toxoplasma encephalitis -mri scott

7/25/2019 Toxoplasma Encephalitis -MRI Scott

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INTRACRANIAL INFECTION

The incidence of central nervous system (CNS) infection has

increased dramatically in the nited States and else!here over the

"ast decade# des"ite advances in anti$iotic thera"y% This is "rimarilydue to the &reater fre'uency of CNS infection in "atients !ith ac'uired

immunodeciency syndrome (AIS) and the increasin& num$ers of

individuals !ith human immunodeciency virus (*I+),related disease%

-rom"t detection and accurate dia&nosis of CNS infection is critical

$ecause most of these disorders are readily treata$le%

Com"uted tomo&ra"hy (CT) and ma&netic resonance

(.R) ima&in& often "rovide com"lementary information concernin&

many "atholo&ic "rocesses# $ut it is clear that .R ima&in& is most

often the "rocedure of choice due to $etter inherent contrastresolution# multi"lanar ima&in&#and the lac/ of artifact from com"act

$one% This is "articularly true in the ima&in& of the "osterior fossa#

!hite matter disease# and small lesions that lac/ a""recia$le mass

e0ect% .R is clearly su"erior to CT in the detection of remote

hemorrha&e and early ischemia and infarction% -ostcontrast .R

ima&in& is also more sensitive to menin&eal "atholo&y than contrast

CT%

In addition to conventional .R ima&in&# advances in .R

technolo&y have "roduced a num$er of .R techni'ues that alsocontri$ute valua$le dia&nostic information to the

evaluation of intracranial disease% .R an&io&ra"hy (.RA) "rovides

essential information re&ardin& vascular s"asm# stenosis# and

occlusion# !hereas di0usion1"erfusion ima&in& ena$les identication of

acute infarction and those areas at &reat ris/ for im"endin& infarction%

.R s"ectrosco"y "rovides an in vivo $iochemical assessment of

intracranial "atholo&y and has emer&ed as an im"ortant dia&nostic

tool in the characteri2ation of CNS disease% This cha"ter descri$es the

.R a""earance of intracranial infection and the contri$ution of

advanced neuroima&in& techni'ues to the evaluation and dia&nosis of s"ecic "atholo&ic entities%

To3o"lasma Ence"halitis

To3o"lasma ence"halitis is caused $y the o$li&ate

intracellular "roto2oan To3o"lasma &ondii !ith a !orld!ide distri$ution%

Sero"ositivity for adults in the nited States ran&es from 456 to 756

(89#48:)% In the immunocom"etent "atient# infection may $e

su$clinical or may result in $eni&n course !ith self,limitin&

adeno"athy# !ith or !ithout fever (48:#898)% After the acute infection#



the "arasite assumes a latent form# the encysted $rady2oite% These

cysts can $e located any!here "rior infection has occurred% As the cell,

mediated immunity declines# the cysts ru"ture# releasin& invasive free

tachy2oites% Thus# to3o"lasma ence"halitis re"resents a recurrence of

latent infection in most cases (89;)% It is usually seen in AIS "atients!hen C; counts fall $elo! <55 cell1mm8 (899)% =efore the era of

AIS# fulminant necroti2in& ence"halitis a a result of to3o"lasma

infection occurred only in those "atients !ith si&nicant

immunodeciency such as colla&en vascular disease# underlyin&

mali&nancy# or&an trans"lantation# and "atients maintained on steroids

or under&oin& chemothera"y or radiation treatment (898#89:#897)%

The ma>or transmission of to3o"lasma is via ra! meat (8:#889)%

Transmission is also "ossi$le via $odily secretions# ra! mil/#

transfusions# or&an trans"lantation# contaminated needles# cat feces#

and via in utero e3"osure (8:)%

In "atients !ith *I+ infection# to3o"lasma ence"halitis

results in a "ro&ressive and often fatal ence"halitis if untreated

(89#:<#89?)% The clinical course includes headache# fever# altered

mental status# confusion# lethar&y# sei2ure# and focal neurolo&ic decit

(89#:<#89?)%

To3o"lasma ence"halitis is the most common

o""ortunistic $rain infection seen in AIS "atients "resentin& !ith

altered mental status# fever# sei2ure# and1or focal neurolo&ic decit

(887#89@#89?)% It is "resent in a""ro3imately <56 to 8;6 of adult AISauto"sies (8;#8:5)% =ecause sero"ositivity for to3o"lasmosis is so

!ides"read# a "ositive titer alone is nondia&nostic# only indictin& "ast

or recent e3"osure% A ne&ative titer# ho!ever# in a "atient !ith a mass

lesion of the CNS should arouse sus"icion of other "ossi$le etiolo&ies% It

should $e noted# ho!ever# that u" to 446 of AIS "atients !ith

to3o"lasma ence"halitis may not have detecta$le antito3o"lasma I&

anti$odies (8:<)% CSF ndin&s in this infection are nons"ecic%

-atholo&ically# "arenchymal to3o"lasma lesions have

three distinct 2onesB a central 2one# !hich is avascular# contains fe!or&anisms# and demonstrates coa&ulative necrosis an intermediate

2one# !hich is en&or&ed !ith $lood vessels# contains numerous free

e3tracellular an intracellular tachy2oites (!ith very fe! encysted

or&anisms)# and has fe!er areas of necrosis and a "eri"heral 2one#

!ith fe! vascular chan&es# more encysted or&anisms ($rady2oites)#

and fe!er tachy2oites# !ith little necrosis (89?)% InDammatory reaction

is most intense in the intermediate 2one% There is endothelial cell

s!ellin& and "roliferation !ith cun& of venules $y lym"hocytes#

"lasma cells# and macro"ha&es% To3o"lasma lesions do not have

ca"sules% hen le"tomenin&itis is "resent# it only involves the



menin&es directly ad>acent to the areas of ence"halitis% Althou&h small

vessel throm$osis and necrosis are characteristically associated !ith

the lesions# arteritis of lar&e vessels is a$sent%

-atholo&ic dia&nosis is made on hemato3ylin and eosinstains% In more dicult cases# electron microsco"y of formalin,3ed

material may $e used# or standard immuno"ero3idase "rocedures may

$e used in dia&nostic evaluation (89?)%

Early ima&in& of "atients !ith acute neurolo&ic

deterioration is im"erative $ecause the results !ill often dictate clinical

mana&ement and a""ro"riate thera"y can $e "rom"tly instituted% On

noncontrast CT# to3o"lasma ence"halitis characteristically a""ears as

multi"le areas of isointense or hy"odensity% There is a "redilection for

the $asal &an&lia (in 796 to ??6) and the corticomedullary >unction(8:#89?)% Lesions may involve the "osterior fossa (885)% *emorrha&e is

uncommon% Lesions vary in si2e from less than < cm to over 8 cm

(89?)% There is surroundin& mass e0ect and edema of varia$le de&ree

(885)%

-ostcontrast CT demonstrates rin& or nodular

enhancement% Rin& enhancement is more common# !ith central

hy"odensity% The rin&s are usually thin and smooth $ut may $e thic/

and irre&ular (89?)# es"ecially in the lar&er lesions% ou$le,dose

delayed techni'ue (usin& 455 mL of intravenous contrast $y$olus1dri" infusion !ith delayed scannin& at < hour) has $een found to

$e e3tremely e0ective in detection of these lesions (<78#885#89?)%

ou$le,dose delayed techni'ue "ermits ma3imal enhancement% The

central "ortion of rin& lesions of to3o"lasma may ll in on delayed

scans (885)%

The radiolo&ic a""earance correlates !ell !ith the

"atholo&ic ndin&s# !ith the central hy"odensity corres"ondin& to the

re&ion of avascular coa&ulative necrosis% The enhancin& rin&

corres"onds to the re&ion of intense inDammation# and the "eri"heral2one may a""ear as edema on neuroima&in& studies (89?)% -atholo&ic,

radiolo&ic correlation has revealed that the "atholo&ic e3tent of these

lesions is often &reater than the area of contrast enhancement evident

on CT (89?)%

.R ima&in& !ithout and !ith &adolinium is more sensitive

to $oth ne! and old lesions of to3o"lasma ence"halitis than

"recontrast, and "ostcontrast CT (89#8:#<78) (Fi&% 4<%;:)% On T4,

!ei&hted ima&es# active lesions are varia$le in si&nal intensity (Fi&%

4<%;7)% Lesions may $e hy"erintense to "arenchyma and thus



indistin&uisha$le from surroundin& hi&h,intensity edema% Lesions may

also $e isointense or hy"ointense# centrally surrounded $y hi&h si&nal

edema (75#<78)% This latter a""earance has $een called a Gtar&etG si&n

(<78) and is nons"ecic% On T<,!ei&hted ima&e the lesions are

isointense to hy"ointense on noncontrast ima&es% -ost&adolinium (5%<mm1/&) studies reveal rin& or nodular enhancement in active lesions#

clearly distin&uisha$le from surroundin& hy"ointense edema% The

enhancement "attern is similar to that seen on CT# !ith either nodule

and1or rin&,enhancin& lesions% *emorrha&e in to3o"lasma lesions is

rare%

A

=



C



Fi&ure 4<,;:% To3o"lasma ence"halitis (ne! and old lesions) AB Initial

T4,!ei&hted scan (4#;551<55) demonstrates focal hy"erintense si&nal

in the ri&ht $asal &an&lia (!hite arro!)% The "atient !as treated !ith

antito3o"lasma medication% The "atient !as noncom"liant# ho!ever#

and returned 8 months later !ith recurrent sei2ures% Su$se'uent study

(=) revealed that the ri&ht,sided lesion diminished in si2e (!hite

arro!)% *o!ever# a ne! lesion has a""eared on the left (o"en arro!)#

!ith edema involvin& the e3ternal ca"sule% CB -ost&adolinium T<,

!ei&hted (?55145) ima&e demonstrates nodular enhancement of the

ne! left,sided lesion (arro!) !ithout a""recia$le enhancement of the

old# ri&ht sided lesion% B Ty"ical "atholo&ic ndin&s seen in

to3o"lasma include an area of central coa&ulative necrosis (asteris/)#

an ad>acent re&ion of neovasculari2ation !ith en&or&ed $lood vessels

(arro!head)# and a relatively una0ected neuro"il !ith to3o"lasma cyst

(lar&e arro!) (hemato3ylin H eosin# 345)%



A

=



C

Fi&ure 4<,;7% To3o"lasma ence"halitis% AB T<,!ei&hted#

(=) "roton density# and (C) T4,!ei&hted ima&es !ere o$tained $efore

initiation of medical thera"y% =ilateral foci !ith hetero&eneous si&nal

are noted to involve the dee" &ray structures# !ith mass e0ect and

edema% B -atholo&ic &ross s"ecimen of another "atient !ith

to3o"lasma reveals the small foci of coa&ulative necrosis (small

arro!s)# ty"ical of to3o"lasma ence"halitis% The lar&est lesion (lar&e

arro!) has a reddish rim due to neovasculari2ation%



.R has a &reater sensitivity than CT# "articularly for small

lesions at the corticomedullary >unction% To3o"lasma is commonly seen

in the $asal &an&lia# and lesions are often multi"le% As a result of

&reater sensitivity# .R is ca"a$le of detectin& a &reater num$er of

lesions as com"ared !ith CT% .R may also $e "ositive in cases !herethe CT is com"letely ne&ative (89#8:)% On "ost&adolinium .R ima&in&#

only <;6 of "atients !ith to3o"lasma ence"halitis !ill demonstrate a

solitary lesion (8:<)# !hereas most !ill have multi"le sites of

involvement (8:<) (Fi&% 4<%;?)% Thus# the lac/ of multi"licity on a hi&h,

'uality .R study should "rom"t sus"icion of other "ossi$le "atholo&y

and may indicate the need for further ima&in& studies# such as .R

s"ectrosco"y or S-ECT thallium ima&in&%

A



=

C



Fi&ure 4<,;?% To3o"lasma ence"halitis% AB T<,!ei&hted

(?55145) "ostcontrast ima&e demonstrates rin&,enhancin& lesions in

the left "arietal lo$e at the corticomedullary >unction and in the

"osterior fossa as !ell% =B A3ial scan throu&h the "osterior fossa a&ain

sho!s a rin&,enhancin& lesion ad>acent to the fourth ventricle !ithmass e0ect% CB Re"eat study o$tained after 4 !ee/s of medical thera"y

("yramethamine1sulfadia2ine) reveals a decrease in the si2e and

de&ree of enhancement% B T4,!ei&hted ima&e (4#;551?5) o$tained at

the same time as C sho!s an isointense lesion surrounded $y edema

!ith minimal mass e0ect%

To3o"lasma ence"halitis is e0ectively treated !ith

"yrimethamine and sulfadia2ine or "yrimethamine and clindamycin

!ith dramatic clinical im"rovement (8:4)% Serial scans (either .R or

CT) o$tained !hile the "atient is on thera"y demonstrate a decrease inthe num$er and si2e of the lesions# !ith a reduction in edema and

mass e0ect% These chan&es usually occur !ithin 4 to ; !ee/s after

initiation of treatment (:7#885#89@) $ut may ta/e u" to : months to

com"letely resolve (89#8:)% Treated lesions have a varia$le a""earance

on CT% Sites of "rior disease may a""ear normal# may demonstrate

ence"halomalacia and focal atro"hy# or may calcify (885)% The

calcications may $e "unctuate or may $e lar&er Gchun/yG ty"e

calcications% The lar&er more com"le3 lesions tend to resolve more

slo!ly and may result in ence"halomalacia% On .R# the minerali2ed

lesions may a""ear as foci of hy"ointense si&nal on T<, and T4,



!ei&hted ima&es and are more "rominent on T4,!ei&hted &radient

echo studies% Some treated lesions may demonstrate $ri&ht si&nal on

T<, and T4,!ei&hted .R ima&es# "ossi$ly due to minerali2ation !ith

"arama&netic s"ecies (i%e%# man&anese# iron# co""er# etc%) (8:8) (Fi&%

4<%;@)% Thus# minerali2ed lesions may have foci of increased ordecreased si&nal on .R% As on CT# the lesions on .R may resolve

com"letely# or there may $e focal ence"halomalacia% es"ite

radio&ra"hic resolution# in the "resence of a "ersistent cellular

immunodeciency# to3o"lasma ence"halitis !ill fre'uently recur if

thera"y is discontinued% This is $ecause medical thera"y is e0ective

a&ainst the free tachy2oites $ut not the encysted forms of

to3o"lasmosis% Thus# the "arasitic infection is never com"letely

eradicated# and life,lon& maintenance medication is re'uired (885)%

A

=



Fi&ure 4<,;@% Treated to3o"lasma ence"halitis% AB

Noncontrast CT sho!s a focal hy"erdensity in the ri&ht frontal !hite

matter (arro!)% =B T<,!ei&hted noncontrast .R (?55145) o$tained ;

months after the CT reveals a hy"erintense focus in the same location%

Althou&h most treated to3o"lasma lesions that calcify are hy"ointense#

some may a""ear as hy"erintense foci due to minerali2ation !ith"arama&netic s"ecies (i%e%# man&anese# iron# co""er# etc%)%

In the "ast# early $io"sy of these enhancin& lesions had

$een advocated to "rom"tly esta$lish the dia&nosis and institute

a""ro"riate thera"y (89#:7#89?)% These cases are no! handled more

conservatively% =ecause to3o"lasmosis is fairly common in AIS

"atients# those !ho "resent !ith ty"ical clinical and radio&ra"hic

ndin&s are "laced on a""ro"riate medical thera"y# and follo!,u"

scans are o$tained in <5 days to 4 !ee/s% Consistent im"rovement on

serial studies is "resum"tive evidence of to3o"lasma ence"halitis% Anim"ortant caveat# ho!ever# is that all lesions need to $e follo!ed to

resolution# $ecause multi"le "atholo&ies may coe3ist in any one

"atient% Lac/ of considera$le im"rovement should "rom"t further

evaluation !ith thallium,45< $rain S-ECT# <?F,Duorodeo3y&lucose

,-ET# or .R s"ectrosco"y# $ecause a focal enhancin& mass lesion may

re"resent "rimary CNS lym"homa or "ossi$ly another ty"e of infection%

A second caveat is that it is im"ossi$le to accurately assess lesion

activity if the "atient is on steroid treatment% Steroids !ill reduce the

de&ree of enhancement and diminish the associated edema and mass



e0ect# and it is therefore im"ossi$le to determine if there has $een a

true res"onse to antito3o"lasma thera"y%

-rimary CNS lym"homa is often dicult to distin&uish

from to3o"lasma ence"halitis on CT and .R ima&in&% Althou&hto3o"lasma is often multicentric $ut may $e solitary# "rimary CNS

lym"homa is often solitary $ut may $e multicentric as !ell (Fi&% 4<%95)%

=ecause treatment of these lesions is com"letely di0erent# it $ecomes

necessary for the radiolo&ist and the clinician to distin&uish $et!een

those t!o entities% Thallium,45< $rain S-ECT has $ecome invalua$le in

ena$lin& this distinction% .eta$olically active tissue# such as tumor# !ill

demonstrate increased u"ta/e relative to the surroundin& "arenchyma

(8:;)# !hereas infectious lesions do not% Althou&h thallium,45< $rain

S-ECT is nons"ecic and !ill $e "ositive for other ty"es of hi&h,&rade

tumors# a "ositive study in an *I+,sero"ositive "atient is hi&hlysu&&estive of a "rimary CNS lym"homa (8:;) (Fi&% 4<%9<)% This study

can $e o$tained 'uic/ly after clinical "resentation and may "reclude

the need for <5 to <; days of thera"y !ith reevaluation% AIS "atients

"resentin& !ith intracranial mass lesions are $e&un on antito3o"lasma

thera"y and sent for nuclear ima&in& !ith thallium,45< $rain S-ECT%

-ositive scans are su&&estive of CNS lym"homa# and $io"sy is ur&ed%

Ne&ative studies

are "resumed to $e due to an infectious a&ent# and the "atient is

continued on medical thera"y for to3o"lasma ence"halitis !ith follo!,

u" scans o$tained in <5 to <; days% The sensitivity of the thalliumscan is limited $y resolution# and tumors less than : to ? mm in si2e

may not $e detected (8:;)% Lym"homatous lesions limited to the

su$e"endymal re&ion may also &o undetected%

A



=

Fi&ure 4<,95% -rimary central nervous system lym"homa

vs% to3o"lasma ence"halitis% AB T<,!ei&hted coronal ima&e (:55145)

"ost&adolinium reveals a lar&e rin&,enhancin& lesion in the ri&ht

"arietal lo$e% Other lesions !ere "resent at other sites# includin& the

left cere$ellum (note edema)% This "atient had $io"sy "roven

to3o"lasma ence"halitis% =B T<,!ei&hted coronal .R (:55145) in a

di0erent "atient reveals solid and rin&,enhancin& lesions and

"eriventricular enhancement surroundin& the ri&ht frontal horn% This

"atient had $io"sy "roven central nervous system lym"homa% The

central nervous system lym"homa seen in AIS "atients is often



necrotic centrally and thus a""ears as a rin&,enhancin& lesion# 'uite

similar to to3o"lasma ence"halitis% =oth to3o"lasma and lym"homa

may $e either unifocal or multifocal% Thus# there can $e diculty in

distin&uishin& $et!een these entities radio&ra"hically% The distinction

is essential# ho!ever# due to the mar/ed di0erence in treatment of these diseases%

A

=

Fi&ure 4<,9<% -rimary central nervous system lym"homa

vs% to3o"lasma ence"halitis $y thallium,45< $rain sin&le "hoton

emission com"uted tomo&ra"hy (S-ECT)% AB Coronal# sa&ittal#

transverse# and "lanar ima&es from thallium,45< $rain S-ECT of an

AIS "atient !ith multifocal enhancin& lesions $y com"uted

tomo&ra"hy% No focal u"ta/e is identied% =rain $io"sy conrmed



to3o"lasma ence"halitis% The "atient res"onded !ell to medical

thera"y% =B Coronal# sa&ittal# transverse#and "lanar ima&es from

thallium,45< $rain S-ECT of an AIS "atient !ith a rin&,enhancin&

lesion in the "ericallosal re&ion%

Note focal u"ta/e in the same re&ion of a$normality# consistent

!ith neo"lasm% =rain $io"sy conrmed "rimary central nervous system

lym"homa%

If the thallium study is e'uivocal# .R s"ectrosco"y may

$e hel"ful in di0erentiatin& to3o"lasmosis from "rimary CNS

lym"homa% S"ectrosco"y may $e "refera$le to the S-ECT,thallium

study in that it does not re'uire in>ection of a radio"harmaceutical and

it can $e "erformed on a clinical .R scanner as "art of the overall .R

study% The s"ectra in "atients !ith to3o"lasmosis reveal elevated li"idand lactate "ea/s# !hereas all other normal $rain meta$olites are

virtually a$sent (8:9)% This is consistent !ith the anaero$ic acellular

environment !ithin an a$scess% *o!ever# this s"ectral "attern is not

com"letely s"ecic and has $een o$served !ithin the necrotic "ortion

of some $rain tumors (<?7)%

In contrast# "rimary CNS lym"homa sho!s a mild to

moderate increase in lactate and li"ids# a mar/edly elevated choline

"ea/# and "reservation of some normal meta$olites !ith varia$ly

decreased levels of NAA and Cr% It is essential# ho!ever# that the vo3elfor s"ectrosco"ic analysis of a lym"homa is "laced over the cellular

"ortion of the lesion rather than the necrotic "ortion# so as not to

overla" !ith the s"ectral ndin&s more characteristic of to3o"lasmosis

(<?7)%

To3o"lasmosis is also a common cause of con&enital CNS

infection# second only to C.+% To3o"lasmosis involves < in <#555 to < in

<5#555 "re&nancies in the nited States "er year (7:)% Clinically

si&nicant ndin&s occur !hen the fetus is infected $efore 4: !ee/s of

&estational a&e (8?)% Si&ns and sym"toms may $e su$clinical initially!ith develo"ment of sei2ures% Chorioretinitis may $e "resent $ilaterally%

Severely a0ected infants have microce"haly% Neuroima&in& studies

reveal hydroce"halus and intracranial calcications# most commonly in

the corte3 and $asal &an&lia# and these calcications are located more

di0usely than those seen in C.+% E"endymitis results is a'ueductal

stenosis and thus hydroce"halus (898)%

toxoplasma encephalitis -mri scott

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