CSF inflammatory response after intraventricular hemorrhage

Abstract

Objective: To investigate the temporal pattern and relevant associations of CSF inflammatory measures after intraventricular hemorrhage (IVH).

Methods: We analyzed prospectively collected CSF cell counts and protein and glucose levels from participants in the Clot Lysis Evaluation of Accelerated Resolution of IVH phase III (CLEAR III) trial. Corrected leukocyte count and cell index were calculated to adjust for CSF leukocytes attributable to circulating blood. Data were chronologically plotted. CSF inflammatory measures (daily, mean, median, maximum, and cases with highest quartile response) were correlated with initial IVH volume, IVH clearance rate, thrombolytic treatment, bacterial infection, and adjudicated clinical outcome at 30 and 180 days.

Results: A total of 11,376 data points of CSF results from 464 trial participants were analyzed. Measures of CSF inflammatory response evolved during the resolution of IVH. This was significantly more pronounced with initial IVH volume exceeding 20 mL. Intraventricular alteplase was associated with a significantly augmented inflammatory response compared to saline, even after correcting for initial IVH volume. There was an association but nonpredictive correlation of CSF inflammation measures with culture-positive CSF bacterial infection. None of the CSF inflammatory measures, including cases with upper quartile inflammatory response, was associated with a significant detrimental effect on 30 or 180 days functional outcome or mortality after multivariate adjustment for measures of disease severity.

Conclusions: Aseptic CSF inflammation after IVH is primarily dependent on the volume of initial bleed. Thrombolysis intensifies the inflammatory response, with no apparent detrimental effect on clinical outcome.

Clinicaltrialsgov identifier: NCT00784134.

Figure 1. General patterns

Overall patterns (mean ± SE) for the trends of (A) white blood cells (WBC), (B) corrected WBC, and (C) cell index during the resolution of IVH over days 1–9 postictus. RBC = red blood cell.

Figure 2. Association of initial intraventricular hemorrhage (iIVH) volume

Temporal trend of white blood cells (WBC), corrected WBC, and cell index in the 3 prearticulated iIVH volume strata (<20 mL, n = 201; 20–50 mL, n = 120; and >50 mL, n = 54) over days 1–9 postictus. The p values listed with each panel refer to the difference in overall trend for the respective measure.

Figure 3. Association of thrombolytic treatment

Temporal trend CSF white blood cells (WBC), corrected WBC, and cell index in cases with alteplase vs saline administered via external ventricular drain over days 1–9 postictus. The p value listed with each panel refers to the difference in overall trend for the respective measure. *Refers to significantly different daily values.

Figure 4. Association of bacterial infection

Temporal trend of CSF (A) white blood cells (WBC), (B) corrected WBC, (C) cell index, (D) protein, and (E) glucose during days 1–9 postictus in cases with and without bacterial infection manifested during the study period (within 10 days postictus, n = 21). The p value listed with each panel refers to the difference in overall trend for the respective measure. *Refers to significantly different daily values − daily value p < 0.05.