Intracerebral Hemorrhage Expansion in Late Presenters

BACKGROUND AND OBJECTIVES: The benefit of therapies targeting hematoma expansion (HE) in acute intracerebral hemorrhage (ICH) is highly time dependent and greatest within the first 2 hours after onset. We aimed to develop imaging-based "target expansion criteria" to identify late presenters (2-12 hours from onset/last seen well) who remain at high risk of HE. To achieve this goal, a practical risk score (target expansion score) was developed. METHODS: We conducted a multicenter, international, retrospective cohort study. To mirror a clinical trial population, we excluded patients with brainstem ICH, anticoagulation, and baseline ICH volume >100 mL. The primary outcome was HE (>33%/6 mL). The following imaging predictors of HE were analyzed: high ultra-early hematoma growth (uHG) (baseline volume/onset to imaging time >10 mL/h), hypodensities on noncontrast CT (NCCT), and spot sign on CT angiography (CTA). The study population was randomly divided into development and validation cohorts, and a weighted score was derived from estimates from multivariable logistic regression. RESULTS: Overall, 492 patients were included: 345 (70.1%) in the development and 147 (29.9%) in the validation cohort. A 4-point score was created, based on independent predictors of HE (high uHG: 1 point, NCCT hypodensities: 1 point, and CTA spot sign: 2 points). The score showed good discrimination in the development and validation cohorts (area under the curve [AUC] 0.77, 95% CI 0.71-0.83, and AUC 0.79, 95% CI 0.71-0.87, respectively). We observed a nonlinear increase in the frequency of HE and mean absolute hematoma growth with higher scores: 9.8% and 0.9 mL (score 0), 17.1% and 3.9 mL (score 1), 48.3% and 11.5 mL (score 2), 70.8% and 13.0 mL (score 3), and 87.5% and 26.9 mL (score 4). These findings were confirmed in the validation cohort. A dichotomized score greater than or equal to 2 predicted HE with 0.61 sensitivity and 0.85 specificity in the development cohort and 0.64 sensitivity with 0.84 specificity in the validation cohort. DISCUSSION: Imaging-based target expansion criteria, defined as a target expansion score ≥2, identified late-presenting patients with ICH at high risk of HE. These findings might inform future trials targeting HE and increase the pool of eligible patients.

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Journal
Neurology
Published
2026-10-15
DOI
https://doi.org/10.1212/wnl.0000000000218675
Primary Topic
Intracerebral and Subarachnoid Hemorrhage Research
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article
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article

Intracerebral Hemorrhage Expansion in Late Presenters

Ilaria Casetta, Umberto Pensato, Andrea Dell’Orco, Andrea Zini et al.
Neurology
Intracerebral and Subarachnoid Hemorrhage Research
article

Intracerebral Hemorrhage Expansion in Late Presenters

Ilaria Casetta, Umberto Pensato, Andrea Dell’Orco, Andrea Zini, Maurizio Paciaroni, Sebastiano Giacomozzi, Anna Maria Cavallini, Michele Romoli, Andrea Morotti, Giorgio Busto, Mariarosaria Valente, Michele Laudisi, Giovanni Merlino, Jawed Nawabi, Simona Sacco, Eugenio Magni, Matteo Paolucci, Enrico Fainardi, Stefano Forlivesi, Raffaele Ornello, Mauro Gentile, Alessandro Padovani, Federico Mazzacane, Qi Li, Emanuele Olivieri, Francesco Berinato, Giovanni Baronchelli
article en

Abstract

BACKGROUND AND OBJECTIVES: The benefit of therapies targeting hematoma expansion (HE) in acute intracerebral hemorrhage (ICH) is highly time dependent and greatest within the first 2 hours after onset. We aimed to develop imaging-based "target expansion criteria" to identify late presenters (2-12 hours from onset/last seen well) who remain at high risk of HE. To achieve this goal, a practical risk score (target expansion score) was developed. METHODS: We conducted a multicenter, international, retrospective cohort study. To mirror a clinical trial population, we excluded patients with brainstem ICH, anticoagulation, and baseline ICH volume >100 mL. The primary outcome was HE (>33%/6 mL). The following imaging predictors of HE were analyzed: high ultra-early hematoma growth (uHG) (baseline volume/onset to imaging time >10 mL/h), hypodensities on noncontrast CT (NCCT), and spot sign on CT angiography (CTA). The study population was randomly divided into development and validation cohorts, and a weighted score was derived from estimates from multivariable logistic regression. RESULTS: Overall, 492 patients were included: 345 (70.1%) in the development and 147 (29.9%) in the validation cohort. A 4-point score was created, based on independent predictors of HE (high uHG: 1 point, NCCT hypodensities: 1 point, and CTA spot sign: 2 points). The score showed good discrimination in the development and validation cohorts (area under the curve [AUC] 0.77, 95% CI 0.71-0.83, and AUC 0.79, 95% CI 0.71-0.87, respectively). We observed a nonlinear increase in the frequency of HE and mean absolute hematoma growth with higher scores: 9.8% and 0.9 mL (score 0), 17.1% and 3.9 mL (score 1), 48.3% and 11.5 mL (score 2), 70.8% and 13.0 mL (score 3), and 87.5% and 26.9 mL (score 4). These findings were confirmed in the validation cohort. A dichotomized score greater than or equal to 2 predicted HE with 0.61 sensitivity and 0.85 specificity in the development cohort and 0.64 sensitivity with 0.84 specificity in the validation cohort. DISCUSSION: Imaging-based target expansion criteria, defined as a target expansion score ≥2, identified late-presenting patients with ICH at high risk of HE. These findings might inform future trials targeting HE and increase the pool of eligible patients.

NeurologyVol. 107(9)
University of Udine (IT), Humanitas University (IT), Anhui Medical University (CN), University of Ferrara (IT), University of L'Aquila (IT), Humboldt-Universität zu Berlin (DE), Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Ospedale “M. Bufalini” di Cesena (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Istituto delle Scienze Neurologiche di Bologna (IT), IRCCS San Camillo Hospital (IT), Fondazione Poliambulanza Istituto Ospedaliero (IT), Second Affiliated Hospital of Anhui Medical University (CN), National Hospital for Neurology and Neurosurgery (GB), IRCCS Humanitas Research Hospital (IT), UCL Queen Square Institute of Neurology (GB), University of Florence (IT), University College London (GB), University of Brescia (IT)
Good health and well-being
Openalex Percentile: Top 14%
Intracerebral and Subarachnoid Hemorrhage Research
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