Intracerebral Hemorrhage Research Articles

Supra-Prophylactic Doses of Enoxaparin Reduces Fibrin Deposition Without Exacerbation of Intracerebral Hemorrhage in a Rat Model of Penetrating Traumatic Brain Injury.

Deep vein thrombosis and pulmonary embolism prophylaxis is an important part of trauma care. Despite an increased risk of thrombotic complications, the use of venous thrombosis chemoprophylaxis in penetrating traumatic brain injury (pTBI) patients is met with reluctance from neurosurgeons because of concern for the exacerbation of intracerebral hemorrhage. The objective of this study was to provide initial pre-clinical evidence of the effects of Lovenox (LVX) administration following pTBI with significant intracerebral hemorrhage. Sprague-Dawley rats received a penetrating ballistic-like brain injury. Animals were randomly divided into two groups following injury: LVX (25 mg/kg) or vehicle (VEH, saline). LVX or vehicle was administered subcutaneously beginning 24 h after the injury and continued daily for 7 days post-injury. A neurological assessment was performed daily and magnetic resonance imaging (MRI) was performed at baseline, 1, 2, 3, and 7 days post-injury. Following the final MRI, brains were isolated and prepared for histological analysis. Thromboelastography demonstrated dramatic anticoagulation effects which were confirmed by significant increases in partial thromboplastin time (p < 0.001). Daily neurological assessment revealed no worsening of functional deficits following LVX treatment. MRI analysis demonstrated no differences in cerebral edema or intracranial hemorrhage volumes between treatment groups at any tested post-injury time points. However, LVX elicited a significant reduction in fibrin deposition in the ipsilateral striatum and lesion site at 7 days post-injury (p < 0.05). Serum levels of beta-amyloid were decreased at 7 days following LVX treatment (p < 0.05) which may indicate neuroprotective effects but was not correlated to brain levels. The results presented indicate that administration of LVX at a dose capable of inducing anticoagulation is safe in a rodent model of pTBI without exacerbation of intracerebral hemorrhage within the first 7 days of injury.

Application of detailed nursing management intervention in neurosurgical nursing.

In the contemporary healthcare environment, optimizing patient care strategies is of importance, particularly in neurosurgical environments. While traditional nursing methods have the foundation of patient care, there exists a growing recognition of the potential benefits of comprehensive nurse management. Despite this acknowledgment, there remains a gap in understanding the comparative effectiveness of comprehensive nurse management versus traditional approaches in reducing postoperative psychological stress, enhancing patient satisfaction, and promoting adherence in neurosurgical patients. This study compares the efficacy of comprehensive nurse management against traditional methods in facilitating the postoperative recovery of neurosurgical patients. Taking the traditional nursing management and detailed nursing management of neurosurgical patients in a municipal neurosurgical hospital from March 2021 to March 2022 as an example, the neurosurgery was divided into 50 patients in the detailed nursing management group and 50 patients in the traditional nursing management group. In the clear nursing management group, there were 50 patients, 20 male patients, with an average age of 58.7 ± 3.8 years, and 30 female patients, with an average age of 60.4 ± 4.3 years; In the traditional nursing management group, there were 50 patients, 26 male patients, with an average age of 59.7 ± 3.7 years, and 24 female patients, with an average age of 59.4 ± 3.9 years; Among the 100 patients, there were 60 cases of cerebral infarction, 25 cases of intracerebral hemorrhage and 15 cases of other neurosurgical diseases. Hundred neurosurgical patients were divided into two groups: comprehensive nursing management group and traditional nursing management group. The results showed that the comprehensive treatment effect of patients with detailed nursing management was better than that of the routine nursing group. At the same time, the complications were reduced, and the patient's satisfaction was higher. Through retrospective analysis and investigation of patients, this paper discusses the clinical application of a detailed nursing management model in neurosurgery, which can reduce the probability of infection and other complications and improve the quality of life and treatment effect of patients.

Plasma metabolites, systolic blood pressure, lifestyle, and stroke risk: A prospective cohort study.

To estimate the associations of stroke risk with plasma metabolites, metabolic risk score (MRS), the combinations of MRS with hypertension or lifestyle, and lifestyle-related metabolic signature. To assess the improvement of the stroke risk prediction model through the incorporation of MRS. A total of 77,315 participants from the UK Biobank were included in this study. Xgboost and LASSO-Cox regression were used to select metabolites and construct MRS. Elastic net regression was utilized to construct the lifestyle-related metabolic signature. Multivariate Cox regression was used to estimate the associations between metabolites, MRS, the combinations of MRS with hypertension or lifestyle, lifestyle-related metabolic signature, and stroke risk. We identified 48, 63, 39, and 4 metabolites associated with the risk of stroke, ischemic stroke (IS), subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH), respectively. High MRS significantly increased the risk of stroke (HR = 2.65 (95% confidence interval (CI): 2.09-3.35)), IS (HR = 2.45 (95% CI: 1.89-3.17)), ICH (HR = 2.74 (95% CI: 1.55-4.85)), and SAH (HR = 4.64 (95% CI: 2.25-9.56)). In the combination analyses, compared with normal systolic blood pressure (SBP) and low MRS, normal/high SBP, and high MRS significantly increased stroke risk (HR = 5.80 (95% CI: 2.75-12.27)/6.37 (95% CI: 3.22-12.62)). A favorable/unfavorable lifestyle and high MRS also significantly increased stroke risk (HR = 2.38 (95% CI: 1.73-3.28)/3.86 (95% CI: 2.63-5.67)) compared with a favorable lifestyle and low MRS. Incorporating MRS into the 15-year stroke and IS risk prediction model increased the areas under the curves (AUCs) from 0.746 to 0.766 and from 0.771 to 0.811, respectively. The metabolic signature was correlated with adherence to a healthy lifestyle (r = 0.414; P = 2.22e-16) and inversely associated with stroke risk (HR = 0.80 (95% CI: 0.73-0.86)). Various metabolites and MRS were significantly associated with the risk of stroke, IS, ICH, and SAH. Individuals with a high MRS may face an elevated stroke risk among populations with high SBP or unhealthy lifestyle, even those with normal SBP or healthy lifestyle. MRS provided modest improvement to the stroke risk prediction model. The lifestyle-related metabolic signature could reduce 20% stroke risk.

Platelet-Function-Monitoring-Guided Therapy After Emergent Carotid Artery Stenting

Background/Objectives: Antiplatelet therapy after emergent carotid stenting (eCAS) represents a challenge in balancing the risk of intracerebral hemorrhages (ICHs) and in-stent thrombosis (IST). Post-procedural platelet function monitoring may guide antiplatelet therapy and could potentially improve outcomes due to fewer post-procedural complications. Methods: Consecutive eCAS patients (2019–2021) were included in a single-center retrospective observational study. Patients treated with eCAS received peri-procedural eptifibatide followed by dual antiplatelet treatment with aspirin and clopidogrel. The effect of platelet ADP inhibition by clopidogrel was monitored using the Multiplate® Analyzer (Roche). Clopidogrel non-responders were changed to ticagrelor treatment. The primary outcome was defined as a favorable outcome at 90 days using the modified Rankin Scale (mRS) of 0–2 versus 3–6. Safety outcomes included ICH, IST, and mortality. Data were analyzed and compared in clopidogrel- and ticagrelor-treated patients using Fischer’s exact test and multivariate logistic regression. Results: A total of 105 patients had eCAS, and 28 patients (27%) were clopidogrel non-responders and were changed to treatment with ticagrelor. The favorable outcome was more frequent in ticagrelor-treated patients, 23 (82%), than in clopidogrel-treated patients, 44 (57%), p = 0.036. Numerically, ICH, IST, and mortality were more frequent in clopidogrel-treated patients, but none of the differences were statistically significant. In multivariate analyses, ticagrelor treatment was significantly associated with the favorable outcome, OR = 3.89 (95% CI: 1.09–13.86), p = 0.036. Conclusions: One in four eCAS patients were clopidogrel non-responders. This study suggests that personalized antiplatelet treatment therapy was safe, and that changing treatment to ticagrelor in clopidogrel non-responders was associated with better outcomes in eCAS patients.

A Five-Point Score Grading System for Predicting Early Hematoma Expansion in Patients with Spontaneous Intracerebral Hemorrhage

Background: Stroke is the second leading cause of mortality and morbidity worldwide, with spontaneous Intracranial Hemorrhage (ICH) accounting for 9%-27% of all strokes. The study evaluates clinical and NCCT markers to predict early Hematoma Expansion (HE) in patients with Intracranial Hemorrhage (ICH), focusing on directing management objectives. Methods: We prospectively evaluated 96 patients with spontaneous ICH who underwent a baseline NCCT within four hours of admission, followed by a follow-up scan within six hours or at the time of clinical deterioration, whichever was earlier. Hematoma volumes were determined using baseline and follow-up CT images and imaging characteristics that predicted HE were evaluated. A grading system score was created to predict HE. Results: Of the ninety-six patients studied, 29 displayed black hole signs, 31 had island signs and 22 had swirl signs on baseline NCCT. On follow-up scans, the total incidence of HE in ICH patients was 53 out of 96 (55.2%). The average baseline hematoma volume in HE patients was 44.1 ml, compared to 12.2 ml in non-hematoma expansion patients. Of the 53 patients with HE, 29 had black hole sign, 16 had swirl sign and 28 had island sign. A higher grading system score (P &lt; 0.001) was associated with a higher likelihood of HE.

Association between Lactate dehydrogenase and 28-day all-cause mortality in patients with non-traumatic Intracerebral hemorrhage: A retrospective analysis of the MIMIC-IV database.

Lactate dehydrogenase (LDH), a nonspecific inflammatory biomarker, has been used in the assessment of acute myocardial infarction, acute hepatitis, acute lung injury, and other severe diseases. However, no studies have evaluated the prognostic value of LDH in patients with non-traumatic intracerebral hemorrhage (ICH). This cohort study aims to assess the association between LDH levels and 28-day all-cause mortality in patients with non-traumatic ICH. Data for this retrospective cohort analysis were obtained from the MIMIC-IV (v2.2) database, and the study included patients with non-traumatic ICH as defined by the International Classification of Diseases, 9th and 10th editions. Patients were categorized into four distinct groups based on their LDH levels. The primary outcome of interest was the 28-day mortality rate. To analyze these associations and assess the consistency of interactions, subgroup analyses, Cox regression analysis, Kaplan-Meier (KM) curves, and nonlinear analysis were conducted. A total of 406 patients with non-traumatic ICH were enrolled in the study and were divided into quartiles based on LDH levels. The KM curve indicated that the 28-day all-cause mortality rate of patients in the Q4 group (LDH > 287.25) was significantly higher than in the Q1 (LDH < 194.7) (P < 0.001) and Q2 (194.7 < LDH < 233.0) (P < 0.001) groups, though not significantly different from Q3 (P = 0.140). Multivariate Cox proportional hazards analysis revealed that patients in the highest LDH quartile had a significantly increased risk of mortality compared to those in the lowest quartile across three models: unadjusted [HR, 3.401; 95% CI, 1.719-6.731; P < 0.001], partially adjusted [HR, 2.422; 95% CI, 1.211-4.846; P = 0.012], and fully adjusted [HR, 3.054; 95% CI, 1.522-6.126; P = 0.002]. Restricted cubic spline (RCS) models revealed an L-shaped association between LDH levels and the 28-day all-cause mortality rate, indicating a non-linear relationship (P < 0.001). No significant interactions were observed between LDH levels and other factors in the subgroup analyses (all P for interaction > 0.05). Our findings indicate a significant association between 28-day all-cause mortality and LDH levels in patients with non-traumatic intracerebral hemorrhage. Specifically, patients with elevated LDH levels within the first 24 hours of ICU admission are at a higher risk of mortality.

Sex Modifies the Severity and Outcome of Spontaneous Intracerebral Hemorrhage.

The limited existing evidence on sex differences in the clinical characteristics of patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH) comes from small, single-center studies. Here, we performed an individual patient data meta-analysis of 3 randomized clinical trials and 1 multi-ethnic observational study of ICH to investigate the impact of sex on ICH severity and outcome. Inclusion criteria in our study were a neuroimaging-confirmed ICH. We evaluated whether sex was associated with ICH severity (hematoma volume and expansion) and poor functional outcomes (modified Rankin Scale >3) 3 or 6 months after the ICH. A total of 4,812 ICH patients were evaluated (mean age 62, 40% female). Males with ICH were younger, more likely to be smokers and have diabetes, and less likely to be on anticoagulants (all p < 0.05). In multivariable analyses, male sex was associated with non-lobar location (odds ratio [OR]: 1.63; 95% confidence interval [CI]: [1.39-1.92]; p < 0.001), larger hemorrhages (beta: 0.16 [0.08-0.23]; p < 0.001) and a higher risk of hematoma expansion (OR: 1.43 [1.20-1.71]; p < 0.001). Despite the larger hemorrhage volume and higher risk of expansion, male sex was associated with a 24% lower risk of poor outcomes (OR: 0.76 [0.64-0.90]; p = 0.002). Compared to females, males with ICH have larger bleeds and higher risk of hematoma expansion. Despite the larger bleeds and higher risk of hematoma expansion, males with ICH have lower risk of poor outcomes. Our results suggest that the biology and clinical trajectory are different in females and males with ICH, supporting sex-specific research in this condition. ANN NEUROL 2024.

Diagnosing Monogenic Stroke at Younger Age.

An increasing number of monogenic conditions underlying stroke are being identified. We explored the possibilities of increasing the diagnostic yield of monogenic stroke in a population under 56 years of age. Fifty probands ≤55 years at their first stroke episode were characterized clinically and investigated by whole genome sequencing. Probands had one or more of: (1) one or more first to second degree relatives with stroke under 60 years or same stroke-causing condition/disease; (2) no hypertension, hypercholesterolemia, diabetes, heart disease, or smoking; or (3) either multiple stroke episodes or multiple arterial dissections. Variants with minor allele frequency under 0.01, identified by using our stroke gene panels, were assessed. The stroke subtypes, including large artery atherosclerotic, large artery nonatherosclerotic (tortuosity, dolichoectasia, aneurysm, nonatherosclerotic dissection, or occlusion), cerebral small vessel disease, cardioembolic (arrhythmia, heart defect, or cardiomyopathy), coagulation dysfunctions (venous thrombosis, arterial thrombosis, or bleeding tendency), intracerebral hemorrhage, vascular malformations (cavernoma or arteriovenous malformations), metabolic disorders, or cryptogenic embolic, were used for genotype-phenotype correlation. In a final step, we combined genetic and clinical information to determine if the genetic variant likely was the cause of stroke in the patients. Whole genome sequencing of younger patients with stroke identified 17 clinically matching genetic variants in 15 of 50 (30%) patients, while a stronger clinical correlation with stroke was established in only 6 (12%) of them. Stroke-related genetic variants were identified in 4 of 5 (80%) patients with cardioembolic stroke subtype, 3 of 4 (75%) with intracerebral hemorrhage, 7 of 18 (39%) with cryptogenic embolic stroke, 1 of 6 (17%) with small vessel disease, and 3 of 15 (20%) of patients with nonatherosclerotic large artery stroke, including 1 of 11 (9%) with cervical dissection stroke. Careful clinical interpretation of whole genome data using stroke gene panels can detect monogenic causes of early stroke, allowing individualized follow-up and opening new possibilities for potential treatment.

Portable ultrasound-guided Trans-sylvian minimally invasive intracerebral hemorrhage surgery: how I do it.

Intracerebral hemorrhage (ICH) is a common neurosurgical emergency with high morbidity and mortality. The trans-sylvian microsurgical evacuation of ICH in the basal ganglia is a classic but technically challenging approach. We describe a novel technique using handheld portable ultrasound to guide trans-sylvian, trans-insular evacuation of basal ganglia hematomas, allowing for rapid identification, precise evacuation, and post-evacuation assessment from a small Sylvian fissure opening. Intraoperative portable ultrasonography is a rapid, simple, and inexpensive technique that provides real-time visualization of ICH and key cortical structures, minimizing potential damage during exposure and exploration.

Comparative Study on Decompressive Craniectomy with Clot Evacuation Versus Medical Management in Hypertensive Intracerebral Hemorrhage: An Institutional Cohort Study

Comparative Study on Decompressive Craniectomy with Clot Evacuation Versus Medical Management in Hypertensive Intracerebral Hemorrhage: An Institutional Cohort Study

Advancing Stroke Safety and Efficacy through Early Tirofiban Administration after Intravenous Thrombolysis: The multicenter, randomized, placebo-controlled, double-blind ASSET IT trial protocol.

Intravenous thrombolysis (IVT) is the cornerstone treatment for the acute ischemic stroke (AIS) within 4.5 hours after onset. Current guidelines recommend administering antiplatelet medications 24 hours after IVT. However, vascular re-occlusion is a common occurrence after IVT. Tirofiban, a platelet glycoprotein IIb/IIIa antagonist, can help deter macrovascular re-occlusion, prevent microvascular thrombosis, and enhance cerebral blood flow. This trial aims to assess whether early administration of tirofiban can improve clinical outcomes in patients with AIS who received IVT. The Advancing Stroke Safety and Efficacy through Early Tirofiban Administration after Intravenous Thrombolysis (ASSET IT) Trial is an investigator-initiated, randomized, placebo-controlled, double-blind, multi-center study. Up to 832 eligible patients will be consecutively randomized in a 1:1 ratio to receive either intravenous tirofiban or placebo over a period of 2 years across 38 stroke centers in China. The primary endpoint is excellent functional status at day 90, defined as a modified Rankin Score of 0-1. Primary safety endpoints include symptomatic intracerebral hemorrhage at 24 hours and mortality at 90 days.

Medial intracranial carotid artery calcifications and hematoma expansion in deep intracerebral hemorrhage.

Medial intracranial carotid artery calcifications (ICAC) are associated with impaired vascular physiology, increased arterial stiffness and pulse pressure. Their presence might therefore be associated with increased risk of intracerebral hemorrhage (ICH) expansion, according to the avalanche model. We explored the association between ICAC presence and pattern and hematoma expansion (HE). Retrospective analysis of a monocentric, prospectively collected cohort of ICH patients admitted between June 2017 and October 2023. ICAC pattern was determined by Kockelkoren's rating scale on admission CT; medial ICAC were defined with a >6 points cutoff. A follow-up CT scan was performed within 72 h. HE was analyzed as a dichotomous (≥6 mL and/or ≥33%) and as a categorical (none/mild/moderate/severe) variable, and its predictors were explored with logistic and ordinal regression respectively, accounting for baseline volume, onset-to-CT time, and anticoagulation. All the analyses were stratified by ICH location (supratentorial deep vs lobar ICH). A total of 201 patients were included (median age 78, 42% females, 59% deep ICH). Medial ICAC were significantly more common in deep ICH with HE compared with non-expanders (72% vs 49%, p = 0.03), whereas there was no association between ICAC and HE in lobar ICH (53% vs 52%, p = 0.85). This association between medial ICAC and HE in deep ICH remained significant in logistic (aOR 3.11, 95% CI [1.19-9.06], p = 0.03) and ordinal regression (acOR 2.42, 95% CI [1.19-4.99], p = 0.01). Ipsilateral medial ICAC are associated with higher odds of HE in deep ICH. Our findings are best interpreted as hypothesis generating, requiring prospective validation and further research to characterize the underlying biological mechanisms.

Impact of Ambient Air Pollution with PM2.5 on Stroke Occurrence: Data from Kaunas (Lithuania) Stroke Register (2010–2022)

Background: Ambient particulate matter of ≤2.5 μm in diameter (PM2.5) is named as a risk factor for cerebrovascular diseases. This investigation aimed to evaluate the impact of ambient air pollution with PM2.5 on stroke occurrence. Methods: The study was performed in Kaunas, Lithuania, from 2010 to 2022. The daily numbers of ISs, subarachnoid hemorrhages (SAHs), and intracerebral hemorrhages (ICHs) were obtained from the Kaunas Stroke Register. The association between stroke occurrence and PM2.5 exposure was assessed by time- and seasonally stratified Poisson regression. Results: Among middle-aged persons, 3377 had a stroke, of which 2686 (79.5%) had an IS, 469 (13.9%) had an ICH, and 222 (6.6%) had SAH. The relative risk (RR) of SAH was increased by 1.7% with an increase in daily PM2.5 by 1 μg/m3 on the same day and at a lag of 1 day, and by 2.2% with an increase in mean PM2.5 concentration at a lag 0–1 days by 1 μg/m3. The RR of having a SAH was increased by 0.7% with an increase in daily PM2.5 by 1 μg/m3 on the same day. Conclusions: Significant associations between stroke occurrence and air pollution with PM2.5 were found in the SAH and HS patients, and only in middle-aged subjects.

Contemporary Management of Acute Ischemic Stroke.

In the past decade, adding mechanical thrombectomy (MT) of intracranial arterial occlusions to intravenous (IV) thrombolysis has revolutionized the treatment of acute ischemic stroke (AIS) by expanding the therapeutic window to 24h. Treatment decisions require establishing a high probability of AIS; confirming time since last known well (LKW); assessing severity of the neurological deficit; determining any contraindications to IV thrombolysis; and performing neuroimaging, usually noncontrast computed tomography (NCCT), to exclude intracerebral hemorrhage. If time since LKW is less than 4.5h, patients with disabling stroke without contraindications can proceed immediately to IV thrombolysis while the decision about MT is under way. For some patients, the MT decision can be made on the basis of clinical assessment, NCCT, and CT angiography showing a large vessel occlusion. Others may require additional neuroimaging. Patients who are not candidates for IV thrombolysis within 4.5h or MT should be immediately evaluated for eligibility for extended-window IV thrombolysis or early antiplatelet treatment.

Predictive factors for shunt dependency in patients with spontaneous intraventricular hemorrhage

Intraventricular hemorrhage (IVH) occurs in approximately 30–50% patients with spontaneous intracerebral hemorrhage (ICH), with a high 30-day mortality rate. Excess accumulation of parenchymal or ventricular blood associated with the development of acute hydrocephalus leads to poor outcomes. The prediction of shunt dependency is important to identify patients susceptible to requiring permanent shunt placement and benefit from the diversion. This retrospective analytical study aimed to establish a predictive model of shunt dependency in patients with IVH. This study included 179 patients with primary IVH with supratentorial origin or spontaneous ICH with extension into the ventricles between 2015 and 2021. Patients were grouped into “shunt required” and “shunt not required” groups. Variables, including age, sex, preexisting hypertension and diabetes, initial Glasgow Coma Scale scores, ICH location and volume, urokinase administration, modified Graeb score (mGraeb score), and bicaudate index, were analyzed. The shunt required group had significantly higher mGraeb scores (12.0 (6.5–15.0) vs. 7.0 (4.0–12.0), p = 0.001) and higher bicaudate index (0.20 (0.17–0.23) vs. 0.16 (0.13–0.18), P < 0.001) than the shunt not required group. The receiver operating characteristic curve (ROC curve) analysis revealed that a cut-off value of 0.16 of the bicaudate index was significantly related to shunt dependency. The subgroup statistical analysis revealed that neither urokinase administration (p = 0.533) nor urokinase dosage (p = 0.117) showed significant relevance in shunt dependency in patients who received external ventricular drainage. In logistic regression adjusted for the confounders, thalamic ICH (odds ratio (OR) 3.55; 95% confidence interval [(95%CI), 1.13–11.18], an mGraeb score greater than 8 (OR, 3.93; 95%CI, 1.84–8.38), and a bicaudate index greater than 0.16 (OR, 9.87; 95%CI, 3.79–25.73) were factors associated with a higher tendency for shunting. The findings of this study may help identify patients at risk for a permanent shunt after IVH.

Endothelial NMMHC IIA dissociation from PAR1 activates the CREB3/ARF4 signaling in thrombin-mediated intracerebral hemorrhage

IntroductionThere is an urgent need for cerebroprotective interventions to improve the suboptimal outcomes with intracerebral hemorrhage (ICH). Despite the important role of nonmuscle myosin heavy chain IIA (NMMHC IIA) in the blood–brain barrier (BBB), its function in ICH remains unclear. ObjectivesThe objective of this study is to explore how NMMHC IIA functions in ICH and to evaluate the effectiveness of targeting NMMHC IIA as a treatment for ICH. MethodsWe firstly examined the protein expression of NMMHC IIA in clinical patients and animal models with ICH. The function of NNMMHC IIA was then corroborated by using overexpress or knockdown NMMHC IIA specifically in ECs mice and pBMECs. In addition, we explored protein interacts with NMMHC IIA and signaling pathways after ICH by LC-MS/MS and transcriptomics analysis with an emphasis on the function of PAR1 and the CREB3/ARF4 signaling pathway, and validated them in three kind of animal models. To support the clinical translation of our results, we targeted NMMHC IIA to bicalutamide selected from a library of marketed drugs and examined to validate its ameliorative effect on ICH. ResultsWe observed an upregulation of endothelial NMMHC IIA in the brain following the onset of ICH in both patients and mice, while inhibited NMMHC ⅡA improved ICH induced by thrombin, warfarin or tissue plasminogen activator (tPA) after ischemic stroke. Mechanistically, the head domain of NMMHC IIA interacted with protease-activated receptor 1 (PAR1) at the 380–430 aa region and subsequently dissociated and activated the CREB3/ARF4 signaling pathway. We found that bicalutamide and blebbistatin could bind to NMMHC IIA and effectively protect mice from thrombin-mediated ICH. ConclusionThe findings indicated that NMMHC IIA dissociated from PAR1 and activated CREB3/ARF4 pathway, which aggravated BBB damage induced by thrombin. This suggested that NMMHC IIA was a novel potential therapeutic target for BBB-related diseases.

Prediction of the outcome of intracerebral hemorrhage by blood neutrophil to lymphocyte ratio: a prospective observational study.

Intracerebral haemorrhage (ICH) is defined as bleeding within the brain parenchyma. Neutrophil lymphocyte ratio (NLR) is a dynamic parameter that can be affected by an underlying condition like microangiopathy (e.g. hemorrhagic stroke). The NLR value at the time of stress (e.g. ICH) could be a predictor among various other factors on the outcome of the disease. The aim of this study is to see if NLR could be a predictor of the outcome of the ICH. This is a prospective observational study conducted in the Department of Neurosurgery and Department of Neurology, from March 2020 to February 2021. The ICH cases presented to the emergency department within 24h of symptoms were included. The baseline haematological and biochemical investigations were sent and the noncontrast computed tomography (NCCT) head was done for the diagnosis of ICH. The NLR was measured. The ICH volume was calculated by ABC/2. Follow-up of the patient to measure outcome was done with a modified Rankin scale (mRS) on 30 days. Student's t-test was used to correlate NLR-mRS. Fischer's exact test was used for a categorical association of NLR to mRS. A total of 89 patients with ICH were enrolled in this study. In this study, 62.92% of patients had good outcomes (NLR of 4.88±3.06), whereas 37.08% of patients had bad outcomes (NLR of 9.09± 4.92). Statistically, higher NLR was significantly predictive of poorer outcomes. ICH causes stress in the body, which alters the value of NLR. Components of NLR are altered after haemorrhage due to a change in homeostasis of brain parenchyma. The NLR value obtained at the time of emergency department visits may help to predict the 30 days outcome of ICH.

Traditional Chinese medicine FYTF-919 (Zhongfeng Xingnao oral prescription) for the treatment of acute intracerebral haemorrhage: a multicentre, randomised, placebo-controlled, double-blind, clinical trial.

There are few proven treatments for acute spontaneous intracerebral haemorrhage, and they all target reducing expansion of the haematoma. The traditional Chinese medicine FYTF-919 (Zhongfeng Xingnao) in an oral solution is comprised of several Chinese herbs that are widely used to treat patients with intracerebral haemorrhage in China on the understanding that they enhance resorption of the haematoma and reduce neuroinflammation. We aimed to provide a reliable assessment of the safety and efficacy of FYTF-919 in patients with moderate to severe acute intracerebral haemorrhage. We did a pragmatic, multicentre, randomised, double-blind, placebo-controlled trial at 26 hospitals in China. We enrolled adults (age ≥18 years) with a diagnosis of symptomatic spontaneous intracerebral haemorrhage (confirmed by brain imaging) within 48 h after the onset of symptoms (or last seen well), which resulted in moderate to severe neurological impairment defined by scores of at least 8 on the National Institute of Health Stroke Scale or between 7 and 14 inclusive on the Glasgow Coma Scale. Randomisation (1:1) was via a central internet-based system with a block grouping method stratified by provincial location of the hospital, severity of neurological impairment, and site of the haematoma in the brain. FYTF-919 and the placebo were masked through consistency in appearance, smell, taste, and other aspects. Participants were allocated to receive 33 mL (or 25 mL via a nasogastric tube if a participant's swallowing was impaired) of either oral liquid FYTF-919 or matching placebo administered at least 30 min after a meal every 8 h (or 6 h via nasogastric tube) over 24 h for 28 days. The primary efficacy outcome was the utility weighted modified Rankin Scale (a seven-level ordinal scale that ranges from 0 [no symptoms] to 6 [death], in which the utility weights of 0·97, 0·88, 0·74, 0·55, 0·20, -0·19, and 0·00 were assigned to the seven levels respectively, with higher scores indicating a better outcome according to the participants' perspective) at 90 days analysed in a general linear model with adjustment for baseline factors. We did several adjusted and sensitivity analyses. Primary analyses were assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT05066620 and is complete. Between Nov 24, 2021, and Dec 28, 2023, of 9000 patients screened, 1648 were randomly assigned to treatment, 817 to the FYTF-919 group and 831 to the placebo group. Before receiving any treatment two patients in the FYTF-919 group and five patients in the placebo group immediately withdrew their consent leaving 1641 participants with available primary outcome data in the intention-to-treat population, 815 in the FYTF-919 group and 826 in the placebo group. 1242 (75·7%) participants consumed 80% or more of the study medication and 994 (60·6%) consumed all of it within 28 days. Mean utility weighted modified Rankin Scale scores at 90 days were 0·44 in the FYTF-919 group and 0·44 in the placebo group (difference 0·01, 95% CI -0·02 to 0·04; p=0·63). The neutral result was consistent in adjusted and sensitivity analyses. There was no significant difference in serious adverse events. This large, randomised, placebo-controlled, double-blind, clinical trial showed no effect of the traditional Chinese medicine herbal compound FYTF-919 on functional recovery, survival, and health-related quality of life in patients with moderate to severe intracerebral haemorrhage. The results reaffirm the need for methodologically rigorous, randomised controlled trials to evaluate the effectiveness of existing therapies, including traditional Chinese medicines that are already in widespread use throughout the world. Key-Area Research and Development Program of Guangdong Province.

The Impact of Functionality and Psychological Outcome on Social Engagement 3-months after Intracerebral Hemorrhage

BackgroundAlthough it is well-known that intracerebral hemorrhage (ICH) is associated with physical and psychological morbidity, there is scant data on factors influencing social engagement after ICH. Understanding the relationship between functionality, psychological outcome and social engagement post-bleed may facilitate identification of patients at high risk for social isolation after ICH. MethodsPatients ≥18-years-old with non-traumatic ICH from January 2015-March 2023 were identified from the Neurological Emergencies Outcomes at NYU (NEON) registry. Data on discharge functionality were collected from the medical record. 3-months post-bleed, patients/their legally-authorized representatives (LARs) were contacted to complete Neuro-QoL social engagement, anxiety, depression, and sleep inventories. Patients were stratified by ability to participate in social roles and activities (good=T-score>50, poor=T-score≤50) and satisfaction with social roles and activities (high=T-score>50 and low=T-score≤50). Univariate comparisons were performed to evaluate the relationship between post-bleed social engagement and both functionality and psychological outcome using Pearson’s chi-square, Fisher’s Exact test, and Mann-Whitney U tests. Multivariate logistic regression was subsequently performed using variables that were significant on univariate analysis (p<0.05). ResultsThe social engagement inventories were completed for 55 patients with ICH; 29 (53%) by the patient alone, 14 (25%) by a LAR alone, and 12 (22%) by both patient and LAR. 15 patients (27%) had good ability to participate in social roles and activities and 10 patients (18%) had high satisfaction with social roles and activities. Social engagement was associated with both functionality and psychological outcome on univariate analysis, but on multivariate analysis, it was only related to functionality; post-bleed ability to participate in social roles and activities was associated with discharge home, discharge GCS score, discharge mRS score, and discharge NIHSS score (p<0.05) and post-bleed satisfaction with social roles and activities was related to discharge mRS score and discharge NIHSS score (p<0.05). ConclusionIn patients with nontraumatic ICH, social engagement post-bleed was related to discharge functionality, even when controlling for depression, anxiety, and sleep disturbance.

Association between Apolipoprotein E gene polymorphism and early MR findings in individuals with acute intracerebral hemorrhage: a retrospective cohort analysis

ObjectiveThe Apolipoprotein E (APOE) gene plays a significant role in the development and prognosis of intracerebral hemorrhage (ICH). Imaging features identified within 48 hours of ICH onset, particularly on magnetic resonance imaging (MRI), are indicative of cerebral small vessel diseases (CSVD). Our study aimed to assess these imaging characteristics and investigate their association with the APOE gene among ICH patients. MethodsClinical and imaging data from patients meeting specific inclusion and exclusion criteria from October 2021 to March 2022 were collected. MR signs or scores were evaluated following international accreditation standards and then analyzed in connection with the APOE allele genes. ResultsIn a cohort of 220 patients, ε2 was identified as an independent risk factor for the "multiple subcortical spots" sign (OR = 13.29, 95% CI 1.88-22.59). Furthermore, ε4 emerged as an independent risk factor for the presence of perivascular space (PVS) in the centrum semiovale (OR = 2.46, 95% CI 1.03-5.89) and basal ganglia (OR = 2.64, 95% CI 1.10-6.35), as well as for cerebral microbleeds (CMB) across all locations (OR = 2.38, 95% CI 1.15-6.97), lobar CMB (OR = 2.92, 95% CI 1.11-7.65), and deep CMB (OR = 2.29, 95% CI 1.12-8.67). ConclusionThe association between APOE ɛ2 and ɛ4 alleles and the presence of "subcortical multiple spots," "PVS," and "CMB" indirectly implies the potential role of APOE gene-related pathological changes in the progression of ICH and small vessel pathology.