Acute Spontaneous Intracerebral Hemorrhage Research Articles

Diagnostic and prognostic value of serum hepcidin concentration in patients with acute spontaneous supratentorial intracerebral hemorrhage

The aim of the study was to evaluate the diagnostic and prognostic value of serum hepcidin concentration in patients with acute spontaneous supratentorial intracerebral hemorrhage (SSICH). Materials and methods. Prospective cohort study of 88 patients with acute SSICH receiving the conservative therapy was conducted. Level of neurological deficit was evaluated using the Full Outline of UnResponsiveness Scale, the Glasgow Coma Scale and the National Institute of Health Stroke Scale. Computed tomography was performed to detect an intracerebral hemorrhage volume (ICHV), secondary intraventricular hemorrhage volume (SIVHV) and total volume of intracranial hemorrhage (TVICH). Laboratory blood samples were taken within 24 hours of hospitalization. Hepcidin levels, serum iron concentrations and total iron-binding capacity were determined, followed by calculations of transferrin saturation coefficient. Early neurological deterioration (END) and unfavorable variants of the acute period of SSICH (lethal outcome, modified Rankin score 4-5 on the 21st day of the disease) were considered as endpoints. Statistical processing of the obtained results included a correlation analysis, logistic regression analysis and ROC-analysis. Results. It was identified, that serum hepcidin level in the patients with SSICH was correlated with ICHV (R = 0.44, P ˂ 0.01), SIVHV (R = 0.45, P ˂ 0.01) and TVICH (R = 0.57, P ˂ 0.01). Hepcidin serum concentrations in the patients with ICHV >30 ml exceeded the value of those in cases of ICHV ≤30 ml by 69.0 % (P ˂ 0.0001). Serum levels of hepcidin were significantly higher in the patients with an unfavorable course and outcome of the disease in the acute period on the 1st day of admission (P ˂ 0.0001). Informative multipredictor models were developed via multiple logistic regression analysis, which include hepcidin values coupled with clinical and neurovisualization findings and are predictive of lethal and unfavorable acute period functional outcomes (AUC = 0,93, P ˂ 0.0001). Conclusions. The level of serum hepcidin in patients with acute SSICH is associated with the severity of cerebral lesions. The integration of serum hepcidin concentration with clinical and neuroimaging findings in the structure of multipredictor logistic regression models allows to determine the vital and functional prognosis of the acute period of SSICH with an accuracy of >85 %

Imaging-Based Outcome Prediction of Acute Intracerebral Hemorrhage

We hypothesized that imaging-only-based machine learning algorithms can analyze non-enhanced CT scans of patients with acute intracerebral hemorrhage (ICH). This retrospective multicenter cohort study analyzed 520 non-enhanced CT scans and clinical data of patients with acute spontaneous ICH. Clinical outcome at hospital discharge was dichotomized into good outcome and poor outcome using different modified Rankin Scale (mRS) cut-off values. Predictive performance of a random forest machine learning approach based on filter- and texture-derived high-end image features was evaluated for differentiation of functional outcome at mRS 2, 3, and 4. Prediction of survival (mRS ≤ 5) was compared to results of the ICH Score. All models were tuned, validated, and tested in a nested 5-fold cross-validation approach. Receiver-operating-characteristic area under the curve (ROC AUC) of the machine learning classifier using image features only was 0.80 (95% CI [0.77; 0.82]) for predicting mRS ≤ 2, 0.80 (95% CI [0.78; 0.81]) for mRS ≤ 3, and 0.79 (95% CI [0.77; 0.80]) for mRS ≤ 4. Trained on survival prediction (mRS ≤ 5), the classifier reached an AUC of 0.80 (95% CI [0.78; 0.82]) which was equivalent to results of the ICH Score. If combined, the integrated model showed a significantly higher AUC of 0.84 (95% CI [0.83; 0.86], P value <0.05). Accordingly, sensitivities were significantly higher at Youden Index maximum cut-offs (77% vs. 74% sensitivity at 76% specificity, P value <0.05). Machine learning–based evaluation of quantitative high-end image features provided the same discriminatory power in predicting functional outcome as multidimensional clinical scoring systems. The integration of conventional scores and image features had synergistic effects with a statistically significant increase in AUC.

Diagnostic and prognostic value of serum interleukins 6 and 10 integrated assessment in patients with acute period of spontaneous supratentorial intracerebral hemorrhage

Prospective cohort research that included 104 patients with spontaneous supratentorial intracerebral hemorrhage (SSICH) on the ground of conservative treatment was carried out. Diagnosis was made by using clinical and neurovisualization investigation. The diagnostic and prognostic informativeness of serum interleukin-6 (IL-6) and interleukin-10 (IL-10) integrated assessment was investigated in patients with acute period of SSICH. Laboratory fasting blood samples were taken on the 1st and 5th day of admission with further detection of serum IL-6 and IL-10 concentrations. Early neurological deterioration and unfavorable acute period spontaneous supratentorial intracerebral hemorrhage outcome as grading 4­6 scores by modified Rankin scale on the 21st day of the disease were chosen as clinical combined endpoints. Lethal outcome and unfavorable functional outcome were also recorded. Three profile types of serum IL-6 and IL-10 concentrations were identified on the ground of cluster analysis in patients with SSICH. It was revealed that profile’s types with reciprocal elevation of cytokines are associated with heavier brain structures affection and increased risk of early neurological deterioration (relative risk (95% Cl) = 3,40 (1,35-8,53), p=0,0091), lethal outcome (relative risk (95% Cl) = 7,50 (1,80-31,17), p=0,0056) and unfavorable acute period functional outcome (relative risk (95% Cl) = 2,28 (1,46-3,57), p=0,0003). Four types of IL-6 and IL-10 serum profile on the 5th day of admission were identified. In this case profiles with elevation IL-6 levels are associated with increased risk of unfavorable acute period SSICH outcome into 2,1 times (relative risk (95% Cl) = 2,13 (1,44-3,15), p=0,0002). Profile’s types of serum IL-6 and IL-10 levels in patients with SSICH are informative integrated parameter for short-term prognosis on the ground of conservative treatment. Keywords: cerebral hemorrhage, interleukin-6, interleukin-10, prognosis.

Naoxueshu relieves hematoma after clot removal in acute spontaneous intracerebral hemorrhage.

ObjectivesSurgical treatment is expected to remove clot immediately in acute spontaneous intracerebral hemorrhage (SICH) patients. The aim of this study was to evaluate whether Naoxueshu could enhance the efficacy of clot removal surgery in acute SICH patients.MethodsOne hundred twenty patients who had been diagnosed as SICH according to neuroimaging were enrolled in this study. They received craniotomy, decompressive craniectomy, or minimally invasive surgical evacuation as appropriate and then were randomized into two groups: the Naoxueshu group (NXS group, n = 60) and the control group (n = 60). All the patients received standard medical management while patients in NXS group also took Naoxueshu oral liquid 10 ml with three times a day for seven consecutive days. The primary outcome was the 7‐day hematoma volume and secondary outcomes were 7‐day National Institutes of Health Stroke Scale (NIHSS) score and 7‐day cerebral edema score.ResultsAfter clot removal surgery, hematoma volume in NXS group (9.5 ± 8.0) was significantly decreased than that in Control group (21.3 ± 22.9, p < .0001) 7 days after surgery. Moreover, cerebral edema was also relieved after 7‐day's Naoxueshu treatment (2.5 ± 0.9 vs. 2.9 ± 0.7, p = .043). Since patients in NXS group had worse baseline NIHSS score (17.2 ± 8.1 vs. 13.7 ± 10.1, p = .039), it was reasonable to conclude that Naoxueshu treatment could improve patients’ neurological function because 7‐day NIHSS score of the two groups was similar.ConclusionNaoxueshu oral liquid could relieve hematoma volume and cerebral edema after clot removal surgery in acute SICH patients. Moreover, it had the potential to improve patients’ short‐term neurological function.

Machine learning models predict coagulopathy in spontaneous intracerebral hemorrhage patients in ER.

AimsCoagulation abnormality is one of the primary concerns for patients with spontaneous intracerebral hemorrhage admitted to ER. Conventional laboratory indicators require hours for coagulopathy diagnosis, which brings difficulties for appropriate intervention within the optimal window. This study evaluates the possibility of building efficient coagulopathy prediction models using data mining and machine learning algorithms.MethodsA retrospective cohort enrolled 1668 cases with acute spontaneous intracerebral hemorrhage from three medical centers, excluding those under antithrombotic therapies. Coagulopathy‐related clinical parameters were initially screened by univariate analysis. Two machine learning algorithms, the random forest and the support vector machine, were deployed via an approach of four‐fold cross‐validation to screen out the most important parameters contributing to the occurrence of coagulopathy. Model discrimination was assessed using metrics, including accuracy, precision, recall, and F1 score.ResultsAlbumin/globulin ratio, neutrophil count, lymphocyte percentage, aspartate transaminase, alanine transaminase, hemoglobin, platelet count, white blood cell count, neutrophil percentage, systolic and diastolic pressure were identified as major predictors to the occurrence of acute coagulopathy. Compared to support vector machine, the model based on the random forest algorithm showed better accuracy (93.1%, 95% confidence interval [CI]: 0.913‐0.950), precision (92.4%, 95% CI: 0.897‐0.951), F1 score (91.5%, 95% CI: 0.889‐0.964), and recall score (93.6%, 95% CI: 0.909‐0.964), and yielded higher area under the receiver operating characteristic curve (AU‐ROC) (0.962, 95% CI: 0.942‐0.982).ConclusionThe constructed models exhibit good prediction accuracy and efficiency. It might be used in clinical practice to facilitate target intervention for acute coagulopathy in patients with spontaneous intracerebral hemorrhage.

Which Parameters of Beat-to-Beat Blood Pressure Best Predict Poor In-Hospital Outcome in Spontaneous Intracerebral Hemorrhage?

Objective: There is increasing evidence that high blood pressure (BP) levels and BP variability (BPV) over 24 h or longer are associated with poor clinical outcomes in patients with intracerebral hemorrhage (ICH). The objective of this study was to examine the association between different beat-to-beat BP parameters and in-hospital outcomes.Methods: Patients with a diagnosis of acute spontaneous ICH were recruited consecutively and prospectively between September 2018 and January 2019. Beat-to-beat recordings were measured non-invasively for 5 min within the first 72 h after the onset of symptoms. BPV was analyzed by standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variation independent of mean (VIM). Outcome was assessed at discharge using the modified Rankin Scale (mRS) score. Multivariate logistic regression analysis was used to assess the association between BP levels, BPV, and clinical outcomes.Results: A total of 66 patients were included, of whom 34 had poor outcomes (mRS score, 3–6). Patients with poor outcomes had significantly higher National Institute of Health Stroke Scale scores (4.5 vs. 9, p < 0.001), a larger ICH volume (8 vs. 14.5 mL, p = 0.004), and an increased systolic BP (SBP) -CV (3.2 vs. 4.8, p < 0.001) and diastolic BP (DBP) -CV (3.7 vs. 4.9, p = 0.015). After adjustment for major covariates, multivariate logistic regression analysis revealed that SBP-CV was independently associated with an increased risk of poor in-hospital outcomes [odds ratio (OR) 2.535; 95% confidence interval (CI), 1.211–5.305; p = 0.014]. The receiver operating characteristic area for SBP-CV in predicting poor in-hospital outcome was 0.827 (95% CI, 0.730–0.925; p < 0.001), and the best cutoff point was 3.551 (sensitivity, 82.35%; specificity, 68.75%).Conclusion: A higher beat-to-beat BPV in the first 72 h of admission was associated with unfavorable in-hospital outcomes in patients with ICH. The stabilization of BPV during the acute phase may be a therapeutic target; this could be tested in future clinical trials.

ELECTROENCEPHALOGRAPHIC MARKERS OF LATERAL SHIFTS OF BRAIN MIDLINE STRUCTURES IN PATIENTS WITH ACUTE SPONTANEOUS SUPRATENTORIAL INTRACEREBRAL HAEMORRHAGE

The aim of this study is to improve the diagnostic approaches in acute period of spontaneous supratentorial intracerebral hemorrhage by detecting the most informative parameters of spectral analysis of the electroencephalographic pattern in the evaluation of cerebral bioelectrical activity changes caused by the lateral shifts of brain midline structures. Materials and methods. We carried out clinical and paraclinical examination of 156 patients (90 men and 66 women, mean age 66,7±0,8 years) with firstly appeared hypertensive spontaneous supratentorial intracerebral hemorrhage. The diagnosis was based on the findings of computed tomography. Lateral shift was evaluated as an average from septum pellucidum and pineal gland displacements. Clinical neurological investigation included the evaluation according to the National Institute of Health Stroke Scale. Computed electroencephalography was carried out within the first 48 hours from the disease onset. Spectral rhythm power, fronto-occipital gradients, interhemispheric rhythm asymmetry parameters were analyzed. Statistical processing included evaluating differences between the groups studied, logistic regression analysis, ROC-analysis. Results. No lateral shift of brain midline structure was found in 57 (36.5%) patients; lateral shift ranged from 1-5mm was diagnosed in 72 (46.2%) patients; the lateral shift over 5 mm was found in 27 (17.3%) patients. We have found out the following values can be used as electroencephalographic criteria of lateral shift of brain midline structures: values of relative spectral power rhythm of alpha band ≤20,5% in affected hemisphere (Se=79,8%, Sp=77,2%) and ≤17,7% in intact hemisphere (Se=71,7%, 75,4%), fronto-occipital rhythm gradients of alpha2 band &gt;–0,085 in affected hemisphere (Se=71,7%, Sp=63,2%) and &gt;–0,266 in intact hemisphere (Se=80,8%, Sp=54,4%), while relative spectral rhythm power of delta band &gt;48,4% in affected hemisphere (Se=88,9%, Sp=74,2%) and &gt;46,8% in intact hemisphere (Se=92,6%, Sp=72,4%), fronto-occipital rhythm gradients of alpha band &gt;–0,001 in affected hemisphere (Se=81,5%, Sp=65,1%). These values demonstrate disturbances in cerebral bioelectrical activity caused by lateral shift over 5 mm. Conclusions. The values of relative spectral rhythm power and fronto-occipital rhythm gradients of alpha band in affected and intact hemispheres are the most informative parameters of spectral electroencephalographic pattern analysis for detection of bioelectrical brain activity deteriorations caused by the lateral shift of brain midline structure due to acute spontaneous supratentorial intracerebral haemorrhage.

Acute spontaneous intracerebral hemorrhage lethal outcome prediction on the ground of bioelectrical brain activity spectral analysis

Aim of the study — to detect electroencephalographic criteria of unfavorable vital outcome of spontaneous supratentorial intracerebral hemorrhage (SSICH). Prospective cohort study of 156 patients (mean age 66,7 ± 0.8 years) in acute period of SSICH on the ground of conservative treatment. Diagnosis was made based on clinical neurological and visualization data. Bioelectrical brain activity was done during first 2 days of the onset. Logistic regressive analysis was used for elaboration of prognostic criteria. It was detected, that risk of lethal SSICH outcome is independently associated with the next spectral EEG‑pattern parameters: relative spectral rhythm of δ-band of intact hemisphere (odds ratio (OR) (95 % confidence interval (CI) is equal to 1.12 (1.08—1.17), p &lt; 0.0001), frontal occipital rhythm gradient of α-band of intact hemisphere (ОR (95 % CI) = 5,96 (1.08—33.04), p = 0.0410) and interhemispheric asymmetry of absolute spectral rhythm power of β2-band (OR (95 % CI) = 0.03 (0.001—0.88), p = 0.0419). These predictors were integrated into the mathematic model for individual prognosis of SSICH lethal outcome (AUC (95 % CI) = 0.95 (0.90—0.98), p &lt; 0.0001, predictive accuracy is equal to 89.7 %). Bilateral predominance of electroencephalographic pattern of δ-band rhythm, inversion of negative frontal occipital rhythm gradients of α-band in both hemispheres, formation of negative interhemispheric asymmetry of absolute spectral rhythm power of δ-band, α2-band in frontal region and θ-, β-bands in parietal occipital regions in first 2 days from the SSICH onset are the EEG criteria for unfavorable vital outcome of SSICH.

Comparison of Functional Outcome between Decompressive Craniectomy and Craniotomy Osteoplasty in Acute Spontaneous Supratentorial Intracerebral Hemorrhage: A Systematic Review and Meta Analysis

Introduction Hemorrhagic stroke is a major cause of long-term disability and is associated with higher mortality compared to ischemic stroke.1 Arteriosclerotic hypertension is the most common cause of primary hemorrhage followed by other causes such as vascular malformations and amyloid angiopath

Association between critical care admission and 6-month functional outcome after spontaneous intracerebral haemorrhage

BackgroundThere is uncertainty about the clinical benefit of admission to critical care after spontaneous intracerebral haemorrhage (ICH). PurposeWe investigated factors associated with critical care admission after spontaneous ICH and evaluated associations between critical care and 6-month functional outcome. MethodsWe included 825 patients with acute spontaneous non-traumatic ICH, recruited to a prospective multicenter observational study. We evaluated the characteristics associated with critical care admission and poor 6-month functional outcome (modified Rankin Scale, mRS > 3) using univariable (chi-square test and Wilcoxon rank-sum test, as appropriate) and multivariable analysis. Results286 patients (38.2%) had poor 6-month functional outcome. Seventy-seven (9.3%) patients were admitted to critical care. Patients admitted to critical care were younger (p < 0.001), had lower GCS score (p < 0.001), larger ICH volume (p < 0.001), more often had intraventricular extension (p = 0.008) and underwent neurosurgery (p < 0.001). Critical care admission was associated with poor functional outcome at 6 months (39/77 [50.7%] vs 286/748 [38.2%]; p = 0.034); adjusted OR 2.43 [95%CI 1.36–4.35], p = 0.003), but not with death (OR 1.29 [95%CI 0.71–2.35; p = 0.4). In ordinal logistic regression, patients admitted to critical care showed an OR 1.47 (95% CI 0.98–2.20; p = 0.07) for a shift in the 6-month modified Rankin Scale. ConclusionsAdmission to critical care is associated with poor 6-month functional outcome after spontaneous ICH but not with death. Patients admitted to critical care were a priori more severely affected. Although adjusted for main known predictors of poor outcome, our findings could still be confounded by unmeasured factors. Establishing the true effectiveness of critical care after ICH requires a randomised trial with clinical outcomes and quality of life assessments.

Mouse nerve growth factor promotes neurological recovery in patients with acute intracerebral hemorrhage: A proof-of-concept study

Backgroundew drugs were confirmed to be effective in the treatments of neurological dysfunction caused by acute intracerebral hemorrhage (ICH). The present prospective clinical trial aims to evaluate the effect of mouse nerve growth factor (mNGF) on neurological function in patients with acute ICH. Methods60 patients with acute spontaneous ICH were randomized to receive mNGF (mNGF group) and citicoline (control group) for 4 weeks within 24–72 h after onset, respectively. The primary outcome was difference in the neurological functional outcome at 3 months by the modified Rankin Scale score (mRS). The secondary outcomes were the changes in hematoma volume at 4 weeks and 3 months. ResultsThere were 55 patients receiving treatment (29 patients in the mNGF group, 26 patients in the control group). Among the patients, 46 patients finished the trial at 3 months; the odds of a shift towards death or dependence (mRS > 3) at 3 months in the mNGF group were lower than that in the control group with adjustment for age, sex, NIHSS at admission, and hematoma volume at admission (adjusted OR, 0.185; 95%CI, 0.059–0.582; P = 0.0039). The hematoma was gradually reduced in all 46 patients and absorbed after non-surgical treatment at 3 months. There was no significant difference in hematoma volume between the two groups. No serious adverse event was found. ConclusionsThe administration of mNGF and citicoline was well-tolerated in patients with acute ICH. mNGF was associated with improved neurological function and less disability in patients with ICH. Therefore, the quality of life of patients with ICH may be improved by mNGF. Trial registrationThe trial is registered with the Chinese Clinical Trial Registry, number ChiCTR1800020258.

Advances in Therapeutic Approaches for Spontaneous Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) results in high rates of morbidity and mortality, with intraventricular hemorrhage (IVH) being associated with even worse outcomes. Therapeutic interventions in acute ICH have continued to emerge with focus on arresting hemorrhage expansion, clot volume reduction of both intraventricular and parenchymal hematomas, and targeting perihematomal edema and inflammation. Large randomized controlled trials addressing the effectiveness of rapid blood pressure lowering, hemostatic therapy with platelet transfusion, and other clotting complexes and hematoma volume reduction using minimally invasive techniques have impacted clinical guidelines. We review the recent evolution in the management of acute spontaneous ICH, discussing which interventions have been shown to be safe and which may potentially improve outcomes.

Rationale and Design of a Randomized, Double-Blind Trial Evaluating the Efficacy of Tranexamic Acid on Hematoma Expansion and Peri-hematomal Edema in Patients with Spontaneous Intracerebral Hemorrhage within 4.5 h after Symptom Onset: The THE-ICH Trial Protocol

BackgroundHematoma expansion (HE) and peri-hematomal edema (PHE) are associated with adverse outcomes of patients with acute spontaneous intracerebral hemorrhage (sICH). Due to a lack of proven treatments, it is critical to explore novel treatments for HE and PHE to improve functional recovery after sICH. MethodsThis is a prospective, multicenter, placebo-controlled, double-blind, and randomized clinical study of approximately 2400 patients with sICH. Patients within 4.5 h of sICH onset that fulfilling the clinical criteria for diagnosis (e.g. age more than 18 years old, the Glasgow Coma Scal>7, and no planned surgery) will randomly receive either intravenous tranexamic acid (TXA) 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo (sodium chloride 0.9%). Clinical data including the ICH score and the Glasgow Coma Scale score will be collected on admission. After assessment of HE and PHE expansion, follow-up will be conducted with enrolled patients for 90 days. ResultsPrimary outcome metrics are HE (defined as either >33% or >6 ml increase from baseline) and PHE expansion rate at 24 ± 3 h and 72 ± 3 h post-sICH. Secondary outcome metrics include mortality and the modified Rankin Scale on day 90 after sICH. Appropriate statistic methods will be used to evaluate the efficacy of TXA on patients with sICH within 4.5 h of symptom onset. ConclusionsHE usually occurs within the first few hours after onset of symptoms. It is essential to evaluate the efficacy of TXA on HE within a narrow window of time. This will be the first trial to evaluate the efficacy of TXA on HE and PHE expansion in sICH patients within 4.5 h after symptom onset. This trial is registered as ChiCTR1900027065 at http://www.chictr.org.cn.

Potential role of serum substance P as a favorable biomarker of functional outcome in acute spontaneous intracerebral hemorrhage

BackgroundSubstance P (SP) is implicated in brain inflammation. We clarified relationship between serum SP concentrations and functional outcome of acute intracerebral hemorrhage (ICH). MethodsWe quantified admission serum SP concentrations in 106 ICH patients. The primary outcome measure was a poor outcome at 90 days (modified Rankin Scale score ≥ 3) after onset. ResultsPatients with a poor outcome compared with the rest had substantially higher serum SP concentrations. The area under the curve for serum SP concentrations with regard to discriminating a poor outcome was 0.795 (95% CI, 0.706 to 0.867). Serum SP concentrations >449 pg/ml predicted the risk of a poor outcome with 63.0% sensitivity and 78.9% specificity, and were independently associated with a poor outcome (odds ratio, 5.437; 95% CI, 2.156 to 13.715). There were the positive associations between serum SP concentrations, National Institutes of Health Stroke Scale score (r = 0.480), hematoma volume (r = 0.464) and serum C-reactive protein concentrations (r = 0.398). ConclusionsHigher serum SP concentrations in the acute phase of ICH were intimately associated with aggravated inflammation response, rising severity and increased risk of a poor functional outcome, suggesting that serum SP could be an inflammatory prognostic factor for ICH.

Proper timing of control of hypertension and outcome in acute spontaneous intracerebral hemorrhage

ObjectiveHypertension is the commonest cause of acute spontaneous intracerebral hemorrhage (ICH) which is life-threatening with a poor prognosis. The aim of this study is to evaluate the prognosis and blood pressure monitoring and control in patients presented by acute spontaneous ICH.MethodsOne hundred and fifty patients presented by acute spontaneous ICH were classified according to the modified Rankin Scale (mRS) score after discharge to 70 patients with better outcomes (mRS = 0–2) while 80 patients with poor outcome (mRS = 3–6). Independent factors that were significantly related to prognosis were assessed by multivariate logistic regression. Spearman’s correlation of the blood pressure monitoring in the acute ICH and the outcome was investigated.ResultsSystolic blood pressure at the onset of ICH was higher in the unfavorable outcome group (P = 0.009). Diastolic blood pressure 1 h after admission, systolic blood pressure 6 h after admission, and the systolic blood pressure 24 h after admission to hospital were lower in the favorable outcome group (P = 0.005, P = 0.007 and 0.01, respectively). The independent variables related to favorable outcomes were younger age patients (P = 0.004), better level of consciousness at admission to hospital (P = 0.0001), and lower systolic blood pressure 6 h after admission to hospital (P = 0.005), decreased volume of hematoma (P = 0.05), supratentorial ICH (P = 0.02), and absence of intraventricular hemorrhage (P = 0.02).ConclusionsProper control and monitoring of the blood pressure in acute intracerebral hemorrhage must be initiated immediately especially in the first 6 h after hospitalization.Trial registrationClinicalTrials.gov ID: NCT04191863 'Retrospectively registered'

Venous thromboembolism prevention in intracerebral hemorrhage: A systematic review and network meta-analysis.

IntroductionTo summarize and compare the effectiveness of pharmacological thromboprophylaxis to pneumatic compression devices (PCD) for the prevention of venous thromboembolism in patients with acute intracerebral hemorrhage.MethodsMEDLINE, PUBMED, EMBASE, and CENTRAL were systematically searched to identify randomized and non-randomized studies that compared each intervention directly to each other or against a common control (hydration, anti-platelet agents, stockings) in adults with acute spontaneous intracerebral hemorrhage. Two investigators independently screened the studies, extracted data, and appraised risk of bias. Studies with a high risk of bias were excluded from our final analysis. The primary outcome was the occurrence of venous thromboembolism (proximal deep vein thrombosis or pulmonary embolism) in the first 30 days.Results8,739 articles were screened; four articles, all randomized control trials, met eligibility criteria. Bayesian network meta-analysis was performed to calculate risk estimates using both fixed and random effects analyses. 607 patients were included in the network analysis. PCD were associated with a significant decrease in venous thromboembolism compared to control (OR: 0.43, 95% Credible Limits [CrI]: 0.23–0.80). We did not find evidence of statistically significant differences between pharmacological thromboprophylaxis and control (OR: 0.93, 95% CrI: 0.19–4.37) or between PCD and pharmacological thromboprophylaxis (OR: 0.47, 95% CrI: 0.09–2.54).ConclusionPCDs are superior to control interventions, but meaningful comparisons with pharmacotherapy are not possible due to a lack of data. This requires further exploration via large pragmatic clinical trialsTrial registrationPROSPERO: CRD42018090960

In-hospital venous thromboembolism is associated with poor outcome in patients with spontaneous intracerebral hemorrhage: A multicenter, prospective study

Background and objectivePatients with intracerebral hemorrhage are susceptible to venous thromboembolism, but the relationship between venous thromboembolism and outcome is largely unknown. We aim to investigate the association of in-hospital venous thromboembolism with functional outcome in patients with intracerebral hemorrhage. MethodsFrom September 2014 through August 2016, we conducted a hospital-based, prospective study by consecutively recruiting eligible patients with first-ever acute spontaneous intracerebral hemorrhage. In-hospital venous thromboembolism was defined as observation of pulmonary embolism or deep vein thrombosis during initial hospitalization. The primary end point was death or disability (modified Rankin Scale 3 to 6) at discharge, 3-month and 1-year follow-up. Logistic analysis was conducted to evaluate the association of venous thromboembolism and poor functional outcome. ResultsAmong 637 participants included in the analysis, the prevalence of venous thromboembolism was 22.6%. After adjusting for confounding factors, venous thromboembolism was independently associated with death or disability at discharge (odds ratio 2.09, 95% confidence interval 1.12–3.85), 3-month follow-up (2.00 [1.12–3.54]) and 1-year follow-up (2.00 [1.14–3.49]). Venous thromboembolism was also an independent indicator of disability (modified Rankin Scale 3–5) among ICH survivors, with odds ratios ranging from 1.93 to 2.08 (all P<0.05). The relationship was stronger in patients with hematoma volume <10 ml (3.24 [1.11–9.46]) and ≥30 ml (2.57 [1.03–6.44]) (P for interaction=0.002) at 1-year follow-up. The results were confirmed by sensitivity analysis. ConclusionIn-hospital venous thromboembolism was independently associated with poor outcome at discharge, 3-month and 1-year in patients with intracerebral hemorrhage.

Long-term chemogenetic activation of M1 glutamatergic neurons attenuates the behavioral and cognitive deficits caused by intracerebral hemorrhage

Acute spontaneous intracerebral hemorrhage (ICH) is a life-threatening disease. It is often accompanied by severe neurological sequelae largely caused by the loss of integrity of the neural circuits. However, these neurological sequelae have few strong medical interventions. Designer receptors exclusively activated by designer drugs (DREADDs) are important chemogenetic tools capable of precisely modulating the activity of neural circuits. They have been suggested to have therapeutic effects on multiple neurological diseases. Despite this, no empirical research has explored the effects of DREADDs on functional recovery after ICH. We aimed to explore whether the long-term excitation of glutamatergic neurons in primary motor cortex (M1) by DREADD could promote functional recovery after ICH. We used CaMKII-driven Gq/Gi-DREADDs to activate/inhibit M1 glutamatergic neurons for 21 consecutive days, and examined their effects on behavioral and cognitive deficits caused by ICH in a mouse model of ICH targeting striatum. Long-term chemogenetic activation of the M1 glutamatergic neurons increased the spatial memory and sensorimotor ability of mice suffering from ICH. It also attenuated the mitochondrial dysfunctions of striatal neurons by raising the ATP levels and mitochondrial membrane potential while decreasing the 8-OHdG levels. These results strongly suggest that selective stimulation of the M1 glutamatergic neurons contributes to functional recovery after ICH presumably through alleviation of mitochondrial dysfunctions.

The Influence of Diffusion Weighted Imaging Lesions on Outcomes in Patients with Acute Spontaneous Intracerebral Hemorrhage.

Diffusion weighted imaging (DWI) lesions have been well described in patients with acute spontaneous intracerebral hemorrhage (sICH). However, there are limited data on the influence of these lesions on sICH functional outcomes. We conducted a prospective observational cohort study with blinded imaging and outcomes assessment to determine the influence of DWI lesions on long-term outcomes in patients with acute sICH. We hypothesized that DWI lesions are associated with worse modified Rankin Scale (mRS) at 3months after hospital discharge. Consecutive sICH patients meeting study criteria were consented for an magnetic resonance imaging (MRI) scan of the brain and evaluated for remote DWI lesions by neuroradiologists blinded to the patients' hospital course. Blinded mRS outcomes were obtained at 3months. Logistic regression was used to determine significant factors (p < 0.05) associated with worse functional outcomes defined as an mRS of 4-6. The generalized estimating equation (GEE) approach was used to investigate the effect of DWI lesions on dichotomized mRS (0-3 vs 4-6) longitudinally. DWI lesions were found in 60 of 121 patients (49.6%). The presence of a DWI lesion was associated with increased odds for an mRS of 4-6 at 3months (OR 5.987, 95% CI 1.409-25.435, p = 0.015) in logistic regression. Using the GEE model, patients with a DWI lesion were less likely to recover over time between 14days/discharge and 3months (p = 0.005). DWI lesions are common in primary sICH, occurring in almost half of our cohort. Our data suggest that DWI lesions are associated with worse mRS at 3months in good grade sICH and are predictive of impaired recovery after hospital discharge. Further research into the pathophysiologic mechanisms underlying DWI lesions may lead to novel treatment options that may improve outcomes associated with this devastating disease.

Convexity subarachnoid hemorrhage in lobar intracerebral hemorrhage: A prognostic marker.

To investigate whether acute convexity subarachnoid hemorrhage (cSAH) associated with acute lobar intracerebral hemorrhage (ICH) increases the risk of ICH recurrence in patients with cerebral amyloid angiopathy (CAA). We analyzed data from a prospective cohort of consecutive survivors of acute spontaneous lobar ICH fulfilling the Boston criteria for possible or probable CAA (CAA-ICH). We analyzed baseline clinical and MRI data, including cSAH (categorized as adjacent or remote from ICH on a standardized scale), cortical superficial siderosis (cSS), and other CAA MRI markers. Multivariable Cox regression models were used to assess the association between cSAH and recurrent symptomatic ICH during follow-up. We included 261 CAA-ICH survivors (mean age 76.2 ± 8.7 years). Of them, 166 (63.6%, 95% confidence interval [CI] 57.7%-69.5%) had cSAH on baseline MRI. During a median follow-up of 28.3 (interquartile range 7.2-57.0) months, 54 (20.7%) patients experienced a recurrent lobar ICH. In Cox regression, any cSAH, adjacent cSAH, and remote cSAH were independent predictors of recurrent ICH after adjustment for other confounders, including cSS. Incidence rate of recurrent ICH in patients with cSAH was 9.9 per 100 person-years (95% CI 7.3-13.0) compared with 1.2 per 100 person-years (95% CI 0.3-3.2) in those without cSAH (adjusted hazard ratio 7.5, 95% CI 2.6-21.1). In patients with CAA-related acute ICH, cSAH (adjacent or remote from lobar ICH) is commonly observed and heralds an increased risk of recurrent ICH. cSAH may help stratify bleeding risk and should be assessed along with cSS for prognosis and clinical management.