Referat TB CNS Syarif Mas'Ud

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REFERAT

Diagnose Complications of Tuberculosis Infection In The Central Nervous

System

Disusun oleh :

ohamma! Syarif as"u!

##$%$###&'

(epaniteraan (lini) Neurologi RS*D +asar Rebo

+embimbing :

Dr, Donny -, -ami! SpS

RS*D +ASAR RE./ 0A(ARTA

FA(*1TAS (ED/(TERAN

*NI2ERSITAS 3ARSI

INTR/D*CTI/N



Tuberculosis is a formi!able !isease 4orl!4i!e because of its highly infectious nature

an! propensity for latency, The increasing prevalence of tuberculosis in both

immunocompetent an! immunocompromise! in!ivi!uals in recent years ma)es this !isease a

topic of universal concern, The !isease has insi!ious onset an! can affect virtually any organ

system in the bo!y5 inclu!ing the central nervous system 6CNS7,

+athogenic organisms may reach the central nervous system by hematogenous

sprea! or local e8tension an! cause infections of the meninges 6meningitis75 infections of the

brain an! spinal cor! parenchyma 6encephalitis5 myelitis75 focal purulent collections 6brain

abscess5 sub!ural empyema5 epi!ural abscess75 or infections of the nerve roots 6ra!iculitis5

polyra!iculitis7, Depen!ing on the causative organism5 the infection may ta)e an acute5

subacute or chronic course an! may be self9limiting or !estructive an! lifethreatening,

any CNS infections can be treate! if !iagnose! in timely fashion, The cerebrospinal flui!

e8amination5 inclu!ing culture5 an! neuroimaging stu!ies 6CT an! RI75 together 4ith the

clinical fin!ings5 are generally sufficient to enable a !ifferentiation among bacterial5 viral5

mycotic5 an! parasitic pathogens an! a precise etiologic !iagnosis, In general5 antimicrobial

therapy is given on an empirical basis until the causative organism is i!entifie! an! the

treatment can be tailore! to it,

#, Tuberculous eningitis



Definition is an inflammation of the arachnoi! membrane5 piamater involving

cerebrospinal flui! cause! by Micobacterium tuberculosis,

This is the commonest manifestation of tuberculous infection of the nervous system, In

Children , it usually results from bacteraemia follo4ing the initial phase of primary

pulmonary tuberculosis, In adults, it may occur many years5 after the primary infection,

Follo4ing bacteraemia5 metastatic foci of infection Io!ge in:

#, eninges

%, Cerebral or spinal tissue

, Choroi! ple8us

Rupture of these encapsulate! foci results in sprea! of infection into the subarachnoi!

space, In a!ults5 reactivity of metastatic foci may occur spontaneously or result from

impaire! immunity 6e,g, recent measles5 alcohol abuse5 a!ministration of steroi!s7,

.rain an! spinal cor! meninges that protects covere! !elicate neural structures5

carrying bloo! vessels an! flui! secretion Cerebrospinal, eningeal consists of three layers5

• Duramater

Is the most outer membrane an! a fibrous layer of !ense an! strong5 that encloses the

spinal cor! an! cau!a e;uina,

• Arachnoi!

Is a thin sheath of connective tissue that non9vascular separating the !ura mater 4ith

+iamater,

• +iamater

is a thin sheath that is rich in bloo! vessels an! imme!iately 4rap the brain an!

spinal cor!,



Fig #, anatomy of the meninges membrane

T. is classifie! into stages accor!ing to the .ritish e!ical Research Council 6RC7

criteria

Stage I: +ro!romal phase 4ith no !efinite neurologic

symptoms,

Stage II: Signs of meningeal irritation 4ith slight or no

clou!ing of sensorium an! minor 6cranial nerve

palsy7 or no neurological !eficit,

Stage III: Severe clou!ing of sensorium5 convulsions5 focal

neurological !eficit an! involuntary movements,

Pathophysiology5 ost tuberculous infections of the central nervous system are

cause! by Mycobacterium tuberculosis, as a result of hematogenous sprea! from a primary

location5 either the lung or gastrointestinal tract, Initially5 small tuberculous lesions 6Rich"s

foci7 !evelop in the CNS5 either !uring the stage of bacteraemia of the primary tuberculous



infection or shortly after4ar!s, These initial tuberculous lesions may be inoculate! in the

meninges< the subpial an! subepen!ymal surface of the brain or the spinal cor!5 an! may

remain !ormant for years, 1ater5 rupture or gro4th of one or more of these small tuberculous

lesions pro!uces various types of CNS tuberculosis, The type an! e8tent of lesion !epen!

upon the number an! virulence of bacilli an! the immune response of the host, A tubercular

rupture into the subarachnoi! space results in T. meningitis< 4here as !eep lesions cause

tuberculoma or abscesses, T. meningitis may cause inflammatory changes in cranial=spinal

nerves an! the bloo! vessels, The inflammation of bloo! vessels 6vasculitis7 subse;uently

results in thrombosis an! infarction, -y!rocephalous can occur secon!ary to impe!ance of

CSF circulation an! absorption, The inflammatory e8u!ates may also surroun! the spinal

cor! pro!ucing tuberculous arachnoi!itis, Infre;uently5 infection sprea!s to the CNS from a

site of !iscal T.5 tuberculous otitis5 or osteogenic tubercular foci in the spine or cranial vault,

+athologically5 a tuberculoma is compose! of central core of caseous necrosis surroun!e! by

a capsule of collagenous tissues an! an outer layer of mononuclear inflammatory cells

6inclu!ing plasma cells > lymphocytes75 epitheloi! cells an! multinucleate! 1angerhans"

giant cells, A tuberculoma harbours fe4 tubercular bacilli 4ithin the necrotic center an! the

capsule, /utsi!e the capsule5 there is parenchymal e!ema an! astrocyte proliferation,

*nli)e caseous tuberculoma5 a tubercular abscess has purulent center rich in tubercular

bacilli5 an! lac)s epithelioi! giant cell granulomatous reaction in its 4all,

Fig %, +athophysiology Tuberculous eningitis

Clinical Features Tuberculous meningitis occurs in persons of all ages, Formerly it 4as

more fre;uent in young chil!ren5 but no4 it is more fre;uent in a!ults5 at least in the *nite!

States, The early manifestations are usually lo49gra!e fever5 malaise5 hea!ache 6more than



one9half the cases75 lethargy5 confusion5 an! stiff nec) 6'? percent of cases75 4ith (ernig an!

.ru!@ins)i signs, Characteristically5 these symptoms evolve less rapi!ly in tuberculous than

in bacterial meningitis5 usually over a perio! of a 4ee) or t4o5 sometimes longer, In young

chil!ren an! infants5 apathy5 hyperirritability5 vomiting5 an! sei@ures are the usual symptoms<

ho4ever5 stiff nec) may not be prominent or may be absent altogether, .ecause of the

inherent chronicity of the !isease5 signs of cranial nerve involvement 6usually ocular palsies5

less often facial palsies or !eafness7 an! papille!ema may be present at the time of a!mission

to the hospital 6in %$ percent of the cases7, /ccasionally the !isease may present 4ith the

rapi! onset of a focal neurologic !eficit !ue to hemorrhagic infarction5 4ith signs of raise!

intracranial pressure or 4ith symptoms referable to the spinal cor! an! nerve roots,

-ypothermia an! hyponatremia have been a!!itional presenting features in several of our

cases, In appro8imately t4o9thir!s of patients 4ith tuberculous meningitis there is evi!ence

of active tuberculosis else4here5 usually in the lungs an! occasionally in the small bo4el5

bone5 )i!ney5 or ear, In some patients5 ho4ever5 only inactive pulmonary lesions are foun!5

an! in others there is no evi!ence of tuberculosis outsi!e of the nervous system, In the

previously mentione! Clevelan! series5 4hich comprise! ? patients5 active pulmonary

tuberculosis 4as foun! in #5 inactive in &5 an! involvement of the nervous system alone in <

only % of the ? patients ha! nonreactive tuberculin tests5 some4hat !ifferent from the

general e8perience note! belo4, Among our a!ult patients5 tuberculous meningitis is no4



seen almost e8clusively in those 4ith AIDS5 in alcoholics5 an! in immigrants from the Far

East an! In!ia, /ne recent case 4ith an atypical organism occurre! in an other4ise healthy

local professor 4ho spent several months in East Africa, E8cept for the emergence of !rug9

resistant organisms5 the -I2 infection !oes not appear to change the clinical manifestations

or the outcome of tuberculous meningitis, -o4ever5 others !isagree5 insisting that the course

of the bacterial infection is accelerate! in AIDS patients5 4ith more fre;uent involvement of

organs other than the lungs, If the illness is untreate!5 its course is characteri@e! by confusion

an! progressively !eepening stupor an! coma5 couple! 4ith cranial nerve palsies5 pupillary

abnormalities5 focal neurologic !eficits5 raise! intracranial pressure5 an! !ecerebrate postures<

invariably5 a fatal outcome then follo4s 4ithin B to 4ee)s of the onset,

Fig , Nuchal nec) rigi!ty Fig B, 1asegue

Fig ?, (ernig Fig &, .ru!@in)i #

Laboratory Studies5 the most important is the lumbar puncture5 4hich preferably

shoul! be performe! before the a!ministration of antibiotics, The CSF is usually un!er

increase! pressure an! contains bet4een ?$ an! ?$$ 4hite cells per cubic millimeter5 rarely

more, Early in the !isease there may be a more or less e;ual number of polymorphonuclear

leu)ocytes an! lymphocytes< but after several !ays5 lymphocytes pre!ominate in the maority

of cases, In some cases5 ho4ever5 M. tuberculosis causes a persistent polymorphonuclear



pleocytosis5 the other usual causes of this CSF formula being Nocardia5 Aspergillus5 an!

Actinomyces 6+eacoc)7, The protein content of the CSF is al4ays elevate!5 bet4een #$$ to

%$$ mg=!1 in most cases5 but much higher if the flo4 of CSF is bloc)e! aroun! the spinal

cor!, lucose is re!uce! to levels belo4 B$ mg=!1 but rarely to the very lo4 values observe!

in pyogenic meningitis< the glucose falls slo4ly an! a re!uction may become manifest only

several !ays after the patient has been a!mitte! to the hospital, The serum so!ium an!

chlori!e an! CSF chlori!e are often re!uce!5 in most instances because of inappropriate AD-

secretion or an a!!isonian state !ue to tuberculosis of the a!renals, ost chil!ren 4ith

tuberculous meningitis have positive tuberculin s)in tests 6? percent75 but the rate is far

lo4er in a!ults 4ith or 4ithout AIDS: B$ to &$ percent in most series, The conventional

metho!s of !emonstrating tubercle bacilli in the spinal flui! are inconsistent an! often too

slo4 for imme!iate therapeutic !ecisions, Success 4ith the tra!itional i!entification of

tubercle bacilli in smears of CSF se!iment staine! by the iehl9 Neelsen metho! is a function

not only of their number but also of the persistence 4ith 4hich they are sought, There are

effective means of culturing the tubercle bacilli< but since their ;uantity is usually small5

attention must be pai! to proper techni;ue, The amount of CSF submitte! to the laboratory is

critical< the more that is culture!5 the greater the chances of recovering the organism, *nless

one of the ne4er techni;ues is utili@e!5 gro4th in culture me!ia is not seen for to B 4ee)s,

+CR5 by DNA amplification5 permits the !etection of small amounts of tubercle bacilli an! is

no4 4i!ely available for clinical use, There is also a rapi! culture techni;ue that allo4s

i!entification of the organisms in less than # 4ee), -o4ever5 even these ne4 !iagnostic

metho!s may give uncertain results or ta)e several !ays to !emonstrate the organism5 an!

they cannot be counte! on to e8clu!e the !iagnosis, For these reasons5 if a presumptive

!iagnosis of tuberculous meningitis has been ma!e an! cryptococcosis an! other fungal

infections an! meningeal neoplasia have been e8clu!e!5 treatment shoul! be institute!



imme!iately5 4ithout 4aiting for the results of bacteriologic stu!y, /ther !iagnostic

proce!ures 6CT5 RI7 may be necessary in patients 4ho present 4ith or !evelop raise!

intracranial pressure5 hy!rocephalus5 or focal neurologic !eficits, /ne or more tuberculomas

may also be visuali@e! 6see belo47, R angiography may !emonstrate vascular occlusive

!isease from granulomatous infiltration of the 4alls of arteries of the circle of Gillis an! their

primary branches,

Table #, Comparative Analysis of CSF in meningitis infective

+N

Count

1ymphocyte

Count

lucose +rotein Culture an!

microscopic

2iral

antibo!y

Acut bacterial

meningitis

H

2iral meningitis N atau N H

Tuberculosis

meningitits

N atau H

Fungal meningitis N atau N atau

H

Imaging Features /n CT scan5 the most common fin!ing in cranial tuberculous

meningitis 6CT.7 is obliteration of the basal cisterns by iso!ense or mil!ly hyper!ense

e8u!ate, After the a!ministration of contrast me!ium5 there is !ense homogeneous

enhancement of the basal meninges 6Figure '7, E8tension of the meningeal enhancement over

the surface of the cerebral an! cerebellar hemispheres may also be observe!, E8tension into

the ventricular system 4ith epen!ymitis may be seen as a linear enhancement along the



ventricular margin, Communicating hy!rocephalus5 the most fre;uent complication of

CT.5 usually cause! by obstruction of CSF flo4 by the meningeal e8u!ate in the basal

cisterns5 may also be seen at the time of !iagnosis, In non9contrast enhance! CT an! RI5

hy!rocephalus may be the only clue for !iagnosis at the initial presentation 6Figure 7,

Chest J9ray: Reveals changes of ol! or recent tuberculosis in ?$ > '$K of a!ults an! $K of

chil!ren,

Fig ', Tuberculous meningitis in a B9year9ol! 4oman, 6a7 Non9contrast enhance! compute!tomography scan sho4s effacement of the basal cisterns cause! by the presence of e8u!ate,

6b7 Contrast9enhance! compute! tomography scan sho4s !ense enhancement of the

thic)ene! inflame! basal meninges



Fig , -y!rocephalus in a B9year9ol! man 4ith cranial tuberculosis, A8ial T# 4eighte!

magnetic resonance imaging reveals !ilatation of the lateral ventricles.

Fig , iliary Tuberculosis

%, Tuberculomas

These are tumor9li)e masses of tuberculous granulation tissue5 most often multiple

but also occurring singly5 that form in the parenchyma of the brain an! range from % to #%

mm in !iameter 6Fig, #$7, The larger ones may pro!uce symptoms of a space9occupying

lesion an! periventricular ones may cause obstructive hy!rocephalus5 but many are

unaccompanie! by symptoms of focal cerebral !isease, In the *nite! States tuberculomas

are rarities< but in !eveloping countries they constitute from ? to $ percent of all intracranial

mass lesions, In some tropical countries5 cerebellar tuberculomas are the most fre;uent

intracranial tumors in chil!ren, .ecause of their pro8imity to the meninges5 the CSF often

contains a small number of lymphocytes an! increase! protein 6serous meningitis75 but the

glucose level is not re!uce!, True tuberculous abscesses of the brain are rare e8cept in AIDS



patients, In t4o of our patients 4ho presente! 4ith a brainstem tuberculoma5 there 4as a

serous meningitis that progresse! to a fatal generali@e! tuberculous meningitis,

Clinical feature are those of any intracranial mass< alternatively tuberculoma may present in

conlunction 4ith tuberculous meningitis, CT scan clearly !emonstratcs an enhancing lesion 9

but this often resembles astrocytoma or metastasis< tubcrculomas have no !istinguishing

features, RI is even more sensitive an! may sho4 a!!itional lesions, /ther investigations:

ESR5 chevt J9ray often fail to confirm the !isgnosis, A antou8 6++D7 test is usually

positive but a negarive test !oes not eliminate the !iagnosis, Ghen tuberculoma is suspecte!5

a trial of antituberculous therapy is 4orth4hile, Follo4 up CT scans shoul! sho4 a re!uction

in the lesion site. /ther patients re;uire an e8ploratory operation an! biopsy follo4e! bv

long9term !rug treatment,

Fig #$, A tuberculoma of the !eep hemisphere in a Caribbean emigrantto the *nite! States,

The mass behave! clinically li)e a primarymalignant brain tumor an! resemble! a tumor on a

ga!olinium9enhance! RI,



Fig ##, Caseating tuberculoma, A8ial T%G R image6a7 of brain sho4s profoun!ly

hypointense lesion in left frontal lobe6blac) arro47 4ith mar)e! perilesional oe!ema, The

lesion !emonstrates isointense core 4ith slight hyperintense rim on T#G image6b75 an!

thin peripheral ring enhancement on ga!olinium9enhance! image6c7, ultiple similar

lesions 4ere present involving both supra an! infratentorial compartments5 note similar

lesion in left occipito9parietal region64hite arro47,

, Tuberculous Spon!ylitis 6pott"s spine7

Chronic epi!ural infection follo4ing tuberculous osteomyelitis t he vertebral bo!ies,

This arises in the lo4er thoracic region5 can e8ten! over several segments an! may sprea!

through the intervertebral foramen into pleura5 peritoneum or psoas muscle, Tuberculous

Spon!ylitis is a lea!ing cause of paraplegia, In !eveloping countries5 spinal tuberculosis

affects younger age groups5 inclu!ing infants an! chil!ren, In !evelope! countries5 it mostly

affects the el!erly, -o4ever5 !ue to -I2 epi!emic5 its inci!ence hasincrease! among younger

age groups, The !isease has insi!ious onset an! in!olent course,

The lo4er !orsal an! lumbar spines are most commonly affecte!5 follo4e! by cervical

spine, The atlanto9a8ial region involvement is relatively uncommon, The !isease process

results from hematogenous sprea! of infection to the vertebral bo!y via paravertebral

venous ple8us of .atson, Infection usually begins in anterior part of vertebral bo!y 4ithin

the cancellous bone a!acent to the en! plate or anteriorly un!er the periosteum of the

vertebral bo!y, Destruction of en! plate allo4s the sprea! of infection to the a!acent

intervertebral !isc5 an! subse;uently to the a!!itional spinal segment, Subse;uent sprea! of

infection to other vertebral bo!ies may also occur via subligamentous route5 4ith sparing of

intervertebral !isc LFigure#%M, Thus the classic pattern of involvement of more than one



vertebral bo!y together 4ith the intervening !isc is seen in T. spine, S)ip lesions

are not uncommon, /ccasionally5 tuberculous spon!ylitis affects only one vertebral bo!y5

sparing the a!acent !isc, The pe!icle an! posterior element involvement is rare, The sprea!

of infection into the paraspinal tissues results in the formation of paravertebral soft tissue

inflammatory mass 6phlegmon7 an!=or fran) abscess LFigure#%M, Intraspinal e8tension is

also fre;uent, Neurological !eficits are commonly associate! 4ith spinal tuberculosis

of cervical region5 particularly 4hen cranio9vertebral unction or C#9C% spine is involve!,

The neurological !eficit is usually cause! by significant thecal or cor!

compression by !isplace! bony fragment5 epi!ural inflammatory mass an!=or abscess, Death

may occur !ue to atlanto9a8ial instability or cervico me!ullary compression,



Fig #%, Tuberculous spon!ylitis 6+ott"s spine7 4ith subligamentous sprea! of the !isease,

Sagittal T#G6a75 T%G6b75 an! Coronal T%G6c7 image of !orso9lumbar spine !emonstrates

primary involvement of D#%91# vertebral bo!ies an! the intervening !iscs 6thin 4hite

arro47 by the !isease process 4ith contiguous sprea! if the infection cranially 6to involve all

!orsal vertebrae7 an! cau!ally6to involve 1% vertebra7 along the subligamentous route6thin

blac) arro47 4ith sparing of intervening !iscs6e8cept at D#%91# level7, Note5 marro4 signal

intensity changes in all the involve! vertebral bo!ies5 an! an epi!ural phlegmon at D#%91#level causing locali@e! cor! compression 6thic) 4hite arro47,

B, Tuberculous yelitis

Infection of the leptomeningens results in an e8u!ate that encases the spinal cor! an! nerve

roots, This pro!uces bac) pain5 paraesthesia5 lo4er limb 4ea)ness an! loss of bo4el an!

bla!!er conrrol, Imaging may be normal 4hile CSF sho4s high protein5 lymphocytes an!

rarely aci! fast bacilli, This !isor!er is no4 more fre;uent in AIDS patients, The cervico9

thoracic segment of the spinal cor! is most commonly involve!, R Imaging features of T.

myelitis are similar to those of cerebritis, There is !iffuse cor! s4elling 4ith signal

abnormality,ost spinal cor! lesions appear as hyperintense on T%5 isointense to hypointense

on T#94eighte! images5 an! sho4 segmental enhancement on post contrast images

LFigure#%M, Differential !iagnosis inclu!es cytomegalovirus5 cryptococcus5 syphilis an!



lymphoma, 1aminnectomy an! meningeal biopsy may be re;uire! to establish !iagnosis,

Ghen suspecte!5 empirical theory 4ith antituberculous !rugs is appropriate

Fig, # Tuberculous yelitis, Sagittal T%G6a75 T#G6b7 an! post contrast6c7 RI of !orso9

lumbar spine sho4s !iffuse cor! s4elling an! e!ema appearing hypointense on T#G an!

hyperintense on T%G image an! sho4ing intense central contrast enhancement on postga!olinium images6thin 4hite arro47, These changes are better appreciate! 6thic) 4hite

arro47 on a8ial T%G6!75 T#G6e7 an! post contrast image6f7

?, Tubercular Abscesses

Tubercular abscess is a rare manifestation of CNS tuberculosis5 occurring in less than

#$K cases, They are foun! more fre;uently in el!erly an! immunocompromise! patients,

The patient is acutely ill 4ith focal neurological !eficit, T. abscesses have a more



accelerate! clinical course, /n imaging5 a T. abscess may be in!istinguishable from a

caseous tuberculoma 4ith central li;uefaction or a pyogenic abscess, -o4ever5 a T. abscess

is usually solitary an! larger than tuberculoma, +erilesional e!ema an! mass effect is more as

compare! to tuberculoma, /n CT an! RI LFigure M5 it is often multinucleate! an! sho4s

thin5 smooth peripheral 4all enhancement on post contrast images,

Fig #B, Tubercular abscess, A8ial T%G6a75 T#G 6b75 an! CER6c7 images of another patient

sho4s solitary ring enhancing lesions 4ith li;uifie! center5 involving right basal ganglia

region6arro47,



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e!ition, 0a)arta +usat,

1in!say ( et al , #', Neurology and Neurosurgery Illustrated. Churcill 1ivingstone, r!

E!ition, E!inburgh,

umentaler et al , %$$B, Neurology, Thieme, Bth revise! an! enlarge! e!ition, Ne4 3or)

Ropper A- an! .ro4n R-, %$$?, Adam and ictor!s "rincples o# Neurology. cra49-ill,

Eight e!ition, *nite! States of America,

Gil)inson 1 an! 1enno8 , %$$?, $ssential Neurology. .lac)4ell +ublsihing, Fourth

E!ition, *nite! States of America,

3oes Ronny, %$$, (apita Sele)ta Neurologi, a!ah a!a *niversity +ress, 3ogya)arta,

uger A, Tuberculosis, In: Schel! GN5 Ghitley R05 arra C5 e!itors, In#ections o# Central

Nervous System. +hila!elphia: 1ippincott5 %$$B, pp, BB#9,

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Referat TB CNS Syarif Mas'Ud