Supervisor :
Dr. dr. Noni N Soeroso, M.Ked(Paru), Sp.P (K)
Journal Reading
Thursday, 24 January 2019
Journal Reading
Name:
Aknowledgement for our supervisor :
1. Felicia
2. Muhammad Faiz Tanjung
Dr. dr. Noni N Soeroso, M.Ked(Paru), Sp,P (K)
3. Yandri Erwin Ginting
Pulmonology and Respiratory Medicine Department
4. Dewi Sartika Medical Faculty of Sumatera Utara
5. Ikke Ajeng Arum Sari Sinaga RSUP HAM/RS USU Medan
6. Sastri Huya Ahwini
7. M Darry Aprilio Pasaribu
8. Ananta Septriandra Ginting
9. Sri Veronica Chindy Sihombing
10. Cindy Clarissa Sirait
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Abstract
Headline!
Introduction
Pathogenesis of Tuberculous Meningitis (TBM)
Host and Pathogen Genetics in TBM
Laboratory diagnosis of TBM
Treatment of TBM
HIV-associated TBM
Adjunctive anti-inflammatory therapies
Conclusion
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ABSTRACT
+ Tuberculous meningitis (TBM) is the most severe form of infection caused
by Mycobacterium tuberculosis in the central nervous system, causing
death or disability in more than half of those infected.
+ The diagnosis of TBM remain difficult as its presentation is non-specific
and may mimic other causes of chronic meningoencephalitis. Rapid
recognition of TBM is crucial, as delays in initiating treatment are
associated with poor outcome.
+ The optimal therapy of TBM has not been established in clinical trials.
+ Laboratory methods to improve the rapid diagnosis of TBM are urgently
required.
+ The use of biomarkers to improve the rapid diagnosis of TBM warrants
further investigation.
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INTRODUCTION
+ TBM is the most frequent form of central nervous system tuberculosis.
+ CNS disease accounts for only 5% of all cases of extra-pulmonary
tuberculosis and peak incidence is children under 4 years of age.
+ TBM is classified into three grades of severity according to the British
Medical Research Council TBM grade.
+ Grade 1 TBM (GCS 15 + no focal neurology)
+ Grade 2 TBM (GCS 15 + focal neurology or GCS 11-14)
+ Grade 3 TBM (GCS ≤ 10)
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Clinical features of tuberculous meningitis
Pathogenesis of Tuberculous Meningitis
3 pathological processes account for the commonly observed
neurological deficits
+ The exudate may obstruct CSF flow resulting in hydrocephalus
+ Granulomas can coalesce to form tuberculoma or abscesses
resulting in focal neurological signs.
+ An obliterative vasculitis can cause infarction and stroke
syndromes.
+ The release of M. tuberculosis into the subarachnoid space results in a
local T lymphocyte-dependent response, characterized by caseating
granulomatous inflammation.
+ TNF-α is thought to be important in granuloma formation.
Host and Pathogen Genetics in TBM
LTA4H
Increase human susceptibility
to tuberculosis
TIRAP
SNP 558T
Increase the possibility of
dissemination and TBM.
TLR 2
Laboratory Diagnosis of TBM
Laboratory Diagnosis of TBM
Treatment of TBM
Drug Dose in Children Dose in Adults Duration Common Side Effects
Rifampicin (R) 10–20 mg/kg/day 450 mg (weight <50 12 months Orange discolouration of
(maximum 600 kg) bodily fluids, hepatoxocity,
mg/day) 600 mg (weight <50 gastrointestinal symptoms,
kg) headache, drowsiness
Isoniazid (H) 10–20 mg/kg/day 300 mg 12 months Hepatotoxicity, peripheral
(maximum 500 neuropathy (with high
mg/day) doses), optic neuropathy,
gastrointestinal symptoms
Pyrazinamid (Z) 15–30 mg/kg/day 1.5 g (weight <50 2 months Hepatoxicity
(maximum 2 g/day) kg)
2 g (weight <50 kg)
Ethambutol (E) 15–20 mg/kg/day 15 mg/kg 2 months Optic neuritis, red/green
(maximum 1 g/day) colour blindness, peripheral
neuritis
Treatment of TBM
+ 2 months of RHZE (initiation phase) and 10 months of RH (continuation
phase). (NICE Guidelines)
+ Two recent studies have investigated the role of intensified therapy for
TBM (adding fluoroquinolones–levofloxacin, gatifloxacin, ciprofloxacin)
+ Study in Vietnam shows that worse outcome with low or high exposure of
fluoroquinolones than with intermediate exposure.
+ Study in Indonesia shows that high-dose rifampicin (600 mg) and high
(800 mg) or standard (400 mg) dose of moxifloxacin resulted in an
increase in plasma and CSF levels and was associated with reduced
mortality.
HIV Associated TBM
+ The treatment of TBM with HIV is complicated by the need to treat
both conditions simultaneously, with the attendant drug
interactions and toxicities, and the risk of immune reconstitution
inflammatory syndrome (IRIS), a potentially fatal condition.
+ There is still controversial whether it is better to initiate the ART
earlier.
Adjunctive Anti-Inflammatory Therapies
+ Trial in Viatnemese adults showed a reduction in mortality but not
in neurological disability in patients treated with dexamethasone,
compared with placebo. This trial only improve the survival until at
least 2 years of follow up but failed to demonstrate 5 year survival
benefit
+ Two recent studies have examined the possible benefits of aspirin
in TBM treatment. Aspirin had no impact on morbidity
(hemiparesis and developmental outcome) or mortality.
Conclusion
+ The current rapid diagnostic methods for TBM (methods to improve the
sensitivity of smear microscopy, the development of automated nucleic
acid amplification platforms and the use of novel biomarkers are
inadequate but some recent developments have shown promise.
+ The ongoing trials of intensified therapy with rifampicin and
fluoroquinolones are promising and needs further investigation.
+ Adjunctive corticosteroids appear to improve survival in HIV-negative
patients with TBM, the role of other adjunctive therapies such as
thalidomide and aspirin remain controversial.
Thanks!
Any questions?
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