Article Commentary: “Association of Biomarkers With Intracerebral Hematoma Expansion and Arterial Thromboembolic Events in Patients With Acute Intracranial Hemorrhage”

 

Associations DO NOTHING FOR RECOVERY! Because you don't have recovery protocols mapped to the problems found. Can't anyone in stroke think at all?

Oops, I'm not playing by the polite rules of Dale Carnegie,  'How to Win Friends and Influence People'. 

Telling stroke medical persons they know nothing about stroke is a no-no even if it is true. 

Politeness will never solve anything in stroke. Yes, I'm a bomb thrower and proud of it. Someday a stroke 'leader' will try to ream me out for making them look bad by being truthful, I look forward to that day.

Send me personal hate mail on this: oc1dean@gmail.com. I'll print your complete statement with your name(If you can't stand by your name don't bother replying anonymously) and my response in my blog. Or are you afraid to engage with my stroke-addled mind? No excuses are allowed! You're medically trained; it should be simple to precisely state EXACTLY WHY you aren't working on 100% recovery protocols with NO EXCUSES!

Article Commentary: “Association of Biomarkers With Intracerebral Hematoma Expansion and Arterial Thromboembolic Events in Patients With Acute Intracranial Hemorrhage”

• Shravan Sivakumar, MD, @sshravanMD

Eikelboom JW, Sharma M, Xu L, Bamberg K, Beyer-Westendorf J, Falkenberg C, Ladenvall P, Narayan R, Penland RC, Verhamme P, Shoamanesh A. Association of Biomarkers With Intracerebral Hematoma Expansion and Arterial Thromboembolic Events in Patients With Acute Intracranial Hemorrhage: The ANNEXA-I Biomarker Substudy. Stroke. 2025.

Despite advances in acute hemorrhagic stroke care, hematoma expansion (HE) remains a major contributor to early neurological deterioration and poor outcomes in patients with intracerebral hemorrhage (ICH) associated with the use of anti-Xa inhibitors. The ANNEXA-I trial, initially aimed at assessing andexanet alfa for reversing factor Xa inhibitor–associated bleeding, provided a valuable platform to explore the underlying pathophysiological mechanisms — especially those driving hematoma expansion and thromboembolic events, which remain poorly understood. In this biomarker substudy, researchers explored the association between circulating biomarkers and both hematoma expansion and arterial thromboembolic events, aiming to provide additional insights into the mechanism of action of andexanet alfa.

Patients with ICH during treatment with a Factor Xa inhibitor were eligible for inclusion in the original ANNEXA-I trial if they underwent baseline brain imaging within 12 hours of symptom onset and had a hematoma volume of ≤60 mL with HE defined as increase in volume of ≥12.5 mL or ≥35% within 12 hours. The authors further modified criteria to include hematoma volume of 0.5 to 60 mL and with a maximum National Institutes of Health Stroke Scale score of 35 who underwent brain imaging within 6 hours of symptom onset. Hemorrhages needed to be confirmed on neuroimaging within 2 hours before randomization, and the last dose of Factor Xa inhibitor had to be taken within 15 hours of randomization. Patients with GCS <7, plan for surgery <12 hours and history of thromboembolic events in prior 2 weeks were excluded. Arterial thromboembolic events included ischemic stroke, myocardial infarction and systemic embolism occurring within 30 days. Analysis was restricted to patients taking apixaban or rivaroxaban, and to availability of anti-Factor Xa activity or endogenous thrombin potential (ETP) data.

438 subjects with anti-Xa activity and 328 with ETP levels met criteria. In patients with apixaban- or rivaroxaban-associated ICH, the mean age was 79.1 years. Baseline characteristics were similar in the anti-Factor Xa and ETP populations and were well balanced by randomized treatment group. The results showed large reduction between baseline and 1 hour in anti-Factor Xa activity (median difference at 1 hour being andexanet 98.3 ng/mL and for usual care 10.9 ng/mL (between group difference, P<0.001) and a large increase in ETP (andexanet 753.1 nmol/L-min and for usual care 126.6 nmol/L-min (between group difference, P<0.001), but by 12 hours, the contrast between randomized treatment in ETP was no longer evident. Reduction in anti-Factor Xa activity between baseline and 1 hour independently predicted reduced risk of hematoma expansion (per 100 ng/mL: OR, 0.69 [95% CI, 0.53–0.92]; P=0.010). While increase in ETP between baseline and 1 hour independently predicted reduced risk of hematoma expansion (per 100 nmol/L-min: OR, 0.94 [95% CI, 0.90–0.99]; P=0.019). After adjustment for age, baseline biomarker level, prior MI, and high-dose andexanet eligibility, change in ETP from baseline to 1 hour independently predicted arterial thromboembolic events, whereas neither change in anti-Xa from baseline to 1 hour nor change in ETP from baseline to 12 hours was significantly associated with arterial thromboembolic events during 30 days of follow-up.

These results suggest an immediate treatment effect of anti-Xa agents that is limited to the first few hours of treatment. The authors further demonstrated that that change between baseline and 1 hour in ETP was independently associated with increased arterial thromboembolic events. Given most of the hematoma expansion is expected to occur within the first few hours of onset of symptoms, this is further supported by the biomarker findings of enhanced benefit with early and specific anticoagulant reversal to prevent hematoma expansion. Prothrombin complex concentrates that can enhance hemostatic by increasing ETP are recommended in the absence of specific reversal agents, and given their use in usual care, the finding of only a minimal increase in ETP at 1 hour in the usual care arm and lack of association between the change between baseline and 12 hours in ETP and risk of hematoma expansion further supports use of specific anti-Xa agents. Furthermore, biomarker analyses from the ANNEXA-4 cohort study have demonstrated that andexanet is associated with reduced tissue factor pathway inhibitor activity, which may contribute to the early increase in ETP, which is a well-documented risk factor for thromboembolism which is supported by the current study findings.

Strengths of the study include the analysis performed as part of a randomized control trial allowing for causal association between biomarker change and hematoma expansion. Their limitations include lack of statistical power as reflected by the wide CIs and that not all patients in the usual care arm received a prothrombin complex concentrate. However, changes in anti-FXa and ETP were similar in sensitivity analyses that excluded patients who did not receive a prothrombin complex concentrate. The next step would include integrating biomarker data with imaging and clinical variables, alongside mechanistic studies to uncover causal pathways, which could pave the way for biomarker-guided therapeutic trials. Picture this: A patient with ICH arrives in the ED, gets a CT and a rapid biomarker panel, and within minutes, a combined score predicts high risk for hematoma expansion. The team immediately starts hemostatic therapy and tailors anticoagulation timing, preventing both expansion and clotting complications. This is the promise of integrating biomarkers, imaging, and clinical data — turning ICH care into precise, proactive treatment.

Associations of Soluble Inflammatory and Endothelial Activation Biomarkers with Cognitive Function Over Three Years After Ischemic Stroke—PROSCIS-B

 Associations DO NOTHING FOR RECOVERY! Because you don't have recovery protocols mapped to the problems found. Can't anyone in stroke think at all?

Associations of Soluble Inflammatory and Endothelial Activation Biomarkers with Cognitive Function Over Three Years After Ischemic Stroke—PROSCIS-B

October 2025 Translational Stroke Research DOI: 10.1007/s12975-025-01388-4 

Authors:Naomi K. Giesers Viktoria SchaeffKaren Gertz Matthias Endres Show all 5 authors 

Abstract and Figures

Vascular inflammation is involved in the pathophysiology of post-stroke cognitive impairment. We aimed to assess whether blood-based biomarkers of inflammation and endothelial dysfunction, such as interleukin 6 (IL-6), vascular cell adhesion molecule (VCAM-1), and tumor necrosis factor-alpha (TNF-α), are associated with cognitive function over time in a prospective cohort of first-ever ischemic stroke patients. Data were obtained from the Prospective Cohort with Incident Stroke Berlin (NCT01363856). Cognitive function was assessed with the Telephone Interview for Cognitive Status–modified (TICS-m) at 1 to 3 years of follow-up. Associations of baseline levels of IL-6, VCAM-1, and TNF-α with cognitive function over time were estimated using a linear mixed model adjusted for demographics, education, vascular risk factors, stroke severity, ischemic stroke subtype, and severity of white matter hyperintensity. We included 570 patients with mild-to-moderate ischemic stroke and baseline data on biomarker levels. The mean age was 67 (± 12 SD), 38.6% were female, and the median National Institutes of Health Stroke Scale (NIHSS) was 2 (IQR 1–4). Frequency of cognitive impairment defined as TICS-m score ≤ 31 was 21.9% at year one, 15.4% at year two, and 11.6% at year three. Higher log-transformed levels of IL-6 and VCAM-1 were associated with lower TICS-m scores over time in the adjusted linear mixed model including white matter hyperintensity burden (IL-6: β = −2.0, 95% CI −3.3 to −0.7, p = 0.003; VCAM-1: β = −4.1, 95% CI −7.3 to −1.0, p = 0.01). In patients with mild-to-moderate first-ever ischemic stroke, higher baseline levels of IL-6 and VCAM-1 were associated with lower Telephone Interview for Cognitive Status–modified during 3 years of follow-up.ClinicalTrials.gov Identifier: NCT01363856

Hematoma Expansion in Intracerebral Hemorrhage: An Update on Prediction and Treatment

With no treatment you don't want your doctor telling you you have this.

Hematoma Expansion in Intracerebral Hemorrhage: An Update on Prediction and Treatment

Zhifang Li^†, Mingfeng You^†, Chunnan Long, Rentang Bi, Haoqiang Xu, Quanwei He^* and Bo Hu^*

• Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Intracerebral hemorrhage (ICH) is the most lethal type of stroke, but there is no specific treatment. After years of effort, neurologists have found that hematoma expansion (HE) is a vital predictor of poor prognosis in ICH patients, with a not uncommon incidence ranging widely from 13 to 38%. Herein, the progress of studies on HE after ICH in recent years is updated, and the topics of definition, prevalence, risk factors, prediction score models, mechanisms, treatment, and prospects of HE are covered in this review. The risk factors and prediction score models, including clinical, imaging, and laboratory characteristics, are elaborated in detail, but limited by sensitivity, specificity, and inconvenience to clinical practice. The management of HE is also discussed from bench work to bed practice. However, the upmost problem at present is that there is no treatment for HE proven to definitely improve clinical outcomes. Further studies are needed to identify more accurate predictors and effective treatment to reduce HE.

Introduction

Intracerebral hemorrhage (ICH) accounts for about 10–20% of all types of stroke (1, 2) and almost 40% of patients who suffer from ICH will die within the first month, while only 12–39% of survivors achieve long-term functional independence (2), which makes it a severe public health problem. Unfortunately, after decades of effort there is no specific treatment yet for ICH, but recently HE has been found to be a modifiable and independent predictor of clinical neurological deterioration in intracerebral hemorrhagic patients. HE prevention has been accepted as one of the most promising therapeutic strategies in ICH treatment (3). Although numerous efforts have been made to select ICH patients at high risk of developing HE, no uniform prediction score model can be concluded from current studies, which therefore impedes the early detection and subsequent active intervention by clinicians. Moreover, once HE occurs in ICH patients, the treatment is extremely limited and the functional prognosis of those patients is unsatisfactory. Thus, it remains a priority to prospectively detect high-risk HE patients as well as administer more active prevention treatment.

This review refers to the definition, prevalence, risk factors/predictors, prediction score models, mechanisms, and treatment progress of HE. In detail, the predictors of HE are summarized to update the view on the prediction, and suggestions are also provided to establish an accurate and easy-to-use prediction score model. Furthermore, we discuss current HE treatment strategies from the viewpoint of clinicians and also point out future directions for the discovery of more effective therapies.

Definition

HE is defined based on visually discernible hematoma volume changes between the baseline and follow-up CT, and the evaluation of hematoma volume growth is diverse across HE related studies. As one of the earliest researchers of HE, Fujii et al. defined it as absolute hematoma volume growth of more than 20 ml or relative hematoma volume growth of more than 50% (4). Later, Brott et al. used relative hematoma volume growth of more than 33% which can be discovered by CT to define HE (5). Using ROC curve analysis, Kazui et al. applied cut point of hematoma volume increase of 12.5 ml or 40% (6). Some recently published large clinical trials also used relative hematoma growth of more than 33% (7), or combined hematoma growth of 6 mL absolute increase and 33% relative increase (8, 9) to define it. Based on CT angiography contrast extravasation, a 6 mL absolute increase of hematoma volume was proposed in the studies of Thompson et al. and Delgado et al. (10, 11). Of all the different definitions, Dowlatshahi et al. found that absolute growth definitions were more preferable to predict the outcome of ICH (12). Considering that intraventricular hemorrhage (IVH) is a predictor of poor prognosis in ICH, the presence of IVH may also be an indicator of HE. Specifically, Vignan et al. found that addition of IVH into the HE definition improves the prediction of 90 days outcome in ICH patients (13).

A uniform definition of HE considering convenience of measurement and effectiveness in predicting outcome is needed for further study.

Prevalence

Hemostasis was once thought to be over within min after ICH occurrence, but recently HE has been found to be a common phenomenon of ICH with advanced radiology (5). The reported incidence of HE within 6 h from ICH symptom onset ranges widely from 13 to 38% (5, 6, 12), which may be largely explained by different definitions of HE and different time interval between hematoma measurement in the different studies. In the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2), the incidence of HE was 33.1% in the control group (14), while it was 25.3% in Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH2) (15). Notably, the incidence of HE is highest at the hyperacute stage (within 6 h after symptom onset) and HE usually occurs at the internal capsule, thalamus, and brainstem. Thus, it is necessary to maintain hematoma surveillance, especially at the hyperacute stage of ICH.

Risk Factors/Predictors

ICH patients with high risk factors of developing HE are predisposed to experience clinical deterioration and closer neurological monitoring is required, while the absence of the predictors may identify ICH patients with low risk of developing HE. Thus, HE predictors have a vital role to play in selecting high-risk ICH patients and subsequently facilitating the individualized treatment. Based on clinical, imaging, and laboratory characteristics, a series of risk factors/predictors of HE have been identified.

Clinical Predictors

Systolic blood pressure (SBP) is positively related to the initial hematoma volume in ICH patients (16) and the risk of HE is much higher in patients with post-admission SBP over 160 mmHg (P = 0.0074) (17, 18), which may be partly explained by the continuous rupturing and hemorrhaging of small vessels, thus making early blood pressure a potential treatment target. Although baseline blood pressure variability (BPV) is not associated with HE (19), post-admission BPV independently predicts HE as well as poor functional outcomes (20). High mean arterial pressure (MAP) is positively related to HE as well (19).

Medication with antiplatelet or anticoagulant drugs also increases the risk of HE. In high-income countries, more than a quarter of patients with ICH are on prior antiplatelet therapy (APT) (21). An observational study by Toyoda et al. showed that APT was an independent predictor of HE (22), while in the Cerebral Hemorrhage and NXY-059 treatment trial, antiplatelet drug use at ICH onset was not associated with HE (23). On account of their methodological difference, recently this controversy has been laid to rest by a meta-analysis which supports prior APT as a predictor of HE (24). For those with prior medication with anticoagulants, prior oral anticoagulation (OAC) use is not only an independent predictor of larger initial hematoma volume (25) but also increases the risk of HE 6.2 times (26). In contrast to OAC, the incidence of ICH in Non-Vitamin K oral anticoagulants (NOACs) patients is dramatically decreased (27). NOACs-ICH has a lower risk of developing HE and is associated with smaller baseline hematoma volume (28) and better functional outcomes (29–31).

Higher baseline NIHSS or GCS scores (32–34), elevated body temperature (35), baseline weight (36), and history of cerebral infarction (37) or alcohol abuse (38) may increase the risk of HE, as found by some observational studies, and further randomized trials are needed to determine their relevance. In a recent retrospective cohort study of ICH patients with liver fibrosis, fibrosis-4 score and Aspartate Aminotransferase-Platelet Ratio Index were associated with HE (39).

Gender (40) and age (41) are also associated with HE, as men and older subjects (age ≥85 years) are more likely to present HE than women and younger subjects (40, 41).

It is interesting to note that ICH occurring during the daytime tends to be more likely to present HE than when occurring at night (OR, 3.53) (42). In addition, HE is mostly found in early initial CT scan (≤3 h of onset) (5, 6, 43), so time interval from ICH onset to initial CT scan should be considered (Abovementioned clinical predictors are summarized in Table 1).

 

Normative NeuroFlexor data for detection of spasticity after stroke: a cross-sectional study

Not sure what good detection of early spasticity is since there is NO treatment or cure for it.
http://jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-016-0133-x

• Gaia Valentina PennatiEmail author,
• Jeanette Plantin,
• Jörgen Borg and
• Påvel G Lindberg

Journal of NeuroEngineering and Rehabilitation201613:30

DOI: 10.1186/s12984-016-0133-x

©  Pennati et al. 2016

Received: 19 October 2015

Accepted: 2 March 2016

Published: 18 March 2016

Abstract

Background and Objective

The NeuroFlexor is a novel instrument for quantification of neural, viscous and elastic components of passive movement resistance. The aim of this study was to provide normative data and cut-off values from healthy subjects and to use these to explore signs of spasticity at the wrist and fingers in patients recovering from stroke.

Methods

107 healthy subjects (age range 28–68 years; 51 % females) and 39 stroke patients (age range 33–69 years; 33 % females), 2–4 weeks after stroke, were assessed with the NeuroFlexor. Cut-off values based on mean + 3SD of the reference data were calculated. In patients, the modified Ashworth scale (MAS) was also applied.

Results

In healthy subjects, neural component was 0.8 ± 0.9 N (mean ± SD), elastic component was 2.7 ± 1.1 N, viscous component was 0.3 ± 0.3 N and resting tension was 5.9 ± 1 N. Age only correlated with elastic component (r = −0.3, p = 0.01). Elasticity and resting tension were higher in males compared to females (p = 0.001) and both correlated positively with height (p  = 0.01). Values above healthy population cut-off were observed in 16 patients (41 %) for neural component, in 2 (5 %) for elastic component and in 23 (59 %) for viscous component. Neural component above cut-off did not correspond well to MAS ratings. Ten patients with MAS = 0 had neural component values above cut-off and five patients with MAS ≥ 1 had neural component within normal range.

Conclusion

This study provides NeuroFlexor cut-off values that are useful for detection of spasticity in the early phase after stroke.