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01-02-2021 | Tuberculosis | Review article

Neurotuberculosis: an update

Authors: Ajith Cherian, Kesi Chellappan Ajitha, Thomas Iype, K. P. Divya

Published in: Acta Neurologica Belgica | Issue 1/2021

Abstract

Tuberculous (TB) meningitis (TBM), accounting for 70–80% of cases of neurotuberculosis, is one of the most severe forms of extrapulmonary tuberculosis. Two-thirds of new TB cases come from eight countries. Polymorphisms in toll–interleukin-1 receptor domain and in leukotriene A4 hydrolase (LTA4H) gene, affect the risk of inflammation in TBM. The common site of tuberculoma in children is cerebellum, and they may rarely develop tuberculous encephalopathy which has a high mortality. Young females with a high cerebrospinal fluid (CSF) protein have an increased predisposition to develop optochiasmatic arachnoiditis. Spinal TB meningitis may mimic transverse myelitis or Guillain–Barre syndrome. An extra-neural focus of TB should be sought clinically and radiologically as it may indicate safer and more accessible sites for diagnostic samplings. Cartridge-based nucleic acid amplification test (CBNAAT), also known as Genexpert test, is a polymerase chain reaction (PCR)-based method for detection of TB which also detects rifampicin resistance as it targets the rpob gene of mycobacteria. Line probe assays, based on PCR and reverse hybridization methods, identify mutations associated with drug resistance within a week. TBM being a paucibacillary disease, often evades a definite diagnosis and empirical treatment for a minimum of 9 months is warranted based on clinical judgement. All TBM patients should receive adjunctive corticosteroids, even those with HIV infection. Drug resistance is strongly associated with previous treatment and bedaquiline as well as delamanid have received approvals for multidrug resistant (MDR) TB. The key principle of managing MDR TB is never to add a single drug to a failing regimen. Correct combination and duration of most effective second line drugs in MDR TB require further modifications. Early shunting should be considered in those with hydrocephalus failing medical management. The single most important determinant of outcome is the stage of TBM at which treatment has been started.

World Health Organization (2018) Global tuberculosis report 2018. World Health Organization. https://apps.who.int/iris/handle/10665/274453

Dastur DK, Manghani DK, Udani PM (1995) Pathology and pathogenetic mechanisms in neurotuberculosis. Radiol Clin North Am 33(4):733–752PubMed

Hawn TR, Dunstan SJ, Thwaites GE et al (2006) A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. J Infect Dis 194:1127CrossRef

Thuong NTT, Heemskerk D, Tram TTB et al (2017) Leukotriene A4 hydrolase genotype and HIV infection influence intracerebral inflammation and survival from tuberculous meningitis. J Infect Dis 215(7):1020–1028. https://doi.org/10.1093/infdis/jix050CrossRefPubMedPubMedCentral

Rajshekhar V (2009) Management of hydrocephalus in patients with tuberculous meningitis. Neurol India 57(4):368–374CrossRef

Rajasekaran S, Soundararajan DCR, Shetty AP, Kanna RM (2018) Spinal tuberculosis: current concepts. Glob Spine J 8(4 Suppl):96S-108SCrossRef

Sharma SK, Ryan H, Khaparde S, Sachdeva K, Singh AD, Mohan A, Sarin R, Paramasivan C, Kumar P, Nischal N (2017) Index-TB guidelines: guidelines on extrapulmonary tuberculosis for India. Indian J Med Res 145:448–463CrossRef

Sharma P, Garg RK, Verma R, Singh MK, Shukla R (2011) Incidence, predictors and prognostic value of cranial nerve involvement in patients with tuberculous meningitis: a retrospective evaluation. Eur J Intern Med 22:289–295CrossRef

Anderson NE, Somaratne J, Mason DF, Holland D, Thomas MG (2010) Neurological and systemic complications of tuberculous meningitis and its treatment at Auckland City Hospital, New Zealand. J Clin Neurosci 17:1114–1118CrossRef

10.

Sheu J-J, Hsu C-Y, Yuan R-Y, Yang C-C (2012) Clinical characteristics and treatment delay of cerebral infarction in tuberculous meningitis. Intern Med J 42:294–300CrossRef

11.

Kalita J, Misra UK, Nair PP (2009) Predictors of stroke and its significance in the outcome of tuberculous meningitis. J Stroke Cerebrovasc Dis 18:251–258CrossRef

12.

Anuradha HK, Garg RK, Agarwal A, Sinha MK, Verma R, Singh MK, Shukla R (2010) Predictors of stroke in patients of tuberculous meningitis and its effect on the outcome. QJM 103:671–678. https://doi.org/10.1093/qjmed/hcq103CrossRefPubMed

13.

Kalita J, Prasad S, Maurya PK, Kumar S, Misra UK (2012) MR angiography in tuberculous meningitis. Acta Radiol 53:324–329. https://doi.org/10.1258/ar.2012.110712CrossRefPubMed

14.

Anuradha HK, Garg RK, Sinha MK, Agarwal A, Verma R, Singh MK, Shukla R (2011) Intracranial tuberculomas in patients with tuberculous meningitis: predictors and prognostic significance. Int J Tuberc Lung Dis 15:234–239PubMed

15.

Ira S (2005) Paradoxical appearance of intracranial tuberculoma in a child with tuberculous meningitis. J Trop Pediatr 51:191–193. https://doi.org/10.1093/tropej/fmi019CrossRefPubMed

16.

Sinha MK, Garg RK, Anuradha HK, Agarwal A, Parihar A, Mandhani PA (2010) Paradoxical vision loss associated with optochiasmatic tuberculoma in tuberculous meningitis: a report of 8 patients. J Infect 60:458–466CrossRef

17.

Takahashi H, Ito S, Kojima S, Tanno T, Hattori T (2008) Intradural extramedullary tuberculoma of the thoracic spine: paradoxical response to antituberculous therapy. Intern Med 47:797–798. https://doi.org/10.2169/internalmedicine.47.0839CrossRefPubMed

18.

Griffiths SJ, Sgouros S, James G, John P (2000) Intraventricular haemorrhage due to ruptured posterior inferior cerebellar artery aneurysm in tuberculous meningitis. Childs Nerv Syst 16:872–874. https://doi.org/10.1007/s003810000267CrossRefPubMed

19.

Zou H, Pan KH, Pan HY, Huang DS, Zheng MH (2015) Cerebral hemorrhage due to tuberculosis meningitis: a rare case report and literature review. Oncotarget 6(42):45005–45009. https://doi.org/10.18632/oncotarget.6528CrossRefPubMedPubMedCentral

20.

Israni AV, Dave DA, Mandal A, Singh A, Sahi PK, Das RR et al (2016) Tubercular meningitis in children: clinical, pathological, and radiological profile and factors associated with mortality. J Neurosci Rural Pract 7:400–404CrossRef

21.

Aulakh R, Chopra S (2018) Pediatric tubercular meningitis: a review. J Pediatr Neurosci 13(4):373–382CrossRef

22.

Seth R, Sharma U (2002) Diagnostic criteria for tuberculous meningitis. Indian J Pediatr 69:299–303. https://doi.org/10.1007/bf02723213CrossRefPubMed

23.

Kim HJ, Shim KW, Lee MK, Park MS, Kim SH, Kim EY et al (2011) Tuberculous encephalopathy without meningitis: pathology and brain MRI findings. Eur Neurol 65:156–159CrossRef

24.

Anupriya A, Sunithi M, Maya T, Goel M, Alexander M, Aaron S, Mathew V (2010) Tuberculous optochiasmatic arachnoiditis. Neurol India 58:732–735. https://doi.org/10.4103/0028-3886.72194CrossRefPubMed

25.

Mahadevan B, Mahadevan S, Serane VT (2002) Prognostic factors in childhood tuberculous meningitis. J Trop Pediatr 48:362–365. https://doi.org/10.1093/tropej/48.6.362CrossRefPubMed

26.

Roca B, Tornador N, Tornador E (2008) Presentation and outcome of tuberculous meningitis in adults in the province of Castellon, Spain: a retrospective study. Epidemiol Infect 136:1455–1462. https://doi.org/10.1017/S0950268807000258CrossRefPubMedPubMedCentral

27.

Sonmez G, Turhan V, Senol MG, Ozturk E, Sildiroglu HO, Mutlu H (2008) Relationship between tuberculous otomastoiditis and tuberculous meningitis. J Laryngol Otol 122:893–897. https://doi.org/10.1017/S0022215107000540CrossRefPubMed

28.

Yasar KK, Pehlivanoglu F, Sengoz G, Ayrancioglu N (2011) A case of tuberculous meningitis with multiple intracranial tuberculomas and miliary tuberculosis and choroid tubercles. Infection 39:395–396. https://doi.org/10.1007/s15010-011-0144-2CrossRefPubMed

29.

Ralot T, Bafna C, Singh S, Sharma S (2017) A rare presentation of tubercular meningitis as persistent neutrophilic meningitis. Malays J Med Sci 24(6):103–106. https://doi.org/10.21315/mjms2017.24.6.13CrossRefPubMedPubMedCentral

30.

Cecchini D, Ambrosioni J, Brezzo C, Corti M, Rybko A, Perez M, Poggi S, Ambroggi M (2009) Tuberculous meningitis in HIV-infected and non-infected patients: comparison of cerebrospinal fluid findings. Int J Tuberc Lung Dis 13:269–271PubMed

31.

Ekermans P, Dusé A, George J (2017) The dubious value of cerebrospinal fluid adenosine deaminase measurement for the diagnosis of tuberculous meningitis. BMC Infect Dis 17(1):104. https://doi.org/10.1186/s12879-017-2221-3CrossRefPubMedPubMedCentral

32.

Panicker JN, Nagaraja D, Subbakrishna DK, Venkataswamy MM, Chandramuki A (2010) Role of the BACTEC radiometric method in the evaluation of patients with clinically probable tuberculous meningitis. Ann Indian Acad Neurol 13(2):128–131. https://doi.org/10.4103/0972-2327.64637CrossRefPubMedPubMedCentral

33.

Ghosh RN, Vyas S, Singh P, Khandelwal N, Sankhyan N, Singhi P (2019) Perfusion magnetic resonance imaging in differentiation of neurocysticercosis and tuberculoma. Neuroradiology 61(3):257–263. https://doi.org/10.1007/s00234-018-2118-xCrossRefPubMed

34.

Chatterjee S, Saini J, Kesavadas C, Arvinda HR, Jolappara M, Gupta AK (2010) Differentiation of tubercular infection and metastasis presenting as ring enhancing lesion by diffusion and perfusion magnetic resonance imaging. J Neuroradiol 37:167–171. https://doi.org/10.1016/j.neurad.2009.08.005CrossRefPubMed

35.

Wasay M, Kheleani BA, Moolani MK, Zaheer J, Pui M, Hasan S, Muzaffar S, Bakshi R, Sarawari AR (2003) Brain CT and MRI findings in 100 consecutive patients with intracranial tuberculoma. J Neuroimaging 13:240–247CrossRef

36.

Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T, Innes J (2009) British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect 59:167–187. https://doi.org/10.1016/j.jinf.2009.06.011CrossRefPubMed

37.

Vibha D, Bhatia R, Prasad K, Srivastava MVP, Tripathi M, Kumar G, Singh MB (2012) Validation of diagnostic algorithm to differentiate between tuberculous meningitis and acute bacterial meningitis. Clin Neurol Neurosurg 114:639–644. https://doi.org/10.1016/j.clineuro.2011.12.033CrossRefPubMed

38.

Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, Fujiwara P, Grzemska M, Hopewell PC, Iseman MD, Jasmer RM, Koppaka V, Menzies RI, O’Brien RJ, Reves RR, Reichman LB, Simone PM, Starke JR, Vernon AA, American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society (2003) American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med 167:603–662. https://doi.org/10.1164/rccm.167.4.603CrossRefPubMed

39.

Jipa R, Olaru ID, Manea E, Merisor S, Hristea A (2017) Rapid clinical score for the diagnosis of tuberculous meningitis: a retrospective cohort study. Ann Indian Acad Neurol 20(4):363–366. https://doi.org/10.4103/aian.AIAN_219_17CrossRefPubMedPubMedCentral

40.

Iype T, George LE, Cherian A, Kumar A, Ajitha BK, Chandy S, Kumar KV (2012) In-hospital mortality of intermittent vs daily antitubercular regimen in patients with meningeal tuberculosis—a retrospective study. Indian J Tuberc. 59(1):6–11PubMed

41.

Iype T, Pillai AK, Cherian A, Nujum ZT, Pushpa C, Dae D, Krishnapillai V (2014) Major outcomes of patients with tuberculous meningitis on directly observed thrice a week regime. Ann Indian Acad Neurol 17(3):281–286CrossRef

42.

Thwaites GE, Bhavnani SM, Chau TTH, Hammel JP, Torok ME, Van Wart SA, Mai PP, Reynolds DK, Caws M, Dung NT, Hien TT, Kulawy R, Farrar J, Ambrose PG (2011) Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis. Antimicrob Agents Chemother 55:3244–3253. https://doi.org/10.1128/AAC.00064-11CrossRefPubMedPubMedCentral

43.

Bastos ML, Hussain H, Weyer K, Garcia-Garcia L, Leimane V, Leung CC, Narita M, Penã JM, Ponce-de-Leon A, Seung KJ (2014) Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first-and second-line drugs: an individual patient data meta-analysis. Clin Infect Dis 59:1364–1374CrossRef

44.

Klopper M, Warren RM, Hayes C et al (2013) Emergence and spread of extensively and totally drug-resistant tuberculosis, South Africa. Emerg Infect Dis 19(3):449–455. https://doi.org/10.3201//EID1903.120246CrossRefPubMedPubMedCentral

45.

Nagarathna S, Rafi W, Veenakumari HB, Mani R, Satishchandra P, Chandramuki A (2008) Drug susceptibility profiling of tuberculous meningitis. Int J Tuberc Lung Dis 12:105–107PubMed

46.

https://www.who.int/tb/areas-of-work/drug-resistant-tb/global-situation/en/

47.

Li Y, Sun F, Zhang W (2019) Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: promising but challenging. Drug Dev Res 80(1):98–105. https://doi.org/10.1002/ddr.21498CrossRefPubMed

48.

Prasad K, Singh MB, Ryan H (2016) Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev 4:CD002244. https://doi.org/10.1002/14651858.CD002244.pub4CrossRefPubMed

49.

Nagotkar L, Shanbag P, Dasarwar N (2008) Cerebral salt wasting syndrome following neurosurgical intervention in tuberculous meningitis. Indian Pediatr 45:598–601PubMed

50.

Schoeman JF, Andronikou S, Stefan DC, Freeman N, van Toorn R (2010) Tuberculous meningitis-related optic neuritis: recovery of vision with thalidomide in 4 consecutive cases. J Child Neurol 25:822–828. https://doi.org/10.1177/0883073809350507CrossRefPubMed

51.

Jorge J-H, Graciela C, Pablo A-P, Luis S-HJ (2012) A life-threatening central nervous system-tuberculosis inflammatory reaction nonresponsive to corticosteroids and successfully controlled by infliximab in a young patient with a variant of juvenile idiopathic arthritis. J Clin Rheumatol 18:189–191. https://doi.org/10.1097/RHU.0b013e318258b725CrossRefPubMed

52.

Misra UK, Kalita J, Nair PP (2010) Role of aspirin in tuberculous meningitis: a randomized open label placebo controlled trial. J Neurol Sci 293(1–2):12–17CrossRef

53.

Rizvi I, Garg RK, Malhotra HS, Kumar N, Uniyal R (2019) Role of aspirin in tuberculous meningitis: a systematic review and meta-analysis. Neurol India 67:993–1002CrossRef

54.

Khatri GD, Krishnan V, Antil N, Saigal G (2018) Magnetic resonance imaging spectrum of intracranial tubercular lesions: one disease, many faces. Pol J Radiol 83:e524–e535. https://doi.org/10.5114/pjr.2018.81408CrossRefPubMedPubMedCentral

55.

Garg RK, Malhotra HS, Kumar N (2014) Paradoxical reaction in HIV negative tuberculous meningitis. J Neurol Sci 340:26–36. https://doi.org/10.1016/j.jns.2014.03.025CrossRefPubMed

56.

Kumar A, Singh K, Sharma V (2013) Surgery in hydrocephalus of tubercular origin: challenges and management. Acta Neurochir (Wien) 155:869–873. https://doi.org/10.1007/s00701-013-1658-4CrossRef

57.

Rizvi I, Garg RK, Malhotra HS, Kumar N, Sharma E, Srivastava C, Uniyal R (2017) Ventriculo-peritoneal shunt surgery for tuberculous meningitis: a systematic review. J Neurol Sci 375:255–263. https://doi.org/10.1016/j.jns.2017.02.008CrossRefPubMed

58.

Yadav YR, Parihar VS, Todorov M, Kher Y, Chaurasia ID, Pande S, Namdev H (2016) Role of endoscopic third ventriculostomy in tuberculous meningitis with hydrocephalus. Asian J Neurosurg 11:325–329. https://doi.org/10.4103/1793-5482.145100CrossRefPubMedPubMedCentral

59.

Aranha A, Choudhary A, Bhaskar S, Gupta L (2018) A randomized study comparing endoscopic third ventriculostomy versus ventriculoperitoneal shunt in the management of hydrocephalus due to tuberculous meningitis. Asian J Neurosurg 13:1140. https://doi.org/10.4103/ajns.AJNS_107_18CrossRefPubMedPubMedCentral

60.

George EL, Iype T, Cherian A, Chandy S, Kumar A, Balakrishnan A et al (2012) Predictors of mortality in patients with meningeal tuberculosis. Neurol India 60:18–22CrossRef

61.

Wang MG, Luo L, Zhang Y, Liu X, Liu L, He JQ (2019) Treatment outcomes of tuberculous meningitis in adults: a systematic review and meta-analysis. BMC Pulm Med 19(1):200. https://doi.org/10.1186/s12890-019-0966-8CrossRefPubMedPubMedCentral

62.

Pehlivanoglu F, Yasar KK, Sengoz G (2012) Tuberculous meningitis in adults: a review of 160 cases. Sci World J 2012:169028. https://doi.org/10.1100/2012/169028CrossRef

63.

Cherian A, Thomas SV (2011) Central nervous system tuberculosis. Afr Health Sci 11(1):116–127PubMedPubMedCentral

Title: Neurotuberculosis: an update
Authors: Ajith Cherian
Kesi Chellappan Ajitha
Thomas Iype
K. P. Divya
Publication date: 01-02-2021
Publisher: Springer International Publishing
Keywords: Tuberculosis
Hydrocephalus
Hydrocephalus
Tuberculosis
Rifampicin
Meningitis
Hydrocephalus
Neurotuberculosis
Published in: Acta Neurologica Belgica / Issue 1/2021
Print ISSN: 0300-9009
Electronic ISSN: 2240-2993
DOI: https://doi.org/10.1007/s13760-020-01575-0

At a glance: The STEP trials

Springer Medicine

Neurotuberculosis: an update

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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