Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group.
Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|2 Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.|3 Department of Experimental Neurology, Charité University Medicine Berlin, Berlin, Germany.
Jens P
JP
Dreier
4 Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark.
Martin
M
Fabricius
5 Neurovascular Research Laboratory, Department of Radiology, and Stroke Service and Neuroscience Intensive Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|6 Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cenk
C
Ayata
7 Department of Neurosurgery, Klinikum Ludwigsburg, Ludwigsburg, Germany.|8 Department of Neurosurgery, University Hospital, Heidelberg, Germany.
Oliver W
OW
Sakowitz
9 Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
C William
CW
Shuttleworth
10 Department of Neurology, University of Cologne, Cologne, Germany.|11 Multimodal Imaging of Brain Metabolism, Max-Planck-Institute for Metabolism Research, Cologne, Germany.
Christian
C
Dohmen
11 Multimodal Imaging of Brain Metabolism, Max-Planck-Institute for Metabolism Research, Cologne, Germany.
Rudolf
R
Graf
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|12 Department of Neurosurgery, Charité University Medicine Berlin, Berlin, Germany.
Peter
P
Vajkoczy
13 Department of Neurology, Neurocritical Care Unit, Medical University Innsbruck, Innsbruck, Austria.
Raimund
R
Helbok
14 Department of Neurosurgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Michiyasu
M
Suzuki
13 Department of Neurology, Neurocritical Care Unit, Medical University Innsbruck, Innsbruck, Austria.
Alois J
AJ
Schiefecker
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|2 Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.|3 Department of Experimental Neurology, Charité University Medicine Berlin, Berlin, Germany.
Sebastian
S
Major
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.
Maren Kl
MK
Winkler
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|3 Department of Experimental Neurology, Charité University Medicine Berlin, Berlin, Germany.
Eun-Jeung
EJ
Kang
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.
Denny
D
Milakara
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|3 Department of Experimental Neurology, Charité University Medicine Berlin, Berlin, Germany.
Ana I
AI
Oliveira-Ferreira
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|3 Department of Experimental Neurology, Charité University Medicine Berlin, Berlin, Germany.
Clemens
C
Reiffurth
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.
Gajanan S
GS
Revankar
14 Department of Neurosurgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Kazutaka
K
Sugimoto
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|12 Department of Neurosurgery, Charité University Medicine Berlin, Berlin, Germany.
Nora F
NF
Dengler
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|12 Department of Neurosurgery, Charité University Medicine Berlin, Berlin, Germany.
Nils
N
Hecht
1 5Department of Neurology and Rehabilitation Medicine, Neurocritical Care Division, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Brandon
B
Foreman
16 Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium.
Bart
B
Feyen
17 Department of Neurology, Rigshospitalet, Copenhagen, Denmark.
Daniel
D
Kondziella
4 Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark.
Christian K
CK
Friberg
4 Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark.
Henning
H
Piilgaard
6 Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Eric S
ES
Rosenthal
6 Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
M Brandon
MB
Westover
18 Department of Neurosurgery, University Hospital and University of Bonn, Bonn, Germany.
Anna
A
Maslarova
8 Department of Neurosurgery, University Hospital, Heidelberg, Germany.
Edgar
E
Santos
8 Department of Neurosurgery, University Hospital, Heidelberg, Germany.
Daniel
D
Hertle
8 Department of Neurosurgery, University Hospital, Heidelberg, Germany.
Renán
R
Sánchez-Porras
19 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Sharon L
SL
Jewell
20 Inserm U10128, CNRS UMR5292, Lyon Neuroscience Research Center, Team TIGER, Lyon, France.|21 Université Claude Bernard, Lyon, France.
Baptiste
B
Balança
22 Department of Neurosurgery, Goethe-University, Frankfurt, Germany.
Johannes
J
Platz
23 Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Jason M
JM
Hinzman
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.
Janos
J
Lückl
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|3 Department of Experimental Neurology, Charité University Medicine Berlin, Berlin, Germany.|24 Neuroscience Research Center, Charité University Medicine Berlin, Berlin, Germany.
Karl
K
Schoknecht
8 Department of Neurosurgery, University Hospital, Heidelberg, Germany.|25 Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
Michael
M
Schöll
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|26 Neurological Center, Segeberger Kliniken, Bad Segeberg, Germany.
Christoph
C
Drenckhahn
11 Multimodal Imaging of Brain Metabolism, Max-Planck-Institute for Metabolism Research, Cologne, Germany.
Delphine
D
Feuerstein
27 Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark.|28 Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Rigshospitalet, Copenhagen, Denmark.
Nina
N
Eriksen
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|29 Department of Neuroradiology, Charité University Medicine Berlin, Berlin, Germany.
Viktor
V
Horst
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|29 Department of Neuroradiology, Charité University Medicine Berlin, Berlin, Germany.
Julia S
JS
Bretz
29 Department of Neuroradiology, Charité University Medicine Berlin, Berlin, Germany.
Paul
P
Jahnke
29 Department of Neuroradiology, Charité University Medicine Berlin, Berlin, Germany.
Michael
M
Scheel
29 Department of Neuroradiology, Charité University Medicine Berlin, Berlin, Germany.
Georg
G
Bohner
27 Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark.
Egill
E
Rostrup
28 Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Rigshospitalet, Copenhagen, Denmark.|30 Faculty of Health and Medical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Bente
B
Pakkenberg
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|24 Neuroscience Research Center, Charité University Medicine Berlin, Berlin, Germany.
Uwe
U
Heinemann
31 Neurocritical Care, Columbia University College of Physicians & Surgeons, New York, NY, USA.
Jan
J
Claassen
32 Department of Neurosurgery, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Andrew P
AP
Carlson
10 Department of Neurology, University of Cologne, Cologne, Germany.|11 Multimodal Imaging of Brain Metabolism, Max-Planck-Institute for Metabolism Research, Cologne, Germany.
Christina M
CM
Kowoll
33 Department of Physiology and Cell Biology, Zlotowski Center for Neuroscience, Beer-Sheva, Israel.|34 Department of Neuroradiology, Soroka University Medical Center and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Svetlana
S
Lublinsky
33 Department of Physiology and Cell Biology, Zlotowski Center for Neuroscience, Beer-Sheva, Israel.|34 Department of Neuroradiology, Soroka University Medical Center and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Yoash
Y
Chassidim
34 Department of Neuroradiology, Soroka University Medical Center and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Ilan
I
Shelef
33 Department of Physiology and Cell Biology, Zlotowski Center for Neuroscience, Beer-Sheva, Israel.|35 Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, Canada.
Alon
A
Friedman
36 Department of Neurosurgery, University of Cologne, Cologne, Germany.
Gerrit
G
Brinker
36 Department of Neurosurgery, University of Cologne, Cologne, Germany.
Michael
M
Reiner
37 Department of Neurosurgery and Brain and Behavior Discovery Institute, Medical College of Georgia, Augusta, GA, USA.
Sergei A
SA
Kirov
38 Department of Biomedical & Molecular Sciences, Queen's University, Kingston, Canada.
R David
RD
Andrew
39 Department of Medical Physics and Informatics, Faculty of Medicine, and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
Eszter
E
Farkas
18 Department of Neurosurgery, University Hospital and University of Bonn, Bonn, Germany.
Erdem
E
Güresir
18 Department of Neurosurgery, University Hospital and University of Bonn, Bonn, Germany.
Hartmut
H
Vatter
40 Department of Neurology, University of Utah, Salt Lake City, UT, USA.
Lee S
LS
Chung
40 Department of Neurology, University of Utah, Salt Lake City, UT, USA.
K C
KC
Brennan
20 Inserm U10128, CNRS UMR5292, Lyon Neuroscience Research Center, Team TIGER, Lyon, France.|21 Université Claude Bernard, Lyon, France.
Thomas
T
Lieutaud
20 Inserm U10128, CNRS UMR5292, Lyon Neuroscience Research Center, Team TIGER, Lyon, France.|41 AniRA-Neurochem Technological Platform, Lyon, France.
Stephane
S
Marinesco
16 Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium.
Andrew Ir
AI
Maas
42 Department of Neurosurgery, Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Juan
J
Sahuquillo
43 Department of Physics, Humboldt University, Berlin, Germany.
Markus A
MA
Dahlem
44 Institute of Physiology I/Neurophysiology, Friedrich Schiller University Jena, Jena, Germany.
Frank
F
Richter
45 Department of Systems Neuroscience, Cajal Institute-CSIC, Madrid, Spain.
Oscar
O
Herreras
46 Department of Bioengineering, Imperial College London, London, UK.
Martyn G
MG
Boutelle
47 Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
David O
DO
Okonkwo
48 Department of Neurological Surgery, University of Miami, Miami, FL, USA.
M Ross
MR
Bullock
49 Hans Berger Department of Neurology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
Otto W
OW
Witte
50 Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
Peter
P
Martus
51 Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.|52 Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
Arn Mjm
AM
van den Maagdenberg
52 Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
Michel D
MD
Ferrari
53 Center for Image Sciences, University Medical Center Utrecht, Utrecht, the Netherlands.
Rick M
RM
Dijkhuizen
47 Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.|54 Department of Critical Care Medicine and Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Lori A
LA
Shutter
23 Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.|55 Mayfield Clinic, Cincinnati, OH, USA.
Norberto
N
Andaluz
56 Department of Spinal Surgery, St. Franziskus Hospital Cologne, Cologne, Germany.
André P
AP
Schulte
57 Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Brian
B
MacVicar
58 Lannister-Finn Corporation, Bryn Mawr, PA, USA.
Tomas
T
Watanabe
1 Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany.|12 Department of Neurosurgery, Charité University Medicine Berlin, Berlin, Germany.
Johannes
J
Woitzik
4 Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark.|59 Department of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Martin
M
Lauritzen
19 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Anthony J
AJ
Strong
23 Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.|55 Mayfield Clinic, Cincinnati, OH, USA.
Jed A
JA
Hartings
D001930:Brain Injuries / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy; D002560:Cerebrovascular Circulation; D013181:Cortical Spreading Depression / Q000502:physiology*; D003422:Critical Care / Q000379:methods*; D000069280:Electrocorticography; D066128:Gray Matter / Q000503:physiopathology*; D006801:Humans; D064926:Neurophysiological Monitoring / Q000379:methods*; D017410:Practice Guidelines as Topic; D020521:Stroke / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy
Spreading depolarization; anoxic depolarization; asphyxial depolarization; brain edema; brain trauma; cerebral blood flow; epilepsy; epileptogenesis; focal ischemia; global ischemia; intracerebral hemorrhage; neurocritical care; neuroprotection; neurovascular coupling; peri-infarct depolarization; spreading depression; spreading ischemia; subarachnoid hemorrhage; vasospasm