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BackgroundChildren with untreated brain arteriovenous malformations (bAVM) are at risk of encountering life-threatening hemorrhage very early in their lives. The primary aim of invasive treatment is to reduce unfavorable outcome associated with a bAVM rupture. A better understanding of the morbidity of bAVM hemorrhage might be helpful for weighing the risks of untreated bAVM and invasive treatment. Our aim was to assess the clinical outcome after bAVM rupture and identify features to predict severe hemorrhage in children.MethodsWe identified all consecutive children admitted to our institution for bAVMs between July 2009 and December 2014. Clinical outcome after hemorrhagic presentation and subsequent hemorrhage was evaluated using the modified Rankin Scale (mRS) for children. The association of demographic characteristics and bAVM morphology with severe hemorrhage (mRS >3 or requiring emergency hematoma evacuation) was studied using univariate and multivariable regression analyses. A nomogram based on multivariable analysis was formulated to predict severe hemorrhage risk for individual patients.ResultsA total of 134 patients were identified with a mean treatment-free follow-up period of 2.1 years. bAVM ruptured in 83 (62%) children: 82 had a hemorrhage at presentation and 6 of them experienced a recurrent hemorrhage during follow-up; 1 patient had other diagnostic symptoms but bled during follow-up. Among them, 49% (41/83) had a severe hemorrhage; emergency hematoma evacuation was required in 28% of them (23/83), and 24% (20/83) remained as disabled (mRS ≥3) at last follow-up. Forty-six percent (38/82) of children with hemorrhagic presentation were severely disabled (mRS >3). Forty-three percent (3/7) were severely disabled after subsequent hemorrhage. The annual rate of severe subsequent hemorrhage was 1% in the overall cohort and 3.3% in children with ruptured presentation. All the subsequent severe hemorrhage events occurred in children with severe hemorrhage history (7%, 3/41). Periventricular location, non-temporal lobe location, and long draining vein were predictors for severe hemorrhage in pediatric untreated bAVMs. A nomogram based on bAVM morphology was contracted to predict severe hemorrhage risk for individual patients, which was well calibrated and had a good discriminative ability (adjusted C-statistic, 0.72).ConclusionsEvaluating bAVM morbidity and morphology might be helpful for weighing the risks of untreated bAVM in pediatric patients.

Arteriovenous malformations (AVMs) are the most common types of cerebral vascular malformations, which are dynamic lesions with de novo growth potentials. The dysfunction of endothelial cells has been postulated to play a role in the pathogenesis of brain AVMs. mTOR-FABP4 signal enhances the angiogenic responses of endothelial cells and is not activated in the normal cerebral vasculature. Herein, we investigated the hypothesis that the mTOR-FABP4 signal may be activated in brain AVMs. The abundance of molecules in mTOR-FABP4 signal expression was detected by immunohistochemistry and Western blotting; special expressing cells were further characterized by double immunofluorescence using antibodies against various cell-specific markers. Next, several functional assays were performed to analyze the influence of the mTOR-FABP4 signal on proliferation, apoptosis, migration, and vascular tube formation of endothelial cells in human umbilical vein endothelial cells (HUVECs) using rapamycin and L-leucine. The expression of mTOR, p-mTOR, and FABP4 was increased in endothelial cells of human brain AVMs. Endothelial cell mTOR and p-mTOR expression were present in 70% and 55% of brain AVMs, respectively. Moreover, a population of FABP4-positive endothelial cells was detected in 80% of brain AVMs. The mTOR-FABP4 signal was activated and inhibited by L-leucine and rapamycin in HUVECs. The proliferation, apoptosis, migration, and vascular tube formation of endothelial cells could be inhibited by rapamycin. The mTOR-FABP4 signal was activated in human brain AVMs, and the mTOR-FABP4 signal was involved in proliferation, apoptosis, migration, and the vascular tube formation of endothelial cells. Taken together, whether rapamycin has therapeutic potential for treating human brain AVMs is worthy of further study. Key messages: We confirmed that the mTOR- FABP4 pathway is activated in human brain arteriovenous malformations. We confirmed that mTOR signaling pathway affects endothelial cell function by regulating proliferation, migration, apoptosis, and tube formation of endothelial cell. Our study can provide theoretical support for mTOR pathway inhibitors in the treatment of human brain arteriovenous malformations. [ABSTRACT FROM AUTHOR]

Comparison in pediatric hemorrhagic arteriovenous malformations (AVMs) to clarify the long-term neurological outcomes and prognostic predictors after surgical intervention was relatively rare, especially in the selection of surgical timing. The objective of this study was to elucidate these points. The authors retrospectively reviewed the pediatric hemorrhagic AVMs resected in their neurosurgical department between March 2010 and June 2017. The natural history was represented by rupture risk. Neurological outcome was assessed with the modified Rankin Scale (mRS) for children. Multivariate logistic regression analyses were used to assess the risk factors for disability (mRS > 2). The hemorrhagic early phase was defined as less than 30 days after bleeding. The corresponding prognosis of different surgical timing (early intervention or delayed intervention) was compared after propensity-score matching (PSM). A total of 111 pediatric hemorrhagic AVM patients were evaluated. The average patient age was 11.1 ± 4.0 years, with a mean follow-up of 4.3 ± 2.1 years. The annualized rupture risk was 9.3% for the pediatric hemorrhagic AVMs, and the annualized re-rupture risk was 9.8%. 7.2% of the patients had disabilities (mRS > 2) and 82.0% achieved neurological deficit-free (mRS < 2) at the last follow-up. Pre-treatment mRS (P = 0.042) and flow-related aneurysms (P = 0.039) were independent factors for long-term disability. In terms of short-term outcomes, early intervention was better than delayed intervention (P = 0.033), but the long-term outcomes were similar between the two groups (P = 0.367). Surgical intervention for pediatric hemorrhagic AVMs is recommended, most of the patients can achieve good neurological outcomes. Moreover, early surgical intervention is preferred after the initial hemorrhage. [ABSTRACT FROM AUTHOR]

Background: More and more elderly patients are being diagnosed with arteriovenous malformation (AVM) in this global aging society, while the treatment strategy remains controversial among these aging population. This study aimed to clarify the long-term outcomes of elderly AVMs after different management modalities. Methods: The authors retrospectively reviewed 71 elderly AVMs (>60 years) in two tertiary neurosurgery centers between 2011 and 2019. Patients were divided into four groups: conservation, microsurgery, embolization, and stereotactic radiosurgery (SRS). The perioperative complications, short-term and long-term neurological outcomes, obliteration rates, annualized rupture risk, and mortality rates were compared among different management modalities in the ruptured and unruptured subgroups. Kaplan-Meier survival analysis was employed to compare the death-free survival rates among different management modalities. Logistic regression analyses were conducted to calculate the odds ratios (ORs) and 95% confidence intervals (CI) for predictors of long-term unfavorable outcomes (mRS > 2). Results: A total of 71 elderly AVMs were followed up for an average of 4.2 ± 2.3 years. Fifty-four (76.1%) presented with hemorrhage, and the preoperative annualized rupture risk was 9.4%. Among these patients, 21 cases (29.6%) received conservative treatment, 30 (42.3%) underwent microsurgical resection, 13 (18.3%) received embolization, and 7 (9.9%) underwent SRS. In the prognostic comparison, the short-term and long-term neurological outcomes were similar between conservation and intervention both in the ruptured and unruptured subgroups (ruptured: p = 0.096, p = 0.904, respectively; unruptured: p = 0.568, p = 0.306, respectively). In the ruptured subgroup, the intervention cannot reduce long-term mortality (p = 0.654) despite the significant reduction of subsequent hemorrhage than conservation (p = 0.014), and the main cause of death in the intervention group was treatment-related complications (five of seven, 71.4%). In the logistic regression analysis, higher admission mRS score (OR 3.070, 95% CI 1.559–6.043, p = 0.001) was the independent predictor of long-term unfavorable outcomes (mRS>2) in the intervention group, while complete obliteration (OR 0.146, 95% CI 0.026–0.828, p = 0.030) was the protective factor. Conclusions: The long-term outcomes of elderly AVMs after different management modalities were similar. Intervention for unruptured elderly AVMs was not recommended. For those ruptured, we should carefully weigh the risk of subsequent hemorrhage and treatment-related complications. Besides, complete obliteration should be pursued once the intervention was initiated. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT04136860 [ABSTRACT FROM AUTHOR]

Background and Purpose: This study sought to identify the efficacy and intraoperative operational details of single-stage combined embolization and microsurgery strategy for Spetzler-Martin (SM) grade III/IV/V arteriovenous malformations (AVMs). Methods: The authors retrospectively reviewed consecutive SM grade III/IV/V AVMs who underwent hybrid procedures and surgical resection alone procedures from January 2016 to February 2018. Outcomes [modified Rankin Scale (mRS)] were compared between hybrid group and surgical resection alone group in ruptured or unruptured subgroup. Factors associated with long-term disability were assessed using multivariable logistic regression analyses. Results: A total of 100 AVM patients (47 corrected using hybrid procedures whereas 53 by surgical resection alone) were evaluated. After a mean follow-up of 2.3 ± 0.6 years, we found no difference in long-term prognosis and incidences of disability rates between these two strategies. However, the hybrid strategy offers significant advantage in accelerating the resection process [ruptured (P = 0.000); unruptured (P = 0.002)]. In the analysis of risk factors, excessive embolization (Grade C, 60–100%) was significantly associated with long-term disability in the hybrid cohorts (P = 0.041; odds ratio, 24.000; 95% CI, 1.140–505.194), and involvement of deep perforating arteries was the significant predictor of long-term disability in the surgical resection alone cohort (P = 0.025; odds ratio, 15.389; 95% CI, 1.412–167.66). In the subgroup analysis of the hybrid cohort, moderate embolization (Grade B, 30–60%) was recommended because of the low risk ratio of major intraoperative bleeding (P = 0.033). Conclusions: Single-stage combined embolization and resection is an efficient strategy for the treatment of SM grade III/IV/V AVMs. Although the long-term outcomes were similar to surgical resection alone, the hybrid strategy had obvious advantages of shorter resection. In the hybrid technique, moderate embolization was recommended, and excessive embolization might be detrimental to the subsequent microsurgical resection. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT04136860. [ABSTRACT FROM AUTHOR]

Background Seizure is the second-most common presentation in patients with arteriovenous malformations (AVMs) and superimposes a significant burden on pediatric patients. Postoperative seizure risk in unruptured AVMs is underreported in the pediatric AVM literature. We aimed to characterize and identify predictive factors for postoperative seizures in this study. Methods We performed a retrospective review of all surgically treated pediatric patients with unruptured AVM at our institution from 2001 to 2014. Patients younger than 18 years of age were included. Baseline variables was compared against our outcome of interest, which was defined as patients with or without follow-up seizures. Multivariable Cox regression was performed to identify potential predictive factors. Results The average age of all patients was 13.1 years, and 68.2% were male. Nine patients were asymptomatic (13.6%), and seizure presentation occurred in 57.6% ( n = 38). During an average follow-up of 4.2 years, 12 (18.2%) patients experienced postoperative seizures, with 5 (17.9%) of 28 patients with seizures being de novo. In patients with seizure presentation, 81.6% were completely seizure-free throughout follow-up. In multivariable analysis, larger AVM size (hazard ratio [HR] 1.63, P = 0.023) and temporal location (HR 8.35, P = 0.007) were found to increase the risk of follow-up seizures. On the contrary, seizure presentation (HR 1.91, P = 0.369) and postoperative infection (HR 2.37, P = 0.265) were not associated. Conclusions Surgery may eliminate most seizures with low risk of inducing de novo seizures in pediatric patients with unruptured AVM. Predictive factors for postoperative seizures included large AVM size and temporal location. For selected unruptured AVMs with small size and nontemporal location, consideration of surgery as primary treatment for persistent seizures is a reasonable option. [ABSTRACT FROM AUTHOR]

Objective We describe our single-center experience treating unruptured brain arteriovenous malformations (uBAVMs) with microsurgical treatment. Methods During a 7-year period, 282 patients with uBAVMs were surgically treated at our institution. Patient clinical features, postsurgical complications, arteriovenous malformation obliteration rate, seizure control, and functional outcome were collected and analyzed. Seizure control was evaluated with the Engel classification system. Patient functional outcome was assessed with modified Rankin Scale score. Results Complete obliteration was achieved in 98.2% of cases. Surgical mortality rate was zero, and overall mortality rate was 1.1%. Good functional outcome (modified Rankin Scale score 0–1) was achieved in 86.9% of all patients, including 92.5% of patients with Spetzler-Martin (S-M) grade I and II uBAVMs, 80.6% of patients with S-M grade III uBAVMs, and 62.5% of patients with S-M grade IV and V uBAVMs. Poor outcome was significantly associated with arteriovenous malformation size ≥6 cm, deep venous drainage, eloquent location, and poor seizure control (all P < 0.05). For 177 patients with presurgical seizures, good seizure outcome (Engel class I) was achieved in 124 (70.1%) patients after microsurgical treatment. A short history of seizure occurrence, fewer presurgical seizures, and generalized tonic-clonic seizure type may be predictors of good seizure outcome (all P < 0.05). Conclusions Good functional outcome can be achieved by microsurgical resection in S-M grade I and II and selected grade III uBAVMs. Surgical resection for high-grade (grade IV and V) uBAVMs is challenging. A high seizure-free rate can be achieved in patients with initial seizure presentation. [ABSTRACT FROM AUTHOR]

Objective We aimed to describe our single-center experience in treating cerebellar arteriovenous malformations (AVMs) with microsurgical resection. Methods During a 16-year period, 181 patients with cerebellar AVMs were surgically treated at the Department of Neurosurgery in Beijing Tiantan Hospital. Patient functional status was evaluated using modified Rankin Scale (mRS) scores both before treatment and at the last follow-up. The mRS scores at the last follow-up were dichotomized as good outcome (mRS <3) and poor outcome (mRS ≥3). The treatment modalities, post-treatment complications, obliteration rate, and follow-up outcomes were analyzed. Results Of the 181 patients, 172 (95%) patients presented with initial hemorrhage and 62 (34%) patients experienced rehemorrhage before microsurgical treatment. Complete obliteration of the AVMs was achieved in 177 (97.8%) patients. Good functional outcome was achieved in 144 (80%) of the patients. The surgical mortality rate was 4.4% (8/181), and overall mortality rate was 6.6% (12/181). Poor outcome was significantly associated with increasing age ( P = 0.035; odds ratio [OR], 1.030; 95% CI 1.002–1.060), presurgical mRS ≥3 ( P = 0.029; OR, 2.563; 95% CI 1.101–5.968), eloquent AVM location ( P = 0.015; OR, 3.058; 95% CI 1.244–7.516), and presurgical rehemorrhage ( P = 0.008; OR, 3.266; 95% CI 1.358–7.858). Conclusion Good outcome can be achieved by microsurgical resection in most patients with cerebellar AVMs. Increasing age at surgery, poor presurgical functional status, eloquent AVM location, and presurgical rehemorrhage are independent predictors of poor outcomes after AVM resection. We recommend early surgical resection for all surgically accessible cerebellar AVMs to prevent subsequent hemorrhage and resultant poor neurologic outcomes. [ABSTRACT FROM AUTHOR]

Objective We aimed to summarize the clinical presentation, risk of hemorrhage, and predictors of posthemorrhage outcome in patients with cerebellar arteriovenous malformations (AVMs). Methods We searched our AVM database at Beijing Tiantan Hospital and identified 225 patients with cerebellar AVMs between the year 2000 and 2015. The clinical presentation and hemorrhage risk were analyzed in all patients. Further analysis of predictors for immediate posthemorrhage outcome was performed in patients with ruptured AVMs. Posthemorrhage modified Rankin Scale (mRS) scores were dichotomized into nonsevere outcome (mRS ≤3) and severe outcome (mRS >3). Univariate and multivariate logistic regression analyses were applied to test the risk factors of hemorrhage and predictors of severe outcome. Results Of the 225 patients, 197 (88%) presented with hemorrhage. Patients with initial hemorrhage were much younger than those with unruptured AVMs (univariate: P = 0.003; multivariate: P = 0.002). Single arterial supply (odds ratio [OR], 2.846; 95% confidence interval [CI], 1.022–7.922) and exclusively deep venous drainage (OR, 3.361; 95% CI, 1.045–10.813) were the other 2 independent risk factors for hemorrhagic presentation. Regarding the neurologic outcome immediately after hemorrhagic presentation, we used 3 models of multivariate logistic regression. Severe neurologic outcome (mRS >3) was associated with eloquent or deep AVM location, associated aneurysm, and the presence of intraventricular hemorrhage (all P < 0.05). Conclusion Cerebellar AVMs have an aggressive nature of hemorrhage. Younger age, single feeding artery, and exclusively deep venous drainage were independent risk factors for hemorrhagic presentation. Eloquent location, associated aneurysm, and presence of intraventricular hemorrhage may predict severe immediate posthemorrhage outcome. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to identify the risk factors for subsequent hemorrhage in patients with untreated cerebellar arteriovenous malformations (AVMs). Methods We searched our AVM database at Beijing Tiantan Hospital and identified 149 patients with cerebellar AVMs who were at least 1 month treatment free after initial diagnosis between 2000 and 2015. The patients were followed up from initial diagnosis until subsequent hemorrhage, initiation of treatment, or the end of 2015. The natural history of cerebellar AVMs was analyzed. Results The overall annual rupture rate was 8.6%, with a mean follow-up period of 4.2 years (range, 1 month to 15 years). The annual rupture rate for previously ruptured AVMs was 10.8% during the whole follow-up period, 12.4% in the first 5 years (18.8% in the first year and 9.0% in the subsequent 4 years) and 6.7% in more than 5 years after initial diagnosis. The overall annual rupture rate for previously unruptured AVMs was 4.0%. Childhood at diagnosis, AVM size ≥3 cm and exclusively deep venous drainage were independent risk factors for subsequent hemorrhage. Previous AVM rupture significantly increased the hemorrhagic risk during the first 5 years but did not significantly affect subsequent hemorrhage thereafter. Conclusions Childhood at diagnosis, large AVM size, and AVMs with exclusively deep venous drainage are independent risk factors for subsequent hemorrhage in patients with cerebellar AVMs. Previous rupture may increase the hemorrhagic risk during the first 5 years after diagnosis but may not significantly increase the risk in the following years. [ABSTRACT FROM AUTHOR]

Objective To explore outcomes after microsurgery of brain arteriovenous malformations (AVMs) that failed to be obliterated by Gamma Knife radiosurgery (GKRS). Methods From January 2000 to January 2014, 42 consecutive patients underwent surgical resection of persistent AVMs after GKRS. These 42 patients with AVMs who underwent radiosurgery (radiosurgery group) were individually matched with 42 patients with AVMs who did not undergo radiosurgery (no radiosurgery group) based on patient and AVM characteristics. The modified Rankin Scale was used to assess neurologic status of patients. The effects of GKRS on AVM resection and surgical outcomes were analyzed. Results After GKRS, the mean AVM volume was significantly reduced by 76.8% ( P < 0.01), the size was reduced by 41% ( P < 0.01), and the Spetzler-Martin grade was reduced in 61.9% of the patients ( P < 0.01). During the time interval from radiosurgery to surgical resection, subsequent hemorrhages led to significant neurologic deterioration ( P = 0.046). Compared with the control group, the frequency of preoperative embolization, operative time, and blood loss were significantly lower in the radiosurgery group (all P < 0.05). The no radiosurgery group had a significantly higher rate of worsening in mRS scores at 6 months after surgery (40.5% vs. 16.7%, P = 0.029). Good neurologic status (mRS score <3) was achieved in 81% of the radiosurgery group and 83% of the no radiosurgery group at the final follow-up evaluation. Conclusions GKRS performed several years before microsurgical resection can facilitate resectability of AVMs and decrease the rate of postoperative neurologic deterioration. For patients with persistent AVMs several years after GKRS, microsurgical resection is recommended to achieve good clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective We reviewed our prospective study of patients with occipital arteriovenous malformations (AVMs) to assess whether the display of optic radiation diffusion tensor imaging (DTI) during neuronavigation-guided surgery can reduce the severity of postoperative visual field deficits (VFDs) and to evaluate the factors associated with visual field preservation. Methods Forty-six consecutive patients with occipital AVMs were randomized in our study. DTI of the optic radiation was displayed during neuronavigation surgery in 24 patients. The other 22 patients were treated surgically without neuronavigation. Modified Rankin Scale (mRS) scores and visual fields were evaluated preoperatively, immediately after surgery, and at the last follow-up. Results The patients' baseline characteristics and AVM features were statistically similar between the 2 surgical groups. The postoperative obliteration rate was 100%. The postoperative mRS scores did not differ between the 2 groups ( P > 0.05). Preexisting VFDs were more common ( P = 0.00004) in patients who bled than in those with unruptured AVMs. The application of DTI-incorporated neuronavigation reduced the frequency and severity of postoperative VFDs ( P = 0.013 and 0.001, respectively). Visual fields were more likely to be preserved in patients with an AVM >5 mm from the optic radiation ( P = 0.025). Conclusions A history of hemorrhage is an independent risk factor for VFDs associated with occipital AVMs. Although not showing superiority in postoperative mRS, functional MRI navigation-guided surgery may help to radically resect occipital AVMs and preserve patient visual fields. A 5-mm distance from the optic radiation may be a suitable safety margin for visual field preservation. [ABSTRACT FROM AUTHOR]