Arterial Spin Labeling for the Etiological Workup of Intracerebral Hemorrhage in Children.

BACKGROUND AND PURPOSE: Pediatric nontraumatic intracerebral hemorrhage accounts for half of stroke in children. Early diagnostic of the causative underlying lesion is the first step toward prevention of hemorrhagic recurrence. We aimed to investigate the performance of arterial spin labeling sequence (ASL) in the acute phase etiological workup for the detection of an arteriovenous shunt (AVS: including malformation and fistula), the most frequent cause of pediatric nontraumatic intracerebral hemorrhage. METHODS: Children with a pediatric nontraumatic intracerebral hemorrhage between 2011 and 2019 enrolled in a prospective registry were retrospectively included if they had undergone ASL-magnetic resonance imaging before any etiological treatment. ASL sequences were reviewed using cerebral blood flow maps by 2 raters for the presence of an AVS. The diagnostic performance of ASL was compared with admission computed tomography angiography, other magnetic resonance imaging sequences including contrast-enhanced sequences and subsequent digital subtraction angiography. RESULTS: A total of 121 patients with pediatric nontraumatic intracerebral hemorrhage were included (median age, 9.9 [interquartile range, 5.8-13]; male sex 48.8%) of whom 76 (63%) had a final diagnosis of AVS. Using digital subtraction angiography as an intermediate reference, visual ASL inspection had a sensitivity and a specificity of, respectively, 95.9% (95% CI, 88.5%-99.1%) and 79.0% (95% CI, 54.4%-94.0%). ASL had a sensitivity, specificity, and accuracy of 90.2%, 97.2%, and 92.5%, respectively for the detection of the presence of an AVS, with near perfect interrater agreement (κ=0.963 [95% CI, 0.912-1.0]). The performance of ASL alone was higher than that of other magnetic resonance imaging sequences, individually or combined, and higher than that of computed tomography angiography. CONCLUSIONS: ASL has strong diagnostic performance for the detection of AVS in the initial workup of intracerebral hemorrhage in children. If our findings are confirmed in other settings, ASL may be a helpful diagnostic imaging modality for patients with pediatric nontraumatic intracerebral hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: 3618210420, 2217698.

Hemodynamic changes during the obliteration process for cerebral arteriovenous malformations after radiosurgery.

OBJECTIVE: The process of cerebral arteriovenous malformation (AVM) obliteration following radiosurgery is poorly understood. Authors of this retrospective study aimed to assess the changes in AVM hemodynamics after stereotactic radiosurgery (SRS) by using 3D flow magnetic resonance imaging (MRI) to elucidate the process of AVM obliteration. METHODS: Twenty-four patients with AVMs treated with SRS between July 2015 and December 2017 were included in this study and classified into two groups depending on the duration of AVM obliteration: group A, obliteration within 3 years (n = 15); and group B, obliteration taking more than 3 years or no obliteration (n = 9). Blood flow (ml/min) in the largest feeding artery was measured before and after SRS by using time-averaged 3D flow MRI. The decreasing rate of blood flow in the feeding artery after SRS was calculated as the percent change from baseline blood flow. A Wilcoxon rank-sum test was used to compare the decreasing blood flow rate between the two groups at 4 and 12 months after SRS. RESULTS: For the entire cohort, the mean decrease in blood flow in the feeding artery from baseline was 29% at 4 months and 71% at 12 months after SRS. In general, blood flow after SRS decreased faster in group A and slower in group B. The decreasing rates in blood flow at 4 and 12 months after SRS were significantly different between the two groups (p = 0.02 and < 0.001, respectively). CONCLUSIONS: Tracking changes in AVM hemodynamics after SRS may be useful for assessing the progress of AVM obliteration and the therapeutic effects of SRS, possibly contributing to the prediction of subsequent obliteration outcome.

De Novo Dural Arteriovenous Fistula on Draining Veins of Previously Treated Pial Arteriovenous Malformation: a Case Report.

A 71-year-old man, with a pial micro-arteriovenous malformation (pAVM) draining into the confluence of the vein of Trolard and the vein of Labbé was surgically removed, sparing these cortical veins. 4-months MR and angiographic controls showed a de novo dural arteriovenous fistula (dAVF) draining into the previously spared cortical veins. It was removed using intraoperative motor evoked potentials (MEP). This is the first case of iatrogenic dAVF developing on the same draining vein of a previously treated pAVM. De novo dAVFs are generally iatrogenic. This case suggests that the unresected venous drainage of an AVM might be the substratum for neo-angiogenetic processes; moreover inflammation related to surgery might be the trigger factor for the development of the dAVF.

Vessel-selective 4D-MR angiography using super-selective pseudo-continuous arterial spin labeling may be a useful tool for assessing brain AVM hemodynamics.

OBJECTIVES: To evaluate the usefulness of 4D-MR angiography based on super-selective pseudo-continuous ASL combined with keyhole and view-sharing (4D-S-PACK) for vessel-selective visualization and to examine the ability of this technique to visualize brain arteriovenous malformations (AVMs). METHODS: In this retrospective study, 15 patients (ten men and five women, mean age 44.0 ± 16.9 years) with brain AVMs were enrolled. All patients were imaged with 4D-PACK (non-selective), 4D-S-PACK, and digital subtraction angiography (DSA). Observers evaluated vessel selectivity, identification of feeding arteries and venous drainage patterns, visualization scores, and contrast-to-noise ratio (CNR) for each AVM component. Measurements were compared between the MR methods. RESULTS: Vessel selectivity was graded 4 in 43/45 (95.6%, observer 1) and 42/45 (93.3%, observer 2) territories and graded 3 in two (observer 1) and three (observer 2) territories. The sensitivity and specificity for identification of feeding arteries for both observers was 88.9% and 100% on 4D-PACK, and 100% and 100% on 4D-S-PACK, respectively. For venous drainage, the sensitivity and specificity was 100% on both methods for observer 1. The sensitivity and specificity for observer 2 was 94.4% and 83.3% on 4D-PACK, and 94.4% and 91.7% on 4D-S-PACK, respectively. The CNRs at the timepoint of 1600 ms were slightly lower in 4D-S-PACK than in 4D-PACK for all AVM components (Feeding artery, p = .02; nidus, p = .001; and draining artery, p = .02). The visualization scores for both observers were not significantly different between 4D-PACK and 4D-S-PACK for all components. CONCLUSIONS: 4D-S-PACK could be a useful non-invasive clinical tool for assessing hemodynamics in brain AVMs. KEY POINTS: • The 4D-MR angiography based on super-selective pseudo-continuous arterial spin labeling combined with CENTRA-keyhole and view-sharing (4D-S-PACK) enabled excellent vessel selectivity. • The 4D-S-PACK enabled the perfect identification of feeding arteries of brain arteriovenous malformation (AVM). • 4D-S-PACK could be a non-invasive clinical tool for assessing hemodynamics in brain AVMs.

Clinical Importance of the Posterior Inferior Cerebellar Artery: A Review of the Literature.

The posterior inferior cerebellar artery (PICA), with its unique anatomical complexity, is of great clinical importance and involved in many diseases including aneurysm, ischemic stroke, neurovascular compression syndrome (NVCS), arteriovenous malformation (AVM), and brain tumor. However, a comprehensive systematic review of the importance of the PICA is currently lacking. In this study, we perform a literature review of PICA by searching all the associated papers in the PUBMED database hoping to provide a better understanding of the artery. The PICA has tortuous and variable course and territory, divided into 5 segments. Various aneurysms involving PICA were not uncommon, of which the treatment is challenging. The PICA infarct typically manifests lateral medullary syndrome (LMS) and is more likely to cause mass effects. The PICA frequently compresses the medulla and the cranial nerves resulting in various neurovascular compression syndromes (NVCS). Arteriovenous malformation (AVM) fed by PICA are associated with aneurysm and dissection which have high risk of rupture and worse outcome. PICA injured by head trauma can cause fatal SAH. VA terminating in PICA probably cause Bow hunter's syndrome (BHS). The PICA supplies many brain tumors and can be used in intracerebellar chemotherapy. The PICA can be exposed and injured during surgeries especially in telovelar approach, and it also plays an important role in bypass surgeries, hinting the surgical importance of PICA. In conclusion, PICA is very important in clinical practice.

Impact of flow and angioarchitecture on brain arteriovenous malformation outcome after gamma knife radiosurgery: the role of hemodynamics and morphology in obliteration.

BACKGROUND: Few studies have evaluated the relationship between brain arteriovenous malformations (bAVMs) angioarchitecture and the response to Gamma Knife Stereotactic Radiosurgery (GKSR). METHODS: A prospectively enrolled single-center cohort of patients with bAVMs treated by GKSR has been studied to define independent predictors of obliteration with particular attention to angioarchitectural variables. Only patients older than 18 years old (y.o.), who underwent baseline digital subtraction angiography (DSA) and clinico-radiological follow-up of at least 36 months, were included in the study. RESULTS: Data of 191 patients were evaluated. After a mean follow-up of 80 months (range 37-173), total obliteration rate after first GKSR treatment was 66%. Mean dose higher than 22 Gy (P = .019, OR = 2.39, 95% CI 1.15-4.97) and flow rate dichotomized into high vs non-high (P < .001, OR = 0.23, 95% CI 0.11-0.51) resulted to be independent predictors of obliteration. Flow-surrogate angioarchitectural features did not emerge as independent outcome predictors. CONCLUSIONS: Flow rate seems to be associated in predicting outcome after GKSR conferring high-flow AVM a lower occlusion rate. Its role should be considered when planning radiosurgical treatment of bAVM, and it could be added to other parameters used in GKRS outcome predicting scales.

Altered Brain Structural Networks in Patients with Brain Arteriovenous Malformations Located in Broca's Area.

Focal brain lesions, such as stroke and tumors, can lead to remote structural alterations across the whole-brain networks. Brain arteriovenous malformations (AVMs), usually presumed to be congenital, often result in tissue degeneration and functional displacement of the perifocal areas, but it remains unclear whether AVMs may produce long-range effects upon the whole-brain white matter organization. In this study, we used diffusion tensor imaging and graph theory methods to investigate the alterations of brain structural networks in 14 patients with AVMs in the presumed Broca's area, compared to 27 normal controls. Weighted brain structural networks were constructed based on deterministic tractography. We compared the topological properties and network connectivity between patients and normal controls. Functional magnetic resonance imaging revealed contralateral reorganization of Broca's area in five (35.7%) patients. Compared to normal controls, the patients exhibited preserved small-worldness of brain structural networks. However, AVM patients exhibited significantly decreased global efficiency (p = 0.004) and clustering coefficient (p = 0.014), along with decreased corresponding nodal properties in some remote brain regions (p < 0.05, family-wise error corrected). Furthermore, structural connectivity was reduced in the right perisylvian regions but enhanced in the perifocal areas (p < 0.05). The vulnerability of the left supramarginal gyrus was significantly increased (p = 0.039, corrected), and the bilateral putamina were added as hubs in the AVM patients. These alterations provide evidence for the long-range effects of AVMs on brain white matter networks. Our preliminary findings contribute extra insights into the understanding of brain plasticity and pathological state in patients with AVMs.

Stereotactic Radiosurgery for Brain Arteriovenous Malformations: Evaluation of Obliteration and Review of Associated Predictors.

BACKGROUND: High arteriovenous malformation (AVM) obliteration rates have been reported with stereotactic radiosurgery (SRS), and multiple factors have been found to be associated with AVM obliteration. These predictors have been inconsistent throughout studies. We aimed to analyze our experience with linear accelerator (LINAC)-based SRS for brain AVMs, evaluate outcomes, assess factors associated with AVM obliteration and review the various reported predictors of AVM obliteration. METHODS: Electronic medical records were retrospectively reviewed to identify consecutive patients with brain AVMs treated with SRS over a 27-year period with at least 2 years of follow-up. Logistic regression analysis was performed to identify factors associated with AVM obliteration. RESULTS: One hundred twenty-eight patients with 142 brain AVMs treated with SRS were included. Mean age was 34.4 years. Fifty-two percent of AVMs were associated with a hemorrhage before SRS, and 14.8% were previously embolized. Mean clinical and angiographic follow-up times were 67.8 months and 58.6 months, respectively. The median Spetzler-Martin grade was 3. Mean maximal AVM diameter was 2.8 cm and mean AVM target volume was 7.4 cm3 with a median radiation dose of 16 Gy. Complete AVM obliteration was achieved in 80.3%. Radiation-related signs and symptoms were encountered in 32.4%, only 4.9% of which consisted of a permanent deficit. Post-SRS AVM-related hemorrhage occurred in 6.3% of cases. In multivariate analysis, factors associated with AVM obliteration included younger patient age (P = .019), male gender (P = .008), smaller AVM diameter (P = .04), smaller AVM target volume (P = .009), smaller isodose surface volume (P = .005), a higher delivered radiation dose (P = .013), and having only one major draining vein (P = .04). CONCLUSIONS: AVM obliteration with LINAC-based radiosurgery was safe and effective and achieved complete AVM obliteration in about 80% of cases. The most prominent predictors of AVM success included AVM size, AVM volume, radiation dose, number of draining veins and patient age.

Cerebral Arteriovenous Malformations as Acquired Lesions: Case Reports and Review of the Literature.

Cerebral arteriovenous malformations (AVMs) are generally attributed to congenital lesions that arise from aberrant vasculogenesis between the fourth and eighth weeks of embryonic life. However, this dogma has been challenged by several recent observations, one of which is de novo formation of AVMs. Forty cases of de novo AVMs were published between 2000 and 2019, all of which involved a history of intracranial insult, such as vascular abnormalities or nonvascular conditions, prior to AVM diagnosis. We hereby present two unique operative cases of ruptured de novo AVMs in older adult patients. Case 1 is novel in the sense that the patient did not experience any kind of environmental trigger ("second hit") such as a previous intracranial insult, while Case 2 serves as the second report of a de novo AVM patient with a medical history of Bell's palsy. Although the exact mechanisms of AVM formation remain to be elucidated, it is likely to be a multifactorial process related to environmental and hemodynamic factors.

R2eD AVM Score.

Background and Purpose- The management of unruptured brain arteriovenous malformations remains unclear. Using a large cohort to determine risk factors predictive of hemorrhagic presentation of arteriovenous malformations, this study aims to develop a predictive tool that could guide hemorrhage risk stratification. Methods- A database of 789 arteriovenous malformation patients presenting to our institution between 1990 and 2017 was used. A hold-out method of model validation was used, whereby the data was randomly split in half into training and validation data sets. Factors significant at the univariable level in the training data set were used to construct a model based on multivariable logistic regression. Model performance was assessed using receiver operating curves on the training, validation, and complete data sets. The predictors and the complete data set were then used to derive a risk prediction formula and a practical scoring system, where every risk factor was worth 1 point except race, which was worth 2 points (total score varies from 0 to 6). The factors are summarized by R2eD arteriovenous malformation (acronym: R2eD AVM). Results- In 755 patients with complete data, 272 (36%) presented with hemorrhage. From the training data set, a model was derived containing the following risk factors: nonwhite race (odds ratio [OR]=1.8; P=0.02), small nidus size (OR=1.47; P=0.14), deep location (OR=2.3; P<0.01), single arterial feeder (OR=2.24; P<0.01), and exclusive deep venous drainage (OR=2.07; P=0.02). Area under the curve from receiver operating curve analysis was 0.702, 0.698, and 0.685 for the training, validation, and complete data sets, respectively. In the entire study population, the predicted probability of hemorrhagic presentation increased in a stepwise manner from 16% for patients with no risk factors (score of 0) to 78% for patients having all the risk factors (score of 6). Conclusions- The final model derived from this study can be used as a predictive tool that supplements clinical judgment and aids in patient counseling.

Brain functional organization and structure in patients with arteriovenous malformations.

PURPOSE: Developmental in nature, brain arteriovenous malformations (AVM) have the potential to affect whole brain organization. Here we investigated the impact of AVM on functional and structural brain organization using resting-state functional MRI (rsfMRI) and cortical thickness measures. METHODS: We investigated brain functional organization and structure using rsfMRI in conjunction with cortical thickness analyses in 23 patients with cerebral arteriovenous malformations (AVMs) and 20 healthy control subjects. RESULTS: Healthy controls showed the expected anti-correlation between activity in the default mode network (DMN) and frontal areas that are part of the attentional control network. By contrast, patients demonstrated a disruption of this anti-correlation. Disruptions to this anti-correlation were even observed in a subgroup of patients with lesions remote from the main nodes of the DMN and were unrelated to differences in perfusion. Functional connectivity differences were accompanied by reduced cortical thickness in frontal attentional areas in patients compared to the controls. CONCLUSIONS: These results contribute to the discussion that AVMs affect whole brain networks and not simply the area surrounding the lesion.

Development of a Psychiatric Disorder Linked to Cerebellar Lesions.

Cerebellar dysfunction plays a critical role in neurodevelopmental disorders with long-term behavioral and neuropsychiatric symptoms. A 43-year-old woman with a cerebellum arteriovenous malformation and history of behavioral dysregulation since childhood is described. After the rupture of the cerebellar malformation in adulthood, her behavior morphed into specific psychiatric symptoms and cognitive deficits occurred. The neuropsychological assessment evidenced impaired performance in attention, visuospatial, memory, and language domains. Moreover, psychiatric assessment indicated a borderline personality disorder. Brain MRI examination detected macroscopic abnormalities in the cerebellar posterior lobules VI, VIIa (Crus I), and IX, and in the posterior area of the vermis, regions usually involved in cognitive and emotional processing. The described patient suffered from cognitive and behavioral symptoms that are part of the cerebellar cognitive affective syndrome. This case supports the hypothesis of a cerebellar role in personality disorders emphasizing the importance of also examining the cerebellum in the presence of behavioral disturbances in children and adults.

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

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

Spontaneous Cystic Arteriovenous Malformation-A Novel Treatment Alternative.

BACKGROUND: Brain arteriovenous malformation (BAVM) is a life-threatening vascular congenital malformation due to the risk of intracerebral hemorrhage. The formation of a spontaneous cyst within a BAVM, without history of hemorrhage or gamma knife surgery, is rare and has an unknown pathophysiology. We suggest a novel theory of spontaneous cystic BAVM formation, subsequently treated with endovascular embolization followed by surgery with a favorable long-term outcome. METHODS: Review of the literature using PUBMED database and comparison between clinical presentation, diagnostic imaging studies, and treatment options. RESULTS: The high flow causing a shear stress over the drainage vein may be responsible for venous ectasia and thus incrementing hydrostatic intranidal pressure causing a serous effusion that develops into a pseudocyst. We hypothesize that hemodynamic factors may be responsible for both origin and growth of such cystic lesions. CONCLUSIONS: Endovascular treatment allowed us to achieve cyst volume reduction by managing its unique flow characteristics. To our knowledge, this is the first case report of combined treatment with endovascular and surgical approach of a cystic BAVM.

Subsequent haemorrhage in children with untreated brain arteriovenous malformation: Higher risk with unbalanced inflow and outflow angioarchitecture.

OBJECTIVES: Children with brain arteriovenous malformations (bAVMs) are at risk of life-threatening haemorrhage in their early lives. Our aim was to analyse various angioarchitectural features of bAVM to predict the risk of subsequent haemorrhage during follow-up in children. METHODS: We identified all consecutive children admitted to our institution for bAVMs between July 2009 and September 2015. Children with at least 1 month of treatment-free follow-up after diagnosis were included in further analysis. Annual rates of AVM rupture as well as several potential risk factors for subsequent haemorrhage were analysed using Kaplan-Meier analyses and Cox proportional hazards regression models. RESULTS: We identified 110 paediatric patients with a mean follow-up period of 2.1 years (range, 1 month-15.4 years). The average annual risk of haemorrhage from untreated AVMs was 4.3 % in children. No generalised venous ectasia in conjunction with fast arteriovenous shunt was predictive of subsequent haemorrhage (RR, 7.55; 95 % CI 1.96-29.06). The annual rupture risk was 11.1 % in bAVMs without generalised venous ectasia but with fast arteriovenous shunt. CONCLUSIONS: bAVM angiographic features suggesting unbalanced inflow and outflow might be helpful to identify children at higher risk for future haemorrhage. KEY POINTS: • Haemorrhage risk stratification is important for children with untreated brain AVM. • Angiographic features suggesting unbalanced inflow and outflow predict paediatric brain AVM haemorrhage. • Identifying AVMs with high rupture risk help patient selection and tailoring treatment.

Constitutively active Notch4 receptor elicits brain arteriovenous malformations through enlargement of capillary-like vessels.

Arteriovenous (AV) malformation (AVM) is a devastating condition characterized by focal lesions of enlarged, tangled vessels that shunt blood from arteries directly to veins. AVMs can form anywhere in the body and can cause debilitating ischemia and life-threatening hemorrhagic stroke. The mechanisms that underlie AVM formation remain poorly understood. Here, we examined the cellular and hemodynamic changes at the earliest stages of brain AVM formation by time-lapse two-photon imaging through cranial windows of mice expressing constitutively active Notch4 (Notch4*). AVMs arose from enlargement of preexisting microvessels with capillary diameter and blood flow and no smooth muscle cell coverage. AV shunting began promptly after Notch4* expression in endothelial cells (ECs), accompanied by increased individual EC areas, rather than increased EC number or proliferation. Alterations in Notch signaling in ECs of all vessels, but not arteries alone, affected AVM formation, suggesting that Notch functions in the microvasculature and/or veins to induce AVM. Increased Notch signaling interfered with the normal biological control of hemodynamics, permitting a positive feedback loop of increasing blood flow and vessel diameter and driving focal AVM growth from AV connections with higher blood velocity at the expense of adjacent AV connections with lower velocity. Endothelial expression of constitutively active Notch1 also led to brain AVMs in mice. Our data shed light on cellular and hemodynamic mechanisms underlying AVM pathogenesis elicited by increased Notch signaling in the endothelium.

Four-dimensional MRI flow examinations in cerebral and extracerebral vessels - ready for clinical routine?

PURPOSE OF REVIEW: To evaluate the feasibility of 4-dimensional (4D) flow MRI for the clinical assessment of cerebral and extracerebral vascular hemodynamics in patients with neurovascular disease. RECENT FINDINGS: 4D flow MRI has been applied in multiple studies to qualitatively and quantitatively study intracranial aneurysm blood flow for potential risk stratification and to assess treatment efficacy of various neurovascular lesions, including intraaneurysmal and parent artery blood flow after flow diverter stent placement and staged embolizations of arteriovenous malformations and vein of Galen aneurysmal malformations. Recently, the technique has been utilized to characterize age-related changes of normal cerebral hemodynamics in healthy individuals over a broad age range. SUMMARY: 4D flow MRI is a useful tool for the noninvasive, volumetric and quantitative hemodynamic assessment of neurovascular disease without the need for gadolinium contrast agents. Further improvements are warranted to overcome technical limitations before broader clinical implementation. Current developments, such as advanced acceleration techniques (parallel imaging and compressed sensing) for faster data acquisition, dual or multiple velocity encoding strategies for more accurate arterial and venous flow quantification, ultrahigh-field strengths to achieve higher spatial resolution and streamlined postprocessing workflow for more efficient and standardized flow analysis, are promising advancements in 4D flow MRI.

Clinical Features of Superficially Located Brain Arteriovenous Malformations with Transdural Arterial Communication.

BACKGROUND: Contrary to deeply located brain arteriovenous malformations (AVMs), superficially located AVMs are more likely to have transdural arterial communications (TACs). However, the clinical and radiologic characteristics of patients presenting with AVMs and TACs are poorly understood. The purpose of this study is to determine whether clinicoradiological features of cerebral AVMs differ according to TAC. METHODS: Between 2002 and 2012, 438 consecutive patients with a brain AVM were treated in our hospital. Among them were 124 patients with superficially located brain AVMs who met the inclusion and exclusion criteria of our study. We retrospectively reviewed the clinicoradiological features of their TACs to explore the variation in characteristics. RESULTS: Thirty-two of the 124 patients with a superficially located AVM (25.8%) had TAC. Radiologic findings of brain AVM images with TAC showed that TAC occurred significantly more frequently among larger AVMs (with vs. without TAC, 11.2 vs. 4.0 ml) and among diffuse AVMs (56.3 vs. 28.3%, p = 0.004). Clinical findings indicate that TAC was associated with chronic headache (43.8 vs. 12.0%, p < 0.001) and older age (43.1 vs. 36.6 years, p = 0.037). CONCLUSIONS: Brain AVM with TAC seems to be accompanied by distinctive clinical features, such as chronic headache and older age. Larger size and diffuseness of the AVM were also associated with TAC. Findings from this study and the prognostic significance of TAC should be further explored in a large prospective study.

Alternatively Activated Macrophages Play an Important Role in Vascular Remodeling and Hemorrhaging in Patients with Brain Arteriovenous Malformation.

BACKGROUND: Angiogenic and immunoactive lesions in brain arteriovenous malformation (BAVM) contribute to hemorrhagic events and the growth of BAVMs. However, the detailed mechanism is unclear. Our objective is to clarify the relationship between hemorrhagic events of BAVM and alternatively activated macrophages in the perinidal dilated capillary network (PDCN). METHODS: We examined microsurgical specimens of BVMs (n = 29) and focused on the PDCN area. Ten autopsied brains without intracranial disease were the controls. We performed immunostaining of the inflammatory and endothelial cell markers, macrophage markers (CD163 and CD68), and vascular endothelial growth factor A (VEGF-A). We evaluated each cell's density and the vessel density in the PDCN and analyzed the relationship to hemorrhagic events of BAVM. RESULTS: The PDCN was involved in all the resected arteriovenous malformations, and these vessels showed a high rate of CD105 expression (72.0 ± 10.64%), indicating newly proliferating vessels. Alternatively activated macrophages were found, with a high rate (85.6%) for all macrophages (controls, 56.6%). In the hemorrhagic cases, the cell density was significantly higher than that in the nonhemorrhagic cases and controls (hemorrhagic group, 290 ± 44 cells/mm(2); nonhemorrhagic group, 180 ± 59 cells/mm(2); and control, 19 ± 8 cells/mm(2)). The cell density of alternatively activated macrophages showed a positive correlation with the vessel density of the PDCN. Double immunostaining showed that VEGF-A was secreted by alternatively activated macrophages. CONCLUSION: Our data suggest that alternatively activated macrophages may have some relationships with angiogenesis of PDCN and hemorrhagic event of BAVM.

Development of Abnormal Hemispheric Vascular Networks Mimicking Cerebral Proliferative Angiopathy in a Child Originally Diagnosed with Deep-Seated Arteriovenous Fistula.

Cerebral proliferative angiopathy (CPA), which is characterized by diffuse vascular abnormalities with intermingled normal brain parenchyma, is a rare clinical entity distinct from classical cerebral arteriovenous malformations. Its pathology at initial state and subsequent course of progression has totally been undetermined. We herein presented a case of a child who was initially diagnosed with deep-seated arteriovenous fistula (AVF), and ultimately developed symptomatic CPA-like vascular lesion over a long period of clinical follow-up. A 7-month-old boy was incidentally found to have an AVF in the right basal ganglia and conservatively followed up. Serial magnetic resonance angiograms revealed the gradual proliferation and enlargement of pial and medullary vessels surrounding the AVF. Seven years later, he had a transient ischemic attack followed by intraventricular hemorrhage. A catheter angiogram showed a diffuse large vascular malformation composed of 2 distinct structures, including AVF in the right basal ganglia and the surrounding proliferated pial and medullary arteries in the right hemisphere. Single-photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine revealed apparent hemodynamic compromise on the right hemisphere. Targeted embolization of the pseudoaneurysm originating from the right A1 perforator was performed to prevent rebleeding without complications. The patient had no further cerebrovascular events. Perinidal hypoperfusion induced by a deep-seated AVF could be one of the underlying pathologies of progressive angiogenic activity. This is the first case showing the development of abnormal hemispheric vascular networks mimicking CPA, which offers insight into the pathogenesis of this new entity.