Faculty Bibliography

BACKGROUND:There is limited data on predictors of symptomatic intracranial haemorrhage (sICH) in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation. METHODS:and t tests to identify independent predictors of sICH with p<0.1. Significant variables were then combined in a multivariate logistic regression model to derive an sICH prediction score. This score was then validated using data from the Blood Pressure After Endovascular Treatment multicentre prospective registry. RESULTS:We identified 578 patients with acute ischaemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: thrombolysis in cerebral ischaemia (TICI) score, Alberta stroke program early CT score (ASPECTS), and glucose level, and from these predictors, we derived the weighted TICI-ASPECTS-glucose (TAG) score, which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48 to 2.66, p<0.001, area under curve ((AUC)=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22 to 1.79, p<0.001, AUC=0.69) cohorts. CONCLUSION/CONCLUSIONS:High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.

BACKGROUND:Neurovascular training models include animal models, synthetics, or computer simulation. In vivo models are expensive and require significant resources. Synthetic/computer models do not reflect the elasticity of fresh vessels. We describe an endovascular and microsurgical training model using a chicken thigh/leg. METHODS:20 chicken thigh/leg models were obtained. Angiography was utilized to understand the anatomy. Proximal cannulation with a 5-French catheter was achieved and connected to a hemostatic valve with a pump to simulate pulsatile flow. Aneurysms were created at the thigh-leg junction. For clipping training, 3 types of aneurysms were created to reproduce anatomy seen in middle cerebral, anterior communicating and posterior communicating aneurysms. RESULTS:The average cost per specimen from was $1.70 ± 0.30. The diameter of the proximal femoral artery (PFA) was 2.4 mm ± 0.2 mm. The length from the PFA to the aneurysm was 9.5 cm ± 0.7 cm. Distal catheterization was successful in all cases (n=6). Successful deployment of coils and a stent was achieved under fluoroscopic guidance. Gross over-sizing of coils and other mistakes led to aneurysm rupture. Each examiner performed an exploration of the pulsatile aneurysm, application and reapplication of a variety of clips and then final inspection of branching vessels to confirm patency. CONCLUSIONS:The chicken thigh/leg model provides training opportunities in microsurgical suturing, endovascular techniques for aneurysm obliteration, and microsurgical reconstruction of aneurysms. It combines affordability, time efficiency and reproducibility. Further studies measuring improvement in technical aneurysm management and comparison to other training models are warranted.

Anatomical vessel obstacles such as an intracranial stenosis in stroke are challenging and may lead to delayed clot access for thrombectomy. We describe a simple and effective technique to overcome the step-off between the intermediate catheter and an intracranial vessel stenosis during thrombectomy. The patient presented with acute embolic left middle cerebral artery occlusion and a favorable penumbral pattern. Clot access was made challenging by focal stenosis in the ipsilateral cavernous segment. The balloon-assisted tracking technique was effective in traversing the step-off to enable TICI 3 aspiration thrombectomy. This simple and effective technique should be kept in mind during stroke procedures where a proximal stenotic obstacle complicates access to the site of occlusion.

PURPOSE/OBJECTIVE:Isocitrate dehydrogenase (IDH) mutant gliomas are a distinct glioma molecular subtype for which no effective molecularly-directed therapy exists. Low-grade gliomas, which are 80-90% IDH mutant, have high RNA levels of the cell surface Notch ligand DLL3. We sought to determine DLL3 expression by immunohistochemistry in glioma molecular subtypes and the potential efficacy of an anti-DLL3 antibody drug conjugate (ADC), rovalpituzumab tesirine (Rova-T), in IDH mutant glioma. EXPERIMENTAL DESIGN/METHODS:We evaluated DLL3 expression by RNA using TCGA data and by immunohistochemistry in a discovery set of 63 gliomas and 20 non-tumor brain tissues and a validation set of 62 known IDH wildtype and mutant gliomas using a monoclonal anti-DLL3 antibody. Genotype was determined using a DNA methylation array classifier or by sequencing. The effect of Rova-T on patient-derived endogenous IDH mutant glioma tumorspheres was determined by cell viability assay. RESULTS:Compared to IDH wildtype glioblastoma, IDH mutant gliomas have significantly higher DLL3 RNA (P<1x10-15) and protein by immunohistochemistry (P=0.0014 and P<4.3x10-6 in the discovery and validation set, respectively). DLL3 immunostaining was intense and homogeneous in IDH mutant gliomas, retained in all recurrent tumors, and detected in only 1 of 20 non-tumor brains. Patient-derived IDH mutant glioma tumorspheres overexpressed DLL3 and were potently sensitive to Rova-T in an antigen-dependent manner. CONCLUSIONS:DLL3 is selectively and homogeneously expressed in IDH mutant gliomas and can be targeted with Rova-T in patient-derived IDH mutant glioma tumorspheres. Our findings are potentially immediately translatable and have implications for therapeutic strategies that exploit cell surface tumor-associated antigens.

OBJECTIVEA systematic analysis on the utility of prophylactic antibiotics for neuroendovascular procedures has not been performed. At the authors' institution there is a unique setup to address this question, with some attending physicians using prophylactic antibiotics (cefazolin or vancomycin) for all of their neurointerventions while others generally do not.METHODSThe authors performed a retrospective review of the last 549 neurointerventional procedures in 484 patients at Tisch Hospital, NYU Langone Medical Center. Clinical and radiological data were collected for analysis, including presence of prophylactic antibiotic use, local or systemic infection, infection laboratory values, and treatment. Overall, 306 aneurysms, 117 arteriovenous malformations/arteriovenous fistulas, 86 tumors, and 40 vessel stenosis/dissections were treated with coiling (n = 109), Pipeline embolization device (n = 197), embolization (n = 203), or stenting (n = 40).RESULTSAntibiotic prophylaxis was used in 265 of 549 cases (48%). There was no significant difference between patients with or without antibiotic prophylaxis in sex (p = 0.48), presence of multiple interventions (p = 0.67), diseases treated (p = 0.11), or intervention device placed (p = 0.55). The mean age of patients in the antibiotic prophylaxis group (53.4 years) was significantly lower than that of the patients without prophylaxis (57.1 years; p = 0.014). Two mild local groin infections (0.36%) and no systemic infections (0%) were identified in this cohort, with one case in each group (1/265 [0.38%] vs 1/284 [0.35%]). Both patients recovered completely with local drainage (n = 1) and oral antibiotic treatment (n = 1).CONCLUSIONSThe risk of infection associated with endovascular neurointerventions with or without prophylactic antibiotic use was very low in this cohort. The data suggest that the routine use of antibiotic prophylaxis seems unnecessary and that to prevent antibiotic resistance and reduce costs antibiotic prophylaxis should be reserved for selected patients deemed to be at increased infection risk.

Introduction The 5 seminal mechanical thrombectomy (MT) trials had a median age of 68 years. Though some of these trials included nonagenarians, there is little data on their outcomes. We aimed to compare the procedural, discharge outcomes and complications, of MT for acute ischemic stroke (AIS) in nonagenarians versus younger patients(<=69) Methods Patients with AIS admitted to two comprehensive stroke centers were enrolled prospectively in a registry. Rates of MT were compared between nonagenarians vs <=69. Among those who underwent MT, procedural outcomes, complications, and discharge disposition were compared in propensity scorematched groups (matched for NIHSS, pre-stroke mRS, IV-tPA administration and T IG grade>=2b) of nonagenarians to patients<=69. Good discharge disposition was defined as a discharge to home/acute rehabilitation. Results Of the 3010 AIS patients, 46/297 (16%) nonagenarians underwent MT compared to 159/1337 (12%) patients <=69 (P=0.091) with TICI>=2b of 89% vs 94%; p=0.238 respectively. 78 patients (N=39 >=90, N=39 <69) were propensity score-matched with a median admission NIHSS of 22 and 19, and median ASPECTS of 9 and 9, respectively (both P>0.05). Those <69 more often had Ml occlusions than nonagenarians (84% vs 50%, P=0.035), whereas ICA (10% vs 13%, p=0.76), and M2 (21% vs 43%, p=0.19) occlusions were similar between the two groups. Time to groin puncture (100+/-65 vs 76+/-34; p=0.124), revascularization time (134+/-72 vs 110+/-54; p=0.145), complication rates (0 vs 5.1%; p=0.494) and inhospital deaths (11% vs 24%; p=0.155) were similar among the two groups. 44% of nonagenarians had good discharge disposition, compared to 51% of patients <69 years (p=0.650) Conclusions We present one of the largest series of MT among nonagenarians with 89% successful recanalization rates. In propensity score analysis almost half of nonagenarians (44%) were discharged to home/rehab, which is comparable to a younger cohort (51%). Aggressive management is warranted in the oldest of the old

Anatomical vessel obstacles such as an intracranial stenosis in stroke are challenging and may lead to delayed clot access for thrombectomy. We describe a simple and effective technique to overcome the step-off between the intermediate catheter and an intracranial vessel stenosis during thrombectomy. The patient presented with acute embolic left middle cerebral artery occlusion and a favorable penumbral pattern. Clot access was made challenging by focal stenosis in the ipsilateral cavernous segment. The balloon-assisted tracking technique was effective in traversing the step-off to enable TICI 3 aspiration thrombectomy. This simple and effective technique should be kept in mind during stroke procedures where a proximal stenotic obstacle complicates access to the site of occlusion.

BACKGROUND AND PURPOSE/OBJECTIVE:Flow diversion is being increasingly used to treat bifurcation aneurysms. Empiric approaches have generally led to encouraging results, and a growing body of animal and ex vivo literature addresses the fate of target aneurysms and covered branches. Our prior investigations highlighted the dynamic nature of metal coverage provided by the Pipeline Embolization Device and suggested strategies for creating optimal single and multidevice constructs. We now address the geometric and hemodynamic aspects of jailing branch vessels and neighboring target aneurysms. MATERIALS AND METHODS/METHODS:Fundamental electric and fluid dynamics principles were applied to generate equations describing the relationships between changes in flow and the degree of vessel coverage in settings of variable collateral support to the jailed territory. Given the high complexity of baseline and posttreatment fluid dynamics, in vivo, we studied a simplified hypothetic system with minimum assumptions to generate the most conservative outcomes. RESULTS:In the acute setting, Pipeline Embolization Devices modify flow in covered branches, principally dependent on the amount of coverage, the efficiency of collateral support, and intrinsic resistance of the covered parenchymal territory. Up to 30% metal coverage of any branch territory is very likely to be well-tolerated regardless of device or artery size or the availability of immediate collateral support, provided, however, that no acute thrombus forms to further reduce jailed territory perfusion. CONCLUSIONS:Basic hemodynamic principles support the safety of branch coverage during aneurysm treatment with the Pipeline Embolization Device. Rational strategies to build bifurcation constructs are feasible.

OBJECTIVE:To clarify the reported experience with keyhole approaches for the treatment of intracranial aneurysms. METHODS:The PubMed and Embase databases were searched up to December 2017 for full-text publications that report the treatment of aneurysms with the eyebrow variant of the supraorbital craniotomy (SOC), the minipterional craniotomy, or the eyelid variant of the SOC. The anatomical distribution of aneurysms, the postoperative aneurysm occlusion rate, and the type and rate of complications were examined using univariate analysis. RESULTS:Sixty-seven publications covering treatment of 5770 aneurysms met the eligibility criteria. The reported experience was the largest for the eyebrow variant of the SOC (69.4% of aneurysms), followed by the minipterional approach (28.2%), and the eyelid variant of the SOC (2.4%). The anterior communicating artery (ACoA) was the most frequent aneurysm location for the SOC (eyebrow variant: 33.2%; eyelid variant: 31.2%). The middle cerebral artery (MCA) was the most frequent aneurysm location in the minipterional cohort (55.2%). In the eyelid variant of the SOC cohort, the rate of complete aneurysm occlusion was the lowest (eyelid variant: 90.8%; eyebrow variant: 97.8%, p < 0.001; minipterional approach: 97.9%, p < 0.001), and the postoperative infarction rate was the highest (eyelid variant: 7.2%; eyebrow variant: 3.5%, p = 0.025; minipterional approach: 2.6%, p = 0.003). CONCLUSION/CONCLUSIONS:Each approach has a specific safety and efficacy profile. Surgeons selected the eyebrow variant of the SOC for many aneurysm locations including in particular the ACoA. There is a recent tendency however to opt for the minipterional approach above all for MCA aneurysms. ABBREVIATIONS/BACKGROUND:SOC: Supraorbital Craniotomy; MPT: Minipterional; MCA: Middle Cerebral Artery; ACoA: Anterior Communicating Artery; PCoA: Posterior Communicating Artery; aSAH: Aneurysmal Subarachnoid Hemorrhage; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; MINORS: Methodological Index For Non-Randomized Studies.