Introduction: Cerebrospinal fluid (CSF) pleocytosis has been consistently observed with intraventricular hemorrhage (IVH) in small case series. Its extent, time course, and relation to IVH volume and infection have never been studied in a large cohort with systematic data collection.
Hypothesis: Inflammatory response in CSF follows a predictable pattern after IVH, and is more enhanced in cases with higher IVH volume and infection
Method: We analyzed prospectively collected samples from 500 patients enrolled in the Clot Lysis Evaluation of Accelerated Resolution (CLEAR) phase III trial. Patients with obstructive IVH requiring external ventricular drainage (EVD) were randomized to receive thrombolytic or placebo injections via EVD. We analyzed 12,291 data points including daily peripheral WBC and RBC counts, CSF RBC, WBC and neutrophil count, protein and glucose. Corrected WBCs (coWBC) reflecting true inflammatory response in the CSF was calculated by controlling for RBC/WBC ratio in a contemporaneous blood sample of the patient. Consecutive values were adjusted to the date of ictus (day 0) and analyzed on days 1-9. Median daily values were chronologically plotted to define the temporal pattern for each parameter. Similar analyses were repeated after stratification based on IVH volume, time to EVD insertion, and presence of culture positive ventriculitis (14 cases, 3%)
Result: CSF protein gradually declined with later clearance of RBCs after IVH. There was a surge in coWBC at days 3-5. All parameters of inflammatory response, and most notably the coWBC peak, were greater with larger volume of IVH. Subgroup analyses defined a threshold for significant inflammatory response with initial IVH volume 27mls (P=0.006). Bacterial ventriculitis resulted in significantly higher coWBCs (P<0.001) and neutrophils (P=0.01), but only in cases with low volume IVH (<27ml)
Conclusion: Inflammation is an integral response to IVH and is more pronounced with large IVH volume. Bacterial ventriculitis is associated with CSF leukocytosis exceeding the aseptic inflammatory response, notably in lower volume bleeds. These results form a basis for future correlation with treatment rendered, rate of IVH clearance and clinical outcome, with upcoming unblinding of the trial.