Familial cerebral cavernous malformation Retrospective analysis of one Chinese pedigree

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.

Outcomes after surgical and nonsurgical treatment of pediatric cerebral cavernous malformation

Importance:Pediatric cerebral cavernous malformation(CCM)is a rarely encountered vascular entity.Comparative study on surgical excision and nonsurgical management outcomes of CCM in pediatrics is limited.Objective:To determine the demographic characteristics,hemorrhage rate,and long-term outcomes of pediatric patients with CCM.Methods:A retrospective study of pediatric patients with CCM in Chinese PLA General Hospital was conducted between January 2004 and January 2019.We compared the clinical characteristics,radiological features,and outcomes of the surgical and nonsurgical groups.Results:Seventy-nine children were included,with 69.6%being boys,and the average age was 11.8±5.5 years.The annual retrospective hemorrhagic rate was 5.7%per patient per year.Fifty-six children(70.9%)underwent surgical excision,and they were more likely to present with seizure symptoms(P=0.011),have a higher proportion of larger lesion size(P=0.008),less likely to have durations≤10 days(P=0.048),and less likely to have supratentorial deep CCM(P=0.014)compared to children who received nonsurgical management.Total resection was achieved in most surgical cases(55,98.2%).During the 143.9±50.8 months of follow-up,44 patients(78.6%)achieved improvement,12 patients(17.8%)remained the same,and two(3.6%)experienced worsening.In the nonsurgical management group,14 children(60.9%)experienced symptom improvement,eight(34.8%)remained the same,and one(4.3%)worsened,with a re-hemorrhagic risk of 8.7%.Interpretation:Surgical removal of pediatric CCM can eliminate the risk of hemorrhage and lead to satisfactory outcomes.For children undergoing nonsurgical management,long-term close monitoring is essential due to the life-long risk of hemorrhage.

Resection of Intracranial Giant Cavernous Malformation: Case Report and Literature Review

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.

Is cerebral cavernous malformation a pre-glioma lesion？

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.

Pregnancy Combined with Epilepsy and Cerebral Cavernous Malformation

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,

Cerebral glioblastoma mimicking a cavernous malformation: A case report and literature review

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.

Novel technologies and models for studying pharmacological activities of traditional Chinese medicine for promoting blood circulation and removing blood stasis

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.

Comparative omics of CCM signaling complex(CSC)

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.