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August 2017; 7 (4) Research

Frequency, determinants, and effects of early seizures after thrombolysis for acute ischemic stroke

The ENCHANTED trial

Ying Xu, Maree L. Hackett, John Chalmers, Richard I. Lindley, Xia Wang, Qiang Li, Thompson Robinson, Hisatomi Arima, Pablo M. Lavados, Craig S. Anderson, For the ENCHANTED Study Group
First published July 19, 2017, DOI: https://doi.org/10.1212/CPJ.0000000000000384
Ying Xu
The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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Maree L. Hackett
The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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John Chalmers
The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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Richard I. Lindley
The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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Xia Wang
The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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Qiang Li
The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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Thompson Robinson
The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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Hisatomi Arima
The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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Pablo M. Lavados
The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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Craig S. Anderson
The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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The George Institute for Global Health (YX, MLH, JC, RIL, XW, QL, HA, CSA), University of New South Wales; Sydney Medical School (YX, MLH, JC, RIL, CSA), the University of Sydney, Australia; Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases (TR), University of Leicester, UK; Department of Preventive Medicine and Public Health (HA), Faculty of Medicine, Fukuoka University, Japan; Clinica Alemana de Santiago, Facultad de Medicina (PML), Clinica Alemana Universidad del Desarrollo; Departamento de Ciencias Neurológicas (PML), Facultad de Medicina, Universidad de Chile, Santiago; Neurology Department (CSA), Royal Prince Alfred Hospital, Sydney, Australia; and The George Institute China at Peking University Health Science Center (CSA), Beijing PR China.
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Frequency, determinants, and effects of early seizures after thrombolysis for acute ischemic stroke
The ENCHANTED trial
Ying Xu, Maree L. Hackett, John Chalmers, Richard I. Lindley, Xia Wang, Qiang Li, Thompson Robinson, Hisatomi Arima, Pablo M. Lavados, Craig S. Anderson, For the ENCHANTED Study Group
Neurol Clin Pract Aug 2017, 7 (4) 324-332; DOI: 10.1212/CPJ.0000000000000384

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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.

Footnotes

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.

  • Coinvestigators are listed at Neurology.org/cp.

  • Supplemental data at Neurology.org/cp

  • Received April 12, 2017.
  • Accepted May 30, 2017.
  • © 2017 American Academy of Neurology
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