title: Neuron-Specific Enolase Is Correlated to Compromised Cerebral Metabolism in Patients Suffering from Acute Bacterial Meningitis; An Observational Cohort Study.
abstract: BACKGROUND
  Patients suffering from acute bacterial meningitis (ABM) with a decreased level of consciousness have been shown to have an improved clinical outcome if treated with an intracranial pressure (ICP) guided therapy. By using intracranial microdialysis (MD) to monitor cerebral metabolism in combination with serum samples of biomarkers indicating brain tissue injury, S100B and Neuron Specific Enolase (NSE), additional information might be provided. The aim of this study was to evaluate biomarkers in serum and MD parameters in patients with ABM.
  
  
  METHODS
  From a prior study on patients (n = 52) with a confirmed ABM and impaired consciousness (GCS ≤ 9, or GCS = 10 combined with lumbar spinal opening pressure > 400 mmH2O), a subgroup of patients (n = 21) monitored with intracerebral MD and biomarkers was included in the present study. All patients were treated in the NICU with intracranial pressure (ICP) guided therapy. Serum biomarkers were obtained at admission and every 12 hours. The MD parameters glucose, lactate, pyruvate and glycerol were analyzed. Outcome was assessed at 12-55 months after discharge from hospital. Mann-Whitney U-Test and Wilcoxon matched-pairs signed rank test were applied.
  
  
  RESULTS
  The included patients had a mean GCS of 8 (range, 3-10) on admission and increased ICP (>20 mmHg) was observed in 62% (n = 13/21) of the patients. Patients with a lactate:pyruvate ratio (LPR) >40 (n = 9/21, 43%) had significantly higher peak levels of serum NSE (p = 0.03), with similar, although non-significant observations made in patients with high levels of glycerol (>500 μmol/L, p = 0.11) and those with a metabolic crisis (Glucose <0.8 mmol/L, LPR >25, p = 0.09). No associations between serum S100B and MD parameters were found. Furthermore, median MD glucose levels decreased significantly between day 1 (0-24 h) and day 3 (48-72 h) after admission to the NICU (p = 0.0001). No correlation between MD parameters or biomarkers and outcome was found.
  
  
  CONCLUSIONS
  In this observational cohort study, we were able to show that cerebral metabolism is frequently affected in patients with ABM. Furthermore, patients with high LPR (LPR>40) had significantly higher levels of NSE, suggesting ongoing deterioration in compromised cerebral tissue. However, the potential clinical impact of MD and biomarker monitoring in ABM patients will need to be further elaborated in larger clinical trials.
authors.affiliation: Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.|Department of Neurosurgery, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jiri
authors.initials: J
authors.lastname: Bartek
authors.affiliation: Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eric Peter
authors.initials: EP
authors.lastname: Thelin
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per Hamid
authors.initials: PH
authors.lastname: Ghatan
authors.affiliation: Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Glimaker
authors.affiliation: Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bo-Michael
authors.initials: BM
authors.lastname: Bellander
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005947:Glucose / Q000032:analysis; D006801:Humans; D007427:Intracranial Pressure; D019344:Lactic Acid / Q000032:analysis; D008297:Male; D016920:Meningitis, Bacterial / Q000473:pathology*; D017551:Microdialysis; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D019289:Pyruvic Acid / Q000032:analysis; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D019344:Lactic Acid; D019289:Pyruvic Acid; D010751:Phosphopyruvate Hydratase; D005947:Glucose