Skip to main content
Top
Published in: Critical Care 2/2007

Open Access 01-04-2007 | Research

Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis

Authors: Michal Holub, Ondřej Beran, Olga Džupová, Jarmila Hnyková, Zdenka Lacinová, Jana Příhodová, Bohumír Procházka, Miroslav Helcl

Published in: Critical Care | Issue 2/2007

Login to get access

Abstract

Introduction

Outcomes following bacterial meningitis are significantly improved by adjunctive treatment with corticosteroids. However, little is known about the levels and significance of intrathecal endogenous cortisol. The aim of this study was to assess cortisol as a biological and diagnostic marker in patients with bacterial meningitis.

Methods

Forty-seven consecutive patients with bacterial meningitis and no prior treatment were evaluated. For comparison, a group of 37 patients with aseptic meningitis and a group of 13 healthy control individuals were included.

Results

The mean age of the bacterial meningitis patients was 42 years, and the mean Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation II, and Sequential Organ Failure Assessment scores on admission were 12, 13 and 4, respectively. Altogether, 40 patients (85%) were admitted to the intensive care unit, with a median (interquartile range) length of stay of 8 (4 to 15) days. A bacterial etiology was confirmed in 35 patients (74%). The median (interquartile range) cortisol concentration in cerebrospinal fluid (CSF) was 133 (59 to 278) nmol/l. CSF cortisol concentrations were positively correlated with serum cortisol levels (r = 0.587, P < 0.001). Furthermore, CSF cortisol levels correlated with Acute Physiology and Chronic Health Evaluation II score (r = 0.763, P < 0.001), Sequential Organ Failure Assessment score (r = 0.650, P < 0.001), Glasgow Coma Scale score (r = -0.547, P < 0.001) and CSF lactate levels (r = 0.734, P < 0.001). CSF cortisol was only weakly associated with intrathecal levels of IL-6 (r = 0.331, P = 0.02) and IL-8 (r = 0.296, P < 0.05). CSF cortisol levels in bacterial and aseptic meningitis significantly differed (P < 0.001). The CSF cortisol concentration of 46.1 nmol/l was found to be the optimal cutoff value for diagnosis of bacterial meningitis.

Conclusion

CSF cortisol levels in patients with bacterial meningitis are highly elevated and correlate with disease severity. Moreover, our findings also suggest that intrathecal cortisol may serve as a valuable marker in discriminating between bacterial and aseptic meningitis.
Appendix
Available only for authorised users
Literature
1.
go back to reference Durand ML, Calderwood SB, Weber DJ, Miller SI, Southwick FS, Caviness VS Jr, Swartz MN: Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 1993, 328: 21-28. 10.1056/NEJM199301073280104CrossRefPubMed Durand ML, Calderwood SB, Weber DJ, Miller SI, Southwick FS, Caviness VS Jr, Swartz MN: Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 1993, 328: 21-28. 10.1056/NEJM199301073280104CrossRefPubMed
3.
go back to reference Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ: Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004, 39: 1267-1284. 10.1086/425368CrossRefPubMed Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ: Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004, 39: 1267-1284. 10.1086/425368CrossRefPubMed
4.
go back to reference Kleine TO, Zwerenz P, Zofel P, Shiratori K: New and old diagnostic markers of meningitis in cerebrospinal fluid (CSF). Brain Res Bull 2003, 61: 287-297. 10.1016/S0361-9230(03)00092-3CrossRefPubMed Kleine TO, Zwerenz P, Zofel P, Shiratori K: New and old diagnostic markers of meningitis in cerebrospinal fluid (CSF). Brain Res Bull 2003, 61: 287-297. 10.1016/S0361-9230(03)00092-3CrossRefPubMed
5.
go back to reference Saez-Llorens X, McCracken GH Jr: Bacterial meningitis in children. Lancet 2003, 361: 2139-2148. 10.1016/S0140-6736(03)13693-8CrossRefPubMed Saez-Llorens X, McCracken GH Jr: Bacterial meningitis in children. Lancet 2003, 361: 2139-2148. 10.1016/S0140-6736(03)13693-8CrossRefPubMed
6.
go back to reference Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J: Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 2004, 39: 206-217. 10.1086/421997CrossRefPubMed Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J: Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 2004, 39: 206-217. 10.1086/421997CrossRefPubMed
7.
go back to reference Viallon A, Zeni F, Lambert C, Pozzetto B, Tardy B, Venet C, Bertrand JC: High sensitivity and specificity of serum procalcitonin levels in adults with bacterial meningitis. Clin Infect Dis 1999, 28: 1313-1316.CrossRefPubMed Viallon A, Zeni F, Lambert C, Pozzetto B, Tardy B, Venet C, Bertrand JC: High sensitivity and specificity of serum procalcitonin levels in adults with bacterial meningitis. Clin Infect Dis 1999, 28: 1313-1316.CrossRefPubMed
8.
go back to reference Schwarz S, Bertram M, Schwab S, Andrassy K, Hacke W: Serum procalcitonin levels in bacterial and abacterial meningitis. Crit Care Med 2000, 28: 1828-1832. 10.1097/00003246-200006000-00024CrossRefPubMed Schwarz S, Bertram M, Schwab S, Andrassy K, Hacke W: Serum procalcitonin levels in bacterial and abacterial meningitis. Crit Care Med 2000, 28: 1828-1832. 10.1097/00003246-200006000-00024CrossRefPubMed
9.
go back to reference Nau R, Bruck W: Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci 2002, 25: 38-45. 10.1016/S0166-2236(00)02024-5CrossRefPubMed Nau R, Bruck W: Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci 2002, 25: 38-45. 10.1016/S0166-2236(00)02024-5CrossRefPubMed
10.
go back to reference Tauber MG, Moser B: Cytokines and chemokines in meningeal inflammation: biology and clinical implications. Clin Infect Dis 1999, 28: 1-11. quiz 12CrossRefPubMed Tauber MG, Moser B: Cytokines and chemokines in meningeal inflammation: biology and clinical implications. Clin Infect Dis 1999, 28: 1-11. quiz 12CrossRefPubMed
11.
go back to reference Havens PL, Wendelberger KJ, Hoffman GM, Lee MB, Chusid MJ: Corticosteroids as adjunctive therapy in bacterial meningitis. A meta-analysis of clinical trials. Am J Dis Child 1989, 143: 1051-1055.CrossRefPubMed Havens PL, Wendelberger KJ, Hoffman GM, Lee MB, Chusid MJ: Corticosteroids as adjunctive therapy in bacterial meningitis. A meta-analysis of clinical trials. Am J Dis Child 1989, 143: 1051-1055.CrossRefPubMed
12.
go back to reference de Gans J, van de Beek D: Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002, 347: 1549-1556. 10.1056/NEJMoa021334CrossRefPubMed de Gans J, van de Beek D: Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002, 347: 1549-1556. 10.1056/NEJMoa021334CrossRefPubMed
13.
go back to reference van Furth AM, Seijmonsbergen EM, Langermans JA, Groeneveld PH, de Bel CE, van Furth R: High levels of interleukin 10 and tumor necrosis factor alpha in cerebrospinal fluid during the onset of bacterial meningitis. Clin Infect Dis 1995, 21: 220-222.CrossRefPubMed van Furth AM, Seijmonsbergen EM, Langermans JA, Groeneveld PH, de Bel CE, van Furth R: High levels of interleukin 10 and tumor necrosis factor alpha in cerebrospinal fluid during the onset of bacterial meningitis. Clin Infect Dis 1995, 21: 220-222.CrossRefPubMed
14.
go back to reference van Woensel JB, Biezeveld MH, Alders AM, Eerenberg AJ, Endert E, Hack EC, von Rosenstiel IA, Kuijpers TW: Adrenocorticotropic hormone and cortisol levels in relation to inflammatory response and disease severity in children with meningococcal disease. J Infect Dis 2001, 184: 1532-1537. 10.1086/324673CrossRefPubMed van Woensel JB, Biezeveld MH, Alders AM, Eerenberg AJ, Endert E, Hack EC, von Rosenstiel IA, Kuijpers TW: Adrenocorticotropic hormone and cortisol levels in relation to inflammatory response and disease severity in children with meningococcal disease. J Infect Dis 2001, 184: 1532-1537. 10.1086/324673CrossRefPubMed
15.
go back to reference Singhi SC, Bansal A: Serum cortisol levels in children with acute bacterial and aseptic meningitis. Pediatr Crit Care Med 2006, 7: 74-78. 10.1097/01.PCC.0000192317.90862.44CrossRefPubMed Singhi SC, Bansal A: Serum cortisol levels in children with acute bacterial and aseptic meningitis. Pediatr Crit Care Med 2006, 7: 74-78. 10.1097/01.PCC.0000192317.90862.44CrossRefPubMed
16.
go back to reference Annane D, Sebille V, Troche G, Raphael JC, Gajdos P, Bellissant E: A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 2000, 283: 1038-1045. 10.1001/jama.283.8.1038CrossRefPubMed Annane D, Sebille V, Troche G, Raphael JC, Gajdos P, Bellissant E: A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 2000, 283: 1038-1045. 10.1001/jama.283.8.1038CrossRefPubMed
17.
go back to reference Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, Kaczmarski EB: Simultaneous detection of Neisseria meningitidis , Haemophilus influenzae , and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol 2001, 39: 1553-1558. 10.1128/JCM.39.4.1553-1558.2001PubMedCentralCrossRefPubMed Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, Kaczmarski EB: Simultaneous detection of Neisseria meningitidis , Haemophilus influenzae , and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol 2001, 39: 1553-1558. 10.1128/JCM.39.4.1553-1558.2001PubMedCentralCrossRefPubMed
18.
go back to reference Holub M, Beran O, Lacinova Z, Cinek O, Chalupa P: Interferon-γ and cortisol levels in cerebrospinal fluid and its relationship to the etiology of aseptic meningoencephalitis. Prague Med Rep 2006, 107: 343-353.PubMed Holub M, Beran O, Lacinova Z, Cinek O, Chalupa P: Interferon-γ and cortisol levels in cerebrospinal fluid and its relationship to the etiology of aseptic meningoencephalitis. Prague Med Rep 2006, 107: 343-353.PubMed
19.
go back to reference Waage A, Halstensen A, Shalaby R, Brandtzaeg P, Kierulf P, Espevik T: Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response. J Exp Med 1989, 170: 1859-1867. 10.1084/jem.170.6.1859CrossRefPubMed Waage A, Halstensen A, Shalaby R, Brandtzaeg P, Kierulf P, Espevik T: Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response. J Exp Med 1989, 170: 1859-1867. 10.1084/jem.170.6.1859CrossRefPubMed
20.
go back to reference Joosten KF, de Kleijn ED, Westerterp M, de Hoog M, Eijck FC, Hop WCJ, Voort EV, Hazelzet JA, Hokken-Koelega AC: Endocrine and metabolic responses in children with meningoccocal sepsis: striking differences between survivors and nonsurvivors. J Clin Endocrinol Metab 2000, 85: 3746-3753. 10.1210/jc.85.10.3746CrossRefPubMed Joosten KF, de Kleijn ED, Westerterp M, de Hoog M, Eijck FC, Hop WCJ, Voort EV, Hazelzet JA, Hokken-Koelega AC: Endocrine and metabolic responses in children with meningoccocal sepsis: striking differences between survivors and nonsurvivors. J Clin Endocrinol Metab 2000, 85: 3746-3753. 10.1210/jc.85.10.3746CrossRefPubMed
21.
go back to reference Hoogendijk WJ, Meynen G, Endert E, Hofman MA, Swaab DF: Increased cerebrospinal fluid cortisol level in Alzheimer's disease is not related to depression. Neurobiol Aging 2006, 27: 780.e1-780.2. 10.1016/j.neurobiolaging.2005.07.017 Hoogendijk WJ, Meynen G, Endert E, Hofman MA, Swaab DF: Increased cerebrospinal fluid cortisol level in Alzheimer's disease is not related to depression. Neurobiol Aging 2006, 27: 780.e1-780.2. 10.1016/j.neurobiolaging.2005.07.017
22.
go back to reference Baker DG, Ekhator NN, Kasckow JW, Dashevsky B, Horn PS, Bednarik L, Geracioti TD Jr: Higher levels of basal serial CSF cortisol in combat veterans with posttraumatic stress disorder. Am J Psychiatry 2005, 162: 992-994. 10.1176/appi.ajp.162.5.992CrossRefPubMed Baker DG, Ekhator NN, Kasckow JW, Dashevsky B, Horn PS, Bednarik L, Geracioti TD Jr: Higher levels of basal serial CSF cortisol in combat veterans with posttraumatic stress disorder. Am J Psychiatry 2005, 162: 992-994. 10.1176/appi.ajp.162.5.992CrossRefPubMed
23.
go back to reference Huitinga I, Erkut ZA, van Beurden D, Swaab DF: The hypothalamo-pituitary-adrenal axis in multiple sclerosis. Ann NY Acad Sci 2003, 992: 118-128.CrossRefPubMed Huitinga I, Erkut ZA, van Beurden D, Swaab DF: The hypothalamo-pituitary-adrenal axis in multiple sclerosis. Ann NY Acad Sci 2003, 992: 118-128.CrossRefPubMed
24.
go back to reference Pardridge WM: Transport of protein-bound hormones into tissues in vivo . Endocr Rev 1981, 2: 103-123.CrossRefPubMed Pardridge WM: Transport of protein-bound hormones into tissues in vivo . Endocr Rev 1981, 2: 103-123.CrossRefPubMed
25.
go back to reference Martensz ND, Herbert J, Stacey PM: Factors regulating levels of cortisol in cerebrospinal fluid of monkeys during acute and chronic hypercortisolemia. Neuroendocrinology 1983, 36: 39-48.CrossRefPubMed Martensz ND, Herbert J, Stacey PM: Factors regulating levels of cortisol in cerebrospinal fluid of monkeys during acute and chronic hypercortisolemia. Neuroendocrinology 1983, 36: 39-48.CrossRefPubMed
26.
go back to reference Karssen AM, Meijer OC, van der Sandt IC, Lucassen PJ, de Lange EC, de Boer AG, de Kloet ER: Multidrug resistance P-glycoprotein hampers the access of cortisol but not of corticosterone to mouse and human brain. Endocrinology 2001, 142: 2686-2694. 10.1210/en.142.6.2686CrossRefPubMed Karssen AM, Meijer OC, van der Sandt IC, Lucassen PJ, de Lange EC, de Boer AG, de Kloet ER: Multidrug resistance P-glycoprotein hampers the access of cortisol but not of corticosterone to mouse and human brain. Endocrinology 2001, 142: 2686-2694. 10.1210/en.142.6.2686CrossRefPubMed
27.
go back to reference Uhr M, Holsboer F, Muller MB: Penetration of endogenous steroid hormones corticosterone, cortisol, aldosterone and progesterone into the brain is enhanced in mice deficient for both mdr1a and mdr1b P-glycoproteins. J Neuroendocrinol 2002, 14: 753-759. 10.1046/j.1365-2826.2002.00836.xCrossRefPubMed Uhr M, Holsboer F, Muller MB: Penetration of endogenous steroid hormones corticosterone, cortisol, aldosterone and progesterone into the brain is enhanced in mice deficient for both mdr1a and mdr1b P-glycoproteins. J Neuroendocrinol 2002, 14: 753-759. 10.1046/j.1365-2826.2002.00836.xCrossRefPubMed
28.
go back to reference Seckl JR: 11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action. Curr Opin Pharmacol 2004, 4: 597-602. 10.1016/j.coph.2004.09.001CrossRefPubMed Seckl JR: 11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action. Curr Opin Pharmacol 2004, 4: 597-602. 10.1016/j.coph.2004.09.001CrossRefPubMed
29.
go back to reference Ho JT, Al-Musalhi H, Chapman MJ, Quach T, Thomas PD, Bagley CJ, Lewis JG, Torpy DJ: Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab 2006, 91: 105-114. 10.1210/jc.2005-0265CrossRefPubMed Ho JT, Al-Musalhi H, Chapman MJ, Quach T, Thomas PD, Bagley CJ, Lewis JG, Torpy DJ: Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab 2006, 91: 105-114. 10.1210/jc.2005-0265CrossRefPubMed
30.
go back to reference Zysk G, Bruck W, Gerber J, Bruck Y, Prange HW, Nau R: Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyrus in experimental pneumococcal meningitis. J Neuropathol Exp Neurol 1996, 55: 722-728.CrossRefPubMed Zysk G, Bruck W, Gerber J, Bruck Y, Prange HW, Nau R: Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyrus in experimental pneumococcal meningitis. J Neuropathol Exp Neurol 1996, 55: 722-728.CrossRefPubMed
31.
go back to reference Drew PD, Chavis JA: Inhibition of microglial cell activation by cortisol. Brain Res Bull 2000, 52: 391-396. 10.1016/S0361-9230(00)00275-6CrossRefPubMed Drew PD, Chavis JA: Inhibition of microglial cell activation by cortisol. Brain Res Bull 2000, 52: 391-396. 10.1016/S0361-9230(00)00275-6CrossRefPubMed
32.
go back to reference Dandona P, Suri M, Hamouda W, Aljada A, Kumbkarni Y, Thusu K: Hydrocortisone-induced inhibition of reactive oxygen species by polymorphonuclear neutrophils. Crit Care Med 1999, 27: 2442-2444. 10.1097/00003246-199911000-00020CrossRefPubMed Dandona P, Suri M, Hamouda W, Aljada A, Kumbkarni Y, Thusu K: Hydrocortisone-induced inhibition of reactive oxygen species by polymorphonuclear neutrophils. Crit Care Med 1999, 27: 2442-2444. 10.1097/00003246-199911000-00020CrossRefPubMed
33.
go back to reference Wellmer A, Prange J, Gerber J, Zysk G, Lange P, Michel U, Eiffert H, Nau R: D- and L-lactate in rabbit and human bacterial meningitis. Scand J Infect Dis 2001, 33: 909-913. 10.1080/00365540110076732CrossRefPubMed Wellmer A, Prange J, Gerber J, Zysk G, Lange P, Michel U, Eiffert H, Nau R: D- and L-lactate in rabbit and human bacterial meningitis. Scand J Infect Dis 2001, 33: 909-913. 10.1080/00365540110076732CrossRefPubMed
Metadata
Title
Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis
Authors
Michal Holub
Ondřej Beran
Olga Džupová
Jarmila Hnyková
Zdenka Lacinová
Jana Příhodová
Bohumír Procházka
Miroslav Helcl
Publication date
01-04-2007
Publisher
BioMed Central
Published in
Critical Care / Issue 2/2007
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc5729

Other articles of this Issue 2/2007

Critical Care 2/2007 Go to the issue