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Cortical Spreading Depolarizations and Clinically Measured Scalp EEG Activity After Aneurysmal Subarachnoid Hemorrhage and Traumatic Brain Injury



Spreading depolarizations (SDs) are associated with worse outcome following subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), but gold standard detection requires electrocorticography with a subdural strip electrode. Electroencephalography (EEG) ictal–interictal continuum abnormalities are associated with poor outcomes after TBI and with both delayed cerebral ischemia (DCI) and poor outcomes after SAH. We examined rates of SD detection in patients with SAH and TBI with intraparenchymal and subdural strip electrodes and assessed which continuous EEG (cEEG) measures were associated with intracranially quantified SDs.


In this single-center cohort, we included patients with SAH and TBI undergoing ≥ 24 h of interpretable intracranial monitoring via eight-contact intraparenchymal or six-contact subdural strip platinum electrodes or both. SDs were rated according to established consensus criteria and compared with cEEG findings rated according to the American Clinical Neurophysiology Society critical care EEG monitoring consensus criteria: lateralized rhythmic delta activity, generalized rhythmic delta activity, lateralized periodic discharges, generalized periodic discharges, any ictal–interictal continuum, or a composite scalp EEG tool for seizure risk estimation: the 2HELPS2B score. Among patients with SAH, cEEG was assessed for validated DCI biomarkers: new or worsening epileptiform abnormalities and new background deterioration.


Over 6 years, SDs were recorded in 5 (18%) of 28 patients recorded with intraparenchymal electrodes and 4 (40%) of 10 patients recorded with subdural strip electrodes. There was no significant association between occurrence of SDs and day 1 cEEG findings (American Clinical Neurophysiology Society main terms lateralized periodic discharges, generalized periodic discharges, lateralized rhythmic delta activity, or seizures, individually or in combination). After SAH, established cEEG DCI predictors were not associated with SDs.


Intraparenchymal recordings yielded low rates of SD, and documented SDs were not associated with ictal–interictal continuum abnormalities or other cEEG DCI predictors. Identifying scalp EEG correlates of SD may require training computational EEG analytics and use of gold standard subdural strip electrocorticography recordings.

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  1. Hartings JA, Strong AJ, Fabricius M, et al. Spreading depolarizations and late secondary insults after traumatic brain injury. J Neurotrauma. 2009;26(11):1857–66.

    Article  Google Scholar 

  2. Roos YBWEM, De Haan RJ, Beenen LFM, et al. Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in The Netherlands. J Neurol Neurosurg Psychiat. 2000;68(3):337–41.

    Article  CAS  Google Scholar 

  3. Lantigua H, Ortega-Gutierrez S, Schmidt JM, et al. Subarachnoid hemorrhage: who dies, and why? Crit Care. 2015;19(1):309.

    Article  Google Scholar 

  4. Maher M, Schweizer TA, Macdonald RL. Treatment of spontaneous subarachnoid hemorrhage: guidelines and gaps. Stroke. 2020;51(4):1326–32.

    Article  Google Scholar 

  5. Sugimoto K, Chung DY. spreading depolarizations and subarachnoid hemorrhage. Neurotherapeutics. 2020;17(2):497–510.

    Article  Google Scholar 

  6. Woitzik J, Dreier JP, Hecht N, et al. Delayed cerebral ischemia and spreading depolarization in absence of angiographic vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2012;32(2):203–12.

    Article  Google Scholar 

  7. Sánchez-Porras R, Zheng Z, Santos E, et al. The role of spreading depolarization in subarachnoid hemorrhage. Eur J Neurol. 2013;20(8):1121–7.

    Article  Google Scholar 

  8. Chung DY, Oka F, Ayata C. Spreading depolarizations: a therapeutic target against delayed cerebral ischemia after subarachnoid hemorrhage. J Clin Neurophysiol. 2016;33(3):196–202.

    Article  Google Scholar 

  9. Bosche B, Graf R, Ernestus RI, et al. Recurrent spreading depolarizations after subarachnoid hemorrhage decreases oxygen availability in human cerebral cortex. Ann Neurol. 2010;67(5):607–17.

    Article  Google Scholar 

  10. Kramer DR, Fujii T, Ohiorhenuan I, Liu CY. Cortical spreading depolarization: pathophysiology, implications, and future directions. J Clin Neurosci. 2016;24:22–7.

    Article  Google Scholar 

  11. Carlson, A.P., Abbas, M., Alunday, R.L., Qeadan, F.Shuttleworth, C.W. 2018 Spreading depolarization in acute brain injury inhibited by ketamine: a prospective, randomized, multiple crossover trial. J Neurosurg 1–7.

  12. Sinha S, Hudgins E, Schuster J, Balu R. Unraveling the complexities of invasive multimodality neuromonitoring. Neurosurg Focus FOC. 2017;43(5):E4.

    Article  Google Scholar 

  13. Brinjikji W, Lanzino G, Rabinstein AA, Kallmes DF, Cloft HJ. Age-related trends in the treatment and outcomes of ruptured cerebral aneurysms: a study of the nationwide inpatient sample 2001–2009. AJNR Am J Neuroradiol. 2013;34(5):1022–7.

    Article  CAS  Google Scholar 

  14. Jeffcote, T., Hinzman, J.M., Jewell, S.L., et al. Detection of Spreading Depolarization with Intraparenchymal Electrodes in the Injured Human Brain. 2013.

  15. Kim JA, Rosenthal ES, Biswal S, et al. Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage. Clin Neurophysiol. 2017;128(6):1091–9.

    Article  CAS  Google Scholar 

  16. Vespa P, Tubi M, Claassen J, et al. Metabolic crisis occurs with seizures and periodic discharges after brain trauma. Ann Neurol. 2016;79(4):579–90.

    Article  Google Scholar 

  17. Dreier JP, Isele T, Reiffurth C, et al. Is spreading depolarization characterized by an abrupt, massive release of gibbs free energy from the human brain cortex? Neuroscientist. 2013;19(1):25–42.

    Article  Google Scholar 

  18. Struck AF, Westover MB, Hall LT, et al. Metabolic correlates of the ictal-interictal continuum: FDG-PET during continuous EEG. Neurocrit Care. 2016;24(3):324–31.

    Article  CAS  Google Scholar 

  19. Dreier JP, Fabricius M, Ayata C, et al. Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group. J Cereb Blood Flow Metab. 2017;37(5):1595–625.

    Article  Google Scholar 

  20. Dreier JP, Major S, Pannek HW, et al. Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex. Brain. 2012;135(Pt 1):259–75.

    Article  Google Scholar 

  21. Muniz CF, Shenoy VA, O’Connor KL, et al. Clinical development and implementation of an institutional guideline for prospective EEG monitoring and reporting of delayed cerebral ischemia. J Clin Neurophysiol. 2016;33(3):217–26.

    Article  Google Scholar 

  22. Hirsch LJ, Fong MWK, Leitinger M, et al. American clinical neurophysiology society’s standardized critical Care EEG terminology: 2021 version. J Clin Neurophysiol. 2021;38(1):1–29.

    Article  Google Scholar 

  23. Rosenthal ES, Biswal S, Zafar SF, et al. Continuous electroencephalography predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective study of diagnostic accuracy. Ann Neurol. 2018;83(5):958–69.

    Article  Google Scholar 

  24. Struck AF, Ustun B, Ruiz AR, et al. Association of an electroencephalography-based risk score with seizure probability in hospitalized patients. JAMA Neurol. 2017;74(12):1419–24.

    Article  Google Scholar 

  25. Moffet, E.W., Subramaniam, T., Hirsch, L.J., et al. Validation of the 2HELPS2B Seizure Risk Score in Acute Brain Injury Patients. Neurocritical Care 2020.

  26. Vergouwen MDI, Vermeulen M, van Gijn J, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke A J Cerebral Circulat. 2010;41(10):2391–5.

    Article  Google Scholar 

  27. Hartings, J.A., Andaluz, N., Bullock, M.R., et al. Prognostic Value of Spreading Depolarizations in Patients with Severe Traumatic Brain Injury. JAMA Neurology 2019.

  28. Dreier JP, Woitzik J, Fabricius M, et al. Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations. Brain. 2006;129(12):3224–37.

    Article  Google Scholar 

  29. Eickhoff M, Kovac S, Shahabi P, et al. Spreading depression triggers ictaform activity in partially disinhibited neuronal tissues. Exp Neurol. 2014;253:1–15.

    Article  Google Scholar 

  30. Drenckhahn C, Winkler MK, Major S, et al. Correlates of spreading depolarization in human scalp electroencephalography. Brain. 2012;135(Pt 3):853–68.

    Article  Google Scholar 

  31. Chamanzar, A., George, S., Venkatesh, P., et al. An algorithm for automated, noninvasive detection of cortical spreading depolarizations based on EEG simulations. IEEE Transactions on Biomedical Engineering 2019 66(4).

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This work was supported by National Institutes of Health National Institute of Neurological Disorders and Stroke Grants 1K23NS105950 (ESR), KL2TR002542 (DYC), and K08NS112601 (DYC); United States Army Grant W81XWH-BAA-15-1 (ESR); the American Heart Association (18POST34030369; DYC); the Andrew David Heitman Foundation (ESR, ABP, DYC); the Aneurysm and AVM Foundation (DYC); and the Brain Aneurysm Foundation’s Timothy P. Susco and Andrew David Heitman Foundation Chairs of Research (DYC).

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Authors and Affiliations



SS conceptualized the study design; conducted the data acquisition, analysis, and interpretation; and drafted and revised the manuscript. ABP, CJS, BLG, and JSS conceptualized the study design, performed intracranial monitoring, and contributed to drafting the manuscript. DYC contributed to the study design and Fig. modeling and conducted the data review, analysis, and interpretation, as well as manuscript revisions. ST contributed to data review and manuscript revisions. ESR conceptualized the study design and performed data analysis and interpretation, as well as manuscript drafting and revisions. DYC and ESR contributed equally to this work.

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Correspondence to Eric S. Rosenthal.

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Conflicts of interest

SS has nothing to disclose. ST has nothing to disclose. DYC has nothing to disclose. BLG has nothing to disclose. ABP has nothing to disclose. CJS has nothing to disclose. JSS has nothing to disclose. ESR reports consulting fees from UCB Pharma, Inc. and Ceribell, Inc.; medicolegal consultation; funding from National Institutes of Health National Institute of Neurological Disorders and Stroke grant 1K23NS105950 and United States Army grant W81XWH-BAA-15–1. ESR’s institution is a subcontract to Moberg ICU Solutions, whose clinical monitoring equipment was used in clinical practice in this patient population.

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The authors adhered to ethical guidelines, and this study was approved by the institutional review board.

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This article is part of the collection “Spreading Cortical Depolarization”.

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Sivakumar, S., Tsetsou, S., Patel, A.B. et al. Cortical Spreading Depolarizations and Clinically Measured Scalp EEG Activity After Aneurysmal Subarachnoid Hemorrhage and Traumatic Brain Injury. Neurocrit Care 37 (Suppl 1), 49–59 (2022).

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