Steroids for treating tubercular meningitisDate: 94.11.17 ( )Reporter: BackgroundDefinition--------------Tuberculous meningitis (TBM) is an inflammation of the meninges covering the brain and spinal cord caused by infection with mycobacteria, most usually Mycobacterium tuberculosis The condition usually presents with headache, fever, and convulsions and is diagnosed clinically, with confirmation by microscopy and culture of cerebrospinal fluid. Background!ncidence--------------TBM is a common cause of admission to neurology and paediatric wards in some hospitals !n the "#$, some researchers have estimated that it accounts for %&' of the tuberculosis (TB) affecting organs other than the lungs HIV-infected patients are at higher ris( of TB, and this has increased the incidence of TBM in these populations TBM was the most common cause of meningitis, accounting for more than )&' of cases Background!ncidence-------------- !n one study comparing the clinical features, laboratory findings, and mortality rates in patients having TB meningitis with or without *!+ infection, cerebral tuberculomas were seen to be more common in the HIV-infected group (60 versus 1 percent!, otherwise, co-infection with *!+ did not alter the clinical manifestations, -#. findings, or response to therapy"pToDate )//&, TB meningitis BackgroundTreatment options (TB Meningitis) ---------------------------0ithout drug treatment patients with TBM die Monotherapy with streptomycin, an early TB drug, reduced the case fatality rate to 12' TB drugs (isonia3id, rifampicin, and pyra3inamide) used in combination are associated with better survival, but the mortality remains substantial 4ecent reports estimate fatality rates varying from )/' to 2)', with permanent neurological deficits in &' to 5/' of the survivors Background-orticosteroids----------------------orticosteroids for TBM since the %6&/s 0hile some believe corticosteroids improve outcome 7 (%) decrease inflammation, especially in the subarachnoid space ()) reduce cerebral and spinal cord oedema (2) reduce inflammation of small blood vessels and therefore reduce damage from blood flow slowing to the underlying brain tissue Background-orticosteroids---------------------!t is possible that steroids may harm TBM patients by suppressing the immune mechanism #teroids may7(%) suppress the immune response to mycobacteria, ma(ing the systemic effects worse,()) reduce inflammation of the meninges, reducing drug penetration into the subarachnoid space,(2) cause gastrointestinal haemorrhage, electrolyte imbalance, hyperglycaemia, infections from fungi or bacteria, and psychosis P.I.C.O.8atients(P)!ntervention (I)-omparison(C)9utcome(O)tubercular meningitis ptsnti !" #rugs$%teroi#nti !" #rugs &ortalit'Disabilit' %earc( #atabaseCoc(rane librar' (ey word7 tuberculous .ound7 6 results :; Steroids for treating TB meningitis :; Interventions for treating TB pericarditis :; Steroids for treating TB pleurisy > pagesD@-7//2/&5 -p!oDate (ey word7 TB meningitis found7 % reslut%earc( #atabase Results..Clinical trial...&eta.anal'sis/ RC!for children adolescents adults !ith or !ithout HIVmerican !(oracic %ociet'/ CDC/ ID%guideline for TB managementConclusion "teroids for treating tuberculous meningitis < 8rasad, C +olmin(, @4 Menon"he #ochrane $atabase of %ystematic &eviews )//& !ssue 5-opyright E )//& The -ochrane -ollaboration 8ublished by Cohn 0iley F #ons, Gtd %/%//)H%51&%I&I-D//))55 This version first published online7 )5 Culy )/// in !ssue 2, )///Date of Most 4ecent $mendment7 )1 May )//& Ob)ecti*esTo assess the effects of steroids on #eat( an# #isabilit' in patients with TBM%election criteria &andomised controlled trials of steroids in people on TB treatment for TBM%earc( strateg' -ochrane !nfectious Diseases @roup speciali3ed trials register (.ebruary )//&), The -ochrane -entral 4egister of -ontrolled Trials (The -ochrane Gibrary !ssue %, )//&), MJDG!DJ (%611 to .ebruary )//&), JMB$#J (%6I/ to .ebruary )//&), G!G$-# (.ebruary )//&)"he #ochrane $atabase of %ystematic &eviews )//& !ssue 5 &ain results#i= trials of &6& patients met the inclusion criteria #teroids were associated with fe!er deaths (relative ris( A44B />6, 6&' confidence interval A-!B /1& to /6>) and a reduced incidence of death and se#ere residual disability (44 /&I, 6&' -! /2I to /II) #ubgroup analysis suggests an effect on mortality in children (44 />>, 6&' -! /1) to /61) but the results in a smaller number of adults are inconclusive (44 /61, 6&' -! /&/ to %I5) There is little evidence that the severity of disease influences the effects of steroids on mortality"he #ochrane $atabase of %ystematic &eviews )//& !ssue 5 n' steroi# *s control Deat("he #ochrane $atabase of %ystematic &eviews )//& !ssue 5JJ47 61H2/%: 2%I6' -J47 %%1H)65: 2651'$447 2651'-2%I6': >&>'++!: 101.17273 14.5 n' steroi# *s control Deat( or #isabling resi#ual #e6icits "he #ochrane $atabase of %ystematic &eviews )//& !ssue 5JJ47 )2HI>: )155'-J47 5/HII: 5&5&'$447 5&5&'-)155': %6/%' ++!: 101.19113 2.4 n' steroi# *s control: strati6ie# b' ageDeat(++!3 14.2"he #ochrane $atabase of %ystematic &eviews )//& !ssue 5++!3 11.4 n' steroi# *s control: strati6ie# b' se*erit'Deat("he #ochrane $atabase of %ystematic &eviews )//& !ssue 5++!3 7.8++!3 15 Conclusions$dKunctive steroids might be of benefit in patients with TBM 'o data are available on the use of steroids in HIV positive persons .uture placebo-controlled studies should include patients with *!+ infection and should be large enough to assess both mortality and disability $dverse effects were reported in only four small trials, and in these cushingoid facies appear to be the most common %ide effects were more pronounced in studies using high doses of steroids. "he #ochrane $atabase of %ystematic &eviews )//& !ssue 5 De9amet(asone 6or t(e !reatment o6 !uberculous &eningitis in #olescents an# #ults@uy J Thwaites, M4-8, Dguyen Duc Bang, MD,D Jngl C Med 2&%,%>7 %>5%-%>&% wwwneKmorg october )%, )//5 &et(o#s0e performed a randomi3ed, double-blind, placebo-controlled trial in +ietnam in patients over 1 years of age who had tuberculous meningitis, with or without HIV infection, to determine whether adKunctive treatment with de$amethasone reduced the ris( of death or severe disability after nine months of follow-up. 0e conducted prespecified subgroup analyses and intention-to-treat analyses' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&% &et(o#s grade I TBM 7@lasgow -oma #cale of %& with no focal neurologic signs (possible range, 2-%&, with higher scores indicating better status) grade II TBM 7 @lasgow -oma #cale of %%-%5, or of %& with focal neurologic signs grade III TBM 7 @lasgow -oma #cale of %/ or less' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&% &et(o#s ----De9amet(asone #osage grade !! or !!! disease7 IV treatment for four wee+s (/5 mgH(gHday for wee( %, /2 mgH(gHday for wee( ), /) mg H(gHday for wee( 2, /% mgH(gHday for wee( 5) and then oral treatment for four wee+s, starting at a total of 5 mgHday and decreasing by % mg each wee( grade ! disease7IV therapy for two wee+s (/2 mgH(gHday for wee( %, /) mgH(gHday for wee( )) and then oral therapy for four wee+s (/% mgH(gHday for wee( 2, then a total of 2 mgHday, decreasing by % mg each wee()' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&% Results $ total of &5& patients , age ;%5 years, were randomly assigned to receive either de=amethasone ()>5 patients) or placebo ()>% patients) Median follow-up was )>5 days (range, )I-55) days) ,rimary outcome- death or severe disability nine months afterrandomi3ation %econdary outcome- coma-clearance time, fever-clearance time, time to discharge from the hospital, time to relapse, the presence of focal neurologic deficit nine months after randomi3ation' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&% ,rimary outcome' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&%++!311 ,rimary outcome' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&% ,rimary outcome' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&%P *alue 1.44 1.981.57 1.11 %econ#ar' Outcome De9amet(asone group Placebo group P *alueTime to fever clearance (days) 6 %% 1.14Time to coma clearance (days) 6 %% /)2Time to hospital discharge (days) 55 &5 /&>4elapse occurred (') %& %>> /5)Time to relapse (days) 5% 2I /%)8atients who had hemiparesis or paraparesis at baselinehemiparesis resolved (') >&I%%/&%paraparesis resolved (')1>6 I%I/518atients without hemiparesis or paraparesis at baselinehemiparesis occurred (') 1) 5> /5Iparaparesis occurred (')5& 5) /I6$dverse rate (') 1>6>6/1.112%econ#ar' Outcome :it( ;I< pt :it(out ;I< pt P *alueMortality rate (') 1&2 (15H6I) )I5 (%)5H521) =1.111' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&%%econdary outcome ' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&% ConclusionThe show that adKunctive treatment with de=amethasone impro#ed sur#i#al in patients over %5 years of age with tuberculous meningitis, but when the outcome measure was broadened to death or severe disability, there was no significant benefit de=amethasone did not affect the incidence or resolution of hemiparesis, paraparesis, or ?uadriparesis, which are the most common causes of severe disability due to tuberculous meningitis De=amethasone may improve outcomes by reducing the fre?uency of adverse events --se#ere clinical hepatitis' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&% ConclusionThe treatment effect of de=amethasone was homogeneous across HIV subsets, and stratified subgroup analysis showed that de=amethasone was associated with a reduction in the ris( of death that was not significant (8://I) however, that de=amethasone is safe and may be of benefit in this group of patients ' (ngl ) *ed )//5, 2&%(%>)7 %>5%-%>&% Treatment of TuberculosisAmerican Thoracic Society, CDC, and InfectiousDiseases Society of AmericaMorbidity and Mortality Weekly Report (MMWR !une "#, "##$ % &ol' (" % )o' RR*++ MMWR "##$, -ol' (".RR*++' MMWR "##$, -ol' (".RR*++' #tudy -orticosteroid Dosage-hotmong(ol %661Pre#nisolone oral on tapering daily dosage for five wee(s (w( %, 1/ mg, w( ), 5& mg, w( 2, 2/ mg, w( 5, )/ mg, w( &, %/ mg)@irgis %66%De9amet(asone given im (%) mgHday to adults and I mgHday to children weighing less than )& (g) for three wee(s and then tapered during the ne=t three wee(s), ++!315)//5 DJCM@read !(8://))@read !!, !!!(8:/>5, 8:/6%)total 8:/)$dverse rate )//5 DJCM01adverse rate (P3 1.112)23severe hepartitis 456789:(P3 1.114) Thank you for your attention