Low-Profile Visualized Intraluminal Support Junior Flow-Diversion Properties Used for Stabilization of a Superior Cerebellar Artery Pseudoaneurysm.

BACKGROUND: Pseudoaneurysms of the posterior circulation pose a unique management challenge. The fragile nature of the pseudoaneurysm wall presents a high risk of rupture and demands treatment. Small vasculature, particularly distal in the posterior circulation, can preclude management with traditional flow diverters, where the alternative of vessel sacrifice is unacceptable. Small stents can have flow-diversion properties and can be used in these high-risk, difficult-to-access aneurysms. METHODS: We describe a 40-year-old woman presenting with a ruptured dissecting right superior cerebellar artery pseudoaneurysm after minor trauma. Given the aneurysm's small size and morphology, it was not amenable to coiling and parent vessel sacrifice was potentially morbid. The pseudoaneurysm was initially stabilized with a Low-Profile Visualized Intraluminal Support Junior (LVIS Jr.) stent due to its reported flow-diverting properties. RESULTS: At six-month follow-up the pseudoaneurysm was stable and the vasospasm had resolved. At this point, definitive treatment with a "FRED Jr." (Flow Re-Direction Endoluminal Device Junior) flow diverter was pursued. Complete obliteration of the pseudoaneurysm was seen at 12 months' follow-up after staged treatment. CONCLUSIONS: Due to the unique challenges associated with ruptured pseudoaneurysms located on small-caliber vessels, the options for definitive treatment are limited. The small size of the LVIS Jr. stent and its flow-diverting properties make it a practical treatment option in a difficult situation. This case report provides further support for the flow-diverting properties of the LVIS Jr. and its potential application in the treatment of ruptured pseudoaneurysms in small-caliber intracranial vessels.

Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish.

Leptomeningeal disease occurs when cancer cells migrate into the ventricles of the brain and spinal cord and then colonize the meninges of the central nervous system. The triple-negative subtype of breast cancer often progresses toward leptomeningeal disease and has a poor prognosis because of limited treatment options. This is due, in part, to a lack of animal models with which to study leptomeningeal disease. Here, we developed a translucent zebrafish casper (roy-/-; nacre-/-) xenograft model of leptomeningeal disease in which fluorescent labeled MDA-MB-231 human triple-negative breast cancer cells are microinjected into the ventricles of zebrafish embryos and then tracked and measured using fluorescent microscopy and multimodal plate reader technology. We then used these techniques to measure tumor area, cell proliferation, and cell death in samples treated with the breast cancer drug doxorubicin and a vehicle control. We monitored MDA-MB-231 cell localization and tumor area, and showed that samples treated with doxorubicin exhibited decreased tumor area and proliferation and increased apoptosis compared to control samples.

Case report: Side-firing intraoperative ultrasound guided endoscopic endonasal resection of a clival chordoma.

Clival chordomas are locally invasive midline skull base tumors arising from remnants of the primitive notochord. Intracranial vasculature and cranial nerve involvement of tumors in the paraclival region necessitates image guidance that provides accurate real-time feedback during resection. Several intraoperative image guidance modalities have been introduced as adjuncts to endoscopic endonasal surgery, including stereotactic neuronavigation, intraoperative ultrasound, intraoperative MRI, and intraoperative CT. Gross total resection of chordomas is associated with a lower recurrence rate; therefore, intraoperative imaging may improve long-term outcomes by enhancing the extent of resection. However, among these options, effectiveness and accessibility vary between institutions. We previously published the first use of an end-firing probe in the resection of a clival chordoma. End-firing probes provide a single field of view, primarily limited to depth estimation. In this case report, we discuss the benefits of employing a novel minimally invasive side-firing ultrasound probe as a cost-effective and time-efficient option to navigate the anatomy of the paraclival region and guide endoscopic endonasal resection of a large complex clival chordoma.

Side-Firing Intraoperative Ultrasonograhy for Resection of Giant Pituitary Adenomas.

BACKGROUND: Suprasellar extension, cavernous sinus invasion, and involvement of intracranial vascular structures and cranial nerves are among the challenges faced by surgeons operating on giant pituitary macroadenomas. Intraoperative tissue shifts may render neuronavigation techniques inaccurate. Intraoperative magnetic resonance imaging can solve this problem, but it may be costly and time consuming. However, intraoperative ultrasonography (IOUS) allows for quick, real-time feedback and may be particularly useful when facing giant invasive adenomas. Here, we present the first study examining technique for IOUS-guided resection specifically focusing on giant pituitary adenomas. OBJECTIVE: To describe the use of a side-firing ultrasound probe in the resection of giant pituitary macroadenomas. METHODS: We describe an operative technique using a side-firing ultrasound probe (Fujifilm/Hitachi) to identify the diaphragma sellae, confirm optic chiasm decompression, identify vascular structures related to tumor invasion, and maximize extent of resection in giant pituitary macroadenomas. RESULTS: Side-firing IOUS allows for identification of the diaphragma sellae to help prevent intraoperative cerebrospinal fluid leak and maximize extent of resection. Side-firing IOUS also aids in confirmation of decompression of the optic chiasm via identification of a patent chiasmatic cistern. Furthermore, direct identification of the cavernous and supraclinoid internal carotid arteries and arterial branches is achieved when resecting tumors with significant parasellar and suprasellar extension. CONCLUSIONS: We describe an operative technique in which side-firing IOUS may assist in maximizing extent of resection and protecting vital structures during surgery for giant pituitary adenomas. Use of this technology may be particularly valuable in settings in which intraoperative magnetic resonance imaging is not available.

Side-firing intraoperative ultrasound applied to resection of pituitary macroadenomas and giant adenomas: A single-center retrospective case-control study.

Introduction: Multiple intraoperative navigation and imaging modalities are currently available as an adjunct to endoscopic transsphenoidal resection of pituitary adenomas, including intraoperative CT and MRI, fluorescence guidance, and neuronavigation. However, these imaging techniques have several limitations, including intraoperative tissue shift, lack of availability in some centers, and the increased cost and time associated with their use. The side-firing intraoperative ultrasound (IOUS) probe is a relatively new technology in endoscopic endonasal surgery that may help overcome these obstacles. Methods: A retrospective analysis was performed on patients admitted for resection of pituitary adenomas by a single surgeon at the University of Mississippi Medical Center. The control (non-ultrasound) group consisted of twelve (n=12) patients who received surgery without IOUS guidance, and the IOUS group was composed of fifteen (n=15) patients who underwent IOUS-guided surgery. Outcome measures used to assess the side-firing IOUS were the extent of tumor resection, postoperative complications, length of hospital stay (LOS) in days, operative time, and self-reported surgeon confidence in estimating the extent of resection intraoperatively. Results: Preoperative data analysis showed no significant differences in patient demographics or presenting symptoms between the two groups. Postoperative data revealed no significant difference in the rate of gross total resection between the groups (p = 0.716). Compared to the non-US group, surgeon confidence was significantly higher (p < 0.001), and operative time was significantly lower for the US group in univariate analysis (p = 0.011). Multivariate analysis accounting for tumor size, surgeon confidence, and operative time confirmed these findings. Interestingly, we noted a trend for a lower incidence of postoperative diabetes insipidus in the US group, although this did not quite reach our threshold for statistical significance. Conclusion: Incorporating IOUS as an aid for endonasal resection of pituitary adenomas provides real-time image guidance that increases surgeon confidence in intraoperative assessment of the extent of resection and decreases operative time without posing additional risk to the patient. Additionally, we identified a trend for reduced diabetes insipidus with IOUS.

External Validation and Modification of Nationwide Inpatient Sample Subarachnoid Hemorrhage Severity Score.

BACKGROUND: The Nationwide Inpatient Sample Subarachnoid Hemorrhage (SAH) Severity Score (NIS-SSS) was developed as a measure of SAH severity for use in administrative databases. The NIS-SSS consists of International Classification of Diseases Ninth Revision (ICD-9) diagnostic and procedure codes derived from the SAH inpatient course and has been validated against the Hunt-Hess score (HH). OBJECTIVE: To externally validate both the NIS-SSS and a modified version of the NIS-SSS (m-NIS-SSS) consisting of codes present only on admission, against the HH in a Canadian province-wide registry and administrative database of SAH patients. METHODS: A total of 1467 SAH patients admitted to Ontario stroke centers between 2003 and 2013 with recorded HH were included. The NIS-SSS and m-NIS-SSS were validated against the HH by testing correlation between the NIS-SSS/m-NIS-SSS and HH, comparing discriminative ability of the NIS-SSS/m-NIS-SSS vs HH for poor outcome by calculating area under the curve (AUC), and comparing calibration of the NIS-SSS, m-NIS-SSS, and HH by plotting predicted vs observed outcome. RESULTS: Correlation with HH was 0.417 (P ≤ .001) for NIS-SSS, and 0.403 (P ≤ .001) for m-NIS-SSS. AUC for prediction of poor outcome was 0.786 (0.764-0.808) for HH, 0.771 (0.748-0.793) for NIS-SSS, and 0.744 (0.721-0.767) for m-NIS-SSS. Calibration plots demonstrated that HH had the most accurate prediction of outcome, whereas the NIS-SSS and m-NIS-SSS did not accurately predict low risk of poor outcome. CONCLUSION: The NIS-SSS and m-NIS-SSS have good external validity, and therefore, may be suitable to approximate traditional clinical scores of disease severity in SAH research using administrative data.

The effect of prophylactic antiepileptic medications in aneurysmal subarachnoid hemorrhage patients: A retrospective review.

OBJECTIVE: The current literary evidence suggests but does not heavily endorse the use of prophylactic antiepileptic drugs (AEDs) after aneurysmal subarachnoid hemorrhage. Literature continues to emerge suggesting not only a lack of efficacy but associated poor outcomes. This study is a retrospective review comparing seizure incidence in aneurysmal subarachnoid patients between those given prophylactic AEDs and those not. METHODS: With IRB approval, a retrospective chart review was performed on all aneurysmal subarachnoid patients from 2012 to 2019 at the University of Mississippi Medical center. Univariate and Multivariate analysis was performed using SAS. Primary outcome was seizure incidence between groups. Factors associated with seizure and poor outcome were also investigated. RESULTS: 348 patients were identified: 120 in the AED group, and 228 patients in the non-AED group. There was no significant difference in mean age, gender, ethnicity, HH scores, treatment modality, or mean aneurysm size. The AED group had a higher history of prior aneurysmal rupture (6.7% vs. 1.3%, p = 0.01) and associated intracranial hemorrhage (22.5% vs. 10.5%, p = 0.0004). There was no significant difference in seizure incidence between the two groups (8.3% vs. 4.8%, p = 0.24). On multivariate analysis, aneurysm clipping compared to coiling (OR 3.8, p = 0.012) and delayed cerebral ischemia (OR 2.77, p = 0.023) were associated with seizures. DCI (OR 8.34), HH grade, Age (OR 1.07), Seizure (8.34), and AED use (1.7) were significantly associated with poor outcome. CONCLUSION: This retrospective review adds to the evidence that prophylactic AED use in aneurysmal subarachnoid hemorrhage patients has not been proven to improve seizure rates and may result in worse patient outcomes.

The impact of craniotomy for brain tumor case volume on patient safety indicators and in-hospital mortality.

OBJECTIVES: The relationship between outcomes, patient safety indicators and volume has been well established in patient's undergoing craniotomy for brain tumor. However, the determination of "high" and "low" volume centers have been subjectively derived. We present a paper with a novel method of objectively determining "high" volume centers for craniotomy for brain tumor. METHODS: Patients from 2002 to 2011 were identified in the Nationwide Inpatient Sample database using ICD-9 codes related to craniotomy for brain tumor. Primary endpoints of interest were hospital PSI event rate, in-hospital mortality rate, observed-to-expected PSI event ratio, and O/E in-hospital mortality ratio. Using a zero-inflated gamma model analysis and a cutpoint analysis we determined the volume threshold between and "high" and "low" volume hospitals. We then completed an analysis using this determined threshold to look at PSI events and mortality as they relate to "high" volume and "low" volume hospitals. RESULTS: 12.4 % of hospitals were categorized as good performers using O/E ratios. Regarding in-hospital mortality, 16.8 % were good performers. Using the above statistical analysis the threshold to define high vs. low volume centers was determined to be 27 craniotomies. High volume centers had significantly lower O/E ratios for both PSI and mortality events. The PSI O/E ratio was reduced 55 % and mortality O/E ratio reduced 73 % at high volume centers as defined by our analysis. CONCLUSIONS: Patients treated at institutions performing >27 craniotomies per year for brain tumors have a lower likelihood of PSI events and decreased in-hospital morbidity and mortality.

Screening duplex ultrasonography in neurosurgery patients does not correlate with a reduction in pulmonary embolism rate or decreased mortality.

OBJECTIVE: Deep vein thrombosis (DVT) is a major focus of patient safety indicators and a common cause of morbidity and mortality. Many practices have employed lower-extremity screening ultrasonography in addition to chemoprophylaxis and the use of sequential compression devices in an effort to reduce poor outcomes. However, the role of screening in directly decreasing pulmonary emboli (PEs) and mortality is unclear. At the University of Mississippi Medical Center, a policy change provided the opportunity to compare independent groups: patients treated under a prior paradigm of weekly screening ultrasonography versus a post-policy change group in which weekly surveillance was no longer performed. METHODS: A total of 2532 consecutive cases were reviewed, with a 4-month washout period around the time of the policy change. Criteria for inclusion were admission to the neurosurgical service or consultation for ≥ 72 hours and hospitalization for ≥ 72 hours. Patients with a known diagnosis of DVT on admission or previous inferior vena cava (IVC) filter placement were excluded. The primary outcome examined was the rate of PE diagnosis, with secondary outcomes of all-cause mortality at discharge, DVT diagnosis rate, and IVC filter placement rate. A p value < 0.05 was considered significant. RESULTS: A total of 485 patients met the criteria for the pre-policy change group and 504 for the post-policy change group. Data are presented as screening (pre-policy change) versus no screening (post-policy change). There was no difference in the PE rate (2% in both groups, p = 0.72) or all-cause mortality at discharge (7% vs 6%, p = 0.49). There were significant differences in the lower-extremity DVT rate (10% vs 3%, p < 0.01) or IVC filter rate (6% vs 2%, p < 0.01). CONCLUSIONS: Based on these data, screening Doppler ultrasound examinations, in conjunction with standard-of-practice techniques to prevent thromboembolism, do not appear to confer a benefit to patients. While the screening group had significantly higher rates of DVT diagnosis and IVC filter placement, the screening, additional diagnoses, and subsequent interventions did not appear to improve patient outcomes. Ultimately, this makes DVT screening difficult to justify.

Relationship between patient safety indicator events and comprehensive stroke center volume status in the treatment of unruptured cerebral aneurysms.

OBJECTIVE The Agency of Healthcare Research and Quality (AHRQ) has defined Patient Safety Indicators (PSIs) for assessments in quality of inpatient care. The hypothesis of this study is that, in the treatment of unruptured cerebral aneurysms (UCAs), PSI events are less likely to occur in hospitals meeting the volume thresholds defined by The Joint Commission for Comprehensive Stroke Center (CSC) certification. METHODS Using the 2002-2011 National (Nationwide) Inpatient Sample, patients treated electively for a nonruptured cerebral aneurysm were selected. Patients were evaluated for PSI events (e.g., pressure ulcers, retained surgical item, perioperative hemorrhage, pulmonary embolism, sepsis) defined by AHRQ-specified ICD-9 codes. Hospitals were categorized by treatment volume into CSC or non-CSC volume status based on The Joint Commission's annual volume thresholds of at least 20 patients with subarachnoid hemorrhage and performance of 15 or more endovascular coiling or surgical clipping procedures for aneurysms. RESULTS A total of 65,824 patients underwent treatment for an unruptured cerebral aneurysm. There were 4818 patients (7.3%) in whom at least 1 PSI event occurred. The overall inpatient mortality rate was 0.7%. In patients with a PSI event, this rate increased to 7% compared with 0.2% in patients without a PSI event (p < 0.0001). The overall rate of poor outcome was 3.8%. In patients with a PSI event, this rate increased to 23.3% compared with 2.3% in patients without a PSI event (p < 0.0001). There were significant differences in PSI event, poor outcome, and mortality rates between non-CSC and CSC volume-status hospitals (PSI event, 8.4% vs 7.2%; poor outcome, 5.1% vs 3.6%; and mortality, 1% vs 0.6%). In multivariate analysis, all patients treated at a non-CSC volume-status hospital were more likely to suffer a PSI event with an OR of 1.2 (1.1-1.3). In patients who underwent surgery, this relationship was more substantial, with an OR of 1.4 (1.2-1.6). The relationship was not significant in the endovascularly treated patients. CONCLUSIONS In the treatment of unruptured cerebral aneurysms, PSI events occur relatively frequently and are associated with significant increases in morbidity and mortality. In patients treated at institutions achieving the volume thresholds for CSC certification, the likelihood of having a PSI event, and therefore the likelihood of poor outcome and mortality, was significantly decreased. These improvements are being driven by the improved outcomes in surgical patients, whereas outcomes and mortality in patients treated endovascularly were not sensitive to the CSC volume status of the hospital and showed no significant relationship with treatment volumes.

Thrombolysis is an Independent Risk Factor for Poor Outcome After Carotid Revascularization.

BACKGROUND: Thrombolysis is the standard of care for acute ischemic stroke patients presenting in the appropriate time window. Studies suggest that the risk of recurrent ischemia is lower if carotid revascularization is performed early after the index event. The safety of early carotid revascularization in this patient population is unclear. OBJECTIVE: To evaluate the safety of carotid revascularization in patients who received thrombolysis for acute ischemic stroke. METHODS: The Nationwide Inpatient Sample database was queried for patients admitted through the emergency room with a primary diagnosis of carotid stenosis and/or occlusion. Each patient was reviewed for administration of thrombolysis, carotid endarterectomy, (CEA) or carotid angioplasty and stenting (CAS). Primary endpoints were intracerebral hemorrhage (ICH), postprocedural stroke (PPS), poor outcome, and in-hospital mortality. Potential risk factors were examined using univariate and multivariate analyses. RESULTS: A total of 310 257 patients were analyzed. Patients who received tissue plasminogen activator (tPA) and underwent either CEA or CAS had a significantly higher risk of developing an ICH or PPS than patients who underwent either CEA or CAS without tPA administration. The increased risk of ICH or PPS in tPA-treated patients who underwent carotid revascularization diminished with time, and became similar to patients who underwent carotid revascularization without tPA administration by 7 d after thrombolysis. Patients who received tPA and underwent CEA or CAS also had higher odds of poor outcome and in-hospital mortality. CONCLUSION: Thrombolysis is a strong risk factor for ICH, PPS, poor outcome, and in-hospital mortality in patients with carotid stenosis/occlusion who undergo carotid revascularization. The increased risk of ICH or PPS due to tPA declines with time after thrombolysis. Delaying carotid revascularization in these patients may therefore be appropriate. This delay, however, will expose these patients to the risk of recurrent stroke. Future studies are needed to determine the relative risks of these 2 adverse events.

Platelet testing in flow diversion: a review of the evidence.

OBJECTIVE Although the use of dual antiplatelet therapy with flow diversion is recommended and commonplace, the testing of platelet inhibition is more controversial. METHODS The authors reviewed the medical literature to establish and describe the physiology of platelet adhesion, the pharmacology of antiplatelet medications, and the mechanisms of the available platelet function tests. Additionally, they present a review of the pertinent neurointerventional and interventional cardiology literature. RESULTS Competing reports in the neurointerventional literature argue for and against the use of routine platelet function testing, with adjustments to the dosage or medications based on the results. The interventional cardiology literature has also wrestled with this dilemma after percutaneous coronary interventions, with conflicting reports of the benefits of platelet function testing. CONCLUSIONS Despite its prevalence, the benefits of platelet function testing prior to flow diversion are unproven. This practice will likely remain controversial until the level of evidence improves through more rigorous testing and reporting.

Predictors of 30-day readmission after aneurysmal subarachnoid hemorrhage: a case-control study.

OBJECTIVE Despite persisting questions regarding its appropriateness, 30-day readmission is an increasingly common quality metric used to influence hospital compensation in the United States. However, there is currently insufficient evidence to identify which patients are at highest risk for readmission after aneurysmal subarachnoid hemorrhage (SAH). The objective of this study was to identify predictors of 30-day readmission after SAH, to focus preventative efforts, and to provide guidance to funding agencies seeking to risk-adjust comparisons among hospitals. METHODS The authors performed a case-control study of 30-day readmission among aneurysmal SAH patients treated at a single center between 2003 and 2013. To control for geographic distance from the hospital and year of treatment, the authors randomly matched each case (30-day readmission) with approximately 2 SAH controls (no readmission) based on home ZIP code and treatment year. They evaluated variables related to patient demographics, socioeconomic characteristics, comorbidities, presentation severity (e.g., Hunt and Hess grade), and clinical course (e.g., need for gastrostomy or tracheostomy, length of stay). Conditional logistic regression was used to identify significant predictors, accounting for the matched design of the study. RESULTS Among 82 SAH patients with unplanned 30-day readmission, the authors matched 78 patients with 153 nonreadmitted controls. Age, demographics, and socioeconomic factors were not associated with readmission. In univariate analysis, multiple variables were significantly associated with readmission, including Hunt and Hess grade (OR 3.0 for Grade IV/V vs I/II), need for gastrostomy placement (OR 2.0), length of hospital stay (OR 1.03 per day), discharge disposition (OR 3.2 for skilled nursing vs other disposition), and Charlson Comorbidity Index (OR 2.3 for score ≥ 2 vs 0). However, the only significant predictor in the multivariate analysis was discharge to a skilled nursing facility (OR 3.2), and the final model was sensitive to criteria used to enter and retain variables. Furthermore, despite the significant association between discharge disposition and readmission, less than 25% of readmitted patients were discharged to a skilled nursing facility. CONCLUSIONS Although discharge disposition remained significant in multivariate analysis, most routinely collected variables appeared to be weak independent predictors of 30-day readmission after SAH. Consequently, hospitals interested in decreasing readmission rates may consider multifaceted, cost-efficient interventions that can be broadly applied to most if not all SAH patients.

Causes of 30-day readmission after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Hospital readmission is a common but controversial quality measure increasingly used to influence hospital compensation in the US. The objective of this study was to evaluate the causes for 30-day hospital readmission following aneurysmal subarachnoid hemorrhage (SAH) to determine the appropriateness of this performance metric and to identify potential avenues for improved patient care. METHODS: The authors retrospectively reviewed the medical records of all patients who received surgical or endovascular treatment for aneurysmal SAH at Barnes-Jewish Hospital between 2003 and 2013. Two senior faculty identified by consensus the primary medical/surgical diagnosis associated with readmission as well as the underlying causes of rehospitalization. RESULTS: Among 778 patients treated for aneurysmal SAH, 89 experienced a total of 97 readmission events, yielding a readmission rate of 11.4%. The median time from discharge to readmission was 9 days (interquartile range 3-17.5 days). Actual hydrocephalus or potential concern for hydrocephalus (e.g., headache) was the most frequent diagnosis (26/97, 26.8%), followed by infections (e.g., wound infection [5/97, 5.2%], urinary tract infection [3/97, 3.1%], and pneumonia [3/97, 3.1%]) and thromboembolic events (8/97, 8.2%). In most cases (75/97, 77.3%), we did not identify any treatment lapses contributing to readmission. The most common underlying causes for readmission were unavoidable development of SAH-related pathology (e.g., hydrocephalus; 36/97, 37.1%) and complications related to neurological impairment and immobility (e.g., thromboembolic event despite high-dose chemoprophylaxis; 21/97, 21.6%). The authors determined that 22/97 (22.7%) of the readmissions were likely preventable with alternative management. In these cases, insufficient outpatient medical care (for example, for hyponatremia; 16/97, 16.5%) was the most common shortcoming. CONCLUSIONS: Most readmissions after aneurysmal SAH relate to late consequences of hemorrhage, such as hydrocephalus, or medical complications secondary to severe neurological injury. Although a minority of readmissions may potentially be avoided with closer medical follow-up in the transitional care environment, readmission after SAH is an insensitive and likely inappropriate hospital performance metric.

A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage.

OBJECTIVE: Studies show that phosphodiesterase-V (PDE-V) inhibition reduces cerebral vasospasm (CVS) and improves outcomes after experimental subarachnoid hemorrhage (SAH). This study was performed to investigate the safety and effect of sildenafil (an FDA-approved PDE-V inhibitor) on angiographic CVS in SAH patients. METHODS: A2-phase, prospective, nonrandomized, human trial was implemented. Subarachnoid hemorrhage patients underwent angiography on Day 7 to assess for CVS. Those with CVS were given 10 mg of intravenous sildenafil in the first phase of the study and 30 mg in the second phase. In both, angiography was repeated 30 minutes after infusion. Safety was assessed by monitoring neurological examination findings and vital signs and for the development of adverse reactions. For angiographic assessment, in a blinded fashion, pre- and post-sildenafil images were graded as "improvement" or "no improvement" in CVS. Unblinded measurements were made between pre- and post-sildenafil angiograms. RESULTS: Twelve patients received sildenafil; 5 patients received 10 mg and 7 received 30 mg. There were no adverse reactions. There was no adverse effect on heart rate or intracranial pressure. Sildenafil resulted in a transient decline in mean arterial pressure, an average of 17% with a return to baseline in an average of 18 minutes. Eight patients (67%) were found to have a positive angiographic response to sildenafil, 3 (60%) in the low-dose group and 5 (71%) in the high-dose group. The largest degree of vessel dilation was an average of 0.8 mm (range 0-2.1 mm). This corresponded to an average percentage increase in vessel diameter of 62% (range 0%-200%). CONCLUSIONS: The results from this Phase I safety and proof-of-concept trial assessing the use of intravenous sildenafil in patients with CVS show that sildenafil is safe and well tolerated in the setting of SAH. Furthermore, the angiographic data suggest that sildenafil has a positive impact on human CVS.

Comparing routine versus selective use of intraoperative cerebral angiography in aneurysm surgery: a prospective study.

INTRODUCTION: While the use of intraoperative angiography (IA) has been shown to be a useful adjunct in aneurysm surgery, its routine use remains controversial. OBJECTIVE: We wished to determine if IA is required in all patients undergoing aneurysm surgery (ie, routine IA) or if intraoperative assessment can reliably predict the need for IA (ie, select IA). METHODS: We prospectively evaluated all patients undergoing craniotomy for aneurysm clipping. In these patients, the treating surgeons were asked to record whether they felt IA was required at two time points: (1) prior to surgery and (2) immediately after clip application but before IA. All patients underwent IA as per the institutional protocol. IA results and the need for post-IA clip adjustments were recorded. RESULTS: Of the 200 patients enrolled, 197 were included for analysis. IA was deemed necessary on preoperative assessment in 144 cases (73%) and on post-clip assessment in 116 cases (59%). Post-clip IA demonstrated 47 (24%) positive findings and post-IA clip adjustments were made in 19 of 198 cases (10%). On preoperative assessment, there were four cases where IA was deemed unnecessary, yet post-IA clip adjustment was required, resulting in a sensitivity of 79% and false negative rate of 8%. Regarding post-clip assessment, there were five cases where IA was thought to be unnecessary and clip adjustment was required, resulting in a sensitivity of 73% and false negative rate of 6%. CONCLUSIONS: The accuracy of a strategy of select IA was not improved by assessing the need for IA immediately after aneurysm clipping versus prior to surgery onset. This suggests that intraoperative assessment regarding the adequacy of aneurysm clip application should be viewed with caution.

Surgical Revascularization in North American Adults with Moyamoya Phenomenon: Long-Term Angiographic Follow-up.

BACKGROUND: North American and Asian forms of moyamoya have distinct clinical characteristics. Asian adults with moyamoya are known to respond better to direct versus indirect revascularization. It is unclear whether North American adults with moyamoya have a similar long-term angiographic response to direct versus indirect bypass. METHODS: A retrospective review of surgical revascularization for adult moyamoya phenomenon was performed. Preoperative and postoperative cerebral angiograms underwent consensus review, with degree of revascularization quantified as extent of new middle cerebral artery (MCA) territory filling. RESULTS: Late angiographic follow-up was available in 15 symptomatic patients who underwent 20 surgical revascularization procedures. In 10 hemispheres treated solely with indirect arterial bypass, 3 had 2/3 revascularization, 4 had 1/3 revascularization, and 3 had no revascularization of the MCA territory. In the 10 hemispheres treated with direct arterial bypass (8 as a stand-alone procedure and 2 in combination with an indirect procedure), 2 had complete revascularization, 7 had 2/3 revascularization, and 1 had 1/3 revascularization. Direct bypass provided a higher rate of "good" angiographic outcome (complete or 2/3 revascularization) when compared with indirect techniques (P = .0198). CONCLUSIONS: Direct bypass provides a statistically significant, more consistent, and complete cerebral revascularization than indirect techniques in this patient population. This is similar to that reported in the Asian literature, which suggests that the manner of presentation (ischemia in North American adults versus hemorrhage in Asian adults) is likely not a contributor to the extent of revascularization achieved after surgical intervention.

Analysis of subarachnoid hemorrhage using the Nationwide Inpatient Sample: the NIS-SAH Severity Score and Outcome Measure.

OBJECT: Studies using the Nationwide Inpatient Sample (NIS), a large ICD-9-based (International Classification of Diseases, Ninth Revision) administrative database, to analyze aneurysmal subarachnoid hemorrhage (SAH) have been limited by an inability to control for SAH severity and the use of unverified outcome measures. To address these limitations, the authors developed and validated a surrogate marker for SAH severity, the NIS-SAH Severity Score (NIS-SSS; akin to Hunt and Hess [HH] grade), and a dichotomous measure of SAH outcome, the NIS-SAH Outcome Measure (NIS-SOM; akin to modified Rankin Scale [mRS] score). METHODS: Three separate and distinct patient cohorts were used to define and then validate the NIS-SSS and NIS-SOM. A cohort (n = 148,958, the "model population") derived from the 1998-2009 NIS was used for developing the NIS-SSS and NIS-SOM models. Diagnoses most likely reflective of SAH severity were entered into a regression model predicting poor outcome; model coefficients of significant factors were used to generate the NIS-SSS. Nationwide Inpatient Sample codes most likely to reflect a poor outcome (for example, discharge disposition, tracheostomy) were used to create the NIS-SOM. Data from 716 patients with SAH (the "validation population") treated at the authors' institution were used to validate the NIS-SSS and NIS-SOM against HH grade and mRS score, respectively. Lastly, 147,395 patients (the "assessment population") from the 1998-2009 NIS, independent of the model population, were used to assess performance of the NIS-SSS in predicting outcome. The ability of the NIS-SSS to predict outcome was compared with other common measures of disease severity (All Patient Refined Diagnosis Related Group [APR-DRG], All Payer Severity-adjusted DRG [APS-DRG], and DRG). RESULTS The NIS-SSS significantly correlated with HH grade, and there was no statistical difference between the abilities of the NIS-SSS and HH grade to predict mRS-based outcomes. As compared with the APR-DRG, APSDRG, and DRG, the NIS-SSS was more accurate in predicting SAH outcome (area under the curve [AUC] = 0.69, 0.71, 0.71, and 0.79, respectively). A strong correlation between NIS-SOM and mRS was found, with an agreement and kappa statistic of 85% and 0.63, respectively, when poor outcome was defined by an mRS score > 2 and 95% and 0.84 when poor outcome was defined by an mRS score > 3. CONCLUSIONS: Data in this study indicate that in the analysis of NIS data sets, the NIS-SSS is a valid measure of SAH severity that outperforms previous measures of disease severity and that the NIS-SOM is a valid measure of SAH outcome. It is critically important that outcomes research in SAH using administrative data sets incorporate the NIS-SSS and NIS-SOM to adjust for neurology-specific disease severity.

Middle cerebral artery bifurcation aneurysms: an anatomic classification scheme for planning optimal surgical strategies.

BACKGROUND: Changing landscapes in neurosurgical training and increasing use of endovascular therapy have led to decreasing exposure in open cerebrovascular neurosurgery. To ensure the effective transition of medical students into competent practitioners, new training paradigms must be developed. OBJECTIVE: Using principles of pattern recognition, we created a classification scheme for middle cerebral artery (MCA) bifurcation aneurysms that allows their categorization into a small number of shape pattern groups. METHODS: Angiographic data from patients with MCA aneurysms between 1995 and 2012 were used to construct 3-dimensional models. Models were then analyzed and compared objectively by assessing the relationship between the aneurysm sac, parent vessel, and branch vessels. Aneurysms were then grouped on the basis of the similarity of their shape patterns in such a way that the in-class similarities were maximized while the total number of categories was minimized. For each category, a proposed clip strategy was developed. RESULTS: From the analysis of 61 MCA bifurcation aneurysms, 4 shape pattern categories were created that allowed the classification of 56 aneurysms (91.8%). The number of aneurysms allotted to each shape cluster was 10 (16.4%) in category 1, 24 (39.3%) in category 2, 7 (11.5%) in category 3, and 15 (24.6%) in category 4. CONCLUSION: This study demonstrates that through the use of anatomic visual cues, MCA bifurcation aneurysms can be grouped into a small number of shape patterns with an associated clip solution. Implementing these principles within current neurosurgery training paradigms can provide a tool that allows more efficient transition from novice to cerebrovascular expert.