{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T15:40:36Z","timestamp":1789573236098,"version":"build-2803163510"},"reference-count":98,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T00:00:00Z","timestamp":1519776000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000765","name":"University College London","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000765","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Treat Options Neurol"],"published-print":{"date-parts":[[2018,3]]},"DOI":"10.1007\/s11940-018-0490-9","type":"journal-article","created":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T03:34:12Z","timestamp":1519788852000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Treatment of Tuberculous Meningitis and Its Complications in Adults"],"prefix":"10.1007","volume":"20","author":[{"given":"Angharad","family":"Davis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Meintjes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,2,28]]},"reference":[{"key":"490_CR1","unstructured":"World Health Organization. Global tuberculosis report 20th edition. World Health Organization, Geneva; 2015."},{"key":"490_CR2","doi-asserted-by":"crossref","unstructured":"Streptomycin in tuberculosis trials committee, Medical Research Council. Streptomycin treatment of tuberculous meningitis. Lancet 1948:251:582\u2013589.","DOI":"10.1016\/S0140-6736(48)92003-0"},{"key":"490_CR3","doi-asserted-by":"crossref","unstructured":"Treatment of pulmonary tuberculosis with isoniazid; an interim report to the Medical Research Council by their Tuberculosis Chemotherapy Trials Committee. Br Med J 1952:2:735\u201346.","DOI":"10.1136\/bmj.2.4787.735"},{"issue":"Suppl","key":"490_CR4","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1159\/000194962","volume":"28","author":"V Nitti","year":"1971","unstructured":"Nitti V. Results and tolerance of prolonged rifampicin treatment in recent and chronic forms of pulmonary tuberculosis. Respiration. 1971;28(Suppl):57\u201369.","journal-title":"Respiration"},{"key":"490_CR5","doi-asserted-by":"publisher","unstructured":"Chiang SS, et al. Treatment outcomes of childhood tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2014:947\u201357. https:\/\/doi.org\/10.1016\/S1473-3099(14)70852-7 .","DOI":"10.1016\/S1473-3099(14)70852-7"},{"key":"490_CR6","doi-asserted-by":"publisher","first-page":"e20077","DOI":"10.1371\/journal.pone.0020077","volume":"6","author":"S Marais","year":"2011","unstructured":"Marais S, Pepper DJ, Schutz C, Wilkinson RJ, Meintjes G. Presentation and outcome of tuberculous meningitis in a high HIV prevalence setting. Plos ONE. 2011;6:e20077. https:\/\/doi.org\/10.1371\/journal.pone.0020077 .","journal-title":"Plos ONE"},{"key":"490_CR7","unstructured":"WHO. Treatment of tuberculosis guidelines. World Health Organisation. Geneva, 2010."},{"key":"490_CR8","doi-asserted-by":"publisher","unstructured":"Prasad K, Singh MB, Ryan H. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev. 23(1):CD002244. https:\/\/doi.org\/10.1002\/14651858.CD002244.pub4 .","DOI":"10.1002\/14651858.CD002244.pub4"},{"key":"490_CR9","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.tube.2010.07.002","volume":"90","author":"PR Donald","year":"2010","unstructured":"Donald PR. Cerebrospinal fluid concentrations of antituberculosis agents in adults and children. Tuberculosis (Edinb). 2010;90:279\u201392. https:\/\/doi.org\/10.1016\/j.tube.2010.07.002 .","journal-title":"Tuberculosis (Edinb)"},{"issue":"3","key":"490_CR10","first-page":"650e5","volume":"148","author":"GA Ellard","year":"1993","unstructured":"Ellard GA, Humphries MJ, Allen BW. Cerebrospinal fluid drug concentrations and the treatment of tuberculous meningitis. Am Rev Resp Dis. 1993;148(3):650e5.","journal-title":"Am Rev Resp Dis"},{"issue":"9","key":"490_CR11","first-page":"796e806","volume":"4","author":"DA Mitchison","year":"2000","unstructured":"Mitchison DA. Role of individual drugs in the chemotherapy of tuberculosis. Int J Tuberc Lung Dis. 2000;4(9):796e806.","journal-title":"Int J Tuberc Lung Dis"},{"key":"490_CR12","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1056\/NEJMoa1507062","volume":"374","author":"AD Heemskerk","year":"2016","unstructured":"Heemskerk AD, et al. Intensified antituberculosis therapy in adults with tuberculous meningitis. N Engl J Med. 2016;374:124\u201334. https:\/\/doi.org\/10.1056\/nejmoa1507062 . A randomized, double-blind, placebo-controlled trial demonstrating no survival benefit in patients treated with higher dose rifampicin (15\u00a0mg\/kg\/day) and levofloxacin in addition to standard treatment for the first 8\u00a0weeks of treatment.","journal-title":"N Engl J Med"},{"key":"490_CR13","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1097\/INF.0000000000000065","volume":"33","author":"R Toorn Van","year":"2014","unstructured":"Van Toorn R, et al. Short intensified treatment in children with drug-susceptible tuberculous meningitis. Pediatr Infect Dis J. 2014;33:248\u201352. https:\/\/doi.org\/10.1097\/INF.0000000000000065 .","journal-title":"Pediatr Infect Dis J"},{"key":"490_CR14","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S1473-3099(12)70264-5","volume":"13","author":"R Ruslami","year":"2013","unstructured":"Ruslami R, et al. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis. 2013;13:27\u201335. https:\/\/doi.org\/10.1016\/S1473-3099(12)70264-5 .","journal-title":"Lancet Infect Dis"},{"issue":"6","key":"490_CR15","first-page":"879","volume":"119","author":"MW Long","year":"1979","unstructured":"Long MW, Snider DE Jr, Farer LS. U.S. public health service cooperative trial of three rifampin-isoniazid regimens in treatment of pulmonary tuberculosis. Am Rev. Respir Dis. 1979;119(6):879\u201394.","journal-title":"Respir Dis"},{"issue":"9","key":"490_CR16","doi-asserted-by":"publisher","first-page":"e194","DOI":"10.1093\/cid\/cir184","volume":"52","author":"J Ingen van","year":"2011","unstructured":"van Ingen J, Aarnoutse RE, Donald PR, Diacon AH, Dawson R, Plemper van Balen G, et al. Why do we use 600\u00a0mg of rifampicin in tuberculosis treatment? Clin Infect Dis. 2011;52(9):e194\u20139. https:\/\/doi.org\/10.1093\/cid\/cir184 .","journal-title":"Clin Infect Dis"},{"issue":"9","key":"490_CR17","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1164\/rccm.201407-1264OC","volume":"191","author":"M Boeree","year":"2015","unstructured":"Boeree M. A dose-ranging trial to optimize the dose of rifampin in the treatment of tuberculosis. Am J of Resp Crit Care Med. 2015;191(9):1058\u201365. https:\/\/doi.org\/10.1164\/rccm.201407-1264OC . A dose finding study suggesting that dose higher than 15\u00a0mg\/kg are safe and may have beneficial outcomes in TBM.","journal-title":"Am J of Resp Crit Care Med"},{"key":"490_CR18","first-page":"1079e85","volume":"1","author":"East African\/British Medical Research Councils","year":"1972","unstructured":"East African\/British Medical Research Councils. Controlled clinical trial of short-course (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis. Lancet. 1972;1:1079e85.","journal-title":"Lancet"},{"key":"490_CR19","first-page":"939e49","volume":"121","author":"A Jindani","year":"1980","unstructured":"Jindani A, Aber VR, Edwards EA, Mitchison DA. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir Dis. 1980;121:939e49.","journal-title":"Am Rev Respir Dis"},{"key":"490_CR20","first-page":"155e8","volume":"86","author":"FJH Botha","year":"1996","unstructured":"Botha FJH, Sirgel FA, Parkin DP, Van de Wal BW, Donald PR, Mitchison DA. Early bactericidal activity of ethambutol, pyrazinamide and the fixed combination of isoniazid, rifampicin and pyrazinamide (Rifater) in patients with pulmonary tuberculosis. S Afr Med J. 1996;86:155e8.","journal-title":"S Afr Med J"},{"issue":"3","key":"490_CR21","doi-asserted-by":"publisher","first-page":"1602308","DOI":"10.1183\/13993003.02308-2016","volume":"49","author":"D Falzon","year":"2017","unstructured":"Falzon D, Sch\u00fcnemann HJ, Harausz E, et al. World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update. The European Respiratory Journal. 2017;49(3):1602308. https:\/\/doi.org\/10.1183\/13993003.02308-2016 .","journal-title":"The European Respiratory Journal"},{"key":"490_CR22","unstructured":"WHO. The shorter MDR-TB shorter regimen. World Health Organization, Geneva; 2016"},{"key":"490_CR23","first-page":"352","volume":"131","author":"M Tsukamura","year":"1985","unstructured":"Tsukamura M, Nakamura E, Yoshii S, Amano H. Therapeutic effect of a new antibacterial substance ofloxacin (DL8280) on pulmonary tuberculosis. Am Rev Resp Dis. 1985;131:352\u20136.","journal-title":"Am Rev Resp Dis"},{"issue":"7","key":"490_CR24","doi-asserted-by":"publisher","first-page":"3244","DOI":"10.1128\/AAC.00064-11","volume":"55","author":"GE Thwaites","year":"2011","unstructured":"Thwaites GE, Bhavnani SM, Chau TTH, et al. Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis. Antimicrobial Agents and Chemotherapy. 2011;55(7):3244\u201353. https:\/\/doi.org\/10.1128\/AAC.00064-11 .","journal-title":"Antimicrobial Agents and Chemotherapy"},{"issue":"7","key":"490_CR25","doi-asserted-by":"publisher","first-page":"e0159827","DOI":"10.1371\/journal.pone.0159827","volume":"11","author":"HW Lee","year":"2016","unstructured":"Lee HW, Lee JK, Kim E, Yim J-J, Lee C-H. The effectiveness and safety of fluoroquinolone-containing regimen as a first-line treatment for drug-sensitive pulmonary tuberculosis: a systematic review and meta-analysis. De Socio GV. PLoS ONE. 2016;11(7):e0159827. https:\/\/doi.org\/10.1371\/journal.pone.0159827.","journal-title":"PLoS ONE"},{"issue":"17","key":"490_CR26","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1056\/NEJMoa1407426","volume":"371","author":"SH Gillespie","year":"2014","unstructured":"Gillespie SH, Crook AM, McHugh TD, et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Eng J Med. 2014;371(17):1577\u201387. https:\/\/doi.org\/10.1056\/NEJMoa1407426 .","journal-title":"N Eng J Med"},{"issue":"5","key":"490_CR27","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.ijantimicag.2014.12.027","volume":"45","author":"L Brake Te","year":"2015","unstructured":"Te Brake L, et al. Pharmacokinetic\/pharmacodynamic analysis of an intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis. Int J of Antimicr Agents. 2015;45(5):496\u2013503.","journal-title":"Int J of Antimicr Agents"},{"key":"490_CR28","doi-asserted-by":"crossref","unstructured":"Ford CW, Zurenko GE, Barbachyn MR. The discovery of linezolid, the first oxazolidinone antibacterial agent. Curr Drug Targets Infect Dis. 2001:181\u201399.","DOI":"10.2174\/1568005014606099"},{"key":"490_CR29","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1021\/jm800038g","volume":"51","author":"SJ Brickner","year":"2008","unstructured":"Brickner SJ, Barbachyn MR, Hutchinson DK, et al. Linezolid (ZYVOX), the first member of a completely new class of antibacterial agents for treatment of serious Gram- positive infections. J Med Chem. 2008;51:1981\u201390.","journal-title":"J Med Chem"},{"key":"490_CR30","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1093\/jac\/dki148","volume":"56","author":"J Fortun","year":"2005","unstructured":"Fortun J, Martin-Davila P, Navas E, et al. Linezolid for the treatment of multidrug-resistant tuberculosis. J Antimicrob Chemother. 2005;56:180\u20135.","journal-title":"J Antimicrob Chemother"},{"key":"490_CR31","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.jinf.2005.04.007","volume":"52","author":"B Lippe von der","year":"2006","unstructured":"von der Lippe B, Sandven P, Brubakk O. Efficacy and safety of linezolid in multidrug resistant tuberculosis (MDR-TB)\u2014a report of ten cases. J Infect. 2006;52:92\u20136.","journal-title":"J Infect"},{"key":"490_CR32","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1378\/chest.07-1988","volume":"134","author":"R Condos","year":"2008","unstructured":"Condos R, Hadgiangelis N, Leibert E, et al. Case series report of a linezolid-containing regimen for extensively drug-resistant tuberculosis. Chest. 2008;134:187\u201392.","journal-title":"Chest"},{"key":"490_CR33","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1183\/09031936.00022912","volume":"40","author":"G Sotgiu","year":"2012","unstructured":"Sotgiu G, Centis R, D\u2019Ambrosio L, et al. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J. 2012;40:1430\u201342.","journal-title":"Eur Respir J"},{"key":"490_CR34","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1086\/648675","volume":"50","author":"GF Schecter","year":"2010","unstructured":"Schecter GF, Scott C, True L, et al. Linezolid in the treatment of multidrug-resistant tuberculosis. Clin Infect Dis. 2010;50:49\u201355.","journal-title":"Clin Infect Dis"},{"key":"490_CR35","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1183\/09031936.00009509","volume":"34","author":"GB Migliori","year":"2009","unstructured":"Migliori GB, Eker B, Richardson MD, et al. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis. Eur Respir J. 2009;34:387\u201393.","journal-title":"Eur Respir J"},{"key":"490_CR36","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1093\/jac\/dkq017","volume":"65","author":"H Anger","year":"2010","unstructured":"Anger H, Dworkin F, Sharma S, et al. Linezolid use for the treatment of multi-drug resistant and extensively drug resistant tuberculosis, New York City, 2000-6. J Antimicrob Chemother. 2010;65:775\u201383.","journal-title":"J Antimicrob Chemother"},{"issue":"16","key":"490_CR37","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1056\/NEJMoa1201964","volume":"367","author":"M Lee","year":"2012","unstructured":"Lee M, Lee J, Carroll MW, Choi H, Min S, Song T, et al. Linezolid for treatment of chronic extensively drug-resistant tuberculosis. N Engl J Med. 2012;367(16):1508\u201318. https:\/\/doi.org\/10.1056\/NEJMoa1201964 .","journal-title":"N Engl J Med"},{"issue":"4","key":"490_CR38","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1183\/09031936.00076811","volume":"39","author":"R Singla","year":"2012","unstructured":"Singla R, Caminero JA, Jaiswal A, Singla N, Gupta S, Bali RK, et al. Linezolid: an effective, safe and cheap drug for patients failing multidrug-resistant tuberculosis treatment in India. Eur Respir J. 2012;39(4):956\u201362. https:\/\/doi.org\/10.1183\/09031936.00076811 .","journal-title":"Eur Respir J"},{"issue":"1","key":"490_CR39","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1183\/09031936.00035114","volume":"45","author":"S Tang","year":"2015","unstructured":"Tang S, Yao L, Hao X, et al. Efficacy, safety and tolerability of\u00a0linezolid\u00a0for the treatment of XDR-TB: a study in China. Eur Respir J. 2015;45(1):161\u201370. https:\/\/doi.org\/10.1183\/09031936.00035114 .","journal-title":"Eur Respir J."},{"issue":"4","key":"490_CR40","first-page":"603","volume":"7","author":"X Zhang","year":"2015","unstructured":"Zhang X, Falagas M, Konstantinos V, Wang R, Win R, Wang J, et al. Systematic review and meta-analysis of the efficacy and safety of therapy with linezolid containing regimens in the treatment of multidrug-resistant and extensively drug-resistant tuberculosis. J Thorac Dis. 2015;7(4):603\u201315.","journal-title":"J Thorac Dis"},{"key":"490_CR41","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13063-017-1811-0","volume":"18","author":"JY Lee","year":"2017","unstructured":"Lee JY, Kim DK, Lee JK, et al. Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: study protocol for a prospective, multicentre, randomized, open-label, phase II trial. Trials. 2017;18:68.","journal-title":"Trials"},{"issue":"6","key":"490_CR42","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1097\/INF.0000000000001114","volume":"35","author":"H Li","year":"2016","unstructured":"Li H, Lu J, Liu J, Zhao Y, Ni X, Zhao S. Linezolid is associated with improved early outcomes of childhood tuberculous meningitis. Pediatr Infect Dis J. 2016;35(6):607\u201310.","journal-title":"Pediatr Infect Dis J"},{"issue":"10","key":"490_CR43","doi-asserted-by":"publisher","first-page":"6297","DOI":"10.1128\/AAC.02784-14","volume":"58","author":"F Sun","year":"2014","unstructured":"Sun F, Ruan Q, Wang J, Chen S, Jin J, Shao L, et al. Linezolid manifests a rapid and dramatic therapeutic effect for patients with life-threatening tuberculous meningitis. Antimicrob Angents Chemother. 2014;58(10):6297\u2013301. A retrospective cohort study of patients with severe TBM demonstrating improved recovery of consciousness and biochemical markers of disease severity in patients treated with linezolid in addition to standard TBM regimens.","journal-title":"Antimicrob Angents Chemother"},{"key":"490_CR44","doi-asserted-by":"publisher","unstructured":"Borislov SE, Dheda K, Enwerem M, Romero Leyet R et al. Effectiveness and safety of bedaquilline-containing regimens in the treatment of MDR- and XDR-TB: a multicenter study. Eur Respir J 2017:48(5) pii: 1,700,387. Doi: https:\/\/doi.org\/10.1183\/13993003.00387-2017 .","DOI":"10.1183\/13993003.00387-2017"},{"issue":"4","key":"490_CR45","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1093\/cid\/civ921.","volume":"62","author":"O Akkerman","year":"2016","unstructured":"Akkerman O, Odish O, Bolhuis M, de Lange W, Kremer H, Luijckx G, et al. of bedaquiline in cerebrospinal fluid and serum in multidrug-resistant tuberculous meningitis. Clin Infect Dis. 2016;62(4):523\u20134. https:\/\/doi.org\/10.1093\/cid\/civ921.","journal-title":"Clin Infect Dis"},{"issue":"1","key":"490_CR46","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1093\/bmb\/ldv003","volume":"113","author":"ME T\u00f6r\u00f6k","year":"2015","unstructured":"T\u00f6r\u00f6k ME. Tuberculous meningitis: advances in diagnosis and treatment. Br Med Bull. 2015;113(1):117\u201331. https:\/\/doi.org\/10.1093\/bmb\/ldv003 .","journal-title":"Br Med Bull"},{"issue":"2","key":"490_CR47","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S2213-2600(13)70295-9","volume":"2","author":"WRJ Host-directed","year":"2014","unstructured":"Host-directed WRJ. therapies against tuberculosis. Lancet Respir Med. 2014;2(2):85\u20137. https:\/\/doi.org\/10.1016\/S2213-2600(13)70295-9 . Epub 2014 Jan 9","journal-title":"Lancet Respir Med."},{"key":"490_CR48","first-page":"13","volume":"67","author":"SJ Shane","year":"1952","unstructured":"Shane SJ, Clowater RA, Riley C. The treatment of tuberculous meningitis with cortisone and streptomycin. Can Med Assoc J. 1952;67:13\u20135.","journal-title":"Can Med Assoc J"},{"issue":"2","key":"490_CR49","first-page":"83","volume":"79","author":"V Chotmongkol","year":"1996","unstructured":"Chotmongkol V, Jitpimolmard S, Thavornpitak Y. Corticosteroid in tuberculous meningitis. Journal of the Medical Association of Thailand. 1996;79(2):83\u201390.","journal-title":"Journal of the Medical Association of Thailand"},{"issue":"3","key":"490_CR50","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1097\/00006454-199103000-00002","volume":"10","author":"NI Girgis","year":"1991","unstructured":"Girgis NI, Farid Z, Kilpatrick ME, Sultan Y, Mikhail IA. Dexamethasone adjunctive treatment for tuberculous meningitis. Pediatric Infectious Disease Journal. 1991;10(3):179\u201383.","journal-title":"Pediatric Infectious Disease Journal"},{"issue":"3","key":"490_CR51","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/0962-8479(94)90009-4","volume":"75","author":"S Kumarvelu","year":"1994","unstructured":"Kumarvelu S, Prasad K, Khosla A, Behari M, Randomized AGK. controlled trial of dexamethasone in tuberculous meningitis. Tubercle and Lung Disease. 1994;75(3):203\u20137.","journal-title":"Tubercle and Lung Disease"},{"key":"490_CR52","first-page":"4","volume":"4","author":"DV Lardizabal","year":"1998","unstructured":"Lardizabal DV, Roxas AA. Dexamethasone as adjunctive therapy in adult patients with probable TB meningitis stage II and stage III: an open randomised controlled trial. Philippines Journal of Neurology. 1998;4:4\u201310.","journal-title":"Philippines Journal of Neurology"},{"issue":"7","key":"490_CR53","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1179\/000349809X12502035776315","volume":"103","author":"HS Malhotra","year":"2009","unstructured":"Malhotra HS, Garg RK, Singh MK, Agarwal A, Verma R. Corticosteroids (dexamethasone versus intravenous methylprednisolone) in patients with tuberculous meningitis. Annals of Tropical Medicine and Parasitology. 2009;103(7):625\u201334. https:\/\/doi.org\/10.1179\/000349809X12502035776315 .","journal-title":"Annals of Tropical Medicine and Parasitology"},{"issue":"2","key":"490_CR54","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1542\/peds.99.2.226","volume":"99","author":"JF Schoeman","year":"1997","unstructured":"Schoeman JF, Van Zyl LE, Laubscher JA, Donald PR. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. Pediatrics. 1997;99(2):226\u201331.","journal-title":"Pediatrics"},{"issue":"12","key":"490_CR55","doi-asserted-by":"publisher","first-page":"e27821","DOI":"10.1371\/journal.pone.0027821","volume":"6","author":"ME T\u00f6r\u00f6k","year":"2011","unstructured":"T\u00f6r\u00f6k ME, Nguyen DB, Tran TH, Nguyen TB, Thwaites GE, Hoang TQ, et al. Dexamethasone and long-term outcome of tuberculous meningitis in Vietnamese adults and adolescents. PLoS One. 2011;6(12):e27821. https:\/\/doi.org\/10.1371\/journal.pone.0027821 .","journal-title":"PLoS One"},{"key":"490_CR56","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1056\/NEJMoa040573","volume":"351","author":"GE Thwaites","year":"2004","unstructured":"Thwaites GE, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004;351:1741\u201351. https:\/\/doi.org\/10.1056\/nejmoa040573 . A randomized, double-blind, placebo-controlled trial demonstrating survival benefit in patients treated with adjunctive dexamethasone in HIV-uninfected individuals. Subgroup analysis in those HIV-coinfection revealed no significant benefit on mortality.","journal-title":"N Engl J Med"},{"key":"490_CR57","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/j.cell.2010.02.013","volume":"140","author":"DM Tobin","year":"2010","unstructured":"Tobin DM, Vary JC Jr, Ray JP, et al. The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell. 2010;140:717\u201330. https:\/\/doi.org\/10.1016\/j.cell.2010.02.013 .","journal-title":"Cell"},{"key":"490_CR58","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.cell.2011.12.023","volume":"148","author":"DM Tobin","year":"2012","unstructured":"Tobin DM, Roca FJ, Oh SF, et al. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. Cell. 2012;148:434\u201346. https:\/\/doi.org\/10.1016\/j.cell.2011.12.023 .","journal-title":"Cell"},{"key":"490_CR59","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1093\/infdis\/jix050","volume":"215","author":"N Thuong","year":"2017","unstructured":"Thuong N, Heemskerk D, Tram T, Thao LTP, Ramakhrishnan L, Ha V, et al. Leukotriene A4 hydrolase genotype and HIV infection influence intracerebral inflammation and survival from tuberculous meningitis. J Inf Dis. 2017;215:1020\u20138. https:\/\/doi.org\/10.1093\/infdis\/jix050 .","journal-title":"J Inf Dis"},{"key":"490_CR60","doi-asserted-by":"publisher","first-page":"5657","DOI":"10.1073\/pnas.96.10.5657","volume":"96","author":"L Tsenova","year":"1999","unstructured":"Tsenova L, Bergtold A, Freedman VH, Young RA, Kaplan G. Tumor necrosis factor alpha is a determinant of pathogenesis and disease progression in mycobacterial infection in the central nervous system. Proc Natl Acad Sci U S A. 1999;96:5657\u201362.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"490_CR61","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1177\/088307380001500801","volume":"15","author":"JF Schoeman","year":"2000","unstructured":"Schoeman JF, Springer P, Ravenscroft A, Donald PR, Bekker LG, van Rensburg AJ, et al. thalidomide therapy of childhood tuberculous meningitis: possible anti-inflammatory role. J Child Neurol. 2000;15(8):497\u2013503.","journal-title":"J Child Neurol"},{"issue":"4","key":"490_CR62","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1177\/088307380401900402","volume":"19","author":"JF Schoeman","year":"2004","unstructured":"Schoeman JF, Springer P, van Rensburg AJ, Swanevelder S, Hanekom WA, Haslett PA, et al. thalidomide therapy for childhood tuberculous meningitis: results of a randomized study. J Child Neurol. 2004;19(4):250\u20137.","journal-title":"J Child Neurol"},{"issue":"2","key":"490_CR63","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1097\/INF.0000000000000539","volume":"34","author":"R Toorn van","year":"2015","unstructured":"van Toorn R, du Plessis AM, Schaaf HS, et al. Clinicoradiologic response of neurologic tuberculous mass lesions in children treated with thalidomide. Pediatr Infect Dis J. 2015;34(2):214\u20138. https:\/\/doi.org\/10.1097\/INF.0000000000000539 .","journal-title":"Pediatr Infect Dis J."},{"issue":"8","key":"490_CR64","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1056\/NEJMoa0905848","volume":"362","author":"SS Abdool Karim","year":"2010","unstructured":"Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010;362(8):697\u2013706. https:\/\/doi.org\/10.1056\/NEJMoa0905848 .","journal-title":"N Engl J Med"},{"issue":"16","key":"490_CR65","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1056\/NEJMoa1013911","volume":"365","author":"FX Blanc","year":"2011","unstructured":"Blanc FX, Sok T, Laureillard D, et al. CAMELIA (ANRS 1295\u2013CIPRA KH001) Study Team. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med. 2011;365(16):1471\u201381. https:\/\/doi.org\/10.1056\/NEJMoa1013911 .","journal-title":"N Engl J Med"},{"issue":"16","key":"490_CR66","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1056\/NEJMoa1013607","volume":"365","author":"DV Havlir","year":"2011","unstructured":"Havlir DV, Kendall MA, Ive P, et al. AIDS Clinical Trials Group Study A5221. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011;365(16):1482\u201391. https:\/\/doi.org\/10.1056\/NEJMoa1013607.","journal-title":"N Engl J Med"},{"key":"490_CR67","doi-asserted-by":"publisher","first-page":"32","DOI":"10.7326\/M14-2979","volume":"163","author":"OA Uthman","year":"2015","unstructured":"Uthman OA, Okwundu C, Gbenga K, et al. Optimal timing of antiretroviral therapy initiation for HIV infected adults with newly diagnosed pulmonary tuberculosis: a systematic review and metanalysis. Ann Int Med. 2015;163:32\u20139. https:\/\/doi.org\/10.7326\/M14-2979 .","journal-title":"Ann Int Med"},{"issue":"3","key":"490_CR68","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1093\/cid\/cis899","volume":"56","author":"S Marais","year":"2013","unstructured":"Marais S, Meintjes G, Pepper DJ, et al. Frequency, severity, and prediction of tuberculous meningitis immune reconstitution inflammatory syndrome. Clin Infect Dis. 2013;56(3):450\u201360. https:\/\/doi.org\/10.1093\/cid\/cis899 .","journal-title":"Clin Infect Dis"},{"issue":"11","key":"490_CR69","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1093\/cid\/cir230","volume":"52","author":"ME T\u00f6r\u00f6k","year":"2011","unstructured":"T\u00f6r\u00f6k ME, Yen NT, Chau TT, et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)-associated tuberculous meningitis. Clin Infect Dis. 2011;52(11):1374\u201383. https:\/\/doi.org\/10.1093\/cid\/cir230 .","journal-title":"Clin Infect Dis"},{"key":"490_CR70","doi-asserted-by":"publisher","first-page":"156","DOI":"10.5694\/mja14.00716","volume":"202","author":"JS Molton","year":"2015","unstructured":"Molton JS, Huggan PJ, Archuleta S. Infliximab therapy in two cases of severe neurotuberculosis paradoxical reaction. Med J Aust. 2015;202:156\u20137.","journal-title":"Med J Aust"},{"issue":"6","key":"490_CR71","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/j.clineuro.2011.12.013","volume":"114","author":"JY Lee","year":"2012","unstructured":"Lee JY, Yim JJ, Yoon BW. Adjuvant interferon-gamma treatment in two cases of refractory tuberculosis of the brain. Clin Neurol Neurosurg. 2012;114(6):732\u20134. https:\/\/doi.org\/10.1016\/j.clineuro.2011.12.013 .","journal-title":"Clin Neurol Neurosurg"},{"issue":"5","key":"490_CR72","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1093\/infdis\/jiw561","volume":"215","author":"S Marais","year":"2017","unstructured":"Marais S, Lai RPJ, Wilkinson KA, Meintjes G, O\u2019Garra A, Wilkinson RJ. Inflammasome activation underlies central nervous system deterioration in HIV-associated tuberculosis. J Infect Dis. 2017;215(5):677\u201386. https:\/\/doi.org\/10.1093\/infdis\/jiw561 . An observation study in HIV-associated TBM to investigate the pathogenesis of immune reconstitution inflammatory syndrome suggesting a dominant role of the innate immune system.","journal-title":"J Infect Dis"},{"key":"490_CR73","volume-title":"The pathogenesis of tuberculosis","author":"AR Rich","year":"1946","unstructured":"Rich AR, The pathogenesis of tuberculosis. Charles C Thomas, 1946."},{"issue":"10","key":"490_CR74","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1007\/s00701-015-2501-x","volume":"157","author":"V Rajshekhar","year":"2015","unstructured":"Rajshekhar V. Surgery for brain tuberculosis: a review. Acta Neurochir (Wien). 2015 Oct;157(10):1665\u201378. https:\/\/doi.org\/10.1007\/s00701-015-2501-x .","journal-title":"Acta Neurochir (Wien)"},{"key":"490_CR75","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/S0140-6736(75)92830-5","volume":"7905","author":"B Jennett","year":"1975","unstructured":"Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet. 1975;7905:480\u20134.","journal-title":"Lancet"},{"key":"490_CR76","doi-asserted-by":"publisher","first-page":"64","DOI":"10.3171\/jns.1991.74.1.0064","volume":"74","author":"R Palur","year":"1991","unstructured":"Palur R, Rajshekhar V, Chandy MJ, Joseph T, Abraham J. Shunt surgery for hydrocephalous in tubercular meningitis: a long-term follow-up study. J Neurosurg. 1991;74:64\u20139.","journal-title":"J Neurosurg"},{"issue":"375","key":"490_CR77","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.jns.2017.02.008","volume":"15","author":"I Rizvi","year":"2017","unstructured":"Rizvi I, Garg RK, Malhotra HS, et al. Ventriculo-peritoneal shunt surgery for tuberculous meningitis: a systematic review. J Neurol Sci. 2017;15(375):255\u201363. https:\/\/doi.org\/10.1016\/j.jns.2017.02.008 .","journal-title":"J Neurol Sci"},{"issue":"5","key":"490_CR78","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.3171\/2014.12.JNS14257","volume":"122","author":"RM Sharma","year":"2015","unstructured":"Sharma RM, Pruthi N, Arimappamagan A, et al. Tubercular meningitis with hydrocephalus with HIV co-infection: role of cerebrospinal fluid diversion procedures. J Neurosurg. 2015;122(5):1087\u201395. https:\/\/doi.org\/10.3171\/2014.12.JNS14257 .","journal-title":"J Neurosurg"},{"issue":"8","key":"490_CR79","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1093\/cid\/cix540","volume":"65","author":"UK Rohlwink","year":"2017","unstructured":"Rohlwink UK, Mauff K, Wilkinson KA, et al. Biomarkers of cerebral injury and inflammation in pediatric tuberculous meningitis. Clin Infect Dis. 2017;65(8):1298\u2013307. https:\/\/doi.org\/10.1093\/cid\/cix540 .","journal-title":"Clin Infect Dis"},{"key":"490_CR80","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1136\/jnnp.2008.156596","volume":"80","author":"M Oddo","year":"2009","unstructured":"Oddo M, Levine JM, Frangos S, et al. Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension. J Neurol, Neurosurg and Psych. 2009;80:916\u201320. https:\/\/doi.org\/10.1136\/jnnp.2008.156596 .","journal-title":"J Neurol, Neurosurg and Psych"},{"key":"490_CR81","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1097\/CCM.0B013E3181643B41","volume":"36","author":"G Francony","year":"2008","unstructured":"Francony G, Fauvage B, Falcon D, et al. Equimolar doses of mannitol and hypertonic saline in the treatment of increased intracranial pressure. Critical Care Med. 2008;36:795\u2013800. https:\/\/doi.org\/10.1097\/CCM.0B013E3181643B41 .","journal-title":"Critical Care Med"},{"key":"490_CR82","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.jns.2016.06.004","volume":"367","author":"UK Misra","year":"2016","unstructured":"Misra UK, Kalita J, Bhoi SK, et al. A study of hyponatremia in tuberculous meningitis. J Neurol Sci. 2016;367:152\u20137. https:\/\/doi.org\/10.1016\/j.jns.2016.06.004 .","journal-title":"J Neurol Sci"},{"key":"490_CR83","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1681\/ASN.2007101118","volume":"19","author":"RH Sterns","year":"2008","unstructured":"Sterns RH, Silver SM. Cerebral salt wasting versus SIADH: what difference? J of the Am Soc of Nephrology. 2008;19:194\u20136. https:\/\/doi.org\/10.1681\/ASN.2007101118 .","journal-title":"J of the Am Soc of Nephrology"},{"key":"490_CR84","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1080\/003655401750064022","volume":"33","author":"K Moller","year":"2001","unstructured":"Moller K, Larsen FS, Bie P, et al. The syndrome of inappropriate secretion of antidiuretic hormone and fluid restriction in meningitis\u2014how strong is the evidence? Scand J Infect Dis. 2001;33:13\u201326.","journal-title":"Scand J Infect Dis"},{"issue":"3","key":"490_CR85","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/S1474-4422(07)70034-0","volume":"6","author":"GE Thwaites","year":"2007","unstructured":"Thwaites GE, Macmullen-Price J, Tran TH, et al. Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis: an observational study. Lancet Neurol. 2007 Mar;6(3):230\u20136.","journal-title":"Lancet Neurol"},{"issue":"4","key":"490_CR86","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1177\/08830738060210040801","volume":"21","author":"JF Schoeman","year":"2006","unstructured":"Schoeman JF, Fieggen G, Seller N, et al. Intractable intracranial tuberculous infection responsive to thalidomide: report of four cases. J Child Neurol. 2006;21(4):301\u20138.","journal-title":"J Child Neurol"},{"issue":"2","key":"490_CR87","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1097\/WNF.0b013e318285caa1","volume":"36","author":"P Riva de la","year":"2013","unstructured":"de la Riva P, Urtasun M, Castillo-Trivino T, et al. Clinical response to thalidomide in the treatment of intracranial tuberculomas: case report. Clin Neuropharmacol. 2013;36(2):70\u20132.","journal-title":"Clin Neuropharmacol"},{"issue":"3","key":"490_CR88","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0163-4453(03)00077-X","volume":"47","author":"MT Roberts","year":"2003","unstructured":"Roberts MT, Mendelson M, Meyer P, et al. The use of thalidomide in the treatment of intracranial tuberculomas in adults: two case reports. J Infect. 2003;47(3):251\u20135.","journal-title":"J Infect"},{"key":"490_CR89","first-page":"633","volume":"25","author":"MD Thomas","year":"1977","unstructured":"Thomas MD, Chopra JS, Tuberculous WBNS. meningitis (TBM): a clinical study of 232 cases. J Assoc Physicians India. 1977;25:633\u20139.","journal-title":"J Assoc Physicians India"},{"key":"490_CR90","unstructured":"Dalal PM. Observations on the involvement of cerebral vessels in tuberculous meningitis in adults. In: Goldstein M, Murray, Bolis, Liana, Fieschi, Gorini, editors. Advances in neurology, vol. 25. Raven Press: 1979. p. 149\u2013159."},{"key":"490_CR91","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.jinf.2008.07.012","volume":"57","author":"R Shukla","year":"2008","unstructured":"Shukla R, Abbas A, Kumar P, et al. Evaluation of cerebral infarction in tuberculous meningitis by diffusion weighted imaging. J Infect. 2008;57:298\u2013306. https:\/\/doi.org\/10.1016\/j.jinf.2008.07.012 .","journal-title":"J Infect"},{"key":"490_CR92","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.jstrokecerebrovasdis.2008.11.007","volume":"18","author":"J Kalita","year":"2009","unstructured":"Kalita J, Misra UK, Nair PP. Predictors of stroke and its significance in the outcome of tuberculous meningitis. J Stroke Cerebrovasc Dis. 2009;18:251\u20138. https:\/\/doi.org\/10.1016\/j.jstrokecerebrovasdis.2008.11.007 .","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"490_CR93","doi-asserted-by":"publisher","unstructured":"Misra UK, Kalita J, Maurya PK. Stroke in tuberculous meningitis. J Neurol Sci 2011:15:303(1-2):22-30. Doi: https:\/\/doi.org\/10.1016\/j.jns.2010.12.015 .","DOI":"10.1016\/j.jns.2010.12.015"},{"key":"490_CR94","doi-asserted-by":"publisher","first-page":"S12","DOI":"10.1159\/000209261","volume":"27","author":"MG Bousser","year":"2009","unstructured":"Bousser MG. Antithrombotic agents in the prevention of ischemic stroke. Cerebrovasc Dis. 2009;27:S12\u20139. https:\/\/doi.org\/10.1159\/000209261.","journal-title":"Cerebrovasc Dis"},{"key":"490_CR95","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1111\/j.1463-1326.2007.00794.x","volume":"10","author":"MM Hovens","year":"2008","unstructured":"Hovens MM, Snoep JD, Groeneveld Y, Fr\u00f6lich M, Tamsma JT, Huisman MV. Effects of aspirin on serum C-reactive protein and interleukin-6 levels in patients with type 2 diabetes without cardiovascular disease: a randomized placebo-controlled crossover trial. Diab Obes Metab. 2008;10:668\u201374.","journal-title":"Diab Obes Metab"},{"key":"490_CR96","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.cell.2011.12.023","volume":"148","author":"DM Tobin","year":"2012","unstructured":"Tobin DM, Roca FJ, Oh SF, et al. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. Cell. 2012;148:434\u201346.","journal-title":"Cell"},{"key":"490_CR97","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jns.2010.03.025","volume":"293","author":"UK Misra","year":"2010","unstructured":"Misra UK, Kalita J, Nair PP. Role of aspirin in tuberculous meningitis: a randomized open label placebo controlled trial. J Neurol Sci. 2010;293:12\u20137. https:\/\/doi.org\/10.1016\/j.jns.2010.03.025 .","journal-title":"J Neurol Sci"},{"key":"490_CR98","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1177\/0883073811398132","volume":"26","author":"JF Schoeman","year":"2011","unstructured":"Schoeman JF, Janse van Rensburg A, Laubscher JA, et al. The role of aspirin in childhood tuberculous meningitis. J Child Neurol. 2011;26:956\u201362. https:\/\/doi.org\/10.1177\/0883073811398132 .","journal-title":"J Child Neurol"}],"container-title":["Current Treatment Options in Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11940-018-0490-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11940-018-0490-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11940-018-0490-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T20:52:37Z","timestamp":1570827157000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11940-018-0490-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,28]]},"references-count":98,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["490"],"URL":"https:\/\/doi.org\/10.1007\/s11940-018-0490-9","relation":{},"ISSN":["1092-8480","1534-3138"],"issn-type":[{"value":"1092-8480","type":"print"},{"value":"1534-3138","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,28]]},"assertion":[{"value":"28 February 2018","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights and Informed Consent"}}],"article-number":"5"}}