Tuberculous Meningitis

  • Derya Ozturk-Engin
  • Corneliu Petru Popescu


Tuberculous meningitis (TBM) seems to be the most devastating form of tuberculosis caused by M. tuberculosis. The clinical picture of TBM is non-specific and may resemble the other causes of chronic meningoencephalitis. The sensitivity of cerebrospinal fluid examination is low and the growth of M. tuberculosis is slow in conventional culture systems. The nucleic acid amplification of CSF by PCR is highly specific and a negative result does not rule out the diagnosis because of its lower sensitivity. The neuroradiological features identified commonly in the course of the disease include basal meningeal enhancement, hydrocephalus, and infarctions. However, in the early period of the disease, 30% of patients have normal brain CT, and 15% of patients have normal brain MRI. In cases suspected of tuberculous meningitis, empirical anti-mycobacterial treatment should be initiated expeditiously. Although no randomized clinical trial showing the optimal combination of drugs and the duration of treatment exists, the treatment is administered for a year in which quadruple-drug regimen are administered for the first 2 months. It is recommended for multidrug-resistant tuberculosis that initial therapy consist of at least five active drugs (pyrazinamide and four second-line drugs) and injectable agents be administered for at least 8 months and total duration of treatment should be at least 18 months. The risk of tuberculosis is high in HIV-infected individuals. As early initiation of antiretroviral therapy in naive patients might lead to immune reconstitution inflammatory syndrome (IRIS), the antiretroviral therapy should not be initiated in the first 2 months. Using corticosteroids as adjuvant treatment prolongs the life-span. Despite all the efforts for diagnosis and treatment, neurological sequelae and mortality rates remain unacceptably high in TBM.


Tuberculous meningitis Epidemiology Clinical manifestations Diagnosis CSF analysis PCR Radiology Antituberculosis treatment Drug-resistant Steroids Prognosis 


  1. 1.
    Abubakar I, Pimpin L, Ariti C, Beynon R, Mangtani P, Sterne JA, Fine PE, Smith PG, Lipman M, Elliman D, Watson JM, Drumright LN, Whiting PF, Vynnycky E, Rodrigues LC. Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guerin vaccination against tuberculosis. Health Technol Assess. 2013;17:1–372, v–vi.PubMedCrossRefGoogle Scholar
  2. 2.
    Andronikou S, Smith B, Hatherhill M, Douis H, Wilmshurst J. Definitive neuroradiological diagnostic features of tuberculous meningitis in children. Pediatr Radiol. 2004;34:876–85.PubMedCrossRefGoogle Scholar
  3. 3.
    Bang ND, Caws M, Truc TT, Duong TN, Dung NH, Ha DT, Thwaites GE, Heemskerk D, Tarning J, Merson L, Van Toi P, Farrar JJ, Wolbers M, Pouplin T, Day JN. Clinical presentations, diagnosis, mortality and prognostic markers of tuberculous meningitis in Vietnamese children: a prospective descriptive study. BMC Infect Dis. 2016;16:573.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Be NA, Kim KS, Bishai WR, Jain SK. Pathogenesis of central nervous system tuberculosis. Curr Mol Med. 2009;9:94–9.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Bernaerts A, Vanhoenacker FM, Parizel PM, Van Goethem JW, Van Altena R, Laridon A, De Roeck J, Coeman V, De Schepper AM. Tuberculosis of the central nervous system: overview of neuroradiological findings. Eur Radiol. 2003;13:1876–90.PubMedCrossRefGoogle Scholar
  6. 6.
    Berwal A, Chawla K, Vishwanath S, Shenoy VP. Role of multiplex polymerase chain reaction in diagnosing tubercular meningitis. J Lab Physicians. 2017;9:145–7.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Brancusi F, Farrar J, Heemskerk D. Tuberculous meningitis in adults: a review of a decade of developments focusing on prognostic factors for outcome. Future Microbiol. 2012;7:1101–16.PubMedCrossRefGoogle Scholar
  8. 8.
    Breathnach CS. Robert Whytt (1714-1766): from dropsy in the brain to tuberculous meningitis. Ir J Med Sci. 2014;183:493–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Bullock MR, Welchman JM. Diagnostic and prognostic features of tuberculous meningitis on CT scanning. J Neurol Neurosurg Psychiatry. 1982;45:1098–101.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Burrill J, Williams CJ, Bain G, Conder G, Hine AL, Misra RR. Tuberculosis: a radiologic review. Radiographics. 2007;27:1255–73.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Cag Y, Ozturk-Engin D, Gencer S, Hasbun R, Sengoz G, Crisan A, Ceran N, Savic B, Yasar K, Pehlivanoglu F, Kilicoglu G, Tireli H, Inal AS, Civljak R, Tekin R, Elaldi N, Ulu-Kilic A, Ozguler M, Namiduru M, Sunbul M, Sipahi OR, Dulovic O, Alabay S, Akbulut A, Sener A, Lakatos B, Andre K, Yemisen M, Oncu S, Nechifor M, Deveci O, Senbayrak S, Inan A, Dragovac G, Hc GL, Mert G, Oncul O, Kandemir B, Erol S, Agalar C, Erdem H. Hydrocephalus and vasculitis delay therapeutic responses in tuberculous meningitis: results of Haydarpasa-III study. Neurol India. 2016;64:896–905.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Cagatay AA, Ozsut H, Gulec L, Kucukoglu S, Berk H, Ince N, Ertugrul B, Aksoz S, Akal D, Eraksoy H, Calangu S. Tuberculous meningitis in adults--experience from Turkey. Int J Clin Pract. 2004;58:469–73.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Caglayan V, Ak O, Dabak G, Damadoglu E, Ketenci B, Ozdemir M, Ozer S, Saygý A. Comparison of tuberculin skin testing and QuantiFERON-TB Gold-In Tube test in health care workers. Tuberk Toraks. 2011;59:43–7.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Calthorpe N. The history of spinal needles: getting to the point. Anaesthesia. 2004;59:1231–41.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Caws M, Thwaites G, Dunstan S, Hawn TR, Lan NT, Thuong NT, Stepniewska K, Huyen MN, Bang ND, Loc TH, Gagneux S, Van Soolingen D, Kremer K, Van Der Sande M, Small P, Anh PT, Chinh NT, Quy HT, Duyen NT, Tho DQ, Hieu NT, Torok E, Hien TT, Dung NH, Nhu NT, Duy PM, Van Vinh Chau N, Farrar J. The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis. PLoS Pathog. 2008;4:e1000034.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Cecchini D, Ambrosioni J, Brezzo C, Corti M, Rybko A, Perez M, Poggi S, Ambroggi M. Tuberculous meningitis in HIV-infected and non-infected patients: comparison of cerebrospinal fluid findings. Int J Tuberc Lung Dis. 2009;13:269–71.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Chatterjee D, Radotra BD, Vasishta RK, Sharma K. Vascular complications of tuberculous meningitis: An autopsy study. Neurol India. 2015;63:926–32.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Christensen AS, Roed C, Omland LH, Andersen PH, Obel N, Andersen AB. Long-term mortality in patients with tuberculous meningitis: a Danish nationwide cohort study. PLoS One. 2011;6:e27900.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Cohen DB, Zijlstra EE, Mukaka M, Reiss M, Kamphambale S, Scholing M, Waitt PI, Neuhann F. Diagnosis of cryptococcal and tuberculous meningitis in a resource-limited African setting. Tropical Med Int Health. 2010;15:910–7.CrossRefGoogle Scholar
  20. 20.
    Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, Mosteller F. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994;271:698–702.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Daniel TM. The history of tuberculosis. Respir Med. 2006;100:1862–70.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Dastur DK, Manghani DK, Udani PM. Pathology and pathogenetic mechanisms in neurotuberculosis. Radiol Clin N Am. 1995;33:733–52.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Davis LE, Rastogi KR, Lambert LC, Skipper BJ. Tuberculous meningitis in the southwest United States: a community-based study. Neurology. 1993;43:1775–8.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Dekker G, Andronikou S, Van Toorn R, Scheepers S, Brandt A, Ackermann C. MRI findings in children with tuberculous meningitis: a comparison of HIV-infected and non-infected patients. Childs Nerv Syst. 2011;27:1943–9.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Di L, Li Y. The risk factor of false-negative and false-positive for T-SPOT.TB in active tuberculosis. J Clin Lab Anal. 2018; 32(2).CrossRefGoogle Scholar
  26. 26.
    Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, Drobniewski F, Lalvani A. A systematic review of rapid diagnostic tests for the detection of tuberculosis infection. Health Technol Assess. 2007;11:1–196.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Donald PR. Cerebrospinal fluid concentrations of antituberculosis agents in adults and children. Tuberculosis (Edinb). 2010a;90:279–92.CrossRefGoogle Scholar
  28. 28.
    Donald PR. The chemotherapy of tuberculous meningitis in children and adults. Tuberculosis (Edinb). 2010b;90:375–92.CrossRefGoogle Scholar
  29. 29.
    Donald PR, Schaaf HS, Schoeman JF. Tuberculous meningitis and miliary tuberculosis: the Rich focus revisited. J Infect. 2005;50:193–5.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Donald PR, Victor TC, Jordaan AM, Schoeman JF, Van Helden PD. Polymerase chain reaction in the diagnosis of tuberculous meningitis. Scand J Infect Dis. 1993;25:613–7.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Elias J, De Coning JP, Vorster SA, Joubert HF. The rapid and sensitive diagnosis of tuberculous meningitis by the detection of tuberculostearic acid in cerebrospinal fluid using gas chromatography-mass spectrometry with selective ion monitoring. Clin Biochem. 1989;22:463–7.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Ellard GA, Humphries MJ, Allen BW. Cerebrospinal fluid drug concentrations and the treatment of tuberculous meningitis. Am Rev Respir Dis. 1993;148:650–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Erdem H, Ozturk-Engin D, Elaldi N, Gulsun S, Sengoz G, Crisan A, Johansen IS, Inan A, Nechifor M, Al-Mahdawi A, Civljak R, Ozguler M, Savic B, Ceran N, Cacopardo B, Inal AS, Namiduru M, Dayan S, Kayabas U, Parlak E, Khalifa A, Kursun E, Sipahi OR, Yemisen M, Akbulut A, Bitirgen M, Dulovic O, Kandemir B, Luca C, Parlak M, Stahl JP, Pehlivanoglu F, Simeon S, Ulu-Kilic A, Yasar K, Yilmaz G, Yilmaz E, Beovic B, Catroux M, Lakatos B, Sunbul M, Oncul O, Alabay S, Sahin-Horasan E, Kose S, Shehata G, Andre K, Alp A, Cosic G, Cem Gul H, Karakas A, Chadapaud S, Hansmann Y, Harxhi A, Kirova V, Masse-Chabredier I, Oncu S, Sener A, Tekin R, Deveci O, Karabay O, Agalar C. The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study. Clin Microbiol Infect. 2014;20:O600–8.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Erdem H, Ozturk-Engin D, Tireli H, Kilicoglu G, Defres S, Gulsun S, Sengoz G, Crisan A, Johansen IS, Inan A, Nechifor M, Al-Mahdawi A, Civljak R, Ozguler M, Savic B, Ceran N, Cacopardo B, Inal AS, Namiduru M, Dayan S, Kayabas U, Parlak E, Khalifa A, Kursun E, Sipahi OR, Yemisen M, Akbulut A, Bitirgen M, Popovic N, Kandemir B, Luca C, Parlak M, Stahl JP, Pehlivanoglu F, Simeon S, Ulu-Kilic A, Yasar K, Yilmaz G, Yilmaz E, Beovic B, Catroux M, Lakatos B, Sunbul M, Oncul O, Alabay S, Sahin-Horasan E, Kose S, Shehata G, Andre K, Dragovac G, Gul HC, Karakas A, Chadapaud S, Hansmann Y, Harxhi A, Kirova V, Masse-Chabredier I, Oncu S, Sener A, Tekin R, Elaldi N, Deveci O, Ozkaya HD, Karabay O, Senbayrak S, Agalar C, Vahaboglu H. Hamsi scoring in the prediction of unfavorable outcomes from tuberculous meningitis: results of Haydarpasa-II study. J Neurol. 2015;262:890–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Falzon D, Jaramillo E, Schunemann HJ, Arentz M, Bauer M, Bayona J, Blanc L, Caminero JA, Daley CL, Duncombe C, Fitzpatrick C, Gebhard A, Getahun H, Henkens M, Holtz TH, Keravec J, Keshavjee S, Khan AJ, Kulier R, Leimane V, Lienhardt C, Lu C, Mariandyshev A, Migliori GB, Mirzayev F, Mitnick CD, Nunn P, Nwagboniwe G, Oxlade O, Palmero D, Pavlinac P, Quelapio MI, Raviglione MC, Rich ML, Royce S, Rusch-Gerdes S, Salakaia A, Sarin R, Sculier D, Varaine F, Vitoria M, Walson JL, Wares F, Weyer K, White RA, Zignol M. WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update. Eur Respir J. 2011;38:516–28.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Figaji AA, Fieggen AG, Peter JC. Endoscopic third ventriculostomy in tuberculous meningitis. Childs Nerv Syst. 2003;19:217–25.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Fitzgerald Dw ST, Haas DW, Bennett EJ, Dolin R, Blaser MJ. Mycobacterium tuberculosis. In: Mandell, Douglas, and Bennett's principles and practice of infectious diseases, vol. 1. 8th ed. Philadelphia: Elsevier Churchill Livingstone; 2015. p. 2787–818.Google Scholar
  38. 38.
    French GL, Teoh R, Chan CY, Humphries MJ, Cheung SW, O'Mahony G. Diagnosis of tuberculous meningitis by detection of tuberculostearic acid in cerebrospinal fluid. Lancet. 1987;2:117–9.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Gambhir S, Ravina M, Rangan K, Dixit M, Barai S, Bomanji J, International Atomic Energy Agency Extra-Pulmonary, T. B. C. Imaging in extrapulmonary tuberculosis. Int J Infect Dis. 2017;56:237–47.PubMedCrossRefGoogle Scholar
  40. 40.
    Garg RK, Malhotra HS, Jain A. Neuroimaging in tuberculous meningitis. Neurol India. 2016;64:219–27.PubMedCrossRefGoogle Scholar
  41. 41.
    Girgis NI, Farid Z, Kilpatrick ME, Sultan Y, Mikhail IA. Dexamethasone adjunctive treatment for tuberculous meningitis. Pediatr Infect Dis J. 1991;10:179–83.PubMedCrossRefGoogle Scholar
  42. 42.
    GT, V. B. Complications in hydrocephalus shunting procedure. In: Wellenbur R, Brock M, Klinger M, editors. Advances in neurosurgery. 6th ed. New York: Springer; 1968. p. 28.Google Scholar
  43. 43.
    Gupta RK, Kathuria MK, Pradhan S. Magnetization transfer MR imaging in CNS tuberculosis. AJNR Am J Neuroradiol. 1999;20:867–75.PubMedGoogle Scholar
  44. 44.
    He Y, Han C, Chang KF, Wang MS, Huang TR. Total delay in treatment among tuberculous meningitis patients in China: a retrospective cohort study. BMC Infect Dis. 2017;17:341.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Heemskerk AD, Bang ND, Mai NT, Chau TT, Phu NH, Loc PP, Chau NV, Hien TT, Dung NH, Lan NT, Lan NH, Lan NN, Phong Le T, Vien NN, Hien NQ, Yen NT, Ha DT, Day JN, Caws M, Merson L, Thinh TT, Wolbers M, Thwaites GE, Farrar JJ. Intensified antituberculosis therapy in adults with tuberculous meningitis. N Engl J Med. 2016;374:124–34.PubMedCrossRefGoogle Scholar
  46. 46.
    Hooijboer PG, Van Der Vliet AM, Sinnige LG. Tuberculous meningitis in native Dutch children: a report of four cases. Pediatr Radiol. 1996;26:542–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Hosoglu S, Geyik MF, Balik I, Aygen B, Erol S, Aygencel TG, Mert A, Saltoglu N, Dokmetas I, Felek S, Sunbul M, Irmak H, Aydin K, Kokoglu OF, Ucmak H, Altindis M, Loeb M. Predictors of outcome in patients with tuberculous meningitis. Int J Tuberc Lung Dis. 2002;6:64–70.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Hsu PC, Yang CC, Ye JJ, Huang PY, Chiang PC, Lee MH. Prognostic factors of tuberculous meningitis in adults: a 6-year retrospective study at a tertiary hospital in northern Taiwan. J Microbiol Immunol Infect. 2010;43:111–8.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
  50. 50.
    Inamdar P, Masavkar S, Shanbag P. Hyponatremia in children with tuberculous meningitis: a hospital-based cohort study. J Pediatr Neurosci. 2016;11:182–7.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Jonas V, Alden MJ, Curry JI, Kamisango K, Knott CA, Lankford R, Wolfe JM, Moore DF. Detection and identification of Mycobacterium tuberculosis directly from sputum sediments by amplification of rRNA. J Clin Microbiol. 1993;31:2410–6.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Jullien S, Ryan H, Modi M, Bhatia R. Six months therapy for tuberculous meningitis. Cochrane Database Syst Rev. 2016;9:CD012091.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Kalita J, Misra UK, Ranjan P. Predictors of long-term neurological sequelae of tuberculous meningitis: a multivariate analysis. Eur J Neurol. 2007;14:33–7.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Karstaedt AS, Valtchanova S, Barriere R, Crewe-Brown HH. Tuberculous meningitis in South African urban adults. QJM. 1998;91:743–7.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Katrak SM, Shembalkar PK, Bijwe SR, Bhandarkar LD. The clinical, radiological and pathological profile of tuberculous meningitis in patients with and without human immunodeficiency virus infection. J Neurol Sci. 2000;181:118–26.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Katti MK. Pathogenesis, diagnosis, treatment, and outcome aspects of cerebral tuberculosis. Med Sci Monit. 2004;10:RA215-29.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Kaushik A, Singh UB, Porwal C, Venugopal SJ, Mohan A, Krishnan A, Goyal V, Banavaliker JN. Diagnostic potential of 16 kDa (HspX, alpha-crystalline) antigen for serodiagnosis of tuberculosis. Indian J Med Res. 2012;135:771–7.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Kennedy DH, Fallon RJ. Tuberculous meningitis. JAMA. 1979;241:264–8.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Kumar NP, Babu S. Influence of diabetes mellitus on the immunity to human tuberculosis. Immunology. 2017;152:13.CrossRefGoogle Scholar
  60. 60.
    Lee YM, Park KH, Kim SM, Park SJ, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH. Risk factors for false-negative results of T-SPOT.TB and tuberculin skin test in extrapulmonary tuberculosis. Infection. 2013;41:1089–95.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Leiguarda R, Berthier M, Starkstein S, Nogues M, Lylyk P. Ischemic infarction in 25 children with tuberculous meningitis. Stroke. 1988;19:200–4.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Lempp JM, Zajdowicz MJ, Hankinson AL, Toney SR, Keep LW, Mancuso JD, Mazurek GH. Assessment of the QuantiFERON-TB Gold In-Tube test for the detection of Mycobacterium tuberculosis infection in United States Navy recruits. PLoS One. 2017;12:e0177752.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Lewinsohn DM, Leonard MK, Lobue PA, Cohn DL, Daley CL, Desmond E, Keane J, Lewinsohn DA, Loeffler AM, Mazurek GH, O'Brien RJ, Pai M, Richeldi L, Salfinger M, Shinnick TM, Sterling TR, Warshauer DM, Woods GL. Official American Thoracic Society/Infectious Diseases Society of America/Centers for disease control and prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017;64:e1–e33.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Lincoln EM, Sordillo VR, Davies PA. Tuberculous meningitis in children. A review of 167 untreated and 74 treated patients with special reference to early diagnosis. J Pediatr. 1960;57:807–23.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Marais S, Meintjes G, Pepper DJ, Dodd LE, Schutz C, Ismail Z, Wilkinson KA, Wilkinson RJ. Frequency, severity, and prediction of tuberculous meningitis immune reconstitution inflammatory syndrome. Clin Infect Dis. 2013;56:450–60.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Marx GE, Chan ED. Tuberculous meningitis: diagnosis and treatment overview. Tuberc Res Treat. 2011;2011:798764.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Mastroianni CM, Paoletti F, Lichtner M, D'Agostino C, Vullo V, Delia S. Cerebrospinal fluid cytokines in patients with tuberculous meningitis. Clin Immunol Immunopathol. 1997;84:171–6.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Mazurek GH, Weis SE, Moonan PK, Daley CL, Bernardo J, Lardizabal AA, Reves RR, Toney SR, Daniels LJ, Lobue PA. Prospective comparison of the tuberculin skin test and 2 whole-blood interferon-gamma release assays in persons with suspected tuberculosis. Clin Infect Dis. 2007;45:837–45.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Merkler AE, Reynolds AS, Gialdini G, Morris NA, Murthy SB, Thakur K, Kamel H. Neurological complications after tuberculous meningitis in a multi-state cohort in the United States. J Neurol Sci. 2017;375:460–3.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Misra UK, Kalita J, Bhoi SK, Singh RK. A study of hyponatremia in tuberculous meningitis. J Neurol Sci. 2016;367:152–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Morgado C, Ruivo N. Imaging meningo-encephalic tuberculosis. Eur J Radiol. 2005;55:188–92.PubMedCrossRefGoogle Scholar
  72. 72.
    Murthy JM. Tuberculous meningitis: the challenges. Neurol India. 2010;58:716–22.PubMedCrossRefGoogle Scholar
  73. 73.
    Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, Chaisson LH, Chaisson RE, Daley CL, Grzemska M, Higashi JM, Ho CS, Hopewell PC, Keshavjee SA, Lienhardt C, Menzies R, Merrifield C, Narita M, O'Brien R, Peloquin CA, Raftery A, Saukkonen J, Schaaf HS, Sotgiu G, Starke JR, Migliori GB, Vernon A. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63:e147–95.PubMedCrossRefGoogle Scholar
  74. 74.
    Nau R, Prange HW, Menck S, Kolenda H, Visser K, Seydel JK. Penetration of rifampicin into the cerebrospinal fluid of adults with uninflamed meninges. J Antimicrob Chemother. 1992;29:719–24.PubMedCrossRefGoogle Scholar
  75. 75.
    Nayak S, Acharjya B. Mantoux test and its interpretation. Indian Dermatol Online J. 2012;3:2–6.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Omar N, Andronikou S, Van Toorn R, Pienaar M. Diffusion-weighted magnetic resonance imaging of borderzone necrosis in paediatric tuberculous meningitis. J Med Imaging Radiat Oncol. 2011;55:563–70.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    ORGANIZATION 2017. WH. Global tuberculosis report.Google Scholar
  78. 78.
    ORGANIZATION, W. H. 2003. Guidelines for the management of sexually transmitted infections, World Health Organization.Google Scholar
  79. 79.
    Pai M, Flores LL, Pai N, Hubbard A, Riley LW, Colford JM Jr. Diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2003;3:633–43.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    PEDIATRICS., A. A. O. Committee on infectious diseases. In: Red book: report of the committee on infectious diseases. 30th ed. Elk Grove Village: AAP; 2015. p. 2015.Google Scholar
  81. 81.
    Pehlivanoglu F, Yasar KK, Sengoz G. Tuberculous meningitis in adults: a review of 160 cases. ScientificWorldJournal. 2012;2012:169028.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Prasad K, Singh MB, Ryan H. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev. 2016;4:CD002244.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Qureshi H, Merwat S, Nawaz S, Rana A, Malik A, Mahmud M, Latif A, Khan A, Sarwari A. Predictors of inpatient mortality in 190 adult patients with tuberculous meningitis. J Pak Med Assoc. 2002;52:159–63.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Rizvi I, Garg RK, Malhotra HS, Kumar N, Sharma E, Srivastava C, Uniyal R. Ventriculo-peritoneal shunt surgery for tuberculous meningitis: a systematic review. J Neurol Sci. 2017;375:255–63.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Roca B, Tornador N, Tornador E. Presentation and outcome of tuberculous meningitis in adults in the province of Castellon, Spain: a retrospective study. Epidemiol Infect. 2008;136:1455–62.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Rock RB, Olin M, Baker CA, Molitor TW, Peterson PK. Central nervous system tuberculosis: pathogenesis and clinical aspects. Clin Microbiol Rev. 2008;21:243–61. table of contents.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Rodrigues LC, Diwan VK, Wheeler JG. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol. 1993;22:1154–8.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Ruslami R, Ganiem AR, Dian S, Apriani L, Achmad TH, Van Der Ven AJ, Borm G, Aarnoutse RE, Van Crevel R. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis. 2013;13:27–35.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Sakula A. Robert koch: centenary of the discovery of the tubercle bacillus, 1882. Can Vet J. 1983;24:127–31.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Sanei Taheri M, Karimi MA, Haghighatkhah H, Pourghorban R, Samadian M, Delavar Kasmaei H. Central nervous system tuberculosis: an imaging-focused review of a reemerging disease. Radiol Res Pract. 2015;2015:202806.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Schoeman J, Donald P, Van Zyl L, Keet M, Wait J. Tuberculous hydrocephalus: comparison of different treatments with regard to ICP, ventricular size and clinical outcome. Dev Med Child Neurol. 1991;33:396–405.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Schoeman JF, Andronikou S, Stefan DC, Freeman N, Van Toorn R. Tuberculous meningitis-related optic neuritis: recovery of vision with thalidomide in 4 consecutive cases. J Child Neurol. 2010;25:822–8.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Schoeman JF, Van Zyl LE, Laubscher JA, Donald PR. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. Pediatrics. 1997;99:226–31.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Scott C, Kirking HL, Jeffries C, Price SF, Pratt R, Centers for Disease, C. & Prevention. Tuberculosis trends--United States, 2014. MMWR Morb Mortal Wkly Rep. 2015;64:265–9.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Seddon JA, Visser DH, Bartens M, Jordaan AM, Victor TC, Van Furth AM, Schoeman JF, Schaaf HS. Impact of drug resistance on clinical outcome in children with tuberculous meningitis. Pediatr Infect Dis J. 2012;31:711–6.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Senbayrak S, Ozkutuk N, Erdem H, Johansen IS, Civljak R, Inal AS, Kayabas U, Kursun E, Elaldi N, Savic B, Simeon S, Yilmaz E, Dulovic O, Ozturk-Engin D, Ceran N, Lakatos B, Sipahi OR, Sunbul M, Yemisen M, Alabay S, Beovic B, Ulu-Kilic A, Cag Y, Catroux M, Inan A, Dragovac G, Deveci O, Tekin R, Gul HC, Sengoz G, Andre K, Harxhi A, Hansmann Y, Oncu S, Kose S, Oncul O, Parlak E, Sener A, Yilmaz G, Savasci U, Vahaboglu H. Antituberculosis drug resistance patterns in adults with tuberculous meningitis: results of haydarpasa-iv study. Ann Clin Microbiol Antimicrob. 2015;14:47.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Shane SJ, Clowater RA, Riley C. The treatment of tuberculous meningitis with cortisone and streptomycin. Can Med Assoc J. 1952;67:13–5.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Singh P, Paliwal VK, Neyaz Z, Srivastava AK, Verma R, Mohan S. Clinical and magnetic resonance imaging characteristics of tubercular ventriculitis: an under-recognized complication of tubercular meningitis. J Neurol Sci. 2014;342:137–40.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Smith HV, Vollum RL. The diagnosis of tuberculous meningitis. Br Med Bull. 1954;10:140–5.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Solomons RS, Goussard P, Visser DH, Marais BJ, Gie RP, Schoeman JF, Van Furth AM. Chest radiograph findings in children with tuberculous meningitis. Int J Tuberc Lung Dis. 2015;19:200–4.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Tan EK, Chee MW, Chan LL, Lee YL. Culture positive tuberculous meningitis: clinical indicators of poor prognosis. Clin Neurol Neurosurg. 1999;101:157–60.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Thwaites G, Chau TT, Mai NT, Drobniewski F, McAdam K, Farrar J. Tuberculous meningitis. J Neurol Neurosurg Psychiatry. 2000;68:289–99.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T, Innes J, British Infection S. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect. 2009;59:167–87.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Thwaites GE, Bhavnani SM, Chau TT, Hammel JP, Torok ME, Van Wart SA, Mai PP, Reynolds DK, Caws M, Dung NT, Hien TT, Kulawy R, Farrar J, Ambrose PG. Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis. Antimicrob Agents Chemother. 2011;55:3244–53.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Thwaites GE, Lan NT, Dung NH, Quy HT, Oanh DT, Thoa NT, Hien NQ, Thuc NT, Hai NN, Bang ND, Lan NN, Duc NH, Tuan VN, Hiep CH, Chau TT, Mai PP, Dung NT, Stepniewska K, White NJ, Hien TT, Farrar JJ. Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis. J Infect Dis. 2005;192:79–88.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Thwaites GE, Nguyen DB, Nguyen HD, Hoang TQ, Do TT, Nguyen TC, Nguyen QH, Nguyen TT, Nguyen NH, Nguyen TN, Nguyen NL, Nguyen HD, Vu NT, Cao HH, Tran TH, Pham PM, Nguyen TD, Stepniewska K, White NJ, Tran TH, Farrar JJ. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004;351:1741–51.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Thwaites GE, Tran TH. Tuberculous meningitis: many questions, too few answers. Lancet Neurol. 2005;4:160–70.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Thwaites GE, Van Toorn R, Schoeman J. Tuberculous meningitis: more questions, still too few answers. Lancet Neurol. 2013;12:999–1010.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Torok ME. Tuberculous meningitis: advances in diagnosis and treatment. Br Med Bull. 2015;113:117–31.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Torok ME, Yen NT, Chau TT, Mai NT, Phu NH, Mai PP, Dung NT, Chau NV, Bang ND, Tien NA, Minh NH, Hien NQ, Thai PV, Dong DT, Anh DT, Thoa NT, Hai NN, Lan NN, Lan NT, Quy HT, Dung NH, Hien TT, Chinh NT, Simmons CP, De Jong M, Wolbers M, Farrar JJ. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)–associated tuberculous meningitis. Clin Infect Dis. 2011;52:1374–83.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Trivedi R, Saksena S, Gupta RK. Magnetic resonance imaging in central nervous system tuberculosis. Indian J Radiol Imaging. 2009;19:256–65.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Tuon FF, Higashino HR, Lopes MI, Litvoc MN, Atomiya AN, Antonangelo L, Leite OM. Adenosine deaminase and tuberculous meningitis--a systematic review with meta-analysis. Scand J Infect Dis. 2010;42:198–207.PubMedCrossRefGoogle Scholar
  113. 113.
    Tyler KL. Chapter 28: a history of bacterial meningitis. Handb Clin Neurol. 2010;95:417–33.PubMedCrossRefGoogle Scholar
  114. 114.
    Van Der Merwe DJ, Andronikou S, Van Toorn R, Pienaar M. Brainstem ischemic lesions on MRI in children with tuberculous meningitis: with diffusion weighted confirmation. Childs Nerv Syst. 2009;25:949–54.PubMedCrossRefGoogle Scholar
  115. 115.
    Van Well GT, Paes BF, Terwee CB, Springer P, Roord JJ, Donald PR, Van Furth AM, Schoeman JF. Twenty years of pediatric tuberculous meningitis: a retrospective cohort study in the western cape of South Africa. Pediatrics. 2009;123:e1–8.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Venkataswamy MM, Rafi W, Nagarathna S, Ravi V, Chandramuki A. Comparative evaluation of BACTEC 460TB system and Lowenstein-Jensen medium for the isolation of M. tuberculosis from cerebrospinal fluid samples of tuberculous meningitis patients. Indian J Med Microbiol. 2007;25:236–40.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Verdon R, Chevret S, Laissy JP, Wolff M. Tuberculous meningitis in adults: review of 48 cases. Clin Infect Dis. 1996;22:982–8.PubMedCrossRefGoogle Scholar
  118. 118.
    Vinnard C, King L, Munsiff S, Crossa A, Iwata K, Pasipanodya J, Proops D, Ahuja S. Long-term mortality of patients with tuberculous meningitis in New York City: a cohort study. Clin Infect Dis. 2017;64:401–7.PubMedPubMedCentralGoogle Scholar
  119. 119.
    Vinnard C, Macgregor RR. Tuberculous meningitis in HIV-infected individuals. Curr HIV/AIDS Rep. 2009;6:139–45.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Vinnard C, Winston CA, Wileyto EP, Macgregor RR, Bisson GP. Isoniazid resistance and death in patients with tuberculous meningitis: retrospective cohort study. BMJ. 2010;341:c4451.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Visudhiphan P, Chiemchanya S. Hydrocephalus in tuberculous meningitis in children: treatment with acetazolamide and repeated lumbar puncture. J Pediatr. 1979;95:657–60.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Wang JT, Hung CC, Sheng WH, Wang JY, Chang SC, Luh KT. Prognosis of tuberculous meningitis in adults in the era of modern antituberculous chemotherapy. J Microbiol Immunol Infect. 2002;35:215–22.PubMedPubMedCentralGoogle Scholar
  123. 123.
    Wilkinson RJ, Rohlwink U, Misra UK, Van Crevel R, Mai NTH, Dooley KE, Caws M, Figaji A, Savic R, Solomons R, Thwaites GE, Tuberculous Meningitis International Research, C. Tuberculous meningitis. Nat Rev Neurol. 2017;13:581–98.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Yaramis A, Bukte Y, Katar S, Ozbek MN. Chest computerized tomography scan findings in 74 children with tuberculous meningitis in southeastern Turkey. Turk J Pediatr. 2007;49:365–9.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Derya Ozturk-Engin
    • 1
  • Corneliu Petru Popescu
    • 2
  1. 1.Fatih Sultan Mehmet Training and Research Hospital, Department of Infectious Diseases and Clinical MicrobiologyIstanbulTurkey
  2. 2.Carol Davila University of Medicine and Pharmacy; Dr Victor Babes Clinical Hospital of Infectious and Tropical DiseasesBucharestRomania

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