other 18 cases had no new neurological deficiencies, seizure control and no hemorrhage occurred after microsurgery at an average follow-up of 3 years.Conclusion Stereotactic radiotherapy for AVMs should have a long period follow-up. If serious complications occur, microsurgery can be performed as salvage treatment.
基金This work was supported by grants from National Natural Science Foundation of China (No. 81172409), and National "863" Key Project (No. 2012AA02A508).
文摘Glioma is the most malignant tumor in the brain, the origin of glioma is still unknown. Recently some papers indicated that glioma may be developed from cerebral cavernous malformation (CCM). We describe a man with a right temporal lobe CCM, after gamma-knife radiotherapy, the patient developed a low-grade astrocytoma in the area of the preexistent CCM. This case, together with other reports, may indicated an oncogenetic properties of CCM, and we proposed that CCM may be a pre-glioma lesion.
文摘INTRODUCTIOIN Cerebral cavernous malformation (CCM), also known as cavernous angioma, is a type of vascular malformation in the central nervous system. To date, rare cases of CCM and seizure have been reported in pregnancies, Nowadays,
文摘OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine(TCM)for promoting blood circulation and removing blood stasis,as exemplified by cryptotanshinone and salvianolic acid B,exerted striking effects on modulating angiogenesis and vascular permeability,which suggests that they may be effective in treating vascular leak-driven diseases(e.g.tumor,cerebral cavernous malformation and diabetic retinopathy).However,the lack of reliable and advanced technologies and models sets up difficult hurdles for better understanding the role of TCM for promoting blood circulation and removing blood stasis.To this end,this study is to outline numerous cutting-edge platforms that can be utilized for exploring the function of TCM for promoting blood circulation and removing blood stasis in vascular leak-driven diseases.METHODS Two-photon laser scanning fluorescence microscopy was used to observe the interactions between neutrophils and blood vessels in a real-time manner.Dynamic flow system was employed to mimic the in vivo behaviors of neutrophils.RIP1-Tag5 spontaneous pancreatic cancer model was used to study the function of tumor blood vessels.CCM2ECKO(deletion of CCM2 in endothelial cells)mice were employed to establish the cerebral cavernous malformation(CCM)animal model.Micro-computed tomography(micro-CT)was utilized to assess the CCM lesion.Müller cell-knockout mouse model was used to study the progression of diabetic retinopathy.Vascular permeability in this model was assessed by fluorescein angiography.RESULTS The interactions between neutrophils and endothelial cells involve a series of complicated processes,including rolling,adhesion,intraluminal crawling and transmigration,which were all monitored in vivo by two-photon laser scanning fluorescence microscopy in a real-time manner.Dynamic flow system was capable of recapitulating the biological behaviors of neutrophils in vitro.Tumor vascular function in particular vascular perfusion could be assessed in the RIP1-Tag5 spontaneous pancreatic cancer model.In terms of CCM studies,specific deletion of CCM2 in endothelial cells resulted in the initiation of CCM lesion.The size and number of CCM lesions could be visualized and quantified by micro-CT.Furthermore,the Müller cell-knockout mouse model was able to precisely reflect the clinical symptoms of diabetic retinopathy.Vascular leak could be monitored at different time points using fluorescein angiography.CONCLUSION An array of high technologies and animal models can be used in investigating the occurrence and progression of multiple vascular leak-driven diseases.The pre-clinical and clinical studies of TCM for promoting blood circulation and removing blood stasis provide fundamental support for the application of the above-mentioned platforms,with the purpose of uncovering the scientific basis of TCM for promoting blood circulation and removing blood stasis.
基金Supported by Tsinghua-Yuquan Medical Research Funds(No.20240000513)
文摘Glioblastomas are highly malignant and invasive brain tumors. Cerebral cavernous malformations(CCMs) are vascular diseases of congenital and occult vascular dysplasia, which may arise sporadically or may be inherited due to autosomal dominant condition. To the best of our knowledge, cases of glioblastoma in the cerebral hemisphere mimicking cavernous malformation have not been reported in the literature. We reported a case of glioblastoma mimicking CCM. The patient was admitted at our hospital in July 2015 due to a 9-day history of intermittent dizziness. The present study reports a case of a glioblastoma on the right temporal lobe mimicking CCM, which was confirmed by postoperative pathology. The diagnosis of glioblastoma was not determined even during surgery, and the lesion was totally resected with no complications. During the surgical procedure, the lesion was very similar to a CCM. In conclusion, it is difficult to distinguish between glioblastoma and CCM. Therefore, when a lesion is present with hemorrhage and the imaging features are very similar to a vascular disease, a tumor must be considered in the differential diagnosis.
文摘Background:Cerebral cavernous malformations(CCMs),a major neurosurgical condition,characterized by abnormally dilated intracranial capillaries,result in increased susceptibility to stroke.KRIT1(CCM1),MGC4607(CCM2),and PDCD10(CCM3)have been identified as causes of CCMs in which at least one of them is disrupted in most familial cases.Our goal is to identify potential biomarkers and genetic modifiers of CCMs,using a global comparative omics approach across several in vitro studies and multiple in vivo animal models.We hypothesize that through analysis of the CSC utilizing various omics,we can identify potential biomarkers and genetic modifiers,by systemically evaluating effectors and binding partners of the CSC as well as second layer interactors.Methods:We utilize a comparative omics approach analyzing multiple CCMs deficient animal models across nine independent studies at the genomic,transcriptomic,and proteomic levels to dissect alterations in various signaling cascades.Results:Our analysis revealed a large set of genes that were validated across multiple independent studies,suggesting an important role for these identified genes in CCM pathogenesis.Conclusion:This is currently one of the largest comparative omics analysis of CCM deficiencies across multiple models,allowing us to investigate global alterations among multiple signaling cascades involved in both angiogenic and non-angiogenic events and to also identify potential biomarker candidates of CCMs,which can be used for new therapeutic strategies.