Clinical and Laboratory Factors in the Differential Diagnosis of Tuberculous and Cryptococcal Meningitis in Adult HIV-negative Patients

Abstract

Objective It is difficult to make the differential diagnosis between tuberculous meningitis (TBM) and cryptococcal meningitis (CM) when the smear is negative. The objective of this study was to create a diagnostic rule for differentiating TBM from CM in adult HIV-negative patients based on clinical and laboratory features. Methods The clinical and laboratory data of 219 adult HIV-negative patients satisfying the diagnostic criteria for tuberculous (n=100) and cryptococcal (n=119) meningitis hospitalized at the Third Affiliated Hospital of Sun Yat-Sen University during the period 2000-2009 were retrospectively analyzed. Features found to be independently predictive of tuberculous meningitis were modeled using a multivariate logistic regression to create a diagnostic rule. The performance of the diagnostic rule was assessed using a prospective test data method. Results Six factors were found to be predictive of a diagnosis of tuberculous meningitis: gender, mental disorders, vision and/or hearing damage, proteins in the cerebrospinal fluid, the total cerebrospinal fluid white cell count and the coexistence of tuberculosis in peripheral organs. The diagnostic rule developed using these features exhibited 78.0% sensitivity, 95.2% specificity, 92.9% positive predictive value and 84.4% negative predictive value. The corresponding values for the diagnostic rule were 70.0% and 88.0% using prospective test data. Conclusion Clinical and laboratory features can be helpful in the differential diagnosis of tuberculous meningitis and cryptococcal meningitis in adult HIV-negative patients.

Comparison of clinical features and prognostic factors in HIV-negative adults with cryptococcal meningitis and tuberculous meningitis: a retrospective study

“…However, CM patients were more likely to suffer headache, vision and hearing damage, TBM patients were more prone to have fever and cough. These results were fairly consistent with previous reports [9, 17, 18]. One review showed headache (87%), fever (74%), meningeal irritation (67%), vomiting (61%) and altered mentation (26%) as the most common clinical manifestations of CM [9].…”

“…Patients with TBM presented with higher CSF WBC and total protein than CM patients, similar to prior studies [18]. A low ratio of CD4/CD8 was also found in the apparently healthy CM patients, it’s possible those patients may have some undetectable underlying disease.…”

“…Which possibly be leukoencephalopathy or immune response to the pathogen [21]. In addition, our patients showed evidence of cerebral ischemia or encephalitis more often than previous studies [9, 18], this was likely related to the increased sensitivity of MRI with diffusion-weighted imaging.…”

Comparison of clinical features and prognostic factors in HIV-negative adults with cryptococcal meningitis and tuberculous meningitis: a retrospective study

“…However, CM patients were more likely to suffer headache, vision and hearing damage, TBM patients were more prone to have fever and cough. These results were fairly consistent with previous reports [9, 17, 18]. One review showed headache (87%), fever (74%), meningeal irritation (67%), vomiting (61%) and altered mentation (26%) as the most common clinical manifestations of CM [9].…”

“…Patients with TBM presented with higher CSF WBC and total protein than CM patients, similar to prior studies [18]. A low ratio of CD4/CD8 was also found in the apparently healthy CM patients, it’s possible those patients may have some undetectable underlying disease.…”

“…Which possibly be leukoencephalopathy or immune response to the pathogen [21]. In addition, our patients showed evidence of cerebral ischemia or encephalitis more often than previous studies [9, 18], this was likely related to the increased sensitivity of MRI with diffusion-weighted imaging.…”

Development and validation of a new scoring system for the early diagnosis of tuberculous meningitis in adults

“…CSF laboratory data are a vital part of the diagnosis of CNS infections. Similar to previous observations, patients with TBM were more likely to show features of high protein [15,19,[23][24][25], and hyponatremia (the manifestation in CSF was a decrease in chloride concentration) [13,17,26]. We focus on the differences between this score and previous TBM score studies.…”

“…We focus on the differences between this score and previous TBM score studies. Most of the previous studies [14,15,17,19,21] only limited the CSF leukocyte count in TBM to a cut-off value (>10-20*10 6 /ml) rather than a range, which was of little signi cance for the differential diagnosis of confusing CNS infection, especially between TBM and BM. The reference range of CSF leukocyte count was limited to 100-500*10 6 /ml in our study, which may more reasonable than that in the other prior scoring model settings.…”

Comparison of clinical features and prognostic factors in HIV-negative adults with cryptococcal meningitis and tuberculous meningitis: a retrospective study

“…However, CM patients were more likely to suffer headache, vision and hearing damage, TBM patients were more prone to have fever and cough. These results were fairly consistent with previous reports [9, 17, 18]. One review showed headache (87%), fever (74%), meningeal irritation (67%), vomiting (61%) and altered mentation (26%) as the most common clinical manifestations of CM [9].…”

“…Patients with TBM presented with higher CSF WBC and total protein than CM patients, similar to prior studies [18]. A low ratio of CD4/CD8 was also found in the apparently healthy CM patients, it’s possible those patients may have some undetectable underlying disease.…”

“…Which possibly be leukoencephalopathy or immune response to the pathogen [21]. In addition, our patients showed evidence of cerebral ischemia or encephalitis more often than previous studies [9, 18], this was likely related to the increased sensitivity of MRI with diffusion-weighted imaging.…”

Development and validation of a new scoring system for the early diagnosis of tuberculous meningitis in adults

“…CSF laboratory data are a vital part of the diagnosis of CNS infections. Similar to previous observations, patients with TBM were more likely to show features of high protein [15,19,[23][24][25], and hyponatremia (the manifestation in CSF was a decrease in chloride concentration) [13,17,26]. We focus on the differences between this score and previous TBM score studies.…”

“…We focus on the differences between this score and previous TBM score studies. Most of the previous studies [14,15,17,19,21] only limited the CSF leukocyte count in TBM to a cut-off value (>10-20*10 6 /ml) rather than a range, which was of little signi cance for the differential diagnosis of confusing CNS infection, especially between TBM and BM. The reference range of CSF leukocyte count was limited to 100-500*10 6 /ml in our study, which may more reasonable than that in the other prior scoring model settings.…”

Comparison of clinical features and prognostic factors in HIV-negative adults with cryptococcal meningitis and tuberculous meningitis: a retrospective study

“…However, CM patients were more likely to suffer headache, vision and hearing damage, TBM patients were more prone to have fever and cough. These results were fairly consistent with previous reports [9, 17, 18]. One review showed headache (87%), fever (74%), meningeal irritation (67%), vomiting (61%) and altered mentation (26%) as the most common clinical manifestations of CM [9].…”

“…Patients with TBM presented with higher CSF WBC and total protein than CM patients, similar to prior studies [18]. A low ratio of CD4/CD8 was also found in the apparently healthy CM patients, it’s possible those patients may have some undetectable underlying disease.…”

“…Which possibly be leukoencephalopathy or immune response to the pathogen [21]. In addition, our patients showed evidence of cerebral ischemia or encephalitis more often than previous studies [9, 18], this was likely related to the increased sensitivity of MRI with diffusion-weighted imaging.…”

Development and validation of a new scoring system for the early diagnosis of tuberculous meningitis in adults

“…CSF laboratory data are a vital part of the diagnosis of CNS infections. Similar to previous observations, patients with TBM were more likely to show features of high protein [15,19,[23][24][25], and hyponatremia (the manifestation in CSF was a decrease in chloride concentration) [13,17,26]. We focus on the differences between this score and previous TBM score studies.…”

“…We focus on the differences between this score and previous TBM score studies. Most of the previous studies [14,15,17,19,21] only limited the CSF leukocyte count in TBM to a cut-off value (>10-20*10 6 /ml) rather than a range, which was of little signi cance for the differential diagnosis of confusing CNS infection, especially between TBM and BM. The reference range of CSF leukocyte count was limited to 100-500*10 6 /ml in our study, which may more reasonable than that in the other prior scoring model settings.…”