scholarly journals Familial cerebral cavernous malformations: Rio de Janeiro study and review of the recommendations for management

2008 ◽  
Vol 66 (4) ◽  
pp. 795-799 ◽  
Author(s):  
Flávio Domingues ◽  
Emerson L. Gasparetto ◽  
Ricardo Andrade ◽  
Fabio Noro ◽  
Antônio Eiras ◽  
...  

OBJECTIVE: Multiple cerebral cavernous malformation (CCM) is the hallmark of familial presentation of cavernous malformation in the brain. We describe an ongoing Familial Cerebral Cavernous Malformation Project in the Rio de Janeiro state showing genetic profile and the pattern of emergent neuroimaging findings of this particular population besides a review of the updated recommendations for management of familial CCM versus patients harboring sporadic lesions. METHOD: Four families of our cohort of 9 families were genetically mapped showing mutational profile linked to CCM1. The neuroimaging paradigm was shifted from T2*gradient-echo (GRE) sequence to susceptibility weighting MR phase imaging (SWI). RESULTS: Only two index cases were subjected to surgery. There was no surgical intervention in any of the kindreds of our entire cohort of 9 families of our Neurovascular Program within seven years of follow-up. The genetic sequencing for mutacional profile in four of these families has demonstrated only CCM1 gene affected. Our management of the familial CCM is according to the review of the literature recommendations. CONCLUSIONS: The Project of Familial Cerebral Cavernous Malformations of Rio de Janeiro detected mutations of the gene CCM1 in the first four families studied. Familial cavernous malformation are to be settled apart from the more common sporadic lesion. A set of recommendations was searched for in the literature in order to deal with these specific patients and kindreds.

2021 ◽  
Vol 129 (1) ◽  
pp. 195-215
Author(s):  
Daniel A. Snellings ◽  
Courtney C. Hong ◽  
Aileen A. Ren ◽  
Miguel A. Lopez-Ramirez ◽  
Romuald Girard ◽  
...  

Cerebral cavernous malformations are acquired vascular anomalies that constitute a common cause of central nervous system hemorrhage and stroke. The past 2 decades have seen a remarkable increase in our understanding of the pathogenesis of this vascular disease. This new knowledge spans genetic causes of sporadic and familial forms of the disease, molecular signaling changes in vascular endothelial cells that underlie the disease, unexpectedly strong environmental effects on disease pathogenesis, and drivers of disease end points such as hemorrhage. These novel insights are the integrated product of human clinical studies, human genetic studies, studies in mouse and zebrafish genetic models, and basic molecular and cellular studies. This review addresses the genetic and molecular underpinnings of cerebral cavernous malformation disease, the mechanisms that lead to lesion hemorrhage, and emerging biomarkers and therapies for clinical treatment of cerebral cavernous malformation disease. It may also serve as an example for how focused basic and clinical investigation and emerging technologies can rapidly unravel a complex disease mechanism.


2021 ◽  
Vol 30 (12) ◽  
pp. 106130
Author(s):  
Pablo Iruzubieta ◽  
David Campo-Caballero ◽  
Jon Equiza ◽  
Inés Albajar ◽  
Naroa Sulibarría ◽  
...  

Neurosurgery ◽  
2000 ◽  
Vol 46 (5) ◽  
pp. 1272-1279 ◽  
Author(s):  
Jun Zhang ◽  
Richard E. Clatterbuck ◽  
Daniele Rigamonti ◽  
Harry C. Dietz

Radiology ◽  
2017 ◽  
Vol 284 (2) ◽  
pp. 443-450 ◽  
Author(s):  
Corinne D. Strickland ◽  
Steven C. Eberhardt ◽  
Mary R. Bartlett ◽  
Jeffrey Nelson ◽  
Helen Kim ◽  
...  

2015 ◽  
Vol 112 (46) ◽  
pp. 14284-14289 ◽  
Author(s):  
Xavier Cullere ◽  
Eva Plovie ◽  
Paul M. Bennett ◽  
Calum A. MacRae ◽  
Tanya N. Mayadas

Three genes, CCM1, CCM2, and CCM3, interact genetically and biochemically and are mutated in cerebral cavernous malformations (CCM). A recently described member of this CCM family of proteins, CCM2-like (CCM2L), has high homology to CCM2. Here we show that its relative expression in different tissues differs from that of CCM2 and, unlike CCM2, the expression of CCM2L in endothelial cells is regulated by density, flow, and statins. In vitro, both CCM2L and CCM2 bind MEKK3 in a complex with CCM1. Both CCM2L and CCM2 interfere with MEKK3 activation and its ability to phosphorylate MEK5, a downstream target. The in vivo relevance of this regulation was investigated in zebrafish. A knockdown of ccm2l and ccm2 in zebrafish leads to a more severe “big heart” and circulation defects compared with loss of function of ccm2 alone, and also leads to substantial body axis abnormalities. Silencing of mekk3 rescues the big heart and body axis phenotype, suggesting cross-talk between the CCM proteins and MEKK3 in vivo. In endothelial cells, CCM2 deletion leads to activation of ERK5 and a transcriptional program that are downstream of MEKK3. These findings suggest that CCM2L and CCM2 cooperate to regulate the activity of MEKK3.


2006 ◽  
Vol 21 (1) ◽  
pp. 1-5 ◽  
Author(s):  
L. Fernando Gonzalez ◽  
Gregory P. Lekovic ◽  
Jennifer Eschbacher ◽  
Stephen Coons ◽  
Randall W. Porter ◽  
...  

✓Cavernous hemangiomas that occur within the cavernous sinus (CS) are different from cerebral cavernous malformations (CMs) clinically, on imaging studies, and in their response to treatment. Moreover, CMs are true vascular malformations, whereas hemangiomas are benign vascular tumors. Because of these differences, the authors suggest that these two entities be analyzed and grouped separately. Unfortunately, despite these differences, much confusion exists in the literature as to the nature, behavior, and classification of these two distinct lesions. This confusion is exacerbated by subtle histological differences and the inconsistent use of nomenclature. The authors use the term “cavernous malformation” to refer to intraaxial lesions only; they prefer to use the term “cavernous sinus hemangioma” to refer to extraaxial, intradural hemangiomas of the CS.


2006 ◽  
Vol 21 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Shervin R. Dashti ◽  
Alan Hoffer ◽  
Yin C. Hu ◽  
Warren R. Selman

✓Cerebral cavernous malformations (CMs) are angiographically occult neurovascular lesions that consist of enlarged vascular channels without intervening normal parenchyma. Cavernous malformations can occur as sporadic or auto-somal-dominant inherited conditions. Approximately 50% of Hispanic patients with cerebral CMs have the familial form, compared with 10 to 20% of Caucasian patients. There is no difference in the pathological findings or presentation in the sporadic and familial forms. To date, familial CMs have been attributed to mutations at three different loci: CCM1 on 7q21.2, CCM2 on 7p15-p13, or CCM3 on 3q25.2-q27. The authors summarize the current understanding of the molecular events underlying familial CMs.


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