Arteriovenous Malformations Hemorrhage Research Articles

Expert consensus on multidisciplinary diagnosis and treatment of brain arteriovenous malformation

Brain arteriovenous malformation (BAVM) is a cerebral vasculature disorder caused by gene mutation. Current available treatment measures include surgical resection, interventional embolization and stereotactic radiosurgery. The three therapeutic methods have their own advantages for different vascular structures.However, due to the complex vascular architecture of the lesion and its close anatomical relationship with brain tissue, any single treatment can not safely and effectively treat all BAVM cases. Therefore, in order to better regulate and guide the clinical diagnosis and treatment of BAVM patients in China, the National Medical School for Neurological Diseases, the Professional Committee of Neurointervention of the Chinese Medical Doctor Association and the radio-neurosurgery Expert Committee of the World Chinese Neurosurgeons Association jointly discussed and formulated this expert consensus. After in-depth analysis of the evidence of evidence-based medicine at home and abroad, the expert group combined with the specific situation of China, and gave 33 recommendations on specific clinical diagnosis and treatment issues such as predictive factors of cerebral arteriovenous malformation hemorrhage, clinical risks during pregnancy, imaging diagnosis measures, and clinical treatment strategies, in order to provide guidance for the diagnosis and treatment of BAVM nationwide.

Rupture-Related Features of Cerebral Arteriovenous Malformations and Their Utility in Predicting Hemorrhage.

Evaluating rupture risk in cerebral arteriovenous malformations currently lacks quantitative hemodynamic and angioarchitectural features necessary for predicting subsequent hemorrhage. We aimed to derive rupture-related hemodynamic and angioarchitectural features of arteriovenous malformations and construct an ensemble model for predicting subsequent hemorrhage. This retrospective study included 3 data sets, as follows: training and test data sets comprising consecutive patients with untreated cerebral arteriovenous malformations who were admitted from January 2015 to June 2022 and a validation data set comprising patients with unruptured arteriovenous malformations who received conservative treatment between January 2009 and December 2014. We extracted rupture-related features and developed logistic regression (clinical features), decision tree (hemodynamic features), and support vector machine (angioarchitectural features) models. These 3 models were combined into an ensemble model using a weighted soft-voting strategy. The performance of the models in discriminating ruptured arteriovenous malformations and predicting subsequent hemorrhage was evaluated with confusion matrix-related metrics in the test and validation data sets. A total of 896 patients (mean±SD age, 28±14 years; 404 women) were evaluated, with 632, 158, and 106 patients in the training, test, and validation data sets, respectively. From the training set, 9 clinical, 10 hemodynamic, and 2912 pixel-based angioarchitectural features were extracted. A logistic regression model was built using 4 selected clinical features (age, nidus size, location, and venous aneurysm), whereas a decision-tree model was constructed from 4 hemodynamic features (outflow time, stasis index, cerebral blood flow, and outflow volume ratio). A support vector machine model was designed using 5 pixel-based angioarchitectural features. In the validation data set, the accuracy, sensitivity, specificity, and area under the curve of the ensemble model for predicting subsequent hemorrhages were 0.840, 0.889, 0.823, and 0.911, respectively. The ensemble model incorporating clinical, hemodynamic, and angioarchitectural features showed favorable performance in predicting subsequent hemorrhage of cerebral arteriovenous malformations.

Abstract 116: Increased Collagen I/Collagen III Ratio is Associated With Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse

Background and purpose: Brain arteriovenous malformation (bAVM) is an important risk factor for hemorrhagic stroke in young adults, but the underlying mechanisms are unclear. Increase of Col I/Col III ratio enhances vessel wall stiffness and renders vessel less resistant to changes of blood flow and pressure. Hypothesis: Col I/Col III ratio is increased in bAVM vessels, which is associated with bAVM hemorrhage. Method: Human bAVMs were collected from HHT and sporadic bAVM patients. Temporal lobe specimens from epilepsy patients were used as controls. Three mouse models were used: 1) PdgfbicreER; Alk1 f/f ; 2) PdgfbicreER; Eng f/f ; 3) Alk 1 f/f . Mice in models 1 and 2 have Pdgfb promoter driving, tamoxifen (TM) inducible cre expression in endothelial cells (ECs). BAVMs were induced by intra-brain injection of AAV-VEGF to induce angiogenesis and i.p. injection of TM to delete Alk1 or Eng in ECs. In model 3, bAVMs were by intra-brain injection of AAV-VEGF and an adenoviral vector expressing Cre to delete Alk1 gene focally. Colony stimulating factor receptor inhibitor (PLX5622) was given to Alk1 f/f mice 8 week after model induction when bAVMs have fully developed to transiently deplete microglia. Vascular Col I and Col III levels were analyzed by immunostaining using anti- CD31 and anti-Col I or Col II antibodies. Brain AVM bleeding was detected by Prussian blue staining, and RNA-Sequencing used to study gene profiles. Results: Col I and Col III levels and the Col I/Col III ratio were higher in the vessels of human HHT and sporadic bAVM than controls. Col I/Col III ratio was higher in ruptured than unruptured sporadic bAVM. RNA-seq data shown that Col I and Co III mRNA levels were higher in Eng deficient bAVMs than normal brain angiogenic regions. Col I and Col III levels were higher on Alk1 and Eng deficient bAVMs compared to normal vessels. Col I/Col III ratio was also increased in the Alk1 deficient bAVMs. Depletion of microglia by PLX5622 reduced Col I and Col III levels and reduced microhemorrhage of Alk1 deficient bAVMs. Conclusion: Col I, Col III and Col I/Col III ratio are increased on human and mouse bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I and Col III and hemorrhage in bAVMs in mice.

Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse.

Background: The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. Hypotheses: The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. Method: COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 (n = 7) or endoglin (n = 7) deleted in the endothelial cells or brain focally (n = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. Results: The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. Conclusions: The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.

Third Stereotactic Radiosurgery for Residual Arteriovenous Malformations: A Retrospective Multicenter Study

BACKGROUND AND OBJECTIVES: There are no studies evaluating the efficacy and safety of more than 2 stereotactic radiosurgery (SRS) procedures for cerebral arteriovenous malformations (AVM). The aim of this study was to provide evidence on the role of third single-session SRS for AVM residual. METHODS: This multicenter, retrospective study included patients managed with a third single-session SRS procedure for an AVM residual. The primary study outcome was defined as AVM nidus obliteration without AVM bleeding or symptomatic radiation-induced changes (RIC). Secondary outcomes evaluated were AVM obliteration, AVM hemorrhage, asymptomatic, and symptomatic RIC. RESULTS: Thirty-eight patients (20/38 [52.6%] females, median age at third SRS 34.5 [IQR 20] years) were included. The median clinical follow-up was 46 (IQR 14.8) months, and 17/38 (44.7%) patients achieved favorable outcome. The 3-year and 5-year cumulative probability rates of favorable outcome were 23% (95% CI = 10%-38%) and 53% (95% CI = 29%-73%), respectively. The cumulative probability of AVM obliteration at 3 and 5 years after the third SRS was 23% (95% CI = 10%-37%) and 54% (95% CI = 29%-74%), respectively. AVM bleeding occurred in 2 patients, and 1 of them underwent subsequent resection. The cumulative probability rate of post-SRS AVM hemorrhage remained constant at 5.3% (95% CI = 1%-16%) during the first 5 years of follow-up. Transient symptomatic RIC managed conservatively occurred in 5/38 patients (13.2%) at a median time of 12.5 (IQR 22.5) months from third SRS. Radiation-induced cyst formation was noted in 1 patient (4.2%) 19 months post-SRS. No mortality, radiation-associated malignancy, or permanent symptomatic RIC was noted during follow-up. CONCLUSION: A third single-session SRS to treat a residual intracranial AVM offers obliteration in most patients. The risk of RIC was low, and these effects were transient. While not often required, a third SRS can be performed in patients with persistent residual AVMs.

A Life Threatening Bleeding Arteriovenous Malformation of the Maxilla Complicated with an Acute Cerebral Ischemic Stroke Recovered: Case Report and Review of Literature

Arteriovenous malformation (AVM) of the head and neck is a rare and potentially life-threatening entity due to massive hemorrhage, which poses a challenge to surgeons treating patients with these lesions. The head and neck region accounts for approximately 50% of all arteriovenous malformations (AVM), and the same region also accounts for about approximately 50% of intraosseous AVM in the maxillary facial region, which can be very dangerous, as a simple tooth extraction or a biopsy can lead to a major hemorrhage that may eventually cause death. The Treatment may be surgical or non-surgical. We present the case of a 27-year-old patient with an AVM of the maxilla complicated during his hospitalization for an acute cerebral ischemic stroke, from which he recovered.

The Natural History of Hemorrhage in Brain Arteriovenous Malformations-Poisson Regression Analysis of 1066 Patients in a Single Institution.

Natural history of hemorrhage in brain arteriovenous malformations (bAVM) is reported at 2%-4% per year. Published studies using survival analysis fail to account for recurrent hemorrhagic events. In this study, we present a large, single institution series to elucidate the natural history of bAVM using multivariable Poisson regression. This is a retrospective cohort study. All patients with bAVM seen at our institution from 1990 to 2021 were included. Hemorrhages after detection of bAVM during the untreated interval were recorded. Natural history of hemorrhage was calculated by dividing number of hemorrhages by untreated interval. The frequency of hemorrhages followed a Poisson distribution. Multivariable Poisson regression with an offset variable of untreated interval in patient-years was constructed. Model selection was through a stepwise Akaike information criterion method. Stratified hemorrhagic rate was presented using different combinations of significant factors. A total of 1066 patients with nonhereditary hemorrhagic telangiectasia harboring a single bAVM were included. Ninety (8.44%) patients had 101 hemorrhages during an untreated interval of 3596.3344 patient-years, translating to an overall hemorrhagic rate of 2.81% per year. Significant factors increasing hemorrhage risk included ruptured presentation ( P < .001), increasing age ( P < .001), female sex ( P = .043), and deep location ( P = .040). Adult male patients with ruptured presentation and deep bAVMs sustained the highest annual risk at 10.81%, whereas no hemorrhages occurred in unruptured pediatric male patients or ruptured pediatric (younger than 18 years) male patients with superficial bAVMs. Hemorrhage after bAVM detection occurs in 8.41% of all patients, and the rate averages 2.81% per year. However, this risk varies from 0.00% to 10.81% per year depending on various risk factor combinations. Efforts should be made to stratify bAVM hemorrhage rate by risk factors for more precise estimation of bleeding risk if left untreated.

Role of artificial intelligence and machine learning in the diagnosis of cerebrovascular disease.

Cerebrovascular diseases are known to cause significant morbidity and mortality to the general population. In patients with cerebrovascular disease, prompt clinical evaluation and radiographic interpretation are both essential in optimizing clinical management and in triaging patients for critical and potentially life-saving neurosurgical interventions. With recent advancements in the domains of artificial intelligence (AI) and machine learning (ML), many AI and ML algorithms have been developed to further optimize the diagnosis and subsequent management of cerebrovascular disease. Despite such advances, further studies are needed to substantively evaluate both the diagnostic accuracy and feasibility of these techniques for their application in clinical practice. This review aims to analyze the current use of AI and MI algorithms in the diagnosis of, and clinical decision making for cerebrovascular disease, and to discuss both the feasibility and future applications of utilizing such algorithms. We review the use of AI and ML algorithms to assist clinicians in the diagnosis and management of ischemic stroke, hemorrhagic stroke, intracranial aneurysms, and arteriovenous malformations (AVMs). After identifying the most widely used algorithms, we provide a detailed analysis of the accuracy and effectiveness of these algorithms in practice. The incorporation of AI and ML algorithms for cerebrovascular patients has demonstrated improvements in time to detection of intracranial pathologies such as intracerebral hemorrhage (ICH) and infarcts. For ischemic and hemorrhagic strokes, commercial AI software platforms such as RapidAI and Viz.AI have bene implemented into routine clinical practice at many stroke centers to expedite the detection of infarcts and ICH, respectively. Such algorithms and neural networks have also been analyzed for use in prognostication for such cerebrovascular pathologies. These include predicting outcomes for ischemic stroke patients, hematoma expansion, risk of aneurysm rupture, bleeding of AVMs, and in predicting outcomes following interventions such as risk of occlusion for various endovascular devices. Preliminary analyses have yielded promising sensitivities when AI and ML are used in concert with imaging modalities and a multidisciplinary team of health care providers. The implementation of AI and ML algorithms to supplement clinical practice has conferred a high degree of accuracy, efficiency, and expedited detection in the clinical and radiographic evaluation and management of ischemic and hemorrhagic strokes, AVMs, and aneurysms. Such algorithms have been explored for further purposes of prognostication for these conditions, with promising preliminary results. Further studies should evaluate the longitudinal implementation of such techniques into hospital networks and residency programs to supplement clinical practice, and the extent to which these techniques improve patient care and clinical outcomes in the long-term.

Quantitative evaluation of the subsequent hemorrhage with arteriography-derived hemodynamic features in patients with untreated cerebral arteriovenous malformation.

Patients with untreated cerebral arteriovenous malformations (AVMs) are at risk of intracerebral hemorrhage. However, treatment to prevent AVM hemorrhage carries risks. This study aimed to analyze the AVM nidus-related hemodynamic features and identify the risk factors for subsequent hemorrhage. We retrospectively identified patients with untreated AVMs who were assessed at our institution between March 2010 and March 2021. Patients with ≥6 months of treatment-free and hemorrhage-free follow-up after diagnosed by digital subtraction angiography were included in subsequent examinations. The hemodynamic features were extracted from five contrast flow-related parameter maps. The Kaplan-Meier analyses and Cox proportional hazards regression models were used to find the potential risk factors for subsequent hemorrhage. Overall, 104 patients with a mean follow-up duration of 3.37 years (median, 2.42 years; range, 6-117 months) were included in study, and the annual risk of rupture was 3.7%. Previous rupture (hazard ratio [HR], 4.89; 95% confidence interval [CI], 1.16-20.72), deep AVM location (HR, 4.02; 95% CI, 1.01-15.99), higher cerebral blood volume (HR, 3.35; 95% CI, 1.15-9.74) in the nidus, and higher stasis index (HR, 1.54; 95% CI, 1.06-2.24) in the nidus were associated with subsequent hemorrhage in untreated AVMs. Higher cerebral blood volume and stasis index in the nidus suggest increased blood inflow and stagnant blood drainage. The combination of these factors may cause subsequent hemorrhage of AVMs.

Risk for Brain Arteriovenous Malformation Rupture During Pregnancy and Puerperium.

The hemorrhage risk of unruptured and untreated cerebral arteriovenous malformations (AVMs) has been shown to be higher for female patients than male patients in their child bearing ages. Although it has been neurosurgical practice to advise female patients in their childbearing ages to postpone pregnancy until proven AVM obliteration, there is no literature consensus regarding this potential hemorrhage risk increase. To accurately quantify the risk increase for AVM hemorrhage during pregnancy. This study is based on data from previous publications, consisting of known age at the first AVM hemorrhage in 3425 patients. The risk increase during pregnancy could be calculated from the difference in age distribution for the first AVM hemorrhage between male patients and female patients, taking the average pregnancy time per female into account. A comparison was also made with data for all hospital discharges (13 751) in Germany 2008 to 2018 with the diagnosis brain AVM. The average pregnancy and puerperium time was 1.54 years per female in the patient population, which was used to determine the annual AVM hemorrhage risk during pregnancy to be around 9%. The increased risk during pregnancy was further evidenced by analysis of a subgroup of 105 female patients, for which pregnancy status at the time of hemorrhage was known. The quantified annual risk for AVM hemorrhage during pregnancy is about 3 times higher than that of male patients at corresponding age. This provides an important basis for advising female patients with patent AVMs about the increased risk for hemorrhage that a pregnancy would entail.

Angiographic factors leading to hemorrhage in AVMs: A systematic review and meta-analysis.

For patients with unruptured intracranial arteriovenous malformations (AVMs), the risk of a hemorrhagic event is approximately 2% to 4% annually. These events have an associated 20-50% morbidity and 10% mortality rate. An understanding of risk factors that predispose these lesions to rupture is important for optimal management. We aimed to pool a large cohort of both ruptured and unruptured AVMs from the literature with the goal of identifying angiographic risk factors that contribute to rupture. A systematic review of the literature was conducted in accordance with the PRISMA guidelines using Pubmed, Embase, Scopus, and Web of Science databases. Studies that presented patient-level data from ruptured AVMs from January 1990 to January 2022 were considered for inclusion. The initial screening of 8,304 papers resulted in a quantitative analysis of 25 papers, which identified six angiographic risk factors for AVM rupture. Characteristics that significantly increase the odds of rupture include the presence of aneurysm (OR = 1.45 [1.19, 1.77], p < 0.001, deep location (OR = 3.08 [2.56, 3.70], p < 0.001), infratentorial location (OR = 2.79 [2.08, 3.75], p < 0.001), exclusive deep venous drainage (OR = 2.50 [1.73, 3.61], p < 0.001), single venous drainage (OR = 2.97 [1.93, 4.56], p < 0.001), and nidus size less than 3cm (OR = 2.54 [1.41, 4.57], p = 0.002). Although previous literature has provided insight into AVM rupture risk factors, obscurity still exists regarding which risk factors pose the greatest risk. We have identified six major angiographic risk factors (presence of an aneurysm, deep location, infratentorial location, exclusive deep venous drainage, single venous drainage, and nidus size less than 3cm) that, when identified by a clinician, may help to tailor patient-specific approaches and guide clinical decisions.

Letter: Risk for Hemorrhage the First 2 Years After Gamma Knife Surgery for Arteriovenous Malformations: An Update.

To the Editor: We have read with great interest the article by Karlsson et al1 titled “Risk for Hemorrhage the First 2 Years After Gamma Knife Surgery for Arteriovenous Malformations: An Update.” The premise of this study was based on the findings of a 2001 study that demonstrated the risk of hemorrhage after gamma knife surgery (GKS) for arteriovenous malformations (AVMs) to be strongly correlated with large AVM size, older age, and lower therapeutic dose.2 However, contradictory data collected 17 years later revealed the risk of hemorrhage was not related to AVM size or patient age.3 To clearly define predictors of hemorrhage, the authors retrospectively reviewed the outcome of 5037 patients treated with GKS for AVM.1 The average rate of hemorrhage was determined to be 2.4%, where larger AVM size, older age, and lower therapeutic dose served as significant (P < .01) risk factors, consistent with findings from the original study.1,2 AVM location (P = .16), embolization (P = .27), and history of pre-GKS hemorrhage (P = .20) were found to be nonsignificant predictors for post-GKS hemorrhage.1 The identification of clear hemorrhage risk factors after GKS for AVM in this large, heterogeneous cohort provides clinicians with more concrete guidelines for AVM management.1 The clinical management of cerebral AVMs remains challenging due to AVM heterogeneity in size, biological composition, anatomic location, and associated symptoms.4 Thus, the treatment of AVMs to reduce hemorrhage risk must be conducted in an individualized manner specific to patient presentation and AVM profile. Although no formal guidelines exist regarding treatment of unruptured AVMs, a landmark randomized trial of unruptured brain arteriovenous malformations (trial) revealed the superiority of medical management compared with interventional therapy.5 Interventional therapy was associated with an increased risk of stroke or death as compared with medical management alone (P < .0001; hazard ratio 3.70; 95% CI 1.85–7.14).5 Five-year follow-up data confirmed these findings.6 With this understanding, along with identifying general risk factors and prevalence rates of AVM hemorrhage after GKS, it would be valuable to investigate the impact of hemorrhage on mortality and morbidity in this cohort of patients undergoing interventional therapy. Doing so, while controlling for confounding variables, such as the Spetzler-Martin grade, AVM nidus morphology or location, would be clinically significant and aid in deciding which patients would truly benefit from GKS. Hemorrhage is the leading cause of morbidity and mortality associated with AVMs.7 Consequently, common symptoms of AVM-related hemorrhage such as seizures and headaches severely impair quality of life (QOL).8,9 While it can be hypothesized that post-GKS AVM hemorrhage would have profound implications for QOL outcomes, there are no reports in the literature detailing this relationship. Future studies should investigate the impact of post-GKS hemorrhage on QOL metrics, especially as GKS continues to improve and be used for more complex disease. This study by Karlsson et al1 provides a strong foundation for the future investigation of invaluable QOL metrics to guide medical decision-making in a manner that targets patient-specific QOL discrepancies while bridging this apparent gap in the literature.

Anaesthetic management of parturient posted for elective caesarean section with cerebral arteriovenous malformation

Sir, Cerebral arteriovenous malformation (AVM) has a prevalence of 0.01–0.05%.[1] We present a case of a 25-year-old primigravida at 37 weeks gestation, a known case of left frontoparietal AVM and epilepsy posted for elective cesarean section. Five years ago, she presented with weakness of the right upper and lower limbs. She was diagnosed with left frontoparietal AVM [Figures 1 and 2]. She had multiple seizure episodes and was started on T. levetiracetam 500 mg BD, T. lacosamide 200 mg BD, T. clobazam 10 mg BD, and T. phenytoin 100 mg OD.Figure 1: MR venogram showing large draining veins joining superior sagittal sinusFigure 2: MRI of the brain showing numerous flow voids along the left frontoparietal lobe and atrophy of neuroparenchyma in the left cerebral hemisphereA pre-anesthetic evaluation was done. She gave a history of seizure attacks 4 days back. She was premedicated with oral pantoprazole 40 mg and metoclopramide 10 mg 1 h before surgery and kept nil per oral for 6 h. All antiepileptic drugs were continued. In the operating room, the wedge was placed under her right hip. Standard pre-induction monitors were attached and intravenous (IV) access was secured. The cesarean section was done under general anesthesia. Rapid sequence induction was performed with IV thiopentone 5 mg/kg and rocuronium 1.2 mg/kg. The patient was intubated with a 7 mm internal diameter endotracheal tube after 1 min. Anesthesia was maintained with oxygen, air, and isoflurane. After delivery of a live female baby of 2.2 kg, IV fentanyl 2 mg/kg, midazolam 2 mg, ondansetron 4 mg, and oxytocin infusion were given. The patient was hemodynamically stable and the postoperative pain was managed with an ultrasound-guided bilateral transverses abdominis plane block. The parturient was extubated and shifted to the intensive care unit (ICU). She had an uneventful postoperative period. Cerebral AVM usually presents with intracranial hemorrhage, seizures, focal neurologic deficits, and headaches.[2] The symptoms of AVM may be mistaken with pregnancy-associated disorders such as eclampsia. computed tomography (CT) and magnetic resonance imaging (MRI) (with abdomen shielding) help to confirm the diagnosis. It is mandatory to document the neurological deficits, optimize antiepileptics, counsel regarding the potential complications, and the need for neurosurgery. The neurosurgeon and intervention radiologist were alerted regarding the patient’s delivery plan and the neurologist’s opinion was taken to optimize the antiepileptics. There are no conclusive data regarding the risk of AVM hemorrhage during pregnancy.[3,4] AVM hemorrhage during pregnancy is associated with 28% maternal and 14% neonatal mortality. Most centers prefer elective cesarean sections even though normal vaginal deliveries do not increase the risk of AVM hemorrhage. Uterine contractions during normal labor may increase the stress on the abnormal veins. Hence, if vaginal delivery is planned, epidural labor analgesia and assisted instrumental vaginal delivery are recommended. For cesarean section, general anesthesia is preferred over regional anesthesia to avoid neurological complications. cerebrospinal fluid (CSF) release with subarachnoid block causes a sudden change in the transmural pressure across the AVM predisposing it to rupture. An accidental intravascular injection of local anesthetic containing epinephrine test dose during the initiation of the test dose following epidural anesthesia could predispose to the rupture of AVM. The main aim of anesthetic management is to maintain the mean arterial and intracranial pressure within the normal range to reduce the risk of hemorrhage and cerebral hypoperfusion. Hypertensive responses to laryngoscopy and extubation should be obtunded. Thiopentone is the preferred induction agent.[5] Ketamine is avoided as it can increase blood pressure and intracranial pressure. Suxamethonium has to be avoided and a high dose of rocuronium 1.2 mg/kg is used for rapid sequence induction.[6] General anesthesia with controlled ventilation is used to keep PaCO2 at a low normal range to minimize cerebral vasodilatation and rise in intracranial pressure. Hypotension during surgery is avoided by optimal fluid resuscitation and vasopressors. Supine hypotension is avoided by the use of a wedge under the hip. Thus, multi-disciplinary care involving an obstetrician, intervention radiologist, neurologist, neurosurgeon, and obstetric anesthesiologist is required to ensure good pregnancy outcomes in these high-risk parturients. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Pituitary macroadenoma causing vision loss in Wyburn-Mason syndrome: illustrative case.

Wyburn-Mason syndrome (WMS) is a neurocutaneous disorder consisting of vascular malformations of the brain, eye, and skin. These include characteristically high-flow intracranial and intraorbital arteriovenous malformations (AVMs) that present commonly with visual deterioration, headache, and hemiplegia. Complete removal of these lesions is challenging. Most patients are followed closely, and intervention occurs only in the setting of worsening symptoms secondary to AVM growth or hemorrhage. Here the authors present the first known case of a patient with WMS and a pituitary macroadenoma. A 62-year-old man with a 30-year history of WMS with right basal ganglia and orbital AVMs and right eye blindness presented for new-onset left-sided vision loss. A pituitary adenoma was identified compressing the optic chiasm and left optic nerve. Magnetic resonance imaging and digital subtraction angiography studies were obtained for surgical planning, and the patient underwent an endoscopic transnasal transsphenoidal resection, with significant postoperative vision improvement. Given the variable presentation and poor characterization of this rare syndrome, patients with WMS presenting with new symptoms must undergo evaluation for growth and hemorrhage of known AVMs, as well as new lesions. Further, in patients undergoing intracranial surgery, extensive preoperative imaging and planning are crucial for safe and successful procedures.

Vessel wall imaging and quantitative flow assessment in arteriovenous malformations: A feasibility study.

Cerebral arteriovenous malformations (AVMs) carry a rupture rate of 2-3% per year. Several architectural factors may influence rupture rate, and a recently theorized model of AVMs describes the influence of vessel wall inflammation. A novel imaging modality, vessel wall imaging (VWI), has been developed to view inflammatory processes in vessel wall foci but has not yet been examined in AVMs, which is the aim of this study. This retrospective review studies prospectively collected data on patients with ruptured and unruptured AVMs between 2019 and 2021. Inclusion criteria included adult patients (≥18 years) with radiographically diagnosed AVM who underwent VWI. Charts were reviewed for medical history, clinical presentation, hospital course, discharge condition, and follow-up. Angioarchitectural features, blood flow, and VWI were compared in patients with and without hemorrhagic patients. Nine patients underwent VWI, mean age 37.7 ± 9.9 years. Four presented with hemorrhage (44.4%). Seven (77.7%) received glue embolization and 6 (66.7%) underwent surgical resection. All patients (4/4) with a history of hypertension presented with hemorrhage (p = 0.0027). Size and Spetzler-Martin grade were not associated with hemorrhage (p = 0.47, p = 0.59). Net AVM flow was higher in patients presenting with hemorrhage, although nonsignificant (p = 0.19). With VWI, 3 (75%) hemorrhagic AVMs showed visible nidus and draining veins, and all three demonstrated positive post-contrast wall enhancement in at least one of their draining veins; conversely, of fivenonhemorrhagic AVMs, only 2 (40%) demonstrated post-contrast wall enhancement in any draining vein (p = 0.090). This pilot study successfully demonstrated capture of venous walls in AVMs using VWI. In this study, draining vein enhancement occurred more often in hemorrhagic AVM and in those with higher venous volumetric flow.

Long-term follow-up of an overexposure radiation incident in a cohort treated with linear accelerator-based stereotactic radiosurgery for intracranial arteriovenous malformations.

Dosimetric radiosurgery incidents are rare and probably insufficiently reported in scientific publications. After a long follow-up (FU), the authors studied the outcomes of patients treated with overexposure radiation for arteriovenous malformation (AVM) administered via stereotactic radiosurgery (SRS) at their department. Between May 2006 and June 2007, 22 patients were treated for AVM with SRS. The mean (range) patient age was 43.5 (11.8-78) years. Previous treatments were embolization (n = 10), SRS (1), and surgery (1). The average (range) volume was 2.1 (0.2-6.4) cm3. The median prescribed minimal dose was 18.0 Gy. An initial error in the estimation of scatter factors led to overexposure to radiation. Due to this incident, the median delivered minimum dose was 25.0 Gy. All patients were prospectively followed with clinical examination and imaging. The mean (range) clinical FU was 14.5 (12.0-15.2) years. AVM obliteration after SRS was completed in 90.9% of patients at a mean (range) of 39.4 (24.4-70.4) months. No patient had post-SRS AVM bleeding. Three patients (13.6%) had new permanent deficits due to radiation-induced changes (RICs). Obliteration without new deficits was achieved in 18 patients (81.8%). Two patients had new epilepsy that was probably due to RIC but well controlled. The median (range) MRI FU was 13.8 (2.5-14.9) years. During MRI FU, two RIC periods were observed: one classic period during the first 3 years showed T1-weighted annular irregular enhancement (13%), and the other period between 5 and 15 years after SRS showed the occurrence of cystic and hemorrhagic lesions (22.7%). There were no cases of radiation-induced tumor. The present long-term report showed that this overexposure incident probably increased the AVM obliteration rate. This overexposure seems to have induced RIC and in particular a higher rate of cystic and hemorrhagic late lesions with nevertheless moderate clinical consequences. Long-term FU for AVM is mandatory due to the risk of late RIC.

Arteriovenous Malformation Hemorrhage in Pregnancy: A Systematic Review and Meta-Analysis.

Hemorrhage of arteriovenous malformation (AVM) is a rare condition during pregnancy. This study was proposed to pool the proportion of AVM hemorrhage per pregnancy. A systematic review and meta-analysis with three databases were performed to review the studies published until April 2022. The Newcastle Ottawa Scale was used for risk assessment of data quality. The meta-analysis was conducted by a generic inverse variance of double arcsine transformation with a random model using Stata software. Twelve studies were included in this review. The pooled proportion of AVM hemorrhage per pregnancy was 0.16 (95% CI: 0.08, 0.26). The subgroup analyses were carried out based on world regions and study designs, and the study duration with the highest proportion of each subgroup was Europe [0.35 (95% CI: 0.02, 0.79)], with retrospective review [0.18 (95% CI: 007, 0.32)] and 10 to 20 years of study duration [0.37 (95% CI: 0.06, 0.77)]. The AVM hemorrhage per pregnancy in this review was considered low. However, the conclusion must be carefully interpreted since this review had a small study limitation.

Risk for Hemorrhage the First 2 Years After Gamma Knife Surgery for Arteriovenous Malformations: An Update.

Knowledge about the natural course of brain arteriovenous malformations (AVMs) have increased during the past 20 years, as has the number of AVMs treated, especially larger ones. It is thus timely to again analyze the risk for hemorrhage after Gamma Knife Surgery (GKS). To confirm or contradict conclusions drawn 20 years ago regarding factors that affect the risk for post-GKS hemorrhage. The outcome after GKS was studied in 5037 AVM patients followed for up to 2 years. The relation between post-treatment hemorrhage rate and a number of patient, AVM, and treatment parameters was analyzed. The results were also compared with the results from our earlier study. The annual post-treatment hemorrhage rate was 2.4% the first 2 years after GKS. Large size, low treatment dose, and old age were independent risk factors for AVM hemorrhage. After having compensated for the factors above, peripheral AVM location and female sex, at least during their child bearing ages, were factors associated with a lower post-GKS hemorrhage rate. Large AVMs (>5 cm 3 ) treated with low doses (≤16 Gy) had higher and small AVMs treated with high doses a lower risk for hemorrhage as compared with untreated AVMs. This was detectable within the first 6 months after GKS. No difference in hemorrhage rate could be detected for the other AVMs. Based on our findings, it is advisable to prescribe >16 Gy to larger AVMs, assuming that the risk for radiation-induced complications can be kept at an acceptable level.

Transvenous embolization of hemorrhagic brain arteriovenous malformations: Case reports and literature review.

IntroductionTransvenous embolization (TVE) has been proven to be safe and feasible as an alternative management of brain arteriovenous malformations (AVMs). We presented four patients with a hemorrhagic brain AVM who underwent TVE and reviewed the relevant literature.MethodsFour patients underwent TVE of a hemorrhagic brain AVM in our center between July 2019 and July 2020. We retrospectively collected and analyzed the clinical and imaging data of these patients and those reported in previously published studies.ResultsFour patients with a hemorrhagic brain AVM were included. Nidus sizes ranged from 0.79 to 2.56 cm. Spetzler-Martin grade ranged from grade II to grade III. The AVM nidus was located in a deep brain region in three patients. One patient underwent TVE alone and three underwent combined transarterial and transvenous approaches. Digital subtraction angiography (DSA) demonstrated complete obliteration of the vascular malformation after embolization in all four patients. Three patients were independent [modified Rankin Scale (mRS) score ≤ 2] at discharge. All four patients were independent at the last follow-up. AVM obliteration was confirmed in all four patients at the last angiographic follow-up.ConclusionTransvenous embolization can be used as an alternative treatment for contemporary management of brain AVMs, appropriate patient selection is essential to achieve a good clinical outcome.

Interventional outcomes for patients eligible for entry into the ARUBA clinical trial: a systematic review and meta-analysis.

A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) suggested that medical management afforded outcomes superior to those following intervention for unruptured arteriovenous malformations (AVMs), but its findings have been controversial. Subsequent studies of AVMs that would have met the eligibility requirements of ARUBA have supported intervention for the management of some cases. The present meta-analysis was conducted with the object of summarizing interventional outcomes for ARUBA-eligible patients reported in the literature. A systematic literature search (PubMed, Web of Science, Google Scholar) for AVM intervention studies that used inclusion criteria identical to those of ARUBA (age ≥ 18 years, no history of AVM hemorrhage, no prior intervention) was performed. The primary outcome was death or symptomatic stroke. Secondary outcomes included AVM obliteration, hemorrhage, death, and poor outcome (modified Rankin Scale score ≥ 2 at final follow-up). Bias assessment was performed with the Newcastle-Ottawa Scale, and the results were synthesized as pooled proportions. Of the 343 articles identified through database searches, 13 studies met the inclusion criteria, yielding an overall study cohort of 1909 patients. The primary outcome occurred in 11.2% of patients (pooled = 11%, 95% CI 8%-13%). The rates of AVM obliteration, hemorrhage, poor outcome, and death were 72.7% (pooled = 78%, 95% CI 70%-85%), 8.4% (pooled = 8%, 95% CI 6%-11%), 9.9% (pooled = 10%, 95% CI 7%-13%), and 3.5% (pooled = 2%, 95% CI 1%-4%), respectively. Annualized primary outcome and hemorrhage risks were 1.85 (pooled = 2.05, 95% CI 1.31-2.94) and 1.34 (pooled = 1.41, 95% CI 0.83-2.13) per 100 patient-years, respectively. Intervention for unruptured AVMs affords acceptable outcomes for appropriately selected patients. The risk of hemorrhage following intervention compared favorably to the natural history of unruptured AVMs. The included studies were retrospective and varied in treatment and AVM characteristics, thereby limiting the generalizability of their data. Future studies from prospective registries may clarify patient, nidus, and intervention selection criteria that will refine the challenging management of patients with unruptured AVMs.