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Antiseizure Medication Treatment and Outcomes in Patients with Subarachnoid Hemorrhage Undergoing Continuous EEG Monitoring

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Abstract

Background

Patients with aneurysmal subarachnoid hemorrhage (aSAH) with electroencephalographic epileptiform activity (seizures, periodic and rhythmic patterns, and sporadic discharges) are frequently treated with antiseizure medications (ASMs). However, the safety and effectiveness of ASM treatment for epileptiform activity has not been established. We used observational data to investigate the effectiveness of ASM treatment in patients with aSAH undergoing continuous electroencephalography (cEEG) to develop a causal hypothesis for testing in prospective trials.

Methods

This was a retrospective single-center cohort study of patients with aSAH admitted between 2011 and 2016. Patients underwent ≥ 24 h of cEEG within 4 days of admission. All patients received primary ASM prophylaxis until aneurysm treatment (typically within 24 h of admission). Treatment exposure was defined as reinitiation of ASMs after aneurysm treatment and cEEG initiation. We excluded patients with non-cEEG indications for ASMs (e.g., epilepsy, acute symptomatic seizures). Outcomes measures were 90-day mortality and good functional outcome (modified Rankin Scale scores 0–3). Propensity scores were used to adjust for baseline covariates and disease severity.

Results

Ninety-four patients were eligible (40 continued ASM treatment; 54 received prophylaxis only). ASM continuation was not significantly associated with higher 90-day mortality (propensity-adjusted hazard ratio [HR] = 2.01 [95% confidence interval (CI) 0.57–7.02]). ASM continuation was associated with lower likelihood for 90-day good functional outcome (propensity-adjusted HR = 0.39 [95% CI 0.18–0.81]). In a secondary analysis, low-intensity treatment (low-dose single ASM) was not significantly associated with mortality (propensity-adjusted HR = 0.60 [95% CI 0.10–3.59]), although it was associated with a lower likelihood of good outcome (propensity-adjusted HR = 0.37 [95% CI 0.15–0.91]), compared with prophylaxis. High-intensity treatment (high-dose single ASM, multiple ASMs, or anesthetics) was associated with higher mortality (propensity-adjusted HR = 6.80 [95% CI 1.67–27.65]) and lower likelihood for good outcomes (propensity-adjusted HR = 0.30 [95% CI 0.10–0.94]) compared with prophylaxis only.

Conclusions

Our findings suggest the testable hypothesis that continuing ASMs in patients with aSAH with cEEG abnormalities does not improve functional outcomes. This hypothesis should be tested in prospective randomized studies.

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Funding

This study received research support from National Institutes of Health Grant K23NS114201 (to Dr. Zafar).

Author information

Author notes

  1. Drs. Elisabetta Patorno and M. Brandon Westover contributed equally as co-senior authors.

Authors and Affiliations

  1. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    Sahar F. Zafar, Eric S. Rosenthal, Muhammad Abubakar Ayub, Daniel B. Rubin & M. Brandon Westover

  2. Department of Neurosurgery, Amsterdam University Medical Centers, Amsterdam, Netherlands

    Eva N. Postma

  3. Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil

    Paula Sanches

  4. Department of Neurology, West Virginia University, Morgantown, WV, USA

    Subapriya Rajan

  5. Department of Neurology, Yale School of Medicine, New Haven, CT, USA

    Jennifer A. Kim

  6. Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Hang Lee & John Hsu

  7. Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA

    Aman B. Patel

  8. Department of Health Care Policy, Harvard Medical School, Harvard University, Boston, MA, USA

    John Hsu

  9. Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Elisabetta Patorno

Authors
  1. Sahar F. Zafar
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Contributions

Dr. Zafar contributed to the conception and design of the study, data collection and analysis, interpretation of data, drafting of the manuscript, and preparation of figures. Dr. Rosenthal contributed to data collection, interpretation of data, and revision of the manuscript for intellectual content. Dr. Postma contributed to data collection, interpretation of data, and revision of the manuscript for intellectual content. Dr. Sanches contributed to data collection, interpretation of data, and revision of the manuscript for intellectual content. Dr. Ayub contributed to data collection, interpretation of data, and revision of the manuscript for intellectual content. Dr. R contributed to data collection, interpretation of data, and revision of the manuscript for intellectual content. Dr. Kim contributed to data collection and interpretation and revision of the manuscript for intellectual content. Dr. Rubin contributed to data collection and interpretation and revision of the manuscript for intellectual content. Dr. Lee contributed statistical analysis, interpretation of data, and revision of the manuscript for intellectual content. Dr. Patel contributed to data collection and revision of the manuscript for intellectual content. Dr. Hsu contributed to study design, interpretation, and revision of the manuscript for intellectual content. Dr. Patorno contributed to study design, analysis, interpretation, and revision of the manuscript for intellectual content. Dr. Westover contributed to study design, analysis, interpretation of data, and revision of the manuscript for intellectual content. The final manuscript was approved by all authors.

Corresponding author

Correspondence to Sahar F. Zafar.

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Conflict of interest

Dr. Zafar is supported by National Institutes of Health grant K23NS114201. Dr. Zafar is a clinical neurophysiologist for Corticare, unrelated to this work. Dr. Rosenthal received consulting fees from UCB Pharma, Inc., and Ceribell, Inc., unrelated to this work. Dr. Postma reports no disclosures. Dr. Sanches reports no disclosures. Dr. Ayub reports no disclosures. Dr. R reports no disclosures. Dr. Kim reports no disclosure. Dr. Rubin has a pending patent for “System and Method for Determining Treatment Outcomes for Neurological Disorders Based on Functional Connectivity Parameters.” Dr. Lee reports no disclosures. Dr. Patel reports no disclosures. Dr. Hsu reports grants from the National Institutes of Health (P01AG032952 and R01AG062282). Dr. Patorno is supported by K08AG055670 from the National Institute on Aging and is the investigator of an investigator-initiated grant to the Brigham and Women’s Hospital from Boehringer Ingelheim, not related to this work. Dr. Westover is cofounder of Beacon Biosignals, unrelated to this work, and was supported by the Glenn Foundation for Medical Research and the American Federation for Aging Research (Breakthroughs in Gerontology Grant); the American Academy of Sleep Medicine (AASM Foundation Strategic Research Award); the Football Players Health Study (FPHS) at Harvard University; the Department of Defense through a subcontract from Moberg ICU Solutions, Inc.; and the National Institutes of Health (1R01NS102190, 1R01NS102574, 1R01NS107291, 1RF1AG064312).

Ethical approval/informed consent

This article adheres to ethical guidelines. The study was approved by the Institutional Review Board of Mass General Brigham. Informed consent was not required for this retrospective study.

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Zafar, S.F., Rosenthal, E.S., Postma, E.N. et al. Antiseizure Medication Treatment and Outcomes in Patients with Subarachnoid Hemorrhage Undergoing Continuous EEG Monitoring. Neurocrit Care 36, 857–867 (2022). https://doi.org/10.1007/s12028-021-01387-x

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