Our data support previous assumptions that sporadic CCMs are systematically associated with local venous abnormalities involving larger outflow vessels. However, the typical appearance of a VM was not confirmed in all cases. The role of the venous environment in the pathomechanism of CCMs remains unclear.

ObjectiveTo determine the role of associated developmental venous anomalies (DVAs) in intracranial hemorrhage (ICH) caused by cerebral cavernous malformations (CCMs).MethodsWe analyzed patient registry data of 1,219 patients with cavernous malformations treated in our institution between 2003 and 2018. Patients with spinal and familial CCM and patients without complete MRI data were excluded. The impact of various variables on ICH as a mode of presentation was assessed with multivariate binary logistic regression analysis. Kaplan Meier/Cox regression analysis was performed to analyze cumulative 5-year-risk for (re)hemorrhage and to identify baseline predictors of this outcome.ResultsSeven hundred thirty-one patients with CCM were included. Multivariate logistic regression confirmed a statistically significant negative correlation with DVA (odds ratio [OR] 0.635 [95% confidence interval (CI) 0.459–0.878]) and positive correlation with brainstem localization (OR 6.277 [95% CI 4.287–9.191]) with ICH as the mode of presentation. Among 731 patients, 76 experienced (re)hemorrhage during 2,338 person-years of follow-up. Overall cumulative 5-year risk was 24.1% (95% CI 21.1%–27.5%). Cox regression analysis revealed initial presentation with ICH (hazard ratio [HR] 8.0 [95% CI 3.549–18.122]) and brainstem localization (HR 2.9 [95% CI 1.756–4.765]) as independent baseline predictors of (re)hemorrhage. Presence of DVA added no independent prognostic information (HR 1.1 [95% CI 0.717–1.885]).ConclusionPatients with CCM with associated DVA are at lower risk to present with ICH. During untreated 5-year follow-up, they showed equal (re)hemorrhage risk compared to patients with CCM without DVA.

BACKGROUND AND PURPOSE: The pathophysiology of wall contrast enhancement in thrombosed intracranial aneurysms is incompletely understood. This in vivo study aimed to investigate wall microstructures with gadolinium-enhanced 7T MR imaging. MATERIALS AND METHODS: Thirteen patients with 14 thrombosed intracranial aneurysms were evaluated using a 7T whole-body MR imaging system with nonenhanced and gadolinium-enhanced high-resolution MPRAGE. Tissue samples were available in 5 cases, and histopathologic findings were correlated with 7T MR imaging to identify the gadolinium-enhancing microstructures. RESULTS: Partial or complete inner wall enhancement correlated with neovascularization of the inner wall layer and the adjacent thrombus. Additional partial or complete outer wall enhancement can be explained by formation of vasa vasorum in the outer aneurysm wall layer. The double-rim enhancement correlated with perifocal edema and wall histologic findings suggestive of instability. CONCLUSIONS: Two distinct aneurysm wall microstructures responsible for gadolinium enhancement not depictable at lower spatial resolutions can be visualized in vivo using high-resolution gadolinium-enhanced 7T MR imaging.

SUMMARY: Giant intracranial aneurysms are rare vascular pathologies associated with high morbidity and mortality. The purpose of this in vivo study was to assess giant intracranial aneurysms and their wall microstructure by 7T MR imaging, previously only visualized in histopathologic examinations. Seven giant intracranial aneurysms were evaluated, and 2 aneurysms were available for histopathologic examination. Six of 7 (85.7%) showed intraluminal thrombus of various sizes. Aneurysm walls were depicted as hypointense in TOF-MRA and SWI sequences with excellent contrast ratios to adjacent brain parenchyma (range, 0.01-0.60 and 0.58 -0.96, respectively). The triple-layered microstructure of the aneurysm walls was visualized in all aneurysms in TOF-MRA and SWI. This could be related to iron deposition in the wall, similar to the findings in 2 available histopathologic specimens. In vivo 7T TOF-MRA and SWI can delineate the aneurysm wall and the triple-layered wall microstructure in giant intracranial aneurysms. ABBREVIATIONS:GA ϭ giant intracranial aneurysm; SEM ϭ standard error of the mean

Somatic gain-of-function (GOF) mutations in phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), the catalytic subunit of phosphoinositide 3-kinase (PI3K), have been recently discovered in cerebral cavernous malformations (CCMs), raising the possibility that the activation of PI3K pathways is a possible universal regulator of vascular morphogenesis. However, there have been contradicting data presented among various groups and studies. To enhance the current understanding of vascular anomalies, it is essential to explore this possible relationship between altered PI3K signalling pathways and its influence on the pathogenesis of CCMs. GOF PIK3CA-mutants have been linked to overgrowth syndromes, allowing this group of disorders, resulting from somatic activating mutations in PIK3CA, to be collectively named as PIK3CA-related overgrowth spectrum disorders. This paper reviews and attempts to conceptualise the relationships and differences among clinical presentations, genotypic and phenotypic correlations and possible coexistence of PIK3CA and CCM mutations/phenotypes in CCM lesions. Finally, we present a model reflecting our hypothetical understanding of CCM pathogenesis based on a systematic review and conceptualisation of data obtained from other studies.

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Background and Purpose: The pathophysiology of development, growth, and rupture of intracranial aneurysms (IAs) is only partly understood. Cyclooxygenase 2 (COX-2) converts arachidonic acid to prostaglandin H 2 , which, in turn, is isomerized to prostaglandin E 2 . In the human body, COX-2 plays an essential role in inflammatory pathways. This explorative study aimed to investigate COX-2 expression in the wall of IAs and its correlation to image features in clinical (1.0T, 1.5T, and 3.0T) magnetic resonance imaging (MRI) and ultra-high-field 7T MRI. Methods: The study group comprised 40 patients with partly thrombosed saccular IAs. The cohort included 17 ruptured- and 24 unruptured IAs, which had all been treated microsurgically. Formaldehyde-fixed paraffin-embedded samples were immunohistochemically stained with a monoclonal antibody against COX-2 (Dako, Santa Clara, CA; Clone: CX-294). We correlated Perls Prussian blue staining, MRI, and clinical data with immunohistochemistry, analyzed using the Trainable Weka Segmentation algorithm. Results: Aneurysm dome size ranged between 2 and 67 mm. The proportion of COX-2 positive cells ranged between 3.54% to 85.09%. An upregulated COX-2 expression correlated with increasing IA dome size ( P =0.047). Furthermore, there was a tendency of higher COX-2 expression in most ruptured IAs ( P =0.064). At all field strengths, MRI shows wall hypointensities due to iron deposition correlating with COX-2 expression ( P =0.022). Conclusions: Iron deposition and COX-2 expression in IAs walls correlate with signal hypointensity in MRI, which might, therefore, serve as a biomarker for IA instability. Furthermore, as COX-2 was also expressed in small unruptured IAs, it could be a potential target for specific medical treatment.

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