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Wilkinson, Robert J, Rohlwink, Ursula, Misra, Usha Kant, van Crevel, Reinout, Mai, Nguyen Thi Hoang, Dooley, Kelly E, Caws, Maxine 
ORCID: https://orcid.org/0000-0002-9109-350X, Figaji, Anthony, Savic, Rada, Solomons, Regan and Thwaites, Guy E
(2017)
'Tuberculous meningitis'. Nature Reviews Neurology, Vol 13, pp. 581-598.
Abstract
Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Study of TBM pathogenesis is hampered by a lack of experimental models that recapitulate all the features of the human disease. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. Antibiotic regimens for TBM are based on those used to treat pulmonary tuberculosis, which probably results in suboptimal drug levels in the cerebrospinal fluid, owing to poor blood-brain barrier penetrance. The role of adjunctive anti-inflammatory, host-directed therapies - including corticosteroids, aspirin and thalidomide - has not been extensively explored. To address this deficit, two expert meetings were held in 2009 and 2015 to share findings and define research priorities. This Review summarizes historical and current research into TBM and identifies important gaps in our knowledge. We will discuss advances in the understanding of inflammation in TBM and its potential modulation; vascular and hypoxia-mediated tissue injury; the role of intensified antibiotic treatment; and the importance of rapid and accurate diagnostics and supportive care in TBM.
| Item Type: | Article |
|---|---|
| Subjects: | QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 247 Anti-inflammatory agents QZ Pathology > Pathogenesis. Etiology > QZ 40 Pathogenesis. Etiology WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WL Nervous System > WL 20 Research (General) WL Nervous System > WL 200 Meninges. Blood-brain barrier |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1038/nrneurol.2017.120 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | Stacy Murtagh |
| Date Deposited: | 20 Sep 2017 15:06 |
| Last Modified: | 10 Nov 2017 14:40 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/7618 |
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