CSF and serum inflammatory response and association with outcomes in spontaneous intracerebral hemorrhage with intraventricular extension: an analysis of the CLEAR-III Trial

Journal of Neuroinflammation

Issam A. Awad¹  Daniel F. Hanley²  Kendel Quirk²  Radhika Avadhani²  Yunis M. Mayasi³  Wendy C. Ziai⁴  Aaron M. Gusdon⁵  Carol B. Thompson⁶ 

[1] Department of Neurosurgery, University of Chicago Pritzker School of Medicine, Chicago, IL, USA;Division of Brain Injury Outcomes (BIOS), Johns Hopkins University School of Medicine, Baltimore, USA;Division of Neurocritical Care, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe St./Phipps 455, 21287, Baltimore, MD, USA;Division of Neurocritical Care, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe St./Phipps 455, 21287, Baltimore, MD, USA;Division of Brain Injury Outcomes (BIOS), Johns Hopkins University School of Medicine, Baltimore, USA;Division of Neurocritical Care, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe St./Phipps 455, 21287, Baltimore, MD, USA;Present address: Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX, USA;Johns Hopkins Biostatistics Center, Bloomberg School of Public Health, Baltimore, USA;

关键词: Intracerebral hemorrhage;    Intraventricular hemorrhage;    Inflammation;    Fibrinolysis;    Clinical outcomes;   

DOI  :  10.1186/s12974-021-02224-w

来源: Springer

【 摘 要 】

BackgroundIntracerebral hemorrhage (ICH) results in a cascade of inflammatory cell activation with recruitment of peripheral leukocytes to the brain parenchyma and surrounding the hematoma. We hypothesized that in patients with ICH and intraventricular hemorrhage (IVH), a robust cerebrospinal fluid (CSF) inflammatory response occurs with leukocyte subtypes being affected by alteplase treatment and contributing to outcomes.MethodsSerum and CSF cell counts from patients in the phase 3 Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III) trial were analyzed. CSF leukocytes were corrected for the presence of red blood cells. Trends in cell counts were plotted chronologically. Associations were evaluated between serum and CSF leukocyte subtypes and adjudicated functional outcome (modified Rankin Scale; mRS) at 30 and 180 days and bacterial infection according to treatment with intraventricular alteplase versus saline.ResultsA total of 279 and 292 patients had ≥3 differential cell counts from serum and CSF, respectively. CSF leukocyte subtypes evolved during IVH resolution with a significantly augmented inflammatory response for all subtypes in alteplase- compared to saline-treated patients. CSF leukocyte subtypes were not associated with detrimental effect on functional outcomes in the full cohort, but all were associated with poor 30-day outcome in saline-treated patients with IVH volume ≥20 mL. Higher serum lymphocytes were associated with good functional outcomes (mRS 0–3) in the entire cohort and saline-treated but not alteplase-treated group. Conversely, increased serum neutrophil-to-lymphocyte ratio (NLR) in the entire cohort and saline group was associated with worse functional outcomes. Higher median serum lymphocytes were associated with the absence of infection at 7 days.ConclusionsAseptic CSF inflammation after IVH involves all leukocyte subtypes. Serum lymphocytes may be associated with better outcomes by mitigating infection. Alteplase augments the inflammatory response without affecting outcomes.

【 授权许可】

CC BY