Thalidomide As An Add On Treatment In The Intensive Phase Of Tuberculous Meningitis – An Open Label Randomized Controlled Trial

Tuberculous Meningitis (TBM) occurs in around 10% of patients with tuberculosis in general. TBM is commonly associated with major neurological sequelae and morbidity and a high mortality ratio 1.79. Meta-analysis from global data of tubercular meningitis reveals around 40% mortality and significant clinical deterioration in first 6 months after diagnosis. Survivors suffers from different kind of permanent brain damage from either raised ICT, basal ganglia infarct, vasculitis infarct.

The present TBM management strategy includes simultaneously administration of conventional anti-TB drugs and anti-inflammatory including corticosteroid. However, CNS penetration of the antitubercular drugs are poor across the protective blood brain barrier. The antibiotic-mediated killing of Mycobacterium bacteria and disease state results in exacerbation of inflammatory response of cerebral tissue. The clinical manifestation of TBM are mostly a result of severe inflammation of meninges and secondary vasculitis. Corticosteroid is the current recommended anti-inflammatory agent used in the initial phase of treatment regimen and results in increased survival and reduced complication during treatment and post treatment period. Adjunctive corticosteroid till now not adequately proven to reduce the inflammatory response caused by mycobacterium tuberculosis and antibiotic treatment. This creates the need for further evaluation regarding option of other anti-inflammatory drugs which can adequately control inflammatory response during treatment course. Corticosteroids have limited efficacy when used as adjunctive therapy, which has led to efforts for identifying alternatives to improve outcome.

Aspirin and thalidomide, both of which have been known to possess anti-inflammatory properties, have been tested to reduce pathogen-mediated inflammation in TBM. Role of aspirin as an adjuvant in the treatment of TBM cases with different levels of disease severity remains unclear. Thalidomide treatment was found to be effective in reducing “TNF-α-associated inflammation in patients with erythema nodosum leprosum (ENL)â€.

In general, results from ongoing studies have suggested that†thalidomide has beneficial effect on TBM during antibiotic treatment in children as well as in adultsâ€. Paediatric TBM cases treated with simultaneous thalidomide showed marked improvement in clinical course and patient showed near clearance of exudates and less vasculitic infarction. “Thalidomide treatment had significantly reduced TNF-α levels in the CSFâ€. Recently, two clinical case studies have suggested some beneficial role of Thalidomide in inflammation control in tubercular meningitis. Administration of “thalidomide, in combination with anti-TB drugs and corticosteroids improved the clinical outcome of patients with chronic TBM symptomsâ€. These observations suggest that “thalidomide might improve patient’s outcome in the management of TBM in addition to corticosteroid therapy in controlling chronic inflammation and other associated neurological complicationsâ€. Future studies are required to evaluate the role and efficacy of thalidomide in the treatment of TBM whether it has potential to change and/or to improve the current treatment strategy for TBM.