scholarly journals The role of MRI in assessing the effectiveness of cerebral cavernous malformations stereotaxic radiosurgical treatment

2021 ◽  
Vol 2 (2S) ◽  
pp. 34-35
Author(s):  
E. N. Girya ◽  
O. L. Evdokimova ◽  
A. A. Kochakova ◽  
V. A. Rak ◽  
E. N. Rozhnova
Keyword(s):  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations

.

scholarly journals Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice

2011 ◽  
Vol 208 (9) ◽  
pp. 1835-1847 ◽  
Author(s):  
Gwénola Boulday ◽  
Noemi Rudini ◽  
Luigi Maddaluno ◽  
Anne Blécon ◽  
Minh Arnould ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Vascular Malformations ◽  
Vascular Lesions ◽  
Developmental Timing ◽  
Cerebral Cavernous Malformations ◽  
Loss Of Function ◽  
Cavernous Malformations ◽  
The Central Nervous System ◽  
Dominant Condition

Cerebral cavernous malformations (CCM) are vascular malformations of the central nervous system (CNS) that lead to cerebral hemorrhages. Familial CCM occurs as an autosomal dominant condition caused by loss-of-function mutations in one of the three CCM genes. Constitutive or tissue-specific ablation of any of the Ccm genes in mice previously established the crucial role of Ccm gene expression in endothelial cells for proper angiogenesis. However, embryonic lethality precluded the development of relevant CCM mouse models. Here, we show that endothelial-specific Ccm2 deletion at postnatal day 1 (P1) in mice results in vascular lesions mimicking human CCM lesions. Consistent with CCM1/3 involvement in the same human disease, deletion of Ccm1/3 at P1 in mice results in similar CCM lesions. The lesions are located in the cerebellum and the retina, two organs undergoing intense postnatal angiogenesis. Despite a pan-endothelial Ccm2 deletion, CCM lesions are restricted to the venous bed. Notably, the consequences of Ccm2 loss depend on the developmental timing of Ccm2 ablation. This work provides a highly penetrant and relevant CCM mouse model.

scholarly journals Radiation diagnostics of cerebral cavernous malformations

2021 ◽  
Vol 2 (1) ◽  
pp. 39-48
Author(s):  
Elena N. Girya ◽  
Valentin E. Sinitsyn ◽  
Alexey S. Tokarev
Keyword(s):  
Pulse Sequences ◽  
Vascular Pathology ◽  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations ◽  
Imaging Sequence ◽  
Magnetic Resonance Imaging Mri ◽  
The Moment ◽  
Ct And Mri ◽  
Selection Of

Cerebral cavernous malformations are a fairly common vascular pathology at the moment, with the number of detected cases increasing dramatically in recent years. This is because modern neuroimaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI) have been introduced into clinical practice and are widely available. Prior to the advent of CT and MRI technologies, it was extremely difficult to diagnose this pathology, and the diagnosis was usually made intraoperatively or based on autopsy data. Further, the literature review is devoted to the radiological diagnosis of cerebral cavernous malformations (CM). The role of neuroimaging methods in the diagnosis of cavernous malformations, as well as the use of MRI for CM visualization, was analyzed. The advantages of MRI over other neuroimaging methods for this pathology have been demonstrated. Pulse sequences of MRI and signaling characteristics of various foci were characterized, depending on the morphological substrate. The significance of the susceptibility-weighted imaging sequence was also evaluated for the detection of multifocal lesions in cases of familial CM. The study of the main pulse sequences of MRI for visualization of CM will improve the protocol algorithm for the timely diagnosis of this pathology and the selection of therapeutic approach.

Role of Delta-Notch signaling in cerebral cavernous malformations

2016 ◽  
Vol 39 (4) ◽  
pp. 581-589 ◽  
Author(s):  
Souvik Kar ◽  
Arpita Baisantry ◽  
Arya Nabavi ◽  
Helmut Bertalanffy
Keyword(s):  
Notch Signaling ◽  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations

Role of aspirin and statin therapy in patients with cerebral cavernous malformations

2020 ◽  
Vol 78 ◽  
pp. 246-251
Author(s):  
Santiago Gomez-Paz ◽  
Mohamed M. Salem ◽  
Georgios A. Maragkos ◽  
Luis C. Ascanio ◽  
Alejandro Enriquez-Marulanda ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations

scholarly journals A Series of 14 Representative Presentations of Cerebral Cavernous Malformations

2021 ◽  
pp. 101298
Author(s):  
Ryan Hudnall ◽  
Eric X. Chen ◽  
Patrick J Opperman ◽  
Sean Kelly ◽  
Justin A. Cramer ◽  
...  
Keyword(s):  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations

Genotype-phenotype correlations in cerebral cavernous malformations patients

2006 ◽  
Vol 60 (5) ◽  
pp. 550-556 ◽  
Author(s):  
Christian Denier ◽  
Pierre Labauge ◽  
Françoise Bergametti ◽  
Florence Marchelli ◽  
Florence Riant ◽  
...  
Keyword(s):  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations

Abstract 159: Exceptional Aggressiveness of CCM3 Phenotype

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Tania J Rebeiz ◽  
Abdul Ghani Mikati ◽  
Darlene Simkhin ◽  
Cornelia Lee ◽  
Amy Akers ◽  
...  
Keyword(s):  
Spontaneous Mutation ◽  
Mutation Screening ◽  
High Sensitivity ◽  
Skin Lesions ◽  
Cerebral Cavernous Malformations ◽  
Cognitive Disability ◽  
Cavernous Malformations ◽  
Patient Advocacy Group ◽  
Sporadic Cases

Introduction: Familial forms of cerebral cavernous malformations (CCM) account for about 1/3 of cases, involving autosomal dominant inheritance at 1 of 3 gene loci. Few studies have examined any special features of the rarest cases with CCM3 (PDCD10 ) mutation at q3, constituting <15 % of probands genotyped by sequential mutation screening, and <2% of CCM cases at large. Hypothesis: We hypothesize that CCM3 cases have unique phenotypic features not recognized in the more common CCM1 and 2 families, or in sporadic cases. Methods: Twelve probands including 17 subjects with confirmed CCM3 mutations were prospectively enrolled through systematic facilitated referral by the patient advocacy group Angioma Alliance. Clinical features were catalogued, including high sensitivity susceptibility weighted imaging (SWI). Rates of overt hemorrhage were determined based on adjudicated criteria. Comparisons were made to systematic literature review of natural history data on non-CCM3 cases. Results: The first overt hemorrhage occurred most often in the 1st decade of life (mean age 5.8). Nine of 17 subjects (52%) suffered 30 overt hemorrhages, with an estimated incidence of 6.7 % /patient/year based on exposure risk since birth, and 17% /patient/year based on risk since first symptom onset. Lesion burden on SWI was exceptionally high, >100 lesions in 28%, and > 20 lesions in 72% of cases, respectively. Adjusted bleed rate was <0.5% /lesion/year. New SWI lesions formed at a rate of 2.7/patient/year in prospective follow-up, and 1.8/patient/year based on years since birth. Scoliosis was found in 47% (an association not recognized previously), skin lesions in 29.4%, and brain tumors in 29.4% of cases, respectively. Cognitive disability affected 47% of cases, mostly in association with high lesion burden. Six of 15 cases with parental screening (40%) represented a spontaneous mutation. Conclusion: CCM3 is exceptionally aggressive compared to other familial and sporadic CCM. High risks of bleeding and cognitive disability mostly reflect severe lesion burden early in life, rather than a higher risk per lesion. These results will inform the design of clinical trials, urgently needed to address this unique CCM cohort.

CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling

2021 ◽  
Author(s):  
Lingfeng Qin ◽  
Haifeng Zhang ◽  
Busu Li ◽  
Quan Jiang ◽  
Francesc Lopez ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Fluorescein Isothiocyanate ◽  
The Body ◽  
Blue Dye ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Cavernous Malformations ◽  
Morphological Alterations ◽  
The Brain

Objective: Cerebral cavernous malformations (CCMs) can happen anywhere in the body, although they most commonly produce symptoms in the brain. The role of CCM genes in other vascular beds outside the brain and retina is not well-examined, although the 3 CCM-associated genes ( CCM1 , CCM2 , and CCM3 ) are ubiquitously expressed in all tissues. We aimed to determine the role of CCM gene in lymphatics. Approach and Results: Mice with an inducible pan–endothelial cell (EC) or lymphatic EC deletion of Ccm3 ( Pdcd10 ECKO or Pdcd10 LECKO ) exhibit dilated lymphatic capillaries and collecting vessels with abnormal valve structure. Morphological alterations were correlated with lymphatic dysfunction in Pdcd10 LECKO mice as determined by Evans blue dye and fluorescein isothiocyanate(FITC)-dextran transport assays. Pdcd10 LECKO lymphatics had increased VEGFR3 (vascular endothelial growth factor receptor-3)-ERK1/2 signaling with lymphatic hyperplasia. Mechanistic studies suggested that VEGFR3 is primarily regulated at a transcriptional level in Ccm3-deficient lymphatic ECs, in an NF-κB (nuclear factor κB)–dependent manner. CCM3 binds to importin alpha 2/KPNA2 (karyopherin subunit alpha 2), and a CCM3 deletion releases KPNA2 to activate NF-κB P65 by facilitating its nuclear translocation and P65-dependent VEGFR3 transcription. Moreover, increased VEGFR3 in lymphatic EC preferentially activates ERK1/2 signaling, which is critical for lymphatic EC proliferation. Importantly, inhibition of VEGFR3 or ERK1/2 rescued the lymphatic defects in structure and function. Conclusions: Our data demonstrate that CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic EC that drives lymphatic hyperplasia and malformation and warrant further investigation on the potential clinical relevance of lymphatic dysfunction in patients with CCM.

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