Neurocritical Care

, 15:308 | Cite as

Vasospasm Versus Delayed Cerebral Ischemia as an Outcome Event in Clinical Trials and Observational Studies

  • Mervyn D. I. VergouwenEmail author
  • The Participants in the International Multi-disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage


Delayed cerebral ischemia occurs in about 30% of patients during the first 2 weeks after subarachnoid hemorrhage, and can result in substantial disability and death. Research studies investigating the incidence of delayed cerebral ischemia and strategies for prevention and treatment are hampered by inconsistent use of terminology and definitions for this complication, and by reliance on indirect surrogate markers of ischemia. A literature review was conducted to search for studies that addressed the issue of inconsistent definitions of delayed cerebral ischemia through December 2010. A total of four studies were identified. Original research studies and consensus panel recommendations for definitions support limiting the use of combined measures that include both clinical and radiographic assessments, as well as indirect measures, and the current usage of the term vasospasm. Cerebral infarction was supported as the most appropriate definition for delayed cerebral ischemia in the context of clinical trials.


Angiography Cerebral infarction Clinical deterioration Transcranial Doppler Vasospasm 


  1. 1.
    Roos YB, de Haan RJ, Beenen LF, Groen RJ, Albrecht KW, Vermeulen M. Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in the Netherlands. J Neurol Neurosurg Psychiatry. 2000;68:337–41.PubMedCrossRefGoogle Scholar
  2. 2.
    Hijdra A, Van Gijn J, Stefanko S, Van Dongen KJ, Vermeulen M, Van Crevel H. Delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: clinicoanatomic correlations. Neurology. 1986;36:329–33.PubMedGoogle Scholar
  3. 3.
    van der Schaaf IC, Ruigrok YM, Rinkel GJ, Algra A, van Gijn J. Study design and outcome measures in studies on aneurysmal subarachnoid hemorrhage. Stroke. 2002;33:2043–6.PubMedCrossRefGoogle Scholar
  4. 4.
    van Gijn J, Bromberg JE, Lindsay KW, Hasan D, Vermeulen M. Definition of initial grading, specific events, and overall outcome in patients with aneurysmal subarachnoid hemorrhage. A survey. Stroke. 1994;25:1623–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Grubb RL Jr, Raichle ME, Eichling JO, Gado MH. Effects of subarachnoid hemorrhage on cerebral blood volume, blood flow, and oxygen utilization in humans. J Neurosurg. 1977;46:446–53.PubMedCrossRefGoogle Scholar
  6. 6.
    Uhl E, Lehmberg J, Steiger HJ, Messmer K. Intraoperative detection of early microvasospasm in patients with subarachnoid hemorrhage by using orthogonal polarization spectral imaging. Neurosurgery. 2003;52:1307–15.PubMedCrossRefGoogle Scholar
  7. 7.
    Vergouwen MD, Vermeulen M, Coert BA, Stroes ES, Roos YB. Microthrombosis after aneurysmal subarachnoid hemorrhage: an additional explanation for delayed cerebral ischemia. J Cereb Blood Flow Metab. 2008;28:1761–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Dreier JP, Major S, Manning A, et al. Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage. Brain. 2009;132:1866–81.PubMedCrossRefGoogle Scholar
  9. 9.
    Sillberg VA, Wells GA, Perry JJ. Do statins improve outcomes and reduce the incidence of vasospasm after aneurysmal subarachnoid hemorrhage: a meta-analysis. Stroke. 2008;39:2622–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Kramer AH. Statins in the management of aneurysmal subarachnoid hemorrhage—not (yet) a standard of care. Stroke. 2009;40:e80–1.PubMedCrossRefGoogle Scholar
  11. 11.
    Bederson JB, Connolly ES Jr, Batjer HH, American Heart Association, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 2009;40:994–1025.PubMedCrossRefGoogle Scholar
  12. 12.
    Frontera JA, Fernandez A, Schmidt JM, et al. Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke. 2009;40:1963–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Vergouwen MD, Vermeulen M, van Gijn J, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010;41:2391–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Hughes JT, Schianchi PM. Cerebral artery spasm. A histological study at necropsy of the blood vessels in cases of subarachnoid hemorrhage. J Neurosurg. 1978;48:515–25.PubMedCrossRefGoogle Scholar
  15. 15.
    Fisher CM, Roberson GH, Ojemann RG. Cerebral vasospasm with ruptured saccular aneurysm—the clinical manifestations. Neurosurgery. 1977;1:245–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Rabinstein AA, Friedman JA, Weigand SD, et al. Predictors of cerebral infarction in aneurysmal subarachnoid hemorrhage. Stroke. 2004;35:1862–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Fergusen S, Macdonald RL. Predictors of cerebral infarction in patients with aneurysmal subarachnoid hemorrhage. Neurosurgery. 2007;60:658–67.PubMedCrossRefGoogle Scholar
  18. 18.
    Vergouwen MDI, Ilodigwe D, Macdonald RL. Cerebral infarction after subarachnoid hemorrhage contributes to poor outcome by vasospasm-dependent and -independent effects. Stroke. 2011;42:924–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Dankbaar JW, Rijsdijk M, van der Schaaf IC, Velthuis BK, Wermer MJ, Rinkel GJ. Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neuroradiology. 2009;51:813–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Dankbaar JW, de Rooij NK, Velthuis BK, Frijns CJ, Rinkel GJ, van der Schaaf IC. Diagnosing delayed cerebral ischemia with different CT modalities in patients with subarachnoid hemorrhage with clinical deterioration. Stroke. 2009;40:3493–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Kreiter KT, Mayer SA, Howard G, et al. Sample size estimates for clinical trials of vasospasm in subarachnoid hemorrhage. Stroke. 2009;40:2362–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Schmidt JM, Wartenberg KE, Fernandez A, et al. Frequency and clinical impact of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage. J Neurosurg. 2008;109:1052–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Vergouwen MD, Etminan N, Ilodigwe D, Macdonald RL. Lower incidence of cerebral infarction correlates with improved functional outcome after aneurysmal subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2011;31:1545–53.CrossRefGoogle Scholar
  24. 24.
    Etminan N, Vergouwen MD, Ilodigwe D, Macdonald RL. Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Cereb Blood Flow Metab. 2011;31:1443–51.PubMedCrossRefGoogle Scholar
  25. 25.
    Lee JY, Lee MS, Whang K, Lee JM, Kim SH, Lee SS. Accuracy of transcranial Doppler sonography for predicting cerebral infarction in aneurysmal subarachnoid hemorrhage. J Clin Ultrasound. 2006;34:380–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Mervyn D. I. Vergouwen
    • 1
    • 2
    Email author
  • The Participants in the International Multi-disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage
  1. 1.Utrecht Stroke Center, Department of NeurologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Department of Experimental Vascular Medicine, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

Personalised recommendations