Faculty Bibliography

Background/UNASSIGNED:Pediatric intracranial aneurysms tend to differ in etiology, size, and location from their adult counterparts, and they are often less amenable to microsurgical clip reconstruction techniques. Endovascular treatment with detachable coils is an accepted treatment technique for pediatric patients, though high recurrence rates have been reported with coil embolization of large and giant aneurysms in this population. While the Pipeline Embolization Device (PED) is FDA-approved for adult intracranial aneurysms, the use of PEDs in pediatric patients is considered off-label. Case Descriptions/UNASSIGNED:We present 3 cases of pediatric intracranial aneurysms in a 5-year-old male, a 12-year-old male, and a 12-year-old female who presented with symptoms including seizure, headache, and blurred vision. The 2 male patients were found to have intradural vertebral artery saccular aneurysms, while the female patient had a paraophthalmic right internal carotid complex aneurysm. After endovascular reconstruction of the aneurysms with PEDs, follow-up angiography showed complete occlusion of the previous aneurysms with no residual aneurysm filling in all 3 cases. Conclusion/UNASSIGNED:While further investigation is needed, the evidence presented here supports the conclusion that the PED can be an effective and viable treatment strategy in the pediatric population.

Neuroendovascular surgery and interventional neuroradiology both describe the catheter-based (most often) endovascular diagnosis and treatment of vascular lesions affecting the brain and spinal cord. This article traces the evolution of these techniques and their current role as the dominant and frequently standard approach for many of these conditions. The article also discusses the important changes that have been brought to bear on open cerebrovascular neurosurgery by neuroendovascular surgery and their effects on resident and fellow training and describes new concepts for clinical care.

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.