Abstract TMP23: Inflammasome-derived Caspase-1 is Elevated in the Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients and Correlated to Outcome

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yonatan Hirsch ◽  
Joseph R Geraghty ◽  
Eitan A Katz ◽  
Jeffrey A Loeb ◽  
Fernando Testai
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
External Ventricular Drain ◽  
Analysis Of Covariance ◽  
Control Group ◽  
Normal Brain ◽  
Poor Outcome ◽  
Caspase 1 ◽  
Initial Severity ◽  
Poor Outcomes

Introduction: The role of neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) and its relationship to outcome is the subject of many ongoing studies. The proteolytic enzyme, caspase-1, activated by the inflammasome complex, is known to contribute to numerous downstream pro-inflammatory effects. In this study, we investigated caspase-1 activity in the cerebrospinal fluid (CSF) of SAH patients and its association to outcome. Methods: SAH patients were recruited from a regional stroke referral center. CSF samples from 18 SAH subjects were collected via an external ventricular drain and obtained within 72 hours of the onset of symptoms. For control subjects, we collected the CSF from 9 patients undergoing lumbar puncture with normal CSF and normal brain MRI. 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). The levels of caspase-1 activity in various groups were analyzed using Mann-Whitney and Pearson correlation tests. Caspase-1 activity was also adjusted by initial severity of bleed using analysis of covariance (ANCOVA). Results: Caspase-1 levels from SAH patients were significantly higher than that measured from the control group (mean 1.06x10-2 vs 1.90x10-3 counts per second (CPS)/μl*min), p = 0.0002). Within the SAH group, 10 patients (55.6%) had good outcomes and 8 patients (44.4%) had poor outcomes. Caspase-1 activity was significantly higher in the poor outcome group (mean 1.54x10-2 vs 1.60x10-3 CPS/μl*min), p = 0.0012). Additionally, caspase-1 activity had a statistically significant correlation with GOS score (r = -0.60; p = 0.0100). When adjusted for initial severity of bleed, the difference in caspase-1 activity in good vs. poor outcome remained significant (adjusted mean 7.10x10-3 vs. 2.54x10-2 CPS/μl*min, p=0.004). Conclusions: The inflammasome-dependent protein caspase-1 is elevated in CSF early after SAH and higher in those with poor functional outcome. Inflammasome activity therefore may serve as a novel biomarker to predict outcome shortly after aneurysm rupture.

scholarly journals Levels of caspase-1 in cerebrospinal fluid of patients with traumatic brain injury: correlation with intracranial pressure and outcome

2020 ◽  
pp. 1-6 ◽  
Author(s):  
Jon Pérez-Bárcena ◽  
Catalina Crespí ◽  
Guillem Frontera ◽  
Juan Antonio Llompart-Pou ◽  
Osman Salazar ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
External Ventricular Drain ◽  
Area Under The Curve ◽  
Protein Levels ◽  
Poor Outcome ◽  
Caspase 1 ◽  
Auc Value ◽  
Poor Outcomes

OBJECTIVEThe objectives of this study were to evaluate levels of inflammasome-signaling proteins in serum and CSF of patients with traumatic brain injury (TBI), and to correlate these protein levels with intracranial pressure (ICP) and clinical outcomes at 6 months after injury.METHODSThis is a prospective and observational study in patients with moderate and severe TBI who required an external ventricular drain as part of their treatment. Serum and CSF samples were collected 3 times a day for the first 5 days after TBI. The authors have determined the protein concentration of caspase-1 in the CSF and serum of patients with TBI by using commercially available enzyme-linked immunosorbent assays. The ICP value was recorded hourly. The 6-month outcome was assessed using the Glasgow Outcome Scale–Extended.RESULTSA total of 21 patients were included in this study, and a total of 234 paired serum-CSF samples were analyzed. The area under the curve (AUC) value of caspase-1 in CSF during the 5-day period was 2452.9 pg/mL·hr in the group of patients with high ICP vs 617.6 pg/mL·hr in the patients with low ICP. The differences were mainly on day 2 (19.7 pg/mL vs 1.8 pg/mL; p = 0.06) and day 3 (13.9 pg/mL vs 1 pg/mL; p = 0.05). The AUC value of caspase in CSF during the 5-day period was 1918.9 pg/mL·hr in the group of patients with poor outcome versus 924.5 pg/mL·hr in the patients with good outcome. The protein levels of caspase-1 in CSF were higher in patients with unfavorable outcomes during the first 96 hours after TBI.CONCLUSIONSIn this cohort of patients with TBI who were admitted to the neurosurgical ICU, the inflammasome protein caspase-1 is increased in the CSF of patients with high ICP, especially on days 2 and 3 after TBI. Also the protein levels of caspase-1 in CSF were higher in patients with poor outcome during the first 96 hours after TBI. Moreover, not only the absolute value of caspase-1 in CSF but also its trend is associated with poor outcomes.

scholarly journals Osteopontin in the Cerebrospinal Fluid of Patients with Severe Aneurysmal Subarachnoid Hemorrhage

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 695 ◽  
Author(s):  
Maria Giulia Abate ◽  
Lorenza Moretto ◽  
Ilaria Licari ◽  
Teresa Esposito ◽  
Lorenzo Capuano ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Time Course ◽  
Independent Predictor ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
External Ventricular Drain ◽  
Aneurysm Rupture ◽  
High Morbidity ◽  
Weak Correlation ◽  
Poor Outcome

Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. In SAH patients, plasma osteopontin (OPN) has been shown to independently predict poor outcome. The aim of the study is to investigate, in a selected population with severe SAH, OPN time course in cerebrospinal fluid (CSF) and plasma during the first week after aneurism rupture, and OPN prognostic value. We included 44 patients with the following criteria: (1) age 18 and 80 years, (2) diagnosis of SAH from cerebral aneurysm rupture, (3) insertion of external ventricular drain. Plasma and CSF were sampled at day 1, 4, and 8. OPN levels, in CSF and plasma, displayed a weak correlation on day 1 and were higher, in CSF, in all time points. Only in poor prognosis patients, OPN levels in CSF significantly increased at day 4 and day 8. Plasma OPN at day 1 and 4 was predictor of poor outcome. In conclusion, plasma and CSF OPN displays a weak correlation, on day 1. The higher levels of OPN found in the CSF compared to plasma, suggest OPN production within the CNS after SAH. Furthermore, plasma OPN, at day 1 and 4, seems to be an independent predictor of poor outcome.

Alanine Aminotransferase Predicts Outcomes in Elderly Patients with Aneurysmal Subarachnoid Hemorrhage

2019 ◽  
Vol 16 (1) ◽  
pp. 89-95
Author(s):  
Jianfeng Zheng ◽  
Rui Xu ◽  
Zongduo Guo ◽  
Xiaochuan Sun
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Elderly Patients ◽  
Clinical Outcomes ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Laboratory Data ◽  
Cardiac Complications ◽  
World Population ◽  
Systemic Complications ◽  
Poor Outcome ◽  
Poor Outcomes

Objective: With the aging of the world population, the number of elderly patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) is gradually growing. We aim to investigate the potential association between plasma ALT level and clinical complications of elderly aSAH patients, and explore its predictive value for clinical outcomes of elderly aSAH patients. Methods: Between January 2013 and March 2018, 152 elderly aSAH patients were analyzed in this study. Clinical information, imaging findings and laboratory data were reviewed. According to the Glasgow Outcome Scale (GOS), clinical outcomes at 3 months were classified into favorable outcomes (GOS 4-5) and poor outcomes (GOS 1-3). Logistic regression analysis was used to assess the indicators associated with poor outcomes, and receiver curves (ROC) and corresponding area under the curve (AUC) were used to detect the accuracy of the indicator. Results: A total of 48 (31.6 %) elderly patients with aSAH had poor outcome at 3 months. In addition to ICH, IVH, Hunt-Hess 4 or 5 Grade and Modified Fisher 3 or 4 Grade, plasma ALT level was also strongly associated with poor outcome of elderly aSAH patients. After adjusting for other covariates, plasma ALT level remained independently associated with pulmonary infection (OR 1.05; 95% CI 1.00–1.09; P = 0.018), cardiac complications (OR 1.05; 95% CI 1.01–1.08; P = 0.014) and urinary infection (OR 1.04; 95% CI 1.00–1.08; P = 0.032). Besides, plasma ALT level had a predictive ability in the occurrence of systemic complications (AUC 0.676; 95% CI: 0.586– 0.766; P<0.001) and poor outcome (AUC 0.689; 95% CI: 0.605–0.773; P<0.001) in elderly aSAH patients. Conclusion: Plasma ALT level of elderly patients with aSAH was significantly associated with systemic complications, and had additional clinical value in predicting outcomes. Given that plasma ALT levels on admission could help to identify high-risk elderly patients with aSAH, these findings are of clinical relevance.

Effect of Cilostazol on Cerebral Vasospasm and Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized, Double-Blind, Placebo-Controlled Trial

2016 ◽  
Vol 42 (1-2) ◽  
pp. 97-105 ◽  
Author(s):  
Naoya Matsuda ◽  
Masato Naraoka ◽  
Hiroki Ohkuma ◽  
Norihito Shimamura ◽  
Katsuhiro Ito ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Infarction ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Control Group ◽  
Independent Factor ◽  
Double Blind ◽  
End Points ◽  
Double Blind Placebo ◽  
Poor Outcome

Background: Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm. Methods: Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment. Results: One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period. Conclusions: Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol.

Role of Cerebrospinal Fluid Markers for Predicting Shunt-Dependent Hydrocephalus in Patients with Subarachnoid Hemorrhage and External Ventricular Drain Placement

2019 ◽  
Vol 121 ◽  
pp. e535-e542 ◽  
Author(s):  
Markus Lenski ◽  
Annamaria Biczok ◽  
Volker Huge ◽  
Robert Forbrig ◽  
Josef Briegel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
External Ventricular Drain ◽  
Drain Placement

scholarly journals Peptidome Analysis of Cerebrospinal Fluid in Neonates with Hypoxic-Ischemic Brain Damage

2020 ◽  
Author(s):  
Xuewen Hou ◽  
Zijun Yuan ◽  
Xuan Wang ◽  
Rui Cheng ◽  
Xiaoguang Zhou ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Expression Profiles ◽  
Annexin V ◽  
Fluorescein Isothiocyanate ◽  
Glucose Deprivation ◽  
Differentially Expressed ◽  
Cell Counting ◽  
Control Group ◽  
Ischemic Brain ◽  
Caspase 1

Abstract Hypoxic-ischemic brain injury (HIBD) causes neonatal death and serious neurological disability; however, there are currently no promising therapies for it excepting cooling. Therefore, in this study, we used peptidome analysis to identify differentially expressed peptides in cerebrospinal fluid (CSF) of neonates with HIBD or controls, which may give a foundation for finding new promising drugs of neonatal HIBD. CSF samples were collected from neonates with HIBD (n = 4) or controls (n = 4). ITRAQ LC-MS/MS was used to identify differentially expressed peptides between two groups. Effects of the peptide from heat shock protein 90-alpha (HSP90α/HSP90AA1) on cell viability and pyroptosis under oxygen and glucose deprivation (OGD) were analyzed using cell counting kit-8 (CCK-8) assay and Annexin V-fluorescein isothiocyanate (FITC) Assay. Expressions of NLRP3, ASC and Caspase-1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Compared with the control group, one peptide significantly up-regulated and thirty-four peptides significantly down-regulated in the CSF of neonates with HIBD. A fragment of HSP90α/HSP90AA1 is the 2671.5 Da peptide (HSQFIGYPITLFVEKER), one of the down-regulated peptides in neonatal HIBD. This peptide, we named it HIBDAP, inhibited pyroptosis of PC12 cells under OGD by suppressing expressions of NLRP3, ASC and Caspase-1. The results of our study identified the characterization and expression profiles of peptides in CSF of neonatal HIBD. Several meaningful peptides such as HIBDAP may play significant roles in neonatal HIBD and may provide new therapeutic targets for neonatal HIBD.

scholarly journals Predictive Value of the Serum Albumin Level on Admission in Patients With Spontaneous Subarachnoid Hemorrhage

2021 ◽  
Vol 8 ◽  
Author(s):  
Feng Shang ◽  
Hao Zhao ◽  
Weitao Cheng ◽  
Meng Qi ◽  
Ning Wang ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Serum Albumin ◽  
Serum Albumin Level ◽  
Length Of Hospital Stay ◽  
Albumin Level ◽  
Control Group ◽  
Number Of Patients ◽  
Poor Outcomes ◽  
Spontaneous Subarachnoid Hemorrhage

Objective: To determine the effect of the serum albumin level on admission in patients with spontaneous subarachnoid hemorrhage (SAH).Methods: A total of 229 patients with SAH were divided into control and hypoalbuminemia groups. The serum albumin levels were measured. The data, including age, gender, co-existing medical conditions, risk factors, Hunt-Hess (H-H) grade on admission, Glasgow coma score (GCS) on admission, complications during hospitalizations, length of hospital stay, length of intensive care unit (ICU) stay, in-hospital mortality, survival rate, outcome at discharge, and the 6-month follow-up outcome, were compared between the two groups.Results: Older age, an increased number of patients who consumed an excess of alcohol, and a lower GCS on admission were findings in the hypoalbuminemia group compared to the control group (p &lt; 0.001). The ratio of patients with H-H grade I on admission in the hypoalbuminemia group was decreased compared to the control group (p &lt; 0.05). Patients with hypoalbuminemia were more likely to be intubated, and have pneumonia and cerebral vasospasm than patients with a normal albumin level on admission (p &lt; 0.001). Furthermore, the length of hospital and ICU stays were longer in the hypoalbuminemia group than the control group (p &lt; 0.001). Hypoalbuminemia on admission significantly increased poor outcomes at discharge (p &lt; 0.001). The number of patients with severe disability was increased and the recovery rate was decreased with respect to in-hospital outcomes in the hypoalbuminemia group than the control group (p &lt; 0.001).Conclusion: Hypoalbuminemia was shown to be associated with a poor prognosis in patients with SAH.

Effect of stress-induced hyperglycemia after non-traumatic non-aneurysmal subarachnoid hemorrhage on clinical complications and functional outcomes

2021 ◽  
Author(s):  
Zeyu Zhang ◽  
Yue Zhao ◽  
Yibo Liu ◽  
Xiaoyu Wang ◽  
Houshi Xu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Infarction ◽  
Functional Outcomes ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Complication Rates ◽  
Poor Outcome ◽  
Clinical Complications ◽  
Symptomatic Vasospasm ◽  
Poor Outcomes

Abstract Background Despite having an overall benign course, non-traumatic non-aneurysmal subarachnoid hemorrhage (naSAH) is still accompanied by a risk of clinical complications and poor outcomes. Risk factors and mechanisms of complications and poor outcomes after naSAH remain unknown. Our aim was to explore the effect of stress-induced hyperglycemia (SIH) on complication rates and functional outcomes in naSAH patients. Methods We retrospectively reviewed patients with naSAH admitted to our institution between 2013 and 2018. SIH was identified according to previous criterion. Symptomatic vasospasm, delayed cerebral infarction, and hydrocephalus were identified as main complications. Outcomes were reviewed using a modified Rankin Scale (mRS) at discharge, 3 months, and 12 months. A statistical analysis of clinical, radiological, and laboratory risk factors of complications and outcomes was conducted. Results 244 naSAH patients were incorporated in the cohort with 74 (30.3%) SIH. After adjusting for age, gender, hypertension, Hunt and Hess (HH) grade, modified Fisher Scale (mFS), intraventricular hemorrhage (IVH), and subarachnoid blood distribution, SIH was significantly associated with symptomatic vasospasm (P < 0.001, 12.176 [4.904–30.231]), delayed cerebral infarction (P < 0.001, 12.434 [3.850-40.161]), hydrocephalus (P = 0.008, 5.771 [1.570-21.222]), and poor outcome at 12 months (P = 0.006, 5.506 [1.632–18.581]), whereas the correlation between SIH and poor outcome at discharge (P = 0.064, 2.409 [0.951-6.100]) or 3 months (P = 0.110, 2.029 [0.852–4.833]) was not significant. Incorporation of SIH increased the area under curve (AUC) of ROC in the combined model for predicting symptomatic vasospasm (P = 0.002), delayed cerebral infarction (P = 0.024), hydrocephalus (P = 0.037), and 12-month poor outcome (P = 0.087). Conclusions SIH is a significant and independent risk factor for symptomatic vasospasm, delayed cerebral infarction, hydrocephalus, and long-term poor outcome in naSAH patients. Identifying SIH early after naSAH is important for decision-making and treatment planning.

Antithrombotic States and Outcomes in Patients With Angiographically Negative Subarachnoid Hemorrhage

Neurosurgery ◽  
2011 ◽  
Vol 68 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Ferdinand K. Hui ◽  
Albert J. Schuette ◽  
Shaye I. Moskowitz ◽  
Rishi. Gupta ◽  
Alejandro M. Spiotta ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Modified Rankin Scale ◽  
The Past ◽  
Cerebrospinal Fluid Diversion ◽  
Fisher Grade ◽  
Poor Outcomes ◽  
Subarachnoid Hemorrhages ◽  
State Experience

Abstract BACKGROUND: Antithrombotic states are encountered frequently, either because of medical therapy or by preexistent pathological states, and may affect the severity of hemorrhagic strokes such as angiographically negative subarachnoid hemorrhages. OBJECTIVE: To determine the effects of antithrombotic states on the outcomes of patients with angiographically negative subarachnoid hemorrhage by examining data pooled from 2 institutions. METHODS: This is a retrospective review of patients who experienced angiographically negative subarachnoid hemorrhage at 2 institutions over the past 5 years. The patients were grouped into those with and those without an antithrombotic state at time of hemorrhage and were stratified according to presentation, clinical grades, outcomes, need for cerebrospinal fluid diversion, and development of vasospasm. Computed tomography of the head was assessed for bleed pattern and modified Fisher grade. Patients were excluded if a causative lesion was subsequently discovered. RESULTS: There is a statistically significant association between antithrombotic states and poorer presentation, higher Hunt and Hess score, increased amount of subarachnoid hemorrhage, higher modified Fisher grade, increased incidence of vasospasm, hydrocephalus, and poor outcomes as assessed by modified Rankin scale (P &lt; .001). Patients with an antithrombotic state experience worse outcomes even with adjustment for the amount of hemorrhage as assessed by modified Fisher grade (P &lt; .001). CONCLUSION: Patients in an antithrombotic state presenting with angiographically negative subarachnoid hemorrhage present with inferior clinical scores, diffuse hemorrhage patterns, and worse modified Fisher grades and have worse outcomes.

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