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The Relationship Between Seizures and Spreading Depolarizations in Patients with Severe Traumatic Brain Injury

  • Cortical Spreading Depolarization
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Abstract

Background

Both seizures and spreading depolarizations (SDs) are commonly detected using electrocorticography (ECoG) after severe traumatic brain injury (TBI). A close relationship between seizures and SDs has been described, but the implications of detecting either or both remain unclear. We sought to characterize the relationship between these two phenomena and their clinical significance.

Methods

We performed a post hoc analysis of a prospective observational clinical study of patients with severe TBI requiring neurosurgery at five academic neurotrauma centers. A subdural electrode array was placed intraoperatively and ECoG was recorded during intensive care. SDs, seizures, and high-frequency background characteristics were quantified offline using published standards and terminology. The primary outcome was the Glasgow Outcome Scale-Extended score at 6 months post injury.

Results

There were 138 patients with valid ECoG recordings; the mean age was 47 ± 19 years, and 104 (75%) were men. Overall, 2,219 ECoG-detected seizures occurred in 38 of 138 (28%) patients in a bimodal pattern, with peak incidences at 1.7–1.8 days and 3.8–4.0 days post injury. Seizures detected on scalp electroencephalography (EEG) were diagnosed by standard clinical care in only 18 of 138 (13%). Of 15 patients with ECoG-detected seizures and contemporaneous scalp EEG, seven (47%) had no definite scalp EEG correlate. ECoG-detected seizures were significantly associated with the severity and number of SDs, which occurred in 83 of 138 (60%) of patients. Temporal interactions were observed in 17 of 24 (70.8%) patients with both ECoG-detected seizures and SDs. After controlling for known prognostic covariates and the presence of SDs, seizures detected on either ECoG or scalp EEG did not have an independent association with 6-month functional outcome but portended worse outcome among those with clustered or isoelectric SDs.

Conclusions

In patients with severe TBI requiring neurosurgery, seizures were half as common as SDs. Seizures would have gone undetected without ECoG monitoring in 20% of patients. Although seizures alone did not influence 6-month functional outcomes in this cohort, they were independently associated with electrographic worsening and a lack of motor improvement following surgery. Temporal interactions between ECoG-detected seizures and SDs were common and held prognostic implications. Together, seizures and SDs may occur along a dynamic continuum of factors critical to the development of secondary brain injury. ECoG provides information integral to the clinical management of patients with TBI.

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References

  1. Taylor CA, Bell JM, Breiding MJ, Xu L. Traumatic brain injury–related emergency department visits, hospitalizations, and deaths—United States, 2007 and 2013. MMWR Surveill Summ. 2017;66(9):1.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Reddy GD, Gopinath S, Robertson C. Critical Care Management of the Patient with Traumatic Brain Injury. Semin Neurol. 2016;36(6):570–6.

    Article  PubMed  Google Scholar 

  3. Le Roux P, Menon DK, Citerio G, Vespa P, Bader MK, Brophy GM, et al. Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care : a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine. Intensive Care Med. 2014;40(9):1189–209.

  4. Herman ST, Abend NS, Bleck TP, Chapman KE, Drislane FW, Emerson RG, et al. Consensus statement on continuous EEG in critically ill adults and children, part I: indications. J Clin Neurophysiol. 2015;32(2):87–95.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Waziri A, Claassen J, Stuart RM, Arif H, Schmidt JM, Mayer SA, et al. Intracortical electroencephalography in acute brain injury. Ann Neurol. 2009;66(3):366–77.

    Article  PubMed  Google Scholar 

  6. Vespa P, Tubi M, Claassen J, Buitrago-Blanco M, McArthur D, Velazquez AG, et al. Metabolic crisis occurs with seizures and periodic discharges after brain trauma. Ann Neurol. 2016;79(4):579–90.

    Article  PubMed  Google Scholar 

  7. Dreier JP. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med. 2011;17(4):439–47.

    Article  CAS  PubMed  Google Scholar 

  8. Hartings JA. Spreading depolarization monitoring in neurocritical care of acute brain injury. Curr Opin Crit Care. 2017;23(2):94–102.

    Article  PubMed  Google Scholar 

  9. Drenckhahn C, Winkler MK, Major S, Scheel M, Kang EJ, Pinczolits A, et al. Correlates of spreading depolarization in human scalp electroencephalography. Brain. 2012;135(Pt 3):853–68.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hartings JA, Wilson JA, Hinzman JM, Pollandt S, Dreier JP, DiNapoli V, et al. Spreading depression in continuous electroencephalography of brain trauma. Ann Neurol. 2014;76(5):681–94.

    Article  PubMed  Google Scholar 

  11. Hartings JA, Andaluz N, Bullock MR, Hinzman JM, Mathern B, Pahl C, et al. Prognostic Value of Spreading Depolarizations in Patients With Severe Traumatic Brain Injury. JAMA Neurol. 2020;77(4):489–99.

    Article  PubMed  Google Scholar 

  12. Leao AAP. SPREADING DEPRESSION OF ACTIVITY IN THE CEREBRAL CORTEX. J Neurophysiol. 1944;7(6):359–90.

    Article  Google Scholar 

  13. Fabricius M, Fuhr S, Willumsen L, Dreier JP, Bhatia R, Boutelle MG, et al. Association of seizures with cortical spreading depression and peri-infarct depolarisations in the acutely injured human brain. Clin Neurophysiol. 2008;119(9):1973–84.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  16. Hablitz JJ, Heinemann U. Alterations in the microenvironment during spreading depression associated with epileptiform activity in the immature neocortex. Dev Brain Res. 1989;46(2):243–52.

    Article  CAS  Google Scholar 

  17. Mody I, Lambert J, Heinemann U. Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices. J Neurophysiol. 1987;57(3):869–88.

    Article  CAS  PubMed  Google Scholar 

  18. Avoli M, Drapeau C, Louvel J, Pumain R, Olivier A, Villemure JG. Epileptiform activity induced by low extracellular magnesium in the human cortex maintained in vitro. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 1991;30(4):589–96.

    Article  CAS  Google Scholar 

  19. Koroleva V, Bureš J. Cortical penicillin focus as a generator of repetitive spike-triggered waves of spreading depression in rats. Exp Brain Res. 1983;51(2):291–7.

    Article  CAS  PubMed  Google Scholar 

  20. Dreier JP, Isele T, Reiffurth C, Offenhauser N, Kirov SA, Dahlem MA, 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  PubMed  Google Scholar 

  21. Tamim I, Chung DY, de Morais AL, Loonen IC, Qin T, Misra A, et al. Spreading depression as an innate antiseizure mechanism. Nat Commun. 2021;12(1):1–15.

    Article  Google Scholar 

  22. Hinzman JM, DiNapoli VA, Mahoney EJ, Gerhardt GA, Hartings JA. Spreading depolarizations mediate excitotoxicity in the development of acute cortical lesions. Exp Neurol. 2015;267:243–53.

    Article  PubMed  Google Scholar 

  23. Hinzman JM, Wilson JA, Mazzeo AT, Bullock MR, Hartings JA. Excitotoxicity and metabolic crisis are associated with spreading depolarizations in severe traumatic brain injury patients. J Neurotrauma. 2016;33(19):1775–83.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Vespa P, McArthur D, Xu Y, Eliseo M, Etchepare M, Dinov I, et al. Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy. Neurology. 2010;75(9):792–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tubi MA, Lutkenhoff E, Blanco MB, McArthur D, Villablanca P, Ellingson B, et al. Early seizures and temporal lobe trauma predict post-traumatic epilepsy: a longitudinal study. Neurobiol Dis. 2019;123:115–21.

    Article  PubMed  Google Scholar 

  26. Lückl J, Lemale CL, Kola V, Horst V, Khojasteh U, Oliveira-Ferreira AI, et al. The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex. Brain. 2018;141(6):1734–52.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Hartings JA, Watanabe T, Bullock MR, Okonkwo DO, Fabricius M, Woitzik J, et al. Spreading depolarizations have prolonged direct current shifts and are associated with poor outcome in brain trauma. Brain. 2011;134(5):1529–40.

    Article  PubMed  Google Scholar 

  28. Helbok R, Hartings JA, Schiefecker A, Balança B, Jewel S, Foreman B, et al., editors. What should a clinician do when spreading depolarizations are observed in a patient? Neurocritical care; 2020: Springer.

  29. Dreier JP, Fabricius M, Ayata C, Sakowitz OW, William Shuttleworth C, Dohmen 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  PubMed  Google Scholar 

  30. Hirsch L, LaRoche S, Gaspard N, Gerard E, Svoronos A, Herman S, et al. American clinical neurophysiology society’s standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol. 2013;30(1):1–27.

    Article  CAS  PubMed  Google Scholar 

  31. Lee H, Mizrahi MA, Hartings JA, Sharma S, Pahren L, Ngwenya LB, et al. Continuous Electroencephalography After Moderate to Severe Traumatic Brain Injury. Crit Care Med. 2019;47(4):574–82.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wickham H, Chang W, Wickham MH. Package ‘ggplot2.’ Create Elegant Data Visualisations Using the Grammar of Graphics Version. 2016;2(1):1–189.

    Google Scholar 

  33. Team RC. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2020.

  34. Venables W, Ripley B, Hornik K, Gebhardt A. Package ‘Mass’. https://cran.r-project.org/web/packages/MASS/.

  35. Steyerberg EW, Mushkudiani N, Perel P, Butcher I, Lu J, McHugh GS, et al. Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics. PLoS Med. 2008;5(8):e165; discussion e.

  36. Struck AF, Tabaeizadeh M, Schmitt SE, Ruiz AR, Swisher CB, Subramaniam T, et al. Assessment of the validity of the 2HELPS2B score for inpatient seizure risk prediction. JAMA Neurol. 2020;77(4):500–7.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Hartings JA, Shuttleworth CW, Kirov SA, Ayata C, Hinzman JM, Foreman B, et al. The continuum of spreading depolarizations in acute cortical lesion development: Examining Leao’s legacy. J Cereb Blood Flow Metab. 2017;37(5):1571–94.

    Article  PubMed  Google Scholar 

  38. Claassen J, Perotte A, Albers D, Kleinberg S, Schmidt JM, Tu B, et al. Nonconvulsive seizures after subarachnoid hemorrhage: Multimodal detection and outcomes. Ann Neurol. 2013;74(1):53–64.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Vespa PM, Miller C, McArthur D, Eliseo M, Etchepare M, Hirt D, et al. Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis. Crit Care Med. 2007;35(12):2830.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Dreier JP, Reiffurth C. The stroke-migraine depolarization continuum. Neuron. 2015;86(4):902–22.

    Article  CAS  PubMed  Google Scholar 

  41. Li Z, Song Y, Xiao G, Gao F, Xu S, Wang M, et al. Bio-electrochemical microelectrode arrays for glutamate and electrophysiology detection in hippocampus of temporal lobe epileptic rats. Anal Biochem. 2018;550:123–31.

    Article  CAS  PubMed  Google Scholar 

  42. Zhou N, Rungta RL, Malik A, Han H, Wu DC, MacVicar BA. Regenerative glutamate release by presynaptic NMDA receptors contributes to spreading depression. J Cereb Blood Flow Metab. 2013;33(10):1582–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Revankar GS, Winkler MK, Major S, Schoknecht K, Heinemann U, Woitzik J, et al. Spreading depolarizations and seizures in clinical subdural electrocorticographic recordings. Seizures in Critical Care: Springer; 2017. p. 77–90.

  44. Revah O, Lasser-Katz E, Fleidervish IA, Gutnick MJ. The earliest neuronal responses to hypoxia in the neocortical circuit are glutamate-dependent. Neurobiol Dis. 2016;95:158–67.

    Article  CAS  PubMed  Google Scholar 

  45. Dietz RM, Weiss JH, Shuttleworth CW. Zn2+ influx is critical for some forms of spreading depression in brain slices. J Neurosci. 2008;28(32):8014–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Aiba I, Shuttleworth CW. Sustained NMDA receptor activation by spreading depolarizations can initiate excitotoxic injury in metabolically compromised neurons. J Physiol. 2012;590(22):5877–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Köhling R, Koch U, Hagemann G, Redecker C, Straub H, Speckmann E-J. Differential sensitivity to induction of spreading depression by partial disinhibition in chronically epileptic human and rat as compared to native rat neocortical tissue. Brain Res. 2003;975(1–2):129–34.

    Article  PubMed  Google Scholar 

  48. Allen NJ, Rossi DJ, Attwell D. Sequential release of GABA by exocytosis and reversed uptake leads to neuronal swelling in simulated ischemia of hippocampal slices. J Neurosci. 2004;24(15):3837–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Fabricius M, Jensen LH, Lauritzen M. Microdialysis of interstitial amino acids during spreading depression and anoxic depolarization in rat neocortex. Brain Res. 1993;612(1–2):61–9.

    Article  CAS  PubMed  Google Scholar 

  50. Jansen NA, Dehghani A, Linssen MM, Breukel C, Tolner EA, van den Maagdenberg AM. First FHM3 mouse model shows spontaneous cortical spreading depolarizations. Annals of clinical and translational neurology. 2020;7(1):132–8.

    Article  CAS  PubMed  Google Scholar 

  51. Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. The American Journal of Human Genetics. 2001;68(6):1327–32.

    Article  CAS  PubMed  Google Scholar 

  52. Escayg A, MacDonald BT, Meisler MH, Baulac S, Huberfeld G, An-Gourfinkel I, et al. Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+ 2. Nat Genet. 2000;24(4):343–5.

    Article  CAS  PubMed  Google Scholar 

  53. Gursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H, Bermpohl D, Jin H, et al. Cortical spreading depression activates and upregulates MMP-9. J Clin Investig. 2004;113(10):1447–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Sadeghian H, Lacoste B, Qin T, Toussay X, Rosa R, Oka F, et al. Spreading depolarizations trigger caveolin-1–dependent endothelial transcytosis. Ann Neurol. 2018;84(3):409–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Dreier JP, Lemale CL, Kola V, Friedman A, Schoknecht K. Spreading depolarization is not an epiphenomenon but the principal mechanism of the cytotoxic edema in various gray matter structures of the brain during stroke. Neuropharmacology. 2018;134:189–207.

    Article  CAS  PubMed  Google Scholar 

  56. Mestre H, Du T, Sweeney AM, Liu G, Samson AJ, Peng W, et al. Cerebrospinal fluid influx drives acute ischemic tissue swelling. Science. 2020;367(6483).

  57. Ullah G, Wei Y, Dahlem MA, Wechselberger M, Schiff SJ. The role of cell volume in the dynamics of seizure, spreading depression, and anoxic depolarization. PLoS computational biology. 2015;11(8):e1004414.

  58. Takizawa T, Qin T, Lopes de Morais A, Sugimoto K, Chung JY, Morsett L, et al. Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex. Journal of Cerebral Blood Flow & Metabolism. 2020;40(5):1117–31.

  59. Claassen J, Albers D, Schmidt JM, De Marchis GM, Pugin D, Falo CM, et al. Nonconvulsive seizures in subarachnoid hemorrhage link inflammation and outcome. Ann Neurol. 2014;75(5):771–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Winkler MK, Chassidim Y, Lublinsky S, Revankar GS, Major S, Kang EJ, et al. Impaired neurovascular coupling to ictal epileptic activity and spreading depolarization in a patient with subarachnoid hemorrhage: possible link to blood–brain barrier dysfunction. Epilepsia. 2012;53:22–30.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Maslarova A, Alam M, Reiffurth C, Lapilover E, Gorji A, Dreier JP. Chronically epileptic human and rat neocortex display a similar resistance against spreading depolarization in vitro. Stroke. 2011;42(10):2917–22.

    Article  PubMed  Google Scholar 

  62. Tomkins O, Friedman O, Ivens S, Reiffurth C, Major S, Dreier J, et al. Blood–brain barrier disruption results in delayed functional and structural alterations in the rat neocortex. Neurobiol Dis. 2007;25(2):367–77.

    Article  CAS  PubMed  Google Scholar 

  63. Wei Y, Ullah G, Schiff SJ. Unification of neuronal spikes, seizures, and spreading depression. J Neurosci. 2014;34(35):11733–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Launey Y, Fryer TD, Hong YT, Steiner LA, Nortje J, Veenith TV, et al. Spatial and Temporal Pattern of Ischemia and Abnormal Vascular Function Following Traumatic Brain Injury. JAMA Neurol. 2020;77(3):339–49.

    Article  PubMed  Google Scholar 

  65. Hartings JA, Li C, Hinzman JM, Shuttleworth CW, Ernst GL, Dreier JP, et al. Direct current electrocorticography for clinical neuromonitoring of spreading depolarizations. J Cereb Blood Flow Metab. 2017;37(5):1857–70.

    Article  PubMed  Google Scholar 

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Funding

This study was funded by the US Army Congressionally Directed Medical Research Program Psychological Health/Traumatic Brain Injury Research Program (W81XWH-08–2-0016). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Defense.

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Authors and Affiliations

  1. Department of Neurology and Rehabilitation Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, USA

    Brandon Foreman, Hyunjo Lee & Laura B. Ngwenya

  2. Collaborative for Research on Acute Neurological Injuries, University of Cincinnati, Cincinnati, OH, USA

    Brandon Foreman, Hyunjo Lee, Laura B. Ngwenya & Jed A. Hartings

  3. Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA

    David O. Okonkwo & Lori A. Shutter

  4. Department of Basic and Clinical Neuroscience, King’s College London, London, UK

    Anthony J. Strong

  5. Department of Intensive Care Medicine, King’s College Hospital, London, UK

    Clemens Pahl

  6. Department of Critical Care Medicine and Neurology, University of Pittsburgh, Pittsburgh, PA, USA

    Lori A. Shutter

  7. Center for Stroke Research Berlin, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany

    Jens P. Dreier

  8. Department of Experimental Neurology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany

    Jens P. Dreier

  9. Department of Neurology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany

    Jens P. Dreier

  10. Bernstein Center for Computational Neuroscience Berlin, Berlin, Germany

    Jens P. Dreier

  11. Einstein Center for Neurosciences Berlin, Berlin, Germany

    Jens P. Dreier

  12. Department of Neurosurgery, University of Cincinnati, Cincinnati, OH, USA

    Laura B. Ngwenya & Jed A. Hartings

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  1. Brandon Foreman
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  2. Hyunjo Lee
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Contributions

Brandon Foreman conceived and designed the analysis, contributed data or analysis tools, performed the analysis, and wrote the article. Hyunjo Lee contributed data or analysis tools and performed the analysis. David O. Okonkwo collected and contributed data and contributed to critical revisions of the manuscript. Anthony J. Strong collected and contributed data and contributed to critical revisions of the manuscript. Clemens Pahl collected and contributed data. Lori A. Shutter collected and contributed data and contributed to critical revisions of the manuscript. Jens P. Dreier conceived and designed the analysis, contributed data or analysis tools, and contributed to critical revisions of the manuscript. Laura B Ngwenya contributed to critical revisions of the manuscript. Jed A. Hartings conceived and designed the study and the analysis, contributed data or analysis tools, and wrote the article. The final manuscript was approved by all authors.

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Correspondence to Brandon Foreman.

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Conflicts of interest

Dr. Foreman reports grant funding from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (K23NS101123), the US Department of Defense (W81XWH1620020, W81XWH1920013), and the National Science Foundation (IIS1838730) and personal fees from UCB Pharma and the Micromed Group outside the submitted work. Dr. Dreier reports grants from the DFG Deutsche Forschungsgemeinschaft (German Research Council) (DFG DR 323/5–1 and DFG DR 323/10–1) and BMBF Bundesministerium fuer Bildung und Forschung (Era-Net Neuron EBio2 with funds from BMBF 0101EW2004).

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Foreman, B., Lee, H., Okonkwo, D.O. et al. The Relationship Between Seizures and Spreading Depolarizations in Patients with Severe Traumatic Brain Injury. Neurocrit Care 37 (Suppl 1), 31–48 (2022). https://doi.org/10.1007/s12028-022-01441-2

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