Thalidomide Use for Complicated Central Nervous System Tuberculosis in Children: Insights From an Observational Cohort

• Published in: Clinical infectious diseases 2021-03, Vol.72 (5), p.e136-e145
• Main Authors: van Toorn, Ronald, Solomons, Regan S, Seddon, James A, Schoeman, Johan F
• Format: Article
• Language: English
• Subjects: Adult; Antitubercular Agents - adverse effects; Child; Humans; Retrospective Studies; Thalidomide - adverse effects; Tuberculosis, Central Nervous System - complications; Tuberculosis, Central Nervous System - drug therapy; Tuberculosis, Meningeal - drug therapy
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciaa1826

Abstract Background Much of the neurological sequelae of central nervous system (CNS) tuberculosis (TB) is due to an excessive cytokine-driven host-inflammatory response. Adjunctive corticosteroids, which reduce cytokine production and thus dampen the inflammation, improve overall survival but do not prevent morbidity. This has prompted investigation of more targeted immunomodulatory agents, including thalidomide. Methods We describe a retrospective cohort of 38 children consecutively treated with adjunctive thalidomide for CNS TB–related complications over a 10-year period. Results The most common presenting symptom was focal motor deficit (n = 16), followed by cranial nerve palsies and cerebellar dysfunction. Three of the 38 children presented with large dural-based lesions, manifesting as epilepsia partialis continua (EPC), 4 presented with blindness secondary to optochiasmatic arachnoiditis, and 2 children developed paraplegia due to spinal cord TB mass lesions. Duration of adjunctive thalidomide therapy (3–5 mg/kg/day) varied according to complication type. In children compromised by TB mass lesions, the median treatment duration was 3.9 months (interquartile range [IQR], 2.0–5.0 months), whereas in children with optic neuritis it was 2.0 months (IQR, 1.3–7.3 months) and in EPC it was 1.0 months (IQR, 1–2.5 months). Satisfactory clinical and radiological response was observed in 37 of the children. None of the children experienced rashes, hepatitis, or hematologic derangements or complained of leg cramps. Conclusions This study is the largest cohort of adult or pediatric patients treated with adjunctive thalidomide for CNS TB–related complications. The drug has proved to be safe and well tolerated and appears to be clinically efficacious. The potential role of thalidomide or analogues in the treatment of other tuberculous meningitis–related complications requires further exploration. We describe 38 children consecutively treated with adjunctive thalidomide for central nervous system tuberculosis–related complications over a 10-year period. Good clinico-radiological response and safety profile were observed. A broader potential role of thalidomide for treatment of tuberculous meningitis–related complications requires further exploration.