title: Early brain injury after aneurysmal subarachnoid hemorrhage: a multimodal neuromonitoring study.
abstract: BACKGROUND
  There is a substantial amount of evidence from animal models that early brain injury (EBI) may play an important role for secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Cerebral microdialysis (CMD) allows online measurement of brain metabolites, including the pro-inflammatory cytokine interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9), which is indicative for disruption of the blood-brain barrier.
  
  
  METHODS
  Twenty-six consecutive poor-grade aSAH patients with multimodal neuromonitoring were analyzed for brain hemodynamic and metabolic changes, including CMD-IL-6 and CMD-MMP-9 levels. Statistical analysis was performed by using a generalized estimating equation with an autoregressive function.
  
  
  RESULTS
  The baseline cerebral metabolic profile revealed brain metabolic distress and an excitatory response which improved over the following 5 days (P <0.001). Brain tissue hypoxia (brain tissue oxygen tension of less than 20 mm Hg) was common (more than 60% of patients) in the first 24 hours of neuromonitoring and improved thereafter (P <0.05). Baseline CMD-IL-6 and CMD-MMP-9 levels were elevated in all patients (median = 4,059 pg/mL, interquartile range (IQR) = 1,316 to 12,456 pg/mL and median = 851 pg/mL, IQR = 98 to 25,860 pg/mL) and significantly decreased over days (P <0.05). A higher pro-inflammatory response was associated with the development of delayed cerebral ischemia (P = 0.04), whereas admission disease severity and early brain tissue hypoxia were associated with higher CMD-MMP-9 levels (P <0.03). Brain metabolic distress and increased IL-6 levels were associated with poor functional outcome (modified Rankin Scale of more than 3, P ≤0.01). All models were adjusted for probe location, aneurysm securing procedure, and disease severity as appropriate.
  
  
  CONCLUSIONS
  Multimodal neuromonitoring techniques allow insight into pathophysiologic changes in the early phase after aSAH. The results may be used as endpoints for future interventions targeting EBI in poor-grade aSAH patients.
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstreet 35, 6020, Innsbruck, Austria. raimund.helbok@uki.at.
authors.forename: Raimund
authors.initials: R
authors.lastname: Helbok
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstreet 35, 6020, Innsbruck, Austria. alois.schiefecker@uki.at.
authors.forename: Alois Josef
authors.initials: AJ
authors.lastname: Schiefecker
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstreet 35, 6020, Innsbruck, Austria. ronny.beer@i-med.ac.at.
authors.forename: Ronny
authors.initials: R
authors.lastname: Beer
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstreet 35, 6020, Innsbruck, Austria. anelia.dietman@i-med.ac.at.
authors.forename: Anelia
authors.initials: A
authors.lastname: Dietmann
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstreet 35, 6020, Innsbruck, Austria. anappantunes@gmail.com.|Department of Neurosciences, Santa Maria Hospital, Hospital de Santa Maria, 1649-028, Lisbon, Portugal. anappantunes@gmail.com.
authors.forename: Ana Patrícia
authors.initials: AP
authors.lastname: Antunes
authors.affiliation: Department of Neurosurgery, Innsbruck Medical University, Anichstreet 35, 6020, Innsbruck, Austria. florian.sohm@i-med.ac.at.
authors.forename: Florian
authors.initials: F
authors.lastname: Sohm
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstreet 35, 6020, Innsbruck, Austria. mar.fischer@uke.de.
authors.forename: Marlene
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Institute of Biomedical Informatics, UMIT-University for Health Sciences, Medical Informatics and Technology, Eduard Wallnöfer-Zentrum I, 6060, Hall in Tirol, Austria. werner.hackl@umit.at.
authors.forename: Werner Oskar
authors.initials: WO
authors.lastname: Hackl
authors.affiliation: Department of Radiology, Innsbruck Medical University, Anichstreet 35, 6020, Innsbruck, Austria. paul.rhomberg@tilak.at.
authors.forename: Paul
authors.initials: P
authors.lastname: Rhomberg
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstreet 35, 6020, Innsbruck, Austria. peter.lackner@i-med.ac.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Lackner
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstreet 35, 6020, Innsbruck, Austria. b.pfausler@i-med.ac.at.
authors.forename: Bettina
authors.initials: B
authors.lastname: Pfausler
authors.affiliation: Department of Neurosurgery, Innsbruck Medical University, Anichstreet 35, 6020, Innsbruck, Austria. claudius.thome@uki.at.
authors.forename: Claudius
authors.initials: C
authors.lastname: Thomé
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Anichstreet 35, 6020, Innsbruck, Austria. christian.humpel@i-med.ac.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Humpel
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstreet 35, 6020, Innsbruck, Austria. erich.schmutzhard@i-med.ac.at.
authors.forename: Erich
authors.initials: E
authors.lastname: Schmutzhard
mesh_terms: D000368:Aged; D001812:Blood-Brain Barrier / Q000378:metabolism; D002545:Brain Ischemia / Q000209:etiology; D016638:Critical Illness; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D017551:Microdialysis / Q000379:methods; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods*; D059906:Neuroimaging; D010100:Oxygen / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D015850:Interleukin-6; D020780:Matrix Metalloproteinase 9; D010100:Oxygen