External Validation and Modification of the EDEMA Score for Predicting Malignant Brain Edema After Acute Ischemic Stroke.

BACKGROUND: Accurate prediction of malignant brain edema (MBE) after stroke is paramount to facilitate close monitoring and timely surgical intervention. The Enhanced Detection of Edema in Malignant Anterior Circulation Stroke (EDEMA) score was useful to predict potentially lethal malignant edema in Western populations. We aimed to validate and modify it to achieve a better predictive value for MBE in Chinese patients. METHODS: Of ischemic stroke patients consecutively admitted in the Department of Neurology, West China Hospital between January 2010 and December 2017, we included patients with anterior circulation stroke, early signs of brain edema on computed tomography within 24 h of onset, and admission National Institutes of Health Stroke Scale (NIHSS) score ≥ 8. MBE was defined as the development of signs of herniation (including decrease in consciousness and/or anisocoria), accompanied by midline shift ≥ 5 mm on follow-up imaging. The EDEMA score consisted of five parameters: glucose, stroke history, reperfusion therapy, midline shift, and cistern effacement. We created a modified score by adding admission NIHSS score to the original EDEMA score. The discrimination of the score was assessed by the area under the receiver operating characteristics curve (AUC). Calibration was assessed by Hosmer-Lemeshow test and calibration plot. We compared the discrimination of the original and modified score by AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Clinical usefulness of the two scores was compared by plotting net benefits at different threshold probabilities in the decision curve analysis. RESULTS: Of the 478 eligible patients (mean age 67.3 years; median NIHSS score 16), 93 (19%) developed MBE. The EDEMA score showed moderate discrimination (AUC 0.72, 95% confidence interval [CI] 0.67-0.76) and good calibration (Hosmer-Lemeshow test, P = 0.77). The modified score showed an improved discriminative ability (AUC 0.80, 95% CI 0.76-0.84, P < 0.001; NRI 0.67, 95% CI 0.55-0.78, P < 0.001; IDI 0.07, 95% CI 0.06-0.09, P < 0.001). Decision curves showed that the modified score had a higher net benefit than the original score in a range of threshold probabilities lower than 60%. CONCLUSIONS: The original EDEMA score showed an acceptable predictive value for MBE in Chinese patients. By adding the admission NIHSS score, the modified score allowed for a more accurate prediction and clinical usefulness. Further validation in large cohorts of different ethnicities is needed to confirm our findings.

Early Prediction of Malignant Brain Edema After Ischemic Stroke.

Background and Purpose- Malignant brain edema after ischemic stroke has high mortality but limited treatment. Therefore, early prediction is important, and we systematically reviewed predictors and predictive models to identify reliable markers for the development of malignant edema. Methods- We searched Medline and Embase from inception to March 2018 and included studies assessing predictors or predictive models for malignant brain edema after ischemic stroke. Study quality was assessed by a 17-item tool. Odds ratios, mean differences, or standardized mean differences were pooled in random-effects modeling. Predictive models were descriptively analyzed. Results- We included 38 studies (3278 patients) with 24 clinical factors, 7 domains of imaging markers, 13 serum biomarkers, and 4 models. Generally, the included studies were small and showed potential publication bias. Malignant edema was associated with younger age (n=2075; mean difference, -4.42; 95% CI, -6.63 to -2.22), higher admission National Institutes of Health Stroke Scale scores (n=807, median 17-20 versus 5.5-15), and parenchymal hypoattenuation >50% of the middle cerebral artery territory on initial computed tomography (n=420; odds ratio, 5.33; 95% CI, 2.93-9.68). Revascularization (n=1600, odds ratio, 0.37; 95% CI, 0.24-0.57) were associated with a lower risk for malignant edema. Four predictive models all showed an overall C statistic >0.70, with a risk of overfitting. Conclusions- Younger age, higher National Institutes of Health Stroke Scale, and larger parenchymal hypoattenuation on computed tomography are reliable early predictors for malignant edema. Revascularization reduces the risk of malignant edema. Future studies with robust design are needed to explore optimal cutoff age and National Institutes of Health Stroke Scale scores and to validate and improve existing models.

Serum magnesium but not calcium was associated with hemorrhagic transformation in stroke overall and stroke subtypes: a case-control study in China.

Association between serum calcium and magnesium versus hemorrhagic transformation (HT) remains to be identified. A total of 1212 non-thrombolysis patients with serum calcium and magnesium collected within 24 h from stroke onset were enrolled. Backward stepwise multivariate logistic regression analysis was conducted to investigate association between calcium and magnesium versus HT. Calcium and magnesium were entered into logistic regression analysis in two models, separately: model 1, as continuous variable (per 1-mmol/L increase), and model 2, as four-categorized variable (being collapsed into quartiles). HT occurred in 140 patients (11.6%). Serum calcium was slightly lower in patients with HT than in patient without HT (P = 0.273). But serum magnesium was significantly lower in patients with HT than in patients without HT (P = 0.007). In logistic regression analysis, calcium displayed no association with HT. Magnesium, as either continuous or four-categorized variable, was independently and inversely associated with HT in stroke overall and stroke of large-artery atherosclerosis (LAA). The results demonstrated that serum calcium had no association with HT in patients without thrombolysis after acute ischemic stroke. Serum magnesium in low level was independently associated with increasing HT in stroke overall and particularly in stroke of LAA.

The burden of non-symptomatic cerebral ischemia on MRI and its effect on clinical outcomes in patients with first-ever intracerebral hemorrhage.

PURPOSE: To compare the burden of non-symptomatic cerebral ischemia (NSCI) detected on magnetic resonance imaging (MRI) and computed tomography (CT), and assess the association of MRI-NSCI with clinical outcomes among patients with first-ever intracerebral hemorrhage (ICH). METHODS: Two thousand three hundred and five consecutive ICH patients admitted to our institution from May 2012 to October 2015 were retrospectively reviewed. Data on clinical characteristics and MRI/CT scans were collected during hospitalization. Information on clinical outcomes at three-month were also obtained. RESULTS: Three hundred and seventy-seven patients performed MRIs and 1966 had CTs during hospitalization. NSCI was detected in 152 (40.3%) patients with MRIs and in 638 (32.5%) with CTs. Comparing with CT, NSCI detected by MRI was more common (40.3% vs. 32.5%; P = 0.011), more likely to be multiple loci (93.4% vs. 79.6%; P < 0.001) and bilateral hemispheres (84.9% vs. 73.2%; P = 0.003). Furthermore, the presence of NSCI, multiple NSCI, bilateral NSCI and bilateral hematoma combined with bilateral NSCI were associated with poor outcomes (P < 0.001, P < 0.001, P < 0.001, P = 0.041, respectively) in univariate analysis. In multivariable logistic regression, bilateral hematoma combined with bilateral NSCI was still associated with poor outcomes (OR 3.983, 95% CI 1.172-13.539; P = 0.027). CONCLUSIONS: Compared with CT, NSCI on MRI tends to be multiple loci and located in bilateral hemispheres. The results of NSCI in ICH may be underestimated based on CT. In addition, the increased poor outcomes at three-month suggest that NSCI may play an important role in reducing clinical outcomes.

Prognosis of 908 patients with intracerebral hemorrhage in Chengdu, Southwest of China.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is the deadliest, most disable and least treatable form of acute cerebral accident. Prognostic risk factors of ICH are not yet fully identified. This study investigated the possible clinical factors leading to poor outcomes in patients with ICH, which can be used to guide clinical treatment and predict prognosis. METHODS: We prospectively enrolled patients with ICH who were admitted within 7 d of stroke onset from January 2012 to April 2014. The prognostic factors of patients with ICH were analyzed in univariate analyses and logistic regression analyses. RESULTS: A total of 908 consecutive patients with ICH (mean age, 57.87 ± 13.92 years) were finally included, of which 616 patients (67.8%) were male. 59.5%, 54.5% and 52.2% patients with ICH had poor outcomes (death/disability) at 3, 6 and 12 months, respectively. Stroke severity and stroke-related complications during hospitalization were independently associated with poor outcomes both at 3 and 12 months. In addition, hyperglycemia, hematocrit and blood urea nitrogen on admission were independently associated with poor outcomes at three months. CONCLUSION: This study found that severity of ICH and stroke-related complications were independent predictors of poor outcomes at three months and one year after ICH. Thereby, it highlights the importance of understanding the role of clinical features in ICH prognostic evaluation.

Liver Function Indicators Performed Better to Eliminate Cardioembolic Stroke than to Identify It from Stroke Subtypes.

BACKGROUND: Identifying the etiology of ischemic stroke is essential to acute management and secondary prevention. The value of liver function indicators in differentiating stroke subtypes remains to be evaluated. METHODS: A total of 1333 acute ischemic stroke patients were included. Liver function indicators collected within 24 hours from stroke onset, including alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin (BILI), were collapsed into quartiles (Q) and also dichotomized by Q1. Multivariate regression analysis was conducted to identify the independent association between liver function indicators and cardioembolic stroke (SCE). Area under the curve (AUC) of receiver operating characteristic analysis was conducted, and sensitivity (Sen), specificity (Spe), positive prospective value (PPV), and negative prospective value (NPV) were determined to evaluate the predictive value of liver function indicators for SCE. RESULTS: AST, GGT, and BILI were associated with SCE. After adjustment, only AST was related to SCE independently. The incidence of SCE in the Q1 of AST, GGT, and BILI, particularly in the Q1 of AST, was quite low. The ability of AST, GGT, and BILI to identify SCE was poor, with low AUC, Sen, and PPV. The value of AST, GGT, and BILI in eliminating SCE from stroke subtypes was good, with high Spe and moderate NPV, and was enhanced after combining each liver function indicator. CONCLUSIONS: Results of present study demonstrated that AST, GGT, and BILI, particularly AST, had a potential to eliminate SCE from stroke subtypes, and the ability of eliminating SCE would be strengthened after combining each liver function indicator together.

Prognostic Significance of Intraventricular Hemorrhage in Vascular Structural Abnormality-Related Intracerebral Hemorrhage.

BACKGROUND: The prognostic significance of intraventricular hemorrhage (IVH) in patients with vascular structural abnormality-related intracerebral hemorrhage (VSARICH) is poorly understood. METHOD: We prospectively included consecutive patients diagnosed with VSARICH. Imaging of initial brain computed tomography (CT) scans within 48 hours of symptom onset was analyzed. The presence and severity of IVH were recorded. Severity of IVH was measured using the modified Graeb (mGraeb) score. Baseline characteristics and 3-month outcomes were compared between the IVH and non-IVH groups. Multivariate logistic regression was used to examine the independent association between IVH and 3-month outcomes. RESULTS: A total of 132 VSARICH patients were included for analysis, and 71 (53.8%) of them had IVH on initial CT imaging. IVH patients had a median mGraeb score of 15 (6-21), and compared to non-IVH patients, they had shorter delay to first CT scan and higher stroke severity on admission (all P ≤ .005). At 3 months, IVH patients had higher death rates (30.3% versus 7.0%; P = .001) and poor outcome rates (48.5% versus 21.1%; P = .002) than non-IVH patients. After multivariate analysis, IVH severity was associated with 3-month death (Model 1 OR 1.112, 95% CI [1.027-1.204], P = .009; Model 2 OR 1.110, 95% CI [1.027-1.200], P = .009) and poor outcome (Model 2 OR 1.053, 95% CI [1.001-1.108], P = .047), although no independent association between IVH presence and outcomes was observed. CONCLUSION: IVH severity measured by mGraeb score independently predicts death and poor functional outcome in patients with VSARICH.

Subclinical change of liver function could also provide a clue on prognosis for patients with spontaneous intracerebral hemorrhage.

Whether subclinical change of liver function is associated with outcome of spontaneous intracerebral hemorrhage remains to be an open question. A total of 639 patients of spontaneous intracerebral hemorrhage within 7 days from stroke onset were finally enrolled. Liver function indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (BIL), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), albumin (ALB), and international normalized ratio (INR), were collected and collapsed into quartiles. The main outcomes were 30-day death, 90-day death, and 90-day poor outcome (modified Rankin Scale score of 3-6). Two adjusted model, Model 1 and Model 2 (Model 1 plus GCS score), were established to identify independent association between liver function indicators and ICH outcomes. The mortality rate was 19.9 % (127/639) at 30 days and 21.3 % (136/639) at 90 days. Rate of 90-day poor outcome was 51.5 % (329/639). Among liver function indicators, AST and ALP were associated with all the three outcomes, which did not alter significantly when adjusted by Model 1. After adjusted by Model 2, ALP was still associated with outcomes. Association between AST and outcomes was, however, weakened significantly by GCS score. In conclusions, among liver function indicators, AST and ALP were associated with outcomes after spontaneous intracerebral hemorrhage.

High Level of Serum Myoglobin in Human Intracerebral Hemorrhage: Implications for Large Hematoma Volume and Growth.

BACKGROUND: Myoglobin and cardiac troponin T are often elevated in patients with ischemic stroke. However, the association, if any, between both myoglobin and troponin T levels and hematoma volume in patients with intracerebral hemorrhage remains to be established. We investigate the possible relationship between admission myoglobin and troponin T levels and hematoma volume and growth. METHODS: A total of 143 patients with intracerebral hemorrhage admitted within 72 hours after symptom onset were divided into 4 groups according to the quartile of myoglobin levels. The information of hematoma was assessed with computed tomography scans. Serum myoglobin and cardiac troponin were tested at admission. The relationship between myoglobin levels and hematoma volume and growth was performed using univariate and multiple logistic regression and linear regression. RESULTS: High levels of serum myoglobin were associated with larger hematoma volume. In the highest quartile compared with the lowest quartile of myoglobin, the crude and adjusted odds ratios for the incidence of baseline hematoma volume greater than 30 mL were 2.14 (95% confidence interval 1.45-3.15) and 2.78 (95% confidence interval 1.57-5.00), respectively, in logistic regression. In linear regression, the adjusted B for the relationship of myoglobin and hematoma volume and the change of hematoma volume was .02 (95% confidence interval .01-.04, P = .007) and .021 (95% confidence interval .01-.03, P < .001), respectively, whereas high level of troponin T was not associated with large hematoma volume. CONCLUSION: Our results first demonstrate that myoglobin is associated with larger hematoma volume and growth after adjusting potential confounding factors.

Predicting the Outcomes of Acute Ischemic Stroke with Rheumatic Heart Disease: The Values of CHADS2, CHA2DS2-VASc, and HAS-BLED Scores.

BACKGROUND AND OBJECTIVE: The CHADS2 and CHA2DS2-VASc score were used to evaluate the atrial fibrillation-related risk of stroke, and HAS-BLED score was used to estimate the oral anticoagulation-bleeding risk. We investigated the relationships between these 3 scores and the outcomes of acute ischemic stroke (AIS) patients with rheumatic heart disease (RHD) at 3 months after stroke. METHODS: We retrospectively included patients admitted within 1 month after stroke from October 2011 to February 2014 who was also diagnosed with RHD. The patients' demographics; National Institutes of Health Stroke Scale score on admission; risk factors; prior anticoagulation; and CHADS2, CHA2DS2-VASc, and HAS-BLED scores on admission were collected, and symptomatic intracranial hemorrhage (sICH) during hospitalization was observed as well. The patients were followed up at 3 months after stroke to assess the clinical outcomes. RESULTS: Of 1425 patients with AIS, 172 patients were diagnosed with RHD. Eleven patients (6.4%) were lost to follow-up at 3 months. One hundred sixty-one patients (48 males, mean age 57.5 years) were finally analyzed in the study. The HAS-BLED score was associated with the occurrence of sICH in both univariate (P = .001; odds ratio [OR] 2.223, 95% confidence interval [CI] 1.40-3.54) and multivariate analysis (P = .031; OR 2.366, 95% CI 1.08-5.17). The CHADS2 and CHA2DS2-VASc scores were both related to the sICH (CHADS2: P = .032; OR 1.522, 95% CI 1.04-2.23; CHA2DS2-VASc: P = .011; OR 1.498, 95% CI 1.10-2.04, respectively), and to the poor outcomes at 3 months (CHADS2: P = .013; OR .688, 95% CI .51-.92; CHA2DS2-VASc: P = .014; OR .754, 95% CI .60-.94, respectively) in the univariate analysis. CONCLUSION: The HAS-BLED score was independently associated with the occurrence of sICH in AIS patients with RHD.

TRUST Technique for Neurointervention: A Promising Alternative for Complex Cases.

BACKGROUND: Neurointervention via Transradial Access (TRA) is becoming increasingly popular as experience with this technique increases. However, approximately 8.6-10.3% of complex TRA cases are converted to femoral access due to a lack of support or radial artery spasm. This study aimed to assess the efficacy and safety of the TRUST (trans-radial coaxial catheter technique using a short sheath, Simmons catheter, and Tethys intermediate catheter) technique in interventional procedures via TRA. METHODS: This was a single-center retrospective analysis of 16 patients admitted to our institute between January 2023 to May 2023 to undergo endovascular interventions with the TRUST technique via the TRA. RESULTS: The mean age of the study population was 63.8 years, and 62.5% were male (10/16). The most common procedure was intracranial atherosclerotic stenosis (93.75%, 15/16). All procedures were performed successfully, and the most common procedures in our cohort were ballooning (50.0%, 8/16), stenting (18.75%, 3/16), and both procedures combined (31.25%, 1/16). All procedures were performed using the TRA, and the distal and proximal radial arteries were used for access in 31.35% (5/16) and 68.75% (11/16) of the cases, respectively. Technical success was achieved in all patients and most cases demonstrated mTICI ≥2b recanalization (93.75%, 15/16). In this case, no major access-site complications occurred. CONCLUSION: The TRUST technique is technically safe and feasible and had a high technical success rate and low complication rate in our study. These results demonstrate that the TRUST technique is a promising alternative for patients undergoing complex neurointerventions.

Association between Peripheral Arterial Lactate Levels and Malignant Brain Edema Following Endovascular Treatment for Ischemic Stroke.

AIMS: To investigate the factors of postoperative malignant brain edema (MBE) in patients with acute ischemic stroke (AIS) treated with endovascular treatment (EVT). BACKGROUND: MBE is a severe complication following EVT for AIS, and it is essential to identify risk factors early. Peripheral arterial lactate (PAL) levels may serve as a potential predictive marker for MBE. OBJECTIVE: To determine whether immediate postoperative PAL levels and the highest PAL level within 24 hours of EVT are independently associated with MBE development in AIS patients. METHODS: We retrospectively analyzed patients with AIS who underwent EVT from October 2019 to October 2022. Arterial blood was collected every 8 h after EVT to measure PAL, and record the immediate postoperative PAL and the highest PAL level within 24 h. Brain edema was evaluated using brain computed tomography scans within 7 days of EVT. RESULTS: The study included 227 patients with a median age of 71 years, of whom 59.5% were male and MBE developed in 25.6% of patients (58/227). Multivariate logistic regression analysis showed that the immediate postoperative PAL (odds ratio, 1.809 [95% confidence interval (CI), 1.215-2.693]; p = 0.004) and the highest PAL level within 24 h of EVT (odds ratio, 2.259 [95% CI, 1.407-3.629]; p = 0.001) were independently associated with MBE. The area under the curve for predicting MBE based on the highest PAL level within 24 hours of EVT was 0.780 (95% CI, 0.711-0.849). CONCLUSION: Early increase in PAL levels is an independent predictor of MBE after EVT in AIS patients.

Predicting the emergence of malignant brain oedema in acute ischaemic stroke: a prospective multicentre study with development and validation of predictive modelling.

Background: We aimed to develop and validate a prognostic model for predicting malignant brain oedema in patients with acute ischaemic stroke in a real-world setting of practice. Methods: A prospective multicentre study enrolled adult patients with acute ischaemic stroke with brain CT < 24 h of onset of symptoms admitted to nine tertiary-level hospitals in China between September 2017 and December 2019. Malignant brain oedema was defined as any patient who had decompressive craniectomy, discharge in coma, or in-hospital death attributed to symptomatic brain swelling. The derivation cohort was a consecutive cohort of patients from one centre and the validation cohort was non-consecutive patients from the other centres. Multivariable logistic regression was used to define independent predictors from baseline clinical characteristics, imaging features, complications, and management. A web-based nomogram and a risk score were developed based on the final model. Model performance was assessed for discrimination and calibration in both derivation and validation cohorts. The study is registered, NCT03222024. Findings: Based on the derivation cohort (n = 1627), the model was developed with seven variables including large infarct (adjusted odds ratio [OR] 40.90, 95% CI 20.20-82.80), National Institutes of Health Stroke Scale (NIHSS) score (OR 1.09, 1.06-1.12), thrombolysis (OR 2.11, 1.18-3.78), endovascular treatment (OR 2.87, 1.47-5.59), pneumonia (OR 2.47, 1.53-3.97), brain atrophy (OR 0.57, 0.37-0.86), and recanalisation (OR 0.36, 0.17-0.75). The classification threshold of a predicted probability ≥0.14 showed good discrimination and calibration in both derivation cohort (area under the receiver-operating curve [AUC] 0.90, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation cohort (n = 556, AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95). The risk score based on this model had a total point that ranged from -1 to 20, with an optimal score of ≥10 showing good discrimination and calibration in both derivation (AUC 0.89, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation (AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95) cohorts. Interpretation: The INTEP-AR model (i.e. large Infarct, NIHSS score, Thrombolysis, Endovascular treatment, Pneumonia, brain Atrophy, and Recanalisation) incorporating multiple clinical and radiological characteristics has shown good prognostic value for predicting malignant brain oedema after acute ischaemic stroke. Funding: National Natural Science Foundation of China; Science and Technology Department of Sichuan Province; West China Hospital.

Association Between Post-procedure Cerebral Blood Flow Velocity and Severity of Brain Edema in Acute Ischemic Stroke With Early Endovascular Therapy.

Objectives: We aimed to investigate the association between post-procedure cerebral blood flow velocity (CBFV) and severity of brain edema in patients with acute ischemic stroke (AIS) who received early endovascular therapy (EVT). Methods: We retrospectively included patients with AIS who received EVT within 24 h of onset between February 2016 and November 2021. Post-procedure CBFV of the middle cerebral artery was measured in the affected and the contralateral hemispheres using transcranial Doppler ultrasound. The severity of brain edema was measured using the three-level cerebral edema grading from the Safe Implementation of Thrombolysis in Stroke-Monitoring Study, with grades 2-3 indicating severe brain edema. The Association between CBFV parameters and severity of brain edema was analyzed. Results: A total of 101 patients (mean age 64.2 years, 65.3% male) were included, of whom 56.3% (57/101) suffered brain edema [grade 1, 23 (22.8%); grade 2, 10 (9.9%); and grade 3, 24 (23.8%)]. Compared to patients with non-severe brain edema, patients with severe brain edema had lower affected/contralateral ratios of systolic CBFV (median 1 vs. 1.2, P = 0.020) and mean CBFV (median 0.9 vs. 1.3, P = 0.029). Multivariate logistic regression showed that severe brain edema was independently associated with affected/contralateral ratios of systolic CBFV [odds ratio (OR) = 0.289, 95% confidence interval (CI): 0.069-0.861, P = 0.028] and mean CBFV (OR = 0.278, 95% CI: 0.084-0.914, P = 0.035) after adjusting for potential confounders. Conclusion: Post-procedure affected/contralateral ratio of CBFV may be a promising predictor of brain edema severity in patients with AIS who received early EVT.

Association of obstructive sleep apnea and cerebral small vessel disease: a systematic review and meta-analysis.

STUDY OBJECTIVES: The objective of the present study was to investigate the association between obstructive sleep apnea (OSA) and the presence of various neuroimaging marker of cerebral small vessel disease (CSVD). METHODS: We systematically searched PubMed, Embase, Web of Science, Scopus, and Cochrane library (from inception to May 2019) for studies evaluating the association between OSA and CSVD, which included white matter hyperintensities (WMH), silent brain infarction (SBI), cerebral microbleeds (CMBs), and perivascular spaces (PVS). Pooled odds ratios (ORs) with 95% confidence interval (CIs) were estimated using random-effects meta-analysis. RESULTS: After screening 7290 publications, 20 studies were finally included involving 6036 subjects. The sample size ranged from 27 to 1763 (median 158, interquartile range: 67-393). The meta-analysis showed that moderate to severe OSA was positively associated with WMH (13 studies, n = 4412, OR = 2.23, 95% CI = 1.53 to 3.25, I2 = 80.3%) and SBI (12 studies, n = 3353, OR 1.54, 95% CI = 1.06 to 2.23, I2 = 52%). There was no association with CMBs (three studies, n = 342, OR = 2.17, 95% CI = 0.61 to 7.73, I2 = 60.2%) or PVS (two studies, n = 267, OR = 1.56, 95% CI = 0.28 to 8.57, I2 = 69.5%). There was no relationship between mild OSA and CSVD. CONCLUSION: Current evidence suggests that moderate to severe sleep apnea is positively related to WMH and SBI, but not CMBs or PVS, which suggests that OSA may contribute to the pathogenesis of CSVD. Further large cohort studies should be prioritized to confirm the findings.

Association of Matrix Metalloproteinase 9 and Cellular Fibronectin and Outcome in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Introduction: The role of matrix metalloproteinase 9 (MMP-9) and cellular fibronectin (c-Fn) in acute ischemic stroke is controversial. We systematically reviewed the literature to investigate the association of circulating MMP-9 and c-Fn levels and MMP-9 rs3918242 polymorphism with the risk of three outcome measures after stroke. Methods: We searched English and Chinese databases to identify eligible studies. Outcomes included severe brain edema, hemorrhagic transformation, and poor outcome (modified Rankin scale score ≥3). We estimated standardized mean differences (SMDs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: Totally, 28 studies involving 7,239 patients were included in the analysis of circulating MMP-9 and c-Fn levels. Meta-analysis indicated higher levels of MMP-9 in patients with severe brain edema (SMD, 0.76; 95% CI, 0.18-1.35; four studies, 419 patients) and hemorrhagic transformation (SMD, 1.00; 95% CI, 0.41-1.59; 11 studies, 1,709 patients) but not poor outcome (SMD, 0.30; 95% CI, -0.12 to 0.72; four studies, 759 patients). Circulating c-Fn levels were also significantly higher in patients with severe brain edema (SMD, 1.55; 95% CI, 1.18-1.93; four studies, 419 patients), hemorrhagic transformation (SMD, 1.75; 95% CI, 0.72-2.78; four studies, 458 patients), and poor outcome (SMD, 0.46; 95% CI, 0.16-0.76; two studies, 210 patients). Meta-analysis of three studies indicated that the MMP-9 rs3918242 polymorphism may be associated with hemorrhagic transformation susceptibility under the dominant model (TT + CT vs. CC: OR, 0.621; 95% CI, 0.424-0.908; P = 0.014). No studies reported the association between MMP-9 rs3918242 polymorphism and brain edema or functional outcome after acute stroke. Conclusion: Our meta-analysis showed that higher MMP-9 levels were seen in stroke patients with severe brain edema and hemorrhagic transformation but not poor outcome. Circulating c-Fn levels appear to be associated with all three outcomes including severe brain edema, hemorrhagic transformation, and poor functional outcome. The C-to-T transition at the MMP-9 rs3918242 gene appears to reduce the risk of hemorrhagic transformation.

Blood Pressure and Outcomes in Patients With Different Etiologies of Intracerebral Hemorrhage: A Multicenter Cohort Study.

Background We aimed to investigate the association between blood pressure (BP) and outcomes in intracerebral hemorrhage (ICH) subtypes with different etiologies. Methods and Results A total of 5656 in-hospital patients with spontaneous ICH were included between January 2012 and December 2016 in a prospective multicenter cohort study. Etiological subtypes of ICH were assigned using SMASH-U (structural lesion, medication, amyloid angiopathy, systemic/other disease, hypertension, undetermined) classification. Elevated systolic BP was defined as ≥140 mm Hg. Hypertension was defined as elevated BP for >1 month before the onset of ICH. The primary outcomes were measured as 1-month survival rate and 3-month mortality. A total of 5380 patients with ICH were analyzed, of whom 4052 (75.3%) had elevated systolic BP on admission and 3015 (56.0%) had hypertension. In multinomial analysis of patients who passed away by 3 months, systolic BP on admission was significantly different in cerebral amyloid angiopathy (P<0.001), structural lesion (P<0.001), and undetermined subtypes (P=0.003), compared with the hypertensive angiopathy subtype. Elevated systolic BP was dose-responsively associated with higher 3-month mortality in hypertensive angiopathy (Ptrend=0.013) and undetermined (Ptrend=0.005) subtypes. In cerebral amyloid angiopathy, hypertension history had significant inverse association with 3-month mortality (adjusted odds ratio, 0.37, 95% CI, 0.20-0.65; P<0.001). Similarly, adjusted Cox regression indicated decreased risk of 1-month survival rate in the presence of hypertension in patients with cerebral amyloid angiopathy (adjusted hazard ratio, 0.47; 95% CI, 0.24-0.92; P=0.027). Conclusions This study suggests that the association between BP and ICH outcomes might specifically depend on its subtypes, and cerebral amyloid angiopathy might be pathologically distinctive from the others. Future studies of individualized BP-lowering strategy are needed to validate our findings.

Impaired consciousness at stroke onset in large hemisphere infarction: incidence, risk factors and outcome.

Impaired consciousness (IC) at stroke onset in large hemispheric infarctions (LHI) patients is common in clinical practice. However, little is known about the incidence and risk factors of IC at stroke onset in LHI. Besides, stroke-related complications and clinical outcomes in relation to the development of IC has not been systematically examined. Data of 256 consecutive patients with LHI were collected. IC at stroke onset was retrospectively collected from the initial emergency department and/or admission records. Of the 256 LHI patients enrolled, 93 (36.3%) had IC at stroke onset. LHI patients with IC at stroke onset were older (median age 66 vs. 61, p = 0.041), had shorter prehospital delay (24 vs. 26 h, p < 0.001and higher baseline National Institutes of Health Stroke Scale (NIHSS) score (19 vs. 12, p < 0.001). Independent risk factors of IC at stroke onset were high NIHSS score (odds ratio, OR 1.17, 95% confidence interval [CI] 1.12 to 1.23) and atrial fibrillation (OR 1.93, 95% CI 1.07 to 3.47). Dyslipidemia appeared to protect against IC at stroke onset (adjusted OR 0.416, 95% CI 0.175 to 0.988). IC at stroke onset was associated with higher frequency of stroke-related complications (90.32% vs. 67.48%, p < 0.001), especially brain edema (45.16% vs. 23.31%, p < 0.001) and pneumonia (63.44% vs. 47.82%, p = 0.019). The IC group had higher rates of in-hospital death (23.66% vs. 11.66%, p = 0.012), 3-month mortality (49.46% vs. 24.87%, p = 0.002), and 3-month unfavorable outcome (64.51% vs. 49.07%, p = 0.017). However, after adjusting for age, baseline NIHSS score and other confounders, IC at stroke onset was not an independent predictor of in-hospital death (adjusted OR 0.56, 95% CI 0.22 to 1.47), 3-month mortality (adjusted OR 0.54, 95% CI 0.25 to 1.14) and 3-month unfavorable outcome (adjusted OR 0.64, 95% CI 0.31 to 1.33) in LHI patients (all p > 0.05). Our results suggested that IC occur in 1 out of every 3 LHI patients at stroke onset and was associated with initial stroke severity and atrial fibrillation. LHI patients with IC at stroke onset more frequently had stroke-related complications, 3-month mortality and unfavorable outcome, whereas IC was not an independent predictor of poor outcomes.

Association Between Preoperative Midline Shift Growing Rate and Outcomes of Decompressive Craniectomy in Patients with Malignant Middle Cerebral Artery Infarction.

BACKGROUND: Whether preoperative midline shift and its growing rate are associated with outcomes of decompressive craniectomy in patients with malignant middle cerebral artery infarction is unknown. METHODS: We retrospectively included patients: 1) who underwent decompressive craniectomy for malignant middle cerebral artery infarction in West China Hospital from August 2010 to December 2, 2018) who had at least two brain computed tomography scans before decompressive craniectomy. Midline shift was measured on the first and last preoperative computed tomography scans. Midline shift growing rate was calculated by dividing Δmidline shift value using Δ time. The primary outcome was inadequate decompression of the mass effect. Secondary outcomes were 3 month death and unfavorable outcomes. RESULTS: Sixty-one patients (mean age 53.7 years, 57.4% (35/61) male) were included. Median time from onset to decompressive craniectomy was 51.8 h (interquartile range: 39.7-77.8). Rates of inadequate decompression, 3 month death, 3 month modified Rankin Scale 5-6 and 4-6 were 50.8% (31/61), 50.9% (29/57), 64.9% (37/57) and 84.2% (48/57), respectively. The inadequate decompression group had a higher midline shift growing rate than the adequate decompression group (median: 2.7 mm/8 h vs. 1.4 mm/8 h, P=0.041). No intergroup difference of 3 month outcomes was found in terms of preoperative midline shift growing rate. CONCLUSION: Higher preoperative midline shift growing rate was associated with inadequate decompression of decompressive craniectomy in patients with malignant middle cerebral artery infarction.

Total Burden of Cerebral Small Vessel Disease in Recurrent ICH versus First-ever ICH.

The relationship between recurrent intracerebral hemorrhage (ICH) and total burden of cerebral small vessel disease (CSVD) is not completely investigated. We aimed to study whether recurrent intracerebral hemorrhage (ICH) had higher CSVD score than first-ever ICH. Lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), cortical superficial siderosis (cSS) and CSVD score were rated on brain magnetic resonance imaging (MRI) in primary ICH patients. Recurrent ICHs were confirmed by reviewing the medical records and MRI scans. Mixed hematomas were defined as follows: deep + lobar, deep + cerebellar, or deep + lobar + cerebellar. Of the 184 patients with primary ICH enrolled (mean age, 61.0 years; 75.5% men), recurrent ICH was present in 45 (24.5%) patients; 26.1% (48/184) had ≥2 hematomas, 93.8% (45/48) of which exhibited recurrent ICH. Mixed hematomas were identified in 8.7% (16/184) of patients and bilateral hematomas in 17.9% (33/184). All mixed hematomas and bilateral hematomas were from cases of recurrent ICH. Patients with mixed etiology-ICH were more likely to have recurrent ICH than patients with cerebral amyloid angiopathy (CAA) or hypertensive angiopathy (HA)-related ICH (36.8% vs17.8%, p=0.008). Multivariate ordinal regression analysis showed that the presence of recurrent ICH (p=0.001), ≥2 hematomas (p=0.002), mixed hematomas (p<0.00001), and bilateral hematomas (p=0.002) were separately significantly associated with a high CSVD score. Recurrent ICH occurs mostly among patients with mixed etiology-ICH and is associated with a higher CSVD burden than first-ever ICH, which needs to be verified by future larger studies.