J Pediatr Infect Dis 2018; 13(02): 141-152
DOI: 10.1055/s-0037-1607235
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Treatment of Central Nervous System Tuberculosis

Amina Ahmed
1   Department of Pediatrics, Levine Children's Hospital at Carolinas Medical Center, Charlotte, North Carolina, United States
2   University of North Carolina at Chapel Hill, North Carolina, United States
› Author Affiliations
Further Information

Publication History

10 April 2017

02 June 2017

Publication Date:
15 January 2018 (online)

Abstract

Central nervous system tuberculosis (CNS-TB) manifests as tuberculous meningitis, intracranial tuberculoma, or spinal tuberculous arachnoiditis. Children are disproportionately affected, with high rates of mortality and morbidity reported even in the era of treatment. Most guidelines for the treatment of drug-susceptible CNS-TB recommend 9 to 12 months of a standard regimen of isoniazid, rifampin, pyrazinamide, and ethambutol, with the adjunctive use of corticosteroids early in therapy. Recent trials have demonstrated improved outcomes with intensified regimens using nonstandard regimens or higher dosages of standard drugs. Accumulating evidence also supports shorter duration of treatment. Further investigation is warranted to identify the optimal regimen and duration of treatment for CNS-TB. Complications such as hydrocephalus may be managed medically or surgically. Although outcomes have improved with effective chemotherapy and immunomodulation of disease, prompt diagnosis and treatment in the early stages of disease remain paramount to improve prognosis.

 
  • References

  • 1 Wallgren A. Some aspects of tuberculous meningitis and the possibility of prevention. J Pediatr 1934; 5 (03) 291-298
  • 2 Donald PR, Schoeman JF. Tuberculous meningitis. N Engl J Med 2004; 351 (17) 1719-1720
  • 3 Wolzak NK, Cooke ML, Orth H, van Toorn R. The changing profile of pediatric meningitis at a referral centre in Cape Town, South Africa. J Trop Pediatr 2012; 58 (06) 491-495
  • 4 Lincoln EM. Tuberculous meningitis in children; with special reference to serous meningitis; serous tuberculous meningitis. Am Rev Tuberc 1947; 56 (02) 95-109
  • 5 Principi N, Esposito S. Diagnosis and therapy of tuberculous meningitis in children. Tuberculosis (Edinb) 2012; 92 (05) 377-383
  • 6 Fox W, Ellard GA, Mitchison DA. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications. Int J Tuberc Lung Dis 1999; 3 (10) (Suppl. 02) S231-S279
  • 7 Mitchison D, Davies G. The chemotherapy of tuberculosis: past, present and future. Int J Tuberc Lung Dis 2012; 16 (06) 724-732
  • 8 Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T, Innes J. ; British Infection Society. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect 2009; 59 (03) 167-187
  • 9 van der Harst JJ, Luijckx GJ. Treatment of central nervous system tuberculosis infections and neurological complications of tuberculosis treatment. Curr Pharm Des 2011; 17 (27) 2940-2947
  • 10 British Medical Research Council. STREPTOMYCIN treatment of tuberculous meningitis. Lancet 1948; 1 (6503): 582-596
  • 11 Thwaites GE, Nguyen DB, Nguyen HD. , et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med 2004; 351 (17) 1741-1751
  • 12 Nahid P, Dorman SE, Alipanah N. , et al. Executive summary: 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 (07) 853-867
  • 13 Thwaites GE, van Toorn R, Schoeman J. Tuberculous meningitis: more questions, still too few answers. Lancet Neurol 2013; 12 (10) 999-1010
  • 14 Garg RK, Jain A, Malhotra HS, Agrawal A, Garg R. Drug-resistant tuberculous meningitis. Expert Rev Anti Infect Ther 2013; 11 (06) 605-621
  • 15 Donald PR. The chemotherapy of tuberculous meningitis in children and adults. Tuberculosis (Edinb) 2010; 90 (06) 375-392
  • 16 Donald PR. Cerebrospinal fluid concentrations of antituberculosis agents in adults and children. Tuberculosis (Edinb) 2010; 90 (05) 279-292
  • 17 Ellard GA, Humphries MJ, Allen BW. Cerebrospinal fluid drug concentrations and the treatment of tuberculous meningitis. Am Rev Respir Dis 1993; 148 (03) 650-655
  • 18 Nau R, Sörgel F, Eiffert H. Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. Clin Microbiol Rev 2010; 23 (04) 858-883
  • 19 Donald PR, Seifart HI. Cerebrospinal fluid concentrations of ethionamide in children with tuberculous meningitis. J Pediatr 1989; 115 (03) 483-486
  • 20 American Academy of Pediatrics. Tuberculosis. In: Kimberlin DW, Brady MT, Jackson MA, Long SS. , eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015: 805-831
  • 21 Canadian Tuberculosis Standards. 7th ed. 2014 . Available at: http://strauss.ca/OEMAC/wp-content/uploads/2013/11/Canadian_TB_Standards_7th-edition_English.pdf . Accessed February 26, 2017
  • 22 Kumar A, Gupta D, Nagaraja SB, Singh V, Sethi GR, Prasad J. ; Indian Academy of Pediatrics. Updated national guidelines for pediatric tuberculosis in India, 2012. Indian Pediatr 2013; 50 (03) 301-306
  • 23 Moore DP, Schaaf HS, Nuttall J, Maris BJ. Childhood tuberculosis guidelines of the Southern African Society for Paediatric Infectious Diseases. South Afr J Epidemiol Infect 2009; 24 (03) 57-68
  • 24 World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children. 2014 . Available at: http://apps.who.int/iris/bitstream/10665/112360/1/9789241548748_eng.pdf . Accessed February 26, 2017
  • 25 Thee S, Seddon JA, Donald PR. , et al. Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger than two years of age with tuberculosis: evidence for implementation of revised World Health Organization recommendations. Antimicrob Agents Chemother 2011; 55 (12) 5560-5567
  • 26 World Health Organization. Rapid advice: treatment of tuberculosis in children. Geneva: World Health Organization, 2010 . Available at: http://whqlibdoc.who.int/publications/2010/9789241500449_eng.pdf ; Accessed February 26, 2017
  • 27 Donald PR, Maritz JS, Diacon AH. The pharmacokinetics and pharmacodynamics of rifampicin in adults and children in relation to the dosage recommended for children. Tuberculosis (Edinb) 2011; 91 (03) 196-207
  • 28 Chiang SS, Khan FA, Milstein MB. , et al. Treatment outcomes of childhood tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect Dis 2014; 14 (10) 947-957
  • 29 Donald PR, Schoeman JF, Van Zyl LE, De Villiers JN, Pretorius M, Springer P. Intensive short course chemotherapy in the management of tuberculous meningitis. Int J Tuberc Lung Dis 1998; 2 (09) 704-711
  • 30 van Toorn R, Schaaf HS, Laubscher JA, van Elsland SL, Donald PR, Schoeman JF. Short intensified treatment in children with drug-susceptible tuberculous meningitis. Pediatr Infect Dis J 2014; 33 (03) 248-252
  • 31 Boeree MJ, Diacon AH, Dawson R. , et al; PanACEA Consortium. A dose-ranging trial to optimize the dose of rifampin in the treatment of tuberculosis. Am J Respir Crit Care Med 2015; 191 (09) 1058-1065
  • 32 Ruslami R, Ganiem AR, Dian S. , et al. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis 2013; 13 (01) 27-35
  • 33 Thwaites GE, Bhavnani SM, Chau TT. , et al. Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis. Antimicrob Agents Chemother 2011; 55 (07) 3244-3253
  • 34 Heemskerk AD, Bang ND, Mai NTH. , et al. Intensified antituberculosis therapy in adults with tuberculous meningitis. N Engl J Med 2016; 374 (02) 124-134
  • 35 Kendig Jr EL. Evolution of short-course antimicrobial treatment of tuberculosis in children, 1951-1984. Pediatrics 1985; 75 (04) 684-686
  • 36 Jullien S, Ryan H, Modi M, Bhatia R. Six months therapy for tuberculous meningitis. Cochrane Database Syst Rev 2016; 9 (09) CD012091
  • 37 Lorber J. Current results in treatment of tuberculous meningitis and miliary tuberculosis. BMJ 1956; 1 (4974): 1009-1011
  • 38 Kendig Jr EL, Burch CD. Short-term antimicrobial therapy of tuberculous meningitis. Am Rev Respir Dis 1960; 82: 672-681
  • 39 Biddulph J. Short course chemotherapy for childhood tuberculosis. Pediatr Infect Dis J 1990; 9 (11) 794-801
  • 40 Jacobs RF, Sunakorn P, Chotpitayasunonah T, Pope S, Kelleher K. Intensive short course chemotherapy for tuberculous meningitis. Pediatr Infect Dis J 1992; 11 (03) 194-198
  • 41 Bose A, Kalita S, Rose W, Tharyan P. Intermittent versus daily therapy for treating tuberculosis in children. Cochrane Database Syst Rev 2014; (01) CD007953
  • 42 Prasad K, Singh MB. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev 2008; (01) CD002244
  • 43 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 (02) 226-231
  • 44 Girgis NI, Farid Z, Kilpatrick ME, Sultan Y, Mikhail IA. Dexamethasone adjunctive treatment for tuberculous meningitis. Pediatr Infect Dis J 1991; 10 (03) 179-183
  • 45 Afghani B, Lieberman JM. Paradoxical enlargement or development of intracranial tuberculomas during therapy: case report and review. Clin Infect Dis 1994; 19 (06) 1092-1099
  • 46 Misra UK, Kalita J, Nair PP. Role of aspirin in tuberculous meningitis: a randomized open label placebo controlled trial. J Neurol Sci 2010; 293 (1-2): 12-17
  • 47 Schoeman JF, Janse van Rensburg A, Laubscher JA, Springer P. The role of aspirin in childhood tuberculous meningitis. J Child Neurol 2011; 26 (08) 956-962
  • 48 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 (07) 822-828
  • 49 Schoeman JF, Springer P, van Rensburg AJ. , et al. Adjunctive thalidomide therapy for childhood tuberculous meningitis: results of a randomized study. J Child Neurol 2004; 19 (04) 250-257
  • 50 Schoeman JF, Ravenscroft A, Hartzenberg HB. Possible role of adjunctive thalidomide therapy in the resolution of a massive intracranial tuberculous abscess. Childs Nerv Syst 2001; 17 (06) 370-372
  • 51 Ettehad D, Schaaf HS, Seddon JA, Cooke GS, Ford N. Treatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12 (06) 449-456
  • 52 Nagarathna S, Rafi W, Veenakumari HB, Mani R, Satishchandra P, Chandramuki A. Drug susceptibility profiling of tuberculous meningitis. Int J Tuberc Lung Dis 2008; 12 (01) 105-107
  • 53 Patel VB, Padayatchi N, Bhigjee AI. , et al. Multidrug-resistant tuberculous meningitis in KwaZulu-Natal, South Africa. Clin Infect Dis 2004; 38 (06) 851-856
  • 54 Seddon JA, Visser DH, Bartens M. , et al. Impact of drug resistance on clinical outcome in children with tuberculous meningitis. Pediatr Infect Dis J 2012; 31 (07) 711-716
  • 55 Seddon JA, Thee S, Jacobs K, Ebrahim A, Hesseling AC, Schaaf HS. Hearing loss in children treated for multidrug-resistant tuberculosis. J Infect 2013; 66 (04) 320-329
  • 56 Thee S, Zöllner EW, Willemse M, Hesseling AC, Magdorf K, Schaaf HS. Abnormal thyroid function tests in children on ethionamide treatment. Int J Tuberc Lung Dis 2011; 15 (09) 1191-1193 , i
  • 57 World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update. October 2016 revision. Available at: http://www.who.int/tb/areas-of-work/drug-resistant-tb/MDRTBguidelines2016.pdf ; Accessed March 2, 2017
  • 58 The Sentinel Project for Pediatric Drug-Resistant Tuberculosis. Management of drug-resistant tuberculosis in children: a field guide, 2016. Available at: http://sentinel-project.org/wp-content/uploads/2016/12/Field Handbook_3rd-Ed-30-Nov2016.pdf . Accessed February 14, 2017
  • 59 Van Deun A, Maug AK, Salim MA. , et al. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med 2010; 182 (05) 684-692
  • 60 Thwaites GE, Duc Bang N, Huy Dung N. , et al. The influence of HIV infection on clinical presentation, response to treatment, and outcome in adults with tuberculous meningitis. J Infect Dis 2005; 192 (12) 2134-2141
  • 61 Abdool Karim SS, Naidoo K, Grobler A. , et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med 2010; 362 (08) 697-706
  • 62 Török ME, Yen NT, Chau TT. , et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis. Clin Infect Dis 2011; 52 (11) 1374-1383
  • 63 van Well GT, Paes BF, Terwee CB. , et al. Twenty years of pediatric tuberculous meningitis: a retrospective cohort study in the western cape of South Africa. Pediatrics 2009; 123 (01) e1-e8
  • 64 Rajshekhar V. Surgery for brain tuberculosis: a review. Acta Neurochir (Wien) 2015; 157 (10) 1665-1678
  • 65 Kumar A, Singh K, Sharma V. Surgery in hydrocephalus of tubercular origin: challenges and management. Acta Neurochir (Wien) 2013; 155 (05) 869-873
  • 66 Thwaites GE, Tran TH. Tuberculous meningitis: many questions, too few answers. Lancet Neurol 2005; 4 (03) 160-170
  • 67 Rock RB, Olin M, Baker CA, Molitor TW, Peterson PK. Central nervous system tuberculosis: pathogenesis and clinical aspects. Clin Microbiol Rev 2008; 21 (02) 243-261