GM2 gangliosidoses, including Tay-Sachs disease and Sandhoff disease, are lysosomal storage disorders caused by deficiencies in β-N-acetylhexosaminidase (Hex). Patients are afflicted primarily with progressive central nervous system (CNS) dysfunction. Studies in mice, cats, and sheep have indicated safety and widespread distribution of Hex in the CNS after intracranial vector infusion of AAVrh8 vectors encoding species-specific Hex α- or β-subunits at a 1:1 ratio. Here, a safety study was conducted in cynomolgus macaques (cm), modeling previous animal studies, with bilateral infusion in the thalamus as well as in left lateral ventricle of AAVrh8 vectors encoding cm Hex α- and β-subunits. Three doses (3.2 × 10 vg [n = 3]; 3.2 × 10 vg [n = 2]; or 1.1 × 10 vg [n = 2]) were tested, with controls infused with vehicle (n = 1) or transgene empty AAVrh8 vector at the highest dose (n = 2). Most monkeys receiving AAVrh8-cmHexα/β developed dyskinesias, ataxia, and loss of dexterity, with higher dose animals eventually becoming apathetic. Time to onset of symptoms was dose dependent, with the highest-dose cohort producing symptoms within a month of infusion. One monkey in the lowest-dose cohort was behaviorally asymptomatic but had magnetic resonance imaging abnormalities in the thalami. Histopathology was similar in all monkeys injected with AAVrh8-cmHexα/β, showing severe white and gray matter necrosis along the injection track, reactive vasculature, and the presence of neurons with granular eosinophilic material. Lesions were minimal to absent in both control cohorts. Despite cellular loss, a dramatic increase in Hex activity was measured in the thalamus, and none of the animals presented with antibody titers against Hex. The high overexpression of Hex protein is likely to blame for this negative outcome, and this study demonstrates the variations in safety profiles of AAVrh8-Hexα/β intracranial injection among different species, despite encoding for self-proteins.

Background Bypassing the emergency department and the computed tomography suite by directly transporting to the neuroangiography suite for imaging assessment and treatment may shorten reperfusion times while maintaining proper patient selection. Objective To determine whether flat-panel detector multiphase computed tomography angiography protocol is associated with reduced treatment times and a similar safety profile as the standard imaging protocol. Methods Single-center prospective study of consecutive patients with anterior circulation large vessel occlusion strokes transferred to our facility for consideration of endovascular therapy from May 2016 to December 2017. Those with basilar strokes and/or presenting to the emergency department were excluded. Patients were categorized into two groups: (1) flat-panel detector CT assessment in stroke to reduce times to intra-arterial treatment group, with patients transferred directly to the suite for multiphase computed tomography angiography; and (2) patients undergoing standard protocol including computed tomography ± computed tomography angiography/CT perfusion. The groups were matched for age, baseline National Institute of Health Stroke Scale, and pretreatment glucose. Baseline characteristics, time metrics, and outcomes were compared. Results Out of 419 patients who underwent endovascular therapy over the study period, 210 patients fit inclusion criteria, with 54 (25.7%) in the flat-panel detector CT assessment in stroke to reduce times to intra-arterial treatment group. After matching, 49 flat-panel detector CT assessment in stroke to reduce times to intra-arterial treatment/control pairs were generated and analyzed. Baseline characteristics were well balanced. Flat-panel detector CT assessment in stroke to reduce times to intra-arterial treatment patients had significantly shorter median door-to-puncture (33 [26.5-47] vs. 55 [44.5–66] min, p < 0.001), door-to-reperfusion (85 [57.5–115.5] vs. 110 [80–153], p = 0.005) and picture-to-puncture (18 [13.5–22.5] vs. 42 [32–47.5] min, p < 0.001) times. There were no differences in rates of successful reperfusion (modified thrombolysis in cerebral infarction 2b-3, 95.9% vs. 100%, p = 0.5), parenchymal hematomas type-2 (4.1% vs. 2%, p = 1.00), good outcome (90-day modified Rankin Scale 0–2, 44.9% vs. 40.8%, p = 0.68), and 90-day mortality (14.3% vs. 22.4%, p = 0.30). Conclusion Directly transferring patients to angiography and using multiphase computed tomography angiography to determine the eligibility for endovascular therapy is safe and may result in a significant reduction in treatment times. Future larger studies are warranted.

Our study shows preliminary data from three centers on recanalization of tandem occlusions in patients presenting with AIS. There was a preference to revascularize the proximal occlusion using a stent followed by distal recanalization with mechanical thrombectomy, intra-arterial thrombolysis or a combination of these. This approach has low periprocedural complications and can achieve an excellent angiographic and clinical outcome.

Background and purpose Developments in flat-panel angiographic c-arm systems have enabled visualization of both the neurovascular stents and host arteries in great detail, providing complementary spatial information in addition to conventional DSA. However, the visibility of these structures may be impeded by artifacts generated by adjacent radio-attenuating objects. We report on the use of a metal artifact reduction (MAR) algorithm for high resolution contrast-enhanced CBCT (VasoCT) for follow-up imaging of stent-assisted coil embolization. Materials and methods VasoCT data was acquired in 25 patients that underwent stent-assisted coiling. Reconstructions were generated with and without MAR and were reviewed by three experienced neuroradiologists using a 3-point scale. Results With MAR, the observers agreed that the visibility had improved by at least one point on the scoring scale in more than 40% of the cases (κ = 0.6) and that the streak artifact was not obscuring surrounding structures in 64% of all cases (κ = 0.6). MAR improved the image quality which allowed for visibility sufficient for evaluation in 65% of the cases, and was preferred over no MAR in 92% (κ = 0.9). Significantly higher scores were given with MAR (p < 0.0001). Conclusion Although MAR is not capable of fully removing artifacts caused by implants with high x-ray absorption, we have shown that the image quality of VasoCT data is improved drastically. The impact of the artifacts on the visibility varied between cases, and yet the overall visibility of the contrast-enhanced CBCT with MAR improved in the majority of the cases.

LC Bead LUMI™ image-able microbeads provide real-time feedback and geographic localization of treatment in real time during treatment. The distribution and density of image-able beads within a tumor need further evaluation as an additional endpoint for embolization.