CHAPTER 1

INTRODUCTION

Global tuberculosis (TB) control focuses on pulmonary tuberculosis (PTB) to prevent

transmission and reduce the number of new cases. Thus, in surveillance, TB cases are classified
as pulmonary TB whenever lungs are involved, irrespective of any additional involvement of
other organs. Therefore, extrapulmonary tuberculosis (EPTB) is a collective term for diverse
manifestations affecting any other anatomic site than the lung parenchyma and the
tracheobronchial tree. In the European Union and European Economic Area, 22% of TB
patients notified in 2010 only had extrapulmonary manifestations. EPTB is more common in
immunocompromised individuals, especially people living with human immunodeficiency
virus (HIV), but also females and different ethnic groups; for example, in the United Kingdom
all non-white ethnic groups were associated with EPTB. Some EPTB forms, such as meningitis
cause severe disease.1 After scrofula, tuberculous meningitis is the most common form of
childhood EPTB. In 2012, a paediatric referral centre in South Africa reported that tuberculosis
was a greater cause of meningitis than Streptococcus pneumoniae, Neisseria meningitides, and
Haemophilus influenzae combined, affecting 22% of children.2 Tuberculous meningitis affects
all age groups, but is especially common in young children and in people with untreated HIV
infection.3

Tuberculous meningitis represents roughly 1% of all cases of tuberculosis, but is

disproportionately important because it kills or severely disables about half of the people
affected.3 Reported case fatality ranges from 20 to 69% in different settings worldwide with up
to half of surviving patients presenting with irreversible sequelae, including paraplegia,
blindness, motor and cognitive deficits.1 Thus, it is important to diagnose tuberculous
meningitis at an early stage, although diagnosis is difficult because clinical features are non-
specific and laboratory tests are insensitive. Giving a proper treatment to the children affected
is very important so that they will be prevented from having irreversible sequelae, and even
death.

1
 CHAPTER 2

LITERATURE REVIEW

A. DEFINITION AND EPIDEMIOLOGY

Tuberculosis of the central nervous system (CNS) is the most serious complication in
children and is fatal without prompt and appropriate treatment. Tuberculous meningitis usually
arises from the formation of a metastatic caseous lesion in the cerebral cortex or meninges that
develops during the lymphohematogenous dissemination of the primary infection.4 In a simpler
words, tuberculous meningitis is when the tuberculosis bacteria invade the membranes and
fluid surrounding the brain and spinal cord.

National TB surveillance in Germany captures extrapulmonary tuberculosis (EPTB)

manifestations as main and secondary site of disease (whereby only up to two sites can be
recorded). If two different extrapulmonary sites are affected, physicians are asked to classify
the more severely affected one as main site of disease. They did some analysis of German TB
notification data between 2002 and 2009 using information on both main and secondary disease
site to describe all individual EPTB forms. They also assessed factors associated with
meningitis using multivariable logistic regression. They reported that of 46,349 TB patients,
422 (0.9%) had meningitis as main or secondary site, and 288 (0.6%) had meningitis as the
main site only. Multivariable analysis showed that meningitis was more likely in children
younger than five years and between five and nine years-old.1 As mentioned before,
tuberculosis was a greater cause of meningitis than Streptococcus pneumoniae, Neisseria
meningitides, and Haemophilus influenzae combined, affecting 22% of children.2

Tuberculous meningitis was most frequent in children, affecting 3.9% of those younger
than five years old, 2.2% of the five to nine year-olds, 1.3% of the 10 to 14 year-olds, and 0.8%
of those aged 15 years old and older. Tuberculous meningitis was also more frequent among
female (1.1%) than among male patients (0.8%).1 In white populations in the USA, tuberculosis
rates are highest among the elderly who acquired the infection decades ago. In contrast, among
nonwhite populations, tuberculosis is most common in young adults and children < 5 year of
age. The age range of 5-14 years is often called the favored age because in all human
populations this group has the lowest rate of tuberculosis disease.4

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B. ETIOLOGY AND RISK FACTORS

The causative organism for tuberculous meningitis is Mycobacterium tuberculosis.

Mycobacterium tuberculosis is an aerobic gram-positive rod that stains poorly with
hematoxylin and eosin because of its thick cell wall that contains lipids, peptidoglycans, and
arabinomannans. They are non-motile and do not form spores. They can appear beaded or
clumped in stained clinical specimens or culture media. These mycobacteria grow best at 37-
41 C, produce niacin, and lack pigmentation. A lipidrich cell wall accounts for resistance to
the bactericidal actions of antibody and complement. A hallmark of all mycobacteria is acid
fastness the capacity to form stable mycolate complexes with arylmethane dyes such as
crystal violet, carbolfuchsin, auramine, and rhodamine. Once stained, they resist decoloration
with ethanol and hydrochloric or other acids. 4

Mycobacteria grow slowly, with a generation time of 12-24 hours. The growth can be
detected in 1-3 weeks in selective liquid medium, and drug susceptibilities can be determined
in an additional 3-5 days. Once mycobacterial growth is detected, the species of mycobacteria
present can be determined within hours using high-pressure liquid chromatography analysis,
based on the fact that each species has a unique fingerprint of mycolic acids. The presence of
M. tuberculosis in clinical specimens sometimes can be detected directly within hours using
nucleic acid amplification (NAA) tests (including polymerase chain reaction) that employ a
DNA probe complementary to mycobacterial DNA or RNA. Data from children are limited,
but the sensitivity of some NAA techniques is similar to that for culture for pulmonary
tuberculosis and is better than culture for extrapulmonary disease. Restriction fragment length
polymorphism (RFLP) profiling of mycobacteria is a helpful tool to study the epidemiology of
tuberculosis.4

The global burden of tuberculosis continues to grow owing to several factors, including
the impact of HIV epidemics, population migration patterns, increasing poverty, social
upheaval and crowded living conditions in developing countries and in inner city populations
in developed countries, inadequate health coverage and poor access to health services, and
inefficient tuberculosis control programs. In the USA, most children are infected with
Mycobacterim tuberculosis in their home by someone close to them.4

3
Table 2.1. Groups at high risk for acquiring tuberculosis infection and developing disease in
countries with low incidence4

The risk factor for tuberculous meningitis is underlying conditions influencing

immunocompetency, especially HIV infection. Other risk factors for developing tuberculous
meningitis are vitamin D deficiencies, diabetes mellitus, malignancy and recent corticosteroid
treatment.1 The strains of the Mycobacterium tuberculosis also contributes to the development
of tuberculous meningitis. Some studies have reported that strains from the Euro-American
lineage of Mycobacterium tuberculosis were significantly less likely than those of the Indo-
Oceanic or East Asian Beijing lineages to cause meningitis.3

C. PATHOGENESIS

Mycobacterium tuberculosis transmits from person to person through a droplet nuclei.

Transmission rarely occurs by direct contact with an infected discharge or a contaminated
fomite. The chance of transmission increases when the patient has a positive acid-fast smear of
sputum, an extensive upper lobe infiltrate or cavity, and severe and forceful cough.
Environmental factors such as poor air circulation is also a factor that enhances the
transmission of Mycobacterium tuberculosis.4

4
 Latent tuberculosis infection (LTBI) occurs after the inhalation of infective droplet
nuclei containing Mycobacterium tuberculosis. A reactive tuberculin skin test (TST) and the
absence of clinical and radiographic manifestations are the hallmark of this stage. The term
tuberculosis refers to the disease that occurs when signs and symptoms or radiographic changes
become apparent. Untreated infants with LTBI have up to a 40% likelihood of developing
tuberculosis, with the risk for progression decreasing gradually through childhood to adult
lifetime rates of 5-10%. The greatest risk for progression occurs in the first 2 years after the
infection of Mycobacterium tuberculosis.4

The primary complex of tuberculosis includes local infection at the site of entry and the
regional lymph nodes at that area. The lungs are the site of entry at > 98% of cases. The hilar
lymph nodes usually involved when the site of entry is in the lungs. The tubercle bacilli
multiply within the alveoli and alveolar ducts. Some of them are successfully killed, but some
of them survived within nonactivated macrophages, which carry them through lymphatic
vessels to the regional lymph nodes.4

Tuberculosis infection is associated with a humoral antibody response, which appears

to play little role in host defense. The tissue reaction in the lung parenchyma and lymph nodes
intensifies over the next 2-12 weeks as the organisms grow in number and tissue
hypersensitivity develops. That is when cell-mediated immunity is develops. The parenchymal
portion of the primary complex often heals completely by fibrosis or calcification.
Occasionally, this portion continues to enlarge, resulting in focal pneumonitis and pleuritis. If
caseation is intense, the center of the lesion liquefies and empties into the associated bronchus,
leaving a residual cavity.4

5
 Figure 2.1. Overview of the immune response in tuberculosis4

During the development of the primary complex, known for the Ghon complex, which
is the combination of a parenchymal pulmonary lesion and a corresponding lymph node site,
tubercle bacilli are often carried to most tissues of the body through the blood and lymphatic
vessels. Bacterial replication is more likely to occur in organs with conditions that favor their
growth, such as the lung apices, brain, kidneys, and also bones. Disseminated tuberculosis
occurs if the number of circulating bacilli is large and the hosts cellular immune response is
not adequate.4

The pathologic events in the initial tuberculosis infection seem to depend on the balance
among the mycobacterial antigen load; cell-mediated immunity, which enhances intracellular
killing; and tissue hypersensitivity, which promotes extracellular killing. Thus, when the
degree of tissue sensitivity is low, as occurs in the case in infants or immunocompromised
persons, the reaction is diffuse and the infection is not well contained, leading to dissemination
and local tissue destruction.4

The time between the initial infection and the clinically apparent disease is variable.
For example, disseminated and meningeal tuberculosis are early manifestations, often

6
occurring within 2-6 months of acquisition, while lesions of the bones and joints occurs after
several years. Extrapulmonary manifestations develop in 25-35% of children with tuberculosis,
compared with about 10% of immunocompetent adults with tuberculosis. The risk for
dissemination of Mycobacterium tuberculosis is very high in persons with HIV infection.4 The
time between the initial infection and the manifestation in several organs can be predicted
through a timetable named The Wallgren Timetable which is shown below.

Figure 2.2. The Wallgren Timetable5

The progression of tuberculous meningitis from a pulmonary tuberculosis depends on

several factors, including the strain of the Mycobacterium tuberculosis itself. Findings from
epidemiological studies lend support to the hypothesis that some strains of Mycobacterium
tuberculosis are more likely than others to cause tuberculous meningitis. A case-control study
in Vietnam reported that strains from the Euro-American lineage of Mycobacterium
tuberculosis were significantly less likely than those of the Indo-Oceanic or East Asian Beijing
lineages to cause meningitis, although they could not provide a mechanistic explanation for
this finding. The genes that enable the bacteria to invade through the blood-brain barrier have
been investigated with transposon mutants and in-vitro and in-vivo models, and it told us about

7
the identification of one bacterial gene, Rv0931c (also known as pknD), that encodes a
serine/threonine protein kinase necessary for brain endothelial invasion.3

The pathogenesis of tuberculous meningitis has been described as a two-step

pathogenesis. The first step of the development of tuberculous meningitis starts when the
primary infection of Mycobacterium tuberculosis in the human lung undergoes a
lymphohematogenous dissemination to the cerebral cortex. The metastatic caseus lesion then
forms some foci named Rich foci, after the original pathological studies of Rich and
McCordick.3,4

The second step of the development of tuberculous meningitis begins when the Rich
foci start to increase in size and discharges small number of tubercle bacilli into the
subarachnoid space. It then forms a gelatinous exudate that infiltrates the corticomeningeal
blood vessel, producing inflammation, destruction, and subsequent infarction of cerebral
cortex. It also interferes with the normal flow of cerebrospinal fluid (CSF) in and out of the
ventricular system at the level of the basilar cisterns, leading to a communicating
hydrocephalus. The combination of vasculitis, infarction, cerebral edema, and hydrocephalus
results in the severe damage that can occur gradually or rapidly.4

D. CLINICAL MANIFESTATIONS AND DIAGNOSIS

1. Clinical features

Tuberculous meningitis complicates about 0.3% of untreated tuberculosis infections in

children. Occasionally, tuberculous meningitis occurs many years after the infection, when
rupture of 1 or more of the subependymal tubercles discharges tubercle bacilli into the
subarachnoid space. The clinical progression of tuberculous meningitis may be rapid or
gradual. Rapid progression tends to occur more often in infants and young children, who can
experience symptoms for only several days before the onset of acute hydrocephalus, seizures,
and cerebral edema.4

Early clinical diagnosis and treatment is very important in the case of tuberculous
meningitis, because it has long been recognized as the single most important factor determining
outcome. Unfortunately, it is sometimes difficult to diagnose tuberculous meningitis at an early
stage because of the blurred symptoms in children. Children who have tuberculous meningitis

8
usually have non-specific symptoms at the early stage of the disease.4 Neck stiffness is usually
absent.3

The signs and symptoms progress slowly over several weeks and can be divided into 3
stages:4

1. Stage 1: typically lasts 1-2 weeks and is characterized by nonspecific symptoms

such as fever, headache, irritability, drowsiness, and malaise. Focal neurologic
signs are absent, but infants can experience a stagnation or loss of
developmental milestones.
2. Stage 2: usually begins more abruptly. The most common features are lethargy,
nuchal rigidity, seizures, positive Kernig and Brudzinski signs, hypertonia,
vomiting, cranial nerve palsies, and other focal neurologic signs. The
accelerating clinical illness usually correlates with the development of
hydrocephalus, increased intracranial pressure, and vasculitis. Some children
have no evidence of meningeal irritation but can have signs of encephalitis, such
as disorientation, movement disorders, or speech impairment.
3. Stage 3: marked by coma, hemiplegia or paraplegia, hypertension, decerebrate
posturing, deterioration of vital signs, and eventually death.

As described above, early stage of tuberculous meningitis has symptoms that are non-
specific, more like common illness such as influenza. In young children, those non-specific
symptoms include poor weight gain, low-grade fever, and listlessness. In infants, most early
symptoms are related to the primary pulmonary infection, which occurs before the development
of tuberculous meningitis. The only factor that differentiate the symptoms of tuberculous
meningitis from common illness is their persistence, although this feature is often missed if a
patient does not see the same doctor consistently.3

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 Table 2.2. Common clinical features of tuberculous meningitis in children and adults3

Several studies have defined the clinical features most predictive of tuberculous
meningitis. These predictive clinical features include duration of symptoms more than 6 days
in children, optic atrophy, abnormal movements, and focal neurological deficit.3 Also, often
the key to the correct diagnosis is identifying an adult who has infectious tuberculosis and is in
contact with the child, the persistence of symptoms, detection of pulmonary or other forms of
tuberculosis.4,2

Table 2.3. Discriminatory clinical features for the diagnosis of tuberculous meningitis in
children and adults3

Meanwhile, some studies have also listed some of the most common symptoms and
diagnostic findings in tuberculous meningitis. They are fever, cerebrospinal fluids (CSF)
leukocytosis, CSF lymphocytosis, hydrocephalus, vomiting, and abnormal chest radiograph.2

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2. Laboratory findings

a. Microscopy

Detection of acid fast bacilli (AFB) in patient samples using ZiehlNeelsen (ZN)
staining is the most widely employed technique for diagnosing tuberculosis. It remains the only
laboratory test for tuberculosis diagnosis in many resource-limited tuberculosis endemic
regions and forms an integral part of the WHO diagnosis and treatment algorithm. AFB
microscopy is, however, insensitive in extrapulmonary tuberculosis especially tuberculous
meningitis, with sensitivity rates of about 1020%, although this figure varies considerably (0
87%), and is highly influenced by the clinical case definition used for diagnosis, the volume of
cerebrospinal fluid (CSF) sent and the skill of the technician examining the slide. However, a
simple modification to the Ziehl-Neelsen stain using cytospin and Triton has been reported to
have an impressive results.6,3

b. Cerebrospinal examination

The most important laboratory test for the diagnosis of tuberculous meningitis is
examination and culture of the lumbar CSF. Culture of Mycobacterium tuberculosis (MTB)
from the CSF of TBM patients is slow and insufficiently sensitive to be used as a rule out
diagnostic test, although it represents the most definitive rule-in test usually in retrospect.
Culture is essential for phenotypic drug susceptibility testing (DST) and to confirm resistance
detected by more rapid molecular techniques. As with microscopy, sensitivity can be increased
by culturing the deposit of relatively large volumes of CSF.4,2

The CSF leukocyte count usually ranges from 10 to 500 cells/mm 3.

Polymorphonuclear leukocytes may be present initially, but lymphocytes predominate in the
majority of cases. The CSF glucose is typically <40mg/dL but rarely <20mg/dL. The protein
level is elevated and may be markedly high (400-5,000mg/dL) secondary to hydrocephalus and
spinal block. Although the lumbar CSF is grossly abnormal, ventricular CSF can have normal
chemistries and cell counts because this fluid is obtained from a site proximal to the
inflammation and obstruction. During early stage I, the CSF can resemble that of viral aseptic
meningitis only to progress to the more-severe CSF profile over several weeks. The success of
the microscopic examination of acid-fast-stained CSF and mycobacterial culture is related
directly to the volume of the CSF sample. Examinations or culture of small amounts of CSF

11
are unlikely to demonstrate M. tuberculosis. When 5-10 mL of lumbar CSF can be obtained,
the acid-fast stain of the CSF sediment is positive in up to 30% of cases and the culture is
positive in 50-70% of cases.4

c. Nucleid acid amplification techniques

In a meta-analysis of studies reported before 2002 that examined the use of nucleic acid
amplification techniques (NAATs) for the diagnosis of tuberculous meningitis, the
investigators calculated that commercial NAATs were 56% sensitive and 98% specific.
Guidelines recommend NAATs can confirm a diagnosis of tuberculous meningitis, but cannot
rule it out. More recent data suggest that sensitivity might be improved by real-time PCR, and
by assaying CSF filtrates rather than sediments, although these findings need to be confirmed.
Limitations of PCR tests for MTB detection include cost, the need for laboratory infrastructure,
trained technical staff and careful quality control to prevent crosscontamination, detect
inhibition and monitor assay performance.6

In 2010, the WHO endorsed the use of Xpert MTB/RIF (Cepheid, CA, USA), a rapid
fully automated NAAT for use on sputum specimens in resource-constrained TB endemic
countries, at concessional pricing. The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA)
uses real-time PCR and is set to become the cornerstone of commercial molecular diagnosis of
tuberculosis. It potentially has sensitivity and specificity values equivalent to those from in-
vitro CSF culture, confirming M. tuberculosis in CSF and its susceptibility to rifampicin within
2 hours, although its value in the diagnosis of tuberculous meningitis is uncertain. A meta-
analysis of studies reported up to October, 2011, estimated that Xpert MTB/RIF was 80.4%
sensitive compared with culture for the diagnosis of extrapulmonary tuberculosis. A study in
India of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis included 142 CSF
samples and reported that the assay was nearly 12 times more sensitive than microscopy for
the diagnosis of tuberculous meningitis. The cost of processing one Xpert MTB/RIF test,
however, was 82 times higher than the cost of microscopy.3,6

d. Interferon-gamma release assays

The measurement of interferon-gamma release in whole blood or peripheral blood

mononuclear cells in response to stimulation with specific MTB antigens, to diagnose latent

12
TB, has been incorporated into screening guidelines in many low-incidence, high-income
countries instead of, or together with, tuberculin skin testing (TST) because of its high
specificity and need for only one healthcare visit.6 A few studies have examined the diagnostic
use of interferon-gamma release assays on CSF for the diagnosis of tuberculous meningitis.
Their findings suggest that indeterminate results are common, unless CSF volumes of 510 mL
are tested, and that the assays are specific (7090%), but have low sensitivity (5070%). South
African investigators have suggested that the specificity of CSF interferon-gamma release
assays is sufficiently high, when combined with other negative microbiological tests, to make
a useful rule-in test. In view of the CSF volumes necessary, however, whether these assays
have any advantage compared with NAATs is unclear.3

e. Neuroimaging

Brain CT can reveal basal hyperdense exudates on precontrast scans, and basal
meningeal enhancement, infarcts, hydrocephalus, and tuberculomas can be seen in contrast-
enhanced CT. In combination, these features are highly suggestive of tuberculous meningitis
in both adults and children. However, about 30% of children with early tuberculous meningitis
will have a normal brain CT.3

MRI is superior to CT at defining the neuroradiological features of tuberculous

meningitis, especially when they involve the brainstem. MRI is also valuable for the
identification and monitoring of tuberculous meningitis-related cranial neuropathies. The most
important of these neuropathies is optochiasmatic arachnoiditis, which requires urgent
intervention to reduce the risk of blindness (seen in Figure 2.3).3

13
 Figure 2.3. Tuberculous meningitis-associated optochiasmatic arachnoiditis3

E. TREATMENT

The principles of tuberculous meningitis treatment are still derived from observational
studies and clinical practice rather than from controlled trials. They include the importance of
starting antituberculosis chemotherapy early; the recognition that isoniazid and rifampicin are
the key components of the regimen; the potentially fatal consequences of interrupting treatment
during the first 2 months; and the perceived need for long-term treatment (912 months) to
prevent disease relapse.3

Table 2.4. shows the recommended first-line treatment regimens for children and adults
with tuberculous meningitis. The ability of the bloodbrain barrier to limit intracerebral
concentrations of antituberculosis drugs is an important consideration in the treatment of
tuberculous meningitis. Table 2.5. shows the estimated CSF penetration of first-line and
second-line antituberculosis agents. CSF penetration has particular relevance for consideration
of which drug should accompany rifampicin, isoniazid, and pyrazinamide in the standard
regimen, and for the treatment of drug-resistant tuberculous meningitis.3

Most regulatory bodies recommend either streptomycin or ethambutol as the fourth

drug in standard treatment, although neither penetrates the CSF well in the absence of

14
inflammation, and both can produce serious adverse reactions, especially in patients with
impaired renal function. Ethambutol-induced optic neuritis is also a concern, especially in the
treatment of comatose patients, although at the standard dose of 1520 mg/kg the incidence is
less than 3%.3

The fluoroquinolones could represent highly effective fourth drugs and are an essential
component of treatment regimens for multidrug-resistant cases. Investigators of a randomized
comparison of ciprofloxacin (750 mg every 12 hours), levofloxacin (500 mg every 12 hours),
and gatifloxacin (400 mg every 12 hours) added to conventional four-drug tuberculous
meningitis treatment noted that CSF penetration (measured by the ratio of plasma to CSF area
under the concentration-time curve) was greater for levofloxacin than for gatifloxacin or
ciprofloxacin. Ciprofloxacin has the least in-vitro activity against M. tuberculosis and, in view
of its poor CSF penetration, should never be used for treatment of tuberculous meningitis.
Overall, however, fluoroquinolones seemed to add antituberculosis activity to the standard
regimen and to improve outcome, provided they were started before the onset of coma.3

Investigators in Indonesia have tested the hypothesis that treatment intensification,

through use of high-dose intravenous rifampicin and the addition of moxifloxacin, would
enhance bacterial killing and improve outcome. High-dose intravenous rifampicin led to a
three-times increase in the plasma and CSF area under the concentration-time curve compared
with the standard oral dose and was associated with a substantial drop in mortality (65% vs
35%), which could not be accounted for by HIV status or baseline disease severity.3

15
Table 2.4. First-line treatment regimens for tuberculous meningitis in children and
adults3

Table 2.5. CSF penetration of first-line and second-line antituberculosis drugs3

16
 Optimum therapy for childhood tuberculous meningitis is unclear, because of no
randomized controlled trials have assessed regimens. For drug-susceptible disease, WHO
recommends 2 months of isoniazid 10 mg/kg per day, rifampicin 15 mg/kg per day,
pyrazinamide 35 mg/kg per day, and ethambutol 20 mg/kg per day, with a subsequent 10-
month course of isoniazid and rifampicin at the same doses. Some experts substitute
ethionamide or an aminoglycoside for ethambutol. Treatment length is also controversial; some
experts advocate 6 months, whereas others recommend at least 9 months.2 Despite
recommendations for 912 months of treatment, some evidence suggests that 6 months of
intensified therapy is safe and effective in HIV-uninfected children with drug-susceptible
disease.3

F. PROGNOSIS

The prognosis of tuberculous meningitis correlates most closely with the clinical stage
of illness at the time treatment is initiated. The majority of patients in the 1st stage have an
excellent outcome, whereas most patients in the 3rd stage who survive have permanent
disabilities, including blindness, deafness, paraplegia, diabetes insipidus, or mental
retardation.4 307 (47%) of 657 patients were diagnosed in stage 3 and were significantly more
likely to die during treatment than were patients diagnosed in stage 1 or 2.2 The prognosis for
young infants is generally worse than for older children. It is imperative that antituberculosis
treatment be considered for any child who develops basilar meningitis and hydrocephalus,
cranial nerve palsy, or stroke with no other apparent etiology. Often the key to the correct
diagnosis is identifying an adult who has infectious tuberculosis and is in contact with the child.
Because of the short incubation period of tuberculous meningitis, the illness has not yet been
diagnosed in the adult in many cases.4

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 CHAPTER 3

CONCLUSION

Tuberculous meningitis usually affects children, especially those who are younger than
five years old, and people with HIV infection. After scrofula, tuberculous meningitis is the
most common form of childhood EPTB. Up to half of surviving patients presenting with
irreversible sequelae, including paraplegia, blindness, motor and cognitive deficits. Thus, it is
very important to diagnose tuberculous meningitis at an early stage and give the proper
treatment, although it is sometimes hard to diagnose it at an early stage because of its blurred
symptoms. Children who are diagnosed at stage 3 often have a very poor outcome. If diagnosed
at an early stage and proper treatment is given, tuberculous meningitis would have an excellent
outcome.

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