title: Early matrix metalloproteinase-9 concentration in the first 48 h after aneurysmal subarachnoid haemorrhage predicts delayed cerebral ischaemia: An observational study.
abstract: Delayed cerebral ischaemia from vasospasm is an important cause of complications and death after aneurysmal subarachnoid haemorrhage. There is currently no established biomarker for identifying patients at high risk of delayed cerebral ischaemia.
  
  
  
  Considering the important role of inflammation in the pathogenesis of delayed cerebral ischaemia, we investigated whether matrix metalloproteinase-9 (MMP-9) may be an efficient biomarker for predicting elayed cerebral ischaemia after subarachnoid haemorrhage.
  
  
  
  Single-centre prospective observational study.
  
  
  
  Neuroscience Critical Care Unit of a teaching hospital.
  
  
  
  Thirty consecutive patients with severe subarachnoid haemorrhage requiring external ventricular drainage were enrolled during 2013 and 2014.
  
  
  
  Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h and between 48 and 72 h after admission. We evaluated the activity and concentrations of MMP-9 and endothelin-1 with zymography and ELISA. Patients were allocated to groups with delayed cerebral ischaemia (n = 16) or without delayed cerebral ischaemia (n = 14).
  
  
  
  Within 24 h, median [interquartile range] MMP-9 concentrations in CSF were significantly higher in patients with delayed cerebral ischaemia (47 [21 to 102] ng ml) than in those without delayed cerebral ischaemia (4 [2 to 13] ng ml, P = 0.001). CSF MMP-9 activity and endothelin-1 concentrations were correlated (r = 0.6, P = 0.02). The areas under the receiver operating characteristic curves were 0.73 (95% confidence interval [0.53 to 0.87]) and 0.91 (95% confidence interval [0.75 to 0.98]) for MMP-9 concentrations in plasma and CSF, respectively, at 24 h to predict delayed cerebral ischaemia CSF MMP-9 concentrations more than 14.3 ng ml at 24 h predicted the occurrence of delayed cerebral ischaemia with a sensitivity and specificity of 88 and 86%, respectively. After multivariate logistic analysis, only CSF MMP-9 concentrations at 24 h predicted the occurrence of delayed cerebral ischaemia (P = 0.01).
  
  
  
  MMP-9 concentrations in both plasma and CSF, measured within 48 h after subarachnoid haemorrhage, were highly predictive of the occurrence of delayed cerebral ischaemia within the first 2 weeks.
  
  
  
  Clinicaltrials.gov identifier: NCT02397759.
authors.affiliation: From the Department of Anaesthesiology and Critical Care Medicine, University Hospital Timone (TT, DL, NB, LV), NORT Inserm 1062, Inra 1260 (AM, JCM, MV, MCA), and Department of Neurosurgery, University Hospital Timone, Aix Marseille University, Marseille, France (HD).
authors.forename: Thibaut
authors.initials: T
authors.lastname: Triglia
authors.forename: Anna
authors.initials: A
authors.lastname: Mezzapesa
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Martin
authors.forename: Monique
authors.initials: M
authors.lastname: Verdier
authors.forename: David
authors.initials: D
authors.lastname: Lagier
authors.forename: Henry
authors.initials: H
authors.lastname: Dufour
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bruder
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.forename: Lionel J
authors.initials: LJ
authors.lastname: Velly
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D002545:Brain Ischemia / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D013997:Time Factors
chemical_list: D015415:Biomarkers; D020780:Matrix Metalloproteinase 9