Analysis of the diagnostic informativity of non-contrast computed tomography markers of intracerebral hemorrhage expansion in assessment of the individual risk of early neurological deterioration in patients with hemorrhagic hemispheric stroke




cerebral hemorrhage, x-ray tomography, prognosis


The aim of the study was to evaluate the diagnostic informativity of non-contrast computed tomography (NCCT) markers of intracerebral hemorrhage (ICH) expansion in assessment of the individual risk of early neurological deterioration (END) in patients with hemorrhagic hemispheric stroke (HHS).

Materials and methods. A prospective, cohort study was conducted involving 333 patients in the acute period of hypertensive spontaneous supratentorial ICH on the background of conservative therapy. The level of neurological deficit was assessed using the Full Outline of Unresponsiveness (FOUR) coma scale and the National Institute of Health Stroke Scale (NIHSS). The computed tomography of the brain was used to verify the ICH volume, the midline shift (MS), the secondary intraventricular hemorrhage volume (IVHV) and NCCT markers of intracerebral hemorrhage expansion. As a combined clinical endpoint, END was considered (decrease of the FOUR scale score ≥2 or/and increase of the NIHSS score ≥4 or/and lethal outcome within 48 hours of hospitalization).

Results. Early neurological deterioration was registered in 112 patients. On the basis of a comparative analysis, it was established that the specific weight of END was significantly higher in subcohorts of patients with individual NCCT markers of intracerebral hemorrhage expansion, than it was in subcohorts of patients without corresponding NCCT signs (p ˂ 0.0001). It was established that the following NCCT markers of ICH expansion are the most sensitive predictors of END: hypodensity, swirl sign and irregular shape (sensitivity >90.0 %). The most specific NCCT markers were island sign, black hole sign, blend sign, satellite sign and heterogeneous density (specificity >87.0 %). In accordance with the multiple logistic regression analysis, hypodensity (OR (95 % CI) = 13.56 (4.54–40.49), p < 0.0001) and island sign (OR (95 % CI) = 5.94 (2.05–17.16), p = 0.0010) are independently associated with the risk of END. A highly sensitive multi-prediction logistic regression model was elaborated in order to predict END in patients with HHS which takes into account the most informative NCCT markers of ICH expansion (hypodensity, island sign) and quantitative neuroimaging indicators (MS, IVHV) (AUC ± SE (95 % CI) = 0.92 ± 0.02 (0.89–0.95), р ˂ 0.0001).

Conclusions. Non-contrast computed tomography markers of ICH expansion are associated with increased risk of END in patients with HHS. Hypodensity and island sign are independent predictors of END. The integration of NCCT markers of ICH expansion with quantitative neuroimaging indicators (MS, IVHV) in the structure of the multi-prediction logistic regression model allows to assess the individual risk of END with an accuracy of >85.0 %.

Author Biography

A. A. Kuznietsov, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, Associate Professor of the Department of Neurology


Magid-Bernstein, J., Girard, R., Polster, S., Srinath, A., Romanos, S., Awad, I. A., & Sansing, L. H. (2022). Cerebral Hemorrhage: Pathophysiology, Treatment, and Future Directions. Circulation research, 130(8), 1204-1229.

Pinho, J., Costa, A. S., Araújo, J. M., Amorim, J. M., & Ferreira, C. (2019). Intracerebral hemorrhage outcome: A comprehensive update. Journal of the neurological sciences, 398, 54-66.

Puy, L., Parry-Jones, A. R., Sandset, E. C., Dowlatshahi, D., Ziai, W., & Cordonnier, C. (2023). Intracerebral haemorrhage. Nature reviews. Disease primers, 9(1), 14.

Koziolkin, О. A., & Kuznietsov, A. A. (2021). Prognostic value of serum S100B concentration in patients with acute spontaneous supratentorial intracerebral hemorrhage. Pathologia, 18(1), 19-25.

Akpinar, E., Gürbüz, M. S., & Berkman, M. Z. (2019). Factors Affecting Prognosis in Patients With Spontaneous Supratentorial Intracerebral Hemorrhage Under Medical and Surgical Treatment. The Journal of craniofacial surgery, 30(7), e667-e671.

Law, Z. K., Dineen, R., England, T. J., Cala, L., Mistri, A. K., Appleton, J. P., Ozturk, S., Bereczki, D., Ciccone, A., Bath, P. M., Sprigg, N., & TICH-2 investigators (2021). Predictors and Outcomes of Neurological Deterioration in Intracerebral Hemorrhage: Results from the TICH-2 Randomized Controlled Trial. Translational stroke research, 12(2), 275-283.

Flaherty, K., Bath, P. M., Dineen, R., Law, Z., Scutt, P., Pocock, S., Sprigg, N., & TICH-2 investigators (2017). Statistical analysis plan for the 'Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage' (TICH-2) trial. Trials, 18(1), 607.

Lord, A. S., Gilmore, E., Choi, H. A., Mayer, S. A., & VISTA-ICH Collaboration (2015). Time course and predictors of neurological deterioration after intracerebral hemorrhage. Stroke, 46(3), 647-652.

Wang, G., & Zhang, J. (2017). Hematoma Expansion: Clinical and Molecular Predictors and Corresponding Pharmacological Treatment. Current drug targets, 18(12), 1367-1376.

Yu, Z., Zheng, J., Xu, Z., Li, M., Wang, X., Lin, S., Li, H., & You, C. (2017). Accuracy of Shape Irregularity and Density Heterogeneity on Noncontrast Computed Tomography for Predicting Hematoma Expansion in Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis. World neurosurgery, 108, 347-355.

Morotti, A., Boulouis, G., Dowlatshahi, D., Li, Q., Barras, C. D., Delcourt, C., Yu, Z., Zheng, J., Zhou, Z., Aviv, R. I., Shoamanesh, A., Sporns, P. B., Rosand, J., Greenberg, S. M., Al-Shahi Salman, R., Qureshi, A. I., Demchuk, A. M., Anderson, C. S., Goldstein, J. N., Charidimou, A., … International NCCT ICH Study Group (2019). Standards for Detecting, Interpreting, and Reporting Noncontrast Computed Tomographic Markers of Intracerebral Hemorrhage Expansion. Annals of neurology, 86(4), 480-492.

Schlunk, F., & Greenberg, S. M. (2015). The Pathophysiology of Intracerebral Hemorrhage Formation and Expansion. Translational stroke research, 6(4), 257-263.

Boulouis, G., Dumas, A., Betensky, R. A., Brouwers, H. B., Fotiadis, P., Vashkevich, A., Ayres, A., Schwab, K., Romero, J. M., Smith, E. E., Viswanathan, A., Goldstein, J. N., Rosand, J., Gurol, M. E., & Greenberg, S. M. (2014). Anatomic pattern of intracerebral hemorrhage expansion: relation to CT angiography spot sign and hematoma center. Stroke, 45(4), 1154-1156.

Yu, Z., Zheng, J., Ma, L., Guo, R., You, C., & Li, H. (2019). Predictive Validity of Hypodensities on Noncontrast Computed Tomography for Hematoma Growth in Intracerebral Hemorrhage: a Meta-Analysis. World neurosurgery, 123, e639-e645.

Zhang, D., Chen, J., Xue, Q., Du, B., Li, Y., Chen, T., Jiang, Y., Hou, L., Dong, Y., & Wang, J. (2018). Heterogeneity Signs on Noncontrast Computed Tomography Predict Hematoma Expansion after Intracerebral Hemorrhage: A Meta-Analysis. BioMed research international, 2018, 6038193.

Boulouis, G., Morotti, A., Brouwers, H. B., Charidimou, A., Jessel, M. J., Auriel, E., Pontes-Neto, O., Ayres, A., Vashkevich, A., Schwab, K. M., Rosand, J., Viswanathan, A., Gurol, M. E., Greenberg, S. M., & Goldstein, J. N. (2016). Association Between Hypodensities Detected by Computed Tomography and Hematoma Expansion in Patients With Intracerebral Hemorrhage. JAMA neurology, 73(8), 961-968.

Morotti, A., Boulouis, G., Romero, J. M., Brouwers, H. B., Jessel, M. J., Vashkevich, A., Schwab, K., Afzal, M. R., Cassarly, C., Greenberg, S. M., Martin, R. H., Qureshi, A. I., Rosand, J., Goldstein, J. N., & ATACH-II and NETT investigators (2017). Blood pressure reduction and noncontrast CT markers of intracerebral hemorrhage expansion. Neurology, 89(6), 548-554.

Delcourt, C., Zhang, S., Arima, H., Sato, S., Al-Shahi Salman, R., Wang, X., Davies, L., Stapf, C., Robinson, T., Lavados, P. M., Chalmers, J., Heeley, E., Liu, M., Lindley, R. I., Anderson, C. S., & INTERACT2 investigators (2016). Significance of Hematoma Shape and Density in Intracerebral Hemorrhage: The Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trial Study. Stroke, 47(5), 1227-1232.

Hallevi, H., Dar, N. S., Barreto, A. D., Morales, M. M., Martin-Schild, S., Abraham, A. T., Walker, K. C., Gonzales, N. R., Illoh, K., Grotta, J. C., & Savitz, S. I. (2009). The IVH score: a novel tool for estimating intraventricular hemorrhage volume: clinical and research implications. Critical care medicine, 37(3), 969-e1.

Barras, C. D., Tress, B. M., Christensen, S., MacGregor, L., Collins, M., Desmond, P. M., Skolnick, B. E., Mayer, S. A., Broderick, J. P., Diringer, M. N., Steiner, T., Davis, S. M., & Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators (2009). Density and shape as CT predictors of intracerebral hemorrhage growth. Stroke, 40(4), 1325-1331.

Ministry of Health of Ukraine. (2014). Unifikovanyi klinichnyi protokol ekstrenoi, pervynnoi, vtorynnoi (spetsializovanoi), tretynnoi (vysokospetsializovanoi) medychnoi dopomohy ta medychnoi reabilitatsii Hemorahichnyi insult (vnutrishnomozkova hematoma, anevryzmalnyi subarakhnoidalnyi krovovylyv) [Unified clinical protocol of emergency, primary, secondary (specialized), tertiary (highly spe-cialized) medical care and medical rehabilitation Hemorrhagic stroke (intrahepatic hematoma, aneurysmal subarachnoid hemorrhage) (No. 275)]. Retrieved from:

Almarzouki, A., Wilson, D., Ambler, G., Shakeshaft, C., Cohen, H., Yousry, T., Al-Shahi Salman, R., Lip, G. Y. H., Houlden, H., Brown, M. M., Muir, K. W., Jäger, H. R., & Werring, D. J. (2020). Sensitivity and specificity of blood-fluid levels for oral anticoagulant-associated intracerebral haemorrhage. Scientific reports, 10(1), 15529.

Chen, Y., Tian, L., Wang, L., Qin, Y., & Cai, J. (2020). Black Hole Sign on Noncontrast Computed Tomography in Predicting Hematoma Expansion in Patients with Intracerebral Hemorrhage: A Meta-analysis. Current medical imaging, 16(7), 878-886.

Dowlatshahi, D., Morotti, A., Al-Ajlan, F. S., Boulouis, G., Warren, A. D., Petrcich, W., Aviv, R. I., Demchuk, A. M., & Goldstein, J. N. (2019). Interrater and Intrarater Measurement Reliability of Noncontrast Computed Tomography Predictors of Intracerebral Hemorrhage Expansion. Stroke, 50(5), 1260-1262.




How to Cite

Kuznietsov AA. Analysis of the diagnostic informativity of non-contrast computed tomography markers of intracerebral hemorrhage expansion in assessment of the individual risk of early neurological deterioration in patients with hemorrhagic hemispheric stroke. Pathologia [Internet]. 2023Dec.22 [cited 2024Mar.2];20(3):250-6. Available from:



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