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To assess the complementary value of high-resolution multi-contrast MRI (hrMRI) in identifying symptomatic patients with intracranial atherosclerosis (ICAS) who are likely to experience recurrent ischemic cerebrovascular events.In this retrospective cohort study, eighty patients with acute ischemic events attributed to ICAS who underwent hrMRI examination between January 2015 and January 2019 were included. Median follow-up for all patients was 30 months (range: 1 to 52 months) and recurrent ischemic cerebrovascular events were recorded. Cox regression analysis and time-dependent ROC were performed to quantify the association between the plaque characteristics and recurrent events.During the follow-up, 14 patients experienced recurrent ischemic cerebrovascular events. Young males and those with diabetes and poor medication persistence were more likely to experience recurrent events. ICAS in patients with recurrence had significantly higher enhancement ratio and steepness which is defined as the ratio between the plaque height and length than those without (p0.001 and p = 0.015, respectively). After adjustment of clinical factors, enhancement ratio (HR, 13.13 [95% CI, 3.58-48.20], p0.001) and plaque steepness (HR, 110.27 [95% CI, 4.75-2560.91], p = 0.003) were independent imaging biomarkers associated with recurrent events. Time-dependent ROC indicated that integrated high enhancement ratio and steepness into clinical risk factors improved discrimination power with the ROC increased from 0.79 to 0.94 (p = 0.008).The enhancement ratio and plaque steepness improved the accuracy over traditional clinical risk factors in predicting recurrent ischemic cerebrovascular events for patients with ICAS.• High-resolution magnetic resonance imaging helps clinicians to evaluate high-risk Intracranial plaque. • The higher enhancement ratio and plaque steepness (= height/length) were the primary biomarkers associated with future ischemic cerebrovascular events. • High-resolution magnetic resonance imaging combined with clinical characteristics showed a higher accuracy for the prediction of recurrent events in patients with intracranial atherosclerosis.

Oligovascular coupling contributes to white matter vascular homeostasis. However, little is known about the effects of oligovascular interaction on oligodendrocyte precursor cell (OPC) changes in chronic cerebral ischemia. Here, using a mouse of bilateral carotid artery stenosis, we show a gradual accumulation of OPCs on vasculature with impaired oligodendrogenesis. Mechanistically, chronic ischemia induces a substantial loss of endothelial caveolin-1 (Cav-1), leading to vascular secretion of heat shock protein 90α (HSP90α). Endothelial-specific over-expression of Cav-1 or genetic knockdown of vascular HSP90α restores normal vascular-OPC interaction, promotes oligodendrogenesis and attenuates ischemic myelin damage. miR-3074(−1)−3p is identified as a direct inducer of Cav-1 reduction in mice and humans. Endothelial uptake of nanoparticle-antagomir improves myelin damage and cognitive deficits dependent on Cav-1. In summary, our findings demonstrate that vascular abnormality may compromise oligodendrogenesis and myelin regeneration through endothelial Cav-1, which may provide an intercellular mechanism in ischemic demyelination.

Traumatic brain injury (TBI) is a worldwide health problem contributing to significant economic burden. TBI is difficult to treat partly due to incomplete understanding of pathophysiology. Ferroptosis is a type of iron-dependent programmed cell death which has gained increasing attention due to its possible role in TBI. Current studies have demonstrated that ferroptosis is related to the pathology of TBI, and inhibition of ferroptosis may improve long term outcomes of TBI. Therefore, clarification of the exact association between ferroptosis and traumatic brain injury is necessary and may provide new targets for treatment. This review describes (1) the ferroptosis pathways following traumatic brain injury, (2) the role of ferroptosis during the chronic phase of traumatic brain injury, and (3) potential therapies targeting the ferroptosis pathways.

Cerebrovascular disease is a significant global public health concern, despite the diagnosis and treatment of stroke has made great progress in recent years, however, its mainly guided by anatomical indicators, which still needs to be further improved, and there is an urgent need to explore a more accurate and comprehensive functional imaging assessment method. Rapid development of coronary CT angiography derived fractional flow reserve (CT-FFR) has become an important technique for noninvasive evaluation of coronary artery disease, and these successful application experiences inspiried neurologists to explore the functional evaluation technique of cerebral arteries and demonstrated broad application prospects. In this paper, by analyzing and comparing the coronary CT-FFR technology, the progress, existing problems and possible solutions of the functional evaluation for cerebral arterial stenosis are discussed from the aspects of coronary CT-FFR study, cerebral artery functional evaluation study, and the comparison and consideration of cerebral arterial and coronary CT-FFR.脑血管疾病是全球重大公共卫生问题，尽管脑卒中诊疗近些年取得很大进展，但以解剖学为指导的脑卒中诊疗仍有待进一步改善，迫切需要更精准、全面的功能影像评估手段。冠状动脉CT血流储备分数（CT-FFR）的快速发展已经成为无创评估冠状动脉疾病的重要技术，这些成功的经验启发神经影像医生探索脑动脉功能评估技术并展示了广阔的应用前景。本文通过分析对比冠状动脉CT-FFR技术，着重从冠状动脉CT-FFR研究、脑动脉功能评估研究及脑动脉与冠状动脉CT-FFR的对照与思考这几个方面探讨了脑动脉狭窄功能评估的进展、存在问题以及可能的解决方案。.

Background Homocysteine is correlated with several imaging features of cerebral small vessel disease including white matter hyperintensities, lacunes, and enlarged perivascular spaces (EPVS) in the basal ganglia. However, little is known about EPVS in the brainstem. This study aimed to investigate the correlation between serum total homocysteine (tHcy) and EPVS in the brainstem in patients with acute isolated pontine infarction. Methods Consecutive patients with isolated pontine infarction were retrospectively enrolled. Clinical characteristics and laboratory tests including tHcy were recorded. Imaging markers of cerebral small vessel disease including EPVS in the basal ganglia (BG-EPVS), EPVS in the centrum semiovale, and EPVS in the midbrain or pons (brainstem-EPVS) were assessed using conventional magnetic resonance imaging. The relation between tHcy and EPVS of different parts in the brain was analyzed using univariate and multivariate regression model. Results A total of 227 patients were included (mean age 67.10 ± 9.38 years, male sex 58.6%). The frequencies of brainstem-EPVS and moderate to severe BG-EPVS accounted for 40.1% (91/227) and 40.5% (92/227) respectively. After controlling for confounding factors, multivariate logistic regression analyses showed that tHcy was an independent risk factor for both moderate to severe BG-EPVS (P = 0.003, P for trend < 0.001) and the presence of brainstem-EPVS (P < 0.001, P for trend < 0.001) in a dose-dependent manner. Furthermore, multivariate linear regression model indicated that the presence of brainstem-EPVS (β = 0.264, 95% confidence interval = 0.143-0.402, P < 0.001) and the severity of BG-EPVS (β = 0.162, 95% confidence interval = 0.024-0.197, P = 0.013) were positively associated with serum tHcy. Conclusions Serum tHcy is correlated with brainstem-EPVS and BG-EPVS dose-dependently. This study may support a contributing role for homocysteine in the pathophysiology of EPVS in the brainstem and the basal ganglia.

Ischemic stroke can cause secondary myelin damage in the white matter distal to the primary injury site. The contribution of astrocytes during secondary demyelination and the underlying mechanisms are unclear. Here, using a mouse of distal middle cerebral artery occlusion, we show that lipocalin-2 (LCN2), enriched in reactive astrocytes, expression increases in nonischemic areas of the corpus callosum upon injury. LCN2-expressing astrocytes acquire a phagocytic phenotype and are able to uptake myelin. Myelin removal is impaired in Lcn2−/− astrocytes. Inducing re-expression of truncated LCN2(Δ2–20) in astrocytes restores phagocytosis and leads to progressive demyelination in Lcn2−/− mice. Co-immunoprecipitation experiments show that LCN2 binds to low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes. Knockdown of Lrp1 reduces LCN2-induced myelin engulfment by astrocytes and reduces demyelination. Altogether, our findings suggest that LCN2/LRP1 regulates astrocyte-mediated myelin phagocytosis in a mouse model of ischemic stroke.

Objective To compare the effects of high-frequency (10 Hz) versus low-frequency (1 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) on motor recovery and functional reorganization of the cortical motor network during the early phase of stroke. Methods Forty-six hospitalized, first-ever ischemic stroke patients in early stage (within two weeks) with upper limb motor deficits were recruited. They were randomly allocated to three groups with 10 Hz ipsilesional rTMS, 1 Hz contralesional rTMS, and sham rTMS of five daily session. All patients underwent motor function (Upper Extremity Fugl–Meyer), neurophysiological and resting-state functional Magnetic Resonance Imaging (fMRI) (rs-fMRI) assessments before and after rTMS intervention. Motor recovery (△Fugl–Meyer Assessment) was defined as motor function changes before and after rTMS intervention. Motor function assessment was reevaluated at time point of three month follow-up. Results The two real rTMS groups manifested greater motor improvements than the sham group. The effect sustained for at least 3 months after the end of the treatment sessions. Compared with the sham group, 10 Hz ipsilesional rTMS group presented increased resting-state functional connectivity (FC) between ipsilesional primary motor cortex (M1) and contralesional M1 (P = .007), whereas 1 Hz contralesional rTMS group presented increased FC between contralesional M1 and ipsilesional supplementary motor area (P = .010), which were positively correlated with motor recovery (P < .05). Conclusion Beneficial effect of rTMS on motor recovery might be underlaid by increased FC between stimulating site and the remote motor areas, highlighting the motor network reorganization mechanism of rTMS in early post-stroke phase.

CT densitometry-based methods to directly quantify net water uptake in ischemic brain tissue have been increasingly applied recently. There is potential for net water uptake to be used as an imaging biomarker for the pathophysiology of infarcted lesions. This review is aimed at summarizing the potential and current status of the application of net water uptake as a biomarker in the management of ischemic stroke and future directions in this context. Specifically, we provide a brief overview of the principle and different methods of net water uptake measurement, followed by a discussion of the role of net water uptake in predicting malignant brain edema and hemorrhagic transformation, evaluating lesion age, and predicting the efficacy of reperfusion therapy and long-term clinical prognosis. Artificial intelligence will help address the lack of automation and standardization in the measurement of net water absorption. Further validation of net water uptake in a prospective multicenter setting is necessary. KEY POINTS: • NWU can be used as a quantitative imaging biomarker for developing malignant brain edema in anterior and posterior circulation strokes. • The difference in NWU in edema arrest or reversibility suggests that rapid and successful revascularization can influence the progression of ischemic edema. • NWU can be used to predict the age of a lesion, with predictive power comparable to that of DWI/FLAIR mismatch.

ObjectiveTo determine the influence of renal impairment (RI) on clinical outcomes at 3 months and the risk of recurrent stroke in patients presenting with emergent large vessel occlusion (ELVO) treated with emergent endovascular treatment (EVT).MethodsConsecutive patients with anterior circulation stroke due to ELVO treated with EVT in 21 endovascular centers were included. Multivariate regressions were used to evaluate the association of RI with mortality, functional independence (modified Rankin Scale [mRS] score 0–2), and functional improvement (shift in mRS score) at 3 months. The association between RI and the risk of recurrent stroke was evaluated with multivariate competing-risk regression analyses.ResultsA total of 628 patients with ELVO (mean age 64.7 ± 12.5 years, median NIH Stroke Scale score 17 points, 99 [15.8%] with RI) who underwent EVT were enrolled. After adjustment for other relevant variables, multivariate regression analysis indicated that RI was independently associated with functional independence (adjusted odds ratio 0.53, 95% confidence interval [CI] 0.29–0.96, p = 0.035) at 3 months but not with mortality or functional improvement. Multivariate competing-risk regression analysis showed that patients with RI who received EVT had a significantly higher risk of recurrent stroke (adjusted hazard ratio 2.56, 95% CI 1.27–5.18, p = 0.009) compared to those with normal renal function.ConclusionOur results suggest that RI is an independent predictor of functional independence at 3 months and long-term risk of recurrent stroke in patients with ELVO treated with EVT.

Introduction: Imaging-based early warning indicators and feasible stratification of acute ischemic stroke (AIS) patients with hemorrhagic transformation (HT), especially high-risk patients with parenchymal hematoma (PH), are crucial in determining subsequent treatment strategies. This study combined automated ASPECTS software with noncontrast CT (NCCT) and CTA source image (CTASI) attenuation changes using Hounsfield unit (HU) values to predict HT and PH in patients with AIS. Materials and Methods: We retrospectively enrolled 172 consecutive patients with anterior circulation large-vessel occlusion between 2016 and 2020. Univariate and multivariate logistic regression and receiver operating characteristic (ROC) analyses were used to investigate the relationship between NCCT and CTASI-ASPECTS-HU, as well as other clinical and radiological parameters of HT and PH. Univariate and multivariate logistic regression analyses were performed to explore risk factors for HT or PH, and an ROC curve was used to evaluate their diagnostic values. Results: A multivariate analysis showed that CTASI-ASPECTS-HU and NIHSS score were independent predictors of HT (CTASI-ASPECTS-HU: odds ratio (OR), 2.22; 95% CI, 1.01–4.92; NIHSS: OR, 1.07; 95% CI, 1.02–1.13) and PH (CTASI-ASPECTS-HU: OR, 6.51; 95% CI, 2.29–18.50; NIHSS: OR, 1.07; 95% CI, 1.01–1.13). According to ROC analysis, CTASI-ASPECTS-HU >0.09 identified HT (area under the curve, 0.70; sensitivity, 70.15%; specificity, 61.90%), and CTASI-ASPECTS-HU >0.10 identified PH (area under the curve, 0.79; sensitivity, 76.19%; specificity, 73.33%). The area under the curve for predicting HT or PH increased when CTASI-ASPECTS-HU was combined with NIHSS score (HT: area under the curve, 0.74; sensitivity, 73.13%; specificity, 70.48%; PH: area under the curve, 0.81; sensitivity, 85.71%; specificity, 72.38%). Conclusion: CTASI-ASPECTS-HU is a reliable radiological predictor of HT and PH in patients with AIS. Its predictive efficacy is moderately improved when combined with NIHSS score.

BackgroundRenal impairment (RI) is associated with worse outcomes in the treatment of intravenous thrombolysis and emergent endovascular treatment (EVT) in anterior circulation stroke. The objective of this study was to investigate the association of RI with short-term and long-term outcomes in patients with vertebrobasilar artery occlusions (VBAO) who received EVT.MethodsConsecutive patients with VBAO receiving EVT involving 21 stroke centers were retrospectively included. Multivariate regression analyses were used to evaluate the association of RI with mortality and symptomatic intracranial hemorrhage (sICH) during the hospital stay, and also mortality, favorable functional outcome (modified Rankin Scale (mRS) score of 0–3), and functional improvement (shift in mRS score) at 3 months and 1 year follow-up. The association between RI and the risk of recurrent stroke was evaluated with multivariate competing-risk regression analyses.ResultsAfter adjustment for potential confounders, RI was independently associated with sICH (OR 3.30, 95% CI 1.55 to 7.18), as well as mortality (OR 2.54, 95% CI 1.47 to 4.38; OR 3.07, 95% CI 1.72 to 8.08), favorable functional outcome (OR 0.33, 95% CI 0.17 to 0.66; OR 0.25, 95% CI 0.12 to 0.51), and functional improvement (OR 0.45, 95% CI 0.28 to 0.74; OR 0.35, 95% CI 0.21 to 0.60) at 3 months and 1 year follow-up, respectively, but RI was not associated with in-hospital mortality. Additionally, there was no significant association between RI and recurrent stroke within 1 year.ConclusionsOur findings suggest that RI is associated with a higher risk of sICH in hospital and a decrease in survival, favorable functional outcome, and functional improvement at 90 days and 1 year follow-up.Trial registration numberURL:http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.

We assessed the value of computed tomography (CT) and automated Alberta Stroke Program Early CT Score (ASPECTS) with net water uptake (NWU) to predict stroke onset time.Two-hundred forty stroke patients with anterior circulation large-vessel occlusion were included. CT-ASPECTS-NWU values were calculated by comparing the mean Hounsfield units of affected ASPECTS regions with unaffected contralateral regions. The correlation between ASPECTS-NWU and stroke onset to CT time was assessed. ASPECTS-NWU predictive values were calculated to identify a stroke onset to CT time of within 4.5/6 h.A correlation existed between stroke onset to CT time and ASPECTS-NWU (r = 0.65, p 0.001), which was affected by collateral status and infarct location. The area under the receiver operating characteristic (ROC) curve (AUC) for distinguishing a stroke onset to CT time of within 4.5 h was 0.837 (95% confidence interval [CI] 0.784-0.881; optimal cutoff 7%; sensitivity 87.10%; specificity 62.36%). The multi-index AUC was 0.884 (95% CI 0.837-0.922). The AUC for distinguishing a stroke onset to CT time of within 6 h was 0.836 (95% CI 0.783-0.880; optimal cutoff 9%; sensitivity 72.73%; specificity 81.16%). The multi-index AUC was 0.881 (95% CI 0.834-0.920).ASPECTS-NWU may be used to determine stroke onset time in patients with unwitnessed or wake-up stroke.

Net water uptake (NWU) has been shown to have a linear relationship with brain edema. Based on an automated-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) technique, we automatically derived NWU from baseline multimodal computed tomography (CT), namely ASPECTS-NWU. We aimed to determine if ASPECTS-NWU can predict the development of malignant cerebral edema (MCE).One hundred and forty-six patients with large-vessel occlusion were retrospectively enrolled. Quantitative NWU based on automated-ASPECTS was measured both on nonenhanced CT (NECT) and CT angiography (CTA), namely NECT-ASPECT-NWU and CTA-ASPECTS-NWU. The correlation between ASPECTS-NWU and cerebral edema (CED) grades was calculated using Spearman rank correlation. Univariate logistic regression was used to assess the effect of radiological and clinical features on MCE, and a multivariable model with significant factors from the univariate regression analysis was built. Receiver operating characteristic (ROC) was obtained and area under curve (AUC) was compared.CTA-ASPECTS-NWU had a moderate positive correlation with CED grades (r = 0.62; 95% confidence interval [CI], 0.51-0.71; p 0.001). The CTA-ASPECTS-NWU performed better than the NECT-ASPECTS-NWU with AUC: 0.88 vs. 0.71 (p 0.001). Multivariable logistic regression model integrating CTA-ASPECTS-NWU, collateral score, and age showed the CTA-ASPECTS-NWU was an independent predictor of MCE with an AUC of 0.94 (95% CI: 0.90-0.98; p 0.001).This study demonstrates that ASPECTS-NWU is a quantitative predictor of MCE after large-vessel occlusion of the middle cerebral artery territory. The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment.• The automated-ASPECTS technique can automatically detect the affected regions with early ischemic changes and NWU could be manually calculated. • The CTA-ASPECTS-NWU performs better than the NECT-ASPECTS-NWU on predicting the development of MCE. • The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment.

This study aimed to use the automated Alberta Stroke Program Early CT Score (ASPECTS) software to assess the value of different CT modalities (non-contrast CT, CT angiography [CTA]-arterial, CTA-venous, and arterial- and venous-phase mismatch-ASPECTS) in predicting the final infarct extent and clinical outcome in large-vessel occlusion stroke.This retrospective study included patients with large-vessel occlusion stroke who underwent reperfusion therapy during 2015 to 2019. Correlations between different CT-ASPECTS modalities and follow-up CT-ASPECTS and outcome were determined using Spearman rank correlation coefficient. Receiver operating characteristic curve analysis was used to assess the ability of different CT-ASPECTS modalities to identify patients with good outcomes.One hundred and thirty-five patients were included. We found almost-perfect correlation between CTA-venous-ASPECTS and follow-up CT-ASPECTS (r = 0.92; 95% CI: 0.89-0.95), better than that in other CT modalities. The 90-day modified Rankin scale (mRS) score substantially correlated with CTA-venous-ASPECTS (r = -0.64; 95% CI: -0.73 to -0.52). The ROC curve analysis showed CTA-venous-ASPECTS had the highest area under the curve (AUC: 0.82; 95% CI: 0.75-0.89; P 0.001), followed by mismatch-ASPECTS (AUC: 0.75; 95% CI: 0.65-0.85; P 0.001). When emphasizing the sensitivity for identifying patients with good outcomes, the best cut-off point of mismatch-ASPECTS was -3 with the highest sensitivity (91.30%).CTA-venous-ASPECTS is a reliable tool to predict the infarct extent and outcome. Furthermore, mismatch-ASPECTS may represent images in different angiographic phases and was sensitive for prognosis prediction.

Malnutrition is associated with poor prognosis of different diseases. This study aimed to investigate the association of malnutrition with long-term mortality of older adults with ischemic stroke in China.We selected patients aged ≥65 years with first-ever ischemic stroke from the Nanjing Stroke Registry Program. Malnutrition was defined according to the controlling nutritional status score (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index score (PNI), respectively. Multivariable Cox proportional hazards regressions and competing risk regressions were performed to explore the relationship between malnutrition and the risk of mortality in older adults with ischemic stroke.Among 1065 enrolled patients, 60.5%, 46.7%, and 30.6% of patients were malnourished according to CONUT, GNRI, and PNI score. During a median follow-up of 4.74 (3.73-5.82) years, 205 (19.2%) patients died. In multivariate analysis, malnutrition (severe risk versus normal nutrition) was associated with significantly increased risk for mortality by the CONUT (adjusted hazard ratio [HR] 4.615, 95% confidence interval [CI] 1.373-15.514, P = 0.013), GNRI (adjusted HR 3.641, 95% CI 1.924-6.891, P 0.001), and PNI score (adjusted HR 1.587, 95% CI, 1.096-2.297, P = 0.014). Furthermore, adding the malnutrition indexes to models modestly improved the predictive ability of mortality.Our study indicated that malnutrition was highly prevalent in older Chinese adults with ischemic stroke and associated with increased mortality. Further research is required to evaluate the efficacy of nutritional management in these patients.

AIM Sarcopenia is a robust prognostic indicator of outcomes after surgery for colorectal cancer (CRC). However, there are no serum markers routinely available for estimating skeletal muscle mass (SMM). The present study aimed to describe a new sarcopenia index (SI), serum creatinine (Scr) × cystatin C-based glomerular filtration rate, and investigate its association with short-term complications after curative resection of CRC. METHOD Consecutive patients who underwent curative resection of CRC from December 2011 to January 2017 were retrospectively identified. Skeletal muscle cross-sectional area was analysed on L3 computed tomographic images. Receiver operating characteristic curve analysis showed that the cutoff points of SI for sarcopenia were below 56.1 in men and below 43.7 in women. Patients were classified into low and high SI groups in accordance with these cutoff values. The association between SI and body composition and the impact of preoperative SI on postoperative outcomes were analysed. RESULTS Among 417 patients, SI showed a stronger correlation with skeletal muscle area (SMA) (r = 0.537, P

Background Preoperative neuroimaging assessment of collateral circulation is important for selecting acute ischemic stroke patients who are appropriate for endovascular treatment. We sought to validate the capillary index score system in an Asian population and compare its ability in predicting clinical outcomes with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system. Methods We continuously enrolled acute ischemic stroke patients from two neurological centers from March 2014 to March 2017. Multivariate analyses were performed to assess the capillary index score system with 90-day clinical outcome (modified Rankin scale score). The scoring systems were compared for predicting good (modified Rankin scale 0–2) and excellent (modified Rankin scale 0–1) functional outcomes using area under the receiver operating characteristic curves. Results We identified 157 patients (median age, 65 years; 96 (61.1%) males), of whom 71 (45.2%) patients with 90-day good functional outcomes were selected. Capillary index score was independently associated with clinical outcome after endovascular treatment (OR 0.63; 95% CI 0.43–0.92; P = 0.016) with its predictive ability for good functional outcome (area under the receiver operating characteristic curve 0.755). For excellent functional outcome, the capillary index score system was not inferior to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system (area under the receiver operating characteristic curve 0.748 versus 0.793, P = 0.09). Conclusions The capillary index score system is a potentially useful tool for predicting 90-day functional outcomes in acute ischemic stroke patients after endovascular treatment.

ObjectiveTo investigate whether thyroid function profiles can predict poststroke fatigue (PSF) in patients with acute ischemic stroke.MethodsPatients with stroke were consecutively recruited within 3 days of onset in Jinling Hospital. Serum levels of thyroid hormones, thyroid antibodies, hematologic indexes, and biochemical indexes were measured on admission. Fatigue was scored using the Fatigue Severity Scale. Associations were analyzed with multivariate regression and restricted cubic splines.ResultsOf the 704 patients with stroke, 292 (41.5%) were diagnosed with fatigue in the acute stage and 224 (35.3%) 6 months after the index stroke. The serum levels of thyroid-stimulating hormone (TSH) were inversely associated with the risk of PSF in both the acute phase and at follow-up evaluations after adjusting for potential confounders (odds ratio 0.30, 95% confidence interval 0.24–0.37 in the acute phase, and odds ratio 0.70, 95% confidence interval 0.58–0.84 at follow-up). The subgroup analysis indicated that in the acute phase of ischemic stroke, TSH was associated with severity of PSF in the groups with euthyroidism (β = −0.70, p < 0.001), subclinical hypothyroidism (β = −0.44, p < 0.001), and low-T3 syndrome (β = −0.34, p = 0.008). Higher TSH was associated with better Fatigue Severity Scale scores in patients with low-T3 syndrome 6 months after the index stroke (β = −0.35, p = 0.01). Furthermore, in the group with low-T3 syndrome, FT3 serum level could also indicate a higher risk of PSF (β = −2.54, p < 0.001 in the acute phase, and β = −2.67, p < 0.001 at follow-up).ConclusionThyroid function profiles may predict fatigue after acute ischemic stroke, suggesting that neuroendocrine responses could have a role in PSF.

Aim Azathioprine can prevent postoperative recurrences in Crohn's disease. We compared the efficacy of azathioprine in preventing surgical recurrence to explore whether immediate prophylaxis after surgery is better than azathioprine started after endoscopic or clinical recurrence. Method Data of patients with intestinal resection and ileocolic anastomosis for Crohn's disease between 2006 and 2015 were retrieved from a prospectively maintained database. Patients were grouped according to the strategies of postoperative therapy with azathioprine. Univariate and multivariate proportional hazard Cox regression analyses were conducted to identify independent predictive factors for surgical recurrence. Results Only age equal to or less than 16 years at diagnosis was an independent risk factor for surgical recurrence in all 166 patients (P = 0.005). In patients with high risk of recurrence (27 in the symptom-driven group, 39 in the endoscopy-driven group and 69 in the immediate prophylaxis group), both immediate and endoscopy-driven azathioprine delayed and reduced surgical recurrence compared with symptom-driven azathioprine (P = 0.035, 0.019). Their efficacy in reducing surgical recurrence was confirmed by Cox regression analyses (hazard ratio 0.465, P = 0.045; hazard ratio 0.352, P = 0.028). Surgical recurrence was similar between the immediate and endoscopy-driven groups. In addition, age ≤ 16 at diagnosis was still an independent risk factor for surgical recurrence in this subgroup. Conclusions In patients with high risk of recurrence, both immediate prophylactic azathioprine after surgery and azathioprine started after endoscopic recurrence can delay and reduce surgical recurrence compared with azathioprine started after clinical recurrence. In addition, azathioprine started immediately after surgery was not superior to azathioprine started after discovery of endoscopic recurrence.

A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear.A case series of acute ischemic stroke patients treated with intravenous rt-PA followed by emergent stenting were prospectively included in Jinling Hospital Stroke Unit. An emergent loading dose of antiplatelets (aspirin 300 mg and clopidogrel 300 mg) were administered to all patients through a nasogastric tube immediately before stenting. Clinical and angiographic outcomes were evaluated in these patients.A total of 12 patients were included. The median of NIHSS score on admission was 15 points (interquartile range 11-19). The median of time from stroke symptom onset to start IV rt-PA and stent placement was 172 min (interquartile range 123.75-189) and 311.5 min (interquartile range 285.5-349.5), respectively. All patients reached complete or partial recanalization (TICI ≥2a). One patient occurred hemorrhagic transformation at 24 h following the emergent loading dose of antiplatelets. A favorable outcome as defined by mRS ≤2 at 90 days was obtained in 58.3% (7/12) of all patients.Our finding preliminary suggested that an emergent loading dose of antiplatelets may be safe and feasible for acute stenting after IV rt-PA.

Aim/background CD99 participate in neutrophil infiltration after inflammatory events; however, despite the important role of inflammation in ischemic stroke, the role of CD99 in ischemic stroke remains unclear. Method In the present study, we detected the protein expression of CD99, ICAM-1, and CD31 (PECAM-1) in oxygen-glucose deprivation (OGD)-induced bEnd.3 cells and neutrophils and explored the influence of HIF-1α and IL-1β on their expression. We also explored the role of CD99 in the OGD-induced transmigration of neutrophils. Results Our results showed that OGD induction upregulated CD99 in bEnd.3 cells and that this effect could be abolished by the preadministration of IL-1β and was not mediated by HIF-1α. However, the activation of ICAM-1 by OGD remained activated with IL-1β treatment. No significant influence of IL-1β on OGD-induced CD31. Finally, we found a significant increase in infiltrated neutrophils after OGD induction compared with the control and OGD + anti-CD99 groups. Conclusion Our results indicated that CD99 mediates neutrophil infiltration and transmigration via OGD induction and thus constitutes a potential therapeutic target for anti-inflammatory treatment after ischemic stroke.

Background and Purpose— Acute ischemic stroke caused by cervical artery dissection tend to result in unfavorable outcomes even with appropriate medical treatment. This study evaluated the safety and effectiveness of endovascular thrombectomy in treating acute ischemic stroke associated with cervical artery dissection. Methods— Patients with acute ischemic stroke and with large artery occlusion associated with dissection were selected. Propensity score matching was performed to increase the comparability. Patients with a 90-day modified Rankin Scale score of 0 to 2 were defined as with favorable outcome. Results— Eighty patients with and 80 patients without thrombectomy were enrolled. After propensity score matching, 48 patients with and 48 patients without thrombectomy were matched for further analysis. Proportion of favorable outcome (modified Rankin Scale score of 0–2) was higher in patients with thrombectomy than in those without (66.7% versus 39.6%; P =0.008). There were no significance differences about the incidence of symptomatic intracranial hemorrhage (8.3% versus 4.2%; P =0.677) and the 90-day mortality (10.4% versus 6.3%; P =0.714) between matched patients with and without thrombectomy. Conclusions— Endovascular thrombectomy seems to be an effective treatment in selected patients with acute ischemic stroke associated with cervical artery dissection, but the safety of thrombectomy needs further research.

Summary Background Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion. Methods We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov , NCT02441556 . Findings Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0–3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81–3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0–3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20–7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31–7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group. Interpretation There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study. Funding Jiangsu Provincial Special Program of Medical Science.

Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used to quantify cerebral blood perfusion by labeling blood water as it flows throughout the brain. Hypoperfusion volume ratio (HVR) can be calculated using proportional hypoperfusion volume on ASL-based cerebral blood flow (CBF). This study aimed to explore the relation between HVR and early neurological deterioration (END) in AIS patients.Patients with AIS were recruited consecutively, and ASL and regular MRI scans were performed. HVR was calculated from 1.5 and 2.5s post labeling delay (PLD) ASL-CBF maps. END was defined as ≥2 points increment of NIHSS within 72 hours of stroke onset. Univariate and multivariate analysis were used to evaluate the relation between HVR and END. Receiver operating characteristic (ROC) curves were used to determine the ability of HVR in predicting END.Of the 52 enrolled patients, 18 (34.5%) were determined with END. In patients with END, the median hypoperfusion volume was 20 mL [Inter Quartile Range)IQR, 6-72.5 mL] at 1.5s PLD, and 11.2 mL (IQR, 5.3-26 mL) at 2.5s PLD; Sixteen (88.9%) patients had HVR ≥50%, and 13 (72.2%) patients hypoperfusion volume at 2.5s PLD ASL were greater than diffusion-weighted imaging (DWI) infarct volume. In patients without END, median hypoperfusion volume was 7 mL (IQR, 4-30 mL) at 1.5s PLD, and 4 mL (IQR, 1.5-8.5 mL) at 2.5s; Eleven (32.4%) patients had HVR ≥50%, and 10 (29.4%) patients hypoperfusion volume at 2.5s PLD ASL were greater than DWI infarct volume. The proportion of HVR ≥50% and hypoperfusion volumeDWI infarct volume were more frequent in patients with END than patients without (all P0.001). After adjusted for age, admission NIHSS, proportion of hypoperfusion volumeDWI infarct and arterial transit artifact (ATA) by logistic regression analysis, HVR ≥50% (OR=13.1, P=0.003) was an independent risk factor for END. ROC analysis demonstrated that the HVR could predict END with an area under the curve of 0.794 (P=0.001).HVR obtained from the 1.5 and 2.5s PLD ASL may be a useful predictor of END in AIS. The value of HVR may be a marker for hemodynamic impairments.

Rationale Endovascular treatment plus standard medical therapy is superior to standard medical therapy alone for acute anterior proximal intracranial large artery occlusion strokes. The benefit of endovascular treatment in acute ischemic stroke caused by basilar artery occlusion remains unproven. Aim This study compares the safety and efficacy of endovascular treatment plus standard medical therapy versus standard medical therapy alone in acute ischemic stroke due to basilar artery occlusion. Design The study is a multicenter randomized control trial with blinded outcome assessment. A projected total 344 subjects with acute basilar arterial occlusion within 8 h of estimated occlusion time will be enrolled over three years in China. Patients will be assigned to endovascular treatment plus standard medical therapy and standard medical therapy alone group in 1:1 ratio for study centers. Study outcomes The primary outcome measure is a favorable functional outcome, defined as a modified Rankin Score of 0–3 at 90 days. The primary safety measure is mortality at 90 days. Trial registration ClinicalTrials.gov (NCT 02441556). Summary The BEST trial will provide valuable insights into the safety and efficacy of endovascular treatment for acute ischemic stroke patients with basilar artery occlusion.

Purpose: To evaluate the rate of stent malapposition, plaque prolapse, and fibrous cap rupture detected by optical coherence tomography (OCT) after carotid artery stenting (CAS) based on the presence of lipid-rich plaque, which may be associated with acute stent thrombosis. Methods: A retrospective study was conducted involving 26 consecutive patients who underwent CAS with OCT imaging acquired before stent deployment and after stent dilation. Adequate imaging quality could not be obtained in 6 patients (out-of-screen images and residual blood), which left 20 patients (mean age 63 years; 13 men) for analysis. Plaque characteristics were determined from 500 selected OCT cross sections; a lipid-rich plaque was defined by lipid present in ≥2 quadrants. Cross-sectional OCT images within the stented segment were evaluated at 1-mm intervals for the presence of malapposition, plaque prolapse, and fibrous cap rupture. The data were compared between patients with and without lipid-rich plaques. The patients were examined at 6 months to determine the degree of in-stent restenosis (ISR). Results: Patients with lipid-rich plaque demonstrated a higher rate of embedded stent struts (29.4% vs 23.7%, p

Recently, a genome-wide association study (GWAS) identified two common variants (rs12425791 and rs11833579) on Chromosome 12p13 that confer risk for stroke. The aim of this study was to evaluate whether these two variants are associated with risk of large artery atherosclerotic (LAA) stroke in a Chinese population. Rs12425791 and rs11833579 were genotyped using the improved multiple ligase detection reaction in 423 patients with LAA stroke and 423 healthy controls. We found a statistically significantly increased risk of LAA stroke associated with the rs12425791AA genotype (OR=2.28, 95% CI=1.15–4.51) and rs11833579 AA genotype (OR=1.92, 95% CI=1.16–3.15) compared with their GG genotype. When we evaluated these two polymorphisms together, we found that the combined genotypes with 3–4 variant alleles (rs12425791A and rs11833579A) were associated with an increased risk of LAA stroke (OR=2.06, 95% CI=1.26–3.36) compared to 0–2 variants. Moreover, genotype–phenotype correlation analysis showed that rs12425791AA and rs11833579AA carriers had significantly decreased NINJ2 mRNA expression levels in the Chinese population ( P =0.003 for rs12425791 and P =0.005 for rs11833579). These results suggested that the rs12425791 and rs11833579 polymorphisms on Chromosome 12p13 may be associated with the risk of LAA stroke and might be used as candidate biomarkers for LAA stroke susceptibility.

BACKGROUND AND PURPOSE: Differing responses to clopidogrel following endovascular treatment of cerebrovascular diseases may increase the risk of vascular complications. CYP2C19 gene polymorphisms influence clopidogrel activity. We aimed to study the clinical impact of CYP2C19 gene polymorphisms in patients undergoing endovascular treatment. MATERIALS AND METHODS: This was a prospective, longitudinal, observational study. Information on demographics and cerebrovascular status was collected as baseline. Clopidogrel response was tested by the VerifyNow P2Y12 assay. CYP2C19 genotyping was undertaken by polymerase chain reaction–restriction fragment length polymorphism. Three-month follow-up data included vascular complications, mortality, and modified Rankin Scale score. Associations were investigated among CYP2C19 genotypes, clopidogrel responsiveness, and clinical outcomes. RESULTS: One hundred and eight participants were included. Median age was 56 years (interquartile range, 48.8–65.0 years), and 35 (32.4%) were male. Forty-four participants were classified into group 1 (homozygous CYP2C19*1/*1); 31, into group 2 (25 with CYP2C19*1/*2, two with CYP2C19*1/*3, three with CYP2C19*3/*3, one with CYP2C19*2/*3); 28, into group 3 (24 with CYP2C19*1/*17, four with CYP2C19*17/*17); and 5, into group 4 (CYP2C19*2/*17). A significantly higher proportion of participants in group 3 experienced ischemic events (9 of 28, 32.1%) compared with group 1 (5 of 44, 11.4%; P = .04; odds ratio, 3.7; 95% confidence interval, 1.1–12.6). There was no significant difference in clopidogrel response among the 4 genotype groups. CONCLUSIONS: Individuals with CYP2C19*17 may have increased risk of ischemic events following endovascular treatment, independent of clopidogrel responsiveness. Larger studies are required to confirm the influence of CYP2C19*17 on clinical outcomes and to understand the mechanisms for increased ischemic events.

Background Maladjustment of matrix metalloproteinases (MMPs) results in cerebral vasculature and blood–brain barrier dysfunction, which is associated with small vessel disease (SVD). This study was to aim at evaluating correlations between matrix metalloproteinase-2 and 9 single nucleotide polymorphisms and the risk of SVD. Methods A total of 178 patients with SVD were enrolled into this study via Nanjing Stroke Registry Program (NSRP) from January 2010 to November 2011. SVD patients were further subtyped as isolated lacunar infarction (ILI, absent or with mild leukoaraiosis) and ischemic leukoaraiosis (ILA, with moderate or severe leukoaraiosis) according to the Fazekas scale. 100 age- and gender-matched individuals from outpatient medical examination were recruited as the control group. The genotypes of MMP-2-1306 T/C and MMP-9-1562 C/T were determined by the TaqMan method. Results Of 178 SVD patients, 86 and 92 patients were classified as ILI and ILA, respectively. Comparison analysis between SVD patients and controls revealed a significant correlation between SVD and hypertension, as well as a prevalence of hypertension in ILA. Further genotype analysis showed that the frequency of MMP-2-1306 CC genotype was higher in ILA patients than in controls ( P =0.009, χ 2 test; P =0.027, the multiple test with Bonferroni correction). Finally, logistic regression analysis with adjustment of age, sex and vascular risk factors showed that the MMP-2-1306 T/C polymorphism was an independent predictor for ILA (OR: 2.605; 95% confidence interval [CI], 1.067–6.364; P =0.036). Conclusion Our findings suggest that the MMP-2-1306 T/C polymorphism is a direct risk factor for ILA.

In 2009, a genome-wide association study (GWAS) identified two variants (rs12425791 and rs11833579) near NINJ2 gene that confer susceptibility to stroke in Caucasian populations. Recently, a number of studies have been conducted to replicate this finding in Asian populations. However, the results are conflicting. Thus, we performed a quantitative analysis to summarize the evidence regarding the association between these two polymorphisms and ischemic stroke risk.Pertinent studies were identified by searching PubMed and Embase through September 2014. Studies that reported odds ratio (OR) with 95% confidence interval (CI) for the association between these two polymorphisms and stroke risk were included.Eight independent publications, with 8626 cases and 8046 controls for rs12425791 and 9142 cases and 8657 controls for rs11833579, were included. Overall, significantly increased ischemic stroke risk was associated with rs12425791 A allele when all studies were pooled into the meta-analysis (AA/GA vs. GG: OR = 1.08, 95% CI: 1.01-1.14). However, rs11833579 was not associated with increased stroke risk in any genetic model.These findings indicate that rs12425791 GA polymorphism may be a low-penetrance susceptibility marker of stroke in Asian populations and further studies are warranted to verify this association.

Objective: To investigate whether dual tissue-defined ischemic attacks, defined as multiple diffusion-weighted imaging lesions of different age and/or arterial territory (dual DWI), are an independent and stronger predictor of 90-day stroke than dual clinical TIAs (dual TIA). Methods: Consecutive patients with clinically defined TIA were enrolled and assessed clinically and by MRI within 3 days. The predictive ability of the ABCD clinical factors, dual TIA, and dual DWI was evaluated by means of multivariate logistic regression. Results: Among 658 patients who were included in the study and completed 90 days of follow-up, a total of 70 patients (10.6%) experienced subsequent stroke by 90 days. Multivariate logistic regression indicated that dual DWI was an independent predictor for subsequent stroke (odds ratio 4.64, 95% confidence interval 2.15–10.01), while dual TIA was not (odds ratio 1.18, 95% confidence interval 0.69–2.01). C statistics was higher when the item of dual TIA in ABCD3-I score was replaced by dual DWI (0.759 vs 0.729, p = 0.035). The net reclassification value for 90-day stroke risk was also improved (continuous net reclassification improvement 0.301, p = 0.017). Conclusion: Dual DWI independently predicted future stroke in patients with TIA. A new ABCD3-I score with dual DWI instead of dual clinical TIA may improve risk stratification for early stroke risk after TIA.

Nut consumption has been inconsistently associated with risk of stroke. Our aim was to carry out a meta-analysis of prospective studies to assess the relation between nut consumption and stroke risk and mortality. Pertinent studies were identified by a search of PubMed and Embase through June 2014 and by reviewing the references of retrieved articles. Prospective cohort studies that reported relative risks (RRs) with 95 % confidence intervals (CIs) for the association between nut consumption and risk of stroke were included. Six articles including nine independent prospective cohorts with 476,181 participants were included in the meta-analysis. The pooled RR of stroke was 0.90 (95 % CI 0.83–0.98) comparing the highest with the lowest nut consumption. Stratifying by gender, significant inverse association was observed for females (RR 0.88; 95 % CI 0.78–0.98). Sensitivity analysis restricted to studies with adjustment for common confounding factors showed similar results, strengthening the association between nut consumption and stroke risk. Moreover, we observed a trend toward an inverse association between higher nut consumption and stroke mortality (RR 0.86; 95 % CI 0.69–1.06), although it is not significant. Current evidence indicated that nut consumption is inversely associated with risk of stroke.

Dietary protein intake has been associated with reduced risk of stroke. This study aimed to examine the relationship between premorbid dietary intake of protein and both stroke severity and neurological outcomes in patients with acute ischemic stroke.Consecutive patients with first-ever ischemic stroke in Jinling Hospital were screened for eligibility of participation. A validated foodfrequency questionnaire (FFQ) was performed to collect necessary data for calculating pre-stroke dietary intakes. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) at baseline. Neurological outcomes were assessed by the modified Rankin scale (mRS) 90 days after stroke onset. Multivariable logistical regression was applied to analyze the impacts of dietary protein intake on stroke severity or neurological outcomes.Of the 201 enrolled patients, 110 (54.7%) were classified as minor (NIHSS ≤5) and 91 (45.3%) as major stroke (NIHSS ≥6). After adjusting for potential confounders, multivariable logistic regression did not detect significant association between total (odds ratio (OR)=0.98, p=0.15), animal (OR=1.01, p=0.87) or plant protein intake (OR=0.96, p=0.07) and stroke severity. According to the 90-day mRS, 127 patients (63.2%) were determined with good (mRS ≤2), and 74 (36.8%) with poor outcomes (mR 3-6). Multivariable logistic regression detected that premorbid dietary intake of total protein was positively associated with good neurological outcomes (OR=1.05, p=0.04).Higher level of premorbid protein intake may be associated with favorable neurological outcomes independent of stroke severity.

Background and Objective: Endovascular treatment (EVT) is proven to be safe and effective for treating acute large vessel occlusion stroke (LVOS). The neutrophil-lymphocyte ratio (NLR) reflects systemic inflammation, which plays an important role in the process of treating ischemic stroke. This study aims to explore the relationship between NLR and the clinical outcomes of LVOS patients undergoing EVT. Methods: Patients were selected from the EVT for acUte Anterior circuLation (ACTUAL) ischemic stroke registry. The laboratory data (neutrophil count, lymphocyte count) before EVT were collected. Poor functional outcome was defined as modified Rankin Scale (mRS) of 3–6 at 3 months. Multivariable logistic regression analyses were performed to explore the relationship of NLR with functional outcome, symptomatic intracranial hemorrhage (sICH), and mortality. Results: We eventually included 616 patients (median of age, 66 years; 40.3% female). There were 350 (56.7%) patients achieving mRS of 3–6 at 3 months, 98 (15.9%) patients with sICH, and the mortality at 3 months was 24.8% (153/616). Baseline NLR was independently associated with poor functional outcome (OR 1.58; 95% CI 1.02–2.45; p = 0.039) and sICH (OR 1.84; 95% CI 1.09–3.11; p = 0.023) but showed a trend for predicting 3-month mortality (OR 1.57; 95% CI 0.94–2.65; p = 0.088). Conclusions: NLR independently predicts 3-month functional outcome and sICH but the existence of a trend association with mortality after EVT for acute anterior circulation LVOS patients.

A 65-year-old man underwent balloon angioplasty and repeat carotid artery stenting (CAS) due to in-stent restenosis (ISR). Intravascular optical coherence tomography (OCT) showed a severe ISR with fibrotic neointimal growth (figure 1). Post 6.0 × 30 mm balloon angioplasty, OCT showed intimal disruption and artery dissection (figure 2). After the 8 × 40 mm stent fully expanded, OCT showed stent struts well apposed, but tissue protrusion from the spaces between stent struts can be observed (figure 2). OCT allowed measurement of intimal hyperplasia after the CAS and observation of intimal disruption and stent strut apposition intraoperatively.1,2

A recent genome-wide association study (GWAS) identified a nonsynonymous SNP (1425G/A) in PRKCH which was associated with increased risk of ischemic stroke. The purpose of this study was to examine whether this functional polymorphism is associated with stroke onset and prognosis in a Chinese population. We genotyped PRKCH 1425G/A using Improved Multiple Ligase Detection Reaction in 919 patients with ischemic stroke. Analyses of genotype association with onset and prognosis outcomes were assessed by the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards models. PRKCH 1425G/A was not associated with age of stroke onset (P = 0.323). However, this functional polymorphism was significantly associated with risk of stroke recurrence in recessive models (hazard ratio [HR] = 2.23; 95 % confidential interval [CI], 1.06 to 4.68; P = 0.014), and this effect was more predominant among smokers (HR = 3.67; 95 % CI, 1.47–9.18; P = 0.005). Moreover, the variant genotypes of PRKCH 1425G/A are an independent prognostic factor for ischemic stroke in the final multivariate Cox regression model. Our findings show that PRKCH 1425G/A may be a useful biomarker for predicting the recurrence of ischemic stroke.

Background Large vessel occlusion (LVO) is associated with poor functional outcome in acute ischemic stroke. Given the uncertainty whether LVO has the same significance in mild and severe stroke, we compared functional outcomes after intravenous thrombolysis, based on severity and LVO. Methods Ischemic stroke patients were thrombolyzed in less than 4.5 hours after onset between 2007 and 2013. LVO was defined as occlusion of one of the following arteries: internal carotid, middle cerebral (M1/M2), anterior cerebral (A1), posterior cerebral (P1), basilar, or vertebral (V4) arteries on prethrombolysis computed tomography angiography. Mild stroke was defined as baseline National Institutes of Health Stroke Scale (NIHSS) score 0-6. Favorable outcome was defined as modified Rankin Scale (mRS) score 0-1 at 3 months or equal to the prestroke mRS. Results There were 175 acute stroke patients, median age 74 years (interquartile range [IQR], 64-83), median baseline NIHSS = 11 (IQR, 5-16), and 63 of 175 patients (36%) with mild stroke. LVO was associated with worse outcome in severe stroke (age-adjusted odds ratio [OR] of favorable outcome, .42; 95% confidence interval [CI], .19-.93; P = .033) and mortality (age-adjusted OR, 3.52; 95% CI, 1.08-11.48; P = .037). Although the difference in favorable outcome between mild stroke patients with and without LVO was not significant (55.6% vs. 74.1%, P = .262; age-adjusted OR of favorable outcome, .42; 95% CI, .1-1.84; P = .251), the similarity of effects across both subgroups cannot be excluded (LVO-by-stroke severity interaction test, P = .906). Conclusions LVO is associated with worse functional outcome and mortality in severe stroke after intravenous thrombolysis. Although significant association between LVO and outcome in mild stroke was not found, there were similar effects on outcome and a larger study might well confirm a relationship.

Background and purpose A recent genome-wide association study identified two genetic variants (rs12425791 and rs11833579) on chromosome 12p13 that confer risk of ischaemic stroke. The purpose of this study was to examine whether these two polymorphisms are associated with stroke onset and prognosis in a Chinese population. Methods rs12425791 and rs11833579 were genotyped using the improved multiple ligase detection reaction in 913 patients with ischaemic stroke. Analyses of genotype association with onset and prognosis outcomes were evaluated by the Kaplan–Meier method, the log-rank test and Cox proportional hazards models. Results rs12425791 and rs11833579 were not associated with age of stroke onset (P = 0.786 and 0.340, respectively). However, these two polymorphisms were significantly associated with risk of stroke recurrence, especially for the large-artery atherosclerosis (LAA) subtype, in recessive models [hazard ratio (HR) 2.52; 95% confidence interval (CI) 1.04–6.12 for rs12425791; HR 2.13; 95% CI 1.03–4.40 for rs11833579]. The combined genotype of these two single-nucleotide polymorphisms showed a locus-dosage effect on recurrence of LAA subtype and was an independent prognostic factor for LAA subtype in the final multivariate Cox regression model. Conclusions These findings indicated that rs12425791 and rs11833579 on chromosome 12p13 may be useful biomarkers for predicting the prognosis of patients with the LAA subtype of ischaemic stroke.

Background and purpose S100B and its scavenger, soluble receptor for advanced glycation end products (sRAGE), participate in various acute and chronic brain disorders. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is unclear. The purpose of this study was to investigate the relationship of CMBs with plasma S100B and sRAGE. Methods A cohort of 147 consecutive patients with first-ever acute lacunar stroke was prospectively enrolled. We collected demographic, clinical, and laboratory data, including plasma levels of S100B and sRAGE, and presence and number of CMBs using susceptibility-weighted imaging (SWI). Associations between plasma S100B, sRAGE levels and the presence, number, and location of CMBs were determined. Results CMBs were present in 58 patients (39.5%). Each 1SD-increase in S100B and sRAGE levels was significantly associated with presence of CMBs (adjusted odds ratio [OR], 3.06; 95% confidence interval [CI], 1.81–5.17 and adjusted OR, 0.29; 95% CI, 0.16–0.53; respectively) and number of CMBs (adjusted relative risk [RR], 4.07; 95% CI, 3.60–5.65 for S100B and RR 0.34; 95% CI, 0.25–0.46 for sRAGE). When stratified by location, plasma S100B and sRAGE levels were similarly associated with presence of deep CMBs (adjusted OR, 3.65; 95% CI, 1.99–6.69 and adjusted OR, 0.23; 95% CI, 0.12–0.46; respectively), but not with strictly lobar CMBs. Conclusions Higher levels of S100B and lower levels of sRAGE are independently associated with presence and number of CMBs in patients with first-ever acute lacunar stroke, particularly in those with deep CMBs.

UNLABELLED The purpose of this study was to determine the effect of colistin-induced intestinal dysbacteriosis on intestinal mucosal barrier function and bacterial translocation in a mouse model. Colistin or saline was administered orally for 7 days, and populations of viable organisms from the caecal mucosa and its content, the ileal segments, the mesenteric lymph nodes (MLNs) and the internal organs were prepared for examination. In the intestinal dysbacteriosis model, intestinal barrier dysfunction was observed and associated with increased bacterial translocation to extraintestinal sites. The extent of bacterial translocation to the MLNs and internal organs in the colistin group was significantly higher than in the saline group. Colistin-induced intestinal dysbacteriosis was shown to injure the intestinal mucosa barrier function and increase bacterial dislocation. SIGNIFICANCE AND IMPACT OF THE STUDY Colistin has been reported to be effective in selective digestive decontamination (SDD), which is an infection prevention measure used in the treatment of certain patients in intensive care. We are the first to report that colistin-induced intestinal dysbacteriosis can injure intestinal mucosal barrier function and increase bacterial translocation, whereas a high dose of colistin does not damage the intestinal mucosal barrier in germ-free (GF) mice raised in a GF environment. These results may indicate that prolonged use of a high dose of a SDD medication should be carefully considered.

Stem cell-based therapy shows great potential in stroke patients. Intra-artery infusion exhibits greater biological distribution compared to intravenous delivery. In addition, umbilical cord mesenchymal stem cells (UCMSCs) have several advantages compared with other types of stem cells. The aim of this study was to evaluate the safety and efficacy of UCMSCs delivered by a catheter to a near lesion site for treatment of an infarction in the middle cerebral artery territory. Four patients with stroke (three with ischemic and one with hemorrhagic stroke) in the middle cerebral artery territory were recruited in this study. One single dose of 2 × 107 UCMSCs was infused within 20 min via catheterization in the M1 segment of the middle cerebral artery. The safety and efficacy of this approach were assessed during the in-hospital and 6-month follow-up evaluation. The cell delivery was successfully performed in all of the patients, and no major accidents (stroke or death) were observed. Moreover, no fever or rash was reported. After cellular therapy, two of the three ischemic stroke patients demonstrated improved muscle strength. The improvement of the modified Rankin scale was observed in two patients, both of whom suffered from ischemic stroke at 90 and 180 days after the stem cell therapy. The hemorrhagic stroke patient failed to demonstrate improved muscle strength and did not amend his daily activities. Intra-artery delivery of UCMSCs via catheterization was a feasible and safe approach and may improve the neurological function of ischemic stroke patients with the middle cerebral artery territory infarcts.

Background: Angioplasty and stenting have recently become attractive options for cerebral large artery stenosis in China. However, there are limited data on safety and long-term outcomes in Chinese patients having undergone cerebral interventional procedures. To address this need, we set up a common database - the China Interventional Stroke Registry (CISR) - to describe patient characteristics, interventional images, periprocedural complications and long-term clinical outcomes and to determine how adherence to guideline-based treatments in the ‘real world' works in China. Methods: Six medical centers have participated since 2004. They entered into an Internet-based database data on demographics, clinical history and angiography of patients undergoing angioplasty with/without stenting in extracranial arteries (carotid, vertebral and subclavian arteries) and/or intracranial arteries (middle cerebral artery, vertebral artery and basilar artery) in China. CISR is a research-funded project. Results: As of October 2012, we have already collected detailed clinical information on 1,356 patients (age: 63.6 ± 10.2 years, male: 1,084, 79.9%). The overall data quality is good. Site data quality control is supported via detailed monthly feedback reports and quarterly data monitoring meetings. Conclusions: The CISR is the first and the largest registry for angioplasty with/without stents in China. The database will provide the characteristics and outcomes of patients and the situation of adherence to guideline-based treatments under ‘real-world' conditions in China.

We read with great interest the study by Giede-Jeppe et al,1 which provided evidence that lymphocytopenia is an independent predictor of unfavorable functional outcome in spontaneous intracerebral hemorrhage (ICH). We would like to highlight 3 important issues raised in the study by Giede-Jeppe et al.1 First, why does the number of circulating lymphocytes decrease in patients with ICH? Two major reasons come to mind: one has to do with the severity and progression of ICH, and the second reason is related to some external environment factors, such as infections that can potentially change lymphocytes. If lymphocytopenia is related to the severity of disease process, then …

Background and purpose: Stroke-associated pneumonia (SAP) is associated with poor functional outcome in patients with acute ischemic stroke (AIS). The objective of this study was to identify predictors of SAP in patients underwent intra-arterial treatment (IAT). Methods: Consecutive patients with AIS within 6 h from the symptom onset underwent IAT were enrolled. Independent predictors of in-hospital SAP after AIS were obtained using multivariable logistic regression. Kaplan–Meier survival curves were calculated and compared by the log-rank test. Results: Of 165 patients with AIS in the study period, 102 (61.8%) underwent IAT. Twenty-two (21.6%; 95% confidence interval [CI], 14.7–29.4) experienced SAP. Patients with SAP were older (69.2 vs 62.9 years, respectively; P = 0.011), more severely affected (National Institutes of Health Stroke Scale score, 18 vs 9, respectively; P = 0.004), more likely to underwent symptom of dysphagia (86.4% vs 15%, respectively; P

Cerebral small vessel disease (SVD) refers to a group of pathological processes that affect small arteries, arterioles, venules, and capillaries of the brain. We hypothesized that imaging markers of SVD could be associated with neurological deterioration during acute phase of mild/moderate ischemic stroke.We performed a prospective cohort with 687 consecutive patients with acute ischemic stroke and also with admission NIHSS score below 12 points. Imaging markers of SVD include silent lacunar infarction, deep cerebral microbleeds (CMBs), brain atrophy, periventricular and semiovale white matter hyperintensities, basal ganglia and semiovale enlarged perivascular spaces as well as SVD burden rating scale, which were evaluated and calculated, respectively. Early neurology deterioration (END) was defined as an increment of NIHSS score ≥2 points in the first 72 h after admission.None of these imaging markers and rating scale of SVD significantly correlated with END after adjusted for major confounders. Post hoc analysis indicated similar negative results in different age, TOAST classification and infarction location subgroups. Only silent infarction (OR 2.42, 95%CI 1.33-5.10) and deep CMBs (OR 2.10, 95%CI 1.08-3.72) seemed to be predictors for END in female patients. However, due to the increased type I error in multiple comparisons, these relationships should not be regarded as statistically significant.In patients with mild/moderate acute ischemic stroke, imaging markers of SVD did not correlate with END.

Our objective was to investigate a method for assessing early improvement and its predictive value for 3-month functional outcome in patients treated with EST. A total of 97 consecutive AIS patients undergoing EST were prospectively collected and retrospective reviewed. Data on demographics, vascular risk factors, admission National Institutes of Health Stroke Scale (NIHSS) score, 24-h NIHSS score, reperfusion and collateral formation were collected. Percent improvement was defined as ([baseline NIHSS score-24-h NIHSS score]/baseline NIHSS score×100%), while absolute improvement was calculated by the difference between scores (baseline NIHSS score-24-h NIHSS score). A 3-month functional outcome was assessed using the modified Rankin Scale (mRS). Favorable outcome was defined as a mRS score of 0-2. Areas under the receiver-operating characteristic (ROC) curve (AUC) for percent improvement and absolute improvement in predicting favorable outcome was compared. Finally, we investigated the independent predictors of improvement at 24h after EST and its relationship with favorable outcome. Pairwise comparison of ROC curves revealed that percent improvement had larger AUC than absolute improvement (p=0.004). Rapid neurological improvement (RNI), defined as percent improvement ⩾30%, was a powerful predictor of favorable outcome (odds ratio [OR] 7.63, confidence interval [CI]: 2.65-21.96; p

We aimed to investigate the association between large-vessel occlusion (LVO) and functional outcome in elderly stroke patients treated with intravenous (IV) tissue plasminogen activator (tPA).This was a retrospective study of acute ischemic stroke patients who received IV tPA within 4.5 hours after stroke onset between 2007 and 2013. Patients were categorized into 2 groups based on age (≥80 or 80 years). LVO was evaluated by computed tomography angiography (CTA) before thrombolysis. Favorable outcome was defined as a modified Rankin Scale (mRS) score of 2 or lower at 3 months, or equal to the prestroke mRS score.Of 359 thrombolysis patients, 175 patients with CTA before a standard dose of IV tPA therapy (0.9 mg/kg body weight; maximum 90 mg) were included. Sixty-five patients were in the group aged 80 years or above with a median age of 84 (interquartile range: 82.5, 86) years. LVO was observed more often in the group with unfavorable outcome compared with the group with favorable outcome in older stroke patients (60.6% versus 21.9%, P = .002). The baseline National Institutes of Health Stroke Scale (NIHSS) score (odds ratio .864; 95% confidence interval [CI], .779-.959; P = .006) and LVO (odds ratio .233; 95% CI, .059-.930; P = .039) were independent associative factors for the unfavorable outcome in older patients treated with IV tPA after adjustment for patient characteristics.The baseline NIHSS score and LVO were independent predictors for functional outcome in elderly stroke patients received IV tPA.

Atherosclerotic subclavian artery stenosis (SAS) accompanied with other craniocervical artery stenosis (OCAS) is not uncommon in practice. We sought to investigate the safety and efficacy of endovascular stenting for SAS in patients with OCAS. Between January 2004 and February 2012, 71 consecutive atherosclerotic SAS patients who underwent primary stenting in our medical center were included. The enrolled patients were divided into combined-SAS group (n = 51) and solitary-SAS group (n = 20) depending on the presence or absence of OCAS. Data of demographics, procedure, and the followed-up were retrieved and analyzed. The technical success rate was 95.8 %; the clinical success rate was 90.1 %. There was no catheter-related major stroke or death. The immediate outcomes had no statistical difference between groups. During a mean of 27 ± 20 months (range 2–88 months) followed-up, 7(10.3 %) restenosis and 12(17.6 %) clinical events were identified. The primary patency rate was 95.3, 84.9 and 84.9 % at 12, 24 months, and final followed-up respectively, which had no statistical difference between groups (odds ratio (OR), 2.60; 95 % confidence interval (CI), 0.54–12.53; P = 0.232). The overall clinical event-free survival rate was 93.5, 86.2 and 54.6 %, respectively, where the result of combined-SAS group was inferior to that of the solitary-SAS group (OR, 3.34; 95 % CI, 1.02–11.00; P = 0.047). Endovascular stenting was safe and feasible for atherosclerotic SAS in patients with OCAS, although the combined OCAS may have a significant influence on the long-term outcome. Further studies are warrant to investigate the effects of revascularization for multiple craniocervical artery stenoses on the cerebral hemodynamics and long-term outcomes.

Background: To investigate the correlation between tortuosity of extracranial internal carotid artery (EICA) and intraprocedural complications in patients undergoing carotid artery stenting (CAS). Methods: The study included 244 EICA in 223 patients undergoing CAS. Tortuosity in EICA was measured by the tortuosity index (TI). Multivariate logistic regression was performed to assess the independent risk factors of vasospasm during CAS. Receiver operating characteristic curve was performed to identify the cut-off of TI to predict vasospasm. Results: During the 244 CAS, 71 EICA presented vasospasm and 114 CAS presented hypotension. High TI, long procedural duration and female are independent risk factors for vasospasm during CAS. TI of 118 was the optimal cut-off to predict vasospasm during CAS (sensitivity: 85.9%, specificity: 78.6%). Linear regression analysis demonstrated that TI is positively correlated with procedural duration (p < 0.001). There was no significant difference in TI between the hypotension and non-hypotension groups (p = 0.145). Conclusion: TI is an independent risk factor for vasospasm during CAS and a TI ≥118 has the high sensitivity and specificity to predict vasospasm. Our results indicate the value of assessing tortuosity of EICA prior to choosing or performing the procedure in patients with carotid stenosis or occlusion.

Background: Decreased brain-derived neurotrophic factor (BDNF) has been demonstrated in animal models and patients with depression. However, little is known about changes in BDNF in post-stroke depression (PSD). This study investigated the changes in serum BDNF in patients with PSD, and evaluated whether serum concentrations of BDNF were associated with BDNF gene Val66Met polymorphism. Methods: PSD patients were diagnosed in accordance with DSM-IV criteria, and the severity of depression was evaluated with the Hamilton Rating Scale for depression. Serum BDNF was measured twice, first at 7 days after the onset of stroke and then at 3–6 months after stroke. Val66Met polymorphisms of the BDNF gene were determined using the polymerase chain reaction-restriction fragment length polymorphism method. BDNF concentrations and Val66Met polymorphisms were also measured in 30 healthly controls. Results: A total of 93 patients admitted as a result of first time acute ischemic stroke were included. During the 6-month follow-up, 35 patients (37.6%) were diagnosed with PSD. Serum BDNF concentrations were decreased in PSD patients at 3–6 months after stroke (p Conclusions: Serum concentrations of BDNF decrease in PSD patients and BDNF may play an important role in the pathogenesis of PSD. However, Val66Met polymorphisms are not associated with serum concentrations of BDNF. The mechanism of decreased serum BDNF requires further study.