Risk of Branch Occlusion and Ischemic Complications with the Pipeline Embolization Device in the Treatment of Posterior Circulation Aneurysms

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Stabilizing DNA–Protein Co-Crystals via Intra-Crystal Chemical Ligation of the DNA

Protein and DNA co-crystals are most commonly prepared to reveal structural and functional details of DNA-binding proteins when subjected to X-ray diffraction. However, biomolecular crystals are notoriously unstable in solution conditions other than their native growth solution. To achieve greater application utility beyond structural biology, biomolecular crystals should be made robust against harsh conditions. To overcome this challenge, we optimized chemical DNA ligation within a co-crystal. Co-crystals from two distinct DNA-binding proteins underwent DNA ligation with the carbodiimide crosslinking agent 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) under various optimization conditions: 5′ vs. 3′ terminal phosphate, EDC concentration, EDC incubation time, and repeated EDC dose. This crosslinking and DNA ligation route did not destroy crystal diffraction. In fact, the ligation of DNA across the DNA–DNA junctions was clearly revealed via X-ray diffraction structure determination. Furthermore, crystal macrostructure was fortified. Neither the loss of counterions in pure water, nor incubation in blood serum, nor incubation at low pH (2.0 or 4.5) led to apparent crystal degradation. These findings motivate the use of crosslinked biomolecular co-crystals for purposes beyond structural biology, including biomedical applications

Reconstructive vs Deconstructive Endovascular Approach to Intradural Vertebral Artery Aneurysms: A Multicenter Cohort Study

BACKGROUND: Parent vessel sacrifice (PVS) has been a traditional way of treating complex aneurysms of the intradural vertebral artery (VA). Flow diversion (FD) has emerged as an alternative reconstructive option. OBJECTIVE: To compare the long-term clinical and radiographic outcomes of intradural VA aneurysms following PVS or FD. METHODS: We retrospectively reviewed and evaluated 43 consecutive patients between 2009 and 2018 with ruptured and unruptured intradural VA aneurysms treated by PVS or FD. Medical records including clinical and radiological details were reviewed. RESULTS: A total of 43 intradural VA aneurysms were treated during this period. In the 14 PVS patients, the mean follow-up was 19.5 mo, and 71.4% of cases achieved modified Rankin scale (mRS) \u3c /=2 at the last follow-up. A total of 86.5% of cases achieved complete occlusion. There was a 14.3% (2 cases) mortality rate, 14.3% (2 cases) postoperative ischemic complication rate, and 0% postoperative hemorrhaging rate. Retreatment was required in 1 case (7.1%). In the 29 FD patients, the mean follow-up was 21.8 mo, and 89.7% of cases achieved mRS \u3c /=2 at the final follow-up. There was a 3.2% (1 case) mortality rate, 19.4% (6 cases) of postoperative ischemic complications, and 6.5% (2 cases) of postoperative hemorrhagic complications. Complete occlusion was seen in 86.5% patients. No cases required retreatment. Mortality and complication rates were not significantly different between PVS and PED (Pipeline Embolization Device) groups. CONCLUSION: PVS was associated with comparable intraprocedural complications for VA aneurysms as compared to FD in the largest multicenter study to date. Both procedures have good long-term clinical and radiological outcomes

Pipeline Embolization in Patients with Posterior Circulation Subarachnoid Hemorrhages: Is Takotsubo Cardiomyopathy a Limiting Factor?

Background: Hemorrhagic vascular lesions in the posterior cerebral circulation such as ruptured aneurysms and dissections can be challenging to treat. Flow diversion has become an important off-label option, but few studies have analyzed the safety of these devices in this setting. Using an international, multicenter cohort, we reviewed posterior circulation subarachnoid hemorrhage (SAH) patients treated with the Pipeline Embolization Device (PED) in the acute setting and assessed the incidence of Takotsubo cardiomyopathy (TCM). Methods: Eleven neurovascular centers were queried to identify cases of posterior circulation aneurysms or dissections treated with the PED in the acute setting of SAH. Among those, 5 centers had cases that matched the inclusion criteria. The following variables were evaluated: demographics, the location and morphology of the aneurysm, the clinical presentation, the specific form of treatment, complications including the development of TCM, antiplatelet medication regimen, and follow-up time. Results: A total of 23 patients were treated with PED after posterior circulation SAH, and 13 of these developed TCM. The lesions were the result of hemorrhagic intracranial dissection (8 patients), ruptured pseudoaneurysm (3), ruptured saccular aneurysm (7), blister aneurysm (4), and fusiform aneurysm (1). Ninety-one percent of patients had complete or near-complete aneurysm occlusion on follow-up imaging. Five patients died in the perioperative period; 16/18 survivors had a favorable outcome. Conclusions: We describe an unexpectedly high incidence of TCM after the placement of PEDs in patients with posterior circulation SAH in our large case series. Further studies will be needed to elucidate possible causes. © 2020 Elsevier Inc

Symmetric collateral pattern on CTA predicts favorable outcomes after endovascular thrombectomy for large vessel occlusion stroke.

Endovascular thrombectomy (EVT) has revolutionized large vessel occlusion (LVO) stroke management, but often requires advanced imaging. The collateral pattern on CT angiograms may be an alternative because a symmetric collateral pattern correlates with a slowly growing, small ischemic core. We tested the hypothesis that such patients will have favorable outcomes after EVT. Consecutive patients (n = 74) with anterior LVOs who underwent EVT were retrospectively analyzed. Inclusion criteria were available CTA and 90-day modified Rankin Scale (mRS). CTA collateral patterns were symmetric in 36%, malignant in 24%, or other in 39%. Median NIHSS was 11 for symmetric, 18 for malignant, and 19 for other (p = 0.02). Ninety-day mRS ≤2, indicating independent living, was achieved in 67% of symmetric, 17% of malignant, and 38% of other patterns (p = 0.003). A symmetric collateral pattern was a significant determinant of 90-day mRS ≤2 (aOR = 6.62, 95%CI = 2.24,19.53; p = 0.001) in a multivariable model that included age, NIHSS, baseline mRS, thrombolysis, LVO location, and successful reperfusion. We conclude that a symmetric collateral pattern predicts favorable outcomes after EVT for LVO stroke. Because the pattern also marks slow ischemic core growth, patients with symmetric collaterals may be suitable for transfer for thrombectomy. A malignant collateral pattern is associated with poor clinical outcomes

Flow Diversion for Treatment of Partially Thrombosed Aneurysms: A Multicenter Cohort

BACKGROUND: Partially thrombosed intracranial aneurysms (PTIA) represent a unique subset of intracranial aneurysms with an ill-defined natural history, posing challenges to standard management strategies. This study aims to assess the efficacy of flow diversion in the treatment of this pathology. METHODS: A retrospective review of patients with flow-diverted PTIA at 6 cerebrovascular centers was performed. Clinical and radiographic data were collected from the medical records, with the primary outcome of aneurysmal occlusion and secondary outcomes of clinical status and complications. RESULTS: Fifty patients with 51 PTIA treated with flow diversion were included. Median age was 56.5 years. Thirty-three (64.7%) aneurysms were saccular and 16 (31.4%) were fusiform/dolichoectatic. The most common location was the internal carotid artery (54.9%) followed by the vertebral and basilar arteries (17.7% and 17.7%, respectively). Last imaging follow-up was performed at a median of 25.1 (interquartile range, 12.8-43) months. Complete occlusion at last radiographic follow-up was achieved in 37 (77.1%) aneurysms. Pretreatment aneurysm thrombosis of \u3e 50% was associated with a significantly lower rate of complete aneurysm occlusion (58.8 vs. 87.1%, P = 0.026) with a trend toward better functional outcome (modified Rankin scale \u3c 2) at last follow-up in patients with \u3c 50% pretreatment aneurysm thrombosis (96.8 vs. 82.4; P = 0.08). Ischemic complications occurred in 5 (9.8%) patients, producing symptoms in 4 (7.8%) and resultant mortality in 2 (4.2%) patients. CONCLUSIONS: Flow diversion treatment of PTIA has adequate efficacy along with a reasonable safety profile. Aneurysms harboring large amounts of pretreatment thrombus were associated with lower rates of complete occlusion

Direct to Angio‐Suite Large Vessel Occlusion Stroke Transfers Achieve Faster Arrival‐to‐Puncture Times and Improved Outcomes

Background For patients with large vessel occlusion (LVO) stroke, time to treatment with endovascular thrombectomy is crucial to prevent infarction and improve outcomes. We sought to evaluate the hub arrival‐to‐puncture times and outcomes for transferred patients accepted directly to the angio‐suite (LVO to operating room, LVO2OR) versus those accepted through the emergency department in a hub‐and‐spoke telestroke network. Methods Consecutive patients transferred for endovascular thrombectomy with spoke computed tomography angiography–confirmed LVO, spoke Alberta Stroke Program Early Computed Tomography score >6, and last known well–to–hub arrival <6 hours were identified. Our LVO2OR protocol began implementation in January 2017. The LVO2OR cohort includes patients who underwent endovascular thrombectomy from July 2017 to October 2020; the emergency department cohort includes those from January 2011 to December 2016. Hub arrival‐to‐puncture time and 90‐day modified Rankin scale score were prospectively recorded. Results The LVO2OR cohort was composed of 91 patients, and the emergency department cohort was composed of 90 patients. LVO2OR patients had more atrial fibrillation (51% versus 32%; P=0.02) and more M2 occlusions (27% versus 10%; P=0.01). LVO2OR patients had faster median hub arrival‐to‐puncture time (11 versus 92 minutes; P<0.001), faster median telestroke consult‐to‐puncture time (2.4 versus 3.6 hours; P<0.001), greater Thrombolysis in Cerebral Infarction score 2b to 3 reperfusion (92% versus 69%; P<0.001), and greater 90‐day modified Rankin scale score <2 (35% versus 21%; P=0.04). In a multivariable model, LVO2OR significantly increased the odds of 90‐day modified Rankin scale score <2 (adjusted odds ratio, 2.77 [95% CI, 1.07–7.20]; P=0.04) even when controlling for age, baseline modified Rankin scale score, atrial fibrillation, National Institutes of Health Stroke Scale score, M2 occlusion location, and Thrombolysis in Cerebral Infarction score 2b to 3. Conclusions In a hub‐and‐spoke telestroke network, accepting transferred patients directly to the angio‐suite was associated with dramatically reduced hub arrival‐to‐puncture time and may lead to improved 90‐day outcomes. Direct–to–angio‐suite protocols should continue to be evaluated in other geographic regions and telestroke network models