Meixia Zhang

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.

Functional analysis of CAX2-like transporters isolated from two ecotypes of Sedum alfredii

Two genes encoding CAX2-like proteins were isolated from a Zn/Cd hyperaccumulating ecotype (HE) and nonhyperaccumulating ecotype (NHE) of Sedum alfredii Hance, and they were named SaCAX2h and SaCAX2n, respectively. Both SaCAX2h:eGFP and SaCAX2n:eGFP proteins were localized to the vacuolar membrane of tobacco epidermal cells and yeast mutants. Heterologous expression of SaCAX2h or SaCAX2n in the Δzrc1 yeast mutant increased Cd content in yeast cells. Yeast complementary assay also revealed that both the transporters could suppress Ca and Mn hypersensitivity and enhance Ca and Mn accumulation in a K667 yeast mutant. The expression patterns of the two genes were different under the Cd treatment. Transcription of SaCAX2h was down-regulated in roots and up-regulated in shoots whereas transcription of SaCAX2n was down-regulated in shoots after the exposition to Cd. Furthermore, over-expression of SaCAX2h enhanced metal accumulation in the tobacco plants. The Cd content increased by 17–19 % in shoots and 31–36 % in roots; the Ca content of the transgenic plants increased by 31–32 % in shoots, and the Mn content increased by 60–79 % in shoots and 22–29 % in roots. These results indicate that SaCAX2h was responsible for Ca and Mn sequestration into vacuoles, and over-expression of SaCAX2h enhanced Cd accumulation in the transgenic tobacco.

Rationale and design of combination of an immune modulator Fingolimod with Alteplase bridging with Mechanical Thrombectomy in Acute Ischemic Stroke (FAMTAIS) trial.

Rationale In acute ischemic stroke patients with large vessel occlusion, although reperfusion within 6 h after stroke onset using combined intravenous alteplase and mechanical thrombectomy (bridging therapy) can improve functional outcome, still approximately 50% patients suffer disability which may result from reperfusion injury. Proof-of-concept clinical trials have indicated that the sphingosine-1-phosphate receptor modulator fingolimod may be efficacious in attenuating brain inflammation and improving clinical outcomes in acute ischemic stroke patients as a single therapy beyond 4.5 h of disease onset, or in combination with alteplase within 4.5 h of disease onset. Aim To assess whether the treatment of fingolimod combined with bridging therapy in large vessel occlusion acute ischemic stroke patients is effective and safe. Design and sample size estimates Fingolimod with Alteplase bridging with Mechanical Thrombectomy in Acute Ischemic Stroke (FAMTAIS) study is a randomized, open-label, multiple central trial. This study includes 98 patients with anterior circulation large vessel occlusion acute ischemic stroke who are eligible for bridging therapy, providing 80% power to reject the null hypothesis that, combined with fingolimod, the bridging therapy has an at least 15% higher penumbra tissue salvage index than receiving bridging therapy alone. Study outcomes The primary outcome is the penumbra tissue salvage index. Key secondary outcomes focus on: infarct growth and extent of clinical improvement from day 1 to day 7, frequency of parenchymal hemorrhage at day 1. Discussion If the hypothesis of FAMTAIS is confirmed, combination of fingolimod with bridging therapy is effective in attenuating reperfusion injury in patients with large vessel occlusion treated with 6 h of stroke onset.

Pseudo-Occlusion of the Internal Carotid Artery Predicts Poor Outcome After Reperfusion Therapy

Background and Purpose— This study aimed to evaluate the occurrence rate of the internal carotid artery pseudo-occlusion (ICA-PO) on 4-dimensional–computed tomography angiography and to investigate its relationship with clinical outcome after reperfusion therapy. Methods— In this case–control study, we retrospectively reviewed our prospectively collected database for consecutive acute ischemic stroke patients who received reperfusion therapy between June 2009 and February 2017. ICA-PO was defined when the arterial segment was not opacified on peak arterial phase yet was subsequently patent after artery peak phase on 4-dimensional–computed tomography angiography. Poor outcome was defined as 3-month modified Rankin Scale of 4 to 6. Binary logistic regression was used to investigate the relationship of ICA-PO with poor outcome and the rate of reperfusion, respectively. Results— A total of 143 patients with isolated middle cerebral artery occlusion were included and 30 (21.0%) had ICA-PO. Patients with ICA-PO were more likely to have poor outcome (80.0% versus 37.2%; P<0.001) and a lower rate of reperfusion (45.8% versus 69.0%; P=0.033) than those without. Binary logistic regression revealed that ICA-PO was independently associated with poor outcome (odds ratio, 7.957; 95% confidence interval, 1.655–34.869; P=0.009) and reperfusion at 24 hours (odds ratio, 0.150; 95% confidence interval, 0.045–0.500; P=0.002) after adjustment. Among patients with no reperfusion, all ICA-PO patients obtained poor outcome, whereas only 45.2% non-PO patients underwent poor outcome (P=0.001). Conclusions— Four dimensional-computed tomography angiography is a useful noninvasive technique to identify ICA-PO. Patients with ICA-PO are prone to undergo poor outcome from reperfusion therapy, especially when reperfusion is not achieved.

Increased blood-brain barrier permeability in contralateral hemisphere predicts worse outcome in acute ischemic stroke after reperfusion therapy

Aims We sought to investigate the risk factors of blood-brain barrier (BBB) disruption, and its potential impact on 90-day clinical outcome in acute ischemic stroke (AIS) patients after reperfusion therapy. Methods Consecutive acute anterior circulation AIS patients imaged with computed tomographic perfusion (CTP) before reperfusion therapy were included. Tmax >6 s was used for the volumetric measurement of the hypoperfusion area. BBB permeability (BBBP) was calculated as the average relative permeability-surface area product (rPS) within the hypoperfusion region (rPShypo-i) and its contralateral mirror region (rPShypo-c) on CTP-derived PS color maps. Modified Rankin Scale (mRS) score was obtained at 90-day post-stroke. Results A total of 187 patients were included, among whom the median age was 73 (61–80) years and 76 (40.6%) were women. Median baseline NIHSS score was 12 (7– 16). Ninety-eight (52.4%) patients had mRS score >2. Increased rPShypo-i and rPShypo-c were both independently associated with males and large infarct volume. The increased rPShypo-i was also independently associated with a history of atrial fibrillation and high NIHSS score. Multivariable analysis showed higher rPShypo-c was independently associated with higher mRS (OR: 1.064, 95% CI 1.011 to 1.121; P=0.018). Conclusion BBBP in both the hypoperfusion region and its contralateral mirror region are associated with stroke severity, but only increased BBBP in the contralateral mirror hypoperfusion region relates to worse outcome after reperfusion therapy.

Corrigendum: Novel Prehospital Prediction Model of Large Vessel Occlusion Using Artificial Neural Network

[This corrects the article DOI: 10.3389/fnagi.2018.00181.].

Novel Prehospital Prediction Model of Large Vessel Occlusion Using Artificial Neural Network

Background: Identifying large vessel occlusion (LVO) patients in the prehospital triage stage to avoid unnecessary and costly delays is important but still challenging. We aim to develop an artificial neural network (ANN) algorithm to predict LVO using prehospital accessible data including demographics, National Institutes of Health Stroke Scale (NIHSS) items and vascular risk factors. Methods: Consecutive acute ischemic stroke patients who underwent CT angiography (CTA) or time of flight MR angiography (TOF-MRA) and received reperfusion therapy within 8 h from symptom onset were included. The diagnosis of LVO was defined as occlusion of the intracranial internal carotid artery (ICA), M1 and M2 segments of the middle cerebral artery (MCA) and basilar artery on CTA or TOF-MRA before treatment. Patients with and without LVO were randomly selected at a 1:1 ratio. The ANN model was developed using backpropagation algorithm, and 10-fold cross-validation was used to validate the model. The comparison of diagnostic parameters between the ANN model and previously established prehospital prediction scales were performed. Results: Finally, 300 LVO and 300 non-LVO patients were randomly selected for the training and validation of the ANN model. The mean Youden index, sensitivity, specificity and accuracy of the ANN model based on the 10-fold cross-validation analysis were 0.640, 0.807, 0.833 and 0.820, respectively. The area under the curve (AUC), Youden index and accuracy of the ANN model were all higher than other prehospital prediction scales. Conclusions: The ANN can be an effective tool for the recognition of LVO in the prehospital triage stage.

Presence of multi-segment clot sign on dynamic CT angiography: a predictive imaging marker of recanalisation and good outcome in acute ischaemic stroke patients

ObjectiveTo investigate the value of multi-segment clot (MSC) sign on dynamic CT angiography (CTA) in predicting recanalisation and outcome after reperfusion therapy in acute ischaemic stroke (AIS) with large artery occlusion (LAO).MethodsWe retrospectively reviewed data of anterior circulation LAO patients from a prospectively collected database for consecutive AIS patients who underwent perfusion CT (CTP) before treatment. MSC sign was defined as the presence of multiple segments on dynamic CTA derived from CTP data. Good outcome was defined as modified Rankin score 0–3 at 90 days.ResultsA total of 181 LAO patients were enrolled. MSC sign was present in 73 (40.3%) patients. When compared with patients without MSC sign, patients with MSC sign had a significantly higher rate of recanalisation (76.7% versus 56.5%, p = 0.005) and good outcome (67.1% versus 51.0%, p = 0.035). Multivariable logistic regression analyses showed that MSC sign was an independent predictor for both recanalisation (OR [95% CI] = 2.237 [1.069–4.681]; p = 0.033) and good outcome (OR [95% CI] = 2.715 [1.154–6.388]; p = 0.022) after adjustment.ConclusionsThe MSC sign is a good indicator for recanalisation and good outcome after reperfusion therapy in anterior circulation LAO patients.Key Points• MSC sign was present in about 40% acute anterior circulation LAO patients.• MSC sign is a predictor for recanalisation after reperfusion treatment.• Patients with MSC sign have a better outcome.

Fingolimod Enhances the Efficacy of Delayed Alteplase Administration in Acute Ischemic Stroke by Promoting Anterograde Reperfusion and Retrograde Collateral Flow: Fingolimod and tPA in AIS

The present study was undertaken to determine the efficacy of coadministration of fingolimod with alteplase in acute ischemic stroke patients in a delayed time window.

Prehospital Notification Procedure Improves Stroke Outcome by Shortening Onset to Needle Time in Chinese Urban Area

Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) can improve clinical outcome in eligible patients with acute ischemic stroke (AIS). However, its efficacy is strongly time-dependent. This study was aimed to examine whether prehospital notification by emergency medical service (EMS) providers could reduce onset to needle time (ONT) and improve neurological outcome in AIS patients who received IVT. We prospectively collected the consecutive clinical and time data of AIS patients who received IVT during one year after the initiation of prehospital notification procedure (PNP). Patients were divided into three groups, including patients that transferred by EMS with and without PNP and other means of transportation (non-EMS). We then compared the effect of EMS with PNP and EMS use only on ONT, and the subsequent neurological outcome. Good outcome was defined as modified Rankin Scale score of 0-2 at 3-months. In 182 patients included in this study, 77 (42.3%) patients were transferred by EMS, of whom 41 (53.2%) patients entered PNP. Compared with non-EMS group, EMS without PNP group greatly shortened the onset to door time (ODT), but EMS with PNP group showed both a significantly shorter DNT (41.3 ± 10.7 min vs 51.9±23.8 min, t=2.583, p=0.012) and ODT (133.2 ± 90.2 min vs 174.8 ± 105.1 min, t=2.228, p=0.027) than non-EMS group. Multivariate analysis showed that the use of EMS with PNP (OR=2.613, p=0.036), but not EMS (OR=1.865, p=0.103), was independently associated with good outcome after adjusting for age and baseline NIHSS score. When adding ONT into the regression model, ONT (OR=0.994, p=0.001), but not EMS with PNP (OR=1.785, p=0.236), was independently associated with good outcome. EMS with PNP, rather than EMS only, improved stroke outcome by shortening ONT. PNP could be a feasible strategy for better stroke care in Chinese urban area.