Thalidomide in the treatment of human immunodeficiency virus-negative tuberculous meningitis

Abstract

Introduction: Tuberculous meningitis (TBM) is the most fatal type of tuberculosis in which corticosteroids are added with antitubercular therapy to prevent permanent brain damage. However, this treatment may produce paradoxical reactions. In such cases, thalidomide use might reduce central nervous system inflammation and improve the outcome. We present the case of a human immunodeficiency virus-negative patient with TBM who developed paradoxical reactions manifesting as multiple intracranial tuberculomas that were resistant to standard care (antitubercular drugs and corticosteroids) but responded well to thalidomide. Patient's main concern and clinical findings: The patient was a 40-year-old Chinese female, who was admitted with a 10-day history of headaches, night sweats, and cough. She was healthy before contracting the infection and had no history of contact with tuberculosis patients. Diagnoses, intervention, and outcome: We diagnosed the patient with TBM complicated by the occurrence of pulmonary tuberculosis. Positive results were obtained from Gram and Ziehl-Neelsen staining of the sputum and acid-fast bacilli sputum culture. Standard treatment was initiated with antitubercular drugs (daily isoniazid, rifampicin, ethionamide, and pyrazinamide) and corticosteroids (dexamethasone). However, 3 months later the magnetic resonance imaging of the head revealed some new tuberculoma lesion. Thus, a specific therapy of antitubercular drugs and thalidomide was introduced. On completion of a 12-month course of antitubercular drugs with 2 months of thalidomide, the patient showed favorable outcomes without neurologic sequelae. Moreover, thalidomide appeared safe and well tolerated in the patient. Conclusion: In addition to the specific anti-tubercular and adjuvant corticosteroid therapies for TBM, thalidomide can be used as a “salvage” antitubercular drug in cases that are unresponsive to corticosteroids.

Predictors of fever response in tuberculous meningitis: A clinical, MRI and biomarker study

“…The association of elevated TNF‐α in lumbar and ventricular CSF and infarction has been reported in earlier studies 35,36 . TNF‐α blocker therefore has been tried in some patients with persistent tuberculoma 37 ,. CSF concentration of 100 unit/ml of TNF‐α can damage human endothelial cells in vitro 38 .…”

“…35,36 TNF-α blocker therefore has been tried in some patients with persistent tuberculoma. 37 , CSF concentration of 100 unit/ml of TNF-α can damage human endothelial cells in vitro. 38 Animal study has shown the role of TNF-α in formation and maintenance of granuloma.…”

Efficacy and Safety of Thalidomide in Patients with Complicated Central Nervous System Tuberculosis: A Systematic Review and Meta-Analysis

“…Subsequently, a full-text review was performed for 26 articles, and finally, 14 articles satisfied all the inclusion criteria for our review (Supplemental Table 1). [6][7][8][9][10][11][12][13][14][15][16][17][18][19] One prospective study by van Toorn et al 16 was excluded, as all the patients included in this study were also part of the retrospective study published by the same author in 2020. 17 Out of these 14 studies, one was a double-blind placebo-controlled RCT, one was a phase II nonrandomized controlled trial comparing various doses of thalidomide between 6 mg/kg/day, 12 mg/kg/day, and 24 mg/kg/ day, one was a retrospective cohort study, five were case series, and six were single case reports.…”

“…Out of all the patients who received thalidomide, 17 were HIV-positive, 14 (82%) had a favorable response, and all of them had some or other evidence of IRIS and had recently started combination ART for HIV status. [7][8][9][10][11][12][13][14][15][16][17][18][19] All of them were severely immunocompromised with a median CD4 count of 71 cells/mm 3 . Overall, the median time from the start of ATT to the development of TB-IRIS was 1.8 months (IQR: 0.8-5.9 months), whereas in HIV-positive cases it occurred after a median of 0.9 months (IQR: 0.3-1.8 months).…”

“…Most studies use a dose of 3-6 mg/kg/day in children or up to 200 mg/day in adults. [6][7][8][9][10][11][12][13][14][15][16][17][18][19] As the results of only RCT exploring high dose of 24 mg/kg/day resulted in increased adverse effects like somnolence, hepatotoxicity, rashes, peripheral neuropathy, and increased deaths, hence it is recommended to monitor clinically and biochemically for these adverse effects even when administered at low doses. 14 Thalidomide often takes few weeks before showing optimum therapeutic effect, hence, all the studies continued high-dose corticosteroid in cases with TB-IRIS even after starting thalidomide, and combination of these two immunomodulatory agents appear to be safe as per the results of our review.…”