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OBJECTIVE Vertebrobasilar dissecting (VBD) aneurysms are rare, and patients with these aneurysms often present with thromboembolic infarcts or subarachnoid hemorrhage (SAH). The morphological nature of VBD aneurysms often precludes conventional clip reconstruction or coil placement and encourages parent artery exclusion or endovascular stenting. Treatment considerations include aneurysm location along the vertebral artery (VA), the involvement of the posterior inferior cerebellar artery (PICA), and collateral blood flow. Outcomes after endovascular treatment have been well described in the neurosurgical literature, but microsurgical outcomes have not been detailed. Patient outcomes from a large, single-surgeon, consecutive series of microsurgically managed VBD aneurysms are presented, and 3 illustrative case examples are provided. METHODS The medical records of patients with dissecting aneurysms affecting the intracranial VA (V4), basilar artery, and PICA that were treated microsurgically over a 19-year period were reviewed. Patient demographics, aneurysm characteristics, surgical procedures, and clinical outcomes (according to modified Rankin Scale [mRS] scores at last follow-up) were analyzed. RESULTS Forty-two patients with 42 VBD aneurysms were identified. Twenty-six aneurysms (62%) involved the PICA, 14 (33%) were distinct from the PICA origin on the V4 segment of the VA, and 2 (5%) were located at the vertebrobasilar junction. Thirty-four patients (81%) presented with SAH with a mean Hunt and Hess grade of 3.2 at presentation. Six (14%) of the 42 patients had been previously treated using endovascular techniques. Nineteen aneurysms (45%) underwent clip wrapping, 17 (40%) were treated with bypass trapping, and 6 (14%) underwent parent artery sacrifice. The complete aneurysm obliteration rate was 95% (n = 40), and the surgical complication rate was 7% (n = 3). The 8 patients with unruptured VBD aneurysms were significantly more likely to be discharged home (n = 6, 75%) compared with 34 patients with ruptured aneurysms (n = 9, 27%; p = 0.01). Good outcomes (mRS score ≤ 2) were observed in 20 patients (48%). Eight patients (19%) died. CONCLUSIONS These data demonstrate that patients with VBD aneurysms often present after a rupture in poor neurological condition, but favorable results can be achieved with open microsurgical repair in almost half of such cases. Microsurgery remains a viable treatment option, with the choice between bypass trapping and clip wrapping largely dictated by the specific location of the aneurysm and its relationship to the PICA.

Anterior lumbar interbody fusion (ALIF) and lateral lumbar interbody fusion are common techniques that typically require staged procedures when performed in combination. Interest is emerging in single-position surgery to increase operative efficiency. We report a novel surgical technique, supine extended reach lateral fusion, to perform ALIF and lateral lumbar interbody fusion with the patient in a single supine position.A man in his fifties presented with degenerative levoscoliosis, spondylolisthesis, sagittal plane deformity, and progressive low back pain. He was offered L3-S1 anterolateral fusion.With the patient supine, a left abdominal paramedian incision was performed to gain anterior retroperitoneal access, and standard L5-S1 and L4-5 ALIFs were performed. The anterior incision was used for direct visualization, retraction, and bimanual dissection. A left lateral incision was then made to perform an L3-4 lateral lumbar interbody fusion. He subsequently underwent a second-stage L3-S1 posterior percutaneous fixation. The patient tolerated the procedures well, without complications. His postoperative radiograph findings confirmed acceptable implant positioning. He was discharged home in stable condition and was doing well at follow-up.This case description is the first report of the supine extended reach technique, which allows incorporation of anterior and lateral fusion constructs at adjacent levels without changing patient positioning. Many surgeons believe the ALIF to be the most powerful technique for achieving lordosis, and this technique enables concomitant lateral access in a supine position. It can also be used as an alternative strategy when anterior access to the disc space is unobtainable. Further clinical investigation of this technique is warranted.

BackgroundVasospasm following aneurysmal subarachnoid hemorrhage (SAH) contributes significant morbidity and mortality after brain aneurysm rupture. However, the association between vascular territory of vasospasm and clinical outcome has not been studied. We present a hypothesis-generating study to determine whether the location of vasospasm within the intracranial circulation is associated with functional outcome after SAH.MethodsA retrospective analysis of a prospective, intention-to-treat trial for aneurysmal SAH was performed to supplement trial outcomes with in-hospital angiographic imaging and treatment variables regarding vasospasm. The location of vasospasm and the position on the vessel (distal vs proximal) were evaluated. Modified Rankin scale (mRS) outcomes were assessed at discharge and 6 months, and predictive models were constructed.ResultsA total of 406 patients were included, 341 with follow-up data at 6 months. At discharge, left-sided vasospasm was associated with poor outcome (odds ratio (OR), 2.37; 95% CI, 1.25 to 4.66; P=0.01). At 6 months, anterior cerebral artery (ACA) vasospasm (OR, 3.87; 95% CI, 1.29 to 11.88; P=0.02) and basilar artery (BA) vasospasm (OR, 6.22; 95% CI, 1.54 to 27.11; P=0.01) were associated with poor outcome after adjustment. A model predicting 6-month mRS score and incorporating vasospasm variables achieved an area under the curve of 0.85 and a net improvement in reclassification of 13.2% (PConclusionsIn aneurysmal SAH, left-sided vasospasm is associated with worse discharge functional status. At 6 months, both ACA and BA vasospasm are associated with unfavorable functional status.

Multidrug resistant organisms are a serious threat to human health1,2. Fast, accurate antibiotic susceptibility testing (AST) is a critical need in addressing escalating antibiotic resistance, since delays in identifying multidrug resistant organisms increase mortality3,4 and use of broad-spectrum antibiotics, further selecting for resistant organisms. Yet current growth-based AST assays, such as broth microdilution5, require several days before informing key clinical decisions. Rapid AST would transform the care of patients with infection while ensuring that our antibiotic arsenal is deployed as efficiently as possible. Growth-based assays are fundamentally constrained in speed by doubling time of the pathogen, and genotypic assays are limited by the ever-growing diversity and complexity of bacterial antibiotic resistance mechanisms. Here we describe a rapid assay for combined genotypic and phenotypic AST through RNA detection, GoPhAST-R, that classifies strains with 94–99% accuracy by coupling machine learning analysis of early antibiotic-induced transcriptional changes with simultaneous detection of key genetic resistance determinants to increase accuracy of resistance detection, facilitate molecular epidemiology and enable early detection of emerging resistance mechanisms. This two-pronged approach provides phenotypic AST 24–36 h faster than standard workflows, with

BackgroundTransradial artery access (TRA) for neurointerventional procedures is gaining widespread acceptance. However, complications that were previously rare may arise as TRA procedures increase. Here we report a series of retained catheter cases with a literature review.MethodsAll patients who underwent a neurointerventional procedure during a 23-month period at a single institution were retrospectively reviewed for a retained catheter in TRA cases. In cases of retained catheters, imaging was reviewed for anatomical variances in the radial artery, and clinical and demographic case details were analyzed.ResultsA total of 1386 nondiagnostic neurointerventional procedures were performed during the study period, 631 (46%) initially via TRA. The 631 TRA cases were performed for aneurysm embolization (n=221, 35%), mechanical thrombectomy (n=116, 18%), carotid stent/angioplasty (n=40, 6%), arteriovenous malformation embolization (n=38, 6%), and other reasons (n=216, 34%). Thirty-nine (6%) TRA procedures crossed over to femoral access, most commonly because the artery of interest could not be catheterized (26/39, 67%). A retained catheter was identified in five cases (1%), and one (0.2%) patient had an entrapped catheter that was recovered. All six patients with a retained or entrapped catheter had aberrant radial anatomy.ConclusionRetained catheters for neurointerventional procedures performed via TRA are rare. However, this complication may be associated with variant radial anatomy. With the increased use of TRA for neurointerventional procedures, awareness of anatomical abnormalities that may lead to a retained catheter is necessary. We propose a simple protocol to avoid catheter entrapment, including in emergent situations such as TRA for stroke thrombectomy.

Background and Purpose— Both low serum calcium and magnesium levels have been associated with the extent of bleeding in patients with intracerebral hemorrhage, suggesting hypocalcemia- and hypomagnesemia-induced coagulopathy as a possible underlying mechanism. We hypothesized that serum albumin-corrected total calcium and magnesium levels are associated with ruptured intracranial aneurysms. Methods— The medical records of 4701 patients, including 1201 prospective patients, diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed and analyzed. One thousand two hundred seventy-five patients had available serum calcium, magnesium, and albumin values within 1 day of diagnosis. Individuals were divided into cases with ruptured aneurysms and controls with unruptured aneurysms. Univariable and multivariable logistic regression analyses were performed to determine the association between serum albumin-corrected total calcium and magnesium levels and ruptured aneurysms. Results— In multivariable analysis, both albumin-corrected calcium (odds ratio, 0.33; 95% confidence interval, 0.27–0.40) and magnesium (odds ratio, 0.40; 95% confidence interval, 0.28–0.55) were significantly and inversely associated with ruptured intracranial aneurysms. Conclusions— In this large case–control study, hypocalcemia and hypomagnesemia at diagnosis were significantly associated with ruptured aneurysms. Impaired hemostasis caused by hypocalcemia and hypomagnesemia may explain this association.

ObjectiveTo determine the association between ruptured saccular aneurysms and aspirin use/aspirin dose.MethodsFour thousand seven hundred one patients who were diagnosed at the Massachusetts General Hospital and Brigham and Women's Hospital between 1990 and 2016 with 6,411 unruptured and ruptured saccular intracranial aneurysms were evaluated. Univariable and multivariable logistic regression analyses were performed to determine the association between aneurysmal subarachnoid hemorrhage and aspirin use, including aspirin dose. Inverse probability weighting using propensity scores was used to adjust for potential differences in baseline characteristics between cases and controls. Additional analyses were performed to examine the association of aspirin use and rerupture before treatment.ResultsIn multivariate analysis with propensity score weighting, aspirin use (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.45–0.80) was significantly associated with decreased risk of ruptured intracranial aneurysms. There was a significant inverse dose-response relationship between aspirin dose and aneurysmal subarachnoid hemorrhage (OR 0.65, 95% CI 0.53–0.81). In contrast, there was a significant association between aspirin use and increased risk of rerupture before treatment (OR 8.15, 95% CI 2.22–30.0).ConclusionsIn this large case-control study, aspirin therapy at diagnosis was associated with a significantly decreased risk of subarachnoid hemorrhage, with an inverse dose-response relationship among aspirin users. However, once rupture has occurred, aspirin is associated with an increased risk of rerupture before treatment.

Following ischemic stroke, the penumbra, at-risk neural tissue surrounding the core infarct, survives for a variable period of time before progressing to infarction. We investigated genetic determinants of the size of penumbra in mice subjected to middle cerebral artery occlusion (MCAO) using a genome-wide approach. 449 male mice from 33 inbred strains underwent MCAO for 6 hours (215 mice) or 24 hours (234 mice). A genome-wide association study using genetic data from the Mouse HapMap project was performed to examine the effects of genetic variants on the penumbra ratio, defined as the ratio of the infarct volume after 6 hours to the infarct volume after 24 hours of MCAO. Efficient mixed model analysis was used to account for strain interrelatedness. Penumbra ratio differed significantly by strain (F = 2.7, P Clint1, Nbea, Smtnl2, Rin3, Dclk1, and Slc24a4.

The goal of this study was to investigate the association of tracheostomy timing with outcomes after aneurysmal subarachnoid hemorrhage (SAH) in a national population.Poor-grade aneurysmal SAH patients were extracted from the Nationwide Inpatient Sample (2002-2011). Multivariable linear regression was used to analyze predictors of tracheostomy timing and multivariable logistic regression was used to evaluate the association of timing of intervention with mortality, complications, and discharge to institutional care. Covariates included patient demographics, comorbidities, severity of subarachnoid hemorrhage (measured using the NIS-SAH severity scale), hospital characteristics, and other complications and length of stay.The median time to tracheostomy among 1380 poor-grade SAH admissions was 11 (interquartile range: 7-15) days after intubation. The mean number of days from intubation to tracheostomy in SAH patients at the hospital (p 0.001) was the strongest predictor of tracheostomy timing for a patient, while comorbidities and SAH severity were not significant predictors. Mortality, neurologic complications, and discharge disposition did not differ significantly by tracheostomy time. However, later tracheostomy (when evaluated continuously) was associated with greater odds of pulmonary complications (p = 0.004), venous thromboembolism (p = 0.04), and pneumonia (p = 0.02), as well as a longer hospitalization (p 0.001). Subgroup analysis only found these associations between tracheostomy timing and medical complications in patients with moderately poor grade (NIS-SAH severity scale 7-9), while there were no significant differences by timing of intervention in very poor-grade patients (NIS-SAH severity scale 9).In this analysis of a large, national data set, variation in hospital practices was the strongest predictor of tracheostomy timing for an individual. In patients with moderately poor grade, later tracheostomy was independently associated with pulmonary complications, venous thromboembolism, pneumonia, and a longer hospitalization, but not with mortality, neurological complications, or discharge disposition. However, tracheostomy timing was not significantly associated with outcomes in very poor-grade patients.

OBJECTIVEThe complex decision analysis of unruptured intracranial aneurysms entails weighing the benefits of aneurysm repair against operative risk. The goal of the present analysis was to build and validate a predictive scale that identifies patients with the greatest odds of a postsurgical adverse event.METHODSData on patients who underwent surgical clipping of an unruptured aneurysm were extracted from the prospective National Surgical Quality Improvement Program registry (NSQIP; 2007–2014); NSQIP does not systematically collect data on patients undergoing intracranial endovascular intervention. Multivariable logistic regression evaluated predictors of any 30-day adverse event; variables screened included patient demographics, comorbidities, functional status, preoperative laboratory values, aneurysm location/complexity, and operative time. A predictive scale was constructed based on statistically significant independent predictors, which was validated using both NSQIP (2015–2016) and the Nationwide Inpatient Sample (NIS; 2002–2011).RESULTSThe NSQIP unruptured aneurysm scale was proposed: 1 point was assigned for a bleeding disorder; 2 points for age 51–60 years, cardiac disease, diabetes mellitus, morbid obesity, anemia (hematocrit < 36%), operative time 240–330 minutes; 3 points for leukocytosis (white blood cell count > 12,000/μL) and operative time > 330 minutes; and 4 points for age > 60 years. An increased score was predictive of postoperative stroke or coma (NSQIP: p = 0.002, C-statistic = 0.70; NIS: p < 0.001, C-statistic = 0.61), a medical complication (NSQIP: p = 0.01, C-statistic = 0.71; NIS: p < 0.001, C-statistic = 0.64), and a nonroutine discharge (NSQIP: p < 0.001, C-statistic = 0.75; NIS: p < 0.001, C-statistic = 0.66) in both validation populations. Greater score was also predictive of increased odds of any adverse event, a major complication, and an extended hospitalization in both validation populations (p ≤ 0.03).CONCLUSIONSThe NSQIP unruptured aneurysm scale may augment the risk stratification of patients undergoing microsurgical clipping of unruptured cerebral aneurysms.

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

Cerebral cavernous malformations, vascular abnormalities comprised of endothelial cells in the absence of connective tissue or muscle, are often epileptogenic and often treated initially with antiepileptic drugs. This chapter discusses the role of pharmacotherapy in managing focal epilepsy secondary to cavernous malformations in adults, children, and pregnant women. Several drugs are available and potentially efficacious in suppressing seizures stemming from cavernous malformations. In addition, antiepileptic pharmacotherapy following surgical resection is indicated to decrease the risk of postoperative seizures. Finally, potential novel therapeutics targeting cavernous malformations are discussed.

OBJECTIVEAlthough reoperation and readmission have been used as quality metrics, there are limited data evaluating the rate of, reasons for, and predictors of reoperation and readmission after microsurgical clipping of unruptured aneurysms.METHODSAdult patients who underwent craniotomy for clipping of an unruptured aneurysm electively were extracted from the prospective National Surgical Quality Improvement Program registry (2011–2014). Multivariable logistic regression and recursive partitioning analysis evaluated the independent predictors of nonroutine hospital discharge, unplanned 30-day reoperation, and readmission. Predictors screened included patient age, sex, comorbidities, American Society of Anesthesiologists (ASA) classification, functional status, aneurysm location, preoperative laboratory values, operative time, and postoperative complications.RESULTSAmong the 460 patients evaluated, 4.2% underwent any reoperation at a median of 7 days (interquartile range [IQR] 2–17 days) postoperatively, and 1.1% required a cranial reoperation. The most common reoperation was ventricular shunt placement (23.5%); other reoperations were tracheostomy, craniotomy for hematoma evacuation, and decompressive hemicraniectomy. Independent predictors of any unplanned reoperation were age greater than 51 years and longer operative time (p ≤ 0.04). Readmission occurred in 6.3% of patients at a median of 6 days (IQR 5–13 days) after discharge from the surgical hospitalization; 59.1% of patients were readmitted within 1 week and 86.4% within 2 weeks of discharge. The most common reason for readmission was seizure (26.7%); other causes of readmission included hydrocephalus, cerebrovascular accidents, and headache. Unplanned readmission was independently associated with age greater than 65 years, Class II or III obesity (body mass index > 35 kg/m2), preoperative hyponatremia, and preoperative anemia (p ≤ 0.04). Readmission was not associated with operative time, complications during the surgical hospitalization, length of stay, or discharge disposition. Recursive partitioning analysis identified the same 4 variables, as well as ASA classification, as associated with unplanned readmission. The most potent predictors of nonroutine hospital discharge (16.7%) were postoperative neurological and cardiopulmonary complications; other predictors were age greater than 51 years, preoperative hyponatremia, African American and Asian race, and a complex vertebrobasilar circulation aneurysm.CONCLUSIONSIn this national analysis, patient age greater than 65 years, Class II or III obesity, preoperative hyponatremia, and anemia were associated with adverse events, highlighting patients who may be at risk for complications after clipping of unruptured cerebral aneurysms. The preponderance of early readmissions highlights the importance of early surveillance and follow-up after discharge; the frequency of readmission for seizure emphasizes the need for additional data evaluating the utility and duration of postcraniotomy seizure prophylaxis. Moreover, readmission was primarily associated with preoperative characteristics rather than metrics of perioperative care, suggesting that readmission may be a suboptimal indicator of the quality of care received during the surgical hospitalization in this patient population.

Cerebral cavernous malformations, vascular abnormalities comprised of endothelial cells in the absence of connective tissue or muscle, are often epileptogenic and often treated initially with antiepileptic drugs. This chapter discusses the role of pharmacotherapy in managing focal epilepsy secondary to cavernous malformations in adults, children, and pregnant women. Several drugs are available and potentially efficacious in suppressing seizures stemming from cavernous malformations. In addition, antiepileptic pharmacotherapy following surgical resection is indicated to decrease the risk of postoperative seizures. Finally, potential novel therapeutics targeting cavernous malformations are discussed.

This is the first nationwide study to evaluate the factors associated with developing hospital-acquired infections (HAIs) after aneurysmal subarachnoid hemorrhage (SAH) and analyze their impact on the efficiency of hospital care.Data from patients with SAH who underwent aneurysm repair were extracted from the Nationwide Inpatient Sample (2008-2011). Urinary tract infections, pneumonia, central venous catheter (CVC)-associated blood stream infection, and meningitis/ventriculitis were evaluated. Independent predictors of HAIs used in multivariable logistic regression modeling were chosen using forward selection; hierarchical multivariable linear regression assessed length of stay and charges.Seven thousand five hundred sixteen admissions were included. Independent predictors in the logistic regression for developing a urinary tract infection (23.9%) included older age, female sex, noninfectious complications (P0.001), intracerebral hemorrhage (P = 0.009), and diabetes with complications (P = 0.04). Pneumonia (23.0%) was associated with older age (P = 0.003), congestive heart failure, severity of SAH, and noninfectious complications (P 0.001). Severity of SAH and noninfectious complications were predictors of meningitis/ventriculitis (4.4%; P ≤ 0.02), whereas intracerebral hemorrhage and noninfectious complications were predictors of CVC-associated infections (1.0%; P ≤ 0.02). All HAIs were associated with significantly longer hospitalizations and higher charges. Pneumonia (odds ratio [OR], 2.85; 95% confidence interval (CI), 2.44-3.34) and CVC-associated infections (OR, 2.42; 95% CI, 1.26-4.66) were also independently associated with greater odds of poor outcome (death or institutional care).In this nationwide analysis, urinary tract infections and pneumonia were the most common hospital-acquired infections after SAH. Although all infections were associated with significantly longer hospitalizations and greater charges, pneumonia and CVC-associated infections were also associated with increased likelihood of a poor outcome.

Although RNA-seq is a powerful tool, the considerable time and cost associated with library construction has limited its utilization for various applications. RNAtag-Seq, an approach to generate multiple RNA-seq libraries in a single reaction, lowers time and cost per sample, and it produces data on prokaryotic and eukaryotic samples that are comparable to those generated by traditional strand-specific RNA-seq approaches.

INTRODUCTION:While obliteration of unruptured aneurysms reduces the risk of subarachnoid hemorrhage, perioperative complications impact the risk-benefit ratio of aneurysm repair, and additional data are needed to optimally risk-stratify patients preoperatively.METHODS:Patients who underwent cranioto