Annual Risk Of Hemorrhage Research Articles

Natural history and management outcomes of patients with ruptured Spetzler-Martin grade IV and V brain arteriovenous malformations.

The natural history of ruptured high Spetzler-Martin grade IV and V brain arteriovenous malformations (bAVMs) is underreported given the scarcity of this pathology, and decision-making for patients with bAVMs remains unclarified. In this study, the authors sought to shed light on this topic. Patients harboring ruptured high-grade bAVMs were identified from an institutional database spanning from 1990 to 2020. The authors examined outcomes of annual hemorrhagic risk in natural history and after treatment, follow-up hemorrhage rate, bAVM obliteration, follow-up modified Rankin Scale (mRS) score > 2, worsened mRS score, and mortality. After reviewing the charts of 1066 patients without hereditary hemorrhagic telangiectasia, 84 patients with ruptured high-grade bAVMs were included in the study for analysis. For cortical bAVMs, the annual risk of hemorrhage during natural history was 2.68%. Surgery decreased the risk to 0.74%, while radiosurgery increased the risk to 5.35%, and embolization only increased the risk to 16.96%. For deep-seated high-grade bAVMs, the annual risk of hemorrhage during natural history was 8.37%. Radiosurgery decreased the risk to 3.11%, surgery decreased the risk to 5.25%, and embolization only increased the risk to 22.33%. Poisson regression analysis demonstrated that embolization only increased the risk of hemorrhage in cortical bAVMs (rate ratio 4.745, 95% CI 1.365-12.819; p = 0.005) and deep-seated bAVMs (rate ratio 6.290, 95% CI 0.997-21.932; p = 0.013). Logistic regression analysis showed that surgery (OR 52.000, 95% CI 8.083-1046.127; p = 0.004) and radiosurgery (OR 11.142, 95% CI 1.804-217.650; p = 0.029) were predictors of obliteration in cortical and deep-seated bAVMs, respectively. The proportions of patients experiencing a worsened mRS score, a follow-up mRS score > 2, and mortality were similar between conservative and treatment groups. The natural history of cortical ruptured high-grade bAVMs bears a risk similar to that of incidental bAVMs, whereas deep-seated ruptured high-grade bAVMs have an increased risk of hemorrhage. With extremely prudent patient selection, surgery might be a viable option for cortical bAVMs to obliterate the bAVM and reduce hemorrhagic risk, while preserving functional status. Radiosurgery might be beneficial to lower hemorrhagic risk in deep-seated bAVMs. Embolization as a single modality should be avoided as it provides no benefit to reduce hemorrhagic risk.

Combined Endovascular-Microsurgical Treatment for a Parietal Brain Arteriovenous Malformation and Neuropsychological Implications: An Operative 2-Dimensional Video Case: 2-Dimensional Operative Video

Brain arteriovenous malformations (AVMs) are complex vascular anomalies characterized by abnormal veins and arteries, lacking capillary beds. With an average 2.4% annual risk of hemorrhage, AVMs pose a significant challenge in treatment, especially in high-grade cases. Risk factors of hemorrhage include young age, previous rupture, and deep or infratentorial locations. 1-10 In this operative video, a 34-year-old man presented with a history of seizures and progressive headaches over 15 years. Clinical examination revealed a Glasgow Coma Scale of 15 and neuropsychological deficits including divided attention, working memory, verbal and semantic memory, and arithmetic skills. Digital subtraction angiography confirmed an AVM Spetzler-Martin III in the right parietal lobe, with venous drainage toward the superior sagittal sinus and involvement of the superior longitudinal fasciculus. After multiple embolizations, microsurgical resection was performed successfully. Postoperatively, the patient experienced no complications, with follow-up angiography demonstrating complete AVM exclusion. The patient consent to the procedure and to the publication of his/her image. This study was approved by the ethics committee of our institution. Despite its size and location in a noneloquent area, the AVM affected neuropsychological function. The combined endovascular-microsurgical approach proved effective, highlighting the importance of considering anatomical, functional, and neuropsychological factors in AVM treatment to maximize success in achieving complete obliteration and curative outcomes.

Management and outcome predictors of patients with ruptured deep-seated brain arteriovenous malformations.

Decision-making for the management of ruptured deep-seated brain arteriovenous malformations (bAVMs) is controversial. This study aimed to shed light on the treatment outcomes of patients with ruptured deep-seated bAVMs. Data on bAVM patients were retrieved from the authors' institutional database, spanning 1990-2021. The outcomes were annual hemorrhage risk (before and after intervention), number of follow-up hemorrhages, bAVM obliteration, poor modified Rankin Scale (mRS) score (i.e., mRS score > 2), worsened mRS score, and mortality. Multivariable Cox and logistic regression analyses were conducted to determine predictors of time-to-event and categorical outcomes, respectively. Of the 1066 patients in the database with brain bAVM, 177 patients harboring ruptured deep-seated bAVMs were included. The pretreatment annual hemorrhage risk was 8.24%, and the posttreatment risk was lowered to 1.65%. In multivariable Cox regression analysis, a prenidal aneurysm (HR 2.388, 95% CI 1.057-5.398; p = 0.036) was associated with a higher risk of follow-up hemorrhage, while definitive treatment (i.e., either surgery or radiosurgery vs endovascular embolization or conservative management) (HR 0.267, 95% CI 0.118-0.602; p = 0.001) was associated with a lower risk of follow-up hemorrhage. In multivariable logistic regression analysis, Spetzler-Martin grades IV and V (OR 0.404, 95% CI 0.171-0.917; p = 0.033) and brainstem arteriovenous malformation (AVM) (OR 0.325, 95% CI 0.128-0.778; p = 0.014) were associated with lower odds of obliteration, while definitive treatment (OR 8.864, 95% CI 3.604-25.399; p = 0.008) was associated with higher obliteration odds. Controlling for baseline mRS score, cerebellar AVM (OR 0.286, 95% CI 0.098-0.731; p = 0.013) and definitive treatment (OR 0.361, 95% CI 0.160-0.807; p = 0.013) were associated with lower odds of a poor mRS score, and definitive treatment (OR 0.208, 95% CI 0.076-0.553; p = 0.001) was associated with lower odds of a worsened mRS score. Furthermore, smoking (OR 6.068, 95% CI 1.531-25.581; p = 0.01) and definitive treatment (OR 0.101, 95% CI 0.024-0.361; p = 0.007) were associated with higher and lower mortality odds, respectively. A definitive treatment strategy seems to be beneficial in achieving higher obliteration and lower hemorrhage rates while decreasing the odds of a poor mRS score, worsened mRS score, and mortality. In this category of patients, prenidal aneurysms warrant treatment, and smoking cessation should be encouraged.

Outcome of 107 conservatively managed unruptured brain arteriovenous malformations: a single center's 30-year experience.

Since the publication of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the management of unruptured brain arteriovenous malformations (bAVMs) has been controversially discussed. Long-term follow-up data on the exclusively conservative management of unruptured bAVMs are scarce. The authors evaluated the long-term outcomes of patients with unruptured untreated bAVMs in a real-life cohort. A retrospective observational cohort of 107 patients (of 897 bAVM patients referred to the authors' institution) with a diagnosis of unruptured and conservatively managed bAVMs is presented. AVMs of all Spetzler-Martin grades were observed. The mean follow-up period was 84 months. In 44% of patients, a follow-up period of 5 years or longer was observed. A national death register comparison completed the outcome analysis. The median age at diagnosis, sex distribution, neurological presentation, and modified Rankin Scale score were comparable to the patients in the medical management arm of the ARUBA study. Patients were mainly young, predominantly male, and in good clinical condition. Similar to the ARUBA cohort, 77% of this study's cohort presented in an excellent clinical status at the time of last follow-up. However, 17% of patients had at least one hemorrhage, resulting in an overall annual hemorrhage risk of 2.7% in the observation period. Moreover, the cumulative 1-, 5-, and 10-year overall hemorrhage rates were 3.0%, 11.3%, and 15.3%, respectively. Consequently, the long-term follow-up AVM-related mortality rate amounted to 8%. The estimated median overall survival after AVM diagnosis was 19.3 years (95% CI 14.0-24.6 years). A multivariate Cox regression model revealed temporal and deep-seated localization as an independent risk factor for AVM hemorrhage, while the presence of seizures reached borderline significance as a risk factor. The authors' results represent the long-term course of unruptured untreated bAVMs. Their data support the conclusion that even in the post-ARUBA era, tailored active treatment options may be offered to patients with unruptured bAVMs. For patient counseling, individual risk factors should be weighed against the center's treatment-specific risks.

Surgical Outcomes of Symptomatic Intramedullary Spinal Cord Cavernous Malformations: Analysis of Consecutive Cases in a Single Center.

Intramedullary spinal cavernous malformations (ISCMs) are rare vascular lesions of the spinal cord with unclear natural history and controversy over treatment. This study aimed to report a series of symptomatic ISCMs underwent microsurgical management to illustrate the natural history, clinical presentation, and surgical outcomes and to evaluate factors associated with hemorrhage events and neurological prognosis. This single-center retrospective study included 29 consecutive patients with whose demographic, symptomology, imaging, neurological, and surgical data were collected. The risk for hemorrhage events and factors affecting surgical outcomes were retrospectively analyzed. There were 12 female (41.4%) and 17 male patients (58.6%), with an average age of 45.2 years (range, 17-69 years). The mean size of the lesion was 9.7 mm (range, 3-20 mm). Most patients had a bowel or/and bladder dysfunction symptom (n = 11, 37.9%), followed by sensory deficits (n = 5, 17.2%), gait disturbance (n = 5, 17.2%), pain (n = 4, 13.8%), and weakness (n = 4, 13.8%), most (n = 15, 51.7%) with a chronic onset. All patients received total resection without rehemorrhages after surgical resection in follow-up. Sixty-five point five percent patients (n = 19) improved, 13.8% (n = 4) remained stable, 20.7% (n = 6) got worsen. The overall annual hemorrhage risk was 2.1% per patient-year. A total of 27 hemorrhages occurred in the 18 patients, of which rehemorrhage rate increased to 50.0% (n = 9) with a previous history of hemorrhage. Patients with smaller lesion sizes were more likely to have hemorrhage or rehemorrhage events (p = 0.008). Recurrent hemorrhage of the lesions was a risk factor for neurological outcomes (p = 0.016). The risk of rehemorrhage was significantly increased in symptomatic ISCM patients with a previous history of hemorrhage. Rehemorrhage was a risk factor for neurological outcomes. Patients can benefit from microsurgical treatment to avoid rehemorrhage and further neurological deterioration.

Unruptured Anterior Communicating Artery Aneurysms: Management Strategy and Results of a Single-Center Experience.

Although anterior communicating artery (AComA) unruptured intracranial aneurysms (UIAs) comprise one of the largest aneurysm subgroups, their complex adjacent neurovasculature and increased risk of rupture impede optimal management. In the present study, we analyzed the results of our diverse strategy in AComA UIAs with the additional goal of assessing the risk of treatment and the incidence of hemorrhage. We analyzed 131 patients, of which each was assessed by a multidisciplinary neurovascular team and assigned to observation (45.8%), endovascular treatment (34.4%) or microsurgery (19.8%). Median aneurysm sizes were 3, 7.2 and 7.75 mm, respectively. In the observation group, four (7.1%) aneurysms (initially <5 mm) grew over a median time of 63.5 months and were treated endovascularly. We found that fewer patients in the observation group were smokers (p = 0.021). The aneurysm size ratio was different between the combined treatment versus the observation group (p < 0.0001). Noteworthily, there were no hemorrhages in the observational group. Mortality for all patients with available follow-up was 2.4% (3/124) and permanent morbidity was 1.6% (2/124) over a mean follow-up of 64.2 months. These compelling rates refer to a high-risk group with potentially devastating consequences in which we have decreased the annual risk of hemorrhage to 0.14%.

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.

Gamma Knife Radiosurgery for Spetzler-Martin Grade III Brain Arteriovenous Malformations

Spetzler-Martin (SM) grade III AVMs exhibit angioarchitecture heterogeneity and lack a clearly defined treatment strategy. This study aims to evaluate outcomes following treatment of SM grade III AVMs with Gamma Knife Radiosurgery (GKRS). A single-institution retrospective analysis was conducted of 307 patients with SM grade III AVMs undergoing GKRS between October 2006 to December 2020 with follow-up times of at least 24 months. SM grade III AVMs were classified into four subtypes: IIIA (S1E1V1), IIIB (S2E0V1), subtype IIIC (S2E1V0), and IIID (S3E0V0). Over a median follow-up time of 50.3 months, complete AVM obliteration was achieved in 211 patients (68.7%). Complete obliteration rates in subtypes IIIA, IIIB, IIIC, and IIID were 80.8%, 55.4%, 53.4%, and 25.0%, respectively. Annual post-GKRS hemorrhage risk was 0.8%. Significant radiosurgery-induced imaging changes occurred in 7 patients (2.3%). Three variables were identified as predictors of obliteration in final forward stepwise regression models, including volume of AVM (B= -0.011, p <0.001), age (B= -0.004, p =0.024) and prior AVM hemorrhage (B= 0.187, p = 0.077). GKRS is a safe and effective treatment for SM grade III AVMs, particularly subtype IIIA (S1E1V1). AVM volume is the key predictor of post-GKRS obliteration.

301 Natural History and Treatments of The Pediatrics’ Deep-Seated Brain Arteriovenous Malformations

INTRODUCTION: Literature is sparse about the hemorrhage risk associated with the pediatrics’ deep-seated brain AVMs (bAVMs) during the natural history and after treatment. METHODS: We retrospectively reviewed our institutional bAVM database from 1990 to 2019 and included pediatrics who had deep-seated bAVMs. We presented the annual hemorrhage risk; during the natural history and after treatments, and functional outcomes. RESULTS: After the screening of 914 patients, 31 pediatric cases; including 13 males and 18 females, with the mean (SD) age of 11.8 (4.4) were included. The most frequent presenting symptoms were headache (54.83%), weakness (38.7%), and seizure (22.5%). The mean (SD) of followed-up duration was 13.14 (12.5) years, during which 7(22.5%) AVMs were found obliterated, 10 (32.2%) individuals sustained hemorrhage, and the modified Rankin Score (mRS) worsened in 8 (25.8%) patients. The annual hemorrhage risk of natural history was 3.26% per patient, and the overall annual hemorrhage risk after treatment was 1.97% per patient. The annual hemorrhage risk in each treatment group was 0.64% per patient in radiosurgery, 6.3% per patient in surgery, and 6.29% per patient in embolization. Those with non-white race showed a trend of higher ruptured presentation (OR = 5 [0.84-41.68], p = 0.09). Female sex was associated with higher (OR = 13.076 [1.424-333.591], p = 0.048) and treatment radiosurgery was associated with lower (OR = 0.21 [0.03-1.02], p = 0.06) odds of follow-up hemorrhage. Headache presentation was associated with the lower odds of poor functional outcome (OR = 0.102 [0.011-0.670], p = 0.024). CONCLUSIONS: Given the substantial cumulative risk of lifelong hemorrhagic stroke in pediatric patients, timely definitive treatment is warranted. Radiosurgery treatment is beneficial when the risk-benefit profile is deemed favorable.

Natural history and treatment of deep-seated brain arteriovenous malformations in pediatric patients.

Pediatric deep brain arteriovenous malformations (bAVMs) represent a unique management challenge given their higher cumulative risk of hemorrhage as well as a higher risk of treatment. Better understanding of hemorrhage risk in this patient population will lead to a better decision-making process for patient management. The authors retrospectively reviewed their institutional bAVM database from 1990 to 2019 and included patients younger than 21 years who had deep-seated bAVMs. They present the annual hemorrhage risk, during the natural history and after treatment, and functional outcomes. Thirty-one pediatric patients were included in this study (13 males and 18 females) with a mean age of 11.8 (SD 4.4) years. The most frequent presenting symptoms were headache (54.8%), weakness (38.7%), and seizure (22.6%). The mean follow-up duration was 13.14 (SD 12.5) years, during which 7 (22.6%) AVMs were obliterated, 10 (32.3%) individuals experienced hemorrhage, and the modified Rankin Scale score worsened in 8 (25.8%) patients. The annual natural history risk of hemorrhage was 3.24% per patient, and the overall annual hemorrhage risk after treatment was 1.98% per patient. In particular, the risk was reduced to 0.64% per patient in the stereotactic radiosurgery (SRS) group. Non-White race showed a trend of higher rupture at presentation (OR 5 [95% CI 0.84-41.68], p = 0.09). Female sex was associated with higher odds (OR 13.076 [95% CI 1.424-333.591], p = 0.048) and SRS was associated with lower odds (OR 0.122 [95% CI 0.011-0.862], p = 0.049) of follow-up hemorrhage. Given the substantial cumulative risk of lifelong hemorrhagic stroke in pediatric patients, timely definitive treatment is warranted. SRS may be beneficial when the risk-benefit profile is deemed acceptable.

Natural history of familial cerebral cavernous malformation syndrome in children: a multicenter cohort study

PurposeThere is limited data concerning neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. Our aim was to study the natural history of pediatric FCCM, with an emphasis on symptomatic hemorrhagic events and associated clinical and imaging risk factors.MethodsWe retrospectively reviewed all children diagnosed with FCCM in four tertiary pediatric hospitals between January 2010 and March 2022. Subjects with first available brain MRI and ge 3 months of clinical follow-up were included. Neuroimaging studies were reviewed, and clinical data collected. Annual symptomatic hemorrhage risk rates and cumulative risks were calculated using survival analysis and predictors of symptomatic hemorrhagic identified using regression analysis.ResultsForty-one children (53.7% males) were included, of whom 15 (36.3%) presenting with symptomatic hemorrhage. Seven symptomatic hemorrhages occurred during 140.5 person-years of follow-up, yielding a 5-year annual hemorrhage rate of 5.0% per person-year. The 1-, 2-, and 5-year cumulative risks of symptomatic hemorrhage were 7.3%, 14.6%, and 17.1%, respectively. The latter was higher in children with prior symptomatic hemorrhage (33.3%), CCM2 genotype (33.3%), and positive family history (20.7%). Number of brainstem (adjusted hazard ratio [HR] = 1.37, P = 0.005) and posterior fossa (adjusted HR = 1.64, P = 0.004) CCM at first brain MRI were significant independent predictors of prospective symptomatic hemorrhage.ConclusionThe 5-year annual and cumulative symptomatic hemorrhagic risk in our pediatric FCCM cohort equals the overall risk described in children and adults with all types of CCM. Imaging features at first brain MRI may help to predict potential symptomatic hemorrhage at 5-year follow-up.

Gamma Knife Radiosurgery for Brain Arteriovenous Malformations: A 15-Year Single-Center Experience in Southern Vietnam

In the present study, we aimed to identify the obliteration outcomes, complications, and predictors in gamma knife radiosurgery (GKRS) treatment of brain arteriovenous malformations (AVMs) at a tertiary center in a developing country in a 15-year experience. We retrospectively reviewed the clinical data and GKRS procedures of patients who had undergone GKRS from 2006 to 2011 (cohort 1) and from 2011 to 2020 (cohort 2) at Cho Ray Hospital, Vietnam. The exclusion criteria included patients with <24 months of follow-up without obliteration or AVM-related hemorrhage during the study period. A total of 870 patients were included in the final analysis. The patients in cohort 1 had had significantly smaller AVMs (8.4 ± 11.6 cm3 vs. 11.2 ± 12.8 cm3; P< 0.001), and the AVMs were less frequently located in eloquent locations (46.6% vs. 65.5%; P < 0.001) than in cohort 2. The mean follow-up time was 49.6 ± 22.6 months (range, 5.9-102.6). The overall AVM obliteration rate was 66.6%. Cohort 1 had a significantly higher rate of complete obliteration compared with cohort 2 (81.0% vs. 55.1%; P<0.001). The post-GKRS annual hemorrhage risk was 1.0%. Significant radiosurgery-induced brain edema and radiosurgery-induced cyst formation was reported in 24 (2.6%) and 4 (0.5%) patients in cohorts 1 and 2, respectively. Using multivariate analysis, we identified prior AVM hemorrhage (hazard ratio [HR], 1.430; 95% confidence interval [CI], 1.182-1.729), a higher margin dose (HR, 1.136; 95% CI, 1.086-1.188), a noneloquent location (HR, 0.765; 95% CI, 0.647-0.905), and smaller AVM volume (HR, 0.982; 95% CI, 0.968-0.997) as predictive factors for obliteration. GKRS is a safe and effective treatment of brain AVMs. The lack of prior AVM hemorrhage, an eloquent location, and higher AVM were unfavorable predictors for post-GKRS obliteration.

Recurrent brainstem cavernous malformations following primary resection: blind spots, fine lines, and the right-angle method.

Proximity of brainstem cavernous malformations (BSCMs) to tracts and cranial nerve nuclei make it costly to transgress normal tissue in accessing the lesion or disrupting normal tissue adjacent to the lesion in the separation plane. This interplay between tissue sensitivity and extreme eloquence makes it difficult to avoid leaving a remnant on occasion. Recurrences require operative intervention, which may increase morbidity, lengthen recovery, and add to overall costs. An approximately 20-year experience with patients with recurrent BSCM lesions following primary microsurgical resection was reviewed. A prospectively maintained database of 802 patients who underwent microsurgical resection of cerebral cavernous malformations during 1997-2018 was queried to identify 213 patients with BSCMs. A retrospective chart review was conducted for patients with recurrent BSCM after primary resection who required a second surgery. Fourteen of 213 patients (6.6%) underwent repeat resection for recurrent BSCM. Thirty-four hemorrhagic events were observed among these 14 patients over 576 patient-years (recurrent hemorrhage rate, 5.9% per year; median discrete hemorrhagic events, 2; median time to rehemorrhage, 897 days). BSCM occurred in the pons in 10 cases, midbrain in 2 cases, and medulla in 2 cases. A blind spot in the operative corridor was the most common cause of residual BSCM (9 patients). All recurrent BSCMs were removed completely, although 2 patients each required 2 operations to treat recurrence. Twelve patients had unchanged or improved modified Rankin Scale scores at last clinical evaluation compared with admission, and 2 patients had worse scores. Recurrence was more common among patients who were operated on in the first versus the second half of the series (8.5% vs 4.7%). The 6.6% rate of BSCM recurrence requiring reoperation reflects the fine lines between complete resection and recurrence and between safe and harmful surgery. The detection of remnants is difficult postoperatively and remains so even at 6 months when the resection bed has healed. The 5.9% annual hemorrhage risk associated with recurrent BSCM in this experience is consistent with that reported for unoperated BSCMs. The right-angle method helps to anticipate blind spots and meticulously inspect the resection cavity for residual BSCM during surgery. A low percentage of recurrent BSCM (5%-10%) ensures ongoing effort toward an acceptable balance of safety and completeness.

Multimodality Management in bAVM Surgery - Recent Experience from International Cerebrovascular Fellowship.

Background:Arteriovenous malformation (bAVM) presents maldevelopment of the brain’s vessels with a direct connection between cerebral arteries and veins. By current data, patients from Spetzler Ponce A (SP) are found to benefit from the treatment. Considering the outcome, most of SP C and some of the SP B are the most debatable.Objective:Arteriovenous malformation presents maldevelopment of the brain’s vessels with a consequent direct connection between cerebral arteries and veins. The annual risk of hemorrhage in adults is reported for 2-3 %. They usually present with unilateral headaches seizures and intracranial hemorrhage. By current data, patients from Spetzler Ponce A (SP) are found to benefit from the treatment. Considering the outcome, most of SP C and some of the SP B are the most debatable.Methods:The study included a cohort of bAVM patients referred to Fujita Health University Bantane Hotokukai Hospital, Nagoya, Aichi, Japan where the main author (AA) has completed an international cerebrovascular fellowship under the mentorship of Professor Yoko Kato. Japanese Stroke Guidelines (JSG) were used for the treatment decision. Patients were graded according to the Spetzler Ponce (SP) system. Considering American Heart Association criteria (AHA), embolization was used as a part of multimodal treatment. Intraoperative microscopic video tools included Indocyanine green ICG, FLOW 800 and dual image video angiography DIVA. Clinical outcomes were measured using Modified Ranking Score (mRs).Results:A total of eleven patients with brain bAVM were studied with a median age of 32 years [IQR = 22-52]. There were ten patients presented with supratentorial and a single patient with infratentorial AVM. Patients were graded according to the Spetzler Ponce (SP) system. There were eight patients in SP A (72,7%), one in group B (9 %) while the rest of them were in C (18 %). Two patients had associated aneurysms that required treatment. The median size of the AVM nidus was 3,50 cm [IQR= 2-5]. Deep venous drainage was found in six patients while three were located in eloquent zones. Clinical outcomes were considered good by mRs <2 in eight patients, seven from the surgically treated group (72,7 % respectively). Surgery median length time was 427, 5 minutes; [IQR =320 - 463] with complete AVM resection in all patients and no mortality recorded in this cohort with the median follow up of 39,5 months [IQR = 19-59].Conclusion:Ideal management of bAVM is still controversial. Those complex vascular lesions require multimodal treatment in a majority of cases in highly specialized centers. In SP A patients, surgery provides the best results with a positive outcome and a small number of complications. With the improvement of endovascular feeder occlusion SP B patients become prone to a more positive outcome. Nowadays, intraoperative microscopic tools such as FLOW 800, ICG and DIVA are irreplaceable while improving safety to deal with bAVM. For SP C patients, a combination of endovascular and stereotactic radiosurgery was found to be a good option in the present time.

Radiosurgery for Cerebral Arteriovenous Malformation (AVM) : Current Treatment Strategy and Radiosurgical Technique for Large Cerebral AVM.

Arteriovenous malformations (AVMs) are congenital anomalies of the cerebrovascular system. AVM harbors 2.2% annual hemorrhage risk in unruptured cases and 4.5% annual hemorrhage risk of previously ruptured cases. Stereotactic radiosurgery (SRS) have been shown excellent treatment outcomes for patients with small- to moderated sized AVM which can be achieved in 80–90% complete obliteration rate with a 2–3 years latency period. The most important factors are associated with obliteration after SRS is the radiation dose to the AVM. In our institutional clinical practice, now 22 Gy (50% isodose line) dose of radiation has been used for treatment of cerebral AVM in single-session radiosurgery. However, dose-volume relationship can be unfavorable for large AVMs when treated in a single-session radiosurgery, resulting high complication rates for effective dose. Thus, various strategies should be considered to treat large AVM. The role of pre-SRS embolization is permanent volume reduction of the nidus and treat high-risk lesion such as AVM-related aneurysm and high-flow arteriovenous shunt. Various staging technique of radiosurgery including volume-staged radiosurgery, hypofractionated radiotherapy and dose-staged radiosurgery are possible option for large AVM. The incidence of post-radiosurgery complication is varied, the incidence rate of radiological post-radiosurgical complication has been reported 30–40% and symptomatic complication rate was reported from 8.1% to 11.8%. In the future, novel therapy which incorporate endovascular treatment using liquid embolic material and new radiosurgical technique such as gene or cytokine-targeted radio-sensitization should be needed.

Abstract TMP117: Subclinical Imaging Changes in Cerebral Cavernous Angiomas During Prospective Surveillance

Introduction: Studies on the natural clinical course of Cavernous Angioma (CA) have reported a &lt;0.5% annual risk of symptomatic hemorrhage (SH). CAs, however, may undergo subclinical changes that can reflect lesional activity. We assess the frequency of asymptomatic hemorrhage or growth (AH) in CAs, and new lesion formation (NLF) during systematic longitudinal follow-up using magnetic resonance imaging (MRI), and correlate with prior SH. Methods: Patients with CA diagnosis were prospectively enrolled in IRB approved database from 09/2009 to 02/2019 (N=327). Imaging and clinical follow-up were recommended annually, or sooner with new symptoms. Patients with 1 or more CA with maximum diameter &gt;4 mm on T2 MRI, not excised or irradiated, and 1 or more clinical/imaging follow-up were included (N=192). New AH and SH were assessed per prospectively articulated criteria, and rates were estimated per lesion-year and patient-year, and NLF in familial cases. Results: There were no demographic or disease confounders among cases included and excluded from the study cohort, except for higher rates of prior SH and greater prevalence of cases with solitary lesion excluded because of surgical treatment. Total follow-up was 410 patient-years (2539 lesion-years). During prospective follow-up, the rate of AH was higher than the rate of SH (12.9% vs. 7.5% per patient-year and 2.1% vs. 1.2% per lesion -year, p=0.02 and p=0.01 respectively). Patients presenting with SH in the prior year had higher rate of AH than those presenting incidentally or with seizures (19.83% and 8.2% per patient-year respectively; p=0.003). A higher rate of NLF on T2 (p=0.0002) and SWI (p=0.0004) was also observed in patients with prior SH compared to stable patients. After an AH, 3 of 6 sporadic patients with solitary lesion and only 2 of 28 familial cases with multiple lesions underwent surgical resection of the lesion with AH. Conclusions: Subclinical imaging changes are more common than SH during prospective follow-up of CAs. They are more common in patients presenting with prior SH, and likely reflect a more sensitive biomarker of CA instability. AH more likely provokes a surgical decision in cases with solitary lesion than in familial cases with multiple lesions.

Abstract WP421: Optimization of Risk Stratification for Anticoagulation-Associated Intracerebral Hemorrhage

Introduction: With more widespread anticoagulant use, anticoagulation-associated intracerebral hemorrhage (ICH) represents an increasing proportion of all ICH. We hypothesized that c ombining ischemic and hemorrhagic stroke risk estimation can guide treatment decisions, with more precision than ischemic risk estimation alone. Methods: We enrolled consecutive patients with anticoagulation-associated ICH in 15 centers in USA, Europe and Asia from 2015-2017. Each patient was assigned annual baseline ischemic stroke and hemorrhage risk based on their CHA 2 DS 2 -VASc and HAS-BLED scores without and with index ICH taken into account. We computed a net risk by subtracting the hemorrhagic from the ischemic risk. If the sum was positive the patient was assigned a “Favorable” indication for anticoagulation; if negative an “Unfavorable”. We compared clinical and neuroimaging characteristics between the two groups. Results: Our cohort comprised 357 patients (59% male, median age 76 [68-82] years). 69% used vitamin-K antagonists (VKA), 31 % Non vitamin K antagonist (NOAC). 191 (53.5%) of patients had a favorable indication for anticoagulation prior to their ICH event; the rest 166 (46.5%) had an unfavorable indication. Those with an unfavorable indication were younger (72[66-80] vs 78[73-84] years, p=0.001, had a lower CHA 2 DS 2 -VASc score (3[3-4] vs 5[4-6], p&lt;0.001) and higher HAS-BLED score (3[2-4] vs 2[2-3], p=0.025). Those with favorable indication had a significantly higher prevalence of all major cardiovascular risk factors and were more likely to use NOAC (35% vs 25%, p=0.045). After including ICH into the HAS-BLED score estimation, 77 of the 191 patients with favorable profile were rendered unfavorable; leaving 114 patients (32% of the cohort) with favorable profile. Conclusions: In this anticoagulation-associated ICH cohort, baseline hemorrhage risk exceeded ischemic risk in ~50% of patients. This finding highlights the need for careful consideration of risk/benefit ratio prior to anticoagulation decisions. The remaining ~ 50% suffered an ICH although their baseline risk of ischemia exceeded that of hemorrhage which stresses the need for imaging, serum or other biomarkers to allow more precise estimation of hemorrhagic complication risk.

The Effect of Flow-Related Aneurysms on Hemorrhagic Risk of Intracranial Arteriovenous Malformations.

Previous reports indicated an association between hemorrhagic presentation and flow-related aneurysms in arteriovenous malformation (AVM) patients. However, it remains unclear whether these flow-related aneurysms result in the hemorrhage of AVM. To characterize this hemorrhage risk using our institutional experience over 25 yr. We retrospectively reviewed records of patients at our institution diagnosed with AVM from 1990 to 2015. Patients without associated aneurysms (AVM only) and those with flow-related aneurysms (AVM-FA) were compared. Those with intranidal or unrelated aneurysms were excluded. Annual risk of AVM-related hemorrhage was calculated using the birth-to-treatment approach and compared using Poisson rate ratio test. Among 526 patients, there were 457 AVM only patients and 69 with flow-related aneurysms. AVM-FA patients were older (P =.005). AVMs with flow-related aneurysms were more likely located in the cerebellar vermis and hemispheres (P =.023 and .001, respectively). Presence of flow-related aneurysms increased the risk of presentation with subarachnoid hemorrhage (P <.001). Interestingly, no significant differences in presenting hemorrhage due to AVM rupture were found (P >.356). The majority of aneurysms were untreated (69.5%), and only 8 (9.8%) had ruptured presentation. At follow-up (mean=5.3 yr), patients with flow-related aneurysms were less likely to develop seizures (P =.004). The annual risk of AVM hemorrhage was 1.33% and 1.05% for AVM only patients and AVM-FA patients, respectively (P =.248). Despite increased risk of subarachnoid hemorrhage at presentation, there was no increased likelihood of rupture in AVMs with flow-related aneurysms. More studies are warranted, as clarifying the competing risks of AVM vs aneurysm rupture may be critical in determining optimal treatment strategy.

Long-Term Outcomes of Indirect Bypass for 629 Children With Moyamoya Disease: Longitudinal and Cross-Sectional Analysis.

Background and Purpose- In pediatric moyamoya disease, there are few reports on the efficacy of surgical intervention for stroke prevention. We evaluated the long-term outcomes of indirect bypass surgery on a relatively large number of children with moyamoya disease in a single center. Methods- From August 1988 to December 2012, 772 children underwent indirect bypass surgery. This study included 629 patients who were followed up for >5 years, excluding patients with moyamoya syndrome. The mean clinical follow-up duration was 12 years (range, 5-29 years). Cross-sectional analysis was performed based on either Karnofsky Performance Scale or Lansky Play Performance Scale to evaluate overall clinical outcomes and factors associated with unfavorable outcomes. To analyze the longitudinal effect of surgery, the annual risk of symptomatic infarction or hemorrhage on the operated hemisphere after indirect bypass surgery was calculated with a person-year method, and the event-free survival rate was evaluated using the Kaplan-Meier method. Results- The overall clinical outcome was favorable in 95% of the patients. The annual risks of symptomatic infarction and hemorrhage on the operated hemispheres were 0.08% and 0.04%, respectively. Furthermore, the 10-year event-free survival rates for symptomatic infarction and hemorrhage were 99.2% and 99.8%. Conclusions- Indirect bypass surgery could provide satisfactory long-term improvement in overall clinical outcome and prevention of recurrent stroke in children with moyamoya disease.

Clinical presentation, natural history and outcomes of intramedullary spinal cord cavernous malformations

ObjectiveThere is a paucity of literature investigating the clinical course of patients with spinal intramedullary cavernous malformations (ISCMs). We present a large case series of ISCMs to describe clinical presentation,...