Code ICH: A Call to Action.

Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.

Perihaematomal oedema evolution over two weeks after spontaneous intracerebral haemorrhage and association with outcome: prospective cohort study.

Introduction We know little about the evolution of perihaematomal oedema (PHO) >24 hours after ICH onset. We aimed to determine the trajectory of PHO after ICH onset and its association with outcome. Methods We did a prospective cohort study using a pre-specified scanning protocol in adults with first-ever spontaneous ICH and measured absolute PHO volumes on CT head scans at ICH diagnosis and 3±2, 7±2 and 14±2 days after ICH onset. We used the largest ICH if ICHs were multiple. The primary outcomes were (a) the trajectory of PHO after ICH onset and (b) the association between PHO (absolute volume at the time when most repeat CT head scans were obtained, and change in PHO volume at this time compared with the first CT head scan) and poor functional outcome (modified Rankin scale 3-6 at 90 days). We pre-specified multivariable logistic regression models of this association adjusting analyses for potential confounders: age, GCS, infratentorial ICH location and intraventricular extension. Results In 106 participants of whom forty nine (46%) were female, with a median ICH volume 7ml (interquartile range [IQR] 2-22ml), the trajectory of median PHO volume was an increase from 14ml (IQR 7-26ml) at diagnosis to 18ml (IQR 8-40ml) at 3±2 days (n=87), 20ml (IQR 8-48ml) at 7±2 days (n=93) and 21ml (IQR 10-54ml) at 14±2 days (n=78) (p=<0.001). PHO volume at each time point was collinear with ICH volume at diagnosis (│r│>0.7) but the change in PHO volume between diagnosis and each time point was not. Given collinearity, we used total lesion (i.e. ICH+PHO) volume instead of PHO volume in a logistic regression model of its association at each time point with outcome. Increasing total lesion (ICH+PHO) volume at day 7±2 was associated with poor functional outcome (adjusted OR per ml 1.02, 95% CI 1.00-1.03; p=0.036) but the increase in PHO volume between diagnosis and day 7±2 was not associated with poor functional outcome (adjusted OR per ml 1.03, 95% CI 0.99-1.07; p=0.132). Conclusion PHO volume increases throughout the first two weeks after onset of mild to moderate ICH. Total lesion (ICH+PHO) volume at day 7±2 was associated with poor functional outcome but the change in PHO volume between diagnosis and day 7±2 was not. Prospective cohort studies with larger sample sizes are needed to investigate these associations and their modifiers.

Early mobilisation is associated with lower subacute blood pressure and variability in ICH: A retrospective cohort study✰.

BACKGROUND: Very early rehabilitation after stroke appears to worsen outcome, particularly in intracerebral haemorrhage (ICH). Plausible mechanisms include increased mean blood pressure (BP) and BP variability. AIMS: To test associations between early mobilisation, subacute BP and survival, in observational data of ICH patients during routine clinical care. METHODS: We collected demographic, clinical and imaging data from 1372 consecutive spontaneous ICH patients admitted between 2 June 2013 and 28 September 2018. Time to first mobilisation (defined as walking, standing, or sitting out-of-bed) was extracted from electronic records. We evaluated associations between early mobilisation (within 24 h of onset) and both subacute BP and death by 30 days using multifactorial linear and logistic regression analyses respectively. RESULTS: Mobilisation at 24 h was not associated with increased odds of death by 30 days when adjusting for key prognostic factors (OR 0.4, 95% CI 0.2 to 1.1, p = 0.07). Mobilisation at 24 h was independently associated with both lower mean systolic BP (-4.5 mmHg, 95% CI -7.5 to -1.5 mmHg, p = 0.003) and lower diastolic BP variability (-1.3 mmHg, 95% CI -2.4 to -0.2 mg, p = 0.02) during the first 72 h after admission. CONCLUSIONS: Adjusted analysis in this observational dataset did not find an association between early mobilisation and death by 30 days. We found early mobilisation at 24 h to be independently associated with lower mean systolic BP and lower diastolic BP variability over 72 h. Further work is needed to establish mechanisms for the possible detrimental effect of early mobilisation in ICH.

Iatrogenic cerebral amyloid angiopathy: an emerging clinical phenomenon.

In the last 6 years, following the first pathological description of presumed amyloid-beta (Aß) transmission in humans (in 2015) and subsequent experimental confirmation (in 2018), clinical cases of iatrogenic cerebral amyloid angiopathy (CAA)-attributed to the transmission of Aß seeds-have been increasingly recognised and reported. This newly described form of CAA is associated with early disease onset (typically in the third to fifth decade), and often presents with intracerebral haemorrhage, but also seizures and cognitive impairment. Although assumed to be rare, it is important that clinicians remain vigilant for potential cases, particularly as the optimal management, prognosis, true incidence and public health implications remain unknown. This review summarises our current understanding of the clinical spectrum of iatrogenic CAA and provides a diagnostic framework for clinicians. We provide clinical details for three patients with pathological evidence of iatrogenic CAA and present a summary of the published cases to date (n=20), identified following a systematic review. Our aims are: (1) To describe the clinical features of iatrogenic CAA, highlighting important similarities and differences between iatrogenic and sporadic CAA; and (2) To discuss potential approaches for investigation and diagnosis, including suggested diagnostic criteria for iatrogenic CAA.

Radiologically defined acute hydrocephalus in aneurysmal subarachnoid haemorrhage.

BACKGROUND: Ventriculomegaly is common in aneurysmal subarachnoid haemorrhage (aSAH). An imaging measure to predict the need for cerebrospinal fluid (CSF) diversion may be useful. The bicaudate index (BCI) has been previously applied to aSAH. Our aim was to derive and test a threshold BCI above which CSF diversion may be required. METHODS: Review of prospective registry. The derivation group (2009-2015) included WFNS grade 1-2 aSAH patients who deteriorated clinically, had a repeat CT brain and underwent CSF diversion. BCI was measured on post-deterioration CTs and the lower limit of the 95% confidence interval (95%CI) was the hydrocephalus threshold. In a separate test group (2016), in WFNS ≥ 2 patients, we compared BCI on diagnostic CTs with CSF diversion within 24 hours. RESULTS: The derivation group (n = 62) received an external ventricular (n = 57, 92%) or lumbar drain (n = 5, 8%). Mean post-deterioration BCI was 0.19 (95%CI 0.17-0.22) for age ≤49 years, 0.22 (95%CI 0.20-0.23) for age 50-64 years and 0.24 (95%CI 0.22-0.27) for age ≥65 years. Hydrocephalus thresholds were therefore 0.17, 0.20 and 0.22, respectively. In the test group (n = 105), there was no significant difference in BCI on the diagnostic CT between good and poor grade patients aged ≤49 years (p = 0.31) and ≥65 years (p = 0.96). 30/66 WFNS ≥ 2 patients underwent CSF diversion, although only 15/30 (50%) exceeded BCI thresholds for hydrocephalus. CONCLUSION: A significant proportion of aSAH patients may undergo CSF diversion without objective evidence of hydrocephalus. Our threshold values require further testing but may provide an objective measure to aid clinical decision making in aSAH.

An Intracerebral Hemorrhage Care Bundle Is Associated with Lower Case Fatality.

OBJECTIVE: Anticoagulation reversal, intensive blood pressure lowering, neurosurgery, and access to critical care might all be beneficial in acute intracerebral hemorrhage (ICH). We combined and implemented these as the "ABC" hyperacute care bundle and sought to determine whether the implementation was associated with lower case fatality. METHODS: The ABC bundle was implemented from June 1, 2015 to May 31, 2016. Key process targets were set, and a registry captured consecutive patients. We compared 30-day case fatality before, during, and after bundle implementation with multivariate logistic regression and used mediation analysis to determine which care process measures mediated any association. Difference-in-difference analysis compared 30-day case fatality with 32,295 patients with ICH from 214 other hospitals in England and Wales using Sentinel Stroke National Audit Programme data. RESULTS: A total of 973 ICH patients were admitted in the study period. Compared to before implementation, the adjusted odds of death by 30 days were lower in the implementation period (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.38-0.97, p = 0.03), and this was sustained after implementation (OR = 0.40, 95% CI = 0.24-0.61, p < 0.0001). Implementation of the bundle was associated with a 10.8 percentage point (95% CI = -17.9 to -3.7, p = 0.003) reduction in 30-day case fatality in difference-in-difference analysis. The total effect of the care bundle was mediated by a reduction in do-not-resuscitate orders within 24 hours (52.8%) and increased admission to critical care (11.1%). INTERPRETATION: Implementation of the ABC care bundle was significantly associated with lower 30-day case fatality after ICH. ANN NEUROL 2019;86:495-503.

Call to Action: SARS-CoV-2 and CerebrovAscular DisordErs (CASCADE).

BACKGROUND AND PURPOSE: The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic. METHODS: This is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center. CONCLUSION: The proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.

Acute intracerebral haemorrhage: diagnosis and management.

Intracerebral haemorrhage (ICH) accounts for half of the disability-adjusted life years lost due to stroke worldwide. Care pathways for acute stroke result in the rapid identification of ICH, but its acute management can prove challenging because no individual treatment has been shown definitively to improve its outcome. Nonetheless, acute stroke unit care improves outcome after ICH, patients benefit from interventions to prevent complications, acute blood pressure lowering appears safe and might have a modest benefit, and implementing a bundle of high-quality acute care is associated with a greater chance of survival. In this article, we address the important questions that neurologists face in the diagnosis and acute management of ICH, and focus on the supporting evidence and practical delivery for the main acute interventions.

Influence of Intracerebral Hemorrhage Location on Outcomes in Patients With Severe Intraventricular Hemorrhage.

Background and Purpose- We investigated the prognostic significance of spontaneous intracerebral hemorrhage location in presence of severe intraventricular hemorrhage. Methods- We analyzed diagnostic computed tomography scans from 467/500 (excluding primary intraventricular hemorrhage) subjects from the CLEAR (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) III trial. We measured intracerebral hemorrhage engagement with specific anatomic regions, and estimated association of each region with blinded assessment of dichotomized poor stroke outcomes: mortality, modified Rankin Scale score of 4 to 6, National Institutes of Health Stroke Scale score of >4, stroke impact scale score of <60, Barthel Index <86, and EuroQol visual analogue scale score of <50 and <70 at days 30 and 180, respectively, using logistic regression models. Results- Frequency of anatomic region involvement consisted of thalamus (332 lesions, 71.1% of subjects), caudate (219, 46.9%), posterior limb internal capsule (188, 40.3%), globus pallidus/putamen (127, 27.2%), anterior limb internal capsule (108, 23.1%), and lobar (29, 6.2%). Thalamic location was independently associated with mortality (days 30 and 180) and with poor outcomes on most stroke scales at day 180 on adjusted analysis. Posterior limb internal capsule and globus pallidus/putamen involvement was associated with increased odds of worse disability at days 30 and 180. Anterior limb internal capsule and caudate locations were associated with decreased mortality on days 30 and 180. Anterior limb internal capsule lesions were associated with decreased long-term morbidity. Conclusions- Acute intracerebral hemorrhage lesion topography provides important insights into anatomic correlates of mortality and functional outcomes even in severe intraventricular hemorrhage causing obstructive hydrocephalus. Models accounting for intracerebral hemorrhage location in addition to volumes may improve outcome prediction and permit stratification of benefit from aggressive acute interventions. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00784134.

SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke): A Randomized Controlled Phase 2 Trial.

BACKGROUND AND PURPOSE: The proinflammatory cytokine IL-1 (interleukin-1) has a deleterious role in cerebral ischemia, which is attenuated by IL-1 receptor antagonist (IL-1Ra). IL-1 induces peripheral inflammatory mediators, such as interleukin-6, which are associated with worse prognosis after ischemic stroke. We investigated whether subcutaneous IL-1Ra reduces the peripheral inflammatory response in acute ischemic stroke. METHODS: SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke) was a single-center, double-blind, randomized, placebo-controlled phase 2 trial of subcutaneous IL-1Ra (100 mg administered twice daily for 3 days) in patients presenting within 5 hours of ischemic stroke onset. Randomization was stratified for baseline National Institutes of Health Stroke Scale score and thrombolysis. Measurement of plasma interleukin-6 and other peripheral inflammatory markers was undertaken at 5 time points. The primary outcome was difference in concentration of log(interleukin-6) as area under the curve to day 3. Secondary outcomes included exploratory effect of IL-1Ra on 3-month outcome with the modified Rankin Scale. RESULTS: We recruited 80 patients (mean age, 72 years; median National Institutes of Health Stroke Scale, 12) of whom 73% received intravenous thrombolysis with alteplase. IL-1Ra significantly reduced plasma interleukin-6 (P<0.001) and plasma C-reactive protein (P<0.001). IL-1Ra was well tolerated with no safety concerns. Allocation to IL-1Ra was not associated with a favorable outcome on modified Rankin Scale: odds ratio (95% confidence interval)=0.67 (0.29-1.52), P=0.34. Exploratory mediation analysis suggested that IL-1Ra improved clinical outcome by reducing inflammation, but there was a statistically significant, alternative mechanism countering this benefit. CONCLUSIONS: IL-1Ra reduced plasma inflammatory markers which are known to be associated with worse clinical outcome in ischemic stroke. Subcutaneous IL-1Ra is safe and well tolerated. Further experimental studies are required to investigate efficacy and possible interactions of IL-1Ra with thrombolysis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: ISRCTN74236229.

Clinical Course and Outcomes of Small Supratentorial Intracerebral Hematomas.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) volume, particularly if ≥30 mL, is a major determinant of poor outcome. We used a multinational ICH data registry to study the characteristics, course, and outcomes of supratentorial hematomas with volumes <30 mL. METHODS: Basic characteristics, clinical and radiological course, and 30-day outcomes of these patients were recorded. Outcomes were categorized as early neurological deterioration (END), hematoma expansion, Glasgow Outcome Scale (GOS), and in-hospital death. Poor outcome was defined as composite of in-hospital death and severe disability (GOS ≤ 3). Comparison was conducted based on hemorrhage location. Logistic regression using dichotomized outcome scales was applied to determine predictors of poor outcome. RESULTS: Among 375 cases of supratentorial ICH with volumes <30 mL, expansion and END rates were 19.2% and 7.5%, respectively. Hemorrhage growth was independently associated with END (odds ratio: 28.7, 95% confidence interval [CI]: 8.51-96.5; P < .0001). Expansion rates did not differ according to ICH location. Overall, 13.9% (exact binomial 95% CI: 10.5-17.8) died in the hospital and 29.1% (CI: 24.5-34.0) had severe disability at 30 days; there was a cumulative poor outcome rate of 42.9% (CI: 37.9-48.1). Age, admission Glasgow Coma Scale, intraventricular extension, and END were independently associated with poor outcome. There was no difference in poor outcome rates between lobar and deep locations (40.2% versus 43.8%, P = .56). CONCLUSION: Patients with supratentorial ICH <30 mL have high rates of poor outcome at 30 days, regardless of location. Nearly 1 in 5 hematomas <30 mL expands, leading to END or death.

Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage.

OBJECTIVE: There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different reversal strategies. METHODS: We pooled individual ICH patient data from 16 stroke registries in 9 countries (n = 10 282), of whom 1,797 (17%) were on VKA. After excluding 250 patients with international normalized ratio < 1.3 and/or missing data required for analysis, we compared all-cause 30-day case fatality using Cox regression. RESULTS: We included 1,547 patients treated with FFP (n = 377, 24%), PCC (n = 585, 38%), both (n = 131, 9%), or neither (n = 454, 29%). The crude case fatality and adjusted hazard ratio (HR) were highest with no reversal (61.7%, HR = 2.540, 95% confidence interval [CI] = 1.784-3.616, p < 0.001), followed by FFP alone (45.6%, HR = 1.344, 95% CI = 0.934-1.934, p = 0.112), then PCC alone (37.3%, HR = 1.445, 95% CI = 1.014-2.058, p = 0.041), compared to reversal with both FFP and PCC (27.8%, reference). Outcomes with PCC versus FFP were similar (HR = 1.075, 95% CI = 0.874-1.323, p = 0.492); 4-factor PCC (n = 441) was associated with higher case fatality compared to 3-factor PCC (n = 144, HR = 1.441, 95% CI = 1.041-1.995, p = 0.027). INTERPRETATION: The combination of FFP and PCC might be associated with the lowest case fatality in reversal of VKA-ICH, and FFP may be equivalent to PCC. Randomized controlled trials with functional outcomes are needed to establish the most effective treatment.

Software output from semi-automated planimetry can underestimate intracerebral haemorrhage and peri-haematomal oedema volumes by up to 41.

INTRODUCTION: Haematoma and oedema size determines outcome after intracerebral haemorrhage (ICH), with each added 10 % volume increasing mortality by 5 %. We assessed the reliability of semi-automated computed tomography planimetry using Analyze and Osirix softwares. METHODS: We randomly selected 100 scans from 1329 ICH patients from two centres. We used Hounsfield Unit thresholds of 5-33 for oedema and 44-100 for ICH. Three raters segmented all scans using both softwares and 20 scans repeated for intra-rater reliability and segmentation timing. Volumes reported by Analyze and Osirix were compared to volume estimates calculated using the best practice method, taking effective individual slice thickness, i.e. voxel depth, into account. RESULTS: There was excellent overall inter-rater, intra-rater and inter-software reliability, all intraclass correlation coefficients >0.918. Analyze and Osirix produced similar haematoma (mean difference: Analyze - Osirix = 1.5 ± 5.2 mL, 6 %, p ≤ 0.001) and oedema volumes (-0.6 ± 12.6 mL, -3 %, p = 0.377). Compared to a best practice approach to volume calculation, the automated haematoma volume output was 2.6 mL (-11 %) too small with Analyze and 4.0 mL (-18 %) too small with Osirix, whilst the oedema volumes were 2.5 mL (-12 %) and 5.5 mL (-25 %) too small, correspondingly. In scans with variable slice thickness, the volume underestimations were larger, -29%/-36 % for ICH and -29 %/-41 % for oedema. Mean segmentation times were 6:53 ± 4:02 min with Analyze and 9:06 ± 5:24 min with Osirix (p < 0.001). CONCLUSION: Our results demonstrate that the method used to determine voxel depth can influence the final volume output markedly. Results of clinical and collaborative studies need to be considered in the context of these methodological differences.

Incidence, predictors and clinical characteristics of orolingual angio-oedema complicating thrombolysis with tissue plasminogen activator for ischaemic stroke.

BACKGROUND: Orolingual angio-oedema is a recognised complication of tissue plasminogen activator (tPA) for ischaemic stroke. We investigated its incidence, clinical characteristics and relationship with other factors in patients receiving tPA at a UK centre. METHODS: 530 consecutive patients (median age 70 years) receiving tPA treatment for confirmed ischaemic stroke were included. Cases were defined as those developing angio-oedema within 24 h of initiation of tPA. Angio-oedema was retrospectively classified as mild, moderate or severe using predefined criteria. The primary analysis was the association between prior ACE inhibitor (ACE-I) treatment and angio-oedema. RESULTS: Orolingual angio-oedema was observed in 42 patients (7.9%; 95% CI 5.5% to 10.6%), ranging from 5 to 189 min after initiation of tPA (median 65 min). 12% of the angio-oedema cases were severe (1% of all patients treated with tPA), requiring urgent advanced airway management. 172 patients (33%) were taking ACE-I. In multifactorial analyses, only prior ACE-I treatment remained a significant independent predictor of angio-oedema (odds ratio (OR) 2.3; 95% CI 1.1 to 4.7). CONCLUSIONS: Angio-oedema occurs more frequently than previously reported and is associated with preceding ACE-I treatment. Angio-oedema may be delayed and progress to life-threatening airway compromise, which has implications for the assessment and delivery of thrombolysis.

Systemic inflammation impairs tissue reperfusion through endothelin-dependent mechanisms in cerebral ischemia.

BACKGROUND AND PURPOSE: Systemic inflammation contributes to diverse acute and chronic brain pathologies, and extensive evidence implicates inflammation in stroke susceptibility and poor outcome. Here we investigate whether systemic inflammation alters cerebral blood flow during reperfusion after experimental cerebral ischemia. METHODS: Serial diffusion and perfusion-weighted MRI was performed after reperfusion in Wistar rats given systemic (intraperitoneal) interleukin-1ß or vehicle before 60-minute transient middle cerebral artery occlusion. The expression and location of endothelin-1 was assessed by polymerase chain reaction, ELISA, and immunofluorescence. RESULTS: Systemic interleukin-1 caused a severe reduction in cerebral blood flow and increase in infarct volume compared with vehicle. Restriction in cerebral blood flow was observed alongside activation of the cerebral vasculature and upregulation of the vasoconstricting peptide endothelin-1 in the ischemic penumbra. A microthrombotic profile was also observed in the vasculature of rats receiving interleukin-1. Blockade of endothelin-1 receptors reversed this hypoperfusion, reduced tissue damage, and improved functional outcome. CONCLUSIONS: These data suggest patients with a raised inflammatory profile may have persistent deficits in perfusion after reopening of an occluded vessel. Future therapeutic strategies to interrupt the mechanism identified could lead to enhanced recovery of penumbra in patients with a heightened inflammatory burden and a better outcome after stroke.

C-reactive protein predicts hematoma growth in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Early hematoma growth (EHG) occurs in about one third of patients with spontaneous intracerebral hemorrhage. The main aim of this study was to investigate the potential of plasma C-reactive protein (CRP) for predicting EHG after acute spontaneous intracerebral hemorrhage. METHODS: Plasma CRP was measured within 6 hours of onset (median, 120 minutes) in 399 patients with primary or vitamin K antagonist-associated spontaneous intracerebral hemorrhage and without recent infection. Computed tomography brain scans were performed at baseline and repeated within 24 hours (median, 22 hours). The primary outcome was EHG, defined as absolute growth>12.5 cm3 or relative growth>33%. Secondary outcomes included early neurological worsening (ENW) using the Glasgow Coma Scale and 30-day mortality. Multivariable regression analyses were used to evaluate associations of CRP concentration and outcomes. Kaplan-Meier analysis was used for survival. RESULTS: EHG occurred in 25.8%, ENW in 19.3%, and mortality was 31.8% at 30 days. Thirty-day mortality was significantly higher in patients with ENW (hazard ratio, 3.21; 95% confidence interval, 2.00-5.17; P<0.0001) and in patients with EHG (hazard ratio, 2.13; 95% confidence interval, 1.42-3.18; P<0.0001, log-rank test). Median CRP was 12 mg/L (interquartile range, 10-17) in the EHG group and 7 mg/L (interquartile range, 4-12.1) in those without EHG (P<0.0001). In multivariable analyses, plasma CRP>10 mg/L independently predicted EHG (odds ratio, 4.71; 95% confidence interval, 2.75-8.06; P<0.0001) and ENW (odds ratio, 2.70; 95% confidence interval, 1.50-4.84; P=0.0009). CONCLUSIONS: CRP>10 mg/L is independently predictive of EHG and ENW, both of which are associated with increased mortality. Inflammation may be important in contributing to EHG and warrants further investigation.

Prehospital identification of intracerebral haemorrhage: a scoping review of early clinical features and portable devices.

INTRODUCTION: Prehospital identification of intracerebral haemorrhage (ICH) in suspected stroke cases may enable the initiation of appropriate treatments and facilitate better-informed transport decisions. This scoping review aims to examine the literature to identify early clinical features and portable devices for the detection of ICH in the prehospital setting. METHODS: Three databases were searched via Ovid (MEDLINE, EMBASE and CENTRAL) from inception to August 2022 using prespecified search strategies. One reviewer screened all titles, abstracts and full-text articles for eligibility, while a second reviewer independently screened 20% of the literature during each screening stage. Data extracted were tabulated to summarise the key findings. RESULTS: A total of 6803 articles were screened for eligibility, of which 22 studies were included for analysis. Among them, 15 studies reported on early clinical features, while 7 considered portable devices. Associations between age, sex and comorbidities with the presence of ICH varied across studies. However, most studies reported that patients with ICH exhibited more severe neurological deficits (n=6) and higher blood pressure levels (n=11) at onset compared with other stroke and non-stroke diagnoses. Four technologies were identified for ICH detection: microwave imaging technology, volumetric impedance phase shift spectroscopy, transcranial ultrasound and electroencephalography. Microwave and ultrasound imaging techniques showed promise in distinguishing ICH from other diagnoses. CONCLUSION: This scoping review has identified potential clinical features for the identification of ICH in suspected stroke patients. However, the considerable heterogeneity among the included studies precludes meta-analysis of available data. Moreover, we have explored portable devices to enhance ICH identification. While these devices have shown promise in detecting ICH, further technological development is required to distinguish between stroke subtypes (ICH vs ischaemic stroke) and non-stroke diagnoses.

Acute care bundles should be used for patients with intracerebral haemorrhage: An expert consensus statement.

PURPOSE: Intracerebral haemorrhage (ICH) is the most devastating form of stroke and a major cause of disability. Clinical trials of individual therapies have failed to definitively establish a specific beneficial treatment. However, clinical trials of introducing care bundles, with multiple therapies provided in parallel, appear to clearly reduce morbidity and mortality. Currently, not enough patients receive these interventions in the acute phase. METHODS: We convened an expert group to discuss best practices in ICH and to develop recommendations for bundled care that can be delivered in all settings that treat acute ICH, with a focus on European healthcare systems. FINDINGS: In this consensus paper, we argue for widespread implementation of formalised care bundles in ICH, including specific metrics for time to treatment and criteria for the consideration of neurosurgical therapy. DISCUSSION: There is an extraordinary opportunity to improve clinical care and clinical outcomes in this devastating disease. Substantial evidence already exists for a range of therapies that can and should be implemented now.