Impact of Balloon Guide Catheter Use on Clinical and Angiographic Outcomes in the STRATIS Stroke Thrombectomy Registry.

Background and Purpose- Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods- STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0-2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results- Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P=0.001) and distal access catheter (83/235 [35%]; P=0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P<0.001) and distal access catheter (129/234 [55%]; P=0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P=0.007) and distal access catheter (113/218 [52%]; P=0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions- BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry.

BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. METHODS: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. RESULTS: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Brain iron metabolism and brain injury following subarachnoid hemorrhage: iCeFISH-pilot (CSF iron in SAH).

INTRODUCTION: Iron-mediated oxidative damage has been implicated in the genesis of cerebral vasospasm in animal models of SAH. We sought to explore the relationship between levels of non-protein bound iron in cerebrospinal fluid and the development of brain injury in patients with aneurysmal SAH. METHODS: Patients admitted with aneurysmal subarachnoid hemorrhage to a Neurointensive care unit of an academic, tertiary medical center, with Hunt and Hess grades 2-4 requiring ventriculostomy insertion as part of their clinical management were included in this pilot study. Samples of cerebrospinal fluid (CSF) were obtained on days 1, 3, and 5. A fluorometric assay that relies on an oxidation sensitive probe was used to measure unbound iron, and levels of iron-handling proteins were measured by means of enzyme-linked immunosorbent assays. We prospectively collected and recorded demographic, clinical, and radiological data. RESULTS: A total of 12 patients were included in this analysis. Median Hunt and Hess score on admission was 3.5 (IQR: 1) and median modified Fisher scale score was 4 (IQR: 1). Seven of 12 patients (58 %) developed delayed cerebral ischemia (DCI). Day 5 non-transferrin bound iron (NTBI) (7.88 ± 1 vs. 3.58 ± 0.8, p = 0.02) and mean NTBI (7.39 ± 0.4 vs. 3.34 + 0.4 p = 0.03) were significantly higher in patients who developed DCI. Mean redox-active iron, as well as day 3 levels of redox-active iron correlated with development of angiographic vasospasm in logistic regression analysis (p = 0.02); while mean redox-active iron and lower levels of ceruloplasmin on days 3, 5, and peak concentration were correlated with development of deep cerebral infarcts. CONCLUSIONS: Our preliminary data indicate a causal relationship between unbound iron and brain injury following SAH and suggest a possible protective role for ceruloplasmin in this setting, particularly in the prevention of cerebral ischemia. Further studies are needed to validate these findings and to probe their clinical significance.

Ruptured Distal Medial Lenticulostriate Artery Aneurysm Treated With Transcortical-Transventricular Approach.

We report a case of a 48-year-old female who presented with abulia and headaches. Head CT (HCT) demonstrated a left caudate intracerebral hemorrhage (ICH) with extension into the left lateral ventricle. Diagnostic cerebral angiogram showed a left distal medial lenticulostriate artery (MLSA) aneurysm with remote left parietal Spetzler-Martin grade 3 arteriovenous malformation (AVM). The patient underwent an endoscope-assisted transcortical-transventricular approach to the distal MLSA aneurysm with complete excision and evacuation of the intraventricular hemorrhage (IVH) postoperatively; the patient had no further neurologic deficits and recovered well from her initial hemorrhage. Ruptured MLSA aneurysms are a very rare cause of spontaneous ICH. Urgent treatment of these aneurysms is needed to prevent further rebleeding. We present a novel operative technique utilizing an endoscope-assisted transcortical-transventricular approach to a ruptured distal MLSA aneurysm with successful excision of the aneurysm.

Intracranial Atherosclerosis: A Disease of Functional, not Anatomic Stenosis? How Trans-Stenotic Pressure Gradients Can Help Guide Treatment.

BACKGROUND: Most trials have assessed intracranial atherosclerotic disease (ICAD) severity based on angiographic stenosis. However, anatomic stenosis might not accurately identify the actual state of functional post-stenotic flow limitation. OBJECTIVE: To investigate whether angiographic stenosis correlates with physiologic distal flow limitation, measured as trans-stenotic pressure gradients, in ICAD patients. METHODS: In patients referred for endovascular treatment of anterior circulation symptomatic ICAD who failed maximal medical therapy (MMT) per SAMMPRIS (Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis) criteria, angiographic luminal diameters and percentages of stenosis were correlated with trans-stenotic pressure gradients, calculated as distal/proximal pressure ratios (DPPR) and proximal minus distal pressure gradients (PDPG), by way of Spearman correlation coefficients. RESULTS: Nine patients (3 men, 6 women) were evaluated. Atherosclerotic lesions' locations included internal carotid artery in 5 subjects (2 cavernous, 3 supraclinoid) and proximal middle cerebral artery (M1) in 4 patients. Mean percentage of stenosis was 80 ± 8% (range 75%-94%). Minimal lumen diameter at the most stenotic ICAD site ranged from 0.2 to 0.9 mm (0.59 ± 0.41 mm). DPPR ranged from 0.38 to 0.63 (0.56 ± 0.14). PDPG ranged from 35 to 57 mm Hg (50 ± 8 mm Hg). Spearman coefficients showed no correlation between DPPR or PDPG and angiographic minimal luminal diameters or percentages of stenosis. There were no procedural complications related to trans-stenotic pressure measurements. CONCLUSION: Angiographic stenosis does not reflect the physiologic severity of distal flow limitation in patients with ICAD. Hemodynamic assessment using trans-stenotic pressure ratios and gradients may serve as a more reliable predictive biomarker for MMT failure and response to revascularization.

Off-Label Use of the WEB Device.

OBJECTIVE: We present our initial experience with the off-label use of the Woven EndoBridge (WEB) device. METHODS: We performed a retrospective study from 2 institutions of patients with intracranial aneurysms who underwent treatment with the WEB device alone or in conjunction with stenting and/or coiling in an off-labeled location. RESULTS: Eleven patients with 12 aneurysms were included. Four (30.8%) aneurysms presented ruptured. Off-labeled locations included 3 aneurysms in the posterior communicating artery, 3 in the supraclinoid ophthalmic artery, 2 in the pericallosal artery, 2 in the posterior inferior cerebellar artery, 1 at the vertebrobasilar junction, and 1 in the cavernous internal carotid artery. Mean dome-to-neck ratio was 1.91 ± 0.9. Average duration of the procedure was 63.9 ± 29.6 minutes. Femoral route was used in 61.5%, and radial access in 48.5% of cases. Five procedures (41.7%) were performed under monitored anesthesia care. We had 1.33 attempts per aneurysm. WEB embolization was supplemented with coiling in 2 cases (16.67%) and stenting in 1 case (8.3%). Based on the O'Kelly-Marotta ("OKM") grading scale, we report a rate of 0% for grade 1, 33.3% for grade 2, and 33.3% for grade 3. Postprocedural occlusion was complete in 4 (33.3%) and adequate in 8 (66.6%) patients. No procedure-related deaths or symptomatic complications were reported. CONCLUSIONS: The WEB device was successfully deployed in off-labeled locations, including posterior communicating artery, ophthalmic artery, and pericallosal aneurysms. The efficacy of this usage must be evaluated in multicenter prospective studies, but our preliminary results are promising. Correct characterization of the aneurysm size/morphology, as well as awareness of possible adjunct treatments, are crucial for successful intervention.