Nina Eriksen1, Bente Pakkenberg1,2, Egill Rostrup3, David O Okonkwo4, Bruce Mathern5, Lori A Shutter4,6,7, Anthony J Strong8, Johannes Woitzik9,10, Clemens Pahl8, Jens P Dreier10,11,12,13,14, Peter Martus15, Martin J Lauritzen16,17, Martin Fabricius18, Jed A Hartings19. 1. Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark. 2. Institute of Clinical Medicine, Faculty of Health, University of Copenhagen, Copenhagen, Denmark. 3. Department of Diagnostics, Glostrup Hospital and Centre for Healthy Aging, University of Copenhagen, Copenhagen, Denmark. 4. Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 5. Department of Neurosurgery, Medical College of Virginia, Richmond, VA, USA. 6. Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 7. Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 8. Department of Clinical Neuroscience, King's College Hospital, London, UK. 9. Department of Neurosurgery, Charité University Medicine, Berlin, Germany. 10. Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. 11. Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. 12. Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. 13. Bernstein Center for Computational Neuroscience Berlin, Berlin, Germany. 14. Einstein Center for Neurosciences Berlin, Berlin, Germany. 15. Institute for Clinical Epidemiology and Applied Biostatistics, University of Tübingen, Tübingen, Germany. 16. Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark. 17. Department of Neuroscience and Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark. 18. Department of Neurophysiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 19. Department of Neurosurgery, University of Cincinnati (UC) College of Medicine, and UC Gardner Neuroscience Institute, Cincinnati, OH, USA. jed.hartings@uc.edu.
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.
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.
Authors: Martin Lauritzen; Jens Peter Dreier; Martin Fabricius; Jed A Hartings; Rudolf Graf; Anthony John Strong Journal: J Cereb Blood Flow Metab Date: 2010-11-03 Impact factor: 6.200
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Authors: Samuel W Cramer; Isabela Peña Pino; Anant Naik; Danielle Carlson; Michael C Park; David P Darrow Journal: BMJ Open Date: 2022-07-13 Impact factor: 3.006