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.

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.

[Safety of tirofiban in patients with acute cerebral infarct receiving endovascular therapy].

OBJECTIVE: To investigate the effect of tirofiban on hemorrhagic transformation and neurological outcome in patients with acute cerebral infarct treated with endovascular therapy. METHODS: One hundred and fifteen patients with acute cerebral infarct who received endovascular stent mechanical thrombectomy in the Second Affiliated Hospital, Zhejiang University School of Medicine during October 2013 and April 2017 were included in the study. Among 115 patients, 30 received tirofiban treatment. Hemorrhagic transformation and neurological outcomes were assessed using the ECASS Ⅱ criteria and modified Rankin scale (mRS), respectively. Unfavorable outcome was defined as mRS>2. Binary logistic regression model was used to analyze the independent predictors of hemorrhagic transformation and neurological outcome. RESULTS: Binary logistic regression analysis showed that tirofiban treatment did not increase the risk of hemorrhagic transformation (OR=0.437, 95% CI:0.168-1.132, P>0.05); baseline NIHSS (OR=1.136, 95% CI:1.014-1.273, P<0.05), recanalization (OR=0.060, 95% CI:0.010-0.365, P<0.01), hypertension (OR=4.233, 95% CI:1.320-13.570, P<0.05) and onset to treatment time(OR=1.006, 95% CI:1.001-1.011, P<0.05) were independently associated with unfavorable outcome, while such association was not observed in tirofiban treatment (OR=1.923, 95% CI:0.536-6.568, P>0.05). CONCLUSIONS: Tirofiban appears to be safe for patients with acute cerebral infarct receiving endovascular therapy.

[Relationship between dynamic CT angiography-based collateral flow evaluation and outcome of patients with stroke induced by acute basilar artery occlusion].

OBJECTIVE: To evaluate the collateral flow in patients with ischemic stroke due to acute basilar artery occlusion by dynamic CT angiography and to predict the outcome after reperfusion therapy. METHODS: Forty-five patients with stroke due to acute basilar artery occlusion undergoing reperfusion treatment in the Second Affiliated Hospital of Zhejiang University School of Medicine during January 2012 and August 2016 were retrospectively reviewed. Univariate and binary logistic regression model were used to identify the independent predictors of patient's outcome, and the receiver operating characteristic (ROC) curve was used to determine the optimal threshold of the posterior circulation collateral score (PC-CS) in predicting the prognosis of the patients. RESULTS: Binary logistic regression analysis indicated that the baseline National Institutes of Health Stroke Scale (NIHSS) score (OR=0.886, 95% CI:0.802-0.979, P<0.05) and PC-CS (OR=1.962, 95%CI:1.026-3.752, P<0.05) were independent predictors of patient's outcome, and PC-CS 4.5 was the optimal threshold (AUC:0.837, sensitivity of 68.2%, specificity of 87.0%). CONCLUSIONS: Dynamic CT angiography based on CT perfusion imaging can be used to evaluate collaterals in posterior circulation, and to predict clinical outcome after reperfusion therapy in patients with acute basilar artery occlusion.

[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.

[Safety of intravenous thrombolysis in cerebral microbleeds patients with prior antiplatelet therapy].

OBJECTIVE: To evaluate the safety of intravenous thrombolysis (IVT) in cerebral microbleeds (CMBs) patients with prior antiplatelet therapy. METHODS: Four hundred and forty nine patients with acute ischemic stroke aged (66.8 ± 12.9) years, including 298 males and 151 females, underwent susceptibility-weighted imaging (SWI) examination and MRI-guided IVT therapy between June 2009 and June 2015. The presence of CMBs, previous antiplatelet therapy, HT subtypes according to ECASS II criteria and functional outcome based on modified Rankin scale (mRS) at 3 months were analyzed in logistic regression model. RESULTS: Total 934 CMBs were detected in 172 (38.3%) patients, among whom 63 (14.0%) previously received antiplatelet therapy. All patients received intravenous recombinant tissue-plasminogen activator (rt-PA) for thrombolysis with the onset-to needle time of (229.0 ± 103.7) min. The pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 10 (IQR 5-15). Logistic regression analysis indicated that prior antiplatelet use increased neither risk of parenchymal hematoma (PH) (OR=0.809,95% CI:0.201-3.262, P=0.766) nor adverse functional outcome (OR=1.517, 95% CI:0.504-4.568, P=0.459) in patients with CMBs; while in patients with multiple CMBs (≥ 3) prior antiplatelet use increased risk of hemorrhagic transformation (OR=9.737, 95% CI: 1.364-69.494, P=0.023), but not adverse functional outcome (OR=1.697, 95% CI:0.275-10.487, P=0.569). CONCLUSION: The study indicates that in patients with CMBs, thrombolytic therapy should not be excluded due to the prior use of antiplatelet; however, the larger prospective studies are needed in future for patients with multiple CMBs.

[Older age is not related to hemorrhagic transformation and favorable outcomes in patients with wake-up ischemic stroke undergoing intravenous thrombolytic therapy].

OBJECTIVE: To investigate factors related to hemorrhagic transformation and favorable outcomes in wake-up ischemic stroke (WUIS) patients undergoing intravenous thrombolytic therapy. METHODS: Clinical data of 600 patients undergoing multimodal image-guided intravenous recombinant tissue plasminogen activator (rt-PA) therapy in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine center from May 2009 to May 2015 were retrospectively analyzed. Among 600 patients, 68 were diagnosed as WUIS including 17 cases aged 80 or older. Hemorrhagic transformation within the first 24 h after thrombolysis was assessed according to ECASS II criteria. Favorable outcome was defined as three-month modified Rankin Scale (mRS) 0-3. Univariate and binary logistic regression were used to analyze the risk factors of hemorrhagic transformation and poor clinical outcomes in WUIS patients. RESULTS: Univariate analysis showed that WUIS patients aged ≥ 80 years had a lower rate in males (41.2% vs 76.5%, P=0.007), smokers (11.8% vs 43.1%, P=0.019) and favorable outcome (52.9% vs 78.4%, P=0.043); and a higher rate of cardiac embolism (64.7% vs 35.3%, P=0.034) compared with those aged <80 years. Binary logistic regression showed that age was not an independent risk factor for favorable outcome (OR=0.524, 95% CI:0.141-1.953, P=0.336) or hemorrhagic transformation (OR=1.039, 95% CI: 0.972-1.111, P=0.262). CONCLUSION: Older age is not related to the favorable outcome or hemorrhagic transformation in WUIS patients undergoing multimodal image-guided intravenous thrombolytic therapy.

Long-term efficacy of venous sinus stenting in the treatment of idiopathic intracranial hypertension.

BACKGROUNDS: Previous studies have suggested that cerebral dural sinus stenosis could be a possible underlying cause of idiopathic intracranial hypertension (IIH). Venous sinus stenting (VSS) has emerged as a potential alternative for treating IIH related to dural sinus stenosis. However, most of the documented studies have been conducted in Western countries. In this study, we present the results of 16 Chinese IIH patients who underwent VSS treatment in our single center. METHODS: We prospectively collected angiographic and manometric data from IIH patients who underwent angioplasty/stenting. All patients had confirmed dural sinus stenosis and had failed maximal medical therapy (MMT). Demographic, clinical, and radiological presentation, as well as long-term follow-up outcomes were collected retrospectively. RESULTS: A total of 16 patients who underwent VSS were enrolled in the present study. Demographic data revealed a mean age of 40 (range 20-55), with 69% (11/16) being female, and a mean body mass index (BMI) of 27.05 (range 19.18-38.04) kg/m2 . All patients presented with papilledema and visual disturbances. During a median follow-up period of 47.5 months, 93.75% (15/16) of patients reported improvement in symptoms, although only 37.5% (6/16) experienced complete resolution. Headaches, blurred vision, and amaurosis related to increased pressure improved in 100% (8/8), 81.25% (13/16), and 75% (3/4) of patients, respectively. However, one patient suffered cerebral infarction and secondary epilepsy soon after VSS, and another patient had recurrence of symptoms due to stent wall thrombosis 2 years later. CONCLUSIONS: The significance of venous sinus stenosis in the development of IIH may be undervalued. Our study, based on a Chinese case series, affirms the long-term safety and effectiveness of VSS in treating IIH patients with relatively lower BMI than those from Western countries.

Perfusion Changes of Unexplained Early Neurological Deterioration After Reperfusion Therapy.

Early neurological deterioration (END) after thrombolysis occurs in 10% acute ischemic stroke (AIS) patients, and its mechanism remains unclear in majority of cases, named as unexplained END. We tested the hypothesis that penumbra/infarct growth beyond the initial penumbra might be the cause of unexplained END. We reviewed the database of AIS patients who received reperfusion therapy. Unexplained END was defined as ≥ 2-point increase of NIHSS from baseline to 24 h, without straightforward causes. For each unexplained END patient, we extracted 2 matched controls based on 4 clinical and radiological characteristics which were strongly associated with unexplained END. We defined extra-penumbra and extra-infarct as penumbra and infarct growth at 24 h beyond baseline penumbral tissue and then investigated the relationship between extra-penumbra and extra-infarct and the presence of unexplained END. Finally, 44 unexplained END patients and 88 matched controls were included. The volume of both extra-infarct (OR, 1.032 per 1-mL increase; p = 0.018) and extra-penumbra (OR, 1.070 per 1-mL increase; p < 0.001) were associated with the presence of unexplained END, while the absence of recanalization was associated with the presence of either extra-infarct or extra-penumbra (OR, 3.291; p = 0.001). Moreover, 51.4% cases with extra-penumbra at 24 h finally progressed to infarct at 7 days, and they underwent higher increase of NIHSS from 24 h to 7 days than those that did not progress to infarct at 7 days (4.0 vs 1.0; p = 0.017). Penumbra/infarct growth beyond the initial penumbra is involved in the unexplained END in AIS patients receiving reperfusion therapy.

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.

Better Correlation of Cognitive Function to White Matter Integrity than to Blood Supply in Subjects with Leukoaraiosis.

Leukoaraiosis is associated with increased risk of cognitive impairment, but its pathophysiological pathway is unclear. The aim of the present study was to determine whether brain structural damage or cerebral blood supply better correlated with the global cognitive outcome in subjects with leukoaraiosis. Seventy-five subjects with leukoaraiosis were included in present study, with age ranged from 43 to 85 years, with mean white matter hyperintensities (WMH) volume 30.69 ± 24.35 mL. Among them, 19(25.33%) subjects presented with cerebral microbleeds (CMB) and 40 (53.33%) subjects presented with lacunes. These participants received arterial spin labeling perfusion MRI, diffusion-tensor imaging (DTI) and diffusion Kurtosis imaging. We analyzed the cerebral blood flow (CBF) by dividing the brain tissue into three regions: WMH, normal appearing white matter (NAWM) and cortex. After adjusting for age and gender, the CBF of NAWM was significantly correlated with fractional anisotropy (FA) (r = 0.336, p = 0.004) and mean diffusion (MD) (r = -0.271, p = 0.020) of NAWM, while there lacked of association between CBF of cortex and mean kurtosis (MK) of cortex (r = -0.015, p = 0.912). Meanwhile, both NAWM-FA (r = -0.443, p < 0.001) and NAWM-MD (r = 0.293, p = 0.012), as well as cortex-MK (r = -0.341, p = 0.012) was significantly correlated with WMH volume. Univariate regression analysis demonstrated that global cognitive function was significantly associated with mean FA or MD of both WMH and NAWM, and cortex-CBF, but neither with the cortex-MK, nor the presences of CMB or lacunes. Finally, multiple linear regression analysis revealed that global cognitive function was independently associated with NAWM-FA (standardized ß = 0.403, p < 0.001) and WMH-FA (Standardized ß = 0.211, p = 0.017), but not with the cortex-CBF. A model that contained NAWM-FA, WMH-FA and years of education explained 49% of the variance of global cognitive function. Cerebral perfusion status might have a significant impact on the maintenance of white matter integrity in subjects with leukoaraiosis. Global cognitive function was more strongly associated with white matter integrity than with blood supply. DTI parameters, especially FA could serve as a potent imaging indicator for detecting the invisible alteration of white matter integrity and implying its potential cognitive relevance.

A Brain Region-Based Deep Medullary Veins Visual Score on Susceptibility Weighted Imaging.

Cerebral venous collagenosis played a role in the pathogenesis of white matter hyperintensities (WMHs) through venous ischemia. Since pathological changes of veins from intramural stenosis to luminal occlusion is a dynamic process, we aimed to create a deep medullary veins (DMVs) visual grade on susceptibility-weighted images (SWI) and explore the relationship of DMVs and WMHs based on venous drainage regions. We reviewed clinical, laboratory and imaging data from 268 consecutive WMHs patients and 20 controls. SWI images were used to observe characteristics of DMVs and a brain region-based DMVs visual score was given by two experienced neuroradiologists. Fluid attenuated inversion recovery (FLAIR) images were used to calculate WMHs volume. Logistic-regression analysis and partial Pearson's correlation analysis were used to examine the association between the DMVs score and WMHs volume. We found that the DMVs score was significantly higher in WMHs patients than in controls (p < 0.001). Increased DMVs score was independently associated with higher WMHs volume after adjusting for total cholesterol level and number of lacunes (p < 0.001). Particularly, DMVs scores were correlated with regional PVHs volumes in the same brain region most. The newly proposed DMVs grading method allows the clinician to monitor the course of DMVs disruption. Our findings of cerebral venous insufficiency in WMHs patients may help to elucidate the pathogenic mechanisms and progression of WMHs.

Multimodal imaging findings in normal-appearing white matter of leucoaraiosis: a review.

Leucoaraiosis (LA), also referred to as white matter hyperintensities (WMHs), are usually seen as patchy or confluent hyperintense areas on T2-weighted or fluid-attenuated inversion recovery MRI in the elderly. It is often asymptomatic in its early stages, yet its persistent evolution to more advanced stages may lead to substantial neurological dysfunction including dementia, stroke and death. Despite its clinical significance, the pathogenic mechanisms underlying LA development are uncertain. In patients with LA, the pathophysiological changes in white matter (WM) are suggested to be continuous from WMHs to its neighbourhood 'normal-appearing white matter (NAWM)' on conventional MRI sequences. Multimodal imaging studies revealed that the so-called 'NAWM' was actually abnormal with regard to underlying haemodynamic and microstructural changes. On the basis of positron emission tomography CT, xenon-CT, perfusion MRI, etc, the cerebral blood flow of NAWM was found to be significantly reduced in patients with LA, compared with healthy controls. Meanwhile, the integrity of microstructures and blood-brain barrier in NAWM was also demonstrated to be impaired with diffusion tensor imaging and dynamic contrast-enhanced MRI studies, respectively. In addition,the integrity of NAWM correlated much stronger with cognitive performance than did WMHs load. It is reasonable to assume that the subtle injury of NAWM would be more reversible than WMHs themselves. Therefore, multimodal imaging modalities could be appropriately applied to future interventional studies targeting at early pathophysiological changes of NAWM. In this paper, we summarise current knowledge about NAWM of LA mainly acquired from multimodal imaging studies in vivo, and attempt to give options for future work.

Association between Leukoaraiosis and Poor Outcome is not due to Reperfusion Inefficiency after Intravenous Thrombolysis.

Leukoaraiosis (LA) is associated with structural and functional cerebrovascular impairment, which may compromise the capacity of ischemic tissue to maximize reperfusion after intravenous thrombolysis (IVT). We aimed to determine whether severe LA is correlated with reperfusion inefficiency, which contributes to infarct growth and poor functional outcome. We analyzed data from our consecutive acute ischemic stroke (AIS) patients who had acquired baseline and 24-h follow-up diffusion- and perfusion-weighted imaging. Reperfusion was defined as reduction of ≥70 % of hypoperfusion lesion at 24 h from baseline. Severe LA was defined as Fazekas score 2 or 3 on FLAIR images. We investigated the relationship between severity of LA and reperfusion status. Multivariate statistical analysis was carried out for modeling the independent predictors of reperfusion, infarct growth, and functional outcome. Finally, 79 patients were included, among them 30 (37.97 %) had severe LA. Reperfusion was observed in 41 (51.89 %) patients, the proportion of reperfusion was very similar in patients with and without severe LA (53.33 vs 51.02 %, p = 1.000). Large artery occlusion was the only independent unfavorable predictor for reperfusion (OR = 0.202, 95 % confidence interval, 0.060-0.673; p = 0.014). Multiple linear regression analysis revealed that severe LA was independently associated with infarct growth (standardized coefficients = 0.191, p = 0.040). Severe LA was also an independent predictor of poor outcome (mRS ≥ 3) (OR = 4.004, 95 % confidence interval, 1.267-12.656, p = 0.018) after adjusting for reperfusion and baseline severity of stroke. Severe LA was associated with infarct growth and poor outcome independent of reperfusion status, which may expand the notion that LA contributes the intrinsic vulnerability of brain tissue to acute ischemic insults. The burden of LA may not serve as an imaging indicator of reperfusion inefficiency after IVT for AIS patients.