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OBJECTIVEInhibition of platelet aggregation is universally used to prevent thromboembolic complications related to stent placement in endovascular neurosurgery, but excessive inhibition potentiates hemorrhagic complications. Previously, the authors demonstrated that two different commercially available measures of adenosine diphosphate (ADP)–dependent platelet inhibition—the VerifyNow P2Y12 clopidogrel assay (measured in platelet reactivity units [PRU]) and maximal amplitude (MA) attributable to ADP activity (MA-ADP) derived from thromboelastography (TEG) with platelet mapping (PM)—yielded wildly different results. This study sought to analyze observed complications to quantify the ideal therapeutic windows for both tests.METHODSNinety-one patients with simultaneous or near-simultaneous PRU and TEG-PM results who underwent craniocervical endovascular stenting at the authors’ institution between September 2015 and November 2017 were identified and retrospectively enrolled. From November 2017 until June 2019, 109 additional patients were prospectively enrolled. For this study, in-hospital thrombotic and hemorrhagic complications (both CNS and non-CNS) were tabulated, and receiver operating characteristic (ROC) curve analysis was used to identify threshold values of the PRU and MA-ADP for predicting each type of complication.RESULTSOf the 200 patients enrolled, 7 were excluded because of anemia or thrombocytopenia outside of the test manufacturer’s specified ranges and 1 was excluded because they did not have a TEG-PM result. Including complications of all severities, there were a total of 15 CNS thrombotic complications, 1 access-site thrombotic complication, 3 CNS hemorrhages, 8 access-site hemorrhagic complications, and 3 hemorrhagic complications not affecting either the CNS or the access site. ROC curve analysis yielded therapeutic threshold values of 118–144 PRU. The results demonstrated PRU has a significant dose-dependent effect on the rates of thrombosis and hemorrhage. Logistic regression models did not demonstrate statistically significant relationships between the MA-ADP and either thrombosis or hemorrhage. ROC analysis based on these models is of little value and did not identify significant threshold values for MA-ADP.CONCLUSIONSThere continues to be poor correlation between the results of TEG-PM and PRU. PRU accurately predicted complications, with a relatively narrow ideal value range of 118–144. The MA-ADP alone does not appear able to accurately predict either hemorrhagic or thrombotic complications in this group.

Objective The aim of this study was to define the structural relationship between the arcuate eminence (AE) and a known fixed external bony landmark, the root of the zygoma (ZR), and to determine its reliability as a consistent guide for guiding surgical approaches. To our knowledge, this is the only anatomical study to quantify the relationship between the AE and the ZR. Method Twenty-one dry temporal bones were measured using digital calipers. The distance from the posterior aspect of the ZR to the midpoint of the AE was measured. Additionally, the anteroposterior distance between the ZR and AE and vertical distance between the two structures were measured. Student's t-test was used to compare the left and right sides. Result An AE was found in every specimen. The mean ZR to AE distance was 30.9 mm. On most sides (91%), the ZR was located more inferiorly than the AE with a mean distance of 3 mm between the two structures. The mean distance between the AE and ZR was 17 mm. On all sides, the AE was located posterior to the ZR. No significant differences were found between sides. No anatomical variations or pathological conditions were noted in any of the specimens. Conclusion The ZR is an easily identifiable and consistent bony landmark often used by skull base surgeons. In this investigation, we measured the anatomical relationships between the ZR and AE. Such data might assist in planning surgical trajectories and minimizing complications when skull base pathologies are approached.

Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent condition requiring rapid intervention and prolonged monitoring. There are few recommendations regarding the management of aSAH in pregnancy. We identified all available literature and compiled management decisions as well as reported outcomes through a systematic literature review without meta-analysis to provide recommendations for management of aSAH during pregnancy. We included a total of 23 articles containing 54 cases of pregnancy-related aSAH in our review. From these reports and other literature, we evaluated information on aSAH pathophysiology, diagnosis, and management with respect to pregnancy. Early transfer to an appropriate facility with neurocritical care, a high-risk obstetric service, and a neurosurgery team available is crucial for the management of aSAH in pregnancy. Intensive monitoring and a multidisciplinary approach remain fundamental to ensure maternal and fetal health.

Cerebral mycotic aneurysms are rare and account for a small percentage of all intracranial aneurysms. Fungal aneurysms occur less often than bacterial aneurysms and are associated with increased morbidity and mortality. Risk factors include an immunocompromised state, prior hematologic or solid organ malignancy, and chronic chemotherapy or steroid use. We present the fourth known case of an intracranial infectious aneurysm associated with Nocardia infection in a middle-aged male patient with previous Nocardia meningitis, and the only known case treated with endovascular coiling of aneurysm. We offer a literature review, case presentation, discussion, and considerations for treatment and management of these patients.

Extracranial-intracranial bypass has been shown to be effective in the surgical treatment of moyamoya disease, complex aneurysms, and tumors that involve proximal vasculature in carefully selected patients. Branches of the superficial temporal artery (STA) are used commonly for the bypass surgery; however, an appropriate length of the donor vessel must be harvested to avoid failure secondary to anastomotic tension. The goal of this cadaveric study was to investigate quantitatively operative techniques that can increase the STA length available to facilitate tension-free STA-middle cerebral artery (MCA) bypass. We conducted a cadaveric study using a total of 16 sides in eight cadavers. Measurements of the STA trunk with its frontal branch (STAfb) were taken before and after skeletonization and detethering of the STA with the STAfb and mobilization of the parietal branch of the STA. A final measurement of the STA with the STAfb was taken for the free length gained toward visible proximal cortical branches of the MCA. Paired student's t-tests were used to compare the mean length before and after mobilization and unpaired t-tests to analyze according to laterality. The mean length of the STA with the STAfb was 9.0 cm prior to modification. After skeletonization and mobilization, the mean lengths increased significantly to 10.5 and 11.3 cm, respectively (p

Background The radial artery is gaining popularity as a vascular access site for neurointerventional procedures. However, recent analyses of wrist position and radial artery anatomy has suggested that the extended position of the wrist is not always necessary. Therefore, the following cadaveric study was performed to verify these findings. Methods Twenty adult cadaveric upper limbs underwent dissection of the radial artery. The radial artery was exposed but left in its anatomical position. With the hand supinated, the wrist was extended to 45 degrees and 90 degrees. Observations were then made of any movement of the artery during these ranges of motion. Next, a tension gauge was attached to the radial artery and any tension on the artery measured during the above noted ranges of motion. Results During extension of the wrist, none of the radial artery specimens was found to move in any direction. Moreover, an average of only 0.28 N of tension on the artery was found with wrist extension up to 90 degrees. Our cadaveric study found that, contrary to popular belief, extension of the wrist during cannulation of the radial artery does not change the position of the artery nor does it significantly alter the tension on the artery. Conclusions These data support several recent clinical studies.

Background The blood supply to the skull base is important to surgeons and those performing interventional and diagnostic procedures in this region. However, 1 vessel with a vast distribution in this area, the dorsal meningeal artery (DMA), has had few anatomic studies performed to investigate not only its normal anatomy but also its variations. Therefore the current study aimed to analyze the DMA via cadaveric dissection. Methods In 10 adults, latex-injected, cadaveric heads (20 sides), the DMA was dissected using a surgical microscope. This artery and its branches were documented and measured. Results A DMA was identified on all sides. In the majority (85%), it was a branch of the meningohypophysial trunk or common stem with either the inferior hypophysial or tentorial arteries and always had branches that traversed the basilar venous plexus. Multiple branches of the DMA were identified and categorized as bony, dural, neural, and vascular. Conclusions Surgeons operating at the skull base or clinicians interpreting imaging of this area should have a good working knowledge of the DMA and its typical and variant anatomy.

Patient selection for endovascular intervention in extracranial carotid disease is centered on vascular anatomy. We review anatomical considerations for non-traumatic disease and offer guidelines in patient selection and management. We conducted a systematic literature review without meta-analysis for studies involving anatomical considerations in extracranial carotid intervention for non-traumatic disease. Anatomical considerations discussed included aortic arch variants, degree of vessel stenosis, angulation, tortuosity, and anomalous origins, and atheromatous plaque morphology, composition, and location. Available literature suggests that anatomical risks of morbidity are largely secondary to increased procedural times and difficulties in intervention system delivery. We recommend the prioritization of endovascular techniques on an individual basis in cases where accessible systems and surgeon familiarity provide an acceptable likelihood of rapid access and device deployment.

Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent condition requiring rapid intervention and prolonged monitoring. There are few recommendations regarding the management of aSAH in pregnancy. We identified all available literature and compiled management decisions as well as reported outcomes through a systematic literature review without meta-analysis to provide recommendations for management of aSAH during pregnancy. We included a total of 23 articles containing 54 cases of pregnancy-related aSAH in our review. From these reports and other literature, we evaluated information on aSAH pathophysiology, diagnosis, and management with respect to pregnancy. Early transfer to an appropriate facility with neurocritical care, a high-risk obstetric service, and a neurosurgery team available is crucial for the management of aSAH in pregnancy. Intensive monitoring and a multidisciplinary approach remain fundamental to ensure maternal and fetal health.

A 73-year-old man with a complex ophthalmologic history presented with several weeks of worsening diplopia, visual acuity, and proptosis bilaterally. Cerebral angiography demonstrated bilateral indirect Barrow type B carotid-cavernous fistulas (CCFs). Transarterial embolization was not attempted due to small arterial diameter and risk of stroke. Multiple attempts were made to access the fistula via a transfemoral venous approach and were unsuccessful. A transorbital puncture was performed, which allowed access to both cavernous sinuses via a unilateral approach. After embolization with Onyx, there was no residual fistula. The patient had a left-sided retrobulbar hematoma from the access. Right eye vision improved postoperatively.

Objective Many external anatomical landmarks have been used for approximating deeper, intracranial structures. Herein, we evaluate the attachment of the longissimus capitis (LC) on the mastoid process as a landmark for the underlying sigmoid sinus. Methods Adult cadavers underwent dissection of the posterior occiput with special attention to the attachment of the LC muscle. Once the periphery of the muscle's tendon of attachment was determined, a burr hole was made in this area and evaluated internally for its relationship to the sigmoid sinus. Results From an intracranial view, burr holes on all sides were over the sigmoid sinus and just slightly lateral to the center of the sinus. The distance from the midline to the medial border of the insertion of the LC had a mean of 63.0 ± 7.2 mm. The width of the tendon of insertion of the LC on the mastoid process had a mean of 17.6 ± 5.7 mm. The length of the tendon insertion of the LC had a mean of 14.7 ± 4.7 mm. The distance from the inferior border of the insertion of the LC to the tip of the mastoid process had a mean of 6.2 ± 4.5 mm. Conclusion To our knowledge, use of the attachment site of the LC on the mastoid process as an external landmark for the underlying sigmoid sinus has not previously been reported. Based on our cadaveric findings, the sigmoid sinus is centered under the attachment of the LC regardless of the width of its tendon.

OBJECTIVEDespite their technical simplicity, cranioplasty procedures carry high reported morbidity rates. The authors here present the largest study to date on complications after cranioplasty, focusing specifically on the relationship between complications and timing of the operation.METHODSThe authors retrospectively reviewed all cranioplasty cases performed at Harborview Medical Center over the past 10.75 years. In addition to relevant clinical and demographic characteristics, patient morbidity and mortality data were abstracted from the electronic medical record. Cox proportional-hazards models were used to analyze variables potentially associated with the risk of infection, hydrocephalus, seizure, hematoma, and bone flap resorption.RESULTSOver the course of 10.75 years, 754 cranioplasties were performed at a single institution. Sixty percent of the patients who underwent these cranioplasties were male, and the median follow-up overall was 233 days. The 30-day mortality rate was 0.26% (2 cases, both due to postoperative epidural hematoma). Overall, 24.6% percent of the patients experienced at least 1 complication including infection necessitating explantation of the flap (6.6%), postoperative hydrocephalus requiring a shunt (9.0%), resorption of the flap requiring synthetic cranioplasty (6.3%), seizure (4.1%), postoperative hematoma requiring evacuation (2.3%), and other (1.6%).The rate of infection was significantly higher if the cranioplasty had been performed < 14 days after the initial craniectomy (p = 0.007, Holm-Bonferroni–adjusted p = 0.028). Hydrocephalus was significantly correlated with time to cranioplasty (OR 0.92 per 10-day increase, p < 0.001) and was most common in patients whose cranioplasty had been performed < 90 days after initial craniectomy. New-onset seizure, however, only occurred in patients who had undergone their cranioplasty > 90 days after initial craniectomy. Bone flap resorption was the least likely complication for patients whose cranioplasty had been performed between 15 and 30 days after initial craniectomy. Resorption was also correlated with patient age, with a hazard ratio of 0.67 per increase of 10 years of age (p = 0.001).CONCLUSIONSCranioplasty performed between 15 and 30 days after initial craniectomy may minimize infection, seizure, and bone flap resorption, whereas waiting > 90 days may minimize hydrocephalus but may increase the risk of seizure.

OBJECTIVEFusiform dolichoectatic vertebrobasilar aneurysms are rare, challenging lesions. The natural history of these lesions and medium- and long-term patient outcomes are poorly understood. The authors sought to evaluate patient prognosis after diagnosis of fusiform dolichoectatic vertebrobasilar aneurysms and to identify clinical and radiographic predictors of neurological deterioration.METHODSThe authors reviewed multiple, prospectively maintained, single-provider databases at 3 large-volume cerebrovascular centers to obtain data on patients with unruptured, fusiform, basilar artery dolichoectatic aneurysms diagnosed between January 1, 2000, and January 1, 2015.RESULTSA total of 50 patients (33 men, 17 women) were identified; mean clinical follow-up was 50.1 months and mean radiographic follow-up was 32.4 months. At last follow-up, 42% (n = 21) of aneurysms had progressed and 44% (n = 22) of patients had deterioration of their modified Rankin Scale scores. When patients were dichotomized into 2 groups— those who worsened and those who did not—univariate analysis showed 5 variables to be statistically significantly different: sex (p = 0.007), radiographic brainstem compression (p = 0.03), clinical posterior fossa compression (p < 0.001), aneurysmal growth on subsequent imaging (p = 0.001), and surgical therapy (p = 0.006). A binary logistic regression was then created to evaluate these variables. The only variable found to be a statistically significant predictor of clinical worsening was clinical symptoms of posterior fossa compression at presentation (p = 0.01).CONCLUSIONSFusiform dolichoectatic vertebrobasilar aneurysms carry a poor prognosis, with approximately one-half of the patients deteriorating or experiencing progression of their aneurysm within 5 years. Despite being high risk, intervention—when carefully timed (before neurological decline)—may be beneficial in select patients.

Background and importance Coil migration is a potential complication of endovascular aneurysm treatment. Dislodged coils into the parent artery require retrieval to prevent thromboembolic complications. A variety of techniques for coil retrieval have been described, including the use of single stentrievers and aspiration catheters. Clinical presentation The use of 2 stentrievers, as opposed to a single device, was thought to be advantageous in coil removal by the additional point of friction due to the extensive length of coil stretching and earlier failure of a single device. Conclusion In this report, 2 synchronous Solitaire FR Revascularization Devices (Covidien/Medtronic, Dublin, Ireland) were deployed, 1 distal and 1 proximal, to retrieve an inadvertently deployed coil.

Background The development of hydrocephalus (HCP) necessitating placement of a ventriculoperitoneal shunt (VPS) after decompressive hemicraniectomy occurs at a rate of approximately 5%–15%. The ideal approach for addressing both HCP and a cranial defect remains unclear, and whether concomitant VPS and cranioplasty (CP) increases the risk of complications is uncertain. Methods This is a retrospective cohort study of adult patients who underwent CP and VPS placement for any indication at Harborview Medical Center, Seattle between March 2004 and November 2014 with at least 30 days of follow-up. The primary variable of interest was the timing of CP relative to VPS placement. The outcomes of interest were CP- and VPS-related infections, early (within 1 year of placement) VPS obstruction, and a composite of any of these complications in a single patient. Results The rate of composite outcomes was 15% in the subgroup of patients with simultaneous CP and VPS placement, compared with 29% in the subgroup of patients in whom CP and VPS placement were performed separately, a non–statistically significant difference (P = 0.24). Similarly, there was no statistically significant difference between the subgroups in any of the 3 individual outcomes of interest, which remained after accounting for potential covariates in a multivariate regression model. Conclusions In our study population, there was no difference between simultaneous and separate CP and VPS placement with respect to CP infection, VPS infection, and VPS mechanical failure/obstruction. There is equipoise in the current literature regarding the safety of performing these 2 common procedures simultaneously, with studies of similar size and design finding variable degrees of safety of this practice.

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

BackgroundDural arteriovenous fistulae (dAVFs) comprise 10–15% of all intracranial arteriovenous malformations. The goal of surgical or endovascular intervention is complete obliteration of the fistulous connection(s). In cases where dAVF venous drainage is separate from normal cortical drainage, transvenous embolization can provide fast and effective fistula obliteration.ObjectiveTo describe a new method of efficient transvenous embolization (the ‘dual microcatheter technique’) for the treatment of dAVFs.MethodsThree patients with dAVFs were treated using the dual microcatheter technique for transvenous embolization. Two microcatheters were placed in the distal aspect of the dAVF venous pouch, after which coil embolization reduced fistula flow, and liquid embolic agent injection with reflux into arterial feeders completed the obliteration of the fistula.ResultsLesion grade ranged from Borden–Shucart grades 2 through 3. In all cases, dAVF venous drainage was isolated from the normal cerebral venous drainage. Dual microcatheter transvenous embolization was successful in all patients, with non-target embolization and no new postoperative deficits. At the last follow-up, all three patients were symptom-free without evidence of radiographic recurrence.ConclusionsThe dual microcatheter technique of transvenous dAVF embolization is safe and feasible in cases where dAVF venous outflow is isolated from normal cerebral venous drainage.

OBJECTIVE Brain arteriovenous malformations (bAVMs) are rare in pediatric patients but represent the most common cause of hemorrhagic stroke in this population. Pediatric patients demonstrate superior outcomes in comparison with adult patients with similar lesions and presentations. Most studies of clinical outcomes of pediatric bAVMs use the modified Rankin Scale (mRS), despite a lack of validation in pediatric patients. METHODS The authors interviewed the parents of 26 pediatric patients who underwent multimodality bAVM treatment and administered the Pediatric Quality of Life Inventory (PedsQL)—a well-validated tool for pediatric outcomes that quantifies performance in a physical, emotional, social, and school domains. They also reviewed clinical information from the patients' medical charts. Statistical analysis was performed using a log-transformed t-test, the Mann-Whitney exact test, the Kruskal-Wallis test, and Spearman correlation. In addition, the literature was reviewed for prior reports of clinical outcome of pediatric cases of bAVM. RESULTS The average PedsQL health-related quality of life score was 71 ± 24, with an average age at diagnosis of 12.5 years and an average follow-up period of 6.8 years. Seventeen patients (65%) presented with hemorrhage and 4 (15%) with seizures. PedsQL scores correlated strongly and at a statistically significant level (p < 0.001) with mRS, Pediatric Overall Performance Category (POPC), Pediatric Cerebral Performance Category (PCPC), and Glasgow Outcome Scale scores. Multivariate modeling validated special education, corrective devices, and cure status as significant predictors of PedsQL scores. Statistically significant risk factors for undergoing placement of a ventriculoperitoneal shunt included lower Glasgow Coma Scale motor scores on admission (p = 0.042), cerebellar location (p = 0.046), and nidus volume (p = 0.017). Neither treatment modality nor location statistically affected clinical outcomes at follow-up. CONCLUSIONS There have been few studies of long-term clinical outcomes of bAVM in pediatric patients, and previously published studies have used conventional metrics that have been validated in the adult population, such as the mRS. Although these metrics can serve as reasonable surrogates, an accurate understanding of overall health-related quality of life is contingent on utilizing validated toolsets, such as the PedsQL.

BACKGROUND Brain arteriovenous malformations (BAVMs) are a frequent cause of pediatric hemorrhagic stroke, which frequently results in significant morbidity and mortality. OBJECTIVE To analyze the results of multimodality treatment for a consecutive series of pediatric patients with ruptured and unruptured BAVMs at a single institution. METHODS Forty patients

ObjectiveThe recently published arteriovenous malformation-related intracerebral haemorrhage (AVICH) score showed better outcome prediction for patients with arteriovenous malformation (AVM)-related intracerebral haemorrhage (ICH) than other AVM or ICH scores. Here we present the results of a multicentre, external validation of the AVICH score.MethodsAll participating centres (n=11) provided anonymous data on 325 patients to form the Spetzler-Martin (SM) grade, the supplemented SM (sSM) grade, the ICH score and the AVICH score. Modified Rankin score (mRS) at last follow-up (mean 25.6 months) was dichotomized into favourable (mRS 0-2, n=210) and unfavourable (mRS 3-6;n=115). Univariate and AUROC analyses were performed to validate the AVICH score.ResultsExcept nidus structure and AVM size, all single parameters forming the SM, sSM, ICH and AVICH score and the scores itself were significantly different between both outcome groups in the univariate analysis. The AVICH score was confirmed to be the highest predictive outcome score with an AUROC of 0.765 compared with 0.705 for the ICH score and 0.682 for the sSM grade.ConclusionThe multicentre-validated AVICH score predicts clinical outcome superior to pre-existing scores. We suggest the routine use of this score for future clinical outcome prediction and in clinical research.Trial registration numberNCT02920645.

Cerebrovascular occlusive disease is a broad category of pathology involving the extracranial and intracranial vasculature of the carotid and vertebral arteries. The common goal of treatment is to prevent stroke in asymptomatic patients and reduce the risk of future stroke in symptomatic patients. This area of neurologic surgery has been the subject of numerous clinical trials, especially cervical carotid artery stenosis and extracranial-intracranial bypass, and continual advances in medical management and technology maintain it as an active subject of research and debate.

Background The design and conclusions of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) trial are controversial, and its structure limits analysis of patients who could potentially benefit from treatment. Objective To analyze the results of a consecutive series of patients with unruptured brain arteriovenous malformations (BAVMs), including a subgroup analysis of ARUBA-eligible patients. Methods One hundred five patients with unruptured BAVMs were treated over an 8-year period. From this series, 90 adult patients and a subgroup of 61 patients determined to be ARUBA eligible were retrospectively reviewed. A subgroup analysis for Spetzler-Martin grades I/II, III, and IV/V was performed. The modified Rankin Scale was used to assess functional outcome. Results Persistent deficits, modified Rankin Scale score deterioration, and impaired functional outcome occurred less frequently in ARUBA-eligible grade I/II patients compared with grade III to V patients combined (P = .04, P = .04, P = .03, respectively). Twenty-two of 39 patients (56%) unruptured grade I and II BAVMs were treated with surgery without and with preoperative embolization, and all had a modified Rankin Scale score of 0 to 1 at the last follow-up. All patients treated with surgery without and with preoperative embolization had radiographic cure at the last follow-up. Conclusion The results of ARUBA-eligible and unruptured grade I/II patients overall show that excellent outcomes can be obtained in this subgroup of patients, especially with surgical management. Functional outcomes for ARUBA-eligible patients were similar to those of patients who were randomized to medical management in ARUBA. On the basis of these data, in appropriately selected patients, we recommend treatment for low-grade BAVMs.

BackgroundComputational modeling of intracranial aneurysms provides insights into the influence of hemodynamics on aneurysm growth, rupture, and treatment outcome. Standard modeling of coiled aneurysms simplifies the complex geometry of the coil mass into a homogeneous porous medium that fills the aneurysmal sac. We compare hemodynamics of coiled aneurysms modeled from high-resolution imaging with those from the same aneurysms modeled following the standard technique, in an effort to characterize sources of error from the simplified model.MaterialsPhysical models of two unruptured aneurysms were created using three-dimensional printing. The models were treated with coil embolization using the same coils as those used in actual patient treatment and then scanned by synchrotron X-ray microtomography to obtain high-resolution imaging of the coil mass. Computational modeling of each aneurysm was performed using patient-specific boundary conditions. The coils were modeled using the simplified porous medium or by incorporating the X-ray imaged coil surface, and the differences in hemodynamic variables were assessed.ResultsX-ray microtomographic imaging of coils and incorporation into computational models were successful for both aneurysms. Porous medium calculations of coiled aneurysm hemodynamics overestimated intra-aneurysmal flow, underestimated oscillatory shear index and viscous dissipation, and over- or underpredicted wall shear stress (WSS) and WSS gradient compared with X-ray-based coiled computational fluid dynamics models.ConclusionsComputational modeling of coiled intracranial aneurysms using the porous medium approach may inaccurately estimate key hemodynamic variables compared with models incorporating high-resolution synchrotron X-ray microtomographic imaging of complex aneurysm coil geometry.

BackgroundEmbolization before stereotactic radiosurgery (SRS) for brain arteriovenous malformations (BAVMs) is controversial.ObjectiveTo compare clinical and radiographic outcomes in patients undergoing pre-SRS embolization with ethylene copolymer (Onyx) with outcomes in patients undergoing SRS alone.MethodsSeventy consecutive patients with BAVMs who underwent SRS were retrospectively reviewed. Univariate and multivariate analyses were performed to assess the factors associated with radiographic obliteration and complication.ResultsForty-one (59%) patients presented without BAVM rupture and 29 (41%) patients presented with rupture. Pre-SRS embolization was used in 20 patients (28.6%; 7 unruptured and 13 ruptured). Twenty-five of 70 (36%) patients sustained a complication from treatment, including 6 (9%) patients with a post-SRS latency period hemorrhage. Ten (14%) patients had persistent neurological deficits after treatment. Functional outcome (as modified Rankin Scale), complication rate, and radiographic obliteration at last follow-up were not significantly different between embolized and non-embolized groups in both unruptured and ruptured BAVMs. For unruptured BAVMs, 3- and 5-year rates of radiographic obliteration were 23% and 73% for non-embolized patients and 20% and 60% for embolized patients, respectively. For ruptured BAVMs, 3- and 5-year rates of radiographic obliteration were 45% and 72% for non-embolized patients and 53% and 82% for embolized patients, respectively.ConclusionPre-SRS embolization with Onyx was not associated with worse clinical or radiographic outcomes than SRS treatment without embolization. Pre-SRS embolization has a low complication rate and can safely be used to target high-risk BAVM features in carefully selected patients destined for SRS.

Background Blood blister type aneurysms (BBAs) and pseudoaneurysms create a unique treatment challenge. Despite many advances in open surgical and endovascular techniques, this subset of patients retains relatively high rates of morbidity and mortality. Recently, BBAs have been treated with flow-diverting stents such as the Pipeline Embolization Device (PED) with overall positive results. Methods Four patients presented with dissecting internal carotid artery (ICA) aneurysms treated with the PED (two BBAs presenting with subarachnoid hemorrhage (SAH), two pseudoaneurysms after injury during endoscopic trans-sphenoidal tumor surgery). Results Three patients had a successful angiographic and neurological outcome. One patient with a BBA re-ruptured during initial PED placement, again in the postoperative period, and later died. Primary PED treatment involved telescoping stents in two patients and coil embolization supplementation in one patient. Conclusions The PED should be used selectively in the setting of acute SAH. Dual antiplatelet therapy can complicate hydrocephalus management, and the lack of immediate aneurysm occlusion creates the risk of short-term re-rupture. PED treatment for iatrogenic ICA pseudoaneurysms can provide a good angiographic and neurological outcome.

Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor. Without treatment, median survival is only 3 months after diagnosis. Even with “gold standard” therapy consisting of maximal surgical resection, fractionated radiotherapy, and temozolomide chemotherapy, median survival is only 14.6 months (4, 10, 12). Diverse tumor biology and intrinsic tumor capabilities to overcome current treatment tactics remain the major obstacle to achieving longer survival periods. New targeted therapies are being investigated with the hope that a more individualized treatment regimen translates into better outcomes. Immunotherapy has long been touted as a potential approach to cancer, stemming from the late 1800s when Coley (2) observed tumor reduction in patients with sarcoma after acute infection with Streptococcus pyogenes. The theory behind tumor vaccines is that the body’s immune system can be stimulated by a tumor-specific peptide sequence/antigen to activate or amplify a humoral and cytotoxic immune response targeted at the specific cancer cells a patient happens to harbor (Figure 1). Despite multiple attempts at developing personalized vaccines with promising results in animal studies (1), peptide and dendritic cell vaccinations have largely failed in human clinical trials. The reasons for these failures vary but include suboptimal antigen selection, inadequate immunogenic responses, and GBM-associated immune evasion (7). However, a new glimmer of hope at overcoming these obstacles can be found in a recent article in Nature by Schumacher et al. (11) from the Department of Neurooncology at the University Hospital Heidelberg and National Center for Tumor Disease in Heidelberg, Germany. They report the exciting results in their quest to develop a tumor vaccine using a peptide target that is intimately affiliated with glioma biology: isocitrate dehydrogenase (IDH1). IDH1 is 1 of 3 isozymes translated from 5 primary genes to form a homodimer involved in cellular metabolism. The protein is present in both the cytoplasm and the peroxisome. The most common and clinically relevant IDH1 gene mutation is a heterozygous missense mutation at codon 132 resulting in replacement of an arginine (R) with a histidine (H), connoted R132H. It is rarely found in primary GBMs and gliosarcomas but is found in diffuse World Health Organization grades II and III gliomas (and secondary GBMs)>70% of the time (3). On a molecular/epigenetic level, IDH1 mutation appears to be tumorigenic, displaying a hypermethylated CpG island methylator phenotype (CIMP) (9) that represses critical tumor suppressor translation (5, 14). Despite this finding, patients with the IDH1 mutation demonstrate a clear overall survival benefit with an increased sensitivity to both chemotherapy (8) and radiation (6). One explanation for this paradoxical finding is that IDH1 mutation

Computational hemodynamic simulations of cerebral aneurysms have traditionally relied on stereotypical boundary conditions (such as blood flow velocity and blood pressure) derived from published values as patient-specific measurements are unavailable or difficult to collect. However, controversy persists over the necessity of incorporating such patient-specific conditions into computational analyses. We perform simulations using both endovascularly-derived patient-specific and typical literature-derived inflow and outflow boundary conditions. Detailed three-dimensional anatomical models of the cerebral vasculature are developed from rotational angiography data, and blood flow velocity and pressure are measured in situ by a dual-sensor pressure and velocity endovascular guidewire at multiple peri-aneurysmal locations in 10 unruptured cerebral aneurysms. These measurements are used to define inflow and outflow boundary conditions for computational hemodynamic models of the aneurysms. The additional in situ measurements which are not prescribed in the simulation are then used to assess the accuracy of the simulated flow velocity and pressure drop. Simulated velocities using patient-specific boundary conditions show good agreement with the guidewire measurements at measurement locations inside the domain, with no bias in the agreement and a random scatter of ≈25%. Simulated velocities using the simplified, literature-derived values show a systematic bias and over-predicted velocity by ≈30% with a random scatter of ≈40%. Computational hemodynamics using endovascularly measured patient-specific boundary conditions have the potential to improve treatment predictions as they provide more accurate and precise results of the aneurysmal hemodynamics than those based on commonly accepted reference values for boundary conditions.

OBJECTIVE The authors' aim was to report the largest study on predictors of infection after cranioplasty and to assess the predictive value of intraoperative bone flap cultures before cryopreservation. METHODS They retrospectively examined all cranioplasties performed between March 2004 and November 2014. Throughout this study period, the standard protocol during initial craniectomy was to obtain a culture swab of the extracted autologous bone flap (ABF)—prior to its placement in cytostorage—to screen for microbial contamination. Two consecutive protocols were employed for the use and interpretation of the intraoperative swab culture results: A) From March 2004 through June 2013, any culture-positive ABF (+ABF) was discarded and a custom synthetic prosthesis was implanted at the time of cranioplasty. B) From July 2013 through November 2014, any ABF with a skin flora organism was not discarded. Instead, cryopreservation was maintained and the +ABF was reimplanted after a 10-minute soak in bacitracin irrigation as well as a 3-minute soak in betadine. RESULTS Over the 10.75-year period, 754 cranioplasty procedures were performed. The median time from craniectomy to cranioplasty was 123 days. Median follow-up after cranioplasty was 237 days for protocol A and 225 days for protocol B. The overall infection rate after cranioplasty was 6.6% (50 cases) occurring at a median postoperative Day 31. Staphylococcus spp. were involved as the causative organisms in 60% of cases. Culture swabs taken at the time of initial craniectomy were available for 640 ABFs as 114 ABFs were not salvageable. One hundred twenty-six (20%) were culture positive. Eighty-nine +ABFs occurred during protocol A and were discarded in favor of a synthetic prosthesis at the time of cranioplasty, whereas 37 +ABFs occurred under protocol B and were reimplanted at the time of cranioplasty. Cranioplasty material did not affect the postcranioplasty infection rate. There was no significant difference in the infection rate among sterile ABFs (7%), +ABFs (8%), and synthetic prostheses (5.5%; p = 0.425). All 3 +ABF infections under protocol B were caused by organisms that differed from those in the original intraoperative bone culture from the initial craniectomy. A cranioplasty procedure ≤ 14 days after initial craniectomy was the only significant predictor of postcranioplasty infection (p = 0.007, HR 3.62). CONCLUSIONS Cranioplasty procedures should be performed at least 14 days after initial craniectomy to minimize infection risk. Obtaining intraoperative bone cultures at the time of craniectomy in the absence of clinical infection should be discontinued as the culture results were not a useful predictor of postcranioplasty infection and led to the unnecessary use of synthetic prostheses and increased health care costs.

Background Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, with a median survival of 13 months despite surgery and chemoradiation. GBMs are often hypervascular tumors caused by abnormal oversecretion of growth factors such as vascular endothelial growth factor. These angiogenic factors are hypothesized to promote increased blood flow and possibly secondary changes to arterial walls, thus facilitating the formation of flow-related aneurysms. Case Description A 59-year-old woman presented with headaches, confusion, nausea and emesis. Computed tomography and magnetic resonance imaging revealed a hypervascular lesion, likely high-grade glioma, in the right frontal lobe, with a dilated vessel within the tumor. Cerebral angiography demonstrated a flow-related aneurysm on the right frontopolar artery supplying the tumor. The aneurysm was embolized with coils and the patient later underwent craniotomy for near total resection of the lesion without complications. Final pathology returned GBM with dilated vessels noted. Conclusions Hypervascular lesions, such as GBMs, may be associated with flow-related aneurysms on feeding arteries, but aneurysms within the gross tumor are unusual. Although rare, this finding needs to be recognized on preoperative imaging before tumor resection to prevent potentially catastrophic intraoperative complications.

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive lung disease in which fibroblasts accumulate in the alveolar wall within a type I collagen–rich matrix. Although lung fibroblasts derived from patients with IPF display durable pathological alterations in proliferative function, the molecular mechanisms differentiating IPF fibroblasts from their normal counterparts remain unknown. Polymerized type I collagen normally inhibits fibroblast proliferation, providing a physiological mechanism to limit fibroproliferation after tissue injury. We demonstrate that β1 integrin interaction with polymerized collagen inhibits normal fibroblast proliferation by suppression of the phosphoinositide 3-kinase (PI3K)–Akt–S6K1 signal pathway due to maintenance of high phosphatase activity of the tumor suppressor phosphatase and tensin homologue (PTEN). In contrast, IPF fibroblasts eluded this restraint, displaying a pathological pattern of β1 integrin signaling in response to polymerized collagen that leads to aberrant activation of the PI3K–Akt–S6K1 signal pathway caused by inappropriately low PTEN activity. Mice deficient in PTEN showed a prolonged fibroproliferative response after tissue injury, and immunohistochemical analysis of IPF lung tissue demonstrates activation of Akt in cells within fibrotic foci. These results provide direct evidence for defective negative regulation of the proliferative pathway in IPF fibroblasts and support the theory that the pathogenesis of IPF involves an intrinsic fibroblast defect.

This study presents validation of endovascular Doppler velocimetry-based volumetric flow rate measurements conducted in a pulsatile flow loop simulating conditions in both the internal carotid and basilar artery. In vitro models of cerebral vessels, each containing an aneurysm, were fabricated from patient anatomies extracted from 3D rotational angiography. Flow velocity measurements were collected with three different experimental techniques: an endovascular Doppler wire, Particle Image Velocimetry, and a time-resolved ultrasonic flow meter. Womersley's theory of pulsatile flow in a cylindrical vessel was used to compute time-resolved volumetric flow rates from the endovascular Doppler velocity. The volumetric flow rates computed from the Doppler measurements were compared to those from the Particle Image Velocimetry profile measurements, and the direct measurements from the ultrasonic flow meter. The study establishes confidence intervals for any systematic or random errors associated with the wire-derived flow rates as benchmarked to the other two modalities. There is an approximately 10% random error in the Doppler-derived peak and time-averaged flow rates. There is a measurable uniform bias, about 15% too low, in the time-averaged Doppler-derived flow rates. There is also a small proportional bias in the peak systolic Doppler-derived flow rates. Potential sources of error are also discussed.

Carotid cavernous fistulae (CCF) are dangerous entities that may cause progressive cranial neuropathy, headache and blindness. Endovascular therapy for CCF is the treatment of choice and can be accomplished with minimal morbidity, but optimal treatment strategies vary according to CCF anatomy. We aimed to define a tailored endovascular treatment algorithm for CCF with a focus on traditional and aberrant venous anatomy. Retrospective cohort analysis of data for 57 patients (age range, 18–90 years, mean 53 years) with CCF (35 direct, 22 indirect) was performed. Treatment was transarterial (n = 31), transvenous (n = 18), combined (n = 2), or observation (n = 6). Non-conventional transvenous access (that is, via the facial vein, pterygoid plexus, or via direct puncture of the inferior ophthalmic or frontal vein) was employed in five patients. Mean follow-up period was 12 months. Radiographic cure rate in treated CCF was 96%. Forty-five patients presented with ophthalmic symptoms (chemosis, proptosis, eye pain); all resolved within 6 weeks of successful treatment. Forty-three patients presented with cranial nerve III, IV and/or VI palsy; complete recovery was seen in 54% and partial recovery in 18%. Five patients presented with blindness and five with declining visual acuity. No patient with blindness regained sight after treatment, but all five patients with declining vision recovered some visual acuity. The complication rate was 10.6% (one transient abducens nerve palsy, two symptomatic cerebral infarctions, and three groin hematomas). The permanent complication rate was 3.5%. Multimodal treatment of CCF, including non-traditional routes of transvenous access, results in excellent outcomes and low morbidity.

A 71-year-old woman presented with headache and dilated vessels on CTA. Angiography demonstrated a complex dural arteriovenous fistula with retrograde cortical venous hypertension, supplied by branches of internal and external carotids bilaterally into a fistulous pouch paralleling the left transverse and sigmoid sinuses, which was occluded at the jugular bulb. The patient refused treatment and was lost to follow-up, returning with sudden confusion and hemianopsia from left temporo-occipital hemorrhage. Transvenous endovascular embolization was performed using the dual-microcatheter technique with a combination of coiling and Onyx copolymer, completely occluding the sinus and fistula while preserving normal venous drainage.The video can be found here: http://youtu.be/u_4Oc7tSmDM.

BACKGROUND AND PURPOSE: Computational fluid dynamics modeling is useful in the study of the hemodynamic environment of cerebral aneurysms, but patient-specific measurements of boundary conditions, such as blood flow velocity and pressure, have not been previously applied to the study of flow-diverting stents. We integrated patient-specific intravascular blood flow velocity and pressure measurements into computational models of aneurysms before and after treatment with flow-diverting stents to determine stent effects on aneurysm hemodynamics. MATERIALS AND METHODS: Blood flow velocity and pressure were measured in peri-aneurysmal locations by use of an intravascular dual-sensor pressure and Doppler velocity guidewire before and after flow-diverting stent treatment of 4 unruptured cerebral aneurysms. These measurements defined inflow and outflow boundary conditions for computational models. Intra-aneurysmal flow rates, wall shear stress, and wall shear stress gradient were calculated. RESULTS: Measurements of inflow velocity and outflow pressure were successful in all 4 patients. Computational models incorporating these measurements demonstrated significant reductions in intra-aneurysmal wall shear stress and wall shear stress gradient and a trend in reduced intra-aneurysmal blood flow. CONCLUSIONS: Integration of intravascular dual-sensor guidewire measurements of blood flow velocity and blood pressure provided patient-specific computational models of cerebral aneurysms. Aneurysm treatment with flow-diverting stents reduces blood flow and hemodynamic shear stress in the aneurysm dome.