title: Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis.
abstract: OBJECTIVE
  The objective of the present study was to determine whether selective inflammatory cytokine concentrations within cerebrospinal fluid are useful markers for the differential diagnosis of aseptic and bacterial meningitis within neurosurgical patients.
  
  
  METHODS
  Prospective, open-label, observational, cohort study.
  
  
  METHODS
  Neurosurgical ICU, Chang Gung Memorial Hospital.
  
  
  METHODS
  Thirty-two consecutive neurosurgical patients who had postoperative fever following external ventricular drain insertion for the treatment of brain injury underwent serial cerebrospinal fluid cytokine analysis pre and post fever to determine the value of such markers in ascertaining the differential diagnosis of meningitis.
  
  
  METHODS
  Cerebrospinal fluid samples were collected on the day of fever onset, as well as on day 2 and 4 pre and post fever development. Tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-8, transforming growth factor-β, and procalcitonin were subsequently analyzed using enzyme-linked immunosorbent assay analysis techniques.
  
  
  RESULTS
  Inflammatory marker levels were compared among febrile aseptic, bacterial, and nonmeningitis patients to determine cerebrospinal fluid inflammatory changes over time. Significant increases in cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, interleukin-6, and interleukin-8 levels were observed within patients with bacterial meningitis at fever onset, which was not evident in aseptic or nonmeningitis patients. Furthermore, significant increases in cerebrospinal fluid tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 levels were detected as early as 4 days prior to fever onset within patients with bacterial meningitis when compared with both aseptic and nonmeningitis groups. Interestingly, procalcitonin was only significantly increased in patients with bacterial meningitis on the fourth day post fever.
  
  
  CONCLUSIONS
  The present study suggests that raised cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, and interleukin-8 in a temporal manner may indicate early bacterial meningitis development in neurosurgical patients, enabling earlier diagnostic certainty and improved patient outcomes.
authors.affiliation: 1Department of Neurosurgery, Chang Gung Memorial Hospital, Chang Gung Medical College and University, Linkou, Taiwan. 2Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. 3Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung Medical College and University, Linkou, Taiwan.
authors.forename: Zhuo-Hao
authors.initials: ZH
authors.lastname: Liu
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Tu
authors.forename: Nan-Yu
authors.initials: NY
authors.lastname: Chen
authors.forename: Ping K
authors.initials: PK
authors.lastname: Yip
authors.forename: Amy L
authors.initials: AL
authors.lastname: Bowes
authors.forename: Cheng-Chi
authors.initials: CC
authors.lastname: Lee
authors.forename: She-Hung
authors.initials: SH
authors.lastname: Chan
authors.forename: Chua-Chi
authors.initials: CC
authors.lastname: Kung
authors.forename: Alvin Yi-Chou
authors.initials: AY
authors.lastname: Wang
authors.forename: Chieh-Tsai
authors.initials: CT
authors.lastname: Wu
authors.forename: Shih-Tseng
authors.initials: ST
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002116:Calcitonin / Q000134:cerebrospinal fluid; D015740:Calcitonin Gene-Related Peptide; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005334:Fever / Q000134:cerebrospinal fluid / Q000209:etiology; D006801:Humans; D018836:Inflammation Mediators / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008582:Meningitis, Aseptic / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000209:etiology / Q000401:mortality; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000209:etiology / Q000401:mortality; D008875:Middle Aged; D019635:Neurosurgical Procedures / Q000009:adverse effects* / Q000379:methods; D011183:Postoperative Complications / Q000134:cerebrospinal fluid / Q000503:physiopathology; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000134:cerebrospinal fluid; D012372:ROC Curve; D018570:Risk Assessment; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C000606589:CALCA protein, human; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide