结核性脑膜炎伴意识障碍患者的预后影响因素分析

doi:10.3969/j.issn.1000-6621.2019.11.011

摘要/Abstract

摘要：

目的分析结核性脑膜炎(tuberculous meningitis, TBM)伴意识障碍患者的预后影响因素。方法回顾性分析2013年1月至2019年1月长沙市中心医院112例临床诊断为TBM伴意识障碍患者的资料,其中21例(18.8%)为确诊TBM患者,84例(75.0%)为高度可能的TBM患者,7例(6.2%)为可能的TBM患者。根据患者出院时改良Rankin量表(mRS)评分情况,将患者分为预后良好组48例(42.9%),预后不良组64例(57.1%)。预后良好组男性24例,中位年龄[M(Q₁,Q₃)]18.50(5.31,33.75)岁,中位病程20.00(11.25,30.00)d。预后不良组男性20例,中位年龄27.00(3.06,49.75)岁,中位病程15.00(10.00,20.00)d。采用logistic回归分析影响患者预后不良的影响因素。结果单因素分析结果显示,住院时间(Z=-1.982,P=0.048)、性别(χ ²=4.043, P=0.044)、疾病分期(χ ²=17.733, P=0.000)、抽搐(χ ²=8.054, P=0.005)、低钠血症(χ ²=9.481, P=0.002)、脑水肿(χ ²=4.386, P=0.036)、脑积液(χ ²=5.992, P=0.014)对TBM伴意识障碍患者预后不良有一定影响。logistic回归分析显示,低钠血症(P=0.043, OR=2.784, 95%CI:1.034~7.495)、疾病分期为Ⅲ期(P=0.002, OR=6.855, 95%CI:2.001~23.480)、脑水肿(P=0.030, OR=3.491, 95%CI:1.132~10.768)是预后不良的危险因素。结论低钠血症、疾病分期为Ⅲ期、脑水肿是TBM伴意识障碍患者的预后不良的影响因素。

关键词: 结核,脑膜, 意识障碍, 预后, 危险因素, 因素分析,统计学

Abstract:

Objective To analyze influencing factors for prognosis of tuberculous meningitis (TBM) with disturbance of consciousness.Methods Clinical data of 112 patients with consciousness disorder and TBM in Changsha Central Hospital from January 2013 to January 2019 was retrospectively analyzed. 21 (18.8%) patients were definite TBM cases while 84 (75.0%) were probable TBM cases, and 7 (6.2%) were possible TBM cases. According to their scores of modified Rankin scale (mRS) assessed at discharge from hospital, patients were divided into 48 (42.9%) patients with good prognosis and 64 (57.1%) patients with poor prognosis. There were 24 males with good prognosis. The median age was 18.50 (5.31, 3.75) years and the median duration of disease was 20.00 (11.25, 30.00) days. There were 20 males in the poor prognosis group, with a median age of 27.00 (3.06, 49.75) years and a duration of 15.00 (10.00, 20.00) days. Logistic regression analysis was used to analyze influencing factors of poor prognosis of patients.Results Univariate analysis showed that hospital stay (Z=-1.982, P=0.048), sex (χ ²=4.043, P=0.044), disease stage (χ ²=17.733, P=0.000), convulsion (χ ²=8.054, P=0.005), hyponatremia (χ ²=9.481, P=0.002), brain edema (χ ²=4.386, P=0.036), hydrocephalus (χ ²=5.992, P=0.014) were influencing factors for poor prognosis among TBM patients with impaired consciousness. Multivariate analysis showed that hyponatremia (P=0.043, OR=2.784, 95%CI:1.034-7.495), stage Ⅲ of consciousness disturbance (P=0.002, OR=6.855, 95%CI:2.001-23.480), encephaledema (P=0.030, OR=3.491, 95%CI:1.132-10.768) were risk factors for poor prognosis. Conclusion Hyponatremia, stage Ⅲ of disease and brain edema are the main influencing factors for poor prognosis for TBM patients with disturbance of consciousness.

Key words: Tuberculosis, meningeal, Consciousness disorders, Prognosis, Risk factors, Factor analysis, statistical

王曼知,陈芳,危松青,周海依,胡锦跃,谢和宾,张小佛,李嘉,石家云,吴蕾. 结核性脑膜炎伴意识障碍患者的预后影响因素分析[J]. 中国防痨杂志, 2019, 41(11): 1203-1210. doi: 10.3969/j.issn.1000-6621.2019.11.011

WANG Man-zhi,CHEN Fang,WEI Song-qing,ZHOU Hai-yi,HU Jin-yue,XIE He-bin,ZHANG Xiao-fo,LI Jia,SHI Jia-yun,WU Lei. Analysis of influencing factors for prognosis of tuberculous meningitis patients with consciousness disorder[J]. Chinese Journal of Antituberculosis, 2019, 41(11): 1203-1210. doi: 10.3969/j.issn.1000-6621.2019.11.011

图/表 6

表1

表2

表3

表4

112例TBM伴意识障碍患者预后的单因素分析

影响因素		预后良好组(48例)	预后不良组(64例)		检验值		P值
年龄[例(构成比,%)]					χ²=0.431		0.512
>18岁		24(50.0)	36(56.2)
≤18岁		24(50.0)	28(43.8)
性别[例(构成比,%)]					χ²=4.043		0.044
女		24(50.0)	20(31.2)
男		24(50.0)	44(68.8)
居住地[例(构成比,%)]					χ²=0.000		1.000
农村		39(81.2)	52(81.2)
城市		9(18.8)	12(18.8)
入院前病程[d, M(Q₁,Q₃)]		20.81(10.00,20.00)	26.22(11.25,30.00)		Z=-1.440		0.150
住院时间[d, M(Q₁,Q₃)]		55.50(41.00,68.25)	39.00(18.75,69.00)		Z=-1.982		0.048
疾病分期[例(构成比,%)]					χ²=17.733		0.000
Ⅰ期		5(10.4)	2(3.1)
Ⅱ期		38(79.2)	32(50.0)
Ⅲ期		5(10.4)	30(46.9)
抽搐[例(构成比,%)]					χ²=8.054		0.005
无		41(85.4)	39(60.9)
有		7(14.6)	25(39.1)
颅神经损伤[例(构成比,%)]					χ²=2.154		0.142
无		42(87.5)	49(76.6)
有		6(12.5)	15(23.4)
颈强直[例(构成比,%)]						χ²=0.239		0.625
无	8(16.7)			13(20.3)
有	40(83.3)			51(79.7)
病理征阳性[例(构成比,%)]						χ²=2.187		0.139
无	30(62.5)			31(48.4)
有	18(37.5)			33(51.6)
并发症[例(构成比,%)]
肺炎						χ²=1.899		0.168
无	31(64.6)			33(51.6)
有	17(35.4)			31(48.4)
贫血						χ²=2.172		0.141
无	21(43.8)			37(57.8)
有	27(56.2)			27(42.2)
低钠血症						χ²=9.481		0.002
无	29(60.4)			20(31.3)
有	19(39.6)			44(68.7)
头颅影像学异常[例(构成比,%)]
脑积液						χ²=5.992		0.014
无	37(77.1)			35(54.7)
有	11(22.9)			29(45.3)
脑水肿						χ²=4.386		0.036
无	40(83.3)			42(65.6)
有	8(16.7)			22(34.4)
脑梗死						χ²=0.321		0.571
无	29(60.4)			42(65.6)
有	19(39.6)			22(34.4)
脑脊液检查
脑脊液压力[cm H₂O, M(Q₁,Q₃)]	212.50(150.00,350.00)			250.00(140.00,337.50)		Z=-0.262		0.793
脑脊液白细胞[×10⁶个/L, M(Q₁,Q₃)]	240.00(30.00,320.00)			185.00(30.00,80.00)		Z=-1.736		0.083
脑脊液白蛋白[g/L, M(Q₁,Q₃)]	1.58(1.06,2.07)			1.44(0.98,2.46)		Z=-0.050		0.960
脑脊液糖[mmol/L, M(Q₁,Q₃)]	1.99(1.32,2.69)			1.81(1.14,2.62)		Z=-0.788		0.431
脑脊液氯(mmo/L, $x ˉ$ ±s)	112.33±10.43			112.01±9.53		t=0.165		0.869
血液检查
白细胞计数[×10⁹个/L, M(Q₁,Q₃)]	8.51(6.19,12.15)			9.99(6.30,12.12)		Z=-0.679		0.497
中性粒细胞比率(%, $x ˉ$ ±s)	73.86±16.03			76.89±13.64		t=-1.082		0.282
淋巴细胞比率[%, M(Q₁,Q₃)]	17.68(7.65,24.93)			15.70(4.78,23.78)		Z=-0.994		0.320
血小板[×10⁹个/L, M(Q₁,Q₃)]	275.50(206.00,392.50)			275.50(200.25,361.75)		Z=-0.079		0.937
白蛋白[g/L, M(Q₁,Q₃)]	38.54(34.70,43.15)			40.29(30.50,41.08)		Z=-1.943		0.052
球蛋白(g/L, $x ˉ$ ±s)	28.16±5.91			28.84±7.19		t=-0.534		0.594
白蛋白/球蛋白( $x ˉ$ ±s)	1.43±0.37			1.31±0.42		t=1.507		0.135
ESR[mm/1h, M(Q₁,Q₃)]	34.65(14.00,44.00)			31.69(12.25,40.00)		Z=-0.579		0.562

表4

表5

表6

TBM伴意识障碍患者预后多因素logistics回归分析

变量	β值	s $x ˉ$ 值	Wald χ²值	P值	OR值	95%CI值
低钠血症	1.024	0.505	4.103	0.043	2.784	1.034~7.495
脑水肿	1.250	0.575	4.734	0.030	3.491	1.132~10.768
性别	-0.961	0.517	3.462	0.063	0.382	0.139~1.053
住院时间	-0.230	0.008	8.325	0.004	0.977	0.961~0.993
抽搐	1.150	0.587	3.841	0.050	3.157	1.000~9.971
疾病分期			10.709	0.005
疾病分期(Ⅱ)	-0.790	1.062	0.553	0.457	0.454	0.057~3.641
疾病分期(Ⅲ)	1.925	0.628	9.392	0.002	6.855	2.001~23.480

表6

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诊断评分	评分
临床表现	该层最高得分6分
症状持续≥5d(以下 1 项或多项临床表现:头痛、呕吐、易激惹、发热、颈项强直、癫痫发作、局灶性神经损害症状、意识改变)	4
疑似结核的全身症状(1项或多项以下表现):体质量下降(或儿童体质量增长不良),盗汗、持续咳嗽>2周	2
过去1年内有结核密切接触史或TST、IGRA阳性者(仅限于10岁以内儿童)	2
局灶神经损伤表现(不包括颅神经麻痹)	2
颅神经麻痹	1
意识改变	1
脑脊液评分	该层最高得分4分
外观清亮	1
白细胞计数10~500个/μl 淋巴细胞比例>50%	1
蛋白>1g/L	1
脑脊液糖<2.2mol/L或低于血糖的50%	1
头部影像学评分	该层最高得分6分
脑积液	1
脑基底膜增厚	2
脑结核瘤	2
脑梗死	1
脑基底部高密度影	2
其他部位结核证据	该层最高得分4分
胸片提示可疑的活动性结核灶:结核征象=2;粟粒型结核=4	2或4
CT/MRI/B超证实存在中枢神经系统外结核	2
其他标本(如痰、淋巴结、胃液、尿、血)中检测到抗酸杆菌或培养出结核分枝杆菌	4
中枢神经系统外的标本通过核酸扩增技术(NAAT)检测到结核分枝杆菌	4
鉴别诊断的排除	该层最高得分4分
采用微生物学(通过染色、培养、核酸扩增)、血清学(如梅毒)、组织学(如淋巴瘤)等方法来确定鉴别诊断。鉴别诊断列表的制定应考虑到年龄、机体免疫状态以及地理位置,包括:化脓性脑膜炎,隐球菌性脑膜炎,梅毒性脑膜炎,病毒性脑膜炎,脑型疟疾,寄生虫引起的或嗜酸细胞性脑膜炎,脑弓形体病和细菌性脑脓肿,恶性肿瘤(如淋巴瘤)

患者类型		病例数(例)
确诊的TBM	满足A或B的所有条件 A:满足临床表现评分标准同时至少符合以下1种情况:脑脊液检查发现抗酸杆菌;脑脊液分离培养到结核分枝杆菌;PCR方法检测到结核分枝杆菌 B:在脑或脊髓的组织学中找到结核分枝杆菌,并伴有可疑临床表现、体征或脑脊液改变,或尸检有肉眼可见的结核性脑膜炎改变	21
高度可能的TBM	满足临床表现评分标准且总诊断评分≥10分(无脑影像学检查结果时)或者总诊断评分≥12分(有脑影像学检查结果时),同时需排除其他疾病。总得分中至少有2分来自脑脊液或脑影像学检查	84
可能的TBM	满足临床表现评分标准且总诊断评分为6~10分(无脑影像学检查结果时)或者总诊断评分6~11分(有脑影像学检查结果时),同时需排除其他疾病。当未做腰椎穿刺或脑影像学检查时,可能的TBM不能被诊断或排除	7

临床表现	患者例数	发生率(%)
发热	102	91.1
头痛	70	62.5
纳差	109	97.3
消瘦	68	60.7
呕吐	55	49.1
抽搐	32	28.6
颅神经损害	21	18.8
颈强直	91	81.3
病理征阳性	51	45.5