Abstract:

Objective: To analyze the dynamic changes of expression of neuron specific enolase (NSE), S100B protein and glial fibrillary acidic protein (GFAP) in serum and cerebrospinal fluid of children with tuberculous meningitis (TBM) and their prognostic value. Methods: A prospective study was conducted in 72 children with TBM admitted to the Department of Pediatric Tuberculosis, Changsha Central Hospital affiliated to South China University from January 1, 2018 to December 31, 2021 (TBM group). And 20 hospitalized children diagnosed with pulmonary tuberculosis and excluded TBM in the corresponding period were collected as pulmonary tuberculosis group. Children in TBM group were divided into complete recovery group (n=47) and poor prognosis group (n=25) according to the prognosis after 6-month treatment. Enzyme-linked immunosorbent assay (ELISA) was used to determine the NSE, S100B and GFAP levels in serum and cerebrospinal fluid of TBM group within 48 h after admission and after treatment (1,2 and 3 weeks) and of pulmonary tuberculosis group within 48 h after admission, the results were compared. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze NSE, S100B and GFAP levels in cerebrospinal fluid of TBM children at admission to predict the threshold, sensitivity and specificity of the poor prognosis. Results: NSE, S100B and GFAP levels (median (quartile)) in serum and cerebrospinal fluid at admission were 15.12 (3.22, 26.90) μg/L, 1.11 (0.40, 3.20) μg/L, 15.34 (3.44, 45.82) μg/L and 37.90 (6.50,142.70) μg/L, 2.31 (1.02, 10.20) μg/L, 65.31 (10.87, 252.60) μg/L, respectively in TBM group, which were all significantly higher than those in pulmonary tuberculosis group (7.03 (2.48, 13.23) μg/L, 0.25 (0.12, 0.36) μg/L, 10.38 (2.41,19.00) μg/L, 7.56 (2.12, 12.79) μg/L, 0.35 (0.05, 0.51) μg/L and 7.86 (2.41, 13.80) μg/L, respectively)(serum levels: Z values were -5.064, -6.817 and -2.693, respectively; P values were 0.000, 0.000 and 0.007, respectively) (cerebrospinal fluid level: Z values were -6.465, -6.816 and -6.778, respectively, all P=0.000). The levels of NSE, S100B and GFAP in cerebrospinal fluid of patients in the poor prognosis group were significantly higher than those in the complete recovery group (60.16 (24.90,142.70) μg/L vs. 29.37 (6.50, 68.82) μg/L, Z=-4.855, P=0.000; 2.59 (1.32, 10.20) μg/L vs. 1.97 (1.02,6.10) μg/L, Z=-3.212, P=0.001; 118.74 (58.83, 252.60) μg/L vs. 45.39 (10.87, 84.93) μg/L, Z=-6.334, P=0.000, respectively). In the poor prognosis group, at the 1st, 2nd and 3rd week after treatment, NSE levels of cerebrospinal fluid were 49.58 (15.38, 87.56) μg/L, 41.53 (9.60, 82.00) μg/L and 25.97 (5.56,58.49) μg/L, respectively; S100B levels were 10.15 (3.63, 15.72) μg/L, 1.60 (0.41, 3.28) μg/L and 0.75 (0.41, 1.60) μg/L, respectively; GFAP levels were 99.75 (65.79, 180.84) μg/L, 63.94 (13.65, 120.59) μg/L and 38.03(10.87,85.40) μg/L, respectively; which were all significantly higher than those in the complete recovery group (NSE: 18.49 (4.87,36.12) μg/L, 14.51 (4.87, 35.70) μg/L and 8.53 (2.12, 21.70) μg/L, Z=-2.496, -3.815, -4.041, P=0.015, 0.000, 0.000, respectively; S100B: 5.34 (2.19, 10.08) μg/L, 0.66 (0.19, 1.56) μg/L and 0.40 (0.11, 0.74) μg/L, Z=-3.331, -4.745, -1.207, P=0.047, 0.000, 0.036, respectively; GFAP: 45.39 (10.87, 84.93) μg/L, 17.77 (5.66, 38.15) μg/L and 12.82 (5.04, 26.90) μg/L, Z=-4.940, -2.337, -3.745, P=0.000, 0.016 and 0.012, respectively). ROC curve analysis showed that the predictive thresholds of NSE, S100B and GFAP levels in cerebrospinal fluid for poor prognosis of TBM children at admission were 51.92 μg/L, 2.75 μg/L, and 77.54 μg/L, respectively under the maximum Youden index. Conclusion: The levels of NSE, S100B and GFAP in serum and cerebrospinal fluid of TBM children were significantly increased, and after treatment, the levels of NSE, S100B and GFAP in serum quickly decreased to normal, while those in cerebrospinal fluid decreased slowly. In cerebrospinal fluid of TBM children, NSE ≥51.92 μg/L, S100B ≥ 2.75 μg/L, or GFAP ≥77.54 μg/L at admission and the levels decreased slowly after treatment, indicating the possibility of poor prognosis.

Key words: Meningitis, bacterial, Mycobacterium tuberculosis, Child, Nerve tissue proteins