Endovascular approaches to pial arteriovenous malformations.

Endovascular approaches to arteriovenous malformations (AVMs) are often necessary to define and help treat these often complex lesions. Angiography provides important information to help plan surgical or radiosurgical approaches. Modern embolization techniques allow AVMs to be treated with the goals of making surgery safer and easier, eliminating high-risk features in patients with AVMs who are otherwise not candidates for treatment, and even potentially curing the patient of the lesion. Liquid embolic agents have significantly advanced what is possible with endovascular treatment of AVMs.

De novo development of dural arteriovenous fistula after endovascular embolization of pial arteriovenous fistula.

BACKGROUND: The development of de novo dural arteriovenous fistula(s) following endovascular embolization of a prior high-flow pial arteriovenous fistula (PAVF) has not previously been reported and the natural history is unknown. The anatomic basis, pathophysiologic mechanism, management and outcome are discussed. METHODS: Treatment-completed congenital PAVFs treated at our center between January 2005 and August 2011 were analyzed retrospectively. Among 16 cases of PAVFs treated by endovascular embolization, four developed de novo dural arteriovenous fistulas during treatment or on follow-up that were not present before treatment. Information was collected from the clinical case records, imaging by MRI on presentation and during follow-up, all angiographic images and records during each of the procedures and during follow-up. RESULTS: The time interval between the last embolization and identification of a dural fistula ranged from 3 to 14 months. Ten fistulas were identified in four patients, seven of which were embolized, four with glue, two with Onyx18 and one with absolute alcohol. None recanalized, while one patient developed fistula in an adjacent location that was subsequently treated with radiosurgery. Not all fistulas need treatment; small fistulas with a minimal flow can safely be observed. CONCLUSIONS: De novo dural fistulas following endovascular embolization of high-flow PAVFs is not an uncommon development. They are mostly asymptomatic and develop anywhere along the drainage of the fistula, maturing over time and diagnosed during follow-up studies, emphasizing the need for follow-up angiography. They can be effectively treated by endovascular embolization. Localized refractory dural fistulas can be dealt with by radiosurgery.

Mixed pial-dural arteriovenous malformation in the anterior cranial fossa--two case reports.

Most arteriovenous malformations (AVMs) associated with the meningeal artery in the anterior cranial fossa are the pure dural type, and mixed pial-dural AVMs are rare. Two types of mixed pial-dural AVM occur in the anterior cranial fossa according to the shunting point: one with the nidus in the brain parenchyma of the frontal lobe, and the other with the shunting point in the dura mater. We describe two patients with AVMs fed by the anterior ethmoidal arteries and the persistent primitive olfactory artery, with the nidus located in the pure brain parenchyma of the inferior aspect of frontal lobe, and drained via an abnormal cortical vein into the cavernous and superior sagittal sinuses. The importance of occluding the venous outflow to obliterate intracranial dural arteriovenous fistula (AVF) is emphasized. However, removal of the nidus in the brain parenchyma is required. The presence of a pial feeder should be considered before diagnosis of dural AVF of the anterior cranial fossa, and preoperative detailed evaluation for the pial supply and shunting point is mandatory.

Time-resolved contrast-enhanced magnetic resonance digital subtraction angiography (MRDSA) in an infant with congenital pial arteriovenous fistula in the brain: a case report.

INTRODUCTION: Evaluation of the congenital vascular lesions of the brain requires multiple conventional intra-arterial digital subtraction angiographic examinations which have many associated risks including exposure to ionizing radiations. Magnetic resonance digital subtraction angiography is a non-invasive procedure with no related risks of radiation exposure. This technique can be of greater clinical significance in diagnosis and treatment planning of neurovascular abnormalities among children who are at far greater risk of invasive procedures like intra-arterial digital subtraction angiography. CASE REPORT: We report a congenital pial arteriovenous fistula in an infant which is a rare vascular lesion and has recently been identified as different from other vascular malformations. Magnetic resonance digital subtraction angiography provided hemodynamic information in absolute agreement with intra-arterial digital subtraction angiography indicating its significance in evaluating vascular lesions. DISCUSSION: Magnetic resonance digital subtraction angiography can be used in children in conjunction with intra-arterial digital subtraction angiography to minimize the cumulative radiation dose and multiple anesthesias.

Mutations in the beta-tubulin gene TUBB2B result in asymmetrical polymicrogyria.

Polymicrogyria is a relatively common but poorly understood defect of cortical development characterized by numerous small gyri and a thick disorganized cortical plate lacking normal lamination. Here we report de novo mutations in a beta-tubulin gene, TUBB2B, in four individuals and a 27-gestational-week fetus with bilateral asymmetrical polymicrogyria. Neuropathological examination of the fetus revealed an absence of cortical lamination associated with the presence of ectopic neuronal cells in the white matter and in the leptomeningeal spaces due to breaches in the pial basement membrane. In utero RNAi-based inactivation demonstrates that TUBB2B is required for neuronal migration. We also show that two disease-associated mutations lead to impaired formation of tubulin heterodimers. These observations, together with previous data, show that disruption of microtubule-based processes underlies a large spectrum of neuronal migration disorders that includes not only lissencephaly and pachygyria, but also polymicrogyria malformations.

Ectopia of meningeal fibroblasts and reactive gliosis in the cerebral cortex of the mouse model of muscle-eye-brain disease.

Congenital muscular dystrophies with brain malformations, such as muscle-eye-brain disease, exhibit neural ectopias caused by overmigration of neurons. Such overmigration is evident in protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGnT1) knockout mouse, a model of muscle-eye-brain disease, caused by breaches in the pial basement membrane. We hypothesize that breaches in pial basement membrane disrupt the neural-meningeal boundary, resulting in ectopia of meningeal fibroblasts in the cerebral cortex and reactive gliosis. To test this hypothesis, the cerebral cortices of developing and adult POMGnT1 knockout mice were analyzed by immunostaining with cell-specific markers and by electron microscopy. The upper half of the cerebral cortex in the knockout mouse contained increased numbers of fibroblasts closely associated with capillaries. During development of the cerebral cortex in the knockout mice, breaches in pial basement membrane allowed emigration of overmigrated neurons into the developing pia-arachnoid, scattering its mesenchymal cells throughout the diffuse cell zone and resulting in ectopia of mesenchyme-derived fibroblasts in the upper half of the cortex. Glial fibrillary acidic protein (GFAP) immunostaining revealed that the upper half of the cerebral cortex in the knockout also contained increased numbers of cells with morphologies typical of reactive astrocytes compared with the wild type. Moreover, most of the GFAP-positive reactive astrocytes were in close contact with ectopic fibroblasts, suggesting that they were induced by the fibroblasts. Collectively, the data support the hypothesis that the cerebral cortex of POMGnT1 knockout mice is characterized by migration defects leading to disruption of the pia-arachnoid, ectopia of fibroblasts in the cortex, and reactive gliosis.

[Bleeding risk of intracranial vascular malformations]. / Das Risiko intrazerebraler Gefässmissbildungen.

In general, intracranial vascular malformations are divided into pial AVM, dural AV fistula, cavernoma and capillary telangiectasias. Developmental venous anomalies are sometimes thought to be vascular malformations. In fact, they are just a variant of venous drainage. In general, pial AVMs have a high risk of intracerebral bleeding. In dural AV fistulas, the individual bleeding risk can be effectively estimated by analyzing the venous drainage. Cavernomas have a low bleeding risk and the bleeding is rarely life-threatening. DVAs do not have any bleeding risk but 30 % are associated with cavernomas. Capillary telangiectasias also have no bleeding risk. Therefore, a radiological finding of an intracranial vascular malformation should not automatically elicit the reaction "time bomb in your head with a bleeding risk" but should be subjected to an analysis of the bleeding risk for the individual patient.

Genetic basis of developmental malformations of the cerebral cortex.

Widespread use of noninvasive brain imaging techniques, in particular magnetic resonance imaging, has led to increased recognition of genetic disorders of cortical development in recent years. The causative genes for many of these disorders have been identified through a combination of detailed clinical and radiological analyses and molecular genetic approaches. These disease genes have been found to affect different steps of cortical development, including proliferation of neuronal progenitor cells, neuronal migration, and maintaining integrity of the pial surface. In many cases, syndromes with similar clinical phenotypes are caused by genes with related biochemical functions. In this article, we review the recent advances in molecular genetic studies of the disorders of cortical development. The identification and functional studies of the genes associated with these developmental disorders will likely lead to improvement in diagnosis and facilitate our understanding of the mechanisms of cortical development.

The role of Glial-Pial barrier lesions and impaired vascularization in anomalous formation of cortical convolutions.

The abnormal patterns of cerebral convolutions range from severe to small anomalies restricted to tertiary gyri and sulci. Lesions within Glial-Pial barrier were found in examined cases with cortical developmental abnormalities. Anomalies and impaired function of vessels penetrating the cortex from meningeal plexus coexisted often with Glial-Pial barrier lesions. We are able to say that our cases constitute a group of graded changes demonstrating that both observed developmental lesions vascular and/or Glial-Pial barrier damage may result in cortical anomalies. Their formation and character depend on the stage of cortical maturation when analyzed lesions occur.

Widespread neuronal ectopia associated with secondary defects in cerebrocortical chondroitin sulfate proteoglycans and basal lamina in MARCKS-deficient mice.

Mice deficient in MARCKS, a prominent neural substrate for protein kinase C (PKC), die before or shortly after birth. They exhibit high frequencies of exencephaly, universal agenesis of forebrain commissures, and abnormalities of cerebral cortical and retinal lamination. We show here that these mice have wide-spread and severe neuronal ectopia in the outer layers of the developing forebrain, manifested by the migration of clusters of developing neuroblasts through the basal lamina and often through the pial membrane and into the subarachnoid space. This abnormality became apparent by Embryonic Day (E) 13 or 14, shortly after the formation of the early marginal zone. MARCKS deficiency was associated with decreased staining for marginal zone chondroitin sulfate proteoglycans; this decrease was detectable earlier in development than the neuronal ectopia. Later in development, there was also marked disruption of the basal lamina at the pial-glial interface, as evidenced by gross abnormalities in laminin and reticulin staining; however, the basal lamina appeared normal at E9.5. These data indicate that MARCKS is required for the prevention of neuronal ectopia during development. Potential mechanisms responsible for the neuronal ectopia in the MARCKS-deficient mice include decreased expression or increased proteolytic destruction of basal lamina proteins and marginal zone chondroitin sulfate proteoglycans in the developing brain.

Pial-glial barrier abnormalities in fetuses with Fukuyama congenital muscular dystrophy.

This report concerns light and electron microscopic studies on the central nervous system of a 20-week and an 18-week fetus with Fukuyama congenital muscular dystrophy (FCMD). The diagnosis of FCMD was established by prenatal molecular genetic analysis. Cerebral lesions containing neurites, subpial granular cells and glias, accompanied by cortical dysplasia were found in both cases. Small irregular defects, readily detectable by periodic acid-methenamine-silver staining or by immunohistochemical staining for S-100 protein, were observed in the cerebral surface. More severe dysplasia was evident at the areas with the larger defects. Surface defects were also observed in the cerebellum and brain stem, with brain tissue extruding into the leptomeninges. The pyramidal tract was aberrant in the pons and medulla oblongata. The spinal cord appeared normal by light microscopy. Electron microscopic examination revealed an abnormal configuration of the basement membrane and glial cytoplasmic membrane of the brain and spinal cord surfaces, including areas with no detectable defects by light microscopy. These findings suggest that abnormalities of the pial-glial barrier, especially the basement membrane and/or basement membrane-related structures, are involved in the genesis of cortical dysplasia.