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.

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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.

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.

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.

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The existing intracerebral hemorrhage (ICH) scores were based on the clinical and anatomical parameters of all primary ICH. We aimed to study whether the original ICH Score can predict cerebral amyloid angiopathy (CAA)-related ICH mortality and functional outcome and whether modified score can improve the predictions. The patients with ICH were consecutively recruited from 21 tertiary and secondary hospitals across Mainland China from January 2012 to December 2014. CAA-related ICH was defined as Boston Criteria. Logistic regression was performed in the derivation cohort of patients with CAA-related ICH to identify predictors of 3-month mortality and good outcome [modified Rankin score (mRS) of 0-2 at 3 months]. The areas under the receiver operating characteristic curves (AUCs) were used to assess model discrimination. A total of 360 CAA-related ICH patients were included. According to AUCs, the original ICH Score was less reliable predictor for mortality (AUCs=0.69) and good outcome (AUCs=0.67) in CAA- related patients. The range of CAA-related ICH score values is 0 to 7. The scale consist of four clinical items and the score points were assigned based on the Glasgow Coma Scale score on admission, age, presence of intraventricular hemorrhage, and presence of midline shift. CAA-related ICH score showed good discrimination in the derivation cohort (AUCs: 0.87 for mortality; 0.80 for good clinical outcome) and validation cohort (AUCs: 0.89 for mortality; 0.81 for good clinical outcome). The original ICH Score may be less reliable in predicting mortality and good clinical outcome at 3 months for CAA-related ICH patients. The modified scores improve its ability to predict clinical outcome at 3 months for CAA-related ICH.

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