Adjunctive thalidomide therapy for childhood tuberculous meningitis: Results of a randomized study
Date
2004
Authors
Schoeman J.F.
Springer P.
van Rensburg A.J.
Swanevelder S.
Hanekom W.A.
Haslett P.A.J.
Kaplan G.
Journal Title
Journal ISSN
Volume Title
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Abstract
Childhood tuberculous meningitis is associated with serious long-term sequelae, including mental retardation, behavior disturbances, and motor handicap. Brain damage in tuberculous meningitis results from a cytokine-mediated inflammatory response, which causes vasculitis and obstructive hydrocephalus. Thalidomide, a potent tumor necrosis factor α inhibitor, was well tolerated and possibly showed some clinical benefit in children with tuberculous meningitis during a pilot study. The purpose of the present study was to assess the effect of adjunctive thalidomide in addition to standard antituberculosis and corticosteroid therapy on the outcome of tuberculous meningitis. Thalidomide (24 mg/kg/day orally) or placebo was administered in a double-blind randomized fashion for 1 month to patients with stage 2 or 3 tuberculous meningitis. The study was terminated early because all adverse events and deaths occurred in one arm of the study (thalidomide group). Thirty of the 47 children enrolled received adjunctive thalidomide, of whom 6 (20%) developed a skin rash, 8 (26%) hepatitis, and 2 (6%) neutropenia or thrombocytopenia. Four deaths (13%) occurred in patients with very severe neurologic compromise at baseline; two deaths were associated with a rash. Motor outcome after 6 months of antituberculosis therapy was similar in the two groups, even though the thalidomide group showed greater neurologic compromise on admission. In addition, the mean IQ of the two treatment groups did not differ significantly (mean IQ thalidomide group 57.8 versus mean IQ control group 67.5; P = .16). These results do not support the use of adjunctive high-dose thalidomide therapy in the treatment of tuberculous meningitis.
Description
Keywords
acetazolamide, aminoglycoside, corticosteroid, ethambutol, ethionamide, furosemide, isoniazid, placebo, prednisone, pyrazinamide, quinolone, rifampicin, thalidomide, tuberculostatic agent, article, brain vasculitis, cerebrospinal fluid analysis, childhood disease, clinical article, clinical trial, coma, consciousness disorder, controlled clinical trial, controlled study, disease exacerbation, double blind procedure, drowsiness, drug dose regimen, drug efficacy, drug eruption, drug fatality, drug hypersensitivity, drug megadose, female, fever, hematologic disease, hepatitis, hepatosplenomegaly, human, hydrocephalus, infant, intelligence quotient, laryngotracheobronchitis, male, mental deterioration, Mycobacterium tuberculosis, neurologic disease, neutropenia, preschool child, priority journal, quadriplegia, randomized controlled trial, seizure, sensory neuropathy, Stevens Johnson syndrome, thrombocytopenia, treatment outcome, tuberculous meningitis, Adrenal Cortex Hormones, Anti-Inflammatory Agents, Antitubercular Agents, Chemotherapy, Adjuvant, Child, Child, Preschool, Cohort Studies, Coma, Cytokines, Double-Blind Method, Exanthema, Hepatitis, Humans, Immunosuppressive Agents, Infant, Intelligence, Paresis, South Africa, Statistics, Nonparametric, Thalidomide, Treatment Outcome, Tuberculosis, Meningeal
Citation
Journal of Child Neurology
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