Embolization as stand-alone strategy for pediatric low-grade brain arteriovenous malformations

ObjectivesWe evaluated the safety and efficacy of endovascular embolization as first-line stand-alone strategy for the treatment of low-grade brain arteriovenous malformations (bAVMs) (Spetzler Martin [SM] grade I and II) in pediatric patients. In addition, we assessed the predictors of procedure-related complications and radiographic complete obliteration in a single session.Material and methodsWe conducted a single center retrospective cohort study of all pediatric (≤18 years) patients who underwent embolization as a stand-alone strategy for low-grade bAVMs between 2010 and 2022. Safety was measured by procedure-related complications and mortality. Efficacy was defined as complete angiographic obliteration after the last embolization session.ResultsSixty-eight patients (41 females; median age 14 years) underwent a total of 102 embolization sessions. There were 24 (35%) SM grade I lesions and 44 (65%) grade II. Six procedure-related complications (5.8% of procedures) were observed and no deaths were reported. All the complications were intraoperative nidus ruptures. A single draining vein was the only significant predictor of procedure-related complications (OR=0.10; 95% CI 0.01 – 0.72; p=0.048). Complete angiographic obliteration was achieved in 44 patients (65%). In 35 patients (51%) the bAVM was completely occluded in one session. The bAVM nidal size was a predictor of complete obliteration in one session (OR=0.44; 95% CI, 0.21–0.80; p=0.017).ConclusionEndovascular treatment as a stand-alone strategy for pediatric low-grade bAVMs is an adequate first-line approach in high volume centers with endovascular expertise. Nidal size evaluation is relevant in order to optimize patient selection for embolization as a stand-alone treatment modality.     

Unruptured brain arteriovenous malformations

Cerebral arteriovenous malformations (AVMs) often become symptomatic in young adults with a variety of neurological symptoms such as epileptic seizures, recurrent headaches, progressive neurological deficits or sudden intracranial hemorrhage. However, recent epidemiological data suggest a large number of AVMs are found without signs of hemorrhage and a relatively low rupture risk of less than 1% per year. Continuous technical progress has led to several specific treatment options for brain AVMs including endovascular embolization, microneurosurgery, and stereotactic radiotherapy, either alone or in any combination. Depending on AVM topography and vascular anatomy, interventional treatment strategies have shown successful occlusion rates ranging between 50 and 100% and a relatively low average procedural morbidity of 10% overall. For unruptured brain AVMs, however, the clinical benefit of invasive treatment remains as yet to be determined. To address this issue, A randomized trial of unruptured brain AVMs (ARUBA) is currently underway evaluating long-term outcome of best possible standard interventional therapy as compared to the natural history risk in a prospective multidisciplinary international study (www.arubastudy.org).     

Radiosurgical management of pediatric arteriovenous malformations

Purpose  

Hemorrhage from an arteriovenous malformation (AVM) is the commonest cause of childhood stroke. Management options for children include observation and medical management, surgical resection, endovascular embolization, or stereotactic radiosurgery, alone or in combination.     

Changing role for preoperative embolisation in the management of arteriovenous malformations of the brain

BACKGROUND: The aim of this study was to analyse the results of the use of preoperative embolisation in the management of arteriovenous malformations of the brain at one institution between 1989 and 1999. METHODS: Two hundred and fifty consecutive cases of angiographically confirmed arteriovenous malformations underwent surgery by one surgeon. Cases of dural or spinal arteriovenous malformations have been excluded. Forty-five cases underwent preoperative embolisation. Embolisation was mostly by particulate embolic material delivered 4 to 6 days before the intended surgery. The incidence of embolisation declined from 21 cases of the first 50 arteriovenous malformation cases surgically treated to five in the last 50 cases. For arteriovenous malformations of less than 3 cm, only the first two temporal quintiles had embolised cases; six in the first and three in the second. Outcome was measured by the Modified Rankin Scale. RESULTS: By 12 months (or last follow up, if less than this time has elapsed) following surgery, 1.6% of patients had died, 2.4% had a Modified Rankin scale score of 4 or 5, 6.4% had a Modified Rankin scale score of 3, 8.4% had a Modified Rankin scale score of 2, 14.4% had a Modified Rankin scale score of 1, and 66.8% were without neurological deficit. There was no difference in outcomes in each of the temporal quintiles. The four deaths were related to intraoperative haemorrhage, ruptured aneurysm, acute myocardial infarction or unrelated infection. Angiographic cure was achieved in 244 of 246 surviving cases. The two cases with residual arteriovenous malformations underwent focussed irradiation. Permanent morbidity could be attributable to embolisation, intraoperative events (resection functional brain, arteriovenous malformation rupture, aneurysm rupture or myocardial infarction) or postoperative events (arterio-capillary-venous hypertensive syndrome or infection). Of these 29 patients 14 had undergone embolisation. Mortality and major morbidity (Modified Rankin scale score greater than 2 due to treatment) occurred in 8.8% undergoing embolisation compared with 1.9% not embolised. The cause for major morbidity in these four embolised cases was intraoperative or postoperative haemorrhage. CONCLUSIONS: These results reflect that cases selected for embolisation were those at most risk from intraoperative haemorrhage. Arteriovenous malformations that are less than 3 cm in maximal diameter should only rarely be considered for preoperative embolisation because of their low surgical morbidity. In the presence of a significant deep perforating artery contribution that cannot be effectively embolised the risks of operative haemorrhage is high irrespective of the effectiveness of embolising ancillary non-perforating arteries.     

Treatment of arteriovenous malformations of the brain

Arteriovenous malformations (AVMs) of the brain are complex, congenital, high-flow vascular lesions in which there is a direct fistulous connection between arteries and veins without an intervening capillary bed. Patients commonly present with hemorrhage or seizures. Treatment must take into account the natural history of these lesions and the risks related to their treatment. To date, there have been no prospective, randomized, controlled clinical trials to determine the optimal method of treatment of brain AVMs. However, multiple retrospective analyses of treatment strategies and surgical results in patients with brain AVMs reveal that the management of brain AVMs requires a multimodal, multidisciplinary treatment approach, utilizing surgical resection, endovascular embolization, and/or stereotactic focused-beam radiosurgery.     

Treatment of arteriovenous malformations of the brain

The treatment of ruptured and unruptured brain arteriovenous malformations (AVMs) is driven by the need to prevent incident or recurrent intracranial hemorrhages. Improving feasibility of the rapidly developing endovascular, neurosurgical, and radiotherapeutic procedures leads to invasive treatment of an increasing number of neurologically intact patients with accidentally diagnosed AVMs. Recent data confirm that the natural history risk of unruptured AVMs is significantly lower than the risk of those presenting with rupture, and the treatment risk of invasive management of unruptured AVMs seems higher than their natural history risk. The treatment decision algorithm for these patients remains unsettled, as no randomized clinical trial data exist on the benefit of invasive AVM treatment for patients with bled or with unbled AVMs. The recently launched study A Randomized Trial of Unruptured Brain AVMs (ARUBA) will be the first trial randomizing patients with nonhemorrhaged AVMs to invasive versus conservative management.     

Angiographically occult arteriovenous malformations of the brain

Six patients with cerebral arteriovenous malformations which did not show any pathological circulation at angiography are described. Computed tomogram appearances of such lesions may be difficult to distinguish from tumours. The need for surgical exploration in localised high attenuation lesions of uncertain nature is stressed, and the literature is reviewed.     

Surgical management of pediatric cerebral arteriovenous malformations

Background  

Arteriovenous malformations (AVMs) are the most common cause of intracerebral hemorrhage in children. Different options exist for their successful management consisting of surgery, endovascular embolization, stereotactic radiosurgery, or a combination of these treatments.     

Radiosurgery of brain arteriovenous malformations in children

OBJECTIVE : The authors describe their experience in treating 22 children with a single brain arteriovenous malformation (bAVM) using a dedicated LINAC stereotactic radiosurgery unit. METHODS : The findings of 22 consecutive patients < or = 18 years of age who underwent radiosurgery for a single bAVM and with at least 24 months of follow-up, or earlier proven obliteration,were reviewed. The median age at radiosurgery was 13.8 years,with a hemorrhagic presentation in 86%. Median bAVM-volume was 1.8 ml, with a median prescribed marginal dose of 19.0 Gy. RESULTS : The crude complete obliteration-rate was 68% (n = 15) after a median follow-up of 24 months. The actuarial obliteration- rate was 45 % after two years and 64 % after three years. Patients with a radiosurgery-based AVM score < or = 1 more frequently had an excellent outcome than patients with a bAVM score > 1 (71% vs. 20%, P = 0.12), as well as an increased obliteration rate (P = 0.03) One patient died from a bAVM-related hemorrhage 27 months after radiosurgery, representing a postradiosurgery hemorrhage rate of 1.3%/year for the complete followup interval. Overall outcome was good to excellent in 68% (n = 15). Radiation-induced changes on MR imaging were seen in 36% (n = 8) after a median interval of 12.5 months, resulting in deterioration of pre-existing neurological symptoms in one patient. CONCLUSIONS : Radiosurgery is a relatively effective, minimally invasive treatment for small bAVMs in children. The rebleeding rate is low, provided that known predilection places for bleeding had been endovascularly eliminated.Our overall results compare unfavourably to recent pediatric microsurgical series, although comparison between series remains imprecise. Nevertheless, when treatment is indicated in a child with a bAVM that is amenable to both microsurgery or radiosurgery, microsurgery should carefully be advocated over radiosurgery, because of its immediate risk reduction.     

Treatment of deep brain arteriovenous malformations

BACKGROUND AND PURPOSE: The results of the treatment of patients with deep, supratentorial arteriovenous malformations (AVMs) located in medial hemisphere or intraventricularly are presented. MATERIAL AND METHODS: The paper presents the results of treatment of 17 patients. AVMs were located in the trigonum of the lateral ventricle in 4 cases (23.5%), in the splenium of the corpus callosum and its neighborhood in 4 cases (23.5%), in the parahippocampal and lingual gyrus in 3 cases (17%), in the head of the caudate nucleus in 2 cases (12%), in the hippocampus and the nucleus amygdalae in 2 cases (12%), in the anterior part of the gyrus cinguli in 1 case (6%) and in the truncus of the corpus callosum in 1 case (6%). RESULTS: AVMs most often manifested as intracerebral or subarachnoid hemorrhage (82%). The surgical treatment has been applied (total removal--90%), embolization with histoacryl glue (total embolization--20%) and irradiation with LINAC. The surgical treatment was performed in all patients with hemiparesis and intracerebral hematomas. CONCLUSION: The results of the surgical treatment are good and it fastest prevents recurrent hemorrhage from deep AVM. Incomplete embolization of AVM without the surgical treatment or radiosurgery is life threatening for the patients.     

Spontaneous regression of brain arteriovenous malformations

Abstract Objective and importance Complete spontaneous obliteration of a brain arteriovenous malformation (AVM) is a rare event, with 67 angiographically proven cases in the world literature. We present a new case and a systematic literature review to determine possible mechanisms underlying this unusual phenomenon. Clinical presentation One patient with a brain AVM was referred for radiosurgical treatment. Shortly before treatment however, complete spontaneous regression occurred. This patient had experienced a hemorrhage in the months before referral. Results We found 38 articles in which 67 cases of complete and spontaneous regression of a brain AVM were presented. Male to female ratio was 1.2, with a mean age of 37 years (range 1–81). Regression occurred in 72% without new neurological events. Median size of the nidus was 2 cm (range 1–7). There was a single arterial feeder in 46 % and a single draining vein in 59%. Conclusion Spontaneous regression of a brain AVM is the result of multiple interacting factors. Intracranial hemorrhage and the presence of a single draining vein seem to play a major role in this process.     

脑动静脉畸形的介入治疗

应用国产医用真丝段行血管内栓塞治疗脑动静脉畸形33例。所有病例均行选择性全脑血管造影,取得主要供血动脉后,采用Magic1．8F微导管超选择进入大脑前、中动脉直至病灶内。栓塞剂为5／0真丝线段,栓塞至畸形血管团消失或减少。本组栓塞后临床症状改善显著,显示了介入放射学的优越性。     

Interleukin-6 involvement in brain arteriovenous malformations

We recently reported that the GG genotype of the interleukin-6 (IL-6)-174G>C promoter polymorphism is associated with clinical presentation of intracranial hemorrhage in brain arteriovenous malformation (AVM) patients. In this study, we investigated whether tissue IL-6 expression was associated with IL-6-174G>C genotype, and whether IL-6 was linked to downstream targets involved in angiogenesis and vascular instability. Our results showed that the highest IL-6 protein levels in brain AVM tissue were associated with IL-6-174GG genotype (GG: 57.7 +/- 20.2; GC: 35.6 +/- 26.6; CC: 13.9 +/- 10.2pg/mg; p = 0.001). IL-6 protein levels were increased in AVM tissue from patients with hemorrhagic presentation compared with patients without hemorrhage (55 +/- 22 vs 40 +/- 27pg/mg; p = 0.038). IL-6 messenger RNA expression strongly correlated with messenger RNA levels of IL-1beta, tumor necrosis factor-alpha, IL-8, matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-12. We further investigated the plausibility of IL-6 being an upstream cytokine responsible for initiating the angiogenic cascade by cell culture and animal experiments. IL-6 induced MMP-3 and MMP-9 expression and activity in mouse brain and increased proliferation and migration of cerebral endothelial cells. Together, our results suggest that the IL-6 genotype associated with intracranial hemorrhage modulates IL-6 expression in brain AVM tissue, which is consistent with the hypothesis that inflammatory processes induce angiogenic activity possibly contributory to brain AVM intracranial hemorrhage.     

New concepts in adult brain arteriovenous malformations

Brain arteriovenous malformations are currently attracting increasing attention among clinicians as modern brain imaging techniques facilitate both diagnostic and follow-up evaluation. Their frequent presentation in young individuals, at times with flagrant clinical effects caused by cerebral hemorrhages or seizure disorders, keeps clinicians alert to any improvement in treatment strategies. Recent technical advances in surgical, endovascular, and radiation therapy add to the constantly accumulating data on clinical features, natural course, and treatment outcome in adult arteriovenous malformation patients. This review focuses on new concepts in arteriovenous malformation etiology, classification, treatment, and study approaches.     

Stereotactic clipping of arteriovenous malformations of the brain

The authors have developed a new technique for the stereotactic clipping of the feeding vessels of deep-seated arteriovenous malformations (AVM), for use when direct attack may be very dangerous or impossible. A special clipping device and the technique for its application are described. The instrument is introduced through a burr hole using the stereotactic apparatus designed by the authors. The clipping is monitored by intraoperative angiography. The method was used in 32 patients with supratentorial AVMs. It is concluded that in selected cases the method is effective, is less traumatic and gives successful results.     

Stereotactic clipping of arteriovenous malformations of the brain

The authors have developed a new technique for the stereotactic clipping of the feeding vessels of deep-seated arteriovenous malformations (AVM), for use when direct attack may be very dangerous or impossible. A special clipping device and the technique for its application are described. The instrument is introduced through a burr hole using the stereotactic apparatus designed by the authors. The clipping is monitored by intraoperative angiography. The method was used in 32 patients with supratentorial AVMs. It is concluded that in selected cases the method is effective, is less traumatic and gives successful results.     

Management of small arteriovenous malformations of the brain

A consecutive series of arteriovenous malformations of the brain, no greater than 3 cm in diameter, referred to the author between January 1989 and October 1994 is reviewed. Of these 42 cases 39 underwent surgical excision of the lesion. The surgical group had mortality, 2.5% morbidity and 100% angiographic cure. Surgery in non-eloquent brain (n=21) resulted in no neurological morbidity and surgery in eloquent brain (n=18) resulted in a 5.5% neurological morbidity. The reason for not operating in three cases was elderly age in one, poor neurological condition in one, and involvement of the posterior limb of the internal capsule in one. Arteriovenous malformations with diameters no greater than 3 cm are considered by some to be suitable for treatment by focussed irradiation. However, surgery is likely to remain the more effective and safer mode of treatment for the majority of cases when factoring in the expected complications of focussed irradiation during the latency period. These risks are discussed.     

Endothelial cells in the context of brain arteriovenous malformations

A subset of brain arteriovenous malformations (AVM) cannot be treated using today’s treatment paradigms. Novel therapies may be developed, however, as the underlying pathophysiology of these lesions becomes better understood. Endothelial cells (EC) are the subject of new biological therapies, such as radiosensitisation and vascular targeting. This work reviews the current research surrounding EC in the context of brain AVM, including both in vitro and AVM specimen analysis, with a particular focus on the effect of radiation on EC. EC are heterogeneous with no recognised common phenotype, which leads to difficulties in applying the results of the common studies using human umbilical vein endothelial cells to AVM research. Human brain EC are observed to have a high rate of proliferation and also have a reduced apoptotic response to inflammatory mediators such as transforming growth factor-beta. The angiogenic factors vascular endothelial growth factor and endothelin-1 (ET-1) are not normally produced by quiescent brain vasculature, but are produced by AVM EC. Radiation causes EC to separate and become disrupted. Leucocyte and platelet adherence is increased for several days post-irradiation due to increased E-selectin and P-selectin and intercellular adhesion molecule-1 expression. ET-1 is highly expressed in irradiated AVM EC. Radiosurgery produces local radiation-induced changes in EC, which may allow these changes to be harnessed in conjunction with other techniques such as vascular targeting.