Assessment and Comparison of the Four Most Extensively Validated Prognostic Scales for Intracerebral Hemorrhage: Systematic Review with Meta-analysis.
Gregório Tiago,Pipa Sara,Cavaleiro Pedro,Atanásio Gabriel,Albuquerque Inês,Chaves Paulo Castro,Azevedo Luís
BACKGROUND/OBJECTIVE:Intracerebral hemorrhage (ICH) is a devastating disorder, responsible for 10% of all strokes. Several prognostic scores have been developed for this population to predict mortality and functional outcome. The aim of this study was to determine the four most frequently validated and most widely used scores, assess their discrimination for both outcomes by means of a systematic review with meta-analysis, and compare them using meta-regression. METHODS:PubMed, ISI Web of Knowledge, Scopus, and CENTRAL were searched for studies validating the ICH score, ICH-GS, modified ICH, and the FUNC score in ICH patients. C-statistic was chosen as the measure of discrimination. For each score and outcome, C-statistics were aggregated at four different time points using random effect models, and heterogeneity was evaluated using the I statistic. Score comparison was undertaken by pooling all C-statistics at different time points using robust variance estimation (RVE) and performing meta-regression, with the score used as the independent variable. RESULTS:Fifty-three studies were found validating the original ICH score, 14 studies were found validating the ICH-GS, eight studies were found validating the FUNC score, and five studies were found validating the modified ICH score. Most studies attempted outcome prediction at 3 months or earlier. Pooled C-statistics ranged from 0.76 for FUNC functional outcome prediction at discharge to 0.85 for ICH-GS mortality prediction at 3 months, but heterogeneity was high across studies. RVE showed the ICH score retained the highest discrimination for mortality (c = 0.84), whereas the modified ICH score retained the highest discrimination for functional outcome (c = 0.80), but these differences were not statistically significant. CONCLUSIONS:The ICH score is the most extensively validated score in ICH patients and, in the absence of superior prediction by other scores, should preferably be used. Further studies are needed to validate prognostic scores at longer follow-ups and assess the reasons for heterogeneity in discrimination.
Clinical Significance of Magnetic Resonance Imaging Markers of Vascular Brain Injury: A Systematic Review and Meta-analysis.
Debette Stéphanie,Schilling Sabrina,Duperron Marie-Gabrielle,Larsson Susanna C,Markus Hugh S
Importance:Covert vascular brain injury (VBI) is highly prevalent in community-dwelling older persons, but its clinical and therapeutic implications are debated. Objective:To better understand the clinical significance of VBI to optimize prevention strategies for the most common age-related neurological diseases, stroke and dementia. Data Source:We searched for articles in PubMed between 1966 and December 22, 2017, studying the association of 4 magnetic resonance imaging (MRI) markers of covert VBI (white matter hyperintensities [WMHs] of presumed vascular origin, MRI-defined covert brain infarcts [BIs], cerebral microbleeds [CMBs], and perivascular spaces [PVSs]) with incident stroke, dementia, or death. Study Selection:Data were taken from prospective, longitudinal cohort studies including 50 or more adults. Data Extraction and Synthesis:We performed inverse variance-weighted meta-analyses with random effects and z score-based meta-analyses for WMH burden. The significance threshold was P < .003 (17 independent tests). We complied with the Meta-analyses of Observational Studies in Epidemiology guidelines. Main Outcomes and Measures:Stroke (hemorrhagic and ischemic), dementia (all and Alzheimer disease), and death. Results:Of 2846 articles identified, 94 studies were eligible, with up to 14 529 participants for WMH, 16 012 participants for BI, 15 693 participants for CMB, and 4587 participants for PVS. Extensive WMH burden was associated with higher risk of incident stroke (hazard ratio [HR], 2.45; 95% CI, 1.93-3.12; P < .001), ischemic stroke (HR, 2.39; 95% CI, 1.65-3.47; P < .001), intracerebral hemorrhage (HR, 3.17; 95% CI, 1.54-6.52; P = .002), dementia (HR, 1.84; 95% CI, 1.40-2.43; P < .001), Alzheimer disease (HR, 1.50; 95% CI, 1.22-1.84; P < .001), and death (HR, 2.00; 95% CI, 1.69-2.36; P < .001). Presence of MRI-defined BIs was associated with higher risk of incident stroke (HR, 2.38; 95% CI, 1.87-3.04; P < .001), ischemic stroke (HR, 2.18; 95% CI, 1.67-2.85; P < .001), intracerebral hemorrhage (HR, 3.81; 95% CI, 1.75-8.27; P < .001), and death (HR, 1.64; 95% CI, 1.40-1.91; P < .001). Presence of CMBs was associated with increased risk of stroke (HR, 1.98; 95% CI, 1.55-2.53; P < .001), ischemic stroke (HR, 1.92; 95% CI, 1.40-2.63; P < .001), intracerebral hemorrhage (HR, 3.82; 95% CI, 2.15-6.80; P < .001), and death (HR, 1.53; 95% CI, 1.31-1.80; P < .001). Data on PVS were limited and insufficient to conduct meta-analyses but suggested an association of high PVS burden with increased risk of stroke, dementia, and death; this requires confirmation. Conclusions and Relevance:We report evidence that MRI markers of VBI have major clinical significance. This research prompts careful evaluation of the benefit-risk ratio for available prevention strategies in individuals with covert VBI.
Green tea consumption and risk of cardiovascular and ischemic related diseases: A meta-analysis.
Pang Jun,Zhang Zheng,Zheng Tong-zhang,Bassig Bryan A,Mao Chen,Liu Xingbin,Zhu Yong,Shi Kunchong,Ge Junbo,Yang Yue-jin,Dejia-Huang ,Bai Ming,Peng Yu
International journal of cardiology
BACKGROUND:The effects of green tea intake on risk of cardiovascular disease (CVD) have not been well-defined. The aim of this meta-analysis was to evaluate the association between green tea consumption, CVD, and ischemic related diseases. METHODS:All observational studies and randomized trials that were published through October 2014 and that examined the association between green tea consumption and risk of cardiovascular and ischemic related diseases as the primary outcome were included in this meta-analysis. The quality of the included studies was evaluated according to the Cochrane Handbook 5.0.2 quality evaluation criteria. RESULTS:A total of 9 studies including 259,267 individuals were included in the meta-analysis. The results showed that those who didn't consume green tea had higher risks of CVD (OR=1.19, 95% CI: 1.09-1.29), intracerebral hemorrhage (OR=1.24, 95% CI: 1.03-1.49), and cerebral infarction (OR=1.15, 95% CI: 1.01-1.30) compared to <1 cup green tea per day. Those who drank 1-3 cups of green tea per day had a reduced risk of myocardial infarction (OR=0.81, 95% CI: 0.67-0.98) and stroke (OR=0.64, 95% CI: 0.47-0.86) compared to those who drank <1 cup/day. Similarly, those who drank ≥4 cups/day had a reduced risk of myocardial infarction compared to those who drank <1 cup/day (OR=0.68, 95% CI: 0.56-0.84). Those who consumed ≥10 cups/day of green tea were also shown to have lower LDL compared to the <3 cups/day group (MD=-0.90, 95% CI: -0.95 to -0.85). CONCLUSIONS:Our meta-analysis provides evidence that consumption of green tea is associated with favorable outcomes with respect to risk of cardiovascular and ischemic related diseases.
Effects of music therapy on anxiety and physiologic parameters in angiography: a systematic review and meta-analysis.
Lieber Adam C,Bose Javin,Zhang Xiangnan,Seltzberg Hayley,Loewy Joanne,Rossetti Andrew,Mocco J,Kellner Christopher P
Journal of neurointerventional surgery
BACKGROUND:Given the anxiety patients experience during angiography, evidence supporting the efficacy of music therapy during these angiographic procedures is potentially of clinical value. OBJECTIVE:To analyze the existing literature forthe use of music therapy during cerebral, coronary, and peripheral angiography to determine whether it improves patient anxiety levels, heart rate, and blood pressure during the procedure. METHODS:PubMed, Embase, and Scopus were searched to identify studies of interest. Inclusion criteria included studies reporting using music therapy in either cerebral, coronary, or peripheral angiography. Studies focused on a pediatric population; animal studies and case reports were excluded. Participant demographics, interventions, and outcomes were collected by two study authors. Bias and study quality of randomized controlled trials (RCTs) were assessed using the Cochrane Risk of Bias Tool. Separate meta-analyses of the RCTs were performed to compare State Trait Anxiety Inventory (STAI), heart rate (HR), and systolic and diastolic blood pressure (SBP and DBP) in the music intervention group versus control group. Heterogeneity was determined by calculating I values, and a random-effects model was used when heterogeneity exceeded 50%. RESULTS:The preprocedure to postprocedure improvement in STAI was significantly greater in the experimental group than the control group (p=0.004), while the decrease in HR, SBP, and DBP was not significant. CONCLUSIONS:Recorded music and/or music therapy in angiography significantly decreases patients' anxiety levels, while it has little to no effect on HR and BP. This meta-analysis is limited by the relatively few RCTs published on this subject. PROSPERO REGISTRATION NUMBER:CRD42018099103.
Effects and Safety of Magnesium Sulfate on Neuroprotection: A Meta-analysis Based on PRISMA Guidelines.
Zeng Xianling,Xue Yan,Tian Quan,Sun Rong,An Ruifang
To evaluate the evidence of effects and safety of magnesium sulfate on neuroprotection for preterm infants who had exposure in uteri. We searched electronic databases and bibliographies of relevant papers to identify studies comparing magnesium sulfate (MgSO4) with placebo or other treatments in patients at high risk of preterm labor and reporting effects and safety of MgSO4 for antenatal infants. Then, we did this meta-analysis based on PRISMA guideline. The primary outcomes included fatal death, cerebral palsy (CP), intraventricular hemorrhage, and periventricular leukomalacia. Secondary outcomes included various neonatal and maternal outcomes. Ten studies including 6 randomized controlled trials and 5 cohort studies, and involving 18,655 preterm infants were analyzed. For the rate of moderate to severe CP, MgSO4 showed the ability to reduce the risk and achieved statistically significant difference (odd ratio [OR] 0.61, 95% confidence interval [CI] 0.42-0.89, P = 0.01). The comparison of mortality rate between the MgSO4 group and the placebo group only presented small difference clinically, but reached no statistical significance (OR 0.92, 95% CI 0.77-1.11, P = 0.39). Summarily, the analysis of adverse effects on babies showed no margin (P > 0.05). Yet for mothers, MgSO4 exhibited obvious side-effects, such as respiratory depression, nausea and so forth, but there exited great heterogeneity. MgSO4 administered to women at high risk of preterm labor could reduce the risk of moderate to severe CP, without obvious adverse effects on babies. Although there exit many unfavorable effects on mothers, yet they may be lessened through reduction of the dose of MgSO4 and could be tolerable for mothers. So MgSO4 is both beneficial and safety to be used as a neuroprotective agent for premature infants before a valid alternative was discovered.
Efficacy and safety of sonothrombolysis in patients with acute ischemic stroke: A systematic review and meta-analysis.
Li Xiaoqiang,Du Hui,Song Zhibin,Wang Hui,Tan Zhijian,Xiao Mufang,Zhang Fu
Journal of the neurological sciences
BACKGROUND:Accumulating clinical evidence has indicated that sonothrombolysis can aid in the treatment of ischemic stroke; however, these findings remain controversial. The purpose of the present meta-analysis was to assess randomized clinical studies concerning the effects of sonothrombolysis on ischemic stroke to evaluate its safety and efficacy. METHODS:We systematically searched the Cochrane Library, PubMed, and EMBASE databases for literature published between the inception of electronic data and May 2019 regarding sonothrombolysis for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on patient characteristics, ultrasound variables (any duration or frequency, without microbubble), and outcome variables (safety and efficacy). RESULTS:Five trials were included in the present study. Clinical functional recovery was evaluated at different time points (several days or 3 months), and heterogeneity was low. Sonothrombolysis did not lead to an increase in symptomatic intracranial hemorrhagic complications or death. Our results demonstrated that patients treated with sonothrombolysis had significantly higher rates of recanalization and asymptomatic intracerebral hemorrhage than patients treated with intravenous thrombolysis alone. In the subgroup of middle cerebral artery (MCA) occlusion patients, sonothrombolysis was found to greatly increase the efficacy outcomes compared to intravenous thrombolysis. CONCLUSIONS:Evidence suggests that sonothrombolysis is a technically feasible and potentially effective treatment that has beneficial effects on recanalization and increases the rate of asymptomatic intracerebral hemorrhage in stroke patients. Additionally, short- and long-term clinical outcome analyses were improved in the MCA occlusion sonothrombolysis subgroup. Larger clinical trials of MCA occlusion patients are necessary to verify these findings.
Intrathecal treatment of cerebral vasospasm.
Zhang Yi Ping,Shields Lisa B E,Yao Tom L,Dashti Shervin R,Shields Christopher B
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
Treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a major therapeutic challenge. Systemic drug administration is the current treatment of choice, but patients often do not respond beneficially to this approach. Intrathecal (IT) drug administration has several anatomic and pharmacodynamic advantages over conventional systemic treatment of cerebral vasospasm. We reviewed the most recent literature describing IT administration of several drugs to treat aneurysm-induced SAH and cerebral vasospasm, including 16 clinical trials using IT fibrinolytic agents and 10 trials using several IT vasodilators. We evaluated the safety and effectiveness of these trials but made no attempt to perform a meta-analysis using these data. IT drug administration of fibrinolytic agents and vasodilators caused lysis of the subarachnoid clot burden and diminished cerebral vasospasm, respectively. The studies reviewed reported a wide range of drug doses, intervals between aneurysm hemorrhage and initiation of treatment, success of clot dissolution, and degree of vasodilation of vessels in vasospasm. Treatment of vasospasm by IT drug administration is safe and largely effective after the aneurysm has been secured. Our findings indicate that IT treatment effectively delivers a higher drug concentration to vessels in vasospasm with minimal systemic effects. Drugs administered by this route are reported to lyse subarachnoid clots, attenuate cerebral vasospasm, improve clinical outcomes, and decrease the incidence of hydrocephalus. With greater understanding of drug pharmacodynamics, the IT route of drug administration may provide a rational, alternative approach to treating aneurysm-induced cerebral vasospasm.
General Anesthesia Versus Conscious Sedation in Endovascular Thrombectomy for Stroke: A Meta-analysis of 4 Randomized Controlled Trials.
Campbell Doug,Diprose William K,Deng Carolyn,Barber P Alan
Journal of neurosurgical anesthesiology
BACKGROUND:In ischemic stroke patients, studies have suggested that clinical outcomes following endovascular thrombectomy are worse after general anesthesia (GA) compared with conscious sedation (CS). Most data are from observational trials, which are prone to measure and unmeasure confounding. We performed a systematic review and meta-analysis of thrombectomy trials where patients were randomized to GA or CS, and compared efficacy and safety outcomes. METHODS:The Medline, Embase, and Cochrane databases were searched for randomized controlled trials comparing GA to CS in endovascular thrombectomy. Efficacy outcomes included successful recanalization (Thrombolysis in Cerebral Infarction score of 2b to 3), and good functional outcome, defined as a modified Rankin Scale score of 0 to 2 at 3 months. Safety outcomes included intracerebral hemorrhage and 3-month mortality. RESULTS:Four studies were identified and included in the random effects meta-analysis. Patients treated with GA achieved a higher proportion of successful recanalization (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.26-3.62; P=0.005) and good functional outcome (OR: 1.71, 95% CI: 1.13-2.59; P=0.01). For every 7.9 patients receiving GA, one more achieved good functional outcome compared with those receiving CS. There were no significant differences in intracerebral hemorrhage (OR: 0.61, 95% CI: 0.20-1.85; P=0.38) or 3-month mortality (OR: 0.62, 95% CI: 0.33-1.17; P=0.14) between GA and CS patients. CONCLUSIONS:In centers with high quality, specialized neuroanesthesia care, GA treated thrombectomy patients had superior recanalization rates and better functional outcome at 3 months than patients receiving CS.
M2 segment thrombectomy is not associated with increased complication risk compared to M1 segment: A meta-analysis of recent literature.
Alexander Christopher,Caras Andrew,Miller William Kyle,Tahir Rizwan,Mansour Tarek R,Medhkour Azedine,Marin Horia
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
INTRODUCTION:Recent clinical comparisons of M1 and M2 segment endovascular thrombectomy have reached incongruous results in rates of complication and functional outcomes. This study aims to clarify the controversy surrounding this rapidly advancing technique through literature review and meta-analysis. METHODS:A Pubmed search was performed (January 2015-September 2019) using the following keywords: "M2 AND ("stroke" OR "occlusion") AND ("thrombectomy" OR "endovascular")". Safety and clinical outcomes were compared between segments via weighted Student's t-test, Chi-square and odds ratio while study heterogeneity was analyzed using Cochran Q and I tests. RESULTS:Pubmed identified 208 articles and eleven studies were included after full-text analysis, comprising 2,548 M1 and 758 M2 mechanical thrombectomy segment cases. Baseline National Institutes of Health Stroke Scale scores were comparatively lower in patients experiencing an M2 occlusion (16 ± 1.25 vs 13.6 ± 0.96, p < 0.01). Patients who underwent M2 mechanical thrombectomy were more likely to experience both good clinical outcomes (modified Rankin Scale 0-2) (48.6% vs 43.5% respectively, OR 1.24; CI 1.05-1.47, p = 0.01) and excellent clinical outcomes (modified Rankin Scale 0-1) (34.7% vs. 26.5%%, OR 1.6; CI 1.28-1.99, p < 0.01) at 90 days compared to M1 mechanical thrombectomy. Neither recanalization rates (75.3% vs 72.8%, OR 0.92, CI 0.75-1.13, p = 0.44) nor symptomatic intracranial hemorrhage rates (5.6% vs 4.9%, OR 0.92; CI 0.61-1.39, p= 0.7) were significantly different between M1 and M2 cohorts. Mortality was less frequent in the M2 cohort compared to M1 (16.3% vs 20.7%, OR 0.73; CI 0.57-0.94, p = 0.01). M1 and M2 cohorts did not differ in symptom onset-to-puncture (238.1 ± 46.7 vs 239.8 ± 43.9 min respectively, p=0.488) nor symptom onset-to recanalization times (318.7 ± 46.6 vs 317.7 ± 71.1 min respectively, p = 0.772), though mean operative duration was shorter in the M2 cohort (61.8 ± 25.5 vs 54.6 ± 24 min, p < 0.01). CONCLUSIONS:Patients who underwent M2 mechanical thrombectomy had a higher prevalence of good and excellent clinical outcomes compared to the M1 mechanical thrombectomy cohorts. Additionally, our data suggest lower mortality rates in the M2 cohort and symptomatic intracranial hemorrhage rates that are similar to the M1 cohort. Therefore, M2 segment thrombectomy likely does not pose a significantly elevated operative risk and may have a positive impact on patient outcomes.
Patient- and Aneurysm-Specific Risk Factors for Intracranial Aneurysm Growth: A Systematic Review and Meta-Analysis.
Backes Daan,Rinkel Gabriel J E,Laban Kamil G,Algra Ale,Vergouwen Mervyn D I
BACKGROUND AND PURPOSE:Follow-up imaging is often performed in intracranial aneurysms that are not treated. We performed a systematic review and meta-analysis on patient- and aneurysm-specific risk factors for aneurysm growth. METHODS:We searched EMBASE and MEDLINE for cohort studies describing risk factors for aneurysm growth. Two authors independently assessed study eligibility and rated quality with the Newcastle Ottawa Scale. With univariable Poisson regression analysis, we calculated risk ratios (RRs) with corresponding 95% confidence intervals (95% CI) of risk factors for aneurysm growth. Heterogeneity was assessed with I(2). RESULTS:Eighteen studies on 15 patient-populations described 3990 patients with 4972 unruptured aneurysms. A total of 437 aneurysms (9%) enlarged during 13 987 aneurysm-years of follow-up. Compared with aneurysms ≤4 mm, RRs were 2.56 (95% CI, 1.93-3.39; I(2)=98%) for ≥5 mm, 2.80 (95% CI, 2.01-3.90; I(2)=96%) for ≥7 mm, and 5.38 (95% CI, 3.76-7.70; I(2)=97%) for ≥10 mm. Compared with aneurysms on the middle cerebral artery, the RR for basilar artery was 1.94 (95% CI, 1.32-2.83; I(2)=57%). RRs were 2.03 (95% CI, 1.52-2.71; I(2)=59%) for smoking at baseline, 2.04 (95% CI, 1.56-2.66; I(2)=90%) for multiple unruptured aneurysms, 1.26 (95% CI, 0.97-1.62; I(2)=59%) for women, 1.24 (95% CI, 0.98-1.58; I(2)=40%) for hypertension, and 2.32 (95% CI, 1.46-3.68; I(2)=91%) for irregular aneurysm shape. Compared with other regions, RR was 0.75 (95% CI, 0.58-0.96) for Japan and 0.64 (95% CI, 0.45-0.90) for Finland. CONCLUSIONS:Most risk factors for aneurysm growth are consistent with risk factors for rupture. In contrast with rupture, the risk of growth was smaller in Japanese and Finnish cohorts compared with other regions. Pooling of individual patient data from low- and high-risk geographical regions is needed to assess independent predictors of aneurysm growth.
Bridging versus Direct Mechanical Thrombectomy in Acute Ischemic Stroke: A Subgroup Pooled Meta-Analysis for Time of Intervention, Eligibility, and Study Design.
Vidale Simone,Romoli Michele,Consoli Domenico,Agostoni Elio Clemente
Cerebrovascular diseases (Basel, Switzerland)
BACKGROUND AND AIM:The risk/benefit profile of intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) in acute ischemic stroke is still unclear. We provide a systematic review and meta-analysis including studies comparing direct EVT (dEVT) vs. bridging treatment (IVT + EVT), defining the impact of treatment timing and eligibility to IVT on functional status and mortality. METHODS:Protocol was registered with PROSPERO (CRD42019135915) and followed PRISMA guidelines. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials (RCTs), retrospective, and prospective studies comparing IVT + EVT vs. dEVT in adults (≥18) with acute ischemic stroke. Primary endpoint was functional independence at 90 days (modified Rankin Scale <3); secondary endpoints were (i) good recanalization (thrombolysis in cerebral infarction >2a), (ii) mortality, and (iii) symptomatic intracranial hemorrhage (sICH). Subgroup analysis was performed according to study type, eligibility to IVT, and onset-to-groin timing (OGT), stratifying studies for similar OGT. ORs for endpoints were pooled with meta-analysis and compared between reperfusion strategies. RESULTS:Overall, 35 studies were included (n = 9,117). No significant differences emerged comparing patients undergoing dEVT and bridging treatment for gender, hypertension, diabetes, National Institute of Health Stroke Scale score at admission. Regarding primary endpoint, IVT + EVT was superior to dEVT (OR 1.44, 95% CI 1.22-1.69, p < 0.001, pheterogeneity<0.001), with number needed to treat being 18 in favor of IVT + EVT. Results were confirmed in studies with similar OGT (OR 1.66; 95% CI 1.21-2.28), shorter OGT for IVT + EVT (OR 1.53, 95% CI 1.27-1.85), and independently from IVT eligibility (OR 1.53, 95% CI 1.29-1.82). Mortality at 90 days was higher in dEVT (OR 1.38; 95% CI 1.09-1.75), but no significant difference was noted for sICH. However, considering data from RCT only, reperfusion strategies had similar primary (OR 0.91, 95% CI 0.6-1.39) and secondary endpoints. Differences in age and clinical severity across groups were unrelated to the primary endpoint. CONCLUSIONS:Compared to dEVT, IVT + EVT associates with better functional outcome and lower mortality. Post hoc data from RCTs point to substantial equivalence of reperfusion strategies. Therefore, an adequately powered RCTs comparing dEVT versus IVT + EVT are warranted.
Plasma endothelin-1 as screening marker for cerebral vasospasm after subarachnoid hemorrhage.
Bellapart J,Jones Lee,Bandeshe H,Boots R
BACKGROUND:Cerebral vasospasm complicating subarachnoid hemorrhage causes ischemic stroke and worsens the neurological outcome. The potential role of endothelin-1 in vasospasm pathogenesis may provide therapeutic opportunities. A recent meta-analysis however, did not support the use of endothelin antagonists. Apart from clinical assessment, transcranial Doppler and interval angiography, there are no sensitive screening markers for evolving vasospasm. We investigate the ability of serial measurement of endothelin-1 to predict the development of vasospasm following subarachnoid hemorrhage. METHODS:Endothelin-1 levels in cerebrospinal fluid and blood were measured daily in 20 patients admitted to the ICU with subarachnoid hemorrhage from days 1 to 10 following the inception bleed. In addition to clinical assessment, patients had daily transcranial Doppler. Digital subtraction angiography was performed on the suspicion of vasospasm based upon clinical or transcranial Doppler assessment. Neuron-specific enolase and SB100 were measured in blood as comparative biomarkers of neurological injury. RESULTS:Mean plasma endothelin-1 on day 5, was 4.2 mcg/L (CI 3.1-5.8) in patients with vasospasm compared to 2.5 mcg/L (CI 1.5-4.0) in those without vasospasm (P = 0.047). There were no time-related differences in cerebrospinal fluid endothelin-1, plasma NSE, or SB100 for patients with and without vasospasm. CONCLUSIONS:In patients with subarachnoid hemorrhage and vasospasm, endothelin-1 is significantly higher in plasma than in CSF on day 5. Neither NSE nor SB100 is associated with the development of vasospasm. Measurement of serial plasma endothelin-1 concentration is a potential screening marker of vasospasm.
Coffee Consumption and Risk of Stroke: A Mendelian Randomization Study.
Qian Yu,Ye Ding,Huang Huijun,Wu David J H,Zhuang Yaxuan,Jiang Xia,Mao Yingying
Annals of neurology
OBJECTIVE:Observational epidemiological studies have reported a relationship between coffee intake and risk of stroke. However, evidence for this association is inconsistent, and it remains uncertain whether the association is causal or due to confounding or reverse causality. To clarify this relationship, we adopted a Mendelian randomization (MR) approach to evaluate the effects of coffee consumption on the risk of stroke and its subtypes. METHODS:A meta-analysis of genome-wide association studies (GWASs) including 91,462 coffee consumers was used to identify instruments for coffee consumption. Summary-level data for stroke, intracerebral hemorrhage, ischemic stroke (IS), and IS subtypes were obtained from GWAS meta-analyses conducted by the MEGASTROKE consortium. MR analyses were performed using the inverse-variance-weighted, weighted-median, MR-PRESSO (Pleiotropy RESidual Sum and Outlier) test and MR-Egger regression. Sensitivity analyses were further performed using alternative instruments to test the robustness of our findings. RESULTS:Genetically predicted coffee consumption (high vs infrequent/no) was not associated with risk of stroke. Similarly, among coffee consumers, MR analysis did not indicate causal associations between coffee consumption (cups/day) and risk of stroke. However, in the subgroup analysis, we found weak suggestive evidence for a potential protective effect of coffee consumption on risk of small vessel (SV)-IS, although the association did not reach statistical significance after correction for multiple comparisons. INTERPRETATION:This study suggests that coffee consumption is not causally associated with risk of stroke or its subtypes. Further studies are warranted to elucidate the possible association between coffee intake and risk of SV-IS, as well as its potential underlying mechanisms. ANN NEUROL 2020;87:525-532.
Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials.
Dong Hongli,Pi Fuhua,Ding Zan,Chen Wei,Pang Shaojie,Dong Wenya,Zhang Qingying
BACKGROUND:Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke. METHODS:A total of 17 trials (86 393 patients) comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions. RESULTS:B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12. CONCLUSIONS:B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied.
Carotid plaque magnetic resonance imaging and recurrent stroke risk: A protocol for systematic review and meta-analysis.
Deng Fengbin,Hao Xinyu,Tang Zhuoran,Mu Changping,Li Kang,Li Huaqiang
BACKGROUND & AIMS:Carotid atherosclerotic plaque is an important cause of carotid artery stenosis. The features of carotid atherosclerotic plaque detected by relevant magnetic resonance imaging (MRI), such as lipid core, plaque hemorrhage, and fibrous cap rupture, have been confirmed to be associated with the occurrence of the first cerebral ischemic event. Meanwhile, the features of carotid atherosclerotic plaque can be used as biomarkers to predict the occurrence of cerebral ischemic event. However, the mechanism of recurrent stroke is still unclear. A systematic review and meta-analysis will be performed to summarize the association between features of carotid artery plaque detected by MRI and recurrent stroke, so as to find biomarkers that can predict recurrent stroke. METHODS:Electronic search will be performed in PUBMED, EMBASE, Cochrane Controlled Register of Trials (CENTRAL) from inception to October 30, 2018. We will include cohort studies with an average follow-up time of >1 month in which lipid-rich/necrotic cores (LRNC), intraplaque hemorrhage (IPH), and thinned or ruptured fibrous caps (TRFC) are associated with recurrent ipsilateral stroke or ischemic events. We will perform heterogeneity assessment before carrying out meta-analysis. According to the heterogeneity, we select random effect model or fixed effect model for meta-analysis of the included cohort studies. RESULTS:Review Manager 5.3 software will be used to calculate the combined hazard ratio value and 95% confidence interval (CI). This meta-analysis will provide high-quality data analysis of LRNC, IPH, and TRFC and ipsilateral recurrent stroke or ischemic events, including biomarkers as major predictors. CONCLUSION:The systematic review will provide evidence to assess the association between features of carotid plaque and ipsilateral recurrent stroke or ischemic events. PROSPERO REGISTRATION NUMBER:PROSPERO CRD42019124043.
Mechanical Thrombectomy in Acute Ischemic Stroke: A Meta-Analysis of Stent Retrievers vs Direct Aspiration vs a Combined Approach.
Texakalidis Pavlos,Giannopoulos Stefanos,Karasavvidis Theofilos,Rangel-Castilla Leonardo,Rivet Dennis J,Reavey-Cantwell John
BACKGROUND:Recent randomized control trials (RCTs) established that mechanical thrombectomy is superior to medical therapy for patients with stroke due to a large vessel occlusion. OBJECTIVE:To compare the safety and efficacy profile of the different mechanical thrombectomy strategies. METHODS:A random-effects meta-analysis was performed and the I2 statistic was used to assess heterogeneity according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS:Nineteen studies with a total of 2449 patients were included. No differences were identified between the stent retrieval and direct aspiration groups in terms of modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3 and mTICI 3 recanalization rates, and favorable outcomes (modified Rankin Scale [mRS] ≤ 2). Adverse event rates, including 90-d mortality, symptomatic intracerebral hemorrhage (sICH), and subarachnoid hemorrhage (SAH), were similar between the stent retrieval and direct aspiration groups. The use of the stent retrieval was associated with a higher risk of vasospasm (odds ratio [OR]: 2.98; 95% confidence interval [CI]: 1.10-8.09; I2: 0%) compared to direct aspiration. When compared with the direct aspiration group, the subgroup of patients who underwent thrombectomy with the combined approach as a first-line strategy had a higher likelihood of successful mTICI 2b/3 (OR: 1.47; 95% CI: 1.02-2.12; I2: 0%) and mTICI 3 recanalization (OR: 3.65; 95% CI: 1.56-8.54), although with a higher risk of SAH (OR: 4.33; 95% CI: 1.15-16.32). CONCLUSION:Stent retrieval thrombectomy and direct aspiration did not show significant differences. Current available evidence is not sufficient to draw conclusions on the best surgical approach. The combined use of a stent retriever and aspiration as a first-line strategy was associated with higher mTICI 2b/3 and mTICI 3 recanalization rates, although with a higher risk of 24-h SAH, when compared with direct aspiration.
Minimally invasive surgery for primary supratentorial intracerebral haemorrhage.
Ramanan Mahesh,Shankar Aparna
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
The use of minimally invasive surgery (MIS) in the treatment of primary supratentorial intracerebral haemorrhage (ICH) is controversial. This review was undertaken to combine all available evidence on this topic and to assess the efficacy of MIS compared to medical treatment or haematoma evacuation via craniotomy for patients with primary supratentorial ICH. The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE databases were searched for randomised controlled trials which compared MIS to any control treatment for intracerebral haemorrhage. Conference proceedings, reference lists and internet-based clinical trial registries were searched for additional studies. Quality was assessed using the Cochrane "risk of bias" analysis tool. The methodological quality of studies was not high, with only two studies conforming to all quality standards assessed. There were 11 studies with 1717 patients. There was a significant reduction in relative risk (RR) for death at end of follow-up when MIS was compared to both medical management (RR = 0.67, 95% confidence interval 0.53-0.84) and craniotomy (RR = 0.57, 95% confidence interval 0.39-0.84) with no significant heterogeneity. Non-significant benefits were observed for the outcomes death or dependent survival (RR = 0.95, 95% confidence interval 0.91-1.00) and independent survival (RR = 1.24, 95% confidence interval 0.99-1.55). There was significant heterogeneity for both these outcomes. MIS for primary supratentorial ICH is associated with a significant reduction in the RR of death when compared to medical management and craniotomy. Other important outcomes need further evaluation.
Do acute stroke patients develop hypocapnia? A systematic review and meta-analysis.
Salinet Angela S M,Minhas Jatinder S,Panerai Ronney B,Bor-Seng-Shu Edson,Robinson Thompson G
Journal of the neurological sciences
PURPOSE:Carbon dioxide (CO) is a potent cerebral vasomotor agent. Despite reduction in CO levels (hypocapnia) being described in several acute diseases, there is no clear data on baseline CO values in acute stroke. The aim of the study was to systematically assess CO levels in acute stroke. MATERIAL AND METHODS:Four online databases, Web of Science, MEDLINE, EMBASE and CENTRAL, were searched for articles that described either partial pressure of arterial CO (PaCO) and end-tidal CO (EtCO) in acute stroke. RESULTS:After screening, based on predefined inclusion and exclusion criteria, 20 studies were retained. There were 5 studies in intracerebral hemorrhage and 15 in ischemic stroke, totalling 660 stroke participants. Acute stroke was associated with a significant decrease in CO levels compared to controls. Cerebral haemodynamic studies using transcranial Doppler ultrasonography demonstrated a significant reduction in cerebral blood flow velocities and cerebral autoregulation in acute stroke patients. CONCLUSION:The evidence from this review suggests that acute stroke patients are significantly more likely than controls to be hypocapnic, supporting the value of routine CO assessment in the acute stroke setting. Further studies are required in order to evaluate the clinical impact of these findings.
Cerebral microbleeds: histopathological correlation of neuroimaging.
Shoamanesh A,Kwok C S,Benavente O
Cerebrovascular diseases (Basel, Switzerland)
BACKGROUND:In recent years, there has been a growing interest in cerebral microbleeds (CMBs) and their role in cerebrovascular disease. A few studies have investigated the histopathological correlation between CMBs and neuroimaging findings. We conducted a systematic review in an attempt to characterize the pathological and radiological correlation. METHODS:A systematic literature search was conducted for studies in which CMBs were characterized histopathologically and correlated with MRI findings. RESULTS:Five studies met the inclusion criteria, with a total of 18 patients. Hemosiderin deposition was reported in 42 CMBs (49%), while 16 CMBs (19%) were described as old hematomas which stained for iron, 13 (15%) had no associated specific pathology, 11 (13%) contained intact erythrocytes, 1 (1%) was due to vascular pseudocalcification, 1 (1%) was a microaneurysm and 1 (1%) was a distended dissected vessel. Lipofibrohyalinosis was the most prominent associated vascular finding. Amyloid angiopathy was present primarily in patients with dementia. CONCLUSIONS:Although histopathological associations have been observed using MRI in patients with CMBs, the findings have yet to be validated and further research is warranted.
Marine-derived n-3 fatty acids therapy for stroke.
Alvarez Campano Celia Gabriela,Macleod Mary Joan,Aucott Lorna,Thies Frank
The Cochrane database of systematic reviews
BACKGROUND:Currently, with stroke burden increasing, there is a need to explore therapeutic options that ameliorate the acute insult. There is substantial evidence of a neuroprotective effect of marine-derived n-3 polyunsaturated fatty acids (PUFAs) in experimental stroke, leading to a better functional outcome. OBJECTIVES:To assess the effects of administration of marine-derived n-3 PUFAs on functional outcomes and dependence in people with stroke.Our secondary outcomes were vascular-related death, recurrent events, incidence of other type of stroke, adverse events, quality of life, and mood. SEARCH METHODS:We searched the Cochrane Stroke Group trials register (6 August 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, January 2019), MEDLINE Ovid (from 1948 to 6 August 2018), Embase Ovid (from 1980 to 6 August 2018), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; from 1982 to 6 August 2018), Science Citation Index Expanded ‒ Web of Science (SCI-EXPANDED), Conference Proceedings Citation Index-Science - Web of Science (CPCI-S), and BIOSIS Citation Index. We also searched ongoing trial registers, reference lists, relevant systematic reviews, and used the Science Citation Index Reference Search. SELECTION CRITERIA:We included randomised controlled trials (RCTs) comparing marine-derived n-3 PUFAs to placebo or open control (no placebo) in people with a history of stroke or transient ischaemic attack (TIA), or both. DATA COLLECTION AND ANALYSIS:At least two review authors independently selected trials for inclusion, extracted data, assessed risk of bias, and used the GRADE approach to assess the quality of the body of evidence. We contacted study authors for clarification and additional information on stroke/TIA participants. We conducted random-effects meta-analysis or narrative synthesis, as appropriate. The primary outcome was efficacy (functional outcome) assessed using a validated scale e.g. Glasgow Outcome Scale Extended (GOSE) dichotomised into poor or good clinical outcome, Barthel Index (higher score is better; scale from 0 to 100) or Rivermead Mobility Index (higher score is better; scale from 0 to 15). MAIN RESULTS:We included 29 RCTs; nine of them provided outcome data (3339 participants). Only one study included participants in the acute phase of stroke (haemorrhagic). Doses of marine-derived n-3 PUFAs ranged from 400 mg/day to 3300 mg/day. Risk of bias was generally low or unclear in most trials, with a higher risk of bias in smaller studies. We assessed results separately for short (up to three months) and longer (more than three months) follow-up studies.Short follow-up (up to three months)Functional outcome was reported in only one pilot study as poor clinical outcome assessed with GOSE (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.36 to 1.68; 40 participants; very low quality evidence). Mood (assessed with GHQ-30, lower score better), was reported by only one study and favoured control (mean difference (MD) 1.41, 95% CI 0.07 to 2.75; 102 participants; low-quality evidence).We found no evidence of an effect of the intervention for the remainder of the secondary outcomes: vascular-related death (two studies, not pooled due to differences in population, RR 0.33, 95% CI 0.01 to 8.00, and RR 0.33, 95% CI 0.01 to 7.72; 142 participants; low-quality evidence); recurrent events (RR 0.41, 95% CI 0.02 to 8.84; 18 participants; very low quality evidence); incidence of other type of stroke (two studies, not pooled due to different type of index stroke, RR 6.11, 95% CI 0.33 to 111.71, and RR 0.63, 95% CI 0.25 to 1.58; 58 participants; very low quality evidence); and quality of life (physical component mean difference (MD) -2.31, 95% CI -4.81 to 0.19, and mental component MD -2.16, 95% CI -5.91 to 1.59; one study; 102 participants; low-quality evidence).Adverse events were reported by two studies (57 participants; very low quality evidence), one trial reporting extracranial haemorrhage (RR 0.25, 95% CI 0.04 to 1.73) and the other one reporting bleeding complications (RR 0.32, 95% CI 0.01 to 7.35).Longer follow-up (more than three months)One small trial assessed functional outcome with both Barthel Index (MD 7.09, 95% CI -5.16 to 19.34) for activities of daily living, and Rivermead Mobility Index (MD 1.30, 95% CI -1.31 to 3.91) for mobility (52 participants; very low quality evidence). We carried out meta-analysis for vascular-related death (RR 1.02, 95% CI 0.78 to 1.35; five studies; 2237 participants; low-quality evidence) and fatal recurrent events (RR 0.69, 95% CI 0.31 to 1.55; three studies; 1819 participants; low-quality evidence).We found no evidence of an effect of the intervention for mood (MD 1.00, 95% CI -2.07 to 4.07; one study; 14 participants; low-quality evidence). Incidence of other type of stroke and quality of life were not reported.Adverse events (all combined) were reported by only one study (RR 0.94, 95% CI 0.56 to 1.58; 1455 participants; low-quality evidence). AUTHORS' CONCLUSIONS:We are very uncertain of the effect of marine-derived n-3 PUFAs therapy on functional outcomes and dependence after stroke as there is insufficient high-quality evidence. More well-designed RCTs are needed, specifically in acute stroke, to determine the efficacy and safety of the intervention.Studies assessing functionality might consider starting the intervention as early as possible after the event, as well as using standardised clinically-relevant measures for functional outcomes, such as the modified Rankin Scale. Optimal doses remain to be determined; delivery forms (type of lipid carriers) and mode of administration (ingestion or injection) also need further consideration.
Migraine and hemorrhagic stroke: a meta-analysis.
Sacco Simona,Ornello Raffaele,Ripa Patrizia,Pistoia Francesca,Carolei Antonio
BACKGROUND AND PURPOSE:Several studies have assessed the possible increased risk of hemorrhagic stroke in migraineurs, drawing differing conclusions. No meta-analysis on the topic has been published to date. METHODS:Multiple electronic databases (MEDLINE, EMBASE, Science Citation Index, and the Cochrane Library) were systematically searched up to March 2013 for studies dealing with migraine and hemorrhagic stroke. We selected case-control and cohort studies with a clear definition of the diagnostic criteria for migraine and hemorrhagic stroke, using an adjusted model or a matching procedure that could control for potential confounders, and reporting effect estimates with 95% confidence intervals (CIs) or enough data to allow calculation of those numbers. Adjusted odds ratios and hazard ratios were used to estimate effect size. RESULTS:Of 11 264 records, we identified 8 studies (4 case-control and 4 cohort studies) involving a total of 1600 hemorrhagic strokes, which were included in the meta-analysis. The overall pooled adjusted effect estimate of hemorrhagic stroke in subjects with any migraine versus control subjects was 1.48 (95% CI, 1.16-1.88; P=0.002), with moderate statistical heterogeneity (I(2)=54.7%; P value for Q test=0.031). The risk of hemorrhagic stroke in subjects with migraine with aura (1.62; 95% CI, 0.87-3.03; P=0.129) was not significant. Compared with control subjects, the risk of hemorrhagic stroke was greater in females with any migraine (1.55; 95% CI, 1.16-2.07; P=0.003) and in female migraineurs aged less than 45 years (1.57; 95% CI, 1.10-2.24; P=0.012). CONCLUSIONS:Available studies suggest that subjects with migraine have an increased risk of hemorrhagic stroke. Further studies are needed to address the hemorrhagic stroke risk according to migraine type, age, sex, and hemorrhagic stroke type.
Role of Apolipoprotein E Genotypes in Aneurysmal Subarachnoid Hemorrhage: Susceptibility, Complications, and Prognosis.
Hu Xin,Xie Zhiyi,Zan Xin,Ma Lu,Li Hao,You Chao,Jiang Yan
BACKGROUND:Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease. Emerging evidence has indicated that the apolipoprotein E (ApoE) genotype might be associated with the risk of aSAH as well as complications and outcomes after aSAH, although the results remain controversial. METHODS:We searched published literature on PubMed, Embase, China National Knowledge Infrastructure, and Wanfang database to identify studies involving the ApoE genotype and aSAH. A meta-analysis was performed to summarize the relationship between ApoE genotype and aSAH, including susceptibility, complications, and prognosis. RESULTS:Eighteen studies were considered eligible for inclusion. Generally, ε4 carriers had increased risk of aSAH (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.01-1.49). White patients with the ε2/ε2 genotype had a greater risk of aSAH (OR 3.38, 95% CI 1.13-10.11). The patients with aSAH carrying the ε4 allele had an increased risk of poor outcome (OR 2.21, 95% CI 1.21-4.05) compared with non-ε4 carriers, especially in Asian patients (OR 4.99, 95% CI 1.73-14.40). ApoE ε4 carriers have increased risk of delayed ischemic neurologic deficit compared with non-ε4 carriers in the overall population. No significant difference was detected regarding the effect of certain ApoE genotypes on aSAH admission severity, rebleeding, or cerebral vasospasm after aSAH. CONCLUSIONS:We found that the ApoE genotype was significantly associated with aSAH risk, whereas its effect on certain ethnic populations differs. Patient carrying the ε4 allele might have a worse outcome, whereas current evidence was insufficient to prove the association between ApoE genotypes and post-SAH complications.
Smoking and stroke: A mendelian randomization study.
Larsson Susanna C,Burgess Stephen,Michaëlsson Karl
Annals of neurology
We used the Mendelian randomization design to explore the potential causal association of smoking with ischemic stroke and intracerebral hemorrhage using summary statistics data for 34,217 ischemic stroke cases and 404,630 noncases, and 1,545 cases of intracerebral hemorrhage and 1,481 noncases. Genetic predisposition to smoking initiation (ever smoking regularly), based on up to 372 single-nucleotide polymorphisms, was statistically significantly positively associated with any ischemic stroke, large artery stroke, and small vessel stroke but not cardioembolic stroke or intracerebral hemorrhage. This study provides genetic support for a causal association of smoking with ischemic stroke, particularly large artery and small vessel stroke. ANN NEUROL 2019;86:468-471.
Genotype-guided antiplatelet therapy compared with conventional therapy for patients with acute coronary syndromes: a systematic review and meta-analysis.
Zheng Lukai,Yang Chunsong,Xiang Lingbao,Hao Zilong
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals
To evaluate whether genotype-guided antiplatelet therapy reduces the rates of cardiovascular events and bleeding events in patients with acute coronary syndrome (ACS). We systematically searched Pubmed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) (searched in September 2018) for controlled studies evaluating genotype-guided antiplatelet therapy in ACS with percutaneous coronary intervention (PCI) or without PCI. The primary endpoint was a composite of death, myocardial infarction (MI), stroke, targeted vessel revascularization and/or major bleeding. A total of five studies involving 2900 patients were included. Compared with the conventional group, the genotype-guided group had a decreased risk of primary composite outcomes (RR= 0.54; 95% CI: 0.41-0.72; = 30%), death (RR = 0.54; 95% CI: 0.32-0.94; = 21%), MI (RR = 0.52; 95% CI: 0.31-0.88; = 49%), targeted vessel revascularization (RR = 0.59; 95% CI: 0.35-0.98; = 0%), but not for stroke (RR = 0.53; 95% CI: 0.22-1.24; = 0%) and bleeding events (RR = 0.80; 95% CI: 0.51-1.25; = 33%). Genotype-guided strategies could reduce the rates of cardiovascular events without increasing bleeding events compared with conventional treatment in ACS. Future multicentre genotype-based randomized control trials are required to confirm these findings.
Efficacy and safety of mechanical thrombectomy for M2 segment of middle cerebral artery: a systematic review and meta-analysis.
Wang Jian,Qian Jiacheng,Fan Lu,Wang Yujie
Journal of neurology
BACKGROUND AND PURPOSE:The efficacy and safety of mechanical thrombectomy (MT) for M2 segment occlusion of middle cerebral artery in patients with acute ischemic stroke (AIS) was investigated. METHODS:We searched PubMed and EMBASE from inception to 16 April 2019 for relevant studies, calculated the pool relative risks (RRs) of 3-month functional independence (modified Rankin scale score 0-2), death and symptomatic intracerebral hemorrhage (sICH) in MT for M2 segment occlusion in patients with AIS versus those of M1 segment or best medical care. RESULTS:Nine studies enrolling 2152 patients compared MT for patients with AIS of M2 segment occlusion and those of M1 segment occlusion. MT for M2 occlusion had a higher rate of 3-month functional independence compared to the patients with M1 occlusion. (RR 1.27, 95% CI 1.11-1.44, P < 0.001) and decreased death (RR 0.74; 95% CI 0.58-0.96, P = 0.022) with similar risk of sICH (RR 1.11; 95% CI 0.65-1.87, P = 0.707). Four studies enrolling 1016 patients compared MT and best medical care for patients with AIS of M2 occlusion. MT for M2 occlusion benefit more than best medical care on 3-month functional independence (RR 1.43, 95% CI 1.08-1.90, P = 0.011) and death (RR 0.46; 95% CI 0.22-0.96, P = 0.022) with similar risk of sICH (RR 1.65; 95% CI 0.66-4.13; P = 0.286). CONCLUSION:MT for M2 segment benefit patients with AIS on 3-month functional independence compared with that of M1 segment or medical care, without increasing the risk of sICH.
Neuroimaging characteristics of ruptured aneurysm as predictors of outcome after aneurysmal subarachnoid hemorrhage: pooled analyses of the SAHIT cohort.
Jaja Blessing N R,Lingsma Hester,Steyerberg Ewout W,Schweizer Tom A,Thorpe Kevin E,Macdonald R Loch,
Journal of neurosurgery
OBJECT Neuroimaging characteristics of ruptured aneurysms are important to guide treatment selection, and they have been studied for their value as outcome predictors following aneurysmal subarachnoid hemorrhage (SAH). Despite multiple studies, the prognostic value of aneurysm diameter, location, and extravasated SAH clot on computed tomography scan remains debatable. The authors aimed to more precisely ascertain the relation of these factors to outcome. METHODS The data sets of studies included in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository were analyzed including data on ruptured aneurysm location and diameter (7 studies, n = 9125) and on subarachnoid clot graded on the Fisher scale (8 studies; n = 9452) for the relation to outcome on the Glasgow Outcome Scale (GOS) at 3 months. Prognostic strength was quantified by fitting proportional odds logistic regression models. Univariable odds ratios (ORs) were pooled across studies using random effects models. Multivariable analyses were adjusted for fixed effect of study, age, neurological status on admission, other neuroimaging factors, and treatment modality. The neuroimaging predictors were assessed for their added incremental predictive value measured as partial R(2). RESULTS Spline plots indicated outcomes were worse at extremes of aneurysm size, i.e., less than 4 or greater than 9 mm. In between, aneurysm size had no effect on outcome (OR 1.03, 95% CI 0.98-1.09 for 9 mm vs 4 mm, i.e., 75th vs 25th percentile), except in those who were treated conservatively (OR 1.17, 95% CI 1.02-1.35). Compared with anterior cerebral artery aneurysms, posterior circulation aneurysms tended to result in slightly poorer outcome in patients who underwent endovascular coil embolization (OR 1.13, 95% CI 0.82-1.57) or surgical clipping (OR 1.32, 95% CI 1.10-1.57); the relation was statistically significant only in the latter. Fisher CT subarachnoid clot burden was related to outcome in a gradient manner. Each of the studied predictors accounted for less than 1% of the explained variance in outcome. CONCLUSIONS This study, which is based on the largest cohort of patients so far analyzed, has more precisely determined the prognostic value of the studied neuroimaging factors. Treatment choice has strong influence on the prognostic effect of aneurysm size and location. These findings should guide the development of reliable prognostic models and inform the design and analysis of future prospective studies, including clinical trials.
APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study.
Biffi Alessandro,Anderson Christopher D,Jagiella Jeremiasz M,Schmidt Helena,Kissela Brett,Hansen Björn M,Jimenez-Conde Jordi,Pires Caroline R,Ayres Alison M,Schwab Kristin,Cortellini Lynelle,Pera Joanna,Urbanik Andrzej,Romero Javier M,Rost Natalia S,Goldstein Joshua N,Viswanathan Anand,Pichler Alexander,Enzinger Christian,Rabionet Raquel,Norrving Bo,Tirschwell David L,Selim Magdy,Brown Devin L,Silliman Scott L,Worrall Bradford B,Meschia James F,Kidwell Chelsea S,Broderick Joseph P,Greenberg Steven M,Roquer Jaume,Lindgren Arne,Slowik Agnieszka,Schmidt Reinhold,Woo Daniel,Rosand Jonathan,
The Lancet. Neurology
BACKGROUND:Carriers of APOE ε2 and ε4 have an increased risk of intracerebral haemorrhage (ICH) in lobar regions, presumably because of the effects of these gene variants on risk of cerebral amyloid angiopathy. We aimed to assess whether these variants also associate with severity of ICH, in terms of haematoma volume at presentation and subsequent outcome. METHODS:We investigated the association of APOE ε2 and ε4 with ICH volume and outcomes in patients with primary ICH in three phases: a discovery phase of 865 individuals of European ancestry from the Genetics of Cerebral Hemorrhage on Anticoagulation study, and replication phases of 946 Europeans (replication 1) and 214 African-Americans (replication 2) from an additional six studies. We also assessed the association of APOE variants with ICH volume and outcomes in meta-analyses of results from all three phases, and the association of APOE ε4 with mortality in a further meta-analysis including data from previous reports. Admission ICH volume was quantified on CT scan. We assessed functional outcome (modified Rankin scale score 3-6) and mortality at 90 days. We used linear regression to establish the effect of genotype on haematoma volume and logistic regression to assess the effect on outcome from ICH. FINDINGS:For patients with lobar ICH, carriers of the APOE ε2 allele had larger ICH volumes than did non-carriers in the discovery phase (p=2·5×10(-5)), in both replication phases (p=0·008 in Europeans and p=0·016 in African-Americans), and in the meta-analysis (p=3·2×10(-8)). In the meta-analysis, each copy of APOE ε2 increased haematoma size by a mean of 5·3 mL (95% CI 4·7-5·9; p=0·004). Carriers of APOE ε2 had increased mortality (odds ratio [OR] 1·50, 95% CI 1·23-1·82; p=2·45×10(-5)) and poorer functional outcomes (modified Rankin scale score 3-6; 1·52, 1·25-1·85; p=1·74×10(-5)) compared with non-carriers after lobar ICH. APOE ε4 was not associated with lobar ICH volume, functional outcome, or mortality in the discovery phase, replication phases, or meta-analysis of these three phases; in our further meta-analysis of 2194 patients, this variant did not increase risk of mortality (1·08, 0·86-1·36; p=0·52). APOE allele variants were not associated with deep ICH volume, functional outcome, or mortality. INTERPRETATION:Vasculopathic changes associated with the APOE ε2 allele might have a role in the severity and clinical course of lobar ICH. Screening of patients who have ICH to identify the ε2 variant might allow identification of those at increased risk of mortality and poor functional outcomes. FUNDING:US National Institutes of Health-National Institute of Neurological Disorders and Stroke, Keane Stroke Genetics Research Fund, Edward and Maybeth Sonn Research Fund, and US National Center for Research Resources.
Treatment of brain arteriovenous malformations: a systematic review and meta-analysis.
van Beijnum Janneke,van der Worp H Bart,Buis Dennis R,Al-Shahi Salman Rustam,Kappelle L Jaap,Rinkel Gabriël J E,van der Sprenkel Jan Willem Berkelbach,Vandertop W Peter,Algra Ale,Klijn Catharina J M
CONTEXT:Outcomes following treatment of brain arteriovenous malformations (AVMs) with microsurgery, embolization, stereotactic radiosurgery (SRS), or combinations vary greatly between studies. OBJECTIVES:To assess rates of case fatality, long-term risk of hemorrhage, complications, and successful obliteration of brain AVMs after interventional treatment and to assess determinants of these outcomes. DATA SOURCES:We searched PubMed and EMBASE to March 1, 2011, and hand-searched 6 journals from January 2000 until March 2011. STUDY SELECTION AND DATA EXTRACTION:We identified studies fulfilling predefined inclusion criteria. We used Poisson regression analyses to explore associations of patient and study characteristics with case fatality, complications, long-term risk of hemorrhage, and successful brain AVM obliteration. DATA SYNTHESIS:We identified 137 observational studies including 142 cohorts, totaling 13,698 patients and 46,314 patient-years of follow-up. Case fatality was 0.68 (95% CI, 0.61-0.76) per 100 person-years overall, 1.1 (95% CI, 0.87-1.3; n = 2549) after microsurgery, 0.50 (95% CI, 0.43-0.58; n = 9436) after SRS, and 0.96 (95% CI, 0.67-1.4; n = 1019) after embolization. Intracranial hemorrhage rates were 1.4 (95% CI, 1.3-1.5) per 100 person-years overall, 0.18 (95% CI, 0.10-0.30) after microsurgery, 1.7 (95% CI, 1.5-1.8) after SRS, and 1.7 (95% CI, 1.3-2.3) after embolization. More recent studies were associated with lower case-fatality rates (rate ratio [RR], 0.972; 95% CI, 0.955-0.989) but increased rates of hemorrhage (RR, 1.02; 95% CI, 1.00-1.03). Male sex (RR, 0.964; 95% CI, 0.945-0.984), small brain AVMs (RR, 0.988; 95% CI, 0.981-0.995), and those with strictly deep venous drainage (RR, 0.975; 95% CI, 0.960-0.990) were associated with lower case fatality. Lower hemorrhage rates were associated with male sex (RR, 0.976, 95% CI, 0.964-0.988), small brain AVMs (RR, 0.988, 95% CI, 0.980-0.996), and brain AVMs with deep venous drainage (0.982, 95% CI, 0.969-0.996). Complications leading to permanent neurological deficits or death occurred in a median 7.4% (range, 0%-40%) of patients after microsurgery, 5.1% (range, 0%-21%) after SRS, and 6.6% (range, 0%-28%) after embolization. Successful brain AVM obliteration was achieved in 96% (range, 0%-100%) of patients after microsurgery, 38% (range, 0%-75%) after SRS, and 13% (range, 0%-94%) after embolization. CONCLUSIONS:Although case fatality after treatment has decreased over time, treatment of brain AVM remains associated with considerable risks and incomplete efficacy. Randomized controlled trials comparing different treatment modalities appear justified.
Dietary magnesium intake and risk of stroke: a meta-analysis of prospective studies.
Larsson Susanna C,Orsini Nicola,Wolk Alicja
The American journal of clinical nutrition
BACKGROUND:Prospective studies of dietary magnesium intake in relation to risk of stroke have yielded inconsistent results. OBJECTIVE:We conducted a dose-response meta-analysis to summarize the evidence regarding the association between magnesium intake and stroke risk. DESIGN:Relevant studies were identified by searching PubMed and EMBASE from January 1966 through September 2011 and reviewing reference lists of retrieved articles. We included prospective studies that reported RRs with 95% CIs of stroke for ≥3 categories of magnesium intake. Results from individual studies were combined by using a random-effects model. RESULTS:Seven prospective studies, with 6477 cases of stroke and 241,378 participants, were eligible for inclusion in the meta-analysis. We observed a modest but statistically significant inverse association between magnesium intake and risk of stroke. An intake increment of 100 mg Mg/d was associated with an 8% reduction in risk of total stroke (combined RR: 0.92; 95% CI: 0.88, 0.97), without heterogeneity among studies (P = 0.66, I(2) = 0%). Magnesium intake was inversely associated with risk of ischemic stroke (RR: 0.91; 95% CI: 0.87, 0.96) but not intracerebral hemorrhage (RR: 0.96; 95% CI: 0.84, 1.10) or subarachnoid hemorrhage (RR: 1.01; 95% CI: 0.90, 1.14). CONCLUSION:Dietary magnesium intake is inversely associated with risk of stroke, specifically ischemic stroke.
Association of MTHFR 677T variant allele with risk of intracerebral haemorrhage: a meta-analysis.
Gao Shan,Li Hongzhao,Xiao Haijun,Yao Guoxiang,Shi Yihai,Wang Yongli,Zhou Xingsheng,Yu Haifu
Journal of the neurological sciences
BACKGROUND:Previous studies concerning the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and risk of intracerebral haemorrhage (ICH) reported conflicting results. A meta-analysis of published studies was performed to allow a more reliable estimate of this association. METHODS:Relevant studies concerning the association between MTHFR C677T polymorphism and risk of ICH were included into this meta-analysis. Odds ratios (OR) and 95% confidence intervals (CI) were determined for this gene-disease association using fixed or random effect models. RESULTS:Finally, 16 studies with a total of 1828 cases and 4067 controls were included. Meta-analyses of a total of 16 studies showed that there was an obvious association of MTHFR 677T allele with risk of ICH under all four comparison models (OR(T vs. C)=1.38, 95% CI 1.17-1.62, P<0.001; OR(TT vs. CC)=1.90 95% CI 1.42-2.55, P<0.001; OR(TT vs. TC/CC)=1.38 95% CI 1.20-1.59, P<0.001; OR(TT/TC vs. CC)=1.41 95% CI 1.12-1.78, P=0.003). Besides, both subgroup analyses and sensitivity analysis further identified the association above. CONCLUSION:The MTHFR 677T allele is associated with risk of ICH, and individuals with TT genotype have an obviously higher risk of ICH than those with the CC genotype.
Systematic Review and Meta-analysis of Methodological Quality in In Vivo Animal Studies of Subarachnoid Hemorrhage.
Grüter Basil E,Croci Davide,Schöpf Salome,Nevzati Edin,d'Allonzo Donato,Lattmann Jacqueline,Roth Tabitha,Bircher Benjamin,Muroi Carl,Dutilh Gilles,Widmer Hans Rudolf,Plesnila Nikolaus,Fandino Javier,Marbacher Serge
Translational stroke research
As a result of increased awareness of wide-spread methodological bias and obvious translational roadblocks in subarachnoid hemorrhage (SAH) research, various checklists and guidelines were developed over the past decades. This systematic review assesses the overall methodological quality of preclinical SAH research. An electronic search for preclinical studies on SAH revealed 3415 potential articles. Of these, 765 original research papers conducted in vivo in mice, rats, rabbits, cats, dogs, pigs, goats, and non-human primates with a focus on brain damage related to delayed cerebral vasospasm and early brain injury met the inclusion criteria. We found methodological shortcomings still to prevail in preclinical SAH research. In addition, basic animal characteristics were typically well described but important technical parameters of SAH induction were often underreported. None of the species, models, or techniques used in preclinical SAH research was methodologically superior to the others. Methodological quality of preclinical SAH research was independent of the number of citations or impact factor of a publication. Consequently, we suggest the SAH research community should consider strategies to improve preclinical research quality in their field, such as public platforms to (pre)register preclinical experiments, consequent support of open science policies, stricter editorial (and reviewer) control of (pre)existing guidelines, and increased efforts in education and training of good laboratory practice for the next generation of researchers.
Evidence of perceived psychosocial stress as a risk factor for stroke in adults: a meta-analysis.
Booth Joanne,Connelly Lesley,Lawrence Maggie,Chalmers Campbell,Joice Sara,Becker Clarissa,Dougall Nadine
BACKGROUND:Several studies suggest that perceived psychosocial stress is associated with increased risk of stroke; however results are inconsistent with regard to definitions and measurement of perceived stress, features of individual study design, study conduct and conclusions drawn and no meta-analysis has yet been published. We performed a systematic review and meta-analysis of studies assessing association between perceived psychosocial stress and risk of stroke in adults.The results of the meta-analysis are presented. METHODS:Systematic searches of MEDLINE, EMBASE, CINAHL, PsycInfo, and Cochrane Database of Systematic Reviews were undertaken between 1980 and June 2014. Data extraction and quality appraisal was performed by two independent reviewers. Hazard ratios (HR) and odds ratios (OR) were pooled where appropriate. RESULTS:14 studies were included in the meta-analysis, 10 prospective cohort, 4 case-control design. Overall pooled adjusted effect estimate for risk of total stroke in subjects exposed to general or work stress or to stressful life events was 1.33 (95 % confidence interval [CI], 1.17, 1.50; P < 0.00001). Sub-group analyses showed perceived psychosocial stress to be associated with increased risk of fatal stroke (HR 1.45 95 % CI, 1.19,1.78; P = 0.0002), total ischaemic stroke (HR 1.40 95 % CI, 1.00,1.97; P = 0.05) and total haemorrhagic stroke (HR 1.73 95 % CI, 1.33,2.25; P > 0.0001).A sex difference was noted with higher stroke risk identified for women (HR 1.90 95 % CI, 1.4, 2.56: P < 0.0001) compared to men (HR 1.24 95 % CI, 1.12, 1.36; P < 0.0001). CONCLUSIONS:Current evidence indicates that perceived psychosocial stress is independently associated with increased risk of stroke.
Factors and measures predicting external CSF drain-associated ventriculitis: A review and meta-analysis.
Dorresteijn Kirsten R I S,Jellema Korné,van de Beek Diederik,Brouwer Matthijs C
OBJECTIVE:To determine the diagnostic value of clinical factors and biochemical or microbiological measures for diagnosing a drain-associated ventriculitis, we summarized the available evidence. METHODS:We performed a systematic review and meta-analysis of studies of patients with external ventricular CSF drains who developed drain-associated ventriculitis by searching MEDLINE, EMBASE, and CENTRAL electronic database. We reported the occurrence of abnormal test results in patients with and without drain-associated ventriculitis. For continuous variables, we recalculated mean values presented in multiple studies. RESULTS:We identified 42 articles published between 1984 and 2018 including 3,035 patients with external CSF drains of whom 697 (23%) developed drain-associated bacterial ventriculitis. Indications for drain placement were subarachnoid, intraventricular or cerebral hemorrhage or hemorrhage not further specified (69%), traumatic brain injury (13%), and obstructive hydrocephalus secondary to a brain tumor (10%). Fever was present in 116 of 162 patients with ventriculitis (72%) compared with 80 of 275 (29%) patients without ventriculitis. The CSF cell count was increased for 74 of 80 patients (93%) with bacterial ventriculitis and 30 of 95 patients (32%) without ventriculitis. CSF culture was positive in 125 of 156 episodes classified as ventriculitis (80%), and CSF Gram stain was positive in 44 of 81 patients (54%). In patients with ventriculitis, PCR on ribosomal RNA was positive on 54 of 78 CSF samples (69%). CONCLUSION:Clinical factors and biochemical and microbiological measures have limited diagnostic value in differentiating between ventriculitis and sterile inflammation in patients with external CSF drains. Prospective well-designed diagnostic accuracy studies in drain-associated ventriculitis are needed.
Predictors of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage with Asymptomatic Angiographic Vasospasm on Admission.
Aldakkan Abdulrahman,Mansouri Alireza,Jaja Blessing N R,Alotaibi Naif M,Macdonald R Loch,
BACKGROUND:Risk of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) with asymptomatic angiographic vasospasm on admission is unclear in the literature. The goal of this study is to identify predictors of clinical DCI in this group of patients. METHODS:An exploratory subgroup analysis was conducted in the SAHIT (Subarachnoid Hemorrhage International Trialists) data repository to identify predictors of clinical DCI in patients with good-grade aSAH (World Federation of Neurological Surgeons grade I and II) with angiographic vasospasm on admission. Predictors considered include age, sex, systolic blood pressure at presentation, World Federation of Neurological Surgeon grade, Fisher grade, aneurysm size and location, treatment modality, hydrocephalus requiring external ventricular drain insertion, and severity of vasospasm. The predictors were ranked based on dominance analysis with R as fit statistics and assessed in a set of logistic regression analysis models. RESULTS:Four data sets out of 16 studies in the SAHIT database were analyzed, with a total of 4125 patients. One hundred and ninety-one patients (4.6%) had asymptomatic angiographic vasospasm at admission. Of those, 78 patients (40.8%) developed clinical DCI. Univariate analysis showed significant associations between severe vasospasm on admission and development of clinical DCI (odds ratio, 9.5, 95% confidence interval, 2.07-43.50; P = 0.004). None of the studied predictors was associated with the development of clinical DCI on multivariate analysis. CONCLUSIONS:Asymptomatic angiographic vasospasm in patients with good-grade aSAH on admission is uncommon. Further studies are needed to identify high-risk patients for the development of DCI in the context of asymptomatic early vasospasm.
Hs-CRP in stroke: A meta-analysis.
Zhou Yongjing,Han Wei,Gong Dandan,Man Changfeng,Fan Yu
Clinica chimica acta; international journal of clinical chemistry
BACKGROUND:Studies on high-sensitivity C-reactive protein (hs-CRP) and stroke risk have yielded conflicting results. OBJECTIVE:To determine whether elevated baseline hs-CRP presents an independent risk for different kinds of strokes by conducting a meta-analysis. METHODS:The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases were systematically searched for prospective observational studies published until January 2015. Studies reporting hs-CRP levels and adjusted risk estimates of different stroke subtypes by hs-CRP were selected. Pooled results were expressed as adjusted risk ratios (RRs), with corresponding 95% confidence intervals (CI) for the highest versus the lowest hs-CRP category. RESULTS:Twelve studies involving 2269 strokes, of which 2436 were ischemic and 655 were hemorrhagic, were identified from 66,560 participants. When comparing the highest with the lowest hs-CRP category, the pooled RR of ischemic strokes was 1.46 (95% CI 1.27-1.67) in a fixed-effect model. The pooled RRs of all strokes and hemorrhagic stroke were 1.23 (95% CI: 0.997-1.51) and 0.82 (95% CI 0.59-1.13), respectively. The risk of ischemic strokes seemed higher in men (RR 1.66; 95% CI 1.23-2.24). CONCLUSIONS:Elevated baseline hs-CRP levels are independently associated with excessive ischemic stroke risk but exhibit no clear effect on hemorrhagic stroke.
Association of Noninvasive Ventilation Strategies With Mortality and Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review and Meta-analysis.
Isayama Tetsuya,Iwami Hiroko,McDonald Sarah,Beyene Joseph
IMPORTANCE:Various noninvasive ventilation strategies are used to prevent bronchopulmonary dysplasia (BPD) of preterm infants; however, the best mode is uncertain. OBJECTIVE:To compare 7 ventilation strategies for preterm infants including nasal continuous positive airway pressure (CPAP) alone, intubation and surfactant administration followed by immediate extubation (INSURE), less invasive surfactant administration (LISA), noninvasive intermittent positive pressure ventilation, nebulized surfactant administration, surfactant administration via laryngeal mask airway, and mechanical ventilation. DATA SOURCES:MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from their inceptions to June 2016. STUDY SELECTION:Randomized clinical trials comparing ventilation strategies for infants younger than 33 weeks' gestational age within 24 hours of birth who had not been intubated. DATA EXTRACTION AND SYNTHESIS:Data were independently extracted by 2 reviewers and synthesized with Bayesian random-effects network meta-analyses. MAIN OUTCOMES AND MEASURES:A composite of death or BPD at 36 weeks' postmenstrual age was the primary outcome. Death, BPD, severe intraventricular hemorrhage, and air leak by discharge were the main secondary outcomes. RESULTS:Among 5598 infants involved in 30 trials, the incidence of the primary outcome was 33% (1665 of 4987; including 505 deaths and 1160 cases of BPD). The secondary outcomes ranged from 6% (314 of 5587) for air leak to 26% (1160 of 4455) for BPD . Compared with mechanical ventilation, LISA had a lower odds of the primary outcome (odds ratio [OR], 0.49; 95% credible interval [CrI], 0.30-0.79; absolute risk difference [RD], 164 fewer per 1000 infants; 57-253 fewer per 1000 infants; moderate quality of evidence), BPD(OR, 0.53; 95% CrI, 0.27-0.96; absolute RD, 133 fewer per 1000 infants; 95% CrI, 9-234 fewer per 1000 infants; moderate-quality), and severe intraventricular hemorrhage (OR, 0.44; 95% CrI, 0.19-0.99; absolute RD, 58 fewer per 1000 births; 95% CrI, 1-86 fewer per 1000 births; moderate-quality). Compared with nasal CPAP alone, LISA had a lower odds of the primary outcome (OR, 0.58; 95% CrI, 0.35-0.93; absolute RD, 112 fewer per 1000 births; 95% CrI, 16-190 fewer per 1000 births; moderate quality), and air leak (OR, 0.24; 95% CrI, 0.05-0.96; absolute RD, 47 fewer per 1000 births; 95% CrI, 2-59 fewer per 1000 births; very low quality). Ranking probabilities indicated that LISA was the best strategy with a surface under the cumulative ranking curve of 0.85 to 0.94, but this finding was not robust for death when limited to higher-quality evidence. CONCLUSIONS AND RELEVANCE:Among preterm infants, the use of LISA was associated with the lowest likelihood of the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings were limited by the overall low quality of evidence and lack of robustness in higher-quality trials.
Corticosteroids in the Management of Hyponatremia, Hypovolemia, and Vasospasm in Subarachnoid Hemorrhage: A Meta-Analysis.
Mistry Akshitkumar M,Mistry Eva A,Ganesh Kumar Nishant,Froehler Michael T,Fusco Matthew R,Chitale Rohan V
Cerebrovascular diseases (Basel, Switzerland)
BACKGROUND:Cerebral vasospasm and sodium and fluid imbalances are common sequelae of aneurysmal subarachnoid hemorrhage (SAH) and cause of significant morbidity and mortality. Studies have shown the benefit of corticosteroids in the management of these sequelae. We have reviewed the literature and analyzed the available data for corticosteroid use after SAH. METHODS:PubMed, EMBASE, and Cochrane electronic databases were searched without language restrictions, and 7 observational, controlled clinical studies of the effect of corticosteroids in the management of SAH patients were identified. Data on sodium and fluid balances, symptomatic vasospasm (SVS), and outcomes were pooled for meta-analyses using the Mantel-Haenszel random effects model. RESULTS:Corticosteroids, specifically hydrocortisone and fludrocortisone, decreased natriuretic diuresis and incidence of hypovolemia. Corticosteroid administration is associated with lower incidence of SVS in the absence of nimodipine, but does not alter the neurological outcome. CONCLUSIONS:Supplementation of corticosteroids with mineralocorticoid activity, such as hydrocortisone or fludrocortisone, helps in maintaining sodium and volume homeostasis in SAH patients. Larger trials are warranted to confirm the effects of corticosteroids on SVS and patient outcomes.
Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis.
Dong Mei-Xue,Hu Qing-Chuan,Shen Peng,Pan Jun-Xi,Wei You-Dong,Liu Yi-Yun,Ren Yi-Fei,Liang Zi-Hong,Wang Hai-Yang,Zhao Li-Bo,Xie Peng
BACKGROUND AND PURPOSE:Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke. METHODS:Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger's test were obtained to detect publication bias. RESULTS:We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate. CONCLUSIONS:This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA.
Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.
Kilarski Laura L,Achterberg Sefanja,Devan William J,Traylor Matthew,Malik Rainer,Lindgren Arne,Pare Guillame,Sharma Pankaj,Slowik Agniesczka,Thijs Vincent,Walters Matthew,Worrall Bradford B,Sale Michele M,Algra Ale,Kappelle L Jaap,Wijmenga Cisca,Norrving Bo,Sandling Johanna K,Rönnblom Lars,Goris An,Franke Andre,Sudlow Cathie,Rothwell Peter M,Levi Christopher,Holliday Elizabeth G,Fornage Myriam,Psaty Bruce,Gretarsdottir Solveig,Thorsteinsdottir Unnar,Seshadri Sudha,Mitchell Braxton D,Kittner Steven,Clarke Robert,Hopewell Jemma C,Bis Joshua C,Boncoraglio Giorgio B,Meschia James,Ikram M Arfan,Hansen Bjorn M,Montaner Joan,Thorleifsson Gudmar,Stefanson Kari,Rosand Jonathan,de Bakker Paul I W,Farrall Martin,Dichgans Martin,Markus Hugh S,Bevan Steve,
OBJECTIVES:To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. METHODS:Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls. RESULTS:In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p = 7.12 × 10(-11)) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p = 0.695). CONCLUSION:Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage.
Beta-Blockade in Aneurysmal Subarachnoid Hemorrhage: a Systematic Review and Meta-Analysis.
Ramesh Aravind V,Banks Charis F K,Mounstephen Peter E,Crewdson Kate,Thomas Matt
BACKGROUND/OBJECTIVE:Sympathetic nervous system activation after aneurysmal subarachnoid hemorrhage (aSAH) is associated with complications and poor outcome. In this systematic review and meta-analysis, we investigate the effect of beta-blockers on outcome after aSAH. METHODS:The review was prospectively registered with PROSPERO (CRD42019111784). We performed a systematic literature search of MEDLINE, EMBASE, the Cochrane Library, published conference proceedings, and abstracts. Eligible studies included both randomized controlled trials and observational studies up to October 2018, reporting the effect of beta-blocker therapy on the following outcomes in aSAH: mortality, vasospasm, delayed cerebral ischemia, infarction or stroke, cardiac dysfunction, and functional outcomes. Studies involving traumatic SAH were excluded. Citations were reviewed, and data extracted independently by two investigators using a standardized proforma. RESULTS:We identified 819 records with 16 studies (four were randomized controlled trials) including 6702 patients selected for analysis. Exposure to beta-blockade either before or after aSAH was associated with a significant reduction in unadjusted mortality (RR 0.63, 95% CI 0.42-0.93, p = 0.02). A significant reduction in unadjusted mortality was also seen in prospective trials of post-event beta-blockade (RR 0.51, 95% CI 0.28-0.93, p = 0.03). Statistically significant differences were not seen for other outcomes investigated. CONCLUSIONS:In adult patients with aSAH, beta-blocker therapy is associated with a mortality benefit. Studies are generally of a low quality with considerable clinical heterogeneity. Prospective large interventional trials with patient centered outcomes are required to validate this finding.
Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Collaboration.
Menon Bijoy K,Hill Michael D,Davalos Antoni,Roos Yvo B W E M,Campbell Bruce C V,Dippel Diederik W J,Guillemin Francis,Saver Jeffrey L,van der Lugt Aad,Demchuk Andrew M,Muir Keith,Brown Scott,Jovin Tudor,Mitchell Peter,White Phil,Bracard Serge,Goyal Mayank
Journal of neurointerventional surgery
BACKGROUND:The Society of Neurointerventional Surgery revised its operational definition of emergent large vessel occlusion (ELVO) recently to include proximal M2 segment middle cerebral artery (MCA) occlusions. We sought to assess the benefit of endovascular thrombectomy (EVT) over best medical care for M2 segment MCA occlusion. METHODS:Patient level data from trials in the HERMES Collaboration were included. The HERMES core laboratory identified patients with M2 segment MCA occlusions and further classified them as proximal versus distal, anterior versus posterior division, and dominant versus co-dominant versus non-dominant. Primary outcome was modified Rankin Scale (mRS) score 0-2 at 90 days. Secondary outcomes were modified Thrombolysis in Cerebral Infarction (mTICI) rates at end of procedure, 90-day mRS shift, 90-day mRS 0-1, 24 hours National Institute of Health Stroke Scale (NIHSS) score 0-2, symptomatic intracerebral hemorrhage (ICH), and death. RESULTS:130 patients with M2 MCA (proximal location n=116 vs distal n=14, anterior division n=72 vs posterior n=58, dominant n=73 vs co-dominant n=50 vs non-dominant n=7) were included. Successful reperfusion (mTICI 2b or 3) among those undergoing EVT was seen in 59.2% of patients. Treatment effect favored EVT (adjusted OR 2.39, 95% CI 1.08 to 5.28, p=0.03) for 90-day mRS 0-2 (58.2% EVT vs 39.7% control). Direction of benefit favored EVT for other outcomes. Treatment effect favoring EVT was maximal in patients with proximal M2 segment MCA occlusions (n=116, adjusted OR 2.68, 95% CI 1.13 to 6.37) and in dominant M2 segment MCA occlusions (n=73, adjusted OR 4.08, 95% CI 1.08 to 15.48). No sICH (0%) was observed in patients treated with EVT compared with five (7.9%) in the control arm. CONCLUSION:Patients with proximal M2 segment MCA occlusions eligible for EVT trial protocols benefited from EVT.
Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.
Dorhout Mees Sanne M,Algra Ale,Wong George K C,Poon Wai S,Bradford Celia M,Saver Jeffrey L,Starkman Sidney,Rinkel Gabriel J E,van den Bergh Walter M, ,van Kooten F,Dirven C M,van Gijn J,Vermeulen M,Rinkel G J E,Boet R,Chan M T V,Gin T,Ng S C P,Zee B C Y,Al-Shahi Salman R,Boiten J,Kuijsten H,Lavados P M,van Oostenbrugge R J,Vandertop W P,Finfer S,O'Connor A,Yarad E,Firth R,McCallister R,Harrington T,Steinfort B,Faulder K,Assaad N,Morgan M,Starkman S,Eckstein M,Stratton S J,Pratt F D,Hamilton S,Conwit R,Liebeskind D S,Sung G,Kramer I,Moreau G,Goldweber R,Sanossian N
BACKGROUND AND PURPOSE:Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS:Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS:We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS:This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.
Association between angiotensin converting enzyme gene insertion/deletion polymorphism and intracerebral haemorrhage in North Indian population: a case control study and meta-analysis.
Kumar A,Prasad K,Vivekanandhan S,Srivastava A,Goswami S,Srivastava M V P,Tripathi M
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
The purpose of this study was to determine the relationship between Angiotensin converting enzyme (ACE) insertion/deletion polymorphism and ICH with an ACE level in a North Indian population. Patient with ICH and age- and sex- matched control subjects were recruited. Case control study design was used. Genotyping was performed by using Polymerase chain reaction. Serum ACE levels were measured by colorimetric method. Our results were integrated with other reported studies across different countries in a meta-analysis. One hundred and six patients with ICH and 106 age- and sex- matched control subjects were recruited. Mean age of cases and control subjects were 53.4 ± 1 and 52.9 ± 13.4, respectively. The DD genotypes were more frequency distributed in cases compared with controls (OR 2; 95 % CI, 1.02-3.8, P = 0.04) under a recessive model of inheritance. Meta-analysis suggests significant association between ACE I/D polymorphism and risk of ICH (OR 1.98; 95 % CI, 1.53-2.57) under the recessive model of inheritance and under the dominant model of inheritance (OR 1.31; 95 % CI, 1.18-1.45). The findings of the present study show a significant association between ACE insertion/deletion polymorphism and ICH. Meta-analysis indicate that ACE I/D polymorphism may be a susceptible marker for risk factor of ICH in Asian population.
Clinical Outcomes of Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations in Pediatric Patients: Systematic Review and Meta-Analysis.
Börcek Alp Özgün,Çeltikçi Emrah,Aksoğan Yiğit,Rousseau Matthew John
BACKGROUND:Arteriovenous malformations (AVMs) in pediatric patients exhibit remarkable differences in terms of management and outcomes. Owing to a paucity of relevant data pertaining to AVMs in pediatric patients, special interest and investigation are required for an improved understanding of the available evidence by clinicians. OBJECTIVE:To determine the clinical outcomes of single-session stereotactic radiosurgery (SRS) for AVMs in pediatric patients. METHODS:A systematic literature review was performed to identify studies that reported the outcomes of SRS for AVMs in pediatric patients. Data pertaining to variables such as obliteration rate, post-SRS new hemorrhage rate, post-SRS new neurological deficit rate, and mortality rate were extracted and analyzed using meta-analysis techniques. RESULTS:Based on pooled data from 20 studies with 1212 patients, single-session SRS resulted in complete obliteration in 65.9% (95% confidence interval [CI], 60.5%-71.1%; I2 = 66.5%) patients. Overall complication rate (including new hemorrhage, new neurodeficit, and mortality) was 8.0% (95% CI, 5.1%-11.5%; I2 = 66.4%). Post-SRS new neurological deficit rate was 3.1% (95% CI, 1.3%-5.4%; I2 = 59.7%), and post-SRS hemorrhage rate was 4.2% (95% CI, 2.5%-6.3%; I2 = 42.7%). There was no significant difference between studies disaggregated by treatment method (Gamma Knife [Elekta AB] vs other), treatment year (before year 2000 vs after year 2000), median AVM volume reported (≥3 vs <3 cm3), median dose reported (≥20 vs <20 Gy), or follow-up period (≥36 vs <36 mo). CONCLUSION:Single-SRS is a safe treatment alternative that achieves high obliteration rates and acceptable complication rates for AVMs in pediatric patients.
Association of angiotensin-converting enzyme insertion/deletion polymorphism (rs4646994) with the risk of primary intracerebral hemorrhage.
Qin Haojie,Zhang Lushun,Xu Guohui,Pan Xinmin
BACKGROUND:Evidence has suggested that angiotensin-converting enzyme (ACE) may be involved in the etiology of primary intracerebral hemorrhage (PICH), but the underlying association between ACE I/D (rs4646994) polymorphism and PICH risk is still ambiguous. This meta-analysis was performed to quantitatively summarize the evidence for such a relationship. METHODS:Eligible studies were identified by searching PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBM (Chinese biomedical literature database), and WANFANG databases within a range of published years from 1990 to August 2012. The odds ratio (OR) corresponding to the 95% confidence interval (CI) was used to assess the different associations. RESULTS:A total of 28 studies with 2806 cases and 3612 controls were included in this meta-analysis. The pooled examination displayed an overall increased PICH risk associated with ACE I/D polymorphism in a recessive model (OR = 1.80, 95% CI = 1.39-2.33, P < 0.001 for DD versus ID/II), however, this association was only present in Asians (OR = 1.91, 95% CI = 1.45-2.51, P < 0.001) and not in Caucasians (OR = 1.16, 95% CI = 0.55-2.44, P = 0.69). Hypertensive intracerebral hemorrhage (HICH) had a much greater risk (OR = 4.26, 95% CI = 2.87-6.32, P < 0.001) than general PICH (OR = 1.65, 95% CI = 1.25-2.18, P < 0.001) in Asians, and subgroup with controls excluding hypertension had a greater risk (OR = 2.65, 95% CI = 1.78-3.95, P < 0.001) than that including hypertension (OR = 1.50, 95% CI = 1.12-2.02, P = 0.01). CONCLUSIONS:This meta-analysis suggests that DD homozygote of ACE I/D polymorphism has an increased PICH risk in Asians, and may have a synergistic effect with hypertension.
Oral Anticoagulation and Functional Outcome after Intracerebral Hemorrhage.
Biffi Alessandro,Kuramatsu Joji B,Leasure Audrey,Kamel Hooman,Kourkoulis Christina,Schwab Kristin,Ayres Alison M,Elm Jordan,Gurol M Edip,Greenberg Steven M,Viswanathan Anand,Anderson Christopher D,Schwab Stefan,Rosand Jonathan,Testai Fernando D,Woo Daniel,Huttner Hagen B,Sheth Kevin N
Annals of neurology
OBJECTIVE:Oral anticoagulation treatment (OAT) resumption is a therapeutic dilemma in intracerebral hemorrhage (ICH) care, particularly for lobar hemorrhages related to amyloid angiopathy. We sought to determine whether OAT resumption after ICH is associated with long-term outcome, accounting for ICH location (ie, lobar vs nonlobar). METHODS:We meta-analyzed individual patient data from: (1) the multicenter RETRACE study (n = 542), (2) a U.S.-based single-center ICH study (n = 261), and (3) the Ethnic/Racial Variations of Intracerebral Hemorrhage study (n = 209). We determined whether, within 1 year from ICH, OAT resumption was associated with: (1) mortality, (2) favorable functional outcome (modified Rankin Scale = 0-3), and (3) stroke incidence. We separately analyzed nonlobar and lobar ICH cases using propensity score matching and Cox regression models. RESULTS:We included 1,012 OAT-related ICH survivors (633 nonlobar and 379 lobar). Among nonlobar ICH survivors, 178/633 (28%) resumed OAT, whereas 86/379 (23%) lobar ICH survivors did. In multivariate analyses, OAT resumption after nonlobar ICH was associated with decreased mortality (hazard ratio [HR] = 0.25, 95% confidence interval [CI] = 0.14-0.44, p < 0.0001) and improved functional outcome (HR = 4.22, 95% CI = 2.57-6.94, p < 0.0001). OAT resumption after lobar ICH was also associated with decreased mortality (HR = 0.29, 95% CI = 0.17-0.45, p < 0.0001) and favorable functional outcome (HR = 4.08, 95% CI = 2.48-6.72, p < 0.0001). Furthermore, OAT resumption was associated with decreased all-cause stroke incidence in both lobar and nonlobar ICH (both p < 0.01). INTERPRETATION:These results suggest novel evidence of an association between OAT resumption and outcome following ICH, regardless of hematoma location. These findings support conducting randomized trials to explore risks and benefits of OAT resumption after ICH. Ann Neurol 2017;82:755-765.
The MTHFR C677T Polymorphism and Risk of Intracerebral Hemorrhage in a Chinese Han Population.
Hu Xin,Tao Chuanyuan,Xie Zhiyi,Li Yunke,Zheng Jun,Fang Yuan,Lin Sen,Li Hao,You Chao
Medical science monitor : international medical journal of experimental and clinical research
BACKGROUND:Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been speculated to be and extensively investigated as a risk factor for various vascular diseases, including intracerebral hemorrhage (ICH). However, results from published studies regarding the role of C677T polymorphism in ICH risk in Chinese populations were contradictory rather than conclusive. MATERIAL/METHODS:In this study, a total of 180 ICH patients and 180 matched controls of Chinese Han ethnicity were enrolled. The MTHFR C677T polymorphism was genotyped by polymerase chain reaction-ligation detection reaction (PCR-LDR). A meta-analysis was conducted by combining our data with previous relevant studies in Chinese populations. RESULTS:In our case-control study, similar allele frequency (p=0.492) and genotype distribution (p=0.748) of MTHFR C677T polymorphism were detected between ICH patients and controls. Further analysis based on hematoma location did not show a significant association. When combined with previous studies, however, C677T polymorphism was found to be significantly associated with an increased risk for ICH in Chinese populations (recessive model: OR=1.57, 95%CI=1.29-1.91). When focusing on the Han ethnicity, carriers of the TT genotype had an increased risk of ICH (recessive model: OR=1.36, 95%CI=1.05-1.75). CONCLUSIONS:In this case-control study we did not observe that the MTHFR C677T polymorphism was associated with ICH risk in people of Chinese Han ethnicity. However, when combined with previous published studies, a significant association of C677T polymorphism with an increased risk of ICH was detected in Chinese populations, and also in the subgroup analysis focusing on Han ethnicity.
Amyloid-PET burden and regional distribution in cerebral amyloid angiopathy: a systematic review and meta-analysis of biomarker performance.
Charidimou Andreas,Farid Karim,Tsai Hsin-Hsi,Tsai Li-Kai,Yen Rouh-Fang,Baron Jean-Claude
Journal of neurology, neurosurgery, and psychiatry
INTRODUCTION:We performed a meta-analysis to synthesise current evidence on amyloid-positron emission tomography (PET) burden and presumed preferential occipital distribution in sporadic cerebral amyloid angiopathy (CAA). METHODS:In a PubMed systematic search, we identified case-control studies with extractable data on global and occipital-to-global amyloid-PET uptake in symptomatic patients with CAA (per Boston criteria) versus control groups (healthy participants or patients with non-CAA deep intracerebral haemorrhage) and patients with Alzheimer's disease. To circumvent PET studies' methodological variation, we generated and used 'fold change', that is, ratio of mean amyloid uptake (global and occipital-to-global) of CAA relative to comparison groups. Amyloid-PET uptake biomarker performance was then quantified by random-effects meta-analysis on the ratios of the means. A ratio >1 indicates that amyloid-PET uptake (global or occipital/global) is higher in CAA than comparison groups, and a ratio <1 indicates the reverse. RESULTS:Seven studies, including 106 patients with CAA (>90% with probable CAA) and 138 controls (96 healthy elderly, 42 deep intracerebral haemorrhage controls) and 72 patients with Alzheimer's disease, were included. Global amyloid-PET ratio between patients with CAA and controls was above 1, with an average effect size of 1.18 (95% CI 1.08 to 1.28; p<0.0001). Occipital-to-global amyloid-PET uptake ratio did not differ between patients with CAA versus patients with deep intracerebral haemorrhage or healthy controls. By contrast, occipital-to-global amyloid-PET uptake ratio was above 1 in patients with CAA versus those with Alzheimer's disease, with an average ratio of 1.10 (95% CI 1.03 to 1.19; p=0.009) and high statistical heterogeneity. CONCLUSIONS:Our analysis provides exploratory actionable data on the overall effect sizes and strength of amyloid-PET burden and distribution in patients with CAA, useful for future larger studies.
Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update.
Vergouwen Mervyn D I,Algra Ale,Rinkel Gabriel J E
BACKGROUND AND PURPOSE:Endothelin is considered to be a key mediator of vasospasm after subarachnoid hemorrhage. A meta-analysis of randomized trials on the effectiveness of endothelin receptor antagonists in subarachnoid hemorrhage has been published previously, but since then new major trials have been published. We present the results of a systematic review and meta-analysis update. METHODS:We searched the Cochrane Library, the Cochrane Central Register of Controlled Trials, and PubMed with the following terms: subarachnoid hemorrhage AND (endothelin receptor antagonist OR clazosentan OR TAK-044 OR bosentan). All randomized, placebo-controlled trials investigating the effect of any endothelin receptor antagonists in patients with subarachnoid hemorrhage were included. Primary outcome was poor functional outcome (defined as death or dependency). Secondary outcomes were vasospasm, cerebral infarction as defined by investigators, and case fatality during follow-up. Data were pooled and effect sizes were expressed as risk ratio (RR) estimates with 95% confidence intervals (CI). We also calculated RR for several common complications. RESULTS:in 5 trials with 2601 patients, endothelin receptor antagonists did not affect functional outcome (RR, 1.06: 95% CI, 0.93-1.22) despite a decreased incidence of angiographic vasospasm (RR, 0.58; 95% CI, 0.48-0.71). No effect was observed on vasospasm-related cerebral infarction (RR, 0.76; 95% CI, 0.53-1.11), any new cerebral infarction (RR, 1.04; 95% CI, 0.91-1.19), or case-fatality (RR, 1.04; 95% CI, 0.78-1.39). Endothelin receptor antagonists increased the risk of lung complications (RR, 1.79; 95% CI, 1.52-2.11), pulmonary edema (RR, 2.12; 95% CI, 1.32-3.39), hypotension (RR, 2.42: 95% CI, 1.78-3.29), and anemia (RR, 1.47; 95% CI, 1.19-1.83). CONCLUSION:These results argue against the use of endothelin receptor antagonists in patients with subarachnoid hemorrhage.
Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis.
Mitra Souvik,Florez Ivan D,Tamayo Maria E,Mbuagbaw Lawrence,Vanniyasingam Thuva,Veroniki Areti Angeliki,Zea Adriana M,Zhang Yuan,Sadeghirad Behnam,Thabane Lehana
Importance:Despite increasing emphasis on conservative management of patent ductus arteriosus (PDA) in preterm infants, different pharmacotherapeutic interventions are used to treat those developing a hemodynamically significant PDA. Objectives:To estimate the relative likelihood of hemodynamically significant PDA closure with common pharmacotherapeutic interventions and to compare adverse event rates. Data Sources and Study Selection:The databases of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until August 15, 2015, and updated on December 31, 2017, along with conference proceedings up to December 2017. Randomized clinical trials that enrolled preterm infants with a gestational age younger than 37 weeks treated with intravenous or oral indomethacin, ibuprofen, or acetaminophen vs each other, placebo, or no treatment for a clinically or echocardiographically diagnosed hemodynamically significant PDA. Data Extraction and Synthesis:Data were independently extracted in pairs by 6 reviewers and synthesized with Bayesian random-effects network meta-analyses. Main Outcomes and Measures:Primary outcome: hemodynamically significant PDA closure; secondary: included surgical closure, mortality, necrotizing enterocolitis, and intraventricular hemorrhage. Results:In 68 randomized clinical trials of 4802 infants, 14 different variations of indomethacin, ibuprofen, or acetaminophen were used as treatment modalities. The overall PDA closure rate was 67.4% (2867 of 4256 infants). A high dose of oral ibuprofen was associated with a significantly higher odds of PDA closure vs a standard dose of intravenous ibuprofen (odds ratio [OR], 3.59; 95% credible interval [CrI], 1.64-8.17; absolute risk difference, 199 [95% CrI, 95-258] more per 1000 infants) and a standard dose of intravenous indomethacin (OR, 2.35 [95% CrI, 1.08-5.31]; absolute risk difference, 124 [95% CrI, 14-188] more per 1000 infants). Based on the ranking statistics, a high dose of oral ibuprofen ranked as the best pharmacotherapeutic option for PDA closure (mean surface under the cumulative ranking [SUCRA] curve, 0.89 [SD, 0.12]) and to prevent surgical PDA ligation (mean SUCRA, 0.98 [SD, 0.08]). There was no significant difference in the odds of mortality, necrotizing enterocolitis, or intraventricular hemorrhage with use of placebo or no treatment compared with any of the other treatment modalities. Conclusions and Relevance:A high dose of oral ibuprofen was associated with a higher likelihood of hemodynamically significant PDA closure vs standard doses of intravenous ibuprofen or intravenous indomethacin; placebo or no treatment did not significantly change the likelihood of mortality, necrotizing enterocolitis, or intraventricular hemorrhage. Trial Registration:PROSPERO Identifier: CRD42015015797.
Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials.
Malhotra Konark,Chang Jason J,Khunger Arjun,Blacker David,Switzer Jeffrey A,Goyal Nitin,Hernandez Adrian V,Pasupuleti Vinay,Alexandrov Andrei V,Tsivgoulis Georgios
Journal of neurology
BACKGROUND:Various randomized-controlled clinical trials (RCTs) have investigated the neuroprotective role of minocycline in acute ischemic stroke (AIS) or acute intracerebral hemorrhage (ICH) patients. We sought to consolidate and investigate the efficacy and safety of minocycline in patients with acute stroke. METHODS:Literature search spanned through November 30, 2017 across major databases to identify all RCTs that reported following efficacy outcomes among acute stroke patients treated with minocycline vs. placebo: National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) scores. Additional safety, neuroimaging and biochemical endpoints were extracted. We pooled mean differences (MD) and risk ratios (RR) from RCTs using random-effects models. RESULTS:We identified 7 RCTs comprising a total of 426 patients. Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend towards 3-month functional independence (mRS-scores of 0-2) (RR = 1.31; 95% CI 0.98-1.74, p = 0.06) and 3-month BI (MD = 6.92; 95% CI - 0.92, 14.75; p = 0.08). In AIS subgroup, minocycline was associated with higher rates of 3-month mRS-scores of 0-2 (RR = 1.59; 95% CI 1.19-2.12, p = 0.002; I = 58%) and 3-month BI (MD = 12.37; 95% CI 5.60, 19.14, p = 0.0003; I = 47%), whereas reduced the 3-month NIHSS (MD - 2.84; 95% CI - 5.55, - 0.13; p = 0.04; I = 86%). Minocycline administration was not associated with an increased risk of mortality, recurrent stroke, myocardial infarction and hemorrhagic conversion. CONCLUSIONS:Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients.
Efficacy and safety of low dose alteplase for intravenous thrombolysis in Asian stroke patients: a meta-analysis.
Tan Ge,Wang Haijiao,Chen Sihan,Chen Deng,Zhu Lina,Xu Da,Zhang Yu,Liu Ling
Whether low dose alteplase is comparable to standard dose in efficacy and safety for intravenous thrombolysis (IVT) in Asian stroke patients remains unverified. PubMed, EMBASE, and Cochrane Library Database from the beginning to June 30, 2017 were searched. IVT efficacy was measured by favorable outcome (modified Rankin Scale scores of 0-1) at 3 months, and safety measured by mortality within 3 months and symptomatic intracerebral hemorrhage (SICH). Pooled estimates were conducted using fixed- or random-effects model depending on heterogeneity. For SICH, studies were pooled separately according to different definitions. Twelve studies involving 7,905 participants were included. No association was found between alteplase dose and favorable outcome (OR = 0.94, 95% CI 0.78-1.14, P = 0.5; heterogeneity: P = 0.01, I = 57.3%) and mortality (OR = 0.87, 95% CI 0.74-1.02, P = 0.08; P = 0.83, I = 0) using random- and fixed-effects models, respectively. Low dose alteplase was associated with lower SICH as defined by the National Institute of Neurological Disorders and Stroke study (OR = 0.79, 95% CI 0.64-0.99, P = 0.04; P = 0.57, I = 0) using fixed-effects model. Subgroup and sensitivity analysis could change the results significantly. Current limited evidence was insufficient to support the speculation that low dose alteplase was comparable to standard dose in thrombolytic efficacy and safety in Asian stroke patients.
Clazosentan for Aneurysmal Subarachnoid Hemorrhage: An Updated Meta-Analysis with Trial Sequential Analysis.
Cho Steve S,Kim Sung-Eun,Kim Heung Cheol,Kim Won Jin,Jeon Jin Pyeong
OBJECTIVE:Clazosentan, an endothelin receptor antagonist, reduced vasospasm and delayed ischemic neurologic deficit (DIND) but did not improve outcome after subarachnoid hemorrhage (SAH) in clinical trials. However, a lack of dose-dependent analysis and potential overestimation of clazosentan's effect are concerning. We used stratified analysis and trial sequential analysis (TSA) of existing data to investigate the effects of clazosentan on SAH outcome. METHODS:Studies from PubMed, Embase, and Cochrane were reviewed for eligibility. Primary outcomes were DIND requiring rescue therapy, all-cause mortality, and vasospasm-related morbidity at 6 weeks. Secondary outcomes were moderate-to-severe angiographic vasospasm, new cerebral infarction, and poor clinical outcome at 3 months. TSA was performed to assess the required information size and the α-spending monitoring boundary effect of relative risk (RR) reduction. A stratified analysis of clazosentan dosage was performed. RESULTS:Five studies (N = 2317) were included. Clazosentan significantly reduced the risk of DIND requiring rescue therapy (RR, 0.625; 95% confidence interval [CI], 0.462-0.846) and vasospasm (RR, 0.543; 95% CI, 0.464-0.635), but did not significantly affect mortality or vasospasm-related morbidity (RR, 0.775; 95% CI, 0.578-1.039), new cerebral infarction (RR, 0.604; 95% CI, 0.383-0.952), or outcome (RR, 1.131; 95% CI, 0.959-1.334). TSA revealed that the studies were underpowered to evaluate the effects of clazosentan on mortality and vasospasm-associated morbidity. We found 10-15 mg/h of clazosentan administration was associated with lower rates of vasospasm and new cerebral infarctions compared with 5 mg/h. CONCLUSIONS:Clazosentan reduced the risk of DIND requiring rescue therapy and moderate-to-severe vasospasm. Further meta-analyses based on individual patient data with different clazosentan doses and more refined outcome measures are necessary to clarify clazosentan's efficacy in improving post-SAH outcome.
Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data.
Campbell Bruce C V,Ma Henry,Ringleb Peter A,Parsons Mark W,Churilov Leonid,Bendszus Martin,Levi Christopher R,Hsu Chung,Kleinig Timothy J,Fatar Marc,Leys Didier,Molina Carlos,Wijeratne Tissa,Curtze Sami,Dewey Helen M,Barber P Alan,Butcher Kenneth S,De Silva Deidre A,Bladin Christopher F,Yassi Nawaf,Pfaff Johannes A R,Sharma Gagan,Bivard Andrew,Desmond Patricia M,Schwab Stefan,Schellinger Peter D,Yan Bernard,Mitchell Peter J,Serena Joaquín,Toni Danilo,Thijs Vincent,Hacke Werner,Davis Stephen M,Donnan Geoffrey A,
Lancet (London, England)
BACKGROUND:Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. METHODS:In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FINDINGS:We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66). INTERPRETATION:Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. FUNDING:None.
Post-thrombolysis hemorrhage risk of unruptured intracranial aneurysms.
Chen Fujian,Yan Shenqiang,Jin Xinchun,Lin Chen,Cao Jin
BACKGROUND/AIMS:It has been questioned whether patients with unruptured intracranial aneurysms (IAs) are at a greater risk for the development of intracerebral hemorrhage (ICH) following thrombolytic therapy. We thus performed a meta-analysis to better quantify the risk of post-thrombolysis ICH in patients with acute ischemic stroke and incidental IAs. METHODS:We searched PubMed, Web of Science and EMBASE for studies assessing ICH risk in patients with acute ischemic stroke treated with thrombolysis, in relation to the presence of pretreatment IAs. A fixed-effects model meta-analysis was performed. RESULTS:We identified four studies totaling 707 participants receiving intravenous thrombolysis. The prevalence of unruptured IAs was 6.8%. Pooled analysis demonstrates relative risk (RR) for the presence of unruptured IAs and the development of any ICH to be 1.204 (95% CI 0.709-2.043; p = 0.492; I(2) = 0.0%). The RR for sICH is 1.645 (95% CI 0.453-5.970; p = 0.449; I(2) = 28.1%). CONCLUSION:Intravenous thrombolysis was safe among patients with acute ischemic stroke and incidental unruptured IAs. Future prospective studies with much larger sample sizes are required to clarify the significance of the association between pre-existing unruptured IAs and the development of post-thrombolysis ICH.
Treatment of intracerebral hemorrhage in animal models: meta-analysis.
Frantzias Joseph,Sena Emily S,Macleod Malcolm R,Al-Shahi Salman Rustam
Annals of neurology
OBJECTIVE:Interventions that improve functional outcome after acute intracerebral hemorrhage (ICH) in animals might benefit humans. Therefore, we systematically reviewed the literature to find studies of nonsurgical treatments tested in animal models of ICH. METHODS:In July 2009 we searched Ovid Medline (from 1950), Embase (from 1980), and ISI Web of Knowledge (from 1969) for controlled animal studies of nonsurgical interventions given after the induction of ICH that reported neurobehavioral outcome. We assessed study quality and performed meta-analysis using a weighted mean difference random effects model. RESULTS:Of 13,343 publications, 88 controlled studies described the effects of 64 different medical interventions (given a median of 2 hours after ICH induction) on 38 different neurobehavioral scales in 2,616 treated or control animals (median 14 rodents per study). Twenty-seven (31%) studies randomized treatment allocation, and 7 (8%) reported allocation concealment; these studies had significantly smaller effect sizes than those without these attributes (p < 0.001). Of 64 interventions stem cells, calcium channel blockers, anti-inflammatory drugs, iron chelators, and estrogens improved both structural outcomes and neurobehavioral scores in >1 study. Meta-regression revealed that together, structural outcome and the intervention used accounted for 65% of the observed heterogeneity in neurobehavioral score (p < 0.001, adjusted r(2) = 0.65). INTERPRETATION:Further animal studies of the interventions that we found to improve both functional and structural outcomes in animals, using better experimental designs, could target efforts to translate effective treatments for ICH in animals into randomized controlled trials in humans.
Association between diabetes mellitus and the occurrence and outcome of intracerebral hemorrhage.
Boulanger Marion,Poon Michael T C,Wild Sarah H,Al-Shahi Salman Rustam
OBJECTIVE:Whether diabetes mellitus (DM) is a risk factor for spontaneous intracerebral hemorrhage (ICH) and influences outcome after ICH remains unclear. METHODS:One reviewer searched Ovid MEDLINE and Embase 1980-2014 inclusive for studies investigating the associations between DM and ICH occurrence or DM and ICH case fatality. Two reviewers independently confirmed each study's eligibility, assessed risk of bias, and extracted data. One reviewer combined studies using random effects meta-analysis. RESULTS:Nineteen case-control studies involving 3,397 people with ICH and 5,747 people without ICH found an association between DM and ICH occurrence (unadjusted odds ratio [OR] 1.23, 95% confidence interval [CI] 1.04-1.45; I(2) = 22%), which did not differ between 17 hospital-based and 2 population-based studies (pdiff = 0.70), and was similar in the 16 studies that controlled for age and sex (unadjusted OR 1.15, 95% CI 0.95-1.40; I(2) = 14%). This association was not identified in 3 population-based cohort studies in which ICH occurred in 38 (0.66%) of 5,724 people with DM and 448 (0.57%) of 78,702 people without DM (unadjusted risk ratio [RR] 1.27, 95% CI 0.68-2.36; I(2) = 69%). DM was associated with a higher case fatality by 30 days or hospital discharge in 18 cohort studies involving 813 people with DM and 3,714 people without DM (unadjusted RR 1.52, 95% CI 1.28-1.81; I(2) = 49%). CONCLUSIONS:The findings suggest that there may be modest associations between DM and ICH occurrence and outcome, but further information from large, population-based studies that account for confounding is required before the association can be confirmed.
Intravenous thrombolysis for ischemic stroke with hyperdense middle cerebral artery sign: A meta-analysis.
Sun Huanhuan,Liu Yukai,Gong Pengyu,Zhang Shuting,Zhou Feng,Zhou Junshan
Acta neurologica Scandinavica
Hyperdense middle cerebral artery sign (HMCAS) on admitting to neuroimaging is reported to have prognostic value for poor outcomes after thrombolysis, while evidence from studies comprising a sufficiently large sample size is limited. To detect prognostic predictors after thrombolysis could help improve therapeutic clinical strategies for acute ischemic stroke. We included prospective and retrospective studies of stroke patients that were treated with intravenous thrombolysis, in which functional outcomes (ie, a modified Rankin scale [mRS]) and systematic intracranial hemorrhage (sICH) were assessed in relation to HMCAS during pretreatment head CT. Random-effects models were used to calculate pooled risk ratios (RR) of poor outcomes and sICH for HMCAS patients as compared to patients without HMCAS. Eleven studies permitted identification of 11 818 patients. The risk of poor outcome at 3 months in the HMCAS-positive group was 1.56-fold the negative group (RR, 1.56; 95% CI 1.50-1.62; P < .001). The sICH risk when comparing both groups was found to be non-significant. Sensitivity analysis regarding studies performing thrombolysis within 3 hours also exhibited significant differences in their functional outcomes (RR, 1.56, 95% CI 1.49-1.62; P < .001) in patients with HMCAS as compared to non-HMCAS patients, although this was true for sICH risk. The presence of HMCAS on pretreatment CT predicts a poor outcome at 3 months after intravenous thrombolysis, while its relationship with the incidence of sICH was found to have no statistic value. Our study implies that more aggressive treatment should be considered for HMCAS patients.
The effect of mannitol in the early stage of supratentorial hypertensive intracerebral hemorrhage: a systematic review and meta-analysis.
Sun Shuwen,Li Yuping,Zhang Hengzhu,Wang Xiaodong,She Lei,Yan Zhengcun,Lu Guangyu
BACKGROUND:Mannitol has been widely applied as a priority drug in the clinical treatment for brain edema and increased intracranial pressure (ICP) after intracerebral hemorrhage (ICH). However, no consensus on the efficacy and safety of mannitol has been achieved. Our meta-analysis was conducted to assess the effect of mannitol in the early stage of supratentorial hypertensive intracerebral hemorrhage (HICH) and provided a treatment reference for clinicians. METHOD:All relevant studies on mannitol treatment of supratentorial HICH were identified from the databases including PubMed, EMBASE, Cochrane Library, VIP, CNKI and Wan Fang. Our outcome measures included the incidence of hematoma enlargement, the neurological function improvement rate, mortality and the incidence of aggravated brain edema. The subgroup analysis was performed to explore the impact of study type, year of publication, intervention time and dose on the outcome measures. Publication bias was assessed by the funnel plot. RESULTS:Thirty-four studies consisting of 3627 patients with supratentorial HICH were included in this study (range from 2000 to 2018). Significant statistical difference was found between mannitol and non-mannitol group in terms of all the outcome measures, including the incidence of hematoma enlargement (p < 0.00001), the neurological function improvement rate (p < 0.00001), mortality (p < 0.00001) and the incidence of aggravated cerebral edema (p = 0.0002). In subgroup analysis, the results showed study type and intervention time did not significantly affect the outcome measures. No significant statistical difference was found in the subgroups of publication time (after 2010) (p = 0.08) and half-dose of mannitol (p = 0.20) on mortality. In addition, the further analysis showed whatever the dose (250ml and 125ml) and intervention time (<24h, <12h, <6h) was, mannitol could lead to the hematoma enlargement. CONCLUSION:For patients without obvious symptoms of intracranial hypertension or cerebral palsy, it is not recommended to use mannitol routinely in the early stage of supratentorial HICH. More high-quality trials should be included to confirm our conclusion and to ascertain the best time and dose of mannitol to use.
Meta-analysis and systematic review of risk factors for shunt dependency after aneurysmal subarachnoid hemorrhage.
Wilson Christopher D,Safavi-Abbasi Sam,Sun Hai,Kalani M Yashar S,Zhao Yan D,Levitt Michael R,Hanel Ricardo A,Sauvageau Eric,Mapstone Timothy B,Albuquerque Felipe C,McDougall Cameron G,Nakaji Peter,Spetzler Robert F
Journal of neurosurgery
OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) may be complicated by hydrocephalus in 6.5%-67% of cases. Some patients with aSAH develop shunt dependency, which is often managed by ventriculoperitoneal shunt placement. The objectives of this study were to review published risk factors for shunt dependency in patients with aSAH, determine the level of evidence for each factor, and calculate the magnitude of each risk factor to better guide patient management. METHODS The authors searched PubMed and MEDLINE databases for Level A and Level B articles published through December 31, 2014, that describe factors affecting shunt dependency after aSAH and performed a systematic review and meta-analysis, stratifying the existing data according to level of evidence. RESULTS On the basis of the results of the meta-analysis, risk factors for shunt dependency included high Fisher grade (OR 7.74, 95% CI 4.47-13.41), acute hydrocephalus (OR 5.67, 95% CI 3.96-8.12), in-hospital complications (OR 4.91, 95% CI 2.79-8.64), presence of intraventricular blood (OR 3.93, 95% CI 2.80-5.52), high Hunt and Hess Scale score (OR 3.25, 95% CI 2.51-4.21), rehemorrhage (OR 2.21, 95% CI 1.24-3.95), posterior circulation location of the aneurysm (OR 1.85, 95% CI 1.35-2.53), and age ≥ 60 years (OR 1.81, 95% CI 1.50-2.19). The only risk factor included in the meta-analysis that did not reach statistical significance was female sex (OR 1.13, 95% CI 0.77-1.65). CONCLUSIONS The authors identified several risk factors for shunt dependency in aSAH patients that help predict which patients are likely to require a permanent shunt. Although some of these risk factors are not independent of each other, this information assists clinicians in identifying at-risk patients and managing their treatment.
Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis.
Cui Han-Jin,He Hao-yu,Yang A-Li,Zhou Hua-Jun,Wang Cong,Luo Jie-Kun,Lin Yuan,Tang Tao
Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX), a ferric-iron chelator, is a candidate drug for the treatment of ICH. We performed a systematic review of studies involving the administration of DFX following ICH. In total, 20 studies were identified that described the efficacy of DFX in animal models of ICH and assessed changes in the brain water content, neurobehavioral score, or both. DFX reduced the brain water content by 85.7% in animal models of ICH (-0.86, 95% CI: -.48- -0.23; P < 0.01; 23 comparisons), and improved the neurobehavioral score by -1.08 (95% CI: -1.23- -0.92; P < 0.01; 62 comparisons). DFX was most efficacious when administered 2-4 h after ICH at a dose of 10-50 mg/kg depending on species, and this beneficial effect remained for up to 24 h postinjury. The efficacy was higher with phenobarbital anesthesia, intramuscular injection, and lysed erythrocyte infusion, and in Fischer 344 rats or aged animals. Overall, although DFX was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality, and the limited number of studies conducting clinical trials.
Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis.
Whiteley William N,Emberson Jonathan,Lees Kennedy R,Blackwell Lisa,Albers Gregory,Bluhmki Erich,Brott Thomas,Cohen Geoff,Davis Stephen,Donnan Geoffrey,Grotta James,Howard George,Kaste Markku,Koga Masatoshi,von Kummer Rüdiger,Lansberg Maarten G,Lindley Richard I,Lyden Patrick,Olivot Jean Marc,Parsons Mark,Toni Danilo,Toyoda Kazunori,Wahlgren Nils,Wardlaw Joanna,Del Zoppo Gregory J,Sandercock Peter,Hacke Werner,Baigent Colin,
The Lancet. Neurology
BACKGROUND:Randomised trials have shown that alteplase improves the odds of a good outcome when delivered within 4·5 h of acute ischaemic stroke. However, alteplase also increases the risk of intracerebral haemorrhage; we aimed to determine the proportional and absolute effects of alteplase on the risks of intracerebral haemorrhage, mortality, and functional impairment in different types of patients. METHODS:We used individual patient data from the Stroke Thrombolysis Trialists' (STT) meta-analysis of randomised trials of alteplase versus placebo (or untreated control) in patients with acute ischaemic stroke. We prespecified assessment of three classifications of intracerebral haemorrhage: type 2 parenchymal haemorrhage within 7 days; Safe Implementation of Thrombolysis in Stroke Monitoring Study's (SITS-MOST) haemorrhage within 24-36 h (type 2 parenchymal haemorrhage with a deterioration of at least 4 points on National Institutes of Health Stroke Scale [NIHSS]); and fatal intracerebral haemorrhage within 7 days. We used logistic regression, stratified by trial, to model the log odds of intracerebral haemorrhage on allocation to alteplase, treatment delay, age, and stroke severity. We did exploratory analyses to assess mortality after intracerebral haemorrhage and examine the absolute risks of intracerebral haemorrhage in the context of functional outcome at 90-180 days. FINDINGS:Data were available from 6756 participants in the nine trials of intravenous alteplase versus control. Alteplase increased the odds of type 2 parenchymal haemorrhage (occurring in 231 [6·8%] of 3391 patients allocated alteplase vs 44 [1·3%] of 3365 patients allocated control; odds ratio [OR] 5·55 [95% CI 4·01-7·70]; absolute excess 5·5% [4·6-6·4]); of SITS-MOST haemorrhage (124 [3·7%] of 3391 vs 19 [0·6%] of 3365; OR 6·67 [4·11-10·84]; absolute excess 3·1% [2·4-3·8]); and of fatal intracerebral haemorrhage (91 [2·7%] of 3391 vs 13 [0·4%] of 3365; OR 7·14 [3·98-12·79]; absolute excess 2·3% [1·7-2·9]). However defined, the proportional increase in intracerebral haemorrhage was similar irrespective of treatment delay, age, or baseline stroke severity, but the absolute excess risk of intracerebral haemorrhage increased with increasing stroke severity: for SITS-MOST intracerebral haemorrhage the absolute excess risk ranged from 1·5% (0·8-2·6%) for strokes with NIHSS 0-4 to 3·7% (2·1-6·3%) for NIHSS 22 or more (p=0·0101). For patients treated within 4·5 h, the absolute increase in the proportion (6·8% [4·0% to 9·5%]) achieving a modified Rankin Scale of 0 or 1 (excellent outcome) exceeded the absolute increase in risk of fatal intracerebral haemorrhage (2·2% [1·5% to 3·0%]) and the increased risk of any death within 90 days (0·9% [-1·4% to 3·2%]). INTERPRETATION:Among patients given alteplase, the net outcome is predicted both by time to treatment (with faster time increasing the proportion achieving an excellent outcome) and stroke severity (with a more severe stroke increasing the absolute risk of intracerebral haemorrhage). Although, within 4·5 h of stroke, the probability of achieving an excellent outcome with alteplase treatment exceeds the risk of death, early treatment is especially important for patients with severe stroke. FUNDING:UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.
Statins and the risk of intracerebral haemorrhage in patients with stroke: systematic review and meta-analysis.
Ziff Oliver Jonathan,Banerjee Gargi,Ambler Gareth,Werring David J
Journal of neurology, neurosurgery, and psychiatry
OBJECTIVE:Whether statins increase the risk of intracerebral haemorrhage (ICH) in patients with a previous stroke remains uncertain. This study addresses the evidence of statin therapy on ICH and other clinical outcomes in patients with previous ischaemic stroke (IS) or ICH. METHODS:A systematic literature review and meta-analysis was performed in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to assess observational and randomised studies comparing statin therapy with control (placebo or no treatment) in patients with a previous ICH or IS. The risk ratios (RR) for the primary outcome (ICH) and secondary outcomes (IS, any stroke, mortality and function) were pooled using random effects meta-analysis according to stroke subtype. RESULTS:Forty-three studies with a combined total of 317 291 patient-years of follow-up were included. In patients with previous ICH, statins had no significant impact on the pooled RR for recurrent ICH (1.04, 95% CI 0.86 to 1.25; n=23 695); however, statins were associated with significant reductions in mortality (RR 0.49, 95% CI 0.36 to 0.67; n=89 976) and poor functional outcome (RR 0.71, 95% CI 0.67 to 0.75; n=9113). In patients with previous IS, statins were associated with a non-significant increase in ICH (RR 1.36, 95% CI 0.96 to 1.91; n=103 525), but significantly lower risks of recurrent IS (RR 0.74, 95% CI 0.66 to 0.83; n=53 162), any stroke (RR 0.82, 95% CI 0.67 to 0.99; n=55 260), mortality (RR 0.68, 95% CI 0.50 to 0.92; n=74 648) and poor functional outcome (RR 0.83, 95% CI 0.76 to 0.91; n=34 700). CONCLUSIONS:Irrespective of stroke subtype, there were non-significant trends towards future ICH with statins. However, this risk was overshadowed by substantial and significant improvements in mortality and functional outcome among statin users. TRIAL REGISTRATION NUMBER:CRD42017079863.
Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis.
Wang Xiang,Dong Yan,Qi Xiangqian,Huang Chengguang,Hou Lijun
BACKGROUND AND PURPOSE:Cholesterol levels are inconsistently associated with the risk of hemorrhagic stroke. The purpose of this study is to assess their relationships using a meta-analytic approach. METHODS:We searched PubMed and Embase for pertinent articles published in English. Only prospective studies that reported effect estimates with 95% confidential intervals (CIs) of hemorrhagic stroke for ≥3 categories of cholesterol levels, for high and low comparison, or for per 1 mmol/L increment of cholesterol concentrations were included. We used the random-effects model to pool the study-specific results. RESULTS:Twenty-three prospective studies were included, totaling 1 430 141 participants with 7960 (5.6%) hemorrhagic strokes. In high versus low analysis, the summary relative risk of hemorrhagic stroke was 0.69 (95% CI, 0.59-0.81) for total cholesterol, 0.98 (95% CI, 0.80-1.19) for high-density lipoprotein cholesterol, and 0.62 (95% CI, 0.41-0.92) for low-density lipoprotein cholesterol. In dose-response analysis, the summary relative risk of hemorrhagic stroke for 1 mmol/L increment of total cholesterol was 0.85 (95% CI, 0.80-0.91), for high-density lipoprotein cholesterol was 1.11 (95% CI, 0.99-1.25), and for low-density lipoprotein cholesterol was 0.90 (95% CI, 0.77-1.05). The pooled relative risk for intracerebral hemorrhage was 1.17 (95% CI, 1.02-1.35) for high-density lipoprotein cholesterol. CONCLUSIONS:Total cholesterol level is inversely associated with risk of hemorrhagic stroke. Higher level of low-density lipoprotein cholesterol seems to be associated with lower risk of hemorrhagic stroke. High-density lipoprotein cholesterol level seems to be positively associated with risk of intracerebral hemorrhage.
Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage.
Marini Sandro,Devan William J,Radmanesh Farid,Miyares Laura,Poterba Timothy,Hansen Björn M,Norrving Bo,Jimenez-Conde Jordi,Giralt-Steinhauer Eva,Elosua Roberto,Cuadrado-Godia Elisa,Soriano Carolina,Roquer Jaume,Kourkoulis Christina E,Ayres Alison M,Schwab Kristin,Tirschwell David L,Selim Magdy,Brown Devin L,Silliman Scott L,Worrall Bradford B,Meschia James F,Kidwell Chelsea S,Montaner Joan,Fernandez-Cadenas Israel,Delgado Pilar,Greenberg Steven M,Lindgren Arne,Matouk Charles,Sheth Kevin N,Woo Daniel,Anderson Christopher D,Rosand Jonathan,Falcone Guido J,
BACKGROUND AND PURPOSE:Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemorrhage (ICH). We performed a genome-wide association study (GWAS) of hematoma volume with the aim of identifying novel biological pathways involved in the pathophysiology of primary brain injury in ICH. METHODS:We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admission head computed tomography to calculate hematoma volume via semiautomated computer-assisted technique. After quality control and imputation, 7 million genetic variants were available for association testing with ICH volume, which was performed separately in lobar and nonlobar ICH cases using linear regression. Signals with <5×10 were pursued in replication and tested for association with admission Glasgow coma scale and 3-month post-ICH dichotomized (0-2 versus 3-6) modified Rankin Scale using ordinal and logistic regression, respectively. RESULTS:The discovery phase included 394 ICH cases (228 lobar and 166 nonlobar) and identified 2 susceptibility loci: a genomic region on 22q13 encompassing (top single-nucleotide polymorphism rs9614326: β, 1.84; SE, 0.32; =4.4×10) for lobar ICH volume and an intergenic region overlying numerous copy number variants on (top single-nucleotide polymorphism rs11655160: β, 0.95; SE, 0.17; =4.3×10) for nonlobar ICH volume. The replication included 240 ICH cases (71 lobar and 169 nonlobar) and corroborated the association for (=0.04; meta-analysis =2.5×10; heterogeneity, =0.16) but not for 22q13 (=0.49). In multivariable analysis, rs11655160 was also associated with lower admission Glasgow coma scale (odds ratio, 0.17; =0.004) and increased risk of poor 3-month modified Rankin Scale (odds ratio, 1.94; =0.045). CONCLUSIONS:We identified as a novel susceptibility risk locus for hematoma volume, clinical severity, and functional outcome in nonlobar ICH. Replication in other ethnicities and follow-up translational studies are needed to elucidate the mechanism mediating the observed association.
Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases.
Math Nikhil,Han Thang S,Lubomirova Irina,Hill Robert,Bentley Paul,Sharma Pankaj
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
BACKGROUND:The influences of genetic variants on functional clinical outcomes following stroke are unclear. In order to reliably quantify these influences, we undertook a comprehensive meta-analysis of outcomes after acute intracerebral haemorrhage (ICH) or ischaemic stroke (AIS) in relation to different genetic variants. METHODS:PubMed, PsycInfo, Embase and Medline electronic databases were searched up to January 2019. Outcomes, defined as favourable or poor, were assessed by validated scales (Barthel index, modified Rankin scale, Glasgow outcome scale and National Institutes of Health stroke scale). RESULTS:Ninety-two publications comprising 31,895 cases met our inclusion criteria. Poor outcome was observed in patients with ICH who possessed the APOE4 allele: OR =2.60 (95% CI = 1.25-5.41, p = 0.01) and in AIS patients with the GA or AA variant at the BDNF-196 locus: OR = 2.60 (95% CI = 1.25-5.41, p = 0.01) or a loss of function allele of CYP2C19: OR = 2.36 (95% CI = 1.56-3.55, p < 0.0001). Poor outcome was not associated with APOE4: OR = 1.02 (95% CI = 0.81-1.27, p = 0.90) or IL6-174 G/C: OR = 2.21 (95% CI = 0.55-8.86, p = 0.26) in patients with AIS. CONCLUSIONS:We demonstrate that recovery of AIS was unfavourably associated with variants of BDNF and CYP2C19 genes whilst recovery of ICH was unfavourably associated with APOE4 gene.
Therapeutic Benefit of Cilostazol in Patients with Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized and Nonrandomized Studies.
Qureshi Adnan I,Ishfaq Ammad,Ishfaq Muhammad F,Pandhi Abhi,Ahmed Sundas I,Singh Savdeep,Kerro Ali,Krishnan Rashi,Deep Aman,Georgiadis Alexandros L
Journal of vascular and interventional neurology
Objective:To assess the effectiveness of cilostazol, a selective inhibitor of phosphodiesterase type III, in preventing cerebral ischemia related to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Methods:A total of six clinical studies met the inclusion criteria and were included in the meta-analysis. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using random-effects models. The primary endpoint was cerebral ischemia related to vasospasm. Secondary endpoints were angiographic vasospasm, new cerebral infarct, mortality, and death or disability at the final follow-up. Results:A total of 136 (22%) of 618 subjects (38 and 98 assigned to cilostazol and control treatments, respectively) with SAH developed cerebral ischemia related to vasospasm. The risk of cerebral ischemia related to vasospasm was significantly lower in subjects assigned to cilostazol treatment ( 0.43; 95% CI 0.31-0.60; < 0.001). The risks of angiographic vasospasm ( 0.67, 95% CI 0.54-0.84, < 0.001 ) and new cerebral infarct ( 0.37, 95% CI 0.24-0.57, < 0.001) were significantly lower in subjects assigned to cilostazol treatment. There was a significantly lower rate of death or disability in subjects assigned to cilostazol treatment at follow-up ( 0.55, 95% 0.39-0.78, = 0.001). Conclusion:The reduction in rates of cerebral ischemia related to vasospasm and death or disability at follow-up support further evaluation of oral cilostazol in patients with aneurysmal SAH in a large randomized clinical trial.
Is there added value in obtaining cervical spine MRI in the assessment of nontraumatic angiographically negative subarachnoid hemorrhage? A retrospective study and meta-analysis of the literature.
Sadigh Gelareh,Holder Chad A,Switchenko Jeffrey M,Dehkharghani Seena,Allen Jason W
Journal of neurosurgery
OBJECTIVE Diagnostic algorithms for nontraumatic angiographically negative subarachnoid hemorrhage (AN-SAH) vary, and the optimal method remains subject to debate. This study assessed the added value of cervical spine MRI in identifying a cause for nontraumatic AN-SAH. METHODS Consecutive patients 18 years of age or older who presented with nontraumatic SAH between February 1, 2009, and October 31, 2014, with negative cerebrovascular catheter angiography and subsequent cervical MRI were studied. Patients with intraparenchymal, subdural, or epidural hemorrhage; recent trauma; or known vascular malformations were excluded. All cervical MR images were reviewed by two blinded neuroradiologists. The diagnostic yield of cervical MRI was calculated. A literature review was conducted to identify studies reporting the diagnostic yield of cervical MRI in patients with AN-SAH. The weighted pooled estimate of diagnostic yield of cervical MRI was calculated. RESULTS For all 240 patients (mean age 53 years, 48% male), catheter angiography was performed within 4 days after admission (median 12 hours, interquartile range [IQR] 10 hours). Cervical MRI was performed within 19 days of admission (median 24 hours, IQR 10 hours). In a single patient, cervical MRI identified a source for SAH (cervical vascular malformation). Meta-analysis of 7 studies comprising 538 patients with AN-SAH produced a pooled estimate of 1.3% (95% confidence interval 0.5%-2.5%) for diagnostic yield of cervical MRI. No statistically significant between-study heterogeneity or publication bias was identified. CONCLUSIONS Cervical MRI following AN-SAH, in the absence of findings to suggest spinal etiology, has a very low diagnostic yield and is not routinely necessary.
Prediction of Delayed Cerebral Ischemia with Cerebral Angiography: A Meta-Analysis.
Kumar Gyanendra,Dumitrascu Oana M,Chiang Chia-Chun,O'Carroll Cumara B,Alexandrov Andrei V
OBJECT:Cerebral catheter angiography is the gold standard for diagnosing cerebral artery vasospasm (vasospasm) in aneurysmal subarachnoid hemorrhage (SAH). We have previously published a meta-analysis of prediction of delayed cerebral ischemia (DCI) from transcranial Doppler (TCD) evidence of vasospasm. Analogous data relating to prediction of DCI have not been previously collated for cerebral angiography nor reconciled against TCD. METHODS:We searched PUBMED, the Cochrane database, and clinicaltrials.gov for studies that used cerebral angiography for diagnosis of vasospasm and evaluated DCI in patients with SAH. We performed a random-effects meta-analysis of prediction of DCI with cerebral angiography, reconciling its accuracy against that of TCD. We also report quality of evidence for the value of cerebral angiography and TCD in SAH based on pooled data from our meta-analyses. RESULTS:A total of 15 studies (n = 5463) were included in the meta-analysis. Sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of cerebral angiography for prediction of DCI are 57, 68, 32, and 90%. These metrics for TCD, based on our previous meta-analysis, are 90, 71, 57, and 92%. We report that test accuracy estimates are "moderate" for TCD and "low" for angiography based on pooled data from our meta-analyses. CONCLUSION:TCD evidence of vasospasm is a better predictor of DCI than angiographic vasospasm. Future comparative effectiveness studies can better define the value of these diagnostic tools in patients with SAH.
Role of Xingnaojing combined with naloxone in treating intracerebral haemorrhage: A systematic review and meta-analysis of randomized controlled trials.
Xu Yu-Min,Wang Xin-Chen,Zhang Shi-Jie,Xu Ting-Ting,Li Hong-Ying,Hei Shang-Yan,Wen Ze-Huai,Ma Yun-Zhi,Wang Qi,Liang Wei-Xiong
BACKGROUND:Xingnaojing injection (XNJ) sharpen the mind and induce consciousness and are widely used in acute phases of intracerebral hemorrhage (ICH). Naloxone hydrochloride injection (NX) performs equally well and replace the effects of morphine-like substances to promote conscious awareness. The applications of XNJ combined with NX for ICH show some advantages compared with NX applied individually. The aim of this systematic review is to evaluate the effectiveness and safety of XNJ combined with NX for ICH. METHODS:Comprehensive searches were conducted in 8 medical databases (PubMed, Cochrane Library, Web of Science, Embase, CNKI, VIP, CBM and Wanfang database) from inceptions to October 2017 for randomized controlled trials (RCTs) that compared the applications of XNJ and NX with NX applied individually in ICH. Literature screening, assessing risk of bias and data extraction were conducted by 2 reviewers independently. According to the Cochrane Collaboration's RevMan5.3 software to perform the data analysis. RESULTS:32 RCTs (3068 cases) were selected and the quality of studies were low. All trials compared XNJ and NX with NX applied individually. The overall meta-analysis results showed that XNJ combined with NX have significant effect on clinical efficacy (OR 3.78, 95% CI: 3.03-4.73; P < .00001), GCS score (MD 3.86, 95% CI: 3.46-4.25; P < .00001), coma duration (MD -5.59, 95% CI: -6.96 to -4.22; P < .00001), NIHSS score (MD -6.24, 95% CI: -8.05 to -4.42; P < .00001), Barthel Index score (MD 14.12, 95% CI: 6.7-21.54; P < .0002), cerebral hematoma volume (MD -6.05, 95% CI: -6.85 to -5.24; P < .00001) than NX applied individually. Adverse events reported in 4 studies and included mild discomfort symptoms. CONCLUSION:The effectiveness and safety of XNJ combined with NX for ICH cannot be determined due to the low quality of literature, publication bias and heterogeneity. More rigorous RCTs are necessary to verify the role of XNJ combined with NX in the treatment of ICH.
Predictors of Outcome With Cerebral Autoregulation Monitoring: A Systematic Review and Meta-Analysis.
Rivera-Lara Lucia,Zorrilla-Vaca Andres,Geocadin Romer,Ziai Wendy,Healy Ryan,Thompson Richard,Smielewski Peter,Czosnyka Marek,Hogue Charles W
Critical care medicine
OBJECTIVE:To compare cerebral autoregulation indices as predictors of patient outcome and their dependence on duration of monitoring. DATA SOURCES:Systematic literature search and meta-analysis using PubMed, EMBASE, and the Cochrane Library from January 1990 to October 2015. STUDY SELECTION:We chose articles that assessed the association between cerebral autoregulation indices and dichotomized or continuous outcomes reported as standardized mean differences or correlation coefficients (R), respectively. Animal and validation studies were excluded. DATA EXTRACTION:Two authors collected and assessed the data independently. The studies were grouped into two sets according to the type of analysis used to assess the relationship between cerebral autoregulation indices and predictors of outcome (standardized mean differences or R). DATA SYNTHESIS:Thirty-three studies compared cerebral autoregulation indices and patient outcomes using standardized mean differences, and 20 used Rs. The only data available for meta-analysis were from patients with traumatic brain injury or subarachnoid hemorrhage. Based on z score analysis, the best three cerebral autoregulation index predictors of mortality or Glasgow Outcome Scale for patients with traumatic brain injury were the pressure reactivity index, transcranial Doppler-derived mean velocity index based on cerebral perfusion pressure, and autoregulation reactivity index (z scores: 8.97, 6.01, 3.94, respectively). Mean velocity index based on arterial blood pressure did not reach statistical significance for predicting outcome measured as a continuous variable (p = 0.07) for patients with traumatic brain injury. For patients with subarachnoid hemorrhage, autoregulation reactivity index was the only cerebral autoregulation index that predicted patient outcome measured with the Glasgow Outcome Scale as a continuous outcome (R = 0.82; p = 0.001; z score, 3.39). We found a significant correlation between the duration of monitoring and predictive value for mortality (R = 0.78; p < 0.001). CONCLUSIONS:Three cerebral autoregulation indices, pressure reactivity index, mean velocity index based on cerebral perfusion pressure, and autoregulation reactivity index were the best outcome predictors for patients with traumatic brain injury. For patients with subarachnoid hemorrhage, autoregulation reactivity index was the only cerebral autoregulation index predictor of Glasgow Outcome Scale. Continuous assessment of cerebral autoregulation predicted outcome better than intermittent monitoring.
Prevalence of Brain Microbleeds in Alzheimer Disease: A Systematic Review and Meta-Analysis on the Influence of Neuroimaging Techniques.
Sepehry A A,Lang D,Hsiung G-Y,Rauscher A
AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE:The literature on the prevalence of Alzheimer disease-associated cerebral microbleeds assessed with MR imaging shows considerable heterogeneity in terms of imaging techniques and parameters. Our aim was to perform a meta-analysis of the role of imaging techniques, including image acquisition, field strength and scanner type, and clinical and demographic factors on the reported prevalence of microbleeds in Alzheimer disease. MATERIALS AND METHODS:The prevalence of microbleeds was examined with respect to a priori-selected moderating variables via meta-analytic tools of literature reports. RESULTS:Fourteen unique studies providing 15 microbleed prevalence rates met the selection criteria for inclusion. The aggregate prevalence of microbleeds was 24% (95% CI, 19%-28%). Scan (SWI = 40%, gradient echo = 18%, EPI = 19%) and field strength (slope = 0.39; standard error = 15, P < .01) influenced the prevalence of microbleeds. The associations between microbleeds and age, sex, and global cognitive status were not significant. After updating the literature, the aggregate prevalence remained in the 95% CI range. CONCLUSIONS:Imaging technique and field strength are strongly associated with the prevalence of microbleeds over the global aggregate. Standardized imaging protocols for identification of microbleeds are recommended to minimize confounds.
Impact of echocardiographic wall motion abnormality and cardiac biomarker elevation on outcome after subarachnoid hemorrhage: a meta-analysis.
Zhang Limin,Zhang Bing,Qi Sihua
Cardiac abnormalities (echocardiographic wall motion abnormality (WMA), biomarker elevation of cardiac troponin (cTn), B-type natriuretic peptide (BNP), or N-terminal prohormone of B-type natriuretic peptide (NT-proBNP)) frequently occur after subarachnoid hemorrhage (SAH). The clinical significance of cardiac abnormalities after SAH remains controversial. This meta-analysis was performed to assess the association between cardiac abnormalities and patient outcomes, including delayed cerebral ischemia (DCI), poor outcome, and death in SAH patients. PubMed and Embase were searched for observational studies reporting an association between cardiac abnormalities and outcome after SAH that were published before 31 December 2017. We extracted data regarding patient characteristics, cardiac abnormalities, and outcome measurements (DCI, poor outcome, or death). Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Twenty-six studies involving 3917 patients were included in our data analysis. WMA showed significant associations with higher rates of DCI (RR, 2.03; 95% CI, 0.99-4.15), poor outcome (RR, 1.45; 95% CI, 1.08-1.93), and death (RR, 2.54; 95% CI, 1.59-4.05). cTn elevation was associated with an increased risk of DCI (RR, 1.48; 95% CI, 1.23-1.79), poor outcome (RR, 1.85; 95% CI, 1.49-2.30), and death (RR, 2.68; 95% CI, 2.19-3.27). Elevation of BNP or NT-proBNT was significantly associated with higher rates of DCI (RR, 1.87; 95% CI, 1.16-3.02). WMA and elevation of cTn, BNP, and NT-proBNP in SAH patients are associated with an increased risk of DCI, poor outcome, and death after SAH.
Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage.
Woo Daniel,Falcone Guido J,Devan William J,Brown W Mark,Biffi Alessandro,Howard Timothy D,Anderson Christopher D,Brouwers H Bart,Valant Valerie,Battey Thomas W K,Radmanesh Farid,Raffeld Miriam R,Baedorf-Kassis Sylvia,Deka Ranjan,Woo Jessica G,Martin Lisa J,Haverbusch Mary,Moomaw Charles J,Sun Guangyun,Broderick Joseph P,Flaherty Matthew L,Martini Sharyl R,Kleindorfer Dawn O,Kissela Brett,Comeau Mary E,Jagiella Jeremiasz M,Schmidt Helena,Freudenberger Paul,Pichler Alexander,Enzinger Christian,Hansen Björn M,Norrving Bo,Jimenez-Conde Jordi,Giralt-Steinhauer Eva,Elosua Roberto,Cuadrado-Godia Elisa,Soriano Carolina,Roquer Jaume,Kraft Peter,Ayres Alison M,Schwab Kristin,McCauley Jacob L,Pera Joanna,Urbanik Andrzej,Rost Natalia S,Goldstein Joshua N,Viswanathan Anand,Stögerer Eva-Maria,Tirschwell David L,Selim Magdy,Brown Devin L,Silliman Scott L,Worrall Bradford B,Meschia James F,Kidwell Chelsea S,Montaner Joan,Fernandez-Cadenas Israel,Delgado Pilar,Malik Rainer,Dichgans Martin,Greenberg Steven M,Rothwell Peter M,Lindgren Arne,Slowik Agnieszka,Schmidt Reinhold,Langefeld Carl D,Rosand Jonathan,
American journal of human genetics
Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.
Angiotensin-converting enzyme insertion/deletion gene polymorphisms and risk of intracerebral hemorrhage: a meta-analysis of epidemiologic studies.
Huang Yi,Li Guang,Lan Huan,Zhao GuanYan,Huang ChunZhen
Journal of the renin-angiotensin-aldosterone system : JRAAS
Studies investigating the association between the intron 16 insertion/deletion (I/D) polymorphism (rs4646994) in the angiotensin-converting enzyme (ACE) gene and risk of intracerebral hemorrhage (ICH) have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. Published literature from the National Library of Medline and Embase databases were retrieved. Odds ratios (OR) and 95% confidence limits (CLs) were calculated in fixed- or random-effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included six case-control studies, which included 744 ICH cases and 1411 controls. The combined results based on all studies showed that ICH cases had a significantly lower frequency of ID genotype (OR (codominant model) = 0.43, 95% CL = 0.22, 0.84, p = 0.01). In the subgroup analysis by race, we found that ICH cases had a significantly lower frequency of II genotype in Asians (OR (recessive model) = 0.50, 95% CL = 0.38, 0.66, p < 0.001; OR (codominant model) = 0.25, 95% CL = 0.09, 0.71, p = 0.009). In conclusion, our meta-analysis suggests that ACE I/D polymorphisms are associated with ICH, especially in Asians.
Ultra-Early Angiographic Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.
Phan Kevin,Moore Justin M,Griessenauer Christoph J,Xu Joshua,Teng Ian,Dmytriw Adam A,Chiu Albert H,Ogilvy Christopher S,Thomas Ajith
OBJECTIVE:After aneurysmal subarachnoid hemorrhage (aSAH), prognosis is affected heavily by the presence of delayed cerebral ischemia (DCI). There is growing recognition of ultra-early angiographic vasospasm (UEAV) occurring within 48 hours of aSAH; however, its relationship with DCI and ultimately prognosis remains unclear. METHODS:Various databases limited to the English language through September 2016 were searched systematically. Eligible studies were those comparing UEAV with control non-UEAV outcomes and follow-up. Two independent reviewers evaluated the quality of studies and abstracted the data, with discrepancies resolved by a third. We calculated odds ratios (ORs) and 95% confidence intervals for all outcomes by using random-effects meta-analyses and performed a heterogeneity analysis. RESULTS:Four comparative studies were selected for analysis. Pooled analysis demonstrated that UEAV compared with no-UEAV was associated with greater proportion of rupture aneurysms sized greater than 12 mm (38.3% vs. 24.3%, P < 0.00001). A significantly greater number of patients with UEAV had ruptured MCA aneurysms compared with patients without UEAV (29.7% vs. 19.9%, P = 0.005). Compared with no-UEAV, patients with UEAV were significantly associated with symptomatic cerebral vasospasm (OR 2.07, P = 0.05) and DCI/infarction (OR 2.52, P = 0.02). A significant association also was found between UEAV and an unfavorable outcome at follow-up (OR 1.64, P = 0.03) and greater mortality (OR 2.65, P < 0.00001). CONCLUSIONS:UEAV was significantly associated with symptomatic cerebral vasospasm, DCI/infarction, unfavorable outcome at follow-up, and greater mortality. Patients with intracerebral hematoma, intraventricular hemorrhage (Fisher Grade IV), larger ruptured aneurysms >12 mm, and an MCA location were more likely to have UEAV.
CT perfusion for detection of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.
Mir D I A,Gupta A,Dunning A,Puchi L,Robinson C L,Epstein H-A B,Sanelli P C
AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE:Delayed cerebral ischemia is a significant cause of morbidity and mortality after aneurysmal SAH, leading to poor outcomes. The purpose of this study was to evaluate the usefulness of CTP in determining delayed cerebral ischemia in patients with aneurysmal SAH. MATERIALS AND METHODS:We conducted a systematic review evaluating studies that assessed CTP in patients with aneurysmal SAH for determining delayed cerebral ischemia. Studies using any of the following definitions of delayed cerebral ischemia were included in the systematic review: 1) new onset of clinical deterioration, 2) cerebral infarction identified on follow-up CT or MR imaging, and 3) functional disability. A random-effects meta-analysis was performed assessing the strength of association between a positive CTP result and delayed cerebral ischemia. RESULTS:The systematic review identified 218 studies that met our screening criteria, of which 6 cohort studies met the inclusion criteria. These studies encompassed a total of 345 patients, with 155 (45%) of 345 patients classified as having delayed cerebral ischemia and 190 (55%) of 345 patients as not having delayed cerebral ischemia. Admission disease severity was comparable across all groups. Four cohort studies reported CTP test characteristics amenable to the meta-analysis. The weighted averages and ranges of the pooled sensitivity and specificity of CTP in the determination of delayed cerebral ischemia were 0.84 (0.7-0.95) and 0.77 (0.66-0.82), respectively. The pooled odds ratio of 23.14 (95% CI, 5.87-91.19) indicates that patients with aneurysmal SAH with positive CTP test results were approximately 23 times more likely to experience delayed cerebral ischemia compared with patients with negative CTP test results. CONCLUSIONS:Perfusion deficits on CTP are a significant finding in determining delayed cerebral ischemia in aneurysmal SAH. This may be helpful in identifying patients with delayed cerebral ischemia before development of infarction and neurologic deficits.
Factors associated with early deterioration after spontaneous intracerebral hemorrhage: a systematic review and meta-analysis.
Specogna Adrian V,Turin Tanvir C,Patten Scott B,Hill Michael D
BACKGROUND AND PURPOSE:Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke with a poor prognosis overall. We conducted a systematic review and meta-analysis to identify and describe factors associated with early neurologic deterioration (END) after ICH. METHODS:We sought to identify any factor which could be prognostic in the absence of an intervention. The Cochrane Library, EMBASE, the Global Health Library, and PubMed were searched for primary studies from the years 1966 to 2012 with no restrictions on language or study design. Studies of patients who received a surgical intervention or specific experimental therapies were excluded. END was defined as death, or worsening on a reliable outcome scale within seven days after onset. RESULTS:7,172 abstracts were reviewed, 1,579 full-text papers were obtained and screened. 14 studies were identified; including 2088 patients. Indices of ICH severity such as ICH volume (univariate combined OR per ml:1.37, 95%CI: 1.12-1.68), presence of intraventricular hemorrhage (2.95, 95%CI: 1.57-5.55), glucose concentration (per mmol/l: 2.14, 95%CI: 1.03-4.47), fibrinogen concentration (per g/l: 1.83, 95%CI: 1.03-3.25), and d-dimer concentration at hospital admission (per mg/l: 4.19, 95%CI: 1.88-9.34) were significantly associated with END after random-effects analyses. Whereas commonly described risk factors for ICH progression such as blood pressure, history of hypertension, and ICH growth were not. CONCLUSIONS:This study summarizes the evidence to date on early ICH prognosis and highlights that the amount and distribution of the initial bleed at hospital admission may be the most important factors to consider when predicting early clinical outcomes.
Selective serotonin reuptake inhibitors and brain hemorrhage: a meta-analysis.
Hackam Daniel G,Mrkobrada Marko
OBJECTIVE:We synthesized the epidemiologic evidence concerning selective serotonin reuptake inhibitor (SSRI) exposure and the risk of CNS hemorrhage. METHODS:We searched for controlled observational studies comparing SSRI therapy with a control group not receiving SSRIs. We used DerSimonian and Laird fixed effect models to compute summary risk associations. RESULTS:Intracranial hemorrhage was related to SSRI exposure in both unadjusted (rate ratio [RR] 1.48, 95% confidence interval [CI] 1.22-1.78) and adjusted analyses (RR 1.51, 95% CI 1.26-1.81). Intracerebral hemorrhage was also associated with SSRI exposure in both unadjusted (RR 1.68, 95% CI 1.46-1.91) and adjusted (RR 1.42, 95% CI 1.23-1.65) analyses. In a subset of 5 studies (3 of intracranial hemorrhage and 1 each reporting hemorrhagic stroke and intracerebral hemorrhage), SSRI exposure in combination with oral anticoagulants was associated with an increased risk of bleeding compared with oral anticoagulants alone (RR 1.56, 95% CI 1.33-1.83). When all studies were analyzed together, increased risk was seen across cohort studies (1.61, 95% CI 1.04-2.51), case-control studies (odds ratio [OR] 1.34, 95% CI 1.20-1.49), and case-crossover studies (OR 4.24, 95% CI 1.95-9.24). CONCLUSIONS:SSRI exposure is associated with an increased risk of intracerebral and intracranial hemorrhage, yet given the rarity of this event, absolute risks are likely to be very low.
Effect of simvastatin in patients with aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.
Liu Hongju,Xu Xiaoli
The American journal of emergency medicine
BACKGROUND:Simvastatin might be beneficial to the patients with aneurysmal subarachnoid hemorrhage. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the efficacy of simvastatin for aneurysmal subarachnoid hemorrhage. METHODS:PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of simvastatin versus placebo on aneurysmal subarachnoid hemorrhage were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were delayed ischaemic deficit and delayed cerebral infarction. Meta-analysis was performed using the random-effect model. RESULTS:Six RCTs involving 1053 patients were included in the meta-analysis. Overall, compared with control intervention, simvastatin intervention had no influence on delayed ischaemic deficit (RR=0.99; 95% CI=0.78 to 1.27; P=0.96), delayed cerebral infarction (RR=1.17; 95% CI=0.60 to 2.29; P=0.65), mRS≤2 (RR=0.97; 95% CI=0.87 to 1.09; P=0.61), vasospasm (RR=0.79; 95% CI=0.49 to 1.29; P=0.35), ICU stay (Std. mean difference=0.04; 95% CI=-0.54 to 0.63; P=0.88), hospital stay (Std. mean difference=0.01; 95% CI=-0.13 to 0.14; P=0.90) and mortality (RR=0.71; 95% CI=0.25 to 2.05; P=0.53) after aneurysmal subarachnoid hemorrhage. CONCLUSIONS:Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS≤2, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage.
Stereotactic aspiration versus craniotomy for primary intracerebral hemorrhage: a meta-analysis of randomized controlled trials.
Wang Jia-Wei,Li Jin-Ping,Song Ying-Lun,Tan Ke,Wang Yu,Li Tao,Guo Peng,Li Xiong,Wang Yan,Zhao Qi-Huang
BACKGROUND:A wealth of evidence based on the randomized controlled trials (RCTs) has indicated that surgery may be a better choice in the management of primary intracerebral hemorrhage (ICH) compared to conservative treatment. However, there is considerable controversy over selecting appropriate surgical procedures for ICH. Thus, this meta-analysis was performed to assess the effects of stereotactic aspiration compared to craniotomy in patients with ICH. METHODS:According to the study strategy, we searched PUBMED, EMBASE and Cochrane Central Register of Controlled Trials. Other sources such as the internet-based clinical trial registries, relevant journals and the lists of references were also searched. After literature searching, two investigators independently performed literature screening, assessment of quality of the included trials and data extraction. The outcome measures included death or dependence, total risk of complication, and the risk of rebleeding, gastrointestinal hemorrhage and systematic infection. RESULTS:Four RCTs with 2996 participants were included. The quality of the included trials was acceptable. Stereotactic aspiration significantly decreased the odds of death or dependence at the final follow-up (odds ratio (OR): 0.80, 95% confidence interval (CI): 0.69-0.93; P = 0.004) and the risk of intracerebral rebleeding (OR: 0.44, 95% CI: 0.26-0.74; P = 0.002) compared to craniotomy with no significant heterogeneity among the study results. CONCLUSIONS:The present meta-analysis provides evidence that the stereotactic aspiration may be associated with a reduction in the odds of being dead or dependent in primary ICH, which should be interpreted with caution. Further trials are needed to identify those patients most likely to benefit from the stereotactic aspiration.
Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage.
Tsivgoulis Georgios,Wilson Duncan,Katsanos Aristeidis H,Sargento-Freitas João,Marques-Matos Cláudia,Azevedo Elsa,Adachi Tomohide,von der Brelie Christian,Aizawa Yoshifusa,Abe Hiroshi,Tomita Hirofumi,Okumura Ken,Hagii Joji,Seiffge David J,Lioutas Vasileios-Arsenios,Traenka Christopher,Varelas Panayiotis,Basir Ghazala,Krogias Christos,Purrucker Jan C,Sharma Vijay K,Rizos Timolaos,Mikulik Robert,Sobowale Oluwaseun A,Barlinn Kristian,Sallinen Hanne,Goyal Nitin,Yeh Shin-Joe,Karapanayiotides Theodore,Wu Teddy Y,Vadikolias Konstantinos,Ferrigno Marc,Hadjigeorgiou Georgios,Houben Rik,Giannopoulos Sotirios,Schreuder Floris H B M,Chang Jason J,Perry Luke A,Mehdorn Maximilian,Marto João-Pedro,Pinho João,Tanaka Jun,Boulanger Marion,Al-Shahi Salman Rustam,Jäger Hans R,Shakeshaft Clare,Yakushiji Yusuke,Choi Philip M C,Staals Julie,Cordonnier Charlotte,Jeng Jiann-Shing,Veltkamp Roland,Dowlatshahi Dar,Engelter Stefan T,Parry-Jones Adrian R,Meretoja Atte,Mitsias Panayiotis D,Alexandrov Andrei V,Ambler Gareth,Werring David J
Annals of neurology
OBJECTIVE:Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. METHODS:We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. RESULTS:We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43). INTERPRETATION:Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.
Role of Genetic Polymorphisms in Predicting Delayed Cerebral Ischemia and Radiographic Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.
Rosalind Lai Pui Man,Du Rose
OBJECTIVE:The pathophysiology on cerebral vasospasm and delayed cerebral ischemia (DCI) remains poorly understood. Much research has been dedicated to finding genetic loci associated with vasospasm and ischemia. We present a systematic review and meta-analysis to identify genetic polymorphisms associated with delayed ischemic neurologic deficit (DIND), radiographic infarction attributed to ischemia, and radiographic vasospasm. METHODS:PubMed, the Cochrane Library, and Excerpta Medica dataBASE (EMBASE) databases were used to identify relevant studies published up to March 2015 containing the subject terms cerebral or intracranial vasospasm and DCI in combination with genetics, gene, polymorphism or marker. Meta-analyses were performed using a random-effects model to calculate summary odds ratio (ORs) and 95% confidence intervals for each respective gene. RESULTS:Of 269 articles initially identified, 20 studies with 1670 patients were included in our comprehensive review, including 27 polymorphisms in 11 genes. The following 6 polymorphisms in 3 genes were selected for subsequent meta-analyses: apolipoprotein E (ApoE2, E4); endothelial nitric oxide (eNOS T786C, VNTR intron 4 a/b, G894T); and haptoglobin (Hp) 1/2 phenotypes. The eNOS VNTR a allele was associated with DIND (a vs. b allele: OR 1.92 [1.31-2.81], padj = 0.008). The Hp 2-2 allele was associated with radiographic vasospasm (2-2 vs. 2-1 and 1-1: OR 3.86 [1.86-8.03], padj = 0.003) but did not reach significance for DIND. CONCLUSIONS:This is the first systemic review and meta-analysis to study and evaluate the associations between genetic polymorphism with DCI and radiographic vasospasm independently. In our study, eNOS VNTR and Hp polymorphisms appear to have the strongest associations with DIND and radiographic vasospasm, respectively.
Association between statin use and intracerebral hemorrhage: a systematic review and meta-analysis.
Lei C,Wu B,Liu M,Chen Y
European journal of neurology
BACKGROUND AND PURPOSE:Accumulating evidence suggests that statins exert neuroprotective effects, but whether their use affects the outcomes of intracerebral hemorrhage (ICH) remains controversial. Therefore, we performed a systematic review and meta-analysis to investigate whether statin use before spontaneous ICH affects unfavorable functional outcome or mortality. METHODS:We searched the Cochrane Library, MEDLINE, EMBASE and China National Knowledge Infrastructure databases for studies examining the effects of pre-ICH statin use on unfavorable functional outcome, mortality or neuroimaging outcomes in consecutively recruited patients with spontaneous ICH, regardless of the duration or dose of statin treatment. RESULTS:A total of 12 studies were included that examined the effects of pre-ICH statin use on post-ICH outcomes in 1652 subjects in the favors pre-statin group and 5309 in the favors no pre-ICH statin group. Meta-analysis of 11 studies suggested that pre-ICH statin use did not significantly affect mortality across all three time points tested [in-hospital, 30 days, 90 days; odds ratio (OR) 0.85, 95% confidence interval (CI) 0.70-1.03]. However, meta-analysis of seven studies showed that pre-ICH statin use did significantly decrease 90-day mortality (OR 0.72, 95% CI 0.59-0.88). Meta-analysis of six studies showed that pre-ICH statin use was not associated with significant changes in unfavorable functional outcome. Moreover, pre-ICH statin use did not significantly affect admission hematoma volume (standardized mean difference 7.75, 95% CI -5.59 to 21.09). CONCLUSION:Available evidence suggests that statin use before spontaneous ICH does not increase short-term mortality, unfavorable functional outcome or post-ICH hematoma volume at admission.
Alpha Calcitonin Gene-Related Peptide Increases Cerebral Vessel Diameter in Animal Models of Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis.
Flynn Liam M C,Begg Caroline J,Macleod Malcolm R,Andrews Peter J D
Frontiers in neurology
Delayed cerebral ischemia (DCI) is a life-threatening complication after subarachnoid hemorrhage. There is a strong association between cerebral vessel narrowing and DCI. Alpha calcitonin gene-related peptide (αCGRP) is a potent vasodilator, which may be effective at reducing cerebral vessel narrowing after subarachnoid hemorrhage (SAH). Here, we report a meta-analysis of data from nine animal studies identified in a systematic review in which αCGRP was administered in SAH models. Our primary outcome was change in cerebral vessel diameter and the secondary outcome was change in neurobehavioral scores. There was a 40.8 ± 8.2% increase in cerebral vessel diameter in those animals treated with αCGRP compared with controls ( < 0.0005, 95% CI 23.7-57.9). Neurobehavioral scores were reported in four publications and showed a standardized mean difference of 1.31 in favor of αCGRP (CI -0.49 to 3.12). We conclude that αCGRP reduces cerebral vessel narrowing seen after SAH in animal studies but note that there is insufficient evidence to determine its effect on functional outcomes.
Untreated brain arteriovenous malformation: patient-level meta-analysis of hemorrhage predictors.
Kim Helen,Al-Shahi Salman Rustam,McCulloch Charles E,Stapf Christian,Young William L,
OBJECTIVE:To identify risk factors for intracranial hemorrhage in the natural history course of brain arteriovenous malformations (AVMs) using individual patient data meta-analysis of 4 existing cohorts. METHODS:We harmonized data from Kaiser Permanente of Northern California (n = 856), University of California San Francisco (n = 787), Columbia University (n = 672), and the Scottish Intracranial Vascular Malformation Study (n = 210). We censored patients at first treatment, death, last visit, or 10-year follow-up, and performed stratified Cox regression analysis of time-to-hemorrhage after evaluating hemorrhagic presentation, sex, age at diagnosis, deep venous drainage, and AVM size as predictors. Multiple imputation was performed to assess impact of missing data. RESULTS:A total of 141 hemorrhage events occurred during 6,074 patient-years of follow-up (annual rate of 2.3%, 95% confidence interval [CI] 2.0%-2.7%), higher for ruptured (4.8%, 3.9%-5.9%) than unruptured (1.3%, 1.0%-1.7%) AVMs at presentation. Hemorrhagic presentation (hazard ratio 3.86, 95% CI 2.42-6.14) and increasing age (1.34 per decade, 1.17-1.53) independently predicted hemorrhage and remained significant predictors in the imputed dataset. Female sex (1.49, 95% CI 0.96-2.30) and exclusively deep venous drainage (1.60, 0.95-2.68, p = 0.02 in imputed dataset) may be additional predictors. AVM size was not associated with intracerebral hemorrhage in multivariable models (p > 0.5). CONCLUSION:This large, individual patient data meta-analysis identified hemorrhagic presentation and increasing age as independent predictors of hemorrhage during follow-up. Additional AVM cohort data may further improve precision of estimates, identify new risk factors, and allow validation of prediction models.
Effects of Intensive Blood Pressure Lowering on Intracerebral Hemorrhage Outcomes: A Meta-Analysis of Randomized Controlled Trials.
Ma Junpeng,Li Hao,Liu Yi,You Chao,Huang Siqing,Ma Lu
AIM:Elevation of blood pressure (BP) is common after intracerebral hemorrhage (ICH). Early BP treatment may be beneficial after ICH, but the effect of intensive BP lowering on ICH outcomes is not known and no systematic review or meta-analysis was published regarding this issue. MATERIAL AND METHODS:We conducted a meta-analysis to compare the effect of more versus less intensive BP targets on clinical outcomes in patients with ICH. Mortality, unfavorable outcome and adverse events were analyzed. Meta-analysis was performed in terms of the odds ratio (OR) and 95% confidence interval (CI). RESULTS:Five eligible studies were included and analyzed, involving 3243 patients to use systolic BP (SBP) < 140 mmHg as target BP and 142 patients to use other BP target in intensive BP target group. The pooled OR of mortality and unfavorable outcome after ICH in intensive BP control group comparing with less intensive BP targets group were 0.99 (95% CI 0.81 to 1.23) and 0.90 (95% CI 0.78 to 1.03) respectively. The pooled OR were 0.97 (95% CI 0.80 to 1.18) for neurological deterioration and 0.83 (95% CI 0.61 to 1.11) for hematoma expansion. There is no difference in other adverse events between two groups. CONCLUSION:Acute lowering of SBP to 140 mmHg is probably beneficial for functional outcome in patients with ICH, but the evidence is still insufficient. Further large multicenter studies are required to enhance the evidence to guide the BP lowering target following ICH.
Efficacy and safety of four interventions for spontaneous supratentorial intracerebral hemorrhage: a network meta-analysis.
Guo Guangyu,Pan Chao,Guo Wenliang,Bai Shuang,Nie Hao,Feng Yangyang,Li Gaigai,Deng Hong,Ma Yang,Zhu Suiqiang,Tang Zhouping
Journal of neurointerventional surgery
OBJECT:To investigate the efficacy and safety of four interventions of spontaneous intracerebral hemorrhage simultaneously. METHODS:PubMed, EmBase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) investigating endoscopic surgery (ES), minimally invasive puncture surgery (MIPS), conventional craniotomy (CC), and/or conservative medical treatment (CMT). Good functional outcome, death, and hemorrhage recurrence rates were evaluated by a network meta-analysis. RESULTS:20 RCTs with 3603 patients were included. Compared with CMT, a higher rate of good functional outcome was found after ES (RR=2.21, 95% CI 1.37 to 3.55) and MIPS (RR=1.47, 95% CI 1.24 to 1.73). Both ES (RR=0.62, 95% CI 0.44 to 0.86) and MIPS (RR=0.72, 95% CI 0.58 to 0.90) markedly reduced the rate of death. However, there was no significant difference in efficacy and safety between ES and MIPS. The top ranked P score for the efficacy outcome was for ES (P score=0.9810). ES (P-score=0.0709) ranked lowest for the primary safety outcome. There was a higher risk of hemorrhage recurrence after CC (RR=3.80, 95% CI 1.90 to 7.63) and MIPS (RR=2.86, 95% CI 1.70 to 4.82) compared with CMT whereas no significant difference was found for ES (RR=1.46, 95% CI 0.53 to 4.02). CONCLUSIONS:The results suggest that both ES and MIPS significantly improve neurological function and reduce the risk of death compared with CMT, and there is no significant difference between ES and MIPS. Ranking of P scores revealed that ES may be the most optimal intervention to improve functional outcome and prevent death. This needs to be evaluated further.
The extravasation of contrast as a predictor of cerebral hemorrhagic contusion expansion, poor neurological outcome and mortality after traumatic brain injury: A systematic review and meta-analysis.
Baldon Isabella Vargas,Amorim Andre Candeas,Santana Larissa Marques,Solla Davi J,Kolias Angelos,Hutchinson Peter,Paiva Wellingson S,Rosa-Júnior Marcos
BACKGROUND:The active extravasation of contrast on CT angiography (CTA) in primary intracerebral hemorrhages (ICH) is recognized as a predictive factor for ICH expansion, unfavorable outcomes and mortality. However, few studies have been conducted on the setting of traumatic brain injury (TBI). PURPOSE:To perform a literature systematic review and meta-analysis of the association of contrast extravasation on cerebral hemorrhagic contusion expansion, neurological outcomes and mortality. DATA SOURCES:The PubMed, Cochrane Library, Medline, Scielo, VHL and IBECS databases up to September 21, 2019, were searched for eligible studies. STUDY SELECTION:A total of 505 individual titles and abstracts were identified and screened. A total of 36 were selected for full text analysis, out of which 4 fulfilled all inclusion and exclusion criteria. DATA ANALYSIS:All 4 studies yielded point estimates suggestive of higher risk for hematoma expansion with contrast extravasation and the summary RR was 5.75 (95%CI 2.74-10.47, p<0.001). Contrast extravasation was also associated with worse neurological outcomes (RR 3.25, 95%CI 2.24-4.73, p<0.001) and higher mortality (RR 2.77, 95%CI 1.03-7.47, p = 0.04). DATA SYNTHESIS:This study is a Systematic Review and Meta-Analysis revealed the extravasation of contrast is a useful imaging sign to predict hematoma expansion, worse neurological outcomes and higher mortality. LIMITATIONS:Only four articles were selected. CONCLUSIONS:The extravasation of contrast in the setting of TBI is a useful imaging sign to predict hematoma expansion, worse neurological outcomes and higher mortality.
Minimally Invasive Surgery is Superior to Conventional Craniotomy in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.
Xia Zhiwei,Wu Xinlong,Li Jing,Liu Zhixiong,Chen Fenghua,Zhang Longbo,Zhang Hongfu,Wan Xin,Cheng Quan
BACKGROUND:Outcomes of minimally invasive surgery (MIS) versus conventional craniotomy (CC) for patients with spontaneous supratentorial intracerebral hemorrhage (SICH) have not been compared previously. We reviewed the current evidence regarding the safety and efficacy of MIS compared with CC in patients with SICH. METHODS:We conducted a meta-analysis of studies comparing MIS and CC in patients with computed tomography-confirmed SICH published between January 2000 and April 2018 in MEDLINE, Embase, and the Cochrane Controlled Trials Register based on PRISMA inclusion and exclusion criteria. Binary outcomes comparisons between MIS and CC were described using odds ratios (ORs). RESULTS:Five randomized controlled trials (RCTs) and 9 prospective controlled studies (non-RCTs), involving a total of 2466 patients, met our inclusion criteria. There was a statistically significant difference in mortality rate between MIS and CC (OR, 0.76; 95% confidence interval [CI], 0.60-0.97). MIS was associated with a lower rate of rebleeding (OR, 0.42; 95% CI, 0.28-0.64) and a higher rate of good recovery compared with CC (OR, 2.27; 95% CI, 1.34-3.83). CONCLUSIONS:Patients with SICH may benefit more from MIS than CC. Our study could help clinicians optimize treatment strategies in SICH.
Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use.
Seiffge David J,Goeldlin Martina B,Tatlisumak Turgut,Lyrer Philippe,Fischer Urs,Engelter Stefan T,Werring David J
Journal of neurology
OBJECTIVE:To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset. METHODS:We conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel-Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference. RESULTS:We identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03-7.07, p < 0.0001, I = 92%, p < 0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24-13.07 ml, p < 0.00001; I = 42%, p = 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p < 0.00001; I = 65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61-2.07, p < 0.00001, I = 20%, p = 0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52-3.31, p < 0.00001, I = 71%, p = 0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH. CONCLUSION:This meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.
MRI for prediction of hemorrhagic transformation in acute ischemic stroke: a systematic review and meta-analysis.
Suh Chong Hyun,Jung Seung Chai,Cho Se Jin,Woo Dong-Cheol,Oh Woo Yong,Lee Jong Gu,Kim Kyung Won
Acta radiologica (Stockholm, Sweden : 1987)
BACKGROUND:Hemorrhagic transformation increases mortality and morbidity in patients with acute ischemic stroke. PURPOSE:The purpose of this study is to evaluate the diagnostic performance of magnetic resonance imaging (MRI) for prediction of hemorrhagic transformation in acute ischemic stroke. MATERIAL AND METHODS:A systematic literature search of MEDLINE and EMBASE was performed up to 27 July 2018, including the search terms "acute ischemic stroke," "hemorrhagic transformation," and "MRI." Studies evaluating the diagnostic performance of MRI for prediction of hemorrhagic transformation in acute ischemic stroke were included. Diagnostic meta-analysis was conducted with a bivariate random-effects model to calculate the pooled sensitivity and specificity. Subgroup analysis was performed including studies using advanced MRI techniques including perfusion-weighted imaging, diffusion-weighted imaging, and susceptibility-weighted imaging. RESULTS:Nine original articles with 665 patients were included. Hemorrhagic transformation is associated with high permeability, hypoperfusion, low apparent diffusion coefficient (ADC), and FLAIR hyperintensity. The pooled sensitivity was 82% (95% confidence interval [CI] 61-93) and the pooled specificity was 79% (95% CI 71-85). The area under the hierarchical summary receiver operating characteristic curve was 0.85 (95% CI 0.82-0.88). Although study heterogeneity was present in both sensitivity (I=67.96%) and specificity (I=78.93%), a threshold effect was confirmed. Studies using advanced MRI showed sensitivity of 92% (95% CI 70-98) and specificity of 78% (95% CI 65-87) to conventional MRI. CONCLUSION:MRI may show moderate diagnostic performance for predicting hemorrhage in acute ischemic stroke although the clinical significance of this hemorrhage is somewhat uncertain.
Efficacy of neuroendoscopic surgery versus craniotomy for supratentorial hypertensive intracerebral hemorrhage: A meta-analysis of randomized controlled trials.
Zhao Xu-Hui,Zhang Su-Zhen,Feng Jin,Li Zhen-Zhong,Ma Zeng-Lu
Brain and behavior
BACKGROUND:Hypertensive cerebral hemorrhage (HCH) is a potentially life-threatening neurological condition with an extremely high morbidity and mortality. In recent years, neuroendoscopy has been used to treat intracerebral hemorrhage (ICH). However, the choice of neuroendoscopic surgery versus craniotomy for patients with intracerebral hemorrhages is controversial. AIM:We conducted this meta-analysis to assess the efficacy of neuroendoscopic surgery compared with craniotomy in patients with supratentorial hypertensive ICH. METHODS:A systematic electronic search was conducted of online electronic databases: PubMed, Embase, and the Cochrane Library updated on December 2017. The meta-analysis only included randomized controlled studies. RESULTS:Three randomized controlled trials met our inclusion criteria. The pooled analysis of death showed that neuroendoscopic surgery decreased the rate of death when compared with craniotomy (RR = 0.58, 95% CI 0.26-1.29; p = .18). The pooled result of complications indicated that neuroendoscopic surgery has a tendency toward lower complications (RR = 0.37, 95% CI 0.28-0.49; p < .001). CONCLUSIONS:Our results suggested that neuroendoscopic surgery has lower complications, but no superior advantages in morbidity rates. Since the advantage of neuroendoscopic surgery has been performed in some area, the continuation of multi-center comparative investigation with craniotomy may be necessary. Moreover, some efforts need to be taken in selecting appropriate patients with different treatments.
High incidence of asymptomatic cerebral microbleeds in patients with hemorrhagic onset-type moyamoya disease: a phase-sensitive MRI study and meta-analysis.
Qin Ying,Ogawa Toshihide,Fujii Shinya,Shinohara Yuki,Kitao Shin-Ichiro,Miyoshi Fuminori,Takasugi Marie,Watanabe Takashi,Kaminou Toshio
Acta radiologica (Stockholm, Sweden : 1987)
BACKGROUND:Moyamoya disease is a relatively rare cerebrovascular occlusive disorder. Several studies have reported cerebral microbleeds (CMBs) in moyamoya disease patients using T2*-weighted imaging (T2*WI) and/or susceptibility-weighted imaging (SWI). PURPOSE:To investigate the incidence, distribution patterns, and influencing factors of asymptomatic CMBs in patients with moyamoya disease. MATERIAL AND METHODS:Phase-sensitive imaging (PSI) was used to investigate 27 consecutive moyamoya disease patients with a 3-T magnetic resonance imaging system, then a meta-analysis of 245 patients (asymptomatic moyamoya disease, n = 23; ischemic moyamoya disease, n = 161; hemorrhagic moyamoya disease, n = 61) from four previous individual studies and our PSI study was performed. The meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Based on the clinical and radiological data, we divided the studies into different model groups to calculate the incidence of CMBs and discuss the distribution patterns of CMBs. RESULTS:Thirty-five asymptomatic CMBs were demonstrated in 14 moyamoya disease patients (51.9%) in our PSI study. Of these, 45.7% were located in the periventricular white matter. In the meta-analysis, the pooled incidence of asymptomatic CMBs in moyamoya disease was 46% (95% confidence interval [CI], 28.2-63.8%) on SWI or PSI and 29.6% (95% CI, 17.4-41.7%) on T2*WI. Statistical analysis showed that PSI or SWI offered better detection of CMBs in moyamoya disease than T2*WI, and 3-T T2*WI offered better detection than 1.5-T T2*WI. Furthermore, hemorrhagic onset-type moyamoya disease correlated with a high incidence of asymptomatic CMBs. CONCLUSION:PSI or SWI can detect CMBs better than T2*WI, and 3-T T2*WI. Hemorrhagic onset-type moyamoya disease seems to correlate with a high incidence of asymptomatic CMBs. The meta-analysis indicates that asymptomatic CMBs may be an important factor for hemorrhagic stroke risk. Long-term evaluation of CMBs using PSI or SWI may contribute to the management of moyamoya disease.
Vasospasm on transcranial Doppler is predictive of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.
Kumar Gyanendra,Shahripour Reza Bavarsad,Harrigan Mark R
Journal of neurosurgery
OBJECT The impact of transcranial Doppler (TCD) ultrasonography evidence of vasospasm on patient-centered clinical outcomes following aneurysmal subarachnoid hemorrhage (aSAH) is unknown. Vasospasm is known to lead to delayed cerebral ischemia (DCI) and poor outcomes. This systematic review and meta-analysis evaluates the predictive value of vasospasm on DCI, as diagnosed on TCD. METHODS MEDLINE, Scopus, the Cochrane trial register, and clinicaltrials.gov were searched through September 2014 using key words and the terms "subarachnoid hemorrhage," "aneurysm," "aneurysmal," "cerebral vasospasm," "vasospasm," "transcranial Doppler," and "TCD." Sensitivities, specificities, and positive and negative predictive values were pooled by a DerSimonian and Laird random-effects model. RESULTS Seventeen studies (n = 2870 patients) met inclusion criteria. The amount of variance attributable to heterogeneity was significant (I(2) > 50%) for all syntheses. No studies reported the impact of TCD evidence of vasospasm on functional outcome or mortality. TCD evidence of vasospasm was found to be highly predictive of DCI. Pooled estimates for TCD diagnosis of vasospasm (for DCI) were sensitivity 90% (95% confidence interval [CI] 77%-96%), specificity 71% (95% CI 51%-84%), positive predictive value 57% (95% CI 38%-71%), and negative predictive value 92% (95% CI 83%-96%). CONCLUSIONS TCD evidence of vasospasm is predictive of DCI with high accuracy. Although high sensitivity and negative predictive value make TCD an ideal monitoring device, it is not a mandated standard of care in aSAH due to the paucity of evidence on clinically relevant outcomes, despite recommendation by national guidelines. High-quality randomized trials evaluating the impact of TCD monitoring on patient-centered and physician-relevant outcomes are needed.
Meta-Analysis of Pre-Clinical Trials of Therapeutic Hypothermia for Intracerebral Hemorrhage.
Melmed Kara R,Lyden Patrick D
Therapeutic hypothermia and temperature management
Therapeutic hypothermia (TH) is a potent neuroprotectant for experimental ischemic stroke, but studies of TH for intracerebral hemorrhage (ICH) are emerging. We systematically reviewed the experimental literature to assess TH efficacy for ICH. We found 18 suitable papers; quality scores were moderately good. Compared with normothermia, TH reduced measures of edema (mean effect size (95% CI) -1.6873 (-2.3640, -1.0106), p < 0.0001) or blood-brain barrier leakage (p < 0.0001) and improved behavioral outcomes (p < 0.0001). There was no evidence of publication bias. In this meta-analysis of available preclinical studies of ICH, TH is potently effective for reducing perihematomal edema and for improving behavioral outcomes.
Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: Systematic review and meta-analysis of diagnostic test accuracy.
Perry Luke A,Lucarelli Tom,Penny-Dimri Jahan C,McInnes Matthew Df,Mondello Stefania,Bustamante Alejandro,Montaner Joan,Foerch Christian,Kwan Patrick,Davis Stephen,Yan Bernard
International journal of stroke : official journal of the International Stroke Society
BACKGROUND AND AIMS:Glial fibrillary acidic protein (GFAP) has shown promise in several studies for its ability to diagnose intracerebral hemorrhage (ICH). We evaluated the diagnostic accuracy of blood GFAP level to differentiate (ICH) from acute ischemic stroke (AIS) and stroke mimics, both overall, and in the first three hours after symptom onset. METHODS:We searched multiple databases, without language restriction, from inception until December 2017. Hierarchical summary receiver operating characteristic (HSROC) modeling was used to meta-analyze results. We conducted subgroup analyses restricted to blood samples collected within 0-60, 60-120, and 120-180 min time groups after symptom onset, to evaluate diagnostic accuracy in the early pre-hospital phase. Between and within study heterogeneity was explored using meta-regression. RESULTS:The search identified 199 potentially relevant citations from which 11 studies involving 1297 participants (350 ICH, 947 AIS, or mimic) were included. The pooled sensitivity, specificity, and area under the HSROC curve were 0.756 (95% CI 0.630-0.849), 0.945 (95% CI 0.858-0.980), and 0.904 (95% CI 0.878-0.931), respectively. Differences in assays used, but not the other covariates, partially explained between-study heterogeneity ( = 0.034). The summary estimates for the 0-60, 60-120, and 120-180 min subgroups were comparable to the primary analysis and there was no statistically significant difference in diagnostic accuracy between subgroups. CONCLUSIONS:GFAP is a promising diagnostic biomarker for ICH diagnosis in the early pre-hospital phase. Test accuracy is affected by assay subtype, but there are still unexplained sources of heterogeneity. High quality, international multi-center trials are warranted to develop and validate a point-of-care GFAP assay for the rapid triage and evaluation of acute stroke in the pre-hospital setting.
Predictive Accuracy of Alpha-Delta Ratio on Quantitative Electroencephalography for Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Analysis.
Yu Zhiyuan,Wen Dingke,Zheng Jun,Guo Rui,Li Hao,You Chao,Ma Lu
OBJECTIVE:Delayed cerebral ischemia (DCI) is significantly related to death and unfavorable functional outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). The association between alpha-delta ratio (ADR) on quantitative electroencephalography (EEG) and DCI has been reported in several previous studies, but their results are conflicting. This meta-analysis was conducted to assess the accuracy of ADR for DCI prediction in patients with aneurysmal SAH. METHODS:PubMed and Embase were systematically searched for related records. Study selection and data collection were completed by 2 investigators. Sensitivity, specificity, and their 95% confidence intervals (CIs) were pooled. A summary receiver operating characteristic curve was plotted to show the pooled accuracy. Deeks funnel plot was used to evaluate publication bias. RESULTS:Five studies were included in this meta-analysis. The pooled sensitivity and specificity of worsening ADR for DCI prediction in patients with aneurysmal SAH were 0.83 (95% CI 0.44-0.97) and 0.74 (95% CI 0.50-0.89), respectively. In addition, the area under the summary receiver operating characteristic curve was 0.84 (95% CI 0.81-0.87). No obvious publication bias was found using Deeks funnel plot (P = 0.29). CONCLUSIONS:Worsening ADR on quantitative EEG is a reliable predictor of DCI in patients with aneurysmal SAH. Further studies are still needed to confirm the role of quantitative EEG in DCI prediction.
CT Perfusion for Identification of Patients at Risk for Delayed Cerebral Ischemia during the Acute Phase after Aneurysmal Subarachnoid Hemorrhage: A Meta-analysis.
Sun Haogeng,Ma Junpeng,Liu Yi,You Chao
Background:It has been acknowledged that delayed cerebral ischemia (DCI) can be diagnosed by computed tomography perfusion (CTP) when it occurs following aneurysmal subarachnoid hemorrhage (aSAH); however, the clinical role of CTP in the prediction of DCI remains unclear. We performed a meta-analysis to investigate the role of CTP in the identification of patients at risk for DCI during the acute phase (<4 days) after aSAH. Materials and Methods:Relevant articles were systematically searched for analysis on PubMed, EMBASE, and Cochrane databases. The best CTP parameter or the definition of abnormal CTP scan result were collected, and the data with the greatest overall predictive value for DCI was extracted to assess the strength of association between a positive CTP result and an impending DCI. In addition, pooled estimates of sensitivity and specificity were determined. Results:Three relevant articles involving 128 patients were included in the analysis wherein DCI developed in 48 patients (37.5%). The pooled odds ratio was 32.15 (95% CI, 9.92-104.21), suggesting that the patients with a positive CTP test in the acute phase after aSAH were approximately 32 times as likely to develop DCI compared with those without aSAH. The pooled sensitivity and specificity of CTP for detecting impending DCI after aSAH was 65% (95% CI: 0.49-0.78) and 91% (95% CI: 0.83-0.96). Conclusions:CTP can detect abnormal brain perfusion before the occurrence of DCI. This may allow close monitoring and preemptive therapy for improvement in the prognosis in patients with aSAH.
Hyperglycemia and Mortality Risk in Patients with Primary Intracerebral Hemorrhage: A Meta-Analysis.
Guo Xiaoming,Li Helin,Zhang Zhiwen,Li Shouchun,Zhang Lizhi,Zhang Jiajing,Han Guiqing
Hyperglycemia may be associated with worse functional outcomes in patients with primary intracerebral hemorrhage. We performed a systematic review and meta-analysis to investigate the relationship between hyperglycemia and mortality risk in patients with primary intracerebral hemorrhage. We searched PubMed and Embase databases for studies investigating the association between hyperglycemia and mortality risk in patients with primary intracerebral hemorrhage. We estimated the pooled relative risk (RR) with its 95% confidence interval (95% CI) to assess the impact of hyperglycemia on mortality risk. Seventeen studies with a total of 6527 primary intracerebral hemorrhage patients were included. Meta-analysis of those studies showed that hyperglycemia significantly increased risk of mortality in patients with primary intracerebral hemorrhage (RR = 2.36, 95% CI 1.79-3.12). Subgroup analysis by time of follow-up showed that hyperglycemia significantly increased risk of short-term mortality (RR = 3.97, 95% CI 2.13-7.43) and long-term mortality (RR = 1.53, 95% CI 1.14-2.05). The RR of mortality for per 1-mmol/L increment in glucose level was 1.14 (95% CI 1.06-1.22). In patients with primary intracerebral hemorrhage, hyperglycemia significantly increases risk of both short-term mortality and long-term mortality.
Accuracy of Shape Irregularity and Density Heterogeneity on Noncontrast Computed Tomography for Predicting Hematoma Expansion in Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.
Yu Zhiyuan,Zheng Jun,Xu Zhao,Li Mou,Wang Xiaoze,Lin Sen,Li Hao,You Chao
OBJECTIVE:This systematic review and meta-analysis was aimed to evaluate the predictive values of shape irregularity and density heterogeneity of hematoma on noncontrast computed tomography (NCCT) for hematoma expansion (HE). METHODS:A literature search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library. Studies about predictive values of shape regularity or density heterogeneity of hematoma on NCCT for HE in spontaneous intracerebral hemorrhage were included. Meta-analysis was performed to pool the data. Publication bias assessment, subgroup analysis, and univariate meta-regression were conducted. RESULTS:A total of 7 studies with 2294 patients were included. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of shape irregularity were 67%, 47%, 1.30, and 0.71, respectively. In contrast, the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of density irregularity were 52%, 69%, 1.70, and 0.69, respectively. CONCLUSIONS:Considering the relatively low sensitivity and specificity, the predictive values of shape irregularity and density heterogeneity of hematoma for HE are limited. Further studies are still needed to find optimal NCCT predictors for HE in spontaneous intracerebral hemorrhage patients.
An Update on the Efficacy and Safety Profile of Clazosentan in Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.
Song Jie,Xue Yue-Qin,Wang Yan-Ju,Xu Peng,Sun De-Ke,Chen Wei
OBJECTIVE:The present meta-analysis was conducted to provide an update on the efficacy and safety profile of clazosentan with different doses in aneurysmal subarachnoid hemorrhage (aSAH). METHODS:We performed a comprehensive and electronic search updated to September 2018 of The Cochrane Library, Embase, and PubMed to identify relevant clinical trials. Trials of the effectiveness of clazosentan in treating cerebral vasospasm after aSAH were studied. The main outcomes included new cerebral infarction (NCI), delayed ischemic neurologic deficit (DIND), vasospasm associated with morbidity/mortality, angiographic vasospasm, rescue therapy, and adverse events. We applied RevMan 5.3 software for this meta-analysis to analyze the combined pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed- or random-effects model on the basis of heterogeneity. RESULTS:A total of 5 randomized placebo-controlled trials were included in this meta-analysis. Beneficial outcome was found in patients who received higher doses of clazosentan (>5 mg/h) after aSAH based on decreased incidence of DINDs (OR, 1.76; 95% CI, 1.16-2.69; P = 0.008), NCIs (OR, 2.31; 95% CI, 1.34-3.95; P = 0.002), and angiographic vasospasms (OR, 1.85; 95% CI, 1.19-2.89; P = 0.007). Meanwhile, other parameters, such as vasospasm-related morbidity/mortality, rescue therapy, and adverse events, showed no statistical significance (P > 0.05) between high and low doses of clazosentan. CONCLUSIONS:The significant beneficial outcomes of high-dose clazosentan have been proven in preventing cerebral vasospasm and subsequent cerebral infarction compared with low-dose clazosentan, with a manageable safety profile. However, high doses of clazosentan had no significant effect on rescue therapy and vasospasm-related morbidity/mortality.
Effects of Prior Antiplatelet Therapy on the Prognosis of Primary Intracerebral Hemorrhage: A Meta-analysis.
Yu Hai-Han,Pan Chao,Tang Ying-Xin,Liu Na,Zhang Ping,Hu Yang,Zhang Ye,Wu Qian,Deng Hong,Li Gai-Gai,Li Yan-Yan,Nie Hao,Tang Zhou-Ping
Chinese medical journal
BACKGROUND:Antiplatelet therapy (APT) was prevalently being used in the prevention of vascular disease, but the influence of prior APT on the prognosis of patients with intracerebral hemorrhage (ICH) remains controversial. This meta-analysis was to explore the effects of prior APT on the prognosis of patients with primary ICH. METHODS:PubMed and Embase were searched to identify the eligible studies. The studies comparing the mortality of ICH patients with or without prior APT were included. The quality of these studies was evaluated by the Newcastle-Ottawa quality assessment scale. The adjusted or unadjusted odds ratio (OR) for mortality between ICH patients with and without prior APT were pooled with 95% confidence interval (95% CI) as the effect of this meta-analysis. RESULTS:Twenty-two studies fulfilled the inclusion criteria and exhibited high qualities. The pooled OR was 1.37 (95% CI: 1.13-1.66, P = 0.001) for univariate analysis and 1.41 (95% CI: 1.05-1.90, P = 0.024) for multivariate analysis. The meta-regression indicated that for each 1-day increase in the time of assessment, the adjusted OR for the mortality of APT patients decreased by 0.0049 (95% CI: 0.0006-0.0091, P = 0.026) as compared to non-APT patients. CONCLUSION:Prior APT was associated with high mortality in patients with ICH that might be attributed primarily to its strong effect on early time.
Meta-Analysis of Accuracy of the Spot Sign for Predicting Hematoma Growth and Clinical Outcomes.
Phan Thanh G,Krishnadas Natasha,Lai Vivian Wai Yun,Batt Michael,Slater Lee-Anne,Chandra Ronil V,Srikanth Velandai,Ma Henry
Background and Purpose- The computed tomography angiographic spot sign refers to contrast leakage within intracerebral hemorrhage (ICH). It has been proposed as a surrogate radiological marker for ICH growth. We conducted a meta-analysis to study the accuracy of the spot sign for predicting ICH growth and mortality. Methods- PubMed, Medline, conference proceedings, and article references in English up to June 2017 were searched for studies reporting "computed tomography angiography" and "spot sign" or "intracerebral hemorrhage" and "spot sign." Each study was ranked on 27 criteria resulting in a quality rating score. Bivariate random effect meta-analysis was used to calculate positive and negative likelihood ratios and area under summary receiver operating characteristics curve for ICH growth and mortality. Hematoma growth was defined using the change in ≥6 mL or ≥33% increase in volume. Results- There were 26 studies describing 5085 patients, including 15 studies not used in previous meta-analyses. Positive likelihood ratio and negative likelihood ratio for ICH growth were 4.85 (95% CI, 3.85-6.02; I=76.1%) and 0.49 (95% CI, 0.40-0.58) and mortality were 4.65 (95% CI, 3.67-5.90) and 0.55 (95% CI, 0.40-0.69), respectively. For ICH growth, the pooled sensitivity was 0.57 (95% CI, 0.49-0.64) and pooled false positive rate was 0.12 (95% CI, 0.09-0.14). The post-test probability of ICH growth was 0.57. The area under the curve for ICH growth and mortality was 0.86 and 0.87 (CIs are not provided in bivariate method). Meta-regression showed sensitivity of the test to decline significantly with subsequent year of publication (β=-0.148; 95% CI, -0.295 to -0.001; P=0.05). Higher quality assessment is associated with lower false positive rate (β=-0.074; 95% CI, -0.126 to -0.022; P=0.006). Conclusions- The high area under the curve potentially suggests that the spot sign can predict hematoma growth and mortality. Caution is recommended in its application given the heterogeneity across studies, which is appropriate given the data.
Heterogeneity Signs on Noncontrast Computed Tomography Predict Hematoma Expansion after Intracerebral Hemorrhage: A Meta-Analysis.
Zhang Danfeng,Chen Jigang,Xue Qiang,Du Bingying,Li Ya,Chen Tao,Jiang Ying,Hou Lijun,Dong Yan,Wang Junyu
BioMed research international
Background and Purpose:Hematoma expansion (HE) is related to clinical deterioration after intracerebral hemorrhage (ICH) and noncontrast computed tomography (NCCT) signs are indicated as predictors for HE but with inconsistent conclusions. We aim to clarify the correlations of NCCT heterogeneity signs with HE by meta-analysis of related studies. Methods:PubMed, Embase, and Cochrane library were searched for eligible studies exploring the relationships between NCCT heterogeneity signs (hypodensity, mixed density, swirl sign, blend sign, and black hole sign) and HE. Poor outcome and mortality were considered as secondary outcomes. Odds ratio (OR) and its 95% confidence intervals (CIs) were selected as the effect size and combined using random effects model. Results:Fourteen studies were included, involving 3240 participants and 435 HEs. The summary results suggested statistically significant correlations of heterogeneity signs with HE (OR, 5.17; 95% CI, 3.72-7.19, < 0.001), poor outcome (OR, 3.60; 95% CI, 1.98-6.54, < 0.001), and mortality (OR, 4.64; 95%, 2.96-7.27, < 0.001). Conclusions:Our findings suggested that hematoma heterogeneity signs on NCCT were positively associated with the increased risk of HE, poor outcome, and mortality rate in ICH.
The relationship between low serum magnesium level and intracerebral hemorrhage hematoma expansion: Protocol for a systematic review and meta-analysis.
Zhu Rending,He Xiaolu,Du Yanqun,Chen Nan,Wang Wei,Sun Yue,Sun Jian,Liu Wanjun,Wang Xun,Fang Chuanqin
BACKGROUND:Hematoma expansion (HE) is related to clinical deterioration and unfavorable prognosis in intracerebral hemorrhage (ICH). Some studies have revealed that low serum magnesium level is associated with larger hematoma volume at admission, HE, and unfavorable outcomes. However, the conclusions remain unsettled. The purpose of this study is to evaluate the association between low serum magnesium level and HE by meta-analysis. METHODS:We will search the following electronic bibliographic databases: PubMed, Medline, Embase, Web of Science, and The Cochrane Library. Studies will be included if they reported a relationship of low serum magnesium level and HE, mortality or poor outcome. RESULTS:The results of this study will be submitted to a peer-reviewed journal for publication. CONCLUSION:This will be the first systematic review and meta-analysis to evaluate the association of HE following ICH with Hypomagnesemia. We look forward to the results will offer scientific proof to predict HE for ICH patients with low serum magnesium level. PROSPERO REGISTRATION NUMBER:This protocol has been registered in the PROSPERO network with number: CRD42019135995.
Efficacy of Cilostazol in Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.
Saber Hamidreza,Desai Aaron,Palla Mohan,Mohamed Wazim,Seraji-Bozorgzad Navid,Ibrahim Muhammed
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
OBJECTIVES:Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and improve outcome in patients with aneurysmal subarachnoid hemorrhage considering its anti-platelet and vasodilatory effects. We aimed to analyze the effects of cilostazol on symptomatic vasospasm and clinical outcome among patients with aneurysmal subarachnoid hemorrhage (aSAH). PATIENTS AND METHODS:We searched PubMed and Embase databases to identify 1) prospective randomized trials, and 2) retrospective trials, between May 2009 and May 2017, that investigated the effect of cilostazol in patients with aneurysmal aSAH. All patients were enrolled after repair of a ruptured aneurysm by clipping or endovascular coiling within 72hours of aSAH. fixed-effect models were used to pool data. We used the I statistic to measure heterogeneity between trials. RESULTS:Five studies were included in our meta-analysis, comprised of 543 patients with aSAH (cilostazol [n=271]; placebo [n=272], mean age, 61.5years [SD, 13.1]; women, 64.0%). Overall, cilostazol was associated with a decreased risk of symptomatic vasospasm (0.31, 95% CI 0.20 to 0.48; P<0.001), cerebral infarction (0.32, 95% CI 0.20 to 0.52; P <0.001) and poor outcome (0.40, 95% CI 0.25 to 0.62; P<0.001). We observed no evidence for publication bias. Statistical heterogeneity was not present in any analysis. CONCLUSION:Cilostazol is associated with a decreased risk of symptomatic vasospasm and may be clinically useful in the treatment of delayed cerebral vasospasm in patients with aSAH. Our results highlight the need for a large multi-center trial to confirm the observed association.
Intracerebral Hemorrhage Location and Functional Outcomes of Patients: A Systematic Literature Review and Meta-Analysis.
Sreekrishnan Anirudh,Dearborn Jennifer L,Greer David M,Shi Fu-Dong,Hwang David Y,Leasure Audrey C,Zhou Sonya E,Gilmore Emily J,Matouk Charles C,Petersen Nils H,Sansing Lauren H,Sheth Kevin N
BACKGROUND AND PURPOSE:Intracerebral hemorrhage (ICH) has the highest mortality rate among all strokes. While ICH location, lobar versus non-lobar, has been established as a predictor of mortality, less is known regarding the relationship between more specific ICH locations and functional outcome. This review summarizes current work studying how ICH location affects outcome, with an emphasis on how studies designate regions of interest. METHODS:A systematic search of the OVID database for relevant studies was conducted during August 2015. Studies containing an analysis of functional outcome by ICH location or laterality were included. As permitted, the effect size of individual studies was standardized within a meta-analysis. RESULTS:Thirty-seven studies met the inclusion criteria, the majority of which followed outcome at 3 months. Most studies found better outcomes on the Modified Rankin Scale (mRS) or Glasgow Outcome Score (GOS) with lobar compared to deep ICHs. While most aggregated deep structures for analysis, some studies found poorer outcomes for thalamic ICH in particular. Over half of the studies did not have specific methodological considerations for location designations, including blinding or validation. CONCLUSIONS:Multiple studies have examined motor-centric outcomes, with few studies examining quality of life (QoL) or cognition. Better functional outcomes have been suggested for lobar versus non-lobar ICH; few studies attempted finer topographic comparisons. This study highlights the need for improved reporting in ICH outcomes research, including a detailed description of hemorrhage location, reporting of the full range of functional outcome scales, and inclusion of cognitive and QoL outcomes.
Promoting blood circulation for removing blood stasis therapy for acute intracerebral hemorrhage: a systematic review and meta-analysis.
Li Hui-qin,Wei Jing-jing,Xia Wan,Li Ji-huang,Liu Ai-ju,Yin Su-bing,Wang Chen,Song Liang,Wang Yan,Zheng Guo-qing,Fan Ji-ping
Acta pharmacologica Sinica
AIM:To conduct a systematic review and meta-analysis to assess the current evidence available regarding the promoting blood circulation and removing blood stasis (PBCRBS) therapy for Chinese patients with acute intracerebral hemorrhage (ICH). METHODS:Six databases were searched from their inception to November 2013. The studies assessed in ≥ 4 domains with 'yes' were selected for detailed assessment and meta-analysis. The herbal compositions for PBCRBS therapy for acute ICH patients were also assessed. RESULTS:From the 6 databases, 292 studies claimed randomized-controlled clinical trials (RCTs). Nine studies with 798 individuals were assessed in ≥ 4 domains with 'yes' by using the Cochrane RoB tool. Meta-analysis showed that PBCRBS monotherapy and adjuvant therapy for acute ICH could improve the neurological function deficit, reduce the volume of hematoma and perihematomal edema, and lower the mortality rate and dependency. Moreover, there were fewer adverse effects when compared with Western conventional medication controls. Xueshuantong Injection and Fufang Danshen Injection, Buyang Huanwu Decoction and Liangxue Tongyu formula, and three herbs (danshen root, sanqi and leech) were the most commonly used Chinese herbal patent injections, herbal prescriptions and single herbs, respectively. CONCLUSION:Despite the apparently positive findings, it is premature to conclude that there is sufficient efficacy and safety of PBCRBS for ICH because of the high clinical heterogeneity of the included studies and small number of trials in the meta-analysis. Further large sample-sizes and rigorously designed RCTs are needed.
Neutrophil-lymphocyte ratio predicts the outcome of intracerebral hemorrhage: A meta-analysis.
Liu Shuo,Liu Xiaoqiang,Chen Shuying,Xiao Yingxiu,Zhuang Weiduan
BACKGROUND:The neutrophil-lymphocyte ratio (NLR) is increasingly recognized as a systemic inflammation factor. It has been used as a predictor for clinical outcomes in cancers. However, its relationship with intracerebral hemorrhage (ICH) is still disputed. We sought to evaluate the prognostic role of NLR in ICH. METHODS:We searched PubMed, Cochrane Library, Medline, and EMBASE for potentially relevant articles from inception to April 8, 2018. Efficacy outcomes included major disability at 90 days, short-term mortality or in-hospital mortality. Odds ratio (OR) with 95% confidence interval (95% CI) were pooled to assess the association between NLR and ICH. RESULTS:A total of 7 trials with 2176 patients were included in this meta-analysis. It revealed that higher NLR had a higher risk of major disability at 90 days (OR: 2.20; 95% CI: 1.27-3.81) and higher mortality at short-term (OR: 1.31; 95% CI: 1.02-1.68) in ICH; without statistically significant association with in-hospital mortality (OR: 1.02; 95% CI: 0.91-1.15). CONCLUSIONS:Our meta-analysis proved that high NLR was a predictor of major disability and mortality at short term in ICH patients, but not a predictor of in-hospital mortality.
Statin use in spontaneous intracerebral hemorrhage: a systematic review and meta-analysis.
Jung Jin-Man,Choi Jeong-Yoon,Kim Hyun Jung,Seo Woo-Keun
International journal of stroke : official journal of the International Stroke Society
BACKGROUND:Nonrandomized observational studies have been conducted to evaluate the effects of statins on clinical outcomes in patients with intracerebral hemorrhage. Several studies on the effects of statin administration in patients with intracerebral hemorrhage have been published recently, but the findings are inconsistent. AIM:To evaluate the effects of statins administered prior to hospital admission and during hospitalization on mortality and functional outcomes in patients with intracerebral hemorrhage. SUMMARY OF REVIEW:We searched for relevant literature using multiple comprehensive databases and performed a systematic review and meta-analysis. Sixteen studies met our selection criteria. Preintracerebral hemorrhage statin use was not associated with mortality (odds ratio: 0·90, 95% confidence interval: 0·63-1·28). However, patients who used statins prior to intracerebral hemorrhage had a decreased risk of mortality at three-months following symptom onset (odds ratio: 0·47, 95% confidence interval: 0·32-0·68) and an increased probability of good functional outcomes (odds ratio: 1·49, 95% confidence interval: 1·01-2·19), as compared with those who did not. In-hospital use of statins was associated with a low risk of mortality (odds ratio: 0·34, 95% confidence interval: 0·26-0·44) irrespective of preadmission statin use or postadmission time-points. Additionally, we were unable to pool the data on statin withdrawal because of differences in study methodologies. CONCLUSIONS:Although careful interpretation is necessary due to several study limitations, we have demonstrated that statin use in patients with intracerebral hemorrhage is likely associated with improved mortality and functional outcomes.
Efficacy of Statins in Cerebral Vasospasm, Mortality, and Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Shen Jianguo,Shen Jian,Zhu Kuncan,Zhou Haihang,Tian Heping,Yu Gongjie
BACKGROUND:Aneurysmal subarachnoid hemorrhage (aSAH) is an acute cerebrovascular disease with frequent cerebral vasospasm and delayed cerebral ischemia (DCI). The use of statins for patients with aSAH is controversial. The present study evaluated the efficacy of statins in aSAH-induced vasospasm, DCI, delayed ischemic neurological deficit (DIND), mortality, and other outcomes. METHODS:A literature search was performed in PubMed, EMBASE, and the Cochrane Library. English reports of patients with aSAH who had been treated with statins without combination were included. The outcomes, including cerebral vasospasm, DIND, DCI, mortality, disability, and creatine kinase/alanine aminotransferase/aspartic transaminase elevation, were extracted for meta-analysis. RESULTS:A total of 13 studies, with 776 versus 821 patients treated with statins versus placebo, were retained for the statistical meta-analysis. The results showed that statin administration significantly reduced the frequency of vasospasm (relative risk [RR], 0.76; 95% confidence interval [CI], 0.63-0.91; P = 0.003), DIND (RR, 0.76; 95% CI, 0.63-0.91; P = 0.003), vasospasm-DCI (RR, 0.49; 95% CI, 0.32-0.74; P = 0.0008), and mortality (RR, 0.73; 95% CI, 0.54-0.98; P = 0.03). Statins showed insignificant efficacy in the prevention of disability (RR, 0.92; 95% CI, 0.71-1.20), a neurological poor prognosis (RR, 0.75; 95% CI, 0.45-1.27), and creatine kinase/alanine aminotransferase/aspartic transaminase elevation (RR, 1.90; 95% CI, 0.55-6.50). CONCLUSIONS:Statins significantly reduced the incidence of vasospasm, DIND, DCI, and mortality in individuals with aSAH, suggesting its efficacy in aSAH.
Predictive Value of Cerebral Autoregulation Impairment for Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.
Yu Zhiyuan,Zheng Jun,Ma Lu,Li Hao,You Chao,Jiang Yan
OBJECTIVE:Delayed cerebral ischemia (DCI) happens in about 30% of patients with aneurysmal subarachnoid hemorrhage (SAH) and is related to higher mortality and disability. Some studies have shown cerebral autoregulation impairment can be a predictor of DCI in aneurysmal SAH. We conducted this meta-analysis to evaluate the predictive value of cerebral autoregulation impairment for DCI based on the current literature. METHODS:A systematic literature search was performed in PubMed and Embase. According to inclusion and exclusion criteria, 2 authors screened the records and extracted data from the included studies. Pooled sensitivity, specificity, and their 95% confidence intervals (CIs) were obtained. To investigate the overall accuracy, a summary receiver operating characteristic (SROC) curve was built and the area under SROC curve was calculated. Deeks' linear regression was used to assess the publication bias. All statistical analyses were performed with Stata 14.0. RESULTS:A total of 7 studies were finally included in this meta-analysis. The pooled sensitivity and specificity values of impaired cerebral autoregulation for DCI prediction were 0.79 (95% CI, 0.65-0.88) and 0.85 (95% CI, 0.615-0.96). Moreover, the area under the SROC curve of cerebral autoregulation impairment for DCI prediction was 0.87 (95% CI, 0.835-0.89). No obvious publication bias was found in Deeks' linear regression (P = 0.99). CONCLUSIONS:Cerebral autoregulation impairment can be a helpful predictor of DCI in aneurysmal SAH. Its accuracy for DCI prediction should be verified by more studies in the future.
Meta-Analysis of Predictive Significance of the Black Hole Sign for Hematoma Expansion in Intracerebral Hemorrhage.
Zheng Jun,Yu Zhiyuan,Guo Rui,Li Hao,You Chao,Ma Lu
OBJECTIVE:Hematoma expansion is related to unfavorable prognosis in intracerebral hemorrhage (ICH). The black hole sign is a novel marker on non-contrast computed tomography for predicting hematoma expansion. However, its predictive values are different in previous studies. Thus, this meta-analysis was conducted to evaluate the predictive significance of the black hole sign for hematoma expansion in ICH. METHODS:A systematic literature search was performed. Original researches on the association between the black hole sign and hematoma expansion in ICH were included. Sensitivity and specificity were pooled to assess the predictive accuracy. Summary receiver operating characteristics curve (SROC) was developed. Deeks' funnel plot asymmetry test was used to assess the publication bias. RESULTS:Five studies with a total of 1495 patients were included in this study. The pooled sensitivity and specificity of the black hole sign for predicting hematoma expansion were 0.30 and 0.91, respectively. The area under the curve was 0.78 in SROC curve. There was no significant publication bias. CONCLUSIONS:This meta-analysis shows that the black hole sign is a helpful imaging marker for predicting hematoma expansion in ICH. Although the black hole sign has a relatively low sensitivity, its specificity is relatively high.
Effect and Feasibility of Endoscopic Surgery in Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.
Yao Zhong,Hu Xin,You Chao,He Min
BACKGROUND:Spontaneous intracerebral hemorrhage remains a major cause of death and dependence. Endoscopic surgery (ES) is potential to improve outcomes, but a consensus on the superiority of ES has not been achieved. We conducted a systematic review to clarify the effect of ES in spontaneous intracerebral hemorrhage and compare it with other treatment options (craniotomy, conservation, and stereotactic aspiration [SA]). METHODS:We performed this review based on the Preferred Reporting Items for Systematic review and Meta-Analysis. The subgroup analyses were stratified by study type, location, hematoma volume, interval to treatment, follow-up time, and stereotactic frame assistance. RESULTS:A total of 18 studies were included containing 1213 patients, most of whom harbored a hematoma greater than 50 mL. Compared with craniotomy and conservation, ES significantly reduced the mortality (P < 0.0001), poor outcomes (P < 0.00001), rebleeding (P = 0.0009), and pneumonia (P < 0.00001). In the subgroup analyses, late surgery (<48 hours) benefited more from ES than early surgery (<24 hours). The study location, hematoma volume, and stereotactic frame assistance insignificantly influenced the therapeutic effect of ES. Comparing ES and SA, we found that differences in mortality, poor outcomes, and rebleeding were insignificant, but ES had a greater evacuation rate and SA had shorter operative times. CONCLUSIONS:ES achieves a better performance than craniotomy and conservation in terms of reducing mortality, dependence, and specific complications. Despite being similarly effective in improving functional outcomes, ES and SA have respective advantages. ES is a feasible alternation to craniotomy and conservation, and the comparison between ES and SA warrants further study.
Plasma homocysteine concentrations and risk of intracerebral hemorrhage: a systematic review and meta-analysis.
Zhou Zhike,Liang Yifan,Qu Huiling,Zhao Mei,Guo Feng,Zhao Chuansheng,Teng Weiyu
Intracerebral hemorrhage (ICH) has the highest mortality rate in all strokes. However, controversy still exists concerning the association between plasma homocysteine (Hcy) and ICH. A systematic review and meta-analysis was conducted using Pubmed, Embase, and Web of Science up to April 18, 2017. Standard mean difference (SMD) for mean differences of plasma Hcy levels with 95% confidence intervals (CI) was calculated. Seven studies including 667 ICH patients and 1821 ischemic stroke patients were identified for meta-analysis. Our results showed that Hcy levels in ICH patients were significantly higher than those in healthy controls (SMD = 0.59, 95% CI = 0.51-0.68, P < 0.001); no statistic differences were found in the comparisons of Hcy levels between ICH and ischemic stroke (SMD = -0.03, 95% CI = -0.13-0.06, P > 0.05); further subgroup analysis of ethnicity (Asians: SMD = 0.57, 95% CI = 0.48-0.66, P < 0.001; Caucasians: SMD = 0.77, 95% CI = 0.51-1.02, P < 0.001) and sample size (small samples: SMD = 0.55, 95% CI = 0.30-0.80, P < 0.001; large samples size: SMD = 0.60, 95% CI = 0.51-0.69, P < 0.001) in relation to Hcy levels between ICH and healthy controls did not change these results. In conclusion, Hcy level may be an aggravating factor in atherosclerosis, which is positively associated with high risk of ICH. Race-specific differences between Asians and Caucasians have no impact on the risk of ICH.
Association Between Circulating Copeptin Level and Mortality Risk in Patients with Intracerebral Hemorrhage: a Systemic Review and Meta-Analysis.
Zhang Ruoyu,Liu Jin,Zhang Ying,Liu Qiang,Li Tianlang,Cheng Lei
Copeptin has been identified as a biomarker of disease severity and is associated with mortality risk in several common diseases. This study sought to determine the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. PubMed, Web of Science, and Wanfang Medicine Database were searched for studies assessing the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. The pooled hazard ratio (HR) of mortality was calculated and presented with 95 % confidence interval (95 % CI). Data from 1332 intracerebral hemorrhage patients were derived from 9 studies. Meta-analysis showed that intracerebral hemorrhage patients with poor prognosis had much higher copeptin levels than those survivors (standardized mean difference = 1.68, 95 % CI 1.26-2.11, P < 0.00001). Meta-analysis of 8 studies with HRs showed that high circulating copeptin level was associated with higher risk of mortality in patients with intracerebral hemorrhage (HR = 2.42, 95 % CI 1.60-3.65, P < 0.0001). Meta-analysis of 6 studies with adjusted HRs showed that high circulating copeptin level was independently associated with higher risk of mortality in patients with intracerebral hemorrhage (HR = 1.67, 95 % CI 1.26-2.22, P = 0.0003). Our study suggests that there is an obvious association between circulating copeptin level and mortality in patients with intracerebral hemorrhage. High circulating copeptin level is independently associated with higher risk of mortality in patients with intracerebral hemorrhage.
Prognostic significance of leukoaraiosis in intracerebral hemorrhage: A meta-analysis.
Yu Zhiyuan,Zheng Jun,Guo Rui,Ma Lu,You Chao,Li Hao
Journal of the neurological sciences
BACKGROUND:Patients with intracerebral hemorrhage (ICH) have high disability and mortality. Leukoaraiosis refers to the diffuse abnormalities of white matter on neuroimaging, which has been suggested to be with poor outcome in patients with ICH. This meta-analysis was performed to summarize the current evidence on the prognostic significance of leukoaraiosis in ICH patients. METHODS:Databases were searched for published studies about leukoaraiosis and prognosis in patients with ICH. Data from eligible studies were extracted. Odds ratios (ORs) and their 95% confidence intervals (CIs) from each study were combined with DerSimonian-Laird method and random effect model for quantitative analysis. Begg's funnel plot was adopted to assess the publication bias. RESULTS:A total of nine studies with 4948 patients were finally included in this meta-analysis. Six studies reported functional outcome, two studies reported mortality, and another study reported both functional outcome and mortality. The meta-analysis showed that leukoaraiosis was significantly associated with worse functional outcome in patients with ICH (OR = 1.40, 95%CI 1.17-1.68, P < .001). In addition, leukoaraiosis was also significantly associated with higher mortality in patients with ICH (OR = 1.59, 95%CI 1.21-2.08, P = .001). CONCLUSIONS:Leukoaraiosis is significantly associated with both worse functional outcome and higher mortality in patients with ICH. Leukoaraiosis can be a useful imaging marker for predicting outcome in patients with ICH.
Antiplatelet Therapy After Spontaneous Intracerebral Hemorrhage and Functional Outcomes.
Murthy Santosh B,Biffi Alessandro,Falcone Guido J,Sansing Lauren H,Torres Lopez Victor,Navi Babak B,Roh David J,Mandava Pitchaiah,Hanley Daniel F,Ziai Wendy C,Kamel Hooman,Rosand Jonathan,Sheth Kevin N,
Background and Purpose- Observational data suggest that antiplatelet therapy after intracerebral hemorrhage (ICH) alleviates thromboembolic risk without increasing the risk of recurrent ICH. Given the paucity of data on the relationship between antiplatelet therapy after ICH and functional outcomes, we aimed to study this association in a multicenter cohort. Methods- We meta-analyzed data from (1) the Massachusetts General Hospital ICH registry (n=1854), (2) the Virtual International Stroke Trials Archive database (n=762), and (3) the Yale stroke registry (n=185). Our exposure was antiplatelet therapy after ICH, which was modeled as a time-varying covariate. Our primary outcomes were all-cause mortality and a composite of major disability or death (modified Rankin Scale score 4-6). We used Cox proportional regression analyses to estimate the hazard ratio of death or poor functional outcome as a function of antiplatelet therapy and random-effects meta-analysis to pool the estimated HRs across studies. Additional analyses stratified by hematoma location (lobar and deep ICH) were performed. Results- We included a total of 2801 ICH patients, of whom 288 (10.3%) were started on antiplatelet medications after ICH. Median times to antiplatelet therapy ranged from 7 to 39 days. Antiplatelet therapy after ICH was not associated with mortality (hazard ratio, 0.85; 95% CI, 0.66-1.09), or death or major disability (hazard ratio, 0.83; 95% CI, 0.59-1.16) compared with patients not started on antiplatelet therapy. Similar results were obtained in additional analyses stratified by hematoma location. Conclusions- Antiplatelet therapy after ICH appeared safe and was not associated with all-cause mortality or functional outcome, regardless of hematoma location. Randomized clinical trials are needed to determine the effects and harms of antiplatelet therapy after ICH.
Accuracy of swirl sign for predicting hematoma enlargement in intracerebral hemorrhage: a meta-analysis.
Yu Zhiyuan,Zheng Jun,He Maiyue,Guo Rui,Ma Lu,You Chao,Li Hao
Journal of the neurological sciences
BACKGROUND:Hematoma enlargement happens in about 30% patients with intracerebral hemorrhage, which is reported to be closely correlated with poor prognosis. Swirl sign has been reported to have correlation with hematoma enlargement. This meta-analysis analyzed the accuracy of swirl sign for predicting hematoma enlargement in intracerebral hemorrhage. METHODS:Five databases were searched for potentially eligible literature. Studies were included if they were about the predictive properties of swirl sign for hematoma enlargement in intracerebral hemorrhage. Sensitivity and specificity of swirl sign for hematoma enlargement prediction were pooled. Pooled positive and negative likelihood ratios were also calculated. RESULTS:Six studies with 2647 patients were finally included in meta-analysis. The pooled sensitivity and specificity of swirl sign were 0.45 (95%CI 0.32-0.59) and 0.79 (95%CI 0.73-0.84), respectively. The pooled positive likelihood ratio of swirl sign was 2.2 (95%CI 1.8-2.5). In contrast, the pooled negative likelihood ratio of swirl sign was 0.69 (95%CI 0.57-0.84). CONCLUSIONS:This meta-analysis suggests that swirl sign has the relatively high specificity for hematoma enlargement prediction in patients with intracerebral hemorrhage.
Local Fibrinolytic Therapy for Intraventricular Hemorrhage: A Meta-Analysis of Randomized Controlled trials.
Wang Deren,Liu Junfeng,Norton Casey,Liu Ming,Selim Magdy
BACKGROUND:The safety and efficacy of intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) are unclear. We aimed to determine these issues and to evaluate whether there are differences between recombinant tissue-plasminogen activator (rt-PA) and urokinase according to subgroup analyses. METHODS:A meta-analysis was undertaken of randomized controlled trials in patients with IVH that compared the administration of rt-PA or urokinase through extraventricular drainage (EVD) with normal saline through EVD or EVD placement alone. RESULTS:Six randomized controlled trials involving 607 patients with IVH were included; 2 trials investigated urokinase and 4 rt-PA. IVF reduced death from any cause at the end of follow-up (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47-0.83), which was driven mostly by rt-PA (RR 0.65, 95% CI 0.48-0.86). Urokinase did not reduce mortality (RR 0.30, 95% CI 0.06-1.53). However, rt-PA did not reduce the proportion of survivors with poor functional outcome (RR 1.36, 95% CI 1.04-1.77), or the composite endpoint of death and poor functional outcome (RR 0.96, 95% CI 0.83-1.11). IVF neither reduced the need for shunt placement (RR 1.06, 95% CI 0.75-1.49) nor increased ventriculitis (RR 0.57, 95% CI 0.35-0.93) and rebleeding (RR 1.65, 95% CI 0.79-3.45). CONCLUSIONS:Although the use of IVF in patients with IVH appears generally safe, its benefit is limited to a reduction in mortality at the expense of an increased number of survivors with moderately-severe to severe disability. Subgroup analyses do not suggest an advantage of IVF with urokinase over rt-PA.
Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF.
Charidimou Andreas,Karayiannis Christopher,Song Tae-Jin,Orken Dilek Necioglu,Thijs Vincent,Lemmens Robin,Kim Jinkwon,Goh Su Mei,Phan Thanh G,Soufan Cathy,Chandra Ronil V,Slater Lee-Anne,Haji Shamir,Mok Vincent,Horstmann Solveig,Leung Kam Tat,Kawamura Yuichiro,Sato Nobuyuki,Hasebe Naoyuki,Saito Tsukasa,Wong Lawrence K S,Soo Yannie,Veltkamp Roland,Flemming Kelly D,Imaizumi Toshio,Srikanth Velandai,Heo Ji Hoe,
OBJECTIVES:To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants. METHODS:This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models. RESULTS:We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19-6.01, = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients ( = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs ( = 0.001). There was no association between CMBs and recurrent ischemic stroke. CONCLUSIONS:The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies.
The relationship between low serum calcium level and intracerebral hemorrhage hematoma expansion: A protocol of systematic review and meta-analysis.
Sun Jian,Liu Wanjun,Zhu Rending,Wu Yao,Yang Liqi
BACKGROUND:To investigate the relationship between intracerebral hemorrhage hematoma expansion with low serum calcium level. METHODS:We will search the following electronic bibliographic databases: MEDLINE, Embase, PubMed, The Cochrane Library, and Web of Science. All sources have to be searched from the earliest date until May 1, 2019. The quality of the included studies will assess by 2 evaluation members according to the Cochrane Collaboration network standard or the Newcastle-Ottawa Scale. The included studies will analysis by using RevMan 5.3 software. RESULTS AND CONCLUSION:This will be the first systematic review and meta-analysis to evaluate the association of hematoma following intracerebral hemorrhage with hypocalcemia. The study will provide more reliable, evidence-based data for clinical decision making. PROSPERO REGISTRATION NUMBER:CRD42019135956.
Cortical superficial siderosis and bleeding risk in cerebral amyloid angiopathy: A meta-analysis.
Charidimou Andreas,Boulouis Gregoire,Greenberg Steven M,Viswanathan Anand
OBJECTIVE:To assess the association of cortical superficial siderosis (cSS) presence and extent with future bleeding risk in cerebral amyloid angiopathy (CAA). METHODS:This was a meta-analysis of clinical cohorts of symptomatic patients with CAA who had T2*-MRI at baseline and clinical follow-up for future intracerebral hemorrhage (ICH). We pooled data in a 2-stage meta-analysis using random effects models. Covariate-adjusted hazard ratios (adjHR) from multivariable Cox proportional hazard models were used. RESULTS:We included data from 6 eligible studies (n = 1,239). cSS pooled prevalence was 34% (95% confidence interval [CI] 26%-41%; 87.94%; < 0.001): focal cSS prevalence was 14% (95% CI 12%-16%; 6.75%; = 0.37), and disseminated cSS prevalence was 20% (95% CI 13%-26%; 90.39%; < 0.001). During a mean follow-up of 3.1 years (range 1-4 years), 162/1,239 patients experienced a symptomatic ICH-pooled incidence rate 6.9% per year (95% CI 3.9%-9.8% per year; 83%; < 0.001). ICH incidence rates per year according to cSS status were 3.9% (95% CI 1.7%-6.1%; 70%; = 0.018) for patients without cSS, 11.1% (95% CI 7%-15.2%; 56.8%; = 0.074) for cSS presence, 9.1% (95% CI 5.5%-12.8%; 0%; = 0.994) for focal cSS, and 12.5% (95% CI 5.3%-19.7%; 73.2%; = 0.011) for disseminated cSS. In adjusted pooled analysis, any cSS presence was independently associated with increased future ICH risk (adjHR 2.14; 95% CI 1.19-3.85; < 0.0001). Focal cSS was linked with ICH risk (adjHR 2.11; 95% CI 1.31-2.41; = 0.002), while disseminated cSS conferred the strongest bleeding risk (adjHR 4.28; 95% CI 2.91-6.30; < 0.0001). CONCLUSION:In patients with CAA, cSS presence and extent are the most important MRI prognostic risk factors for future ICH, likely useful in treatment planning. CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that in symptomatic CAA survivors with baseline T2*-MRI, cSS (particularly if disseminated, i.e., affecting >3 sulci) increases the risk of future ICH.
Impact of antiepileptic drugs for seizure prophylaxis on short and long-term functional outcomes in patients with acute intracerebral hemorrhage: A meta-analysis and systematic review.
Spoelhof Brian,Sanchez-Bautista Julian,Zorrilla-Vaca Andres,Kaplan Peter W,Farrokh Salia,Mirski Marek,Freund Brin,Rivera-Lara Lucia
PURPOSE:The purpose of this analysis is to assess the effect of antiepileptics (AEDs) on seizure prevention and short and long term functional outcomes in patients with acute intracerebral hemorrhage. METHOD:The meta-analysis was conducted using the PRISMA guidelines. A literature search was performed of the PubMed, the Cochrane Library, and EMBASE databases. Search terms included "Anticonvulsants", "Intracerebral Hemorrhage", and related subject headings. Articles were screened and included if they were full-text and in English. Articles that did not perform multivariate regression were not included. Overall effect size was evaluated with forest plots and publication bias was assessed with the Begg's and Egger's tests. RESULTS:A total of 3912 articles were identified during the initial review. After screening, 54 articles remained for full review and 6 articles were included in the final analysis. No significant association between the use of AEDs after ICH and functional outcome (OR 1.53 [95%CI: 0.81-2.88] P = 0.18, I = 81.7%). Only one study evaluated the effect AEDs had in preventing post-ICH seizures. CONCLUSIONS:The use of prophylactic AEDs was not associated with improved short and long outcomes after acute ICH. This analysis supports the 2015 AHA/ASA recommendation against prophylactic AEDs (class III; level of evidence b).
Association Between Blood Glucose and Functional Outcome in Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.
Zheng Jun,Yu Zhiyuan,Ma Lu,Guo Rui,Lin Sen,You Chao,Li Hao
BACKGROUND:Intracerebral hemorrhage (ICH) is a devastating subtype of stroke. Patients with ICH have poor functional outcomes. The association between blood glucose level and functional outcome in ICH remains unclear. This systematic review and meta-analysis aimed to investigate the association between blood glucose level and functional outcomes in patients with ICH. METHODS:Literature was searched systemically in PubMed, EMBASE, Web of Science, and Cochrane Library. Published cohort studies evaluating the association between blood glucose and functional outcome in patients with ICH were included. This meta-analysis was performed using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:A total of 16 studies were included in our meta-analysis. Our data show that hyperglycemia defined by cutoff values was significantly associated with unfavorable functional outcome (OR, 1.80; 95% CI, 1.36-2.39; P < 0.001). Our analysis also suggested a significant association between increased blood glucose levels and functional outcomes (OR, 1.05; 95% CI, 1.03-1.07; P < 0.001). CONCLUSIONS:High blood glucose level is significantly associated with poor functional outcome in ICH. Further studies with larger sample sizes, more time points, and longer follow-up times are necessary to confirm this association.
Prognostic impact of leukocytosis in intracerebral hemorrhage: A PRISMA-compliant systematic review and meta-analysis.
Yu Zhiyuan,Zheng Jun,Guo Rui,Ma Lu,You Chao,Li Hao
BACKGROUND:Intracerebral hemorrhage (ICH) is correlated with high rate of death and poor outcome. Leukocytes participate in secondary brain injury in ICH. It is still not clear that whether leukocytosis can predict outcome in ICH. This study was performed to summarize that current evidences about the association between baseline leukocytosis and outcome in ICH patients in a systematic review and meta-analysis. METHODS:Published studies were searched in 5 databases. Original studies about association between baseline leukocytosis and outcome in ICH were included. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were achieved to evaluate the association between leukocytosis and prognosis. RESULTS:A total of 19 eligible studies with 6417 patients were analyzed in this study. Meta-analysis showed baseline leukocyte count increase was significantly associated with worse overall (OR = 1.13, 95% CI 1.05-1.21, P = .001), short-term (OR = 1.20, 95% CI 1.05-1.38, P = .009), and long-term functional outcome (OR = 1.12, 95% CI 1.04-1.20, P = .004). Baseline leukocytosis defined by cut-off values had significant association with worse overall functional outcome (OR = 1.95, 95% CI 1.01-3.76, P = .046). Baseline leukocyte count increase was significantly associated with higher overall (OR = 1.10, 95% CI 1.02-1.18, P = .011) and long-term mortality (OR = 1.12, 95% CI 1.03-1.22, P = .007). Baseline leukocytosis defined by cut-off values was significantly associated with higher overall (OR = 1.67, 95% CI 1.23-2.27, P = .001) and short-term mortality (OR = 1.74, 95% CI 1.12-2.70, P = .014). CONCLUSION:Baseline leukocytosis could be helpful in predicting prognosis in ICH patients. However, its prognostic value should be verified by further studies.
Intracranial Hypertension After Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis of Prevalence and Mortality Rate.
Godoy Daniel Agustín,Núñez-Patiño Rafael A,Zorrilla-Vaca Andres,Ziai Wendy C,Hemphill J Claude
The objective of this study was to determine the prevalence of intracranial hypertension (IHT) and the associated mortality rate in patients who suffered from primary intracerebral hemorrhage (ICH). A secondary objective was to assess predisposing factors to IHT development. We conducted a systematic literature search of major electronic databases (MEDLINE, EMBASE, and Cochrane Library), for studies that assessed intracranial pressure (ICP) monitoring in patients with acute ICH. Study level and outcome measures were extracted. The meta-analysis was performed using a random-effects model. A total of six studies comprising 381 patients were pooled to estimate the overall prevalence of any episode of IHT (ICP > 20 mmHg) after ICH. The pooled prevalence rate for any episode of IHT after ICH was 67% (95% CI 51-84%). Four studies comprising 239 patients were pooled in order to estimate the overall mortality rate associated with IHT. Pooled mortality rate was 50% (95% CI 24-76%). For both outcomes, heterogeneity was statistically significant, and risk of bias was nonsignificant. Reported variables correlated significantly with increased ICP were lower Glasgow Coma Scale score at admission, midline shift, hemorrhage volume, and hydrocephalus. The prevalence and mortality rates associated with IHT after ICH are high and may be underestimated. Predicting factors for the development of IHT reflect the magnitude of the primary injury. However, the results of present meta-analysis should be interpreted with caution due to methodological limitations such as selection bias of patients who had ICP monitoring, and lack of standardized IHT definition.
Performance of blend sign in predicting hematoma expansion in intracerebral hemorrhage: A meta-analysis.
Yu Zhiyuan,Zheng Jun,Guo Rui,Ma Lu,Li Mou,Wang Xiaoze,Lin Sen,Li Hao,You Chao
Clinical neurology and neurosurgery
OBJECTIVES:Hematoma expansion is independently associated with poor outcome in intracerebral hemorrhage (ICH). Blend sign is a simple predictor for hematoma expansion on non-contrast computed tomography. However, its accuracy for predicting hematoma expansion is inconsistent in previous studies. This meta-analysis is aimed to systematically assess the performance of blend sign in predicting hematoma expansion in ICH. MATERIAL AND METHODS:A systematic literature search was conducted. Original studies about predictive accuracy of blend sign for hematoma expansion in ICH were included. Pooled sensitivity, specificity, positive and negative likelihood ratios were calculated. Summary receiver operating characteristics curve was constructed. Publication bias was assessed by Deeks' funnel plot asymmetry test. RESULTS:A total of 5 studies with 2248 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive and negative likelihood ratios of blend sign for predicting hematoma expansion were 0.28, 0.92, 3.4 and 0.78, respectively. The area under the curve (AUC) was 0.85. No significant publication bias was found. CONCLUSION:This meta-analysis demonstrates that blend sign is a useful predictor with high specificity for hematoma expansion in ICH. Further studies with larger sample size are still necessary to verify the accuracy of blend sign for predicting hematoma expansion.
Tranexamic Acid in Cerebral Hemorrhage: A Meta-Analysis and Systematic Review.
Hu Wenyu,Xin Yanguo,Chen Xin,Song Zhuyin,He Zhiyi,Zhao Yinan
BACKGROUND:Tranexamic acid functions as an antifibrinolytic medication and is widely used to treat or prevent excessive blood loss in menorrhagia and during the perioperative period. The efficacy of tranexamic acid in reducing mortaligy and disability, and the occurrence of complications during treatment of cerebral hemorrhage remains controversial. OBJECTIVE:The objective of this systematic literature review and meta-analysis was to evaluate the efficacy and safety of tranexamic acid in patients with cerebral hemorrhage, aiming to improve the evidence-based medical knowledge of treatment options for such patients. METHODS:A systematic literature search was performed in English through 31 August 2018, with two reviewers independently extracting data and assessing risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias. RESULTS:In total, 14 randomized controlled trials with 4703 participants were included in the meta-analysis. Tranexamic acid did not improve mortality by day 90 (odds ratio (OR) 0.99; 95% confidence interval (CI) 0.84-1.18; p = 0.95) or day 180 (OR 1.01; 95% CI 0.51-2.01; p = 0.98) or overall death endpoints of different follow-up times (OR 0.82; 95% CI 0.62-1.08; p = 0.15), which was supported by sensitivity analysis of studies published during or after 2000 (OR 0.92; 95% CI 0.77-1.09; p = 0.33). A lower incidence of hematoma expansion (OR 0.54; 95% CI 0.37-0.80; p = 0.002) and less change in volume from baseline (mean difference (MD) - 1.98; 95% CI - 3.00 to - 0.97; p = 0.0001) were observed, but no change was seen in poor functional outcomes (OR 0.95; 95% CI 0.79-1.14; p = 0.55) in the tranexamic acid group. The risk of hydrocephalus (OR 1.21; 95% CI 0.90-1.62; p = 0.21), ischemic stroke (OR 1.43; 95% CI 0.87-2.34; p = 0.16), deep vein thrombosis (OR 1.25; 95% CI 0.75-2.08; p = 0.40), and pulmonary embolism (OR 0.97; 95% CI 0.59-1.58; p = 0.89) was similar, whereas the risk of combined ischemic events increased in the tranexamic acid group (OR 1.47; 95% CI 1.07-2.01; p = 0.02). CONCLUSIONS:Treatment with tranexamic acid could reduce rebleeding and hematoma expansion in cerebral hemorrhage without an increase in single ischemic adverse events, but it could increase the risk of combined ischemic events; however, the lack of improvement in mortality and the poor functional outcomes limit the value of clinical application. These findings indicate that the most pertinent issue is the risk-to-benefit ratio with tranexamic acid treatment in cerebral hemorrhage.
Efficacy and safety of anticoagulants in the prevention of venous thromboembolism in patients with acute cerebral hemorrhage: a meta-analysis of controlled studies.
Paciaroni M,Agnelli G,Venti M,Alberti A,Acciarresi M,Caso V
Journal of thrombosis and haemostasis : JTH
AIM:The role of anticoagulants for the prevention of venous thromboembolism in acute hemorrhagic stroke is uncertain. We performed an updated meta-analysis of studies to obtain the best estimates of the efficacy and safety of anticoagulants for the prevention of venous thromboembolism in patients with acute hemorrhagic stroke. METHODS:Using electronic and manual searches of the literature, we identified randomized and non-randomized studies comparing anticoagulants (unfractionated heparin or low-molecular-weight heparin or heparinoids) with treatments other than anticoagulants (elastic stockings, intermittent pneumatic compression or placebo) in patients with acute hemorrhagic stroke. Study outcomes included symptomatic and asymptomatic deep venous thrombosis (DVT), symptomatic and asymptomatic pulmonary embolism (PE), any hematoma enlargement or death. Risk ratios (RRs) for individual outcomes were calculated for each study and data from all studies were pooled using the Mantel-Haenszel method. RESULTS:Four studies (two randomized) involving 1000 patients with acute hemorrhagic stroke met the criteria for inclusion in this meta-analysis. Compared with other treatments, anticoagulants were associated with a significant reduction in PE (1.7% vs. 2.9%; RR, 0.37; 95% CI, 0.17-0.80; P = 0.01), a DVT rate of 4.2% compared with 3.3% (RR, 0.77; 95% CI, 0.44-1.34; P = 0.36), an increase in any hematoma enlargement (8.0% vs. 4.0%; RR, 1.42; 95% CI, 0.57-3.53; P = 0.45), and a non-significant reduction in mortality (16.1% vs. 20.9%; RR, 0.76; 95% CI, 0.57-1.03; P = 0.07). CONCLUSIONS:Our findings indicate that in patients with hemorrhagic stroke, early anticoagulation is associated with a significant reduction in PE and a non-significant reduction in mortality, with the trade-off of a non-significant increase in hematoma enlargement. These results must be taken with caution and should encourage the assessment of the clinical benefit of antithrombotic prophylaxis in patients with cerebral bleeding by properly designed clinical trials.
Outcomes of intraparenchymal hemorrhage after direct oral anticoagulant or vitamin K antagonist therapy: A systematic review and meta-analysis.
DiRisio Aislyn C,Harary Maya,Muskens Ivo S,Yunusa Ismaeel,Gormley William B,Aglio Linda S,Smith Timothy R,Connors Jean M,Mekary Rania A,Broekman Marike L D
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
Direct Oral Anticoagulants (DOAC) are increasingly used as an alternative to vitamin-K antagonists (VKA) for anticoagulation and have shown lower rates of intracranial hemorrhage; however, there is disagreement in the literature over the outcomes of the intraparenchymal hemorrhages (IPH) associated with DOACs, and clinical concern regarding the lack of standardized reversal strategies for DOACs. Thus, the aim of this meta-analysis was to compare mortality, hematoma volume, and risk of hematoma expansion in patients who developed an IPH on DOACs versus VKA. A systematic review of the literature was conducted in accordance with the PRISMA guidelines. Studies were selected that reported on mortality, hematoma expansion, and hematoma volume in DOAC-associated IPH. Pooled risk ratios (RR) were calculated for mortality and hematoma expansion and pooled mean difference (MD) was calculated for hematoma volume (ml) using random-effect models. 15 studies reporting on 1238 patients were included in the systematic review. Eleven of these compared DOAC-IPH to VKA-IPH and were pooled quantitatively. DOAC-IPH was not associated with increased mortality risk (RR: 0.95, 95%-CI: 0.72 -1.27) or increased hematoma expansion risk (RR: 0.92; 95%-CI: 0.75-1.12) compared to VKA-IPH. The hematoma volume of DOAC- IPH was statistically significantly smaller than VKA-IPH (MD: -12.14 ml; 95%-CI: -15.38; -8.89). In conclusion, DOAC-IPH was not associated with increased mortality or hematoma expansion compared to VKA-IPH and may be associated with a smaller hematoma volume.
Lipid Lowering Therapy, Low-Density Lipoprotein Level and Risk of Intracerebral Hemorrhage - A Meta-Analysis.
Judge Conor,Ruttledge Sarah,Costello Maria,Murphy Robert,Loughlin Elaine,Alvarez-Iglesias Alberto,Ferguson John,Gorey Sarah,Nolan Aoife,Canavan Michelle,O'Halloran Martin,O'Donnell Martin J
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND:The association of lipid lowering therapy and intracerebral hemorrhage risk is controversial. METHODS:We performed a cumulative meta-analysis of lipid lowering trials that reported intracerebral hemorrhage. Statin, fibrate, ezetimibe, PCSK9, and CETP trials were included. We explored whether the association of lipid lowering therapy and risk of intracerebral hemorrhage may vary by baseline low-density lipoprotein (LDL) level, mean change in LDL or baseline cardiovascular risk of population. RESULTS:Among 39 trials (287,651 participants), lipid lowering therapy was not associated with a statistically significant increased risk of intracerebral hemorrhage (ICH) in primary and secondary prevention trials combined (odds ratio [OR], 1.12; 95% confidence interval [CI], .98-1.28). Lipid lowering was associated with an increased risk of ICH in secondary prevention trials (OR, 1.18; 95% CI, 1.00-1.38), but not in primary prevention trials (OR, 1.01; 95% CI, .78-1.30), but the test for interaction was not significant (P for interaction = .31). Meta-regression of baseline LDL or difference in LDL reduction between active and control did not explain significant heterogeneity between studies for ICH risk. Of 1000 individuals treated for 1 year for secondary prevention, we estimated 9.17 (95% CI, 5.78-12.66) fewer ischemic strokes and .48 (95% CI, .06-1.02) more ICH, and a net reduction of 8.69 in all stroke per 1000 person-years. CONCLUSIONS:The benefits of lipid lowering therapy in prevention of ischemic stroke greatly exceed the risk of ICH. Concern about ICH should not discourage stroke clinicians from prescribing lipid lowering therapy for secondary prevention of ischemic stroke.
Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: A meta-analysis.
Charidimou Andreas,Imaizumi Toshio,Moulin Solene,Biffi Alexandro,Samarasekera Neshika,Yakushiji Yusuke,Peeters Andre,Vandermeeren Yves,Laloux Patrice,Baron Jean-Claude,Hernandez-Guillamon Mar,Montaner Joan,Casolla Barbara,Gregoire Simone M,Kang Dong-Wha,Kim Jong S,Naka H,Smith Eric E,Viswanathan Anand,Jäger Hans R,Al-Shahi Salman Rustam,Greenberg Steven M,Cordonnier Charlotte,Werring David J
OBJECTIVE:We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH survivors, stratified by the presence, distribution, and number of cerebral microbleeds (CMBs) on MRI (i.e., the presumed causal underlying small vessel disease and its severity). METHODS:This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We estimated annualized recurrent symptomatic ICH rates for each study and compared pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed etiology based on CMB distribution (strictly lobar CMBs related to probable or possible cerebral amyloid angiopathy [CAA] vs non-CAA) and burden (1, 2-4, 5-10, and >10 CMBs), using random effects models. RESULTS:We pooled data from 10 studies including 1,306 patients: 325 with CAA-related and 981 CAA-unrelated ICH. The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH (7.4%, 95% confidence interval [CI] 3.2-12.6 vs 1.1%, 95% CI 0.5-1.7 per year, respectively; = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none) were associated with ICH recurrence during follow-up (range 1-3 years): OR 3.1 (95% CI 1.4-6.8; = 0.006), 4.3 (95% CI 1.8-10.3; = 0.001), and 3.4 (95% CI 1.4-8.3; = 0.007) for 2-4, 5-10, and >10 CMBs, respectively. In CAA-unrelated ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95% CI 2.1-15; = 0.001). The presence of 1 CMB (versus none) was not associated with recurrent ICH in CAA-related or CAA-unrelated cohorts. CONCLUSIONS:CMB burden and distribution on MRI identify subgroups of ICH survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials.
Pre-Intracerebral Hemorrhage and In-Hospital Statin Use in Intracerebral Hemorrhage: A Systematic Review and Meta-analysis.
Lei Chunyan,Chen Tao,Chen Chun,Ling Yifan
BACKGROUND:The association between pre-intracerebral hemorrhage (ICH) statin use and clinical outcomes after intracerebral hemorrhage (ICH) is still conflicting. Recently, some studies investigating the effects of in-hospital statin use after the onset of ICH have been published. To provide a more complete picture of the clinical effects of statin use in ICH, we performed a systematic review to examine whether statin use influences clinical outcomes. METHODS:We conducted a systematic review of literature in the Cochrane Library, MEDLINE, EMBASE, and the China National Knowledge Infrastructure database. RESULTS:Twenty-one studies were included in our systematic review. Meta-analysis of 12 studies suggested that pre-ICH statins use did not significantly decrease mortality when aggregated across all time points tested-that is, in-hospital or at 30 or 90 days (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.70-1.03). Meta-analysis of 7 studies suggested that pre-ICH statins use did not significantly affect poor functional outcomes, defined as a modified Rankin Scale (mRS) score of 3-6 (OR, 0.93; 95% CI, 0.72-1.18) or mRS score of 4-6 (OR, 0.92; 95% CI, 0.60-1.40). Meta-analysis of 7 studies suggested that in-hospital statin use significantly decreased mortality when aggregated across all time points tested (OR, 0.37; 95% CI, 0.28-0.50). Statin discontinuation was independently associated with poor clinical outcome. CONCLUSIONS:The patients with pre-ICH statin use did not improve clinical outcomes. However, in-hospital statin use can significantly decrease mortality after ICH. In-hospital statin therapy might be beneficial for patients with ICH.
Imaging features of intracerebral hemorrhage with cerebral amyloid angiopathy: Systematic review and meta-analysis.
Samarasekera Neshika,Rodrigues Mark Alexander,Toh Pheng Shiew,Al-Shahi Salman
BACKGROUND:We sought to summarize Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) features of intracerebral hemorrhage (ICH) associated with cerebral amyloid angiopathy (CAA) in published observational radio-pathological studies. METHODS:In November 2016, two authors searched OVID Medline (1946-), Embase (1974-) and relevant bibliographies for studies of imaging features of lobar or cerebellar ICH with pathologically proven CAA ("CAA-associated ICH"). Two authors assessed studies' diagnostic test accuracy methodology and independently extracted data. RESULTS:We identified 22 studies (21 cases series and one cross-sectional study with controls) of CT features in 297 adults, two cross-sectional studies of MRI features in 81 adults and one study which reported both CT and MRI features in 22 adults. Methods of CAA assessment varied, and rating of imaging features was not masked to pathology. The most frequently reported CT features of CAA-associated ICH in 21 case series were: subarachnoid extension (pooled proportion 82%, 95% CI 69-93%, I2 = 51%, 12 studies) and an irregular ICH border (64%, 95% CI 32-91%, I2 = 85%, five studies). CAA-associated ICH was more likely to be multiple on CT than non-CAA ICH in one cross-sectional study (CAA-associated ICH 7/41 vs. non-CAA ICH 0/42; χ2 = 7.8, p = 0.005). Superficial siderosis on MRI was present in 52% of CAA-associated ICH (95% CI 39-65%, I2 = 35%, 3 studies). CONCLUSIONS:Subarachnoid extension and an irregular ICH border are common imaging features of CAA-associated ICH, but methodologically rigorous diagnostic test accuracy studies are required to determine the sensitivity and specificity of these features.
Association Between Baseline Serum Ferritin and Short-term Outcome of Intracerebral Hemorrhage: A Meta-Analysis.
Zhang Mijuan,Li Wei,Wang Tao,Zhang Qian
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND:Intracerebral hemorrhage is a devastating disease. In recent years, the association of between baseline serum ferritin and prognosis of intracerebral hemorrhage is an interesting issue. Although some of the studies have shown that baseline serum ferritin can predict the prognosis of intracerebral hemorrhage, there is no clear evidence that baseline serum ferritin can be used as an independent predictor of intracerebral hemorrhage. METHODS:Electronic databases through November 2018 were searched to identify relevant studies that examined association between baseline serum ferritin and prognosis of intracerebral hemorrhage. RESULTS:We found 7 eligible studies that included 411 participants. Our results showed that among them, 216 patients with intracerebral hemorrhage of poorer functional outcome were associated with elevated serum ferritin at admission. The results of 7 literature meta-analysis showed that intracerebral hemorrhage (ICH) patients with favorable shot-term functional outcome had lower baseline serum ferritin levels, with significant mean differences of -70.85 (95% confidence intervals -134.26, -7.43). CONCLUSIONS:This meta-analysis showed that baseline serum ferritin level at admission may predict the short-term prognosis of patients with ICH, and may provide a new target for intracerebral hemorrhage therapy.
Angong Niuhuang Pill as adjuvant therapy for treating acute cerebral infarction and intracerebral hemorrhage: A meta-analysis of randomized controlled trials.
Liu Hanwei,Yan Yan,Pang Pengfei,Mao Junjie,Hu Xiaojun,Li Dan,Zhou Bin,Shan Hong
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Angong Niuhuang Pill (ANP) is a well-known traditional Chinese patent medicine. This meta-analysis aimed to evaluate the efficacy and safety of ANP as an adjuvant therapy in patients with acute cerebral infarction (ACI) and acute intracerebral hemorrhage (AIH). MATERIALS AND METHODS:We performed a literature search in Embase, Pubmed, Cochrane Library, CNKI, Wanfang, and VIP database from their inceptions to April 2018. Randomized controlled trials evaluating ANP as an adjuvant therapy for acute stroke were selected. Risk ratio (RR) or weighted mean difference (WMD) with their 95% confidence interval (CI) was calculated between with and without ANP therapy. RESULTS:Eighteen trials involving 1,601 patients were identified and analyzed. Meta-analysis showed that ANP plus usual treatment significantly improved the total response rate in patients with ACI (RR 1.27; 95% CI 1.14-1.41) and AIH (RR 1.26; 95% CI 1.14-1.38) compared with the usual treatment alone. Adjuvant treatment with ANP also significantly reduced the neurologic deficit score in patients with ACI (WMD -3.64; 95% CI -4.97 to - 2.31) and AIH (WMD -3.52; 95% CI -5.51 to -1.54). Moreover, ANP significantly improved the Glasgow Coma Scale in patients with ACI (WMD 1.18; 95% CI 0.79-1.56) and AIH (WMD 2.28; 95% CI 1.37-3.19). CONCLUSIONS:Adjuvant treatment with ANP appears to improve the total response rate and neurologic deficit score in patients with ACI and AIH. More well-designed trials are required due to the suboptimal methodological quality of the included trials.
Leukoaraiosis, Cerebral Hemorrhage, and Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke: A Meta-Analysis (v1).
Charidimou Andreas,Pasi Marco,Fiorelli Marco,Shams Sara,von Kummer Rüdiger,Pantoni Leonardo,Rost Natalia
BACKGROUND AND PURPOSE:We performed a meta-analysis to assess whether leukoaraiosis on brain computed tomographic scans of acute ischemic stroke patients treated with intravenous thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome at 3 to 6 months after stroke, or both. METHODS:We searched PubMed and pooled relevant data in meta-analyses using random effects models. Using odds ratios (OR), we quantified the strength of association between the presence and severity of leukoaraiosis and post-thrombolysis sICH or 3- to 6-month modified Rankin Score >2. RESULTS:Eleven eligible studies (n=7194) were pooled in meta-analysis. The risk of sICH was higher in patients with leukoaraiosis (OR, 1.55; 95% confidence interval [CI], 1.17-2.06; P=0.002) and severe leukoaraiosis (OR, 2.53; 95% CI, 1.92-3.34; P<0.0001) compared with patients without leukoaraiosis. Leukoaraiosis was an independent predictor of sICH in 6 included studies (n=4976; adjusted OR, 1.75; 95% CI, 1.35-2.27; P<0.0001). OR for leukoaraiosis and poor 3- to 6-month outcome was 2.02 (95% CI, 1.54-2.65; P<0.0001), with significant statistical heterogeneity (I(2), 75.7%; P=0.002). In adjusted analyses, leukoaraiosis was an independent predictor of poor outcome (n=3688; adjusted OR, 1.61; 95% CI, 1.44-1.79; P<0.0001). In post hoc analyses, including only leukoaraiosis patients in randomized controlled trials (IST-3 [third International Stroke Trial], NINDS [National Institute of Neurological Disorders and Stroke], ECASS-1-2 [European Cooperative Acute Stroke Study]; n=2234), tissue-type plasminogen activator versus control was associated with higher sICH risk (OR, 5.50; 95% CI, 2.49-12.13), but lower poor outcome risk (OR, 0.75; 95% CI, 0.60-0.95). CONCLUSIONS:Leukoaraiosis might increase post-intravenous thrombolysis sICH risk and poor outcome poststroke. Despite increased sICH risk, intravenous tissue-type plasminogen activator treatment has net clinical benefit in patients with leukoaraiosis. Given the risk of bias/confounding, these results should be considered hypothesis-generating and do not justify withholding intravenous thrombolysis.
Cortical superficial siderosis and recurrent intracerebral hemorrhage risk in cerebral amyloid angiopathy: Large prospective cohort and preliminary meta-analysis.
Charidimou Andreas,Boulouis Gregoire,Roongpiboonsopit Duangnapa,Xiong Li,Pasi Marco,Schwab Kristin M,Rosand Jonathan,Gurol M Edip,Greenberg Steven M,Viswanathan Anand
International journal of stroke : official journal of the International Stroke Society
BACKGROUND:We aimed to investigate cortical superficial siderosis as an MRI predictor of lobar intracerebral hemorrhage (ICH) recurrence risk in cerebral amyloid angiopathy (CAA), in a large prospective MRI cohort and a systematic review. METHODS:We analyzed a single-center MRI prospective cohort of consecutive CAA-related ICH survivors. Using Kaplan-Meier and Cox regression analyses, we investigated cortical superficial siderosis and ICH risk, adjusting for known confounders. We pooled data with eligible published cohorts in a two-stage meta-analysis using random effects models. Covariate-adjusted hazard rations (adj-HR) from pre-specified multivariable Cox proportional hazard models were used. RESULTS:The cohort included 240 CAA-ICH survivors (cortical superficial siderosis prevalence: 36%). During a median follow-up of 2.6 years (IQR: 0.9-5.1 years) recurrent ICH occurred in 58 patients (24%). In prespecified multivariable Cox regression models, cortical superficial siderosis presence and disseminated cortical superficial siderosis were independent predictors of increased symptomatic ICH risk at follow-up (HR: 2.26; 95% CI: 1.31-3.87, p = 0.003 and HR: 3.59; 95% CI: 1.96-6.57, p < 0.0001, respectively). Three cohorts including 443 CAA-ICH patients in total were eligible for meta-analysis. During a mean follow-up of 2.5 years (range: 2-3 years) 92 patients experienced recurrent ICH (pooled risk ratio: 6.9% per year, 95% CI: 4.2%-9.7% per year). In adjusted pooled analysis, any cortical superficial siderosis and disseminated cortical superficial siderosis were the only independent predictors associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95% CI: 1.5-3.7; p < 0.0001, and adj-HR: 4.4; 95% CI: 2-9.9; p < 0.0001, respectively). CONCLUSIONS:In CAA-ICH patients, cortical superficial siderosis presence and extent are the most important MRI prognostic risk factors for lobar ICH recurrence. These results can help guide clinical decision making in patients with CAA.
How Should We Lower Blood Pressure after Cerebral Hemorrhage? A Systematic Review and Meta-Analysis.
Lattanzi Simona,Cagnetti Claudia,Provinciali Leandro,Silvestrini Mauro
Cerebrovascular diseases (Basel, Switzerland)
BACKGROUND:The optimal treatment of high blood pressure (BP) after acute intra-cerebral hemorrhage (ICH) is controversial. SUMMARY:The aim of the study was to evaluate the safety and efficacy of early intensive vs. conservative BP lowering treatment in patients with ICH. Randomized controlled trials with active and control groups receiving intensive and conservative BP lowering treatments were identified. The following outcomes were assessed: 3-month mortality and combined death or major disability, 24-h hematoma growth, early neurological deterioration, occurrence of hypotension, severe hypotension, and serious treatment-emergent adverse events. Five trials were included involving 4,350 participants, 2,162 and 2,188 for intensive and conservative treatment groups, respectively. The pooled risk ratio of 3-month death or major disability was 0.96 (0.91-1.01) and the weighted mean difference in absolute hematoma growth was -1.53 (95% CI -2.94 to -0.12) mL in the intensive compared to conservative BP-lowering. There were no differences across the treatments in the incidence rates of 3-month mortality, early neurological deterioration, hypotension, and treatment-related adverse effects other than renal events. Key Messages: The early intensive anti-hypertensive treatment was overall safe and reduced the hematoma expansion in patients presenting with acute-onset spontaneous ICH and high BP levels.
Original Intracerebral Hemorrhage Score for the Prediction of Short-Term Mortality in Cerebral Hemorrhage: Systematic Review and Meta-Analysis.
Gregório Tiago,Pipa Sara,Cavaleiro Pedro,Atanásio Gabriel,Albuquerque Inês,Castro Chaves Paulo,Azevedo Luís
Critical care medicine
OBJECTIVES:To systematically assess the discrimination and calibration of the Intracerebral Hemorrhage score for prediction of short-term mortality in intracerebral hemorrhage patients and to study its determinants using heterogeneity analysis. DATA SOURCES:PubMed, ISI Web of Knowledge, Scopus, and CENTRAL from inception to September 15, 2018. STUDY SELECTION:Adult studies validating the Intracerebral Hemorrhage score for mortality prediction in nontraumatic intracerebral hemorrhage at 1 month/discharge or sooner. DATA EXTRACTION:Data were collected on the following aspects of study design: population studied, level of care, timing of outcome measurement, mean study year, and mean cohort Intracerebral Hemorrhage score. The summary measures of interest were discrimination as assessed by the C-statistic and calibration as assessed by the standardized mortality ratio (observed:expected mortality ratio). Random effect models were used to pool both measures. Heterogeneity was measured using the I statistic and explored using subgroup analysis and meta-regression. DATA SYNTHESIS:Fifty-five studies provided data on discrimination, and 35 studies provided data on calibration. Overall, the Intracerebral Hemorrhage score discriminated well (pooled C-statistic 0.84; 95% CI, 0.82-0.85) but overestimated mortality (pooled observed:expected mortality ratio = 0.87; 95% CI, 0.78-0.97), with high heterogeneity for both estimates (I 80% and 84%, respectively). Discrimination was affected by study mean Intracerebral Hemorrhage score (β = -0.05), and calibration was affected by disease severity, with the score overestimating mortality for patients with an Intracerebral Hemorrhage score greater than 3 (observed:expected mortality ratio = 0.84; 95% CI, 0.78-0.91). Mortality rates were reproducible across cohorts for patients with an Intracerebral Hemorrhage score 0-1 (I = 15%). CONCLUSIONS:The Intracerebral Hemorrhage score is a valid clinical prediction rule for short-term mortality in intracerebral hemorrhage patients but discriminated mortality worse in more severe cohorts. It also overestimated mortality in the highest Intracerebral Hemorrhage score patients, with significant inconsistency between cohorts. These results suggest that mortality for these patients is dependent on factors not included in the score. Further studies are needed to determine these factors.
Role of Xingnaojing Injection in treating acute cerebral hemorrhage: A systematic review and meta-analysis.
Ma Xiao,Wang Tao,Wen Jianxia,Wang Jian,Zeng Nan,Zou Wenjun,Yang Yuxue
BACKGROUND:Xingnaojing injection (XNJi) is widely used for acute cerebral hemorrhage. However, the efficacy of XNJi for acute cerebral hemorrhage has not been comprehensively proved by systematic analysis yet. Therefore, it is essential to evaluate the efficacy and safety of XNJi in an evidence-based method. METHODS:Six databases were searched with XNJi used for acute cerebral hemorrhage in randomized controlled trials (RCTs). Meta-analysis was performed by Review Manager 5.3. The efficacy rate, brain edema, cerebral hematoma, neurological deficit score, hs-crp, Glasgow Coma Scale (GCS), and activities of daily living (ADL) were systematically evaluated. The Cochrane risk of bias was used to evaluate the methodological quality of eligible studies. RESULTS:This study is registered with PROSPERO (CRD42018098737). Twenty-nine studies with a total of 2638 patients were included in this meta-analysis. Compared with conventional treatment, XNJi got higher efficacy rate (OR = 3.37, 95% CI [2.65, 4.28], P < .00001). Moreover, XNJi showed significant enhancement of efficacy rate via subgroup analysis in course and dosage. In addition, XNJi demonstrated significant improvement in Chinese stroke scale (CSS) and National Institutes of Health Stroke Scale (NHISS) (mean difference [MD] = -4.74, 95% CI [-5.89, -3.60], P < .00001; MD = -4.45, 95% CI [-5.49, -3.41], P < .00001), GCS (MD = 2.72, 95% CI [2.09, 3.35], P < .00001). It also remarkably decreased the level of hs-crp (MD = -6.50, 95% CI [-7.79, -5.21], P < .00001), enhanced ADL (MD = 20.38, 95% CI [17.98, 22.79], P < .00001), and alleviated hematoma and edema (MD = -2.53, 95% CI [-4.75, -0.31] P < .05; MD = -1.74 95% CI [-2.42, -1.07] P < .00001) compared with conventional treatment. CONCLUSION:XNJi is effective in treating acute cerebral hemorrhage with significant improvement of CSS, NHISS and impairment of hs-crp, hematoma, and edema compared with conventional treatment. Moreover, XNJi got remarkable efficacy at the dose of 20, 30, 60 mL and from 7 to 28 days. No serious adverse reactions occurred. These results were mainly based on small-sample and low-quality studies. Therefore, more rigorous, large-scale RCTs were further needed to confirm its efficacy, safety, and detailed characteristic of application.
Influence of tranexamic acid on cerebral hemorrhage: A meta-analysis of randomized controlled trials.
Huang Beilei,Xu Qiusheng,Ye Ru,Xu Jun
Clinical neurology and neurosurgery
Tranexamic acid might be beneficial for cerebral hemorrhage. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the influence of tranexamic acid on cerebral hemorrhage. PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of tranexamic acid on cerebral hemorrhage were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. This meta-analysis was performed using the random-effect model. Seven RCTs involving 1702 patients were included in the meta-analysis. Overall, compared with control intervention in cerebral hemorrhage, tranexamic acid could significantly reduce growth of hemorrhagic mass (RR = 0.78; 95% CI = 0.61-0.99; P = 0.04) and unfavorable outcome (RR = 0.75; 95% CI = 0.61-0.93; P = 0.008), but demonstrated no substantial influence on volume of hemorrhagic lesion (Std. MD = -0.10; 95% CI = -0.27 to 0.08; P = 0.28), neurologic deterioration (RR = 1.25; 95% CI = 0.60-2.60; P = 0.56), rebleeding (RR = 0.62; 95% CI = 0.35-1.09; P = 0.10), surgery requirement (RR = 0.78; 95% CI = 0.40-1.51; P = 0.46), and mortality (RR = 0.86; 95% CI = 0.69-1.05; P = 0.14). Compared to control intervention in cerebral hemorrhage, tranexamic acid was found to significantly decrease growth of hemorrhagic mass and unfavorable outcome, but showed no notable impact on volume of hemorrhagic lesion, neurologic deterioration, rebleeding, surgery requirement and mortality.