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Introduction: Vein of Galen malformation occurs rarely and accounts for 1% of intracranial vascular abnormalities, and they usually have poor outcome. Therefore, we focused on the prenatal features that might suggest favourable prognosis. Material and methods: We analysed fetal echocardiograms and neonatal management from 10 fetuses with diagnosis of vein Galen malformations. Results: The size of Galen malformation was mean 35 mm ×19 mm. Five fetuses had transplacental digoxin treatment. Cardiovascular profile score (CVPS) at the initial evaluation was mean 6 ±2, the minimum value was 4, and the maximum value was 10. Cardiovascular profile score at the last evaluation was mean 7.3 ±2.4, but an increase was seen only in two survivors (the third survivor had only one echo examination and did not undergo transplacental treatment). There were two intrauterine demises and eight pregnancies with live born newborns. Mean gestational time of delivery for live born newborns was in the 37th week. There were four neonatal deaths on days 1, 2, and 3 before attempted neurosurgery. Three newborns had neurosurgery procedures on day 3 (two newborns) and on day 7 (one newborn). The last one died on day 27. Based on our prenatal data we suggested a new scale to predict a prognosis for newborns with vein of Galen malformation. Conclusions: Prenatal detection of Galen aneurysm, CVPS of seven or more before birth, transfer in utero, delivery at term, and earliest possible neurosurgical treatment might be beneficial and change the poor natural outcome known from the past in these cases. Good cooperation between members of the perinatology team might be crucial for saving lives in prenatally diagnosed AVGM. [ABSTRACT FROM AUTHOR]

Background Preoperative embolization is established as an advantageous adjunct in multimodality treatment of cerebral arteriovenous malformations (AVMs). However, the benefit of preoperative embolization in AVMs with favorable surgical risk profile is debatable, because it has yet to be supported by evidence in comparative studies. In this study, we assessed outcome of surgically treated patients in a comparative setting. Methods Our institutional AVM database of retrospectively and prospectively collected data between 1990 and 2015 was reviewed. Patients with complete clinical data who underwent surgical resection for AVMs were included. We performed a 1:1 ratio propensity score match for baseline variables that differed between patients with or without preoperative embolization. Differences in surgical risk and outcomes were evaluated between these 2 groups. Results AVM size, eloquence, deep drainage, middle cerebral artery feeder, and ruptured presentation differed significantly between the 2 groups. Forty-eight patients without preoperative embolization were matched to 48 with embolization, with no significant differences in baseline variables or AVM characteristics between the 2 groups. We found no significant differences in AVM obliteration and postoperative modified Rankin Scale (mRS) score between embolized and nonembolized patients, respectively. Change in mRS score from preoperative score was also not significant, although more embolized patients had a decline in mRS score. Secondary outcome measures including duration of surgery ( P = 0.172), intraoperative bleeding ( P = 0.280), duration of hospitalization ( P = 0.368), and postoperative symptoms were also similar between both groups. Conclusions Our data do not support substantial benefit of preoperative embolization for patients with a favorable surgical risk profile. Because of risks and costs with this intervention, the prudent use of preoperative embolization should be individually considered. [ABSTRACT FROM AUTHOR]

Objective ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) found better short-term outcomes after conservative management compared with intervention for unruptured arteriovenous malformations (AVMs). However, because Spetzler-Martin (SM) grade I–II AVMs have the lowest treatment morbidity, sufficient follow-up of these lesions may show a long-term benefit from intervention. The aim of this multicenter, retrospective cohort study is to assess the outcomes after stereotactic radiosurgery (SRS) for ARUBA-eligible SM grade I–II AVMs. Methods We pooled SRS data for patients with AVM from 7 institutions and selected ARUBA-eligible SM grade I–II AVMs with ≥12 months follow-up for analysis. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. Results The ARUBA-eligible SM grade I–II AVM cohort comprised 232 patients (mean age, 42 years). The mean nidus volume, SRS margin dose, and follow-up duration were 2.1 cm 3 , 22.5 Gy, and 90.5 months, respectively. The actuarial obliteration rates at 5 and 10 years were 72% and 87%, respectively; annual post-SRS hemorrhage rate was 1.0%; symptomatic and permanent radiation-induced changes occurred in 8% and 1%, respectively; and favorable outcome was achieved in 76%. Favorable outcome was significantly more likely in patients treated with a margin dose >20 Gy (83%) versus ≤20 Gy (62%; P < 0.001). Stroke or death occurred in 10% after SRS. Conclusions For ARUBA-eligible SM grade I–II AVMs, long-term SRS outcomes compare favorably with the natural history. SRS should be considered for adult patients harboring unruptured, previously untreated low-grade AVMs with a minimum life expectancy of a decade. [ABSTRACT FROM AUTHOR]

This study aimed to explore the protective effect of total flavonoids in Caragana against hypoxia/reoxygenation (H/R)-induced injury in human brain microvascular endothelial cells (BMECs). Human BMECs were selected and assigned into control, H/R, H/R + NMP, H/R + Low dose, H/R + Moderate dose, H/R + High dose groups. MTT and Transwell assays were used to detect cell viability and migration, respectively. Cell adhesion rate and tube formation were also detected. Real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to test HIF-1α, VEGF and Notch1 mRNA and protein expressions. Compared with the H/R group, the cell viability rates in the H/R + NMP, H/R + Moderate dose and H/R + High dose groups were increased. The cell adhesion rates in the H/R + NMP, H/R + Moderate dose and H/R + High dose groups were significantly different from those in the H/R group. As compared to the H/R group, the cell migration abilities in the H/R + NMP, H/R + Moderate dose and H/R + High dose groups were enhanced. Compared with the H/R group, the number and length of tubes of BMECs in the H/R + NMP, H/R + High dose and H/R + Moderate dose groups were increased. HIF-1α, VEGF and Notch1 mRNA and protein expressions were higher in the H/R + Low dose, H/R + Moderate dose and H/R + High dose groups than in the H/R group. These findings revealed that total flavonoids in Caragana can protect BMECs from H/R-induced injury in a dose-dependent manner and it also may promote angiogenesis in BMECs by activating HIF- 1α-VEGF-Notch 1 signaling pathway. [ABSTRACT FROM AUTHOR]

Background The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) is not known. Published cases have documented coexisting cervical artery dissection and unruptured aneurysms, raising the possibility that ultrastructural vessel wall abnormalities underlie the development of vascular lesions as well as RCVS. Methods In this retrospective study we compared the frequency of neurovascular abnormalities in 158 consecutive RCVS patients, 44 patients with primary angiitis of the central nervous system (PACNS, positive controls), and 177 non-stroke patients with acute neurological symptoms (non-arteriopathy controls). Results Coexisting neurovascular abnormalities were significantly higher ( p < 0.001) in RCVS (23%) as compared to the PACNS (5%) or non-arteriopathy groups (8%). Cervical artery dissections were noted only in the RCVS group (8%, p < 0.001). The RCVS group had more unruptured aneurysms than PACNS (13% vs. 5%, p = 0.099) or non-arteriopathy controls (13% vs. 7%, p = 0.05). Seven RCVS patients also had other vascular malformations (venous anomaly, cavernous malformations, fibromuscular dysplasia). There was no significant association between coexisting vascular abnormalities and brain lesions or discharge clinical outcome in the RCVS group. Conclusion The high prevalence and heterogeneous anatomy of coexisting vascular lesions suggest that subtle ultrastructural arterial wall abnormalities may contribute to their development and also predispose to RCVS. [ABSTRACT FROM AUTHOR]

Background: The middle meningeal artery (MMA) is often sacrificed during neurosurgical procedures in the region of the pterion. This maneuver, herein, is hypothesized to be a potential reason for the development of postoperative hydrocephalus by injuring the vascular supply to the arachnoid granulations near the vertex of the skull, and thus disrupting their ability to allow for transfer of CSF from the subarachnoid space to the venous system. Materials and methods: To test this theory, the middle meningeal artery was isolated at the skull base and injected with India ink. Next, the superior sagittal sinus was opened and the arachnoid granulations inspected. Results: All specimens demonstrated ink within the arachnoid granulations indicating that their blood supply is completely or at least partially via the middle meningeal artery. This finding with an illustrative case of surgical cautery of the middle meningeal artery at the skull base with subsequent development of hydrocephalus supports our hypothesis of potential role of iatrogenic MMA injury causing hydrocephalus. Conclusions: Our cadaveric study shows that the blood supply of the arachnoid granulations of the superior sagittal sinus is via the middle meningeal artery. Additional cases of postoperative hydrocephalus following middle meningeal artery sacrifice are needed to support our hypothesis. [ABSTRACT FROM AUTHOR]

Objective : Increased expression of angiogenic factors, such as vascular endothelial growth factor (VEGF), is associated with the pathogenesis of cerebral cavernous malformations (CCMs). The purpose of this study was to investigate plasma levels of VEGF in normal subjects and in patients with CCM and to evaluate change in these levels following stereotactic radiosurgery (SRS). Methods : Peripheral venous blood was collected from 6 patients with CCM before SRS using Gamma Knife and at the 1 week, 1 month, 3month, and 6 month follow-up visits. Plasma VEGF levels were measured using commercially available enzyme-linked immunosorbent assay kits. Peripheral blood samples were obtained from 10 healthy volunteers as controls. Results : Mean plasma VEGF level of 41.9 pg/mL (range, 11.7–114.9 pg/mL) in patients with CCM at baseline was higher than that of the healthy controls (29.3 pg/mL, range, 9.2–64.3 pg/mL), without significant differences between CCM patients and controls (p=0.828). Plasma VEGF level following SRS dropped to 24.6 pg/mL after 1 week, and decreased to 18.5 pg/mL after 1 month, then increased to 24.3 pg/mL after 3 months, and 32.6 pg/mL after 6 months. Two patients suffering from rebleeding after SRS showed a higher level of VEGF at 6 months after SRS than their pretreatment level. Conclusion : Plasma VEGF levels in patients with CCM were elevated over controls at baseline, and decreased from baseline to 1 month after SRS and increased further for up to 6 months. Theses results indicated that anti-angiogenic effect of SRS might play a role in the treatment of CCMs. [ABSTRACT FROM AUTHOR]

Objective To quantify the risk of a first or recurrent hemorrhage and the associated functional impairment in patients with sporadic solitary cerebral cavernous malformations (CCMs) and to investigate the potential risk factors. Methods We undertook an observational study (n = 199) of consecutive patients with the diagnosis of a single, sporadic CCM using clinical and magnetic resonance imaging follow-up to identify prospective hemorrhage events and associated functional impairment. We calculated the annual hemorrhage risk rates, calculated cumulative risks, and performed uni- and multivariate analysis to assess outcome predictors. Results There were 199 adults identified, and 712.5 person years of follow-up were analyzed. Overall annual rates of hemorrhage were 6.03%, 11.95%, and 1.03% in the complete cohort, in those presenting with previous hemorrhage, and in those without, respectively. The 5-year risk of hemorrhage was higher in those presenting with previous hemorrhage than those without (40.9%; 95% confidence interval [CI], 31.78–50.73 vs. 8.6%; 95% CI, 3.97–16.95; P < 0.0001) and in those with a brainstem CCM compared with nonbrainstem CCM (51.6%; 95% CI, 37.61–65.46 vs. 17.1%; 95% CI, 4.55–32.04; P < 0.0001). In the multivariate analysis, previous hemorrhage (odds ratio, 7.18; 95% CI, 1.8–28.11; P = 0.005), age less than 45 years (odds ratio, 2.61; 95% CI, 1.03–6.61; P = 0.042), and brainstem location (odds ratio, 7.44; 95% CI, 2.09–26.50; P = 0.002) increased the risk of hemorrhage. Of the patients, 30% showed a moderate or severe disability associated with a CCM hemorrhage (5-year risk of severe hemorrhage, 8.9%; 95% CI, 5.50–13.99). Conclusions This study provides an estimate of symptomatic hemorrhage risk and the associated disability in patients with sporadic solitary CCM and an investigation of risk factors. [ABSTRACT FROM AUTHOR]

An increasing number of studies have reported blood-brain barrier (BBB) dysfunction after blast-induced traumatic brain injury (bTBI). Despite this evidence, there is limited quantitative understanding of the extent of BBB opening and the time course of damage after blast injury. In addition, many studies do not report kinematic parameters of head motion, making it difficult to separate contributions of primary and tertiary blast-loading. Detailed characterization of blast-induced BBB damage may hold important implications for serum constituents that may potentially cross the compromised barrier and contribute to neurotoxicity, neuroinflammation, and persistent neurologic deficits. Using an in vivo bTBI model, systemic administration of sodium fluorescein (NaFl; 376 Da), Evans blue (EB; 69 kDa when bound to serum albumin), and dextrans (3-500 kDa) was used to estimate the pore size of BBB opening and the time required for recovery. Exposure to blast with 272 ± 6 kPa peak overpressure, 0.69 ± 0.01 ms duration, and 65 ± 1 kPa*ms impulse resulted in significant acute extravasation of NaFl, 3 kDa dextran, and EB. However, there was no significant acute extravasation of 70 kDa or 500 kDa dextrans, and minimal to no extravasation of NaFl, dextrans, or EB 1 day after exposure. This study presents a detailed analysis of the time course and pore size of BBB opening after bTBI, supported by a characterization of kinematic parameters associated with blast-induced head motion. [ABSTRACT FROM AUTHOR]

Background: Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations and perform a meta-analysis including all previously published results.Methods: We included 167 Dutch patients and 1038 Dutch controls. Case genotyping was performed by KASPar assays. Controls had been previously genotyped with a genome wide single nucleotide polymorphisms (SNP) array. Differences in genotype frequencies between cases and controls were estimated by χ(2) testing in Plink V.1.07. Meta-analysis was performed in RevMan V.5.3.Results: In our case-control study we found no significant association with brain AVM (BAVM) for previously discovered SNPs near ANGPTL4, IL-1β, GPR124, VEGFA and MMP-3. The meta-analysis revealed a statistically significant association with BAVMs for the polymorphism rs11672433 near ANGPTL4 (OR 1.39; 95% CI 1.10 to 1.75, p value 0.005).Conclusions: The results of this study support a role for the previously identified SNP near ANGPTL4 in the pathogenesis of AVMs. Previously found associations with SNPs near IL-1β, GPR124, VEGFA and MMP-3 genes could not be substantiated in our replication cohort or in the meta-analysis. [ABSTRACT FROM AUTHOR]

Background: The occurrence of concomitant multiple cerebral arteriovenous malformations (mAVMs) is often associated with hereditary hemorrhagic telangiectasia (HHT) or craniofacial arteriovenous metameric syndrome (CAMS) and frequently occurs in the pediatric population. Methods: Between 1995 and 2013, demographic, clinical, and angiographic data of cerebral AVMs have been prospectively collected. We retrospectively analyzed data of patients presenting multiple cerebral AVMs. Results: Six patients (mean age, 44 years, male-to-female ratio, 5) presented an angiographic diagnosis of cerebral mAVMs. Only one of them was known to have a HHT. Five patients presented two cerebral AVMs and one patient had three. Three AVMs (23.1 %) presented bleeding at admission. Three patients had supratentorial mAVMs only and the three others had supra and infratentorial AVMs. Only one patient suffered from bleeding of more than one of his mAVMs with an interval of 23 years. Conclusions: For asymptomatic AVMs discovered incidentally without angiographic bleeding risk, we propose a therapeutic abstention. In case of AVM rupture and bleeding, the other 'associated' AVMs (discovered through a complete angiographic assessment) should also be treated if they are not located in an eloquent area and if the treatment does not present technical difficulties. AVMs with a history of bleeding or associated to angiographic risks have to be treated more aggressively. [ABSTRACT FROM AUTHOR]

Developmental venous anomalies (DVAs) are the most common vascular malformation of the brain and are commonly identified on routine imaging of the brain. They are typically considered incidental findings, usually with no clinical significance. However the increasing identification of DVAs as a result of improved imaging technology has led to recognition of their association with a variety of abnormal imaging findings and clinically important conditions. This pictorial essay explores the suspected embryological origin, associated imaging features, and proposed pathophysiological mechanisms of DVAs in the pediatric population. This paper emphasizes newer physiological imaging data, which suggest that DVA drainage has less physiological flexibility than otherwise normal venous drainage development. [ABSTRACT FROM AUTHOR]

Objective: To evaluate prospectively 7 Tesla time-of-flight (TOF) magnetic resonance angiography (MRA) and 7 Tesla non-contrast-enhanced magnetization-prepared rapid acquisition gradient-echo (MPRAGE) for delineation of intracerebral arteriovenous malformations (AVMs) in comparison to 1.5 Tesla TOF MRA and digital subtraction angiography (DSA).Methods: Twenty patients with single or multifocal AVMs were enrolled in this trial. The study protocol comprised 1.5 and 7 Tesla TOF MRA and 7 Tesla non-contrast-enhanced MPRAGE sequences. All patients underwent an additional four-vessel 3D DSA. Image analysis of the following five AVM features was performed individually by two radiologists on a five-point scale: nidus, feeder(s), draining vein(s), relationship to adjacent vessels, and overall image quality and presence of artefacts.Results: A total of 21 intracerebral AVMs were detected. Both sequences at 7 Tesla were rated superior over 1.5 Tesla TOF MRA in the assessment of all considered AVM features. Image quality at 7 Tesla was comparable with DSA considering both sequences. Inter-observer accordance was good to excellent for the majority of ratings.Conclusion: This study demonstrates excellent image quality for depiction of intracerebral AVMs using non-contrast-enhanced 7 Tesla MRA, comparable with DSA. Assessment of untreated AVMs is a promising clinical application of ultra-high-field MRA.Key Points: • Non-contrast-enhanced 7 Tesla MRA demonstrates excellent image quality for intracerebral AVM depiction. • Image quality at 7 Tesla was comparable with DSA considering both sequences. • Assessment of intracerebral AVMs is a promising clinical application of ultra-high-field MRA. [ABSTRACT FROM AUTHOR]

Background: Suprasellar cavernous malformation in the optic pathway is not commonly encountered. To date, there are only few reports present in the literature. Case Description: The authors report a rare case of suprasellar optic pathway cavernous malformation in a 33-year-old female who presented with progressive visual loss. Her imaging revealed a large heterogeneous, hyperintense, hemorrhagic right suprasellar extra-axial complex cystic structure, causing mass effect on the adjacent hypothalamus and third ventricle displacing these structures. Gross total resection of the lesion was achieved utilizing a right frontal craniotomy approach. Histopathological examination confirmed the diagnosis of suprasellar chiasmal cavernous malformation. Conclusion: Although visual pathway cavernous malformation is a rare event, it should be included in the differential diagnosis of lesions occurring suprasellarly in the visual pathway and hypothalamus. [ABSTRACT FROM AUTHOR]

Objective - Inflammation has received increasing attention as a cause of stroke. Although several lines of evidence suggest that inflammatory processes have a role in arteriosclerotic vascular events, their involvement remains to be determined. The purpose of this study was to examine the associations between serum high-sensitive C-reactive protein (hs-CRP) levels and cerebral small vessel (CSV)- related lesions as a manifestation of arteriosclerosis. Materials and Methods - Neurologically normal subjects without any history of neurologic or psychiatric diseases were enrolled (n = 519). All the participants underwent magnetic resonance imaging (MRI), and their CSV-related lesions (i.e., lacunar infarcts, cerebral microbleeds, deep white matter hyperintensity, and periventricular hyperintensity) were evaluated. The serum levels of hs-CRP were evaluated as common inflammatory markers. Results - Subjects with higher C-reactive protein (CRP) levels had more lacunar infarcts (P = 0.02). After adjusting for the traditional cardiovascular risk factors, higher hs- CRP levels were still associated with the presence of lacunar infarcts [odds ratio for the highest vs the lowest tertile of hs-CRP, 3.57 (95% confidence interval: 1.30-9.80)]. These associations did not change when the logarithmically transformed values for hs-CRP were included. Furthermore, subjects with higher CRP levels had more cerebral microbleeds (P = 0.03), more severe deep white matter hyperintensity (P = 0.04), and periventricular hyperintensity (P = 0.04); however, these associations were not observed after adjusting for the cardiovascular risk factors. Conclusions - Higher levels of hs-CRP were associated with lacunar infarcts. Thus, inflammatory processes may be involved in the pathogenesis of small-vessel disease. [ABSTRACT FROM AUTHOR]

An 11-year-old child presented with chronic occipital headache and vomiting. Computed tomography (CT) scan revealed a cystic mass lesion in the right occipital region. Magnetic resonance imaging brain revealed a cystic mass lesion which was hypointense on T1-weighted images and hyperintense on T2-weighted images. A mural nodule was noted in the inferolateral wall of the lesion. CT angiography revealed small arteriovenous malformations (AVM) related to the lesion. The AVM associated with the cyst was excised. The patient recovered well. Cystic AVM is a rare vascular lesion, and only five such cases have been reported in the past. AVMs should be considered in the differential diagnosis of cystic lesions of the brain, especially when associated with a mural nodule. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformations are fragile blood vessel conglomerates in the central nervous system that are caused by mutations in the CCM1/KRIT1, CCM2 or CCM3 genes. The gene products form a protein complex at adherens junctions and loss of either CCM protein disrupts endothelial cell quiescence leading to increased permeability and excessive angiogenesis. We performed a yeast 2-hybrid screen to identify novel proteins directly interacting with KRIT1. The ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B) was identified as a novel binding partner of KRIT1. Silencing of ANKS1B or the related gene ANKS1A in primary human endothelial cells had no significant effects on cellular proliferation, migration and sprouting angiogenesis. However, silencing of ANKS1B expression disturbed endothelial cell barrier functions leading to increased permeability. Forced ANKS1B expression reduced permeability. This was independent of Rho kinase activity and the presence of KRIT1. Taken together, ANKS1B was identified as a novel KRIT1-interacting protein that selectively controls endothelial permeability but not angiogenesis. [ABSTRACT FROM AUTHOR]

Epilepsy is part of the clinical phenotype in nearly 40% of children with mitochondrial disease, yet the underlying molecular mechanisms remain poorly understood. Energy depletion has been postulated as the cause of mitochondrial epilepsy, but if this were the case, then 100% of patients with mitochondrial disease would be expected to present with seizures. This review explores other potential disease mechanisms underlying mitochondrial epilepsy, including oxidative stress, impaired calcium homeostasis, immune dysfunction, and deficiency of vitamins, cofactors, reducing equivalents, and other metabolites. Different mechanisms are likely to predominate in different mitochondrial disorders, since mitochondrial function varies between neurons and astrocytes, between different types of neurons, and in different brain regions. Systematic studies in cell and animal models of mitochondrial disease are needed in order to develop effective therapies for mitochondrial epilepsy. This article is part of a Special Issue entitled “Status Epilepticus”. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the feasibility of the non-adhesive temperature-sensitive liquid embolic material, chitosan/β-glycerophosphate (C/GP), in embolizing the basicranial rete mirabile (REM) in a swine model of cerebral arteriovenous malformation (cAVM). A total of 24 domestic swines were used as the experimental animals, among which 12 pigs underwent direct embolization of one side of the REM, while the other 12 pigs underwent embolization of the bilateral REM following anastomosis of the carotid artery and jugular vein. A super-selective microcatheter was introduced into the REM during the embolization procedure, and the C/GP hydrogel was injected until an image of the REM disappeared in the angiography examination. Further angiography examinations were performed after 2 and 6 weeks, and histological examination of the REM was performed after 6 weeks. Of the 24 domestic swines, 23 cases underwent successful thrombosis. Convulsions occurred in one case and that pig died during the embolization procedure. Following embolization, the angiography observations revealed that the embolized REM was no longer able to be developed, and adhesion of the microcatheter tip with the embolic agent did not occur. In addition, no apparent revascularization was observed in the angiography examinations performed at weeks 2 and 6. Therefore, the current preliminary study indicated that use of the non-adhesive temperature-sensitive embolic material was feasible for the embolization of cAVM; thus, C/GP may be used as an ideal embolic material for the treatment of cAVM. [ABSTRACT FROM AUTHOR]

Introduction: Brain arteriovenous malformations (AVMs) represent a serious health problem all around the world. Experimental models help to better understand the pathophysiology of these lesions. Experiment: We performed an experimental model of AVM using biological grafts, arteries and veins harvested from chicken wings at the elbow joint. We used 14 vessels and we performed 20 end-to-end anastomoses to create a nidus with a single feeding artery and a single draining vein. The system was irrigated with colored solution. The experiment was done according with law in force regarding experimental research activity. Conclusions: Experimental models allow us to understand the hemodynamics and predict the outcome of brain AVMs in humans. This experimental model is a useful tool in understanding the hemodynamic properties of brain AVMs. It is very useful in vascular anastomosis training [ABSTRACT FROM AUTHOR]

There has been strong pre-clinical research on mechanisms of initial cell death and tissue injury in intracerebral hemorrhage (ICH). This data has led to the evaluation of several therapeutics for neuroprotection or the mitigation of early tissue damage. Most of these studies have been done in the rat. Also, there has been little study of the mechanisms of tissue repair and recovery. This review examines the testing of candidate therapeutics in mouse models of ICH for their effect on tissue protection and repair. This review will help the readers compare it to the extensively researched rat model of ICH and thus enhance work that are pending in mouse model. [ABSTRACT FROM AUTHOR]

Cerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND Previous studies have demonstrated that cerebral dural sinus stenosis (DSS) may be a potential patho-physiological cause of idiopathic intracranial hypertension (IIH). Endovascular therapy for DSS is emerging as a potential alternative to treat IIH. Here, we present the results of our case series. METHOD We prospectively collected angiographic and manometric data on patients that underwent angioplasty/stenting for IIH. All patients had failed maximal medical therapy (MMT) and had confirmed sinus stenosis. Demographic, clinical and radiological presentation, and outcomes were collected retrospectively. RESULTS A total of 18 patients underwent 25 procedures. Demographics revealed a mean age of 30 (range 15-59), 83% (15/18) were female, 72% (13/18) were white, and mean body mass index of 36 (range 23-59.2). All patients presented with classic IIH. Symptom improvement or resolution was reported in 94% (17/18) of patients. All patients had resolution and/or stabilization/improvement of their papilledema. Headaches related to increased pressure improved in 56% (10/18). Re-stenosis and retreatment occurred in 33% (6/18). No procedural related complications were reported. CONCLUSION Dural sinus angioplasty and stenting is relatively safe, feasible, and clinically efficacious for patients with symptomatic sinus stenosis who have failed standard therapy. The long-term durability of patency and clinical improvement remains unknown. [ABSTRACT FROM AUTHOR]

Background: Senescent changes in brain microvascular circulation may cause or contribute to age-related cognitive decline. Such changes are promoted partly by aging, but also by chronic hypertension, a leading treatable cause of cognitive decline. Objectives: We aimed to non-invasively detect in vivo the senescent changes in brain microvascular circulation associated with age and hypertension, and inquired whether decrements driven by aging would be exacerbated by chronic hypertension. Methods: In this longitudinal study, absolute near infrared spectroscopy (NIRS) was used to quantify in vivo cerebral blood volume (CBV) and assess the hemodynamic response to a hypercapnic respiratory challenge in normotensive Wistar-Kyoto (WKY) and spontaneous-hypertensive (SHR) rats. The impact of age and hypertension were evaluated by repeating these measurements on the same animals at 4- and 16-months of age. Results: CBV decreased markedly with age in both strains, from 4.5 ± 0.2 to 2.6 ± 0.1 ml/100g tissue, on average. Chronic hypertension, however, did not significantly exacerbate this age-related decrease in CBV (-48.1 ± 3.7% in WKYs versus -53.3 ± 5.4% in SHRs). In contrast, vasoreactivity was already impaired in the young hypertensive rats (ΔVMR 0.017 ± 0.014 in young SHRs versus 0.042 ± 0.005 in young WKYs) and further worsened by middle-age (ΔVMR 0.011 ± 0.017 middle-aged SHRs). Conclusion: Whereas a decrease in brain blood volume correlated with age but not hypertension, vasodilatory capacity was diminished due to hypertension but did not appear affected by age alone. The ability of absolute NIRS to distinguish between such senescent changes in brain (micro)vascular circulation in life may allow early detection and intervention to preserve cerebrovascular health with age. [ABSTRACT FROM AUTHOR]

A patient presented with signs and symptoms of a left carotid cavernous fistula (CCF). Computed tomography angiography confirmed filling of the cavernous sinus in the arterial phase. Cerebral digital subtraction angiography demonstrated no evidence of CCF. The workup, diagnosis, and treatment of this patient are discussed, and the literature is reviewed. [ABSTRACT FROM AUTHOR]

Several letters to the editor are presented in response to the article "Medical Management With or Without Interventional Therapy for Unruptured Brain Arteriovenous Malformations (ARUBA): A Multicentre, Non-Blinded, Randomised Trial" in the April 15, 2014 issue.

Background and Purpose Intravenous tissue plasminogen activator is the most effective treatment for acute ischemic stroke, and its use may therefore serve as an indicator of the available level of acute stroke care. The greatest burden of stroke is in low- and middle-income countries, but the extent to which intravenous tissue plasminogen activator is used in these countries is unreported. Summary of Review A systematic review was performed searching each country name AND 'stroke' OR 'tissue plasminogen activator' OR 'thrombolysis' using PubMed, Embase, Global Health, African Index Medicus, and abstracts published in the International Journal of Stroke ( Jan. 1, 1996- Oct. 1, 2012). The reported use of intravenous tissue plasminogen activator was then analyzed according to country-level income status, total expenditure on health per capita, and mortality and disability-adjusted life years due to stroke. There were 118 780 citations reviewed. Of 214 countries and independent territories, 64 (30%) reported use of intravenous tissue plasminogen activator for acute ischemic stroke in the medical literature: 3% (1/36) low-income, 19% (10/54) lower-middle-income, 33% (18/54) upper-middle-income, and 50% (35/70) high-income-countries (test for trend, P < 0·001). When considering country-level determinants of reported intravenous tissue plasminogen activator use for acute ischemic stroke, total healthcare expenditure per capita (odds ratio 3·3 per 1000 international dollar increase, 95% confidence interval 1·4-9·9, P = 0·02) and reported mortality rate from cerebrovascular disease (odds ratio 1·02, 95% confidence interval 0·99-1·06, P = 0·02) were significant, but reported disability-adjusted life years from cerebrovascular diseases and gross national income per capita were not ( P > 0·05). Of the 10 countries with the highest disability-adjusted life years due to stroke, only one reported intravenous tissue plasminogen activator use. Conclusions By reported use, intravenous tissue plasminogen activator for acute ischemic stroke is available to some patients in approximately one-third of countries. Access to advanced acute stroke care is most limited where the greatest burden of cerebrovascular disease is reported. [ABSTRACT FROM AUTHOR]

Acute stroke is one of the main causes of death and chronic disability. Thrombolysis with recombinant tissue plasminogen activator within the first hours after onset of symptoms is an effective therapeutic option for ischemic stroke. However, fewer than 2% to 7% of patients receive this treatment, primarily because most patients reach the hospital too late for the initiation of successful therapy. Several measures can reduce detrimental delay until treatment. It is of importance to use continual public awareness campaigns to reduce delays in patients' alarm of emergency medical services. Further relevant measures are repetitive education of emergency medical services teams to ensure the systematic use of scales designed for recognition of stroke symptoms and the proper triage of patients to stroke centers. A most important time-saving measure is prenotification of the receiving hospital by the emergency medical services team. In the future, treatment already at the emergency site may allow more than a small minority of patients to benefit from available treatment. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10−6 was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10−8); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10−8). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10−4; meta-analysis p = 2.2 × 10−10) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10−5). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly. [ABSTRACT FROM AUTHOR]

A 26-year-old right-handed female presented with alien hand syndrome (AHS) secondary to corpus callosum (CC) hematoma. The patient had abnormal feelings in the left upper limb and exhibited intermanual conflict. Imaging studies demonstrated acute hemorrhage in the genu and body of the CC secondary to cerebral venous malformation. Callosal hemorrhage is usually caused by head trauma or a ruptured arteriovenous that extends beyond the CC. We report what may be the first case of AHS caused by callosal hemorrhage due to venous malformation. [ABSTRACT FROM PUBLISHER]

Degenerative dementia is mainly caused by Alzheimer's disease and/or cerebrovascular abnormalities. Disturbance of the intracellular calcium homeostasis is central to the pathophysiology of neurodegeneration. In Alzheimer's disease, enhanced calcium load may be brought about by extracellular accumulation of amyloid-β. Recent studies suggest that soluble forms facilitate influx through calcium-conducting ion channels in the plasma membrane, leading to excitotoxic neurodegeneration. Calcium channel blockade attenuates amyloid-β-induced neuronal decline in vitro and is neuroprotective in animal models. Vascular dementia, on the other hand, is caused by cerebral hypoperfusion and may benefit from calcium channel blockade due to relaxation of the cerebral vasculature. Several calcium channel blockers have been tested in clinical trials of dementia and the outcome is heterogeneous. Nimodipine as well as nilvadipine prevent cognitive decline in some trials, whereas other calcium channel blockers failed. In trials with a positive outcome, BP reduction did not seem to play a role in preventing dementia, indicating a direct protecting effect on neurons. An optimization of calcium channel blockers for the treatment of dementia may involve an increase of selectivity for presynaptic calcium channels and an improvement of the affinity to the inactivated state. Novel low molecular weight compounds suitable for proof-of-concept studies are now available. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformation (CCM) is a vascular dysplasia, mainly localized within the brain and affecting up to 0.5% of the human population. CCM lesions are formed by enlarged and irregular blood vessels that often result in cerebral haemorrhages. CCM is caused by loss-of-function mutations in one of three genes, namely CCM1 (also known as KRIT1), CCM2 (OSM) and CCM3 (PDCD10), and occurs in both sporadic and familial forms. Recent studies have investigated the cause of vascular dysplasia and fragility in CCM, but the in vivo functions of this ternary complex remain unclear. Postnatal deletion of any of the three Ccm genes in mouse endothelium results in a severe phenotype, characterized by multiple brain vascular malformations that are markedly similar to human CCM lesions. Endothelial-to-mesenchymal transition (EndMT) has been described in different pathologies, and it is defined as the acquisition of mesenchymal- and stem-cell-like characteristics by the endothelium. Here we show that endothelial-specific disruption of the Ccm1 gene in mice induces EndMT, which contributes to the development of vascular malformations. EndMT in CCM1-ablated endothelial cells is mediated by the upregulation of endogenous BMP6 that, in turn, activates the transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling pathway. Inhibitors of the TGF-β and BMP pathway prevent EndMT both in vitro and in vivo and reduce the number and size of vascular lesions in CCM1-deficient mice. Thus, increased TGF-β and BMP signalling, and the consequent EndMT of CCM1-null endothelial cells, are crucial events in the onset and progression of CCM disease. These studies offer novel therapeutic opportunities for this severe, and so far incurable, pathology. [ABSTRACT FROM AUTHOR]

Abstract: Stroke therapy may be optimized by combination therapy with both a neuroprotective neurotrophin and an anti-inflammatory agent. In the present work, the model neurotrophin is glial cell line-derived neurotrophic factor (GDNF), and the model anti-inflammatory agent is the type II tumor necrosis factor receptor (TNFR) decoy receptor. Both the GDNF and the TNFR are large molecules that do not cross the blood–brain barrier (BBB), which is intact in the early hours after stroke when neural rescue is still possible. The GDNF and the TNFR decoy receptor were re-engineered for BBB transport as IgG fusion proteins, wherein the GDNF or the TNFR are fused to the heavy chain of a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), and these fusion proteins are designated cTfRMAb–GDNF and cTfRMAb–TNFR, respectively. Mice were treated intravenously with (a) saline, (b) GDNF alone, (c) the cTfRMAb–GDNF fusion protein alone, or (d) the combined cTfRMAb–GDNF and cTfRMAb–TNFR fusion proteins, following a 1-h reversible middle cerebral artery occlusion (MCAO). The cTfRMAb–GDNF fusion protein alone caused a significant 25% and 30% reduction in hemispheric and cortical stroke volumes. Combined treatment with the cTfRMAb–GDNF and cTfRMAb–TNFR fusion proteins caused a significant 54%, 69% and 30% reduction in hemispheric, cortical and subcortical stroke volumes. Conversely, intravenous GDNF had no therapeutic effect. In conclusion, combination treatment with BBB penetrating IgG–GDNF and IgG–TNFR fusion proteins enhances the therapeutic effect of single treatment with the IgG–GDNF fusion protein following delayed intravenous administration in acute stroke. [Copyright &y& Elsevier]

This article describes the anatomical and clinical aspects of cerebral arteriovenous malformations which from the start won the role of an important cause of death or severe morbidity in the long term due to intracranial hemorrhage and secondary epilepsy. It is the second leading cause of aneurysms after subarachnoid hemorrhage. Cerebral arteriovenous malformations present a nidus fed by one or more nourishing arteries ("feeders") with deep or superficial venous drainage. Symptoms are determined by the presence of seizures and intraparenchimatous and/ or subarachnoid bleeding. Progressive neurological deterioration can exist, which is attributed to ischemic disorders due to "vascular theft ". Also, it is described the grading system of arteriovenous malformations depending on size, eloquence and venous drainage by Spetzler-Martin system. Also described, a number of other scales with prognostic role and evaluation of the patient's consciousness, but in was in 1988 when the World Federation of Neurological Surgeons proposed a simplified scale, based on clinical findings of Hunt and Hess scale, translated into GCS, WFNS grading scale SAH. [ABSTRACT FROM AUTHOR]

Abstract: Although the role of cerebral small vessel disease (SVD), including white matter lesions (WMLs) and lacunar infarcts, in mild parkinsonian signs (MPS) is increasingly being recognized, not all individuals with SVD have MPS. Using diffusion tensor imaging (DTI), we investigated whether the presence of MPS was dependent on the microstructural integrity underlying WMLs, the early loss of integrity of the normal-appearing white matter (NAWM) and location of this damage. We examined 483 elderly subjects with SVD and without parkinsonism. Subjects with severe loss of integrity within their WMLs had a higher risk of MPS, regardless of WML volume (fractional anisotropy odds ratios = 1.9; 95% confidence interval, 1.1–3.4). The same was found in the normal-appearing white matter, but this association disappeared after adjustment for WMLs and lacunar infarcts. The integrity of the periventricular frontal regions-of-interest was significantly lower in subjects with MPS than without, independent of WMLs and lacunar infarcts. This study indicates that integrity of WMLs, especially in the frontal lobe, is associated with MPS. Diffusion tensor imaging may be of added value in investigating the underlying mechanisms of parkinsonian signs in subjects with SVD. [Copyright &y& Elsevier]

Abstract: The Fragile X syndrome (FXS) is the leading form of inherited mental retardation. To date, the most prominent neuronal phenotype associated with the syndrome is an abundance of long thin spines exhibiting an immature morphology. However, in addition to synaptic abnormalities, recent case studies have demonstrated that Fragile X (FX) patients also exhibit abnormal cerebral blood flow (CBF). To examine the role of the Fragile X mental retardation protein (FMRP) in altering CBF, we examined blood vessel density (BVD) in the visual cortex of Adult and Middle-aged FX mice. Analysis of Middle-aged FX mice demonstrated elevated BVD compared to wildtype controls, suggesting that FX mice exhibit a lack of age-induced BVD plasticity. However, Adult FX and wildtype mice did not exhibit consistent differences in BVD. These data demonstrate that FMRP is required for age-induced neocortical vasculature plasticity. Furthermore, these data suggest a new role for FMRP in blood vessel regulation that would have profound implications towards appropriately timed delivery of neuronal nutrients, thus contributing to or exacerbating FX cognitive and neuronal abnormalities. [Copyright &y& Elsevier]

Abstract: We for the first time report evidence for existence of novel structures, primo vessels (PVs) and primo nodes (PNs) floating inside the venous sinuses of rat brains. For this purpose, we applied a chromium–hematoxylin (Cr–Hx) solution to stain the PVs and the PNs floating inside the venous sinuses (superior sagittal sinus, strait sinus, and transverse sinus) of seven rats’ brains preferentially compared to the blood clots that easily form during surgery. Cr–Hx-stained PVs and PNs were examined by light and transmission electron microscopies: (1) we were consistently able to visualize the PVs and the PNs in the venous sinuses of all seven rats’ brains. (2) The PVs and PNs consisted of rod-shaped and some round-shaped cells, respectively, as demonstrated by using 4′,6-diamidino-2-phenylindole (DAPI). (3) Cross sections of the PVs showed that the sinuses contained loose fibrous materials and clusters of nano-sized granules enveloped by the cortex. The above data imply that thrombus of the venous sinuses may be related with these novel floating structures. However, the functions of the PVs and PNs floating in the venous sinuses remain to be investigated in terms of normal or thrombus-provoked diseases. [Copyright &y& Elsevier]

Background: The aim of this article was to review the clinical practice of 'bone flap decompression' in Regional Neurosurgical Units with no particular protocol in use. Methods: From January 2005 to December 2008, a retrospective and multicentre study was conducted on patients who were treated with decompressive craniectomy (DC) in seven departments of neurosurgery in Italy. This study included patients with traumatic brain injury, stroke, aneurysmal subarachnoid haemorrhage and cerebral arteriovenous malformations. Data were retrieved from individual medical records. Results: We identified 526 patients with DC. Age was the most significant predictor factor of survival, together with pupil reactivity, time of decompression and size of the bone flap. The effect of age in predicting survival was so important that in patients over 65 years old we did not find any other significant factor related to survival. In younger patients, the survival rate was much better with a large bone flap (p = 0.01). Unfortunately, 57% of patients were decompressed with a bone flap of less than 12 cm in diameter. This was probably due to the association in 80% of cases between haematoma evacuation and decompression. Conclusions: The current practice in many centres is different from published papers. Decompression is common over the age of 65 years, is associated with haematoma evacuation and often the bone flaps are inadequate in terms of size. [ABSTRACT FROM AUTHOR]

Summary: Background: Cerebral cavernous malformations (CCMs) are prone to bleeding but the risk of intracranial haemorrhage and focal neurological deficits, and the factors that might predict their occurrence, are unclear. We aimed to quantify these risks and investigate whether they are affected by sex and CCM location. Methods: We undertook a population-based study using multiple overlapping sources of case ascertainment (including a Scotland-wide collaboration of neurologists, neurosurgeons, stroke physicians, radiologists, and pathologists, as well as searches of registers of hospital discharges and death certificates) to identify definite CCM diagnoses first made in Scottish residents between 1999 and 2003, which study neuroradiologists independently validated. We used multiple sources of prospective follow-up both to identify outcome events (which were assessed by use of brain imaging, by investigators masked to potential predictive factors) and to assess adults'' dependence. The primary outcome was a composite of intracranial haemorrhage or focal neurological deficits (not including epileptic seizure) that were definitely or possibly related to CCM. Findings: 139 adults had at least one definite CCM and 134 were alive at initial presentation. During 1177 person-years of follow-up (completeness 97%), for intracranial haemorrhage alone the 5-year risk of a first haemorrhage was lower than the risk of recurrent haemorrhage (2·4%, 95% CI 0·0–5·7 vs 29·5%, 4·1–55·0; p<0·0001). For the primary outcome, the 5-year risk of a first event was lower than the risk of recurrence (9·3%, 3·1–15·4 vs 42·4%, 26·8–58·0; p<0·0001). The annual risk of recurrence of the primary outcome declined from 19·8% (95% CI 6·1–33·4) in year 1 to 5·0% (0·0–14·8) in year 5 and was higher for women than men (p=0·01) but not for adults with brainstem CCMs versus CCMs in other locations (p=0·17). Interpretation: The risk of recurrent intracranial haemorrhage or focal neurological deficit from a CCM is greater than the risk of a first event, is greater for women than for men, and declines over 5 years. This information can be used in clinical practice, but further work is needed to quantify risks precisely in the long term and to understand why women are at greater risk of recurrence than men. Funding: UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association. [Copyright &y& Elsevier]

Abstract: Kabuki syndrome (KS) comprises multiple congenital abnormalities and is characterized by a peculiar facial appearance, dermatoglyphic anomalies, mental retardation, skeletal abnormalities and postnatal growth retardation. We describe the case of a 23-month-old boy with the typical features of KS who had several malformations in the veins of the brain, which had not previously been described in patients with this syndrome. The MRI phlebogram of this patient showed that the vein of Galen was dilated and that it drained anomalously. The sinus rectus was abnormal and the longitudinal inferior venous sinus was absent. In view of this finding, together with the fact that structural brain abnormalities in KS are more frequent than in other congenital syndromes with multiple malformations, we propose that MRI be used in the diagnostic work-up of all patients with KS. [Copyright &y& Elsevier]

Abstract: The aim of the present study was to describe the clinical features and to evaluate the surgical treatment outcomes of pediatric patients with cerebral cavernous malformations (CCM). We investigated 85 children (53 boys and 32 girls), aged from 6months to 17.9years with CCM. Seizures and symptomatic hemorrhages, which were the most frequent symptoms, occurred in 81 patients. Nine patients had a positive family history of CCM. Eighty patients underwent microsurgical treatment after strict operative indications were met. Neuronavigation, combined with intraoperative ultrasonography or functional MRI, was used for precise localization of the lesions. The principles of minimally invasive techniques were followed during surgery. A total of 89 lesions were removed in 80 patients, and there were no deaths. During their hospital stay, only nine patients suffered from postoperative seizures, which were controlled with medication. Postoperative neurological deficits improved in 27 patients, were unchanged in nine, and worsened in two. With the help of advanced neuroimaging, a satisfactory surgical outcome was achieved for 10 lesions located in eloquent brain areas and four lesions in the brain stem. A follow-up study of 66 patients showed that all of these patients remained seizure-free, and nine patients with postoperative neurological deficits gradually recovered. Microsurgical treatment should be performed early for pediatric patients with CCM. Accurate localization of the lesions and the use of minimally invasive techniques and functional MRI monitoring were the key features of the surgical procedures. [Copyright &y& Elsevier]

Abstract: Between March 2009 and January 2010, 36 patients with 38 supratentorial cavernous malformations in eloquent brain areas underwent surgery with the aid of intraoperative MRI (iMRI), functional neuronavigation, and electrocorticography (ECoG). To optimize outcomes, the hemosiderin-stained tissue surrounding the lesion in addition to the cavernous malformation itself (lesion) was microsurgically removed, leaving behind only small areas adjacent to, or overlapping with, functional areas. According to the Zabramski classification, there were 13 type I lesions, which all underwent total resection. There were 25 type II or III lesions with a surrounding hypointense rim, and all of these lesions were completely removed; the surrounding hypointense rims were completely removed in 15 patients and partially removed in 10. No new neurologic disorders occurred postoperatively. Twenty patients had preoperative epileptic seizures, nine of whom were refractory to treatment. During follow-up, seizure outcome was assessed using the Engel classification, and 11 patients with non-refractory epilepsy had a class I outcome. Of the nine patients with refractory epilepsy, seven (77.8%) had a class I outcome, one (11.1%) had a class II outcome, and one (11.1%) had a class III outcome. [Copyright &y& Elsevier]

Introduction. Persistence of fetal cerebral carotid basilar anastomoses is rare. When it occurs, it is often associated with other vascular malformations, and other pathological conditions. Trigeminal primitive artery persistence is the most often among them. Coincidence of primitive trigeminal artery with cerebellar arteriovenous malformation is extremely rare. Case report. We reported a case of a 31-year-old woman with subarachnoid hemorrhage and cerebellar hematoma admitted in serious condition. Angiography demonstrated cerebellar arteriovenous malformation, primitive trigeminal artery and other malformation of Willis circle. After a complete surgical removal of arteriovenous malformation the patient was discharged without neurological or any other deficit. Conclusion. We reported an extremely rare condition, which had been reported very few times in the literature. The importance of primitive artery persistence is in changed anatomical and physiological condition of cerebral circulation, that is especially important in surgical procedures. [ABSTRACT FROM AUTHOR]

Aim:To evaluate the influence of the vascular endothelial growth factor A (VEGFA) polymorphisms on risk of presentation with intracerebral hemorrhage (ICH).Methods:Nine selected VEGFA single-nucleotide polymorphisms (SNPs) were genotyped in 311 patients with brain arteriovenous malformations (BAVM) in a Chinese population. Associations between individual SNPs/haplotypes and the hemorrhage risk of BAVMs were evaluated using logistic regression analysis.Results:In the single-locus analysis, rs1547651 was associated with increased risk of ICH (adjusted OR=2.11, 95% CI=1.01-4.42 compared with the AA genotype). In particular, an increased risk for ICH was associated with this variant in female patients (adjusted OR=3.21, and 95% CI=0.99-10.36). Haplotype-based analyses revealed that haplotype 'GC' in block 1 and haplotype 'ACC' in block 2 were associated with a 30%-38% reduction in the risk of ICH in patients with BAVMs compared to the most common haplotype (Psim=0.033 and Psim=0.005, respectively). The protective effect of haplotype 'ACC' in block 2 was more evident in male patients and subjects with BAVMs of a size ≥3 cm (adjusted OR=0.57, 95% CI=0.34-0.97 and adjusted OR=0.57, 95% CI=0.31-0.86, respectively).Conclusion:The results suggest that VEGFA gene variants may contribute to ICH risk of BAVM. [ABSTRACT FROM AUTHOR]

Abstract: The uncommon simultaneous occurrence of an exuberant, angioma-like proliferation of superficial cerebral microvessels along with absence of the kidneys has been proposed to constitute a syndromic complex for which the term “meningocerebral angiodysplasia (or angiomatosis) with renal agenesis” (MCA-RA) is being descriptively used. We observed this constellation in one of a pair of dichorionic male twins following postpartal death in the 38th week of pregnancy. General autopsy revealed rudimentary metanephric anlagen made up of few residual glomeruli, cysts lined by flattened tubular epithelium, and islands of cartilage – corresponding to renal aplastic dysplasia. Largely inconspicuous with respect to its gyral pattern, as well as the configuration of the ventricular system, the brain microscopically showed extensive replacement of the cortex by a lattice of proliferating capillaries with necrosis of the intervening parenchyma. Minute foci of calcified necrosis were scattered in the deep subcortical white matter as well, while the ventricular ependyma and the subventricular germ cell layer remained remarkably intact. The cerebellum and brain stem appeared unaffected as well. Karyotyping of skin fibroblasts indicated a normal chromosome set of 46XY without gross structural anomalies. We interpret these findings as ones apt to being reasonably accommodated within the spectrum of MCA-RA. Although exceedingly rare, accurate identification of individual cases of MCA-RA is relevant both to differential diagnosis from its prognostically different look-alike “proliferative vasculopathy and hydranencephaly-hydrocephaly” (PVHH), and to refine the nosology of unconventional pediatric vascular malformations, for which the rather nonspecific label “angiodysgenetic necrotizing encephalopathy” is still commonly used. [Copyright &y& Elsevier]

Infections of central nervous system are rare complications of endovascular procedures. Review of literature revealed only four reported cases of brain abscesses after embolization of intracranial arteriovenous malformations (AVMs). We report two new cases of delayed brain abscess after embolization of AVM. In one of the patients, it was due to an unusual organism, Burkholderia caeci. [ABSTRACT FROM AUTHOR]

Objective: Our interest is to investigate through the history of our specialty by the review of bibliographical sources and documents in prestigious provincial, national and international institutions related fundamentally to the neurosciences. Development: Skull trepanation is the most ancient surgical procedure that we know. The first skull trepanations were found in Peru 500 or more years B. C. Since then there's a long way about neurosurgical report cases in the history of humankind. In Cuba since the first half of the XIX century began to appear articles about patient with neurological pathologies, but it was not until 1891 that the fact of a neurological procedure was published in the Cuban medical press as a remarkable deed. We searched about the first work of scientific character, appeared in the Cuban medical literature dealing with a procedure on the brain. His author is Dr. Manuel Moreno de La Torre and the clinical discussion of the case, and the details of surgical procedure are in volume 17 of the magazine "Crónica Médico-Quirúrgica de la Habana" of 1891 under the title· "Abceso cerebral, trepanación, curación, recidiva y muerte". Conclusions: We hope that our investigation will be a source of motivation for doctors and historians to go deep in the roots of each of the medical specialties, a lovely and instructive way to respect our predecessors. [ABSTRACT FROM AUTHOR]

Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes various signs of toxicity in early life stages of vertebrates through activation of the aryl hydrocarbon receptor (AHR). The AHR also plays important roles in normal development in mice, and AHR−/− mice show abnormal development of vascular structures in various blood vessels. Our previous studies revealed that Ahr type 2 (Ahr2) activation by TCDD and β-naphthoflavone (BNF) caused a significant decrease in blood flow in the dorsal midbrain of zebrafish embryos. Here we report effects of TCDD exposure on the morphology of some blood vessels in the head of developing zebrafish. TCDD caused concentration-dependent anatomical rearrangements in the shape of the prosencephalic artery in zebrafish larvae. In contrast, no major vascular defects were recognized in the trunk and tail regions following exposure to TCDD at least at the concentrations used. Essentially, the same observations were also confirmed in BNF-exposed larvae. Knock-down of either Ahr2 or Ahr nuclear translocator type 1 (Arnt1) by morpholino oligonucleotides (MOs) protected larvae against abnormal shape of the prosencephalic artery caused by TCDD and BNF. On the other hand, knock-down of Ahr2 or Arnt1 in vehicle-exposed zebrafish larvae had no clear effect on morphology of the prosencephalic artery or trunk vessels. Ascorbic acid, an antioxidant, protected against the TCDD-induced decrease in blood flow through the prosencephalic artery, but not the abnormal morphological changes in the shape of this artery. These results indicate that activation of Ahr2/Arnt1 pathway by TCDD and BNF affects the shape of certain blood vessels in the brain of developing zebrafish. [Copyright &y& Elsevier]

Abstract: Objectives: To analyze and evaluate the role of Gamma knife radiosurgery (GKRS) and clinical outcome in patients with intracranial cavernous malformations. Patients and methods: The medical records of 96 patients who underwent radiosurgery at our institute were reviewed retrospectively. Results: After a mean follow-up period of 4.3 years, 33 cases out of 44 (75.0%) with complaint of seizure had cleared or got improved, 9 (20.5%) were not improved and 2 (4.5%) got worse. Of the 100 lesions in the 96 patients, 24 (24.0%) had the lesions shrinkage on the follow-up imagings. One patient (1.6%) with symptom of headache and dizziness got worse and three patients (3.1%) presented with new cranial nerve palsy. We have compared the treatment results between different marginal dose groups and find that low marginal dose can get better therapeutic efficacy but with less complications. Conclusion: GKRS is an effective and microinvasive treatment option for intracranial cavernous malformations. [Copyright &y& Elsevier]

Estimating risk of intracranial hemorrhage (ICH) for patients with unruptured brain arteriovenous malformations (AVMs) in the natural course is essential for assessing risks and benefits of treatment. Traditionally, the survival period starts at the time of diagnosis and ends at ICH, but most patients are quickly censored because of treatment. Alternatively, a survival period from birth to first ICH, censoring at the date of diagnosis, has been proposed. The authors quantitatively compared these 2 timelines using survival analysis in 1,581 Northern California brain AVM patients (2000–2007). Time-shift analysis of the birth-to-diagnosis timeline and maximum pseudolikelihood identified the point at which the 2 survival curves overlapped; the 95% confidence interval was determined using bootstrapping. Annual ICH rates per 100 patient-years were similar for both the birth-to-diagnosis (1.27, 95% confidence interval (CI): 1.18, 1.36) and the diagnosis-to-ICH (1.17, 95% CI: 0.89, 1.53) timelines, despite differences in curve morphology. Shifting the birth-to-diagnosis timeline an optimal amount (10.3 years, 95% CI: 3.3, 17.4) resulted in similar ICH survival curves (P = 0.979). These results suggest that the unconventional birth-to-diagnosis approach can be used to analyze risk factors for natural history risk in unruptured brain AVM patients, providing greater statistical power. The data also suggest a biologic change around age 10 years influencing ICH rate. [ABSTRACT FROM PUBLISHER]