title: The prediction of malignant cerebral infarction by molecular brain barrier disruption markers.
abstract: OBJECTIVE
  Space-occupying brain edema is a life-threatening complication in patients with large hemispheric stroke. The aim of the study was to determine whether molecular markers of endothelial damage may help to predict secondary brain edema and, secondly, to identify patients who could benefit from aggressive therapies such as decompressive hemicraniectomy or hypothermia.
  
  
  METHODS
  We studied 40 consecutive patients with malignant middle cerebral artery (MCA) infarction and 35 controls with massive MCA infarctions <70 years of age and matched by stroke severity on admission. Cranial computed tomography (CT) was performed at entry and repeated between days 4 and 7, or earlier if there was neurological worsening. Malignant MCA (m-MCA) infarction was diagnosed when follow-up CT detected a more than two-thirds space-occupying MCA infarction with midline shift, compression of the basal cisterns, and neurological deterioration. Plasma concentrations of glutamate, glycine, gamma-aminobutyric acid, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha, matrix metalloproteinase-9 (MMP-9), and cellular-fibronectin (c-Fn) were determined in blood samples obtained at admission.
  
  
  RESULTS
  Mean time from stroke onset to blood sampling was 6.3+/-4.8 in m-MCA and 7.7+/-6.0 hours in the control group (P=0.63). Baseline characteristics were comparable in both groups. c-Fn and MMP-9 levels were significantly higher in patients with m-MCA than in controls (all P<0.001). c-Fn >16.6 microg/mL had the highest sensitivity (90%), specificity (100%), and negative and positive predictive values (89% and 100%, respectively) for the prediction of m-MCA infarction.
  
  
  CONCLUSIONS
  A plasma c-Fn concentration >16.6 microg/mL at admission is associated with the development of m-MCA infarction with high sensitivity and specificity, suggesting that c-Fn might be useful in therapeutic decision making.
authors.affiliation: Department of Neurology, Hospital Universitari Doctor Josep Trueta, Girona, Spain. nrl.jserena@htrueta.scs.es
authors.forename: Joaquín
authors.initials: J
authors.lastname: Serena
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanco
authors.forename: Mar
authors.initials: M
authors.lastname: Castellanos
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Silva
authors.forename: José
authors.initials: J
authors.lastname: Vivancos
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Moro
authors.forename: Rogelio
authors.initials: R
authors.lastname: Leira
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lizasoain
authors.forename: José
authors.initials: J
authors.lastname: Castillo
authors.forename: Antonio
authors.initials: A
authors.lastname: Dávalos
mesh_terms: D000368:Aged; D015415:Biomarkers; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D004487:Edema; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis / Q000097:blood; D018698:Glutamic Acid / Q000097:blood; D005998:Glycine / Q000097:blood; D006801:Humans; D007036:Hypothermia, Induced; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000175:diagnosis* / Q000601:surgery* / Q000628:therapy; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D020521:Stroke / Q000150:complications* / Q000473:pathology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D005680:gamma-Aminobutyric Acid / Q000097:blood
chemical_list: D015415:Biomarkers; D005353:Fibronectins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D020780:Matrix Metalloproteinase 9; D005998:Glycine