Frequency, determinants, and effects of early seizures after thrombolysis for acute ischemic stroke
The ENCHANTED trial
Abstract
Background:
Seizures after ischemic stroke have not been well-studied. We aim to determine the frequency, determinants, and significance of early seizures after thrombolysis for acute ischemic stroke.
Methods:
Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, multicenter, randomized controlled trial where patients with acute ischemic stroke were randomized to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) IV alteplase. The protocol prespecified prospective data collection on in-hospital seizures over 7 days postrandomization. Logistic regression models were used to determine variables associated with seizures and their significance on poor outcomes of death or disability (modified Rankin scale scores 3–6), symptomatic intracerebral hemorrhage (sICH), and European Quality of Life 5-Dimensions questionnaire [EQ-5D] over 90 days.
Results:
Data were available for 3,139 acute ischemic stroke participants, of whom 42 (1.3%) had seizures at a median 22.7 hours after the onset of symptoms. Baseline variables associated with seizures were male sex (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.07–4.50), severe neurologic impairment (NIH Stroke Scale score ≥10; OR 2.16, 95% CI 1.06–4.40), and fever (OR 4.55, 95% CI 2.37–8.71). Seizures independently predicted poor recovery: death or major disability (OR 2.88, 95% CI 1.28–6.47), unfavorable ordinal shift of mRS scores (OR 1.94, 95% CI 1.10–3.39), and lower than median EQ-5D health utility index score (OR 3.50, 95% CI 1.37–8.91). There was no association of seizures with sICH in adjusted analysis.
Conclusions:
In thrombolysis-treated patients with acute ischemic stroke, seizures are uncommon, occur early, and predict poor recovery.
Clinicaltrials.gov identifier:
NCT01422616.
Get full access to this article
View all available purchase options and get full access to this article.
Supplementary Material
REFERENCES
1.
Huang CW, Saposnik G, Fang J, Steven DA, Burneo JG. Influence of seizures on stroke outcomes: a large multicenter study. Neurology 2014;82:768–776.
2.
Bladin CF, Alexandrov AV, Bellavance A, et al. Seizures after stroke: a prospective multicenter study. Arch Neurol 2000;57:1617–1622.
3.
Lancman ME, Golimstok A, Norscini J, Granillo R. Risk factors for developing seizures after a stroke. Epilepsia 1993;34:141–143.
4.
Burneo JG, Fang J, Saposnik G. Impact of seizures on morbidity and mortality after stroke: a Canadian multi-center cohort study. Eur J Neurol 2010;17:52–58.
5.
Goswami RP, Karmakar PS, Ghosh A. Early seizures in first-ever acute stroke patients in India: incidence, predictive factors and impact on early outcome. Eur J Neurol 2012;19:1361–1366.
6.
Zhang C, Wang X, Wang Y, et al. Risk factors for post-stroke seizures: a systematic review and meta-analysis. Epilepsy Res 2014;108:1806–1816.
7.
Arboix A, Garcia-Eroles L, Massons JB, Oliveres M, Comes E. Predictive factors of early seizures after acute cerebrovascular disease. Stroke 1997;28:1590–1594.
8.
De Herdt V, Dumont F, Henon H, et al. Early seizures in intracerebral hemorrhage: incidence, associated factors, and outcome. Neurology 2011;77:1794–1800.
9.
Alberti A, Paciaroni M, Caso V, Venti M, Palmerini F, Agnelli G. Early seizures in patients with acute stroke: frequency, predictive factors, and effect on clinical outcome. Vasc Health Risk Manag 2008;4:715–720.
10.
Couillard P, Almekhlafi MA, Irvine A, et al. Subacute seizure incidence in thrombolysis-treated ischemic stroke patients. Neurocrit Care 2012;16:241–245.
11.
Anderson CS, Robinson T, Lindley RI, et al. Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke. N Engl J Med 2016;374:2313–2323.
12.
Anderson CS, Woodward M, Arima H, et al. Statistical analysis plan for evaluating low- vs. standard-dose alteplase in the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Int J Stroke 2015;10:1313–1315.
13.
Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the commission on classification and terminology of the international league against epilepsy. Epilepsia 1981;22:489–501.
14.
Quinn TJ, Dawson J, Walters MR, Lees KR. Functional outcome measures in contemporary stroke trials. Int J Stroke 2009;4:200–205.
15.
Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275–282.
16.
Rabin R, de Charro F. EQ-5d: a measure of health status from the EuroQoL group. Ann Med 2001;33:337–343.
17.
Alvarez V, Rossetti AO, Papavasileiou V, Michel P. Acute seizures in acute ischemic stroke: does thrombolysis have a role to play? J Neurol 2013;260:55–61.
18.
Lamy C, Domigo V, Semah F, et al. Early and late seizures after cryptogenic ischemic stroke in young adults. Neurology 2003;60:400–404.
19.
Cheung CM, Tsoi TH, Au-Yeung M, Tang ASY. Epileptic seizure after stroke in Chinese patients. J Neurol 2003;250:839–843.
20.
El-Khayat HA, Shatla HM, Ali GK, Abdulgani MO, Tomoum HY, Attya HA. Physical and hormonal profile of male sexual development in epilepsy. Epilepsia 2003;44:447–452.
21.
Reith J, Jorgensen HS, Nakayama H, et al. Seizures in acute stroke: predictors and prognostic significance: the Copenhagen Stroke Study. Stroke 1997;28:1585–1589.
22.
Wang G, Jia H, Chen C, et al. Analysis of risk factors for first seizure after stroke in Chinese patients. Biomed Res Int 2013;2013:702871.
23.
Grau AJ, Buggle F, Schnitzler P, Spiel M, Lichy C, Hacke W. Fever and infection early after ischemic stroke. J Neurol Sci 1999;171:115–120.
24.
Krakow K, Sitzer M, Rosenow F, Steinmetz H, Foerch C, Arbeitsgruppe Schlaganfall H. Predictors of acute poststroke seizures. Cerebrovasc Dis 2010;30:584–589.
25.
Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014;384:1929–1935.
26.
Tan ML, Ng A, Pandher PS, et al. Tissue plasminogen activator does not alter development of acquired epilepsy. Epilepsia 2012;53:1998–2004.
27.
Labovitz DL, Hauser WA, Sacco RL. Prevalence and predictors of early seizure and status epilepticus after first stroke. Neurology 2001;57:200–206.
28.
Carrera E, Michel P, Despland PA, et al. Continuous assessment of electrical epileptic activity in acute stroke. Neurology 2006;67:99–104.
Information & Authors
Information
Published In
Neurology® Clinical Practice
Volume 7 • Number 4 • August 2017
Pages: 324-332
Copyright
© 2017 American Academy of Neurology.
Publication History
Received: April 12, 2017
Accepted: May 30, 2017
Published online: July 19, 2017
Published in print: August 2017
Disclosure
Y. Xu reports no disclosures. M.L. Hackett has received reimbursement for travel expenses from Boehringer Ingelheim; serves/has served as an Associate Editor and Editorial Board member of Cochrane Stroke Group; receives a National Heart Foundation Future Leader Fellowship; and receives research support from Google, National Health and Medical Research Council, Australia Swedish Research Council Framework, Sweden National Institute for Health Research, United Kingdom, National Heart Foundation, Australia Cochrane Chest, and Heart and Stroke, Scotland. J. Chalmers has received funding for travel and speaker honoraria from Servier; serves as Associate Editor for the Journal of Hypertension; and receives research support from Servier and National Health and Medical Research Council of Australia. R.I. Lindley has received speaker honoraria from Pfizer and Covidien; serves as an Associate Editor for the Australasian Journal on Ageing; receives publishing royalties from Stroke: The Facts (Oxford University Press, 2008, 2017) and Understanding Stroke, The British Medical Association Family Doctor Series (Family Doctor Publications Ltd. in association with the British Medical Association, 2000, 2002, 2003, and 2005); and receives research support from National Health and Medical Research Council of Australia. X. Wang and Q. Li report no disclosures. T.G. Robinson serves on scientific advisory boards for Bayer and Daiichi Sankyo; has received speaker honoraria from Bayer and Boehringer Ingelheim; and receives research support from the Stroke Association. H. Arima serves on a scientific advisory board for Kyowa Kirin Pharma; serves on the editorial board of Journal of Hypertension and as an Associate Editor for BMC Public Health and Journal of Epidemiology; serves on the speakers' bureaus for Takeda, Daiichi Sankyo, Asuka, and Bayer; and has received research support from National Health and Medical Research Council of Australia. P. Lavados has received funding for travel and speaker honoraria from Bayer; receives institutional support from Clinica Alemana, Universidad del Desarrollo, to perform stroke administration and research; and receives research support from Boehringer Ingelheim, Astra Zeneca, Bayer, CONICYT, Clinica Alemana-Universiad del Desarrollo, and The George Institute for Global Health. C.S. Anderson serves on scientific advisory boards for Astra Zeneca and Medtronic; has received funding for travel or speaker honoraria from Takeda China and Boehringer Ingelheim; serves on the editorial boards of Stroke, Cerebrovascular Diseases, and International Journal of Stroke; and receives research support from National Health and Medical Research Council of Australia. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
Study Funding
The study is funded by the National Health and Medical Research Council (NHMRC) of Australia (project grant 1020462), the Stroke Association of the United Kingdom (reference TSA 2012/01), the National Council for Scientific and Technological Development of Brazil (CNPq grant number 467322/2014-7), and the Ministry for Health, Welfare, and Family Affairs of South Korea.
Authors
Author Contributions
Y. Xu: statistical analysis, interpretation of data, first draft, and revision of the manuscript. M.L. Hackett: interpretation of data, supervision, and revision of the manuscript. J. Chalmers: design/conceptualization of the study, interpretation of data, supervision, and revision of the manuscript. R.I. Lindley: revision of the manuscript. X. Wang: check of statistical analysis and interpretation of data. Q. Li: check of statistical analysis and interpretation of data. T. Robinson: design/conceptualization of the study and revision of the manuscript. H. Arima: design/conceptualization of the study and revision of the manuscript. P.M. Lavados: design/conceptualization of the study and revision of the manuscript. C.S. Anderson: design/conceptualization of the study, interpretation of data, supervision, and revision of the manuscript.
Metrics & Citations
Metrics
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
Cited By
- Posterior circulation lesions are more frequently associated with early seizures after a stroke, Italian Journal of Medicine, 18, 1, (2024).https://doi.org/10.4081/itjm.2024.1683
- Systematic Literature Review of the Association of Fever and Elevated Temperature with Outcomes in Critically Ill Adult Patients, Therapeutic Hypothermia and Temperature Management, 14, 1, (10-23), (2024).https://doi.org/10.1089/ther.2023.0004
- The Primary Prevention of Poststroke Epilepsy in Patients With Middle Cerebral Artery Infarct: Protocol for a Randomized Controlled Trial, JMIR Research Protocols, 12, (e49412), (2023).https://doi.org/10.2196/49412
- Outcomes in Patients With Poststroke Seizures, JAMA Neurology, 80, 11, (1155), (2023).https://doi.org/10.1001/jamaneurol.2023.3240
- La thrombolyse intraveineuse de l’infarctus cérébral : des recommandations à la pratique clinique, Pratique Neurologique - FMC, 13, 1, (28-32), (2022).https://doi.org/10.1016/j.praneu.2021.12.013
- Critical Care of the Patient With Acute Stroke, Stroke, (800-830.e10), (2022).https://doi.org/10.1016/B978-0-323-69424-7.00056-9
- Effect of Reperfusion Therapies on Incidence of Early Post-Stroke Seizures, Frontiers in Neurology, 12, (2021).https://doi.org/10.3389/fneur.2021.758181
- Effectiveness of intravenous r-tPA versus UK for acute ischaemic stroke: a nationwide prospective Chinese registry study, Stroke and Vascular Neurology, 6, 4, (603-609), (2021).https://doi.org/10.1136/svn-2020-000640
- Assessment of the incidence and risk factors of early poststroke seizures in Lebanese patients, Brain and Behavior, 11, 11, (2021).https://doi.org/10.1002/brb3.2204
- Risk Factors for Epilepsy After Thrombolysis for Ischemic Stroke: A Cohort Study, Frontiers in Neurology, 10, (2020).https://doi.org/10.3389/fneur.2019.01256
- See more
Loading...
View Options
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.
If you need immediate support or to place an order, please call or email customer service:
- 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
- 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
- [email protected]
We appreciate your patience during this time and apologize for any inconvenience.