Burden of Epileptiform Activity Predicts Discharge Neurologic Outcomes in Severe Acute Ischemic Stroke

Abstract

Background/Objectives

Clinical seizures following acute ischemic stroke (AIS) appear to contribute to worse neurologic outcomes. However, the effect of electrographic epileptiform abnormalities (EAs) more broadly is less clear. Here, we evaluate the impact of EAs, including electrographic seizures and periodic and rhythmic patterns, on outcomes in patients with AIS.

Methods

This is a retrospective study of all patients with AIS aged ≥ 18 years who underwent at least 18 h of continuous electroencephalogram (EEG) monitoring at a single center between 2012 and 2017. EAs were classified according to American Clinical Neurophysiology Society (ACNS) nomenclature and included seizures and periodic and rhythmic patterns. EA burden for each 24-h epoch was defined using the following cutoffs: EA presence, maximum daily burden < 10% versus > 10%, maximum daily burden < 50% versus > 50%, and maximum daily burden using categories from ACNS nomenclature (“rare” < 1%; “occasional” 1–9%; “frequent” 10–49%; “abundant” 50–89%; “continuous” > 90%). Maximum EA frequency for each epoch was dichotomized into ≥ 1.5 Hz versus < 1.5 Hz. Poor neurologic outcome was defined as a modified Rankin Scale score of 4–6 (vs. 0–3 as good outcome) at hospital discharge.

Results

One hundred and forty-three patients met study inclusion criteria. Sixty-seven patients (46.9%) had EAs. One hundred and twenty-four patients (86.7%) had poor outcome. On univariate analysis, the presence of EAs (OR 3.87 [1.27–11.71], p = 0.024) and maximum daily burden > 10% (OR 12.34 [2.34–210], p = 0.001) and > 50% (OR 8.26 [1.34–122], p = 0.035) were associated with worse outcomes. On multivariate analysis, after adjusting for clinical covariates (age, gender, NIHSS, APACHE II, stroke location, stroke treatment, hemorrhagic transformation, Charlson comorbidity index, history of epilepsy), EA presence (OR 5.78 [1.36–24.56], p = 0.017), maximum daily burden > 10% (OR 23.69 [2.43–230.7], p = 0.006), and maximum daily burden > 50% (OR 9.34 [1.01–86.72], p = 0.049) were associated with worse outcomes. After adjusting for covariates, we also found a dose-dependent association between increasing EA burden and increasing probability of poor outcomes (OR 1.89 [1.18–3.03] p = 0.009). We did not find an independent association between EA frequency and outcomes (OR: 4.43 [.98–20.03] p = 0.053). However, the combined effect of increasing EA burden and frequency ≥ 1.5 Hz (EA burden * frequency) was significantly associated with worse outcomes (OR 1.64 [1.03–2.63] p = 0.039).

Conclusions

Electrographic seizures and periodic and rhythmic patterns in patients with AIS are associated with worse outcomes in a dose-dependent manner. Future studies are needed to assess whether treatment of this EEG activity can improve outcomes.

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Funding

This work was supported by NIH-NINDSK23NS114201 (SFZ) and research support from SAGE therapeutics (SFZ, MBW, ESR).

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Affiliations

Authors

Contributions

MT, SFZ, ESR, MBW conceptualized and designed the study, performed data collection and management, performed analysis, and drafted the original, revised, and final manuscript. HN, MS, HS, JJ,FJ,SK,EB, ME, JG, VJM. MG, YS performed data collection and management, reviewed and revised the manuscript. AJC conceptualized and designed the study and reviewed and revised the manuscript.

Corresponding author

Correspondence to Sahar F. Zafar.

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Conflict of interest

Dr. Tabaeizadeh, Dr. Aboul Nour, Dr. Shoukat, Dr. Sun, Dr. Javed, Dr. Kassa, Dr. Edhi, Dr. Bordbar, J. Gallagher, V Moura, M. Ghanta, YP Shao, Dr. Jin, Dr. Cole, Dr. Rosenthal reports grants from Sage Therapeutics, during the conduct of the study, Dr. Westover reports grants from Sage Therapeutics, grants from NIH-NINDS 1K23NS090900, grants from NIH-NINDS1R01NS102190, during the conduct of the study; Dr. Zafar reports grants from Sage Therapeutics, grants from NIH-NINDS 1K23NS114201 during the conduct of the study.

Ethical approval/Informed consent

This manuscript adheres to ethical guidelines. The study was conducted under a protocol approved by the institutional review board. Informed consent was not required for this retrospective study.

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Tabaeizadeh, M., Aboul Nour, H., Shoukat, M. et al. Burden of Epileptiform Activity Predicts Discharge Neurologic Outcomes in Severe Acute Ischemic Stroke. Neurocrit Care 32, 697–706 (2020). https://doi.org/10.1007/s12028-020-00944-0

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Keywords

  • Ischemic stroke
  • Seizures
  • Epileptiform abnormalities
  • Continuous electroencephalogram
  • Outcomes