Dural arteriovenous fistulas are not observed to convert to a higher grade after partial embolization.

OBJECTIVE: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

Nonconvulsive status epilepticus in patients with acute subarachnoid hemorrhage is associated with negative arterial spin labeling on peri-ictal magnetic resonance images.

Purpose: Non-convulsive status epilepticus (NCSE) is characterized by repetitive or continuous seizures without convulsions. Arterial spin labeling (ASL) is useful for assessing hyperperfusion due to neurovascular unit coupling in patients with NCSE; subarachnoid hemorrhage (SAH) impairs the neurovascular unit. We hypothesized that the sensitivity of ASL in detecting NCSE is low in patients with SAH during the acute phase. Methods: Based on ASL findings obtained within 48 h after the clinical suspicion of focal-onset NCSE, we divided 34 patients into ASL-negative (no hyperperfusion; n = 10) and ASL-positive (confirmed hyperperfusion; n = 24) groups. We further divided the two groups according to the NCSE etiology: patients who were diagnosed with NCSE within 14 days after SAH onset (acute SAH, n = 11) and patients with NCSE due to factors other acute SAH (n = 23) and compared their characteristics. Results: In 10 of the 34 patients (29.4 %) the ASL findings were normal. The rate of acute SAH was significantly higher in ASL-negative- (n = 8, 80.0 %) than ASL-positive patients (n = 3, 12.5 %). The rate of patients in aphasic status was significantly lower in ASL-negative patients (n = 1, 10 %) than in ASL-positive patients (n = 12, 50.0 %). Conclusion: Normal ASL findings alone should not be used to exclude a diagnosis of NCSE particularly in patients in the acute phase of SAH with deterioration or no improvement in consciousness.

The VEBAS score: a practical scoring system for intracranial dural arteriovenous fistula obliteration.

BACKGROUND: Tools predicting intracranial dural arteriovenous fistulas (dAVFs) treatment outcomes remain scarce. This study aimed to use a multicenter database comprising more than 1000 dAVFs to develop a practical scoring system that predicts treatment outcomes. METHODS: Patients with angiographically confirmed dAVFs who underwent treatment within the Consortium for Dural Arteriovenous Fistula Outcomes Research-participating institutions were retrospectively reviewed. A subset comprising 80% of patients was randomly selected as training dataset, and the remaining 20% was used for validation. Univariable predictors of complete dAVF obliteration were entered into a stepwise multivariable regression model. The components of the proposed score (VEBAS) were weighted based on their ORs. Model performance was assessed using receiver operating curves (ROC) and areas under the ROC. RESULTS: A total of 880 dAVF patients were included. Venous stenosis (presence vs absence), elderly age (<75 vs ≥75 years), Borden classification (I vs II-III), arterial feeders (single vs multiple), and past cranial surgery (presence vs absence) were independent predictors of obliteration and used to derive the VEBAS score. A significant increase in the likelihood of complete obliteration (OR=1.37 (1.27-1.48)) with each additional point in the overall patient score (range 0-12) was demonstrated. Within the validation dataset, the predicted probability of complete dAVF obliteration increased from 0% with a 0-3 score to 72-89% for patients scoring ≥8. CONCLUSION: The VEBAS score is a practical grading system that can guide patient counseling when considering dAVF intervention by predicting the likelihood of treatment success, with higher scores portending a greater likelihood of complete obliteration.

Dural Arteriovenous Fistulas With Cognitive Impairment: Angiographic Characteristics and Treatment Outcomes.

BACKGROUND AND OBJECTIVES: Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs. METHODS: Patients with dAVFs-CI were analyzed from the CONDOR Consortium, a multicenter repository comprising 1077 dAVFs. A propensity score matching analysis was conducted to compare dAVFs-CI with Borden type II and type III dAVFs without cognitive impairment (controls). Logistic regression was used to identify angiographic characteristics specific to dAVFs-CI. Furthermore, post-treatment outcomes were analyzed. RESULTS: A total of 60 patients with dAVFs-CI and 60 control dAVFs were included. Outflow obstruction leading to venous hypertension was observed in all dAVFs-CI. Sinus stenosis was significantly associated with dAVFs-CI (OR 2.85, 95% CI: 1.16-7.55, P = .027). dAVFs-CI were more likely to have a higher number of arterial feeders (OR 1.56, 95% CI 1.22-2.05, P < .001) and draining veins (OR 2.05, 95% CI 1.05-4.46, P = .004). Venous ectasia increased the risk of dAVFs-CI (OR 2.38, 95% CI 1.13-5.11, P = .024). A trend toward achieving asymptomatic status at follow-up was observed in patients with successful closure of dAVFs (OR 2.86, 95% CI 0.85-9.56, P = .09). CONCLUSION: Venous hypertension is a key angiographic feature of dAVFs-CI. Moreover, these fistulas present at a mean age of 58 years-old, and exhibit a complex angioarchitecture characterized by an increased number of arteriovenous connections and stenosed sinuses. The presence of venous ectasia further exacerbates the impaired drainage and contributes to the development of dAVFs-CI. Notably, in certain cases, closure of the dAVF has the potential to reverse symptoms.

Natural history, angiographic presentation and outcomes of anterior cranial fossa dural arteriovenous fistulas.

BACKGROUND: Anterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) are aggressive vascular lesions. The pattern of venous drainage is the most important determinant of symptoms. Due to the absence of a venous sinus in the anterior cranial fossa, most ACF-dAVFs have some degree of drainage through small cortical veins. We describe the natural history, angiographic presentation and outcomes of the largest cohort of ACF-dAVFs. METHODS: The CONDOR consortium includes data from 12 international centers. Patients included in the study were diagnosed with an arteriovenous fistula between 1990-2017. ACF-dAVFs were selected from a cohort of 1077 arteriovenous fistulas. The presentation, angioarchitecture and treatment outcomes of ACF-dAVF were extracted and analyzed. RESULTS: 60 ACF-dAVFs were included in the analysis. Most ACF-dAVFs were symptomatic (38/60, 63%). The most common symptomatic presentation was intracranial hemorrhage (22/38, 57%). Most ACF-dAVFs drained through cortical veins (85%, 51/60), which in most instances drained into the superior sagittal sinus (63%, 32/51). The presence of cortical venous drainage predicted symptomatic presentation (OR 9.4, CI 1.98 to 69.1, p=0.01). Microsurgery was the most effective modality of treatment. 56% (19/34) of symptomatic patients who were treated had complete resolution of symptoms. Improvement of symptoms was not observed in untreated symptomatic ACF-dAVFs. CONCLUSION: Most ACF-dAVFs have a symptomatic presentation. Drainage through cortical veins is a key angiographic feature of ACF-dAVFs that accounts for their malignant course. Microsurgery is the most effective treatment. Due to the high risk of bleeding, closure of ACF-dAVFs is indicated regardless of presentation.

Activation of the NLRP3/IL-1ß/MMP-9 pathway and intracranial aneurysm rupture associated with the depletion of ERα and Sirt1 in oophorectomized rats.

OBJECTIVE: Subarachnoid hemorrhage (SAH) due to intracranial aneurysm (IA) rupture is often a devastating event. Since the incidence of SAH increases especially in menopause, it is crucial to clarify the detailed pathogenesis of these events. The activation of vascular nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes has been studied in ischemic stroke and cardiovascular disease. However, the role of NLRP3 in IA rupture still needs to be explained. The authors sought to test their hypothesis that, under estrogen-deficient conditions, activation of NLRP3 inflammasomes via downregulation of the estrogen receptor (ER) facilitates IA rupture. METHODS: Ten-week-old female Sprague Dawley rats with and without oophorectomy were subjected to hemodynamic changes and hypertension (OVX+/HT and OVX-/HT, respectively) and fed a high-salt diet. Separately, using human brain endothelial cells (HBECs) and human brain smooth muscle cells (HBSMCs), the authors tested the effect of NLRP3 under estrogen-free conditions and in the presence of estradiol or of ER agonists. RESULTS: In OVX+/HT rats, the frequency of IA rupture was significantly higher than in OVX-/HT rats (p = 0.03). In the left posterior cerebral artery prone to rupture in OVX+/HT rats, the levels of the mRNAs encoding ERα and Sirt1, but not of that encoding ERß, were decreased, and the levels of the mRNAs encoding NLRP3, interleukin-1ß (IL-1ß), and matrix metalloproteinase 9 (MMP-9) were elevated. Immunohistochemical analysis demonstrated that the expression profiles of these proteins correlated with their mRNA levels. Treatment with an ER modulator, bazedoxifene, normalized the expression profiles of these proteins and improved SAH-free survival. In HBECs and HBSMCs under estrogen-free conditions, the depletion of ERα and Sirt1 and the accumulation of NLRP3 were counteracted by exposure to estradiol or to an ERα agonist but not to an ERß agonist. CONCLUSIONS: To the authors' knowledge, this work represents the first demonstration that, in an aneurysm model under estrogen-deficient conditions, the depletion of ERα and Sirt1 may contribute to activation of the NLRP3/IL-1ß/MMP-9 pathway, facilitating the rupture of IAs in the estrogen-deficient rat IA rupture model.

An imbalance between RAGE/MR/HMGB1 and ATP1α3 is associated with inflammatory changes in rat brain harboring cerebral aneurysms prone to rupture.

BACKGROUND AND PURPOSE: An aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na+/K+-ATPase (ATP1α3). METHODS: Ten-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet. RESULTS: Six weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05). CONCLUSIONS: Regulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs.

Risk of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage.

BACKGROUND: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage. METHODS: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference. RESULTS: Of 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2-14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3-5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7-12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4-37.7; P, 0.026). CONCLUSIONS: The risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.

Seizure types associated with negative arterial spin labeling and positive diffusion-weighted imaging on peri-ictal magnetic resonance imaging.

PURPOSE: Arterial spin labeling (ASL) and diffusion-weighted imaging (DWI) are useful for assessing hyperperfusion and cytotoxic edema, respectively, caused by acute seizures. This study investigated the clinical characteristics associated with normal ASL findings and DWI abnormalities in patients with acute seizures. METHODS: Overall, 41 patients with ASL and DWI images that were obtained within 48 h of focal onset seizure diagnosis, due to epilepsy or acute symptomatic seizures, were divided into groups based on initial ASL findings (ASL-negative vs. ASL-positive), and DWI abnormalities (DWI-negative vs. DWI-positive). The diagnosis was made based on seizure semiology, electroencephalography, and conventional imaging modalities. ASL and DWI abnormalities were based on visual assessment. RESULTS: Of the 41 patients, eight (19.5%) displayed normal ASL findings. The proportion of patients with focal aware seizures (FAS) was significantly higher among ASL-negative patients (62.5%) than that in ASL-positive patients (15.2%); the proportion of patients with focal impaired awareness seizures (FIAS) was significantly lower among ASL-negative patients (12.5%) than that among ASL-positive patients (57.6%). Hyperintensity findings on DWI were observed in 12 patients (29.3%, DWI-positive). The proportion of patients with FIAS was significantly higher among DWI-positive patients (75.0%) than that among DWI-negative patients (37.9%). Multivariate analysis revealed that FAS and FIAS were associated with normal ASL findings (odds ratio [OR]: 21.37, P = 0.010) and DWI abnormalities (OR = 6.11, P = 0.028). CONCLUSION: A diagnosis of seizures should not be excluded based on normal ASL findings, especially in patients with FAS. FIAS may be a risk factor for neuronal damage caused by seizure activity.

Dural arteriovenous fistulas without cortical venous drainage: presentation, treatment, and outcomes.

OBJECTIVE: Current evidence suggests that intracranial dural arteriovenous fistulas (dAVFs) without cortical venous drainage (CVD) have a benign clinical course. However, no large study has evaluated the safety and efficacy of current treatments and their impact over the natural history of dAVFs without CVD. METHODS: The authors conducted an analysis of the retrospectively collected multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database. Patient demographics and presenting symptoms, angiographic features of the dAVFs, and treatment outcomes of patients with Borden type I dAVFs were reviewed. Clinical and radiological follow-up information was assessed to determine rates of new intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit (NHND), worsening of venous hyperdynamic symptoms (VHSs), angiographic recurrence, and progression or spontaneous regression of dAVFs over time. RESULTS: A total of 342 patients/Borden type I dAVFs were identified. The mean patient age was 58.1 ± 15.6 years, and 62% were women. The mean follow-up time was 37.7 ± 54.3 months. Of 230 (67.3%) treated dAVFs, 178 (77%) underwent mainly endovascular embolization, 11 (4.7%) radiosurgery alone, and 4 (1.7%) open surgery as the primary modality. After the first embolization, most dAVFs (47.2%) achieved only partial reduction in early venous filling. Multiple complementary interventions increased complete obliteration rates from 37.9% after first embolization to 46.7% after two or more embolizations, and 55.2% after combined radiosurgery and open surgery. Immediate postprocedural complications occurred in 35 dAVFs (15.2%) and 6 (2.6%) with permanent sequelae. Of 127 completely obliterated dAVFs by any therapeutic modality, 2 (1.6%) showed angiographic recurrence/recanalization at a mean of 34.2 months after treatment. Progression to Borden-Shucart type II or III was documented in 2.2% of patients and subsequent development of a new dAVF in 1.6%. Partial spontaneous regression was found in 22 (21.4%) of 103 nontreated dAVFs. Multivariate Cox regression analysis demonstrated that older age, NHND, or severe venous-hyperdynamic symptoms at presentation and infratentorial location were associated with worse prognosis. Kaplan-Meier curves showed no significant difference for stable/improved symptoms survival probability in treated versus nontreated dAVFs. However, estimated survival times showed better trends for treated dAVFs compared with nontreated dAVFs (288.1 months vs 151.1 months, log-rank p = 0.28). This difference was statistically significant for treated dAVFs with 100% occlusion (394 months, log-rank p < 0.001). CONCLUSIONS: Current therapeutic modalities for management of dAVFs without CVD may provide better symptom control when complete angiographic occlusion is achieved.

Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR): rationale, design, and initial characterization of patient cohort.

OBJECTIVE: Cranial dural arteriovenous fistulas (dAVFs) are rare lesions, hampering efforts to understand them and improve their care. To address this challenge, investigators with an established record of dAVF investigation formed an international, multicenter consortium aimed at better elucidating dAVF pathophysiology, imaging characteristics, natural history, and patient outcomes. This report describes the design of the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) and includes characterization of the 1077-patient cohort. METHODS: Potential collaborators with established interest in the field were identified via systematic review of the literature. To ensure uniformity of data collection, a quality control process was instituted. Data were retrospectively obtained. RESULTS: CONDOR comprises 14 centers in the United States, the United Kingdom, the Netherlands, and Japan that have pooled their data from 1077 dAVF patients seen between 1990 and 2017. The cohort includes 359 patients (33%) with Borden type I dAVFs, 175 (16%) with Borden type II fistulas, and 529 (49%) with Borden type III fistulas. Overall, 852 patients (79%) presented with fistula-related symptoms: 427 (40%) presented with nonaggressive symptoms such as tinnitus or orbital phenomena, 258 (24%) presented with intracranial hemorrhage, and 167 (16%) presented with nonhemorrhagic neurological deficits. A smaller proportion (224 patients, 21%), whose dAVFs were discovered incidentally, were asymptomatic. Many patients (85%, 911/1077) underwent treatment via endovascular embolization (55%, 587/1077), surgery (10%, 103/1077), radiosurgery (3%, 36/1077), or multimodal therapy (17%, 184/1077). The overall angiographic cure rate was 83% (758/911 treated), and treatment-related permanent neurological morbidity was 2% (27/1467 total procedures). The median time from diagnosis to follow-up was 380 days (IQR 120-1038.5 days). CONCLUSIONS: With more than 1000 patients, the CONDOR registry represents the largest registry of cranial dAVF patient data in the world. These unique, well-annotated data will enable multiple future analyses to be performed to better understand dAVFs and their management.

Recurrence after cure in cranial dural arteriovenous fistulas: a collaborative effort by the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR).

OBJECTIVE: Cranial dural arteriovenous fistulas (dAVFs) are often treated with endovascular therapy, but occasionally a multimodality approach including surgery and/or radiosurgery is utilized. Recurrence after an initial angiographic cure has been reported, with estimated rates ranging from 2% to 14.3%, but few risk factors have been identified. The objective of this study was to identify risk factors associated with recurrence of dAVF after putative cure. METHODS: The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) data were retrospectively reviewed. All patients with angiographic cure after treatment and subsequent angiographic follow-up were included. The primary outcome was recurrence, with risk factor analysis. Secondary outcomes included clinical outcomes, morbidity, and mortality associated with recurrence. Risk factor analysis was performed comparing the group of patients who experienced recurrence with those with durable cure (regardless of multiple recurrences). Time-to-event analysis was performed using all collective recurrence events (multiple per patients in some cases). RESULTS: Of the 1077 patients included in the primary CONDOR data set, 457 met inclusion criteria. A total of 32 patients (7%) experienced 34 events of recurrence at a mean of 368.7 days (median 192 days). The recurrence rate was 4.5% overall. Kaplan-Meier analysis predicted long-term recurrence rates approaching 11% at 3 years. Grade III dAVFs treated with endovascular therapy were statistically significantly more likely to experience recurrence than those treated surgically (13.3% vs 0%, p = 0.0001). Tentorial location, cortical venous drainage, and deep cerebral venous drainage were all risk factors for recurrence. Endovascular intervention and radiosurgery were associated with recurrence. Six recurrences were symptomatic, including 2 with hemorrhage, 3 with nonhemorrhagic neurological deficit, and 1 with progressive flow-related symptoms (decreased vision). CONCLUSIONS: Recurrence of dAVFs after putative cure can occur after endovascular treatment. Risk factors include tentorial location, cortical venous drainage, and deep cerebral drainage. Multimodality therapy can be used to achieve cure after recurrence. A delayed long-term angiographic evaluation (at least 1 year from cure) may be warranted, especially in cases with risk factors for recurrence.

Assessing the rate, natural history, and treatment trends of intracranial aneurysms in patients with intracranial dural arteriovenous fistulas: a Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) investigation.

OBJECTIVE: There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system. METHODS: The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non-flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected. RESULTS: Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%). CONCLUSIONS: Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%-5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.

Intervention for unruptured high-grade intracranial dural arteriovenous fistulas: a multicenter study.

OBJECTIVE: The risk-to-benefit profile of treating an unruptured high-grade dural arteriovenous fistula (dAVF) is not clearly defined. The aim of this multicenter retrospective cohort study was to compare the outcomes of different interventions with observation for unruptured high-grade dAVFs. METHODS: The authors retrospectively reviewed dAVF patients from 12 institutions participating in the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR). Patients with unruptured high-grade (Borden type II or III) dAVFs were included and categorized into four groups (observation, embolization, surgery, and stereotactic radiosurgery [SRS]) based on the initial management. The primary outcome was defined as the modified Rankin Scale (mRS) score at final follow-up. Secondary outcomes were good outcome (mRS scores 0-2) at final follow-up, symptomatic improvement, all-cause mortality, and dAVF obliteration. The outcomes of each intervention group were compared against those of the observation group as a reference, with adjustment for differences in baseline characteristics. RESULTS: The study included 415 dAVF patients, accounting for 29, 324, 43, and 19 in the observation, embolization, surgery, and SRS groups, respectively. The mean radiological and clinical follow-up durations were 21 and 25 months, respectively. Functional outcomes were similar for embolization, surgery, and SRS compared with observation. With observation as a reference, obliteration rates were higher after embolization (adjusted OR [aOR] 7.147, p = 0.010) and surgery (aOR 33.803, p < 0.001) and all-cause mortality was lower after embolization (imputed, aOR 0.171, p = 0.040). Hemorrhage rates per 1000 patient-years were 101 for observation versus 9, 22, and 0 for embolization (p = 0.022), surgery (p = 0.245), and SRS (p = 0.077), respectively. Nonhemorrhagic neurological deficit rates were similar between each intervention group versus observation. CONCLUSIONS: Embolization and surgery for unruptured high-grade dAVFs afforded a greater likelihood of obliteration than did observation. Embolization also reduced the risk of death and dAVF-associated hemorrhage compared with conservative management over a modest follow-up period. These findings support embolization as the first-line treatment of choice for appropriately selected unruptured Borden type II and III dAVFs.

Onyx embolization for dural arteriovenous fistulas: a multi-institutional study.

BACKGROUND: Although the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance. OBJECTIVE: To carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs. METHODS: From the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database, we identified patients who were treated for DAVF with Onyx-only embolization as the primary treatment between 2000 and 2013. Obliteration rate after initial embolization was determined based on the final angiographic run. Factors predictive of complete obliteration, complications, and functional independence were evaluated with multivariate logistic regression models. RESULTS: A total 146 patients with DAVFs were primarily embolized with Onyx. Mean follow-up was 29 months (range 0-129 months). Complete obliteration was achieved in 80 (55%) patients after initial embolization. Major cerebral complications occurred in six patients (4.1%). At last follow-up, 84% patients were functionally independent. Presence of flow symptoms, age over 65, presence of an occipital artery feeder, and preprocedural home anticoagulation use were predictive of non-obliteration. The transverse-sigmoid sinus junction location was associated with fewer complications, whereas the tentorial location was predictive of poor functional outcomes. CONCLUSIONS: In this multicenter study, we report satisfactory performance of Onyx as a primary DAVF embolic agent. The tentorium remains a more challenging location for DAVF embolization, whereas DAVFs located at the transverse-sigmoid sinus junction are associated with fewer complications.

Chronic subdural hematoma associated with dural metastasis leads to early recurrence and death: A single-institute, retrospective cohort study.

The prevalence of chronic subdural hematoma (CSDH) associated with dural metastasis is uncertain, and appropriate treatment strategies have not been established. This study aimed to investigate the characteristics of and appropriate treatment strategies for CSDH associated with dural metastasis. We retrospectively reviewed the charts of 214 patients who underwent surgery for CSDH. The patients were divided into the dural metastasis group (DMG; n = 5, 2.3%) and no dural metastasis group (No-DMG; n = 209, 97.3%). Patient characteristics, treatment, and outcomes were compared between the two groups. Active cancer was detected in 31 out of 214 patients, 5 of whom (16.1%) had dural metastasis. In-hospital death (80.0% vs. 0%; p < 0.001) and recurrence within 14 days (80.0% vs. 2.9%; p < 0.001) and 60 days (80.0% vs. 13.9%; p = 0.002) were significantly prevalent in the DMG. All patients in the DMG developed subdural hematoma re-accumulation requiring emergent surgery because of brain herniation, and patients in the DMG had significantly worse recurrence-free survival (p < 0.001). This relationship remained significant (p < 0.001) even when the analysis was limited to the active cancer cohort (n = 31). CSDH associated with dural metastasis leads to early recurrence and death because of the difficulty in controlling subdural hematoma re-accumulation by common drainage procedures. Depending on the primary cancer status, withdrawal of active treatment and change to palliative care should be discussed after diagnosing CSDH associated with dural metastasis.

Involvement of Neutrophil Extracellular Traps in Cerebral Arteriovenous Malformations.

BACKGROUND: Cerebral arteriovenous malformations (cAVMs) represent tangles of abnormal vasculature without intervening capillaries. High-pressure vascular channels due to abnormal arterial and venous shunts can lead to rupture. Multiple pathways are involved in the pathobiology of cAVMs including inflammation and genetic factors such as KRAS mutations. Neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs), plays a multifunctional role in infection, inflammation, thrombosis, intracranial aneurysms, and tumor progression. However, the relationship between NETs and the pathobiology of cAVMs remains unknown. We tested whether NETs play a role in the pathobiology of cAVMs. METHODS: We analyzed samples from patients who had undergone surgery for cAVM and immunohistochemically investigated expression of citrullinated histone H3 (CitH3) as a marker of NETs. CitH3 expression was compared among samples from cAVM patients, epilepsy patients, and normal human brain tissue. Expressions of thrombotic and inflammatory markers were also examined immunohistochemically in samples from cAVM patients. RESULTS: Expression of CitH3 derived from neutrophils was observed intravascularly in all cAVM samples but not other samples. Nidi of AVMs showed migration of many Iba-I-positive cells adjacent to the endothelium and endothelial COX2 expression, accompanied by expression of IL-6 and IL-8 in the endothelium and intravascular neutrophils. Unexpectedly, expression of CitH3 was not necessarily localized to the vascular wall and thrombus. CONCLUSIONS: Our results offer the first evidence of intravascular expression of NETs, which might be associated with vascular inflammation in cAVMs.

Coil embolization with overlapping horizontal low-profile stents to treat a giant thrombosed fetal posterior cerebral artery aneurysm using contralateral approach through anterior communicating artery: Case report.

BACKGROUND: The treatment of internal carotid artery (ICA) - posterior communicating artery aneurysms (ICPC aneurysms) is challenging when a fetal posterior cerebral artery (PCA) arises from the saccular neck. This complex angioarchitecture renders endovascular approaches difficult. Giant thrombosed IC-PC aneurysms are also hard to treat by endovascular coiling because its flow-diversion effect is insufficient. CASE DESCRIPTION: We report the first case of a ruptured giant thrombosed IC-PC aneurysm associated with a fetal PCA that was successfully treated by coil embolization with retrograde overlap horizontal stenting using low-profile stents introduced through the contralateral ICA. The aneurysm was completely occluded and follow-up MRI scans demonstrated the reduction of the aneurysmal size. CONCLUSION: Our technique is advantageous because low-profile stents can be used to treat lesions not accessible with flow-diverter stents due their presence in complex angioarchitectures, and overlap stenting may have flow-diversion effects that can result in the complete occlusion of giant thrombosed aneurysms.

Observation Versus Intervention for Low-Grade Intracranial Dural Arteriovenous Fistulas.

BACKGROUND: Low-grade intracranial dural arteriovenous fistulas (dAVF) have a benign natural history in the majority of cases. The benefit from treatment of these lesions is controversial. OBJECTIVE: To compare the outcomes of observation versus intervention for low-grade dAVFs. METHODS: We retrospectively reviewed dAVF patients from institutions participating in the CONsortium for Dural arteriovenous fistula Outcomes Research (CONDOR). Patients with low-grade (Borden type I) dAVFs were included and categorized into intervention or observation cohorts. The intervention and observation cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was modified Rankin Scale (mRS) at final follow-up. Secondary outcomes were excellent (mRS 0-1) and good (mRS 0-2) outcomes, symptomatic improvement, mortality, and obliteration at final follow-up. RESULTS: The intervention and observation cohorts comprised 230 and 125 patients, respectively. We found no differences in primary or secondary outcomes between the 2 unmatched cohorts at last follow-up (mean duration 36 mo), except obliteration rate was higher in the intervention cohort (78.5% vs 24.1%, P < .001). The matched intervention and observation cohorts each comprised 78 patients. We also found no differences in primary or secondary outcomes between the matched cohorts except obliteration was also more likely in the matched intervention cohort (P < .001). Procedural complication rates in the unmatched and matched intervention cohorts were 15.4% and 19.2%, respectively. CONCLUSION: Intervention for low-grade intracranial dAVFs achieves superior obliteration rates compared to conservative management, but it fails to improve neurological or functional outcomes. Our findings do not support the routine treatment of low-grade dAVFs.

Basic research and surgical techniques for brain arteriovenous malformations.

Arteriovenous malformations (AVMs) are hemorrhagic vascular diseases in which arteries and veins are directly connected with no capillary bed between the two. We herein introduce the results of basic research of this disease and surgical techniques based on our data and experiences. The results obtained from our research show that cell death- and inflammation-related molecules changed or became activated compared with control specimens. These findings indicate that chronic inflammation occurs in and around the nidus of AVMs. Various molecules are involved in the mechanisms of cell death and angiogenesis during this process. Confirmation of blood flow in the nidus is very important to avoid hemorrhagic complications during surgical removal of the nidus. The risk of hemorrhage increases when the blood flow in the nidus is not reduced. We reported the advantages of serial indocyanine green videoangiography, which is used to assess the blood flow during AVM nidus removal. Since publication of the ARUBA trial and Scottish Audit, treatments with high morbidity have not been allowed. It is especially important for neurosurgeons to treat low Spetzler-Martin grade AVMs with low morbidity. J. Med. Invest. 67 : 222-228, August, 2020.