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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.

Angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed cerebral ischemia (DCI)-related cerebral infarction (radiological DCI) and worsened neurological outcome. Transcranial Doppler (TCD) measurements of cerebral blood flow velocity are commonly used after aSAH to screen for vasospasm; however, their association with cerebral infarction is not well characterized. We sought to determine whether time-varying TCD-measured vasospasm severity is associated with cerebral infarction and investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction. We conducted a retrospective single-center cohort study of consecutive adult patients with aSAH with at least one TCD study between 2011 and 2020. The primary outcome was radiological DCI, defined as a cerebral infarction developing at least 2 days after any surgical or endovascular intervention without an alternative cause. Cox proportional hazards models were used to examine associations between time-varying vasospasm severity and radiological DCI. Optimal TCD-based time/severity thresholds for predicting radiological DCI were then determined. Of 262 patients with aSAH who underwent TCD studies, 27 (10%) developed radiological DCI. Patients with radiological DCI had higher modified Fisher scale scores and trended toward earlier onset of vasospasm. Adjusted for age, Hunt and Hess scores, and modified Fisher scale scores, the worst-vessel vasospasm severity was associated with radiological DCI (adjusted hazard ratio 1.7 [95% confidence interval 1.1–2.4]). Vasospasm severity within a specific vessel was associated with risk of delayed infarction in the territory supplied by that vessel. Optimal discrimination of patients with radiological DCI was achieved with thresholds of mild vasospasm on days 4–5 or moderate vasospasm on days 6–9, with negative predictive values greater than 90% and positive predictive values near 20%. TCD-measured vasospasm severity is associated with radiological DCI after aSAH. An early, mild TCD-based vasospasm severity threshold had a high negative predictive value, supporting its role as a screening tool to identify at-risk patients.

Objective Spontaneous subarachnoid hemorrhage is often due to rupture of an intracranial aneurysm, but some patients present with no identifiable source. Increased incidence of nonaneurysmal subarachnoid hemorrhage (naSAH) has been reported over time. Methods We performed a retrospective analysis of naSAH from 2008−2017 to determine the rate of naSAH change over time and its association with cannabis use. Univariable and multivariable regression analyses were performed to study the trend over time, radiographic patterns of hemorrhage, and clinical outcome at the time of discharge. In addition, we compared the rate of naSAH with the rate of aneurysmal SAH (aSAH) to adjust for changes in hospital volume and prevalence/reporting of cannabis use in the population over time. Results A total of 86 naSAH and 328 aSAH patients were identified, with an increase in naSAH over time compared with aSAH (P = 0.0034). Increased cannabis use was associated with naSAH (odds ratio [OR] 2.1, 95% confidence interval 1.1, 4.1, P = 0.035) but not aSAH over time. Cannabis use was also associated with different subarachnoid hemorrhage patterns (P = 0.0065) in naSAH. Multivariable analysis demonstrated good neurologic outcome after naSAH to be inversely associated with cocaine use (OR 0.008 [0.002−0.4]), ventriculostomy placement (OR 0.004 [0.03−0.50]), and anticoagulant use (OR 0.016 [0.003−0.54]) but not with cannabis use. Conclusions As cannabis use becomes more prevalent with legalization, it is important to further investigate this association with spontaneous SAH.

Background In adults with ischemic moyamoya disease (MMD), the efficacy of direct vs indirect revascularization procedures remains a matter of debate. Objective To investigate the outcomes of ischemic MMD in a North American cohort treated by direct and indirect revascularizations. Methods We retrospectively reviewed medical records of adult patients with MMD with ischemic presentation from 1984 to 2018 at the Brigham and Women's Hospital and Massachusetts General Hospital who underwent either direct or indirect bypasses. Early postoperative events and outcome at more than 6 mo postoperatively were evaluated using multivariable logistic regression analyses. Multivariable Cox proportional hazards regression analyses were used to evaluate delayed ischemic and hemorrhagic events. Analyses were performed per hemisphere. Results A total of 95 patients with MMD and 127 hemispheres were included in this study. A total of 3.5% and 8.6% of patients had early surgical complications in the direct and indirect bypass cohorts, respectively (P = .24). Hemispheres with direct bypasses had fewer long-term ischemic and hemorrhagic events at latest follow-up (adjusted hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.058-0.63, P = .007; median follow-up 4.5 [interquartile range, IQR 1-8] yr). There was no difference between the direct and indirect bypass groups when the endpoint was limited to infarction and hemorrhage only (P = .12). There was no difference in outcome (modified Rankin Scale [mRS] ≥ 3) between the 2 cohorts (P = .92). Conclusion There was no difference in early postoperative events, long-term infarction or hemorrhage, or clinical outcome between direct and indirect revascularization. However, there was a significant decrease in all ischemic and hemorrhagic events combined in direct revascularizations compared to indirect revascularizations.

BackgroundHemodynamic stress, conditioned by the morphology of the surrounding vasculature, plays an important role in aneurysm formation. Our goal was to identify image-based location-specific parameters that are associated with posterior communicating artery (PCoA) aneurysms.MethodsThree-dimensional morphological parameters obtained from CT angiography or digital subtraction angiography from 187 patients with unilateral PCoA aneurysms, diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016, were evaluated. In order to control for genetic and clinical risk factors, we chose the contralateral unaffected PCoA as a control group. We examined diameters and angles of the surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with small aneurysms (≤5 mm) only and an unmatched analysis of 432 PCoA aneurysms and 197 control patients without PCoA aneurysms were also performed.ResultsIn a multivariable conditional logistic regression model we showed that smaller diameter size ratio (OR 1.45×10−5, 95% CI 1.12×10−7 to 1.88×10−3) and larger daughter-daughter angle (OR 1.04, 95% CI 1.02 to 1.07) were significantly associated with PCoA aneurysm presence after correcting for other variables. In subgroup analyses of small aneurysms (≤5 mm) and in an unmatched analysis the significance and direction of these results were preserved.ConclusionsLarger daughter-daughter angles and smaller diameter size ratio are significantly associated with the presence of PCoA aneurysms. These simple parameters can be utilized to guide the risk assessment for the formation of PCoA aneurysms in high risk patients.

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.

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.

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.

We present a cohort of patients with anterior communicating artery (ACoA) aneurysms to investigate morphological characteristics and clinical factors associated with rupture of the aneurysms. 505 patients with ACoA aneurysms were identified at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016, with available CT angiography (CTA). Three-dimensional (3D) reconstructions were performed to evaluate aneurysmal morphologic features, including location, projection, irregularity, the presence of daughter dome, height, height/width ratio, and relationships between surrounding vessels. Patient risk factors assessed included patient age, sex, tobacco use, alcohol use, and family history of aneurysms and aneurysmal subarachnoid hemorrhage. Logistic regression was used to build a predictive ACoA score for rupture. Morphologic features associated with ruptured ACoA aneurysms were the presence of a daughter dome (OR 21.4, 95% CI 10.6–43.1), smaller neck diameter (OR 0.55, 95% CI 0.42–0.71), larger aspect ratio (OR 3.57, 95% CI 2.05–6.24), larger flow angle (OR 1.03, 95% CI 1.02–1.05), and smaller ipsilateral A2-ACoA angle (OR 0.98, 95% CI 0.97–1.00). Tobacco use was predominantly associated with morphological factors intrinsic to the aneurysm that were associated with rupture while younger age was also associated with morphologic features extrinsic to the aneurysm that were associated with rupture. The ACoA score had good predictive capacity for rupture with AUC = 0.92 using the 0.632 bootstrap cross-validation for correction of overfitting bias. Ruptured ACoA aneurysms were associated with morphological features that are simple to assess using a simple scoring system. Tobacco use and younger age were predominantly associated with intrinsic and extrinsic morphological features characteristic of rupture, respectively.

Morphological factors of intracranial aneurysms and the surrounding vasculature could affect aneurysm rupture risk in a location specific manner. Our goal was to identify image-based morphological parameters that correlated with ruptured basilar tip aneurysms. Three-dimensional morphological parameters obtained from CT-angiography (CTA) or digital subtraction angiography (DSA) from 200 patients with basilar tip aneurysms diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016 were evaluated. We examined aneurysm wall irregularity, the presence of daughter domes, hypoplastic, aplastic or fetal PCoAs, vertebral dominance, maximum height, perpendicular height, width, neck diameter, aspect and size ratio, height/width ratio, and diameters and angles of surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. In multivariable analysis, presence of a daughter dome, aspect ratio, and larger flow angle were significantly associated with rupture status. We also introduced two new variables, diameter size ratio and parent-daughter angle ratio, which were both significantly inversely associated with ruptured basilar tip aneurysms. Notably, multivariable analyses also showed that larger diameter size ratio was associated with higher Hunt-Hess score while smaller flow angle was associated with higher Fisher grade. These easily measurable parameters, including a new parameter that is unlikely to be affected by the formation of the aneurysm, could aid in screening strategies in high-risk patients with basilar tip aneurysms. One should note, however, that the changes in parameters related to aneurysm morphology may be secondary to aneurysm rupture rather than causal.

Background Arteriovenous malformation (AVM) rupture is highly morbid. Outcomes after AVM rupture differ from other types of brain hemorrhage. There are no specific widely used grading systems designed to predict clinical outcome after AVM rupture. Objective To develop an all-comers scoring system to grade patients with AVM rupture and predict clinical outcome more accurately than grading systems currently in use. Methods We retrospectively reviewed patients who presented to our institution with a ruptured AVM. Using change in modified Rankin Score (mRS) as our response variable, we generated an ordinal logistic regression model to test for significant predictor variables. The full model was sequentially condensed until the simplest model with the highest area under the receiver operating curve (AUROC) was achieved. Results A total of 115 patients who presented with ruptured AVMs were included in the study, with a mean follow-up time of 4 yr. The Ruptured AVM Grading Scale (RAGS) consists of the Hunt and Hess (HH) score (1-5), patient age ( 70 = 2), deep venous drainage (1), and eloquence (1). The RAGS score outperformed other neurosurgical grading scales in predicting change in mRS, with an AUROC greater than 0.80 across all follow-up periods. Conclusion The RAGS score is a simple extension of the HH scale that predicts clinical outcome after AVM rupture more accurately than other grading systems.

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.

BackgroundThe presence of angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed-cerebral ischemia (DCI)-related cerebral infarction and worsened neurological outcome. Transcranial doppler (TCD) measurements of cerebral blood velocity are commonly used after aSAH to screen for vasospasm. We sought to determine whether time-varying TCD measured vasospasm severity is associated with cerebral infarction and to investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction.MethodsWe used a retrospective, single-center cohort of consecutive adult aSAH patients with angiographic vasospasm and at least one TCD study. Our primary outcome was DCI-related cerebral infarction, defined as an infarction developing at least 2 days after any surgical intervention without an alternative cause. Time-varying TCD vasospasm severity was defined ordinally (absent, mild, moderate, severe) by the most abnormal vessel on each post-admission hospital day. Cox proportional-hazards models were used to examine associations between time-varying vasospasm severity and infarction. The optimal TCD-based time/severity thresholds for predicting infarction were then identified using the Youden J statistic.ResultsOf 218 aSAH patients with angiographic vasospasm, 27 (12%) developed DCI-related infarction. As compared to those without infarction, patients with infarction had higher modified Fisher scale (mFS) scores, and an earlier onset of more-severe vasospasm. Adjusted for mFS, vasospasm severity was associated with infarction (aHR 1.9, 95% CI: 1.3-2.6). A threshold of at least mild vasospasm severity on hospital day 4 had a negative predictive value of 92% for the development of infarction, but a positive predictive value of 25%.ConclusionsIn aSAH, TCD-measured vasospasm severity is associated with DCI-related infarction. In a single-center dataset, a TCD-based threshold for predicting infarction had a high negative predictive value, supporting its role as an early screening tool to identify at-risk patients.

BackgroundAlthough 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.ObjectiveTo carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs.MethodsFrom 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.ResultsA 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.ConclusionsIn 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.

Hemodynamic stress is thought to play an important role in the formation of intracranial aneurysms, which is conditioned by the geometry of the surrounding vasculature. Our goal was to identify image-based morphological parameters that were associated with basilar artery tip aneurysms (BTA) in a location-specific manner. Three-dimensional morphological parameters obtained from CT-angiography (CTA) or digital subtraction angiography (DSA) from 207 patients with BTAs and a control group of 106 patients with aneurysms elsewhere to control for non-morphological factors, who were diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016, were evaluated. We examined the presence of hypoplastic, aplastic or fetal PCoAs, vertebral dominance, and diameters and angles of surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with small (≤ 3 mm) aneurysms only and with angles excluded, were also performed. In multivariable analysis, daughter–daughter angle was directly, and parent artery diameter and diameter size ratio were inversely associated with BTAs. These results remained significant in the subgroup analysis of small aneurysms (width ≤ 3 mm) and when angles were excluded. These easily measurable and robust parameters that are unlikely to be affected by aneurysm formation could aid in risk stratification for the formation of BTAs in high-risk patients.

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.

Risk of intracranial aneurysm rupture could be affected by geometric features of intracranial aneurysms and the surrounding vasculature in a location specific manner. Our goal is to investigate the morphological characteristics associated with ruptured posterior communicating artery (PCoA) aneurysms, as well as patient factors associated with the morphological parameters. Three-dimensional morphological parameters in 409 patients with 432 PCoA aneurysms diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016 who had available CT angiography (CTA) or digital subtraction angiography (DSA) were evaluated. Morphological parameters examined included aneurysm wall irregularity, presence of a daughter dome, presence of hypoplastic or aplastic A1 arteries and hypoplastic or fetal PCoA, perpendicular height, width, neck diameter, aspect and size ratio, height/width ratio, and diameters and angles of surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine the association of morphological parameters with rupture of PCoA aneurysms. Additional analyses were performed to determine the association of patient factors with the morphological parameters. Irregular, multilobed PCoA aneurysms with larger height/width ratios and larger flow angles were associated with ruptured PCoA aneurysms, whereas perpendicular height was inversely associated with rupture in a multivariable model. Older age was associated with lower aspect ratio, with a trend towards lower height/width ratio and smaller flow angle, features that are associated with a lower rupture risk. Morphological parameters are easy to assess and could help in risk stratification in patients with unruptured PCoA aneurysms. PCoA aneurysms diagnosed at older age have morphological features associated with lower risk.

Objective Return to work and driving are major rehabilitation goals for patients after an aneurysmal subarachnoid hemorrhage (aSAH). Our goal is to identify factors that may predict return to work or driving after aSAH. Methods Medical records of patients with aSAH were retrospectively reviewed from 2010 to 2018. Information on return to work and driving were prospectively collected. Univariate analyses were performed to assess the association between return to work or driving with patient characteristics, social factors, and admission clinical and radiographic severity. Multivariate regression models were used to evaluate return to work and driving and generate predictive models. Results A total of 193 patients were included, of whom 32% (62/193) resumed work and 57% (110/193) returned to driving. Median follow-up time was 3.4 years (interquartile range, 0.7–7.5 years). Return to work was associated with younger age (odds ratio [OR], 0.89; 95% CI, 0.85–0.94), lower Hunt and Hess grade (OR, 0.34; 95% CI, 0.23–0.54), and lack of seizures (OR, 0.09; 95% CI, 0.02–0.47). Return to driving was associated with younger age (OR, 0.94; 95% CI, 0.91–0.98), lower Hunt and Hess grade (OR, 0.36; 95% CI, 0.23–0.56), married status (OR, 3.4; 95% CI, 1.2–9.4), current or former smoking (OR, 3.9; 95% CI, 1.5–10.1), lack of recreational drug use (OR, 0.08; 95% CI, 0.01–0.77), and lack of seizures (OR, 0.28; 95% CI, 0.08–0.96). Admission risk factors were predictive of return to driving and return to work in the final multivariate models generated (area under the receiver operating characteristic curve 88% vs. 89%, respectively). Conclusions Because work may be highly dependent on complex individual and social factors, driving is a simple and more accurate assessment for an individual’s status after aSAH.

Objectives Aneurysms associated with hemorrhagic moyamoya disease (MMD) are reported to stabilize or recede following revascularization. Case report/results A 29 year-old male with no past medical history presented obtunded with diffuse intraventricular hemorrhage and vascular imaging demonstrating bilateral MMD without any associated aneurysms. He underwent a delayed right-sided STA-MCA bypass and pial synangiosis, and was subsequently discharged on hospital day 24 with a modified Rankin Scale score (mRS) of 2. He returned eleven days later from a rehabilitation facility with recurrent IVH. A saccular 5 mm right P4 segment posterior cerebral artery aneurysm was seen on a diagnostic angiogram and embolized with Onyx glue. Conclusions Distal posterior circulation artery aneurysmal rupture is a rare cause of hemorrhagic MMD. This case demonstrates the capacity of these aneurysms to re-rupture following revascularization and underscores the importance of treating the aneurysms directly.

Background Subarachnoid hemorrhage (SAH) from an intracranial aneurysmal rupture is the most common nontraumatic etiology for SAH, but up to 15% of patients with SAH have no identifiable source. Objective To assess familial predisposition to spontaneous nonaneurysmal SAH (naSAH) and to evaluate whether family history affects the severity of presentation and prognosis of this condition. Methods We conducted a retrospective analysis of all spontaneous SAH with negative digital subtraction angiography from 2004 to 2018. Patients were divided into 2 groups: patients with first- or second-degree relatives with intracranial aneurysms and patients with no family history. Univariate and multivariate regression analyses were used to study patient presentation, radiographic patterns of hemorrhage, and clinical outcome. Results A total of 100 patients met the inclusion criteria. There were no individuals with family history of naSAH. A total of 15 patients (15%) had at least one family member with an intracranial aneurysm, of which 12 (12%) presented as SAH. Patients without family history had a higher percentage of perimesencephalic presentation, whereas those with family history had a higher percentage of nonperimesencephalic SAH presentation (47% vs 13%, odds ratio [OR] 0.17 [95% CI 0.04, 0.81]). Conclusion We found a high rate of family history of intracranial aneurysms in patients who presented with naSAH. Although there was no difference in clinical outcome in patients with and without family history, there appears to be a higher percentage of nonperimesencephalic radiographic patterns of SAH in those with family history, suggesting possible different etiologies of these hemorrhages.

Iron and its derivatives play a significant role in various physiological and biochemical pathways, and are influenced by a wide variety of inflammatory, infectious, and immunological disorders. We hypothesized that iron and its related factors play a role in intracranial aneurysm pathophysiology and investigated if serum iron values are associated with ruptured intracranial aneurysms. 4,701 patients with 6,411 intracranial aneurysms, including 1201 prospective patients, who were diagnosed at the Massachusetts General Hospital and Brigham and Women’s Hospital between 1990 and 2016 were evaluated. A total of 366 patients with available serum iron, ferritin and total iron binding capacity (TIBC) values were ultimately included in the analysis. 89% of included patients had anemia. Patients were categorized into ruptured and non-ruptured groups. Univariable and multivariable logistic regression analyses were performed to determine the association between ruptured aneurysms and iron, ferritin, and TIBC. TIBC values (10−3 g/L) within 1 year of diagnosis (OR 0.41, 95% CI 0.28–0.59) and between 1 and 3 years from diagnosis (OR 0.52, 95% CI 0.29–0.93) were significantly and inversely associated with intracranial aneurysm rupture. In contrast, serum iron and ferritin were not significant. In this case-control study, low TIBC was significantly associated with ruptured aneurysms, both in the short- and long term. However, this association may not apply to the general population as there may be a selection bias as iron studies were done in a subset of patients only.

Objective Recent literature suggests there are sex differences in delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Our study serves to compare sex differences in radiographic vasospasm, DCI, and clinical outcome after aSAH, and to determine whether there are age-dependent differences. Methods A total of 328 patients with ruptured cerebral aneurysms were evaluated for radiographic vasospasm, clinical deterioration, cerebral infarction, and modified Rankin Scale–determined clinical outcome at 6 months to 1 year after rupture. Multivariate regression analyses were performed to evaluate the associations between these outcome measures and sex, adjusting for age, hypertension, aneurysm location, admission Hunt and Hess grade, and modified Fisher grade. Results After multivariate adjustment, women had higher rates of radiographic vasospasm (β = 0.35; 95% confidence interval [CI], 0.068–0.63; P = 0.015), clinical deterioration (odds ratio [OR], 2.8; 95% CI, 1.3–6.0; P = 0.008) and cerebral infarction (OR, 2.4; 95% CI, 1.0–5.5; P = 0.039), but no difference was observed in follow-up modified Rankin Scale (mRS) outcome score at 6 months to 1 year (P = 0.96). Older women (age >55 years) have a higher rate of clinical deterioration than men in the same age group (OR, 3.5; 95% CI, 1.0–12; P = 0.043). In contrast, younger women (age ≤55 years) had increased radiographic vasospasm (β = 0.55; 95% CI, 0.17–0.93; P = 0.005) and worse mRS outcome score (β = 0.042; 95% CI, -0.021 to 1.1; P = 0.042) compared with men. Conclusions Female sex is associated with a higher risk of radiographic vasospasm, clinical deterioration, and cerebral infarction. Furthermore, this association appears to be age-dependent. This study further supports the unique role of sex, and highlights the need to better understand the possible role of female hormones in the development of complications of subarachnoid hemorrhage.

Hyponatremia occurs commonly in patients with aneurysmal subarachnoid hemorrhage (aSAH). Our objective was to determine the time course of, and factors associated with, hyponatremia after aSAH. We performed a retrospective review of 259 patients with ruptured aneurysms at a single institution. Multivariate regression analysis was performed to determine the factors associated with hyponatremia. Increasing age was significantly associated with lower initial sodium (p=0.04) and incidence of delayed hyponatremia (p=0.01) while smoking was associated with longer duration of hyponatremia (p=0.02). Older patients should therefore be monitored closely for hyponatremia and patients who smoke should be treated more aggressively for hyponatremia given the greater frequency and longer duration of hyponatremia in these two groups, respectively.

Background The pathophysiology of cerebral aneurysm formation remains to be elucidated. Estrogen is thought to be protective against the development of aneurysms. The aim of this study is to identify differentially expressed genes in the estrogen receptor pathway that may be linked to the development of cerebral aneurysms. Methods Data from 6 Gene Expression Omnibus (GEO) databases with gene expression profiles of cerebral aneurysm tissue were analyzed ( GSE6551 , GSE15629 , GSE26969 , GSE46337 , GSE54083 , and GSE75436 ). Ninety-four genes associated with the estrogen receptor pathway were identified from the Kyoto Encyclopedia of Genes and Genomes pathway database. A meta-analysis using a random-effects model was used to evaluate the association of the estrogen receptor pathway genes with aneurysm formation. Results Four genes related to the estrogen receptor pathway were significantly associated with intracranial aneurysms, 2 of which were downregulated (PIK3R1: fold change [FC] = 0.41, false discovery rate [FDR] = 6.1 × 10–5, ADCY9: FC = 0.55, FDR = 2.3 × 10–4) and 2 of which were upregulated (HBEGF: FC = 1.46, FDR = 4.9 × 10–4; ADCY7: FC = 2.11, FDR = 6.0 × 10–3). Furthermore, subgroup analysis of 2 GEO databases with information provided about sex demonstrated PIK3R1 to be significant independently in both men (FC = 0.46, FDR = 6.3 × 10–5) and women (FC = 0.46, FDR = 2.3 × 10–4), whereas JUN, ADCY5, and MMP9 were significant in women only. Conclusions The analysis of 6 GEO databases revealed 4 differentially expressed genes (PIK3R1, HBEGF, ADCY7, and ADCY9) in cerebral aneurysm tissue that are associated with the estrogen receptor pathway. Further analysis of estrogen-associated differentially expressed genes may provide information about the protective effects of estrogen on cerebral aneurysm development.

OBJECTIVEAlthough cigarette smoking is one of the strongest risk factors for cerebral aneurysm development and rupture, there are limited data evaluating the impact of smoking on outcomes after aneurysmal subarachnoid hemorrhage (SAH). Additionally, two recent studies suggested that nicotine replacement therapy was associated with improved neurological outcomes among smokers who had sustained an SAH compared with smokers who did not receive nicotine.METHODSPatients who underwent endovascular or microsurgical repair of a ruptured cerebral aneurysm were extracted from the Nationwide Inpatient Sample (NIS, 2009–2011) and stratified by cigarette smoking. Multivariable logistic regression analyzed in-hospital mortality, complications, tracheostomy or gastrostomy placement, and discharge to institutional care (a nursing or an extended care facility). Additionally, the composite NIS-SAH outcome measure (based on mortality, tracheostomy or gastrostomy, and discharge disposition) was evaluated, which has been shown to have excellent agreement with a modified Rankin Scale score greater than 3. Covariates included in regression constructs were patient age, sex, race/ethnicity, insurance status, socioeconomic status, comorbidities (including hypertension, drug and alcohol abuse), the NIS-SAH severity scale (previously validated against the Hunt and Hess grade), treatment modality used for aneurysm repair, and hospital characteristics. A sensitivity analysis was performed matching smokers to nonsmokers on age, sex, number of comorbidities, and NIS-SAH severity scale score.RESULTSAmong the 5784 admissions evaluated, 37.1% (n = 2148) had a diagnosis of tobacco use, of which 31.1% (n = 1800) were current and 6.0% (n = 348) prior tobacco users. Smokers were significantly younger (mean age 51.4 vs 56.2 years) and had more comorbidities compared with nonsmokers (p < 0.001). There were no significant differences in mortality, total complications, or neurological complications by smoking status. However, compared with nonsmokers, smokers had significantly decreased adjusted odds of tracheostomy or gastrostomy placement (11.9% vs 22.7%, odds ratio [OR] 0.63, 95% confidence interval [CI] 0.51–0.78, p < 0.001), discharge to institutional care (OR 0.71, 95% CI 0.57–0.89, p = 0.002), and a poor outcome (OR 0.65, 95% CI 0.55–0.77, p < 0.001). Similar statistical associations were noted in the matched-pairs sensitivity analysis and in a subgroup of poor-grade patients (the upper quartile of the NIS-SAH severity scale).CONCLUSIONSIn this nationwide study, smokers experienced SAH at a younger age and had a greater number of comorbidities compared with nonsmokers, highlighting the negative ramifications of cigarette smoking among patients with cerebral aneurysms. However, smoking was also associated with paradoxical superior outcomes on some measures, and future research to confirm and further understand the basis of this relationship is needed.

Neurenteric cysts, also known as enterogenous cysts, are uncommon, benign, congenital lesions that usually occur in the posterior mediastinum but can be seen at any level of the neuraxis. Here, we report a pediatric patient with a neurenteric cyst in the dorsal craniocervical junction as the only third reported pediatric case in the literature in this rare location, and describe the clinical course and pathologic findings with a review of the literature on this rare entity.

Objective Vasospasm is the leading source of neurological morbidity after aneurysmal subarachnoid hemorrhage. Our objective was to evaluate the impact of treatment modality on vasospasm, delayed cerebral infarction, and clinical deterioration caused by delayed cerebral ischemia (CD-DCI). Methods We reviewed an institutional cohort, comparing rates of vasospasm, delayed cerebral infarction, and CD-DCI between patients managed with only microsurgical clipping and those treated with only endovascular coiling within 72 hours of rupture. Age, sex, smoking status, Hunt-Hess grade, and Fisher grade were adjusted for in a multivariate regression model. Results Two hundred three patients were treated with clipping and 52 with coiling. There was no significant difference in patient age, sex, smoking status, aneurysm location, and presenting clinical (Hunt-Hess) and radiographic (Fisher) grade between these two groups. Sixty-percent of patients had moderate or severe vasospasm after clipping compared with 38% after coiling (Multivariate odds ratio [OR] 2.32, 95% confidence interval [95% CI] 1.21–4.47, P = 0.01). Clipping was associated with a greater number of territories with vasospasm (mean of 3.1 vs. 2.3, P = 0.03 after multivariate analysis). Delayed radiographic cerebral infarction was more common in the clipping group (17% vs. 6%, multivariate OR 3.66, 95% CI 1.06–12.71, P = 0.04). For CD-DCI, a trend was seen as 16% of patients treated with clipping had CD-DCI compared with 6% of patients treated with coiling (multivariate OR 3.11, 95% CI 0.89–10.86, P = 0.07). Conclusion We demonstrate significantly lower rates of vasospasm and delayed infarction after endovascular coiling of ruptured aneurysms.

Objective Recent evidence has suggested a potential beneficial effect of aspirin on the risk of aneurysm rupture. This benefit must be weighed against its potential adverse effects as an antiplatelet agent in the setting of acute aneurysmal subarachnoid hemorrhage (SAH). Methods A total of 747 consecutive patients with cerebral aneurysms were reviewed, comparing demographics, aneurysm features, presenting clinical and radiographic grades, vasospasm, and outcome at 1 year between patients with aneurysmal SAH taking aspirin on presentation and those who were not. Results The rate of hemorrhagic presentation was significantly greater in patients not taking aspirin (40% vs. 28%; P = 0.016). Among 274 patients presenting with aneurysmal SAH, there was no significant difference in presenting clinical (Hunt and Hess) and radiographic (Fisher) grade between patients taking aspirin and those who were not. There was also no significant difference in the rate of subsequent angiographic and delayed cerebral ischemia. Multivariate analysis of outcome at 1 year found only increasing age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04–1.12), Hunt and Hess grade (OR 3.01, 95% CI 1.81–5.03), and associated hypertension (OR 3.30, 95% CI 1.39–7.81) to be statistically significant risk factors for poor outcome (death or dependence), whereas aspirin use was not associated with poor outcome (OR 1.19, 95% CI 0.35–4.09; P = 0.78). Conclusions In the present study, patients taking aspirin had a lower rate of hemorrhagic presentation. In addition, taking aspirin did not adversely impact presenting clinical grade or radiographic grade, vasospasm, and outcome in the setting of aneurysmal SAH.

Recent studies have reinforced anterior communicating (AComm) artery location as a significant risk factor for aneurysm rupture in addition to posterior circulation/posterior communicating (PComm) artery location. However, studies stratifying aneurysm location in greater detail are sparse.We reviewed the records of 747 consecutive patients with 1013 aneurysms seen at our institution over a 7 year period, noting aneurysm location and rupture status at the time of presentation.High proportions of ruptured aneurysms were seen among frontopolar/pericallosal (59%, OR 3.07, p=0.011), vertebral/posteroinferior cerebellar (PICA; 53%, OR 2.49, p=0.0037), AComm (50%, OR 2.46, p0.0001), and PComm aneurysms (44%, OR 1.77, p=0.0016). Low proportions of ruptured aneurysms were seen among superior hypophyseal artery (SHA; 6%, OR 0.12, p=0.0001), internal carotid artery (ICA) bifurcation (12%, OR 0.27, p=0.0012), and ophthalmic artery aneurysms (15%, OR 0.33, p=0.0002). The proportion of ruptured PComm aneurysms demonstrated a trend toward being greater than anterior choroidal artery aneurysms (OR 2.14, p=0.09); however the proportion was significantly greater among anterior choroidal artery aneurysms as compared to nonPComm intradural ICA aneurysms (OR 2.78, p=0.03). Notably, the lower rupture rate of SHA aneurysms as compared to ophthalmic artery aneurysms neared statistical significance (OR 0.38, p=0.10).Aneurysm location has a significant impact on risk of rupture and should be stratified in greater detail in future studies of aneurysm natural history.

The quality of research in hospital epidemiology (infection control) must be improved to be robust enough to influence policy and practice. In order to raise the standards of research and publication, a CONSORT equivalent for these largely quasi-experimental studies has been prepared by the authors of two relevant systematic reviews, following consultation with learned societies, editors of journals, and researchers. The ORION (Outbreak Reports and Intervention Studies Of Nosocomial infection) statement consists of a 22 item checklist, and a summary table. The emphasis is on transparency to improve the quality of reporting and on the use of appropriate statistical techniques. The statement has been endorsed by a number of professional special interest groups and societies. Like CONSORT, ORION should be considered a "work in progress", which requires ongoing dialogue for successful promotion and dissemination. The statement is therefore offered for further public discussion. Journals and research councils are strongly recommended to incorporate it into their submission and reviewing processes. Feedback to the authors is encouraged and the statement will be revised in 2 years.

Background: Patients with dementia often receive poor end-of-life care, with inadequate pain control and without access to the palliative care services that patients with cancer are offered. This has been identified as an area of need in recent U.K. Government reports and by the Alzheimer's Society (U.K.). Our objective was to perform a systematic review of the scientific literature regarding the efficacy of a palliative care model in patients with dementia.Methods: A systematic review was carried out to identify controlled trials that investigated the efficacy of palliative care in patients with dementia. Data sources included were Medline, EMBASE, PsycINFO, CINAHL, British Nursing Index, AMED, Cochrane Database of Systematic Reviews, Web of Science, Cochrane Central Register of Controlled Trials, International Standard Randomised Controlled Trial register, the NHS Economic Evaluation Database and the System for Information on Grey Literature in Europe. Other data was sourced from hand searches of papers identified on electronic databases and review articles.Results: The search identified 30 review articles, but only four papers were eligible for full appraisal and only two of these met the full criteria for inclusion. These papers gave equivocal evidence of the efficacy for a palliative model of care in dementia.Conclusion: Despite the increased interest in palliative care for patients with dementia there is currently little evidence on which to base such an approach. This may in part be due to the ethical difficulties surrounding such research, prognostic uncertainty in clinicians and the lack of clear outcome measures for patients who are unable to express their needs or wishes. Further systematic research is urgently needed to educate an important and developing area of clinical practice.

Prior research has suggested that regional weather patterns impact the risk of rupture of cerebral aneurysms, but the findings in the literature have been inconsistent. Furthermore, no nationwide analysis to date has examined the association between meteorological factors and the post-procedural outcomes of patients after the treatment for ruptured cerebral aneurysms. The purpose of this study was to use a nationwide sample to analyze the association between specific meteorological parameters--temperature, precipitation, sunlight, and humidity--and hospital admission rate for and outcome after aneurysmal subarachnoid hemorrhage. Patients were identified using the Nationwide Inpatient Sample (2001-2010): Those with an ICD-9 diagnosis code for subarachnoid hemorrhage and a procedural code for aneurysm repair were included. Climate data were obtained from the State of the Climate Report 2010 released by the National Climatic Data Center. Multivariate regression models were constructed to analyze the association between average state monthly temperature, precipitation, and percent possible sunlight, as well as relative morning humidity and both monthly hospital admission rate, adjusted for annual state population in millions, and in-hospital mortality. 16,970 admissions were included from 723 hospitals across 41 states. Decreased daily sunlight and lower relative humidity were associated with an increased rate of admission for ruptured cerebral aneurysms (p

Isolated cases of transient pupillary changes after local intracisternal papaverine administration during aneurysm surgery have been reported. This study aimed to determine the prevalence and factors associated with this phenomenon. We assessed a total of 103 consecutive patients who underwent craniotomy for cerebral aneurysm clipping for the presence of postoperative pupillary dilation (mydriasis) after intracisternal papaverine administration. Univariate and multivariate logistic regression were conducted to evaluate the association of mydriasis with patient age, sex, duration of surgery, and aneurysm location. We observed either ipsilateral or bilateral pupillary dilation in the immediate postoperative period in nine out of 103 patients (8.7%). This phenomenon was not associated with patient age or sex. There was a trend towards positive correlation with aneurysms located at the anterior communicating artery (odds ratio 3.76, p=0.10), and a negative correlation with the duration of surgery (odds ratio 0.57, p=0.08). All pupillary dilation resolved within several hours, and the onset and resolution were consistent with the half-life of papaverine. To our knowledge, this represents the largest study of posteropative pupillary changes due to papaverine. The current findings are consistent with the small number of prior case reports of transient pupillary changes after papaverine administration and appear to reflect the local anesthetic action of papaverine on the oculomotor nerve.

Neurogenic stress cardiomyopathy (NSC) is a known complication of aneurysmal subarachnoid hemorrhage (SAH). Detailed analyses of risk factors for its occurrence across large cohorts are relatively sparse.A consecutive group of 300 patients with aneurysmal SAH was reviewed for the presence of markers of myocardial injury, including electrocardiogram changes (long QT, T-wave inversion), elevated plasma troponin levels (≥0.1), and echocardiogram findings (decreased ejection fraction and wall motion abnormalities). NSC was defined as the presence of at least 1 marker of myocardial injury. Univariate and multivariate analyses were conducted to assess the correlation of NSC and individual markers of myocardial injury with age, gender, medical comorbidities, medications, current smoking status, Hunt-Hess grade, and Fisher grade. Medical comorbidities were assessed based on reported medical history or reported use of comorbidity-specific medications at the time of presentation.Across the cohort, 27% of patients had a plasma troponin elevation of at least 0.1; 13%, a prolonged QT interval; 16%, new T-wave inversions; 18%, a depressed ejection fraction (55%); and 15%, echocardiographic wall motion abnormalities. After a multivariate analysis, significant risk factors for NSC included higher Hunt-Hess grade on presentation (odds ratio [OR] = 2.33, P = 4.52 × 10(-6)), current smoking status (OR = 2.00, P = 0.030), and older age (OR = 1.03, P = 0.048). Hypertension was protective against NSC (OR = 0.48, P = 0.031). Patient gender, hyperlipidemia, diabetes, coronary artery disease, statin use, beta blocker use, angiotensin-converting enzyme inhibitor use, aspirin use, and thicker SAH (Fisher grade 3) were not significant risk factors for NSC.Higher Hunt-Hess grade, current smoking status, lack of hypertension, and older age were the strongest predictors of NSC.

Object The rates and risk factors for external ventricular drain (EVD) placement and long-term shunt dependence in patients with ruptured arteriovenous malformations (AVMs) have not been systematically studied. In this study the authors evaluated the rates of EVD placement and shunt dependence, and risk factors for them, in a cohort of patients with ruptured AVMs. Methods The records of 87 consecutive patients with ruptured AVMs were reviewed for patient demographics, hemorrhage pattern, AVM angioarchitectural features, and surgical treatment. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors for EVD placement, permanent shunt dependence, and long-term outcome (as measured by the modified Rankin Scale). Results Thirty-eight patients (44%) required EVD placement, and 16 (18%) required a permanent shunt. Statistically significant risk factors for EVD placement in the univariate analysis included initial Glasgow Coma Scale (GCS) score (p = 0.002), the presence of intraventricular hemorrhage (IVH; p < 0.001), AVM-associated aneurysms (p = 0.002), and early surgery (p = 0.01). Multivariate analysis revealed only AVM-associated aneurysms as statistically significant (p = 0.006). Risk factors for shunt placement included initial GCS score (p = 0.003), IVH (p = 0.01), deep supratentorial location (p = 0.034), and associated aneurysms (p = 0.03). Multivariate analysis revealed initial GCS score as a statistically significant risk factor (p = 0.041) as well as a strong trend for associated aneurysms (p = 0.06). Patient age, sex, associated subarachnoid hemorrhage, AVM grade, AVM size, and deep venous drainage were not associated with EVD placement or long-term shunt dependence. Conclusions Hydrocephalus from AVM rupture was associated with initial GCS score, IVH, and AVM-associated aneurysms. Arteriovenous malformations with associated aneurysms thus not only have a greater risk of hemorrhage but also a greater risk of hemorrhage-associated morbidity as a result of hydrocephalus.

Objective There is increasing literature supporting the importance in triaging patients to teaching hospitals for complex surgical procedures. This study analyzes the effect of teaching hospital status on outcome of endovascular coiling and microsurgical clipping of ruptured and unruptured intracranial aneurysms using the Nationwide Inpatient Sample database. Methods We analyzed patients with cerebral aneurysms using the Nationwide Inpatient Sample 2001 to 2010. Patients with ruptured aneurysms were identified by International Classification of Diseases, 9th revision codes for diagnoses of subarachnoid hemorrhage or intracerebral hemorrhage and at least one procedural code for aneurysm repair. Patients with unruptured cerebral aneurysms were identified by diagnosis code 437.3 and at least one procedural code. Multivariate linear models were used to analyze the association of in-hospital death, nonroutine discharge, and length of stay with teaching hospital status, adjusting for patient age, sex, race, comorbidities, household income, time to aneurysm repair procedure, aneurysm procedure volume, hospital region, and location. Results There were 34,843 hospitalizations for treatments of unruptured (14,763 in teaching and 1794 in nonteaching hospitals) and ruptured (15,628 in teaching and 2658 in nonteaching hospitals) aneurysms. In patients with ruptured aneurysms, the odds ratio of in-hospital death and nonroutine discharges were 0.69 (95% confidence interval 0.54–0.88) and 0.77 (95% confidence interval 0.60–0.99) in teaching hospitals, respectively, independent of hospital aneurysm procedure volume. Conclusions Our results suggest that the teaching status of a hospital is an independent factor for favorable outcome in the treatment of ruptured aneurysms. The difference in in-hospital death is accentuated in patients who underwent microsurgical clipping.

S100 calcium binding protein B (S100B), a well-studied marker for neurologic injury, has been suggested as a candidate for predicting outcome after subarachnoid hemorrhage. We performed a pooled analysis summarizing the associations between S100B protein in serum and cerebrospinal fluid (CSF) with radiographic vasospasm, delayed ischemic neurologic deficit (DIND), delayed cerebral infarction, and Glasgow Outcome Scale (GOS) outcome. A literature search using PubMed, the Cochrane Library, and the EMBASE databases was performed to identify relevant studies published up to May 2015. The weighted Stouffer's Z method was used to perform a pooled analysis of outcome measures with greater than three studies. A total of 13 studies were included in this review. Higher serum S100B level was found to be associated with cerebral infarction as diagnosed by CT (padj = 3.1 x 10(-4)) and worse GOS outcome (padj = 5.5 x 10(-11)). There was no association found between serum and CSF S100B with radiographic vasospasm or DIND. S100B is a potential prognostic marker for aSAH outcome.

Leptomeningeal venous drainage and symptomatic presentation are known risk factors for cerebral dural arteriovenous fistula (dAVF) hemorrhage. An evaluation of potentially modifiable risk factors such as hypertension and medication usage has not been undertaken to our knowledge. The authors thus reviewed a cohort of 45 consecutive patients with cerebral dAVF with leptomeningeal venous drainage and compared the rate of hemorrhagic presentation for patients with and without a history of hypertension, hyperlipidemia or the usage of certain medications. Logistic regression was performed to determine the statistical significance of associations of each factor with hemorrhagic presentation. On univariate analysis, angiotensin-converting enzyme (ACE)-inhibitors (odds ratio [OR] 0.100, 95% confidence interval [CI] 0–0.764 , p = 0.024) and statins (OR 0.142, 95% CI 0.025–0.825 , p = 0.030) were associated with a statistically significant lower rate of hemorrhagic presentation. A trend toward a lower rate of hemorrhagic presentation was seen for patients taking aspirin (OR 0.153, 95% CI 0.016–1.43, p = 0.10). These trends continued on multivariate analysis; however they did not meet statistical significance ( p > 0.05). Beta-blockers, calcium channel blockers, warfarin and selective serotonin reuptake inhibitors did not have a statistically significant association with the rate of hemorrhagic presentation ( p > 0.05). Although limited by small sample size, these results may suggest a beneficial effect of statins and ACE-inhibitors on the rate of dAVF hemorrhagic presentation, potentially as a result of anti-inflammatory, anti-angiogenic or even venous antithrombotic mechanisms. Despite this study’s limitations, we hope it encourages further evaluation of potentially modifiable risk factors for vascular malformation hemorrhage.

This study aims to quantify the unique useful yield from the Cumulative Index to Nursing and Allied Health Literature (CINAHL) database to National Institute for Health and Clinical Excellence (NICE) clinical guidelines. A secondary objective is to investigate the relationship between this yield and different clinical question types. It is hypothesized that the unique useful yield from CINAHL is low, and this database can therefore be relegated to selective rather than routine searching.A retrospective sample of 15 NICE guidelines published between 2005 and 2009 was taken. Information on clinical review question type, number of references, and reference source was extracted.Only 0.33% (95% confidence interval: 0.01-0.64%) of references per guideline were unique to CINAHL. Nursing- or allied health (AH)-related questions were nearly three times as likely to have references unique to CINAHL as non-nursing- or AH-related questions (14.89% vs. 5.11%), and this relationship was found to be significant (P0.05). No significant relationship was found between question type and unique CINAHL yield for drug-related questions.The very low proportion of references unique to CINAHL strongly suggests that this database can be safely relegated to selective rather than routine searching. Nursing- and AH-related questions would benefit from selective searching of CINAHL.

Objective The pathophysiology on cerebral vasospasm and delayed cerebral ischemia (DCI) remains poorly understood. Much research has been dedicated to finding genetic loci associated with vasospasm and ischemia. We present a systematic review and meta-analysis to identify genetic polymorphisms associated with delayed ischemic neurologic deficit (DIND), radiographic infarction attributed to ischemia, and radiographic vasospasm. Methods PubMed, the Cochrane Library, and Excerpta Medica dataBASE (EMBASE) databases were used to identify relevant studies published up to March 2015 containing the subject terms cerebral or intracranial vasospasm and DCI in combination with genetics, gene, polymorphism or marker. Meta-analyses were performed using a random-effects model to calculate summary odds ratio (ORs) and 95% confidence intervals for each respective gene. Results Of 269 articles initially identified, 20 studies with 1670 patients were included in our comprehensive review, including 27 polymorphisms in 11 genes. The following 6 polymorphisms in 3 genes were selected for subsequent meta-analyses: apolipoprotein E (ApoE2, E4); endothelial nitric oxide (eNOS T786C, VNTR intron 4 a/b, G894T); and haptoglobin (Hp) 1/2 phenotypes. The eNOS VNTR a allele was associated with DIND ( a vs. b allele: OR 1.92 [1.31-2.81], p adj = 0.008). The Hp 2-2 allele was associated with radiographic vasospasm (2-2 vs. 2-1 and 1-1: OR 3.86 [1.86-8.03], p adj = 0.003) but did not reach significance for DIND. Conclusions This is the first systemic review and meta-analysis to study and evaluate the associations between genetic polymorphism with DCI and radiographic vasospasm independently. In our study, eNOS VNTR and Hp polymorphisms appear to have the strongest associations with DIND and radiographic vasospasm, respectively.

ContextAllocation on the basis of randomization rather than patient choice is the gold standard of unbiased estimates of efficacy in clinical medicine. However, randomly allocating patients to treatments that do not accord with their preferences may influence internal and external validity.ObjectiveTo determine whether preferences affect recruitment to trials (external validity) and outcomes in trials (internal validity)Data SourcesWe searched MEDLINE, EMBASE, PsycINFO, CINAHL, AMED, and the Cochrane Library for articles published between 1966 and September 2004. We also hand-searched several major medical journals, searched reference lists of relevant articles, and contacted authors of published preference designs. The 2 themes in the first filter of the search strategy were preferences and possible determinants of preferences.Study SelectionComprehensive cohorts and 2-stage trials that measured or recorded patient or physician preference, included allocation of participants to random and preference cohorts, and followed up all participants. We excluded trials with no recording of preference; of decision aids; with measurements of preferences for economic analyses; in which patients who refused randomization were followed up without reference to preferences; and of nonclinical populations.Data ExtractionUp to 4 reviewers independently evaluated the articles, and disagreements were resolved at project steering group meetings. We extracted data on study design, measurement of preference, recruitment, attrition, and summary data on the primary outcome(s) at baseline and each follow-up point.Data SynthesisOf 10 023 citations identified, 170 articles met screening criteria and 32 (27 comprehensive cohorts and 5 two-stage trials) were determined to be eligible and were used in the final review. Although treatment preferences led to a substantial proportion of people refusing randomization, there was less evidence of bias in the characteristics of individuals agreeing to be randomized. Differences in outcome across the trials between randomized and preference groups were generally small, particularly in large trials and after accounting for baseline measures of outcome. Therefore, there was little evidence that preferences substantially interfere with the internal validity of randomized trials.ConclusionsPreferences influence whether people participate in randomized trials, but there is little evidence that they significantly affect validity.

Investigation into the association of insurance status with the outcomes of patients undergoing neurosurgical intervention has been limited: this is the first nationwide study to analyze the impact of primary payer on the outcomes of patients with aneurysmal subarachnoid hemorrhage who underwent endovascular coiling or microsurgical clipping. The Nationwide Inpatient Sample (2001–2010) was utilized to identify patients; those with both an ICD-9 diagnosis codes for subarachnoid hemorrhage and a procedure code for aneurysm repair (either via an endovascular or surgical approach) were included. Hierarchical multivariate regression analyses were utilized to evaluate the impact of primary payer on in-hospital mortality, hospital discharge disposition, and length of hospital stay with hospital as the random effects variable. Models were adjusted for patient age, sex, race, comorbidities, socioeconomic status, hospital region, location (urban versus rural), and teaching status, procedural volume, year of admission, and the proportion of patients who underwent ventriculostomy. Subsequent models were also adjusted for time to aneurysm repair and time to ventriculostomy; subgroup analyses evaluated for those who underwent endovascular and surgical procedures separately. 15,557 hospitalizations were included. In the initial model, the adjusted odds of in-hospital mortality were higher for Medicare (OR 1.23, p

BACKGROUND: Interactive Health Communication Applications (IHCAs) are computer-based, usually web-based health information packages for patients that combine information with at least one of social support, decision support, or behaviour change support. These are innovations in health care and their effects on health are uncertain. OBJECTIVES: To assess the effects of IHCAs for people with chronic disease. SEARCH STRATEGY: We designed a four-part search strategy. First, we searched electronic bibliographic databases for published work; second, we searched the grey literature and third, we searched for ongoing and recently completed clinical trials in the appropriate databases. Finally, researchers of included studies were contacted, and reference lists from relevant primary and review articles were followed up. As IHCAs require relatively new technology, the search commenced at 1990 where possible. SELECTION CRITERIA: Randomised controlled trials (RCTs) of Interactive Health Communication Applications for adults and children with chronic disease. DATA COLLECTION AND ANALYSIS: One reviewer screened abstracts. Two reviewers screened all candidate studies to determine eligibility, apply quality criteria, and extract data from included studies. Authors of included RCTs were contacted for missing data. Results of RCTs were pooled using a random effects model and standardised mean differences (SMDs) were calculated to provide net effect sizes. MAIN RESULTS: We screened 24,757 unique citations and retrieved 958 papers for further assessment, yielding 28 RCTs involving 4042 participants. One of these had an inadequate method of concealment of allocation, and sensitivity analyses were performed to determine the effects of including or excluding these data in the meta-analyses. Results in the abstract are from the meta-analyses excluding data from this study.IHCAs were found to have a positive effect on knowledge (SMD 0.49; 95% confidence interval (CI) 0.14 to 0.84) and on social support (SMD 0.47; 95% CI 0.28 to 0.66). IHCAs were found to have no effect on self-efficacy (SMD 0.15; 95% CI -0.13 to 0.43) or behavioural outcomes (SMD -0.09; 95% CI -0.49 to 0.32). IHCAs had a negative effect on clinical outcomes (SMD -0.32; 95% CI -0.63 to -0.02). REVIEWERS' CONCLUSIONS: The number and range of IHCAs is increasing rapidly; however there is a shortage of high quality evaluative data. Consumers who wish to increase their knowledge or social support amongst people with a similar problem may find an IHCA helpful. However, consumers whose primary aim is to achieve optimal clinical outcomes should not use an IHCA at present. Further research is needed to determine the reason for this negative effect on clinical outcomes, whether an optimal IHCA can achieve behaviour change and improved health outcomes, and if so, what are the essential features of such an IHCA, and the extent to which they differ according to patient group or condition.