Citations

Abstract Background Flow diversion is a common endovascular treatment for cerebral aneurysms, but studies comparing different types of flow diverters are scarce. Objective To perform a propensity score matched cohort study comparing the Pipeline Embolization Device (PED) and Flow Redirection Intraluminal Device (FRED) for posterior circulation aneurysms. Methods Consecutive aneurysms of the posterior circulation treated at 25 neurovascular centers with either PED or FRED were collected. Propensity score matching was used to control for age, duration of follow-up imaging, adjunctive coiling, and aneurysm location, size, and morphology; previously ruptured aneurysms were excluded. The two devices were compared for the following outcomes: procedural complications, aneurysm occlusion, and functional outcome. Results A total of 375 aneurysms of the posterior circulation were treated in 369 patients. The PED was used in 285 (77.2%) and FRED in 84 (22.8%) procedures. Aneurysms treated with the PED were more commonly fusiform and larger than those treated with FRED. To account for these important differences, propensity score matching was performed resulting in 33 PED and FRED unruptured aneurysm pairs. No differences were found in occlusion status and neurologic thromboembolic or hemorrhagic complications between the two devices. The proportion of patients with favorable functional outcome was higher with FRED (100% vs 87.9%, p=0.04). Conclusion Comparative analysis of PED and FRED for the treatment of unruptured posterior circulation aneurysms did not identify significant differences in aneurysm occlusion or neurologic complications. Variations in functional outcomes warrant additional investigations.

Abstract BACKGROUND The Pipeline Embolization Device (PED; Medtronic) has been used off-label for the treatment of challenging posterior circulation aneurysms. Data on this modality are primarily limited to small retrospective single-center series. OBJECTIVE To assess safety and efficacy of this treatment by establishing an international, multicenter collaboration. METHODS Consecutive posterior circulation aneurysms treated with the PED from 2012 to 2019 across 11 neurovascular centers were retrospectively reviewed. Baseline demographics, aneurysm and treatment characteristics, complications, occlusion status, and functional outcome were assessed. RESULTS There were 149 posterior circulation aneurysms treated with PED in 146 patients. A total of 24 (16.4%) patients presented with subarachnoid hemorrhage. Most aneurysms were dissecting/blister (36.2%) in morphology, followed by saccular (35.6%) and fusiform (28.2%). The most common locations were the vertebral (51.7%) and basilar arteries (22.8%). Complete or near-complete occlusion (>90%) was achieved in 90.9% of aneurysms at a median follow-up of 12 mo. Dissecting/blister aneurysms were most likely to occlude ( P = .06). Symptomatic neurologic complications occurred in 9.4% of aneurysms, associated with larger size, ruptured presentation, presentations with brain stem compression, cranial nerve palsy, or stroke. Favorable functional outcome (modified Rankin Score 0-2) was achieved in 86.2% of patients. There were 6 fatalities of which 4 occurred in aneurysmal subarachnoid hemorrhage patients. CONCLUSION This multicenter study shows that PED for the treatment of posterior circulation is preferentially used for the treatment of fusiform and dissecting/blister aneurysm morphologies. Despite the challenges presented by these less-common morphologies, flow diversion may be performed with a neurologic complication rate of about 10% and favorable long-term aneurysm occlusion rates.

Abstract BACKGROUND There is a paucity of literature regarding treatment options for extracranial pseudoaneurysms of the internal carotid artery (ICA). To date, Pipeline Embolization Device (PED; Medtronic Inc) use for the treatment of extracranial pseudoaneurysms of the ICA has only been reported from single-center case series. OBJECTIVE To evaluate the safety and efficacy of PED for the treatment of extracranial ICA pseudoaneurysms. METHODS This is a multicenter retrospective study involving 6 high-volume tertiary academic institutions in the United States. We analyzed patients with extracranial ICA pseudoaneurysms treated with PED between January 1, 2011, and January 1, 2019. Clinical assessment was performed pre- and postintervention using the modified Rankin Scale (mRS) and National Institution of Health Stroke Scale (NIHSS) at a minimum of 4-mo follow-up. RESULTS A total of 28 pseudoaneurysms with a mean diameter of 17.7 mm (range: 4.1-52.5 mm) were treated with PED in 24 patients at 6 participating centers. The mean age was 52.1 yr (17-73) ± 14.3 with 14 females and 10 males. At a mean of 21-mo (range 4-66 mo) follow-up, complete occlusion was achieved in 89% (n = 25/28), with near-complete occlusion (>90% occlusion) in the remainder. There were no periprocedural complications. Postprocedure NIHSS was 0 in 88% (n = 21/24) and 1 in 12% (n = 3/24) of patients, and mRS was 0 in 83% (n = 20/24) and 1 in 17% (n = 4/24) of patients. CONCLUSION The treatment of extracranial ICA pseudoaneurysms with PED is safe and effective in selected patients. Randomized controlled trials and prospective cohort studies are needed to establish the role of flow diversion for ICA pseudoaneurysms.

OBJECTIVE Traditionally, stent-assisted coiling and balloon remodeling have been the primary endovascular treatments for wide-necked intracranial aneurysms with complex morphologies. PulseRider is an aneurysm neck reconstruction device that provides parent vessel protection for aneurysm coiling. The objective of this study was to report early postmarket results with the PulseRider device. METHODS This study was a prospective registry of patients treated with PulseRider at 13 American neurointerventional centers following FDA approval of this device. Data collected included clinical presentation, aneurysm characteristics, treatment details, and perioperative events. Follow-up data included degree of aneurysm occlusion and delayed (> 30 days after the procedure) complications. RESULTS A total of 54 aneurysms were treated, with the same number of PulseRider devices, across 13 centers. Fourteen cases were in off-label locations (7 anterior communicating artery, 6 middle cerebral artery, and 1 A 1 segment anterior cerebral artery aneurysms). The average dome/neck ratio was 1.2. Technical success was achieved in 52 cases (96.2%). Major complications included the following: 3 procedure-related posterior cerebral artery strokes, a device-related intraoperative aneurysm rupture, and a delayed device thrombosis. Immediately postoperative Raymond-Roy occlusion classification (RROC) class 1 was achieved in 21 cases (40.3%), class 2 in 15 (28.8%), and class 3 in 16 cases (30.7%). Additional devices were used in 3 aneurysms. For those patients with 3- or 6-month angiographic follow-up (28 patients), 18 aneurysms (64.2%) were RROC class 1 and 8 (28.5%) were RROC class 2. CONCLUSIONS PulseRider is being used in both on- and off-label cases following FDA approval. The clinical and radiographic outcomes are comparable in real-world experience to the outcomes observed in earlier studies. Further experience is needed with the device to determine its role in the neurointerventionalist’s armamentarium, especially with regard to its off-label use.

Objective: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0–38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×10 3 cells/μL emerged as independent predictors for thrombus formation or embolism. Conclusions: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01947621.

Background Clinical characteristics and outcomes of takotsubo syndrome ( TTS ) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short‐ and long‐term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short‐ and long‐term mortality. A subanalysis was performed comparing long‐term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long‐term mortality was higher in patients with malignancy ( P <0.001), while short‐term outcome was comparable ( P =0.17). In a subanalysis, long‐term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies ( P =0.13). Malignancy emerged as an independent predictor of long‐term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS , and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL : http://www.clinicaltrial.gov . Unique identifier: NCT 01947621.

Abstract Aims We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). Methods and results We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P &lt; 0.001) and 5-year mortality (68.9% vs. 16.7%, P &lt; 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission. Conclusions Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

Purpose Ocular vestibular evoked myogenic potentials (oVEMPs) are used to describe utricular/superior vestibular nerve function; however, optimal recording parameters have not been fully established. This study investigated the effect of repetition rate on air-conducted oVEMPs. Method Ten healthy adults were evaluated using 500-Hz tone bursts (4-ms duration, Blackman gating, 122 dB pSPL). Four repetition rates were used (1.6, 4.8, 8.3, and 26.6 Hz) and resulting oVEMP response presence, amplitude, amplitude asymmetry, and n1/p1 latency were assessed. Results Response presence was significantly reduced for 26.6 Hz using monaural stimulation and for 8.3 Hz and 26.6 Hz for binaural stimulation. For monaural stimulation using 1.6, 4.8, and 8.3 Hz, no significant differences were noted for amplitude or latency. Responses obtained using binaural stimulation demonstrated a significant effect of rate on amplitude, with 8.3 Hz producing significantly reduced amplitude. Binaural amplitudes were significantly larger than monaural contralateral responses but with reduced response presence. No significant differences were noted for latency or amplitude asymmetry. Conclusion Using repetition rates of approximately 5 Hz or less may produce more consistent oVEMP response presence with minimal effects on amplitude for monaural or binaural recordings.

Abstract The Tec family kinase Itk is an important regulator of Ca2+ mobilization and is required for in vivo responses to Th2-inducing agents. Recent data also implicate Itk in TCR-induced regulation of the actin cytoskeleton. We have evaluated the requirements for Itk function in TCR-induced actin polarization. Reduction of Itk expression via small interfering RNA treatment of the Jurkat human T lymphoma cell line or human peripheral blood T cells disrupted TCR-induced actin polarization, a defect that correlated with decreased recruitment of the Vav guanine nucleotide exchange factor to the site of Ag contact. Vav localization and actin polarization could be rescued by re-expression of either wild-type or kinase-inactive murine Itk but not by Itk containing mutations affecting the pleckstrin homology or Src homology 2 domains. Additionally, we find that Itk is constitutively associated with Vav. Loss of Itk expression did not alter gross patterns of Vav tyrosine phosphorylation but appeared to disrupt the interactions of Vav with SLP-76. Expression of membrane-targeted Vav, Vav-CAAX, can rescue the small interfering RNA to Itk-induced phenotype, implicating the alteration in Vav localization as directly contributing to the actin polarization defect. These data suggest a kinase-independent scaffolding function for Itk in the regulation of Vav localization and TCR-induced actin polarization.