• Inflammatory Response in Cerebro-Spinal Fluid Following Intra-Ventricular Hemorrhage

    Final Number:

    Javed Khader Eliyas MD; Maged Delour Fam MBChB; Agnieszka Stadnik MS; Michael Jesselson BS; Lingjiao Zhang MPH; Issam A. Awad MD, MSc, FACS, MA

    Study Design:
    Clinical Trial

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2015 Annual Meeting

    Introduction: IVH is a common affliction in adults, often seen in association with hemorrhagic stroke. The inflammatory response in CSF has never been systematically studied. We hypothesized that inflammatory response in CSF occurs after IVH and is exaggerated by higher volume of hemorrhage and infection.

    Methods: We analyzed prospectively collected blood and CSF data of patients enrolled in CLEAR III trial - RCT investigating outcome of intra-ventricular thrombolysis. Per trial design, blood and CSF are analyzed daily. The results, in chronological order, were utilized in our study. Corrected WBC count was calculated as CSF WBC – (Blood WBC x CSF RBC)/Blood RBC. Effects of infection and IVH volume were additionally examined.

    Results: Cohort of 250 patients provided 6209 data points for ten days from ictus (Table 1 and Table 2). Due to paucity of values, days 0 and 10 were excluded from analysis. Also excluded were 21 values that were 3 SD over mean for each parameter, on individual days. Overall analysis showed WBC peak around day 3 with plateauing by day 7. RBC peaks similarly but declines steadily, without stability. Glucose showed no change throughout the monitoring epoch (Figure 1). There was significant positive correlation between IVH volume and CSF WBC, RBC and protein when comparing IVH volume <20 and 20-50 ml. Similar differences did not exist between IVH volume 20-50ml and >50ml (Figure 2). Infection cases (n=10) consistently ran lower glucose levels than overall. CSF WBC, neutrophil and protein in infected cases also showed similar separation, often-preceding positive culture by days (Figure 3).

    Conclusions: This is the first prospective description of normal response to IVH, based on systematic surveillance. The response is greatest with higher IVH volume. Cases with infection showed separation in WBC, glucose and protein, from overall study group, but too few cases, and greater variability amongst them, prevents any positive predictions.

    Patient Care: Understanding the inflammatory process is the initial step towards deciphering any possible influence on outcome. This will pave way for modulators of such inflammation, if outcome is adversely affected otherwise. Studying similar processes in other hemorrhagic strokes with help in comparing these pathologies to understand differential effects of each one.

    Learning Objectives: 1. To systematically describe the existence of inflammation in CSF to IVH. 2. To present the relationship between CSF inflammation and IVH volume. 3. To understand differences in patients with infection to those without infection, in relation to CSF inflammation.

    References: 1. Simard PF, Tosun C, Melnichenko L, Ivanova S, Gerzanich V, Simard JM. Inflammation of the choroid plexus and ependymal layer of the ventricle following intraventricular hemorrhage. Translational stroke research 2011;2:227-31. 2. Hallevi H, Walker KC, Kasam M, Bornstein N, Grotta JC, Savitz SI. Inflammatory response to intraventricular hemorrhage: time course, magnitude and effect of t-PA. Journal of the neurological sciences 2012;315:93-5. 3. Ziai WC, Tuhrim S, Lane K, et al. A multicenter, randomized, double-blinded, placebo-controlled phase III study of Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III). International journal of stroke : official journal of the International Stroke Society 2014;9:536-42. 4. Mayfrank L, Kissler J, Raoofi R, et al. Ventricular dilatation in experimental intraventricular hemorrhage in pigs. Characterization of cerebrospinal fluid dynamics and the effects of fibrinolytic treatment. Stroke; a journal of cerebral circulation 1997;28:141-8.

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