Association Between Hypodensities Detected by Computed Tomography and Hematoma Expansion in Patients With Intracerebral Hemorrhage.

IMPORTANCE Hematoma expansion is a potentially modifiable predictor of poor outcome following an acute intracerebral hemorrhage (ICH). The ability to identify patients with ICH who are likeliest to experience hematoma expansion and therefore likeliest to benefit from expansion-targeted treatments remains an unmet need. Hypodensities within an ICH detected by noncontrast computed tomography (NCCT) have been suggested as a predictor of hematoma expansion. OBJECTIVE To determine whether hypodense regions, irrespective of their specific patterns, are associated with hematoma expansion in patients with ICH. DESIGN, SETTING, AND PARTICIPANTS We analyzed a large cohort of 784 patients with ICH (the development cohort; 55.6% female), examined NCCT findings for any hypodensity, and replicated our findings on a different cohort of patients (the replication cohort; 52.7% female). Baseline and follow-up NCCT data from consecutive patients with ICH presenting to a tertiary care hospital between 1994 and 2015 were retrospectively analyzed. Data analyses were performed between December 2015 and January 2016. MAIN OUTCOMES AND MEASURES Hypodensities were analyzed by 2 independent blinded raters. The association between hypodensities and hematoma expansion (>6 cm3 or 33% of baseline volume) was determined by multivariable logistic regression after controlling for other variables associated with hematoma expansion in univariate analyses with P ≤ .10. RESULTS A total of 1029 patients were included in the analysis. In the development and replication cohorts, 222 of 784 patients (28.3%) and 99 of 245 patients (40.4%; 321 of 1029 patients [31.2%]), respectively, had NCCT scans that demonstrated hypodensities at baseline (κ = 0.87 for interrater reliability). In univariate analyses, hypodensities were associated with hematoma expansion (86 of 163 patients with hematoma expansion had hypodensities [52.8%], whereas 136 of 621 patients without hematoma expansion had hypodensities [21.9%]; P < .001). The association between hypodensities and hematoma expansion remained significant (odds ratio, 3.42 [95% CI, 2.21-5.31]; P < .001) in a multivariable model; other independent predictors of hematoma expansion were a CT angiography spot sign, a shorter time to CT, warfarin use, and older age. The independent predictive value of hypodensities was again demonstrated in the replication cohort (odds ratio, 4.37 [95% CI, 2.05-9.62]; P < .001). CONCLUSION AND RELEVANCE Hypodensities within an acute ICH detected on an NCCT scan may predict hematoma expansion, independent of other clinical and imaging predictors. This novel marker may help clarify the mechanism of hematoma expansion and serve as a useful addition to clinical algorithms for determining the risk of and treatment stratification for hematoma expansion.

[1]  Dar Dowlatshahi,et al.  Swirls and spots: relationship between qualitative and quantitative hematoma heterogeneity, hematoma expansion, and the spot sign , 2015 .

[2]  A. Laupacis,et al.  Validation of the 9-Point and 24-Point Hematoma Expansion Prediction Scores and Derivation of the PREDICT A/B Scores , 2015, Stroke.

[3]  A. Demchuk,et al.  Intracerebral Hematoma Morphologic Appearance on Noncontrast Computed Tomography Predicts Significant Hematoma Expansion , 2015, Stroke.

[4]  A. Flint,et al.  Prediction of Intracerebral Haemorrhage Expansion with Clinical, Laboratory, Pharmacologic, and Noncontrast Radiographic Variables , 2015, International journal of stroke : official journal of the International Stroke Society.

[5]  C. J. Ortiz,et al.  Rate of Contrast Extravasation on Computed Tomographic Angiography Predicts Hematoma Expansion and Mortality in Primary Intracerebral Hemorrhage , 2015, Stroke.

[6]  Qi Li,et al.  Blend Sign on Computed Tomography: Novel and Reliable Predictor for Early Hematoma Growth in Patients With Intracerebral Hemorrhage , 2015, Stroke.

[7]  E. Gökçe,et al.  Evaluation of Oral Anticoagulant-Associated Intracranial Parenchymal Hematomas Using CT Findings , 2015, Clinical Neuroradiology.

[8]  M. Selim,et al.  The HEP Score: A Nomogram-Derived Hematoma Expansion Prediction Scale , 2015, Neurocritical Care.

[9]  Soojin Park,et al.  Intraventricular hemorrhage expansion in patients with spontaneous intracerebral hemorrhage , 2015, Neurology.

[10]  Hui ZHANG,et al.  Kappa coefficient: a popular measure of rater agreement , 2015, Shanghai archives of psychiatry.

[11]  M. Woodward,et al.  Clinical Prediction Algorithm (BRAIN) to Determine Risk of Hematoma Growth in Acute Intracerebral Hemorrhage , 2015, Stroke.

[12]  D. Krieger,et al.  European Stroke Organisation (ESO) Guidelines for the Management of Spontaneous Intracerebral Hemorrhage , 2014, International journal of stroke : official journal of the International Stroke Society.

[13]  A. van der Zwan,et al.  CT angiography spot sign in intracerebral hemorrhage predicts active bleeding during surgery , 2014, Neurology.

[14]  D. Hanley,et al.  Interpretation and Implementation of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT II). , 2014, Journal of vascular and interventional neurology.

[15]  Eric E. Smith,et al.  Anatomic Pattern of Intracerebral Hemorrhage Expansion: Relation to CT Angiography Spot Sign and Hematoma Center , 2014, Stroke.

[16]  S. Greenberg,et al.  Predicting hematoma expansion after primary intracerebral hemorrhage. , 2014, JAMA neurology.

[17]  A. Demchuk,et al.  Evolution of Computed Tomography Angiography Spot Sign Is Consistent With a Site of Active Hemorrhage in Acute Intracerebral Hemorrhage , 2014, Stroke.

[18]  Theresa M. Beckie,et al.  American Heart Association Council on Cardiovascular and Stroke Nursing. , 2013 .

[19]  M. Woodward,et al.  Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. , 2013, The New England journal of medicine.

[20]  B. Tress,et al.  Quantitative CT Densitometry for Predicting Intracerebral Hemorrhage Growth , 2013, American Journal of Neuroradiology.

[21]  P. Böelle,et al.  Prediction of evolution toward brain death upon admission to ICU in comatose patients with spontaneous intracerebral hemorrhage using simple signs , 2013, Transplant international : official journal of the European Society for Organ Transplantation.

[22]  S. Greenberg,et al.  Hematoma Expansion following Acute Intracerebral Hemorrhage , 2013, Cerebrovascular Diseases.

[23]  J. Rosand,et al.  SCORE-IT: the Spot Sign score in restricting ICH growth─an Atach-II ancillary study. , 2012, Journal of vascular and interventional neurology.

[24]  Matthew P. Frosch,et al.  Modeling Intracerebral Hemorrhage Growth and Response to Anticoagulation , 2012, PloS one.

[25]  Eufrozina Selariu,et al.  Swirl sign in intracerebral haemorrhage: definition, prevalence, reliability and prognostic value , 2012, BMC Neurology.

[26]  A. Demchuk,et al.  Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study , 2012, The Lancet Neurology.

[27]  Bijoy K Menon,et al.  Computed Tomography Angiography in the Assessment of Patients With Stroke/TIA , 2011, The Neurohospitalist.

[28]  Y. Palesch,et al.  Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II: Design, Methods, and Rationale , 2011, Neurocritical care.

[29]  Eric E. Smith,et al.  Defining hematoma expansion in intracerebral hemorrhage , 2011, Neurology.

[30]  C. Anderson,et al.  Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association , 2010, Stroke.

[31]  J. Goldstein,et al.  Effect of systolic blood pressure reduction on hematoma expansion, perihematomal edema, and 3-month outcome among patients with intracerebral hemorrhage: results from the antihypertensive treatment of acute cerebral hemorrhage study. , 2010, Archives of neurology.

[32]  C. Anderson,et al.  The Second (Main) Phase of an Open, Randomised, Multicentre Study to Investigate the Effectiveness of an Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (Interact2) , 2010, International journal of stroke : official journal of the International Stroke Society.

[33]  Ale Algra,et al.  Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis , 2010, The Lancet Neurology.

[34]  A. Qureshi Antihypertensive treatment of acute cerebral hemorrhage* , 2010, Critical care medicine.

[35]  P. Schaefer,et al.  Systematic Characterization of the Computed Tomography Angiography Spot Sign in Primary Intracerebral Hemorrhage Identifies Patients at Highest Risk for Hematoma Expansion: The Spot Sign Score , 2009, Stroke.

[36]  S. Mayer,et al.  Density and Shape as CT Predictors of Intracerebral Hemorrhage Growth , 2009, Stroke.

[37]  S. Mayer,et al.  Can a Subset of Intracerebral Hemorrhage Patients Benefit From Hemostatic Therapy With Recombinant Activated Factor VII? , 2009, Stroke.

[38]  S. Mayer,et al.  Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. , 2008, The New England journal of medicine.

[39]  C. Anderson,et al.  Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial , 2008, The Lancet Neurology.

[40]  M. Wintermark,et al.  Contrast Extravasation on CT Predicts Mortality in Primary Intracerebral Hemorrhage , 2008, American Journal of Neuroradiology.

[41]  S. Pocock,et al.  The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. , 2007, Bulletin of the World Health Organization.

[42]  D. Gladstone,et al.  CT Angiography “Spot Sign” Predicts Hematoma Expansion in Acute Intracerebral Hemorrhage , 2007, Stroke.

[43]  Eric E. Smith,et al.  Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage , 2007, Neurology.

[44]  J. Broderick,et al.  Asymptomatic sinovenous thrombosis in a healthy neonate , 2006, Neurology.

[45]  S. Mayer,et al.  Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage , 2006, Neurology.

[46]  Pamela J. McCabe,et al.  American Heart Association Council on cardiovascular nursing. , 2004 .

[47]  C. Fisher,et al.  Hypertensive Cerebral Hemorrhage. Demonstration of the Source of Bleeding , 2003, Journal of neuropathology and experimental neurology.

[48]  N. Al-Nakshabandi,et al.  The swirl sign. , 2001, Radiology.

[49]  A. Kleindienst,et al.  Spontaneous intracerebral hemorrhage , 1997 .

[50]  J. Broderick,et al.  Volume of Intracerebral Hemorrhage: A Powerful and Easy‐to‐Use Predictor of 30‐Day Mortality , 1993, Stroke.

[51]  C. Fisher,et al.  PATHOLOGICAL OBSERVATIONS IN HYPERTENSIVE CEREBRAL HEMORRHAGE , 1971, Journal of neuropathology and experimental neurology.

[52]  Fisher Cm Pathological observations in hypertensive cerebral hemorrhage. , 1971 .

[53]  C. Anderson,et al.  Pressure Lowering in Patients with Acute Intracerebral Hemorrhage , 2013 .