Acute Spontaneous Intracerebral Hemorrhage Research Articles

Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data

SummaryBackgroundIntracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.MethodsIn a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.FindingsOf 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).InterpretationIn this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials.FundingUK Medical Research Council and British Heart Foundation.

The systolic blood pressure sweet spot after intracerebral hemorrhage

Acute spontaneous intracerebral hemorrhage (ICH), the most severely disabling type of stroke, has few proven therapies. The mainstay of care remains acute blood pressure (BP)–lowering treatment, in order to mitigate hematoma expansion, perihematomal edema, and the attendant mass effects, each linked to early neurologic deterioration (END), death, and major disability.1,2 More than 5 randomized clinical trials (RCTs) have proven the safety and support the efficacy of early intensive BP-lowering treatment, as opposed to conservative BP control. These trials include the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT-2) and Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-2) trials, which were recently compared3 and compiled in a large meta-analysis.4 Mounting evidence,1 particularly ad hoc analyses of INTERACT-2,5,6 suggests that the earlier the treatment, the steeper the drop, and the lower the BP achieved, the better the outcome,1,6 halting radiologic or clinical deterioration2 and, more importantly, improving quality of life and shifting toward better functional physical outcome at 3 months.4–6 Furthermore, INTERACT-2 data revealed a dose effect with linear relationship between achieved systolic BP (SBP) and reducing hematoma growth5 and improved functional outcome.6

New Prediction Score for Hematoma Expansion and Neurological Deterioration after Spontaneous Intracerebral Hemorrhage: A Hospital-Based Retrospective Cohort Study

To ensure hematoma expansion and neurological deterioration in the management of acute spontaneous intracerebral hemorrhage, accurate prediction is crucial for initial assessment on admission. We conducted this study to develop a new clinical prediction score using only noncontrast computed tomography image and simply measurable variables. This study was a retrospective cohort analysis. The study took place in a single academic medical center in Japan. Development of the prediction score was conducted based on patients who presented between October 2010 and June 2015, using univariate and multivariate logistic regression. We then validated the results in a second cohort between July 2015 and April 2017. The primary outcome was hematoma expansion and the secondary outcome was neurological deterioration up to 14 days after onset. In total, 622 patients were included in the analysis after excluding unsuitable cases. Of these, 457 patients were included in the development cohort and 165 were included in the validation cohort, with 10.8% meeting the criteria for hematoma expansion and 8.8% showing neurological deterioration. In the multivariate analysis, predictors of expansion or deterioration were as hematoma heterogeneity on computed tomography, niveau formation, peripheral edema, hematoma volume of more than 30 mL, and anticoagulant use. We then created the HEAVN score based on the univariate regression coefficients. The C-statistics for the hematoma expansion scores were .81 and .80 in the development and validation cohorts, respectively. Similar results were obtained for neurological deterioration. The HEAVN score is simple and useful for predicting hematoma expansion and neurological deterioration based on imaging and background data.

Haemostatic therapies for acute spontaneous intracerebral haemorrhage.

Outcome after spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume; up to one-third of ICHs enlarge within 24 hours of onset. Early haemostatic therapy might improve outcome by limiting haematoma growth. This is an update of a Cochrane Review first published in 2006, and last updated in 2009. To examine 1) the effectiveness and safety of individual classes of haemostatic therapies, compared against placebo or open control, in adults with acute spontaneous intracerebral haemorrhage, and 2) the effects of each class of haemostatic therapy according to the type of antithrombotic drug taken immediately before ICH onset (i.e. anticoagulant, antiplatelet, or none). We searched the Cochrane Stroke Trials Register, CENTRAL; 2017, Issue 11, MEDLINE Ovid, and Embase Ovid on 27 November 2017. In an effort to identify further published, ongoing, and unpublished randomised controlled trials (RCT), we scanned bibliographies of relevant articles and searched international registers of RCTs in November 2017. We sought randomised controlled trials (RCTs) of any haemostatic intervention (i.e. pro-coagulant treatments such as coagulation factors, antifibrinolytic drugs, or platelet transfusion) for acute spontaneous ICH, compared with placebo, open control, or an active comparator, reporting relevant clinical outcome measures. Two authors independently extracted data, assessed risk of bias, and contacted corresponding authors of eligible RCTs for specific data if they were not provided in the published report of an RCT. We included 12 RCTs involving 1732 participants. There were seven RCTs of blood clotting factors versus placebo or open control involving 1480 participants, three RCTs of antifibrinolytic drugs versus placebo or open control involving 57 participants, one RCT of platelet transfusion versus open control involving 190 participants, and one RCT of blood clotting factors versus fresh frozen plasma involving five participants. We were unable to include two eligible RCTs because they presented aggregate data for adults with ICH and other types of intracranial haemorrhage. We identified 10 ongoing RCTs. Across all seven criteria in the 12 included RCTs, the risk of bias was unclear in 37 (44%), high in 16 (19%), and low in 31 (37%). Only one RCT was at low risk of bias in all criteria.In one RCT of platelet transfusion versus open control for acute spontaneous ICH associated with antiplatelet drug use, there was a significant increase in death or dependence (modified Rankin Scale score 4 to 6) at day 90 (70/97 versus 52/93; risk ratio (RR) 1.29, 95% confidence interval (CI) 1.04 to 1.61, one trial, 190 participants, moderate-quality evidence). All findings were non-significant for blood clotting factors versus placebo or open control for acute spontaneous ICH with or without surgery (moderate-quality evidence), for antifibrinolytic drugs versus placebo (moderate-quality evidence) or open control for acute spontaneous ICH (moderate-quality evidence), and for clotting factors versus fresh frozen plasma for acute spontaneous ICH associated with anticoagulant drug use (no evidence). Based on moderate-quality evidence from one trial, platelet transfusion seems hazardous in comparison to standard care for adults with antiplatelet-associated ICH.We were unable to draw firm conclusions about the efficacy and safety of blood clotting factors for acute spontaneous ICH with or without surgery, antifibrinolytic drugs for acute spontaneous ICH, and clotting factors versus fresh frozen plasma for acute spontaneous ICH associated with anticoagulant drug use.Further RCTs are warranted, and we await the results of the 10 ongoing RCTs with interest.

Serum Magnesium Levels and Outcomes in Patients With Acute Spontaneous Intracerebral Hemorrhage.

BackgroundMagnesium (Mg) has potential hemostatic properties. We sought to investigate the potential association of serum Mg levels (at baseline and at 48 hours) with outcomes in patients with acute spontaneous intracerebral hemorrhage (ICH).Methods and ResultsWe reviewed data on all patients with spontaneous ICH with available Mg levels at baseline, over a 5‐year period. Clinical and radiological outcome measures included initial hematoma volume, admission National Institutes of Health Stroke Scale and ICH scores, in‐hospital mortality, favorable functional outcome (modified Rankin Scale scores, 0–1), and functional independence (modified Rankin Scale scores, 0–2) at discharge. Our study population consisted of 299 patients with ICH (mean age, 61±13 years; mean admission serum Mg, 1.8±0.3 mg/dL). Increasing admission Mg levels strongly correlated with lower admission National Institutes of Health Stroke Scale score (Spearman's r, −0.141; P=0.015), lower ICH score (Spearman's r, −0.153; P=0.009), and lower initial hematoma volume (Spearman's r, −0.153; P=0.012). Higher admission Mg levels were documented in patients with favorable functional outcome (1.9±0.3 versus 1.8±0.3 mg/dL; P=0.025) and functional independence (1.9±0.3 versus 1.8±0.3 mg/dL; P=0.022) at discharge. No association between serum Mg levels at 48 hours and any of the outcome variables was detected. In multiple linear regression analyses, a 0.1‐mg/dL increase in admission serum Mg was independently and negatively associated with the cubed root of hematoma volume at admission (regression coefficient, −0.020; 95% confidence interval, −0.040 to −0.000; P=0.049) and admission ICH score (regression coefficient, −0.053; 95% confidence interval, −0.102 to −0.005; P=0.032).ConclusionsHigher admission Mg levels were independently related to lower admission hematoma volume and lower admission ICH score in patients with acute spontaneous ICH.

Effect of mild hypothermia on expression of inflammatory factors in surrounding tissue after minimally invasive hematoma evacuation in the treatment of hypertensive intracerebral hemorrhage.

Mild hypothermia combined with minimally invasive hematoma evacuation was evaluated in the treatment of hypertensive intracerebral hemorrhage to reduce inflammatory response of brain tissue around hematoma and ameliorate brain function, and to investigate its safety, effectiveness and feasibility. A total of 206 patients with acute spontaneous hypertensive intracerebral hemorrhage were collected clinically and randomly divided into minimally invasive hematoma evacuation group (group A) and mild hypothermia combined with minimally invasive hematoma evacuation (group B). The National Institutes of Health Stroke Scale (NIHSS) score was used before and after treatment. Group A was treated with minimally invasive intracranial hematoma evacuation using intracranial hematoma grinding puncture needle while group B received whole body water circulation type cooling blanket plus local cerebral mild hypothermia therapy with ice cap on the basis of minimally invasive surgery. Patients brain tissue fragments around hematoma taken out with rinsing during operation and at postoperative 1, 3 and 7 days were investigated. The contents of tumor necrosis factor-α (TNF-α) in serum at postoperative 1, 3 and 7 days were evaluated by enzyme-linked immunosorbent assay (ELISA). For the degree of nerve function defect of patients in the two groups, NIHSS score was lower in group B than that in group A at days 3 and 7, and the differences were statistically significant (P<0.05). The serum TNF-α content and expression of nuclear factor-κB (NF-κB) in brain tissue around hematoma reached the peak on the 3rd day. The TNF-α content and NF-κB expression were lower in group B than those in group A at each time-point (P<0.05). Mild hypothermia combined with minimally invasive hematoma evacuation can reduce the damage of hematoma to the surrounding brain tissue, effectively alleviate inflammatory response and decrease brain tissue injury, thus ameliorating brain function.

Efficacy of platelet transfusion for acute intracerebral hemorrhage among patients on antiplatelet therapy.

Clinical questionIn patients taking antiplatelet therapy, does a platelet transfusion after acute spontaneous primary intracerebral hemorrhage reduce the risk of death or dependence?Article chosenBaharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral hemorrhage associated with antiplatelet therapy (PATCH): a randomized, open-label, phase 3 trial. Lancet 2016;387(10038):2605-13.Study objectiveThe primary objective of this study was to investigate whether a platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral hemorrhage associated with antiplatelet therapy use.

Higher low-density lipoprotein cholesterol levels are associated with decreased mortality in patients with intracerebral hemorrhage

Background and aimsThe relationship between lipoprotein levels, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and clinical outcome after intracerebral hemorrhage (ICH) remains controversial. We sought to evaluate the association of lipoprotein cholesterol levels and statin dosage with clinical and neuroimaging outcomes in patients with ICH. MethodsData on consecutive patients hospitalized with spontaneous acute ICH was prospectively collected over a 5-year period and retrospectively analyzed. Demographic characteristics, clinical severity documented by NIHSS-score and ICH-score, neuroimaging parameters, pre-hospital statin use and doses, and LDL-C and HDL-C levels were recorded. Outcome events characterized were hematoma volume, hematoma expansion, in-hospital functional outcome, and in-hospital mortality. ResultsA total of 672 patients with acute ICH [(mean age 61.6 ± 14.0 years, 43.6% women, median ICH score 1 (IQR: 0–2)] were evaluated. Statin pretreatment was not associated with neuroimaging or clinical outcomes. Higher LDL-C levels were associated with several markers of poor clinical outcome and in-hospital mortality. LDL-C levels were independently and negatively associated with the cubed root of hematoma volume (linear regression coefficient −0.021, 95% CI: −0.042−-0.001; p = 0.049) on multiple linear regression models. Higher admission LDL-C (OR 0.88, 95% CI 0.77–0.99; p = 0.048) was also an independent predictor for decreased hematoma expansion. Higher admission LDL-C levels were independently (p < 0.001) associated with lower likelihood of in-hospital mortality (OR per 10 mg/dL increase 0.68, 95% CI: 0.57–0.80) in multivariable logistic regression models. ConclusionsHigher LDL-C levels at hospital admission were an independent predictor for lower likelihood of hematoma expansion and decreased in-hospital mortality in patients with acute spontaneous ICH. This association requires independent confirmation.

Practice Patterns for Neurosurgical Utilization and Outcome in Acute Intracerebral Hemorrhage: Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials 1 and 2 Studies.

The prognosis in acute spontaneous intracerebral hemorrhage (ICH) is related to hematoma volume, where >30 mL is commonly used to define large ICH as a threshold for neurosurgical decompression but without clear supporting evidence. To determine the factors associated with large ICH and neurosurgical intervention among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT). We performed pooled analysis of the pilot INTERACT1 (n = 404) and main INTERACT2 (n = 2839) studies of ICH patients (<6 h of onset) with elevated systolic blood pressure (SBP, 150-220 mm Hg) who were randomized to intensive (target SBP < 140 mm Hg) or contemporaneous guideline-recommended (target SBP < 180 mm Hg) management. Neurosurgical intervention data were collected at 7 d postrandomization. Multivariable logistic regression was used to determine associations. There were 372 (13%) patients with large ICH volume (>30 mL), which was associated with nonresiding in China, nondiabetic status, severe neurological deficit (National Institutes of Health stroke scale [NIHSS] score ≥ 15), lobar location, intraventricular hemorrhage extension, raised leucocyte count, and hyponatremia. Significant predictors of those patients who underwent surgery (226 of 3233 patients overall; 83 of 372 patients with large ICH) were younger age, severe neurological deficit (lower Glasgow coma scale score, and NIHSS score ≥ 15), baseline ICH volume > 30 mL, and intraventricular hemorrhage. Early identification of severe ICH, based on age and clinical and imaging parameters, may facilitate neurosurgery and intensive monitoring of patients.

Statistical analysis plan for the \u2018Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage\u2019 (TICH-2) trial

RationaleAside from blood pressure lowering, treatment options for intracerebral haemorrhage remain limited and a proportion of patients will undergo early haematoma expansion with resultant significant morbidity and mortality. Tranexamic acid (TXA), an anti-fibrinolytic drug, has been shown to significantly reduce mortality in patients, who are bleeding following trauma, when given rapidly. TICH-2 is testing whether TXA is effective at improving outcome in spontaneous intracerebral haemorrhage (SICH).Methods and designTICH-2 is a pragmatic, phase III, prospective, double-blind, randomised placebo-controlled trial. Two thousand adult (aged ≥ 18 years) patients with an acute SICH, within 8 h of stroke onset, will be randomised to receive TXA or the placebo control. The primary outcome is ordinal shift of modified Rankin Scale score at day 90. Analyses will be performed using intention-to-treat.ResultsThis paper and its attached appendices describe the statistical analysis plan (SAP) for the trial and were developed and published prior to database lock and unblinding to treatment allocation. The SAP includes details of analyses to be undertaken and unpopulated tables which will be reported in the primary and key secondary publications. The database will be locked in early 2018, ready for publication of the results later in the same year.DiscussionThe SAP details the analyses that will be done to avoid bias arising from prior knowledge of the study findings. The trial will determine whether TXA can improve outcome after SICH, which currently has no definitive therapy.Trial registrationISRCTN registry, ID: ISRCTN93732214. Registered on 17 January 2013.

Effect of Baroreceptor Sensitivity on Outcomes in Patients with Acute Spontaneous Intracerebral Hemorrhage.

Reduced baroreflex sensitivity (BRS) has been reported in patients with acute cardiovascular events. We tested the hypothesis that BRS is substantially reduced in patients with spontaneous intracerebral hemorrhage (ICH) and that BRS can predict treatment outcomes. We examined BRS and other cardiovascular autonomic parameters in 35 patients with ICH over the course of 30 days. Cardiovascular autonomic parameters also were evaluated in 30 healthy volunteer subjects during the study period. Outcome was assessed at 30 days with the modified Rankin Scale (mRS). Good outcome was defined as an mRS <1, whereas patients defined as having a poor outcome had either an mRS ≥2 or died shortly after the stroke event. Twenty patients had a poor outcome, and 15 patients had a good outcome. BRS values in the patients with poor outcome group were lower in comparison with the healthy subjects, and BRS values in patients with poor outcomes were significantly lower than that those in patients with good outcomes on day 1, day 4, and day 10. BRS was associated independently with outcome and the cut-off value of BRS on day 1 in the poor outcome group was 6.79. Based on our results, BRS value at admission is a more powerful predictor of outcome than the Glasgow Coma Scale score at admission. An assay of BRS could be added as a biomarker for outcome prediction among patients with spontaneous ICH in clinical practice.

Assessing clinical outcome using brain score as a predictor of hematoma growth in acute spontaneous intracerebral hemorrhage (ICH) patients in a tertiary hospital in Manila

Background: Spontaneous intracerebral hemorrhage (ICH), the second most common cause of stroke, has a high rate of morbidity and mortality. One of the independent predictors of poor outcome in ICH patients is hematoma expansion. Wang et al developed a simple algorithm, BRAIN, which is a 24-point score based on Baseline ICH volume, Recurrent ICH, Anticoagulation with warfarin at symptom onset, Intraventricular extension, and Number of hours to baseline computed tomography from symptom onset, which predicts in percentage the probability of hematoma expansion in ICH patients within the next 24 hours (Table 1).

Dual Antiplatelet Therapy Is Associated With Coagulopathy Detectable by Thrombelastography in Acute Stroke.

Thrombelastography (TEG) provides a global, dynamic measure of coagulation. We examined the effect of antiplatelet (AP) medications on coagulation in patients with acute stroke as measured by TEG. We reviewed prospectively collected data on patients presenting with acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH) between 2009 and 2014. Patient demographics and baseline TEG values were compared among 4 different drug use groups: aspirin only, clopidogrel only, both aspirin and clopidogrel, and no AP. Multivariable regression models were conducted to compare the differences in TEG components. A total of 202 patients were included, 139 with AIS and 63 with ICH. Forty-eight (24%) patients were taking aspirin alone, 12 (6%) were taking clopidogrel, 16 (8%) dual AP, and 126 (62%) no AP. Dual AP use was associated with prolonged mean R (time to initiate clotting) of 5.5 minutes as compared to no AP use (4.6 minutes, P = .04). Additionally, mean maximal amplitude (MA; final clot strength) and angle (rate of clot formation) were decreased in the dual AP group (MA = 59.3 mm, angle = 57.8°) as compared to the no AP group (MA = 64.5 mm, angle = 64.5°; P = .04 and P = .01, respectively). Patients on single AP therapy (either aspirin or clopidogrel) did not differ from those on no AP therapy in any TEG parameters measured. Dual AP therapy is associated with a detectable coagulopathy which may have implications in the management of patients with AIS and hemorrhagic stroke. The effects of single AP therapy may not be demonstrated by TEG.

Developing an algorithm to identify patients with intracerebral haemorrhage secondary to a macrovascular cause.

Determining the cause of spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is critical to guide treatment and prognosis. We investigated whether small vessel disease (SVD) in addition to clinical and other radiological findings on acute neuroimaging predicts a low risk of a macrovascular cause (e.g. an arterio-venous malformation, aneurysm or dural arteriovenous fistula). We identified patients with acute spontaneous ICH who underwent acute non-contrast CT, CT angiography (CTA) and intra-arterial digital subtraction angiography (IADSA) at our institution from January 2010 to April 2014. Logistic regression including CTA result, SVD, age, pre-ICH hypertension and ICH location was used to derive a prediction model, validated using bootstrapping. 173 patients (46% female, median age 49) of whom 78 had a macrovascular cause on IADSA were included. Predictors of a macrovascular cause were: abnormal CTA (OR 67.4; p < 0.001); absence of SVD (OR 5.0; p = 0.019); and absence of pre-ICH hypertension (OR 3.4; p = 0.05). In our internally derived prediction model, the combination of CTA, SVD and pre-ICH hypertension predicted the likelihood of an underlying macrovascular cause (optimism-adjusted ROC area 0.919). Patients with negative CTA, SVD and pre-ICH hypertension have a low likelihood of an underlying macrovascular cause (1.8%). A combination of CTA, SVD and pre-ICH hypertension predict the likelihood of finding a macrovascular cause in patients with acute spontaneous ICH, allowing informed decisions regarding the likely benefit and risk of IADSA.

Association between serum periostin concentrations and outcome after acute spontaneous intracerebral hemorrhage

BackgroundHigher serum periostin concentrations are associated with mortality after head trauma. We further determined the relationship between periostin concentrations, severity, and clinical outcome in patients with intracerebral hemorrhage (ICH). MethodsWe prospectively included 128 controls and 128 consecutive patients with acute ICH within the first 24h after onset. At admission, we measured serum periostin concentrations. ResultsSerum periostin concentrations were significantly higher in the patients than in the controls. Serum periostin concentrations were positively related to National Institutes of Health Stroke Scale (NIHSS) score (r=0.526) and hematoma volume (r=0.586). An unfavorable outcome (defined as modified Rankin scale >2) was observed in 65 (50.8%) patients. Serum periostin [odds ratio (OR), 1.008; 95% confidence interval (CI), 1.002–1.013], NIHSS score (OR, 1.462; 95% CI, 1.209–1.767), hematoma volume (OR, 1.134; 95% CI, 1.047–1.227) and age (OR, 1.060; 95% CI, 1.015–1.108) emerged as independent predictors for 6-month unfavorable outcome. In terms of ROC AUC, serum periostin concentrations had significantly higher predictive value compared with age and showed similar predictive value compared with NIHSS score and hematoma volume. ConclusionsHigh concentrations of serum periostin in acute ICH patients are associated with increasing severity and a poor functional prognosis.

Satellite Sign: A Poor Outcome Predictor in Intracerebral Hemorrhage

Background: The presence of high-density starry dots around the intracerebral hemorrhage (ICH), which we termed as a satellite sign, is occasionally observed in CT. The relationship between ICH with a satellite sign and its functional outcome has not been identified. This study aimed to determine whether the presence of a satellite sign could be an independent prognostic factor for patients with ICH. Methods: Patients with acute spontaneous ICH were retrospectively identified and their initial CT scans were reviewed. A satellite sign was defined as scattered high-density lesions completely separate from the main hemorrhage in at least the single axial slice. Functional outcome was evaluated using the modified Rankin Scale (mRS) at discharge. Poor functional outcome was defined as mRS scores of 3-6. Univariate and multivariate logistic regression analyses were applied to assess the presence of a satellite sign and its association with poor functional outcome. Results: A total of 241 patients with ICH were enrolled in the study. Of these, 98 (40.7%) had a satellite sign. Patients with a satellite sign had a significantly higher rate of poor functional outcome (95.9%) than those without a satellite sign (55.9%, p < 0.0001). Multivariate logistic regression analysis revealed that higher age (OR 1.06; 95% CI 1.03-1.10; p = 0.00016), large hemorrhage size (OR 1.06; 95% CI 1.03-1.11; p = 0.00015), and ICH with a satellite sign (OR 13.5; 95% CI 4.42-53.4; p < 0.0001) were significantly related to poor outcome. A satellite sign was significantly related with higher systolic blood pressure (p = 0.0014), higher diastolic blood pressure (p = 0.0117), shorter activated partial thromboplastin time (p = 0.0427), higher rate of intraventricular bleeding (p < 0.0001), and larger main hemorrhage (p < 0.0001). Conclusions: The presence of a satellite sign in the initial CT scan is associated with a significantly worse functional outcome in ICH patients.

Quantitative assessment on blood-brain barrier permeability of acute spontaneous intracerebral hemorrhage in basal ganglia: a CT perfusion study.

Blood-brain barrier (BBB) damage aggravates perihematomal edema, and edema volume predicts prognosis independently. But the BBB permeability at the late stage of acute intracerebral hemorrhage (ICH) patients is uncertain. We aimed to assess the BBB permeability of spontaneous basal ganglia ICH using computed tomographic perfusion (CTP) and investigates its relationship with hematoma and perihematomal edema volume. We performed CTP on 54 consecutive ICH patients within 24 to 72h after symptom onset. Permeability-surface area product (PS) derived from CTP imaging was measured in hematoma, "high-PS spot," perihematoma, normal-appearing, hemispheric, and contralateral regions. Hematoma and edema volumes were calculated from non-contrast CT. "High-PS spot" and perihematoma regions had higher PS than the contralateral regions (p<0.001). Hematoma PS was lower than that in the contralateral regions (p<0.001). Perihematoma PS of the large-hematoma group was higher than that of the small-hematoma group (p=0.011). Perihematomal edema volume correlated positively with hematoma volume (β=0.864, p<0.001) and perihematoma PS (β=0.478, p<0.001). Perihematoma PS correlated positively with hematoma volume (β=0.373, p=0.005). Locally elevated perihematoma PS was found in most spontaneous basal ganglia ICH patients within 24 to 72h after symptom onset. Perihematoma PS was higher in larger hematomas and was associated with larger edema volume. At this period, BBB leakage is likely to be an important factor in edema formation.

Randomized trial to assess safety and clinical efficacy of intensive blood pressure reduction in acute spontaneous intracerebral haemorrhage

BackgroundHaematoma expansion due to raised blood pressure in spontaneous intracerebral haemorrhage may determine outcome. The aim of this study was to determine safety and efficacy of lowering blood pressure in acute spontaneous intracerebral haemorrhage. MethodsThis open label, multicentric trial randomized patients ≥18 years with spontaneous intracerebral haemorrhage with no secondary cause within 72h of onset to tight BP control arm where treatment was initiated if mean arterial pressure (MAP) was ≥115mm of Hg and conventional BP control arm where treatment was initiated if MAP was ≥130mm of Hg. The MAP was maintained in the respective arm for another 72h after which both arms had MAP below 115mm of Hg. Primary outcome was modified Rankin Scale at 90 days. Results118 patients, 59 in each arm were included. Follow up was available for all. Baseline characteristics were similar. At 90 days there was no significant difference between median mRS between the two arms. Odds Ratio for “poor outcome” (mRS 3–6) in the tight control arm (safety of the intervention) against “good outcome” (mRS 0–2) was not significant (OR 0.70 [95% CI 0.34–1.47] p=0.35). Efficacy of the intervention in the form of Odds Ratio for “good outcome” in the tight control arm was not significant (OR 1.43 [95% CI 0.68–2.99], p=0.35). ConclusionIn patients with spontaneous intracerebral haemorrhage who present within 72h of the onset of symptoms, MAP can be safely lowered if it crosses 115mm of Hg but it does not improve clinical outcome.

Elevated Pulse Pressure Levels Are Associated With Increased In-Hospital Mortality in Acute Spontaneous Intracerebral Hemorrhage.

Clinical outcome after intracerebral hemorrhage (ICH) remains poor. Definitive phase-3 trials in ICH have failed to demonstrate improved outcomes with intensive systolic blood pressure (SBP) lowering. We sought to determine whether other BP parameters-diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP)-showed an association with clinical outcome in ICH. We retrospectively analyzed a prospective cohort of 672 patients with spontaneous ICH and documented demographic characteristics, stroke severity, and neuroimaging parameters. Consecutive hourly BP recordings allowed for computation of SBP, DBP, PP, and MAP. Threshold BP values that transitioned patients from survival to death were determined from ROC curves. Using in-hospital mortality as outcome, BP parameters were evaluated with multivariable logistic regression analysis. Patients who died during hospitalization had higher mean PP compared to survivors (68.5 ± 16.4 mm Hg vs. 65.4 ± 12.4 mm Hg; P = 0.032). The following admission variables were associated with significantly higher in-hospital mortality (P < 0.001): poorer admission clinical condition, intraventricular hemorrhage, and increased admission normalized hematoma volume. ROC analysis showed that mean PP dichotomized at 72.17 mm Hg, provided a transition point that maximized sensitivity and specific for mortality. The association of this increased dichotomized PP with higher in-hospital mortality was maintained in multivariable logistic regression analysis (odds ratio, 3.0; 95% confidence interval, 1.7-5.3; P < 0.001) adjusting for potential confounders. Widened PP may be an independent predictor for higher mortality in ICH. This association requires further study.

Low cholesterol level associated with severity and outcome of spontaneous intracerebral hemorrhage: Results from Taiwan Stroke Registry.

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with <160, 160–200 and >200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC <160 mg/dL. Patients with TC <160 mg/dL presented more often severe neurological deficit (NIHSS >15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41–2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11–1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI) <22 kg/m2 had higher risk of 3-month mortality (aOR 3.94, 95% CI 1.76–8.80). Prior use of lipid-lowering drugs (2.8% of the ICH population) was not associated with initial severity and 3-month outcomes. A total cholesterol level lower than 160 mg/dL was common in patients with acute ICH and was associated with greater neurological severity on presentation and poor 3-month outcomes, especially with lower BMI.