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Case Discussion

T O PI C : T U B E RC U LOU S M E N IN GIT IS
( T BM )
B A IT I L AT I Q
M ON DAY, N OV E MB E R 16 T H 20 15
Background
Tuberculous meningitis (TBM) is one of the most common
forms of central nervous system infections,especially in
many developing countries where tuberculosis remains
highly endemic, and it is a severe form of extrapulmonary
tuberculosis.

Most of patients suffer from the adverse squelae of the


disease.

Beneficial effects of steroid have been documented in


tuberculous meningitis, but there is no evidence regarding
the most effective dose
R.Galimi.Eur Rev Med Pharmacol Sci. 2011;15:365-86
Case Illustration
An 11 years old girl
Chief complain:
Deterioration of conciousness since 2 hours prior to
admission
History of present
illness

2 weeks p.a. Day of


Subtle fever admission
(temperature wasnt
measured) Fever (+), no
Cough (+) vomiting/diarhea, no
Patient was seizure
admitted to RS Pasar Deterioration of
Rebo for pulmonary consiousness
disease discharge
for personal reason
History of past illness

No trauma
No ENT infection, other
diseases e.g.
measles/varicella
Family history

Close contact of
tuberculosis is denied
No history of seizures
No history of bleeding
disorder
Pregnancy and birth

Immunization

Growth and development

Nutrition
No Completed Within Family
Family food
medication normal limit
limit
was taken
during
pregnancy,
no infection
First child
At
At term,
term,
delivered
spontaneou
sly, birth
weight 2800
g, birth
length 48
cm
No history
cyanosis or
icteric
Physical examination
Vital Signs

GCS E1M3V1
No pale
No dyspnea or cyanosis
Heart rate : 110 beats/minute,
regular, weak pulse
Respiratory rate :22 breaths/minute,
regular
Temperature : 37,8 ooC
Physical examination
No
No deformities
deformities Pale
Pale conjunctivae
conjunctivae -/--/- No
No paresis
paresis of
of cranial
cranial Neck
Neck stiffness
stiffness (+)
(+)
icteric
icteric sclera
sclera -/-,
-/-, nerve
nerve
isocoric
isocoric pupils
pupils diameter
diameter
33 mm
mm // 3mm,
3mm, light
light
reflex
reflex +/+
+/+ normal,
normal,
dolls
dolls eye
eye movement
movement +/ +/
+,
+, positive
positive papil
papil
edema
edema

Face &
Head Eyes Neck
ENT

Heart
Heart within
within normal
normal No
No organomegaly
organomegaly Warm
Warm extremities,
extremities, good
good Normal
Normal
Lungs
Lungs within
within normal
normal Normal
Normal bowel
bowel sounds
sounds perfusion
perfusion
physiological
physiological
reflexes
reflexes + +
extremities,
extremities,
Babinsky
Babinsky reflex+/+,
reflex+/+,
clonus
clonus -/-,
-/-, spastic
spastic +/+
+/+
Brundzinsky/Kernig/Las
Brundzinsky/Kernig/Las
eque
eque (-)
(-)
Abdome Extremi
Thorax Skin
n ties
Laboratory findings
Laboratory ( Sept 25th,
findings 2015)
Hemoglobin 10,8
(g/dL) 32,8%
Hematocrite (%) 66,5/20,5/30,5
MCV/MCH/MCHC
Leucocyte (/L) 3,720
Platelet (/L) 114,000
Ur/Cr (g/dL) 12,7/0,142
GDS (mg/dL) 145
Diff count (%) 0/0/0/69/27/4
Na/K/Cl (mEq/L) 140/4,8/95
Cerebrospinal fluid
(CSF) Analysis
No color, clear
Cell : 188
PMN : 158/ul
MN : 30/ul
Nonne: negative
Pandy : positive
Protein: 30 mg/ul
Glucose: 49 mg/dl
Cl : 106 mEq/L
Anthropometric status

Body weight (BW) = 21 kg ( <P5 CDC)


Body height (BH) = 140 cm ( P5<x<P10
CDC)
BW/BH = 21/40 kg (50,5%)
Upper arm circumference= 11 cm
Baggy pants or other signs of severe
malnutrition (+)
Diagnosis

Tuberculous meningitis dd/ bacterial


Severe malnutrition
Treatment
Diagnostics :
Head CT Scan with contrast, chest x-ray,
consult respirology division and neurosurgery
Therapeutics :
SIMV Mode 13/5 RR 20 FiO2 30%
Liquid formula 8x250 mL/NGT
Paracetamol 3x250 mg IV
Ceftriaxone 2x1 g IV (100 mg/kg/day)
Dexamethasone 3x7 mg IV (0.5
mg/kgBW/day)
Mannitol 20% 50 mL/8 hours (0,5 g/kgBW/x 3
days)
Head CT Scan
Lateralis ventricles
bilateral and third
ventricle widening
Periventricular edema
Enhancement at basal
Consultation
Respirology
TBM still cant be excluded
Check mantoux test, start antituberculosis drugs

Neurosurgery
Head CT Scan enhancement at basal TBM
Reconsult after the patient is stabilized
Analysis of
cases
Tuberculous infection (TB)
Tuberculosis remains one of the most prevalent infections
worldwide.
9,27 million people/ year new infected TB
The most incidence of TB in the world: India, China, Indonesia

TB infection in central nervous system


(CNS)
CNS involvement is a life-threatening extrapulmonary

manifestation of tuberculosis
Tuberculous meningitis is rare before 3 months of age
but increases
during the first 5 years of life
TB infection in CNS 2-5% TB infection
Pediatric Department Cipto Mangunkusumo Hospital
Cherian A.African Health Sci.2011;11:116-25.
(2006-2010) 35 cases of TB meningitis
Debora, dkk.. Pediatr indones. 2011;51:260. Abstrak.
Risk factor for TB infection

Environme
Genetic Immunity
nt

Individual Age Prevalence


Family history Nutritional status
HIV co-infection Closed contact
Cancer adult with active
Immunosuppresive agentTB Infection

Cherian A,. Central nervous system tuberculosis, African Health Sci. 2011;11:116-25.
Debora, dkk. Profile of tuberculous meningitis patient in child health CMH. Pediatr indones. 2011;51:260. Abstrak.
Well GTJ, dkk. Pediatrics. 2009;123:1-8.
Be NA, dkk. Pathogenesis of central nervous system tuberculosis. Curr Mol Med.
209;9:94-9.
Clinical manisfestation of TB
meningitis
Not spesific
Three phases in TBM
Prodrom 2-3 weeks
al Malaise, cephalgia, fever, personality change

Meningiti Meningismus, cephalgia, vomiting, cranial nerve


s paresis

Accelerated of disease
Paralitic Stupor, coma, convulsion, hemiparesis

Severity of TBM :
1 GCS 15 without focal neurological deficit; generally poor health, irritability,
and
apathy. In young infants fever, cough, altered consciousness, bulging
anterior
fontanel, and generalized tonic-clonic seizures.
2 GCS 11-14 or GCS 15 with unilateral or bilateral cranial nerve deficits result
from the
basilar meningitis
Bathla G. Singapore Med J. 2011;52:124-30.
3 GCS < 11 or depression of consciousness,
Rahajoe NN, Tuberkulosis dalam keadaan convulsions, possibly
khusus. Dalam: Pedoman nasional tuberkulosis anak.
Algorithm for deterioration
of conciousness

KC Chan, et al.HK J Paedtr.2013;18:105-18


Clinical manisfestation
of TB meningitis
Spinal cord involvement by pressure from vertebral
abscess and by the production of arachnoiditis.
Hyponatremia SIADH or cerebral salt-wasting
syndrome.

Tauber MG and Urs BS. Bacterial infection of nervous system. In: Swaiman, KF.Pediatric Neurology: Principles
and Practice.2012: 1255-57.
Clinical manisfestation
of TB meningitis
Cipto Mangunkusumo Hospital Research (CMH) 35
patients with TB meningitis (2006-2010)
Prolonged fever (18/18), depression of conciousness
(17/18), convulsion (14/18)
Well (2009) 554 children with TB meningitis:
Not spesific clinical manisfestation (58%), lost of
weight (91%), depression of conciousness (96%),
neurological deficit (63%), meningeal sign (98%),
elevated of intracranial pressure (23%).5
Debora, dkk. Profile of tuberculos meningitis patient in child health department CMH. Pediatr indones.
2011;51:260.
Well GTJ, Paes BF, Terwee CB. Pediatrics. 2009;123:1-8.
Cerebrospinal fluid analysis
CSF analysis

Spesific elevated of cell numbers (10-500 cells/l,


lymphocytosis), elevated protein (100-300mg/dl), low glucose
(<50 mg/dl).
Thillotamal (1994) 85% cases with pleocytosis, dominated with
lymphocyte (54%) or PMN (46%)
BTA stain

Positive 13% TB meningitis


18 cases of TB at RSCM negative results
Problem: difficult technique of examination (centrifuge 10-20 ml
CSFs)
Culture of M. tuberculosis

Definitive diagnosis
Baveja (2008) Culture (+) 27,3% cases of TB meningitis, 18%
resistance > 1 drugs

Baveja CP,dkk. Multi drug resistant tuberculous meningitis in pediatric age group. Iran J Pediatr.
2008;18:309-14.
Yaramis A, dkk. Central nervous system tuberculosis in children: a review of 214 cases. Pediatrics.
Radiograph examination
Head CT scan or MRI with
contrast

Ventricular dilatation or
hydrocephalus (87% cases),
infarct (28%),
tuberculoma,enhancement
of basal.
Enhancement of basal
and meningen sensitive
indicator 90% TB
meningitis.
Enhancement of basal or
tuberculoma sensitifity
89,2% and specificity
100% TB meningitis Saharso D,dkk. Infeksi susunan saraf pusat.Buku ajar
neurologi anak 2000. h.339-85.
Head CT-scan 18 patients Well GTJ, dkk.. Pediatrics. 2009;123:1-8.
TB meningitis at CMH Bathla G, dkk. Manifestation of cerebral tuberculosis.
Singapore Med J. 2011;52:124-30.
enhancement of basal
(10/14) and hidrocephalus
Examination of tuberculous
infection
Gastric lavage BTA smears and culture

Positive for 10% cases


M. tuberculosis culture 3-8 weeks

Thorax examination

Hillus enlargement (92%), lung parenchym


involvement (70%)
Subjective
Uji tuberkulin

Mantoux test (PPD-RT 23 intracutaneus)


Senstivity and spesificity 90% detection of TB
infection
Jaramillo E, dkk. Tuberculosis in children. Int J Tuberc Lung Dis. 2001;5:594-603.
Rahajoe NN,dkk. Tuberkulosis dalam keadaan khusus.. 2008. h. 65-92.
Treatment of TB
meningitis
The use of corticosteroids is advocated, particularly in
patients with a decreased level of consciousness,
papilledema, focal deficits, or tuberculomas.
A course of prednisone or dexamethasone for 6 weeks,
with subsequent tapering over several weeks, is the most
common regimen recommended.

Tauber MG and Urs BS. Bacterial infection of nervous system. In: Swaiman, KF.Pediatric Neurology: Principles
and Practice.2012: 1255-57.
Treatment of TB
meningitis
In the large study in Vietnam, patients with mild disease
received intravenous dexamethasone
0.3 mg/kg/day 1 week
0.2 mg/kg/day 1 week
Four weeks of tapering oral therapy
For patients with more severe TBM, intravenous
dexamethasone was given for:
Four weeks (1 week each of 0.4 mg/ kg/day, 0.3 mg/kg/day,
0.2 mg/kg/day, and 0.1 mg/kg/day),
Followed by four weeks of tapering oral dexamethasone
therapy.

Marc GE, Edward DC. Hindawi. 2011.


GE Thwaites, DB Nguyen, HD
Complication and
prognosis
The most common complication TB meningitis
hydrocephalus.
The mortality of tuberculous meningitis is 1020%.
Major sequelae occur and are most common in children in
stage III.
Hemiparesis, mental retardation, and seizures
Involvement of the hypothalamus and basal cisternae
endocrinopathies (diabetes insipidus,growth retardation,
sexual precocity, and obesity)

Tauber MG and Urs BS. Bacterial infection of nervous system. In: Swaiman, KF.Pediatric Neurology: Principles
and Practice.2012: 1255-57.
Population
Children with TBM

Intervention
High dose steroid therapy

Comparison
Low dose steroid therapy

Outcome
Complications
Introduction
Background

The high incidence of TBM


The reported mortality rate in TBM is 15
75%.
Adverse sequelae occur in 1085% of
patients.
Though the beneficial effects of steroids have
been documented in TBM, to our knowledge
there is no direct evidence to guide selection
of the dose of prednisolone to be used
Objective

To evaluate the efficacy of steroids in various


doses and durations in TBM patients.
Material and methods(1)
Type of Prospective study
study
Time Wadia hospital for
and Children, Mumbai, India
May 2009 to May 2011
place
Patients with ages of 4
months to 14 years
Subject diagnosed with TBM
Material and methods(2)
Age 4 months to 14
Inclusio years
n Diagnosed with TBM
criteria

Exclusi
on Not clear
criteria
Material and methods(3)
Comprehensiv A diagnosis of TBM
e clinical was based on the
assessment uniform research
Routine case All patients were
randomly assigned to 3
investigations definition: groups by blinded
CSF was Definite health care worker
evaluated in Group I
Probable
all patients Prednisolone 2
mg/kg/day for 4 weeks
including
TBM was staged Group II
(macroscopic Prednisolone 4
according to revised
appearance, mg/kg/day for 1 week
British MRC criteria
total and and 2 mg/kg/day for 3
as: weeks
differential cell
Stage I Group III
count,protein,
glucose, Prednisolone 4
Stage II mg/kg/day for 4 weeks
chloride, Gram
Stage III
stain, India ink
All patients Neurological imaging
examination, and deficits was
auramine BO^ diagnosed evaluated after 3
fluorescence with TBM were months
microscopy and treated with a
culture for M. standard short-
Results(1)
Results(2)
Results(3)
Discussion(1)
Prednisolone at 4 mg/kg/day for 1 month had no additional benefit in
terms of prevention of hydrocephalus or in decreasing the incidence
of new tuberculomas,new infarcts, mortality and morbidity over a
period of
3 months.
In this study we did find that prednisolone at a dose of
4 mg/kg/day for 1 week followed by 2 mg/kg/day for the next
3 weeks and then tapering, was associated with a lesser
incidence
of tuberculomas and new infarcts, though hearing loss was
higher
in these patients
Discussion(2)
Study limitations: lack of control group without
steroid therapy and lack number of subjects
Conclusion
Prednisolone at 4 mg/kg/day for 1 month does not offer
any benefit in patients with TBM and can in fact be
detrimental due to an increased risk of optic disturbances
and adverse effects from steroid treatment.
However, prednisolone at 4 mg/kg/day for 1 week
decreases the incidence of new tuberculomas and new
infarcts on follow-up at 3 months.
This finding needs to be confirmed in further studies.
Mortality of patients with TBM does not vary with dose or
duration of steroids
Critical
appraisal
Are the results of the trial valid?
What were the results?
Importance
Are test characteristics presented?
For accuracy of the test we can use sensitivity and specificity
and how the test performs in the population being tested and
is reflected in predictive values (also called post-test
probabilities)
Comment Yes
Will the results help me in caring for
my patient?
Applicability
Were the methods for performing the test Yes
described in sufficient detail to permit
replication?
Comment Applicability