Tuberculous Meningitis: Diagnostic and Radiological Features, Pathogenesis and Biomarkers

Mei-Ling Sharon Tai

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia..

DOI: 10.4236/nm.2013.42016                

Abstract

Central nervous system tuberculosis is the most severe form of extrapulmonary tuberculosis disease. We aim to review the diagnostic and radiological features, pathogenesis, and biomarkers of tuberculous meningitis. We also aim to look at the latest development of research of the disease. The diagnosis of tuberculous (TB) meningitis is difficult because the disease presents with unspecific clinical features. However, the disease has excellent clinical response to antituberculous therapy. Good prognosis depends on prompt diagnosis with treatment and radiological findings are very important. There is an increase in the levels of serum and cerebrospinal fluid (CSF) TNF-in TB meningitis patients. IL-6 level is also increased in patients with tuberculoma and exudates. There is an increase in the levels of serum and CSF TNF-α and IFN-γ in TB meningitis patients. There is also a rise in the levels of IL-8, IFN-alpha, IFN-gamma, IL-10, CSF matrix metalloproteinases, CSF tissue inhibitors of matrix Metalloproteinases, VEGF level, caspase-1 and IL-1β. Signal-regulatory protein alpha is overexpressed at mRNA level. High dose intravenous rifampicin (800 mg daily) is associated with reduced mortality in patients with advanced disease.

Keywords

Tuberculous Meningitis; TB; Infection; Cerebrospinal Fluid

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	R. Galimi, “Extrapulmonary Tuberculosis: Tuberculous Meningitis New Developments,” European Review for Medical and Pharmacological Sciences, Vol. 15, No. 4, 2011, pp. 365-386.
[2]	R. Abdelmalek, F. Kanoun, B. Kilani, H. Tiouiri, F. Zouiten, A. Ghoubantini and T. B. Chaabane, “Tuberculous Meningitis in Adults: MRI Contribution to the Diagnosis in 29 Patients,” International Journal of Infectious Diseases, Vol. 10, No. 5, 2006, pp. 372-377. doi:10.1016/j.ijid.2005.07.009
[3]	L. Chaidir, A. R. Ganiem, A. V. Zanden, S. Muhsinin, T. Kusumaningrum, I. Kusumadewi, A. van der Ven, B. Alisjahbana, I. Parwati and R. van Crevel, “Comparison of Real Time IS6110-PCR, Microscopy, and Culture for Diagnosis of Tuberculous Meningitis in a Cohort of Adult Patients in Indonesia,” PLoS One, Vol. 7, No. 12, 2012, Article ID: e52001. doi:10.1371/journal.pone.0052001
[4]	B. Lakatos, G. Prinz, C. Sárvári, K. Kamotsay, P. Molnár, A. Abrahám and J. Budai, “Central Nervous System Tuberculosis in Adult Patients,” Orvosi Hetilap, Vol. 152, No. 15, 2011, pp. 588-596. doi:10.1556/OH.2011.29076
[5]	R. K. Garg, “Tuberculous Meningitis,” Acta Neurologica Scandinavica, Vol. 122, No. 2, 2010, pp. 75-90.
[6]	Y. Suzuki, “Tuberculosis Infection in the Nervous System,” Nihon Rinsho, Vol. 69, No. 8, 2011, pp. 1422-1426.
[7]	M. E. Hurmuzache, C. Luca, I. Lovin and C. Dorobat, “Tuberculosis Meningo-Encephalitis with Positive CSF for KB and Slowly Favourable Evolution. Case Report,” Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi, Vol. 116, No. 3, 2012, pp. 804-807.
[8]	G. E. Thwaites and T. T. Hien, “Tuberculous Meningitis: Many Questions, Too Few Answers,” The Lancet Neurology, Vol. 4, No. 3, 2005, pp. 160-170.
[9]	M. R. R. Bullock and J. M. Welchman, “Diagnostic and Prognostic Features of Tuberculous Meningitis of CT Scanning,” Journal of Neurology, Neurosurgery & Psychiatry, Vol. 45, No. 12, 1982, pp. 1098-1101. doi:10.1136/jnnp.45.12.1098
[10]	R. Kumar, S. N. Singh and N. Kohli, “A diagnostic rule for tuberculous meningitis,” Archives of Disease in Childhood, Vol. 81, No. 3, 1999, pp. 221-224. doi:10.1136/adc.81.3.221
[11]	G. E. Thwaites, T. T. Chau, K. Stepniewska, N. H. Phu, L. V. Chuong, D. X. Sinh, N. J. White, C. M. Parry and J. J. Farrar, “Diagnosis of Adult Tuberculous Meningitis by Use of Clinical and Laboratory Features,” Lancet, Vol. 360, No. 9342, 2002, pp. 1287-1292. doi:10.1016/S0140-6736(02)11318-3
[12]	A. Moghtaderi, R. Alavi-Naini, S. Izadi and L. E. Cuevas, “Diagnostic Risk Factors to Differentiate Tuberculous and Acute Bacterial Meningitis,” Scandinavian Journal of Infectious Diseases, Vol. 41, No. 3, 2009, pp. 188-194. doi:10.1080/00365540902721384
[13]	G. K. Ahuja, K. K. Mohan, K. Prasad and M. Behari, “Diagnostic Criteria for Tuberculousmeningitis and Their Validation,” Tubercle and Lung Disease, Vol. 75, No. 2, 1994, pp. 149-152. doi:10.1016/0962-8479(94)90045-0
[14]	G. E. Thwaites, T. T. Chau and J. J. Farrar, “Improving the Bacteriological Diagnosis of Tuberculous Meningitis,” Journal of Clinical Microbiology, Vol. 42, No. 1, 2004, pp. 378-379. doi:10.1128/JCM.42.1.378-379.2004
[15]	S. Haldar, N. Sharma, V. K. Gupta and J. S. Tyagi, “Efficient Diagnosis of Tuberculous Meningitis by Detection of Mycobacterium Tuberculosis DNA in Cerebrospinal Fluid Filtrates Using PCR,” Journal of Medical Microbiology, Vol. 58, Pt. 5, 2009, pp. 616-624. doi:10.1099/jmm.0.006015-0
[16]	A. Hannan, A. Hafeez, S. Chaudary and M. Rashid, “Rapid Confirmation of Tuberculous Meningitis in Children by Liquid Culture Media,” Journal of Ayub Medical College, Abbottabad, Pakistan, Vol. 22, No. 4, 2010, pp. 171-175.
[17]	P. García, L. Bahamondes, P. Reyes, J. C. Román, H. Poblete and M. E. Balcells, “A Comparative Study for Adenosine Deaminase and Anti-Antigen A-60 Antibodies Detection for the Diagnosis of Tuberculous Meningitis,” Revista Chilena de Infectología, Vol. 29, No. 5, 2012, pp. 521-526. doi:10.4067/S0716-10182012000600007
[18]	D. H. Kennedy and R. J. Fallon, “Tuberculous Meningitis,” JAMA, Vol. 241, No. 3, 1979, pp. 264-268. doi:10.1001/jama.1979.03290290032021
[19]	P. R. Donald and J. F. Schoeman, “Tuberculous Meningitis,” New England Journal of Medicine, Vol. 351, 2004, p. 17.
[20]	D. K. Dastur, D. K. Manghani and P. M. Udani, “Pathology and Pathogenetic Mechanisms in Neurotuberculosis,” Radiologic Clinics of North America, Vol. 33, No. 4, 1995, pp. 733-752.
[21]	G. A. Lammie, R. H. Hewlett, J. F. Schoeman and P. R. Donald, “Tuberculous Cerebrovascular Disease: A Review,” Journal of Infection, Vol. 59, No. 3, 2009, pp. 156-166. doi:10.1016/j.jinf.2009.07.012
[22]	D. K. Dastur, “The Pathology and Pathogenesis of Tuberculous Encephalopathy and Radiculomyelopathy: A Comparison with Allergic Encephalomyelitis,” Child’s Nervous System, Vol. 2, No. 1, 1986, pp. 13-19. doi:10.1007/BF00274027
[23]	F. Y. Hsieh, L. G. Chia and W. C. Shen, “Locations of Cerebral Infarctions in Tuberculousmeningitis,” Neuroradiology, Vol. 34, No. 3, 1992, pp. 197-199. doi:10.1007/BF00596334
[24]	K. L. Roos, “Pearls and Pitfalls in the Diagnosis and Management of Central Nervous System Infectious Diseases,” Seminars in Neurology, Vol. 18, No. 2, 1998, pp. 185-196. doi:10.1055/s-2008-1040872
[25]	U. K. Misra, J. Kalita and P. K. Maurya, “Stroke in Tuberculous Meningitis,” Journal of the Neurological Sciences, Vol. 303, No. 1, 2011, pp. 22-30. doi:10.1016/j.jns.2010.12.015
[26]	P. Nair, J. Kalita, S. Kumar and U. K. Misra, “MRI Pattern of Infarcts in Basal Ganglia Region in Patients with Tuberculous Meningitis,” Neuroradiology, Vol. 51, No. 4, 2009, pp. 221-225. doi:10.1007/s00234-009-0495-x
[27]	M. Wasay, B. A. Kheleani, M. K. Moolani, J. Zaheer, M. Pui, S. Hasan, et al., “Brain CT and MRI Findings in 100 Consecutive Patients with Intracranial Tuberculoma,” Journal of Neuroimaging, Vol. 13, No. 3, 2003, pp. 240-247.
[28]	P. B. Kingsley, T. C. Shah and R. Woldenberg, “Identification of Diffuse and Focal Brain Lesions by Clinical Magnetic Resonance Spectroscopy,” NMR in Biomedicine, Vol. 19, No. 4, 2006, pp. 435-462. doi:10.1002/nbm.1039
[29]	U. K. Misra, J. Kalita, R. Srivastava, P. P. Nair, M. K. Mishra and A. Basu, “A Study of Cytokines in Tuberculous Meningitis: Clinical and MRI Correlation,” Neuroscience Letters, Vol. 483, No. 1, 2010, p. 610. doi:10.1016/j.neulet.2010.07.029
[30]	G. N. Babu, A. Kumar, J. Kalita and U. K. Misra, “Proinflammatory Cytokine Levels in the Serum and Cerebrospinal Fluid of Tuberculous Meningitis Patients,” Neuroscience Letters, Vol. 436, No. 1, 2008, pp. 48-51. doi:10.1016/j.neulet.2008.02.060
[31]	S. G. Kumar, A. K. Venugopal, A. Mahadevan, S. Renuse, G. H. Harsha, N. A. Sahasrabuddhe, H. Pawar, R. Sharma, P. Kumar, S. Rajagopalan, K. Waddell, Y. L. Ramachandra, P. Satishchandra, R. Chaerkady, K. T. Prasad, S. K. Shankar and A. Pandey, “Quantitative Proteomics for Identifying Biomarkers for Tuberculous Meningitis,” Clinical Proteomics, Vol. 9, No. 1, 2012, p. 12. doi:10.1186/1559-0275-9-12
[32]	H. M. Lee, J. Kang, S. J. Lee and E. K. Jo, “Microglial Activation of the NLRP3 Inflammasome Bythe Priming Signals Derived from Macrophages Infected with Mycobacteria,” Glia, Vol. 61, No. 3, 2013, pp. 441-452. doi:10.1002/glia.22448
[33]	U. K. Misra, J. Kalita, A. P. Singh and S. Prasad, “Vascular Endothelial Growth Factor in Tuberculous Meningitis,” International Journal of Neuroscience, Vol. 123, No. 2, 2013, pp. 128-132.
[34]	G. E. Marx and E. D. Chan, “Tuberculous Meningitis: Diagnosis and Treatment Overview,” Tuberculosis Research and Treatment, Vol. 2011, 2011, Article ID: 798764.
[35]	G. Thwaites, M. Fisher, C. Hemingway, G. Scott, T. Solomon and J. Innes, “British Infection Society Guidelines for the Diagnosis and Treatment of Tuberculosis of the Central Nervous System in Adults and Children”. www.elsevierhealth.com/journals/jinf
[36]	R. Ruslami, A. R. Ganiem, S. Dian, L. Apriani, T. H. Achmad, A. J. van der Ven, G. Borm, R. E. Aarnoutse and R. van Crevel, “Intensified Regimen Containing Rifampicin and Moxifloxacin for Tuberculous Meningitis: An Open-Label, Randomised Controlled Phase 2 Trial,” Lancet Infectious Disease, Vol. 13, No. 1, 2013, pp. 27-35. doi:10.1016/S1473-3099(12)70264-5
[37]	G. N. Babu, A. Kumar, J. Kalita and U. K. Misra, “Proinflammatory Cytokine Levels in the Serum and Cerebrospinal Fluid of Tuberculous Meningitis Patients,” Neuroscience Letters, Vol. 436, No. 1, 2008, pp. 48-51. doi:10.1016/j.neulet.2008.02.060
[38]	P. C. Hsu, C. C. Yang, J. J. Ye, P. Y. Huang, P. C. Chiang and M. H. Lee, “Prognostic Factors of Tuberculous Meningitis in Adults: A 6-Year Retrospective Study at a Tertiary Hospital in Northern Taiwan,” Journal of Microbiology, Immunology and Infection, Vol. 43, No. 2, 2010, pp. 111-118.
[39]	G. A. Lammie, R. H. Hewlett, J. F. Schoeman and P. R. Donald, “Tuberculous Cerebrovascular Disease: A Review,” Journal of Infection, Vol. 59, No. 3, 2009, pp. 156-166. doi:10.1016/j.jinf.2009.07.012
[40]	T. Raut, R. K. Garg, A. Jain, R. Verma, M. K. Singh, H. S. Malhotra, N. Kohli and A. Parihar, “Hydrocephalus in Tuberculous Meningitis: Incidence, Its Predictive Factors and Impact on the Prognosis,” Journal of Infection, Vol. 66, No. 4, 2013, pp. 330-337.
[41]	T. C. Morgado, M. Kinsky, H. Carrara, S. Rothemeyer and P. Semple, “Prognostic Value of Computed Tomography-Evident Cerebral Infarcts in Adult Patients with Tuberculous Meningitis and Hydrocephalus Treated with an External Ventricular Drain,” World Neurosurgery, 2012.
[42]	P. Ranjan, J. Kalita and U. K. Misra, “Serial Study of Clinical and CT Changes in Tuberculous Meningitis,” Neuroradiology, Vol. 45, No. 5, 2003, pp. 277-282.
[43]	J. Kalita, U. K. Misra and P. Ranjan, “Predictors of Long-Term Neurological Sequelae of Tuberculous Meningitis: A Multivariate Analysis,” European Journal of Neurology, Vol. 14, No. 1, 2007, pp. 33-37. doi:10.1111/j.1468-1331.2006.01534.x
[44]	X. R. Wu, Q. Q. Yin, A. X. Jiao, B. P. Xu, L. Sun, W. W. Jiao, J. Xiao, Q. Miao, C. Shen, F. Liu, D. Shen and A. Shen, “Pediatric Tuberculosis at Beijing Children’s Hospital: 2002-2010,” Paediatrics, Vol. 130, No. 6, 2012, pp. e1433-e1440. doi:10.1542/peds.2011-3742