S Keddie1,2, V Bharambe3, A Jayakumar4, A Shah1, V Sanchez1, A Adams1, S Gnanapavan1,3. 1. Emergency Care and Acute Medicine Clinical Academic Group, Neuroscience, The Royal London Hospital, Barts Health NHS Trust, London. 2. National Hospital for Neurology and Neurosurgery, MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London Hospitals NHS Foundation Trust, London. 3. The Walton Centre NHS Foundation Trust, Liverpool. 4. Division of Infection, The Royal London Hospital, Barts Health NHS Trust, London, UK.
Abstract
BACKGROUND AND PURPOSE: Central nervous system (CNS) tuberculosis (TB) accounts for over 4% of all TB notifications in the UK and causes death or significant disability in over half of those affected. Tumour necrosis factor alpha is a critical cytokine involved in the neuropathogenesis of CNS TB. Thalidomide has been trialled in CNS TB due to its immunomodulatory and immune reconstitution effects through the inhibition of tumour necrosis factor alpha. Despite animal models demonstrating dramatic improvement in survival, studies in paediatric patients have been associated with higher levels of mortality. The effects of thalidomide have not yet been studied in adults with CNS TB. This narrative case series guides clinicians through a range of CNS TB clinical cases seen in a large London teaching hospital, serving a region with a high incidence of TB (32 per 100 000) with 55% of TB cases manifesting as extrapulmonary disease. We aimed to illustrate our experiences of using thalidomide to treat a range of severe CNS TB complications. METHODS: Five inpatients at The Royal London Hospital, London, UK treated with thalidomide in addition to standard TB treatment are described in detail. The rationale for treatment initiation with thalidomide is explained. RESULTS: The case examples are used to guide our reflections and lessons learnt regarding the use of thalidomide. Responses to treatment and functional outcomes suggest that thalidomide may be a useful adjunct to standard TB therapy in selected adult cases. CONCLUSIONS: The experience gained from using thalidomide in this small case series may provide evidence leading to more research into using thalidomide to treat severe CNS TB.
BACKGROUND AND PURPOSE:Central nervous system (CNS) tuberculosis (TB) accounts for over 4% of all TB notifications in the UK and causes death or significant disability in over half of those affected. Tumour necrosis factor alpha is a critical cytokine involved in the neuropathogenesis of CNS TB. Thalidomide has been trialled in CNS TB due to its immunomodulatory and immune reconstitution effects through the inhibition of tumour necrosis factor alpha. Despite animal models demonstrating dramatic improvement in survival, studies in paediatric patients have been associated with higher levels of mortality. The effects of thalidomide have not yet been studied in adults with CNS TB. This narrative case series guides clinicians through a range of CNS TB clinical cases seen in a large London teaching hospital, serving a region with a high incidence of TB (32 per 100 000) with 55% of TB cases manifesting as extrapulmonary disease. We aimed to illustrate our experiences of using thalidomide to treat a range of severe CNS TB complications. METHODS: Five inpatients at The Royal London Hospital, London, UK treated with thalidomide in addition to standard TB treatment are described in detail. The rationale for treatment initiation with thalidomide is explained. RESULTS: The case examples are used to guide our reflections and lessons learnt regarding the use of thalidomide. Responses to treatment and functional outcomes suggest that thalidomide may be a useful adjunct to standard TB therapy in selected adult cases. CONCLUSIONS: The experience gained from using thalidomide in this small case series may provide evidence leading to more research into using thalidomide to treat severe CNS TB.
Authors: Xu Li; Jinchao Yu; Zhiming Zhang; Jing Ren; Alex E Peluffo; Wen Zhang; Yujie Zhao; Jiawei Wu; Kaijing Yan; Daniel Cohen; Wenjia Wang Journal: Med Drug Discov Date: 2021-03-30