结核性脑膜炎评分系统对儿童结核性脑膜炎的诊断价值

doi:10.3969/j.issn.1000-6621.2018.09.005

摘要/Abstract

摘要：

目的评价结核性脑膜炎(TBM)评分系统对儿童TBM与病毒性脑炎进行鉴别的价值。方法回顾性分析2010年1月1日至2017年12月31日天津市儿童医院呼吸科收住院的确诊及临床诊断TBM的患儿102例(TBM组),以及同期病毒性脑炎患儿125例(病毒性脑炎组)。TBM评分系统采用包括临床表现、脑脊液检测结果、影像学表现、肺结核或肺外结核的其他表现进行综合评分来诊断TBM(分值越高,越支持TBM诊断;评分≥12分可以临床诊断TBM)。采用病例对照研究的方法,比较该评分系统诊断TBM的敏感度及特异度;同时比较该评分系统与结核菌素皮肤试验(TST)、γ干扰素释放试验(IGRA)及脑脊液病原学检测敏感度的差异。结果 TBM组患儿中,16例(15.69%,16/102)脑脊液病原学检测阳性,确诊为TBM患儿;其余86例(84.31%,86/102)TBM患儿经评分系统评估,分值为(13.25±2.22)分,明显高于病毒性脑炎组患儿的评分[(3.79±2.48)分],差异有统计学意义(t=29.97,P<0.001)。86例患儿中,76例患儿TBM评分≥12分,判断为临床诊断TBM患儿;TBM诊断的敏感度为90.20%(92/102),特异度为100.00%(102/102)。脑脊液病原学检查中,抗酸杆菌染色的敏感度为15.69%(16/102),结核分枝杆菌培养的敏感度为10.78%(11/102),DNA检测的敏感度为16.47%(14/85),均明显低于TBM评分系统(χ ²值分别为113.65、128.66、100.64,P值均<0.001)。免疫学检查方法中,TST的敏感度为50.00%(51/102),特异度为99.20%(124/125);IGRA的敏感度为72.55%(74/102),特异度为99.20%(124/125);敏感度均明显低于TBM评分系统(χ ²值分别为39.31、10.48,P值均<0.001)。结论 TBM评分系统对TBM诊断价值较好,其敏感度明显高于脑脊液抗酸染色、脑脊液结核分枝杆菌培养、脑脊液DNA检测、TST及IGRA等检测方法。

关键词: 儿童, 结核, 脑膜, 脑炎, 病毒性, 诊断, 鉴别, 专家系统, 诊断技术和方法, 对比研究

Abstract:

Objective The purpose of this study was to evaluate the value of tuberculous meningitis (TBM) scoring system in differentiating TBM from viral meningitis.Methods This was a retrospective analysis on 102 TBM children who admitted to the Department of Respiration, Children’s Hospital of Tianjin between January 1, 2010 and December 31, 2017 (defined as the TBM group) and 125 children with viral encephalitis in the same period (defined as the viral encephalitis control group). TBM was diagnosed using a comprehensive scoring system that included clinical manifestations, cerebrospinal fluid (CSF) test results, imaging findings, and other manifestations of pulmonary tuberculosis/extrapulmonary tuberculosis. The higher the score, the more TBM diagnosis was supported. TBM could be clinically diagnosed if the score was greater than or equal to 12. In this case-control study, the sensitivity and specificity of the scoring system in the diagnosis of TBM were analyzed. At the same time, the difference in test sensitivity among the scoring system and the tuberculin skin test (TST), the tests for release of interferon (IGRA) and the CSF etiology was compared.Results Among the children in the TBM group, 16 (15.69%, 16/102) of them were positive in the CSF etiology test and were confirmed as definite TBM by the scoring system. The score of the remaining 86 (84.31%, 86/102) patients with TBM was (13.25±2.22), which was higher than that of the children with viral encephalitis (3.79±2.48). The difference was statistically significant (t=29.97, P<0.001). Seventy-six of the 86 cases had a TBM score of ≥12, and thus were clinically diagnosed as TBM. The sensitivity of the TBM scoring system for the diagnosis of TBM was 90.20% (92/102) and the specificity was 100.00% (102/102). In the examination of CSF etiology, the sensitivity of anti-acid staining of Mycobacterium tuberculosis was 15.69% (16/102), the sensitivity of culture was 10.78% (11/102), and the sensitivity of DNA testing was 16.47% (14/85), which were significantly lower than that of TBM scoring system (χ ²=113.65, 128.66, 100.64, Ps<0.001). In the immunological examination, the sensitivity of TST test was 50.00% (51/102) and the specificity was 99.20% (124/125). IGRA had a sensitivity of 72.55% (74/102) and a specificity of 99.20% (124/125). The sensitivities were significantly lower than that of the TBM scoring system (χ ²=39.31, 10.48, Ps<0.001).Conclusion The TBM scoring system has a good diagnostic value for TBM, and its sensitivity is significantly higher than those of CSF acid stain, CSF culture, CSF DNA test, TST and IGRA detection methods.

Key words: Child, Tuberculosis, meningeal, Encephalitis, viral, Diagnosis, differential, Expert systems, Diagnostic techniques and procedures, Comparative study

张同强,孙琳,郭伟,周彩丽,任立歆,付卓,李淑静,申阿东,徐勇胜. 结核性脑膜炎评分系统对儿童结核性脑膜炎的诊断价值[J]. 中国防痨杂志, 2018, 40(9): 932-939. doi: 10.3969/j.issn.1000-6621.2018.09.005

Tong-qiang ZHANG,Lin SUN,Wei GUO,Cai-li ZHOU,Li-xin REN,Zhuo FU,Shu-jing LI,A-dong SHEN,Yong-sheng XU. The evaluation of tuberculous meningitis scoring system in the diagnose of tuberculous meningitis in children[J]. Chinese Journal of Antituberculosis, 2018, 40(9): 932-939. doi: 10.3969/j.issn.1000-6621.2018.09.005

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分类	评分指标	得分
临床标准(最高6分)	症状超过5d	4
	提示存在结核全身中毒症状(1个及多个):体质量减轻或者不增长;盗汗、持续咳嗽>2周	2
	近1年内有与肺结核患者密切接触史或者TST或(和)IGRA阳性者(仅限于<10岁儿童)	2
	神经系统检查有局灶性神经系统缺失症状与体征表现(除外脑神经麻痹)	1
	脑神经麻痹	1
	意识改变	1
脑脊液标准(最高4分)	清亮	1
	白细胞计数(10~500)×10⁶ 个/L	1
	淋巴细胞比例(>0.50)	1
	蛋白浓度>1g/L	1
	脑脊液葡萄糖/血葡萄糖浓度<0.5,或脑脊液葡萄糖浓度<2.2mmol/L	1
头颅影像学表现(最高6分)	脑积水	1
	基底脑膜强化	2
	结核瘤	2
	脑梗死	1
	强化前基底部高密度影	2
其他部位结核感染的证据	胸片有活动性肺结核的表现:肺结核=2,粟粒型肺结核=4	2/4
(最高4分)	神经系统外CT/MRI/B型超声检查发现有结核病表现	2
	从痰、淋巴结、胃液、尿液、血等培养出MTB或者抗酸杆菌染色阳性	4
	从神经系统外标本中检测到MTB核酸^b	4

TBM评分系统参数	TBM组 (102例)	比率 (%)	病毒性脑炎组(125例)	比率 (%)	χ²值	P值
临床标准
症状超过5d	95	93.14	43	34.40	81.30	<0.001
结核全身中毒症状	48	47.06	2	1.60	67.58	<0.001
结核病接触史	21	20.59	2	1.60	17.82	<0.001
TST阳性	51	50.00	1	0.80	76.99	<0.001
IGRA	74	72.55	1	0.80	130.79	<0.001
神经系统局灶缺失表现	11	10.78	1	0.80	11.18	0.001
脑神经麻痹	24	23.53	1	0.80	26.61	<0.001
意识改变	58	56.86	30	24.00	25.55	<0.001
脑脊液标准
清亮	98	96.08	125	100.00	4.99	0.025
白细胞数(10~500)×10⁶个/L	94	92.16	77	61.60	28.22	<0.001
淋巴细胞比例(>50%)	90	88.24	96^a	88.89	0.02	0.882
蛋白浓度>1.0g/L	76	74.51	0	0.00	140.01	<0.001
脑脊液葡萄糖/血葡萄糖浓度<0.5,或脑脊液葡萄糖浓度<2.2mmol/L	85	83.33	2	1.60	158.74	<0.001
脑影像学表现
脑积水	41	40.20	1	0.80	57.81	<0.001
基底脑膜强化	78	76.47	7	5.60	120.44	<0.001
结核瘤	11	10.78	0	0.00	14.17	<0.001
脑梗死	7	6.86	0	0.00	8.85	0.003
强化前基底高密度	4	3.92	0	0.00	4.99	0.025
肺结核或肺外结核的其他表现
肺结核	48	47.06	0	0.00	74.60	<0.001
粟粒型肺结核	24	23.53	0	0.00	32.89	<0.001
神经系统外CT/MR/B型超发现有结核病表现	11	10.78	0	0.00	11.92	0.001
其他部位标本抗酸杆菌染色阳性或(和)培养出MTB	15	14.71	0	0.00	19.78	<0.001
神经系统外标本中检测到MTB核酸	21	20.59	2	1.60	20.18	<0.001

诊断方法	ROC曲线下面积	Z值^a	P值^a
TBM评分系统	0.951
脑脊液DNA	0.564	9.11	<0.001
脑脊液MTB培养	0.554	9.33	<0.001
脑脊液抗酸染色	0.570	8.96	<0.001
TST	0.746	5.27	<0.001
IGRA	0.859	2.81	0.005
基底脑膜强化	0.854	2.96	0.003