Recanalization Of Large Vessel Occlusions Research Articles

Corrigendum: Machine learning to predict futile recanalization of large vessel occlusion before and after endovascular thrombectomy

Corrigendum: Machine learning to predict futile recanalization of large vessel occlusion before and after endovascular thrombectomy

RapidpulseTM cyclic aspiration system for acute ischemic stroke due to large vessel occlusions.

The best strategy to achieve optimal reperfusion outcomes during mechanical thrombectomy remains to be defined. The RapidPulseTM Cyclic Aspiration System is a novel technology, delivering high-frequency pulsed vacuum forces to increase the efficiency of aspiration thrombectomy. Prospective, multicenter, open-label, core lab-adjudicated, two-arm study comparing safety and efficacy of a feasibility version of the RapidPulseTM system compared with contemporary controls. Primary endpoint was the rate of mTICI ≥ 2c after first-pass effect (FPE). Additional efficacy endpoints were the rates of mTICI 2b after first pass (modified FPE (mFPE)), last pass with study device defined as frontline technical success, and after all passes including rescue therapy. The primary safety endpoints included symptomatic ICH (sICH) within 24 h post-procedure. Between February 2022 to December 2022, 80 subjects were consented and enrolled in the study (n = 40 treatment arm, n = 40 control arm). In the intent to treat (ITT) population, mean age was 67.8 ± 11.5 years; 19 (47.5%) were male. Median NIHSS score was 16 (IQR: 13-22). Median ASPECTS score was 9 (IQR: 8-10). The rate of mTICI ≥ 2c after first pass was 53.9% in ITT population (60.0% in per-protocol population) versus 38.5% in the corresponding control population. Functional independence (mRS 0-2) at 90 days was achieved in 61.1% (22/36) in the RapidPulseTM arm and 52.8% (19/36) in the control arm. In the RapidPulseTM arm, no sICH within 24 h and no device-related morbidity or mortality occurred. Preliminary data suggests RapidPulseTM Aspiration System is highly effective and safe for recanalization of large vessel occlusions.

Strict blood pressure control following thrombectomy is associated with neuronal injury and poor functional outcome.

Mechanical thrombectomy (MT) has become standard treatment in acute ischemic stroke due to large vessel occlusion (LVO). However, optimal blood pressure (BP) management following successful recanalization remains unclear. We aim to investigate the association of strictly achieving BP targets of ≤160/90 mmHg with the extent of neuronal loss and functional outcome. In patients prospectively enrolled in the Gutenberg-Stroke-Study (May 2018-November 2019), BP was measured half-hourly for 24 h following MT. Based on achieving BP target of ≤160/90 mmHg, patients with successful recanalization of LVO were divided into "low-BP" group (BP ≤ 160/90 mmHg) or "high-BP" group (BP > 160/90 mmHg). Neuronal loss was quantified by serum-based measurement of neurofilament light chain (sNfL) after three days. BP groups and association of BP parameters with sNfL were investigated by correlation analyses and multiple regression modeling. Of 253 enrolled patients (mean age 73.1 ± 12.9 years, 53.4% female), 165 met inclusion criteria. 21.2% (n = 35) strictly achieved "low-BP" target. "low-BP" was associated with unfavorable functional outcome at 90-day follow-up (aOR [95%CI]: 5.88 [1.88-18.32], p = 0.002) and decreased health-related quality of life (mean EQ-5D-index 0.45 ± 0.28 vs 0.63 ± 0.31, p = 0.009). sNfL levels were increased in "low-BP" patients (median [IQR] 239.7 [168.4-303.4] vs 118.8 [52.5-220.5] pg/mL, p = 0.026). Hypotensive episodes were more frequent in the "low-BP" group (48.6% vs 29.2%, p = 0.031). sNfL level could identify patients who had experienced hypotensive episodes with high discriminative ability (AUC [95%CI]: 0.68 [0.56-0.78], p = 0.007). Strict BP control (≤160/90 mmHg) within 24 h following successful recanalization of LVO by MT is associated with increased neuronal injury, displayed by higher sNfL levels, and poorer functional outcome, potentially indicating hypotension-induced neuronal loss during post-MT phase.

Series of fast reperfusion with simultaneous proximal and distal aspiration in patients with acute ischemic stroke

BackgroundVarious endovascular techniques for the recanalization of large vessel occlusion in patients with acute ischemic stroke have been established. In this series a combined distal and proximal aspiration technique was used as a novel approach. The aim of this study was to investigate, whether this technique achieves reperfusion faster and if embolization in distal territories can be reduced.ResultsThe success of the treatment was dependent on the localization of the clot. Fast reperfusion was achieved in all patients when the clot was located at the level of the middle cerebral artery. Aspiration failed when the vessel occlusion was located at the level of the carotid-T and subsequent rescue treatment was performed. Median groin puncture to reperfusion time was 20 min (range 9–66). No Embolization to new territories (ENT) and no intracerebral hemorrhage were observed. One patient died. In all other patients favorable neurological outcome was observed as measured by a modified Rankin score at discharge (mRS 0, range 0–1).ConclusionSimultaneous proximal and distal aspiration appears to be fast and effective. Furthermore, it reliably prevented ENT in patients with vessel occlusion at the level of the middle cerebral artery in a small cohort.

The proximal balloon occlusion together with direct thrombus aspiration (protect plus) technique: Experience at a tertiary comprehensive stroke center.

Timely restoration of cerebral blood flow using reperfusion therapy is the most effective maneuver for salvaging penumbra. We re-evaluated the previously described PROTECT (PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy) Plus technique at a tertiary comprehensive stroke center. We retrospectively analyzed all patients who underwent mechanical thrombectomy with stentrievers between May 2011 and April 2020. Patients were divided between those who underwent PROTECT Plus and those who did not (proximal balloon occlusion with stent retriever only). We compared the groups in terms of reperfusion, groin to reperfusion time, symptomatic intracranial hemorrhage (sICH), modified Rankin Scale (mRS) score at discharge. Within the study period, 167 (71.4%) PROTECT Plus and 67 (28.6%) non-PROTECT patients which met our inclusion criteria. There was no statistically significant difference in the number of patients with successful reperfusion (mTICI >2b) between the techniques (85.0% vs 82.1%; p = 0.58). The PROTECT Plus group had lower rates of mRS ≤2 at discharge (40.1% vs 57.6%; p = 0.016). The rate of sICH was comparable (p = 0.35) between the PROTECT Plus group (7.2%) and the non-PROTECT group (3.0%). The PROTECT Plus technique using a BGC, a distal reperfusion catheter and stent retriever is feasible for recanalization of large vessel occlusions. Successful recanalization, first-pass recanalization and complication rates are similar between PROTECT Plus and non-PROTECT stent retriever techniques. This study adds to an existing body of literature detailing techniques that use both a stent retriever and a distal reperfusion catheter to maximize recanalization for patients with large vessel occlusions.

Abstract Number ‐ 249: Differential Ischemic Vulnerability depicted by White Matter‐Sparing Infarction following Alteplase Recanalization

Introduction Gray and white matter possess different ischemic thresholds and therefore will undergo infarction at different rates of cerebral blood flow. We present a patient that presented with a large vessel occlusion and recanalized following alteplase administration within hours of symptom onset. Follow‐up imaging revealed a white matter‐sparing infarction, visually depicting the differential ischemic vulnerability between gray and white matter. Methods Case Report. Results An 83‐year‐old woman with a medical history of dementia, hypertension, and atrial fibrillation, not on anticoagulation due to recent gastrointestinal hemorrhage, presented with speech difficulty and right sided weakness. Her blood pressure was elevated at 170/86 and neurological exam demonstrated mixed aphasia, right homonymous hemianopia, left gaze deviation, and dense right hemiparesis with a National Institutes of Health Stroke Scale of 23. Non‐contrast CT of the head showed a hyperdense left terminal internal cerebral artery (ICA) and was otherwise unremarkable (Figure 1, A). CT angiography of the head and neck revealed an ICA “T” occlusion with no flow seen at the ICA terminus, the left anterior cerebral (A1) and middle cerebral (M1) segments (Figure 1, B). She was treated with intravenous alteplase 132 minutes from when she was last known normal. She was transferred to our comprehensive stroke center for mechanical thrombectomy, however, catheter angiography showed spontaneous recanalization of left ICA (Figure 1, C). Brain MRI the following day showed a white matter‐sparing infarction involving the left ICA territory (Figure 1, D‐F). She was discharged to rehab with moderate improvement in her aphasia and right hemiparesis. Conclusions This case visually depicts the differential ischemic vulnerability between gray and white matter since recanalization likely occurred at a cerebral blood flow level below the gray matter ischemic threshold while remaining above the white matter threshold. While pretreatment ischemic core volumes are inversely correlated with functional outcomes after recanalization of large vessel occlusions,1 selective white matter‐sparing infarction on post‐treatment MRI is associated with more favorable outcomes.2 Predicting ischemic core volume with perfusion imaging using the same CBF threshold for both gray and white matter may over‐estimate the ischemic core if CBF is between the gray and white matter thresholds.

Abstract TP6: Recanalization Of Large Vessel Occlusion After Intravenous Alteplase Therapy In Acute Ischemic Stroke Patients Transferred From Primary Stroke Centers

Background and Purpose: Early recanalization of occluded intracranial arteries predicts favorable outcome in acute ischemic stroke (AIS) patients treated with intravenous alteplase therapy within 4.5 hours from stroke onset. Prior studies have shown recanalization of large vessel occlusion (LVO) with alteplase ranging from 0% for internal carotid artery and 33% for distal blood vessels. We performed an analysis to examine the characteristics of stroke patients and the location of LVO that predicts early recanalization in patients treated with intravenous alteplase alone. Methods: This single-center, retrospective study solely included AIS patients with LVO who were transferred to our institution for mechanical thrombectomy evaluation after treated with alteplase at a primary stroke center between January 2019 and January 2021. Recanalization was identified by repeated computed tomographic angiography (CTA) or digital subtraction angiography (DSA) at our institution upon arrival. Results: One hundred and six patients were included in the analysis, 15 (14.1%) patients had partial or complete recanalization of LVO. Cardioembolic was the most common cause of ischemic stroke (46%), followed by large vessel atherosclerosis (33%) in this group. They were more likely to have a medical history of hypertension (73.3% vs. 59.3%), better baseline function as measured by pre-modified Rankin Score 0-2 (73.3% vs. 68.1%), and receive early treatment (105 minutes vs. 135 minutes), compared to their counterparts with no recanalization. Proximal and distal middle cerebral artery had the same rate of recanalization in this cohort. Conclusion: The highest incidence of early recanalization of occluded intracranial arteries was found in cardioembolic strokes with middle cerebral artery being the most common location of recanalization. Early recanalization with intravenous alteplase was also associated with improved functional recovery at discharge.

Preliminary experience with recanalization of large vessel occlusion due to underlying long-segment dissection using a standby microwire technique.

This study aimed at investigating a novel standby microwire technique to facilitate revascularization of large vessel occlusion due to underlying long-segment dissection. Patients with acute ischemic stroke with emergent large vessel occlusion (ELVO) due to underlying long-segment dissection were screened from the prospectively established database between January 2021 and May 2022. The clinical and radiological data of eligible patients who underwent endovascular treatment by using a standby microwire technique were investigated. Of the 165 acute ischemic stroke patients who underwent mechanical thrombectomy, the standby microwire technique was used in five patients aged 33-55 years old with occlusion due to underlying long-segment dissection. Of them, three patients were diagnosed with tandem lesions and three were located at the anterior circulation. A 300 cm exchange microwire was used as the standby microwire. Stent deployment was performed in all five patients. Groin puncture to reperfusion time ranged from 10-68 min. Technical success and favorable clinical outcomes were achieved in all five patients (100%). No technique-related complication was observed. Our preliminary experience showed that the standby microwire technique was a useful ancillary approach to facilitate the revascularization of large vessel occlusion due to underlying long-segment dissection.

Machine learning to predict futile recanalization of large vessel occlusion before and after endovascular thrombectomy.

Background and purposeFutile recanalization occurs when the endovascular thrombectomy (EVT) is a technical success but fails to achieve a favorable outcome. This study aimed to use machine learning (ML) algorithms to develop a pre-EVT model and a post-EVT model to predict the risk of futile recanalization and to provide meaningful insights to assess the prognostic factors associated with futile recanalization.MethodsConsecutive acute ischemic stroke patients with large vessel occlusion (LVO) undergoing EVT at the National Advanced Stroke Center of Nanjing First Hospital (China) between April 2017 and May 2021 were analyzed. The baseline characteristics and peri-interventional characteristics were assessed using four ML algorithms. The predictive performance was evaluated by the area under curve (AUC) of receiver operating characteristic and calibration curve. In addition, the SHapley Additive exPlanations (SHAP) approach and partial dependence plot were introduced to understand the relative importance and the influence of a single feature.ResultsA total of 312 patients were included in this study. Of the four ML models that include baseline characteristics, the “Early” XGBoost had a better performance {AUC, 0.790 [95% confidence intervals (CI), 0.677–0.903]; Brier, 0.191}. Subsequent inclusion of peri-interventional characteristics into the “Early” XGBoost showed that the “Late” XGBoost performed better [AUC, 0.910 (95% CI, 0.837–0.984); Brier, 0.123]. NIHSS after 24 h, age, groin to recanalization, and the number of passages were the critical prognostic factors associated with futile recanalization, and the SHAP approach shows that NIHSS after 24 h ranks first in relative importance.ConclusionsThe “Early” XGBoost and the “Late” XGBoost allowed us to predict futile recanalization before and after EVT accurately. Our study suggests that including peri-interventional characteristics may lead to superior predictive performance compared to a model based on baseline characteristics only. In addition, NIHSS after 24 h was the most important prognostic factor for futile recanalization.

Clinical and radiological factors predicting stroke outcome after successful mechanical intervention in anterior circulation.

The recanalization effect of large-vessel occlusion (LVO) in anterior circulation is well documented but only some patients benefit from endovascular treatment. We analysed clinical and radiological factors determining clinical outcome after successful mechanical intervention. We included 146 patients from the Prague 16 study enrolled from September 2012 to December 2020, who had initial CT/CTA examination and achieved good recanalization status after mechanical intervention (TICI 2b-3). One hundred and six (73%) patients achieved a good clinical outcome (modified Rankin Scale 0–2 in 3 months). It was associated with age, leptomeningeal collaterals (LC), onset to intervention time, ASPECTS, initial NIHSS, and leukoaraiosis (LA) in univariate analysis. The regression model identified good collateral status [odds ratio (OR) 5.00, 95% confidence interval (CI) 1.91–13.08], late thrombectomy (OR 0.24, 95% CI 0.09–0.65), LA (OR 0.44, 95% CI 0.19–1.00), ASPECTS (OR 1.45, 95% CI 1.08–1.95), and NIHSS score (OR 0.86, 95% CI 0.78–0.95) as independent outcome determinants. In the late thrombectomy subgroup, 14 out of 33 patients (42%) achieved a favourable clinical outcome, none of whom with poor collateral status. The presence of LC and absence of LA predicts a good outcome in acute stroke patients after successful recanalization of LVO in anterior circulation. Late thrombectomy was associated with higher rate of unfavourable clinical outcome. Nevertheless, collateral status in this subgroup was validated as a reliable selection criterion.

Collateral Circulation Augmentation and Neuroprotection as Adjuvant to Mechanical Thrombectomy in Acute Ischemic Stroke.

Mechanical thrombectomy (MT)-mediated endovascular recanalization has dramatically transformed treatment and outcomes after acute ischemic stroke caused by a large vessel occlusion (LVO). Current guidelines recommend MT up to 24 hours from stroke onset in carefully selected patients based on favorable clinical and imaging parameters. Despite optimal patient selection and low complication rates with current recanalization technology, approximately 1 in 2 patients with LVO stroke do not achieve functional independence at 3 months. This ceiling effect of MT efficacy may be explained by ischemic core expansion into the ischemic penumbra before recanalization and neuronal loss occurring after recanalization. Factors affecting the efficacy of MT, or the degree of irreversible injury, include time from symptom onset to recanalization, collateral circulation status, and differences in neuronal vulnerability. The purpose of this brief review is to discuss potential targets for neuroprotection, present and future potential pharmacologic and nonpharmacologic agents, and the data available in the literature. In experimental ischemia models, several authors reported that pharmacologic and nonpharmacologic agents are able to slow the progression of ischemic core expansion. However, in the era of unsuccessful recanalization of the occluded artery, several neuroprotective agents that were promising in the preclinical stage failed phase II/III clinical trials. Providing neuroprotection before and after recanalization of an LVO may play an important role in improving outcomes in the era of MT. Neuroprotection is classically defined as a process that results in the salvage, recovery, or regeneration of neuronal (and other supporting CNS cell) structure or function. The advent of successful recanalization of acute LVO by MT in the majority of patients may spur the growth of effective neuroprotection.

Acute Recanalization of Large Vessel Occlusion in the Anterior Circulation Stroke: Is Mechanical Thrombectomy Alone Better in Patients over 80 Years of Age? Findings from a Retrospective Observational Study.

Real-world data report worse 3-month clinical outcomes in elderly patients with acute ischemic stroke (AIS) treated with mechanical thrombectomy (MT). The aim was to identify factors influencing clinical outcome in elderly patients with anterior circulation AIS treated with MT (±intravenous thrombolysis (IVT)). In a retrospective, monocentric study, analysis of prospectively collected data of 138 patients (≥80 years) was performed. IVT was an independent negative predictor (OR 0.356; 95% CI: 0.134–0.942) and female sex an independent positive predictor (OR 4.179, 95% CI: 1.300–13.438) of 3-month good clinical outcome (modified Rankin scale 0–2). Female sex was also an independent negative predictor of 3-month mortality (OR 0.244, 95% CI: 0.100–0.599). Other independent negative predictors of 3-month good clinical outcome were older age, lower pre-stroke self-sufficiency, more severe neurological deficit and longer procedural intervals. Mortality was also independently predicted by longer procedural interval and by the occurrence of symptomatic intracerebral hemorrhage (p < 0.05 in all cases). Our results demonstrated, that in patients aged ≥80 years with anterior circulation AIS undergoing MT (±IVT), IVT reduced the chance of 3-month good clinical outcome and female sex was associated with a greater likelihood of 3-month good clinical outcome and lower probability of 3-month mortality.

Efficacy of a Direct Aspiration First-Pass Technique (ADAPT) for Endovascular Treatment in Different Etiologies of Large Vessel Occlusion: Embolism vs. Intracranial Atherosclerotic Stenosis

Background and Aims: Aspiration thrombectomy is an effective method of recanalizing large vessel occlusion (LVO). However, the efficacy of a direct aspiration first-pass technique (ADAPT) for recanalization of LVO of different etiologies is not properly understood.Methods: The prospectively collected database on ADAPT was reviewed retrospectively. We defined two groups of enrolled patients: the embolism-related occlusions (EMB-O) group and the intracranial atherosclerotic stenosis (ICAS)-related occlusion (ICAS-O) group. Baseline characteristics, procedural variables, and post-procedural variables were collected. Multivariate logistic regression analysis was used to identify first-pass recanalization predictors.Results: Of 114 registered patients, 94 were eligible for this study (51 patients in the EMB-O group and 43 patients in the ICAS-O group). Achieving successful reperfusion immediately after direct aspiration was more frequent in the EMB-O group than in the ICAS-O group (64.71 vs. 27.91%, respectively, p = 0.006), with fewer additional rescue treatments needed (35.29 vs. 70.09%, respectively, p = 0.001). The EMB-O group also showed a higher final successful reperfusion rate (96.8 vs. 74.41%, p = 0.006). However, the 90-day good functional outcomes were not affected by the groups. Independent predictors of first-pass success of aspiration included the isolated middle cerebral artery site of occlusion, embolic etiology, and use of larger bore catheters.Conclusions: The efficacy of ADAPT recanalization approach was better in EMB-O than in ICAS-O. In case of embolic etiology and the isolated MCA site of occlusion, using a larger aspiration catheter for direct aspiration thrombectomy may be reasonable.

Mechanical Thrombectomy in Distal Residual Occlusions of the Middle Cerebral Artery after Large Vessel Recanalization in Acute Stroke: 2b or not 2b? A Pragmatic Approach in Real-Life Scenarios

Recent studies have suggested that a recanalization grade of modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2c is strongly related with good clinical outcome rather than the current therapeutic angiography target ≥2b. To achieve better recanalization, additional further maneuvers on distal residual vessel occlusion (RVO) may be required. The aim of this study was to evaluate the safety and efficacy of rescue treatment in RVOs after recanalization of large vessel occlusions in the anterior circulation. A single-center retrospective review of a prospectively maintained stroke databank was performed. Patients presenting with RVOs after mechanical thrombectomy on the M1/internal carotid artery terminus were included and further divided into treated and untreated groups: the former underwent additional maneuvers on RVOs, whereas the latter did not. Baseline and posttreatment clinical, radiologic, and angiographic data were compared between the 2 groups. End points included good functional outcome (modified Rankin Scale [mRS] score ≤2) rates of hemorrhagic transformations, neurologic deterioration and mortality. RVOs were observed in 183/488 patients (37.5%). 74/183 (40.4%) underwent rescue treatment, showing a better outcome in terms of median 24 hours National Institutes of Health Stroke Scale score (13 vs. 18; P < 0001), 24 hours Alberta Stroke Programme Early CT Score (6 vs. 5; P < 0.001) and 3 months mRS score 0-2 (47.3% vs. 33.1%; P= 0.06). Recanalization of the superior (frontal) branch of the middle cerebral artery was particularly critical in terms of outcome. Hemorrhagic transformation was higher in the untreated group (53.6% vs. 66.6%; P= 0.1) as well as symptomatic intracranial hemorrhage (13.1% vs. 29.4%; P= 0.01). Neurologic deterioration occurred more often among untreated patients (16.2% vs. 25.7%; P= 0.1). Three complications (1.3%) occurred during rescue treatment. When feasible, improving mTICI score 2a-2b recanalization to mTICI 2c/3 is safe and associated with a better clinical outcome, particularly for residual occlusions involving the superior branch of bifurcation.

Abstract 3: Early Recanalization of Large Vessel Occlusions by tPA on the Mobile Stroke Unit

Introduction: The benefit of intravenous tPA in acute ischemic stroke patients with large vessel occlusions (LVOs) is limited but time dependent. We evaluated pre-hospital treatment with tPA on the Mobile Stroke Unit (MSU) to explore the recanalization rate in patients with LVOs and its effect on clinical improvement upon ED arrival. Methods: Prospectively derived data were analyzed from patients on the Houston MSU who were treated with tPA and had LVOs identified by hyperdense artery on MSU CT or arterial occlusion on MSU CTA. The primary outcome was early recanalization, categorized as resolution of LVO on repeat vascular imaging in the ED or on emergent angiography versus no recanalization. Secondary outcome was change in baseline NIHSS at 24 hours. Differences in NIHSS were evaluated using Wilcoxon rank sum test with continuity correction. Results: Seventy-one patients received tPA and had proximal LVOs both in the anterior and posterior circulation. Eleven had recanalization on CTA upon ED arrival (15.5%), while 7 had recanalization on emergent angiography (9.9%). The total early recanalization rate with tPA was 25.4%. Forty-seven patients with persistent LVOs on ED arrival (66.2%) underwent endovascular thrombectomy (EVT). Time from symptom onset (last known normal) to tPA bolus did not differ significantly between the early recanalization vs non-early recanalization groups (64.5 minutes [IQR 43.0-78.5] vs 64.0 minutes [52.5-92.0]; p = 0.41). Early recanalization resulted in greater improvement in baseline to ED arrival NIHSS (median NIHSS change 4.0 [0-11.8] vs 0 [0-3.5]; p = 0.01). There were no differences in ED arrival to 24 hour NIHSS between the early recanalization versus non-early recanalization groups irrespective of EVT. Conclusions: Recanalization by ED arrival occurs in 25% of LVO patients with tPA treatment on a MSU and was associated with early clinical improvement. Subsequent EVT did not “make up” for the clinical benefit of early recanalization.

Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy

Despite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41–1.4) min−1 and was found in all 7 cases of hypoperfusion (100%), in 10 of 16 cases of hyperperfusion (63%), and in only three of 13 cases with unaffected perfusion (23%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56–0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10–0.82]) compared to hyperperfusion (PPV = 0.93 [0.68–1.0]) or unaffected perfusion (PPV = 1.0 [0.75–1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression.

Early Recanalization With Alteplase in Stroke Because of Large Vessel Occlusion in the ESCAPE Trial.

Quantitating the effect of intravenous alteplase on the technical outcome of early recanalization of large vessel occlusions aids understanding. We report the prevalence of early recanalization in patients with stroke because of large vessel occlusion treated with and without intravenous alteplase and endovascular thrombectomy, and its association with clinical outcome. Patients with acute ischemic stroke with large vessel occlusion from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times Trial) were included in this post hoc analysis. Outcomes of interest were the prevalence of early recanalization (1) and good outcome (2), defined as modified Rankin Scale score of 0 to 2 at 90 days. Among 147 patients who did not receive endovascular thrombectomy, early recanalization occurred in 4/30 (13.3%) patients without and 48/117 (41.0%) patients with intravenous alteplase (adjusted risk ratios, 3.2 [95% CI, 1.2-8.1]). Good outcome was achieved by 34/116 (29.3%) of patients who received intravenous alteplase versus 10/29 (34.5%) who did not receive alteplase (adjusted risk ratios, 1.0 [95% CI, 0.6-1.5) and by 20/52 (38.5%) patients with versus 24/93 (25.8%) without early recanalization (adjusted risk ratios, 1.9 [95% CI, 1.2-2.9]). Early recanalization was confirmed as a strong predictor of good outcome in patients who did not undergo endovascular thrombectomy and was improved with intravenous alteplase, yet a majority of patients (59.0%) did not achieve early reperfusion. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Tenecteplase Thrombolysis for Acute Ischemic Stroke.

Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment-elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.

Endovascular stroke treatment using balloon guide catheters may reduce penumbral tissue damage and improve long-term outcome

ObjectivesDuring mechanical recanalization of large vessel occlusions (LVO), the use of proximal flow arrest with balloon guide catheters (BGC) was shown to be associated with better angiographic and even clinical outcome. The aim of the study was to analyze the impact of BGC use on microstructural alterations in the salvaged penumbra.MethodsAll patients who underwent mechanical recanalization of LVO of the anterior circulation were reviewed within a prospective stroke registry of a single comprehensive stroke center. Fifty-two patients received an admission CT perfusion together with post-interventional diffusion tensor imaging. Technical details such as BGC usage were correlated with microstructural integrity changes of the salvaged gray matter through the mean diffusivity (MD) index. Moderation analysis was performed to test the interaction of BGC on the correlation between angiographic and clinical outcomes.ResultsFor all patients with complete reperfusion, microstructural integrity changes with lowered MD index were found within the salvaged penumbra for cases of non-BGC usage (mean − 0.02) compared to cases with BGC usage (0.01, p = 0.04). The importance of complete reperfusion for good clinical outcome is predominantly based on patients treated with BGC (effect 2.78, p = 0.01 vs. for non-BGC: 0.3, p = 0.71).ConclusionsThe lowered MD index early after mechanical recanalization without BGC usage can be interpreted as microstructural ischemic damage of the salvaged penumbra. It was shown that achieving complete reperfusion in a setting of BGC usage with proximal flow arrest minimizes penumbral damage and improves long-term outcomes.Key Points• Microstructural ischemic damage can be reduced by using proximal flow arrest during endovascular treatment with balloon guide catheter.• Complete reperfusion in a setting of balloon guide catheter minimizes penumbral damage and improves long-term outcome.

Abstract WP287: Modeling the Impact of Pre-Hospital Triage on a True Life Drip and Ship Thrombectomy Patient Cohort

Introduction: Patients with emergent large vessel occlusions (ELVO) are often brought to the closest hospital, possibly given intravenous tPA, and transferred to a hospital capable of performing endovascular intervention. This results in significant delays to thrombectomy and worse patient outcomes when compared with patients brought directly to endovascular centers. In New York City, the pre-hospital system has created a protocol for EMS to use a clinical screening tool to triage stroke patients, and bring those with suspected ELVO directly to comprehensive (CSC) or thrombectomy-capable stroke centers (TSC). Objective: To model the impact of EMS triage protocols on administration of tPA, initiation of endovascular therapy, and recanalization of large vessel occlusions using a real life cohort of thrombectomy patients. Methods: Using our system wide prospectively collected stroke database, we selected a consecutive cohort of 80 thrombectomy patients who were brought by EMS to a primary stroke center then transferred to a TSC or CSC for endovascular intervention. The patient’s initial EMS pickup address was used to calculate the closest TSC or CSC using Google Maps API. Driving time was calculated based on traffic patterns at the time of pickup. Using data from a cohort of 69 consecutive patients that were brought directly to a TSC or CSC by EMS and underwent endovascular intervention, we derived median door to needle and door to groin puncture times. These times, combined with calculated driving distance, were used to model the timing of treatment in the triage model. Timings in the actual cohort versus the model were compared. Results: In the “actual” drip and ship cohort versus our model, first medical contact (FMC) to endovascular center door was 211 versus 32 minutes (p&lt;0.01), first medical contact (FMC) to tPA was 91 versus 81 minutes (p=0.07), FMC to groin puncture was 265 versus 154 minutes (p&lt;0.01), and FMC to TICI2B+ recanalization was 313 versus 205 minutes (p&lt;0.01). Conclusions: Modeled EMS pre-hospital triage of ELVO patients results in a significant decrease in endovascular treatment times without change in tPA times. As triage tools increase in sensitivity and specificity, EMS triage protocols stand to improve patient outcomes.