Motivation: This year, I have seen two patients with community acquired meningitis - both had viral meningitis. When we stopped antibiotics on both, I had slight trepidation about what if we were wrong. After all, microbiologic data on CSF can be misleading. For example, in about 10% of patients, bacterial meningitis can present with lymphocytic predominance. Low plasma glucose is present in only 50-60% of patients with bacterial meningitis. Recently, I came across this article evaluating CSF cortisol as a specific marker of acute bacterial meningitis.
Paper: Holub, M., Beran, O., Dzupova, O., et. al. "Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis." Critical Care (2007) 11:R41
Methods: Study conducted in an academic hospital in Prague. Inclusion criteria were symptoms of menigitis (fever, headache, meningismus) for less than 72 hours and lumbar puncture performed on admission prior to administration of steroids as part of meningitis treatment. Bacterial meningitis was diagnosed by positive bacterial CSF culture or detection of bacterial DNA in CSF using PCR. These patients were compared retrospectively to data from 37 patients with asceptic meningitis as well as data from CSF of 13 control patients who had received LP as part of headache workup.
Results:
Cohort: In total, 47 patients were diagnosed with bacterial meningitis (mean age of 42) with mean APACHE II score of 12.3. At day 28, there was 15% mortality. For the asceptic meningitis group, 37 patients were included with mean age of 38 and average APACHE II score of 3. There were no deaths at 28 days.
CSF Cortisol: Mean CSF cortisol level was 8.45 ug/dL (interquartile range: 2.14-10.08 ug/dL) in patients with bacterial meningitis compared to mean CSF cortisol level of 0.62 ug/dL (interquartile range: 0.47-1.02 ug/dL), p = 0.001. Control patients had mean CSF cortisol level of 0.36 ug/dL (interquartile range: 0.29 - 0.44 ug/dL).
Correlation: CSF cortisol level correlated with APACHE II score - a measure of severity of sickness ( r = 0.763, p < 0.001). CSF cortisol also correlated with serum cortisol (r = 0.587, p < 0.001).
Sensitivity/Specificity: After analyzing receptor operating curves, the best sensitivity/specificity for discriminating bacterial and asceptic meningitis are obtained by setting a threshold of 1.67 ug/dL, which resulted in sensitivity of 82% and specificity of 100%. When comparing bacterial meningitis and control patients, a threshold value of 0.47 ug/dL results in sensitivity and specificity of 100%.
Discussion: This paper adds cortisol to one of the panel of factors in CSF chemistry that can aid in discriminating bacterial and asceptic meningitis. While neutrophilia has higher sensitivity than cortisol, the cortisol level is more sensitive than CSF glucose in detecting bacterial meningitis. Perhaps, more importantly, the very high specificity makes elevated cortisol a very strong indicator of bacterial meningitis. The etiology of elevated CSF cortisol appears to be directly related to the overall systemic inflammatory insult in bacterial infection (elevated APACHE II score and serum cortisol). While this study is a good start, some of the weakness of the design itself are the retrospective nature and generally different clinical condition of bacterial and asceptic meningitis patients (vastly different APACHE scores and 28 day mortality). If patients are very sick with viral meningitis, do they also have non-specific cortisol elevation? This paper does not address and was not powered to evaluate this comparable subgroup of patients. Nonetheless, next time, I do a lumbar puncture to evaluate for meningitis, I will add on a CSF cortisol.
Paper: Holub, M., Beran, O., Dzupova, O., et. al. "Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis." Critical Care (2007) 11:R41
Methods: Study conducted in an academic hospital in Prague. Inclusion criteria were symptoms of menigitis (fever, headache, meningismus) for less than 72 hours and lumbar puncture performed on admission prior to administration of steroids as part of meningitis treatment. Bacterial meningitis was diagnosed by positive bacterial CSF culture or detection of bacterial DNA in CSF using PCR. These patients were compared retrospectively to data from 37 patients with asceptic meningitis as well as data from CSF of 13 control patients who had received LP as part of headache workup.
Results:
Cohort: In total, 47 patients were diagnosed with bacterial meningitis (mean age of 42) with mean APACHE II score of 12.3. At day 28, there was 15% mortality. For the asceptic meningitis group, 37 patients were included with mean age of 38 and average APACHE II score of 3. There were no deaths at 28 days.
CSF Cortisol: Mean CSF cortisol level was 8.45 ug/dL (interquartile range: 2.14-10.08 ug/dL) in patients with bacterial meningitis compared to mean CSF cortisol level of 0.62 ug/dL (interquartile range: 0.47-1.02 ug/dL), p = 0.001. Control patients had mean CSF cortisol level of 0.36 ug/dL (interquartile range: 0.29 - 0.44 ug/dL).
Correlation: CSF cortisol level correlated with APACHE II score - a measure of severity of sickness ( r = 0.763, p < 0.001). CSF cortisol also correlated with serum cortisol (r = 0.587, p < 0.001).
Sensitivity/Specificity: After analyzing receptor operating curves, the best sensitivity/specificity for discriminating bacterial and asceptic meningitis are obtained by setting a threshold of 1.67 ug/dL, which resulted in sensitivity of 82% and specificity of 100%. When comparing bacterial meningitis and control patients, a threshold value of 0.47 ug/dL results in sensitivity and specificity of 100%.
Discussion: This paper adds cortisol to one of the panel of factors in CSF chemistry that can aid in discriminating bacterial and asceptic meningitis. While neutrophilia has higher sensitivity than cortisol, the cortisol level is more sensitive than CSF glucose in detecting bacterial meningitis. Perhaps, more importantly, the very high specificity makes elevated cortisol a very strong indicator of bacterial meningitis. The etiology of elevated CSF cortisol appears to be directly related to the overall systemic inflammatory insult in bacterial infection (elevated APACHE II score and serum cortisol). While this study is a good start, some of the weakness of the design itself are the retrospective nature and generally different clinical condition of bacterial and asceptic meningitis patients (vastly different APACHE scores and 28 day mortality). If patients are very sick with viral meningitis, do they also have non-specific cortisol elevation? This paper does not address and was not powered to evaluate this comparable subgroup of patients. Nonetheless, next time, I do a lumbar puncture to evaluate for meningitis, I will add on a CSF cortisol.
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