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

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  • 1 Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, India;
  • | 2 Department of Neurology, King George Medical University, Lucknow, India;
  • | 3 Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India;
  • | 4 Department of Neurosurgery, All India Institute of Medical Sciences, Rishikesh, India

ABSTRACT.

Thalidomide, an anti-inflammatory and immunomodulatory agent, has a potential role in cases with central nervous system tuberculosis (CNS-TB) with paradoxical reactions. Although several articles have described the use of thalidomide in CNS-TB, no systematic review has been performed in this regard. Different electronic databases were searched for articles describing the use of thalidomide in patients with CNS-TB. For determining pooled estimates in the quantitative review, studies with a minimum sample size of 5 were only considered, whereas for qualitative synthesis even single case reports were included. Fixed or random effect models were used suitably depending on the degree of heterogeneity. Fourteen articles describing a total of 107 patients (98 children and 9 adults) were selected from 156 records. A favorable clinical response was observed in 89% of patients with CNS-TB who had paradoxical reactions refractory to corticosteroids. Majority of the studies used a dose of 2–6 mg/kg/day and around 24% suffered from at least one adverse effect, with a mortality of 5%. Predominant adverse effects were rash (9.5%), neuropathy (6%), and elevated liver transaminases (9.5%). Only one placebo-controlled trial has been performed till now, which showed that high-dose thalidomide has numerous adverse effects, without any clinically significant improvement as compared with placebo. While in HIV-positive patients with TB-immune reconstitution inflammatory syndrome thalidomide was helpful in around 82% of cases. Low-dose thalidomide is helpful in patients with CNS-TB who had a paradoxical reaction and unresponsive to corticosteroids. Large, randomized trials are needed to provide more concrete information regarding the safety and efficacy of thalidomide.

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Author Notes

Address correspondence to Indar Kumar Sharawat, Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh 249203, India. E-mail: sherawatdrindar@gmail.com

Disclaimer: We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Authors’ addresses: Prateek Kumar Panda and Indar Kumar Sharawat, Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, India, E-mails: drprateekpanda@gmail.com and sherawatdrindar@gmail.com. Pragnya Panda, Department of Neurology, King George Medical University, Lucknow, India, E-mail: pandapragnya543@gmail.com. Lesa Dawman, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India, E-mail: lesadawman@gmail.com. Rakesh Kumar Sihag, Department of Neurosurgery, All India Institute of Medical Sciences, Rishikesh, India, E-mail: drrakeshsihag@gmail.com.

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