Early focal brain injury after subarachnoid hemorrhage correlates with spreading depolarizations

Nina Eriksen; Egill Rostrup; Martin Fabricius; Michael Scheel; Sebastian Major; Maren K L Winkler; Georg Bohner; Edgar Santos; Oliver W Sakowitz; Vasilis Kola; Clemens Reiffurth; Jed A Hartings; Peter Vajkoczy; Johannes Woitzik; Peter Martus; Martin Lauritzen; Bente Pakkenberg; Jens P Dreier

doi:10.1212/WNL.0000000000006814

Early focal brain injury after subarachnoid hemorrhage correlates with spreading depolarizations

Neurology. 2019 Jan 22;92(4):e326-e341. doi: 10.1212/WNL.0000000000006814. Epub 2018 Dec 28.

Authors

Nina Eriksen¹, Egill Rostrup¹, Martin Fabricius¹, Michael Scheel¹, Sebastian Major¹, Maren K L Winkler¹, Georg Bohner¹, Edgar Santos¹, Oliver W Sakowitz¹, Vasilis Kola¹, Clemens Reiffurth¹, Jed A Hartings¹, Peter Vajkoczy¹, Johannes Woitzik¹, Peter Martus¹, Martin Lauritzen¹, Bente Pakkenberg¹, Jens P Dreier²

Affiliations

¹ From the Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital (N.E., B.P.), University of Copenhagen; Departments of Clinical Physiology and Nuclear Medicine (E.R.) and Clinical Neurophysiology (M.F., M.L.), Rigshospitalet, University of Copenhagen, Denmark; Department of Neuroradiology (M.S., G.B.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Center for Stroke Research Berlin (S.M., M.K.L.W., V.K., C.R., P.V., J.W., J.P.D.) and Departments of Experimental Neurology (S.M., C.R., J.P.D.), Neurology (S.M., J.P.D.), and Neurosurgery (P.V., J.W.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurosurgery (E.S., O.W.S.), University Hospital Heidelberg, Ruprecht Karls University Heidelberg; Neurosurgery Center Ludwigsburg-Heilbronn (O.W.S.), RKH Klinikum Ludwigsburg, Germany; UC Gardner Neuroscience Institute (J.A.H.) and Department of Neurosurgery (J.A.H.), University of Cincinnati (UC) College of Medicine, OH; Institute for Clinical Epidemiology and Applied Biostatistics (P.M.), University of Tübingen, Germany; Department of Neuroscience and Center for Healthy Aging, Panum Institute (M.L.), and Faculty of Health and Medical Sciences (B.P.), University of Copenhagen, Denmark; Bernstein Center for Computational Neuroscience Berlin (J.P.D.), Berlin; and Einstein Center for Neurosciences Berlin (J.P.D.), Germany.
² From the Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital (N.E., B.P.), University of Copenhagen; Departments of Clinical Physiology and Nuclear Medicine (E.R.) and Clinical Neurophysiology (M.F., M.L.), Rigshospitalet, University of Copenhagen, Denmark; Department of Neuroradiology (M.S., G.B.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Center for Stroke Research Berlin (S.M., M.K.L.W., V.K., C.R., P.V., J.W., J.P.D.) and Departments of Experimental Neurology (S.M., C.R., J.P.D.), Neurology (S.M., J.P.D.), and Neurosurgery (P.V., J.W.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Neurosurgery (E.S., O.W.S.), University Hospital Heidelberg, Ruprecht Karls University Heidelberg; Neurosurgery Center Ludwigsburg-Heilbronn (O.W.S.), RKH Klinikum Ludwigsburg, Germany; UC Gardner Neuroscience Institute (J.A.H.) and Department of Neurosurgery (J.A.H.), University of Cincinnati (UC) College of Medicine, OH; Institute for Clinical Epidemiology and Applied Biostatistics (P.M.), University of Tübingen, Germany; Department of Neuroscience and Center for Healthy Aging, Panum Institute (M.L.), and Faculty of Health and Medical Sciences (B.P.), University of Copenhagen, Denmark; Bernstein Center for Computational Neuroscience Berlin (J.P.D.), Berlin; and Einstein Center for Neurosciences Berlin (J.P.D.), Germany. jens.dreier@charite.de.

PMID: 30593517
DOI: 10.1212/WNL.0000000000006814

Abstract

Objective: To investigate whether spreading depolarization (SD)-related variables at 2 different time windows (days 1-4 and 5-8) after aneurysmal subarachnoid hemorrhage (aSAH) correlate with the stereologically determined volume of early focal brain injury on the preinterventional CT scan.

Methods: In this observational multicenter study of 54 patients, volumes of unaffected brain tissue, ventricles, cerebellum, aSAH, intracerebral hemorrhage, and focal parenchymal hypodensity were stereologically estimated. Patients were electrocorticographically monitored using subdural electrodes for 81.8 hours (median) (interquartile range: 70.6-90.5) during days 1-4 (n = 54) and for 75.9 (59.5-88.7) hours during days 5-8 (n = 51). Peak total SD-induced depression duration of a recording day (PTDDD) and peak numbers of (1) SDs, (2) isoelectric SDs, and (3) spreading depressions of a recording day were determined following the recommendations of the Co-Operative Studies on Brain Injury Depolarizations.

Results: Thirty-three of 37 patients with early focal brain injury (intracerebral hemorrhage and/or hypodensity) in contrast to 7 of 17 without displayed SDs during days 1-4 (sensitivity: 89% [95% confidence interval, CI: 75%-97%], specificity: 59% [CI: 33%-82%], positive predictive value: 83% [CI: 67%-93%], negative predictive value: 71% [CI: 42%-92%], Fisher exact test, p < 0.001). All 4 SD-related variables during days 1-4 significantly correlated with the volume of early focal brain injury (Spearman rank order correlations). A multiple ordinal regression analysis identified the PTDDD as the most important predictor.

Conclusions: Our findings suggest that early focal brain injury after aSAH is associated with early SDs and further support the notion that SDs are a biomarker of focal brain lesions.

Publication types

Multicenter Study

MeSH terms

Aged
Brain Injuries / etiology*
Cortical Spreading Depression / physiology*
Electrocorticography
Female
Humans
Male
Middle Aged
Subarachnoid Hemorrhage / complications*
Subarachnoid Hemorrhage / diagnostic imaging
Time Factors
Tomography Scanners, X-Ray Computed