儿童结核性脑膜炎临床特征及预后不良危险因素分析

doi:10.19982/j.issn.1000-6621.20250057

中国防痨杂志 ›› 2025, Vol. 47 ›› Issue (7): 907-913.doi: 10.19982/j.issn.1000-6621.20250057

儿童结核性脑膜炎临床特征及预后不良危险因素分析

王美霁¹^,²^,³^,⁴, 刘美君¹^,²^,³^,⁴, 陈睿¹^,³^,⁴, 夏露⁴^,⁵, 刘旭辉⁴^,⁵, 杨杨⁴^,⁵, 刘华瑞⁴^,⁵, 叶丹⁴^,⁵, 费镇涛⁴^,⁵, 谢师琪³^,⁴, 杨舒琪³^,⁴, 潘磊³^,⁴, 张晓林³^,⁴, 徐飚²(), 李锋¹^,³^,⁴()

¹ 复旦大学上海市重大传染病和生物安全研究院,上海 200032
² 复旦大学公共卫生学院流行病学教研室,上海 200032
³ 上海市(复旦大学附属)公共卫生临床中心呼吸与重症医学科,上海 201508
⁴ 上海市(复旦大学附属)公共卫生临床中心结核病研究中心,上海 201508
⁵ 上海市(复旦大学附属)公共卫生临床中心结核科,上海 201508

收稿日期:2025-02-16 出版日期:2025-07-10 发布日期:2025-07-03
通信作者: 徐飚,Email: bxu@shmu.edu.cn; 李锋, Email: lifeng@shaphc.org
基金资助:
上海市科技重大专项(ZD2021CY001);上海市科技计划项目(21Y11901700);上海市科技计划项目(20Z11901002);国家重点研发计划项目(2024YFC3044600)

Functional outcomes and predictors of tuberculous meningitis in children and young adolescents: a hospital-based retrospective study

Wang Meiji¹^,²^,³^,⁴, Liu Meijun¹^,²^,³^,⁴, Chen Rui¹^,³^,⁴, Xia Lu⁴^,⁵, Liu Xuhui⁴^,⁵, Yang Yang⁴^,⁵, Liu Huarui⁴^,⁵, Ye Dan⁴^,⁵, Fei Zhentao⁴^,⁵, Xie Shiqi³^,⁴, Yang Shuqi³^,⁴, Pan Lei³^,⁴, Zhang Xiaolin³^,⁴, Xu Biao²(), Li Feng¹^,³^,⁴()

¹ Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China
² Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032, China
³ Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
⁴ Tuberculosis Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
⁵ Department of Tuberculosis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China

Received:2025-02-16 Online:2025-07-10 Published:2025-07-03
Contact: Xu Biao,Email: bxu@shmu.edu.cn; Li Feng, Email: lifeng@shaphc.org
Supported by:
Shanghai Municipal Science and Technology Major Project(ZD2021CY001);Shanghai Science and Technology Project(21Y11901700);Shanghai Science and Technology Project(20Z11901002);National Key Research and Development Program Project of China(2024YFC3044600)

摘要/Abstract

摘要：

目的:通过分析儿童结核性脑膜炎(tuberculous meningitis, TBM)患者的临床特征和预后相关的危险因素,为儿童TBM高危患者的早期识别和干预提供有效依据。方法:回顾性收集2013年1月1日至2023年12月31日上海市(复旦大学附属)公共卫生临床中心首次诊断为TBM儿童患者的资料。根据门诊和电话相结合的方式,采用改良兰金量表(modified Rankin scale, mRS)评估儿童TBM抗结核治疗12个月后的神经系统结局,比较预后良好和预后不良两组患儿的临床特征,采用单因素和多因素分析识别和预后不良相关的因素。结果:研究共纳入TBM儿童患者91例,其中,62例预后良好,29例预后不良。患儿年龄的中位数(四分位数)为3.00(1.00, 8.00)岁,51例为男性患儿。入院时预后不良组发生肌力异常(12/29,41.38%)、神志不清(16/29,55.17%)、脑积水(17/29,58.62%)的比例均高于预后良好组[分别为(9/62,14.52%)、(13/62,20.97%)和(22/62,35.48%)](χ²=8.032,P=0.005;χ²=10.647,P<0.001;χ²=4.319,P=0.038);发生咳嗽≥2周(4/29,13.79%)和咳痰(1/29,3.45%)的比例则低于预后良好组[分别为(21/62,33.87%)、(13/62,20.97%)](χ²=3.997,P=0.046;χ²=4.659,P=0.031);预后不良组的格拉斯哥昏迷量表(Glasgow Coma Scale, GCS)评分比预后良好组更低(13 和15;Z=-4.190,P<0.001),英国医学研究委员会(Medical Research Council,MRC)疾病分期差异具有统计学意义(χ²=22.327,P<0.001)。此外,预后不良组的脑脊液(cerebrospinal fluid,CSF)乳酸脱氢酶含量[中位数(四分位数):60.00(29.50,128.00)IU/L]、使用外脑室引流术(7/29,24.14%)以及机械通气(19/29,65.52%)的比例均高于预后良好组[分别为39.50(20.75,64.00)IU/L、(2/62,3.23%)、(25/62,40.32%)](Z=-2.100,P=0.036;χ²=9.696,P=0.002;χ²=5.022,P=0.025)。多因素logistic分析结果显示入院神志不清(OR=3.690;95%CI:1.045~13.034;P=0.043)和使用外脑室引流(OR=8.041;95%CI:1.064~60.760;P=0.043)是儿童TBM患者预后不良的独立危险因素。结论:预后不良儿童TBM患者更多表现为严重神经系统症状(如肌力异常、低GCS评分)、脑积水及CSF乳酸脱氢酶升高,且机械通气需求更高。而预后良好组呼吸道症状(如咳嗽、咳痰)更突出,可能提示早期就诊或疾病较轻。入院神志不清、外脑室引流是提示预后不良的独立危险因素。

关键词: 儿童, 结核, 脑膜, 预后, 危险因素

Abstract:

Objective: To analyze the clinical features and risk factors associated with the prognosis of tuberculous meningitis (TBM) in children, and to provide evidence for early detection and intervention on high-risk TBM in pediatric patients. Methods: Clinical records of TBM children diagnosed in Shanghai Public Health Clinical Center (Fudan University) between 01/01/2013 and 12/31/2023 were reviewed retrospectively. The neurological outcomes of anti-TB treatment at month-12 were evaluated by the modified Rankin Scale (mRS) through outpatient visit and telephone interview. The clinical characteristics of children with good prognosis and poor prognosis were compared, univariate and multivariate analyses were used to determine factors associated with poor prognosis. Results: A total of 91 patients were eligible for the study. Among them, 62 had a good prognosis while the left 29 had a poor prognosis. The median (quartile) age was 3.00 (1.00, 8.00) years old, and 51 were boys. On admission, the poor prognosis group had higher proportion of abnormal muscle strength (12/29, 41.38%), confusion (16/29, 55.17%), and hydrocephalus (17/29, 58.62%) compared to the good prognosis group ((9/62, 14.52%), (13/62, 20.97%), and (22/62, 35.48%), respectively)(χ²=8.032, P=0.005; χ²=10.647, P<0.001; χ²=4.319, P=0.038). In contrast, the frequency of cough ≥2 weeks (4/29, 13.79%) and expectoration (1/29, 3.45%) were lower in the poor prognosis group than in the good prognosis group ((21/62, 33.87%) and (13/62, 20.97%), respectively)(χ²=3.997, P=0.046; χ²=4.659, P=0.031). The Glasgow Coma Scale scores of the poor prognosis group were 13, lower than the 15 in the good prognosis group (Z=-4.190, P<0.001), and the difference in Medical Research Council (MRC) disease stage was statistically significant (χ²=22.327, P<0.001). In addition, the median (quartile) cerebrospinal fluid (CSF) lactate dehydrogenase level of 60.00 (29.50, 128.00) IU/L, the use of external ventricular drainage (7/29, 24.14%), and the frequency of mechanical ventilation (19/29, 65.52%) were higher in the poor prognosis group than in the good prognosis group (39.50 (20.75, 64.00) IU/L, (2/62, 3.23%), and (25/62, 40.32%), respectively)(Z=-2.100, P=0.036; χ²=9.696, P=0.002; χ²=5.022, P=0.025). Multivariate logistic regression analysis showed that confusion on admission (OR=3.690; 95%CI: 1.045-13.034; P=0.043) and external ventricular drainage (OR=8.041; 95%CI: 1.064-60.760; P=0.043) were independent risk factors for poor prognosis in children with TBM. Conclusion: Children with poor prognosis of TBM were more likely to have severe neurologic symptoms (e.g., muscle strength abnormalities, low GCS scores), hydrocephalus, and elevated CSF lactate dehydrogenase, and require higher mechanical ventilation. In contrast, respiratory symptoms (e.g., cough, sputum) were more prominent in the good prognosis group, which may suggest early consultation or milder disease. Admission confusion and external ventricular drainage were independent risk factors for poor prognosis.

Key words: Children, Tuberculosis, meningeal, Prognosis, Risk factors

中图分类号:

R529.3

王美霁, 刘美君, 陈睿, 夏露, 刘旭辉, 杨杨, 刘华瑞, 叶丹, 费镇涛, 谢师琪, 杨舒琪, 潘磊, 张晓林, 徐飚, 李锋. 儿童结核性脑膜炎临床特征及预后不良危险因素分析[J]. 中国防痨杂志, 2025, 47(7): 907-913. doi: 10.19982/j.issn.1000-6621.20250057

Wang Meiji, Liu Meijun, Chen Rui, Xia Lu, Liu Xuhui, Yang Yang, Liu Huarui, Ye Dan, Fei Zhentao, Xie Shiqi, Yang Shuqi, Pan Lei, Zhang Xiaolin, Xu Biao, Li Feng. Functional outcomes and predictors of tuberculous meningitis in children and young adolescents: a hospital-based retrospective study[J]. Chinese Journal of Antituberculosis, 2025, 47(7): 907-913. doi: 10.19982/j.issn.1000-6621.20250057

图/表 2

表1

预后良好和预后不良的儿童TBM患者之间人口统计学和临床特征比较

项目	合计(91例)	预后良好(62例)	预后不良(29例)	统计检验值	P值
性别[例(构成比,%)]				χ²=0.013	0.909
男性	51(56.04)	27(43.55)	13(44.83)
女性	40(43.96)	35(56.45)	16(55.17)
年龄[岁,M(Q₁,Q₃)]	3.00(1.00,8.00)	4.00(1.00,10.00)	2.00(1.00,6.00)	Z=-1.814	0.070
疾病相关资料
住院时间[d,M(Q₁,Q₃)]	23.00(14.00,31.00)	23.00(16.75,32.25)	22.00(7.00,27.50)	Z=-1.939	0.053
卡介苗接种史[例(构成比,%)]	89(97.80)	60(96.77)	29(100.00)	χ²=0.957	0.328
近期结核病患者接触史[例(构成比,%)]	23(25.27)	16(25.81)	7(24.14)	χ²=0.029	0.864
并发肺结核[例(构成比,%)]	53(58.24)	33(53.23)	20(68.97)	χ²=2.013	0.156
血行播散性肺结核[例(构成比,%)]	12(13.19)	10(16.13)	2(6.90)	χ²=1.471	0.225
临床表现[例(发生率,%)]
发热>38.5℃	52(57.14)	35(56.45)	17(58.62)	χ²=0.038	0.846
咳嗽≥2周	25(27.47)	21(33.87)	4(13.79)	χ²=3.997	0.046
盗汗	6(6.59)	4(6.45)	2(6.90)	χ²=0.006	0.936
体质量减轻>5%	9(9.89)	6(9.68)	3(10.34)	χ²=0.010	0.921
头痛	32(35.16)	23(37.10)	9(31.03)	χ²=0.318	0.573
呕吐	46(50.55)	32(51.61)	14(48.28)	χ²=0.088	0.767
抽搐	34(37.36)	19(30.65)	15(51.72)	χ²=3.751	0.053
咳痰	14(15.38)	13(20.97)	1(3.45)	χ²=4.659	0.031
乏力	24(26.37)	15(24.19)	9(31.03)	χ²=0.476	0.490
头晕头昏	5(5.49)	4(6.45)	1(3.45)	χ²=0.343	0.558
视力下降	5(5.49)	3(4.84)	2(6.90)	χ²=0.161	0.688
营养不良	18(19.78)	9(14.52)	9(31.03)	χ²=3.398	0.065
脑膜刺激征阳性	29(31.87)	18(29.03)	11(37.93)	χ²=0.721	0.396
肌力异常	21(23.08)	9(14.52)	12(41.38)	χ²=8.032	0.005
入院神志不清晰	29(31.87)	13(20.97)	16(55.17)	χ²=10.647	<0.001
Glasgow评分[分,M(Q₁,Q₃)]	15.00 (13.00,15.00)	15.00 (15.00,15.00)	13.00 (8.00,15.00)	Z=-4.190	<0.001
MRC疾病分期[例(构成比,%)]				χ²=22.327	0.000
Ⅰ期	38(41.76)	34(54.84)	4(13.79)
Ⅱ期	39(42.86)	25(40.32)	14(48.28)
Ⅲ期	14(15.38)	3(4.84)	11(37.93)
TBM诊断准确性[例(构成比,%)]				χ²=2.602	0.272
确诊	62(68.13)	39(62.90)	23(79.31)
高度疑似	17(18.68)	13(20.97)	4(13.79)
疑似	12(13.19)	10(16.13)	2(6.90)
mRS量表评分[例(构成比,%)]				χ²=86.516	<0.001
0分	38(41.76)	37(59.68)	1(3.45)
1分	19(20.88)	19(30.64)	0(0.00)
2分	6(6.59)	6(9.68)	0(0.00)
3分	11(12.09)	0(0.00)	11(37.93)
4分	3(3.30)	0(0.00)	3(10.34)
5分	10(10.98)	0(0.00)	10(34.49)
6分	4(4.40)	0(0.00)	4(13.79)

表1

表2

预后良好和预后不良儿童TBM患者之间实验室检测、影像学检查和非药物干预措施比较

项目	合计(91例)	预后良好(62例)	预后不良(29例)	统计检验值	P值
外周血常规
白细胞计数[×10⁹/L,M(Q₁,Q₃)]	8.67(5.88,12.41)	9.06(5.89,12.43)	8.24(5.58,12.98)	Z=-0.673	0.501
红细胞计数[×10¹²/L,M(Q₁,Q₃)]	4.21(4.00,4.64)	4.36(4.05,4.74)	4.08(3.96,4.47)	Z=-1.789	0.074
血红蛋白[g/L,$\bar{x}±s$]	113.11±17.54	114.81±18.28	109.48±15.52	t=1.355	0.179
血小板计数[×10⁹/L,M(Q₁,Q₃)]	337.00(261.00,434.00)	345.50(268.25,421.50)	333.00(220.00,515.50)	Z=-0.089	0.929
NLR[M(Q₁,Q₃)]	1.88(0.84,3.97)	1.87(0.82,3.87)	1.88(0.84,4.04)	Z=-0.153	0.878
外周血生化
谷丙转氨酶[IU/L,M(Q₁,Q₃)]	8.67(5.88,12.41)	9.06(5.89,12.43)	8.24(5.58,12.98)	Z=-0.673	0.501
谷草转氨酶[IU/L,M(Q₁,Q₃)]	4.21(4.00,4.64)	4.36(4.05,4.74)	4.08(3.96,4.47)	Z=-1.789	0.074
总胆红素(μmol/L,$\bar{x}±s$)	113.11±17.54	114.81±18.28	109.48±15.52	t=1.355	0.179
白蛋白[g/L,M(Q₁,Q₃)]	1.88(0.84,3.97)	1.87(0.82,3.87)	1.88(0.84,4.04)	Z=-0.153	0.878
血钠[mmol/L,M(Q₁,Q₃)]	28.00(19.00,38.00)	24.50(18.00,33.00)	35.00(19.50,70.50)	Z=-1.905	0.057
血钾[mmol/L,M(Q₁,Q₃)]	6.00(3.90,8.60)	6.15(4.02,8.40)	4.90(3.70,9.30)	Z=-0.341	0.733
血氯[mmol/L,M(Q₁,Q₃)]	2.60(1.70,4.30)	2.80(1.90,4.13)	2.50(1.40,4.45)	Z=-0.170	0.865
尿素[mmol/L,M(Q₁,Q₃)]	3.00(2.10,4.60)	3.30(2.05,4.53)	2.70(2.15,5.10)	Z=-0.294	0.769
肌酐[μmol/L,M(Q₁,Q₃)]	66.70(62.82,70.70)	66.80(63.17,71.13)	66.40(61.20,69.30)	Z=-0.890	0.373
葡萄糖[mmol/L,M(Q₁,Q₃)]	41.10(37.60,43.70)	41.10(38.95,43.05)	41.00(36.47,44.90)	Z=-0.158	0.875
尿酸[μmol/L,M(Q₁,Q₃)]	166.00(126.00,214.00)	178.70(133.75,214.50)	160.00(114.00,216.50)	Z=-0.882	0.378
红细胞沉降率[mm/1h,M(Q₁,Q₃)]	137.00(133.00,139.00)	137.00(133.75,138.00)	136.00(131.00,141.00)	Z=-0.222	0.824
脑脊液检查
潘氏试验阳性[例(构成比,%)]	72(79.12)	48(77.42)	24(82.76)	χ²=0.341	0.559
白细胞计数[×10⁶/L,M(Q₁,Q₃)]	70.00(20.00,150.00)	71.00(29.00,179.50)	32.00(15.00,120.00)	Z=-1.563	0.118
乳酸脱氢酶[IU/L,M(Q₁,Q₃)]	44.00(26.00,90.00)	39.50(20.75,64.00)	60.00(29.50,128.00)	Z=-2.100	0.036
腺苷脱氨酶[IU/L,M(Q₁,Q₃)]	3.00(1.00,7.00)	3.00(1.00,6.63)	3.00(2.00,9.45)	Z=-1.221	0.222
脑脊液氯化物(mmol/L,$\bar{x}±s$)	116.16±7.74	116.61±7.17	115.18±8.88	t=0.824	0.412
脑脊液蛋白[g/L,M(Q₁,Q₃)]	900.50 (457.00,1742.00)	1042.50 (542.00,1740.00)	771.00 (363.50,1956.50)	Z=-0.843	0.399
脑脊液葡萄糖[mmol/L,M(Q₁,Q₃)]	1.84(1.32,2.63)	1.75(1.32,2.56)	1.90(1.23,2.71)	Z=-0.375	0.708
糖比值[M(Q₁,Q₃)]	0.38(0.26,0.54)	0.35(0.26,0.50)	0.42(0.26,0.55)	Z=-0.732	0.464
影像学检查[例(发生率,%)]
脑梗死	6(6.59)	3(4.84)	3(10.34)	χ²=0.973	0.324
脑积水	39(42.86)	22(35.48)	17(58.62)	χ²=4.319	0.038
脑膜强化	21(23.08)	15(24.19)	6(20.69)	χ²=0.137	0.712
脑室扩张	31(34.07)	19(30.65)	12(41.38)	χ²=1.014	0.314
外脑室引流[例(构成比,%)]	9(9.89)	2(3.23)	7(24.14)	χ²=9.696	0.002
机械通气[例(构成比,%)]	44(48.35)	25(40.32)	19(65.52)	χ²=5.022	0.025

表2

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儿童结核性脑膜炎临床特征及预后不良危险因素分析

Functional outcomes and predictors of tuberculous meningitis in children and young adolescents: a hospital-based retrospective study

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