Thalidomide use for complicated central nervous system tuberculosis in children: insights from an observational cohort
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Accepted version
Accepted version
Author(s)
van Toorn, Ronald
Solomons, Regan
Seddon, James
Schoeman, Johan
Type
Journal Article
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 dampens 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 whilst two 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); whilst in children with optic neuritis it was 2.0 months (IQR: 1.3-7.3) and in EPC it was 1.0 months (IQR: 1-2.5). Satisfactory clinical and radiological response was observed in 37 of the children. None of the children experienced rashes, hepatitis, hematologic derangements or complained of leg cramps.
Conclusion
This study is the largest cohort of adult or paediatric patients treated with adjunctive thalidomide for CNS TB-related complications. The drug has proved safe, well tolerated and appears to be clinically efficacious. The potential role of thalidomide or analogues in the treatment of other TBM-related complications requires further exploration.
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 dampens 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 whilst two 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); whilst in children with optic neuritis it was 2.0 months (IQR: 1.3-7.3) and in EPC it was 1.0 months (IQR: 1-2.5). Satisfactory clinical and radiological response was observed in 37 of the children. None of the children experienced rashes, hepatitis, hematologic derangements or complained of leg cramps.
Conclusion
This study is the largest cohort of adult or paediatric patients treated with adjunctive thalidomide for CNS TB-related complications. The drug has proved safe, well tolerated and appears to be clinically efficacious. The potential role of thalidomide or analogues in the treatment of other TBM-related complications requires further exploration.
Date Issued
2021-03-01
Date Acceptance
2020-11-24
Citation
Clinical Infectious Diseases, 2021, 72 (5), pp.e136-e145
ISSN
1058-4838
Publisher
Oxford University Press (OUP)
Start Page
e136
End Page
e145
Journal / Book Title
Clinical Infectious Diseases
Volume
72
Issue
5
Copyright Statement
© 2020 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model). This is a pre-copy-editing, author-produced version of an article accepted for publication in Clinical Infectious Diseases following peer review. The definitive publisher-authenticated version [Ronald van Toorn, Regan S Solomons, James A Seddon, Johan F Schoeman, Thalidomide use for complicated central nervous system tuberculosis in children: insights from an observational cohort, Clinical Infectious Diseases, , ciaa1826, https://doi.org/10.1093/cid/ciaa1826] is available online at: https://doi.org/10.1093/cid/ciaa1826
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model). This is a pre-copy-editing, author-produced version of an article accepted for publication in Clinical Infectious Diseases following peer review. The definitive publisher-authenticated version [Ronald van Toorn, Regan S Solomons, James A Seddon, Johan F Schoeman, Thalidomide use for complicated central nervous system tuberculosis in children: insights from an observational cohort, Clinical Infectious Diseases, , ciaa1826, https://doi.org/10.1093/cid/ciaa1826] is available online at: https://doi.org/10.1093/cid/ciaa1826
Identifier
https://academic.oup.com/cid/article/72/5/e136/6024997
Subjects
blindness
neurological
thalidomide
treatment
tuberculosis
06 Biological Sciences
11 Medical and Health Sciences
Microbiology
Publication Status
Published
Article Number
ciaa1826
Date Publish Online
2020-12-06