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 ◽  
...  

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.

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yonatan Hirsch ◽  
Joseph R Geraghty ◽  
Eitan A Katz ◽  
Jeffrey A Loeb ◽  
Fernando Testai

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.


Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 291-291
Author(s):  
Diane Aum ◽  
Ananth K Vellimana ◽  
Alexander Padovano ◽  
Eric J Arias ◽  
Umeshkumar Athiraman ◽  
...  

Abstract INTRODUCTION Aneurysmal subarachnoid hemorrhage (SAH) is associated with significant morbidity and mortality. Delayed cerebral ischemia (DCI) is a major cause for poor outcome after SAH. Cerebral vasospasm is the primary driver of DCI, and the largest independent contributor to poor outcome after SAH. Prior studies have reported an association between fever and leukocytosis, and cerebral vasospasm. In this study, we assessed the utility of fever and/or leukocytosis to predict DCI after SAH. METHODS We performed a retrospective analysis of 187 SAH patients. Univariate and multivariate logistic regression was performed to identify potential risk factors for three different endpoints - (a) Mild, Moderate, or Severe Angiographic Vasospasm, (b) Moderate or Severe Angiographic Vasospasm, and (c) Symptomatic DCI. Multiple independent variables including age, Hunt-Hess grade, modified Fisher grade, fever (T>/= 38.0 °C), WBC >/= 10, WBC >/= 15, fever and WBC >/= 10, fever and WBC >/= 15 were examined over the course of each hospital stay. RESULTS >Presence of fever and/or leukocytosis were both significant predictors of symptomatic DCI. In addition, number of days with fever following aneurysm rupture was strongly associated with angiographic vasospasm, while number of days with WBC>/= 15 was strongly associated with symptomatic DCI. When these variables were combined, number of days with concurrent fever and WBC>/= 10 was an independent predictor of angiographic vasospasm, and number of days with concurrent fever and WBC>/= 15 was an independent predictor of both angiographic vasospasm and symptomatic DCI. Time intervals of Day 0–3 and Day 3–7 after aneurysm rupture had the highest odds ratios for angiographic vasospasm. CONCLUSION Patients with aneurysmal SAH who had higher number of days with fever and/or leukocytosis after aneurysm rupture were more likely to have angiographic vasospasm and symptomatic DCI. Presence of fever and/or leukocytosis may have utility in assessing the risk of DCI following SAH.


2007 ◽  
Vol 107 (6) ◽  
pp. 1074-1079 ◽  
Author(s):  
Jari Siironen ◽  
Matti Porras ◽  
Joona Varis ◽  
Kristiina Poussa ◽  
Juha Hernesniemi ◽  
...  

Object Identifying ischemic lesions after subarachnoid hemorrhage (SAH) is important because the appearance of these lesions on follow-up imaging correlates with a poor outcome. The effect of ischemic lesions seen on computed tomography (CT) scans during the first days of treatment remains unknown, however. Methods In 156 patients with SAH, clinical course and outcome, as well as the appearance of ischemic lesions on serial CT scans, were prospectively monitored for 3 months. At 3 months after SAH, magnetic resonance imaging was performed to detect permanent lesions that had not been visible on CT. Results Of the 53 patients with no lesions on any of the follow-up CT scans, four (8%) had a poor outcome. Of the 52 patients with a new hypodense lesion on the first postoperative day CT, 23 (44%) had a poor outcome. Among the remaining 51 patients with a lesion appearing later than the first postoperative morning, 10 (20%) had a poor outcome (p < 0.001). After adjusting for patient age; clinical condition on admission; amounts of subarachnoid, intracerebral, and intraventricular blood; and plasma glucose and D-dimer levels, a hypodense lesion on CT on the first postoperative morning was an independent predictor of poor outcome after SAH (odds ratio 7.27, 95% confidence interval 1.54–34.37, p < 0.05). Conclusions A new hypodense lesion on early postoperative CT seems to be an independent risk factor for poor outcome after SAH, and this early lesion development may be more detrimental to clinical outcome than a later lesion occurrence.


2014 ◽  
Vol 7 (5) ◽  
pp. 346-350 ◽  
Author(s):  
Karam Moon ◽  
Felipe C Albuquerque ◽  
Mario Mitkov ◽  
Andrew F Ducruet ◽  
David A Wilson ◽  
...  

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Weston R Gordon ◽  
Shweta Goswami ◽  
Jane Yang ◽  
Bailey Yekzamen ◽  
Michael G Abraham ◽  
...  

Introduction: Cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH) is associated with a high degree of morbidity and mortality. In an adequate oxidative environment, certain products of bilirubin metabolism have been hypothesized to be a cause of CV. To our knowledge no prospective CSF collection has been performed to establish a time course for their formation in the clinical context of CV. We aimed to design a pilot study assessing the feasibility of collecting and storing CSF for analysis of potential biochemical markers for CV, and to evaluate which variables can accurately and reliably be measured for a larger prospective study. Methods: Adult patients with aSAH and an external ventricular drain (EVD) were enrolled. Patients who had complications following treatment of aSAH or who developed any neurological deterioration unrelated to the aSAH were excluded. CSF was extracted from patients on the initial day of EVD placement and then daily for a total of 10 days and frozen until data analysis. Heme, Heme Oxygenase (HO-1) and Cu/Zn-Superoxide Dismutase (SOD) were measured using commercially available assay kits. Results: Patients 1, 2 and 3 had modified Fisher grades of 2, 3 and 4, respectively. Patients 1 and 3 underwent endovascular coiling and patient 2 had surgical clipping. There were no complications and no CV. Heme concentrations were 40.0 ± 8.5 μm, 55.6 ± 7.7 μm, and 64.7 ± 0.4 μm on day of bleed (day 0) for patients 1, 2, and 3, respectively, and decreased in patients 1 and 2 on day 1. SOD concentrations peaked on day 2 for patient 1 (140.2 ± 15.6 ng/mL), on day 0 for patient 2 (25.8 ± 14.9 ng/mL), and on day 1 for patient 3 (215.9 ± 24.4 ng/mL). HO-1 concentrations peaked for all three patients on day 2 (14.6 ± 0.4, 17.6 ± 12.0 and 23.6 ± 5.4 ng/mL, respectively). Conclusions: The study was successful in completing our objective of establishing a protocol for collection, storage, and measurement of three potential biochemical markers in CSF. A larger prospective study will be performed to establish the time course of bilirubin metabolism and oxidation in the CSF relative to the clinical condition of CV in patients after aSAH.


2021 ◽  
pp. 0271678X2110206
Author(s):  
Kevin Akeret ◽  
Raphael M Buzzi ◽  
Christian A Schaer ◽  
Bart R Thomson ◽  
Florence Vallelian ◽  
...  

Secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH-SBI) contributes to poor outcomes in patients after rupture of an intracranial aneurysm. The lack of diagnostic biomarkers and novel drug targets represent an unmet need. The aim of this study was to investigate the clinical and pathophysiological association between cerebrospinal fluid hemoglobin (CSF-Hb) and SAH-SBI. In a cohort of 47 patients, we collected daily CSF-samples within 14 days after aneurysm rupture. There was very strong evidence for a positive association between spectrophotometrically determined CSF-Hb and SAH-SBI. The accuracy of CSF-Hb to monitor for SAH-SBI markedly exceeded that of established methods (AUC: 0.89 [0.85-0.92]). Temporal proteome analysis revealed erythrolysis accompanied by an adaptive macrophage response as the two dominant biological processes in the CSF-space after aneurysm rupture. Ex-vivo experiments on the vasoconstrictive and oxidative potential of Hb revealed critical inflection points overlapping CSF-Hb thresholds in patients with SAH-SBI. Selective depletion and in-solution neutralization by haptoglobin or hemopexin efficiently attenuated the vasoconstrictive and lipid peroxidation activities of CSF-Hb. Collectively, the clinical association between high CSF-Hb levels and SAH-SBI, the underlying pathophysiological rationale, and the favorable effects of haptoglobin and hemopexin in ex-vivo experiments position CSF-Hb as a highly attractive biomarker and potential drug target.


2020 ◽  
Vol 11 ◽  
Author(s):  
Wing Mann Ho ◽  
Alice S. Görke ◽  
Bernhard Glodny ◽  
Herbert Oberacher ◽  
Raimund Helbok ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sami Ridwan ◽  
Alexander Grote ◽  
Matthias Simon

AbstractInterleukin 6 (IL-6) is a prominent proinflammatory cytokine and has been discussed as a potential biomarker for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage. In the present study we have analyzed the time course of serum and cerebrospinal fluid (CSF) IL-6 levels in 82 patients with severe aneurysmal subarachnoid hemorrhage (SAH) requiring external ventricular drains in correlation to angiographic vasospasm, delayed cerebral ischemia, secondary infarctions and other clinical parameters. We observed much higher daily mean IL-6 levels (but also large interindividual variations) in the CSF than the serum of the patients with a peak between days 4 and 14 including a maximum on day 5 after SAH. Individual CSF peak levels correlated significantly with DCI (mean day 4–14 peak, DCI: 26,291 ± 24,159 pg/ml vs. no DCI: 16,184 ± 13,163 pg/ml; P = 0.023). Importantly, CSF IL-6 levels differed significantly between cases with DCI and infarctions and patients with DCI and no infarction (mean day 4–14 peak, DCI with infarction: 37,209 ± 26,951 pg/ml vs. DCI, no infarction: 15,123 ± 11,239 pg/ml; P = 0.003), while findings in the latter patient group were similar to cases with no vasospasm (mean day 4–14 peak, DCI, no infarction: 15,123 ± 11,239 vs. no DCI: 15,840 ± 12,979; P = 0.873). Together, these data support a potential role for elevated CSF IL-6 levels as a biomarker for DCI with infarction rather than for DCI in general. This fits well with a growing body of evidence linking neuroinflammation to ischemia and infarction, but (together with the large interindividual variations observed) limits the diagnostic usefulness of CSF IL-6 levels in SAH patients.


2021 ◽  
Vol 12 ◽  
pp. 547
Author(s):  
Ahmad Kh Alhaj ◽  
Waleed Yousef ◽  
Abdulrahman Alanezi ◽  
Mariam Almutawa ◽  
Salem Zaidan ◽  
...  

Background: Failure to prevent rebleeding after cerebral subarachnoid hemorrhage (SAH) is the most frequent reason for high morbidity and mortality of aneurysmal SAH. Our study aims to identify the outcome after surgical clipping of aneurysmal SAH before and after the establishment of the neurovascular unit. The clarifications of the positive turnover in the outcome will be discussed. Methods: A retrospective cohort analysis was carried out on our experience with a controlled group of patients who underwent clipping for ruptured cerebral aneurysms (n = 61) from January 2015 to December 2019. A modified Rankin scale (mRS) was used to determine the outcome after 6 months of follow-up. Results: The median mRS score (i.e., outcome) on admission was 4, whereas it was with a median score of 2 six months after clipping (P ≤ 0.001). Overall, the cases with a good outcome were 63.9% of the sample, while the poor outcome conditions were 36.1%. The most cases with an improved outcome were after introducing the neurovascular unit, representing a transition of aneurysmal clipping practice in our center. The good outcome was changed from 42% to 76.7%, and the poor outcome was changed from 58% to 23.3% (P = 0.019). The crude mortality rate was similar to the rate worldwide (18%), with a noticeable decrease after organizing a neurovascular subspecialty. Conclusion: The outcome after clipping of ruptured SAH can be largely affected by the surgeon’s experience and postoperative intensive care. Organizing a neurovascular team is one of the major factors to achieve good outcomes.


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