Outcome In Intracerebral Hemorrhage Patients Research Articles

Prognostic biomarkers of intracerebral hemorrhage identified using targeted proteomics and machine learning algorithms.

Early prognostication of patient outcomes in intracerebral hemorrhage (ICH) is critical for patient care. We aim to investigate protein biomarkers' role in prognosticating outcomes in ICH patients. We assessed 22 protein biomarkers using targeted proteomics in serum samples obtained from the ICH patient dataset (N = 150). We defined poor outcomes as modified Rankin scale score of 3-6. We incorporated clinical variables and protein biomarkers in regression models and random forest-based machine learning algorithms to predict poor outcomes and mortality. We report Odds Ratio (OR) or Hazard Ratio (HR) with 95% Confidence Interval (CI). We used five-fold cross-validation and bootstrapping for internal validation of prediction models. We included 149 patients for 90-day and 144 patients with ICH for 180-day outcome analyses. In multivariable logistic regression, UCH-L1 (adjusted OR 9.23; 95%CI 2.41-35.33), alpha-2-macroglobulin (aOR 5.57; 95%CI 1.26-24.59), and Serpin-A11 (aOR 9.33; 95%CI 1.09-79.94) were independent predictors of 90-day poor outcome; MMP-2 (aOR 6.32; 95%CI 1.82-21.90) was independent predictor of 180-day poor outcome. In multivariable Cox regression models, IGFBP-3 (aHR 2.08; 95%CI 1.24-3.48) predicted 90-day and MMP-9 (aOR 1.98; 95%CI 1.19-3.32) predicted 180-day mortality. Machine learning identified additional predictors, including haptoglobin for poor outcomes and UCH-L1, APO-C1, and MMP-2 for mortality prediction. Overall, random forest models outperformed regression models for predicting 180-day poor outcomes (AUC 0.89), and 90-day (AUC 0.81) and 180-day mortality (AUC 0.81). Serum biomarkers independently predicted short-term poor outcomes and mortality after ICH. Further research utilizing a multi-omics platform and temporal profiling is needed to explore additional biomarkers and refine predictive models for ICH prognosis.

Autonomic dysfunction and treatment strategies in intracerebral hemorrhage.

Autonomic dysfunction with central autonomic network (CAN) damage occurs frequently after intracerebral hemorrhage (ICH) and contributes to a series of adverse outcomes. This review aims to provide insight and convenience for future clinical practice and research on autonomic dysfunction in ICH patients. We summarize the autonomic dysfunction in ICH from the aspects of potential mechanisms, clinical significance, assessment, and treatment strategies. The CAN structures mainly include insular cortex, anterior cingulate cortex, amygdala, hypothalamus, nucleus of the solitary tract, ventrolateral medulla, dorsal motor nucleus of the vagus, nucleus ambiguus, parabrachial nucleus, and periaqueductal gray. Autonomic dysfunction after ICH is closely associated with neurological functional outcomes, cardiac complications, blood pressure fluctuation, immunosuppression and infection, thermoregulatory dysfunction, hyperglycemia, digestive dysfunction, and urogenital disturbances. Heart rate variability, baroreflex sensitivity, skin sympathetic nerve activity, sympathetic skin response, and plasma catecholamine concentration can be used to assess the autonomic functional activities after ICH. Risk stratification of patients according to autonomic functional activities, and development of intervention approaches based on the restoration of sympathetic-parasympathetic balance, would potentially improve clinical outcomes in ICH patients. The review systematically summarizes the evidence of autonomic dysfunction and its association with clinical outcomes in ICH patients, proposing that targeting autonomic dysfunction could be potentially investigated to improve the clinical outcomes.

CT-based deep learning model for predicting hospital discharge outcome in spontaneous intracerebral hemorrhage.

To predict the functional outcome of patients with intracerebral hemorrhage (ICH) using deep learning models based on computed tomography (CT) images. A retrospective, bi-center study of ICH patients was conducted. Firstly, a custom 3D convolutional model was built for predicting the functional outcome of ICH patients based on CT scans from randomly selected ICH patients in H training dataset collected from H hospital. Secondly, clinical data and radiological features were collected at admission and the Extreme Gradient Boosting (XGBoost) algorithm was used to establish a second model, named the XGBoost model. Finally, the Convolution model and XGBoost model were fused to build the third "Fusion model." Favorable outcome was defined as modified Rankin Scale score of 0-3 at discharge. The prognostic predictive accuracy of the three models was evaluated using an H test dataset and an external Y dataset, and compared with the performance of ICH score and ICH grading scale (ICH-GS). A total of 604 patients with ICH were included in this study, of which 450 patients were in the H training dataset, 50 patients in the H test dataset, and 104 patients in the Y dataset. In the Y dataset, the areas under the curve (AUCs) of the Convolution model, XGBoost model, and Fusion model were 0.829, 0.871, and 0.905, respectively. The Fusion model prognostic performance exceeded that of ICH score and ICH-GS (p = 0.043 and p = 0.045, respectively). Deep learning models have good accuracy for predicting functional outcome of patients with spontaneous intracerebral hemorrhage. The proposed deep learning Fusion model may assist clinicians in predicting functional outcome and developing treatment strategies, thereby improving the survival and quality of life of patients with spontaneous intracerebral hemorrhage. • Integrating clinical presentations, CT images, and radiological features to establish deep learning model for functional outcome prediction of patients with intracerebral hemorrhage. • Deep learning applied to CT images provides great help in prognosing functional outcome of intracerebral hemorrhage patients. • The developed deep learning model performs better than clinical prognostic scores in predicting functional outcome of patients with intracerebral hemorrhage.

Impact of early cognitive impairment on outcome trajectory in patients with intracerebral hemorrhage.

To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short-term recovery trajectories among ICH patients with early cognitive impairment. We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini-mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1-year increase, 1.037; 95% confidence interval [CI], 1.003-1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1-point increase, 1.146; 95% CI, 1.065-1.233; p < 0.001) and lobar ICH location (OR, 4.774; 95% CI, 1.810-12.593; p = 0.002) were associated with early cognitive impairment in ICH patients. Patients with ≥10 years of education were less likely to experience early cognitive impairment (OR, 0.323; 95% CI, 0.133-0.783; p = 0.012). Participants with early cognitive impairment had a higher risk of poor outcome (OR, 4.315; 95% CI, 1.503-12.393; p = 0.005) than those without. Furthermore, there was a significantly faster functional recovery rate for those without early cognitive impairment compared with those with at 3 and 6 months (p < 0.05). Early cognitive impairment was prevalent and associated with poor outcomes in ICH patients, which decelerated short-term functional recovery.

Korelasi antara Skor ICH C-Reactive Protein, D-Dimer terhadap Luaran Pasien Perdarahan Intraserebral

Background and Objective: Intracerebral hemorrhage (ICH) accounts for 10% to 15% of all strokes and has a high mortality and morbidity rate in the world. The ICH score is valid for predicting the severity of intracerebral hemorrhage patients treated in the ICU. The increase in C-reactive protein (CRP) value is a predictor in the outcome of ICU patients. The aim of this study was to find out how the ICH, CRP and D-dimer scores correlated with the outcome in intracerebral hemorrhage patients. Subjects and Methods: The subjects of this study were 27 patients with intracerebral hemorrhage who were treated in the ICU of H. Adam Malik Hospital and the University of North Sumatra Hospital. Data were collected using consecutive sampling, then ICH, CRP, D-dimer scores were measured and the examination was analyzed by length of stay. Results: Out of a total of 27 patients, 22 (81.5%) patients moved to the ward and 5 (18.5%) patients died. The mean for ICH score was 2.70(0.67), CRP was 1.41(0.72), and D-dimer was 2757.96(1230.73). The results of the correlation between ICH score and length of stay found a positive correlation (r = 0.498; p = 0.008), a correlation between CRP and length of stay had a weak correlation (r = 0.315; p = 0.109) and a correlation between D-dimer and length of stay and found a correlation positive (r = 0.546; p = 0.003). Conclusion: It was found that ICH, CRP and D-dimer scores had an effect on the length of stay of patients with intracerebral hemorrhage.

Predictors Of Outcome In ICH Patients Initially Admitted To The ICU Who Are Transferred To Inpatient Rehab (P5-7.002)

<h3>Objective:</h3> Assess factors associated with good functional outcomes after ICH requiring ICU admission. <h3>Background:</h3> Intracerebral hemorrhage (ICH) is associated with high mortality, with patients requiring intensive care unit (ICU) admission having worse outcomes. However, current scores are limited in their ability to predict functional outcomes. <h3>Design/Methods:</h3> We collected data using a prospectively maintained registry of stroke patients admitted to 5 inpatient rehabs (IR)s in our hospital system between 1/2018 to 6/2019. We performed predictive modeling with RIDGE regression analysis to predict the rehab discharge motor functional independence measure (FIM). Variables used to perform predictive modeling included age, ICU length of stay (LOS), concurrent IVH, ICH expansion, decompressive surgery, laterality of ICH, symptom onset to rehab admission, rehab admission motor FIM score, initial NIHSS, and total therapy days. <h3>Results:</h3> We identified 166 patients with ICH admitted to IR, of which a significant number (51%) were initially admitted to the ICU. After excluding patients with incomplete variables, 61 patients were included in the model. The median age was 59[47–71] years, and 44% were female. The median initial NIHSS was 12 [5–18], and the length of stay in the ICU was 6 [3–10] days. 34 (55.7%) of the patient had IVH, and 7 (11.5%) had hematoma expansion. 7 (11.5%) needed decompressive surgery. The median admit motor FIM score was 24 [17–36], and after a median of 14 [14–14] days in IR, the median discharge motor FIM score more than doubled to 58 [46–69]. Our predictive model had an r-squared of 0.65. Decompressive surgery patients had better scores by 4 points than patients without decompressive surgery. As therapy days increase by one day, discharge motor FIM scores increase by approximately 2 points. <h3>Conclusions:</h3> Our model can satisfactorily predict rehab discharge motor FIM. However, additional factors involved in the process will be explored to improve the model. <b>Disclosure:</b> Dr. Ahmad has nothing to disclose. Dr. Tariq has nothing to disclose. Christin Silos has nothing to disclose. Ms. Hernandez has nothing to disclose. Ms. Contreras has nothing to disclose. Dr. Savitz has nothing to disclose.

Research advances in imaging markers for predicting hematoma expansion in intracerebral hemorrhage: a narrative review.

Stroke is a major global health concern and is ranked as the second leading cause of death worldwide, with the third highest incidence of disability. Intracerebral hemorrhage (ICH) is a devastating form of stroke that is responsible for a significant proportion of stroke-related morbidity and mortality worldwide. Hematoma expansion (HE), which occurs in up to one-third of ICH patients, is a strong predictor of poor prognosis and can be potentially preventable if high-risk patients are identified early. In this review, we provide a comprehensive summary of previous research in this area and highlight the potential use of imaging markers for future research studies. Imaging markers have been developed in recent years to aid in the early detection of HE and guide clinical decision-making. These markers have been found to be effective in predicting HE in ICH patients and include specific manifestations on Computed Tomography (CT) and CT Angiography (CTA), such as the spot sign, leakage sign, spot-tail sign, island sign, satellite sign, iodine sign, blend sign, swirl sign, black hole sign, and hypodensities. The use of imaging markers holds great promise for improving the management and outcomes of ICH patients. The management of ICH presents a significant challenge, and identifying high-risk patients for HE is crucial to improving outcomes. The use of imaging markers for HE prediction can aid in the rapid identification of such patients and may serve as potential targets for anti-HE therapies in the acute phase of ICH. Therefore, further research is needed to establish the reliability and validity of these markers in identifying high-risk patients and guiding appropriate treatment decisions.

High plasma complement C4 levels as a novel predictor of clinical outcome in intracerebral hemorrhage.

The complement cascade is activated and contributes to the brain injury after intracerebral hemorrhage (ICH). Complement component 4 (C4), an important component of complement cascade, has been associated with severity of neurological impairment that occurs during ICH. However, the correlation of plasma complement C4 levels with hemorrhagic severity and clinical outcome in ICH patients has not been reported. This study is a monocentric, real-world, cohort study. In this study, we measured the plasma complement C4 levels of 83 ICH patients and 78 healthy controls. The hematoma volume, the National Institutes of Health Stroke Scale (NIHSS) score, the Glasgow Coma Scale (GCS) score, and the permeability surface (PS) were used to assess and quantify neurological deficit following ICH. Logistic regression analysis was configured to determine the independent relation of plasma complement C4 levels to hemorrhagic severity and clinical outcomes. The contribution of complement C4 to secondary brain injury (SBI) was assessed by changes in plasma C4 levels between admission and at day 7 after ICH. There was a significant elevation of plasma complement C4 levels in ICH patients than in healthy controls (40.48 ± 1.07 vs. 35.25 ± 0.60, p < 0.0001), and the plasma complement C4 levels were closely related to the hemorrhagic severity. Moreover, plasma complement C4 levels of patients were positively correlated with the hematoma volume (r = 0.501, p < 0.001), NIHSS score (r = 0.362, p < 0.001), the GCS score (r = -0.490, p < 0.001), and PS (r = 0.683, p = 0.045) following ICH. Logistic regression analysis also confirmed that patients with high plasma complement C4 levels show a poor clinical outcome after ICH (p < 0.001). Meanwhile, the elevated plasma levels at day 7 after ICH indicated the correlation of complement C4 with SBI (p < 0.01). Plasma complement C4 levels are significantly elevated in ICH patients and positively correlated with the illness severity. Thus, these findings highlight the importance of complement C4 in brain injury after ICH and provide a novel predictor of clinical outcome for this disease.

P7C3-A20 Attenuates Microglial Inflammation and Brain Injury after ICH through Activating the NAD+/Sirt3 Pathway.

Intracerebral hemorrhage (ICH) is lethal but lacks effective therapies. Nicotinamide adenine dinucleotide (NAD+) is a central metabolite indispensable for a broader range of fundamental intracellular biological functions. Reduction of NAD+ usually occurs after acute brain insults, and supplementation of NAD+ has been proven neuroprotective. P7C3-A20 is a novel compound featuring its ability to facilitate the flux of NAD+. In this study, we sought to determine the potential therapeutic value of P7C3-A20 in ICH. In collagenase-induced ICH mouse models, we found that P7C3-A20 treatment could diminish lesion volume, reduce blood-brain barrier (BBB) damage, mitigate brain edema, attenuate neural apoptosis, and improve neurological outcomes after ICH. Further, RNA sequencing and subsequent experiments revealed that ICH-induced neuroinflammation and microglial proinflammatory activities were significantly suppressed following P7C3-A20 treatment. Mitochondrial damage is an important trigger of inflammatory response. We examined mitochondrial morphology and function and found that P7C3-A20 could attenuate OxyHb-induced impairment of mitochondrial dynamics and functions in vitro. Mechanistically, Sirt3, an NAD+-dependent deacetylase located in mitochondria, was then found to play a vital role in the protection of P7C3-A20 against mitochondrial damage and inflammatory response. In rescue experiments, P7C3-A20 failed to exert those protective effects in microglia-specific Sirt3 conditional knockout (CKO) mice. Finally, preclinical research revealed a correlation between the plasma NAD+ level and the neurological outcome in ICH patients. These results demonstrate that P7C3-A20 is a promising therapeutic agent for neuroinflammatory injury after ICH and exerts protective actions, at least partly, in a Sirt3-dependent manner.

Abstract TP126: Rising Incidence Of Hydrocephalus In Patients With Intracerebral Hemorrhage In 20-year Analysis Of The National Inpatient Sample

Introduction: Hydrocephalus (HCP) is a common consequence of intracerebral hemorrhage (ICH) and is a predictor of poor outcomes in ICH patients. We aimed to characterize ICH patients with HCP and assess their clinical outcomes over a 20-year period. Methods: A query of the 2000-2019 National Inpatient Sample was performed for patients admitted with ICH (ICD9 431, 432.9, ICD-10 I61, I62.9). Demographics, comorbidities, and outcomes were identified. Univariate analysis with t-tests or chi-square performed as appropriate. A 1:1 nearest neighbor propensity score matched cohort was generated. Variables with standardized mean differences &gt;0.1 used in multivariate regression to generate adjusted odds ratios (AOR)/β-coefficients for the presence of hydrocephalus on outcomes. Significance set at an alpha level of &lt;0.001. All analysis performed in R version 4.1.3. Results: 2,000,868 patients with ICH were identified; 9.2% had HCP. Patients with HCP had higher NIHSS (17.16±11.13 vs 10.77±9.14) and Elixhauser Comorbidity Score (10.64±8.79 vs. 10.4±9.12) at presentation, longer hospital stays (13.92±18.13 vs 8.13± 11.3 days) and higher hospital charges ($160,604.36± 225,493.62 vs $74,930.99± 137,200.59) (all p&lt;0.001). After propensity matching, HCP patients had higher rates of surgical intervention (including EVD and ventricular shunt placement), and higher tracheostomy and PEG/G-tube requirement (all p&lt;0.001). On multivariate analysis, HCP patients had higher in-hospital mortality (2.21; 95% CI: 1.85-2.65) and lesser likelihood of discharge home or short-term hospital (0.46; 95% CI: 0.35-0.61) (p&lt;0.001). Conclusion: In this 20-year nationally representative propensity matched analysis of patients with ICH, those with concomitant HCP had higher rates of surgical procedures (EVD, ventricular shunt, tracheostomy and PEG). Incidence of HCP increased more than two-fold from2000-2019, suggesting worsening disease severity over the study period.

Homocysteine and Clinical Outcomes in Intracerebral Hemorrhage Patients: Results from the China Stroke Center Alliance.

Elevated homocysteine (Hcy) levels play a detrimental role in ischemic stroke. Acute spontaneous intracerebral hemorrhage (ICH) accounts for nearly 25% of all stroke cases. However, the influence of Hcy levels and ICH severity on clinical outcomes is unclear. Data were obtained from 85,705 ICH patients enrolled in the China Stroke Center Alliance (CSCA) study, a national, hospital-based, multicenter, voluntary, quality assessment and improvement initiative performed in China. Patients were divided into high and normal Hcy groups according to their Hcy levels observed at admission. The outcome indices included severe ICH, in-hospital mortality, and a poor functional outcome at discharge. Multivariable logistic regression was used to analyze the association of different Hcy levels with outcomes. The final analysis included 55,793 ICH patients. High homocysteine (HHcy) levels had higher adjusted odds ratios for severe ICH (OR 1.09, 95% CI 1.01-1.10, P<0.0001) and a poor functional outcome at discharge (OR 1.06, 95% CI 1.01-1.10, P=0.0100) compared with normal Hcy levels. There was no significant difference between HHcy and in-hospital mortality. In the subgroup analysis, stratified by sex and history of hypertension, significant interactions were observed between HHcy and severe ICH (P for interactions was 0.0138 and 0.0120, respectively). HHcy levels exhibited greater associations for severe ICH in female patients (OR 1.07, 95% CI 1.02-1.12) and patients without hypertension (OR 1.20, 95% CI 1.09-1.33). An elevated Hcy level exhibited significant association with severe ICH on admission and a poor functional outcome at discharge. The relationship between HHcy and ICH severity on admission was more robust in female patients and patients without hypertension. Hcy might be a valuable biomarker for ICH patients to predict severity at onset and functional outcome at discharge.

Association between non-HDLC and 1-year prognosis in patients with spontaneous intracerebral haemorrhage: a prospective cohort study from 13 hospitals in Beijing

ObjectivesPrevious studies suggested an inverse association between lipoprotein cholesterols and bleeding risk, while limited data were available about the predictive value of lipoproteins on intracerebral haemorrhage (ICH). Our recent research...

Cognitive Outcome of Intracerebral Hemorrhage Patients with and without Pneumonia

Background: There are high prevalence of cognitive impairment in patients with intracerebral hemorrhage (ICH) that may worsen the patients’ outcomes. Pneumonia, as the significant infection complication in stroke patients, may aggravate the decline in the cognitive outcome of patients. This study aimed to explore the cognitive outcomes among patients with or without pneumonia among patients with intracerebral hemorrhage.Methods: A cross-sectional retrospective analytical comparative numeric study was conducted from September 2020 to February 2021, using secondary data of patients with intracerebral hemorrhage admitted to the Department of Neurology Dr. Hasan Sadikin General Hospital in the year 2019. A total sampling method was employed. Data on pneumonia in stroke patients was retrieved, consisting of patients with pneumonia and without pneumonia. Data on Mini-Mental State Examination (MMSE) scores as the measures of cognitive outcomes were compared using the Mann-Whitney U test.Results: There were 108 patients with intracerebral hemorrhage included. There was a statistically significant difference (p value 0.049) in MMSE scores with median MMSE score for pneumonia patients (n = 27) and non-pneumonia patients (n = 81) were 25 and 21, respectively.Conclusions: Cognitive outcome is worse in patients with pneumonia than those without pneumonia. Early intervention is needed for intracerebral hemorrhage patients who develop pneumonia as a complication to improve the cognitive outcome.

Time course of beat-to-beat blood pressure variability and outcome in patients with spontaneous intracerebral haemorrhage.

Increased blood pressure variability (BPV) over 24 h or longer was associated with poor clinical outcomes in patients with intracerebral haemorrhage (ICH). However, the characteristics of beat-to-beat BPV, a rapid assessment of BPV and its association with outcome in ICH patients remain unknown. We consecutively and prospectively recruited patients with ICH between June 2014 and December 2020. Five-minute noninvasive beat-to-beat recordings were measured serially at three time points, 1-2, 4-6 and 10-12 days after ICH onset. BPV was calculated using standard deviation (SD) and variation independent of mean (VIM). Favourable outcome was defined as modified Rankin Scale score of less than 2 at 90 days. The analysis included 66 participants (54.12 ± 10.79 years; 71.2% men) and 66 age and sex-matched healthy controls. Compared with that in healthy adults, beat-to-beat BPV was significantly increased 1-2 days after ICH and was completely recovered 10-12 days later. BPV recorded 1-2 days after ICH onset was higher among patients with unfavourable outcomes than among those with favourable outcomes (all P < 0.05) and higher BPV on days 1-2 was independently associated with a 3-month unfavourable outcome after adjustment for major covariates. Beat-to-beat BPV was significantly increased among patients with ICH and could be completely recovered 10-12 days later. In addition, beat-to-beat BPV 1-2 days after ICH was independently associated with prognosis and could be regarded as a potential prognostic predictor and effective therapeutic target in the future.

Plasma PRPC Levels Correlate With Severity and Prognosis of Intracerebral Hemorrhage.

BackgroundCellular prion protein (PRPC) exerts brain-protective effects. We determined the relationship between plasma PRPC levels and disease severity plus clinical outcome after acute intracerebral hemorrhage (ICH).MethodsA total of 138 ICH patients and 138 healthy controls were included in this prospective, observational study. Hematoma volume and Glasgow coma scale (GCS) score were used to assess disease severity. Glasgow outcome scale (GOS) scores of 1–3 and 4–5 at 90 days after stroke were defined as a poor outcome and good outcome, respectively. Using multivariate analysis, we discerned the relation of plasma PRPC levels to disease severity and poor outcome. The receiver operating characteristic (ROC) curve was built to evaluate the prognostic predictive capability.ResultsPlasma PRPC levels in ICH patients were significantly higher than those in healthy controls (median, 4.20 vs. 2.02 ng/ml; P < 0.001), and were independently correlated with GCS score (r = −0.645, P < 0.001) and hematoma volume (r = 0.627, P < 0.001). Plasma PRPC levels were highly correlated with GOS score (r = −0.762, P < 0.001), and were substantially higher in patients with poor outcomes than in those with the good outcomes. Using maximum Youden index, plasma PRPC levels >3.893 ng/ml distinguished the risk of poor outcome at 90 days, with a sensitivity of 86.4% and a specificity of 65.8% (area under the curve, 0.809; 95% confidence interval (CI), 0.737–0.881, P < 0.001). Plasma PRPC levels >3.893 ng/ml were independently associated with a poor 90-day outcome with an odds ratio of 12.278 (95% CI, 5.101–29.554).ConclusionElevated plasma PRPC levels are significantly associated with disease severity and poor 90-day outcome in ICH patients, indicating that plasma PRPC may be used as a potential prognostic biomarker after ICH.

Role of plasma Apo-J as a biomarker of severity and outcome after intracerebral hemorrhage: A prospective and cohort study

BackgroundApolipoprotein J (Apo-J) may act as a neuroprotective factor after acute brain injury. We gauged plasma Apo-J concentrations in patients with acute intracerebral hemorrhage (ICH) and investigated its predictive value for 90-day outcome and disease severity. MethodsThis prospective cohort study included 123 ICH patients and 123 healthy controls. The severity of ICH was assessed using the Glasgow Coma Scale (GCS) score and hematoma volume. Poor outcome was referred to as a Glasgow Outcome Scale (GOS) score of 1–3 at 90 days after stroke. Multivariate analysis was performed to identify associations of plasma Apo-J concentrations with disease severity and poor outcome. ResultsThe plasma Apo-J concentrations of patients were significantly higher than those of healthy controls (median, 95.50 mg/l versus 55.71 mg/l; P < 0.001), and were independently correlated with hematoma volume (t = 2.716; P = 0.008) and GCS score (t = −5.978; P < 0.001). Plasma Apo-J significantly differentiated patients at risk of poor outcome (area under receiver operating characteristic curve (AUC), 0.772; 95% confidence interval (CI), 0.688–0.843; P < 0.001), and its predictive ability was similar to those of GCS score (AUC, 0.851; 95% CI, 0.776–0.909; P = 0.056) and hematoma volume (AUC, 0.849; 95% CI, 0.774–0.907, P = 0.089). Using maximum Youden index, plasma Apo-J concentrations >113.21 mg/l distinguished the development of poor outcome, with a sensitivity of 67.3% and a specificity of 87.3%. Plasma Apo-J concentrations >113.21 mg/l (odds ratio, 4.042; 95% CI, 1.093–14.951; P = 0.036) and hematoma volume (odds ratio, 1.124; 95% CI, 1.014–1.247; P = 0.027) were independently associated with poor outcome. ConclusionsPlasma Apo-J concentrations are markedly associated with disease severity and 90-day poor outcome in ICH patients. Hence, plasma Apo-J is presumed to be used as a potential prognostic biomarker of ICH.

Pilot Study of Remote Ischemic Conditioning in Acute Spontaneous Intracerebral Hemorrhage.

Spontaneous Intracerebral hemorrhage (ICH) is a devastating injury that accounts for 10–15% of all strokes. The rupture of cerebral blood vessels damaged by hypertension or cerebral amyloid angiopathy creates a space-occupying hematoma that contributes toward neurological deterioration and high patient morbidity and mortality. Numerous protocols have explored a role for surgical decompression of ICH via craniotomy, stereotactic guided endoscopy, and minimally invasive catheter/tube evacuation. Studies including, but not limited to, STICH, STICH-II, MISTIE, MISTIE-II, MISTIE-III, ENRICH, and ICES have all shown that, in certain limited patient populations, evacuation can be done safely and mortality can be decreased, but functional outcomes remain statistically no different compared to medical management alone. Only 10–15% of patients with ICH are surgical candidates based on clot location, medical comorbidities, and limitations regarding early surgical intervention. To date, no clearly effective treatment options are available to improve ICH outcomes, leaving medical and supportive management as the standard of care. We recently identified that remote ischemic conditioning (RIC), the non-invasive, repetitive inflation-deflation of a blood pressure cuff on a limb, non-invasively enhanced hematoma resolution and improved neurological outcomes via anti-inflammatory macrophage polarization in pre-clinical ICH models. Herein, we propose a pilot, placebo-controlled, open-label, randomized trial to test the hypothesis that RIC accelerates hematoma resorption and improves outcomes in ICH patients. Twenty ICH patients will be randomized to receive either mock conditioning or unilateral arm RIC (4 cycles × 5 min inflation/5 min deflation per cycle) beginning within 48 h of stroke onset and continuing twice daily for one week. All patients will receive standard medical care according to latest guidelines. The primary outcome will be the safety evaluation of unilateral RIC in ICH patients. Secondary outcomes will include hematoma volume/clot resorption rate and functional outcomes, as assessed by the modified Rankin Scale (mRS) at 1- and 3-months post-ICH. Additionally, blood will be collected for exploratory genomic analysis. This study will establish the feasibility and safety of RIC in acute ICH patients, providing a foundation for a larger, multi-center clinical trial.

Cardiovascular Predictors of Intracerebral Hematoma Expansion

BackgroundThere is limited evidence on the effect and relevance of cardiovascular parameters on the cerebrovascular system when an intracerebral hemorrhage (ICH) occurs. While recent studies evaluating this relationship are conflicting, one evaluating the effect of systolic cardiac function on clinical outcomes in ICH patients, found low cardiac ejection fractions to be associated with poor clinical outcomes. Our primary objective was to study such correlations and identify various cardiovascular disease states that may be associated with hematoma expansion. MethodsThis is an IRB-approved single-center retrospective study utilizing our institutional “Get with the Guidelines”-Stroke registry between 2013 and 2017. Patients included were older than 18 years of age, admitted with an acute ICH, and had an echocardiogram during their hospitalization. Univariate and multivariate logistical regression analyses were used to identify cardiovascular predictors of hematoma expansion. ResultsTwo-hundred forty-nine patients were identified from our GWTG-S registry that met initial inclusion criteria. Of these patients, a history of peripheral arterial disease (PAD) (p = 0.015), presence of aortic stenosis (AS) on the echocardiogram (p = 0.025), and a positive spot sign on the CT-angiogram (CTA) of the head (p < 0.001) were found to be independently associated with ICH expansion. Both a history of hypertension and elevated blood pressure on presentation were not significant predictors. Additionally, patients with a history of congestive heart failure had decreased odds of hematoma expansion (p = 0.027). ConclusionThis exploratory study highlights potential novel cardiac predictors of hematoma expansion, including PAD and AS, which warrant further study. Larger prospective studies are needed to further investigate such associations to ultimately optimize cardio-cerebral health.

Revisiting Minocycline in Intracerebral Hemorrhage: Mechanisms and Clinical Translation.

Intracerebral hemorrhage (ICH) is an important subtype of stroke with an unsatisfactory prognosis of high mortality and disability. Although many pre-clinical studies and clinical trials have been performed in the past decades, effective therapy that meaningfully improve prognosis and outcomes of ICH patients is still lacking. An active area of research is towards alleviating secondary brain injury after ICH through neuroprotective pharmaceuticals and in which minocycline is a promising candidate. Here, we will first discuss new insights into the protective mechanisms of minocycline for ICH including reducing iron-related toxicity, maintenance of blood-brain barrier, and alleviating different types of cell death from preclinical data, then consider its shortcomings. Finally, we will review clinical trial perspectives for minocycline in ICH. We hope that this summary and discussion about updated information on minocycline as a viable treatment for ICH can facilitate further investigations.

Role of Procalcitonin in Intracerebral Hemorrhage Stroke with COVID-19

Introduction: As COVID-19 has rapidly spread worldwide, it is an urgent health problem. Some evidence suggests that SARS-CoV-2 also affects the central nervous system. Stroke is the most common disease of the central nervous system. In contrast to ischemic stroke, which can occur due to the hypercoagulation effect of COVID-19, the study of Intracerebral Hemorrhage (ICH) associated with COVID-19 is still unclear. Objective: This paper investigated the characteristics of an inflammatory biomarker and compared the outcomes of ICH patients with COVID-19 and ICH patients without COVID-19. Methods: We conducted a retrospective, observational analysis case-control of patients (n = 42) admitted with ICH with positive COVID-19 and ICH with negative COVID-19 at the National Brain Center Hospital Prof.Dr.dr. Mahar Mardjono from March 2020 to August 2021. We took blood samples and COVID-19 swab PCR on the first day of admission, and GOS was measured when the patients were discharged. Results: There were 21 ICH patients with positive COVID-19 who had a significantly procalcitonin (p &lt; 0.05) compared to control patients. From Spearman’s correlational analysis, there is a significant value between early procalcitonin and the Barthel Index (rs = -0,374, p &lt; 0.05), early CRP and GOS (rs =- 0.329, p &lt; 0.05), which indicates weak-inverse correlation, and between early PCT and GOS (rs = -0.438, p &lt; 0.05) which indicates moderate-inverse correlation. Conclusion: The level of procalcitonin was increased in ICH patients with COVID-19. Maybe PCT could be a predictor of outcome in ICH patients with COVID-19.