Association of Epileptiform Abnormality on Electroencephalography with Development of Epilepsy After Acute Brain Injury

Abstract

Background/Objectives

Epileptiform abnormalities (EA) on continuous electroencephalography (cEEG) are associated with increased risk of acute seizures; however, data on their association with development of long-term epilepsy are limited. We aimed to investigate the association of EA in patients with acute brain injury (ABI): ischemic or hemorrhagic stroke, traumatic brain injury, encephalitis, or posterior reversible encephalopathy syndrome, and subsequent development of epilepsy.

Methods

This was a retrospective, single-center study of patients with ABI who had at least 6 hours of cEEG during the index admission between 1/1/2017 and 12/31/2018 and at least 12 months of follow-up. We compared patients with EAs; defined as lateralized periodic discharges (LPDs), lateralized rhythmic delta activity (LRDA), generalized periodic discharges (GPDs), and sporadic interictal epileptiform discharges (sIEDs) to patients without EAs on cEEG. The primary outcome was the new development of epilepsy, defined as the occurrence of spontaneous clinical seizures following hospital discharge. Secondary outcomes included time to development of epilepsy and use of anti-seizure medications (ASMs) at the time of last follow-up visit.

Results

One hundred and one patients with ABI met study inclusion criteria. Thirty-one patients (30.7%) had EAs on cEEG. The median (IQR) time to cEEG was 2 (1–5) days. During a median (IQR) follow-up period of 19.1 (16.2–24.3) months, 25.7% of patients developed epilepsy; the percentage of patients who developed epilepsy was higher in those with EAs compared to those without EAs (41.9% vs. 18.6%, p = 0.025). Patients with EAs were more likely to be continued on ASMs during follow-up compared to patients without EAs (67.7% vs. 38.6%, p = 0.009). Using multivariable Cox regression analysis, after adjusting for age, mental status, electrographic seizures on cEEG, sex, ABI etiology, and ASM treatment on discharge, patients with EAs had a significantly increased risk of developing epilepsy compared to patients without EA (hazard ratio 3.39; 95% CI 1.39–8.26; p = 0.007).

Conclusions

EAs on cEEG in patients with ABI are associated with a greater than three-fold increased risk of new-onset epilepsy. cEEG findings in ABI may therefore be a useful risk stratification tool for assessing long-term risk of seizures and serve as a biomarker for new-onset epilepsy.

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Funding

No grant support was received from any funding agency for this work in the public, commercial, or not-for-profit sectors.

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Contributions

Dr. Monica B. Dhakar has full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to the concept and design. Polly Kumari, Julia Lega, Denise F. Chen and Monica B. Dhakar contributed to the acquisition, analysis, or interpretation of data. Denise F. Chen and Monica B. Dhakar contributed to the drafting of the manuscript. All authors contributed to the critical revision of the manuscript for important intellectual content. Monica B. Dhakar contributed to the statistical analysis.

Corresponding author

Correspondence to Monica B. Dhakar.

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Ethical Approval

Emory University Institutional Review Board and Grady Memorial Hospital Research Oversight Committee approved the study and granted waiver of consent.

Conflict of interest

Denise F. Chen reports no disclosures. Polly Kumari reports no disclosures. Hiba A. Haider receives consultant support from Ceribell, Inc., author royalties from UpToDate, Inc. and Springer Publishing. Andres Rodriguez has participated in an education symposium sponsored by Neuropace Inc and has financial stake at Rodzi LLC. Julia Lega reports no disclosures. Monica B. Dhakar has received honoraria for consultancy from Adamas Pharmaceuticals and research support from Marinus Pharmaceuticals, UCB Biopharma for clinical trials. She also receives funding from NIH for work unrelated to this project.

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Chen, D.F., Kumari, P., Haider, H.A. et al. Association of Epileptiform Abnormality on Electroencephalography with Development of Epilepsy After Acute Brain Injury. Neurocrit Care (2021). https://doi.org/10.1007/s12028-020-01182-0

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Keywords

  • Acute brain injury
  • Seizures
  • Epileptiform abnormalities
  • Outcomes
  • Continuous electroencephalogram