scholarly journals Secondary mechanisms of injury and viable pathophysiological targets in intracerebral hemorrhage

2021 ◽  
Vol 14 ◽  
pp. 175628642110492
Author(s):  
Wendy Bautista ◽  
P. David Adelson ◽  
Nathan Bicher ◽  
Marios Themistocleous ◽  
Georgios Tsivgoulis ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Trial Design ◽  
Secondary Phase ◽  
Pressure Control ◽  
Primary Phase ◽  
Hematoma Expansion ◽  
Secondary Injury ◽  
Hematoma Volume ◽  
Receptor Modulation

Intracerebral hemorrhage (ICH) can be divided into a primary and secondary phase. In the primary phase, hematoma volume is evaluated and therapies are focused on reducing hematoma expansion. In the secondary, neuroprotective phase, complex systemic inflammatory cascades, direct cellular toxicity, and blood-brain barrier disruption can result in worsening perihematomal edema that can adversely affect functional outcome. To date, all major randomized phase 3 trials for ICH have targeted primary phase hematoma volume and incorporated clot evacuation, intensive blood pressure control, and hemostasis. Reasons for this lack of clinical efficacy in the major ICH trials may be due to the lack of therapeutics involving mitigation of secondary injury and inflexible trial design that favors unilateral mechanisms in a complex pathophysiology. Potential pathophysiological targets for attenuating secondary injury are highlighted in this review and include therapies increasing calcium, antagonizing microglial activation, maintaining macrophage M1 versus M2 balance by decreasing M1 signaling, aquaporin inhibition, NKCCl inhibition, endothelin receptor inhibition, Sur1-TRPM4 inhibition, matrix metalloproteinase inhibition, and sphingosine-1-phosphate receptor modulation. Future clinical trials in ICH focusing on secondary phase injury and, potentially implementing adaptive trial design approaches with multifocal targets, may improve insight into these mechanisms and provide potential therapies that may improve survival and functional outcome.

Abstract WP418: Characteristic of Intracerebral Hemorrhage Related to Direct Oral Anticoagulant versus Warfarin: Results From the PASTA Registry

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Satoshi Suda ◽  
Yasuyuki Iguchi ◽  
Shigeru Fujimoto ◽  
Yoshiki Yagita ◽  
Takayuki Mizunari ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Oral Anticoagulant ◽  
Hematoma Expansion ◽  
Direct Oral Anticoagulant ◽  
Registry Study ◽  
Stroke Patients ◽  
Hematoma Volume ◽  
Imaging Characteristics ◽  
Warfarin Treatment ◽  
Patient Enrollment

Background and Purpose: The characteristics of direct oral anticoagulant (DOAC)-related intracerebral hemorrhage (ICH) have not been fully clarified. We planned to recruit patients prospectively and to investigate the characteristics and outcomes in patients with ICH receiving direct oral anticoagulant (DOAC) and warfarin treatment. Methods: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke patients receiving OAC. Patient enrollment started in April 2016 at 25 tertiary centers across Japan. We compared imaging, clinical characteristics, and discharge modified Rankin Scale (mRS) between DOAC- and warfarin-related ICH patients with atrial fibrillation (AF). Results: A total of 154 patients (51 women; median age 77 [quartiles 69-87] years) were analyzed. Of these, 111 patients (72%) received prior DOAC treatment and the remaining 43 (28%) received prior warfarin treatment (Fig. A, B and C). There were no relevant differences in clinical and hematoma characteristics between DOAC- and warfarin-related ICH regarding baseline hematoma volume (median [quartiles]: DOAC, 11 [5-23] mL vs. warfarin, 12 [5-30] mL; P =0.95), rate of hematoma expansion (DOAC, 12/111 [11%] vs. warfarin, 4/43 [9%]; P =0.80), rate of subcortical hemorrhage (DOAC, 15/111 [11%] vs. warfarin, 10/43 [9%]; P =0.80) and the proportion of patients with unfavorable outcome (mRS, 4-6: DOAC 76/108 [70%] vs. warfarin 23/38 [61%]; P =0.26). Cerebral microbleeds (CMBs) were detected more frequently in DOAC group than in warfarin (47/76 [62%] vs. 11/32 [34%]; P <0.01). Subgroup analyses showed that type of DOAC agent did not result in relevant differences in imaging characteristics or outcome (Fig. D and E). Conclusions: Our results showed that there were no significant differences in hematoma characteristics and functional outcome among AF patients with DOAC- or warfarin-related ICH.

Abstract 3543: Imaging Correlates of Early Neurologic Deterioration among Patients with Intracerebral Hemorrhage

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Nerses Sanossian ◽  
Adrian M Burgos ◽  
David S Liebeskind ◽  
Sidney Starkman ◽  
Pablo Villablanca ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Hematoma Expansion ◽  
Hematoma Volume ◽  
Phase 3 ◽  
Neurologic Deterioration ◽  
Irregular Border ◽  
History Of ◽  
Initial Imaging ◽  
Fazekas Scale ◽  
Frequent Presence

Background: Early neurologic deterioration (END) occurs commonly in intracerebral hemorrhage (ICH) patients being transported by EMS ambulances, but the imaging correlates of END have not been previously delineated. Methods: We analyzed consecutive ICH patients in the Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Trial, a phase 3, multicenter of paramedic-initiated magnesium sulfate vs. placebo for stroke patients presenting within 2 hours of symptom onset. END was defined as a 2-point or greater decrease in the Glasgow Coma Scale (GCS) from paramedic evaluation to ED evaluation. Baseline imaging studies were independently analyzed by 2 neurologists for ICH location, volume, presence of intraventricular hemorrhage (IVH), heterogeneity (defined as >20 point difference in Hounsfield units), irregular hematoma borders, multilobulated appearance, and substantial edema (defined as >0.5cm thickness). Leukoaraiosis was graded using the Fazekas scale for periventricular and deep white matter changes (0-3 for each). Results: Among 127 patients, mean age was 66 (SD 14) years, 34% were women, 35% were Hispanic ethnicity, 83% white, and 84% had a history of HTN. Patients were evaluated by paramedics a median of 23 (IQR 16, 39) minutes after last known well time (LKWT). At that time, the median GCS was 15 (IQR 15-15) and mean SBP/DBP was 177/95 (SD 34/22). Initial post-arrival brain imaging was performed a median of 94 (IQR 77, 117) min after LKWT. Post-arrival study GCS scores were obtained at a median of 108 (IQR 70, 144) min after LWKT. Early neurologic deterioration occurred in 37 (29%) patients. Among these patients, median first ED GCS was 3 (IQR 3-10). On first imaging, compared with neurologically stable patients, END patients had larger hematoma volume (33 cc v 16 cc, p<0.0001), and more frequent presence of intraventricular extension (45% v 20%, p=0.003), midline shift (58% v 22%), substantial edema (54% v 26%, p=0.038), heterogeneous density (50% v 22%, p=0.006), multilobulated appearance (44% v 18%, p=0.002), and irregular border (39% v 14%, p=0.010). Leukoaraiosis and cortical v subcortical location did not affect rates of END. In multivariate analysis, hematoma volume and presence of IVH were imaging findings independently associated with early neurologic deterioration. Conclusions: About 3 in 10 patients with hyperacute ICH neurologically deteriorate during the prehospital and early emergency department course, often before neuroimaging is obtained. Patients with early neurologic deterioration have larger hematoma volume and occurrence of IVH on initial imaging. These findings suggest hematoma expansion prior to ED arrival drives early neurologic deterioration in ICH and emphasize the need for prehospital interventions.

scholarly journals Mediation effects of mean Hounsfield unit on relationship between hemoglobin and expansion of intracerebral hemorrhage

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yong Soo Kim ◽  
Han-Gil Jeong ◽  
Hee-Yun Chae ◽  
Beom Joon Kim ◽  
Jihoon Kang ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Mediation Analysis ◽  
Hounsfield Unit ◽  
Mediation Effect ◽  
Hematoma Expansion ◽  
Hematoma Volume ◽  
Mediation Effects ◽  
Potential Marker ◽  
Baseline Systolic Blood Pressure ◽  
The Mean

AbstractLow hemoglobin levels are known to be associated with hematoma expansion (HE) and poor functional outcome in patients with intracerebral hemorrhage (ICH). However, it is not yet known whether low hemoglobin itself causes HE directly or is merely a confounder. Thus, we investigated the mediation effect of the mean Hounsfield unit (HU) of hematoma on the relationship between low hemoglobin and expansion of ICH. Overall, 232 consecutive patients with ICH who underwent non-contrast computed tomography (NCCT) within 12 h since onset were included. The mean HU and hematoma volume on NCCT were investigated using semi-automated planimetry. HE was defined as an increase in hematoma volume > 33% or 6 mL. The respective associations among the hemoglobin level, mean HU, and HE were analyzed using multivariable regression analysis, adjusting for age, sex, and known HE predictors. Mediation analysis was performed to examine the potential causal association among the three. HE occurred in 34.5% of patients; hemoglobin levels were inversely associated with HE occurrence (adjusted odds ratio, 0.90; p = 0.03). The mean HU of the hematoma was lower in patients with HE than in patients without HE (58.5 ± 3.3 vs. 56.8 ± 3.0; p < 0.01). Hemoglobin levels on admission were linearly related to the mean HU (adjusted β, 0.33; p < 0.01) after adjusting for known HE predictors (time from onset to CT, antithrombotic use, hematoma volume). Causal mediation analysis showed a significant mediation effect of the mean HU on the association between hemoglobin levels and HE (p = 0.04). The proportion of indirect effect through the mean HU among the total effect was 19% (p = 0.05). The mediation effect became nonsignificant in the when the multivariable model was adjusted with additional covariates (baseline systolic blood pressure and hematoma location). The mean HU of the hematoma mediated the association between hemoglobin levels and HE occurrence. Therefore, the mean HU of the hematoma may be a potential marker of impaired hemostasis in patients with ICH.

scholarly journals Outcome of intracerebral hemorrhage associated with different oral anticoagulants

Neurology ◽  
2017 ◽  
Vol 88 (18) ◽  
pp. 1693-1700 ◽  
Author(s):  
Duncan Wilson ◽  
David J. Seiffge ◽  
Christopher Traenka ◽  
Ghazala Basir ◽  
Jan C. Purrucker ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Scale Score ◽  
Vitamin K ◽  
Pooled Analysis ◽  
Vitamin K Antagonist ◽  
Cox Proportional Hazards Model ◽  
Hematoma Expansion ◽  
All Cause Mortality ◽  
International Collaborative

Objective:In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non–vitamin K antagonist oral anticoagulation–related ICH (NOAC-ICH) and vitamin K antagonist–associated ICH (VKA-ICH).Methods:We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours.Results:We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6–38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0–27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52–1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18–1.19 [p = 0.11]).Conclusions:In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH.

Abstract TP358: Prehospital Diagnosis of Intracerebral Hemorrhage in a Mobile Stroke Treatment Unit

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Daniel Vela-Duarte ◽  
Ramnath Santosh Ramanathan ◽  
Atif Zafar ◽  
Ather Taqui ◽  
Stacey Winners ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Hematoma Expansion ◽  
Hospital Treatment ◽  
Treatment Team ◽  
Hematoma Volume ◽  
Treatment Unit ◽  
Stroke Treatment ◽  
Imaging Characteristics ◽  
Mobile Stroke Unit ◽  
The Impact

Introduction: The mobile stroke unit (MSTU) is an on-site pre-hospital treatment team that incorporates laboratory and CT scanner and reduces times to treatment for ischemic stroke thrombolysis. The impact of MSTU on treatment and outcomes of intracerebral hemorrhage (ICH) remains unknown. We report our initial experience with ICH encountered on MSTU. Hypothesis: ICH can be quickly identified using MSTU. Hypertension and coagulopathy are common in ICH evaluated on MSTU. Methods: We identified ICH cases from the prospectively collected database encounters. Demographics, clinical features, MSTU imaging and repeat imaging characteristics were reviewed. Initial and follow-up hematoma volume was calculated by the ABC/2 method. Results: Of 295 encounters on MSTU from July 2014 to July 2015, 20 (6.7%) had intracranial hemorrhage, which comprised of 17 intracerebral, 1 subarachnoid and 2 subdural hemorrhages. Median time to CT diagnosis of ICH from emergency medical dispatch was 31 minutes (interquartile range (IQR) 28-36) and that from last known well was 118 minutes (IQR 39-301). Of the 17 ICH patients, 15 (88%) were hypertensive, with a mean systolic blood pressure of 178.1 and diastolic 91.0 mm Hg. Five (29.4%) individuals were found with INR>1.4, 1 of whom received 4-factor prothrombin complex concentrate. Median NIH Stroke Scale was 11 (IQR 7.5-14.5), and median hematoma volume was 10.7 cc (IQR 4.3-30.8). One patient had significant hematoma expansion as defined by >6 cc or 33% relative volume increase. Conclusions: Over 5% of the cases evaluated in the unit presented with ICH, most of whom were hypertensive and had small hematoma volume. MSTU enables early diagnosis of ICH after activation of emergency system, can provide early treatment, and appropriate triage.

Abstract TP308: Reduced Estimated Glomerular Filtration Rate And Outcomes Of Intracerebral Hemorrhage: The SAMURAI-ICH Study

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
TETSUYA MIYAGI ◽  
Masatoshi Koga ◽  
Hiroshi Yamagami ◽  
Satoshi Okuda ◽  
Yasushi Okada ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Intracerebral Hemorrhage ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Hematoma Expansion ◽  
Hematoma Volume ◽  
Nihss Score ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background and Purpose: The association between chronic kidney disease and clinical outcomes in acute intracerebral hemorrhage (ICH) remains uncertain. We aimed to assess associations of renal dysfunction and outcomes in acute ICH patients treated with intensive BP lowering. Methods: The SAMURAI-ICH study was a prospective, multicenter, observational study. A total of 211 patients with acute supratentorial ICH were recruited. BP was targeted between 120 mmHg and 160 mmHg during initial 24 h using intravenous nicardipine. Glomerular filtration rate (eGFR) was calculated using admission serum creatinine. After 23 patients on maintenance hemodialysis were excluded, the remaining 188 were divided into 3 groups as follows: Group 1, eGFR of <60; Group 2, 60 to 75; and Group 3, ≥75 mL/min/1.73m 2 . Clinical outcomes were hematoma expansion of ≥33% at 24 h, neurological deterioration within 72 h (GCS decrement ≥2 points or NIHSS increment ≥4 points), and favorable (modified Rankin Scale [mRS] ≤2) and unfavorable (mRS ≥5) outcomes at 3 months. Results: Of 188 patients, 35 (18 women) were allocated to Group 1, 58 (20) to Group 2, and 95 (33) to Group 3. Significant differences among 3 groups were found in age (73.1±13.6, 63.3±13.2, 63.8±9.8 yo; p <0.001) and initial systolic BP (208.9±18.1, 201.2±15.6, 200.2±14.8 mmHg; p=0.018). Initial hematoma volume (14.9±11.9, 15.5±14.9, 14.3±12.3 mL) and initial median NIHSS score (14, 11, 13) were similar among 3 groups. For outcomes, significant differences among 3 groups were found in favorable outcome (17.7%, 51.7%, 41.3%; p=0.004) and unfavorable outcome (22.9%, 10.3%, 5.3%; p=0.021), but not in hematoma expansion (17.1%, 10.3%, 22.1%) and neurological deterioration (11.4%, 8.6%, 7.4%). After adjustment with initial hematoma volume, initial systolic BP and initial NIHSS score, eGFR <60 ml/min/1.73m 2 was inversely associated with favorable outcome (OR 0.20, 95% CI 0.07-0.54) and positively associated with unfavorable outcome (4.27, 1.36-13.53). Conclusions: Although decreased eGFR on admission was not associated with initial hematoma volume or initial NIHSS score, it was associated with poor outcomes at 3 months of ICH onset.

Abstract TP331: Plasma IL-6 Levels are Independently Associated With Functional Outcome and Markers of Secondary Injury in Spontaneous Intracerebral Hemorrhage

Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Audrey C Leasure ◽  
Arthur F Steinschneider ◽  
Guido J Falcone ◽  
Emily J Gilmore ◽  
Lauren H Sansing ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Secondary Injury ◽  
Spontaneous Intracerebral Hemorrhage

scholarly journals Intracerebral Hemorrhage: A Brief Evidence-Based Review of Common Etiologies, Mechanisms of Secondary Injury, and Medical and Surgical Management

2019 ◽  
Vol 06 (02) ◽  
pp. 119-130
Author(s):  
Anand K. Sarma ◽  
Shivani Ghoshal ◽  
Spencer J. Craven ◽  
Aarti Sarwal
Keyword(s):  
Intracerebral Hemorrhage ◽  
Surgical Management ◽  
Surgical Care ◽  
Pressure Control ◽  
Treatment Modalities ◽  
Initial Contact ◽  
Secondary Injury ◽  
Golden Hour ◽  
Blood Aspiration ◽  
Perihematomal Edema

AbstractIntracerebral hemorrhage (ICH) accounts for only 10 to 15% of all strokes but remains a significant cause of morbidity and mortality. Despite lengthy stays in critical care units, only one-half of those experiencing an ICH survive after 30 days, and those who do are often left with considerable disability. Treatment has traditionally focused on minimizing the hemorrhage expansion and reducing clot volume through both medical and surgical means. Management of ICH is a complex and multidisciplinary process. This review will discuss a few common etiologies, explore the pathophysiology of secondary neuronal injury after ICH, review the basics of ICH imaging with computed tomography and magnetic resonance imaging, and highlight latest practices in medical and surgical management. Secondary injury mechanisms such as perihematomal edema and disordered cerebral autoregulation are discussed as potential targets for new treatment modalities. Emergent treatment in the “golden hour” after ictus provides a template of measures to adopt from initial contact with emergency medical services, to the emergency department, and thereafter, triage to the intensive care unit. Medical management including blood pressure control, hemostasis, and coagulopathy reversal are discussed and evidence from trials such as INTERACT 2, ATACH 2, and ANNEXA-4 are given a clinical context. Surgical management including intracranial pressure monitoring, surgical evacuation with open craniotomy, and minimally invasive approaches such as stereotactic-guided aspiration and thrombolysis, ultrasound-induced thrombolysis, image-guided stereotactic endoscopic aspiration, and stereotactic ICH underwater blood aspiration are enumerated. The outcomes and relevance of STICH, MISTIE, and CLEAR trials to present surgical care are elaborated. The review summarizes the current guidelines for the treatment of ICH and the latest literature in the field they are based upon. It aims to provide a concise article beneficial to the emergency physicians and neurointensivists/neuroanesthesiologists.

The Effect of Age on Characteristics and Mortality of Intracerebral Hemorrhage in the Oldest-Old

2016 ◽  
Vol 42 (5-6) ◽  
pp. 485-492 ◽  
Author(s):  
Paola Forti ◽  
Fabiola Maioli ◽  
Michele Domenico Spampinato ◽  
Carlotta Barbara ◽  
Valeria Nativio ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Intracerebral Hemorrhage ◽  
Ct Scan ◽  
Symptom Onset ◽  
Oldest Old ◽  
Hematoma Expansion ◽  
Elderly Subjects ◽  
Supporting Evidence ◽  
Hematoma Volume ◽  
Young Old

Background: Incidence of acute intracerebral hemorrhage (ICH) increases with age, but there is a lack of information about ICH characteristics in the oldest-old (age ≥85 years). In particular, there is a need for information about hematoma volume, which is included in most clinical scales for prediction of mortality in ICH patients. Many of these scales also assume that, independent of ICH characteristics, the oldest-old have a higher mortality than younger elderly patients (age 65-74 years). However, supporting evidence from cohort studies is limited. We investigated ICH characteristics of oldest-old subjects compared to young (<65 years), young-old (65-74 years) and old-old (75-84 years) subjects. We also investigated whether age is an independent mortality predictor in elderly (age ≥65 years) subjects with acute ICH. Methods: We retrospectively collected clinical and neuroimaging data of 383 subjects (age 34-104 years) with acute supratentorial primary ICH who were admitted to an Italian Stroke Unit (SU) between October 2007 and December 2014. Measured ICH characteristics included hematoma location, volume and intraventricular extension of hemorrhage on admission CT scan; admission Glasgow Coma Scale ≤8 and hematoma expansion (HE) measured on follow-up CT-scans obtained after 24 h. General linear models and logistic models were used to investigate the association of age with ICH characteristics. These models were adjusted for pre-admission characteristics, hematoma location and time from symptom onset to admission CT scan. Limited to elderly subjects, Cox models were used to investigate the association of age with in-SU and 1-year mortality: the model for in-SU mortality adjusted for pre-admission and ICH admission characteristics and the model for 1-year mortality additionally adjusted for functional status and disposition at SU discharge. Results: Independent of pre-admission characteristics, hematoma location and time from symptom onset to admission CT-scan, oldest-old subjects had the highest admission hematoma volume (p < 0.01). Age was unrelated to all other ICH characteristics including HE. In elderly patients, multivariable adjusted risk of in-SU and 1-year mortality did not vary across age categories. Conclusions: Oldest-old subjects with acute supratentorial ICH have higher admission hematoma volume than young and young-old subjects but do not differ for other ICH characteristics. When taking into account confounding from ICH characteristics, risk of in-SU and 1-year mortality in elderly subjects with acute supratentorial ICH does not differ across age categories. Our findings question use of age as an independent criterion for stratification of mortality risk in elderly subjects with acute ICH.

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