Neurological Complications of Tuberculosis in Quetta, Pakistan: Clinical Profile, Outcomes, and Mortality Predictors from a Prospective Cohort Study
DOI:
https://doi.org/10.70749/ijbr.v3i6.1521Keywords:
Neurotuberculosis, Tuberculous Meningitis, Multidrug-Resistant Tuberculosis, Malnutrition, Mortality, Quetta, Pakistan, Treatment Delay, HydrocephalusAbstract
Background: Neurotuberculosis remains a severe manifestation of tuberculosis with high morbidity and mortality, particularly in resource-limited settings. This study aimed to characterize the clinical, diagnostic, and prognostic aspects of neurological complications of tuberculosis at Bolan Medical Complex (BMC), Quetta, Pakistan. Methods: This prospective observational cohort study, conducted from December 2022 to December 2024, enrolled 168 adult patients with microbiologically or histopathologically confirmed neurotuberculosis. Data on demographics, clinical presentation, diagnostic findings (neuroimaging, CSF analysis), treatment, and outcomes were collected. Statistical analysis included descriptive statistics, group comparisons, and Cox Proportional Hazards models to identify mortality predictors. Results: The majority of patients were male (58.3%) and from rural areas (66.7%). Afghan refugees, who made up 22.0% of the population, were 3.1 times more likely to have MDR-TB. In 51.8% of cases, malnutrition increased the risk of death on its own (RR=2.3, p=0.002). With 30.5% of cases presenting at Stage III, tuberculous meningitis (TBM) was the most common consequence (56.5%). The prevalence of MDR-TB was 8.9%, and it was a strong predictor of mortality (aHR=2.6, p=0.009). 53.0% experienced critical treatment delays (>28 days), which increased mortality by 2.4 times (p=0.007). Mortality was highly predicted by hydrocephalus (39.9%) (OR=4.9, p<0.001). At six months, the overall death rate was 23.8%. TBM Stage III (aHR=5.27), MDR-TB (aHR=2.6), treatment delay >28 days (aHR=2.41), and malnutrition (aHR=2.05) were independent predictors of mortality. Mortality was considerably decreased by VP shunting and corticosteroid usage. Conclusion: Malnutrition, MDR-TB, advanced TBM stage, and delayed presentation are important independent indicators of higher mortality among neurotuberculosis patients in Quetta. Improving patient survival and functional results requires timely diagnosis, effective anti-tuberculosis treatment, prudent corticosteroid administration, and surgical intervention.
Downloads
References
Magodoro, I. M., Kotze, L. A., Stek, C. J., West, A., Le Roux, A., Sobratee, N., Taliep, A., Hamada, Y., Dave, J. A., Rangaka, M. X., Parihar, S. P., & Wilkinson, R. J. (2025). Clinical, metabolic, and immune interaction between tuberculosis and diabetes mellitus: Implications and opportunities for therapies. Expert Opinion on Pharmacotherapy, 1-14.
https://doi.org/10.1080/14656566.2025.2508904
Frigati, L., Greybe, L., Andronikou, S., Eber, E., Sunder B. Venkatakrishna, S., & Goussard, P. (2025). Respiratory infections in low and middle-income countries. Paediatric Respiratory Reviews, 54, 43-51.
https://doi.org/10.1016/j.prrv.2024.08.002
Al-Worafi, Y. M. (2023). Tuberculosis management in developing countries. Handbook of Medical and Health Sciences in Developing Countries, 1-40.
https://doi.org/10.1007/978-3-030-74786-2_52-1
Roberts, J. A., Kapadia, R. K., Pastula, D. M., & Thakur, K. T. (2024). Public health trends in neurologically relevant infections: A global perspective. Therapeutic Advances in Infectious Disease, 11.
https://doi.org/10.1177/20499361241274206
Naidoo, K., Perumal, R., Cox, H., Mathema, B., Loveday, M., Ismail, N., Omar, S. V., Georghiou, S. B., Daftary, A., O'Donnell, M., & Ndjeka, N. (2024). The epidemiology, transmission, diagnosis, and management of drug-resistant tuberculosis—lessons from the South African experience. The Lancet Infectious Diseases, 24(9), e559-e575.
https://doi.org/10.1016/s1473-3099(24)00144-0
Omoteso, O. A., Fadaka, A. O., Walker, R. B., & Khamanga, S. M. (2025). Innovative Strategies for Combating Multidrug-Resistant Tuberculosis: Advances in Drug Delivery Systems and Treatment. Microorganisms, 13(4), 722.
https://doi.org/10.3390/microorganisms13040722
Tan, D. T., & See, K. C. (2024). Diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients: A mini review for clinicians. World Journal of Critical Care Medicine, 13(2).
https://doi.org/10.5492/wjccm.v13.i2.91435
Sharma, S. K., Mohan, A., & Kohli, M. (2021). Extrapulmonary tuberculosis. Expert Review of Respiratory Medicine, 15(7), 931-948.
https://doi.org/10.1080/17476348.2021.1927718
Ramos, A. P., & Burneo, J. G. (2023). Seizures and epilepsy associated with central nervous system tuberculosis. Seizure: European Journal of Epilepsy, 107, 60-66.
https://doi.org/10.1016/j.seizure.2023.03.006
Chandrasiri, D. (2025). Paradoxical reactions in central nervous system tuberculosis: Insights into pathogenesis, diagnosis, and clinical management. Sri Lanka Journal of Neurology, 11(2), 55-67.
https://doi.org/10.4038/sljon.v11i2.180
Cherian, A., Ajitha, K. C., Iype, T., & Divya, K. P. (2021). Neurotuberculosis: An update. Acta Neurologica Belgica, 121(1), 11-21.
https://doi.org/10.1007/s13760-020-01575-0
Urs, V. L., Kumar, N., & Garg, R. K. (2024). Tuberculosis of central nervous system. A Review on Diverse Neurological Disorders, 103-120.
https://doi.org/10.1016/b978-0-323-95735-9.00042-5
Dian, S., Ganiem, A. R., Te Brake, L. H., & Van Laarhoven, A. (2023). Current insights into diagnosing and treating Neurotuberculosis in adults. CNS Drugs, 37(11), 957-972.
https://doi.org/10.1007/s40263-023-01047-y
Corona-Nakamura, A. L., Arias-Merino, M. J., Miranda-Novales, M. G., Nava-Jiménez, D., Delgado-Vázquez, J. A., Bustos-Mora, R., Cisneros-Aréchiga, A. G., Aguayo-Villaseñor, J. F., Hernández-Preciado, M. R., & Mireles-Ramírez, M. A. (2023). Intraspinal and intracranial Neurotuberculosis, clinical and imaging characteristics and outcomes in hospitalized patients: A cohort study (2000–2022). Journal of Clinical Medicine, 12(13), 4533.
https://doi.org/10.3390/jcm12134533
Shi, Y., Zhang, C., Pan, S., Chen, Y., Miao, X., He, G., Wu, Y., Ye, H., Weng, C., Zhang, H., Zhou, W., Yang, X., Liang, C., Chen, D., Hong, L., & Su, F. (2023). The diagnosis of tuberculous meningitis: Advancements in new technologies and machine learning algorithms. Frontiers in Microbiology, 14.
https://doi.org/10.3389/fmicb.2023.1290746
Schaller, M. A., Wicke, F., Foerch, C., & Weidauer, S. (2018). Central nervous system tuberculosis. Clinical Neuroradiology, 29(1), 3-18.
https://doi.org/10.1007/s00062-018-0726-9
Gupta, M., Tobin, E. H., & Munakomi, S. (2024). CNS tuberculosis. In StatPearls [Internet]. StatPearls Publishing.
https://www.ncbi.nlm.nih.gov/sites/books/NBK585138/
Nijman, G., Imran, D., Dian, S., Ganiem, A. R., Estiasari, R., Maharani, K., Yolanda, R., Supriatin, M., Alisjahbana, B., Lestari, B. W., Hamers, R. L., Hill, P. C., & Van Crevel, R. (2023). Tuberculous meningitis patient pathways and delays to diagnosis in Indonesia: A retrospective cohort study. BMJ Public Health, 1(1), e000052.
https://doi.org/10.1136/bmjph-2023-000052
Zhu, X., He, N., Tong, L., Gu, Z. H., & Li, H. (2023). Clinical characteristics of tuberculous meningitis in older patients compared with younger and middle-aged patients: A retrospective analysis. BMC Infectious Diseases, 23(1).
https://doi.org/10.1186/s12879-023-08700-3
Huynh, J. (2024). Improving The Diagnosis And Prognosis Of Tuberculous Meningitis In Children (Doctoral dissertation, The Open University).
Howard, R., Benjamin, L., De Saram, S., Houlihan, C., & Manji, H. (2024). Infection in the nervous system. Neurology, 369-432.
https://doi.org/10.1002/9781119715672.ch12
Mandal, S., Biswas, P., Ansar, W., Mukherjee, P., & Jawed, J. J. (2024). Tuberculosis of the central nervous system: Pathogenicity and molecular mechanism. A Review on Diverse Neurological Disorders, 93-102.
https://doi.org/10.1016/b978-0-323-95735-9.00050-4
Boyles, T. H., Lynen, L., & Seddon, J. A. (2020). Decision-making in the diagnosis of tuberculous meningitis. Wellcome Open Research, 5, 11.
https://doi.org/10.12688/wellcomeopenres.15611.1
Palacios, C. F., & Saleeb, P. G. (2020). Challenges in the diagnosis of tuberculous meningitis. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 20, 100164.
https://doi.org/10.1016/j.jctube.2020.100164
Kumar, M. S., & Vigneswaran, L. V. (2025). Multidrug resistance complexity of mycobacterium tuberculosis and oxidative stress: The need for innovative drug delivery strategies. Emerging Paradigms in Delivery Systems for Antitubercular Therapy, 235-265.
https://doi.org/10.1016/b978-0-443-24035-5.00011-6
Dheda, K., et al., (2024). Multidrug-resistant tuberculosis. Nature Reviews Disease Primers, 10(1), p. 22.
https://doi.org/10.1038/s41572-024-00512-2
Mulk, J.U., B. Ali, and A. Ullah, Impacts of Afghan refugees on security situation of Pakistan. Pakistan Journal of Society, Education and Language (PJSEL), 2020. 6(1): p. 37-46.
Muhammad, E., Andam, G., Haq, N., Saleem, M., Ullah, K., Babar, D. A., Afzal, M., & Jafar, S. (2025). Assessing the Hepatotoxic effects of anti-tuberculosis treatment in multi-drug-Resistant patients: Evidence from Fatimah Jinnah hospital, Quetta. Indus Journal of Bioscience Research, 3(5), 576-582.
https://doi.org/10.70749/ijbr.v3i5.1396
Ullah, S., Ullah, N., Tariq, A., Panezai, S., Tahir, P., & Khan, B. (2025). Spatial assessment of the availability of healthcare facilities at district level in Balochistan using GIS: Identifying gaps and way forward. Spatial Information Research, 33(2).
https://doi.org/10.1007/s41324-025-00602-7
Raees, M., Cheserem, B., Mutiso, B., Laeke, T., & Brotherton, B. J. (2022). The next frontier in Neurocritical care in resource-constrained settings. Critical Care Clinics, 38(4), 721-745.
https://doi.org/10.1016/j.ccc.2022.06.016
Machlaurin, A. (n.d.). Health economic evaluations of tuberculosis control in Indonesia.
https://doi.org/10.33612/diss.257346205
Malik, M. S., Afzal, M., Farid, A., Khan, F. U., Mirza, B., & Waheed, M. T. (2019). Disease status of Afghan refugees and migrants in Pakistan. Frontiers in Public Health, 7.
https://doi.org/10.3389/fpubh.2019.00185
Hermsen, E. D., Amos, J., Townsend, A., Becker, T., & Hargreaves, S. (2025). Antimicrobial resistance among refugees and asylum seekers: A global systematic review and meta-analysis. The Lancet Infectious Diseases, 25(1), e34-e43.
https://doi.org/10.1016/s1473-3099(24)00578-4
Rajabali, A., Moin, O., Ansari, A. S., Khanani, M. R., & Ali, S. H. (2009). Communicable disease among displaced afghans: Refuge without shelter. Nature Reviews Microbiology, 7(8), 609-614.
https://doi.org/10.1038/nrmicro2176
Suresh, S. R. (2014). Study Of Adenosine Deaminase (ADA) Levels in Tubercular Meningitis (Doctoral dissertation, Rajiv Gandhi University of Health Sciences (India)).
Bovula, S. (2022). Clinical determinants distinguishing communicating and non-communicating hydrocephalus in childhood tuberculous meningitis at presentation (Doctoral dissertation, Stellenbosch: Stellenbosch University).
Mwenda, L. A. (2019). An Examination of Lumbar and Ventricular Cerebrospinal Fluid Findings in Children with Tuberculous Meningitis and Hydrocephalus.
https://open.uct.ac.za/server/api/core/bitstreams/42b0d027-48ff-40a1-bfda-f5de3329e21e/content
Paliwal, V. K., & Garg, R. K. (2021). Hydrocephalus in tuberculous meningitis - Pearls and nuances. Neurology India, 69(Suppl 2), S330-S335.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Indus Journal of Bioscience Research

This work is licensed under a Creative Commons Attribution 4.0 International License.