Small Nidus Research Articles

Abstract TMP86: Stratifying risk of hemorrhage of pedatriac brain arteriovenous malformation using quantitative color-coded digital subtraction angiography and iflow analysis

Background: Pediatric brain arteriovenous malformation (bAVM) patients often present with intracranial hemorrhage. While certain angioarchitectural features, such as aneurysms, deep venous drainage, a single draining vein, venous outflow stenosis, or small nidus size, increase hemorrhage risk, they do not fully predict it. Hemodynamic factors, particularly those assessed by quantitative color-coded digital subtraction angiography (cDSA), have also been linked to hemorrhage risk. This study evaluated the relationship between nidal mean transit time (MTT) and hemorrhage history in pediatric bAVM patients. Methods: We retrospectively analyzed 40 pediatric bAVM patients using flow analysis software (syngo iFlow®; Siemens) to generate cDSA images. A neurointerventional radiologist identified regions of interest (ROIs) in each bAVM’s major arterial afferent and venous efferent. ROI peak time and MTT were obtained. ROI peak time was defined as the time that contrast intensity of the selected ROI reached the peak value and MTT was defined as the difference between venous and arterial peak times. Multivariable logistic regression analysis assessed the association between MTT and prior hemorrhage, adjusting for bAVM size. Results: Among the 40 patients (median age 13 years ; 42.5% female), 47.5% (n=19) had a history of hemorrhage. The median bAVM size was 2.7 cm (IQR: 1.8-4.2), and the median nidal MTT was 0.97 seconds (IQR: 0.79-1.27). In logistic regression analysis, each 0.25-second increase in nidal MTT time was associated with a 24% reduction in the risk of prior hemorrhage (OR=0.76, 95% CI: 0.53-1.08, p=0.122), although not statistically significant. Larger bAVM size was significantly associated with a lower risk of prior hemorrhage (OR=0.48 per cm increase, 95% CI: 0.27-0.87, p=0.014). Conclusion: Our findings suggest that prolonged nidal MTT may be associated with a reduced risk of prior bleeding in pediatric bAVM patients after accounting for bAVM size. Larger bAVM size was significantly associated with a lower likelihood of prior hemorrhage.

Comparison of silent MRA and time-of-flight MRA in the depiction and grading of brain arteriovenous malformations.

Preliminary small-sample studies suggest that silent magnetic resonance angiography (MRA) has an advantage over time-of-flight MRA (TOF MRA) in the characterization of brain arteriovenous malformation (BAVM), but did not examine whether the imaging performance of silent MRA was affected by the intrinsic features of BAVM or common clinical factors. This study sought to compare silent MRA and TOF MRA in terms of the visualization and grading of BAVMs in various clinical settings. In total, 85 participants (50 males, 35 females; mean age: 33.5±15.2 years) with BAVM who underwent both silent MRA and TOF MRA using a 3 Tesla (3T) magnetic resonance imaging (MRI) system were consecutively recruited from the Capital Medical University Xuanwu Hospital between April 2020 and October 2022 to participate in this cross-sectional retrospective study. The patients were divided into subgroups according to new hemorrhage presentation, embolization, size, and nidus compactness. Image quality scoring on a 4-point scale, and the accuracy of characteristic visulization and Spetzler-Martin grading were compared between the two MRA techniques and each MRA subgroup using the rank-sum Wilcoxon test and Fisher's exact test with digital subtraction angiography (DSA) as the reference standard. A multivariable chi-square test was used to examine the interactions between the grouping factors. A P value <0.05 was considered statistically significant. The average image quality scores were significantly higher for silent MRA than those for TOF MRA overall (2.83±0.42 versus 2.46±0.66, P<0.001) and in each subgroup (P<0.05). For silent MRA, the average image quality score for BAVM in each subgroup did not differ significantly (P>0.05). For TOF MRA, the image quality scores for the new hemorrhage, small nidus, and diffuse nidus groups was significantly reduced (P=0.001, <0.001, and 0.037, respectively). The accuracy of silent MRA was significantly better than that of TOF MRA in terms of nidus size and Spetzler-Martin grading (P<0.001), but did not differ significantly in terms of deep venous drainage and associated aneurysm (P=0.402, 0.098, respectively). In relation to silent MRA, the image quality, detection of BAVM characteristics, and grading were similar across the new hemorrhage, embolization, size, and compactness subgroups (P=0.066-0.959). In relation to TOF MRA, the accuracy of nidus size grading was significantly lower in the medium-size subgroup than the small-size subgroup (P<0.001). Silent MRA performed well in imaging BAVM, and high performance in determining nidus size and Spetzler-Martin grading, but its ability to detect deep venous drainage was limited.

A case of spontaneous brain arteriovenous malformation occlusion: Imaging analysis and clinical debate.

The spontaneous occlusion of brain arteriovenous malformations (bAVMs) is a rare event, particularly for unruptured ones. Associated factors include single-venous drainage and small nidus size. Most of the previously reported cases were ruptured bAVMs. We report the case of a middle-aged male patient with an unruptured, rolandic, left-sided bAVM associated with a 30-year history of refractory epilepsy. We documented the spontaneous thrombosis of the venous drainage of the AVM without any sign of bleeding. Finally, we underline the difference between ruptured-induced occlusion and truly spontaneous thrombosis of the bAVMs.

Machine Learning Models for Brain Arteriovenous Malformations Presenting with Hemorrhage Based on Clinical and Angioarchitectural Characteristics

This study aims to develop the best diagnostic model for brain arteriovenous malformations (bAVMs) rupture by using machine learning (ML) algorithms. We retrospectively included 353 adult patients with ruptured and unruptured bAVMs. The clinical and radiological data on patients werecollected. The significant variables were selected using univariable logistic regression. We constructed and compared the predictive models using five supervised ML algorithms, multivariable logistic regression, and R2eDAVM scoring system. A complementary systematic review and meta-analysis of studies was aggregated to explore the potential predictors for bAVMs rupture. We found that a small nidus size of <3cm, deep and infratentorial location, longer filling time, and deep and single venous drainage were associated with a higher risk of bAVMs rupture. The multilayer perceptronmodel showed the best performance with an area under the curvevalue of 0.736 (95% CI 0.67-0.801) and 0.713 (95% CI 0.647-0.779) in the training and test dataset, respectively. In our pooled analysis, we also found that the male sex, a single feeding artery, hypertension, non-White race, low Spetzler-Martin grade, and coexisting aneurysms are risk factors for bAVMs rupture. This study further demonstrated the clinical and angioarchitectural characteristics in predicting bAVMs hemorrhage.

Association of nidus size and rupture in brain arteriovenous malformations: Insight from angioarchitecture and hemodynamics.

This study aims to investigate the correlation between AVM size and rupture by examining natural history, angioarchitecture characteristics, and quantitative hemodynamics. A retrospective review of 90 consecutive AVMs from the MATCH registry was conducted. Patients were categorized into small nidus (< 3cm) and large nidus (≥ 3cm) groups based on the Spetzler-Martin grading system. Natural history analysis used prospective cohort survival data, while imaging analysis examined angioarchitecture characteristics and quantitative hemodynamic parameters measured with QDSA. The small-nidus group had a significantly higher annualized rupture risk (2.3% vs. 1.0%; p = 0.011). Cross-sectional imaging revealed independent hemorrhagic risk factors, including small nidus (OR, 4.801; 95%CI, 1.280-18.008; p = 0.020) and draining vein stenosis (OR, 6.773; 95%CI, 1.179-38.911; p = 0.032). Hemodynamic analysis identified higher stasis index in the feeding artery (OR, 2.442; 95%CI, 1.074-5.550; p = 0.033), higher stasis index in the draining vein (OR, 11.812; 95%CI, 1.907-73.170; p = 0.008), and lower outflow gradient in the draining vein (OR, 1.658; 95%CI, 1.068-2.574; p = 0.024) as independent predictors of AVM rupture. The small nidus group also showed a higher likelihood of being associated with hemorrhagic risk factors. Small AVM nidus has a higher risk of rupture based on natural history, angioarchitecture, and hemodynamics. Clinical Trial Registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT04572568.

Clinical Characteristics and Multimodality Therapy Outcomes in 304 Pediatric Patients with Cerebral Arteriovenous Malformations

Clinical follow-up data of pediatric patients with cerebral arteriovenous malformations (AVMs) are limited. This study investigated the characteristics of AVMs in children and analyzed the clinical outcomes of multimodality therapy in pediatric patients with AVMs at a single center. This retrospective study included consecutive patients diagnosed with AVMs at our institution between August 2008 and June 2018. Data on demographic characteristics, AVM features, and clinical outcomes were collected. Patients aged <18years at admission were defined as children. Overall, 1009 patients with AVMs were included, with 304 (30.1%) patients aged <18years. AVMs in pediatric patients were more likely to present with intracranial hemorrhage, mostly located in deep areas of the brain. A small nidus, exclusively deep drainage, and deep AVM location were associated with hemorrhage in children; Kaplan-Meier analysis revealed that patients with ruptured AVMs had a higher risk of developing a follow-up hemorrhage than those with unruptured AVMs. Among 290 children who were followed up, the multivariate regression analysis showed that a higher pretreatment modified Rankin Scale score, deep AVM location, and conservative treatment were significantly associated with unfavorable outcomes. In pediatric patients, AVMs were more likely to present with intracranial hemorrhage than that in adults. Hemorrhagic presentation in children was associated with a small nidus, exclusively deep drainage, and deep AVM location. Pediatric patients with ruptured AVMs had significantly higher risks of follow-up hemorrhage than those with unruptured AVMs. Our clinical results suggest that nonconservative treatment is better for pediatric patients with AVMs.

Comprehensive proteomic quantification of bladder stone progression in a cystinuric mouse model using data-independent acquisitions.

Cystinuria is one of various disorders that cause biomineralization in the urinary system, including bladder stone formation in humans. It is most prevalent in children and adolescents and more aggressive in males. There is no cure, and only limited disease management techniques help to solubilize the stones. Recurrence, even after treatment, occurs frequently. Other than a buildup of cystine, little is known about factors involved in the formation, expansion, and recurrence of these stones. This study sought to define the growth of bladder stones, guided by micro-computed tomography imaging, and to profile dynamic stone proteome changes in a cystinuria mouse model. After bladder stones developed in vivo, they were harvested and separated into four developmental stages (sand, small, medium and large stone), based on their size. Data-dependent and data-independent acquisitions allowed deep profiling of stone proteomics. The proteomic signatures and pathways illustrated major changes as the stones grew. Stones initiate from a small nidus, grow outward, and show major enrichment in ribosomal proteins and factors related to coagulation and platelet degranulation, suggesting a major dysregulation in specific pathways that can be targeted for new therapeutic options.

Spontaneous disappearance of brain arteriovenous malformation: A case series

ObjectiveBrain arteriovenous malformation (BAVM) is defined as abnormal communication between cerebral of arteries and veins, without capillaries. Clinically, it may involve intracranial hemorrhage or seizures. Complete spontaneous resolution, known as BAVM disappearance, has been reported in rare cases. MethodsWe retrospectively collated all cases of BAVM in Lille University Hospital, from 2005 to 2018, and identified all cases of spontaneous BAVM disappearance on angiography (nidus and early venous drainage). ResultsThere were 4 cases of spontaneous BAVM disappearance, in 3573 patients: i.e., prevalence of 0.1%. Sex ratio was 2:2; ages ranged from 14 to 46 years; nidus size was generally small (<20mm); 3 of the 4 patients had superficial venous drainage. Revelation of BAVM was by hemorrhage in 3 cases and by seizure in 1. There were no cases of recanalization at 1 year's follow-up. ConclusionSpontaneous BAVM disappearance is rare. Associated factors may include small nidus, superficial venous drainage and hemorrhage.

Surgical selection and outcomes among elderly patients with brain arteriovenous malformations.

Studies of resection of brain arteriovenous malformations (AVMs) in the elderly population are scarce. This study examined factors influencing patient selection and surgical outcome among elderly patients. Patients 65 years of age and older who underwent resection of an unruptured or ruptured brain AVM treated by two surgeons at two centers were identified. Patient demographic characteristics, AVM characteristics, clinical presentation, and outcomes measured using the modified Rankin Scale (mRS) were analyzed. For subgroup analyses, patients were dichotomized into two age groups (group 1, 65-69 years old; group 2, ≥ 70 years old). Overall, 112 patients were included in this study (group 1, n = 61; group 2, n = 51). Most of the patients presented with hemorrhage (71%), a small nidus (< 3 cm, 79%), and a low Spetzler-Martin (SM) grade (grade I or II, 63%) and were favorable surgical candidates according to the supplemented SM grade (supplemented SM grade < 7, 79%). A smaller AVM nidus was statistically significantly more likely to be present in patients with infratentorial AVMs (p = 0.006) and with a compact AVM nidus structure (p = 0.02). A larger AVM nidus was more likely to be treated with preoperative embolization (p < 0.001). Overall outcome was favorable (mRS scores 0-3) in 71% of the patients and was statistically independent from age group or AVM grading. Patients with ruptured AVMs at presentation had significantly better preoperative mRS scores (p < 0.001) and more favorable mRS scores at the last follow-up (p = 0.04) than patients with unruptured AVMs. Outcomes were favorable after AVM resection in both groups of patients. Elderly patients with brain AVMs treated microsurgically were notable for small nidus size, AVM rupture, and low SM grades. Microsurgical resection is an important treatment modality for elderly patients with AVMs, and supplemented SM grading is a useful tool for the selection of patients who are most likely to achieve good neurological outcomes after resection. AVM = arteriovenous malformation; BNI = Barrow Neurological Institute; LY = Lawton-Young; mRS = modified Rankin Scale; SM = Spetzler-Martin; supp-SM = supplemented SM; UCSF = University of California, San Francisco.

Late complications of radiosurgery for cerebral arteriovenous malformations: report of 5 cases of chronic encapsulated intracerebral hematomas and review of the literature

BackgroundChronic encapsulated intracerebral hematomas (CEIHs) are a rare, late complication of radiosurgery for intracranial AVM. We present 5 cases treated mostly by surgical excision and review the literature.MethodsPatients (age 39, 42, 36, 31, 62) presented with headache, paresthesia, hemiparesis or were asymptomatic. CEIHs presented 10 to 13 years (median 12 years) post radiosurgery. Three patients had demonstrated early radiation induced changes post radiosurgery. Angiographic cure, assessed with DSA, was present in all cases except 1 case with a small nidus remnant. MRI demonstrated mixed lesions with a solid enhancing part, organized hematoma and extensive surrounding edema while three cases had also a cystic component.ResultsExcision of the CEIHs with complete or partial removal of the capsule was performed in 4 patients and resulted in marked clinical improvement. One patient was managed conservatively with administration of steroids as surgery was judged excessively hazardous with eventual stabilization of his symptoms.ConclusionsCEIHs are rare, late complications of radiosurgery for cranial AVM. They may be asymptomatic or provoke symptoms and may be preceded by early radiation induced changes. Complete removal of CEIHS is an effective treatment. Because of the long latency period of CEIHs, patients who had radiosurgery for brain AVMs should be followed by MRI at least 10 years even after complete obliteration.

Association between draining vein diameters and intracranial arteriovenous malformation hemorrhage: a multicentric retrospective study.

Intracranial arteriovenous malformations (AVMs) cause hemorrhage, and the role of draining vein diameters in rupture risk is controversial. The aims of the present study were to investigate the variables related with intracranial AVM rupture and to examine the association of draining vein diameters and AVM hemorrhage. Two hundred three patients were included in this study, of which 117 (57%) had unruptured AVMs, and 86 (43%) had ruptured AVMs. In an adjusted (multivariate) analysis, the variables significantly associated with AVM hemorrhagic presentation were age (OR per year increase 0.97, 95%CI 0.95-0.99, p = 0.007), a deep nidus compared with superficial nidus (OR 3.21, 95%CI 1.13-9.06, p = 0.028), the nidus diameter (OR per each mm increase 0.95, 95%CI 0.92-0.97, p < 0.001), a single draining vein compared with multiple draining veins (OR 2.14, 95%CI 1.02-4.50, p = 0.044), the draining vein diameter (OR per mm increase 1.52, 95%CI 1.26-1.83, p < 0.001), and a draining vein diameter ≥ 5mm compared with < 5mm (OR 5.80, 95%CI 2.70-12.47, p < 0.001). In this study, after adjusted analysis, the variables associated with intracranial AVM hemorrhagic presentation were a young age, a small nidus diameter, a deeply located nidus, a single draining vein, and large draining vein diameters. A draining vein diameter cutoff ≥ 5mm was positively associated with the risk of AVM rupture. A large and prospective study is now necessary to confirm if draining vein diameter is a risk factor for AVM hemorrhage.

Intracranial Arteriovenous Malformation RUpture riSk Study (ICARUSS): A Multicentric Case-Control Study

Introduction: Intracranial arteriovenous malformations (AVMs) cause intracranial hemorrhage, and the factors that have been associated with a high rupture risk are prior hemorrhage, a small nidus, a deep location of the nidus, a single draining vein, deep venous drainage, aneurysms associated with AVMs, or draining vein stenosis. The role of draining vein diameters in rupture risk is unknown. The aim of the present study was to investigate the predictors for intracranial AVM rupture and to examine the role of draining vein diameters as a surrogate measure of flow-shear stress in the nidus in predicting the risk of AVM rupture. Materials and Methods: Two hundred three patients were included in this multicenter case-control study, of which 117 (57%) had unruptured AVMs, and 86 (43%) had ruptured AVMs. Clinical and angiographic data were registered by 5 independent investigators who were blinded regarding the endpoints of the study. Results: In the univariate analysis, the variables associated with AVM rupture were age, a deep nidus, the nidus diameter, a deep draining vein, a single draining vein, deep and single draining veins, the draining vein diameter, and a draining vein diameter > 5 mm. The variables significantly associated with AVM hemorrhage risk after adjusted (multivariate) analysis were age (OR 0.97, 95% CI 0.95-0.99, p=0.015), a deep nidus (OR 3.21, 95% CI 1.11-9.22, p=0.030), nidus diameter (OR 0.94, 95% CI 0.91-0.96, p 5 mm (OR 5.80, 95% CI 2.70-12.47, p 5 mm was positively associated with the risk of AVM rupture. A prospective study is necessary to confirm these findings. Funding Statement: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Declaration of Interests: The authors state: There are no competing interests to declare. Ethics Approval Statement: This was a multicentric, observational, case-control study. The study protocol was approved by the institutional review board, which waived the need for written informed consent from participants. The article was prepared accordingly, with recommendations from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

Interval angioarchitectural evolution of brain arteriovenous malformations following rupture.

The goal of this study was to describe changes in the angioarchitecture of brain arteriovenous malformations (bAVMs) between acute and delayed cerebral digital subtraction angiography (DSA) obtained after hemorrhage, and to examine bAVM characteristics predicting change. This is a retrospective study of a prospective institutional bAVM database. The authors included all patients with ruptured bAVMs who had DSA in both acute and delayed phases, with no interval treatment of their bAVM, between January 2000 and April 2017. The authors evaluated the existence or absence of angioarchitectural changes. Demographic data, radiological characteristics of hemorrhages, and angioarchitectural features of the bAVMs of the two patients' groups were analyzed. Univariate and multivariate logistic analyses were performed to identify predictors of angioarchitectural change. A total of 42 patients were included in the series. Seventeen (40.5%) patients had angioarchitectural changes including bAVM only visible on the delayed DSA study (n = 8), spontaneous thrombosis of the AVM (n = 3), or alteration of the size or the opacification of the nidus (n = 6). The factors associated with angioarchitectural changes were a small nidus (3.8 ± 7.9 ml vs 6.1 ± 9.5 ml, p = 0.046), a superficial location (94.1% vs 5.9%, p = 0.016), and a single superficial draining vein (58.8% vs 24.0%, p = 0.029). Angioarchitectural changes can be seen in 40% of ruptured bAVMs between the acute- and delayed-phase DSA. A small nidus, a superficial location, and a single superficial draining vein were statistically associated with the occurrence of angioarchitectural changes. These changes included either enlargement or spontaneous occlusion of the bAVM, as well as subsequent diagnosis of a bAVM following an initial negative DSA study.

Right Retrosigmoid Approach for In Situ Occlusion of Brainstem Arteriovenous Malformation Surrounding the Trigeminal Nerve: 3-Dimensional Operative Video.

Arteriovenous malformations (AVMs) of the trigeminal root entry zone are rare and can be associated with neurovascular compression syndromes as well as intracranial hemorrhage.1 They generally have a small nidus located on and around the pial surface of the brainstem; thus, they are feasible for surgery. Nevertheless, they represent a challenge given the vicinity and involvement of cranial nerves and brainstem perforators.2-4This video demonstrates the case of a 57-yr-old man with new onset of a severe headache without neurological deficit associated with MRI evidence of a vascular malformation around the cisternal right trigeminal nerve. The nerve showed an altered signal on the MRI. Angiography revealed a Spetzler-Martin grade II AVM with a 16-mm nidus supplied by basilar artery perforators, right anterior inferior cerebellar artery, and the superior cerebellar artery (SCA), with drainage into the superior petrosal vein and sigmoid sinus. After an unsuccessful attempted embolization, the patient was referred for and elected microsurgical treatment. With the patient in a lateral position, a right retrosigmoid approach was performed. After cisternal dissection and identification of the nidus, the feeders were occluded by alternating cauterization and clipping to avoid damage to the critical surrounding structures. The AVM in-situ occlusion was carried on without resection, given the involvement of the trigeminal nerve. The intraoperative indocyanine green angiography allowed recognition of the venous drainage and helped to localize and differentiate the feeders from normal perforators. In the immediate postoperative course, the patient suffered from mild numbness with a V2-V3 distribution that progressively improved. Angiography showed no residual AVM.

Multimodality Management of Spetzler-Martin Grade 3 Brain Arteriovenous Malformations with Subgroup Analysis

Spetzler-Martin grade 3 (SM3) lesions entail 4 distinct subtypes described based on size, eloquence, and deep venous drainage (3A-3D). The ideal management of each is contentious, and the results of A Randomized Trial of Unruptured Brain AVMs (ARUBA) introduced additional controversy and attention toward management strategies of unruptured brain arteriovenous malformations (bAVMs). We retrospectively reviewed 114 patients with treated SM3 bAVMs, including both ruptured and unruptured lesions. Primary outcomes included modified Rankin score at most recent follow-up, angiographic cure,and permanent treatment-related complications (morbidity). Other outcomes included mortality, bAVM recurrence or rebleed, and transient treatment-related complications. We used univariate and multivariate modeling to determine whether any specific features were predictive of outcomes. For unruptured bAVMs, an "ARUBA eligible" subgroup analysis was performed. We also reviewed the literature on management of ruptured and unruptured SM3 bAVMs. Of the 114 identified SM3 bAVMs, 40% were unruptured. Most (43.5%) lesions in the unruptured group were type 3C, whereas most ruptured bAVMs (66.2%) were type 3A. Unruptured lesions were mostly managed with radiosurgery (47.8%) and ruptured ones with preoperative embolization and surgery (36.7%). Surgical intervention was predictive of angiographic cure in multivariate modeling, even after controlling for ≥2 years of follow-up, although associated with a slightly higher rate of morbidity. Focal neurological deficit was the only predictor of a worse (modified Rankin score ≥2) functional outcome in follow-up for unruptured bAVMs. For ruptured bAVMs, superficial and cerebellar locations were predictive of better outcomes in multivariate models, in the absence of a focal neurological deficit at presentation and new after surgery deficit. ARUBA SM3 bAVMs specifically underwent more embolization as a monotherapy and less microsurgical resection than the present series. In spite of a heterogeneous array of angioarchitectural and anatomic features, SM3 bAVMs can be treated safely and effectively with surgery and radiosurgery either without or with pretreatment embolization. Ruptured lesions are more often type 3A, with smaller nidus, deep brain location, and deep venous drainage. Focal neurological deficit predicts worse clinical outcomes. Contemporary multimodality management of SM3 bAVMs is not adequately represented in the results of ARUBA, likely due to differences in treatment strategies.

Stereotactic radiosurgery for cerebellar arteriovenous malformations: an international multicenter study.

OBJECTIVE Cerebellar arteriovenous malformations (AVMs) represent the majority of infratentorial AVMs and frequently have a hemorrhagic presentation. In this multicenter study, the authors review outcomes of cerebellar AVMs after stereotactic radiosurgery (SRS). METHODS Eight medical centers contributed data from 162 patients with cerebellar AVMs managed with SRS. Of these patients, 65% presented with hemorrhage. The median maximal nidus diameter was 2 cm. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent radiation-induced complications (RICs). Patients were followed clinically and radiographically, with a median follow-up of 60 months (range 7-325 months). RESULTS The overall actuarial rates of obliteration at 3, 5, 7, and 10 years were 38.3%, 74.2%, 81.4%, and 86.1%, respectively, after single-session SRS. Obliteration and a favorable outcome were more likely to be achieved in patients treated with a margin dose greater than 18 Gy (p < 0.001 for both), demonstrating significantly better rates (83.3% and 79%, respectively). The rate of latency preobliteration hemorrhage was 0.85%/year. Symptomatic post-SRS RICs developed in 4.5% of patients (n = 7). Predictors of a favorable outcome were a smaller nidus (p = 0.0001), no pre-SRS embolization (p = 0.003), no prior hemorrhage (p = 0.0001), a higher margin dose (p = 0.0001), and a higher maximal dose (p = 0.009). The Spetzler-Martin grade was not found to be predictive of outcome. The Virginia Radiosurgery AVM Scale score (p = 0.0001) and the Radiosurgery-Based AVM Scale score (p = 0.0001) were predictive of a favorable outcome. CONCLUSIONS SRS results in successful obliteration and a favorable outcome in the majority of patients with cerebellar AVMs. Most patients will require a nidus dose of higher than 18 Gy to achieve these goals. Radiosurgical and not microsurgical scales were predictive of clinical outcome after SRS.

Endovascular Management of Deep Arteriovenous Malformations: Single Institution Experience in 22 Consecutive Patients.

The management of arteriovenous malformations (AVMs) in the basal ganglia, insula, and thalamus is demanding for all treatment modalities. To define safety and outcomes of embolization used as a stand-alone therapy for deep-seated AVMs. A cohort of 22 patients with AVMs located in the basal ganglia, thalamus, and insula who underwent embolization between January 2008 and December 2013. Eighteen of 22 (82%) patients had anatomic exclusion. The mean size was 2.98 ± 1.28 cm, and the mean number of sessions was 2.1 per patient. Most patients presented with hemorrhage (82%, n = 18), and 3 (14%) patients were in a deteriorated neurological status (modified Rankin Scale >2) at presentation. Sixty-eight percent of ruptured AVMs had size ≤3 cm. A single transarterial approach was performed in 9 (41%) cases, double catheterization was used in 4 (18%), and the transvenous approach was required in 8 (36%) cases. Procedure-related complications were registered in 3 (14%) cases. One death was associated with treatment, and complementary radiosurgery was required in 2 (9%) patients. Embolization therapy appears to be safe and potentially curative for certain deep AVMs. Our results demonstrate a high percentage of anatomic obliteration with rates of complications that may approach radiosurgery profile. In particular, embolization as stand-alone therapy is most suitable to deep AVMs with small nidus size (≤3 cm) and/or associated with single venous drainage in which microsurgery might not be indicated.

Lung metastasectomy paradoxes in practice: reflections on the Catania conference.

Senior surgeons and medical students and every grade in between, basic scientists and clinicians, researchers and practitioners from many countries met in Catania, Sicily, in April 2014. This was a focus meeting to share knowledge, experience and opinions centered around one question: how best to manage lung metastases? It is my privilege to have been invited to write some personal reflections by way of introduction to the report of the symposium. t he biological basis of metastasis The presence of metastates in the lung is dependent on a number of steps, all of which must be successfully completed to give rise to a metastatic growing tumor. The tumor cells have to enter the circulatory system directly or indirectly via the lymphatic system. They need to survive in the circulation until they can arrest in the lung. There they have to extravasate from the circulation into the surrounding tissue. Then they have to become established and the cells must continue to replicate until they become discernible on imaging. The fate of cancer cells that have survived to reach the lung is uncertain. Cells may stay quiescent and eventually die, they may grow to form a small nidus of metastatic cells, a nidus may regress or it may through angiogenesis develop its own blood supply and proliferate to eventually form a clinically detectable metastasis. Studies using cancer cells labelled with 125 I-deoxyuridine, which is incorporated into DNA, showed that within 24 h after entry of tumor cells into circulation less than 1% of tumor cells are viable and that one in a thousand of these cells survive to produce metastases. The process of cancer metastasis is thus seen to be highly inefficient. Many hundreds of thousands of cancer cells may be disseminated into the circulatory system, but only a small fraction of these cells will actually form growing metastatic colonies [1]. These observations prompt the question of whether the development of metastases represents the fortuitous survival and growth of very few tumor cells or whether the primary tumor progresses to a more malignant state from which metastases arise. Metastases may not share the properties of the primary cancer and possibly in ways that make them more resistant to chemotherapy [2]. Evidence gained from gene studies in renal cancer showed heterogeneity and branched evolution which suggests that the challenges of implementing personalized or targeted therapies and biomarker development may have been underestimated [3]. t he interval between primary resection & metastasectomy Against the uncertain direction of medical management of metastases, surgical metastasectomy has followed a fairly steady course based on the presumption that if the detected metastases are the only cancerous masses in the body, surgical removal or other local treatment could potentially cure the patient. How can that be other than true? It’s the ‘if’ that’s the problem. Here is an analogy which, like all analogies, cannot be tested too far but let’s see if it helps. When fall/autumn comes, if you stand under a solitary tree, there will probably be a point in time when there is the first leaf

Embolization with Gamma Knife Radiosurgery of Giant Intracranial Arteriovenous Malformations.

Giant arteriovenous malformations (i.e., those greater than 6 cm maximum diameter or volume > 33 cc) are difficult to treat and often carry higher treatment morbidity and mortality rates. In our study, we reviewed the angiographic results and clinical outcomes for 11 patients with giant arteriovenous malformations who were treated between 1994 and 2012. The patients selected included 9 males (82%) and 2 females (18%). Their presenting symptoms were hemorrhage (n=2; 18%), seizure (n=7; 64%), and headache (n=2; 12%). Nine patients were Spetzler-Martin Grade III, 2 were Spetzler-Martin Grade IV. The mean arteriovenous malformation volume was 41 cc (33-52 cc). The mean age of the patients was 45.1 years (24-57 years) and the mean radiation dose delivered to the margin of the nidus was 14.2 Gy. Ten patients received pre-Gamma Knife radiosurgery embolization and Gamma Knife radiosurgery, 1 patient received pre-Gamma Knife radiosurgery embolization and Gamma Knife radiosurgery twice and the interval between Gamma Knife radiosurgeries was 3 months. The complete obliteration rate following Gamma Knife radiosurgery was 36%, subtotal obliteration ( > 70% decreased size of nidus) was 36%, and partial obliteration was 28%. One patient experienced a small hemorrhage after embolization. Combined embolization and Gamma Knife radiosurgery showed successful obliteration of the arteriovenous malformation nidus. The use of embolization to initially reduce nidus size followed by Gamma Knife radiosurgery improves the treatment results. Repeated Gamma Knife radiosurgery should be a treatment option when there is a small nidus remnant.

Gamma Knife surgery for incidental cerebral arteriovenous malformations.

A relatively benign natural course of unruptured cerebral arteriovenous malformations (AVMs) has recently been recognized, and the decision to treat incidentally found AVMs has been questioned. This study aims to evaluate the long-term imaging and clinical outcomes of patients with asymptomatic, incidentally discovered AVMs treated with Gamma Knife surgery (GKS). Thirty-one patients, each with an incidentally diagnosed AVM, underwent GKS between 1989 and 2009. The nidus volumes ranged from 0.3 to 11.1 cm(3) (median 3.2 cm(3)). A margin dose between 15 and 26 Gy (median 20 Gy) was used to treat the AVMs. Four patients underwent repeat GKS for still-patent AVM residuals after the initial GKS procedure. Clinical follow-up ranged from 24 to 196 months, with a mean of 78 months (median 51 months) after the initial GKS. Following GKS, 19 patients (61.3%) had a total AVM obliteration on angiography. In 7 patients (22.6%), no flow voids were observed on MRI but angiographic confirmation was not available. In 5 patients (16.1%), the AVMs remained patent. A small nidus volume was significantly associated with increased AVM obliteration rate. Thirteen patients (41.9%) developed radiation-induced imaging changes: 11 were asymptomatic (35.5%), 1 had only headache (3.2%), and 1 developed seizure and neurological deficits (3.2%). Two patients each had 1 hemorrhage during the latency period (116.5 risk years), yielding an annual hemorrhage rate of 1.7% before AVM obliteration. The decision to treat asymptomatic AVMs, and if so, which treatment approach to use, remain the subject of debate. GKS as a minimally invasive procedure appears to achieve a reasonable outcome with low procedure-related morbidity. In those patients with incidental AVMs, the benefits as well as the risks of radiosurgical intervention will only be fully defined with long-term follow-up.