结核性脑膜炎患者行脑脊液腺苷脱氨酶及其他生化项目检测的临床意义

Clinical significance of cerebrospinal fluid adenosine deaminase and other biochemical markers in patients with tuberculous meningitis

目的研究结核性脑膜炎患者脑脊液生化检测结果及其动态变化特点,探讨其对临床判断患者病情的指导意义。方法收集2011年1月至2014年9月河北省胸科医院神经内科收治入院的确定诊断和可能诊断(Thwaites诊断标准)的46例结核性脑膜炎患者,对患者脑脊液生化指标[包括氯化物、蛋白、葡萄糖、腺苷脱氨酶(ADA)]、病情分级[按照英国医学研究委员会(MRC)的分期标准:Ⅰ期、Ⅱ期和Ⅲ期]情况进行相关性分析,以及对治疗过程中脑脊液生化检测指标的动态变化及临床意义进行探讨。结果仅脑脊液ADA水平[中位数(四分位数)]随MRC分期增高而明显增高,分别为:Ⅰ期2.00(1.00,5.50)U/L;Ⅱ期3.00(2.00,5.75)U/L;Ⅲ期7.50(4.33,10.00)U/L(H=6.695,P=0.035)。经不同分期两两比较后发现,Ⅲ期患者脑脊液ADA、氯化物水平[102.70(98.10,115.45)mmol/L]明显高于Ⅰ期患者的ADA和氯化物[118.00(111.80,122.60)mmol/L](U=13.609,P=0.033;U=2.122,P=0.035)。46例患者经规范治疗后脑脊液生化指标均逐渐好转,表现为在治疗1、2、4周时脑脊液氯化物分别为118.10(110.30,121.55)、120.00(115.93,122.55)、121.95(117.78,125.90)mmol/L;葡萄糖分别为2.48(2.11,2.91)、2.79(2.31,3.35)、3.03(2.49,3.43)mmol/L;均较入院时[分别为114.75(103.05,118.55)、2.14(1.67,2.99)mmol/L]明显升高(χ^2=34.103、27.642,P值均<0.01);而蛋白[分别为0.62(0.34,0.93)、0.48(0.26,0.85)、0.47(0.27,0.80)g/L]、ADA[分别为2.50(1.00,5.25)、2.00(1.00,4.00)、1.00(1.00,2.00)U/L]均较入院时[分别为0.95(0.56,1.34)g/L、3.50(2.00,7.25)U/L]明显降低(χ^2=29.221、26.209,P值均<0.01)。从治疗过程看,相较于入院时的各项指标,治疗1周后各项指标均无明显变化(t=0.609、0.565、0.228、0.359,P值均>0.05);治疗2周后的各项指标开始有明显变化(t=1.076、1.239、0.946、0.761,P值均<0.05);在治疗4周时,各项指标水平也明显高于入院时(t=1.489、1.152、1.261、1.228,P值均<0.01),但与治疗第2周时的氯化物、蛋白、葡萄糖、ADA指标水平差异均无统计学意义(t值分别为0.413、0.087、0.315、0.467,P值均>0.05)。相较于治疗1周时的各项指标,治疗4周时的葡萄糖和氯化物明显增高(t=1.033,P=0.001;t=0.880,P=0.006)、ADA明显降低(t=0.870,P=0.007),而蛋白无明显变化(t=0.587,P=0.175)。结论脑脊液ADA水平与病情严重程度相关,动态检测脑脊液生化指标有助于评估病情变化。

Objective To investigate the biochemical test results of cerebrospinal fluid (CSF) in patients with tuberculous meningitis (TBM) and their dynamic changes, and to explore its clinical significance for the diagnosis of the patients’ condition. Methods A total of 46 patients with definite or suspected TBM (Thwaites diagnostic criteria) who were admitted to the Department of Neurology, Chest Hospital of Hebei Province from January 2011 to September 2014, were enrolled in this study. CSF biochemical markers(chloride, protein, glucose, adenosine deaminase (ADA)), severity grading (Stage Ⅰ,Ⅱ and Ⅲ, according to the Staging Standards of the British Medical Research Council (MRC))were recorded for correlation analysis. In addition, the dynamic changes of CFS biochemical markers and their clinical significance during the treatment were explored. Results CSF ADA level (M(Q1,Q3)) alone was significantly increased with the increase of MRC stage, which was 2.00 (1.00, 5.50) U/L in stage Ⅰ, 3.00 (2.00, 5.75) U/L in stage Ⅱ, and 7.50 (4.33, 10.00) U/L in stage Ⅲ(H=6.695, P=0.035). After pairwise comparisons between different stages, the CSF ADA and chloride levels (102.70 (98.10, 115.45) mmol/L) in patients with stage Ⅲ were significantly higher than those with stage Ⅰ(chloride 118.00 (111.80, 122.60) mmol/L)(U=13.609, P=0.033;U=2.122, P=0.035). CSF biochemical markers in 46 patients were gradually attenuated after standard treatment. The CSF chlorides were 118.10 (110.30, 121.55), 120.00 (115.93, 122.55), and 121.95 (117.78, 125.90) mmol/L at 1, 2, and 4 weeks after treatment, respectively. The levels of glucose were 2.48 (2.11, 2.91), 2.79 (2.31, 3.35), and 3.03 (2.49, 3.43) mmol/L, respectively, which were significantly higher than those on admission (114.75 (103.05, 118.55), 2.14 (1.67, 2.99) mmol/L), respectively (χ^2=34.103, 27.642;all P<0.01). In addition, at 1, 2, and 4 weeks after treatment, the levels of proteins were 0.62 (0.34, 0.93), 0.48 (0.26, 0.85), and 0.47 (0.27, 0.80) g/L, respectively and those of ADA were 2.50 (1.00, 5.25), 2.00 (1.00, 4.00), and 1.00 (1.00, 2.00) U/L, respectively, which were significantly lower than those on admission (0.95 (0.56, 1.34) g/L, and 3.50 (2.00, 7.25) U/L)(χ^2=29.221, 26.209;all P<0.01). In terms of the treatment process, as compared with the indicators on admission, there was no significant change in various indicators at 1 week after treatment (t=0.609, 0.565, 0.228, 0.359;all P>0.05). After 2 weeks after treatment, the indicators began to change remarkably (t=1.076, 1.239, 0.946, 0.761;all P<0.05). At 4 weeks after treatment, the indicators were also significantly higher than those on admission (t=1.489, 1.152, 1.261, 1.228;all P<0.01), whereas no significant difference were found in chloride, protein, glucose and ADA levels at the 2nd week after treatment (t=0.413, 0.087, 0.315, and 0.467, respectively;all P>0.05). Compared with the indicators at 1 week after treatment, the glucose and chloride levels at 4 weeks after treatment were significantly increased (t=1.033, P=0.001;t=0.880, P=0.006, respectively), and the level of ADA was significantly reduced (t=0.870, P=0.007), while there was no significant difference in the level of protein (t=0.587, P=0.175). Conclusion CSF ADA level is related to the severity of the disease. Therefore, dynamic measurement of CSF biochemical markers is helpful to evaluate the changes of TBM in patients.