Skip to main content

Detection of Spreading Depolarization with Intraparenchymal Electrodes in the Injured Human Brain



Spreading depolarization events following ischemic and traumatic brain injury are associated with poor patient outcome. Currently, monitoring these events is limited to patients in whom subdural electrodes can be placed at open craniotomy. This study examined whether these events can be detected using intra-cortical electrodes, opening the way for electrode insertion via burr hole.


Animal work was carried out on adult Sprague–Dawley rats in a laboratory setting to investigate the feasibility of recording depolarization events. Subsequently, 8 human patients requiring craniotomy for traumatic brain injury or aneurysmal subarachnoid hemorrhage were monitored for depolarization events in an intensive care setting with concurrent strip (subdural) and depth (intra-parenchymal) electrode recordings.


(1) Depolarization events can be reliably detected from intra-cortically placed electrodes. (2) A reproducible slow potential change (SPC) waveform morphology was identified from intra-cortical electrodes on the depth array. (3) The depression of cortical activity known to follow depolarization events was identified consistently from both intra-cortical and sub-cortical electrodes on the depth array.


Intra-parenchymally sited electrodes can be used to consistently identify depolarization events in humans. This technique greatly extends the capability of monitoring for spreading depolarization events in injured patients, as electrodes can be sited without the need for craniotomy. The method provides a new investigative tool for the evaluation of the contribution of these events to secondary brain injury in human patients.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6


  1. For the purposes of this study no distinction was made between events of short and long duration [10] and all are referred to as “SD.”


  1. Faul M, Xu L, Wald MM, Coronado V, Dellinger AM. Traumatic brain injury in the United States: National estimates of prevalence and incidence, 2002–2006. Inj Prev. 2010;16:A268.

    Article  Google Scholar 

  2. Coronado VG, Xu L, Basavaraju SV, et al. Surveillance for traumatic brain injury-related deaths–United States, 1997–2007. MMWR Surveill Summ. 2011;60:1–32.

    PubMed  Google Scholar 

  3. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation. 2012;125:e2–220.

    PubMed  Article  Google Scholar 

  4. Kurland D, Hong C, Aarabi B, Gerzanich V, Simard JM. Hemorrhagic progression of a contusion after traumatic brain injury: a review. J Neurotrauma. 2012;29:19–31.

    PubMed  Article  Google Scholar 

  5. von Oettingen G, Bergholt B, Gyldensted C, Astrup J. Blood flow and ischemia within traumatic cerebral contusions. Neurosurgery. 2002;50:781–8 discussion 788–790.

    Article  Google Scholar 

  6. Holmin S, Soderlund J, Biberfeld P, Mathiesen T. Intracerebral inflammation after human brain contusion. Neurosurgery. 1998;42:291–8 discussion 298–299.

    CAS  PubMed  Article  Google Scholar 

  7. Obrenovitch TP, Urenjak J. Is high extracellular glutamate the key to excitotoxicity in traumatic brain injury? J Neurotrauma. 1997;14:677–98.

    CAS  PubMed  Article  Google Scholar 

  8. Vespa P, Bergsneider M, Hattori N, et al. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab. 2005;25:763–74.

    CAS  PubMed  Article  Google Scholar 

  9. Menon DK. Procrustes, the traumatic penumbra, and perfusion pressure targets in closed head injury. Anesthesiology. 2003;98:805–7.

    PubMed  Article  Google Scholar 

  10. 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;32:203–12.

    PubMed  Article  Google Scholar 

  11. Strong AJ, Boutelle MG, Vespa PM, Bullock MR, Bhatia R, Hashemi P. Treatment of critical care patients with substantial acute ischemic or traumatic brain injury. Crit Care Med. 2005;33:2147–9 author reply 2149.

    PubMed  Article  Google Scholar 

  12. Dohmen C, Sakowitz OW, Fabricius M, et al. Spreading depolarizations occur in human ischemic stroke with high incidence. Ann Neurol. 2008;63:720–8.

    PubMed  Article  Google Scholar 

  13. Lauritzen M, Dreier JP, Fabricius M, Hartings JA, Graf R, Strong AJ. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab. 2011;31:17–35.

    PubMed  Article  Google Scholar 

  14. Dreier JP, Major S, Manning A, et al. Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage. Brain. 2009;132:1866–81.

    PubMed  Article  Google Scholar 

  15. Takano T, Tian GF, Peng W, et al. Cortical spreading depression causes and coincides with tissue hypoxia. Nat Neurosci. 2007;10:754–62.

    CAS  PubMed  Article  Google Scholar 

  16. Feuerstein D, Manning A, Hashemi P, et al. Dynamic metabolic response to multiple spreading depolarizations in patients with acute brain injury: an online microdialysis study. J Cereb Blood Flow Metab. 2010;30:1343–55.

    CAS  PubMed  Article  Google Scholar 

  17. Hartings JA, Bullock MR, Okonkwo DO, et al. Spreading depolarisations and outcome after traumatic brain injury: a prospective observational study. Lancet Neurol. 2011;10:1058–64.

    PubMed  Article  Google Scholar 

  18. Strong AJ, Fabricius M, Boutelle MG, et al. Spreading and synchronous depressions of cortical activity in acutely injured human brain. Stroke. 2002;33:2738–43.

    PubMed  Article  Google Scholar 

  19. Fabricius M, Fuhr S, Bhatia R, et al. Cortical spreading depression and peri-infarct depolarization in acutely injured human cerebral cortex. Brain. 2006;129:778–90.

    PubMed  Article  Google Scholar 

  20. Kudo C, Nozari A, Moskowitz MA, Ayata C. The impact of anesthetics and hyperoxia on cortical spreading depression. Exp Neurol. 2008;212:201–6.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  21. Hartings JA, Watanabe T, Dreier JP, Major S, Vendelbo L, Fabricius M. Recovery of slow potentials in AC-coupled electrocorticography: application to spreading depolarizations in rat and human cerebral cortex. J Neurophysiol. 2009;102:2563–75.

    PubMed  Article  Google Scholar 

  22. Nakamura H, Strong AJ, Dohmen C, et al. Spreading depolarizations cycle around and enlarge focal ischaemic brain lesions. Brain. 2010;133:1994–2006.

    PubMed  Article  Google Scholar 

  23. Hartings JA, Watanabe T, Bullock MR, et al. Spreading depolarizations have prolonged direct current shifts and are associated with poor outcome in brain trauma. Brain. 2011;134:1529–40.

    PubMed  Article  Google Scholar 

  24. Dreier JP, Major S, Manning A, et al. Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage. Brain. 2009;132:1866–81.

    PubMed  Article  Google Scholar 

  25. Stuart RM, Waziri A, Weintraub D, et al. Intracortical EEG for the detection of vasospasm in patients with poor-grade subarachnoid hemorrhage. Neurocrit Care. 2010;13:355–8.

    PubMed  Article  Google Scholar 

  26. Waziri A, Claassen J, Stuart RM, et al. Intracortical electroencephalography in acute brain injury. Ann Neurol. 2009;66:366–77.

    PubMed  Article  Google Scholar 

  27. Woitzik J, Hecht N, Pinczolits A, et al. Propagation of cortical spreading depolarization in the human cortex after malignant stroke. Neurology. 2013;80:1095–102.

    PubMed  Article  Google Scholar 

  28. Valadka AB, Robertson CS. Surgery of cerebral trauma and associated critical care. Neurosurgery. 2007;61:203–20 discussion 220–201.

    PubMed  Article  Google Scholar 

  29. Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99:4–9.

    CAS  PubMed  Article  Google Scholar 

  30. Hertle DN, Dreier JP, Woitzik J, et al. Effect of analgesics and sedatives on the occurrence of spreading depolarizations accompanying acute brain injury. Brain. 2012;135:2390–8.

    PubMed  Article  Google Scholar 

Download references


This work was funded in part by a Wellcome Trust/Department of Health Healthcare Innovation Challenge Fund (Grant HICF—1010-080) and in part by the U.S. Army CDMRP PH/TBI Research Program (contract number W81XWH-08-2-0016) and the Mayfield Education and Research Foundation. We thank Chi Leng Leong for help with the figures. All animal work was carried out at the University of Cincinnati. All human clinical investigations were carried out at Kings College Hospital, London, UK.

Conflict of interest

Toby Jeffcote, Jason M Hinzman, Sharon L Jewell, Robert M Learney, Clemens Pahl, Christos Tolias, Daniel C Walsh, Agnieszka Zakrzewska, Martin E Fabricius, Anthony J Strong, Jed A Hartings, and Martyn G Boutelle declare that they have no conflict of interest.

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Jed A. Hartings or Martyn G. Boutelle.

Additional information

Jed A. Hartings and Martyn G. Boutelle contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 134 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jeffcote, T., Hinzman, J.M., Jewell, S.L. et al. Detection of Spreading Depolarization with Intraparenchymal Electrodes in the Injured Human Brain. Neurocrit Care 20, 21–31 (2014).

Download citation

  • Published:

  • Issue Date:

  • DOI:


  • Cortical spreading depolarization
  • Traumatic brain injury
  • Secondary brain injury