Hemorrhagic Stroke In Children Research Articles

Abstract 17479: Angiographic Factors Influencing Treatment Decisions in Pediatric Brain Arteriovenous Malformation (pAVM): Insights From Cart Analysis

Introduction: Pediatric cerebral AVM (pAVM) are the most common cause of hemorrhagic stroke in children. Their optimal management approach remains controversial. Determining the angiographic factors that impact outcomes for the various treatment strategies is crucial. Hypothesis: To identify angiographic factors for modality-treatment decision-making Methods: Cross-sectional study of patients diagnosed with pAVM at a pediatric stroke center between 2016 and 2021. Patients’ demographics, angiographic characteristics (volume, location, nidal aneurysms, non-plexiform rapid fistulas, venous drainage, and nidus diffuseness), treatment, and clinical outcomes were collected. Classification and Regression Tree Analysis (CART) was used to identify impactful angiographic factors, multivariate regression was applied to evaluate their significance in treatment decision-making. Results: Thirty-seven consecutive patients were included, 25 were male, with a median age of 10.3 years (IQR 7.9-13.3). Median follow-up was 30.3 months (IQR 8.6-53.8). Twenty patients presented with a ruptured pAVM. Endovascular embolization was the most common treatment (19, 51.4%), followed by radiosurgery (14, 37.8%), and observation (8, 21.6%). Twenty-seven patients (81.8%) had improved or stable functional neurologic status at last follow-up, and six (18.2%) declined (none of them by more than one point on the mRS). Only one patient had post-treatment hemorrhage during follow-up.The angiographic features associated with specific treatments were: the presence of non-plexiform rapid fistulas (endovascular in 94.0% of patients p=0.01), basal ganglia or pons location (excluded from endovascular in 86% of patients p=0.30), absence of a nidal aneurysm (radiation in 98% p=0.03). CART did not identify other potentially impactful angiographic factors. Conclusions: Our study shows generally favorable outcomes and low complication rates in pAVM patients who underwent multimodal treatment. The presence of non-plexiform rapid fistulas and nidal aneurysms should be considered when determining the appropriate treatment approach. Further prospective confirmatory analyses are warranted.

Magnetic resonance imaging in assessing the staging of intracerebral hemorrhages in children

The purpose of the study was to evaluate the possibilities of MRI in determining the stage of hemorrhagic stroke (HS) depending on structural and perifocal changes in children.Materials and methods. The study included 46 patients (including 19 boys and 27 girls) aged from the 29th day of life to 18 years, with a clinical picture of cerebrovascular accident and the presence of HS in the brain substance (BS) during an MRI study. For statistical analysis, patients were divided into two groups: group 1 – patients examined in the first 48 hours from the onset of neurological symptoms (21 people), group 2 – after 48 hours (26 people). Comparison in two groups was carried out according to MR signs: the presence of perifocal cytotoxic edema, the presence of perifocal hemorrhagic impregnation, the presence of a cytoplasmic rim. Intergroup comparisons on a qualitative basis were carried out using Fisher's exact test.Results. As a result of the study, differential diagnostic criteria for the stages of HS in children were determined by analyzing the MRI semiotics of hematoma in combination with the symptom complex of perifocal changes (CPC) in the form of perifocal cytotoxic edema, perifocal hemorrhagic impregnation and cytoplasmic rim. Statistically significant differences in the frequency of occurrence of signs of perifocal cytotoxic edema and perifocal hemorrhagic impregnation in the groups were found. The presence of perifocal cytotoxic edema was statistically significant (p = 0.027) more common in group 1 (47% (n = 10), 95% CI 26–69) than in group 2 (16% (n = 4), 95% CI 5–36). The presence of perifocal hemorrhagic soaking was statistically significantly (p = 0.003) more common in group 1 (81% (n = 17), 95% CI 57–93) than in group 2 (36% (n = 9), 95% CI 18–57). In addition, a statistically significant (p = 0.005) difference was found in the incidence of CPC, which was observed in group 1 (28% (n = 6), CI 12–52) and was not observed in group 2 (0%, (n = 0), 95% CI 0–17).Conclusions. The use of T2, T1, FLAIR, SWI and DWI modes (b = 1000) in combination with ADC in the protocol of MRI examination of children is mandatory, and only a comparison of the characteristics of the MR signal from a hematoma in combination with an analysis of perifocal changes allows us to differentiate the stage of hemorrhage. HS in the acute and early subacute stages has a similar MRI semiotics, therefore, it is necessary to assess the complex of perifocal changes, which allows to differentiate these stages, as it is determined in patients examined in the first 48 hours (p < 0.05) and is not observed after two days. SWI analysis makes it possible to differentiate the late subacute stage of hematoma from chronic due to different characteristics of the MR signal, and also allows you to establish the presence of perifocal hemorrhagic impregnation, which contributes to the differential diagnosis of hemorrhage in the early stages of the pathological process.

The Role and Therapeutic Implications of Inflammation in the Pathogenesis of Brain Arteriovenous Malformations.

Brain arteriovenous malformations (bAVMs) are focal vascular lesions composed of abnormal vascular channels without an intervening capillary network. As a result, high-pressure arterial blood shunts directly into the venous outflow system. These high-flow, low-resistance shunts are composed of dilated, tortuous, and fragile vessels, which are prone to rupture. BAVMs are a leading cause of hemorrhagic stroke in children and young adults. Current treatments for bAVMs are limited to surgery, embolization, and radiosurgery, although even these options are not viable for ~20% of AVM patients due to excessive risk. Critically, inflammation has been suggested to contribute to lesion progression. Here we summarize the current literature discussing the role of the immune system in bAVM pathogenesis and lesion progression, as well as the potential for targeting inflammation to prevent bAVM rupture and intracranial hemorrhage. We conclude by proposing that a dysfunctional endothelium, which harbors the somatic mutations that have been shown to give rise to sporadic bAVMs, may drive disease development and progression by altering the immune status of the brain.

Hemorrhagic Stroke in Children and Adults With Sickle Cell Anemia: The Post-STOP Cohort.

Hemorrhagic stroke in young patients with sickle cell anemia remains poorly characterized. The Post-STOP (Stroke Prevention Trial in Sickle Cell Anemia) retrospective study collected follow-up data on STOP and STOP II clinical trial cohorts. From January 2012 to May 2014, a team of analysts abstracted data from medical records of prior participants (all with sickle cell anemia). Two vascular neurologists reviewed data to confirm hemorrhagic strokes defined as spontaneous intracerebral, subarachnoid, or intraventricular hemorrhage. Incidence rates were calculated using survival analysis techniques Results: Follow-up data were collected from 2850 of 3835 STOP or STOP II participants. Patients (51% male) were a median of 19.1 (interquartile range, 16.6-22.6) years old at the time of last known status. The overall hemorrhagic stroke incidence rate was 63 per 100 000 person-years (95% CI, 45-87). Stratified by age, the incidence rate per 100 000 person-years was 50 (95% CI, 34-75) for children and 134 (95% CI, 74-243) for adults >18 years. Vascular abnormalities (moyamoya arteriopathy, aneurysm or cavernous malformation) were identified in 18 of 35 patients with hemorrhagic stroke. The incidence rate of hemorrhagic stroke in patients with sickle cell anemia increases with age. Structural vascular abnormalities such as moyamoya arteriopathy and aneurysms are common etiologies for hemorrhage and screening may be warranted.

Hemorrhagic stroke in children: A case report

Purpose: The purpose of this report is to present a case of hemorrhagic stroke in a child.Case report: We present a 13-year-old child with a hemorrhagic stroke, which resulted from spontaneous bleeding of congenital arteriovenous malformations in the brain.Conclusion: Although a brain stroke in children is rare, it is an important cause of disability and mortality. Clinical, neurologic, and radiologic examinations are key for the detection and treatment of arteriovenous malformations, which are the most important cause of hemorrhagic stroke in children and may threaten a child's health and life.

A human model of arteriovenous malformation (AVM)-on-a-chip reproduces key disease hallmarks and enables drug testing in perfused human vessel networks

Brain arteriovenous malformations (AVMs) are a disorder wherein abnormal, enlarged blood vessels connect arteries directly to veins, without an intervening capillary bed. AVMs are one of the leading causes of hemorrhagic stroke in children and young adults. Most human sporadic brain AVMs are associated with genetic activating mutations in the KRAS gene. Our goal was to develop an in vitro model that would allow for simultaneous morphological and functional phenotypic data capture in real time during AVM disease progression. By generating human endothelial cells harboring a clinically relevant mutation found in most human patients (activating mutations within the small GTPase KRAS) and seeding them in a dynamic microfluidic cell culture system that enables vessel formation and perfusion, we demonstrate that vessels formed by KRAS4AG12V mutant endothelial cells (ECs) were significantly wider and more leaky than vascular beds formed by wild-type ECs, recapitulating key structural and functional hallmarks of human AVM pathogenesis. Immunofluorescence staining revealed a breakdown of adherens junctions in mutant KRAS vessels, leading to increased vascular permeability, a hallmark of hemorrhagic stroke. Finally, pharmacological blockade of MEK kinase activity, but not PI3K inhibition, improved endothelial barrier function (decreased permeability) without affecting vessel diameter. Collectively, our studies describe the creation of human KRAS-dependent AVM-like vessels in vitro in a self-assembling microvessel platform that is amenable to phenotypic observation and drug delivery.

Neurologic Manifestations of COVID-19 in Children: Emerging Pathophysiologic Insights.

The COVID-19 pandemic has affected mortality and morbidity across all ages, including children. Neurologic manifestations of coronavirus disease 2019, ranging from headaches to cerebrovascular stroke, may involve the CNS or peripheral nervous system. Neurologic involvement is also noted in the multisystem inflammatory syndrome in children, a pediatric condition that occurs weeks after infection with severe acute respiratory syndrome coronavirus 2, the virus that causes COVID-19. Knowledge about mechanisms of neurologic disease and immunologic response to severe acute respiratory syndrome coronavirus 2 is scarce but rapidly growing. Here, we concisely review experimental and clinical data relevant to pathophysiologic hypotheses regarding neurologic manifestations of coronavirus disease 2019. We highlight important knowledge gaps in differences between adults and children in their response to coronavirus disease 2019.

Early Outcomes and Complications of Endovascular Treatment of Cerebral Arteriovenous Malformations in Pediatric Patients

Introduction: Arteriovenous malformations (AVMs) are the commonest cause of hemorrhagic stroke in children. Endovascular embolization is a feasible treatment modality, but cure rates are heterogenous from one series to another. We aimed to describe the immediate obliteration rates and periprocedural complications of embolization of pediatric AVMs. Methods: Between 2011 and 2019, participants below 18 years of age with AVMs treated by the same neurosurgeon at a single center were included. The clinical features, immediate angiographic results, and periprocedural complications were retrospectively collected from the clinical records. Results: Thirty-four embolization sessions were performed on 20 children (12 females with a mean age of 13). Intracranial hemorrhage was the most common presentation (75%), and the majority were frontal (30%) and basal ganglia (30%) lesions. An immediate complete angiographic obliteration was achieved in 9 patients (45%) with low-grade lesions (Spetzler-Martin grade I and II). NBCA was the most common embolic agent used (52.9%). Complications were reported in 3 (8.8%) out of 34 sessions. Two of them were intraoperative perforations with clinical consequences. A slight cortical hemorrhage during the procedure was observed in 1 patient without clinical repercussions. Discussion: This single-surgeon single-center experience suggests that endovascular treatment is a safe and efficient treatment for pediatric AVMs. Pediatric prognostic scores for a suitable selection of candidates are needed. Further studies are required to validate these results.

Monogenetic Stroke Syndromes in Children and Young Adults.

OBJECTIVE. The purpose of this article is to review the characteristic CT and MRI findings associated with monogenetic causes of ischemic and hemorrhagic stroke in children and young adults. CONCLUSION. Ischemic and hemorrhagic stroke in children and young adults remains a common cause of acquired disability but is underrecognized. Brain parenchymal and vascular imaging is commonly performed as part of the comprehensive evaluation of young patients presenting with stroke. Familiarity with these patterns of disease enables early recognition of an underlying inherited condition.

Functional and educational outcomes after treatment for intracranial arteriovenous malformations in children

BackgroundArteriovenous malformations (AVMs) in the pediatric population are rare, yet they form the most frequent cause of hemorrhagic stroke in children. Compared to adults, children have been suggested to have beneficial neurological outcomes. However, few studies have focused on other variables than neurological outcomes. This study aims to assess the long-term functional and educational outcomes of children after multimodality approach of treatment for intracranial AVMs.MethodsAll children treated in our center between 1998 and 2016 for intracranial AVMs were reviewed. Patient characteristics, as well as AVM specifics, were collected. Functional outcomes were compared using the modified Rankin scale (mRs). Educational levels, using the International Standard Classification of Education (ISCED), were compared to the age-matched general population of the Netherlands.ResultsIn total, 25 children were included at mean age of 10 years (range 2–16 years). Nineteen patients (76%) presented with intracranial bleeding. Mean follow-up was 11.5 ± 5.3 years (range 4.1–24.4). Four (16%) of patients were treated with embolization, three (12%) with microsurgery, and 18 patients (72%) received a combination of different treatment modalities. Altogether, 21 (84%) were embolized, 14 (56%) were treated with microsurgery, and eight (32%) received stereotactic radiosurgery. One child had a worse mRs at discharge compared to admission; all others improved (n = 11) or were stable (n = 13). At follow-up, all patients scored a stable or improved mRs compared to discharge, with 23 children (92%) scoring mRs 0 or 1. These 23 children followed regular education during follow-up without specialized or adapted schooling. No significant differences in educational level with the age-matched general population were found.ConclusionThis retrospective review shows positive long-term results of both functional and educational outcomes after multidisciplinary treatment of pediatric brain AVMs.

A role of infection in the development of hemorrhagic stroke in children

To identify a role of infection in the development of hemorrhagic stroke (HS) in infants. A retrospective analysis of case histories of 145 infants hospitalized with hemorrhagic stroke was performed. The analysis of HS risk factors shows the importance of infectious-inflammatory factor both for local and generalized forms of inflammation of the organs associated with disseminated intravascular coagulation, hypocoagulation and an increase in anticoagulant and fibrinolytic potentials.

Impact of TCD Screening Protocol on the Incidence of Hemorrhagic Stroke in Children and Young Adults with Sickle Cell Disease

Background: Primary hemorrhagic stroke is a rare complication of sickle cell disease (SCD) that usually occurs in adults. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) established routine transcranial Doppler ultrasound (TCD) screening with indefinite chronic red cell transfusions (CRCT) for patients with abnormal TCD as standard of care. Despite a notable improvement in the incidence of infarctive stroke in children with SCD after the introduction of TCD screening protocols, it is unclear how this protocol will affect the rate of hemorrhagic stroke. Presumably, early TCD screening and subsequent initiation of CRCT in high risk patients will prevent the progression of cerebral vasculopathy, which should decrease the risk of hemorrhagic stroke; however this has not been proven. Using the large multicenter cohort of children who participated in STOP and/or STOP 2 trials, we sought to assess whether the rate of hemorrhagic stroke was impacted by the use of TCD screening and/or CRCT.Subjects and Methods: Between 1995 and 2005, STOP and STOP 2 (STOP/2) were conducted at 26 sites in the US and Canada. These studies included 3835 children, ages 2 to 16 y with SCD type SS or S-beta-0-thalassemia. Participation in STOP/2 required at least a single screening TCD for randomization. Patients on STOP 2 also had an observational arm for children started on CRCT who had an abnormal TCD. The Post-STOP study was designed to follow-up the outcomes of children who participated in one or both of trials. For all participants the date of their last encounter in STOP/2 was defined as the start of their Post-STOP period. 19 of the 26 original study sites participated in Post-STOP, contributing a total of 3539 (92%) of the STOP/2 subjects. After exit from STOP/2, these children received TCD screening and treatment according to local practices. Data abstractors visited each clinical site and obtained retrospective data from STOP/2 study exit to 2012-2014 including follow-up TCD and brain imaging results, clinical information, and laboratory results. Two separate neurologists, blinded to STOP/2 status and prior TCD and neuroimaging results adjudicated all suspected strokes.Results: Follow-up data were available for 2850 of the 3539 subjects (81%). Twelve children who had a stroke during the STOP study period were further excluded from this analysis resulting 2838 subjects. The mean age at the start of Post-STOP was 10.5 years and mean duration of follow-up after exiting STOP/2 until time of last medical encounter was 9.1 years. A total of 31 patients had a primary hemorrhagic stroke during the Post-STOP observation period (incidence 0.12 per 100 pt years). The mean age at time of stroke was 16.2+5.6 (median 15.3 range (4.8-30.2) years of age. Of those 31 patients, only 52% had a TCD during Post-STOP prior to the event. Seven of those children who underwent screening had documentation of an abnormal TCD prior to the event (5 during STOP era and/or 3 Post-STOP). However, only 1/7 patients (14%) were documented on CRCT at the time of the stroke (4 patients were receiving HU and 2 patients had unknown treatment).Discussion: Although less common than infarctive stroke, patients with SCD are at increased risk for hemorrhagic stroke. There is an increased risk of mortality for patients who suffer from hemorrhagic stroke (up to 26% in some reports in the 2 weeks after the event). It is unclear if TCD screening and subsequent initiation of CRCT will impact the rate of hemorrhagic stroke in the long term. In our results, a similar incidence of primary hemorrhagic stroke was noted although the patients were overall younger than previously reported (16.5+/- 5.5 years versus 20-29 years in Cooperative Study of Sickle Cell Disease). Many patients who had a hemorrhagic stroke (48%) had not undergone TCD screening during the Post-Stop period. Additionally, although a safe stopping point for CRCT has not been established in patients who have had an abnormal TCD, only 1 patient was documented on CRCT at the time of the event (14%). Thus, it is unclear at this time whether TCD screening and subsequent, lifelong continuation of CRCT could have prevented these other events. Clearly, these results demonstrate that improved implementation of STOP protocol is needed as well as further evaluation of the impact of this protocol on the incidence of hemorrhagic stroke. DisclosuresNo relevant conflicts of interest to declare.

Structural causes of ischemic and hemorrhagic stroke in children: moyamoya and arteriovenous malformations.

Moyamoya and arteriovenous malformations represent, respectively, significant sources of ischemic and hemorrhagic stroke in children after the first year of life. Although rarely encountered in routine pediatric practice, the potential severe morbidity of these entities, coupled with the typical acuity of their presentation, merit ongoing awareness of current relevant diagnostic and therapeutic strategies. Mutations in RNF213, ACTA2, and GUCY are implicated in moyamoya. Several common pediatric conditions - trisomy 21, sickle-cell disease, and neurofibromatosis type I - demonstrate an increased risk of moyamoya development. Advances in imaging have improved the diagnosis of moyamoya and surgical revascularization has been further supported as the primary treatment.Genetic associations with arteriovenous malformations (AVMs) are few outside of hereditary hemorrhagic telangiectasia. Within this population, the majority harbor mutations in ENG and ACVRL. Once screened, if no AVM is found, repeat scanning may not be needed for 5 years. Trauma and infection may not be 'triggers' for inducing hemorrhage in patients with untreated AVMs. If found in children, evidence supports the treatment of the AVM, ideally with surgery. Moyamoya and AVMs are rare but important causes of stroke in children. If identified, it is important to refer the children to pediatric centers with experienced neurovascular teams. Surgical revascularization of moyamoya and resection of AVMs should be strongly considered, including incidentally discovered asymptomatic disease.

Hemorrhagic stroke in children caused by Bothrops marajoensis envenoming: a case report

According to the World Health Organization, snakebites are considered neglected diseases. Bothrops, the genus most frequently implicated in envenomations in Brazil, includes the species B. marajoensis Hoge, 1966, part of the complex B. atrox, which is found in the savannas of Marajó Island, Pará state, Brazil, a region that presents scarce epidemiological data. This work reports the first case of hemorrhagic stroke in a child, attributed to delayed medical care after snakebite envenoming by Bothrops marajoensis in Anajás city, Marajó Island, Pará, Brazil, which led to permanent hemiplegia as a sequela.

Management of Hemorrhagic Stroke in Children

Management of Hemorrhagic Stroke in Children

Stroke Prevalence, Mortality and Disability-Adjusted Life Years in Children and Youth Aged 0-19 Years: Data from the Global and Regional Burden of Stroke 2013

Background: There is increasing recognition of stroke as an important contributor to childhood morbidity and mortality. Current estimates of global childhood stroke burden and its temporal trends are sparse. Accurate and up-to-date estimates of childhood stroke burden are important for planning research and the resulting evidence-based strategies for stroke prevention and management. Objectives: To estimate the prevalence, mortality and disability-adjusted life years (DALYs) for ischemic stroke (IS), hemorrhagic stroke (HS) and all stroke types combined globally from 1990 to 2013. Methodology: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease 2013 methods. All available data on stroke-related incidence, prevalence, excess mortality and deaths were collected. Statistical models and country-level covariates were employed to produce comprehensive and consistent estimates of prevalence and mortality. Stroke-specific disability weights were used to estimate years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. Results: In 2013, there were 97,792 (95% UI 90,564-106,016) prevalent cases of childhood IS and 67,621 (95% UI 62,899-72,214) prevalent cases of childhood HS, reflecting an increase of approximately 35% in the absolute numbers of prevalent childhood strokes since 1990. There were 33,069 (95% UI 28,627-38,998) deaths and 2,615,118 (95% UI 2,265,801-3,090,822) DALYs due to childhood stroke in 2013 globally, reflecting an approximately 200% decrease in the absolute numbers of death and DALYs in childhood stroke since 1990. Between 1990 and 2013, there were significant increases in the global prevalence rates of childhood IS, as well as significant decreases in the global death rate and DALYs rate of all strokes in those of age 0-19 years. While prevalence rates for childhood IS and HS decreased significantly in developed countries, a decline was seen only in HS, with no change in prevalence rates of IS, in developing countries. The childhood stroke DALY rates in 2013 were 13.3 (95% UI 10.6-17.1) for IS and 92.7 (95% UI 80.5-109.7) for HS per 100,000. While the prevalence of childhood IS compared to childhood HS was similar globally, the death rate and DALY rate of HS was 6- to 7-fold higher than that of IS. In 2013, the prevalence rate of both childhood IS and HS was significantly higher in developed countries than in developing countries. Conversely, both death and DALY rates for all stroke types were significantly lower in developed countries than in developing countries in 2013. Men showed a trend toward higher childhood stroke death rates (1.5 (1.3-1.8) per 100,000) than women (1.1 (0.9-1.5) per 100,000) and higher childhood stroke DALY rates (120.1 (100.8-143.4) per 100,000) than women (90.9 (74.6-122.4) per 100,000) globally in 2013. Conclusions: Globally, between 1990 and 2013, there was a significant increase in the absolute number of prevalent childhood strokes, while absolute numbers and rates of both deaths and DALYs declined significantly. The gap in childhood stroke burden between developed and developing countries is closing; however, in 2013, childhood stroke burden in terms of absolute numbers of prevalent strokes, deaths and DALYs remained much higher in developing countries. There is an urgent need to address these disparities with both global and country-level initiatives targeting prevention as well as improved access to acute and chronic stroke care.

Intracranial haemorrhage in a children suffering from heamofilia

Haemophilia is a hereditary X-linked desease manifested in coagulatory hemostasis disorder. Haemophilia A is a recessive mutation in X-chromosome which results in the absence or malfunction of blood clotting factor VIII. Its frequency from 1:5000 to 1:10,000 of born boys. Haemophilia B is caused by the factor IX deficiency (recessive mutation in X-chromosome), with an incidence from 1:25,000 to 1:30,000 of born boys. Frequency of occurrence hemorrhagic stroke in children is 0.7–5.1 (average – 2.9) per 100,000. Reported intracranial hemorrhages (ICH) boys with haemophilia are rare, however, according to foreign authors encountered in 1.7–11.7 % of patients that with appropriate recalculation was 290–2142:100,000 per year. Thus, the risk of ICH patients with hemophilia in 56–420 times higher than the general population. The median age of children with ICH ranges from 5.9 months to 8 years. Operational tactics not developed.

Abstract 161: Effects of Radiation Dose on Gene Expression in Cultured Murine Brain Endothelial Cells

Brain arteriovenous malformations (AVMs) are direct connections between arteries and veins that allow high pressure arterial blood to flow into fragile cerebral veins. AVMs are the leading cause of hemorrhagic stroke in children and young adults. Treatment of large and deep AVMs is challenging; new treatment methods are required. It is proposed that stereotactic radiosurgery could be used to selectively alter the AVM endothelial cell phenotype, allowing targeted molecular therapies which stimulate thrombosis. We have previously shown that irradiation of endothelial cell cultures with 25Gy results in up-regulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In this study we hypothesise that a lower dose of radiation is similarly effective at causing up-regulation in ICAM-1 and VCAM-1 expression. Murine brain endothelial cell cultures were irradiated with 15Gy (n = 4) or 25Gy (n = 4) using a linear accelerator; non-irradiated cells were used as controls (n = 4). The relative gene expression at 96, 120, 144 and 168h after radiation was measured by quantitative real-time PCR. Genes encoding for ICAM-1 and VCAM-1 were found to be significantly up-regulated post-radiation with either 15Gy or 25Gy (p <0.001). Maximum gene expression of ICAM-1 and VCAM-1 was observed at 144h (7-fold) and at 120h (23-fold), respectively. There was no significant difference between the two doses. These results support the hypothesis that a 15Gy dose is as effective as a 25Gy dose. Therefore a lower dose of radiation might be equally effective at causing changes in endothelial cell phenotype. This is important from a clinical perspective because lower doses of radiation will be safer for the treatment of large AVMs.

Angiographic features help predict outcome after stereotactic radiosurgery for the treatment of pediatric arteriovenous malformations

Arteriovenous malformations (AVMs) are a frequent cause of hemorrhagic stroke in children. Stereotactic radiosurgery (SRS) is an established treatment for these lesions, particularly those that are surgically inaccessible. Because only complete AVM obliteration is believed to protect against the future risk of hemorrhage, identifying lesion characteristics that predict response to therapy is an important objective. The goal of this study is to evaluate the influence of angiographic features of AVMs on the rate of obliteration following treatment with SRS. This is a retrospective cohort study of pediatric patients (age ≤18 years) treated with Gamma Knife SRS for cerebral AVMs between 2000 and 2012. Detailed angiographic data at the time of initial angiographic evaluation were prospectively recorded by experienced neurointerventional radiologists. The primary outcome was the rate of obliteration on a 3-year follow-up angiogram. We identified 42 pediatric patients treated with SRS for cerebral AVMs. Twenty-seven patients completed 3-year angiographic follow-ups. Complete obliteration was seen in 30%, partial response in 67%, and no response in 4%. Higher SRS dose was associated with complete obliteration. Larger AVM diameter, presence of multiple draining veins, and presence of multiple draining veins reaching a sinus were associated with partial response. In this small cohort, diffuse AVM borders, presence of aneurysm, and pre-SRS embolization were not associated with obliteration. Our study identifies AVMs in the pediatric population with a nidus diameter of <2.5 cm and a solitary draining vein as the most likely to undergo complete obliteration after SRS treatment.

Role of trauma and infection in childhood hemorrhagic stroke due to vascular lesions

Trauma and infection have been postulated as "triggers" for hemorrhage from underlying brain vascular lesions (arteriovenous malformations, cavernous malformations, and aneurysms) in pediatric hemorrhagic stroke. We decided to perform an association study examining these environmental risk factors. In this case-control study nested within the cohort of 2.3 million children enrolled in a Northern California integrated health plan (1993-2004), we identified childhood hemorrhagic stroke cases through electronic searches of diagnostic and radiology databases, confirmed through chart review. Three age- and facility-matched controls per case were randomly selected from the study population. Exposure variables were measured using medical records documented before stroke diagnosis. Main outcome measure was hemorrhagic stroke. Of 132 childhood, non-neonatal hemorrhagic stroke cases, 65 had underlying vascular lesions: 34 arteriovenous malformations, 16 cavernous malformations, and 15 aneurysms. A documented exposure to head and neck trauma in the prior 12 weeks was present in 3 cases (4.6%) with underlying vascular lesions, compared with no controls (p < 0.015). However, all 3 vascular lesions were aneurysms, and traumatic pseudoaneurysms were possible. Recent minor infection (prior 4 weeks) was present in 5 cases (7.7%) and 9 controls (4.6%) (p = 0.34). Our observed association between trauma and hemorrhagic stroke with a vascular lesion may be explained by traumatic pseudoaneurysms. Neither recent head or neck trauma nor infection appeared to be a "trigger" for pediatric hemorrhagic stroke due to underlying vascular malformations.