Table I.
Treatment outcomes among children with TBM in various studies across different parts of the world
| Author(s) and country | Study design and study duration | Study population | Staging/grading of disease severity (%) | ATT and steroids | Treatment outcome (%) | Factors associated with outcome | ||
|---|---|---|---|---|---|---|---|---|
| Complete recovery | Death | Neurologic sequelae/disability | ||||||
| Ramachandran et al89, Chennai, India | Three chemotherapy studies | 180 children with TBM aged between 1 and 12 yr | 1-13 2-77 3-9 (Modified BMRC staging) | 2SHR/4S2EH/6EH or 2SHRZ/10EH or 2R2SHZ/10EH Steroids for 6-12 wk | 34 | 27 | 39 | Presentation at Stage 1 - Better outcome Presentation at Stage 3 - Poor outcome |
| Mihailidou et al7, Greece | Retrospective record review, 1984-2008 | 43 children with TBM aged between 7 months to 13 yr | 1-37.2 2-37.2 3-25.6 (BMRC staging) | 2HRSZ or E/10HR (47%) 2HRS or Z/10HR (26%) HR (27%) Steroids for 3-4 wk | 5 | 14 | Presentation at Stage 3 - Poor outcome | |
| Ramzan et al18, Kashmir, India | Prospective study, 2007-2011 | 65 children diagnosed with TBM, aged 19 months to 13 yr | 1-32 2-51 3-17 (Modified criteria of MRC staging) | 3HRZE/9HR steroids for initial 4-6 wk | 6 | Low GCS, seizures and basal exudates, infarcts in CT - Poor outcomes | ||
| Farinha et al19, London, UK** | Retrospective cohort study (last 9 patients prospective) 1977-1997 | 38 children with CNS TB, 23 with TBM, 10 TBM with tuberculomas, 5 with tuberculomas, aged between 8 months and 16 yr | 1-6 2-30 3-64 (BMRC staging) | ATT with concurrent steroids | 13 | 47 | Past history of BCG vaccination - Better outcome Stage 3 disease - Poor outcome | |
| Karande et al20, Mumbai, India | Prospective observational study, 2000-2003 | 123 children with TBM, aged between 3 months and 12 yr | 1-4 2-10 3-86.2 (BMRC staging) | 2 HRZE/4 HR steroids for 4 wk | 20 | 23 | 57 | Hypertonia - Predictor of neurological sequelae Deep coma - Poor outcome |
| Thilothammal et al25, Chennai, India | Case-control study, 1990-1992 | 107 children with TBM, aged between 6 months and 12 yr | 1-20 2-60 3-20 (Gordon and Parson)88 | 2HRZS/10HR steroids for the first 4-6 wk | 22 | 53 | Young age, late stage of the disease and high CSF protein value - Poor outcome | |
| Yaramiş A et al26, Turkey | Retrospective record review, 1988-1996 | 214 children with CNS TB aged between 3 months and 15 yr | *** 1-10 2-56 3-34 | 2HRS or Z/10 HR steroid therapy in the first month | 23 | Early VP shunting for hydrocephalus - Better outcome Children less than five years - Poor outcome | ||
| van Well et al32, Cape Town, South Africa | Retrospective cohort study, 1985-2005 | 554 children diagnosed with TBM, 2 months to 15 yr | 1-2.6 2-57.3 3-40.1 (Modified criteria of MRC staging) | 6 HRZEth steroid in the first month | 16 | 13 | 71 | African ethnicity, stage 3 of disease, motor deficits, brainstem dysfunction, and cerebral infarctions - Poor outcome |
| Miftode et al33, Romania | Retrospective record review, 2004-2013 | 77 children diagnosed with TBM, 3 months to 15 yr | 1-26 2-52 3-22 (Gordon and Parson)88 | 2-3HRZE/7-9 HR3 | 8 | 36 | - | |
| Güneş et al59, Turkey | Retrospective record review, 1998-2008 | 185 children with TBM, 4 months to 18 yr | 1-36.8 2-30.8 3-32.4 (BMRC staging) | 2HRS, Z or E/10 HR steroids in the first month | 13 | Diagnosis at early stage - Better outcome | ||
| Nabukeera- Barungi et al90, Cape town, South Africa** | Retrospective record review, 2009 | 40 children with TBM aged between 6 wk to 12 yr | 2-50# 3-50 (Modified criteria of MRC staging) | RHZEth with steroids Neurosurgical procedures-25% | 43 | 8 | 49 | Stage 3 on admission, longer mean hospital stay, surgery - Poor outcome |
| Faella et al91, Italy | Retrospective study, 1986-2001 | 32 children with TBM aged between 8 and 160 months | 1-16 2-30 3-53 (MRC staging) | 2 HRS (with E or Z for 10 patients)/10-18 HR, Steroids for 3-6 wk | 13 | 19 | Quick normalization of CSF parameters (proteins, glucose, cells) - better outcome Long-lasting pre-admission non-specific symptoms, elevated CSF protein, stage 3 disease and ventricular dilation - Poor outcome | |
| Rohlwink et al92, South Africa | Prospective cohort study, October 2010 and August 2013 | 44 children with TBM and associated hydrocephalus aged between 3 months to 13 yr | 1-9 2a-38.6 2b-31.8 3-20.5 (Refined criteria of MRC staging) | 2 HRZEth/4-6 HR Steroids for 3 wk | 16 | 36.6 | Elevated polymorphonuclear cells in CSF - Better outcome Multiple or large infarcts, - Poor outcome | |
| Bang et al93, Vietnam | Prospective descriptive study, October 2009-March 2011 | 100 children with TBM, aged between 2 and 180 months | Children >5 yr (Modified MRC staging) 1-48 2-33 3-18 Children <5 yr (Blantyre coma score) 1-64 2-18 3-18 | 2HRZES/1HRZE/5HRE with adjuvant steroids Outcome Death - 15.7% Severe disability -7.4% Intermediate disability - 26% | 15.7 | History of coma, seizures, neck stiffness, decreased level of consciousness, FND, Stage 3 disease - Poor outcome | ||
| Dhawan et al94, India | Prospective cohort study (October 2010 to June 2012) | 130 children | 1-20 3-36.9 (Modified MRC staging) | 2HREZ/10 HR with adjuvant steroids Outcome at discharge: Death - 29% | 29 | 26.5 | Stage 3 at presentation, infarcts in neuroimaging - Poor outcome | |
**Treatment recommendations as per the National Guidelines changed over the period surveyed and patients received various combinations of anti-TB drugs, ***Staging of disease severity explained but name of the staging method not mentioned, #Staging was done for only 18 patients, for whom GCS was available. VP ratio - ventricular diameter at the midportion of the body of the lateral ventricles and P is the biparietal diameter measured from inner table to inner table. MRC, Medical Research Council; ATT, antituberculosis therapy; BMRC, British MRC; CNS, central nervous system; CSF, cerebrospinal fluid; FND, focal neurological deficit; R, rifampicin; H, isoniazid; E, ethambutol; Eth, ethionamide; Z, pyrazinamide; S, streptomycin; TBM, tuberculous meningitis; GCS, Glasgow Coma Scale; CT, computed tomography; TB, tuberculosis; BCG, Bacillus Calmette-Guérin