Venous pathologies in paediatric neuroradiology: from foetal to adolescent life.

The interpretation of cerebral venous pathologies in paediatric practice is challenging as there are several normal anatomical variants, and the pathologies are diverse, involving the venous system through direct and indirect mechanisms. This paper aims to provide a comprehensive review of these entities, as their awareness can avoid potential diagnostic pitfalls. We also propose a practical classification system of paediatric cerebral venous pathologies, which will enable more accurate reporting of the neuroimaging findings, as relevant to the underlying pathogenesis of these conditions. The proposed classification system comprises of the following main groups: arterio-venous shunting-related disorders, primary venous malformations and veno-occlusive disorders. A multimodal imaging approach has been included in the relevant subsections, with a brief overview of the modality-specific pitfalls that can also limit interpretation of the neuroimaging. The article also summarises the current literature and international practices in terms of management options and outcomes in specific disease entities.

Characterization of Endothelial Cilia Distribution During Cerebral-Vascular Development in Zebrafish ( Danio rerio).

Objective- Endothelial cells (ECs) sense and respond to flow-induced mechanical stress, in part, via microtubule-based projections called primary cilia. However, many critical steps during vascular morphogenesis occur independent of flow. The involvement of cilia in regulating these stages of cranial vascular morphogenesis is poorly understood because cilia have not been visualized in primary head vessels. The objective of this study was to investigate involvement of cilia in regulating the early stages of cranial vascular morphogenesis. Approach and Results- Using high-resolution imaging of the Tg(kdrl:mCherry-CAAX) y171 ;(bactin::Arl13b:GFP) zebrafish line, we showed that cilia are enriched in the earliest formed cranial vessels that assemble via vasculogenesis and in angiogenic hindbrain capillaries. Cilia were more prevalent around the boundaries of putative intravascular spaces in primary and angiogenic vessels. Loss of cardiac contractility and blood flow, because of knockdown of cardiac troponin T type 2a ( tnnt2a) expression, did not affect the distribution of cilia in primary head vasculature. In later stages of development, cilia were detected in retinal vasculature, areas of high curvature, vessel bifurcation points, and during vessel anastomosis. Loss of genes crucial for cilia biogenesis ( ift172 and ift81) induced intracerebral hemorrhages in an EC-autonomous manner. Exposure to high shear stress induced premature cilia disassembly in brain ECs and was associated with intracerebral hemorrhages. Conclusions- Our study suggests a functional role for cilia in brain ECs, which is associated with the emergence and remodeling of the primary cranial vasculature. This cilia function is flow-independent, and cilia in ECs are required for cerebral-vascular stability.

De novo intracerebral arteriovenous malformations and a review of the theories of their formation.

PURPOSE: Arteriovenous malformations (AVM) are still frequently described as congenital lesions in medical texts despite little evidence existing for their congenital nature. Increasing numbers of case reports of de novo AVMs add weight to the notion that they are dynamic lesions and that they can form postnatally. A thorough review of all reported cases of de novo AVM formation and a review of articles relating to AVM pathogenesis was planned to summarise current research on AVM pathogenesis and provide insight into the future implications for AVM research and treatment. METHODS AND RESULTS: MEDLINE was searched to find 29 cases of de novo AVM formation with prior MRI imaging, nine of which also had prior digital subtraction angiography. A discussion of AVM pathogenesis is undertaken through a review of articles relating to AVM embryology, postnatal angiogenesis, syndromic forms of AVMs and studies of AVM molecular biology and genetics in human and animal models. CONCLUSIONS: There is little evidence for an embryological origin through dysregulated vasculogenesis, whereas there is a raft of evidence to support dysregulated angiogenesis in childhood or even adulthood. Translational implications include risk stratification by biomarkers for predicting haemorrhage and novel therapeutic approaches to suppress AVM proliferation and initiate reversal.

Embryological Consideration of Dural AVF.

BACKGROUND: The distribution of intracranial dural AVFs (DAVFs) may be affected by the embryological bony structures that consist of membranous bone and endochondral bone. METHODS: We retrospectively analyzed the distribution of the shunt points in 58 consecutive cases of DAVFs. Shunt points were identified with selective digital subtraction angiography, high-resolution cone beam computed tomography (CT), or three-dimensional rotation angiography. All the shunt points were plotted on the map of the skull base in relation to the topography of the endochondral bone and the membranous bone. If the shunt point was localized on the surface of endochondral bone, this was categorized as the endochondral bone group. If it was located on membranous bone, this was categorized as the membranous bone group. If the shunt point was independent from both bony structures, this was categorized as the independent group. FINDINGS: In 55 of 58 cases, shunt points were identified angiographically. Three cases had multiple shunts. There were 33 shunt points (60 %) belonging to endochondral bone. In this group, 16 cases of sigmoid, 11 of carotid cavernous, 3 of petrosal apex, and 3 of sigmoid DAVF were observed. There were 12 shunt points (22 %) localized on membranous bone; in this group, there were nine cases of transverse sinus, two of superior sagittal sinus, and one case of confluence DAVF. There were ten shunt points (18 %) independent from these two bony structures: four cases of olfactory groove, four . of middle fossa, and two of hypoglossal canal DAVF. CONCLUSIONS: There were correlations between the localization of shunt points of DAVFs and the topography of endochondral bone and the membranous bone. The histological difference of endochondral bone and membranous bone at the level of epidural space might cause the formation of DAVFs.

Ultrasound of the Fetal Veins Part 3: The Fetal Intracerebral Venous System.

The study of the intracerebral venous system in the fetus can only be achieved by means of high-resolution ultrasound equipment with sensitive color Doppler. In the past two decades, there has been a growing interest in the ultrasound examination of the fetal brain with few studies reporting on the brain vasculature during various stages of gestation. In comparison to other fetal venous systems, reports on the assessment of the fetal cerebral venous system are still scarce. This article presents a review on the fetal intracranial venous system with detailed discussions on the anatomy of the superficial and deep cerebral veins. Color Doppler of the main fetal cerebral veins to include the superior sagittal sinus, the straight sinus, the vein of Galen, the internal cerebral veins, the transverse sinuses and others is also discussed. Furthermore, this article highlights abnormal clinical conditions such as aneurysm of the vein of Galen, thrombosis of the dural sinus and variation in the course of some veins such as the straight sinus and falcine sinus. The role of pulsed Doppler examination in normal and growth-restricted fetuses is also discussed.

A hierarchical model for the development of cerebral arteriovenous malformations.

OBJECTIVE: Cerebral arteriovenous malformations (AVMs) are vascular lesions whose pathogenesis, although not fully elucidated, is likely multifactorial. Recent research investigating vessel development suggests a potential hierarchical model in which capillary sprouts from higher-flow arteries give rise to lower-flow veins. It is possible that an embryologic structural vascular dysgenesis in this hierarchical development heavily contributes to the formation of AVMs. Subsequent genetic "second hits" may then allow development of a clinically significant cerebral AVM. We review this vascular developmental process and describe a novel proposal for the embryogenesis of AVMs and its implications in relation to recent research on polymorphisms and AVMs. METHODS: A comprehensive literature search was performed using PubMed for recent research relative to cerebral AVMs, embryologic vascular development, and polymorphisms involved in AVM pathology. RESULTS: It has recently been shown that both centrally, in the axial embryo, and peripherally, in the embryonic yolk sac, veins form via capillary sprouting from parent arteries. In developing intracranial vessels, a derangement in this embryonic process may lead to a primitive arteriovenous shunt. After this structural "first hit," we suggest that single nucleotide polymorphisms (SNPs) are a major component in allowing AVM growth into symptomatic clinical lesions. CONCLUSIONS: This is a novel theory for the embryologic formation of cerebral AVMs. Hierarchical vessel development, where higher-flow parent arteries give rise to lower-flow veins, provides a potential mechanism for the formation of primitive arteriovenous shunts that, with the influence of polymorphisms, allows AVMs to develop.

The fundamentals of fetal MR imaging: Part 1.

Congenital malformations detected in any fetal system using ultrasound may be further evaluated with magnetic resonance imaging (MRI) to improve counseling, to plan deliveries appropriately, and sometimes to enable fetal interventions. In this first half of a 2-part review, the history and safety factors regarding fetal MRI, as well as the practical aspects of image acquisition, are discussed. In addition, as central nervous system anomalies are most commonly and best evaluated using fetal MRI, challenging central nervous system anomalies, such as fetal ventriculomegaly, posterior anomalies, and neural tube defects, detected using prenatal ultrasound are also reviewed with a focus on the fundamental implications of these diagnoses.

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.

Balloon-assisted coil embolization of a posterior cerebral artery aneurysm via a persistent primitive trigeminal artery: technical note.

INTRODUCTION: We present a patient with an acutely ruptured, wide-necked aneurysm of the left posterior cerebral artery (PCA) treated with Guglielmi detachable coils using the remodeling technique. METHODS: Since the left vertebral artery was compressed due to a tumor in the cerebellopontine angle and the right vertebral artery was hypoplastic, we used a carotid artery approach via a persistent primitive trigeminal artery (PPTA) to selectively catheterize the aneurysm. RESULTS: The aneurysm was occluded completely. CONCLUSION: To our knowledge this is the first case of a wide-necked PCA aneurysm treated via a PPTA and using the remodeling technique. In patients with hypoplastic vertebral arteries and a PPTA, this approach may represent an alternative for selective embolization of posterior circulation aneurysms not amenable to the conventional approach.

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.

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.

Absence of the common carotid artery: a rare vascular anomaly.

Although absence of the common carotid artery (CCA) is a rare anomaly, the specific configuration in our case makes it extremely rare. Clinical, angiographic, ultrasonographic, and embryologic correlations of this anomaly are discussed after the case report.

[Complete imaging study of internal carotid artery agenesis with intercavernous anastomosis]. / Imagerie complète de l'agénésie de l'artère carotide interne avec anastomose inter-caverneuse.

We report a complete imaging study of an exceptional developmental anomaly of the internal carotid artery in a 42-year-old man presenting with a few days history of left visual blurring. MRI and conventional angiography demonstrated unilateral cervical and petrous agenesis of the left internal carotid artery, with an intercavernous anastomosis. CT-scan revealed total absence of the bony carotid canal. We briefly review the embryological hypotheses and discuss clues to correct diagnosis.

Congenital vascular malformations in childhood.

Congenital vascular malformations are an important group of vascular anomalies that occur very early in the pregnancy. Most of these malformations occur between the third and the seventh weeks of the embryonic development. Malformations can affect the arteries, veins, capillaries, and venous sinuses, involving an isolated vessel or a part of the vascular system. There are malformations that affect the vessel size or course, and others that show pathology of the wall anatomy of the vessel. Magnetic resonance angiography (MRA) is improving the study conditions of this pathology. Treatment of most of the vascular malformations--some of them giving clinical symptoms during adulthood--still constitutes a challenge.

Comparative effects of valproic acid sodium for Chiari-like malformation at 9 and 10 days of gestation in the rat.

Our study was conducted to compare structural changes of brain exposed to 500 mg/kg valproic acid sodium (VA) at 10 days of gestation and 2x600 mg/kg VA at 9 days of gestation for Chiari-like malformation (CLM). Brains, each still in the cranium, were placed under the dissecting microscope in such a way that the midsagittal surface for angular morphology was seen, and video images were recorded for both study groups. Distances and angles in each brain were then measured on video image photographs both manually and by means of a computer. The vertebral arch distances following exposure to 500 mg/kg VA at 10 days of gestation were measured. VA on day 9 of gestation group was not followed by significantly different angular morphology or point-to-point distances from those in fetuses exposed to saline. In contrast, the angle formed between the frontal pole and cerebellum at the pons is more -acute in animals treated with VA 500 mg/kg on day 10 of gestation than in controls, but the distances were not reduced. However, the group exposed to VA 500 mg/kg on day 10 of gestation appeared to have sustained only minimal effects on the vertebral arch distances; specifically, spina bifida aperta was not produced in this group. These analyses may indicate that the anterior neural tube is more sensitive to the mechanism of action by which VA produces neural tube defects (NTDs) than is the posterior neural tube. Also, we can conclude that in these rat models, experimental CLM does not correspond to the Chiari malformation (CM) type 2. An animal model has its own species specificity and teratogenic environment, and the embryopathogenesis of NTD in the experimental animal model may not be directly applicable to the human condition.

[Genetic factors related to intracranial arteriovenous malformations]. / Les facteurs génétiques associés aux malformations artério-veineuses cérébrales.

Genetic studies are interesting not only in the diagnosis and screening of new cases within a family harboring a particular disease, but also in understanding the underlying genetic and molecular factors related to that disease. Such studies revealed 3 categories of cerebral arteriovenous malformations in relationship to possible genetic factors. The first one concerns cerebral arteriovenous malformations in relationship to inherited diseases where a genetic support is clearly identified. Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) represents the most classical picture. The second category corresponds to familial cases of cerebral arteriovenous malformations were several members and relatives of the same family harboring the pathology without clear demonstration of any genetic basis. The third category includes cerebral arteriovenous malformations described in association with neurocutaneous disorders issued from maldevelopment events. Sturge-Weber disease and Wyburn-Mason syndrome best illustrate this category. A review of these categories will help in a better understanding of some genetic issues related to cerebral arteriovenous malformations.

Variations of the basal vein: identification using three-dimensional CT angiography.

BACKGROUND AND PURPOSE: The basal vein of Rosenthal (BVR) presents with many variations because of its origin in the secondary longitudinal anastomoses between embryonic veins. The variations were evaluated by 3D CT angiography imaging. METHODS: Three-dimensional CT angiograms in the axial stereoscopic view and other directions constructed by the voxel transmission method and maximum intensity projection (MIP) images were obtained in 500 sides of 250 patients. RESULTS: The BVR flowed into the great vein of Galen in 87.8%, but the anastomoses between the first and second segments were not confirmed in 36.9% of this type. The first segments with hypoplastic or aplastic anastomoses flowed into the cavernous sinus or the sphenoparietal sinus. Therefore, typical BVRs with these anastomoses accounted only for 55.4% of all sides. More than one fourth of the typical type also entered the anterior veins such as the cavernous sinus. Drainage was to the lateral mesencephalic vein in 5.6%, peduncular vein in 1.6%, and lateral or medial tentorial sinus in 5.0%. CONCLUSION: Variations of the BVR can be classified on the basis of the five drainage pathways formed during the early embryonic stage. Three-dimensional CT angiography can show the stereoscopic anatomy and the main drainage routes, but not hypoplastic veins, which are only visible on MIP images.