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Intraoperative flow measurement has proven utility in extracranial-intracranial bypass, particularly in assessing the adequacy of donors by measurement of cut flow. The nature of intracranial-intracranial (IC-IC) bypass precludes cut flow measurement, but quantitative intraoperative flow measurements may evaluate augment assessment of the bypass.To retrospectively evaluate flow measurements performed in IC-IC bypass to determine the adequacy of the constructs in preserving flow.With institutional review board approval, we performed a retrospective review of our bypass database from 2001 to 2021 for aneurysms treated with IC-IC bypass and with intraoperative flow measurements. Patients' preoperative characteristics, bypass indications, prebypass and postbypass intraoperative flow measurements, and patient outcomes were recorded.Of 346 bypasses, 21 cases using 22 IC-IC bypasses were included. The median age was 55 years; 13 of 21 cases were ruptured aneurysms. Aneurysms involved posterior inferior cerebellar artery (n = 7), middle cerebral artery (n = 6), distal anterior cerebral artery (n = 5), and anterior communicating artery (n = 3). Six bypasses were end-to-side (ETS), 10 were side-to-side (STS), and 6 were excisional with reanastomosis (end-to-end, ETE). Intraoperatively, 21 of the bypasses were patent; the postbypass/prebypass flow index averaged 1.15 (±0.32): ETE (n = 6) 1.22 ± 0.34 and ETS/STS bypasses (n = 15) 1.11 ± 0.32. All intraoperatively patent bypasses were patent on postoperative angiography. One occluded on delayed angiography without clinical sequelae.Despite advances in endovascular therapy, IC-IC bypass remains essential to the treatment of large and fusiform aneurysms. We demonstrate quantitatively that IC-IC donors provide adequate direct (ETE) and redistributed (STS ETS) flow to the recipient territory. Flow measurement provides valuable information regarding the patency and adequacy of IC-IC bypass for flow preservation.

Purpose Flow diverting stents have revolutionized the treatment of intracranial aneurysms through endoluminal reconstruction of the parent vessel. Despite this, certain aneurysms require retreatment. The purpose of this study was to identify clinical and radiologic determinants of aneurysm retreatment following flow diversion. Methods A multicenter flow diversion database was evaluated to identify patients presenting with an unruptured, previously untreated aneurysm with a minimum of 12 months’ clinical and angiographic follow-up. Univariate and multivariate logistic regression modeling was performed to identify determinants of retreatment. Results We identified 189 aneurysms treated in 189 patients with a single flow-diverting stent. Mean age was 54 years, and 89% were female. Complete occlusion was achieved in 70.3% and 83.6% of patients at six and 12 months, respectively. Aneurysm retreatment with additional flow-diverting stents occurred in 5.8% of cases. Univariate analysis revealed that dome diameter [Formula: see text]10 mm ( p = 0.012), pre-clinoid internal carotid artery location ( p = 0.012), distal > proximal parent vessel diameter ( p = 0.042), and later dual antiplatelet therapy (DAPT) discontinuation ( p Conclusions Prolonged DAPT is the most important determinant of aneurysm retreatment following single-device flow diversion. Abbreviating DAPT duration to only six months should be a consideration in this population, especially for patients with a large aneurysm dome diameter.

BackgroundBleb presence in intracranial aneurysms (IAs) is a known indication of instability and vulnerability.ObjectiveTo develop and evaluate predictive models of bleb development in IAs based on hemodynamics, geometry, anatomical location, and patient population.MethodsCross-sectional data (one time point) of 2395 IAs were used for training bleb formation models using machine learning (random forest, support vector machine, logistic regression, k-nearest neighbor, and bagging). Aneurysm hemodynamics and geometry were characterized using image-based computational fluid dynamics. A separate dataset with 266 aneurysms was used for model evaluation. Model performance was quantified by the area under the receiving operating characteristic curve (AUC), true positive rate (TPR), false positive rate (FPR), precision, and balanced accuracy.ResultsThe final model retained 18 variables, including hemodynamic, geometrical, location, multiplicity, and morphology parameters, and patient population. Generally, strong and concentrated inflow jets, high speed, complex and unstable flow patterns, and concentrated, oscillatory, and heterogeneous wall shear stress patterns together with larger, more elongated, and more distorted shapes were associated with bleb formation. The best performance on the validation set was achieved by the random forest model (AUC=0.82, TPR=91%, FPR=36%, misclassification error=27%).ConclusionsBased on the premise that aneurysm characteristics prior to bleb formation resemble those derived from vascular reconstructions with their blebs virtually removed, machine learning models can identify aneurysms prone to bleb development with good accuracy. Pending further validation with longitudinal data, these models may prove valuable for assessing the propensity of IAs to progress to vulnerable states and potentially rupturing.

Background Transradial access for neurointerventional procedures was adopted and modified from cardiovascular intervention and is increasingly established as a safe and effective alternative to transfemoral catheterization. As social media influences public opinion on medical treatment, this study analyzes Twitter conversations to elucidate social media’s depiction of transradial access as a neurointerventional tool. Materials and methods Twitter hashtags #RadialFirst and #RadialForNeuro were evaluated using a mixed-method analysis of quantitative social media metrics and qualitative thematic analysis. Results Between January 2015 and April 2020, 104,146 tweets from 141 countries employed the hashtag #RadialFirst (2015 (1); 2016 (0); 2017 (22,804); 2018 (33,074); 2019 (38,352); 2020 (9,915 January-April)). These generated 226,909,374 impressions and were retweeted 80,120 times by 13,707 users. Media was present in 62.5% of tweets (e.g. wrist image, angiographic runs) but only 14.5% had a reference article. Physicians authored 70.8% of tweets; interventional cardiologists accounted for 83% of top 100 influencers. #RadialForNeuro is more nascent (6 posts in 2019; 323 posts January–April 2020), with 392,662 impressions, and 254 retweets by 177 users; physicians authored 35.6%. Compared to #RadialFirst, #RadialforNeuro tweets were more likely to include media (76%), less likely to include citations (9.7%), and more likely to discuss complications and troubleshooting techniques. Conclusion Twitter activity regarding transradial access permits information dissemination and discussion on approach benefits and challenges. However, many posts arise from non-physician sources and lack links to peer-reviewed publication. The public should be mindful that tweets may reflect opinions, rather than experience or scientific evidence.

Background Following non-traumatic subarachnoid hemorrhage (SAH), in-hospital delayed cerebral ischemia is predicted by two chief events on continuous EEG (cEEG): new or worsening epileptiform abnormalities (EAs) and deterioration of cEEG background frequencies. We evaluated the association between longitudinal outcomes and these cEEG biomarkers. We additionally evaluated the association between longitudinal outcomes and other in-hospital complications. Methods Patients with nontraumatic SAH undergoing ≥ 3 days of cEEG monitoring were enrolled in a prospective study evaluating longitudinal outcomes. Modified Rankin Scale (mRS) was assessed at discharge, and at 3- and 6-month follow-up time points. Adjusting for baseline severity in a cumulative proportional odds model, we modeled the mRS ordinally and measured the association between mRS and two forms of in-hospital cEEG deterioration: (1) cEEG evidence of new or worsening epileptiform abnormalities and (2) cEEG evidence of new background deterioration. We compared the magnitude of these associations at each time point with the association between mRS and other in-hospital complications: (1) delayed cerebral ischemia (DCI), (2) hospital-acquired infections (HAI), and (3) hydrocephalus. In a secondary analysis, we employed a linear mixed effects model to examine the association of mRS over time (dichotomized as 0–3 vs. 4–6) with both biomarkers of cEEG deterioration and with other in-hospital complications. Results In total, 175 mRS assessments were performed in 59 patients. New or worsening EAs developed in 23 (39%) patients, and new background deterioration developed in 24 (41%). Among cEEG biomarkers, new or worsening EAs were independently associated with mRS at discharge, 3, and 6 months, respectively (adjusted cumulative proportional odds 4.99, 95% CI 1.60–15.6; 3.28, 95% CI 1.14–9.5; and 2.71, 95% CI 0.95–7.76), but cEEG background deterioration lacked an association. Among hospital complications, DCI was associated with discharge, 3-, and 6-month outcomes (adjusted cumulative proportional odds 4.75, 95% CI 1.64–13.8; 3.4; 95% CI 1.24–9.01; and 2.45, 95% CI 0.94–6.6), but HAI and hydrocephalus lacked an association. The mixed effects model demonstrated that these associations were sustained over longitudinal assessments without an interaction with time. Conclusion Although new or worsening EAs and cEEG background deterioration have both been shown to predict DCI, only new or worsening EAs are associated with a sustained impairment in functional outcome. This novel finding raises the potential for identifying therapeutic targets that may also influence outcomes. Electronic supplementary material The online version of this article (10.1007/s12028-020-01177-x) contains supplementary material, which is available to authorized users.

Background Subcortical mapping of the corticospinal tract has been extensively used during craniotomies under general anesthesia to achieve maximal resection while avoiding postoperative motor deficits. To our knowledge, similar methods to map the thalamocortical tract (TCT) have not yet been developed. Objective To describe a neurophysiologic technique for TCT identification in 2 patients who underwent resection of frontoparietal lesions. Methods The central sulcus (CS) was identified using the somatosensory evoked potentials (SSEP) phase reversal technique. Furthermore, monitoring of the cortical postcentral N20 and precentral P22 potentials was performed during resection. Subcortical electrical stimulation in the resection cavity was done using the multipulse train (case #1) and Penfield (case #2) techniques. Results Subcortical stimulation within the postcentral gyrus (case #1) and in depth of the CS (case #2), resulted in a sudden drop in amplitudes in N20 (case #1) and P22 (case #2), respectively. In both patients, the potentials promptly recovered once the stimulation was stopped. These results led to redirection of the surgical plane with avoidance of damage of thalamocortical input to the primary somatosensory (case #1) and motor regions (case #2). At the end of the resection, there were no significant changes in the median SSEP. Both patients had no new long-term postoperative sensory or motor deficit. Conclusion This method allows identification of TCT in craniotomies under general anesthesia. Such input is essential not only for preservation of sensory function but also for feedback modulation of motor activity.

BackgroundFlow diversion is a common endovascular treatment for cerebral aneurysms, but studies comparing different types of flow diverters are scarce.ObjectiveTo perform a propensity score matched cohort study comparing the Pipeline Embolization Device (PED) and Flow Redirection Intraluminal Device (FRED) for posterior circulation aneurysms.MethodsConsecutive aneurysms of the posterior circulation treated at 25 neurovascular centers with either PED or FRED were collected. Propensity score matching was used to control for age, duration of follow-up imaging, adjunctive coiling, and aneurysm location, size, and morphology; previously ruptured aneurysms were excluded. The two devices were compared for the following outcomes: procedural complications, aneurysm occlusion, and functional outcome.ResultsA total of 375 aneurysms of the posterior circulation were treated in 369 patients. The PED was used in 285 (77.2%) and FRED in 84 (22.8%) procedures. Aneurysms treated with the PED were more commonly fusiform and larger than those treated with FRED. To account for these important differences, propensity score matching was performed resulting in 33 PED and FRED unruptured aneurysm pairs. No differences were found in occlusion status and neurologic thromboembolic or hemorrhagic complications between the two devices. The proportion of patients with favorable functional outcome was higher with FRED (100% vs 87.9%, p=0.04).ConclusionComparative analysis of PED and FRED for the treatment of unruptured posterior circulation aneurysms did not identify significant differences in aneurysm occlusion or neurologic complications. Variations in functional outcomes warrant additional investigations.

IntroductionWe describe our initial experience with the React 68 catheter (Medtronic, Dublin, Ireland), an FDA-approved catheter designed for aspiration in cases of emergent large vessel occlusion, as compared with the ACE 68 catheter (Penumbra, Alameda, CA).MethodsThis observational study followed consecutive patients treated with the React catheter over a seven-month period at a comprehensive stroke center. Use of the device was per discretion of the operator. Patient demographics, thrombectomy technique, reperfusion scoring, and disposition were assessed. Performance was compared with patients treated with the ACE 68 catheter over a comparable period.ResultsWe treated 47 patients using the React 68 catheter using either aspiration alone or a combination of aspiration and stent retriever technique. The catheter was used in a variety of circumstances including proximal and distal occlusions involving the anterior and posterior circulation. Modified TICI 2b-3 was achieved in 45 of the 47 patients. The React 68 was comparable to the ACE 68 by all performance measures.ConclusionThe React 68 catheter is a large-bore reperfusion catheter with trackability suitable for use in direct aspiration for recanalization of emergent large vessel occlusion.

Background Rathke cleft cysts (RCCs) are sellar-based cystic lesions that are often found incidentally but occasionally become symptomatic with significant visual and/or endocrine deficits. The standard of treatment is surgery, but rare cases of multiply recurrent RCCs can be refractory to surgical drainage, leading to significant morbidity. Objective To demonstrate the safety and feasibility of fractionated stereotactic radiotherapy (SRT) as salvage therapy in multiply recurrent RCCs refractory to surgical drainage. Methods An IRB-approved retrospective review at a single institution was conducted to identify and describe patients with multiply recurrent RCCs refractory to surgical drainage who underwent SRT. Results From 1994 to 2015, 6 patients (5 female) who underwent SRT for recurrent RCCs were identified. A total of 4 presented with visual deficits, and 2 presented with endocrine dysfunction and severe headaches prior to their initial drainage. All patients had initial postoperative improvement but then developed multiple, symptomatic recurrences. Median number of surgical drainage procedures prior to radiotherapy was 3. A total of 3 patients underwent LINAC-based SRT, and 3 had proton-based SRT. Treatment doses were 45 Gy over 25 fractions (n = 5) and 50.4 Gy over 28 fractions (n = 1). Median follow-up after radiation therapy was 69 mo (range 24-154 mo). In the follow-up period, stabilization of the RCC was achieved, although 2 patients required additional drainage procedures. Only 1 patient developed new hypothyroidism and hypoadrenalism after SRT. Conclusion In rare cases of multiply recurrent RCCs refractory to repeat surgical drainage, stereotactic fractionated radiation therapy is a safe and effective salvage therapy.

Flow diversion is a safe and effective treatment for many types of brain aneurysms. Even so, there remain some aneurysms that persist despite initial treatment. In studies with the longest follow-up (5 yr), at least 5% of aneurysms persist with this treatment modality. As the cumulative experience and clinical indications for flow diversion continue to expand, the anatomic and functional characteristics that are associated with aneurysm persistence are increasingly described. Identification of these factors preoperatively can help to guide initial treatment decisions, enhance monitoring protocols in the follow-up period, and establish best practices for re-treatment when necessary. Herein, we review published clinical series and provide examples to highlight variables implicated in aneurysm persistence after treatment with flow diversion.

Background and Purpose: Dural arteriovenous fistulae can present with hemorrhage, but there remains a paucity of data regarding subsequent outcomes. We sought to use the CONDOR (Consortium for Dural Arteriovenous Fistula Outcomes Research), a multi-institutional registry, to characterize the morbidity and mortality of dural arteriovenous fistula–related hemorrhage. Methods: A retrospective review of patients in CONDOR who presented with dural arteriovenous fistula–related hemorrhage was performed. Patient characteristics, clinical follow-up, and radiographic details were analyzed for associations with poor outcome (defined as modified Rankin Scale score ≥3). Results: The CONDOR dataset yielded 262 patients with incident hemorrhage, with median follow-up of 1.4 years. Poor outcome was observed in 17.0% (95% CI, 12.3%–21.7%) at follow-up, including a 3.6% (95% CI, 1.3%–6.0%) mortality. Age and anticoagulant use were associated with poor outcome on multivariable analysis (odds ratio, 1.04, odds ratio, 5.1 respectively). Subtype of hemorrhage and venous shunting pattern of the lesion did not affect outcome significantly. Conclusions: Within the CONDOR registry, dural arteriovenous fistula–related hemorrhage was associated with a relatively lower morbidity and mortality than published outcomes from other arterialized cerebrovascular lesions but still at clinically consequential rates.

A 70-year-old gentleman with history of hypothyroidism, hyperlipidemia, hypertension, and right superior cerebellar aneurysm presented to the neurosurgery service in 2008 with vertigo. Diagnostic cerebral angiography performed that year demonstrated a vermian arteriovenous malformations (AVM). The patient underwent stereotactic proton beam radiosurgery, which resulted in a decrease in flow and size of the lesion, and the patient was lost to follow-up. Now at the age of 80, the patient presented with acute gait instability. Cerebral angiogram demonstrated his stable vermian AVM and a new 1.1 cm AVM nidus in the region of the left posterior thalamus. Although AVMs are often described as congenital lesions, there is a growing body of literature suggesting that AVMs can grow, spontaneously regress, and even arise de novo in response to some insult. Understanding what leads to the growth, remodeling, regression, and hemorrhage of AVMs is crucial in order to better direct therapeutic endeavors. We would argue that this patient's AVM is secondary to endothelial cell damage from radiation therapy. Radiation can cause endothelial cell injury and upregulation of factors, such as vascular endothelial growth factor and transforming growth factor beta expression, which are implicated in AVM development pathways. We believe that this patient's new AVM is secondary to entrance radiation dosing affecting the thalamus during radiation therapy for the original vermian AVM.

BACKGROUND: Recurrent atypical and malignant meningiomas have poor outcomes with surgical therapy alone. Neither adjuvant chemotherapy nor postoperative radiation therapy remedies this problem. OBJECTIVE: To evaluate our experience with the treatment of 15 patients treated with I-125 or Cs-131 brachytherapy radiation seeds as an adjuvant in these difficult cases. METHODS: Patients with high-grade recurrent meningioma who underwent resection and intraoperative placement of brachytherapy seeds at our institution from 2002 to 2014 were identified and studied by retrospective chart review. RESULTS: Fifteen patients with median age of 68.8 yr were treated with I-125 (n = 13) or Cs-131 (n = 2) brachytherapy seeds for cases of recurrent, grade II (n = 8), or grade III (n = 7) meningioma at our institution from 2002 to 2014. These lesions originated from a variety of locations including, convexity (3), falcine (3), frontal (2), occipital (1), parietal (2), 2 sphenoid wing (2), and temporal (2), based recurrent meningiomas. Patients had a median of 2 prior open surgical interventions and received local radiation therapy with a median dose of 55 Gy prior to brachytherapy. Survival at 2.5 yr was 56% for grade II and 17% for grade III lesions. Survival was significantly associated with patient age but not tumoral pathology. Forty percent of patients required reoperations for wound complications following brachytherapy. CONCLUSION: Brachytherapy with implantation of permanent radiation seeds provides a viable alternative treatment for recurrent meningioma while carrying a significant clinical risk of wound infection and need for reoperation.

In this study, we derived and validated a composite EBI risk score. In addition to confirming the importance of EBI in determining long-term SAH recovery, the risk score could be used for patient selection or risk stratification in future clinical trials. The score was derived and validated in 2 independent cohorts, highlighting its ability to perform across separate patient populations. Future studies should focus on validating the application of EBI in clinical settings, examining other biomarkers in addition to sST2, and deepening our understanding of the pathophysiologic factors that lead to EBI and impact patient outcomes.

Background The Penumbra SMART coil is a novel device that becomes progressively softer from its distal to proximal end to maximize coil packing and prevent microcatheter prolapse or coil migration. Here, we report a large series of patients detailing the long-term experience of a single institution using the SMART coil among patients with intracranial aneurysms (IAs). Methods Prospective data of 105 consecutive patients with 106 IAs treated using SMART coils was collected between March 2015 and July 2018. Clinical and angiographic data were analyzed. Results Forty-nine patients (46.7%) presented with subarachnoid hemorrhage and 16 (14.2%) had recurrent aneurysms. Two patients had minor intraprocedural ruptures and remained neurologically stable. One patient had a thromboembolic complication with progressive neurologic decline. There was only one case microcatheter prolapse related to placement of a stent before coiling. An initial post-treatment modified Raymond-Roy Occlusion Classification (mRROC) I or II closure was achieved in 56 (52.8%) aneurysms. The average time to last follow-up was 8.4 months at which 70 (81.4%) aneurysms had mRROC I or II occlusion and a major recurrence was seen in 5 (5.8%) patients. Thirteen (12.3%) aneurysms required re-treatment of which one aneurysm was clipped. Conclusions The Penumbra SMART coil is safe and effective for the endovascular treatment of appropriately selected IAs. Additional studies at multiple centers comparing safety and efficacy profile over long-term periods to other mainstream coils are necessary.

The genetics of intracranial aneurysms is complex. Much work has been done looking at the extracellular matrix surrounding cerebral vasculature as well as the role of matrix metalloproteinases. This comprehensive review summarizes what is known to date about the important genetic components that predispose to aneurysm formation and critically discusses the published findings. We discuss promising pre-clinical models of aneurysm formation and subarachnoid hemorrhage, and highlight avenues for future discovery, while considering limitations in the research to date. This review will further serve as a comprehensive reference guide to understand the genetic underpinnings for aneurysm pathophysiology and act as a primer for further investigation.

BACKGROUND: The Pipeline Embolization Device (PED; Medtronic) has been used off-label for the treatment of challenging posterior circulation aneurysms. Data on this modality are primarily limited to small retrospective single-center series. OBJECTIVE: To assess safety and efficacy of this treatment by establishing an international, multicenter collaboration. METHODS: Consecutive posterior circulation aneurysms treated with the PED from 2012 to 2019 across 11 neurovascular centers were retrospectively reviewed. Baseline demographics, aneurysm and treatment characteristics, complications, occlusion status, and functional outcome were assessed. RESULTS: There were 149 posterior circulation aneurysms treated with PED in 146 patients. A total of 24 (16.4) patients presented with subarachnoid hemorrhage. Most aneurysms were dissecting/blister (36.2) in morphology, followed by saccular (35.6) and fusiform (28.2). The most common locations were the vertebral (51.7) and basilar arteries (22.8). Complete or near-complete occlusion (>90) was achieved in 90.9 of aneurysms at a median follow-up of 12 mo. Dissecting/blister aneurysms were most likely to occlude (P =.06). Symptomatic neurologic complications occurred in 9.4 of aneurysms, associated with larger size, ruptured presentation, presentations with brain stem compression, cranial nerve palsy, or stroke. Favorable functional outcome (modified Rankin Score 0-2) was achieved in 86.2 of patients. There were 6 fatalities of which 4 occurred in aneurysmal subarachnoid hemorrhage patients. CONCLUSION: This multicenter study shows that PED for the treatment of posterior circulation is preferentially used for the treatment of fusiform and dissecting/blister aneurysm morphologies. Despite the challenges presented by these less-common morphologies, flow diversion may be performed with a neurologic complication rate of about 10 and favorable long-term aneurysm occlusion rates. © 2020 by the Congress of Neurological Surgeons

BACKGROUND Older age has been associated with worse outcomes in low-grade gliomas (LGGs). Given their rarity in the older population, determining optimal treatment plans and patient outcomes remains difficult. OBJECTIVE To retrospectively study LGG survival outcomes in an older population stratified by molecular genetic profiles. METHODS We included patients age ≥40 yr with pathologically confirmed World Health Organization grade II gliomas treated at a single institution between 1995 and 2015. We collected tumor genomic information when available. RESULTS Median overall survival for the entire group (n = 111, median age 51 yr, range 40-77 yr) was 15.75 yr with 5- and 10-yr survival rates of 84.3% and 67.7%, respectively. On univariate analysis, patients with isocitrate dehydrogenase (IDH) mutation had significantly increased survival compared to IDH wildtype (hazard ratio [HR] 0.17 [0.07-0.45], P

IntroductionThe LVIS Blue is an FDA-approved stent with 28% metallic coverage that is indicated for use in conjunction with coil embolization for the treatment of intracranial aneurysms. Given a porosity similar to approved flow diverters and higher than currently available intracranial stents, we sought to evaluate the effectiveness of this device for the treatment of intracranial aneurysms.MethodsWe performed an observational single-center study to evaluate initial occlusion and occlusion at 6-month follow-up for patients treated with the LVIS Blue in conjunction with coil embolization at our institution using the modified Raymond–Roy classification (mRRC), where mRRC 1 indicates complete embolization, mRRC 2 persistent opacification of the aneurysm neck, mRRC 3a filling of the aneurysm dome within coil interstices, and mRRC 3b filling of the aneurysm dome.ResultsSixteen aneurysms were treated with the LVIS Blue device in conjunction with coil embolization with 6-month angiographic follow-up. Aneurysms were treated throughout the intracranial circulation: five proximal internal carotid artery (ICA) (ophthalmic or communicating segments), two superior cerebellar artery, two ICA terminus, two anterior communicating artery, two distal middle cerebral artery, one posterior inferior cerebellar artery, and two basilar tip aneurysms. Post-procedurally, there was one mRRC 1 closure, five mRRC 2 closures, and 10 mRRC 3a or 3b occlusion. At follow-up, all the mRRC 1 and mRRC 3a closures, 85% of the mRRC 3b closures and 75% of the mRRC 2 closures were stable or improved to an mRRC 1 or 2 at follow-up.ConclusionsThe LVIS Blue represents a safe option as a coil adjunct for endovascular embolization within both the proximal and distal anterior and posterior circulation.

Background Aneurysmal subarachnoid hemorrhage (aSAH) is associated with a high mortality and poor neurologic outcomes. The biologic underpinnings of the morbidity and mortality associated with aSAH remain poorly understood. Objective To ascertain potential insights into pathological mechanisms of injury after aSAH using an approach of metabolomics coupled with machine learning methods. Methods Using cerebrospinal fluid (CSF) samples from 81 aSAH enrolled in a retrospective cohort biorepository, samples collected during the peak of delayed cerebral ischemia were analyzed using liquid chromatography-tandem mass spectrometry. A total of 138 metabolites were measured and quantified in each sample. Data were analyzed using elastic net (EN) machine learning and orthogonal partial least squares-discriminant analysis (OPLS-DA) to identify the leading CSF metabolites associated with poor outcome, as determined by the modified Rankin Scale (mRS) at discharge and at 90 d. Repeated measures analysis determined the effect size for each metabolite on poor outcome. Results EN machine learning and OPLS-DA analysis identified 8 and 10 metabolites, respectively, that predicted poor mRS (mRS 3-6) at discharge and at 90 d. Of these candidates, symmetric dimethylarginine (SDMA), dimethylguanidine valeric acid (DMGV), and ornithine were consistent markers, with an association with poor mRS at discharge (P = .0005, .002, and .0001, respectively) and at 90 d (P = .0036, .0001, and .004, respectively). SDMA also demonstrated a significantly elevated CSF concentration compared with nonaneurysmal subarachnoid hemorrhage controls (P = .0087). Conclusion SDMA, DMGV, and ornithine are vasoactive molecules linked to the nitric oxide pathway that predicts poor outcome after severe aSAH. Further study of dimethylarginine metabolites in brain injury after aSAH is warranted.

OBJECTIVE: To investigate whether soluble growth stimulation expressed gene 2 (sST2), a prognostic marker in cardiovascular and inflammatory disorders, is associated with neurological injury after aneurysmal subarachnoid hemorrhage (SAH).METHODS: We studied SAH patients from 2 independent cohorts. Outcome assessments included functional status at 90 days using the modified Rankin Scale (mRS), mortality, and delayed cerebral ischemia (DCI). The relationships between sST2 plasma level and outcome measures were assessed in both cross-sectional and longitudinal analysis. Primary blood mononuclear cells from SAH patients and elective aneurysm controls were analyzed by multiparameter flow cytometry.RESULTS: In the discovery cohort, sST2 predicted 90-day mRS 3-6 (C index = 0.724, p INTERPRETATION: Plasma sST2 predicts DCI, functional outcome, and mortality after SAH, independent of clinical and radiographic markers. Elevated sST2 is also associated with changes in CD14+ CD16+ monocytes. ANN NEUROL 2019;86:384-394.

OBJECTIVES: Endovascular thrombectomy (EVT) has revolutionized stroke care for large vessel occlusions (LVOs). However, over half treated remain functionally disabled or die. Patients with tandem lesions, or severe stenosis/occlusion of the cervical internal carotid artery (ICA) with intracranial LVO, may have technical EVT challenges and worse outcomes. We sought to compare treatments and outcomes for patients with anterior circulation tandem lesions versus isolated LVOs. MATERIALS AND METHODS: Consecutive tandem lesion and isolated LVO patients were identified at a single center. Demographics, medical history, presentations, treatments, and outcomes were collected and analyzed. RESULTS: From 381 EVT patients, 62 had tandem lesions related to atherosclerosis (74%) or dissection (26%). Compared to isolated intracranial LVOs, they were younger (63 vs 70, p=0.003), less atrial fibrillation (13% vs 40%, p

Cerebral arteriovenous malformations (AVM) are traditionally considered primary congenital lesions that result from embryological aberrations in vasculogenesis. Recent insights, however, suggest that these lesions may be secondary to a vascular insult such as ischemia or trauma. Herein, the authors present a rare case of a secondary cerebral AVM, occurring in a young girl who received prior cranial radiation therapy. At age 3years, she underwent surgical resection, chemotherapy, and photon radiation therapy for treatment of a fourth ventricular ependymoma. At age 19years, she developed new onset seizures and was found to have a left medial temporal lobe AVM. Her seizures were managed successfully with anti-epileptic medications and the AVM was treated with proton radiation therapy. This case highlights a rare but possible vascular sequela of radiation therapy and adds to the growing body of evidence that cerebral AVM may arise as secondary lesions.

Tumor-to-tumor metastasis is an uncommon phenomenon, and a metastasis from an extracranial donor tumor to an intracranial recipient tumor is extremely rare. In particular, there are only 14 cases reported in the literature that describe a tumor-to-tumor metastasis involving a glioma. We present a rare case of an 83-year-old man with an 11-year history of lentigo maligna melanoma who presented with impaired balance and cognitive slowing and was found to have rapid progression of a previously known indolent right frontal brain mass. Pathologic examination of the tumor after resection revealed the presence of both malignant melanoma and an oligodendroglioma WHO grade II. To the best of our knowledge, this is the first reported case of malignant melanoma metastasizing to an oligodendroglioma that has been confirmed by immunohistochemistry and genetic analysis.

Background While technological advances have improved the efficacy of endovascular techniques for tentorial dural arteriovenous fistulae (DAVF), superior petrosal sinus (SPS) DAVF with dominant internal carotid artery (ICA) supply frequently require surgical intervention to achieve a definitive cure. Methods To compare the angiographic and clinical outcomes of endovascular and surgical interventions in patients with SPS DAVF, the records of all patients with tentorial DAVF from August 2010 to November 2015 were reviewed. Results Within this cohort, eight patients with nine SPS DAVF were eligible for evaluation. Five DAVF were initially treated with endovascular embolization, while four underwent surgical occlusion without embolization. Of the SPS DAVF treated with embolization, two (40%) remained occluded on follow-up, while the remaining three (60%) persisted/recurred and required surgical intervention for definitive closure. Of the four SPS DAVF treated with primary surgical occlusion, all four (100%) remained closed on follow-up. In addition, of the three SPS DAVF that persisted/recurred following embolization and required subsequent surgical closure, all three (100%) remained occluded on follow-up. Two (100%) SPS DAVF that were successfully treated with embolization had major or minor external carotid artery supply, while the three (100%) persistent lesions had major ICA supply via the meningohypophyseal trunk (MHT). Three (75%) of the four SPS DAVF treated with primary surgical occlusion had dominant MHT supply. Conclusion Complete endovascular closure of SPS DAVF with dominant ICA supply via the MHT may be difficult to achieve, while upfront surgical intervention is associated with a high rate of complete occlusion.

Background and purposeBRANCH (wide-neck bifurcation aneurysms of the middle cerebral artery and basilar apex treated by endovascular techniques) is a multicentre, retrospective study comparing core lab evaluation of angiographic outcomes with self-reported outcomes.Materials and methodsConsecutive patients were enrolled from 10 US centres, aged between 18 and 85 with unruptured wide-neck middle cerebral artery (MCA) or basilar apex aneurysms treated endovascularly. Patient demographics, aneurysm morphology, procedural information, mortality and morbidity data and core lab and self-reported modified Raymond Roy (RR) outcomes were obtained.Results115 patients met inclusion criteria. Intervention-related mortality and significant morbidity rates were 1.7% (2/115) and 5.8% (6/103) respectively. Core lab adjudicated RR1 and 2 occlusion rates at follow-up were 30.6% and 32.4% respectively. The retreatment rate within the follow-up window was 10/115 (8.7%) and in stent stenosis at follow-up was 5/63 (7.9%). Self-reporting shows a statistically significant direction to angiographic RR one outcomes at follow-up compared with core lab evaluation, with OR 1.75 (95% CI 1.08 to 2.83).ConclusionEndovascular treatment of wide-neck MCA and basilar apex aneurysms resulted in a core lab adjudicated RR1 occlusion rate of 30.6%. Self-reported results at follow-up favour better angiographic outcomes, with OR 1.75 (95% CI 1.08 to 2.83). These data demonstrate the need for novel endovascular devices specifically designed to treat complex intracranial aneurysms, as well as the importance of core lab adjudication in assessing outcomes in such a trial.

Background Traditionally, lumbar discectomy has involved overnight hospital admission. Recent literature supports the shift to same-day lumbar discectomy because of improved outcomes and better patient satisfaction scores. A successful protocol for outpatient lumbar discectomies was proposed and implemented at a single institution. The aim of this study is to perform a quantitative and qualitative analysis of this institutional model. Methods Retrospective clinical data were collected for patients who underwent a lumbar discectomy during the period 2008–2012. Admission and readmission rates, emergency department (ED) visit rates, surgical complications, and differences between neurosurgeons specializing in spinal procedures and neurosurgeons not specializing in spinal procedures were analyzed before and after implementation of the outpatient surgery protocol. Results Of 1011 cases identified, 643 cases of lumbar discectomy were performed before the implementation of the protocol, and 368 cases were performed after implementation. The admission rate before the start date of the outpatient protocol was 96.4% versus 50.3% after implementation. After protocol implementation, the most common reasons for admission were uncontrolled pain (18.9%), late operative start times (14.1%), comorbidities (13%), and intraoperative operating room complications (11.9%). Intraoperative complications consisted almost exclusively of dural tears. The 30-day readmission rate after protocol initiation was 4.6% ( n = 17 of 368) versus 2.3% ( n = 15 of 643) before initiation ( P = 0.046), and ED visit rate not requiring an admission was 2.2% ( n = 8 of 368) versus 1.1% ( n = 7 of 643) before initiation ( P = 0.170). Conclusions Our data demonstrate that a collaborative protocol for outpatient discectomy can be implemented in a safe and effective manner despite a statistical increase in hospital readmissions. The percentage rates of readmissions and ED visits accounted for a very small percentage of the overall number of cases after protocol implementation. Improvements in perioperative pain management and ensuring that outpatient lumbar discectomies are scheduled early in the day may further decrease the number of admissions. Future studies should examine the societal and financial impact of same-day discectomy versus overnight hospital stays.

Endoscopic third ventriculostomy (ETV) is a common treatment for noncommunicating hydrocephalus. Although rare, vascular injury and traumatic pseudoaneurysm development during ETV have been reported. The authors present the case of a 13-year-old boy who underwent repeat ETV (rETV) for shunt and ETV failure, and who suffered an intraoperative subarachnoid hemorrhage due to iatrogenic injury to the basilar tip, with subsequent development of a pseudoaneurysm. Despite initial primary coil embolization, the aneurysm recurred and was definitively treated with flow diversion. In this report, the authors review complication rates associated with ETV and rETV as well as the emerging use of flow diversion and its applications in vessel reconstruction within the pediatric population.

OBJECTIVE Vascular malformations of the spine represent rare clinical entities with profound neurological implications. Previously reported studies on management strategies for spinal dural arteriovenous fistulas (sDAVFs) appeared before the advent of modern liquid embolic agents. Authors of the present study review their institutional experience with endovascularly and surgically treated sDAVFs. METHODS The authors performed a retrospective, observational, single-center case series on sDAVFs treated with endovascular embolization, microsurgical occlusion, or both between 2004 and 2013. The mode, efficacy, and clinical effect of treatment were evaluated. RESULTS Forty-seven patients with spinal arteriovenous malformations were evaluated using spinal angiography, which demonstrated 34 Type I sDAVFs (thoracic 20, lumbar 12, and cervical 2). Twenty-nine of the patients (85%) were male, and the median patient age was 63.3 years. Twenty patients underwent primary endovascular embolization (16 Onyx, 4 N-butyl cyanoacrylate [NBCA]), and 14 underwent primary surgical clipping. At a mean follow-up of 36 weeks, according to angiography or MR angiography, 5 patients treated with endovascular embolization demonstrated persistent arteriovenous shunting, whereas none of the surgically treated patients showed lesion persistence (p = 0.0237). Thirty patients (88%) experienced some resolution of their presenting symptoms (embolization 17 [85%], surgery 13 [93%], p = 1.00). CONCLUSIONS Microsurgical occlusion remains the most definitive treatment modality for sDAVFs, though modern endovascular techniques remain a viable option for the initial treatment of anatomically amenable lesions. Treatment of these lesions usually results in some clinical improvement.

Flow diversion is a novel treatment for brain aneurysms that works by redirecting blood flow away from the aneurysm. Immediately after placement of the stent, blood flow stagnates within the aneurysm dome and it undergoes thrombosis. Over time, a new endothelium develops across the neck, thereby reconstructing the parent vessel and curing the aneurysm. The use of this treatment method for ruptured aneurysms has two specific concerns: 1) risk of hemorrhage from the aneurysm after treatment because of potential delayed aneurysm occlusion; and 2) hemorrhagic complications from antiplatelet use, which is required to prevent thromboembolic complications from the device. In this review, we explore these two concerns based on the emerging published literature. Optimal peri-procedural management of these issues in the neurocritical care setting is vital to improving outcomes. We also identify ongoing clinical trials of flow diversion for the treatment of ruptured aneurysms. Flow diversion is an alternative to clipping or coiling for many ruptured aneurysms and may be potentially more efficacious in certain aneurysm subtypes.

Objectives Ischemic stroke due to large-vessel occlusion (LVO) is a complication after cardiothoracic surgery (CTS). Recently published endovascular stroke trials have major implications for treating LVO strokes; we evaluated our experience in patients undergoing CTS. Methods Our prospective institutional CTS database was reviewed between July 2013 and April 2018 for ischemic strokes. Patients with LVO were identified and their course and outcomes analyzed. Results A total of 5947 patients were reviewed; 148 (2.48%) had a cerebrovascular complication; 92.5% were ischemic. Of these 10.9% had an LVO. Prolonged aortic crossclamp was associated with LVO (odds ratio, 1.012 for every minute of prolonged aortic crossclamp time; confidence interval, 1.001-1.023) and remained significant in patients with ejection fraction >45%; prolonged cardiac bypass time was only associated with LVO in patients with ejection fraction >45% (odds ratio, 1.012 for every minute of prolonged cardiac bypass time; confidence interval, 1.003-1.021). Patients fell into 2 categories: detection of neurologic deficit in the stable postoperative patient or detection of deficit on emergence from anesthesia. Seven patients met criteria for emergent revascularization, with median National Institutes of Health Stroke Scale score 15, and shorter times from last seen well to deficit detection compared with patients not meeting criteria (P = .032). Median National Institutes of Health Stroke Scale day 7 score improved to 5. There was a trend toward better modified Rankin Scale scores at 3 months in patients who underwent thrombectomy. Conclusions LVO complicates a small proportion of patients after CTS and may be more likely with prolonged aortic crossclamp and cardiac bypass times. Both early and late window endovascular stroke treatment has the potential to positively modify the complication profile of CTS. Greater awareness of this treatment option is needed.

Progression of anaplastic glioma (World Health Organization [WHO] grade III) is typically determined radiographically, and transformation to glioblastoma (GB) (WHO grade IV) is often presumed at that time. However, the frequency of actual histopathologic transformation of anaplastic glioma and the subsequent clinical impact is unclear. To determine these associations, we retrospectively reviewed all anaplastic glioma patients who underwent surgery at our center at first radiographic progression, and we examined the effects of histological diagnosis, clinical history, and molecular factors on transformation rate and survival. We identified 85 anaplastic glioma (39 astrocytoma, 24 oligodendroglioma, 22 oligoastrocytoma), of which 38.8% transformed to GB. Transformation was associated with shorter overall survival (OS) from the time of diagnosis (3.4 vs. 10.9 years, p = 0.0005) and second surgery (1.0 vs. 3.5 years, p < 0.0001). Original histologic subtype did not significantly impact the risk of transformation or OS. No other factors, including surgery, adjuvant therapy or molecular markers, significantly affected the risk of transformation. However, mutations in isocitrate dehydrogenase 1 (IDH1) was associated with longer time to progression (median 4.6 vs. 1.4 years, p = 0.008) and OS (median 10.0 vs. 4.2 years, p = 0.046). At radiographic progression, tissue diagnosis may be warranted as histologic grade may provide valuable prognostic information and affect therapeutic clinical trial selection criteria for this patient population.

BackgroundArterial bifurcations are common locations for aneurysm development given the altered hemodynamic forces and shear stress variations present at these locations. Recent reports indicate that a wide basilar artery bifurcation angle is an independent predictor of aneurysm development, growth, and subsequent rupture.MethodsTo determine the effect of basilar artery bifurcation angle on rates of initial occlusion, recanalization, and retreatment of basilar artery apex aneurysms following coil embolization, the records of 46 patients with basilar artery apex aneurysms treated with endovascular coil embolization from 2007 to 2013 were analyzed.ResultsA wide basilar artery bifurcation angle was associated with a Raymond–Roy Occlusion Classification (RROC) III occlusion in univariate analysis, but was not a statistically significant factor in multivariate modeling. An increasing basilar artery bifurcation angle was not associated with aneurysm recanalization or retreatment following coil embolization. Increasing packing density ( p ConclusionBasilar artery bifurcation angle fails to predict rates of initial occlusion, recanalization, and retreatment on multivariate modeling in our series. Basilar artery apex aneurysm neck size independently correlates with basilar artery bifurcation angle.

A 1-year, single-center, randomized trial demonstrated that the calcineurin inhibitor or adjuvant immunosuppression, independently, does not affect BK-viruria or viremia and that monitoring and pre-emptive withdrawal of immunosuppression was associated with resolution of BK-viremia and absence of clinical BK-nephropathy without acute rejection or graft loss. A retrospective 5-year review of this trial was conducted. In cases of BK viremia, the antimetabolite was withdrawn and for sustained viremia, the calcineurin inhibitor was minimized. Five-year follow-up was available on 97% of patients. Overall 5-year patient survival was 91% and graft survival was 84%. There were no differences in patient-survival by immunosuppressive regimen or presence of BK-viremia. Immunosuppression and viremia did not influence graft survival. Acute rejection occurred in 12% by 5-years after transplant, was less common with tacrolimus versus cyclosporine (9% vs. 18%; p = 0.082), and was lowest with the tacrolimus-azathioprine regimen (5%, p = 0.127). Tacrolimus was associated with better renal function at 5-years (eGFR 63 FK vs. 52 CsA mL/min, p = 0.001). Minimization of immunosuppression upon detection of BK-viremia was associated with excellent graft survival at 5-years, low rejection rates and excellent renal function. It is a safe, short and long-term strategy that resulted in freedom from clinically evident BK-virus nephropathy.

Diffuse peritubular capillary C4d deposition in renal allograft biopsies is associated with donor-specific antibodies (DSA) and graft failure. The significance of focal C4d+ is unclear. We reviewed 368 biopsies from 301 patients performed for renal dysfunction or proteinuria over 5 years. Diffuse C4d+, focal C4d+ and C4d- detected by immunofluorescence occurred in 9.5%, 20.9% and 69.4% of biopsies, respectively. Patients were similar in gender, age, cause of renal disease, donor source, HLA mismatch, serum creatinine at baseline and interval from transplantation to biopsy. Diffuse and focal C4d+ were associated with acute cellular rejection (p < 0.001). Transplant glomerulopathy was associated with diffuse C4d+. DSA at the time of biopsy, were positive in 79.3% of diffusely C4d+ patients, 68.8% of those with focal C4d+ (p = 0.27) and 9.9% of patients with C4d- (p < 0.001, compared to either the focal or diffuse groups, respectively). Allograft survival at 40 months was lower in diffuse C4d+ compared to the C4d- group (p = 0.014), but not when compared to the focal C4d+ group. There was a clear trend toward worse graft survival in patients with focal C4d+ in this time interval, but focal C4d+ compared to both diffuse C4d+ and C4d-groups was not statistically significant (p = 0.08).

Neurosurgeons encounter a number of pigmented tumors of the central nervous system in a variety of locations, including primary central nervous system melanoma, blue nevus of the spinal cord, and melanotic schwannoma. When examined through the lens of embryology, pigmented lesions share a unifying connection: They occur in structures that are neural crest cell derivatives. Here, we review the important progress made in the embryology of neural crest cells, present 3 cases of pigmented tumors of the nervous system, and discuss these clinical entities in the context of the development of melanoblasts. Pigmented lesions of the nervous system arise along neural crest cell migration routes and from neural crest-derived precursors. Awareness of the evolutionary clues of vertebrate pigmentation by the neurosurgical and neuro-oncological community at large is valuable for identifying pathogenic or therapeutic targets and for designing future research on nervous system pigmented lesions. When encountering such a lesion, clinicians should be aware of the embryological basis to direct additional evaluation, including genetic testing, and to work with the scientific community in better understanding these lesions and their relationship to neural crest developmental biology.

Prophylaxis reduces cytomegalovirus (CMV) disease, but is associated with increased costs and risks for side effects, viral resistance and late onset CMV disease. Preemptive therapy avoids drug costs but requires frequent monitoring and may not prevent complications of asymptomatic CMV replication. Kidney transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to prophylaxis (valganciclovir 900 mg q.d. for 100 days, n=49) or preemptive therapy (900 mg b.i.d. for 21 days, n=49) for CMV DNAemia (CMV DNA level>2000 copies/mL in >or=1 whole blood specimens by quantitative PCR) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. More patients in the preemptive group, 29 (59%) than in the prophylaxis group, 14 (29%) developed CMV DNAemia, p=0.004. Late onset of CMV DNAemia (>100 days after transplant) occurred in 11 (24%) randomized to prophylaxis, and none randomized to preemptive therapy. Symptomatic infection occurred in five patients, four (3 D+/R- and 1 D+/R+) in the prophylactic group and one (D+/R-) in the preemptive group. Peak CMV levels were highest in the D+/R- patients. Both strategies were effective in preventing symptomatic CMV. Overall costs were similar and insensitive to wide fluctuations in costs of either monitoring or drug.

BACKGROUND The relative benefit versus safety of induction therapy in live-donor renal transplant recipients is controversial. This paper presents observational data of live-donor recipients who received Thymoglobulin induction and standard maintenance immunosuppressive therapy. METHODS Review and analysis of clinic records and electronic databases of live-donor renal transplants that received Thymoglobulin induction from May 1996 through 2003. RESULTS Data analysis included 214 live-donor recipients (146 related, 68 unrelated) with a mean follow-up of 3.0+/-1.9 years. The average age of recipients was 44+/-13 years, with a majority being Caucasian (86%) and male (64%). Nineteen (9%) received previous transplants. No patients experienced delayed graft function and 10 (5%) developed acute rejection. Overall, predicted five-year patient survival was 96% and graft survival was 82%. The rates of CMV infection (5%), malignancy (3%), and lymphoproliferative disorder (0.5%) were low. When compared to live-donor kidney transplant recipients nationwide, the center cohort demonstrated improved five year patient (96% center versus 90% national, P=0.0326) and graft survival (82% center versus 79% national, P=0.0901), and a lower one-year acute rejection rate (2% center versus 21 % national, P

Background Nonaneurysmal subarachnoid hemorrhage (SAH) has been historically associated with a benign clinical course. However, recent studies have suggested that nonaneurysmal SAH can present with different hemorrhage patterns that may be associated with differential rates of morbidity. Herein, we analyze a retrospective consecutive cohort of patients with nonaneurysmal SAH to determine outcomes. We also seek to evaluate a validated radiographic grading scale to determine its utility in predicting vasospasm in the setting of different hemorrhage patterns. Methods After institutional review board approval, the records of 563 consecutive patients admitted with spontaneous SAH between January 2007 and 2014 were retrospectively reviewed. A total of 138 of these patients had no identifiable source of hemorrhage and were further divided into 2 groups depending on their pattern of hemorrhage: perimesencephalic or diffuse. Clinical characteristics and outcomes were assessed. Results In nonaneurysmal SAH, 70 patients (50.7%) had a perimesencephalic pattern of hemorrhage, whereas 68 (49.3%) experienced diffuse SAH. Radiographic vasospasm developed in 6 patients (8.6%) with perimesencephalic SAH and in 14 patients (20.6%) with a diffuse SAH pattern. When comparing historical rates of vasospasm based on the Barrow Neurological Institute (BNI) scale and rates in the nonaneurysmal diffuse pattern in this series, there was no significant difference in distribution (chi-square; P = .149), compared with a difference seen with the perimesencephalic group ( P Conclusions Nonaneurysmal SAH is associated with the potential for vasospasm, with higher rates in the diffuse versus perimesencephalic SAH patterns. The BNI grading scale for aneurysmal SAH can be used to predict the risk of vasospasm in diffuse, nonaneurysmal SAH.

Chordomas and chondrosarcomas are rare skull base tumors, with similar radiographic and clinical presentations. We investigated factors influencing long-term survival in these 2 tumors using the Surveillance Epidemiology and End Results (SEER) database.Patients with chordoma (n = 416) and chondrosarcoma (n = 269) within the skull base from 1983 to 2009 were identified within the SEER database. Kaplan-Meier curves and Cox proportional hazards models were used to test associations with survival. t tests and χ(2) tests were used to compare groups.Chordoma and chondrosarcoma patients were similar demographically. Survival at 5 years was 65% for chordomas and 81.8% (P0.0001) for chondrosarcomas and at 10 years was 32.3% and 49.5% (P = 0.004). Multivariate analysis demonstrated chordomas had a worse prognosis even when we controlled for age and tumor size (hazard ratio 3.0, 95% confidence interval 1.9-4.7, P0.0001). For chordomas, multivariate analysis demonstrated increasing age and tumor size were significantly associated with reduced survival. For chondrosarcomas, multivariate analysis demonstrated older age, earlier decade of diagnosis, and mesenchymal subtype were significantly associated with reduced survival. Postoperative radiation was given to 42% and 41% of patients with chordomas and chondrosarcomas, respectively. The addition of radiation did not improve survival.Consistent with previous case series, skull base chordomas have significantly worse prognosis than chondrosarcomas. Patients in the SEER database had worse survival overall compared with existing case series for both chordomas and chondrosarcomas, suggesting selection bias in the existing literature.

Posterior sternoclavicular fracture displacement can present as a posterior sternoclavicular joint dislocation and is rare in the pediatric population. This article provides an algorithm for evaluation and management. A 14-year-old boy with a previously undiagnosed posterior sternoclavicular displacement presented with persistent 7/10 shoulder pain extending into his neck after undergoing nonoperative treatment for an unconfirmed diagnosis at another emergency department. Plain radiographs revealed a displacement of the right medial clavicle, and the position of the clavicular head indicated advanced imaging. Computed tomography showed the posterior portion of the clavicular head butting against the left braciocephalic vein at its confluence with the superior vena cava. The patient underwent open reduction and internal fixation. After exposing the sternoclavicular joint, a Salter-Harris I fracture with no evidence of vascular injury was confirmed. The fracture was reduced and stabilized using figure-eight #5 Ethibond sutures (Ethicon, Somerville, New Jersey), and the patient was placed in an immobilizer for 1 week. At 1 year postoperatively, the patient regained full range of motion and was completely healed. Posterior clavicle displacements are potentially devastating injuries that are difficult to diagnose. Coordinating operative treatment with orthopedic and general surgery is indicated to manage the fracture or displacement and potential vascular injury. Due to difficulties in maintaining a closed reduction, open reduction and internal fixation is the preferred mode of treatment for the reduction of all posterior clavicular fracture displacements.

Serum sickness after rabbit antithymocyte globulin administration has a reported incidence of 7% to 27% in kidney transplant recipients. We describe 4 patients with previous exposure to rabbits who developed serum sickness after primary rabbit antithymocyte globulin induction. All patients presented with jaw pain. Three of 4 patients treated with plasmapheresis and steroids had prompt recovery, and 1 patient treated with steroids had slower recovery. We performed a telephone interview of 214 patients who contemporaneously underwent transplantation between November 2006 and July 2008 regarding rabbit exposure. More than half the patients had some type of previous rabbit exposure. There was a suggestion that patients with serum sickness were exposed more frequently to rabbits than those without. Jaw pain appears to be a hallmark symptom, and treatment with plasmapheresis and steroids relieves symptoms more rapidly than steroids alone.

Routine success in kidney transplantation has significantly improved the quality and length of life for the majority of recipients and made this option the treatment of choice for suitable candidates. Improved patient survival combined with a relative static improvement in long-term graft outcomes has led to an increasing number of transplant recipients with failed allografts who face the eventual option of either returning to dialysis or seeking retransplantation. Although retransplantation is presumed to be a favorable option for many, data to support this belief is limited. Given the wide variance in predicted outcomes for retransplantation, on the basis of the underlying kidney disease and other individual patient comorbidities as well as the expected wait time for a second transplant, each case should be evaluated independently. This review discusses available data and individual considerations that should be taken into account when retransplantation is proposed after failure of a primary allograft.

Background: Changes in serum parathyroid hormone (PTH) within minutes are known only to be mediated by changes in ionized calcium. Recent animal studies show ingestion of a low phosphorus meal can lower serum PTH within 15 min, before changes in serum ionized calcium or phosphorus occur, suggesting a rapid gastrointestinal signal may regulate PTH. Methods: Eight hemodialysis patients with secondary hyperparathyroidism were admitted twice to a metabolic unit and ate a high and low phosphorus meal after an overnight fast. Serum PTH, total and ionized calcium, phosphorus, pH, and glucose were measured at 0, 15, 30, 60, 120 and 240 min. In the second protocol, we examined the possible role of volume or glucose changes in rapid PTH suppression by administering intravenous saline and glucose after an overnight fast to 6 patients, with similar testing. Results: Intact PTH decreased 24% from 419 ± 331 at baseline to 312 ± 221 pg/ml (p = 0.002) 15 min after a meal. Total and ionized calcium and pH did not change, glucose rose by 15 min, and phosphorus changed only after 60–90 min. During the second protocol, saline and glucose infusions failed to change PTH. Conclusions: In dialysis patients, a glucose-containing meal, with or without phosphorus, rapidly suppresses serum PTH ∼25% within 15 min. This effect is not mediated by changes in ionized calcium, phosphorus, pH, glucose, or insulin. These data suggest there may be an as yet unknown enteral signal that rapidly suppresses PTH.

BACKGROUND Targeting 2-hr postdose cyclosporine (C2) levels to 1,000 to 1,700 mg/dL during the first 6 months after renal transplantation is recommended for triple immunosuppressive regimens. This trial determines whether lower C2 levels could be targeted safely in de novo kidney transplant recipients under a quadruple regimen compared with a similar cohort monitored with trough (C0) levels. METHODS This single-center, sequential, cohort-designed trial included patients who received Thymoglobulin, corticosteroids, an antimetabolite, and cyclosporine monitored by C2 (n=50) or C0 (n=50). Cyclosporine was tapered to maintain the C2 between 1,000 and 1,200 ng/mL months 0 to 3 and between 600 and 1,000 ng/mL thereafter and C0 between 250 and 350 ng/mL months 0 to 3 and between 100 and 250 ng/mL thereafter. RESULTS Baseline patient and donor characteristics were similar. There were no differences in graft survival (100% C2 vs. 100% C0), acute rejection (4% C2 vs. 6% C0), allograft function, or adverse events at 6 months. C2 levels were lower than the suggested guidelines throughout the study (33% lower at 1 month and 48% lower at 6 months). Lower cyclosporine doses were achieved in the C2 arm compared with the C0 arm by 1 month and were sustained throughout the trial, which translated into an average cyclosporine cost savings of USD $773 in the C2 arm during the 6-month period (P

The past decade has witnessed the introduction of several new immunosuppressive agents. The availability of these new pharmacologic offerings has not diminished the challenge of achieving a balance of adequate graft protection while minimizing the consequences of excessive immunosuppression. For renal transplant recipients, maintenance immunosuppression generally consists of a calcineurin inhibitor in combination with an antiproliferative agent and a corticosteroid; more recently, mammalian target of rapamycin inhibitors have been used. Excellent results have been achieved at many transplant centers with combinations of these agents in a variety of protocols. Regimens designed to limit or eliminate calcineurin inhibitor and/or corticosteroid therapy are actively being pursued in the transplant community. Allograft tolerance and xenotransplantation are being studied, and the knowledge gained from the effort may help in the development of innovative strategies and new immunosuppressive agents.

Background. One-year results of a randomized, double-blinded trial of Thymoglobulin versus Atgam for induction therapy in renal transplantation revealed that Thymoglobulin was associated with higher event-free survival (94% vs. 63%), less acute rejection (4% vs. 25%), and better graft survival. This article compares the safety and efficacy of Thymoglobulin versus Atgam induction through 5 years. Methods. Review and analysis of clinic records and electronic databases. Results. At 5 years, event-free survival (73% vs. 33%, P

Tacrolimus a macrolide immunosuppressant that is routinely given in two equally divided doses every 12 h. However, the time-dependent pharmacokinetics of tacrolimus suggest that once daily morning administration of tacrolimus may produce appropriate drug exposure. The purpose of this pilot study was to compare the pharmacokinetics and safety of twice vs. once daily administration of tacrolimus in stable kidney transplant recipients. Steady-state tacrolimus pharmacokinetic parameters were estimated on two occasions in an open-label, three-arm, two-period sequential study: twice daily dosing (Phase I) and once daily dosing (Phase II). In phase II, 18 patients were assigned to one of three arms: those taking 67%, 85% and 100% of their total twice daily dose once in the morning. In phase I, the mean area under the blood concentration-time curve (AUC) was higher after the morning dose, AUC(0-12) 117 +/- 40 vs. AUC(12-24) 97 +/- 30 ng/h/mL, p=0.012. In the 85% Group, the mean AUC ratio between twice and once daily was 1.0 (95% CI, 0.9-1.1) which predicted the best conversion ratio. Tacrolimus given once daily in the morning, at 85% of the twice daily dose, provides safe and equivalent drug exposure to twice daily dosing. This convenient dosing schedule may help to increase compliance and lower costs.