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Neurostereologic Lesion Volumes and Spreading Depolarizations in Severe Traumatic Brain Injury Patients: A Pilot Study

  • Nina Eriksen
  • Bente Pakkenberg
  • Egill Rostrup
  • David O. Okonkwo
  • Bruce Mathern
  • Lori A. Shutter
  • Anthony J. Strong
  • Johannes Woitzik
  • Clemens Pahl
  • Jens P. Dreier
  • Peter Martus
  • Martin J. Lauritzen
  • Martin Fabricius
  • Jed A. HartingsEmail author
Original Work
  • 43 Downloads

Abstract

Background

Spreading depolarizations (SDs) occur in 50–60% of patients after surgical treatment of severe traumatic brain injury (TBI) and are independently associated with unfavorable outcomes. Here we performed a pilot study to examine the relationship between SDs and various types of intracranial lesions, progression of parenchymal damage, and outcomes.

Methods

In a multicenter study, fifty patients (76% male; median age 40) were monitored for SD by continuous electrocorticography (ECoG; median duration 79 h) following surgical treatment of severe TBI. Volumes of hemorrhage and parenchymal damage were estimated using unbiased stereologic assessment of preoperative, postoperative, and post-ECoG serial computed tomography (CT) studies. Neurologic outcomes were assessed at 6 months by the Glasgow Outcome Scale-Extended.

Results

Preoperative volumes of subdural and subarachnoid hemorrhage, but not parenchymal damage, were significantly associated with the occurrence of SDs (P’s < 0.05). Parenchymal damage increased significantly (median 34 ml [Interquartile range (IQR) − 2, 74]) over 7 (5, 8) days from preoperative to post-ECoG CT studies. Patients with and without SDs did not differ in extent of parenchymal damage increase [47 ml (3, 101) vs. 30 ml (− 2, 50), P = 0.27], but those exhibiting the isoelectric subtype of SDs had greater initial parenchymal damage and greater increases than other patients (P’s < 0.05). Patients with temporal clusters of SDs (≥ 3 in 2 h; n = 10 patients), which included those with isoelectric SDs, had worse outcomes than those without clusters (P = 0.03), and parenchymal damage expansion also correlated with worse outcomes (P = 0.01). In multivariate regression with imputation, both clusters and lesion expansion were significant outcome predictors.

Conclusions

These results suggest that subarachnoid and subdural blood are important primary injury factors in provoking SDs and that clustered SDs and parenchymal lesion expansion contribute independently to worse patient outcomes. These results warrant future prospective studies using detailed quantification of TBI lesion types to better understand the relationship between anatomic and physiologic measures of secondary injury.

Keywords

Cortical spreading depression Brain contusion Subdural hematoma Subarachnoid hemorrhage Electroencephalography Computed tomography volume 

Notes

Acknowledgements

The authors thank Claus Holst at Frederiksberg Hospital, Copenhagen, Denmark, for statistical advice and Dr. Achala Vagal at the University of Cincinnati Medical Center, OH, USA, for radiologic guidance.

Author Contributions

NE performed stereologic assessments, analyzed data, and drafted the manuscript. BP and ER conceived the project, advised on design and methods, supervised CT analysis, and edited and approved the manuscript. DOO, DM, LAS, AJS, JW, and CP recruited subjects into the study, provided associated data, and edited and approved the manuscript. JPD performed data analysis, contributed to writing and interpretation, and edited and approved the manuscript. PM performed the primary statistical analyses and edited and approved the manuscript. MJL conceived and supervised the project, and edited and approved the manuscript. MF performed data analysis, contributed to writing, and edited and approved the manuscript. JAH recruited subjects into the study, organized data, prepared figures, and drafted and approved the manuscript.

Source of Support

Research was supported by the US Army CDMRP PH/TBI Research Program (Contract No. W81XWH-08-2-0016), the Agnes and Poul Friis´Foundation, the Aase and Ejnar Danielsens Foundation, the Dagmar Marshall’s Foundation, Deutsche Forschungsgemeinschaft (DFG DR 323/5-1), Bundesministerium für Bildung und Forschung (BMBF CSB 01 EO 0801) and FP7 No. 602150 CENTER-TBI.

Conflicts of Interest

The authors report no conflicts of interest concerning the materials or methods used in this study or the findings specified in this paper.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2019

Authors and Affiliations

  • Nina Eriksen
    • 1
  • Bente Pakkenberg
    • 1
    • 2
  • Egill Rostrup
    • 3
  • David O. Okonkwo
    • 9
  • Bruce Mathern
    • 8
  • Lori A. Shutter
    • 9
    • 10
    • 11
  • Anthony J. Strong
    • 6
  • Johannes Woitzik
    • 7
    • 14
  • Clemens Pahl
    • 6
  • Jens P. Dreier
    • 14
    • 15
    • 16
    • 17
    • 18
  • Peter Martus
    • 13
  • Martin J. Lauritzen
    • 4
    • 5
  • Martin Fabricius
    • 12
  • Jed A. Hartings
    • 19
    Email author
  1. 1.Research Laboratory for Stereology and NeuroscienceBispebjerg-Frederiksberg HospitalCopenhagenDenmark
  2. 2.Institute of Clinical Medicine, Faculty of HealthUniversity of CopenhagenCopenhagenDenmark
  3. 3.Department of Diagnostics, Glostrup Hospital and Centre for Healthy AgingUniversity of CopenhagenCopenhagenDenmark
  4. 4.Department of Clinical NeurophysiologyRigshospitaletCopenhagenDenmark
  5. 5.Department of Neuroscience and Center for Healthy AgingUniversity of CopenhagenCopenhagenDenmark
  6. 6.Department of Clinical NeuroscienceKing’s College HospitalLondonUK
  7. 7.Department of NeurosurgeryCharité University MedicineBerlinGermany
  8. 8.Department of NeurosurgeryMedical College of VirginiaRichmondUSA
  9. 9.Department of Neurological SurgeryUniversity of Pittsburgh School of MedicinePittsburghUSA
  10. 10.Department of NeurologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  11. 11.Department of Critical Care MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  12. 12.Department of Neurophysiology, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  13. 13.Institute for Clinical Epidemiology and Applied BiostatisticsUniversity of TübingenTübingenGermany
  14. 14.Center for Stroke Research BerlinCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthBerlinGermany
  15. 15.Department of NeurologyCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthBerlinGermany
  16. 16.Department of Experimental NeurologyCharité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthBerlinGermany
  17. 17.Bernstein Center for Computational Neuroscience BerlinBerlinGermany
  18. 18.Einstein Center for Neurosciences BerlinBerlinGermany
  19. 19.Department of NeurosurgeryUniversity of Cincinnati (UC) College of Medicine, and UC Gardner Neuroscience InstituteCincinnatiUSA

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