title: Hepatocyte growth factor in cerebrospinal fluid differentiates community-acquired or nosocomial septic meningitis from other causes of pleocytosis.
abstract: BACKGROUND
  Due to anatomical restrictions, the inflammatory response to intracerebral bacterial infections exposes swollen brain tissues to pressure and ischemia, resulting in life-threatening damage. Rapid diagnosis and immediate empirical antibiotic therapy is highly important. However, diagnosing meningitis in patients after neurosurgery is complicated, due to brain tissue damage and changes in cerebrospinal fluid (CSF) caused by surgery. Hepatocyte growth factor (HGF) is a local, acute-phase protein with healing properties. Previous studies on community-acquired septic meningitis reported high levels of intrathecally produced HGF. The present study focused on nosocomial meningitis in assessing the levels of HGF in the CSF.
  
  
  METHODS
  HGF concentrations (ELISA) and HGF binding to receptors; c-Met receptor and heparan sulfate proteoglycan were determined in CSF samples (surface plasmon resonance). CSF samples from patients with community-acquired or nosocomial meningitis (217 samples from 135 patients) were compared to those from controls without signs of cerebral nervous system involvement (N = 36) and patients with Alzheimer's disease (N = 20).
  
  
  RESULTS
  Compared to samples from patients that had undergone neurosurgery and had other infectious diseases, CSF samples from patients with nosocomial meningitis had significantly higher HGF concentrations (p < 0.001) and binding affinity to c-Met (p < 0.001) and HSPG (p = 0.043) receptors. The sensitivity and specificity to identify nosocomial septic meningitis were 69.7 and 93.4%, respectively. The HGF concentration and binding affinity to HGF receptors were significantly higher in CSF from patients with community-acquired septic meningitis compared to patients with aseptic (viral and subacute) meningitis as well as controls (p < 0.001). The sensitivity and specificity to identify community-acquired septic meningitis were 95.4 and 95.7%, respectively.
  
  
  CONCLUSIONS
  In febrile nosocomial infections that occurred post neurosurgery, HGF assessment could substantially improve the differentiation of meningitis from other infections and therefore might be a tool for rapid diagnosis, limiting injuries and guiding antibiotic therapy.
authors.affiliation: Department of Neurosurgery, Region Östergötland, University Hospital, Linköping University, Linköping, Sweden. amir.ramezani@regionostergotland.se.
authors.forename: Amir
authors.initials: A
authors.lastname: Ramezani
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden. Katarina.nagga@med.lu.se.
authors.forename: Katarina
authors.initials: K
authors.lastname: Nägga
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden. oskar.hansson@med.lu.se.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
authors.affiliation: Department of Biomedicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden. johanna.lonn@oru.se.
authors.forename: Johanna
authors.initials: J
authors.lastname: Lönn
authors.affiliation: Clinic of Infectious Diseases, Region Östergötland, University Hospital, Linköping University, 58185, Linköping, Sweden. johanna.sjowall@liu.se.
authors.forename: Johanna
authors.initials: J
authors.lastname: Sjöwall
authors.affiliation: The Institute of Protein Environment Affinity Surveys (PEAS Institut), Linköping, Sweden. fatemekatouzian@gmail.com.
authors.forename: Fateme
authors.initials: F
authors.lastname: Katoozian
authors.affiliation: The Institute of Protein Environment Affinity Surveys (PEAS Institut), Linköping, Sweden. a.mansouran@gmail.com.
authors.forename: Sepahdar
authors.initials: S
authors.lastname: Mansouri
authors.affiliation: Clinic of Infectious Diseases, Region Östergötland, University Hospital, Linköping University, 58185, Linköping, Sweden. fariba.nayeri@regionostergotland.se.|The Institute of Protein Environment Affinity Surveys (PEAS Institut), Linköping, Sweden. fariba.nayeri@regionostergotland.se.
authors.forename: Fariba
authors.initials: F
authors.lastname: Nayeri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003428:Cross Infection / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis*; D006801:Humans; D007223:Infant; D007964:Leukocytosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D008297:Male; D008582:Meningitis, Aseptic / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met