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January 22, 2019; 92 (4) Article

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, View ORCID ProfileJens P. Dreier
First published December 28, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006814
Nina Eriksen
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.
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Egill Rostrup
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.
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Martin Fabricius
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.
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Michael Scheel
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.
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Sebastian Major
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.
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Maren K.L. Winkler
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.
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Georg Bohner
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.
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Edgar Santos
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.
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Oliver W. Sakowitz
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.
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Vasilis Kola
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.
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Clemens Reiffurth
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.
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Jed A. Hartings
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.
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Peter Vajkoczy
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.
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Johannes Woitzik
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.
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Peter Martus
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.
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Martin Lauritzen
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.
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Bente Pakkenberg
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.
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Jens P. Dreier
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.
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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
Neurology Jan 2019, 92 (4) e326-e341; DOI: 10.1212/WNL.0000000000006814

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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.

Glossary

AC=
alternating current;
ACoA=
anterior communicating artery;
aSAH=
aneurysmal subarachnoid hemorrhage;
CI=
confidence interval;
COSBID=
Co-Operative Studies on Brain Injury Depolarizations;
DC=
direct current;
DCI=
delayed cerebral ischemia;
ECoG=
electrocorticography;
eGOS=
extended Glasgow Outcome Scale;
GCE=
global cerebral edema;
GCS=
Glasgow Coma Scale;
ICH=
intracerebral hemorrhage;
IVH=
intraventricular hemorrhage;
PTDDD=
peak total spreading depolarization–induced depression duration of a recording day;
SD=
spreading depolarization;
TBI=
traumatic brain injury;
TDDD=
total spreading depolarization–induced depression duration of a recording day;
WFNS=
World Federation of Neurosurgical Societies

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial page 161

  • Received April 16, 2018.
  • Accepted in final form September 11, 2018.
  • © 2018 American Academy of Neurology
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