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The diagnosis of such lesions, which include tuberculoma and tuberculous abscesses, is often presumptive and based on radiological features, supportive evidence of TB elsewhere and response to TB treatment. However, the treatment response is unpredictable, with lesions frequently enlarging paradoxically or persisting for many years despite appropriate TB treatment and corticosteroid therapy. Most international guidelines recommend a 9-12 month course of TB treatment for central nervous system TB when the infecting\n                    <ns3:italic>Mycobacterium tuberculosis<\/ns3:italic>\n                    (\n                    <ns3:italic>M.tb<\/ns3:italic>\n                    ) strain is sensitive to first-line drugs. However, there is variation in opinion and practice with respect to the duration of TB treatment in patients with tuberculomas or tuberculous abscesses. A major reason for this is the lack of prospective clinical trial evidence. Some experts suggest continuing treatment until radiological resolution of enhancing lesions has been achieved, but this may unnecessarily expose patients to prolonged periods of potentially toxic drugs. It is currently unknown whether persistent radiological enhancement of intracranial tuberculomas after 9-12 months of treatment represents active disease, inflammatory response in a sterilized lesion or merely revascularization. The consequences of stopping TB treatment prior to resolution of lesional enhancement have rarely been explored. These important issues were discussed at the 3\n                    <ns3:sup>rd<\/ns3:sup>\n                    International Tuberculous Meningitis Consortium meeting. Most clinicians were of the opinion that continued enhancement does not necessarily represent treatment failure and that prolonged TB therapy was not warranted in patients presumably infected with\n                    <ns3:italic>M.tb<\/ns3:italic>\n                    strains susceptible to first-line drugs. In this manuscript we highlight current medical treatment practices, benefits and disadvantages of different TB treatment durations and the need for evidence-based guidelines regarding the treatment duration of patients with intracranial tuberculous mass lesions.\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.15501.3","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T10:45:11Z","timestamp":1582713911000},"page":"158","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Management of intracranial tuberculous mass lesions: how long should we treat for?"],"prefix":"10.12688","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8050-9610","authenticated-orcid":false,"given":"Suzaan","family":"Marais","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Van Toorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9440-9349","authenticated-orcid":false,"given":"Felicia C.","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abi","family":"Manesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9696-563X","authenticated-orcid":false,"given":"Omar K.","family":"Siddiqi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3357-6490","authenticated-orcid":false,"given":"Anthony","family":"Figaji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan F.","family":"Schoeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Meintjes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Tuberculous Meningitis International Research Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2020,2,26]]},"reference":[{"key":"ref-1","doi-asserted-by":"crossref","first-page":"733-52","DOI":"10.1016\/S0033-8389(22)00616-9","article-title":"Pathology and pathogenetic mechanisms in neurotuberculosis.","volume":"33","author":"D Dastur","year":"1995","journal-title":"Radiol Clin North Am."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"111-7","DOI":"10.1007\/BF01742762","article-title":"Diagnosis and neurosurgical treatment of tuberculous disease of the CNS.","volume":"6","author":"H Dastur","year":"1983","journal-title":"Neurosurg Rev."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"92-6","DOI":"10.1016\/j.jns.2007.09.012","article-title":"Multiple ring enhancing brain lesions on computed tomography: an Indian perspective.","volume":"266","author":"R Garg","year":"2008","journal-title":"J Neurol Sci."},{"key":"ref-4","first-page":"1284-8","article-title":"Intracranial mass lesions in HIV-positive patients--the KwaZulu\/Natal experience. 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.17274.r38037, Jerome H. Chin, Department of Neurology, NYU Langone Health, New York City, NY, USA, 28 Feb 2020, version 3, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-158\/v3#referee-response-38037","order":0,"name":"referee-response-38037","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17008.r37112, Benedict Michael, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK, 18 Dec 2019, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-158\/v2#referee-response-37112","order":1,"name":"referee-response-37112","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Suzaan Marais<\/b>; <i>Posted: 21 Feb 2020<\/i>; In this excellent and thorough overview, the authors accurately summarise the clinical presentation, neuroimaging findings, and pathogenesis of CNS TB, and focus on the data (and lack thereof) to guide the duration of TB therapy.&nbsp; <b>RESPONSE<\/b>: We thank the reviewer for this comment.&nbsp;The manuscript would be strengthened if, in addition to the serial MRI scans in one patient, a figure was included to demonstrate the specific neuroimaging findings described in the text (Figure allowance permitting). This is of particular interest given that they describe, at least theoretical, rationale for cessation\/continuing TB therapy based on the nature of the lesions.&nbsp; <b>RESPONSE:<\/b>&nbsp;We have added additional images showing various stages of intracranial tuberculous mass lesions (Figures 1 and 3).&nbsp;&nbsp;The manuscript (space permitting) would also benefit from a more descriptive outline of the nature of the RCT investigating TB therapy duration proposed by these authors, who represent leaders in the field. For example, inclusion\/exclusion, how to address HIV\/ART status, imaging and clinical sub-group analyses, and controlling for corticosteroid use. This would be in the discussion as opposed to the conclusion.&nbsp; <b>RESPONSE:<\/b>&nbsp;A RCT investigating TB therapy duration will, as the reviewer rightly points out, require careful consideration of multiple potential confounders. Such a detailed description is outside the scope of this manuscript but could be the subject of a future manuscript.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-158\/v3#referee-comment-4087","order":2,"name":"referee-comment-4087","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17274.r38036, Julie Higashi, Tuberculosis Control Program, Division of Dental and Medical Affairs, Los Angeles County Department of Public Health, Los Angeles, CA, USA, 04 Mar 2020, version 3, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-158\/v3#referee-response-38036","order":3,"name":"referee-response-38036","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust [098316 and 203135 to GM, 097254 to SM]. FCC was supported by National Institutes of Health\/Fogarty International Center [R21TW011035]. OKS was supported by the National Institutes of Health [K23 NS084054-01]. AF was supported by the National Research Foundation SARChI Chair in Clinical Neurosciences. GM is also supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa [64787], NRF incentive funding [UID: 85858] and the South African Medical Research Council through its TB and HIV Collaborating Centres Programme with funds received from the National Department of Health [RFA# SAMRC-RFA-CC: TB\/HIV\/AIDS-01-2014]. The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The opinions, findings and conclusions expressed in this manuscript reflect those of the authors alone. This work was supported by the Wellcome Trust through funding to the Tuberculous Meningitis International Research Consortium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}