结核性脑膜炎的诊治进展_West China Medical Journal

Authors：

 何兰英 ,  王健 , 董为伟

成都市第二人民医院神经内科（成都 610017）;

Corresponding author：

王健, Email: jian.wx@icloud.com

Keywords：

结核性脑膜炎; 诊断; 治疗; 综述

DOI：

10.7507/1002-0179.20160068

Video：

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结核性脑膜炎（TBM）是最常见的中枢神经系统结核病，其发病率和死亡率均较高。TBM的临床表现缺乏特异性，实验室检查敏感性不足，因此其诊断仍较困难。此外，随着结核杆菌耐药及人类免疫缺陷病毒的合并感染的增多，TBM的治疗亦受到极大挑战。近年来关于TBM的诊治有一些新的研究进展，现综述如下。

Citation： 何兰英, 王健, 董为伟. 结核性脑膜炎的诊治进展. West China Medical Journal, 2016, 31(2): 248-252. doi: 10.7507/1002-0179.20160068 Copy

1.	Miftode EG, Dorneanu OS, Leca DA, et al. Tuberculous meningitis in children and adults:a 10-year retrospective comparative analysis[J]. PLoS One, 2015, 10(7):e0133477.
2.	Be NA, Bishai WR, Jain SK. Role of Mycobacterium tuberculosis pknD in the pathogenesis of central nervous system tuberculosis[J]. BMC Microbiol, 2012, 12(1):7.
3.	沙巍, 唐神结, 肖和平, 等. 结核病发生的宿主遗传学机制研究进展[J]. 中华临床医师杂志:电子版, 2009, 3(9):1553-1558.
4.	Thuong NT, Hawn TR, Thwaites GE, et al. A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis[J]. Genes Immun, 2007, 8(5):422-428.
5.	Hawn TR, Dunstan SJ, Thwaites GE, et al. A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis[J]. J Infect Dis, 2006, 194(8):1127-1134.
6.	Rich AR, Mccordock HA. The pathogenesis of tuberculous meningitis[J]. Bull Johns Hopkins Hosp, 1993, 52(1):32-37.
7.	Donald PR, Schaaf HS, Schoeman JF. Tuberculous meningitis and miliary tuberculosis:the Rich focus revisited[J]. J Infect, 2005, 50(3):193-195.
8.	Zhang J, Hu X, Hu X, et al. Clinical features, outcomes and molecular profiles of drug resistance in tuberculoses meningitis in non-HIV patients[J]. Sci Rep, 2016, 6(1):19072.
9.	Marais S, Meintjes G, Lesosky M, et al. Interleukin-17 mediated differences in the pathogenesis of HIV-1-associated tuberculous and cryptococcal meningitis[J]. AIDS, 2016, 30(3):395-404.
10.	Mahale RR, Mehta A, Uchil S. Estimation of cerebrospinal fluid cortisol level in tuberculous meningitis[J]. J Neurosci Rural Pract, 2016, 6(4):541-544.
11.	Caudie C, Tholance Y, Quadrio I, et al. Contribution of CSF analysis to diagnosis and follow-up of tuberculous meningitis[J]. Ann Biol Clin (Paris), 2010, 68(1):107-111.
12.	Luma HN, Tchaleu BC, Ngahane BH, et al. Tuberculous meningitis:presentation, diagnosis and outcome in hiv-infected patients at the douala general hospital, Cameroon:a cross sectional study[J]. AIDS Res Ther, 2013, 10(1):16.
13.	Schoen EJ. Spinal fluid chloride:a test 40 years past its time[J]. JAMA, 1984, 251(1):37-38.
14.	Zou Y, He J, Guo L, et al. Prediction of cerebrospinal fluid parameters for tuberculous meningitis[J]. Diagn Cytopathol, 2015, 43(9):701-704.
15.	Leonard JM. Tuberculosis of the central nervous system[M]//Aminoff MJ. Neurology and general medicine. 4th ed. New York, Edinbgh, London, Melbourne:Churchill Livingstone 2007:803-814.
16.	Chen P, Shi M, Feng GD, et al. A highly efficient Ziehl-Neelsen stain:identifying de novo intracellular Mycobacterium tuberculosis and improving detection of extracellular M. tuberculosis in cerebrospinal fluid[J]. J Clin Microbiol, 2012, 50(4):1166-1170.
17.	Alvarez-Uria G, Azcona JM, Midde M, et al. Rapid diagnosis of pulmonary and extrapulmonary tuberculosis in HIV-Infected patients. comparison of LED fluorescent microscopy and the GeneXpert MTB/RIF assay in a district hospital in India[J]. Tuberc Res Treat, 2012(1):932862.
18.	Corral I, Quereda C, Navas E, et al. Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients:limited value for diagnosis of tuberculous meningitis[J]. Eur J Clin Microbiol Infect Dis, 2004, 23(6):471-476.
19.	Bahr NC, Tugume L, Boulware DR. A Word of caution in considering the use of the lipoarabinomannan lateral flow assay on cerebrospinal fluid for detection of tuberculous meningitis[J]. J Clin Microbiol, 2016, 54(1):241-242.
20.	Cox JA, Lukande RL, Kalungi S, et al. Accuracy of lipoarabinomannan and xpert MTB/RIF testing in cerebrospinal fluid to diagnose tuberculous meningitis in an autopsy cohort of HIV-Infected adults[J]. J Clin Microbiol, 2015, 53(8):2667-2673.
21.	Blok N, Visser DH, Solomons R, et al. Lipoarabinomannan enzyme-linked immunosorbent assay for early diagnosis of childhood tuberculous meningitis[J]. Int J Tuberc Lung Dis, 2014, 18(2):205-210.
22.	Thwaites GE, van Toorn R, Schoeman J. Tuberculous meningitis:more questions, still too few answers[J]. Lancet Neurol, 2013, 12(10):999-1010.
23.	Bernaerts A, Vanhoenacker FM, Parizel PM, et al. Tuberculosis of the central nervous system:overview of neuroradiological findings[J]. Eur Radiol, 2003, 13(8):1876-1890.
24.	Thwaites GE, Chau TT, Stepniewska K, et al. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features[J]. Lancet, 2002, 360(9342):1287-1292.
25.	Iseman MD. A clinician's guide to tuberculosis[M]. Philadelphia:Lippencott Williams & Wilkins, 2000:271-321.
26.	Philip N, William T, William DV. Diagnosis of tuberculous meningitis:challenges and promises[J]. Malays J Pathol, 2015, 37(1):1-9.
27.	Delance AR, Safaee M, Oh MC, et al. Tuberculoma of the central nervous system[J]. J Clin Neurosci, 2013, 20(10):1333-1341.
28.	Blecharz KG, Haghikia A, Stasiolek M, et al. Glucocorticoid effects on endothelial barrier function in the murine brain endothelial cell line cEND incubated with sera from patients with multiple sclerosis[J]. Mult Scler, 2010, 16(3):293-302.
29.	Tobin DM, Vary JC, Ray JP, et al. The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans[J]. Cell, 2010, 140(5):717-730.
30.	Tobin DM, Roca FJ, Oh SF, et al. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections[J]. Cell, 2012, 148(3):434-446.
31.	Schoeman JF, Andronikou S, Stefan DC, et al. Tuberculous meningitis-related optic neuritis:recovery of vision with Thalidomide in 4 consecutive cases[J]. J Child Neurol, 2010, 25(7):822-828.
32.	Stefan DC, Andronikou S, Freeman N, et al. Recovery of vision after adjuvant Thalidomide in a child with tuberculous meningitis and acute lymphoblastic leukemia[J]. J Child Neurol, 2009, 24(2):166-169.
33.	van Toorn R, du Plessis AM, Schaaf HS, et al. Clinicoradiologic response of neurologic tuberculous mass lesions in children treated with Thalidomide[J]. Pediatr Infect Dis J, 2015, 34(2):214-218.
34.	Tsenova L, Harbacheuski R, Sung N, et al. BCG vaccination confers poor protection against M. tuberculosis HN878-induced central nervous system disease[J]. Vaccine, 2007, 25(28):5126-5132.
35.	Perera PY, Derrick SC, Kolibab K, et al. A multi-valent vaccinia virus-based tuberculosis vaccine molecularly adjuvanted with interleukin-15 induces robust immune responses in mice[J]. Vaccine, 2009, 27(15):2121-2127.
36.	Lee JY, Yim JJ, Yoon BW. Adjuvant interferon-γ treatment in two cases of refractory tuberculosis of the brain[J]. Clin Neurol Neurosurg, 2012, 114(6):732-734.
37.	Kashyap RS, Deshpande PS, Ramteke SR, et al. Changes in cerebrospinal fluid cytokine expression in tuberculous meningitis patients with treatment[J]. Neuroimmunomodulation, 2010, 17(5):333-339.
38.	Szukiewicz D, Wojciechowska M, Bilska A, et al. Aspirin action in endothelial cells:different patterns of response between chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 signaling pathways[J]. Cardiovasc Drugs Ther, 2015, 29(3):219-229.
39.	Domínguez J, Boettger EC, Cirillo D, et al. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis:a TBNET/RESIST-TB consensus statement[J]. Int J Tuberc Lung Dis, 2016, 20(1):24-42.
40.	Homorodean D, Pop CM, Jodal AM, et al. The concordance between phenotypic and genotypic M. tuberculosis drug susceptibility tests results:observational study[J]. Pneumologia, 2015, 64(2):26-29.
41.	Dos Santos JL, Lima MM, Trindade AB, et al. Tuberculosis:challenges to improve the treatment[J]. Curr Clin Pharmacol, 2013, 10(3):242-251.
42.	Drobniewski F, Cooke M, Jordan J, et al. Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis[J]. Health Technol Assess, 2015, 19(34):1-188, vii-viii.
43.	Lacoma A, Garcia-Sierra N, Prat C, et al. GenoType MTBDRplus assay for molecular detection of rifampin and isoniazid resistance in Mycobacterium tuberculosis strains and clinical samples[J]. J Clin Microbiol, 2008, 46(11):3660-3667.
44.	Thwaites GE, Lan NT, Dung NH, et al. Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis[J]. J Infect Dis, 2005, 192(1):79-88.
45.	Lin J, Zhang N, Sheng HS, et al. Modified external ventricular drainage in pediatric tuberculous meningitis:is it possible to avoid ventriculoperitoneal shunt placement?[J]. Pediatr Neurosurg, 2011, 47(2):108-112.
46.	Bhagwati S, Mehta N, Shah S. Use of endoscopic third ventriculostomy in hydrocephalus of tubercular origin[J]. Childs Nerv Syst, 2010, 26(12):1675-1682.
47.	Jha DK, Mishra V, Choudhary A, et al. Factors affecting the outcome of neuroendoscopy in patients with tuberculous meningitis hydrocephalus:a preliminary study[J]. Surg Neurol, 2007, 68(1):35-41.
48.	Bémer P, Boutoille D, Lepelletier D, et al. Clinical aspects and management of patients with tuberculous meningitis. Retrospective analysis from 1994 to 2005[J]. Rev Pneumol Clin, 2006, 62(4):223-229.
49.	Marais S, Meintjes G, Pepper DJ, et al. Frequency, severity, and prediction of tuberculous meningitis immune reconstitution inflammatory syndrome[J]. Clin Infect Dis, 2013, 56(3):450-460.
50.	Meintjes G, Scriven J, Marais S. Management of the immune reconstitution inflammatory syndrome[J]. Curr HIV/AIDS Rep, 2012, 9(3):238-250.

1. Miftode EG, Dorneanu OS, Leca DA, et al. Tuberculous meningitis in children and adults:a 10-year retrospective comparative analysis[J]. PLoS One, 2015, 10(7):e0133477.
2. Be NA, Bishai WR, Jain SK. Role of Mycobacterium tuberculosis pknD in the pathogenesis of central nervous system tuberculosis[J]. BMC Microbiol, 2012, 12(1):7.
3. 沙巍, 唐神结, 肖和平, 等. 结核病发生的宿主遗传学机制研究进展[J]. 中华临床医师杂志:电子版, 2009, 3(9):1553-1558.
4. Thuong NT, Hawn TR, Thwaites GE, et al. A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis[J]. Genes Immun, 2007, 8(5):422-428.
5. Hawn TR, Dunstan SJ, Thwaites GE, et al. A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis[J]. J Infect Dis, 2006, 194(8):1127-1134.
6. Rich AR, Mccordock HA. The pathogenesis of tuberculous meningitis[J]. Bull Johns Hopkins Hosp, 1993, 52(1):32-37.
7. Donald PR, Schaaf HS, Schoeman JF. Tuberculous meningitis and miliary tuberculosis:the Rich focus revisited[J]. J Infect, 2005, 50(3):193-195.
8. Zhang J, Hu X, Hu X, et al. Clinical features, outcomes and molecular profiles of drug resistance in tuberculoses meningitis in non-HIV patients[J]. Sci Rep, 2016, 6(1):19072.
9. Marais S, Meintjes G, Lesosky M, et al. Interleukin-17 mediated differences in the pathogenesis of HIV-1-associated tuberculous and cryptococcal meningitis[J]. AIDS, 2016, 30(3):395-404.
10. Mahale RR, Mehta A, Uchil S. Estimation of cerebrospinal fluid cortisol level in tuberculous meningitis[J]. J Neurosci Rural Pract, 2016, 6(4):541-544.
11. Caudie C, Tholance Y, Quadrio I, et al. Contribution of CSF analysis to diagnosis and follow-up of tuberculous meningitis[J]. Ann Biol Clin (Paris), 2010, 68(1):107-111.
12. Luma HN, Tchaleu BC, Ngahane BH, et al. Tuberculous meningitis:presentation, diagnosis and outcome in hiv-infected patients at the douala general hospital, Cameroon:a cross sectional study[J]. AIDS Res Ther, 2013, 10(1):16.
13. Schoen EJ. Spinal fluid chloride:a test 40 years past its time[J]. JAMA, 1984, 251(1):37-38.
14. Zou Y, He J, Guo L, et al. Prediction of cerebrospinal fluid parameters for tuberculous meningitis[J]. Diagn Cytopathol, 2015, 43(9):701-704.
15. Leonard JM. Tuberculosis of the central nervous system[M]//Aminoff MJ. Neurology and general medicine. 4th ed. New York, Edinbgh, London, Melbourne:Churchill Livingstone 2007:803-814.
16. Chen P, Shi M, Feng GD, et al. A highly efficient Ziehl-Neelsen stain:identifying de novo intracellular Mycobacterium tuberculosis and improving detection of extracellular M. tuberculosis in cerebrospinal fluid[J]. J Clin Microbiol, 2012, 50(4):1166-1170.
17. Alvarez-Uria G, Azcona JM, Midde M, et al. Rapid diagnosis of pulmonary and extrapulmonary tuberculosis in HIV-Infected patients. comparison of LED fluorescent microscopy and the GeneXpert MTB/RIF assay in a district hospital in India[J]. Tuberc Res Treat, 2012(1):932862.
18. Corral I, Quereda C, Navas E, et al. Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients:limited value for diagnosis of tuberculous meningitis[J]. Eur J Clin Microbiol Infect Dis, 2004, 23(6):471-476.
19. Bahr NC, Tugume L, Boulware DR. A Word of caution in considering the use of the lipoarabinomannan lateral flow assay on cerebrospinal fluid for detection of tuberculous meningitis[J]. J Clin Microbiol, 2016, 54(1):241-242.
20. Cox JA, Lukande RL, Kalungi S, et al. Accuracy of lipoarabinomannan and xpert MTB/RIF testing in cerebrospinal fluid to diagnose tuberculous meningitis in an autopsy cohort of HIV-Infected adults[J]. J Clin Microbiol, 2015, 53(8):2667-2673.
21. Blok N, Visser DH, Solomons R, et al. Lipoarabinomannan enzyme-linked immunosorbent assay for early diagnosis of childhood tuberculous meningitis[J]. Int J Tuberc Lung Dis, 2014, 18(2):205-210.
22. Thwaites GE, van Toorn R, Schoeman J. Tuberculous meningitis:more questions, still too few answers[J]. Lancet Neurol, 2013, 12(10):999-1010.
23. Bernaerts A, Vanhoenacker FM, Parizel PM, et al. Tuberculosis of the central nervous system:overview of neuroradiological findings[J]. Eur Radiol, 2003, 13(8):1876-1890.
24. Thwaites GE, Chau TT, Stepniewska K, et al. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features[J]. Lancet, 2002, 360(9342):1287-1292.
25. Iseman MD. A clinician's guide to tuberculosis[M]. Philadelphia:Lippencott Williams & Wilkins, 2000:271-321.
26. Philip N, William T, William DV. Diagnosis of tuberculous meningitis:challenges and promises[J]. Malays J Pathol, 2015, 37(1):1-9.
27. Delance AR, Safaee M, Oh MC, et al. Tuberculoma of the central nervous system[J]. J Clin Neurosci, 2013, 20(10):1333-1341.
28. Blecharz KG, Haghikia A, Stasiolek M, et al. Glucocorticoid effects on endothelial barrier function in the murine brain endothelial cell line cEND incubated with sera from patients with multiple sclerosis[J]. Mult Scler, 2010, 16(3):293-302.
29. Tobin DM, Vary JC, Ray JP, et al. The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans[J]. Cell, 2010, 140(5):717-730.
30. Tobin DM, Roca FJ, Oh SF, et al. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections[J]. Cell, 2012, 148(3):434-446.
31. Schoeman JF, Andronikou S, Stefan DC, et al. Tuberculous meningitis-related optic neuritis:recovery of vision with Thalidomide in 4 consecutive cases[J]. J Child Neurol, 2010, 25(7):822-828.
32. Stefan DC, Andronikou S, Freeman N, et al. Recovery of vision after adjuvant Thalidomide in a child with tuberculous meningitis and acute lymphoblastic leukemia[J]. J Child Neurol, 2009, 24(2):166-169.
33. van Toorn R, du Plessis AM, Schaaf HS, et al. Clinicoradiologic response of neurologic tuberculous mass lesions in children treated with Thalidomide[J]. Pediatr Infect Dis J, 2015, 34(2):214-218.
34. Tsenova L, Harbacheuski R, Sung N, et al. BCG vaccination confers poor protection against M. tuberculosis HN878-induced central nervous system disease[J]. Vaccine, 2007, 25(28):5126-5132.
35. Perera PY, Derrick SC, Kolibab K, et al. A multi-valent vaccinia virus-based tuberculosis vaccine molecularly adjuvanted with interleukin-15 induces robust immune responses in mice[J]. Vaccine, 2009, 27(15):2121-2127.
36. Lee JY, Yim JJ, Yoon BW. Adjuvant interferon-γ treatment in two cases of refractory tuberculosis of the brain[J]. Clin Neurol Neurosurg, 2012, 114(6):732-734.
37. Kashyap RS, Deshpande PS, Ramteke SR, et al. Changes in cerebrospinal fluid cytokine expression in tuberculous meningitis patients with treatment[J]. Neuroimmunomodulation, 2010, 17(5):333-339.
38. Szukiewicz D, Wojciechowska M, Bilska A, et al. Aspirin action in endothelial cells:different patterns of response between chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 signaling pathways[J]. Cardiovasc Drugs Ther, 2015, 29(3):219-229.
39. Domínguez J, Boettger EC, Cirillo D, et al. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis:a TBNET/RESIST-TB consensus statement[J]. Int J Tuberc Lung Dis, 2016, 20(1):24-42.
40. Homorodean D, Pop CM, Jodal AM, et al. The concordance between phenotypic and genotypic M. tuberculosis drug susceptibility tests results:observational study[J]. Pneumologia, 2015, 64(2):26-29.
41. Dos Santos JL, Lima MM, Trindade AB, et al. Tuberculosis:challenges to improve the treatment[J]. Curr Clin Pharmacol, 2013, 10(3):242-251.
42. Drobniewski F, Cooke M, Jordan J, et al. Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis[J]. Health Technol Assess, 2015, 19(34):1-188, vii-viii.
43. Lacoma A, Garcia-Sierra N, Prat C, et al. GenoType MTBDRplus assay for molecular detection of rifampin and isoniazid resistance in Mycobacterium tuberculosis strains and clinical samples[J]. J Clin Microbiol, 2008, 46(11):3660-3667.
44. Thwaites GE, Lan NT, Dung NH, et al. Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis[J]. J Infect Dis, 2005, 192(1):79-88.
45. Lin J, Zhang N, Sheng HS, et al. Modified external ventricular drainage in pediatric tuberculous meningitis:is it possible to avoid ventriculoperitoneal shunt placement?[J]. Pediatr Neurosurg, 2011, 47(2):108-112.
46. Bhagwati S, Mehta N, Shah S. Use of endoscopic third ventriculostomy in hydrocephalus of tubercular origin[J]. Childs Nerv Syst, 2010, 26(12):1675-1682.
47. Jha DK, Mishra V, Choudhary A, et al. Factors affecting the outcome of neuroendoscopy in patients with tuberculous meningitis hydrocephalus:a preliminary study[J]. Surg Neurol, 2007, 68(1):35-41.
48. Bémer P, Boutoille D, Lepelletier D, et al. Clinical aspects and management of patients with tuberculous meningitis. Retrospective analysis from 1994 to 2005[J]. Rev Pneumol Clin, 2006, 62(4):223-229.
49. Marais S, Meintjes G, Pepper DJ, et al. Frequency, severity, and prediction of tuberculous meningitis immune reconstitution inflammatory syndrome[J]. Clin Infect Dis, 2013, 56(3):450-460.
50. Meintjes G, Scriven J, Marais S. Management of the immune reconstitution inflammatory syndrome[J]. Curr HIV/AIDS Rep, 2012, 9(3):238-250.

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