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中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2024, Vol. 18 ›› Issue (01) : 49 -53. doi: 10.3877/cma.j.issn.1674-1358.2024.01.008

病例报告

结核性脑膜炎并发矛盾反应一例
陈艳1, 侍效春2,†(), 刘晓清3   
  1. 1. 100730　北京，中国医学科学院北京协和医学院，北京协和医院，疑难重症及罕见病国家重点实验室，感染内科
    2. 100730　北京，中国医学科学院北京协和医学院，北京协和医院，疑难重症及罕见病国家重点实验室，感染内科；100730　北京，中国医学科学院北京协和医学院，结核病研究中心
    3. 100730　北京，中国医学科学院北京协和医学院，北京协和医院，疑难重症及罕见病国家重点实验室，感染内科；100730　北京，中国医学科学院北京协和医学院，结核病研究中心；100730　北京，中国医学科学院北京协和医学院，国际临床流行病学网，临床流行病学教研室
  • 收稿日期:2023-07-13 出版日期:2024-02-15
  • 通信作者: 侍效春
  • 基金资助:
    中央高水平医院临床科研专项(No. 2022-PUMCH-A-043)

A case of tuberculous meningitis complicated with paradoxical reaction

Yan Chen1, Xiaochun Shi2,†(), Xiaoqing Liu3   

  1. 1. Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Unison Medical College, Beijing 100730, China
    2. Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Unison Medical College, Beijing 100730, China; Centre for Tuberculosis Research, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
    3. Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Unison Medical College, Beijing 100730, China; Centre for Tuberculosis Research, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing 100730, China
  • Received:2023-07-13 Published:2024-02-15
  • Corresponding author: Xiaochun Shi
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引用本文：

陈艳, 侍效春, 刘晓清. 结核性脑膜炎并发矛盾反应一例[J]. 中华实验和临床感染病杂志(电子版), 2024, 18(01): 49-53.

Yan Chen, Xiaochun Shi, Xiaoqing Liu. A case of tuberculous meningitis complicated with paradoxical reaction[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2024, 18(01): 49-53.

目的

分析1例结核性脑膜炎并发矛盾反应患者的临床特征，以提升临床对结核性脑膜炎并发矛盾反应的关注度。

方法

回顾性分析中国医学科学院北京协和医院2020年9月8日收治的1例结核性脑膜炎并发矛盾反应患者的临床资料、诊疗经过和预后。

结果

该患者以发热、头痛起病，脑脊液检查提示颅压明显升高，白细胞总数、蛋白水平高，氯化物水平降低，脑脊液及外周血结核分枝杆菌感染T细胞检测阳性，头颅核磁共振提示多发异常信号，其余病原学检查均为阴性，考虑结核性脑膜炎可能性大，予诊断性抗结核治疗，临床症状和脑脊液指标一度好转，糖皮质激素减量后病情再度恶化，经系统检查除外其他感染后，考虑矛盾反应，糖皮质激素再次加量后好转。出院后1年复查头颅核磁共振未见明显异常。

结论

结核性脑膜炎并发矛盾反应的病例临床较少见，易漏诊、误诊而延误治疗。对抗结核治疗启动后反而出现病情加重者应警惕并发矛盾反应，治疗首选糖皮质激素。

关键词: 结核性脑膜炎, 矛盾反应, 治疗
Objective

To analyze a case with tuberculous meningitis complicated with paradoxical reaction, and to raise the attention to tuberculous meningitis complicated with paradoxical reaction.

Methods

The clinical data, diagnosis and treatment process and prognosis of a patient with tuberculous meningitis complicated with paradoxical reaction admitted to Peking Union Medical College Hospital, Chinese Academy of Medical Sciences on September 8th 2020 were analyzed, retrospectively.

Results

The patient presented clinically with headache and fever, the cerebrospinal fluid examination showed that the intracranial pressure was significantly increased, the white blood cells and protein level were high, and the chlorine level was low. Mycobacterium tuberculosis infection of T cells spot test were positive both in peripheral blood and cerebrospinal fluid, brain Magnetic Resonance Imaging (MRI) showed multiple abnormal signals, while the rest of the etiological examination was negative. The patient was considered tuberculous meningitis and started diagnostic anti-tuberculosis treatment. The clinical symptoms and cerebrospinal fluid tests improved for a while, but the condition deteriorated again after the reduction of glucocorticoids. The patient was considered paradoxical reaction. After increased doses of glucocorticoid, the patient improved rapidly. MRI at 1 year was essentially unremarkable.

Conclusions

Tuberculous meningitis complicated with paradoxical reaction is rare, which is easy to be misdiagnosed and delayed to receive treatment. Therefore, clinicians are reminded to be alert to tuberculous meningitis complicated by paradoxical reaction for patient with aggravation of the disease after anti-tuberculosis treatment, high-dose glucocorticoids is the preferred treatment.

Key words: Tuberculous meningitis, Paradoxical reaction, Treatment
图1 本病例治疗前后头颅核磁共振影像学注：A：2020年9月10日患者头颅核磁共振示基底节区异常信号；B：2020年10月21日患者头颅核磁共振示基底节区大片异常信号；C：2020年11月26日患者头颅核磁共振示病变范围明显缩小
表1 本病例住院期间脑脊液化验结果和治疗
日期 压力（mmH2O） 白细胞总数（× 106/L） 单核细胞数（× 106/L） 多核细胞数（× 106/L） 葡萄糖（mmol/L） 氯化物（mmol/L） 蛋白（g/L） 治疗
2020年9月9日 320 60 46 4 2.2 117 1.59 HRZE，地塞米松5 mg/次、1次/d
2020年9月16日 210 60 48 12 2.3 123 1.28 HRZE +利奈唑胺，地塞米松5 mg/次、1次/d
2020年9月23日 210 36 34 2 2.6 122 1.09 HRZE +利奈唑胺，地塞米松5 mg/次、1次/d
2020年9月30日 275* 42 40 2 2.4 121 1.02 HRZE +利奈唑胺，地塞米松5 mg/次、1次/d
2020年10月13日 230* 72 66 6 2.4 122 1.39 HRZE +利奈唑胺，泼尼松20 mg/次、1次/d
2020年10月20日 250* 146 130 16 2.0 121 2.44 HRZE +利奈唑胺，泼尼松15 mg/次、1次/d
2020年10月27日 > 330* 136 109 27 2.2 123 2.07 HRZE +利奈唑胺，地塞米松5 mg/次、1次/d
2020年11月3日 260* 156 126 30 1.7 122 2.04 HRZE +利奈唑胺，地塞米松5 mg/次、1次/d
2020年11月16日 220* 44 42 2 1.9 122 1.12 HRZE，地塞米松5 mg/次、1次/d
2020年11月30日 265 30 28 2 2.2 123 0.80 HRZE，泼尼松30 mg/次、1次/d
[1]
Donovan J, Figaji A, Imran D, et al. The neurocritical care of tuberculous meningitis[J]. Lancet Neurol, 2019,18(8):771-783.
[2]
中华医学会结核病学分会结核性脑膜炎专业委员会. 2019中国中枢神经系统结核病诊疗指南[J]. 中华传染病杂志,2020,38(7):400-408.
[3]
Organization WH (2021). Tuberculosis deaths rise for the first time in more than a decade due to the COVID-19 pandemic[EB/OL]. 2021.

URL    
[4]
Organization WH (2019). World Health Statistics 2019: Monitoring health for the SDGs, sustainable development goals[EB/OL]. 2019.

URL    
[5]
Schaller MA, Wicke F, Foerch C, et al. Central nervous system tuberculosis: etiology, clinical manifestations and neuroradiological features[J]. Clin Neuroradiol,2019,29(1):3-18.
[6]
Navarro-Flores A, Fernandez-Chinguel JE, Pacheco-Barrios N, et al. Global morbidity and mortality of central nervous system tuberculosis: a systematic review and meta-analysis[J]. J Neurol, 2022,269(7):3482-3494.
[7]
Centers for Disease Control and Prevention. Reported tuberculosis in the United States, 2018[EB/OL]. 2019.

URL    
[8]
Pang Y, An J, Shu W, et al. Epidemiology of extrapulmonary tuberculosis among inpatients, China. 2008-2017[J]. Emerg Infect Dis,2019,25(3):457-464.
[9]
Basu Roy R, Thee S, Blázquez-Gamero D, et al. Performance of immune-based and microbiological tests in children with tuberculosis meningitis in Europe: a multicentre Paediatric Tuberculosis Network European Trials Group (ptbnet) study[J]. Eur Respir J,2020,56(1):1902004.
[10]
Thwaites GE, Chau TT, Farrar JJ. Improving the bacteriological diagnosis of tuberculous meningitis[J]. J Clin Microbiol, 2004,42(1):378-379.
[11]
Erdem H, Ozturk-Engin D, Elaldi N, et al. The microbiological diagnosis of tuberculous meningitis of Haydarpasa-1 study[J]. Clin Microbiol Infect,2014,20(10):O600-O608.
[12]
Kennedy DH, Fallon RJ. Tuberculous meningitis[J]. JAMA,1979, 241(3):264-268.
[13]
Hernandez AV, Laurentis L, Souza I, et al. Diagnostic accuracy of Xpert MTB/RIF for tuberculous meningitis: systematic review and meta-analysis[J]. Trop Med Int Health,2021,26(2):122-132.
[14]
Donovan J, Cresswell FV, Thuong NTT, et al. Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis: A small step forward[J]. Clin Infect Dis,2020,71(8):2002-2005.
[15]
Chen Y, Wang Y, Liu X, et al. Comparative diagnostic utility of metagenomic next-generation sequencing, GeneXpert, modified Ziehl-Neelsen staining, and culture using cerebrospinal fluid for tuberculous meningitis: A multi-center, retrospective study in China[J]. J Clin Lab Anal,2022,36(4):e24307.
[16]
Ramachandran PS, Ramesh A, Creswell FV, et al. Integrating central nervous system metagenomics and host response for diagnosis of tuberculosis meningitis and its mimics[J]. Nat Commun,2022,13(1):1675.
[17]
Wilson MR, Sample HA, Zorn KC, et al. Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis[J]. N Engl J Med,2019,380(24):2327-2340.
[18]
林爱清, 张璐, 成宝涛, 等. 二代测序技术应用于脑脊液检测在结核性脑膜炎中的早期诊断价值[J/CD]. 中华实验和临床感染病杂志(电子版),2020,14(4):291-295.
[19]
Arai M, Inaba R. A case of tuberculous meningitis with pleural effusion as a manifestation of a paradoxical reaction during anti-tuberculosis therapy[J]. Rinsho Shinkeigaku,2019,59(8):541-544．
[20]
Pepper DJ, Marais S, Maartens G, et al. Neurologic manifestations of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome: a case series[J]. Clin Infect Dis,2009,48(11): e96-e107.
[21]
徐勇胜. 结核病治疗中的矛盾反应[J]. 中华实用儿科临床杂志,2019,34(9):646-649.
[22]
Liu Y, Wang Z, Yao G, et al. Paradoxical reaction in HIV-negative tuberculous meningitis patients with spinal involvement[J]. Int J Infect Dis,2019,79:104-108．
[23]
Nahid P, Dorman SE, Alipanah N, et al. Official American thoracic society/centers for disease control and prevention/infectious diseases society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis[J]. Clin Infect Dis,2016,63(7):e147-e195.
[24]
Lee JY. Diagnosis and treatment of extrapulmonary tuberculosis[J]. Tuberc Respir Dis (Seoul),2015,78(2):47-55.
[25]
Ravimohan S, Tamuhla N, Nfanyana K, et al. Robust reconstitution of tuberculosis-specifc polyfunctional CD4+ T-cell responses and rising systemic interleukin 6 in paradoxical tuberculosis-associated immune reconstitution infammatory syndrome[J]. Clin Infect Dis,2016,62(6):795-803.
[26]
中华医学会结核病学分会. 结核病免疫治疗专家共识(2022年版)[J]. 中华结核和呼吸杂志,2022,45(7):651-666.
[27]
Armange L, Lacroix A, Petitgas P, et al. The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome: a case series and literature review[J]. Eur J Clin Microbiol Infect Dis,2023,42(4):413-422.
[28]
Abo YN, Curtis N, Osowicki J, et al. Infliximab for paradoxical reactions in pediatric central nervous system tuberculosis[J]. J Pediatric Infect Dis Soc,2021,10(12):1087-1091.
[29]
Marais BJ, Cheong E, Fernando S, et al. Use of infliximab to treat paradoxical tuberculous meningitis reactions[J]. Open Forum Infect Dis,2020,8(1):ofaa604.
[30]
Garg RK, Malhotra HS, Kumar N. Paradoxical reaction in HIV negative tuberculous meningitis[J]. J Neurol Sci,2014,340(1-2):26-36.
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