Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration.

Importance: Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose. Objective: To assess the risk of sICH following ischemic stroke in patients treated with tenecteplase compared to those treated with alteplase. Design, Setting, and Participants: This was a retrospective observational study using data from the large multicenter international Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) collaboration comprising deidentified data on patients with ischemic stroke treated with intravenous thrombolysis. Data from more than 100 hospitals in New Zealand, Australia, and the US that used alteplase or tenecteplase for patients treated between July 1, 2018, and June 30, 2021, were included for analysis. Participating centers included a mix of nonthrombectomy- and thrombectomy-capacity comprehensive stroke centers. Standardized data were abstracted and harmonized from local or regional clinical registries. Consecutive patients with acute ischemic stroke who were considered eligible and received thrombolysis at the participating stroke registries during the study period were included. All 9238 patients who received thrombolysis were included in this retrospective analysis. Main Outcomes and Measures: sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributed to parenchymal hematoma, subarachnoid, or intraventricular hemorrhage. Differences between tenecteplase and alteplase in the risk of sICH were assessed using logistic regression, adjusted for age, sex, NIHSS score, and thrombectomy. Results: Of the 9238 patients included in the analysis, the median (IQR) age was 71 (59-80) years, and 4449 patients (48%) were female. Tenecteplase was administered to 1925 patients. The tenecteplase group was older (median [IQR], 73 [61-81] years vs 70 [58-80] years; P < .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P < .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P < .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P < .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P < .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P < .01). Similar results were observed in both thrombectomy and nonthrombectomy subgroups. Conclusions and Relevance: In this large study, ischemic stroke treatment with 0.25-mg/kg tenecteplase was associated with lower odds of sICH than treatment with alteplase. The results provide evidence supporting the safety of tenecteplase for stroke thrombolysis in real-world clinical practice.

Implications of limiting mechanical thrombectomy to patients with emergent large vessel occlusion meeting top tier evidence criteria.

BACKGROUND: Recent guidelines for endovascular management of emergent large vessel occlusion (ELVO) award top tier evidence to the same selective criteria in recent trials. We aimed to understand how guideline adherence would have impacted treatment numbers and outcomes in a cohort of patients from a comprehensive stroke center. METHODS: A retrospective observational study was conducted using consecutive emergent endovascular patients. Mechanical thrombectomy (MT) was performed with stent retrievers or large bore clot aspiration catheters. Procedural outcomes were compared between patients meeting, and those failing to meet, top tier evidence criteria. RESULTS: 126 patients receiving MT from January 2012 to June 2015 were included (age 31-89 years, National Institutes of Health Stroke Scale (NIHSS) score 2-38); 62 (49%) patients would have been excluded if top tier criteria were upheld: pretreatment NIHSS score <6 (10%), Alberta Stroke Program Early CT score <6 (6.5%), premorbid modified Rankin Scale (mRS) score ≥2 (27%), M2 occlusion (10%), posterior circulation (32%), symptom to groin puncture >360 min (58%). 26 (42%) subjects had more than one top tier exclusion. Symptomatic intracerebral hemorrhage (sICH) and systemic hemorrhage rates were similar between the groups. 3 month mortality was 45% in those lacking top tier evidence compared with 26% (p=0.044), and 3 month mRS score 0-2 was 33% versus 46%, respectively (NS). After adjusting for potential confounders, top tier treatment was not associated with neurological improvement during hospitalization (ß -8.2; 95% CI -24.6 to -8.2; p=0.321), 3 month mortality (OR=0.38; 95% CI 0.08 to 1.41), or 3 month favorable mRS (OR=0.97; 95% CI 0.28 to 3.35). CONCLUSIONS: Our study showed that with strict adherence to top tier evidence criteria, half of patients may not be considered for MT. Our data indicate no increased risk of sICH and a potentially higher mortality that is largely due to treatment of patients with basilar occlusions and those treated at an extended time window. Despite this, good functional recovery is possible, and consideration of MT in patients not meeting top tier evidence criteria may be warranted.

Admission systolic blood pressure and outcomes in large vessel occlusion strokes treated with endovascular treatment.

BACKGROUND AND PURPOSE: High admission blood pressure (BP) levels have been associated with lower recanalization rates after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) with emergent large vessel occlusion (ELVO). We sought to evaluate the association of admission BP with early outcomes in patients with ELVO treated with EVT. METHODS: Consecutive patients with AIS presenting with ELVO in a tertiary stroke center during a 4-year period were prospectively evaluated. Admission systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using automated cuff recordings. A blinded neuroradiologist calculated the final infarct volume (FIV) using standardized ABC/2 methodology. A favorable functional outcome (FFO) at 3 months was defined as modified Rankin Scale score of 0-2. RESULTS: Our study population consisted of 116 patients with AIS (mean age 63±13 years, median NIH Stroke Scale score 17 points (IQR 14-21), median FIV 30 cm3 (IQR 8-94)). Higher admission SBP correlated with higher FIV (r +0.225; p=0.020). Patients with FFO had lower admission SBP (151±24 mm Hg vs 165±28 mm Hg; p=0.010), while admission SBP levels were higher in patients who died during hospitalization (169±34 mm Hg vs 156±24 mm Hg; p=0.043). A 10 mm Hg increment in admission SBP was independently (p=0.010) associated with an increase of 12 cm3 in FIV (95% CI 3 to 21) in multiple linear regression models adjusting for potential confounders. A 10 mm Hg increment in admission SBP was independently (p=0.012) associated with a lower likelihood of FFO at 3 months (OR 0.64; 95% CI 0.45 to 0.91) in multiple logistic regression models adjusting for potential confounders. CONCLUSIONS: Higher admission SBP is an independent predictor of increased FIV and lower likelihood of 3-month FFO in patients with ELVO treated with EVT.

Posterior circulation CT angiography collaterals predict outcome of endovascular acute ischemic stroke therapy for basilar artery occlusion.

INTRODUCTION: The natural history of acute ischemic stroke (AIS) due to basilar artery occlusion (BAO) is poor. Endovascular reperfusion therapy (EVT) improves recanalization rates in patients with emergent large vessel intracranial occlusion. OBJECTIVE: To examine the hypothesis that good collateral patterns identified by pretreatment CT angiography (CTA) might be associated with favorable outcomes after EVT. METHODS: We conducted a retrospective chart review of patients presenting with AIS due to BAO in a tertiary care stroke center during a 4-year period. BAO was diagnosed by CTA in all cases. Admission stroke severity was documented using the National Institute of Health Stroke Scale (NIHSS) score. Pretreatment collateral score for posterior circulation was defined as follows: 0, no posterior communicating artery (PCOM); 1, unilateral PCOM; 2, bilateral PCOM. Favorable outcome was defined as modified Rankin Scale score of 0-2 at 3 months. RESULTS: A total of 21 patients with AIS due to BAO (age range 31-84 years, median admission NIHSS score: 18 points, range 2-38) underwent EVT. Eleven of 21 patients (52.4%) had bilateral PCOMs, while unilateral PCOM was seen in 3 patients (14.3%). Patients with bilateral PCOMs tended (p=0.261) to have less severe stroke at admission than those with absent/unilateral PCOM (median NIHSS score 18 vs 27 points). Neurological improvement during hospitalization (quantified by the median decrease in NIHSS score) and the rate of 3-month functional independence were greater in patients with good collaterals (16 vs 0 points (p=0.016) and 72.7% vs 0% (p=0.001)). CONCLUSIONS: The presence of bilateral PCOMs on pretreatment CTA appears to be associated with more favorable outcomes in BAO treated with EVT.

Separating the wheat from the chaff: region of interest combined with metal artifact reduction for completion angiography following cerebral aneurysm treatment.

INTRODUCTION: Following complicated endovascular or microsurgical treatments, assessment of radiographic outcome can be challenging due to device resolution and metallic artifact. Two-dimensional and three-dimensional angiography can reveal information about flow and aneurysm obliteration, but may be limited by beam hardening, overlapping vessels, and image degradation in the region of metallic implants. In this study, we investigated the combination of a collimated volumetric imaging (volume of interest, VOI) protocol followed by metal artifact reduction (MAR) post-processing to evaluate the correct positioning of stents, flow diverters, coils, and clips while limiting the radiation dose to the patient. METHODS: 9 patients undergoing 10 procedures were included in our study. All patients underwent endovascular or surgical treatment of a cerebral aneurysm involving stents, flow diverting stents, coils, and/or clips followed by either immediate or early postoperative evaluation of our protocol. RESULTS: Image datasets corrected for metallic artifacts (VOI-MAR) were judged to be better-a statistically significant finding-than image datasets only corrected for field of view truncation (VOI alone). Qualitatively, images were more interpretable and informative with regards to device position and apposition to the vessel wall for those cases involving a pipeline, and with regards to encroachment on the parent artery and possible residual aneurysm, in all cases. CONCLUSIONS: VOI acquisition combined with MAR post-processing provides for accurate and informative evaluation of cerebral aneurysm treatment while limiting the radiation dose to patients.

Comparison of Intraoperative Indocyanine Green Angiography and Digital Subtraction Angiography for Clipping of Intracranial Aneurysms.

BACKGROUND: Residual aneurysm after microsurgical clipping carries a risk of aneurysm growth and rupture. Digital subtraction angiography (DSA) remains the standard to determine the adequacy of clipping. Intraoperative indocyanine green (ICG) angiography is increasingly utilized to confirm optimal clip positioning across the neck and to evaluate the adjacent vasculature. OBJECTIVE: We evaluated the correlation between ICG and DSA in clipped intracranial aneurysms. METHODS: A retrospective study of patients who underwent craniotomy and microsurgical clipping of intracranial aneurysms with ICG for 2 years. Patient characteristics, presentation details, operative reports, and pre- and postclipping angiographic images were reviewed to determine the adequacy of the clipping. RESULTS: Forty-seven patients underwent clipping with ICG and postoperative DSA: 57 aneurysms were clipped; 23 patients (48.9%) presented with subarachnoid hemorrhage. Nine aneurysms demonstrated a residual on DSA not identified on ICG (residual sizes ranged from 0.5 to 4.3 mm; average size: 1.8 mm). Postoperative DSA demonstrated no branch occlusions. CONCLUSION: Intraoperative ICG is useful in the clipping of intracranial aneurysms to ensure a gross patency of branch vessels; however, the presence of residual aneurysms and subtle changes in flow in branch vessels is best seen by DSA. This has important clinical implications with regard to follow-up imaging and surgical/endovascular management.

Endovascular treatment of cerebral venous thrombosis: Contemporary multicenter experience.

Endovascular therapy of cerebral venous thrombosis using modern approaches to intracranial recanalization, such as stent retrievers and aspiration thrombectomy, is not well described. We performed a retrospective review of data for consecutive patients with venous sinus thrombosis who underwent endovascular treatment between 1 January 2010 and 31 December 2013 at participating institutions. We identified a total of 13 patients with a diagnosis of cerebral venous thrombosis. The most frequently utilized type of endovascular intervention was the Penumbra aspiration system (Penumbra Inc., Alameda, California, USA) (nine cases), followed by local infusion of tissue plasminogen activator (bolus and/or drip in six cases) and stent retrievers (Solitaire FR (Covidien, Irvine, California, USA) in three cases and Trevo (Stryker, Kalamazoo, Michigan, USA) in one case). Overall, multimodality treatment (two or more different types of devices or approaches) was performed in 62% of cases. Follow-up data were available for 11 patients; of those, five had a favorable clinical outcome (defined as modified Rankin Scale score of 0-2) and three patients died. Various endovascular approaches are utilized in current clinical practice. A multimodal approach to endovascular therapy for the treatment of cerebral venous thrombosis resulted in partial or complete restoration of flow in all cases, yet the mortality rate of 27% indicates the need for improvement in recanalization strategies for this disorder.

Rupture of giant vertebrobasilar aneurysm following flow diversion: mechanical stretch as a potential mechanism for early aneurysm rupture.

A patient with a giant symptomatic vertebrobasilar aneurysm was treated by endoscopic third ventriculostomy for obstructive hydrocephalus followed by treatment of the aneurysm by flow diversion using a Pipeline Embolization Device. After an uneventful procedure and initial periprocedural period, the patient experienced an unexpected fatal subarachnoid hemorrhage 1 week later. Autopsy demonstrated extensive subarachnoid hemorrhage and aneurysm rupture (linear whole wall rupture). The patent Pipeline Embolization Device was in its intended location, as was the persistent coil occlusion of the distal left vertebral artery. The aneurysm appeared to rupture in a linear manner and contained a thick large expansile clot that seemed to disrupt or rupture the thin aneurysm wall directly opposite the basilar artery/Pipeline Embolization Device. We feel the pattern of aneurysm rupture in our patient supports the idea that the combination of flow diversion and the resulting growing intra-aneurysmal thrombus can create a mechanical force with the potential to cause aneurysm rupture.

Distal aspiration with retrievable stent assisted thrombectomy for the treatment of acute ischemic stroke.

OBJECTIVE: Flexible large lumen aspiration catheters and stent retrievers have recently become available in the USA for the revascularization of large vessel occlusions presenting within the context of acute ischemic stroke (AIS). We describe a multicenter experience using a combined aspiration and stent retrieval technique for thrombectomy. DESIGN: A retrospective analysis to identify patients receiving combined manual aspiration and stent retrieval for treatment of AIS between August 2012 and April 2013 at six high volume stroke centers was conducted. Outcome variables, including recanalization rate, post-treatment National Institutes of Health Stroke Scale (NIHSS) score, symptomatic intracranial hemorrhage, discharge 90 day modified Rankin Scale (mRS) score, and mortality were evaluated. RESULTS: 105 patients were found that met the inclusion criteria for this retrospective study. Successful recanalization (Thrombolysis in Cerebral Infarction score 2B) was achieved in 92 (88%) of these patients. 44% of patients had favorable (mRS score 0-2) outcomes at 90 days. There were five (4.8%) symptomatic intracerebral hemorrhages and three procedure related deaths (2.9%). CONCLUSIONS: Mechanical thrombectomy utilizing combined manual aspiration with a stent retriever is an effective and safe strategy for endovascular recanalization of large vessel occlusions presenting within the context of AIS.

Rupture of giant vertebrobasilar aneurysm following flow diversion: mechanical stretch as a potential mechanism for early aneurysm rupture.

A patient with a giant symptomatic vertebrobasilar aneurysm was treated by endoscopic third ventriculostomy for obstructive hydrocephalus followed by treatment of the aneurysm by flow diversion using a Pipeline Embolization Device. After an uneventful procedure and initial periprocedural period, the patient experienced an unexpected fatal subarachnoid hemorrhage 1 week later. Autopsy demonstrated extensive subarachnoid hemorrhage and aneurysm rupture (linear whole wall rupture). The patent Pipeline Embolization Device was in its intended location, as was the persistent coil occlusion of the distal left vertebral artery. The aneurysm appeared to rupture in a linear manner and contained a thick large expansile clot that seemed to disrupt or rupture the thin aneurysm wall directly opposite the basilar artery/Pipeline Embolization Device. We feel the pattern of aneurysm rupture in our patient supports the idea that the combination of flow diversion and the resulting growing intra-aneurysmal thrombus can create a mechanical force with the potential to cause aneurysm rupture.

Intraprocedural parenchymal blood volume as a marker of reperfusion status in acute ischemic stroke intervention.

Parenchymal blood volume (PBV) mapping with flat panel detectors may provide real-time estimates of tissue perfusion during endovascular ischemic stroke procedures. We present two cases of acute middle cerebral artery (MCA) occlusion to demonstrate how PBV may: (1) be used in acute stroke; (2) influence intraprocedural decision-making; and (3) potentially serve as a predicator of clinical outcome. Both cases were successfully recanalized with endovascular embolectomy. Intraprocedural PBV maps were obtained immediately before and after recanalization. Pre-intervention reductions in PBV were seen throughout the MCA territory in both cases, with significant improvement in PBV in one case with good radiographic and clinical outcome and a lack of improvement in PBV in the second case with a large infarct volume. PBV deficit normalization may occur with recanalization of the parent artery and probably represents successful reperfusion. Baseline PBV maps should therefore be interpreted with caution and not interpreted to represent irreversible core infarct.

Serial endovascular embolization as stand-alone treatment of a sacral aneurysmal bone cyst.

Aneurysmal bone cysts (ABCs) are destructive cystic lesions of the bone and are common in children. They are expansile in nature and, therefore, may become symptomatic. These have traditionally been treated surgically; but recently, endovascular embolization has shown promise as a stand-alone therapy. The authors describe a case of an ABC highlighting the effectiveness and efficiency of endovascular treatment. A 16-year-old boy was referred for a 4-month history of radiating back pain and urinary hesitancy. Findings from his neurological examination were normal, but he had problems ambulating because of pain. Magnetic resonance imaging and CT scanning showed a cystic mass in the sacrum; a biopsy was performed and diagnosis of ABC was confirmed. Treatment options were then discussed with the family. The patient underwent 2 endovascular embolizations in approximately 1 month: Onyx 18 was involved in the first session, and N-butyl cyanoacrylate glue was used in the second session. After the first treatment, the patient experienced a dramatic decrease in pain and concomitant improvement in function. The patient went from being mildly symptomatic after the first treatment to completely asymptomatic after the second treatment. Clinical and radiographic follow-up obtained at 2, 6, and 18 months after initial treatment revealed the patient to be asymptomatic with progressive ossification. Endovascular treatment can be effective in treating symptomatic cases of ABC in which surgery would carry significant risk. Selective arterial embolization can promote sclerosis and result in an immediate and significant decrease in pain.

Acute carotid stenting for treatment of stuttering transient ischemic attacks after recent carotid endarterectomy.

Carotid endarterectomy (CEA) is the established standard to treat occlusive extracranial atherosclerotic carotid disease. Complications of CEA must be recognized and dealt with efficiently due to the potentially catastrophic neurologic sequelae. A 67-year-old African American man was transferred from an outside hospital for an acute stroke. He had initially presented with a small right frontal subcortical infarct and had undergone a right CEA 2 days prior to transfer. He had a fluctuating examination with left-sided hemiplegia to slight hemiparesis and inconsistent neglect. Head CT demonstrated a watershed infarct of the right hemisphere. CT angiography demonstrated high grade stenosis at the distal aspect of the CEA anastomosis. He was promptly taken for angiography and underwent acute stenting of the right internal carotid artery. This case demonstrates that carotid artery stenting is a safe management strategy for the treatment of complications associated with failed distal anastomosis during CEA.

Acute carotid stenting for treatment of stuttering transient ischemic attacks after recent carotid endarterectomy.

Carotid endarterectomy (CEA) is the established standard to treat occlusive extracranial atherosclerotic carotid disease. Complications of CEA must be recognized and dealt with efficiently due to the potentially catastrophic neurologic sequelae. A 67-year-old African American man was transferred from an outside hospital for an acute stroke. He had initially presented with a small right frontal subcortical infarct and had undergone a right CEA 2 days prior to transfer. He had a fluctuating examination with left-sided hemiplegia to slight hemiparesis and inconsistent neglect. Head CT demonstrated a watershed infarct of the right hemisphere. CT angiography demonstrated high grade stenosis at the distal aspect of the CEA anastomosis. He was promptly taken for angiography and underwent acute stenting of the right internal carotid artery. This case demonstrates that carotid artery stenting is a safe management strategy for the treatment of complications associated with failed distal anastomosis during CEA.

Intraprocedural parenchymal blood volume as a marker of reperfusion status in acute ischemic stroke intervention.

Parenchymal blood volume (PBV) mapping with flat panel detectors may provide real-time estimates of tissue perfusion during endovascular ischemic stroke procedures. We present two cases of acute middle cerebral artery (MCA) occlusion to demonstrate how PBV may: (1) be used in acute stroke; (2) influence intraprocedural decision-making; and (3) potentially serve as a predicator of clinical outcome. Both cases were successfully recanalized with endovascular embolectomy. Intraprocedural PBV maps were obtained immediately before and after recanalization. Pre-intervention reductions in PBV were seen throughout the MCA territory in both cases, with significant improvement in PBV in one case with good radiographic and clinical outcome and a lack of improvement in PBV in the second case with a large infarct volume. PBV deficit normalization may occur with recanalization of the parent artery and probably represents successful reperfusion. Baseline PBV maps should therefore be interpreted with caution and not interpreted to represent irreversible core infarct.