Vascular compactness of unruptured brain arteriovenous malformation predicts risk of hemorrhage after stereotactic radiosurgery.

The aim of the study was to investigate whether morphology (i.e. compact/diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients receiving Stereotactic Radiosurgery (SRS) for unruptured bAVMs. This retrospective study included 262 adult patients with unruptured bAVMs who underwent upfront SRS. Hemorrhagic events were defined as evidence of blood on CT or MRI. The morphology of bAVMs was evaluated using automated segmentation which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as the ratio of vessel to brain tissue, categorized bAVMs into compact and diffuse types based on the optimal cutoff. Cox proportional hazard model was used to identify the independent factors for post-SRS hemorrhage. The median clinical follow-ups was 62.1 months. Post-SRS hemorrhage occurred in 13 (5.0%) patients and one of them had two bleeds, resulting in an annual bleeding rate of 0.8%. Multivariable analysis revealed bAVM morphology (compact versus diffuse), bAVM volume, and prescribed margin dose were significant predictors. The post-SRS hemorrhage rate increased with larger bAVM volume only among the diffuse nidi (1.7 versus 14.9 versus 30.6 hemorrhage per 1000 person-years in bAVM volume < 20 cm3 versus 20-40 cm3 versus > 40 cm3; p = 0.022). The significantly higher post-SRS hemorrhage rate of Spetzler-Martin grade IV-V compared with grade I-III bAVMs (20.0 versus 3.3 hemorrhages per 1000 person-years; p = 0.001) mainly originated from the diffuse bAVMs rather than the compact subgroup (30.9 versus 4.8 hemorrhages per 1000 person-years; p = 0.035). Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. The post-SRS hemorrhage rate exceeded 2.2% annually within the diffuse and large (> 40 cm3) bAVMs and the diffuse Spetzler-Martin IV-V bAVMs. These findings may help guide patient selection of SRS for the unruptured bAVMs.

Sporadic multiple cerebral arteriovenous malformations: case report and systematic review of additional 80 cases.

INTRODUCTION: In absence of hereditary diseases multiple brain arteriovenous malformations are extremely rare. The case series that would include more than 13 patients are unlikely to be found, which causes an obstacle to comprehensively analyzing the peculiarities of epidemiology, symptoms and treatment options for this disorder. We describe patent with two independent arteriovenous malformations in frontal and parietal lobes that have been treated with combination of preoperative embolization, surgical excision and stereotactic radiosurgery. Systematic review of literature was also performed, focusing on epidemiology of sporadic multiple arteriovenous malformations, niduses location, clinical presentation, treatment and outcomes. EVIDENCE ACQUISITION: We systematically analyzed relevant literature using the PubMed database, encompassing studies in English (published between 1956 and 2023) reporting incidence, epidemiological features, symptomatology and treatment of sporadic multiple brain arteriovenous malformations. EVIDENCE SYNTHESIS: Forty-eight studies with a total of 80 sporadic multiple cerebral arteriovenous malformations were extracted from the literature. Twenty-two papers reported incidence of multiple brain arteriovenous malformations. The average incidence (including our data) was 2.4%, varying significantly between children and adults. Hemorrhage from one AVM was the most frequent debut of multiple cerebral arteriovenous malformations. Surgical removal of niduses remains a valuable treatment option even considering the enhancement of embolization techniques and the development of radiosurgery. CONCLUSIONS: Sporadic multiple cerebral arteriovenous malformations represent a difficult problem to solve. The possibility of persistence of multiple brain arteriovenous malformations should be taken into account when diagnosing and following-up.

Impact of COVID-19 pandemic on treatment and outcomes of cerebral arteriovenous malformations.

BACKGROUND: There has been a recent decrease in interventional management of cerebral arteriovenous malformations (AVMs). The objective of our study was to evaluate the changing patterns in management of AVMs in the first year of the COVID-19 pandemic. METHODS: The National Inpatient Sample (NIS) database was used. From 2016 to 2020, patients with an International Classification of Diseases, 10th revision (ICD-10) diagnosis code for a cerebral AVM were included. An intervention was defined as ICD-10 code for surgical, endovascular, or stereotactic radiosurgery treatment. Odds ratios (ORs) were calculated using a logistic regression model with covariates deemed to be clinically relevant. RESULTS: 63 610 patients with AVMs were identified between 2016 and 2020, 14 340 of which were ruptured. In 2020, patients had an OR of 0.69 for intervention of an unruptured AVM (P<0.0001) compared with 2016-19. The rate of intervention for unruptured AVMs decreased to 13.5% in 2020 from 17.6% in 2016-19 (P<0.0001). The rate of AVM rupture in 2020 increased to 23.9% from 22.2% in 2016-19 (P<0.0001). In 2020, patients with ruptured AVMs had an OR for inpatient mortality of 1.72 compared with 2016-19. Linear regression analysis from 2016 to 2020 showed an inverse relationship between intervention rate and rupture rate (slope -0.499, R2=0.88, P=0.019). CONCLUSION: In 2020, the rate of intervention for unruptured cerebral AVMs decreased compared with past years, with an associated increase in the rate of rupture. Patients with ruptured AVMs also had a higher odds of mortality.

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

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

Prevalence and Predictors of Hereditary Hemorrhagic Telangiectasia and Capillary-Malformation Arteriovenous Malformation Syndrome Among Children with Neurovascular Malformations.

OBJECTIVE: To investigate the prevalence and predictors of hereditary hemorrhagic telangiectasia (HHT) and capillary-malformation arteriovenous malformation (CM-AVM) syndrome among children with no prior personal or family history of these diseases who presented with an arteriovenous shunt lesion. STUDY DESIGN: A retrospective chart review was completed on patients aged 0 through 21 years with arteriovenous shunt lesions evaluated at our Cerebrovascular Center. Diagnosis of definite or suspected HHT or CM-AVM was based on clinical features and genetic testing. Associations between final diagnosis and type and number of lesions, epistaxis, telangiectasias, CM, and pulmonary AVMs were assessed. RESULTS: Eighty-nine patients were included. Thirteen (14.6%) had definite HHT, 11 (12.4%) suspected HHT, and 4 (4.5%) definite CM-AVM. Having ≥2 episodes of epistaxis/year and ≥ 2 sites with telangiectasias were each associated with definite HHT (P < .001). Having ≥ 2 CM was associated with definite CM-AVM (P < .001). Pulmonary AVM was associated with increased odds of having definite HHT (OR = 6.3, 95% CI: 1.2-33.4). Multiple lesions (OR = 24.5, 95% CI: 4.5-134.8) and arteriovenous fistulas (OR = 6.2, 95% CI: 1.9-20.3) each increased the likelihood of having definite HHT or CM-AVM. Genetic testing was positive in 31% of patients tested. CONCLUSIONS: We recommend that children with neurovascular shunt lesions be offered genetic testing and undergo further evaluation for HHT and CM-AVM. Awareness and early diagnosis of these conditions is a critical step toward improving long-term outcomes and preventing disease-associated complications.

Postoperative de novo epilepsy after resection of brain arteriovenous malformations: A national database study of 536 patients.

OBJECTIVE: We aimed to assess the incidence and risk factors for de novo epilepsy after arteriovenous malformation (AVM) resection and compare them with a nonresection cohort after propensity score matching, utilizing a national database. METHODS: Utilizing the TriNetX Research Network, we queried cases from January 1, 2004 to March 1, 2022. We included patients of all ages who underwent supratentorial AVM resection, presenting without seizures on or before surgery and without being on antiseizure medications at least 1 day before surgery. The primary outcome was seizures manifesting at least 6 weeks after surgery. Patient characteristics and outcomes were compared between the cohorts with and without postoperative epilepsy. Further cohorts were created to compare cohorts with and without embolization or rupture. After propensity score matching, we compared an additional cohort of patients with an AVM diagnosis who did not undergo resection. RESULTS: Of the 536 patients (mean age = 38.9 ± 19.6, 52% females) presenting without seizure who underwent AVM resection, 99 (18.5%) developed de novo epilepsy, with a 1-year cumulative incidence of 13.8%. Patients with epilepsy had higher rates of intracerebral hemorrhage, and intracerebral hemorrhage was less common in the embolization cohort. Patients in the ruptured cohort were older and more often males. After propensity score matching with 18 588 patients with AVM diagnosis but no resection, each group consisted of 529 patients, and de novo epilepsy at 1 year was significantly higher in the AVM resection cohort compared to the nonresection cohort (11.5% vs. 3.4%, p < .001). SIGNIFICANCE: This analysis of 536 patients provides evidence that de novo epilepsy after brain AVM resection occurs at a 1-year cumulative incidence of 13.8%, with a total of 19.4% developing de novo epilepsy. Intracerebral hemorrhage was inconsistently associated with postoperative de novo epilepsy. De novo epilepsy was significantly less frequent after AVM diagnosis without resection.

Recurrence of brain arteriovenous malformations in pediatric patients: a long-term follow-up study.

BACKGROUND: Previously thought to be congenital, AVMs have shown evidence of de-novo formation and continued growth, thus shifting thoughts on their pathophysiology. Pediatric AVM patients have been reported to be more prone to develop AVM recurrence after a seemingly complete cure. Therefore, we assessed the risk of AVM treated in childhood to recur in adulthood after a long-term follow-up in our own cohort. METHODS: Control DS-angiography was arranged during 2021-2022 as part of a new protocol for all AVM patients who were under 21 years of age at the time of their treatment and in whom the treatment had occurred at least five years earlier. Angiography was offered only to patients under 50 years of age at the time of the new protocol. The complete eradication of AVM after the primary treatment had been originally confirmed with DSA in every patient. RESULTS: A total of 42 patients participated in the late DSA control, and 41 of them were included in this analysis after excluding the patient diagnosed with HHT. The median age at the time of admission for AVM treatment was 14.6 (IQR 12-19, range 7-21 years) years. The median age at the time of the late follow-up DSA was 33.8 years (IQR 29.8-38.6, range 19.4-47.9 years). Two recurrent sporadic AVMs and one recurrent AVM in a patient with hereditary hemorrhagic telangiectasia (HHT) were detected. The recurrence rate was 4.9% for sporadic AVMs and 7.1% if HHT-AVM was included. All the recurrent AVMs had originally bled and been treated microsurgically. The patients with sporadic AVM recurrence had been smoking their whole adult lives. CONCLUSIONS: Pediatric and adolescent patients are prone to develop recurrent AVMs, even after complete AVM obliteration verified by angiography. Therefore, imaging follow-up is recommended.

Risk for Brain Arteriovenous Malformation Rupture During Pregnancy and Puerperium.

BACKGROUND: 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. OBJECTIVE: To accurately quantify the risk increase for AVM hemorrhage during pregnancy. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Haemorrhage risk of brain arteriovenous malformation during pregnancy and puerperium.

BACKGROUND: This study aimed to assess whether pregnancy and puerperium were associated with the risk of brain arteriovenous malformation (bAVM) haemorrhage. METHODS: A retrospective review was conducted in Xiangya Hospital, Central South University from January 2012 to December 2021. A case-crossover design was adopted to calculate the incidence density of bAVM-related haemorrhage among female patients in risk (pregnancy and puerperium) and control (non-pregnancy and non-puerperium) periods, according to four scenarios observed in different populations (scenario I: patients with haemorrhagic bAVM of all ages; scenario II: patients with haemorrhagic bAVM of all ages, with at least one previous pregnancy; scenario III: patients with haemorrhagic bAVM who are of reproductive age (15-45 years); scenario IV: patients with haemorrhagic bAVM of reproductive age (15-45 years), with at least one previous pregnancy. Next, a comprehensive literature aggregation (up to April 2022) was performed for evidence synthesis. RESULTS: Among the 311 female patients with haemorrhagic bAVM, a significant haemorrhage risk during pregnancy and puerperium was found in Scenarios I (relative risk [RR], 2.08; 95% CI, 1.28 to 3.39), II (RR, 3.21; 95% CI, 1.95 to 5.31) and IV (RR, 2.92; 95% CI, 1.73 to 4.93); however, a suggestive risk was found in scenario III (RR, 1.62; 95% CI, 0.99 to 2.67). Evidence synthesis revealed a consistent haemorrhage risk among patients of all ages (RR, 3.15; 95% CI, 1.93 to 5.15) and those of reproductive age (RR, 1.29; 95% CI, 0.89 to 1.86). CONCLUSION: Compared with most previous studies, a higher but relatively moderate risk for bAVM-related haemorrhage was identified during pregnancy and puerperium. Individualised prevention and treatment strategies should be preferred when neurosurgeons make clinical decisions.

Risk factors of seizure presentation in brain arteriovenous malformation patients and seizure outcomes after single-modality treatments.

BACKGROUND: Epileptic seizures are common symptoms in brain arteriovenous malformation patients and seizure control was an important issue in the treatments. This retrospective study attempted to define the risk factors of seizure presentation and to evaluate the effects of treatment modalities on seizure outcomes. METHODS: Patients receiving single treatment modality during 2013-2016 years, followed up more than 2 years were recruited. Logistic regression analysis was used to detect independent predictors. The factors associated with seizure control were analyzed in patients with pre-treatment seizures, and the factors associated with de novo seizures were analyzed in patents without pre-treatment seizures. RESULTS: Multivariate analysis identified that the independent predictors of seizure presentation were unruptured (ruptured vs. unruptured, OR = 0.314), and in the frontal (frontal vs. parietal, OR = 3.982) or temporal lobe (temporal vs parietal, OR = 3.313). In 47 patients with seizure presentation, good seizure outcomes were achieved in 26 cases. Partial obliteration of nidus (partial vs complete, OR = 32.301) and headache presentation were independent predictors of poor outcome. In 169 patients without seizure presentation, de novo seizures occurred in 22 cases. Treatments of microsurgery or radiosurgery led to a higher incidence of de novo seizures than intravascular embolization. CONCLUSIONS: Patients with unruptured and frontal/temporal lobe located nidus were more likely to manifest seizure presentation. Incomplete nidus obliteration was an independent risk factor of poor outcomes in patients with pre-existing seizures. However, compared to microsurgery or radiosurgery, endovascular embolization was less likely to cause de novo seizures in patients without pre-existing seizures.

Impact of ARUBA trial on trends and outcomes in symptomatic non-ruptured brain AVMs: A national sample analysis.

INTRODUCTION: The real-world evolution of management and outcomes of patients with unruptured brain arteriovenous malformations (AVMs) has not been well-delineated following the ARUBA trial findings of no general advantage of initial interventional (surgical/endovascular/radiotherapy) vs. initial conservative medical therapy. METHODS: We analyzed the National Inpatient Sample from 2009-2018, capturing 20% of all admissions in the U.S. Validated ICD-9 and -10 codes defined brain AVMs, comorbidities, and the use of interventional modalities. Analyses were performed by year and for the dichotomized periods of pre-ARUBA (2009-2013) vs. post-ARUBA (2014-2018). RESULTS: Among the national projected 88,037 AVM admissions, 72,812 (82.7%) were unruptured AVMs and 15,225 (17.3%) were ruptured AVMs. Among uAVMs, 51.4% admitted pre-ARUBA and 48.6% in post-ARUBA period. The post-ARUBA patients were mildly older (median age 53.3 vs. 51.8 (p = 0.001) and had more comorbidities including hypertension, diabetes, obesity, renal impairment, and smoking. Before the first platform report of ARUBA (2009-2012), rates of use of interventional treatments during uAVM admissions trended up from 31.8% to 35.4%. Thereafter, they declined significantly to 26.4% in 2018 (p = 0.02). The decline was driven by a reduction in the frequency of endovascular treatment from 18.8% to 13.9% and inpatient stereotactic radiosurgery from 0.5% to 0.1%. No change occurred in the frequency of microsurgery or combined endovascular and surgical approaches. Adjusted multivariable model of uAVMs showed increased odds of discharge to a long-term inpatient facility or in-hospital death [OR 1.14 (1.02-1.28), p = 0.020] in post-ARUBA. A significantly increased proportion of ruptured AVMs from 17.0% to 23.3% was observed consistently in post-ARUBA. CONCLUSION: Nationwide practice in the management of unruptured AVMs changed substantially with the publication of the ARUBA trial in a durable and increasing manner. Fewer admissions with the interventional treatment of unruptured AVMs occurred, and a corresponding increase in admission for ruptured AVMs transpired, as expected with a strategy of watchful waiting and treatment only after an index bleeding event. Further studies are needed to determine whether these trends can be considered to be ARUBA trial effect or are merely coincidental.

Incidence and risk factors of epilepsy following brain arteriovenous malformation rupture in adult patients.

BACKGROUND: Little is known about incidence, time of onset, clinical presentation, and risk factors of epileptic seizure following brain arteriovenous malformation (bAVM) rupture. METHODS: We performed a monocentric retrospective cohort study from January 2003 to March 2021. The main objective of this study was to determine the incidence of seizures after spontaneous bAVM rupture in nonepileptic adult patients and describe the corresponding clinical features. The secondary objective was to identify clinical, radiological, or biological predictors for the occurrence of de novo seizures after bAVM rupture. RESULTS: Of the 296 cases of bAVM rupture registered during the study period, 247 nonepileptic patients (male 53%, median age 40) were included in the study. Fifty-nine patients (23.9%) had at least one seizure after bAVM rupture. The use of preventive antiepileptic drugs (10.3 [1.5-74.1]; P = 0.02) and decompressive craniectomy (15.4 [2.0-125]; P < 0.009) were independently associated with the occurrence of epilepsy after the bAVM rupture. The factors independently associated with the absence of any seizure after the rupture were isolated intraventricular hemorrhage (0.3 [0.1-0.99]; P = 0.04) and infratentorial location of the bAVM (0.2 [0.1-0.5]; P = 0.09). The first seizure occurred within the first year or within 5 years in, respectively, 83.1% and 98.3% of the patients. CONCLUSIONS: Epilepsy affects nearly a quarter of patients after bAVM rupture. Decompressive craniectomy represents an independent risk factor significantly associated with the occurrence of epilepsy after bAVM rupture. The introduction of preventive AEDs after rupture could be considered in these most severe patients who have a decompressive craniectomy.

Patient frailty association with cerebral arteriovenous malformation microsurgical outcomes and development of custom risk stratification score: an analysis of 16,721 nationwide admissions.

OBJECTIVE: Patient frailty is associated with poorer perioperative outcomes for several neurosurgical procedures. However, comparative accuracy between different frailty metrics for cerebral arteriovenous malformation (AVM) outcomes is poorly understood and existing frailty metrics studied in the literature are constrained by poor specificity to neurosurgery. This aim of this paper was to compare the predictive ability of 3 frailty scores for AVM microsurgical admissions and generate a custom risk stratification score. METHODS: All adult AVM microsurgical admissions in the National (Nationwide) Inpatient Sample (2002-2017) were identified. Three frailty measures were analyzed: 5-factor modified frailty index (mFI-5; range 0-5), 11-factor modified frailty index (mFI-11; range 0-11), and Charlson Comorbidity Index (CCI) (range 0-29). Receiver operating characteristic curves were used to compare accuracy between metrics. The analyzed endpoints included in-hospital mortality, routine discharge, complications, length of stay (LOS), and hospitalization costs. Survey-weighted multivariate regression assessed frailty-outcome associations, adjusting for 13 confounders, including patient demographics, hospital characteristics, rupture status, hydrocephalus, epilepsy, and treatment modality. Subsequently, k-fold cross-validation and Akaike information criterion-based model selection were used to generate a custom 5-variable risk stratification score called the AVM-5. This score was validated in the main study population and a pseudoprospective cohort (2018-2019). RESULTS: The authors analyzed 16,271 total AVM microsurgical admissions nationwide, with 21.0% being ruptured. The mFI-5, mFI-11, and CCI were all predictive of lower rates of routine discharge disposition, increased perioperative complications, and longer LOS (all p < 0.001). Their AVM-5 risk stratification score was calculated from 5 variables: age, hydrocephalus, paralysis, diabetes, and hypertension. The AVM-5 was predictive of decreased rates of routine hospital discharge (OR 0.26, p < 0.001) and increased perioperative complications (OR 2.42, p < 0.001), postoperative LOS (+49%, p < 0.001), total LOS (+47%, p < 0.001), and hospitalization costs (+22%, p < 0.001). This score outperformed age, mFI-5, mFI-11, and CCI for both ruptured and unruptured AVMs (area under the curve [AUC] 0.78, all p < 0.001). In a pseudoprospective cohort of 2005 admissions from 2018 to 2019, the AVM-5 remained significantly associated with all outcomes except for mortality and exhibited higher accuracy than all 3 earlier scores (AUC 0.79, all p < 0.001). CONCLUSIONS: Patient frailty is predictive of poorer disposition and elevated complications, LOS, and costs for AVM microsurgical admissions. The authors' custom AVM-5 risk score outperformed age, mFI-5, mFI-11, and CCI while using threefold less variables than the CCI. This score may complement existing AVM grading scales for optimization of surgical candidates and identification of patients at risk of postoperative medical and surgical morbidity.

De novo epilepsy after microsurgical resection of brain arteriovenous malformations.

OBJECTIVE: Seizures are the second most common presenting symptom of brain arteriovenous malformations (bAVMs) after hemorrhage. Risk factors for preoperative seizures and subsequent seizure control outcomes have been well studied. There is a paucity of literature on postoperative, de novo seizures in initially seizure-naïve patients who undergo resection. Whereas this entity has been documented after craniotomy for a wide variety of neurosurgically treated pathologies including tumors, trauma, and aneurysms, de novo seizures after bAVM resection are poorly studied. Given the debilitating nature of epilepsy, the purpose of this study was to elucidate the incidence and risk factors associated with de novo epilepsy after bAVM resection. METHODS: A retrospective review of patients who underwent resection of a bAVM over a 15-year period was performed. Patients who did not present with seizure were included, and the primary outcome was de novo epilepsy (i.e., a seizure disorder that only manifested after surgery). Demographic, clinical, and radiographic characteristics were compared between patients with and without postoperative epilepsy. Subgroup analysis was conducted on the ruptured bAVMs. RESULTS: From a cohort of 198 patients who underwent resection of a bAVM during the study period, 111 supratentorial ruptured and unruptured bAVMs that did not present with seizure were included. Twenty-one patients (19%) developed de novo epilepsy. One-year cumulative rates of developing de novo epilepsy were 9% for the overall cohort and 8.5% for the cohort with ruptured bAVMs. There were no significant differences between the epilepsy and no-epilepsy groups overall; however, the de novo epilepsy group was younger in the cohort with ruptured bAVMs (28.7 ± 11.7 vs 35.1 ± 19.9 years; p = 0.04). The mean time between resection and first seizure was 26.0 ± 40.4 months, with the longest time being 14 years. Subgroup analysis of the ruptured and endovascular embolization cohorts did not reveal any significant differences. Of the patients who developed poorly controlled epilepsy (defined as Engel class III-IV), all had a history of hemorrhage and half had bAVMs located in the temporal lobe. CONCLUSIONS: De novo epilepsy after bAVM resection occurs at an annual cumulative risk of 9%, with potentially long-term onset. Younger age may be a risk factor in patients who present with rupture. The development of poorly controlled epilepsy may be associated with temporal lobe location and a delay between hemorrhage and resection.

Cerebral vasospasm following arteriovenous malformation rupture: a population-based cross-sectional study.

OBJECTIVE: Studies examining the risk factors and clinical outcomes of arterial vasospasm secondary to cerebral arteriovenous malformation (cAVM) rupture are scarce in the literature. The authors used a population-based national registry to investigate this largely unexamined clinical entity. METHODS: Admissions for adult patients with cAVM ruptures were identified in the National Inpatient Sample during the period from 2015 to 2019. Complex samples multivariable logistic regression and chi-square automatic interaction detection (CHAID) decision tree analyses were performed to identify significant associations between clinical covariates and the development of vasospasm, and a cAVM-vasospasm predictive model (cAVM-VPM) was generated based on the effect sizes of these parameters. RESULTS: Among 7215 cAVM patients identified, 935 developed vasospasm, corresponding to an incidence rate of 13.0%; 110 of these patients (11.8%) subsequently progressed to delayed cerebral ischemia (DCI). Multivariable adjusted modeling identified the following baseline clinical covariates: decreasing age by decade (adjusted odds ratio [aOR] 0.87, 95% CI 0.83-0.92; p < 0.001), female sex (aOR 1.68, 95% CI 1.45-1.95; p < 0.001), admission Glasgow Coma Scale score < 9 (aOR 1.34, 95% CI 1.01-1.79; p = 0.045), intraventricular hemorrhage (aOR 1.87, 95% CI 1.17-2.98; p = 0.009), hypertension (aOR 1.77, 95% CI 1.50-2.08; p < 0.001), obesity (aOR 0.68, 95% CI 0.55-0.84; p < 0.001), congestive heart failure (aOR 1.34, 95% CI 1.01-1.78; p = 0.043), tobacco smoking (aOR 1.48, 95% CI 1.23-1.78; p < 0.019), and hospitalization events (leukocytosis [aOR 1.64, 95% CI 1.32-2.04; p < 0.001], hyponatremia [aOR 1.66, 95% CI 1.39-1.98; p < 0.001], and acute hypotension [aOR 1.67, 95% CI 1.31-2.11; p < 0.001]) independently associated with the development of vasospasm. Intraparenchymal and subarachnoid hemorrhage were not associated with the development of vasospasm following multivariable adjustment. Among significant associations, a CHAID decision tree algorithm identified age 50-59 years (parent node), hyponatremia, and leukocytosis as important determinants of vasospasm development. The cAVM-VPM achieved an area under the curve of 0.65 (sensitivity 0.70, specificity 0.53). Progression to DCI, but not vasospasm alone, was independently associated with in-hospital mortality (aOR 2.35, 95% CI 1.29-4.31; p = 0.016) and lower likelihood of routine discharge (aOR 0.62, 95% CI 0.41-0.96; p = 0.031). CONCLUSIONS: This large-scale assessment of vasospasm in cAVM identifies common clinical risk factors and establishes progression to DCI as a predictor of poor neurological outcomes.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Children with Arteriovenous Malformations of the Central Nervous System: A Retrospective Study of 12 Pediatric Cases from a Single Tertiary Center in Slovenia.

BACKGROUND Arteriovenous malformation (AVM) of the central nervous system (CNS) is a developmental condition that consists of a focal mass of interconnected veins and arteries. This retrospective study was conducted at the only tertiary center in Slovenia and included 12 pediatric cases of AVM of the CNS, diagnosed between 2000 and 2020. MATERIAL AND METHODS The patients were collected based on the ICD coding system. All available medical documentation was reviewed. RESULTS Our cohort included 6 boys and 6 girls. The mean age of patients was 9.1 years, range 1 month to 16.3 years. The estimated incidence of pediatric AVM of the CNS in Slovenia is 0.22/100 000 children per year. Ten patients had brain AVM and 2 patients had spinal AVM. At first presentation, 7 patients presented with intracerebral hemorrhage, 2 with focal neurological deficits, 1 with epilepsy, 1 with chronic headache, and 1 patient was asymptomatic. Two patients had their first hemorrhage after an already-established diagnosis of AVM. Endovascular embolization was performed in 50%, surgical resection in 33%, and conservative treatment in 17% of patients. Five patients had no residual neurological sequelae, 6 had some neurological deficits, and 1 patient died. Complete obliteration of AVM was achieved in 3 patients treated with surgery. They all had a favorable outcome, with no or mild deficit. CONCLUSIONS The study findings support that early diagnosis and management are required to prevent neurological deterioration and vessel rupture from AVM. Endovascular embolization was the most commonly used procedure. Complete obliteration was associated with good neurological outcome.

Validation of the Ruptured Arteriovenous Malformation Grading Scale in a pediatric cohort.

OBJECTIVE: Pediatric brain arteriovenous malformations (AVMs) are the leading cause of spontaneous intracranial hemorrhage (SICH) in children. Although the incidence of SICH is low in pediatric populations, such events cause substantial morbidity. The recently created Ruptured Arteriovenous Malformation Grading Scale (RAGS) is proposed as a reliable and novel grading system to specifically serve as a predictor of clinical outcomes in patients following AVM rupture, similar to the Hunt and Hess (HH) grade for ruptured aneurysms. While these data are promising, pediatric patients were notably absent from the original study validating the RAGS. Therefore, correlation of the RAGS score with clinical outcomes following AVM rupture in individuals younger than 18 years of age using the RAGS score is needed. The objective of this study was to validate the RAGS in a cohort of pediatric patients with AVMs who presented with hemorrhage, thereby demonstrating the score's generalizability, and expanding its external validity. METHODS: A cohort of children with ruptured AVMs were retrospectively reviewed. Using disability, measured by the modified Rankin Scale (mRS), as the response variable, the area under the receiver operating characteristic curve (AUROC) was calculated for patients based on their RAGS scores for three time periods. The AUROC values were then compared with those generated by two commonly used clinical grading systems, the HH classification and Glasgow Coma Scale. RESULTS: A total of 81 children who presented with ruptured AVMs were included in the study, with a mean follow-up duration of 4 years. The RAGS score outperformed other clinical grading scales in predicting mRS scores, with AUROC values of 0.81, 0.82, and 0.81 at three distinct follow-up periods. CONCLUSIONS: The RAGS score correlated well with the clinical outcome after AVM rupture in pediatric patients. Additional validation studies across multiple treatment centers are needed to further demonstrate the generalizability of the scoring system.

Neurovascular Manifestations in Pediatric Patients With Hereditary Haemorrhagic Telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a multiorgan vascular dysplasia with limited data regarding its neurovascular manifestations and genotype-phenotype correlation in children. The objective of this study was to describe the neurovascular findings in a large cohort of children with HHT and correlate between phenotype and genotype. METHODS: This retrospective study was conducted on 221 children (<18 years) with a definite or possible diagnosis of HHT based on Curacao criteria, or with positive genetics for the mutated genes of ENG, ACVRL-1, and SMAD-4, who also underwent brain MRI and/or conventional angiography. Demographic and clinical information, imaging findings, and follow up information were gathered. RESULTS: Two hundred twenty-one children with HHT (70.6% genetically confirmed, and 99.5% positive family history) were included, with a median age of 7 years (interquartile range: 3 to 11 years) and 58.8% male predominance. Neurovascular lesions were found in 64 of 221 (28.9%), with 3.1% prevalence of intracranial hemorrhage. The most commonly observed vascular malformations were developmental venous anomalies (48.5%) and brain arteriovenous malformations (AVMs) (31.2%), followed by capillary malformations (14.1%). Multiple AVMs were seen in 10.0% of the cohort. We found no instances of de novo AVM (1281.8 patient-years).A significantly higher proportion of patients with ENG mutations (19.7%) had brain AVM than those with ACVRL-1 (4.9%) and SMAD-4 (0%) mutations (P < 0.01). There was no significant difference in the hemorrhagic risk of shunting lesions associated with ENG (35.3%) or ACVRL-1 (33.3%) positivity (P = 0.9). CONCLUSIONS: We describe the neurovascular imaging and genetic findings from a large pediatric cohort of HHT, to enhance clinical awareness and guide management of patients with HHT.

Interest of awake surgery for ruptured cerebral arteriovenous malformations close to speech areas - Surgical note.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are rare, with incidence of 1.12-1.42 cases per 100,000 person-years (Ozpinar et al., 2017). Few studies report applications of awake surgery. The goal of this report was to assess the interest of awake surgery in complete resection of cortical AVMs located close to eloquent speech areas, enabling detection of real functional cortical reorganization due to the AVM and parenchymal hematoma. CASE REPORT: A 38-year-old right-handed patient was admitted to the University Hospital of Besançon for dysphasia due to a ruptured left temporal arteriovenous malformation. The patient underwent asleep-awake-asleep surgery. Intraoperative cortical mapping revealed the presence of functional language areas in uncommon locations compared to known neuro-functional anatomy. DISCUSSION: In this patient, speech areas were redistributed, probably due to neuroplasticity after cerebral hemorrhage, leading to a new cortical architecture, which would have been unrecognized based on preoperative radiological imaging alone. CONCLUSION: We report the interest of awake surgery to achieve complete safe resection of ruptured AVMs located close to eloquent speech areas, using intraoperative cortical mapping.