Patients and samples
A total of 12 patients with BM and 24 patients with TM fulfilled the inclusion criteria. One patient with TM was excluded from the analysis because of having been treated at a hospital abroad; the medical record of this patient could not be accessed. The CSF protein in 34 patients (11 patients with BM and all of the patients with TM) has been analyzed, with the CSF ADA in 19 patients with TM. While blood neutrocyte and lymphocyte counts were analyzed in all patients with TM, they were analyzed only in seven patients with BM (5 with enhancement and 2 without).
On their initial MRI, contrast enhancement was detected in 7 out of 12 patients with BM and 9 out of 23 patients with TM. Among those with BM, four cases showed pia-subarachnoid space enhancement, which is known to be a typical finding in BM. Moreover, a dura-arachnoid space enhancement was found in two cases, while one patient showed cortical enhancement in suspected laminar necrosis. Another one patient showed enhancement only on spinal MRI. Among those with TM, all cases showed pia-subarachnoid space enhancement on head MRI, especially in the basal cisterns and sylvian fissure. Five patients also showed intracranial tuberculomas and their enhancement. Furthermore, six patients developed hydrocephalus as a sequela during their clinical courses. Examples of contrast enhancement on MRI in patients with BM and those with TM are shown in Figure 1.
The whole characteristics of our cases (12 BM cases and 23 TM cases) are shown in Tables 1 and 2. As for patient background, those with enhancement in patients with TM were younger (p = 0.045). Other characteristics did not show any differences. Some of the CSF or blood parameters clearly differed between the patients with and without new enhancement among those with TM. Compared with the patients without enhancement, CSF protein, leukocyte, lymphocyte, and blood leukocyte counts were higher (p < 0.05) in those with enhancement, while CSF glucose value was lower (p = 0.005). The additional data file shows their profile in more detail [see Additional file 1].
Table 1. Characteristics of patients with bacterial meningitis
|
With new enhancement
(n = 7)
|
Without new enhancement
(n = 5)
|
p value
|
Age
|
57.7 ± 15.3
|
58.2 ± 16.1
|
0.962
|
No (%) of women
|
2 (29)
|
1 (20)
|
0.079
|
Underlying condition
|
4 (57)
|
1 (20)
|
0.163
|
Blood leukocytes, 10^3/µL
|
17.2 ± 4.84
|
15.5 ± 5.21
|
0.608
|
Blood CRP, mg/dL
|
14.2 ± 9.87
|
15.7 ± 16.9
|
0.867
|
CSF glucose, mg/dL
|
13 ± 19
|
73 ± 77
|
0.098
|
CSF protein, mg/dL
|
523 (47–1672)
|
201 (28–255)
|
0.117
|
CSF leukocytes, cells/μL
|
535 (3.4–25327)
|
1276 (9–6213)
|
0.989
|
CSF neutrocytes, cells/μL
|
529 (0.7–22848)
|
472 (7–5643)
|
0.991
|
CSF lymphocytes, cells/μL
|
13 (3–2479)
|
523 (2–804)
|
0.711
|
Duration of antibiotic administration, days
|
49.7 ± 24.2
|
24.4 ± 3.1
|
0.060
|
No (%) of patients with sequela
|
2 (29)
|
4 (80)
|
0.079
|
Abbreviations: CRP, C reactive protein; CSF, cerebrospinal fluid
Table 2. Characteristics of patients with tuberculous meningitis
|
With new enhancement
(n = 10)
|
Without new enhancement
(n = 13)
|
p value
|
Age
|
45.8 ± 19.0
|
65.5 ± 22.4
|
0.045
|
No (%) of women
|
5 (50)
|
5 (38)
|
0.405
|
Underlying condition
|
3 (30)
|
7 (54)
|
0.195
|
Blood leukocytes, 10^3/µL
|
8.38 ± 2.63
|
6.01 ± 2.47
|
0.045
|
Blood neutrocytes, 10^3/µL
|
7.18 ± 2.30
|
4.86 ± 2.23
|
0.030
|
Blood lymphocytes, 10^3/µL
|
0.75 ± 0.46
|
0.65 ± 0.49
|
0.633
|
Blood CRP, mg/dL
|
3.73 ± 4.12
|
3.29 ± 4.05
|
0.811
|
CSF glucose, mg/dL
|
24.8 ± 10.8
|
44.7 ± 16.5
|
0.005
|
CSF protein, mg/dL
|
234 (166–1006)
|
139 (57–428)
|
0.013
|
CSF leukocytes, cells/μL
|
107.2 (10–658.7)
|
37.0 (3.7–238)
|
0.020
|
CSF neutrocytes, cells/μL
|
24.7 (0.7–474.7)
|
5.0 (0.4–36)
|
0.092
|
CSF lymphocytes, cells/μL
|
79.5 (6–259.4)
|
37.0 (2–205)
|
0.045
|
CSF ADA, IU/L
|
12.0 ± 4.0
|
12.4 ± 7.5
|
0.916
|
No (%) of patients with sequela
|
7 (70)
|
4 (31)
|
0.061
|
Abbreviations: CRP, C reactive protein; CSF, cerebrospinal fluid; ADA, adenosine deaminase
The correlation coefficient of each parameter has also been calculated. In patients with BM, correlations were found among CSF leukocytes, neutrocytes, and lymphocytes (leukocytes vs neutrocytes: ρ = 0.99 (p < 0.001), leukocytes vs lymphocytes: ρ = 0.86 (p < 0.001), neutrocytes vs lymphocytes: ρ = 0.81 (p = 0.001)). Moreover, a correlation was found between CSF protein and glucose (ρ = −0.68 (p = 0.02)). However, correlation was not observed among other parameters. In patients with TM, correlations were found between CSF leukocytes and lymphocytes (ρ = 0.91 (p < 0.001)), leukocytes and neutrocytes (ρ = 0.68 (p < 0.001)), and protein and ADA (ρ = 0.68 (p = 0.001)). Correlation was not observed among other parameters. In particular, correlations could not be found between ADA and CSF cell counts (ADA vs leukocytes: ρ = 0.22 (p = 0.373); ADA vs lymphocytes: ρ = 0.15 (p = 0.536); ADA vs neutrocytes: ρ = −0.03 (p = 0.895)).
Receiver operating characteristics
The diagnostic value of each CSF or blood test parameter has also been analyzed using AUC.
Figure 2 shows the ROC curves for each parameter in BM. An area of 0.90 (95% confidence interval (CI): 0.71–1) and 0.89 (95% CI: 0.67–1) was found for CSF glucose and CSF protein, respectively. No discriminant ability was shown in other parameters, including CSF leukocyte count (0.46 (95% CI: 0.10–0.82)) and its fractionations (neutrocytes: 0.57 (95% CI: 0.22–0.92); lymphocytes: 0.59 (95% CI: 0.20–0.97)) and blood test parameters (leukocytes: 0.57 (95% CI: 0.18–0.96); CRP: 0.54 (95% CI: 0.15–0.93)). As for the significance between each parameter, the AUC of CSF leukocytes was lower than that of the CSF protein (p = 0.046).
Figure 3 shows the ROC curves for each parameter in TM. Areas of 0.85 (95% CI: 0.69–1), 0.76 (95% CI: 0.56–0.96), 0.77 (95% CI: 0.56–0.97), 0.75 (95% CI: 0.54–0.96), 0.74 (95% CI: 0.52–0.96), and 0.78 (95% CI: 0.57–0.99) were found for CSF glucose, CSF protein, CSF leukocytes, CSF lymphocytes, blood leukocytes, and blood neutrocytes, respectively. No discriminant ability was shown in other parameters, including CSF neutrocytes (0.68 (95% CI: 0.43–0.92)), CSF ADA (0.42 (95% CI: 0.15–0.68)), CRP (0.56 (95% CI: 0.31–0.81)), and blood lymphocytes (0.54 (95% CI: 0.27–0.81)). As for the significance between each parameter, the AUC of the CSF lymphocytes was higher than that of the CSF ADA (p = 0.018).