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BackgroundHemorrhage from an arteriovenous malformation of the brain (bAVM) has been associated with focal inflammation of the bAVM. Intrigued by the possibility of anti-inflammatory drug therapy to stabilize bAVMs and prevent hemorrhage, we investigated the association of bAVM inflammation with other histological features and clinical presentation.Materials and methodsTissue samples from 85 surgically treated bAVMs were studied with histology and CD45 immunostainings. The histological data was compared with the clinical history of the patient. Univariate analysis and logistic regression were performed.ResultsInflammation was found in all studied bAVMs and did not associate with rupture (p = 0.442). While multiple types of inflammatory cells were present, macrophages were clearly the dominant inflammatory cell type, especially in samples with strong inflammation (87% of the samples). Of those bAVMs that had strong inflammation, only 56% had presented with clinically evident rupture. However, hemosiderin which is a sign of prior hemorrhage was detected in 78.4% (58/74) of samples with strong inflammation and was associated with it (p = 0.003). Inflammation in the nidus and parenchyma was associated with perivascular inflammation (p < 0.001). Multivariate analysis did not reveal any independent histological or clinical risk factor for inflammation.ConclusionsSince strong inflammation is present in both unruptured and ruptured bAVMs, it is not just a reaction to rupture. Our observations suggest that inflammation of the bAVM may indeed predispose to fragility and hemorrhage of the nidal vessels. Further studies in the role of inflammation in the untreated clinical course of bAVMs are indicated.

Purpose While Ruptured Arteriovenous Malformation Grading Scale (RAGS) has recently been validated in children, the literature lacks validation on adults exclusively. Therefore, we aimed to determine the validity of RAGS on the external multicenter adult cohort and compare its accuracy with other scales. Methods A retrospective analysis was performed in five neurosurgical departments to extract patients who presented with the first episode of acute brain arteriovenous malformation (bAVM) rupture between 2012 and 2019. Standard logistic regression and area under the receiver operating curve (AUROC) calculations were performed to determine the value of the following scales: intracerebral hemorrhage (ICH), AVM-associated ICH (AVICH), Spetzler-Martin (SM), Supplemented SM (Supp-SM), Hunt and Hess (HH), Glasgow Coma Scale (GCS), World Federation of Neurological Surgeons (WFNS), and RAGS to predict change in categorical and dichotomized modified Rankin Scale (mRS) across three follow-up periods: within the 6 months, 6 months to 1 year, and above 1 year. Results Sixty-one individuals with a mean age of 43.6 years were included. The RAGS outperformed other grading scales during all follow-up time frames. It showed AUROC of 0.78, 0.74, and 0.71 at the first 6 months, between 6 and 12 months, and after 12 months of follow-up, respectively, when categorized mRS was applied, while corresponding values were 0.79, 0.76, and 0.73 for dichotomized mRS, respectively. Conclusion The RAGS constitutes a reliable scale predicting clinical outcomes following bAVM rupture among adults. Furthermore, the RAGS proved its generalizability across medical centers with varying treatment preferences.

Background We wanted to understand how patients with different modified Rankin Scale (mRS) grades differ regarding their health-related quality of life (HRQoL) and how this affects the interpretation and dichotomization of the grade. Methods In 2016, all adult patients in our brain arteriovenous malformation (AVM) database ( n  = 432) were asked to fill in mailed letters including a questionnaire about self-sufficiency and lifestyle and the 15D HRQoL questionnaire. The follow-up mRS was defined in 2016 using the electronic patient registry and the questionnaire data. The 15D profiles of each mRS grade were compared to those of the general population and to each other, using ANCOVA with age and sex standardization. Results Patients in mRS 0 (mean 15D score = 0.954 ± 0.060) had significantly better HRQoL than the general population (mean = 0.927 ± 0.028), p  < 0.0001, whereas patients in mRS 1–4 had worse HRQoL than the general population, p  < 0.0001. Patients in mRS 1 (mean = 0.844 ± 0.100) and mRS 2 (mean = 0.838 ± 0.107) had a similar HRQoL. In the recently published AVM research, the most commonly used cut points for mRS dichotomization were between mRS 1 and 2 and between mRS 2 and 3. Conclusions Using 15D, we were able to find significant differences in the HRQoL between mRS 0 and mRS 1 AVM patients, against the recent findings on stroke patients using EQ-5D in their analyses. Although the dichotomization cut point is commonly set between mRS 1 and 2, patients in these grades had a similar HRQoL and a decreased ability to continue their premorbid lifestyle, in contrast to patients in mRS 0.

BackgroundArteriovenous malformations of the brain (bAVM) may rupture from aneurysms or ectasias of the feeding, draining, or nidal vessels. Moreover, they may rupture from the immature, fragile nidal vessels that are characteristic to bAVMs. How the histopathological changes of the nidal vessels associate with clinical presentation and hemorrhage of the lesion is not well known.Materials and methodsWe investigated tissue samples from surgically treated bAVMs (n = 85) using standard histological and immunohistochemical stainings. Histological features were compared with the clinical presentation of the patient.ResultsMicrohemorrhages from nidal vessels were found both in bAVMs with a history of clinically evident rupture and in bAVMs considered unruptured. These microhemorrhages were associated with presence of immature, pathological nidal vessels (p = 0.010) and perivascular inflammation of these vessels (p = 0.001), especially with adhesion of neutrophils (p < 0.001). In multivariate analysis, perivascular inflammation (OR = 19, 95% CI 1.6 to 230), neutrophil infiltration of the vessel wall (OR = 13, 95% CI 1.9 to 94), and rupture status (OR = 0.13, 95% CI 0.017 to 0.92) were significantly associated with microhemorrhages.ConclusionsClinically silent microhemorrhages from nidal vessels seem to be very common in bAVMs, and associate with perivascular inflammation and neutrophil infiltration. Further studies on the role of perivascular inflammation in the clinical course of bAVMs are indicated.

Background Brain arteriovenous malformations (bAVM) may rupture causing disability or death. BAVM vessels are characterized by abnormally high flow that in general triggers expansive vessel remodeling mediated by cyclo-oxygenase-2 (COX2), the target of non-steroidal anti-inflammatory drugs. We investigated whether COX2 is expressed in bAVMs and whether it associates with inflammation and haemorrhage in these lesions. Methods Tissue was obtained from surgery of 139 bAVMs and 21 normal Circle of Willis samples. The samples were studied with immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR). Clinical data was collected from patient records. Results COX2 expression was found in 78% (109/139) of the bAVMs and localized to the vessels’ lumen or medial layer in 70% (95/135) of the bAVMs. Receptors for prostaglandin E2, a COX2-derived mediator of vascular remodeling, were found in the endothelial and smooth muscle cells and perivascular inflammatory cells of bAVMs. COX2 was expressed by infiltrating inflammatory cells and correlated with the extent of inflammation ( r  = .231, p  = .007, Spearman rank correlation). COX2 expression did not associate with haemorrhage. Conclusion COX2 is induced in bAVMs, and possibly participates in the regulation of vessel wall remodelling and ongoing inflammation. Role of COX2 signalling in the pathobiology and clinical course of bAVMs merits further studies.

PurposeTo externally validate the arteriovenous malformation-related intracerebral haemorrhage (AVICH), intracerebral haemorrhage (ICH), and novel haemorrhage presentation risk score (R2eD) in brain arteriovenous malformations.MethodsAdult patients diagnosed radiologically with an arteriovenous malformation (AVM) at a tertiary neurosurgical centre between 2007 and 2018 were eligible for inclusion. Both the AVICH and ICH scores were calculated for AVM-related symptomatic haemorrhage (SH) and compared against the modified Rankin scale (mRS) at discharge and last follow-up, with unfavourable outcome defined as mRS > 2. R2eD scores were stratified based on presentation with SH. External validity was assessed using Harrel’s C-statistic.ResultsTwo hundred fifty patients were included. Mean age at diagnosis was 46.2 years [SD = 16.5]). Eighty-seven patients (34.8%) had a SH, with 83 included in the analysis. Unfavourable mRS outcome was seen in 18 (21.6%) patients at discharge and 18 (21.6%) patients at last follow-up. The AVICH score C-statistic was 0.67 (95% confidence interval [CI], 0.53–0.80) at discharge and 0.70 (95% CI, 0.56–0.84) at last follow-up. The ICH score C-statistic was 0.78 (95% CI 0.67–0.88), at discharge and 0.80 (95% CI 0.69–0.91) at last follow-up. The R2eD score C-statistic for predicting AVM haemorrhage was 0.60 (95% CI, 0.53–0.67).ConclusionsThe AVICH score showed fair-poor performance, while the ICH score showed good-fair performance. The R2eD score demonstrated poor performance, and its clinical utility in predicting AVM haemorrhage remains unclear.

BackgroundFew studies have evaluated the relationship between brain arteriovenous malformations (bAVMs) angioarchitecture and the response to Gamma Knife Stereotactic Radiosurgery (GKSR).MethodsA 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.ResultsData 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.ConclusionsFlow 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.

IntroductionThere is little data on the cost of treating brain arteriovenous malformations (AVMs). The goal of this study then is to identify cost determinants in multimodal management of brain AVMs.MethodsOne hundred forty patients with brain AVMs prospectively enrolled in the UCSF brain AVM registry and treated between 2012 and 2015 were included in the study. Patient and AVM characteristics, treatment type, and length of stay and radiographic evidence of obliteration were collected from the registry. We then calculated the cost of all inpatient and outpatient encounters, interventions, and imaging attributable to the AVM. We used generalized linear models to test whether there was an association between patient and AVM characteristics, treatment type, and cost and length of stay. We tested whether the proportion of patients with radiographic evidence of obliteration differed between treatment modalities using Fisher’s exact test.ResultsThe overall median cost of treatment and interquartile range was $77,865 (49,566–107,448). Surgery with preoperative embolization was the costliest treatment at $91,948 (79,914–140,600), while radiosurgery was the least at $20,917 (13,915–35,583). In multi-predictor analyses, hemorrhage, Spetzler-Martin grade, and treatment type were significant predictors of cost. Patients who had surgery had significantly higher rates of obliteration compared with radiosurgery patients.ConclusionsHemorrhage, AVM grade, and treatment modality are significant cost determinants in AVM management. Surgery with preoperative embolization was the costliest treatment and radiosurgery the least; however, surgical cases had significantly higher rates of obliteration.

Background Studies have questioned the effectiveness of surgery for the management of unruptured brain arteriovenous malformation (ubAVM). Few studies have examined functional outcomes and quality of life (QOL) prior and 12 months after surgical repair of ubAVM. Objective This study examined the effectiveness of surgical management of ubAVM by measuring patients’ perceived QOL and their ability to perform everyday activities. Methods Between 2011 and 2016, patients diagnosed with an unbAVM were assessed using the Quality Metric Short Form 36 (SF36), the DriveSafe component of the off-road driver screening tool DriveSafeDriveAware (DSDA), the modified Barthel Index (mBI) and the modified Rankin Scale (mRS). Reassessments were conducted at the 6-week post-operative follow-up for surgical patients and at 12-month follow-up for surgical and conservatively managed patients. Results Forty-five patients enrolled in the study, of which 35 (78%) had their ubAVM surgically treated. Patients undergoing surgery had a significantly lower ubAVM Spetzler-Ponce Class (SPC). There was no significant difference 12 months after presentation in function or QOL for either the conservative or surgical group. The surgical group had significantly higher QOL of life scores from pre-surgery to 12 months post-surgery (PCS p < 0.01; MCS p = 0.02). Higher SP grade ubAVM was significantly related to poorer function in the surgical group (SP C compared with SP A; p = 0.04, mean difference − 12.4, 95%CI − 24.3 to − 0.4). Conclusion Function and QOL are not diminished after surgical treatment of low Spetzler-Ponce Class unruptured brain arteriovenous malformations. QOL is higher 12 months after surgery for ubAVM than for those who do not have treatment for their ubAVM.

Background Posterior fossa dural arteriovenous fistulas (dAVFs) are rare vascular lesions with variable risk of hemorrhage, mostly depending on the pattern of the venous drainage. While endovascular embolization is the mainstay treatment for most dAVFs, some posterior fossa lesions require a multidisciplinary approach including surgery. The goal of our study was to examine the outcome of an interdisciplinary treatment for posterior fossa dAVFs. Methods A retrospective review of patients treated for posterior fossa dAVFs was conducted. Results A total of 28 patients with a mean age of 57.8 years were included. Patients presented with a Cognard grade I in 2 (7%), II a in 5 (18 %), II b in 7 (25%), II a + b in 5 (18%), III in 3 (11%), and IV in 6 (21%) cases. Hemorrhage was the initial presentation in 2 (22%) patients with Cognard grade IV, in 3 with Cognard grade III (33%), in 1 (11%) with Cognard II a + b, and 3 (33%) with Cognard II b. A complete angiographic cure was achieved in 24 (86%) patients—after a single-session embolization in 16 (57%) patients, multiple embolization sessions in 2 (7%), a multimodal treatment with embolization and surgical disconnection in 3 (11%), and with an upfront surgery in 3 (11%). Complete long-term obliteration was demonstrated in 18/22 (82%) at the mean follow-up of 17 months. Fistulas were converted into asymptomatic Cognard I lesion in 4 (14%) patients. Conclusion Posterior fossa dAVFs represent a challenging vascular pathology; however, despite their complexity, an interdisciplinary treatment can achieve high rates of angiographic and symptomatic cure with low morbidity and mortality rates. Long-term surveillance is warranted as late recurrences may occur.