Neurocritical Care

, Volume 19, Issue 3, pp 299–305 | Cite as

Predictors of Late Neurological Deterioration After Spontaneous Intracerebral Hemorrhage

  • Weiping Sun
  • Wenqin Pan
  • Peter G. Kranz
  • Claire E. Hailey
  • Rachel A. Williamson
  • Wei Sun
  • Daniel T. Laskowitz
  • Michael L. JamesEmail author
Original Article



Although intracerebral hemorrhage (ICH) is a common form of cerebrovascular disease, little is known about factors leading to neurological deterioration occurring beyond 48 h after hematoma formation. The purpose of this study was to characterize the incidence, consequences, and associative factors of late neurological deterioration (LND) in patients with spontaneous ICH.


Using the Duke University Hospital Neuroscience Intensive Care Unit database from July 2007 to June 2012, a cohort of 149 consecutive patients with spontaneous supratentorial ICH met criteria for analysis. LND was defined as a decrease of two or more points in Glasgow Coma Scale score or death during the period from 48 h to 1 week after ICH symptom onset. Unfavorable outcome was defined as a modified Rankin Scale score of >2 at discharge.


Forty-three subjects (28.9 %) developed LND. Logistic regression models revealed hematoma volume (OR = 1.017, 95 % CI 1.003–1.032, p = 0.019), intraventricular hemorrhage (OR = 2.519, 95 % CI 1.142–5.554, p = 0.022) and serum glucose on admission (OR = 2.614, 95 % CI 1.146–5.965, p = 0.022) as independent predictors of LND. After adjusting for ICH score, LND was independently associated with unfavorable outcome (OR = 4.000, 95 % CI 1.280–12.500, p = 0.017). In 65 subjects with follow-up computed tomography images, an increase in midline shift, as a surrogate for cerebral edema, was independently associated with LND (OR = 3.822, 95 % CI 1.157–12.622, p = 0.028).


LND is a common phenomenon in patients with ICH; further, LND appears to affect outcome. Independent predictors of LND include hematoma volume, intraventricular hemorrhage, and blood glucose on admission. Progression of perihematomal edema may be one mechanism for LND.


Intracerebral hemorrhage Neurological deterioration Predictors Outcome Brain edema 



Funding for this study was provided by NIH D43-TW008308-01 (WS/DTL) and the American Heart Association—Scientist Development Grant (MLJ).

Conflict of Interest

All the authors are declare that they have no conflict of interest.


  1. 1.
    Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet. 2009;373:1632–44.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Leira R, Dávalos A, Silva Y, et al. Early neurologic deterioration in intracerebral hemorrhage: predictors and associated factors. Neurology. 2004;63:461–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Sorimachi T, Fujii Y. Early neurological change in patients with spontaneous supratentorial intracerebral hemorrhage. J Clin Neurosci. 2010;17:1367–71.PubMedCrossRefGoogle Scholar
  4. 4.
    Mayer SA, Sacco RL, Shi T, Mohr JP. Neurologic deterioration in non-comatose patients with supratentorial intracerebral hemorrhage. Neurology. 1994;44:1379–84.PubMedCrossRefGoogle Scholar
  5. 5.
    Sun W, Peacock A, Becker J, Philips-Bute B, Laskowitz DT, James ML. Correlation of leukocytosis with early neurological deterioration following supratentorial intracerebral hemorrhage. J Clin Neurosci. 2012;19:1096–100.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke. 2007;38:2001–23.PubMedCrossRefGoogle Scholar
  7. 7.
    Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001;32:891–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Siegler JE, Martin-Schild S. Early Neurological Deterioration (END) after stroke: the END depends on the definition. Int J Stroke. 2011;6:211–2.PubMedCrossRefGoogle Scholar
  9. 9.
    Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358:2127–37.PubMedCrossRefGoogle Scholar
  10. 10.
    Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368:2355–65.PubMedCrossRefGoogle Scholar
  11. 11.
    Mendelow AD, Gregson BA, Rowan EN, et al. Early surgery versus initial consservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013. doi: 10.1016/S0140-6736(13)60986-1.Google Scholar
  12. 12.
    James ML, Sullivan PM, Lascola CD, Vitek MP, Laskowitz DT. Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage. Stroke. 2009;40:632–9.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    James ML, Wang H, Cantillana V, et al. TT-301 inhibits microglial activation and improves outcome after central nervous system injury in adult mice. Anesthesiology. 2012;116:1299–311.PubMedCrossRefGoogle Scholar
  14. 14.
    James ML, Wang H, Venkatraman T, Song P, Lascola CD, Laskowitz DT. Brain natriuretic peptide improves long-term functional recovery after acute CNS injury in mice. J Neurotrauma. 2010;27:217–28.PubMedCrossRefGoogle Scholar
  15. 15.
    Hwang BY, Appelboom G, Kellner CP, et al. Clinical grading scales in intracerebral hemorrhage. Neurocrit Care. 2010;13:141–51.PubMedCrossRefGoogle Scholar
  16. 16.
    Staykov D, Wagner I, Volbers B, et al. Natural course of perihemorrhagic edema after intracerebral hemorrhage. Stroke. 2011;42:2625–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Venkatasubramanian C, Mlynash M, Finley-Caulfield A, et al. Natural history of perihematomal edema after intracerebral hemorrhage measured by serial magnetic resonance imaging. Stroke. 2010;42:73–80.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Gebel JM Jr, Jauch EC, Brott TG, et al. Natural history of perihematomal edema in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002;33:2631–5.PubMedCrossRefGoogle Scholar
  19. 19.
    Balami JS, Buchan AM. Complications of intracerebral haemorrhage. Lancet Neurol. 2012;11:101–18.PubMedCrossRefGoogle Scholar
  20. 20.
    Tuhrim S, Horowitz DR, Sacher M, Godbold JH. Volume of ventricular blood is an important determinant of outcome in supratentorial intracerebral hemorrhage. Crit Care Med. 1999;27:617–21.PubMedCrossRefGoogle Scholar
  21. 21.
    Steiner T, Diringer MN, Schneider D, et al. Dynamics of intraventricular hemorrhage in patients with spontaneous intracerebral hemorrhage: risk factors, clinical impact, and effect of hemostatic therapy with recombinant activated factor VII. Neurosurgery. 2006;59:767–73.PubMedCrossRefGoogle Scholar
  22. 22.
    Godoy DA, Pinero GR, Svampa S, Papa F, Di Napoli M. Hyperglycemia and short-term outcome in patients with spontaneous intracerebral hemorrhage. Neurocrit Care. 2008;9:217–29.PubMedCrossRefGoogle Scholar
  23. 23.
    Fogelholm R, Murros K, Rissanen A, Avikainen S. Admission blood glucose and short term survival in primary intracerebral haemorrhage: a population based study. J Neurol Neurosurg Psychiatr. 2005;76:349–53.PubMedCrossRefGoogle Scholar
  24. 24.
    Stead LG, Jain A, Bellolio MF, et al. Emergency Department hyperglycemia as a predictor of early mortality and worse functional outcome after intracerebral hemorrhage. Neurocrit Care. 2010;13:67–74.PubMedCrossRefGoogle Scholar
  25. 25.
    Lee SH, Kim BJ, Bae HJ, et al. Effects of glucose level on early and long-term mortality after intracerebral haemorrhage: the acute brain bleeding analysis study. Diabetologia. 2010;53:429–34.PubMedCrossRefGoogle Scholar
  26. 26.
    Araki N, Greenberg JH, Sladky JT, Uematsu D, Karp A, Reivich M. The effect of hyperglycemia on intracellular calcium in stroke. J Cereb Blood Flow Metab. 1992;12:469–76.PubMedCrossRefGoogle Scholar
  27. 27.
    Zazulia AR, Diringer MN, Derdeyn CP, Powers WJ. Progression of mass effect after intracerebral hemorrhage. Stroke. 1999;30:1167–73.PubMedCrossRefGoogle Scholar
  28. 28.
    Arima H, Wang JG, Huang Y, et al. Significance of perihematomal edema in acute intracerebral hemorrhage: the INTERACT trial. Neurology. 2009;73:1963–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Gill MR, Reiley DG, Green SM. Interrater reliability of Glasgow Coma Scale scores in the emergency department. Ann Emerg Med. 2004;43:215–22.PubMedCrossRefGoogle Scholar
  30. 30.
    Moon JS, Janjua N, Ahmed S, et al. Prehospital neurologic deterioration in patients with intracerebral hemorrhage. Crit Care Med. 2008;36:172–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Mehdiratta M, Kumar S, Hackney D, Schlaug G, Selim M. Association between serum ferritin level and perihematoma edema volume in patients with spontaneous intracerebral hemorrhage. Stroke. 2008;39:1165–70.PubMedCrossRefGoogle Scholar
  32. 32.
    James ML, Blessing R, Bennett E, Laskowitz DT. Apolipoprotein E modifies neurological outcome by affecting cerebral edema but not hematoma size after intracerebral hemorrhage in humans. J Stroke Cerebrovasc Dis. 2009;18:144–9.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Walberer M, Blaes F, Stolz E, et al. Midline-shift corresponds to the amount of brain edema early after hemispheric stroke–an MRI study in rats. J Neurosurg Anesthesiol. 2007;19:105–10.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Weiping Sun
    • 1
    • 6
  • Wenqin Pan
    • 1
  • Peter G. Kranz
    • 2
  • Claire E. Hailey
    • 3
  • Rachel A. Williamson
    • 3
  • Wei Sun
    • 6
  • Daniel T. Laskowitz
    • 1
    • 3
    • 4
    • 5
  • Michael L. James
    • 3
    • 4
    • 5
    Email author
  1. 1.Duke Clinical Research InstituteDuke UniversityDurhamUSA
  2. 2.Department of Radiology (Neuroradiology)Duke UniversityDurhamUSA
  3. 3.Department of AnesthesiologyDuke UniversityDurhamUSA
  4. 4.Department of NeurologyDuke UniversityDurhamUSA
  5. 5.Brain Injury Translational Research CenterDuke UniversityDurhamUSA
  6. 6.Department of NeurologyPeking University First HospitalBeijingPeople’s Republic of China

Personalised recommendations