Acute Spontaneous Intracerebral Hemorrhage Research Articles

The relationship between perihematomal edema and hematoma expansion in acute spontaneous intracerebral hemorrhage: an exploratory radiomics analysis study.

The relationship between early perihematomal edema (PHE) and hematoma expansion (HE) is unclear. We investigated this relationship in patients with acute spontaneous intracerebral hemorrhage (ICH), using radiomics. In this multicenter retrospective study, we analyzed 490 patients with spontaneous ICH who underwent non-contrast computed tomography within 6 h of symptom onset, with follow-up imaging at 24 h. We performed HE and PHE image segmentation, and feature extraction and selection to identify HE-associated optimal radiomics features. We calculated radiomics scores of hematoma (Radscores_HEA) and PHE (Radscores_PHE) and constructed a combined model (Radscore_HEA_PHE). Relationships of the PHE radiomics features or Radscores_PHE with clinical variables, hematoma imaging signs, Radscores_HEA, and HE were assessed by univariate, correlation, and multivariate analyses. We compared predictive performances in the training (n = 296) and validation (n = 194) cohorts. Shape_VoxelVolume and Shape_MinorAxisLength of PHE were identified as optimal radiomics features associated with HE. Radscore_PHE (odds ratio = 1.039, p = 0.032) was an independent HE risk factor after adjusting for the ICH onset time, Glasgow Coma Scale score, baseline hematoma volume, hematoma shape, hematoma density, midline shift, and Radscore_HEA. The areas under the receiver operating characteristic curve of Radscore_PHE in the training and validation cohorts were 0.808 and 0.739, respectively. After incorporating Radscore_PHE, the integrated discrimination improvements of Radscore_HEA_PHE in the training and validation cohorts were 0.009 (p = 0.086) and -0.011 (p < 0.001), respectively. Radscore_PHE, based on Shape_VoxelVolume and Shape_MinorAxisLength of PHE, independently predicts HE, while Radscore_PHE did not add significant incremental value to Radscore_HEA.

Cognitive Outcome after Acute Spontaneous Intracerebral Hemorrhage: Analysis of the iDEF Randomized Trial.

The impact of intracerebral hemorrhage (ICH) on cognition and the determinants of cognitive recovery early after ICH remain elusive. In this post hoc analysis of the intracerebral hemorrhage deferoxamine (iDEF) trial, we examined the trajectories of cognitive impairment and the determinants of early cognitive recovery after ICH. We examined baseline factors associated with a 90-day cognitive outcome and constructed generalized linear mixed models to examine the trajectory of cognitive function over time among iDEF participants. Cognition was measured by the Montreal Cognitive Assessment (MoCA) scores on days 7, 30, and 90. 291 were available for analysis under the trial's modified intention-to-treat definition (38% female, mean age 60.3 ± 12.0 years, median NIHSS 13, IQR 8-18). The median baseline ICH volume was 12.9 IQR (6.4-26.0) mL; 59 (20%) of the ICH cases were lobar, 120 (41%) had intraventricular extension. There was an overall significant increase in total MOCA score with time (p &lt; 0.0001). Total MOCA score increased by an estimated 3.9 points (95% CI: 3.1, 4.7) between the day 7 and day 30 assessments and by an additional 2.9 points (95% CI: 2.2, 3.6) between the day 30 and day 90 assessments. Despite the overall improvement, 134 of 205 (65%) patients with an available 90-day MoCA score remained cognitively impaired with a score &lt;26 on day 90. Older age, higher NIHSS score, baseline ICH volume, intraventricular hemorrhage, and perihematoma edema had an adjusted negative impact on cognitive recovery. Although ICH survivors exhibit significant improvement of cognitive status over the first 3 months, cognitive performance remains impaired in the majority of patients. Among factors independently associated with worse cognitive recovery, higher baseline ICH, intraventricular blood and perihematomal edema volumes, are potential therapeutic targets that merit further exploration.

Tranexamic acid versus placebo in individuals with intracerebral haemorrhage treated within 2 h of symptom onset (STOP-MSU): an international, double-blind, randomised, phase 2 trial

Tranexamic acid, an antifibrinolytic agent, might attenuate haematoma growth after an intracerebral haemorrhage. We aimed to determine whether treatment with intravenous tranexamic acid within 2 h of an intracerebral haemorrhage would reduce haematoma growth compared with placebo. STOP-MSU was an investigator-led, double-blind, randomised, phase 2 trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam. Eligible participants had acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT, were aged 18 years or older, and could be treated with the investigational product within 2 h of stroke onset. Using randomly permuted blocks (block size of 4) and a concealed pre-randomised assignment procedure, participants were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 min followed by 1 g over 8 h) or placebo (saline; matched dosing regimen) commencing within 2 h of symptom onset. Participants, investigators, and treating teams were masked to group assignment. The primary outcome was haematoma growth, defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 h (target range 18-30 h) from the baseline CT. The analysis was conducted within the estimand framework with primary analyses adhering to the intention-to-treat principle. The primary endpoint and secondary safety endpoints (mortality at days 7 and 90 and major thromboembolic events at day 90) were assessed in all participants randomly assigned to treatment groups who did not withdraw consent to use any data. This study was registered with ClinicalTrials.gov, NCT03385928, and the trial is now complete. Between March 19, 2018, and Feb 27, 2023, 202 participants were recruited, of whom one withdrew consent for any data use. The remaining 201 participants were randomly assigned to either placebo (n=98) or tranexamic acid (n=103; intention-to-treat population). Median age was 66 years (IQR 55-77), and 82 (41%) were female and 119 (59%) were male; no data on race or ethnicity were collected. CT scans at baseline or follow-up were missing or of inadequate quality in three participants (one in the placebo group and two in the tranexamic acid group), and were considered missing at random. Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio [aOR] 1·31 [95% CI 0·72 to 2·40], p=0·37). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0·02 [95% CI -0·02 to 0·06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1·08 [95% CI 0·35 to 3·35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1·61 [95% CI 0·65 to 3·98]). Intravenous tranexamic acid did not reduce haematoma growth when administered within 2 h of intracerebral haemorrhage symptom onset. There were no observed effects on other imaging endpoints, functional outcome, or safety. Based on our results, tranexamic acid should not be used routinely in primary intracerebral haemorrhage, although results of ongoing phase 3 trials will add further context to these findings. Australian Government Medical Research Future Fund.

Peripheral T cell immune repertoire is associated with the outcomes of acute spontaneous intracerebral hemorrhage.

Systematic immune responses have been identified in patients with acute spontaneous intracerebral hemorrhage (ICH). T cells have been established to participate in central nervous system damage and repair following brain injury. However, their contribution to the prognosis of patients with ICH remains to be elucidated. In this study, peripheral blood mononuclear cells (PBMCs) were collected from 45 patients with acute spontaneous ICH (<24 h from symptom onset). Our results exposed significant negative correlations between hematoma volume/white blood cell (WBC) density and Glasgow Coma Scale (GCS) score. Contrastingly, lymphocyte density was negatively correlated with hematoma volume and positively correlated with GCS score. Moreover, flow cytometry determined that ICH activated T cells despite their proportion being lower in blood. Afterward, immune repertoire sequencing (IR-seq) revealed a significant decrease in VJ, VDJ usage, and TCR clonotypes in ICH patients. Finally, variations in the complementarity-determining region 3 (CDR3) amino acid (aa) were also detected in ICH patients. This study reveals the occurrence of peripheral T-cell diminishment and activation in response to acute hematoma. ICH lesion also alters the T cell receptor (TCR) immune repertoire, which is associated with patient prognosis.

Independent Factors Associated with 30-Day In-Hospital Mortality from Acute Spontaneous Intracerebral Hemorrhage

ObjectiveThis study aims to investigate independent factors associated with 30-day mortality in patients with acute spontaneous intracerebral hemorrhage before treatment. MethodsA retrospective analysis was performed on medical records of patients hospitalized with acute spontaneous intracerebral hemorrhage between 2019 and 2021. Data included personal history, hospital stay duration, symptom onset, chief complaint, underlying diseases, medication, and alcohol/smoking habits. Physical examination records comprised baseline blood pressure, Glasgow Coma Scale assessment, and pupil reaction evaluation. Diagnostic imaging, specifically CT brain scans, was examined for hemorrhage details. Multivariable logistic analysis was utilized for data analysis. ResultsAmong 663 cases, 185 (27.9%) experienced mortality. Risk factors for mortality included chronic kidney disease, ischemic heart disease, loss of follow-up in hypertension clinic, and pontine hemorrhage. Conversely, motor response, reactive pupils, and basal cistern persistence significantly decreased the risk of mortality in multivariable analysis. ROC analysis identified a motor response score of 5 as the cutoff for predicting survival. ConclusionChronic kidney disease, ischemic heart disease, loss of hypertension follow-up, motor response, reactive pupils, pontine hemorrhage, and basal cistern persistence were independent variables associated with the 30-day mortality rate in spontaneous intracerebral hemorrhage patients before treatment initiation. A motor response, pupil reaction, and basal cistern persistence serve as predictive tools for assessing mortality in SICH before treatment.

Predicting hematoma expansion in acute spontaneous intracerebral hemorrhage: integrating clinical factors with a multitask deep learning model for non-contrast head CT

PurposeTo predict hematoma growth in intracerebral hemorrhage patients by combining clinical findings with non-contrast CT imaging features analyzed through deep learning.MethodsThree models were developed to predict hematoma expansion (HE) in 572 patients. We utilized multi-task learning for both hematoma segmentation and prediction of expansion: the Image-to-HE model processed hematoma slices, extracting features and computing a normalized DL score for HE prediction. The Clinical-to-HE model utilized multivariate logistic regression on clinical variables. The Integrated-to-HE model combined image-derived and clinical data. Significant clinical variables were selected using forward selection in logistic regression. The two models incorporating clinical variables were statistically validated.ResultsFor hematoma detection, the diagnostic performance of the developed multi-task model was excellent (AUC, 0.99). For expansion prediction, three models were evaluated for predicting HE. The Image-to-HE model achieved an accuracy of 67.3%, sensitivity of 81.0%, specificity of 64.0%, and an AUC of 0.76. The Clinical-to-HE model registered an accuracy of 74.8%, sensitivity of 81.0%, specificity of 73.3%, and an AUC of 0.81. The Integrated-to-HE model, merging both image and clinical data, excelled with an accuracy of 81.3%, sensitivity of 76.2%, specificity of 82.6%, and an AUC of 0.83. The Integrated-to-HE model, aligning closest to the diagonal line and indicating the highest level of calibration, showcases superior performance in predicting HE outcomes among the three models.ConclusionThe integration of clinical findings with non-contrast CT imaging features analyzed through deep learning showed the potential for improving the prediction of HE in acute spontaneous intracerebral hemorrhage patients.

Abstract WP176: Hemoglobin Decrement is Associated With Ischemic Lesions on Brain MRI of Patients With Acute Intracerebral Hemorrhage

Background: We have previously identified that hemoglobin decrements and new-onset anemia during an intracerebral hemorrhage (ICH) hospitalization is frequent, rapid, and associates with poor outcome. Though this association may be related to impaired cerebral oxygen delivery, it is unclear whether these changes relate to cerebral ischemia. We investigated the relationship of hemoglobin decrements over time and ischemic lesions on brain MRI during an ICH hospitalization. Methods: Consecutive patients with acute spontaneous ICH enrolled into a single-center, prospective cohort study between 2009 and 2019 were assessed. Patients who had a brain MRI and serial hemoglobin measurements were included. Change in hemoglobin from admission to date of brain MRI (delta Hgb) was defined as the exposure. The outcome was the presence of remote ischemic lesions, defined as foci of diffusion restriction &gt;10 mm away from the hematoma on brain MRI. A regression model assessed relationships between delta Hgb and DWI brain lesions, adjusting for baseline demographics, ICH severity, and time to MRI. Separate sensitivity models were adjusted for admission systolic blood pressure and hemoglobin. Results: We identified 189 ICH patients with brain MRI and serial hemoglobin measurements during their hospitalization. The mean age was 66.5 (SD 14.8) and 49.2% were female. Mean admission hemoglobin was 13.5 g/dL (SD 2.0), mean change in hemoglobin from admission to day of MRI was -1.6 (SD 1.6), median time from ICH onset to MRI was 2 (IQR 1-4) days, and 31.7% of patients had ischemic lesions on MRI. We identified an association of greater decrements in hemoglobin with ischemic lesions in our primary model (adjusted OR 0.79, 95%CI 0.64-0.99, p=0.04). Sensitivity analyses adjusting for admission systolic blood pressure and hemoglobin did not change this association. Conclusions: Greater hemoglobin decrements associate with remote ischemic lesions on brain MRI of patients with acute ICH. Further work is needed to assess drivers of anemia after ICH and possible causal mechanisms for ischemic brain injury to assess whether anemia is a modifiable treatment target to improve ICH outcomes.

Association of inflammatory cytokines expression in cerebrospinal fluid with the severity and prognosis of spontaneous intracerebral hemorrhage

ObjectiveTo investigate the potential diagnostic and prognostic implications of inflammatory cytokine levels in the cerebrospinal fluid (CSF) of patients with spontaneous intracerebral hemorrhage (SICH) upon their initial hospital admission.MethodsOur cohort included 100 patients diagnosed with acute SICH, presenting to the Department of Neurosurgery. Additionally, we recruited 50 individuals without central nervous system (CNS) pathology, treated concurrently at our facility, as controls. CSF samples, collected upon hospital entry, were quantitatively assessed for 10 inflammatory cytokines using the Mesoscale Discovery Platform (MSD, Rockville, MD, USA) electrochemiluminescence technology, followed by validation through enzyme-linked immunosorbent assay (ELISA).ResultsWe observed a marked elevation of IL-6, IL-8, IL-10, and TNF-α in the CSF of the SICH subgroup compared to controls. Higher Glasgow Coma Scale (GCS) scores in SICH patients corresponded with lower CSF concentrations of IL-6, IL-8, IL-10, and TNF-α, indicating an inverse relationship. Notably, CSF inflammatory cytokine levels were consistently higher in SICH patients with hydrocephalus than in those without. Increases in IL-6, IL-8, IL-10, and TNF-α in the CSF were notably more pronounced in the poor prognosis group (Glasgow Outcome Scale, GOS 1–3) compared to those with a favorable prognosis (GOS 4–5). The AUC values for these cytokines in predicting SICH prognosis were 0.750, 0.728, 0.717, and 0.743, respectively.ConclusionsInitial CSF levels of IL-6, IL-8, IL-10, and TNF-α upon admission provide significant insights into the severity of neural damage and are robust indicators for prognosis in SICH patients.

Mechanistic Evaluation of Diffusion Weighted Hyperintense Lesions After Large Spontaneous Intracerebral Hemorrhage: A Subgroup Analysis of MISTIE III.

Ischemic lesions on diffusion weighted imaging (DWI) are common after acute spontaneous intracerebral hemorrhage (ICH) but are poorly understood for large ICH volumes (> 30mL). We hypothesized that large blood pressure drops and effect modification by cerebral small vessel disease markers on magnetic resonance imaging (MRI) are associated with DWI lesions. This was an exploratory analysis of participants in the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial with protocolized brain MRI scans within 7days from ICH. Multivariable logistic regression analysis was performed to assess biologically relevant factors associated with DWI lesions, and relationships between DWI lesions and favorable ICH outcomes (modified Rankin Scale 0-3). Of 499 enrolled patients, 300 had MRI at median 7.5days (interquartile range 7-8), and 178 (59%) had DWI lesions. The incidence of DWI lesions was higher in patients with systolic blood pressure (SBP) reduction ≥ 80mm Hg in first 24h (76%). In adjusted models, factors associated with DWI lesions were as follows: admission intraventricular hematoma volume (p = 0.03), decrease in SBP ≥ 80mm Hg from admission to day 1 (p = 0.03), and moderate-to-severe white matter disease (p = 0.01). Patients with DWI lesions had higher odds of severe disability at 1month (p = 0.04), 6months (p = 0.036), and 12months (p < 0.01). No evidence of effect modification by cerebral small vessel disease on blood pressure was found. In patients with large hypertensive ICH, white matter disease, intraventricular hemorrhage volume, and large reductions in SBP over the first 24h were independently associated with DWI lesions. Further investigation of potential hemodynamic mechanisms of ischemic injury after large ICH is warranted.

Clinical Trial Protocol for BEACH: A Phase 2a Study of MW189 in Patients with Acute Nontraumatic Intracerebral Hemorrhage

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability of MW189 in patients with acute ICH, identify trends in potential mitigation of neuroinflammation and cerebral edema, and assess effects on functional outcomes. A total of 120 participants with nontraumatic ICH will be randomly assigned 1:1 to receive intravenous MW189 (0.25 mg/kg) or placebo (saline) within 24 h of symptom onset and every 12 h for up to 5 days or until hospital discharge. The 120-participant sample size (60 per group) will allow testing of the null hypothesis of noninferiority with a tolerance limit of 12% and assuming a “worst-case” safety assumption of 10% rate of death in each arm with 10% significance and 80% power. The primary outcome is all-cause mortality at 7 days post randomization between treatment arms. Secondary end points include all-cause mortality at 30 days, perihematomal edema volume after symptom onset, adverse events, vital signs, pharmacokinetics of MW189, and inflammatory cytokine concentrations in plasma (and cerebrospinal fluid if available). Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury.

Correlation Between the Degree of Midline Shift in Computed Tomography Scan of Brain and Level of Consciousness of the Patients with Acute Spontaneous Intracerebral Haemorrhage

Background: Intracerebral hemorrhage (ICH) is the second most common cause of stroke, following ischemic stroke, but accounts for a disproportionate amount of cerebrovascular mortality and morbidity. The extent of midline shift, observed on computed tomography (CT) scans, has been recognized as an important radiological finding associated with the severity of ICH. Objective: To evaluate correlation between the degree of midline shift in computed tomography scan of brain and level of consciousness of the patients with acute spontaneous intracerebral haemorrhage. Material and method: This cross-sectional study was carried out in 100 patients, out of this 50 had spontaneous intracerebral hemorrhage with mass effect and 50 had spontaneous intracerebral hemorrhage without mass effect taken as the control group, the age range from 30-75 years. These patients were purposively collected from the Department of Radiology and Imaging in collaboration with Department of Medicine, Neuromedicine and Neurosurgery of Dhaka Medical College Hospital, Dhaka. All the patients were evaluated by CT findings. On admission Glasgow Coma Scale (GCS) score were recorded from participant’s treatment sheet and reviewed by the senior Neurologist after taking permission of the authority. Results: This study shows there is significant inversely correlation of the GSC score with degree of midline shift measure using septum pellucidum shift (P&lt;0.05). The GCS score of &lt;10 mm of septum pellucidum shift compared to greater than 10 mm of septum pellucidum shift is significantly different (P&lt;0.05). The GCS score of SICH with mass effect compared to the GCS score of SICH without mass effect is significantly different (P&lt;0.05). Conclusion: Radiologist should carefully and elaborately interpret the spontaneous intracerebral hemorrhage with midline shift at CT-scan brain and help clinicians to evaluate the level of consciousness which is significant predictor of outcome of our valuable patients. Sir Salimullah Med Coll J 2023; 31: 94-99

Telemedicine Protocols for the Management of Patients with Acute Spontaneous Intracerebral Hemorrhage in Rural and Medically Underserved Areas in Gangwon State: Recommendations for Doctors with Less Expertise at Local Emergency Rooms.

Previously, we reported the concept of a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local emergency rooms in rural and medically underserved areas in Gangwon state by combining artificial intelligence and remote consultation with a neurosurgeon. Developing a telemedicine ICH treatment protocol exclusively for doctors with less ICH expertise working in emergency rooms should be part of establishing this system. Difficulties arise in providing appropriate early treatment for ICH in rural and underserved areas before the patient is transferred to a nearby hub hospital with stroke specialists. This has been an unmet medical need for decade. The available reporting ICH guidelines are realistically possible in university hospitals with a well-equipped infrastructure. However, it is very difficult for doctors inexperienced with ICH treatment to appropriately select and deliver ICH treatment based on the guidelines. To address these issues, we developed an ICH telemedicine protocol. Neurosurgeons from four university hospitals in Gangwon state first wrote the guidelines, and professors with extensive ICH expertise across the country revised them. Guidelines and recommendations for ICH management were described as simply as possible to allow more doctors to use them easily. We hope that our effort in developing the telemedicine protocols will ultimately improve the quality of ICH treatment in local emergency rooms in rural and underserved areas in Gangwon state.

Prevention of venous thromboembolism in acute spontaneous intracerebral haemorrhage: A survey of opinion

IntroductionPeople immobilized following acute spontaneous intracerebral haemorrhage (ICH) are at risk of venous thromboembolism (VTE) but the role of short-term prophylactic anticoagulation remains uncertain. We surveyed UK clinical practice and opinion regarding preventing VTE after ICH. Patients and methodsAn online survey was sent to stroke healthcare professionals within the United Kingdom and Ireland via a professional society (British and Irish Association of Stroke Physicians (BIASP)). ResultsOne hundred and twenty-three staff members responded to the survey, of whom 80% were consultant stroke physicians. All responders except one considered the issue to be important or extremely important, but only 5 (4%) were “extremely certain” and 51 (41%) “fairly certain” regarding the optimal treatment approach. Intermittent pneumatic compression (IPC) devices alone were the most used method (in 60%) followed by IPC devices and switching to low molecular weight heparin (LMWH) (in 30%). We identified high levels of uncertainty regarding the role of anticoagulation, and its optimal timing; uncertainty was greater in lobar compared to deep ICH. Most respondents (93%) consider a randomised controlled trial investigating the role of pharmacological VTE prophylaxis after acute ICH as important and would consider participation. Discussion and conclusionThe optimal method for the prevention of VTE in non-traumatic ICH patients remains an area of clinical uncertainty. Clinical trials assessing short-term anticoagulation in patients after acute ICH would be beneficial in providing evidence to resolve this clinical dilemma.

Early Detection of Underlying Cavernomas in Patients with Spontaneous Acute Intracerebral Hematomas.

Early identification of the etiology of spontaneous acute intracerebral hemorrhage is essential for appropriate management. This study aimed to develop an imaging model to identify cavernoma-related hematomas. Patients 1-55 years of age with acute (≤7 days) spontaneous intracerebral hemorrhage were included. Two neuroradiologists reviewed CT and MR imaging data and assessed the characteristics of hematomas, including their shape (spherical/ovoid or not), their regular or irregular margins, and associated abnormalities including extralesional hemorrhage and peripheral rim enhancement. Imaging findings were correlated with etiology. The study population was randomly split to provide a training sample (50%) and a validation sample (50%). From the training sample, univariate and multivariate logistic regression was performed to identify factors predictive of cavernomas, and a decision tree was built. Its performance was assessed using the validation sample. Four hundred seventy-eight patients were included, of whom 85 had hemorrhagic cavernomas. In multivariate analysis, cavernoma-related hematomas were associated with spherical/ovoid shape (P < .001), regular margins (P = .009), absence of extralesional hemorrhage (P = .01), and absence of peripheral rim enhancement (P = .002). These criteria were included in the decision tree model. The validation sample (n = 239) had the following performance: diagnostic accuracy of 96.1% (95% CI, 92.2%-98.4%), sensitivity of 97.95% (95% CI, 95.8%-98.9%), specificity of 89.5% (95% CI, 75.2%-97.0%), positive predictive value of 97.7% (95% CI, 94.3%-99.1%), and negative predictive value of 94.4% (95% CI, 81.0%-98.5%). An imaging model including ovoid/spherical shape, regular margins, absence of extralesional hemorrhage, and absence of peripheral rim enhancement accurately identifies cavernoma-related acute spontaneous cerebral hematomas in young patients.

Effects of blood pressure and tranexamic acid in spontaneous intracerebral haemorrhage: a secondary analysis of a large randomised controlled trial

BackgroundTranexamic acid reduced haematoma expansion and early death, but did not improve functional outcome in the tranexamic acid for hyperacute spontaneous intracerebral haemorrhage-2 (TICH-2) trial. In a predefined subgroup, there...

The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial

Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

Acute spontaneous intracerebral haemorrhage: does a care bundle approach work?

A care bundle is a small but crucial set of treatments that, when implemented together, can improve outcomes. 1 NHS Modernisation Agency10 high impact changes for service improvement and delivery: a guide for NHS leaders. http://www.nursingleadership.org.uk/publications/HIC.pdfDate: 2004 Date accessed: April 24, 2023 Google Scholar Acute spontaneous intracerebral haemorrhage has few effective treatments and intracerebral haemorrhage-specific recommendations for care bundles. 2 Parry-Jones AR Sammut-Powell C Paroutoglou K et al. Intracerebral hemorrhage care bundle is associated with lower case fatality. Ann Neurol. 2019; 86: 495-503 Crossref PubMed Scopus (40) Google Scholar , 3 Middleton S McElduff P Ward J et al. Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial. Lancet. 2011; 378: 1699-1706 Summary Full Text Full Text PDF PubMed Scopus (266) Google Scholar In clinical practice, intracerebral haemorrhage is often approached with negativity. 4 Willie JT Gross RE Beyond therapeutic nihilism? The neurosurgical treatment of intracerebral hemorrhage. World Neurosurg. 2013; 80: e135-e137 Crossref PubMed Scopus (1) Google Scholar Moreover, the synergistic benefits of specialised nursing care, neurointensive and neurosurgical care, blood pressure control, reversal of coagulopathy, and other interventions have not been ascertained. 5 Greenberg SM Ziai WC Cordonnier C et al. 2022 guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke. 2022; 53: e282-e361 Crossref PubMed Scopus (107) Google Scholar The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trialImplementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. Full-Text PDF Open Access

Non-contrast computed tomography features predict intraventricular hemorrhage growth

ObjectivesNon-contrast computed tomography (NCCT) markers are robust predictors of parenchymal hematoma expansion in intracerebral hemorrhage (ICH). We investigated whether NCCT features can also identify ICH patients at risk of intraventricular hemorrhage (IVH) growth.MethodsPatients with acute spontaneous ICH admitted at four tertiary centers in Germany and Italy were retrospectively included from January 2017 to June 2020. NCCT markers were rated by two investigators for heterogeneous density, hypodensity, black hole sign, swirl sign, blend sign, fluid level, island sign, satellite sign, and irregular shape. ICH and IVH volumes were semi-manually segmented. IVH growth was defined as IVH expansion > 1 mL (eIVH) or any delayed IVH (dIVH) on follow-up imaging. Predictors of eIVH and dIVH were explored with multivariable logistic regression. Hypothesized moderators and mediators were independently assessed in PROCESS macro models.ResultsA total of 731 patients were included, of whom 185 (25.31%) suffered from IVH growth, 130 (17.78%) had eIVH, and 55 (7.52%) had dIVH. Irregular shape was significantly associated with IVH growth (OR 1.68; 95%CI [1.16–2.44]; p = 0.006). In the subgroup analysis stratified by the IVH growth type, hypodensities were significantly associated with eIVH (OR 2.06; 95%CI [1.48–2.64]; p = 0.015), whereas irregular shape (OR 2.72; 95%CI [1.91–3.53]; p = 0.016) in dIVH. The association between NCCT markers and IVH growth was not mediated by parenchymal hematoma expansion.ConclusionsNCCT features identified ICH patients at a high risk of IVH growth. Our findings suggest the possibility to stratify the risk of IVH growth with baseline NCCT and might inform ongoing and future studies.Clinical relevance statementNon-contrast CT features identified ICH patients at a high risk of intraventricular hemorrhage growth with subtype-specific differences. Our findings may assist in the risk stratification of intraventricular hemorrhage growth with baseline CT and might inform ongoing and future clinical studies.Key Points• NCCT features identified ICH patients at a high risk of IVH growth with subtype-specific differences.• The effect of NCCT features was not moderated by time and location or indirectly mediated by hematoma expansion.• Our findings may assist in the risk stratification of IVH growth with baseline NCCT and might inform ongoing and future studies.

Acute Intracerebral Hemorrhage (ICH) and Systemic Acidosis: Associations with Functional Outcomes and Mortality (P7-5.026)

<h3>Objective:</h3> With this study we aimed to assess the association of respiratory and metabolic acidosis in ICH with functional outcome and mortality. <h3>Background:</h3> Systemic Acidosis is common in critical care settings and patients with intracerebral hemorrhage (ICH) frequently require intubation and ICU admission. The association between ICH and systemic acidosis has not been investigated. <h3>Design/Methods:</h3> Retrospective single center cohort of patients with acute spontaneous ICH. We examined the relationship between acidosis on admission and (1) hospital mortality and (2) 90-day modified Rankin Scale (mRS) dichotomized as unfavorable (&gt;3) vs favorable (≤3). Metabolic acidosis was defined by the presence of one of the following: Serum bicarbonate &lt;22 mEq/L, lactic acid &gt;2 mmol/L or pH &lt;7.35. Respiratory acidosis was defined by pCO2 &gt;45 mmHg. We further stratified our analysis by ICU vs general ward admission and intubation status. <h3>Results:</h3> There was a total of 406 patients, average age 80.5 (±1.5) years, 174 (43%) females and 232 (57%) males. 134 (33%) patients were acidotic on admission, 42 (10%) had respiratory acidosis and the remaining 92 (23%) had metabolic acidosis. There was no statistically significant association between metabolic acidosis with either hospital mortality (p=0.21, 95% CI [0.37–1.24]) or 90-day favorable functional outcome (p=0.61, 95% CI [0.37–1.24]) after adjustment for hematoma volume and expansion, Glasgow Coma Scale, and presence of interventricular hemorrhage. There was no association between respiratory acidosis with either hospital mortality (p=1.00) or functional outcome (p=1.00) before the adjustment for confounders. There was no effect modification after stratifying by ICU and intubation status. <h3>Conclusions:</h3> In this retrospective cohort study, we found that systemic acidosis was present in one third of patients with spontaneous ICH. Unlike other critical neurological conditions such as traumatic brain injury, there was no significant association between metabolic and respiratory acidosis with mortality and 90-day functional outcome in ICH. <b>Disclosure:</b> Dr. Andreev has nothing to disclose. Dr. Wilson has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Forsman has stock in Eli Lilly and Co. Dr. Forsman has stock in Moderna Inc. Dr. McMillan has nothing to disclose. Dr. Sahni has nothing to disclose. Dr. Selim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedRhythms Inc.. Dr. Lioutas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Qmetis. Dr. Lioutas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association.

Interaction between cerebral small vessel disease, blood pressure, and remote ischemic lesions in acute spontaneous intracerebral hemorrhage.

Acute blood pressure (BP) reduction is the first-line treatment for acute spontaneous intracerebral hemorrhage (ICH); however, recent research suggests that intensive BP reduction along with cerebral small vessel disease (cSVD) is a risk factor for remote DWI lesions (RDWILs). We aimed to delineate the interplay between cSVD and BP reduction therapy on the risk of RDWILs. We enrolled 303 patients who underwent brain magnetic resonance imaging within 7 days after acute spontaneous ICH. RDWILs were categorized as occurring in borderzone (BZ) or non-BZ areas. We examined the effect of cSVD, acute BP reduction, and their interaction on RDWILs. RDWILs were observed in 34 (11%) patients (59.8 ± 10.3-years-old, 24% male). RDWILs were associated with a larger acute weighted average mean arterial pressure (MAP) reduction in the initial 24 h after ICH onset and a higher total cerebral microbleed (CMB) count. Intensive MAP changes (odds ratio (OR) per 10 mmHg 1.76, 95% confidence interval (CI) 1.03-3.20), total CMBs burden (OR per 10 CMBs 1.21, 95% CI 1.08-1.39), and presence of lobar CMBs (OR 7.33, 95% CI 1.59-55.6) were risk factors for RDWILs at BZ, but not at non-BZ. Furthermore, a significant interaction was observed between lobar CMBs and MAP reduction on increased risk of RDWILs at BZ (p = 0.030). cSVD modulates the effect of acute BP reduction on the risk of RDWILs. Patients with extensive microangiopathy have a higher risk of developing cerebral ischemic changes in BZ during unstable hemodynamic status.