Neuron-Specific Enolase Is Correlated to Compromised Cerebral Metabolism in Patients Suffering from Acute Bacterial Meningitis; An Observational Cohort Study

<div><p>Introduction</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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 (0–24h) and day 3 (48–72h) after admission to the NICU (p = 0.0001). No correlation between MD parameters or biomarkers and outcome was found.</p><p>Conclusion</p><p>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.</p></div

Outcome.

<p>Outcome.</p

Biomarkers vs MD parameters.

<p>Illustrates NSE (A-C) and S100B (D-F) levels in patients (n = 21) with either increased LPR (>40), metabolic crisis (LPR >25, MD-glucose <0.8 mmol/L) and increased glycerol (>500 μmol/L). In general, increased NSE levels were correlated to worse metabolic conditions.</p

Outcome.

<p>Outcome.</p

MD parameters, fever and serum glucose over time.

<p>Illustrating parameter change over time (median 0–24h, Day 1, vs median 48–72h, Day 3) from insertion of microdialysis (MD) catheters. MD-glucose (2A) and serum-glucose (2B) levels were significantly lower on Day 3 compared to Day 1 (p<0.01 respectively, Wilcoxon matched-pairs signed rank test). No other parameter presented any significant difference over time. For all parameters n = 15 patients are compared except pyrexia (n = 13).</p

Demographics.

<p>Demographics.</p

The intracranial pressure (ICP; mmHg) as noted at operation (external ventricular drainage: n = 48; parenchymal ICP-monitor: n = 4), and the highest levels of ICP, noted continuously during episodes >5 min, at the neuro-intensive care unit (NICU), related to the outcome at follow-up after 2–6 months in the intervention per protocol group.

<p>GOS = Glasgow outcome score.</p><p>*These patients ended up as follows;</p><p>a) Two with GOS 3, two with GOS 4.</p><p>b) Four with GOS 4.</p><p>c) One with GOS 3, four with GOS 4.</p><p>d) Two with GOS 4.</p

The main characteristics regarding demographic, etiological, clinical, and laboratory data, not identifying any significant difference between the intervention and control group, including comparison of the reaction level scale (RLS) values that were converted from Glasgow coma score (GCS) in the intervention group [27], [43].

<p>LP = lumbar puncture. Csf = cerebrospinal fluid.</p><p>When data was missing the numbers of patients with available data are shown [in brackets].</p>a<p>Malignancy/immunosuppresion: n = 10, Alcoholism: n = 5, Diabetes: n = 3, Splenectomized: n = 1, CSF-leakage: n = 1,</p>b<p>Malignancy/immunosuppresion: n = 5, Alcoholism: n = 3, Diabetes: n = 3, Splenectomized: n = 2, CSF leakage: n = 2.</p>c<p><i>S aureus</i>: n = 2, <i>L monocytogenes</i>: n = 1.</p>d<p><i>S aureus</i>: n = 4, <i>H influenzae</i>: n = 2, <i>L monocytogenes</i>: n = 1, <i>S pyogenes</i> geoup C: n = 1, <i>E cloacae</i>: n = 1.</p>e<p>Two tailed Fisher's exact test for proportions and Student T-test for normally distributed values.</p

The algorithm for inclusion and exclusion of patients.

<p>Inclusion criteria were: 1) age 16–75 years, 2) severely impaired mental status on admission, and 3) confirmed acute bacterial meningitis (ABM). Patients were initially included in the intervention group based on clinical suspicion of ABM with or without cerebrospinal fluid analysis. SQRM = Swedish National Quality Registry for ABM. ICP = intracranial pressure. NICU = neuro-intensive care unit. ICU = intensive care unit.</p

Outcomes at follow-up after 2–6 months in the intervention group and in the controls.

<p>NICU = neuro-intensive care unit. GOS = Glasgow outcome score.</p><p>*p<0.05 with two-tailed Fisher's exact test when comparing the intention to treat group, and the per protocol group, with the control group.</p>a<p>Patients included as final controls according to inclusion and exclusion criteria.</p