Time Course of Metabolomic Alterations in Cerebrospinal Fluid After Aneurysmal Subarachnoid Hemorrhage

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.

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

Cells ◽

10.3390/cells8070695 ◽

2019 ◽

Vol 8 (7) ◽

pp. 695 ◽

Cited By ~ 4

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.

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The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.1992.77.1.0096 ◽

1992 ◽

Vol 77 (1) ◽

pp. 96-100 ◽

Cited By ~ 174

Author(s):

Ryuta Suzuki ◽

Hiroyuki Masaoka ◽

Yukio Hirata ◽

Fumiaki Marumo ◽

Eiji Isotani ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Time Course ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Normal Range ◽

Content Type ◽

Patient Groups ◽

Group 3 ◽

Fine Print

✓ Plasma and cerebrospinal fluid (CSF) endothelin (ET)-1-like immunoactivity in 27 patients with aneurysmal subarachnoid hemorrhage (SAH) was measured serially by radioimmunoassay for 2 weeks after SAH onset. Mean ET-1-like immunoactivity levels in plasma of patients with SAH were highly elevated during the whole study period, while the levels in CSF of the same patients were not. Plasma ET-1-like immunoactivity levels in patients with SAH classified as Fisher computerized tomography (CT) Group 3 were higher than those in patients with SAH classified as Fisher CT Groups 1 and 2. There were no significant differences in plasma ET-1-like immunoactivity levels between the patient groups stratified by Hunt and Kosnik grade. In this series, plasma ET-1-like immunoactivity levels in the 12 patients with vasospasm were higher than those in the 15 patients without vasospasm during the 1st week; CSF ET-1-like immunoactivity levels in patients with vasospasm were in the normal range on Days 0 to 3 after SAH onset, then became elevated on Days 5 to 7 and remained high until the end of the 2nd week. In contrast, CSF ET-1-like immunoactivity levels in patients without vasospasm were within the normal range during the entire period of study. The time course of the occurrence of vasospasm and that of the increase in CSF ET-1-like immunoactivity coincided precisely. The possible role of endogenous ET-1 in the pathogenesis of vasospasm due to SAH is discussed.

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Increased concentration of atrial natriuretic factor in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage and raised intracranial pressure

Neurosurgery ◽

10.1097/00006123-198807000-00003 ◽

1988 ◽

Vol 23 (1) ◽

pp. 16???9

Author(s):

T D??czi ◽

F Jo?? ◽

M Vecserny??s ◽

M Bodosi

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Intracranial Pressure ◽

Atrial Natriuretic Factor ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Raised Intracranial Pressure ◽

Natriuretic Factor ◽

Atrial Natriuretic

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Cerebrospinal Fluid Concentrations of Nimodipine Correlate With Long-term Outcome in Aneurysmal Subarachnoid Hemorrhage

Clinical Neuropharmacology ◽

10.1097/wnf.0000000000000356 ◽

2019 ◽

Vol 42 (5) ◽

pp. 157-162 ◽

Cited By ~ 1

Author(s):

Roberto Riva ◽

Marianna Pegoli ◽

Manuela Contin ◽

Alessandro Perrone ◽

Susan Mohamed ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Term Outcome ◽

Long Term Outcome

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Correlation Among Systemic Inflammatory Parameter, Occurrence of Delayed Neurological Deficits, and Outcome After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1227/neu.0b013e31828048ce ◽

2012 ◽

Vol 72 (3) ◽

pp. 367-375 ◽

Cited By ~ 48

Author(s):

Carl Muroi ◽

Michael Hugelshofer ◽

Martin Seule ◽

Ilhan Tastan ◽

Masayuki Fujioka ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Confidence Interval ◽

Early Phase ◽

Odds Ratio ◽

Time Course ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Unfavorable Outcome ◽

Neurological Deficits ◽

Inflammatory Parameters ◽

Leukocyte Counts

Abstract BACKGROUND: The role and impact of systemic inflammatory response after aneurysmal subarachnoid hemorrhage remain to be elucidated. OBJECTIVE: To assess the time course and correlation of systemic inflammatory parameters with outcome and the occurrence of delayed ischemic neurological deficits (DINDs) after subarachnoid hemorrhage. METHODS: Besides the baseline characteristics, daily interleukin-6 (IL-6), procalcitonin, C-reactive protein levels, and leukocyte counts were prospectively measured until day 14 after subarachnoid hemorrhage. Occurrence of infectious complications and application of therapeutic hypothermia were assessed as confounding factors. The primary end point was outcome after 3 months, assessed by Glasgow Outcome Scale; the secondary end point was the occurrence of DINDs. RESULTS: During a 3-year period, a total of 138 patients were included. All inflammatory parameters measured were higher in patients with unfavorable outcome (Glasgow Outcome Scale score, 1-3). After adjustment for confounding factors, elevated IL-6 and leukocyte counts remained significant risk factors for unfavorable outcome. The odds ratio for log IL-6 was 4.07 (95% confidence interval, 1.18 to 14.03; P = .03) and for leukocyte counts was 1.24 (95% confidence interval, 1.06-1.46, P = .008). The analysis of the time course established that IL-6 was the only significantly elevated parameter in the early phase in patients with unfavorable outcome. Higher IL-6 levels in the early phase (days 3-7) were associated with the occurrence of DINDs. The adjusted odds ratio for log IL-6 was 4.03 (95% confidence interval, 1.21-13.40; P = .02). CONCLUSION: Higher IL-6 levels are associated with worse clinical outcome and the occurrence of DINDs. Because IL-6 levels were significantly elevated in the early phase, they might be a useful parameter to monitor.

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