Comparing Outcomes of Thrombectomy Versus Intravenous Thrombolysis Based on Middle Cerebral Artery M2 Occlusion Features.

BACKGROUND: Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT. METHODS: We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy. Patients were stratified into the intravenous thrombolysis (IVT) group (IVT alone) and EVT group (IVT plus EVT or EVT alone). The primary outcome was a modified Rankin Scale score 0 to 2 at 90 days. Secondary outcomes included additional thresholds and distribution of modified Rankin Scale scores, 24-hour recanalization, early neurological deterioration, and relevant complications during hospitalization. Safety outcomes encompassed intracranial hemorrhagic events at 24 hours and mortality at 90 days. Binary logistic regression analyses with propensity score matching were used. Subgroup analyses were performed based on the anatomic site of occlusion, including right versus left, proximal versus distal, dominant/co-dominant versus nondominant, single versus double/triple branch(es), and anterior versus central/posterior branch. RESULTS: Among 734 patients (43.3% were females; median age, 73 years) with M2 segment occlusion, 342 (46.6%) were in the EVT group. Propensity score matching analysis revealed no statistical difference in the primary outcome (odds ratio, 0.860 [95% CI, 0.611-1.209]; P=0.385) between the EVT group and IVT group. However, EVT was associated with a higher incidence of subarachnoid hemorrhage (odds ratio, 6.655 [95% CI, 1.487-29.788]; P=0.004) and pneumonia (odds ratio, 2.015 [95% CI, 1.364-2.977]; P<0.001). Subgroup analyses indicated that patients in the IVT group achieved better outcomes when presenting with right, distal, or nondominant branch occlusion (Pall interaction<0.05). CONCLUSIONS: Our study showed similar efficiency of EVT versus IVT alone in acute M2 segment middle cerebral artery occlusion. This suggested that only specific patient subpopulations might have a potentially higher benefit of EVT over IVT alone. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04487340.

Influencing factors of futile recanalization after endovascular intervention in patients with acute basilar artery occlusion. / æ€¥æ€§åŸºåº•åŠ¨è„‰é—­å¡žæ‚£è€ è¡€ç®¡å† æ²»ç–—åŽå‘ç”Ÿæ— æ•ˆå†é€šçš„å½±å“å› ç´ .

OBJECTIVES: To explore the influence factors for futile recanalization following endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO). METHODS: Clinical data of patients with acute BAO, who underwent endovascular treatment within 24 h of onset from January 2017 to November 2022, were retrospectively analyzed. The futile recanalization was defined as modified thrombolysis in cerebral infarction (mTICI) grade ≥2b or 3 after successful reperfusion, but the modified Rankin Scale score >2 at 3 months after EVT. Binary logistic regression model was used to analyze the influencing factors of futile recanalization. RESULTS: A total of 471 patients with a median age of 68 (57, 74) years were included and 68.9% were males, among whom 298 (63.27%) experienced futile recanalization. Multivariate analysis revealed that concomitant atrial fibrillation (OR=0.456, 95%CI: 0.282-0.737, P<0.01), bridging thrombolysis (OR=0.640, 95%CI: 0.416-0.985, P<0.05), achieving mTICI grade 3 (OR=0.554, 95%CI: 0.334-0.918, P<0.05), arterial occlusive lesion (AOL) grade 3 (OR=0.521, 95%CI: 0.326-0.834, P<0.01), and early postoperative statin therapy (OR=0.509, 95%CI: 0.273-0.948, P<0.05) were protective factors for futile recanalization after EVT in acute BAO patients. High baseline National Institutes of Health Stroke Scale (NIHSS) score (OR=1.068, 95%CI: 1.049-1.087, P<0.01), coexisting hypertension (OR=1.571, 95%CI: 1.017-2.427, P<0.05), multiple retrieval attempts (OR=1.237, 95%CI: 1.029-1.488, P<0.05) and postoperative hemorrhagic transformation (OR=8.497, 95%CI: 2.879-25.076, P<0.01) were risk factors. For trial of ORG 10172 in acute stroke treatment (TOAST) classification, cardiogenic embolism (OR=0.321, 95%CI: 0.193-0.534, P<0.01) and other types (OR=0.499, 95%CI: 0.260-0.961, P<0.05) were related to lower incidence of futile recanalization. CONCLUSIONS: The incidence of futile recanalization after EVT in patients with acute BAO is high. Bridging venous thrombolysis before operation and an early postoperative statin therapy may reduce the incidence of futile recanalization.

Reperfusion Injury Is Associated With Poor Outcome in Patients With Recanalization After Thrombectomy.

BACKGROUND: The existence of cerebral reperfusion injury in human beings remains controversial. Thus, we aimed to explore the presence of reperfusion injury in acute ischemic stroke patients with recanalization after mechanical thrombectomy and analyzed its impact on neurological outcome. METHODS: We reviewed our prospectively collected database CIPPIS (Comparison Influence to Prognosis of CTP and MRP in AIS Patients, NCT03367286), and enrolled anterior circulation large artery occlusion patients with recanalization after mechanical thrombectomy who underwent (1) computed tomography (CT) perfusion on admission and immediately after recanalization to determine reperfusion region, and (2) CT and/or magnetic resonance imaging (MRI) immediately and 24 hours after recanalization to determine lesion areas. The expansion of lesion between recanalization and 24 hours within reperfusion region was potentially caused by reperfusion, thus termed as radiological observed reperfusion injury (RORI). Based on the imaging modality immediately after recanalization, RORI was further divided into RORICT and RORIMRI. We first included a small cohort who had performed both CT and MRI immediately after recanalization to validate the consistency between RORICT and RORIMRI (Study 1). Then the association with RORICT and poor outcome, defined as 3-month modified Rankin Scale score of 3 to 6, was explored in a larger cohort (Study 2). RESULTS: Study 1 included 23 patients and good consistency was found between RORICT and RORIMRI (intraclass correlation=0.97, P<0.001). Among 226 patients included in Study 2, a total of 106 (46.9%) were identified with RORI. The ratio of RORI to reperfusion region was 30.1 (16.2, 51.0)% and was independently associated with poor outcome (odds ratio=1.55 per 10% [95% CI' 1.30-1.84]; P<0.001). CONCLUSIONS: Our findings suggested that RORI was relatively frequent in stroke patients with recanalization after mechanical thrombectomy and associated with poor outcome despite successful recanalization. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03367286.

Effect of Imaging Markers on Reperfusion Therapy in Basilar Artery Occlusion.

OBJECTIVE: We aimed to investigate the effectiveness of endovascular therapy (EVT) versus intravenous thrombolysis (IVT) in patients with basilar artery occlusion (BAO), based on the information of advanced imaging. METHODS: We analyzed data of stroke patients with radiologically confirmed BAO within 24 hours. BAO subjects were categorized into "top-of-the-basilar" syndrome (TOBS) and other types. An initial infarct size of <70ml and a ratio of ischemic tissue to infarct volume of ≥1.8 was defined as "target mismatch." The primary outcome was a good outcome, defined as a modified Rankin Scale score of 0 to 3 at 3 months. Propensity score adjustment and inverse probability of treatment weighting (IPTW) propensity score methods were used. RESULTS: Among 474 BAO patients, 93 (19.6%) were treated with IVT prior to EVT, 91 (19.2%) were treated with IVT alone, 95 (20.0%) were treated with EVT alone, and 195 (41.1%) were treated with antithrombotic therapy. In IPTW analyses, we found no benefit of EVT over IVT for good outcome in either TOBS patients (odds ratio = 1.08, 95% confidence interval [CI] = 0.88-1.31) or those with other types (odds ratio = 1.13, 95% CI = 0.94-1.36). However, in patients with other types, if there existed a target mismatch, EVT was independently related to good outcome (odds ratio = 1.46, 95% CI = 1.17-1.81). INTERPRETATION: The "target mismatch profile" seems to be a possible candidate selection standard of EVT for those with other types of BAO. Future studies should separate TOBS from other types of BAO, and try to use advanced imaging. ANN NEUROL 2022;92:97-106.

Evaluation of a multicomponent intervention to shorten thrombolytic door-to-needle time in stroke patients in China (MISSION): A cluster-randomized controlled trial.

BACKGROUND: Rapid intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is crucial for improving outcomes. However, few randomized trials of interventions aimed at reducing in-hospital delay have been carried out in China. We aimed to evaluate the effect of a multicomponent intervention on thrombolytic door-to-needle time (DNT) of AIS patients via video teleconference based on the Behavior Change Wheel (BCW) method. METHODS AND FINDINGS: This cluster-randomized trial, conducted between January 1, 2019 and December 31, 2019, randomly allocated 22 hospitals equally to PEITEM (Persuasion Environment reconstruction Incentivization Training Education Modeling) intervention or routine care plus stroke registry and subsequently enrolled 1,634 AIS patients receiving IVT within 4.5 hours upon stroke onset from participant hospitals. The PEITEM group received a 1-year PEITEM 6-component intervention based on the behavioral theory monthly via video teleconference. The primary outcome was the proportion of patients with a DNT of 60 minutes or less. A total of 987 patients participated in the PEITEM group (mean age, 69 years; female, 411 [41.6%]) and 647 patients in the control group (mean age, 70 years; female, 238 [36.8%]). Of all participants, the proportion of DNT ≤60 minutes in the PEITEM group was higher than in the control group (82.0% versus 73.3%; adjusted odds ratio, 1.77; 95% confidence interval (CI), 1.17 to 2.70; ICC, 0.04; P = 0.007). Among secondary outcomes, the average DNT was 43 minutes in the PEITEM group and 50 minutes in the control group (adjusted mean difference: -8.83; 95% CI, -14.03 to -3.64; ICC, 0.12; P = 0.001). Favorable functional outcome (score of 0 to 1 on the modified Rankin scale (mRS)) was achieved in 55.6% patients of the PEITEM group and 50.4% of the control group (adjusted odds ratio, 1.38; 95% CI, 1.00 to 1.90; ICC, 0.01; P = 0.049). Main study limitations include non-blinding of clinicians, and that specific interventions component responsible for the observed changes could not be determined. CONCLUSIONS: The teleconference-delivered PEITEM intervention resulted in a moderate but clinically relevant shorter DNT and better functional outcome in AIS patients receiving IVT. TRIAL REGISTRATION: Clinicaltrials.gov NCT03317639.

Stroke outcome of early antiplatelet in post-thrombolysis haemorrhagic infarction.

BACKGROUND AND PURPOSE: Initiation of early antiplatelet (EA) therapy after acute ischaemic stroke (AIS) is essential. We aimed to investigate the safety and effectiveness of EA therapy in patients who had an AIS with haemorrhagic infarction (HI) after intravenous thrombolysis (IVT). METHODS: Based on a multicentre stroke registry database, patients who had an AIS with post-thrombolysis HI at 24 hours were identified. EA users and non-EA users were defined as patients with HI who received or did not receive antiplatelet therapy between 24 and 48 hours after IVT. Primary outcome was favourable outcome defined as modified Rankin Scale scores 0-2 at 3 months. Secondary outcomes were early neurological deterioration (END) and haemorrhagic transformation expansion. RESULTS: A total of 842 patients with HI were identified from 24 061 thrombolytic patients within 4.5 hours, and 341 (40.5%) received EA therapy. EA users were more likely to have a favourable outcome (55.7% vs 39.5%, OR 1.565; 95% CI 1.122 to 2.182; p=0.008) and lower rate of END (12.6% vs 21.4%, OR 0.585; 95% CI 0.391 to 0.875; p=0.009) compared with non-EA users. EA therapy was not associated with haemorrhagic transformation expansion (p=0.125). After propensity score matching, EA therapy was still independently associated with favourable outcome (54.3% vs 46.3%, OR 1.495; 95% CI 1.031 to 2.167; p=0.038) and lower risk of END (13.5% vs 21.2%, OR 0.544; 95% CI 0.350 to 0.845; p=0.007). CONCLUSIONS: Antiplatelet therapy can be safely used between 24 and 48 hours when HI occurs after IVT, and such therapy is associated with reduced risk of END and improved neurological outcome in patients who had an AIS.

Efficacy of Intra-Arterial Thrombolysis for Acute Central Retinal Artery Occlusion: A Meta-Analysis.

INTRODUCTION: The best management strategy still remains strong controversy for acute nonarteritic central retinal artery occlusion (CRAO). We thus performed a meta-analysis to determine the efficacy of intra-arterial thrombolysis (IAT) for visual improvement according to different times from symptom onset. METHODS: We searched EMBASE, PubMed, and Web of Science for relevant studies assessing efficiency of IAT in patients with CRAO compared with standard therapy. Fixed-effects and random-effects models were performed. RESULTS: Five eligible studies including 459 patients with acute CRAO were pooled in the meta-analysis. In all, 219 (47.7%) received IAT, and the mean time from symptom onset to IAT was 13 h. The pooled analysis demonstrates odds ratio (OR) for the procedure of IAT and any visual improvement to be 1.520 (95% confidence intervals [CIs] 1.258-1.837; p < 0.001). Subgroup analyses further indicated that the CRAO patients who received IAT achieved any visual improvement more easily within 6 h from symptom onset (OR = 1.703, 95% CI 1.219-2.381; p = 0.002), but not those beyond 6 h (OR = 1.260, 95% CI 0.973-1.632; p = 0.080). CONCLUSION: Our meta-analysis of available published data supports IAT to be an alternative treatment option for CRAO patients within 6 h from symptom onset.

Early NT-ProBNP (N-Terminal Probrain Natriuretic Peptide) Elevation Predicts Malignant Edema and Death After Reperfusion Therapy in Acute Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: We aimed to investigate the relationship between early NT-proBNP (N-terminal probrain natriuretic peptide) and all-cause death in patients receiving reperfusion therapy, including intravenous thrombolysis and endovascular thrombectomy (EVT). METHODS: This study included 1039 acute ischemic stroke patients with early NT-proBNP data at 2 hours after the beginning of alteplase infusion for those with intravenous thrombolysis only or immediately at the end of EVT for those with EVT. We performed natural log transformation for NT-proBNP (Ln(NT-proBNP)). Malignant brain edema was ascertained by using the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) criteria. RESULTS: Median serum NT-proBNP level was 349 pg/mL (interquartile range, 89-1250 pg/mL). One hundred twenty-one (11.6%) patients died. Malignant edema was observed in 78 (7.5%) patients. Ln(NT-proBNP) was independently associated with 3-month mortality in patients with intravenous thrombolysis only (odds ratio, 1.465 [95% CI, 1.169-1.836]; P=0.001) and in those receiving EVT (odds ratio, 1.563 [95% CI, 1.139-2.145]; P=0.006). The elevation of Ln(NT-proBNP) was also independently associated with malignant edema in patients with intravenous thrombolysis only (odds ratio, 1.334 [95% CI, 1.020-1.745]; P=0.036), and in those with EVT (odds ratio, 1.455 [95% CI, 1.057-2.003]; P=0.022). CONCLUSIONS: An early increase in NT-proBNP levels was related to malignant edema and stroke mortality after reperfusion therapy.

Impairment of the Glymphatic Pathway and Putative Meningeal Lymphatic Vessels in the Aging Human.

OBJECTIVE: Aging is a major risk factor for numerous neurological disorders, and the mechanisms underlying brain aging remain elusive. Recent animal studies demonstrated a tight relationship between impairment of the glymphatic pathway, meningeal lymphatic vessels, and aging. However, the relationship in the human brain remains uncertain. METHODS: In this observational cohort study, patients underwent magnetic resonance imaging before and at multiple time points after intrathecal administration of a contrast agent. Head T1-weighted imaging was performed to assess the function of the glymphatic pathway and head high-resolution T2-fluid attenuated inversion recovery imaging to visualize putative meningeal lymphatic vessels (pMLVs). We measured the signal unit ratio (SUR) of 6 locations in the glymphatic pathway and pMLVs, defined the percentage change in SUR from baseline to 39 hours as the clearance of the glymphatic pathway and pMLVs, and then analyzed their relationships with aging. RESULTS: In all patients (N = 35), the SUR of the glymphatic pathway and pMLVs changed significantly after intrathecal injection of the contrast agent. The clearance of both the glymphatic pathway and pMLVs was related to aging (all p < 0.05). The clearance of pMLVs was significantly related to the clearance of the glymphatic pathway (all p < 0.05), and the clearance of the glymphatic pathway was significantly faster in patients with early filling of pMLVs than those with late filling (all p < 0.05). INTERPRETATION: We revealed that both the glymphatic pathway and pMLVs might be impaired in the aging human brain through the novel, clinically available method to simultaneously visualize their clearance. Our findings also support that in humans, pMLVs are the downstream of the glymphatic pathway. Ann Neurol 2020;87:357-369.

Comparison of various reconstructions derived from dual-energy CT immediately after endovascular treatment of acute ischemic stroke in predicting hemorrhage.

OBJECTIVES: Predicting 24-h hemorrhage immediately after endovascular treatment (EVT) of ischemic stroke is important but difficult for clinicians. We thus aimed to identify better image markers in predicting hemorrhage from different reconstructions derived from dual-energy CT. METHODS: We reviewed our prospectively collected database for anterior circulation ischemic stroke patients who received EVT and analyzed patients who underwent dual-energy CT immediately after EVT. Parenchymal hyperdensities were assessed on non-contrast CT and virtual non-contrast (VNC) which was constructed from dual-energy CT, respectively. Metallic hyperdensity sign was defined when a maximum density > 90 Hounsfield units was identified within the nonpetechial intracerebral hyperdense lesion in the basal ganglia on non-contrast CT. RESULTS: A total of 147 patients were included. Hemorrhagic transformation (HT) was identified in 81 (55.1%) patients, and parenchymal hemorrhage (PH) in 35 (23.8%) patients. The rate of HT at 24 h was higher in patients with parenchymal hyperdensities on non-contrast CT or VNC or with metallic hyperdensity sign than those without (72.4% vs 11.9%, p < 0.001; 82.0% vs 41.2%, p < 0.001; 100.0% vs 44.5%, p < 0.001). Parenchymal hyperdensities on non-contrast CT had a higher accuracy in predicting HT than those on VNC (76.9% vs 66.7%). Metallic hyperdensity sign on non-contrast CT also had a higher accuracy in predicting PH than parenchymal hyperdensities on VNC (88.4% vs 69.4%). CONCLUSIONS: Image markers on non-contrast CT (parenchymal hyperdensities and metallic hyperdensity sign) performed immediately post-EVT of ischemic stroke might be not inferior to dual-energy CT (parenchymal hyperdensities) to predict follow-up hemorrhage. KEY POINTS: • Image markers (parenchymal hyperdensities and metallic hyperdensity sign) on NCCT performed immediately post-EVT of ischemic stroke can predict follow-up hemorrhage. • Metallic hyperdensity sign on NCCT can accurately predict parenchymal hemorrhage. • Parenchymal hyperdensities on NCCT can accurately predict hemorrhagic transformation.

Early Fibrinogen Depletion and Symptomatic Intracranial Hemorrhage After Reperfusion Therapy.

Background and Purpose- We aimed to thoroughly investigate the relationship between early fibrinogen depletion and symptomatic intracranial hemorrhage (sICH) in patients receiving reperfusion therapy including intravenous thrombolysis (IVT) with or without endovascular thrombectomy (EVT). Methods- This study included 1135 stroke patients with baseline and follow-up fibrinogen levels at 2 hours after the beginning of alteplase infusion for those with IVT only or immediately after the end of EVT for those with combined IVT and EVT. Patients received alteplase up to 9 hours after the onset or on awakening based on automated perfusion imaging. sICH was ascertained using ECASS II (The Second European-Australasian Acute Stroke Study) criteria. Δfibrinogen was calculated as follow-up fibrinogen minus baseline fibrinogen. Results- In patients with IVT only, baseline fibrinogen level was 3.36±0.94 g/L and decreased to 2.47±0.80 g/L at 2 hours after the beginning of alteplase infusion. In patients with IVT followed by EVT, baseline fibrinogen level was 3.35±0.82 g/L and decreased to 2.52±0.83 g/L immediately after the end of EVT. sICH was observed in 44 (3.9%) patients. The extent of Δfibrinogen was associated with sICH in patients with IVT only (odds ratio, 1.929; 95% CI, 1.402-2.654; P<0.001) and in those with IVT followed by EVT (odds ratio, 1.765; 95% CI, 1.135-2.743; P=0.012). Conclusions- An early decrease in fibrinogen levels was related to sICH after reperfusion therapy with alteplase. More fibrin-specific thrombolytic agents are warranted to be tested in acute ischemic stroke patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03367286.

Longer Length of Delayed-Contrast Filling of Clot on 4-Dimensional Computed Tomographic Angiography Predicts Cardiogenic Embolism.

Background and Purpose- We hypothesized the length of delayed-contrast filling sign (DCFS) of intraarterial clot, indicating contrast medium penetration into the thrombus, was associated with stroke etiology. Methods- We retrospectively included patients with large vessel occlusion in anterior circulation who underwent computed tomographic perfusion within 24 hours poststroke onset. We defined DCFS as contrast medium diffusion through the thrombi after the arterial peak phase on 4-dimensional computed tomographic angiography derived from computed tomographic perfusion. We measured the length of DCFS and investigated its value for predicting the stroke etiology. Results- Three hundred twenty-one patients were analyzed, and their stroke etiologies included cardiogenic embolism (CE, n=167), large artery atherosclerosis (n=64), other etiology group (n=4), and undetermined etiology (n=86). CE patients had longer length of DCFS than non-CE patients (2.3 versus 0.5 mm; P<0.001). The optimal cutoff value of DCFS length for predicting CE was 1.5 mm. The sensitivity, specificity, positive predictive value, and negative predictive value of a length of DCFS >1.5 mm for predicting CE were 83.2%, 70.8%, 75.5%, and 79.6%. Conclusions- Longer length of DCFS was associated with CE in patients with large vessel occlusion in anterior circulation, which may provide stroke etiology information.

Acute Stroke: Prognostic Value of Quantitative Collateral Assessment at Perfusion CT.

Purpose To develop a quantitative assessment of collateral perfusion at CT and to investigate its value in the prediction of outcome in patients with acute ischemic stroke (AIS). Materials and Methods This retrospective study reviewed data from consecutive patients with AIS and an occluded M1 segment of the middle cerebral artery who underwent pretreatment perfusion CT between May 2009 and August 2017. The maximum cerebral blood flow (CBF) of collateral vessels (cCBFmax) within the Sylvian fissure was calculated for each patient. Good outcome was defined as a 90-day modified Rankin scale score of 0-2. Multivariable logistic regression analysis was used to determine the relationship between cCBFmax and (a) hemorrhagic transformation and (b) clinical outcome. Results The final analysis included 204 patients (median age, 73 years; interquartile range, 62-80 years; 82 [40.2%] women). Multivariable logistic regression analysis showed that higher cCBFmax was an independent predictor for (a) a lower risk of hemorrhagic transformation (odds ratio [OR], 0.99; 95% confidence interval [CI]: 0.98, 1.00; P = .009) after adjusting for baseline National Institutes of Health Stroke Scale (NIHSS), endovascular thrombectomy, baseline infarct core volume, and recanalization and (b) better outcome (OR, 1.02; 95% CI: 1.01, 1.03; P = .001) after adjusting for age, baseline NIHSS score, endovascular thrombectomy, hypertension, baseline infarct core volume, and recanalization, respectively. Conclusion The measurement of maximum cerebral blood flow of collateral vessels within the Sylvian fissure is a feasible quantitative collateral assessment at perfusion CT. Maximum cerebral blood flow of collateral vessels was associated with clinical outcome in patients with acute ischemic stroke. © RSNA, 2019 Online supplemental material is available for this article.

Identification of Corticospinal Tract Lesion for Predicting Outcome in Small Perfusion Stroke.

Background and Purpose- Whether patients with small perfusion lesions benefit from thrombolysis remains an uncertainty. We assessed acute ischemic stroke patients with a total perfusion lesion of <15 mL and tested the hypothesis the pattern of corticospinal tract (CST) involvement might predict outcome in thrombolysis-eligible patients. Methods- We used a prospectively collected cohort of acute ischemic stroke patients being assessed for thrombolysis at 7 centers. Three neurologists categorized the presence of hypoperfusion and infarction within CST. Excellent outcome was defined as 90-day modified Rankin Scale score 0 to 1. Results- Of 2654 patients, 407 had a perfusion lesion <15 mL and were clinically eligible for thrombolysis (243 being treated). Median National Institutes of Health Stroke Scale was 5.0, and 312 (76.7%) patients achieved excellent outcome. Alteplase treatment was an independent unfavorable factor for excellent outcome (alteplase-treated 72.0% versus untreated 83.5%; odds ratio, 0.541; P=0.025). For patients with CST hypoperfusion without CST infarction, alteplase treatment was an independent favorable factor for excellent outcome (alteplase-treated 75.6% versus untreated 47.1%; odds ratio, 4.096; P=0.045). Among patients with CST infarction, alteplase treatment was an independent unfavorable factor for excellent outcome (alteplase-treated 30.6% versus untreated 88.9%; odds ratio, 0.002; P=0.003). Among patients without either CST hypoperfusion or CST infarction, alteplase treatment was not an independent influencing factor for excellent outcome (alteplase-treated 80.1% versus untreated 87.7%; P=0.258). Conclusions- Only patients with CST hypoperfusion without CST infarction among eligible acute ischemic stroke patients with small perfusion lesions could benefit from thrombolysis, which needs to be confirmed in future prospective studies. Patient selection, including an assessment of lesion location rather than purely lesion volume, may be ideal.

Reperfusion facilitates reversible disruption of the human blood-brain barrier following acute ischaemic stroke.

OBJECTIVES: We aimed to detect early changes of the blood-brain barrier permeability (BBBP) in acute ischaemic stroke (AIS), with or without reperfusion, and find out whether BBBP can predict clinical outcomes. METHODS: Consecutive AIS patients imaged with computed tomographic perfusion (CTP) before and 24 h after treatment were included. The relative permeability-surface area product (rPS) was calculated within the hypoperfused region (rPShypo-i), non-hypoperfused region of ischaemic hemisphere (rPSnonhypo-i) and their contralateral mirror regions (rPShypo-c and rPSnonhypo-c). The changes of rPS were analysed using analysis of variance (ANOVA) with repeated measures. Logistic regression was used to identify independent predictors of unfavourable outcome. RESULTS: Fifty-six patients were included in the analysis, median age was 76 (IQR 62-81) years and 28 (50%) were female. From baseline to 24 h after treatment, rPShypo-i, rPSnonhypo-i and rPShypo-c all decreased significantly. The decreases in rPShypo-i and rPShypo-c were larger in the reperfusion group than non-reperfusion group. The rPShypo-i at follow-up was a predictor for unfavourable outcome (OR 1.131; 95% CI 1.018-1.256; P = 0.022). CONCLUSION: Early disruption of BBB in AIS is reversible, particularly when greater reperfusion is achieved. Elevated BBBP at 24 h after treatment, not the pretreatment BBBP, predicts unfavourable outcome. KEY POINTS: • Early disruption of blood-brain barrier (BBB) in stroke is reversible after treatment. • The reversibility of BBB permeability is associated with reperfusion. • Unfavourable outcome is associated with BBB permeability at 24 h after treatment. • Contralateral non-ischaemic hemisphere is not 'normal' during an acute stroke.

Overestimation of Susceptibility Vessel Sign: A Predictive Marker of Stroke Cause.

BACKGROUND AND PURPOSE: The extent of blooming artifact may reflect the amount of paramagnetic material. We thus assessed the overestimation ratio of susceptibility vessel sign (SVS) on susceptibility-weighted imaging, defined as the extent of SVS width beyond the lumen and examined its value for predicting the stroke cause in acute ischemic stroke patients. METHODS: We included consecutive acute ischemic stroke patients with proximal large artery occlusion who underwent both susceptibility-weighted imaging and time-of-flight magnetic resonance angiography within 8 hours poststroke onset. We calculated the length, width, and overestimation ratio of SVS on susceptibility-weighted imaging and then investigated their values for predicting the stroke cause, respectively. RESULTS: One-hundred eleven consecutive patients (72 female; mean age, 66.6±13.4 years) were enrolled, among whom 39 (35.1%) were diagnosed with cardiogenic embolism, 43 (38.7%) with large artery atherosclerosis, and 29 (26.1%) with undetermined cause. The presence, length, width, and overestimation ratio of SVS were all independently associated with the cause of cardiogenic embolism after adjusting for baseline National Institute of Health Stroke Scale and infarct volume. After excluded patients with undetermined cause, the sensitivity and specificity of overestimation ratio of SVS for cardiogenic embolism were 0.971 and 0.913; for the length of SVS, they were 0.629 and 0.739; for the width of SVS, they were 0.829 and 0.826, respectively. CONCLUSIONS: The overestimation ratio of SVS can predict cardiogenic embolism, with both high sensitivity and specificity, which can be helpful for the management of acute ischemic stroke patients in hyperacute stage.

Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis.

Background and Purpose- We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods- We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2). Results- In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH ( P=0.014), PH ( P=0.013), and PHr ( P<0.00001). Five or more and >10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions- Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

Impact of perfusion lesion in corticospinal tract on response to reperfusion.

OBJECTIVES: We aimed to examine the impact of corticospinal tract (CST) involvement in acute ischaemic stroke (AIS) patients on functional outcome and the interaction with reperfusion. METHODS: We retrospectively examined data in consecutive anterior circulation AIS patients undergoing thrombolysis. MR perfusion (time to maximum of tissue residue function, Tmax) and apparent diffusion coefficient (ADC) images were transformed into standard space and the volumes of CST involvement by Tmax > 6 s (CST-Tmax) and ADC < 620 × 10-6 mm2/s (CST-ADC) lesions were calculated. Good outcome was defined as modified Rankin scale ≤ 2 at 3 months. Reperfusion was defined as a reduction in Tmax > 6 s lesion volume of ≥70% between baseline and 24 h. RESULTS: 82 patients were included. Binary logistic regression revealed that both CST-Tmax and CST-ADC volume at baseline were significantly associated with poor outcome (p < 0.05). The 24-h CST-ADC volume was correlated with baseline CST-ADC volume in patients with reperfusion (r = 0.79, p < 0.001) and baseline CST-Tmax volume in patients without reperfusion (r = 0.67, p < 0.001). In patients with CST-Tmax volume > 0 mL and CST-ADC volume < 3 mL, the rate of good outcome was higher in patients with reperfusion than those without (70.4% vs 38.1%, p = 0.04). CONCLUSIONS: The use of CST-Tmax in combination with CST-ADC provides prognostic information in patients considered for reperfusion therapies. KEY POINTS: • Examine the impact of corticospinal tract involvement in acute ischaemic stroke patients. • Spatially registered Tmax images can identify corticospinal tract hypoperfusion injury. • Corticospinal tract salvage through reperfusion is associated with improved outcome.

Late recanalisation beyond 24 hours is associated with worse outcome: an observational study.

OBJECTIVES: We evaluated the rate of late recanalisation beyond 24 h after intravenous thrombolysis (IVT) and its relationship with haemorrhagic transformation and outcome. METHODS: We reviewed prospectively collected clinical and imaging data from acute ischaemic stroke patients with distal internal carotid artery or proximal middle cerebral artery occlusion who underwent angiography on admission, 24 h and 1 week after IVT. Patients were trichotomised according to vascular status: timely recanalisation (<24 h), late recanalisation (24 h-7 days), and no recanalisation. RESULTS: Non-invasive angiography revealed timely recanalisation in 52 (50.0 %) patients, late recanalisation in 25 (24.0 %) patients, and no recanalisation in 27 (26.0 %) patients. Pre-existing atrial fibrillation was associated with the occurrence of late recanalisation (odds ratio 6.674; 95 % CI: 1.197 to 37.209; p = 0.030). In patients without timely recanalisation, shift analysis indicated that late recanalisation led to a worse modified Rankin Scale score (odds ratio 6.787; 95 % CI: 2.094 to 21.978; p = 0.001). CONCLUSIONS: About half of all patients without recanalisation by 24 h after IVT may develop late recanalisation within 1 week, along with higher mRS scores by 3 months. Pre-existing atrial fibrillation is an independent predictor for late recanalisation. KEY POINTS: • About half of patients may develop late recanalisation within 1 week. • Pre-existing atrial fibrillation was associated with the occurrence of late recanalisation. • Late recanalisation led to a higher mRS score than no recanalisation.

[Association of serum folate level with severity of white matter hyperintensity and presence of cerebral microbleeds].

OBJECTIVE: To investigate the association of serum folate level with the severity of white matter hyperintensity (WMH) and presence of cerebral microbleeds (CMB). METHODS: Clinical data of WMH patients from the second affiliated Hospital, Zhejiang University school of Medicine during July 2011 and February 2016 were retrospectively reviewed. According to Fazekas score based on T2-Flair images, patients were classified into mild WMH (0-3) and severe WMH (4-6). The presence of CMB was assessed on susceptibility weighted imaging (SWI). Binary logistic analysis was conducted to identify the independent predictors for severe WMH and the presence of CMB. RESULTS: Two hundred and twenty eight patients with WMH were included, among whom 149(65.35%)had severe WMH. In patients with high folate (≥ 15.68 nmol/L), low folate (6.8-15.67 nmol/L) and folate deficiency (<6.8 nmol/L), the proportions of severe WMH were 52.88%, 73.33% and 89.47%, respectively. Binary logistic regression analysis revealed that compared with high folate group, severe WMH was more common in groups with low folate (OR=2.109, 95% CI:1.112-4.001,P<0.05) and folate deficiency (OR=6.383, 95% CI:1.168-34.866, P<0.05). Eighty-eight(48.09%) of 183 patients receiving SWI scan presented with CMB. Although the subjects with CMB had lower serum folate level than those without CMB(13.42 vs 16.51 nmol/L, P<0.01), binary logistic regression analysis did not reveal the independent association between serum folate level and the presence of CMB after adjusting for hyperhomocysteinemia (P>0.05). CONCLUSIONS: Lower serum folate level is independently associated with severe WMH, but not with the CMB concurrence.