Yonatan Hirsch1, Joseph R Geraghty2,3, Eitan A Katz1, Fernando D Testai1. 1. Department of Neurology and Rehabilitation, College of Medicine, University of Illinois at Chicago, 912 S. Wood St. Suite 174 N, Chicago, IL, 60612, USA. 2. Department of Neurology and Rehabilitation, College of Medicine, University of Illinois at Chicago, 912 S. Wood St. Suite 174 N, Chicago, IL, 60612, USA. jgerag2@uic.edu. 3. Medical Scientist Training Program, University of Illinois at Chicago, Chicago, IL, USA. jgerag2@uic.edu.
Abstract
BACKGROUND/ OBJECTIVE: Subarachnoid hemorrhage (SAH) is a devastating neurological injury, further complicated by few available methods to objectively predict outcomes. With the recent shift in focus to neuroinflammation as a potential cause of adverse outcomes following SAH, we investigated the inflammasome-derived enzyme, caspase-1, as a potential biomarker for poor functional outcome. METHODS: SAH patients were recruited from a regional stroke referral center. Cerebrospinal fluid (CSF) samples from 18 SAH subjects were collected via an external ventricular drain and obtained as close as possible to admission (within 72 h). For control subjects, we collected CSF from 9 patients undergoing lumbar puncture with normal CSF. Caspase-1 activity was measured using commercially available luminescence assays. SAH subjects were categorized at hospital discharge into those with good outcomes (Glasgow Outcome Scale, GOS, of 4-5) and poor outcomes (GOS of 1-3). RESULTS: CSF analysis demonstrated a nearly seven-fold increase in caspase-1 activity in SAH patients compared to controls (p < 0.0001). Within the SAH group, 10 patients (55.6%) had good outcomes and 8 patients (44.4%) had poor outcomes. Mean caspase-1 activity in the poor outcome group was approximately three-times higher than the good outcome group (p = 0.001). Caspase-1 activity was significantly correlated with GOS score (r = - 0.705, p = 0.001). Receiver operating characteristic curve analysis showed that caspase-1 activity can accurately differentiate between patients with good versus poor functional outcome (area under the curve 0.944, p = 0.002). CONCLUSIONS: Inflammasome-derived caspase-1 activity is elevated in the CSF of SAH patients compared to controls and higher levels correlate with worse functional outcome.
BACKGROUND/ OBJECTIVE: Subarachnoid hemorrhage (SAH) is a devastating neurological injury, further complicated by few available methods to objectively predict outcomes. With the recent shift in focus to neuroinflammation as a potential cause of adverse outcomes following SAH, we investigated the inflammasome-derived enzyme, caspase-1, as a potential biomarker for poor functional outcome. METHODS: SAH patients were recruited from a regional stroke referral center. Cerebrospinal fluid (CSF) samples from 18 SAH subjects were collected via an external ventricular drain and obtained as close as possible to admission (within 72 h). For control subjects, we collected CSF from 9 patients undergoing lumbar puncture with normal CSF. Caspase-1 activity was measured using commercially available luminescence assays. SAH subjects were categorized at hospital discharge into those with good outcomes (Glasgow Outcome Scale, GOS, of 4-5) and poor outcomes (GOS of 1-3). RESULTS: CSF analysis demonstrated a nearly seven-fold increase in caspase-1 activity in SAH patients compared to controls (p < 0.0001). Within the SAH group, 10 patients (55.6%) had good outcomes and 8 patients (44.4%) had poor outcomes. Mean caspase-1 activity in the poor outcome group was approximately three-times higher than the good outcome group (p = 0.001). Caspase-1 activity was significantly correlated with GOS score (r = - 0.705, p = 0.001). Receiver operating characteristic curve analysis showed that caspase-1 activity can accurately differentiate between patients with good versus poor functional outcome (area under the curve 0.944, p = 0.002). CONCLUSIONS: Inflammasome-derived caspase-1 activity is elevated in the CSF of SAH patients compared to controls and higher levels correlate with worse functional outcome.
Authors: Thomas Kapapa; Martin Tjahjadi; Ralph König; Christian Rainer Wirtz; Dieter Woischneck Journal: World Neurosurg Date: 2012-09-25 Impact factor: 2.104
Authors: Georgios A Maragkos; Alejandro Enriquez-Marulanda; Mohamed M Salem; Luis C Ascanio; Kohei Chida; Raghav Gupta; Abdulrahman Y Alturki; Kimberly P Kicielinski; Christopher S Ogilvy; Justin M Moore; Ajith J Thomas Journal: World Neurosurg Date: 2018-09-27 Impact factor: 2.104
Authors: Caron M Hong; Cigdem Tosun; David B Kurland; Volodymyr Gerzanich; David Schreibman; J Marc Simard Journal: Biomarkers Date: 2014-02-05 Impact factor: 2.658
Authors: Blessing N R Jaja; Michael D Cusimano; Nima Etminan; Daniel Hanggi; David Hasan; Don Ilodigwe; Hector Lantigua; Peter Le Roux; Benjamin Lo; Ada Louffat-Olivares; Stephan Mayer; Andrew Molyneux; Audrey Quinn; Tom A Schweizer; Thomas Schenk; Julian Spears; Michael Todd; James Torner; Mervyn D I Vergouwen; George K C Wong; Jeff Singh; R Loch Macdonald Journal: Neurocrit Care Date: 2013-02 Impact factor: 3.210
Authors: Mario Di Napoli; Mark Slevin; Aurel Popa-Wagner; Puneetpal Singh; Simona Lattanzi; Afshin A Divani Journal: Front Immunol Date: 2018-09-11 Impact factor: 7.561
Authors: Yonatan Hirsch; Joseph R Geraghty; Cory R Reiter; Eitan A Katz; Conner F Little; Matthew K Tobin; Fernando D Testai Journal: Transl Stroke Res Date: 2022-05-06 Impact factor: 6.829
Authors: Joseph R Geraghty; Tyler J Lung; Yonatan Hirsch; Eitan A Katz; Tiffany Cheng; Neil S Saini; Dilip K Pandey; Fernando D Testai Journal: Neurosurgery Date: 2021-11-18 Impact factor: 5.315