Cerebrovascular Malformations Research Articles

Dural sinus malformation with arteriovenous fistulae in a newborn: Positive outcome following endovascular management

Dural sinus malformation (DSM) is an extremely rare and congenital cerebrovascular malformation that is associated with dural arteriovenous fistula and a large dural lake, which may mimic the clinical malformations of an infantile dural arteriovenous shunt or the vein of Galen. Early diagnosis and treatment of DSM is crucial in order to avoid irreversible brain injuries or heart failure. Here, we report an unusual case of extensive DSM that showed good clinical and angiographic results after endovascular embolization.

Cavernous Malformations: A Paradigm for Progress

Cavernous Malformations: A Paradigm for Progress

Progress on children traumatic cerebral infarction

There are many causes of children cerebral infarction, including cerebrovascular malformation,autoimmune cerebrovascular phlogistic, infection, trauma and the high state of blood coagulation. Because the brain development is not mature, the children is the high-risk group of traumatic cerebral infarction. The early diagnosis of traumatic cerebral infarctions relies on the dynamic performance of the clinical observation, taking head CT or MRI quickly, especially diffusion-weighted imaging, which is more sensitive on the judgement of acute cerebral infarction period. Common sites of traumatic cerebral infarction are basal ganglia. The infarcts are usually small. Treatment on traumatic cerebral infarction must give priority to non-operation. Early diagnosis and prompt treatment can provide better prognosis than adults. Key words: Children; Craniocerebral injury; Cerebral Infarction

An inSPECTion: Is Propranolol Safe in PHACES Syndrome?

Since 2008, propranolol has been increasingly used to treat infantile hemangiomas (JW Dermatol Jun 20 2008). Facial hemangioma is part of the constellation of congenital anomalies that make up PHACES syndrome (Posterior fossa malformations, facial Hemangioma, Arterial anomalies, Cardiac anomalies, Eye anomalies, and Sternal/ventral defects). Because cerebrovascular malformations, the main risk factor for stroke in healthy children, are associated …

589 Congenital Central Hypoventilation Syndrome in Three Infants

Background and aims: Congenital central hypoventilation syndrome (CCHS) is a rare syndrome characterized by the failure of automatic control of breathing with absent or negligible sensitivity to hypercapnia and hypoxaemia, primarily during sleep. It is associated with a number of conditions affecting or derived from the autonomic nervous system. Methods: Three infants with CCHS were diagnosed in our tertiary pediatric hospital over five years. Results: All three infants were born full term. During neonatal period they presented prolonged apneas and intermittent cyanosis, in the absence of cardiac, pulmonary or neuromuscular disease. They were treated by tracheostomy and mechanical ventilation. After initial respiratory dependency, they became able to sustain normal gas exchange during wakefulness. Two of three cases had Hirschsprung disease and mild generalized hypotonia. One experienced seizures unrelated to antecedent hypoxemia and cardiac arrhythmias. Dilated, nonreactive pupils and lack of circadian temperature variation occurred in one. Cerebrovascular malformations, tumors of neural crest origin and pulmonary hypertension were not observed. Mutations of the PHOX2B gene were detected in all cases. At the age of 2 to 5 years, they are still under ventilatory support during sleep. The eldest child has been successfully decannulated and he is on NIV through a nasal mask. Al three children are managed at home, with adequate growth, progress in achieving motor milestones and low morbidity. Conclusions: Infants with CCHS represent a spectrum of severity. With early diagnosis and careful ventilatory management these children can engage in activities typical of children of their age.

Factors predicting language lateralization in patients with perisylvian vascular malformations

The authors conducted a study to determine the factors associated with right-sided language dominance in patients with cerebrovascular malformations. Twenty-two patients with either arteriovenous malformations (AVMs [15 cases]) or cavernous malformations (7 cases) underwent functional MR (fMR) imaging studies of language function; a 3.0-T head-only unit was used. Lateralization indices were calculated separately for Broca and Wernicke areas. Lesion size, Spetzler-Martin grade, and the distance between the lesion and anatomically defined language cortex were calculated for each patient. Right-sided language dominance occurred in 5 patients, all of whom had AVMs within 10 mm of canonical language areas. Three patients had right-sided language dominance in the Wernicke area alone whereas 2 had right-sided language dominance in both Broca and Wernicke areas. Wada testing and intraoperative electrocortical stimulation were performed as clinically indicated to corroborate fMR imaging findings. The primary factor associated with right-sided language dominance was the AVM being within 10 mm of anatomically defined language areas. The lesion size and the Spetzler-Martin grade were not significant factors. Anomalous fMR imaging laterality was typically confined to the language area proximate to the lesion, with the distal language area remaining in the left hemisphere dominant. This study emphasizes the need to map each case individually in patients with left perisylvian AVMs. Assumptions about eloquent cortex based on anatomical landmarks (a key component of Spetzler-Martin grading) may have to be reconsidered.

Upregulation of transmembrane endothelial junction proteins in human cerebral cavernous malformations

Cerebral cavernous malformations (CCMs) are among the most prevalent cerebrovascular malformations, and endothelial cells seem to play a major role in the disease. However, the underlying mechanisms, including endothelial intercellular communication, have not yet been fully elucidated. In this article, the authors focus on the endothelial junction proteins CD31, VE-cadherin, and occludin as important factors for functional cell-cell contacts known as vascular adhesion molecules and adherence and tight junctions. Thirteen human CCM specimens and 6 control tissue specimens were cryopreserved and examined for the presence of VE-cadherin, occludin, and CD31 by immunofluorescence staining. Protein quantification was performed by triplicate measurements using western blot analysis. Immunofluorescent analyses of the CCM sections revealed a discontinuous pattern of dilated microvessels and capillaries as well as increased expression of occludin, VE-cadherin, and CD31 in the intima and in the enclosed parenchymal tissue compared with controls. Protein quantification confirmed these findings by showing upregulation of the levels of these proteins up to 2-6 times. A protocol enabling the molecular and morphological examination of the intercellular contact proteins in human CCM was validated. The abnormal and discontinuous pattern in these endothelial cell-contact proteins compared with control tissue explains the loose intercellular junctions that are considered to be one of the causes of CCM-associated bleeding or transendothelial oozing of erythrocytes. Despite the small number of specimens, this study demonstrates for the first time a quantitative analysis of endothelial junction proteins in human CCM.

Anomalous origins of the calcarine and parieto-occipital arteries

Understanding cerebrovascular anatomy and its variations is of utmost importance in treating vascular malformations. The two patients presented here demonstrate yet to be reported anomalous origins of the cortical branches of the posterior cerebral artery. In one patient, fetal calcarine arteries were identified arising from the internal carotid arteries bilaterally with no calcarine branches arising from the posterior circulation and the basilar artery giving rise to terminal parieto-occipital arteries. Additionally, with vertebral artery injections, we found the dominant arterial supply to the right parieto-occipital artery arose from the right internal carotid artery and right posterior communicating artery and the dominant arterial supply to the left parieto-occipital artery arose from the right vertebral artery. A second patient demonstrated anomalous origins of the calcarine and parietal occipital branches from the supraclinoid left internal carotid artery. Understanding this complex cerebrovascular anatomy is important in the endovascular treatment of cerebrovascular aneurysms and malformations.

Diagnosis and treatment of chronic expanding intracerebral hematoma: report on 37 cases

Objective To improve the diagnosis and treatment level of chronic expanding intracerebral hematoma (CEICH). Methods The clinical data of 37 cases with CEICH were analyzed retrospectively with literature review, we wanted to find the evidence for diagnosis and the effective method for treatment. Results CEICH could involved in anywhere of brain, most of them were solitary, seldom seen multiple. 24 cases were misdiagnosed as CEICH before operation (65%). All the 37 cases were operatived, and small vascular malformation was detected in 13 cases in pathological examination. All cases were followed - up after operation, 29 patients recovered quite well, 7 patients suffered focal neurological deficit, 1 patient died of rebleeding of contralateral cerebral hemisphere. Conclusion We supposed the three points can be the evidence of diagnosis. (1) Developed slowly of the clinical presentation of increased intracranial pressure. (2) The radiological characteristics can include mass effect of encapsulated or liquefied lesion with unisodensity, low density, high density or isodensity (CT value 20 ～ 70 Hu). (3) Irregular ringed round or similar to round enhancement. We should think about CEICH if included two above points,and we should make a definite diagnosis of CEICH if three points were included. Surgery to evacuate the hematoma and remove the capsule should be the effective method to CEICH. Key words: Intracerebral hematoma; Cerebrovascular malformation; Diagnosis; Surgical procedures, operative

Temporal Expression of Angiogenesis-Related Genes in Developing Neonatal Rodent Retina

Experimental models to study cerebrovascular malformations are limited therefore we used the neonatal rodent retina as a model to study cerebral angiogenesis. We performed a gene expression analysis to define temporal changes in the expression of 96 angiogenesis-related genes during retinal vascularization. A total of 72 retinas from 36 newborn C57BL/6 mice were used. Sets of neonatal mouse retinas were surgically isolated by 2-day intervals starting from postnatal day 0 to day 20 and at the 32nd day (representing adult retinas). For each of these 12 time points in the postnatal developmental period of mouse retinas, separate sets of 6 retinas from 3 mice were pooled, and their RNA was hybridized to an angiogenesis-specific gene array. Temporal expression patterns of each of the 96 angiogenesis-related genes were analyzed. For confirmation, vascular endothelial growth factor protein expression was also studied by immunohistochemistry. Twenty-two of the 96 genes analyzed displayed a significantly different temporal expression profile, and the rest exhibited a static expression, as compared to the human glyceraldehyde-3-phosphate dehydrogenase gene. Among these genes, the temporal pattern of expression was variable, but peaks were seen mostly on days 8, 10, 12, and 16. This timing corresponds well to morphologic changes that occur in the retina during different stages of angiogenesis. The neonatal rodent retina, which has a cellular architecture similar to that of the brain, has active and quantifiable angiogenic activity during the neonatal period and can be used as a simple and convenient model to study cerebral angiogenesis.

Primary Intraventricular Hemorrhage Due to Rupture of Angiographically Occult Vascular Malformation: Report of a Case

Primary intraventricular hemorrhage (PIVH) is a rare neurological disease. Most articles in the literature recommend angiography as a standard examination to exclude potential vascular lesions. We present a 48-year-old male with PIVH disclosed by non-contrast brain computerized tomography (CT). CT angiography was performed because of the patient's comatous status and high suspicion of a vascular lesion. Contrast extravasation into the ventricles associated with severe hydrocephalus was noted. Cerebral angiography was performed soon after surgery for the cause of acute hydrocephalus. However, no vascular lesion was detected. One week later, a magnetic resonance imaging of the brain demonstrated one hyperintense lesion in the left lateral ventricle near the foramen of Monro. A vascular lesion was documented by histopathological examination. Two weeks after surgery, the patient was discharged. About 10% of cerebrovascular malformations are angiographically occult. A normal angiographic examination does not necessarily indicate the absence of a vascular lesion. We suggest performing brain MRI for PIVH patients if the cerebral angiography appears ”normal”.

Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome previously diagnosed as Seckel syndrome: Report of a novel mutation of the PCNT gene

We report on a 3-year-old boy with prenatal onset of proportionate dwarfism, postnatal severe microcephaly, high forehead with receded hairline, sparse scalp hair, beaked nose, mild retrognathia and hypotonia diagnosed at birth as Seckel syndrome. At age 3 years, he became paralyzed due to a cerebrovascular malformation. Based on the clinical and radiological features showing evidence of skeletal dysplasia, the diagnosis was revised to Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome. Western blot analysis of the patient's lymphoblastoid cell line lysate showed the absence of the protein pericentrin. Subsequent molecular analysis identified a novel homozygous single base insertion (c.1527_1528insA) in exon 10 of the PCNT gene, which leads to a frameshift (Treo510fs) and to premature protein truncation. PCNT mutations must be considered diagnostic of MOPD II syndrome. A possible role of pericentrin in the development of cerebral vessels is suggested.

De novo arteriovenous malformations: case report and review of the literature

Intracerebral arteriovenous malformations (AVMs) are traditionally recognized as congenital lesions. However, with the advent of frequent, noninvasive imaging of the brain, that notion has been challenged. We describe another patient with a de novo cerebral arteriovenous malformation and evaluate the reported literature for trends in the development of these lesions. Cases were selected from the English literature using the PUBMED database using the search term "acquired or de novo cerebrovascular arteriovenous malformations". A total of seven patients (including the one reported in this study) with de novo arteriovenous malformations are reported. Majority of patients were female, and mostly diagnosed as children. Their mean age at diagnosis was 18 years (6-32), and the mean time from the initial intracranial study to the diagnosis of an AVM was 8 years (3-17). De novo formation of AVMs is being increasingly reported, especially in young females. We present only the seventh such case reported in the literature and challenge the traditional view that all arteriovenous malformations are congenital in nature.

Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course

Brain arteriovenous malformations (BAVMs) are an important cause of intracerebral hemorrhage (ICH) in young adults. Biological predictors of future ICH risk are lacking, and controversy exists over previous studies of natural history risk among predominantly ruptured BAVM cohorts. Recent studies have suggested that the majority of BAVMs are now diagnosed as unruptured lesions, and that the risk according to natural history among these lesions may be less than previously assumed. In the first part of this review, the authors discuss available data on the natural history of BAVMs and highlight the need for future studies that aim to develop surrogate biomarkers of disease progression that accurately predict future risk of ICH in BAVMs. The etiology of BAVM remains unknown. Recent studies have suggested a role for genetic factors in the pathogenesis of sporadic BAVM, which is further supported by reports of familial occurrence of BAVM and association with known systemic genetic disorders (such as Osler-Weber-Rendu disease, Sturge-Weber disease, and Wyburn-Mason syndrome). Molecular characterization of BAVM tissue demonstrates a highly angiogenic milieu with evidence of increased endothelial cell turnover. Taken together with a number of reports of de novo BAVM formation, radiographic growth after initial BAVM diagnosis, and regrowth after successful treatment of BAVM, these findings challenge the long-held assumption that BAVMs are static lesions of congenital origin. In the second part of this review, the authors discuss available data on the origins of BAVM and offer insights into future investigations into genetics and endothelial progenitor cell involvement in the pathogenesis of BAVM. Current treatment options for BAVM focus on removal or obliteration of the lesion in an attempt to protect against future ICH risk, including microsurgical resection, endovascular embolization, and stereotactic radiosurgery (SRS). In the third part of this review, the authors discuss available data on SRS in BAVMs and highlight the need for future studies on the radiobiology of BAVMs, especially in regard to biomarker detection for tracking SRS response during the latency period. Insights from future investigations in BAVM may not only prove important for the development of novel therapies and relevant biomarkers for BAVM, but could also potentially benefit a variety of other disorders involving new vessel formation in the CNS, including stroke, tumors, moyamoya disease, and other cerebrovascular malformations.

Effects of Visual Pathway Lesions on the Visual Aura of Migraine

The aim was to to determine if the visual aura of migraine is altered by disease of the afferent visual pathways and if visual aura changes are associated with pre- or postgeniculate lesions. Functional neuroimaging during migraine demonstrates primary visual/extrastriate cortex as an anatomical substrate of visual aura. Neuro-ophthalmological records (including kinetic and static perimetry) of 25 patients with visual loss and typical aura with or without migraine headache were reviewed. Twenty-five patients (16 women, nine men) (mean age 59.8 years) with typical aura had visual loss from pregeniculate (72%) or postgeniculate lesions (28%). Eight patients (four postgeniculate cerebrovascular accidents or arteriovenous malformations, two lifelong optic neuropathy/retinopathy, one childhood ocular trauma, one anisometropic amblyopia) reported absence or alteration of visual aura. Postgeniculate lesions were significantly associated (P = 0.017) with visual aura changes. The association of postgeniculate lesions with altered auras points to a postgeniculate effect on aura appearance (consistent with functional neuroimaging findings). Although statistically significant, this series' association of postgeniculate disease and aura changes is even more robust (P = 0.0002) when structural changes of ocular dominance columns are posited in three patients with optic neuropathy, retinopathy and keratopathy of congenital or childhood origin.

Spontaneous intracerebral hemorrhage

To determine the prognostic value of etiology and localization in spontaneous intracerebral hemorrhage, 896 patients with spontaneous intracerebral hemorrhage, as proven by CT, operation or autopsy, were retrospectively studied using univariate data analysis. Etiologies were hypertension in 63.5%, cerebrovascular malformations in 8.5% and abnormal hemostasis in 15% of the patients. In 23% no etiology was determined. Main localizations were cerebral lobes in 49.2%, basal ganglia in 34.4%, brain stem in 6.9%, cerebellum in 6.7% and primary intraventricular in 2.3% of the patients. Ventricular extension was present in 47.0%. A higher case fatality correlated with: 1) ventricular extension (P < 0.00001), 2) increasing age (P = 0.00005), 3) surgical treatment (P = 0.00010), 4) localization in basal ganglia (P = 0.0108) and 5) hypertension as only etiology (P = 0.01471). A lower case fatality was found in patients with cerebrovascular malformations (P = 0.00006) and when the hemorrhage was localized to the cerebral lobes (P = 0.0050). We conclude that etiology and localization are of prognostic value in spontaneous intracerebral hemorrhage.

Letters to the Editor

4 June 2008 Dear Editor, PHACE SYNDROME: A CONSTELLATION OF CEREBRAL AND CARDIOVASCULAR ANOMALIES AND SEGMENTAL HAEMANGIOMAS PHACE syndrome is an uncommon neurocutaneous syndrome that manifests with multi-system involvement. It refers to the association of large, plaque-like, ‘segmental’ haemangiomas of the face, posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies and ventral developmental defects.1 This letter describes a male baby who was born to a 41-year-old mother by elective section at term gestation and who weighed 2.88 kg. A prenatal diagnosis of posterior fossa malformation had been made at a 19-week anomaly scan. The infant was delivered breech by LSCS with forceps lift-out and was noted to have extensive bruising on left side of the face with an ipsilateral facial palsy. Over the next week the bruising was replaced by fine telangiectasia, which became darker and evolved into a confluent segmental facial haemangioma in the distribution of trigeminal cranial nerve extending into the oral cavity (Fig. 1). The important differential diagnosis at this stage was Sturge-Weber syndrome. Left sided segmental haemangioma with oral mucosal extension. MRI brain was consistent with Dandy Walker malformation. In addition, a soft tissue mass encircling cranial nerves VI and VII (possible acoustic neuroma, Fig. 2) along with hypoplasia of left vertebral artery was noted. The facial haemangioma was seen to extend internally to the left cavernous sinus, the extraconal spaces of the left eye and the superior mediastinum. While carotid Doppler showed no evidence of stenosis, the echocardiogram showed features consistent with coarctation of aorta. The ophthalmology review was unremarkable, showing no evidence of raised intraocular pressure or retinal detachment/optic neuropathy. He was started on laser therapy for the surface hemangioma after which it showed signs of gradual resolution. He was readmitted at 8 weeks of age with stridor and bronchoscopy revealed a large sub-glottic haemangioma obstructing most of the airway, which was managed by placement of a tracheostomy tube. MRI brain showing soft tissue mass encircling VI and VII nerves. While the acronym PHACE (OMIM 606519) was suggested by Frieden in 1995,2 the exact incidence of PHACE syndrome is unknown. Pathogenesis too is unknown, while the constellation of anomalies generally represents a ‘developmental field defect’, whereby an insult in embryogenesis at a critical time gives rise to similar developmental outcomes.3 The timing of these errors in morphogenesis occurs early, probably between 3 and 12 weeks of gestation, prior to or during early vasculogenesis. The syndrome represents a spectrum of disease, with few infants manifesting the entire constellation of anomalies, some components appearing later. The marked female preponderance (>80%) suggests a possibility of X-linked inheritance with lethality in males.1 Both sporadic and X-linked or autosomal inheritance patterns are reported, the X-linked form being typically bilateral and diffuse, and often associated with a mutation of filament A gene (FLNA) on Xq28.4 The hallmark of PHACE syndrome, a large, segmental facial haemangioma, may involve one to several facial dermatomes, and an early presentation may be mistaken for the port wine stain associated with the Sturge-Weber syndrome. Structural and cerebrovascular brain malformations occur in at least half. Posterior fossa malformations, including the Dandy-Walker complex, are the most common, and others include agenesis of corpus callosum and polymicrogyria. Developmental delay is a common association. Cerebrovascular defects present primarily as carotid artery anomalies, but also include aberrant/anomalous origins and aneurysm of cerebral vessels. The cerebrovascular anomalies, especially carotid artery anomalies, are of particular concern because of predisposition to progressive arterial occlusion and stroke.5, 6 Cardiac anomalies include coarctation of the aorta and septal defects, while ophthalmologic anomalies include retinal vascular abnormalities, optic nerve atrophy, and colobomas, among others. Infants with PHACE syndrome could represent up to 20% of infants with segmental facial hemangiomas, and both progressive and regressive vascular phenomena may occur in this syndrome.1 The most common therapeutic option directed at regression of haemangioma is prednisolone/ methylprednisolone, while others include topical steroids, pulsed dye laser, interferon alpha, vincristine, excision surgery and wound care.1 To summarise, a segmental hemangioma may be an initial presentation of PHACE syndrome, and a high index of suspicion and thorough investigation would optimise management.

Venous-predominant parenchymal arteriovenous malformation: a rare subtype with a venous drainage pattern mimicking developmental venous anomaly

Considerable confusion exists in the literature regarding the classification of cerebrovascular malformations and their clinical significance. One example is provided by the atypical developmental venous anomaly (DVA) with arteriovenous shunt, because it remains controversial whether these lesions should be classified as DVAs or as atypical cases of other subtypes of cerebrovascular malformations. The purpose of this study was to clarify the classification of these challenging vascular lesions in an effort to suggest an appropriate diagnosis and management strategy. The authors present a series of 15 patients with intracranial vascular malformations that were angiographically classified as atypical DVAs with arteriovenous shunts. This type of vascular malformation shows a fine arterial blush without a distinct nidus and early filling of dilated medullary veins that drain these arterial components during the arterial phase on angiography. Those prominent medullary veins converge toward an enlarged main draining vein, which together form the caput medusae appearance of a typical DVA. Based on clinical, angiographic, surgical, and histological findings, the authors propose classifying these vascular malformations as a subtype of an arteriovenous malformation (AVM), rather than as a variant of DVA or as a combined vascular malformation. Correct recognition of this AVM subtype is required for its proper management, and its clinical behavior appears to follow that of a typical AVM. Gamma Knife radiosurgery appears to be a good alternative to resection, although long-term follow-up results require verification.

Diagnostic imaging in the study of visceral involvement of hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal-dominant vascular disease characterised by mucocutaneous or visceral angiodysplastic lesions. Its diagnosis is exclusively based on clinical criteria. The brain, lungs and liver, in growing order of prevalence, are the most frequently involved organs. Diagnostic imaging based on ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and digital subtraction angiography (DSA) has a fundamental role in detecting visceral involvement in HHT patients and is therefore crucial for the prognostic assessment and therapeutic approach. Arteriovenous shunts are the most common cerebrovascular malformations (CVMs). MRI and CT angiography are the methods of choice for diagnosing cerebral involvement, and it is debated whether MRI could be considered as a screening examination on account of its noninvasiveness. Pulmonary arteriovenous malformations, diffuse telangiectases or high-flow, low-pressure shunts between pulmonary arteries and veins can be studied with contrast-enhanced US, but multidetector CT seems to provide the most comprehensive evaluation of their angioarchitecture, whereas angiography has a predominant role in treatment. Liver involvement is frequent and characterised by the presence of intrahepatic shunts, disseminated intraparenchymal telangiectases and other vascular lesions. US is useful for detecting hepatic lesions but should be completed by more accurate imaging methods such as multidetector CT and MRI.

Cerebrovascular dysplasia in neurofibromatosis type 1

Objective:To assess the frequency and clinical characteristics of the increasingly recognised complication of cerebrovascular dysplasia in children with neurofibromatosis type 1 (NF1).Methods:A series of seven patients with NF1 and cerebrovascular...