Heightened activation of embryonic megakaryocytes causes aneurysms in the developing brain of mice lacking podoplanin.

During early embryonic development in mammals, including humans and mice, megakaryocytes (Mks) first originate from primitive hematopoiesis in the yolk sac. These embryonic Mks (eMks) circulate in the vasculature with unclear function. Herein, we report that podoplanin (PDPN), the ligand of C-type lectin-like receptor (CLEC-2) on Mks/platelets, is temporarily expressed in neural tissue during midgestation in mice. Loss of PDPN or CLEC-2 resulted in aneurysms and spontaneous hemorrhage, specifically in the lower diencephalon during midgestation. Surprisingly, more eMks/platelets had enhanced granule release and localized to the lower diencephalon in mutant mouse embryos than in wild-type littermates before hemorrhage. We found that PDPN counteracted the collagen-1-induced secretion of angiopoietin-1 from fetal Mks, which coincided with enhanced TIE-2 activation in aneurysm-like sprouts of PDPN-deficient embryos. Blocking platelet activation prevented the PDPN-deficient embryo from developing vascular defects. Our data reveal a new role for PDPN in regulating eMk function during midgestation.

Embryological basilar apex disposition as a risk factor of basilar apex aneurysm.

The pathogenesis of basilar apex aneurysm (BAA) are still poorly understood. Embryologically, basilar apex anatomical disposition is formed by the fusion of both caudal internal carotid divisions on the midline. To compare basilar apex morphology by embryological classification among patients with BAAs, anterior circulation aneurysms (ACAs), and controls. Prospectively collected data of 47 consecutive patients with unruptured BAAs (42 females and five males), age- and gender-matched 47 patients with unruptured ACAs, and 47 controls without any aneurysms were analyzed. Based on embryology, basilar apex morphology was classified into symmetric cranial fusion (SCrF), symmetric caudal fusion, and asymmetric fusion type. Posterior communicating artery (Pcom) was classified into hypoplastic, adult, or fetal type. The asymmetrical Pcom was defined as bilaterally different type Pcom. The ACAs located at the anterior communicating artery (n = 18), paraclinoid portion (n = 12), middle cerebral artery (n = 8), anterior cerebral artery (n = 5), the top of internal carotid artery (n = 2), and anterior choroidal artery (n = 2). Compared with the ACA group and controls, smoking, asymmetrical Pcom (fetal and adult type), and SCrF type were more prevalent in patients with BAAs by residual analysis. The multinomial logistic regression comparative analysis demonstrated that SCrF type was associated with BAAs (vs. ACA group; odds ratio, 13; 95% confidence interval, 3.8-41 and vs. controls; odds ratio, 25; 95% confidence interval, 5.4-121). The assessment of basilar apex morphology may aid in the understanding of the pathogenesis of BAA and the prediction of BAA formation.

Flow-related intracranial aneurysms associated with unfused arterial twigs relevant to different vascular anomalies: embryologic and hemodynamic considerations.

OBJECT: Cerebrovascular anomalies resulting from the persistence of unfused embryonic twig-like vessels are associated with intracranial aneurysms. All records of patients with ruptured intracranial aneurysms who were treated at our institution were retrospectively reviewed for the presence of aneurysm-associated, unfused, twig-like vessels in the middle cerebral artery (MCA). Such vessels were recorded as twig-like MCA (T-MCA) or twig-like networks of an anomalous collateral artery (T-NACA). Additionally, we sought to characterize vulnerable intracranial aneurysms associated with those vascular anomalies. METHODS: A total of 442 ruptured aneurysms were treated from June 2006 to November 2013; of these, 4 ruptured aneurysms exhibited the presence of ipsilateral, unfused, twig-like vessels. Computed tomography (CT) scans, three-dimensional CT angiography, and digital subtraction angiography (DSA) were performed immediately after the initial ictus. Data analysis included age, sex, Hunt and Hess grade (HHG), Fisher grade (FG), medical risk factors, angiographic architecture, operative methods and findings, radiologic outcomes, and Glasgow outcome scale (GOS). The average follow-up period was 26 months. RESULTS: Patient ages ranged from 26 to 49 years with a mean age of 41; there were two females and two males. All four patients showed FG IV, and three patients had unfavorable HHG (IV in 2 and V in one) at admission. An M1 segmental occlusion and an adjacent small aneurysmal pouch were detected with three-dimensional CT angiography in three patients. Hypertension was recorded in all patients. The initial DSA revealed T-MCA in one patient and T-NACA in three patients. Six aneurysms in all, including two unruptured aneurysms, were found; three ruptured aneurysms existed inside of the twigs. All but one patient required diverse treatment modalities, and four of the five aneurysms were completely occluded after treatment. The remaining aneurysm, treated only with gluing, disappeared during follow-up. In two of the three patients with T-NACA, atresia of the M1 segment was confirmed intraoperatively. The GOS during follow-up was recorded as favorable (good recovery) in two patients and unfavorable (severe disability and permanent vegetative state) in two patients. CONCLUSIONS: These unique vascular anomalies, T-MCA and T-NACA, which are caused by heterogeneous maldevelopment of the primitive cerebral vessels, are not benign because of their frequent association with flow-related aneurysms, which are vulnerable to rupture. Microsurgical or endovascular treatments for this type of flow-related aneurysm associated with twigs are mandatory to prevent fatal rebleeding, and more attention has to be given when physicians encounter steno-occlusive MCA lesions in patients with subarachnoid hemorrhage to detect any vulnerable aneurysms associated with twig-like vessels.

Pediatric intracranial aneurysms: new and enlarging aneurysms after index aneurysm treatment or observation.

BACKGROUND AND PURPOSE: Children with brain aneurysms may be at higher risk than adults to develop new or enlarging aneurysms in a relatively short time. We sought to identify comorbidities and angiographic features in children that predict new aneurysm formation or enlargement of untreated aneurysms. MATERIALS AND METHODS: Retrospective analysis of the University of California-San Francisco Pediatric Aneurysm Cohort data base including medical records and imaging studies was performed. RESULTS: Of 83 patients harboring 114 intracranial aneurysms not associated with brain arteriovenous malformations or intracranial arteriovenous fistulas, 9 (8.4%) developed new or enlarging brain aneurysms an average of 4.2 years after initial presentation. Comorbidities that may be related to aneurysm formation were significantly higher in patients who developed new aneurysms (89%) as opposed to patients who did not develop new or enlarging aneurysms (41%; RR, 9.5; 95% CI, 1.9%-48%; P = .0099). Patients with multiple aneurysms at initial presentation were more likely than patients with a single aneurysm at presentation to develop a new or enlarging aneurysm (RR, 6.2; 95% CI, 2.1%-185; P = .0058). Patients who initially presented with at least 1 fusiform aneurysm were more likely to develop a new or enlarging aneurysm than patients who did not present with a fusiform aneurysm (RR, 22; 95% CI, 3.6%-68%; P = .00050). Index aneurysm treatment with parent artery occlusion also was associated with higher risk of new aneurysm formation (RR, 4.2; 95% CI, 1.3%-13%; P = .024). New aneurysms did not necessarily arise near index aneurysms. The only fatality in the series was due to subarachnoid hemorrhage from a new posterior circulation aneurysm arising 20 months after index anterior circulation aneurysm treatment in an immunosuppressed patient. CONCLUSIONS: Patients who presented with a fusiform aneurysm had a significantly greater incidence of developing a new aneurysm or enlargement of an index aneurysm than did those who presented with a saccular aneurysm. In our patient cohort, 8 of the 9 children who eventually developed new or enlarging brain aneurysms initially presented with fusiform aneurysm morphology. Other comorbidities or multiple aneurysms were also common in these patients at initial presentation.

Confirmation of communication between deep venous drainage and the vein of galen after treatment of a vein of Galen aneurysmal malformation in an infant presenting with severe pulmonary hypertension.

Vein of Galen aneurysmal malformations (VGAM) are characterized by multiple arteriovenous connections draining into a markedly enlarged median draining vein. This ectatic vein is not the vein of Galen, but its embryonic precursor, the median prosencephalic vein of Markowski. During normal development, the posterior portion of the median prosencephalic vein persists as the vein of Galen, while its anterior portion regresses in parallel with the formation of the internal cerebral veins (ICV). It has been traditionally thought that, in children with a VGAM, the deep venous system does not connect to and, a fortiori, does not drain into the ectatic median prosencephalic vein/vein of Galen. This report describes a case of successfully treated VGAM in which the drainage of an ICV into the vein of Galen was only demonstrated by follow-up MR imaging and venography. The potential implications of this finding for the management of VGAMs are discussed.

Distal aneurysms of the unpaired ACA: embryologic and therapeutic aspects.

Anatomical variants of the cerebral arteries in general are frequent and due to the complex ontogenesis of these structures. Although encountered in many mammals, a single anterior cerebral artery (ACA) trunk is an infrequent finding in humans with an incidence of 3-5%. This vessel, giving rise to the arteries of both frontal lobes, is subjected to high flow volumes and distal arterial aneurysms have repetitively been encountered, mostly however before the introduction of endovascular treatment strategies. We report on five patients with acute SAH and arterial aneurysms of an unpaired ACA, who underwent coil embolisation. In all cases endovascular treatment using detachable platinum coils resulted in an at least satisfactory degree of aneurysm obliteration without parent artery occlusion or embolic infarcts. All patients had clinical and angiographic follow-up with median follow-up time of 29 months during which no aneurysm regrowth was encountered. In spite of a small patient group our results suggest, that altered flow dynamics due to enlarged single intracranial vessels may predispose to aneurysm formation and that endovascular embolisation is an appropriate treatment option in distal aneurysms of an unpaired ACA.

Persistent carotid-vertebrobasilar anastomoses: how and why differentiating them?

The persistent carotid-vertebrobasilar anastomoses (PCVBA) can be explained by an interruption of the vertebrobasilar system (VBS) embryogenesis. We present two very rare cases of persistent anastomoses: a hypoglossal artery and a type I proatlantal artery, insisting on the angiographic criteria allowing differentiation. After a brief review of the embryogenesis of the VBS, we describe the different types of persistent anastomoses (hypoglossal, type I and II proatlantal, trigeminal and otic arteries). We will insist on the potential risks, not well-known, but typical of each anastomosis. PCVBA usually are incidental findings but imaging follow-up may be required since aneurysms may develop.

Cerebral aneurysm associated with persistent primitive olfactory artery aneurysm.

Persistent primitive olfactory artery is a rare vascular anomaly but has a clinical importance because of its high association with cerebral aneurysm. We describe a patient with bilateral persistent primitive olfactory arteries associated with an unruptured saccular aneurysm on the left persistent primitive olfactory artery. Seven reported cases with this anomalous artery including ours are reviewed and classified into two variants. This anomalous artery arises from the terminal portion of the internal carotid artery and courses anteromedially along the ipsilateral olfactory tract and makes a hair-pin curve posterior to the olfactory bulb, becoming the distal anterior cerebral artery (variant 1) or the ethmoidal artery (variant 2). Out of 7 reported cases, 4 cases are associated with saccular aneurysms. The aneurysm in variant 1 is located on the hair-pin curve at which an apparent arterial branch is sometimes absent. Two patients suffer from anosmia. Persistent primitive olfactory artery should be kept in mind because of its high association with intracranial saccular aneurysms and unique clinical presentation.

Anatomy of segmental duplication in the human basilar artery. Possible site of aneurysm formation.

Segmental duplications of the basilar artery, previously reported exclusively as anatomical variations, owe their clinical interest to the possible association with aneurysms localized at the junctions of the fenestrated segments. The morphological characteristics of 5 cases of basilar artery segmental duplication without aneurysms, found at autopsy, are reported. In 3 of these the proximal junction of the fenestrated segment was studied with scanning electron microscopy and morphometry. In all cases the tunica media of the medial wall of the 2 branches showed a progressive thinning towards the junctions of the fenestrated segments and a small muscular gap at their apex. The limited medial defect might be embryologically ascribed to the persistence of the morphological individuality of the tunica media of the 2 branches at the point where the fusion of the primitive longitudinal neural arteries stopped. The review of the literature shows that the morphology of the junctions of the fenestrated segments is in conformity with that of the intracranial arterial bifurcations. For this reason the basilar artery fenestration exposes to the blood flow a new distal bifurcation where the same etiologic factors that are still under discussion in the origin of saccular intracranial aneurysms may be active.

Anterior communicating artery aneurysm in early childhood. Report of a case.

A case of an aneurysm of the anterior communicating artery in a 13-month-old child is presented. Sixty-six cases of cerebral saccular aneurysm in children under the age of 2 years found in the literature were analyzed. The characteristics that define this group of patients are a high frequency of large or giant aneurysms, a large proportion of aneurysms of the middle cerebral artery and the posterior circulation, and the frequent location at the peripheral site. Only three cases of anterior communicating artery aneurysm were reported in the literature. The authors discuss these characteristics on the basis of development of fetal cerebral vessels.

Saccular aneurysms in basilar artery fenestration.

Of 59 cases of vertebrobasilar junction aneurysms diagnosed and treated from January 1977 to April 1986, 21 (35.5%) saccular aneurysms arose in a fenestration of the proximal basilar artery. Defects of the media at the junctures of the fenestrated segments, as well as the possible presence of turbulent flow at the vertebrobasilar junction, may explain the high incidence of vertebrobasilar aneurysms associated with proximal basilar artery fenestration.