Faculty Bibliography

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.

BACKGROUND AND PURPOSE/OBJECTIVE:Our aim was to propose a conceptually new angioarchitectural model of some dural arteriovenous fistulas based on subset analysis of transverse and sigmoid type lesions. The "common collector" notion argues for convergence of multiple smaller caliber arterial vessels on a common arterial collector vessel within the sinus wall. Communication of this single collector (or constellation of terminal collectors) with the sinus proper defines the site of arteriovenous fistula, which can be closed by highly targeted embolization, preserving the sinus and avoiding unnecessary permeation of indirect arterial feeders. MATERIALS AND METHODS/METHODS:One hundred consecutive dural arteriovenous shunts were examined. Thirty-six transverse/sigmoid fistulas were identified within this group and analyzed for the presence of a common arterial collector as well as other parameters, including demographics, grade, treatment approach, and outcome. RESULTS:A common collector was identified in nearly all Cognard type I lesions (15 fistulas with 14 single collector vessels seen) and progressively less frequently in higher grade fistulas. Identification of the common collector requires careful angiographic analysis, including supraselective and intraprocedural angiographies during treatment, and final embolic material morphology. CONCLUSIONS:Detailed evaluation of imaging studies allows frequent identification of a vascular channel in the sinus wall, which we argue reflects a compound, common arterial channel (rather than a venous collector) with 1 or several discrete fistulous points between this vessel and the sinus proper. Targeted closure of this channel is often feasible, with sinus preservation and avoidance of embolic material penetration into arteries remote from fistula site.

The authors present the unusual case of a complex unruptured basilar artery terminus (BAT) aneurysm in a 42-year-old symptomatic female patient presenting with symptoms of mass effect. Due to the fusiform incorporation of both the BAT and left superior cerebellar artery (SCA) origin, simple surgical or endovascular treatment options were not feasible in this case. A 2-staged (combined deconstructive/reconstructive) procedure was successfully performed: first occluding the left SCA with a Pipeline embolization device (PED) coupled to a microvascular plug (MVP) in the absence of antiplatelet coverage, followed by reconstruction of the BAT by deploying a second PED from the right SCA into the basilar trunk. Six-month follow-up angiography confirmed uneventful aneurysm occlusion. The patient recovered well from her neurological symptoms. This case report illustrates the successful use of a combined staged deconstructive/reconstructive endovascular approach utilizing 2 endoluminal tools, PED and MVP, to reconstruct the BAT and occlude a complex aneurysm.

OBJECTIVE:Minimally invasive alternatives to the pterional craniotomy include the minipterional and the supraorbital craniotomy (SOC). The latter is performed via either an eyebrow or an eyelid skin incision. The purpose of this systematic review was to analyze the type and the incidence of approach-related complications of these keyhole craniotomies. METHODS:We review pertinent publications retrieved by search in the PubMed/Medline database. Inclusion criteria were all full-text publications, abstracts, and posters in English, up to 2016, reporting clinical results. RESULTS:105 publications containing data on 5837 surgeries performed via a minipterional or either of the two variants of the SOC met the eligibility criteria. Pain on mastication was the most commonly reported approach-related complication of the minipterional approach, where it occurred in 7.5% of cases. Temporary palsy of the frontal branch of the facial nerve and temporary supraorbital hypesthesia were associated with the SOC eyebrow variant, where it occurred in 6.5%, respectively in 4.6% of cases. Transient postoperative periorbital edema and transient ophthalmoparesis occurred in 36.8%, respectively in 17.4% of cases when the SOC was performed via an eyelid skin incision. The risk of occurrence of the latter two approach-related complications was related to the removal of the orbital rim, which is obligate part of the SOC through the eyelid approach but optional with the SOC eyebrow variant. CONCLUSION/CONCLUSIONS:Each of three "keyhole" approaches has a specific set and incidence of approach-related complications. It is essential to be aware of these complications to make the safest individual choice.