IL-6 Levels in the Cerebrospinal Fluid and their Association with Brain Oxygen Partial Pressure and Cerebral Vasospasm Development in Patients with Aneurysmal Subarachnoid Haemorrhage

Czech version

Authors: K. Ďuriš ^1,2; E. Neuman ²; V. Vybíhal ²; V. Juráň ²; J. Gottwaldová ³; M. Kýr ⁴; A. Vašků ¹; M. Smrčka ²
Authors‘ workplace: Ústav patologické fyziologie, LF MU, Brno ¹; Neurochirurgická klinika LF MU a FN Brno ²; Oddělení klinické biochemie, LF MU a FN Brno ³; Klinika dětské onkologie LF MU a FN Brno ⁴
Published in: Cesk Slov Neurol N 2016; 79/112(5): 573-578
Category: Original Paper

Overview

Aim:
The aim of this study was to evaluate whether levels of IL-6 in the cerebrospinal fluid are associated with parameters of transcranial dopplermetry or brain oxygen partial pressure (PbtO2) in patients with subarachnoid haemorrhage.

Patients and methods:
Patients with aneurysmal subarachnoid haemorrhage, who were unconscious during the fourth day after the onset of bleeding, were enrolled in the study. We explored associations between levels of IL-6 in the cerebrospinal fluid as measured on the fourth day after subarachnoid hemorrhage and transcranial dopplermetry parameters or brain oxygen partial pressure meassured one day later.

Results:
A total of 20 patients were enrolled into this study. There was a trend to higher levels of IL-6 in patients with cerebral vasospasm (med: 3,544; 25%/75% = perc: 2,106/6,907 vs. med: 10,080; 25%/75% perc: 2,540/13,958; p = 0.0946), however, no correlation between the levels of IL-6 and mean velocities in magistral vessels was observed. There was a tendency to higher levels of IL-6 related to PbtO2 lower than 20 mm Hg (med: 2,860; 25%/75% perc.: 940/8,580 vs. med: 6,937; 25%/75% perc: 3,811/14,524, p = 0.0587) and there was a significant correlation between the levels of IL-6 and PbtO2 in our study group (rs = –0,626; p = 0.002).

Conclusion:
In this study group, there was a correlation between levels of IL-6 in the cerebrospinal fluid and subsequent PbtO2 values at the beginning of the period representing the highest risk of delayed cerebral ischemia development. Based on these results we assume that IL-6 might be considered as a promising marker to predict risk of developing delayed cerebral ischemia.

Key words:
subarachnoid hemorrhage – infl ammation – interleukin-6 – brain tissue oxygen monitoring – Licox – transcranial doppler-metry – cerebral vasospasm

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Sources

1. Al-Khindi T, Macdonald RL, Schweizer TA. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke 2010; 41 (8): e519–36. doi: 10.1161/STROKEAHA.110.581975.

2. van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet 2007; 369 (9558): 306–18.

3. Rowland MJ, Hadjipavlou G, Kelly M, et al. Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm. Br J Anaesth 2012; 109 (3): 315–29. doi: 10.1093/bja/aes264.

4. Dankbaar JW, Rijsdijk M, van der Schaaf IC, et al. Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neuroradiology 2009; 51 (12): 813–9. doi: 10.1007/s00234-009-0575-y.

5. Jurák L, Buchvald P, Beneš V, et al. Vasospasms as a Complication of Subarachnoid Hemorrhage – a Case Report. Cesk Slov Neurol N 2014; 77/110 (6): 642–6.

6. Cahill WJ, Calvert JH, Zhang JH. Mechanisms of Early Brain Injury after Subarachnoid Hemorrhage. J Cereb Blood Flow Metab 2006; 26 (11): 1341–53.

7. Ostrowski RP, Colohan AR, Zhang JH. Molecular mechanisms of early brain injury after subarachnoid hemorrhage. Neurol Res 2006; 28 (4): 399–414.

8. Sehba FA, Bederson JB. Mechanisms of acute brain injury after subarachnoid hemorrhage. Neurol Res 2006; 28 (4): 381–98.

9. Sercombe R, Dinh YR, Gomis P. Cerebrovascular Inflammation Following Subarachnoid Hemorrhage. Jpn J Pharmacol 2002; 88 (3): 227–49.

10. Gallia GL, Tamargo RJ. Leukocyte-endothelial cell interactions in chronic vasospasm after subarachnoid hemorrhage. Neurol Res 2006; 28 (4): 750–8.

11. Hendryk S, Jarzab B, Josko J. Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH. Neuro Endocrinol Lett 2004; 25 (1–2): 141–7.

12. Wu W, Guan Y, Zhao G, et al. Elevated IL-6 and TNF-α Levels in Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients. Mol Neurobiol 2016; 53 (5): 3277-85.

13. Ni W, Gu YX, Song DL, et al. The relationship between IL-6 in CSF and occurrence of vasospasm after subarachnoid hemorrhage. Acta Neurochir Suppl 2011; 110 (1): 203–8. doi: 10.1007/978-3-7091-0353-1_35.

14. Mathiesen T, Andersson B, Loftenius A, et al. Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage. J Neurosurg 1993; 78 (4): 562–7.

15. Sarrafzadeh A, Schlenk F, Gericke C, et al. Relevance of Cerebral Interleukin-6 After Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care 2010; 13 (3): 339–46. doi: 10.1007/s12028-010-9432-4.

16. Malhotra K, Conners JJ, Lee VH, et al. Relative Changes in Transcranial Doppler Velocities Are Inferior to Absolute Thresholds in Prediction of Symptomatic Vasospasm after Subarachnoid Hemorrhage. J Stroke Cerebrovasc Dis 2014; 23 (1): 31–6. doi: 10.1016/j.jstrokecerebrovasdis.2012.08.004.

17. Nakagawa K, Ishibashi T, Matsushima M, et al. Does long-term continuous transcranial Doppler monitoring require a pause for safer use? Cerebrovasc Dis Basel Switz 2007; 24 (1): 27–34.

18. Osuka K, Suzuki Y, Tanazawa T, et al. Interleukin-6 and development of vasospasm after subarachnoid haemorrhage. Acta Neurochir (Wien) 1998; 140 (9): 943–51.

19. Schoch B, Regel JP, Wichert M, et al. Analysis of intrathecal interleukin-6 as a potential predictive factor for vasospasm in subarachnoid hemorrhage. Neurosurgery 2007; 60 (5): 828–36.

20. Smrcka M. Monitoring of Patients with Severe Head Injury. Cesk Slov Neurol N 2011; 74/107 (1): 9–20.

21. Hejčl A, Bolcha M, Procházka J, et al. Multimodální monitorování mozku u pacientů s těžkým kraniocerebrálním traumatem a subarachnoidálním krvácením v neurointenzivní péči. Cesk Slov Neurol N 2009; 72/105 (3): 383–7.

22. Schmidt JM, Ko SB, Helbok R, et al. Cerebral perfusion pressure thresholds for brain tissue hypoxia and metabolic crisis after poor-grade subarachnoid hemorrhage. Stroke 2011; 42 (5): 1351–6. doi: 10.1161/STROKEAHA.110.596874.

23. Hillman J, Åneman O, Persson M, et al. Variations in the response of interleukins in neurosurgical intensive care patients monitored using intracerebral microdialysis. J Neurosurg 2007; 106 (5): 820–5.

24. Helbok R, Schiefecker AJ, Beer R, et al. Early brain injury after aneurysmal subarachnoid hemorrhage: a multimodal neuromonitoring study. Crit Care 2015; 19: 75. doi: 10.1186/s13054-015-0809-9.

25. Perez-Barcena J, Ibáñez J, Brell M, et al. Lack of correlation among intracerebral cytokines, intracranial pressure, and brain tissue oxygenation in patients with traumatic brain injury and diffuse lesions. Crit Care Med 2011; 39 (3): 533–40. doi: 10.1097/CCM.0b013e318205c 7a4.

26. Vergouwen MDI, Vermeulen M, Gijn J van, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies proposal of a multidisciplinary research group. Stroke 2010; 41 (10): 2391–5. doi: 10.1161/STROKEAHA.110.589275.