Maged D Fam1, Hussein A Zeineddine1, Javed Khader Eliyas1, Agnieszka Stadnik1, Michael Jesselson1, Nichol McBee1, Karen Lane1, Ying Cao1, Meijing Wu1, Lingjiao Zhang1, Richard E Thompson1, Sayona John1, Wendy Ziai1, Daniel F Hanley1, Issam A Awad2. 1. From the Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery (M.D.F., H.A.Z., J.K.E., A.S., M.J., Y.C., M.W., L.Z., Y.C., M.W., L.Z., I.A.A.), University of Chicago Medicine and Biological Sciences, IL; Brain Injury Outcomes (BIOS) Division, Department of Neurology (N.M., K.L., W.Z., D.F.H.), and The Bloomberg School of Public Health (R.E.T.), Johns Hopkins University Medical Institutions, Baltimore, MD; and Department of Neurology (S.J.), Rush University Medical Center, Chicago, IL. 2. From the Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery (M.D.F., H.A.Z., J.K.E., A.S., M.J., Y.C., M.W., L.Z., Y.C., M.W., L.Z., I.A.A.), University of Chicago Medicine and Biological Sciences, IL; Brain Injury Outcomes (BIOS) Division, Department of Neurology (N.M., K.L., W.Z., D.F.H.), and The Bloomberg School of Public Health (R.E.T.), Johns Hopkins University Medical Institutions, Baltimore, MD; and Department of Neurology (S.J.), Rush University Medical Center, Chicago, IL. iawad@uchicago.edu.
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.
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.
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