Manifestasi dan Tatalaksana

TB pada Sistem Saraf

Rivan Danuaji

Staff Bagian Neurologi RSUD Dr Moewardi / FK UNS

Outline
• Introduction
• Pathogenesis of TB of The Nervous System
• Clinical Features
• Diagnosis
• Treatment
• Conclusion

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Introduction
• Tuberculosis remains a major global problem and a public health
issue of considerable magnitude, not mention in Indonesia
• Several risk factors have been observed for this serious phenomenon.
• The increasing prevalence of HIV infection,
• over-crowding in the urban population and in abnormal communities (such
as prisons, concentration camps, refugee colonies),
• poor nutritional status,
• appearance of drug-resistant strains of tuberculosis,
• ineffective tuberculosis control programmes, and
• an increase in migration from countries where tuberculosis is prevalent to the
developed world.
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Introduction
• The incidence of tuberculosis varies from 9 cases per 100 000
population per year in the US; to 110–165 cases per 100 000
population in the developing countries of Asia and Africa.
• In Indonesia there were 156.733 new cases (Ministry of Health, 2017)
• Tuberculous involvement of the central nervous system (CNS) is an
important and serious type of extra-pulmonary involvement.
• It has been estimated that approximately 10% of all patients with
tuberculosis have CNS involvement (Wood M, Anderson M, 1998).

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Statistic of TB
in Indonesia

• New cases:
156.733 (2017)
• Case Detection
Rate: 60,59%
• Success rate :
75,4%

• CNS TB: ± 15.000

cases

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Introduction
• CNS Tuberculosis
has a good result
if treated
carefully, but it
will be fatal, both
mortality or
serious sequels,
for bad
management.

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Pathogenesis of CNS Tuberculosis

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Pathogenesis of CNS Tuberculosis
• Most tuberculous infections of the CNS
are caused by Mycobacterium
tuberculosis. Less frequently, other
mycobacteria may be involved.
• It is believed that the bacilli reach the
CNS by the haematogenous route
secondary to disease elsewhere in the
body

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Pathogenesis of CNS Tuberculosis
• CNS tuberculosis develops in two stages:
• Initially small tuberculous lesions (Rich’s foci) develop in the CNS, either
during the stage of bacteremia of the primary tuberculous infection or
shortly afterwards.
• These initial tuberculous lesions may be in the meninges, the sub-pial or sub-
ependymal surface of the brain or the spinal cord, and may remain dormant for
years after initial infection
• Later, rupture or growth of one or more of these small tuberculous
lesions produces development of various types of CNS tuberculosis.
• The specific stimulus for rupture or growth of Rich’s foci is not known, although
immunological mechanisms are believed to play an important role.
• Rupture into the subarachnoid space or into the ventricular system results in
meningitis.
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Pathogenesis of CNS
Tuberculosis
• The type and extent of lesions that result
from the discharge of tuberculous bacilli
into the cerebrospinal fluid (CSF), depend
upon the number and virulence of the
bacilli, and the immune response of the
host
• The pathogenesis of localized brain
lesions is also thought to involve
haematogenous spread from a primary
focus in the lung (which is visible on the
chest radiograph in only 30% of cases)
Classification of CNS tuberculosis:
• Intracranial
• Tuberculous meningitis (TBM)
• TBM with miliary tuberculosis
• Tuberculous encephalopathy
• Tuberculous vasculopathy
• Space-occupying lesions:
• tuberculoma (single or
multiple);
• multiple small tuberculoma
with miliary tuberculosis;
• tuberculous abscess
• Spinal
• Pott’s spine and Pott’s paraplegia
• Tuberculous arachnoiditis
(myeloradiculopathy)
• Non-osseous spinal tuberculoma
• Spinal meningitis
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Risk factors
• Age (children> adults)
• HIV-coinfection,
• Malnutrition,
• Recent measles in children,
• Alcoholism,
• Malignancies,
• The use of immunosuppressive agents in adults
and disease prevalence in the community

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Clinical Features

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Clinical features • Adults with tuberculous
meningitis (TBM) can often
• These nonspecific symptoms present with the classic
include meningitis symptoms:
• fever,
• malaise,
• headache and stiff neck along with
• anorexia,
focal neurological deficits,
• fatigue,
• behavioral changes, and
• fever,
• alterations in consciousness
• myalgias, and
• headache. • Cerebrovascular complications of tuberculous
meningitis that occur typically as multiple or
bilateral lesions in the territories of the middle
cerebral artery perforating vessels are termed
as tuberculous vasculopathy
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 Clinical features
• Children with TBM often present:
• fever,
• stiff neck,
• seizures, and
• abdominal symptoms such as nausea and
vomiting
• Headache occurs less often than in adults
• neurological symptoms range from
lethargy and agitation to coma
• TBM in children develops most often
within 3 months of primary tuberculosis
infection
• Contemporary criterion for staging TBM
Modified MRC criteria
Stage Criteria
1 Alert and oriented without focal
neurological deficits
2 Glasgow coma score of 14-11 or 15
with focal neurological deficits
3 Glasgow coma score of 10 or less, with
or without focal neurological deficits
Thwaites, G. E., T. H. Tran. Tuberculous meningitis: many
questions, too few answers. Lancet Neurol. 2005;4:160–70.
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Staging of TBM
TBM is classified into 3 stages according to the British Medical
Research Council (MRC) criteria
Stage I: Prodromal phase with no definite neurologic
symptoms.

Stage II: Signs of meningeal irritation with slight or no

clouding of sensorium and minor (cranial nerve
palsy) or no neurological deficit.

Stage III: Severe clouding of sensorium, convulsions, focal

neurological deficit and involuntary movements.
 Tuberculous meningitis
• Clinical • Imaging
• fever and headache (for more than 14 • exudates in basal cisterns or in sylvian
days) fissure hydrocephalus
• Vomiting • infarcts (basal ganglionic)
• altered sensorium or focal • gyral enhancement
neurological deficit • tuberculoma formation
• CSF • Evidence of tuberculosis elsewhere
• pleocytosis (more than 20 cells, more Adapted
than 60% lymphocytes)
• increased proteins (more than 100
mg/dl)
• low sugar (less than 60% of
corresponding blood sugar)
• India ink studies and microscopy for
malignant cells should be negative

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Tuberculous meningitis

Clinical manifestations of tuberculoma or tuberculous

brain abscess depend largely on their location, and
patients often present with headache, seizures,
papilledema, or other signs of increased intracranial
pressure.
The presentation of brain abscess is more sub acute (1
week to 3 months) than tuberculoma but slower in onset
than pyogenic brain abscesses
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Tuberculous meningitis
• TB Bacillemia (primary or late reactivation)  subependymal
tubercles  rupture into the subarachnoid space  meningitis

Tuberculous Meningitis. Donald and Shoerman,

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NEJM. 351:17. 10/21/2004
Tuberculous Encephalopathy (TBE)
• TBE is a rare outcome usually more common in younger population
and is characterized by diffuse brain edema and demyelination,
which usually is extensive
• Clinical features:
Impaired consciousness, seizures, disseminated intravascular
coagulation, signs and symptoms of meningitis with or without spinal
fluid changes characterize this syndrome.
• This syndrome may be one of the leading causes of neurologic
devastation and death in CNS TB patients

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Spinal tuberculosis
• Involvement of the spine occurs in less than 1% of TB patients and it
can be secondary to Pott’s spine or as non-osseous spinal cord
tuberculosis or spinal tuberculous meningitis.
• It is a leading cause of paraplegia
• Spinal cord compression in Pott’s spine is mainly caused by pressure
from a paraspinal abscess.
• Neurological deficits may also result from dural invasion by
granulation tissue and compression from the debris of sequestrated
bone, a destroyed intervertebral disc, or a dislocated vertebra
• Neurological involvement can occur at any stage of Pott’s spine and
even years later, when there has been apparent healing, because of
stretching of the cord in the deformed spinal canal.
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Spinal tuberculosis
• Typically, there is a history of local pain, tenderness over the affected spine
or even overlying bony deformity in the form of gibbus.
• Paravertebral abscess may be palpated on the back of a number of
patients.
• These patients usually have acute or subacute, progressive, spastic type of
sensorimotor paraparesis.
• The incidence of paraparesis in patients with Pott’s spine varies from 27%
to 47%.
• Non-osseous spinal cord tuberculosis canoccur in the form of
tuberculomas:
• extradural tuberculomas
• arachnoid lesions without dural involvement
• subdural/extramedullary lesions
• Intramedullary tuberculomas
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Tuberculous myelitis

Sagittal T2WI Sagittal T1WI

Spinal tuberculosis
• The acute form presents with:
• fever,
• headache, and
• radiating root pains,
• accompanied by myelopathy
• The chronic form:
• usually localised to a few
segments,
• presents with progressive spinal
cord compression and
• may suggest a spinal cord tumour.
Tuberculous CSF exudate
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Diagnosis

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Investigation
CSF Analysis
• Definitive diagnosis of tuberculous
meningitis depends upon the
detection of the tubercle bacilli in the
CSF, either by smear examination or
by bacterial culture.
• Rates of CSF culture positivity for
clinically diagnosed cases range from
25% to 70%
• Once anti-tuberculosis medication is
commenced, the sensitivity of smear
and culture falls rapidly
Molecular and Biochemical Analysis:
• nucleic acid amplification (NAA)
• polymerase chain reaction
(PCR)
• antibody detection,
• antigen detection, or
• chemical assays such as
• adenosine deaminase (ADA)
and
• tuberculostearic acid
measurements
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Tuberculin skin test (TST)
• The diagnostic utility of skin testing • TST provide indication of previous
being positive for CNS tuberculosis tuberculosis infection; neither is
varies from 10-20% to 50%. sufficiently sensitive nor specific to
• The performance of the tuberculin diagnose active disease
skin test for the diagnosis of
tuberculosis varies according to:
• age,
• vaccination with BCG,
• nutritional status,
• HIV infection, and
• technique of administration

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Radiological Evaluation
• Every patient with TBM should
preferably be evaluated with
contrast enhanced CT imaging
before the start or within the first
48 hours of treatment
• MRI shows diffuse, thick,
meningeal enhancement
• Contrast enhanced MRI is
generally considered as the
modality of choice. It is useful for
assessment of the location of
lesions and their margins, as well
as ventriculitis, meningitis and
spinal involvement (sensitivity
86%, specificity 90%)
• All patients should have a chest-X-
ray as part of the diagnostic
assessment.
• Serial transcranial doppler
ultrasonography (TCD) with blood
flow velocity (Vm) and pulsatility
index (PI) measurments, can be
efficiently utilized to prognosticate
outcome in tuberculous meningitis-
related vasculopathy
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Radiological Evaluation
MENINGITIS TB

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Radiological Evaluation
MENINGITIS TB

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Radiological Evaluation
TUBERCULOMA

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Radiological Evaluation

TUBERCULOMA

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Radiological Evaluation SPINAL TUBERCULOSIS

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Treatment of CNS TB

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Treatment of CNS TB
• Rationale use of steroids in CNS TB:
• All patients with TBM may receive
adjunctive corticosteroids regardless of
disease severity at presentation
• Adults (>14 years) should start
treatment with dexamethasone 0.4
mg/kg/24 hours with a tapering course
over 6 to 8 weeks
• Children (d”14 years) should be given
prednisolone 4mg/ kg/24 hrs (or
equivalent dose dexamethasone: 0.6
mg/kg/24 hrs) for 4 weeks, followed by
a tapering course over 4 weeks

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Prognosis and sequelae
• The single most important
determinant of outcome, for
both survival and sequelae, is
the stage of tuberculous
meningitis at which treatment
has been started.
• If treatment is started in stage I,
mortality and morbidity is very
low,
• while in stage III almost 50% of
patients die, and those who
recover may have some form of
neurological deficit
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Conclusion
• Early recognition and timely treatment of CNS TB is critical if the
considerable mortality and morbidity associated with the condition is
to be prevented
• A minimum of 10 month-treatment is warranted, and the single most
important determinant of outcome is the stage of tuberculous
meningitis at which treatment has been started

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