Skip to main content

Advertisement

SpringerLink
Log in

Prophylactic Antiepileptic Drug Use is Associated with Poor Outcome Following ICH

  • Original Article
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Introduction

Intracerebral hemorrhage (ICH) is associated with a risk of early seizure and guidelines recommend consideration of prophylactic antiepileptic drugs (AEDs) for some patients, although the utility is uncertain.

Methods

We analyzed data from the placebo arm of the Cerebral Hemorrhage and NXY-059 Trial (CHANT), an international multicenter randomized trial of a potential neuroprotectant that enrolled patients within 6 h of the onset of acute ICH. Logistic regression analyses were performed to determine whether early AED use was associated with poor outcome at day 90, defined as a modified Rankin Scale of 5 or 6 (severely disabled or dead).

Results

Excluding patients who were previously on AEDs, the primary analysis included 295 patients. The median ICH volume at admission was 14.9 (interquartile range, IQR 7.9–32.7) ml and the mean was 23.3 (±SD 22.8) ml. Seizures occurred in 5 patients (1.7%) after enrollment and 82 patients (28%) had a poor outcome at day 90. AEDs were initiated on 23 patients (8%) without documented seizure during the first 10 days of the trial. In logistic regression, initiation of AEDs was robustly associated with poor outcome (OR 6.8; 95% CI: 2.2–21.2, P = 0.001) after adjustment for other known predictors of outcome after ICH (age, initial hematoma volume, presence of intraventricular blood, initial Glasgow coma score, and prior warfarin use).

Conclusions

In this clinical trial cohort, seizures were rare after the first few hours following ICH. In addition, prophylactic AED use was associated with poor outcome independent of other established predictors. Given the potential for residual confounding in this cohort, a randomized trial needs to be performed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. 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. Circulation. 2007;116:e391–413. doi:10.1161/CIRCULATIONAHA.107.183689.

    Article  PubMed  Google Scholar 

  2. Passero S, Rocchi R, Rossi S, Ulivelli M, Vatti G. Seizures after spontaneous supratentorial intracerebral hemorrhage. Epilepsia. 2002;43:1175–80. doi:10.1046/j.1528-1157.2002.00302.x.

    Article  PubMed  Google Scholar 

  3. Berger AR, Lipton RB, Lesse ML, Lantos G, Portenoy RK. Early seizures following intracerebral hemorrhage: implications for therapy. Neurology. 1988;38:1363–5.

    PubMed  CAS  Google Scholar 

  4. Steiner T, Kaste M, Forsting M, et al. Recommendations for the management of intracranial haemorrhage—part I: spontaneous intracerebral haemorrhage. The European Stroke Initiative writing committee and the writing committee for the EUSI executive committee. Cerebrovasc Dis. 2006;22:294–316.

    Article  PubMed  Google Scholar 

  5. Bladin CF, Alexandrov AV, Bellavance A, et al. Seizures after stroke: a prospective multicenter study. Arch Neurol. 2000;57:1617–22. doi:10.1001/archneur.57.11.1617.

    Article  PubMed  CAS  Google Scholar 

  6. Camilo O, Goldstein LB. Seizures and epilepsy after ischemic stroke. Stroke. 2004;35:1769–75. doi:10.1161/01.STR.0000130989.17100.96.

    Article  PubMed  Google Scholar 

  7. Naidech AM, Kreiter KT, Janjua N, et al. Phenytoin exposure is associated with functional and cognitive disability after subarachnoid hemorrhage. Stroke. 2005;36:583–7. doi:10.1161/01.STR.0000141936.36596.1e.

    Article  PubMed  CAS  Google Scholar 

  8. Rosengart AJ, Huo JD, Tolentino J, et al. Outcome in patients with subarachnoid hemorrhage treated with antiepileptic drugs. J Neurosurg. 2007;107:253–60. doi:10.3171/JNS-07/08/0253.

    Article  PubMed  Google Scholar 

  9. NINDS ICH Workshop Participants. Priorities for clinical research in intracerebral hemorrhage: Report from a National Institute of Neurological Disorders and Stroke workshop. Stroke. 2005;36:e23–41. doi:10.1161/01.STR.0000155685.77775.4c.

    Article  Google Scholar 

  10. Lyden PD, Shuaib A, Lees KR, et al. Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT trial. Stroke. 2007;38:2262–9. doi:10.1161/STROKEAHA.106.472746.

    Article  PubMed  CAS  Google Scholar 

  11. 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. doi:10.1056/NEJMoa0707534.

    Article  PubMed  CAS  Google Scholar 

  12. Hosmer DW, Lemshow S. Applied logistic regression. New York: John Wiley & Sons, Inc.; 1989.

    Google Scholar 

  13. Hemphill JC III, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001;32:891–7.

    PubMed  Google Scholar 

  14. Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med. 2004;164:880–4. doi:10.1001/archinte.164.8.880.

    Article  PubMed  CAS  Google Scholar 

  15. Clarke JL, Johnston SC, Farrant M, Bernstein R, Tong D, Hemphill JC 3rd. External validation of the ICH score. Neurocrit Care. 2004;1:53–60. doi:10.1385/NCC:1:1:53.

    Article  PubMed  Google Scholar 

  16. Vespa PM, O’Phelan K, Shah M, et al. Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome. Neurology. 2003;60:1441–6.

    PubMed  CAS  Google Scholar 

  17. Leira R, Davalos A, Silva Y, et al. Early neurologic deterioration in intracerebral hemorrhage: predictors and associated factors. Neurology. 2004;63:461–7.

    PubMed  CAS  Google Scholar 

  18. Szaflarski JP, Rackley AY, Kleindorfer DO, et al. Incidence of seizures in the acute phase of stroke: a population-based study. Epilepsia. 2008;49:974–81. doi:10.1111/j.1528-1167.2007.01513.x.

    Article  PubMed  Google Scholar 

  19. Labovitz DL, Allen Hauser W, Sacco RL. Prevalence and predictors of early seizure and status epilepticus after first stroke. Neurology. 2001;57:200–6.

    PubMed  CAS  Google Scholar 

  20. Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C. Epileptic seizures after a first stroke: the Oxfordshire Community Stroke Project. BMJ. 1997;315:1582–7.

    PubMed  CAS  Google Scholar 

  21. Kilpatrick CJ, Davis SM, Tress BM, Rossiter SC, Hopper JL, Vandendriesen ML. Epileptic seizures in acute stroke. Arch Neurol. 1990;47:157–60.

    PubMed  CAS  Google Scholar 

  22. Claassen J, Jette N, Chum F, et al. Electrographic seizures and periodic discharges after intracerebral hemorrhage. Neurology. 2007;69:1356–65. doi:10.1212/01.wnl.0000281664.02615.6c.

    Article  PubMed  CAS  Google Scholar 

  23. Ryvlin P, Montavont A, Nighoghossian N. Optimizing therapy of seizures in stroke patients. Neurology. 2006;67:S3–9.

    PubMed  Google Scholar 

  24. Castellanos M, Leira R, Tejada J, Gil-Peralta A, Davalos A, Castillo J. Predictors of good outcome in medium to large spontaneous supratentorial intracerebral haemorrhages. J Neurol Neurosurg Psychiatry. 2005;76:691–5. doi:10.1136/jnnp.2004.044347.

    Article  PubMed  CAS  Google Scholar 

  25. Broderick JP, Adams HP, Barsan W, et al. Guidelines for the management of spontaneous intracerebral hemorrhage. Stroke. 1999;30:905.

    PubMed  CAS  Google Scholar 

  26. Sung CY, Chu NS. Epileptic seizures in intracerebral haemorrhage. J Neurol Neurosurg Psychiatry. 1989;52:1273–6. doi:10.1136/jnnp.52.11.1273.

    Article  PubMed  CAS  Google Scholar 

  27. Faught E, Peters D, Bartolucci A, Moore L, Miller PC. Seizures after primary intracerebral hemorrhage. Neurology. 1989;39:1089–93.

    PubMed  CAS  Google Scholar 

  28. Arboix A, Comes E, Massons J, Garcia L, Oliveres M. Relevance of early seizures for in-hospital mortality in acute cerebrovascular disease. Neurology. 1996;47:1429–35.

    PubMed  CAS  Google Scholar 

  29. Strom BL. Methodologic challenges to studying patient safety and comparative effectiveness. Med Care. 2007;45:S13–5.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Astra Zeneca, PLC was the primary sponsor of the Cerebral Hemorrhage and NXY-059 Trial (CHANT). They provided no funding for this analysis of the placebo arm of the CHANT study.

Author information

Authors and Affiliations

  1. Department of Neurology, University of Pennsylvania Medical Center, 3W Gates Building, 3400 Spruce Street, Philadelphia, PA, 19104, USA

    Steven R. Messé, Lauren H. Sansing, Brett L. Cucchiara & Scott E. Kasner

  2. Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Susan T. Herman

  3. Department of Neurology, University of California at San Diego, San Diego, CA, USA

    Patrick D. Lyden

  4. Department of Neurology, University of Pennsylvania Medical Center, 3W Gates Building, 3400 Spruce Street, Philadelphia, PA, 19104, USA

    Steven R. Messé

Authors
  1. Steven R. Messé
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lauren H. Sansing
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brett L. Cucchiara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susan T. Herman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Patrick D. Lyden
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Scott E. Kasner
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the CHANT investigators

Corresponding author

Correspondence to Steven R. Messé.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Messé, S.R., Sansing, L.H., Cucchiara, B.L. et al. Prophylactic Antiepileptic Drug Use is Associated with Poor Outcome Following ICH. Neurocrit Care 11, 38–44 (2009). https://doi.org/10.1007/s12028-009-9207-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-009-9207-y

Keywords

Search

Navigation