~ "
C A S E
R R P O R 1 '
V a ld ir G o lin , S a n d ra R e g in a S c h w a rz w a ld e r S p ro v ie ri, J o s e E d u a rd o D e lfin i C a m ;a d o , J e ffe rs o n W a lte r D a n ie l, L y c ia M a ria J e n n e M im ic a
A s p e r g illo s is o f th e c e n tr a l n e r v o u s s y s te m
Emergency
Clinical Service, Department
of Medical Clinic
Department
of Microbiology
and Department
of Neurosurgery
of the Faculdade de Ciencias Medicas
da Santa Casa de Sao Paulo - Sao Paulo, Brazil
T h e a u th o rs re p o rt a n u n u s u a l c a s e in v o lv in g a 3 8 y e a r-o ld m a n w h o d e v e lo p e d a in tra c ra n ia l a b s c e s s c a u s e d b yA s p e rg illu s o f th e p a rie ta l lo b e . C e re b ra l a s p e rg illo m a o f a n in itia l p u lm o n a ry o rig in d e v e lo p e d in a p a tie n t w ith "F u n g u s B a ll" s e c o n d a ry to tu b e rc u lo s is s e q u e la e . T h e d ia g n o s is w a s m a d e th ro u g h th e is o la tio n o fA s p e rg illu s fro m th e s e c re tio n o f th e b ra in a b s c e s s e s . T h e p a tie n t w a s tre a te d w ith d ra in a g e o f th e a b s c e s s e s a n d A m p h o te ric in B . H e p re s e n te d a p ro g re s s iv e re g re s s io n o f th e ra d io lo g ic a l im a g e s (b ra in a n d p u lm o n a ry ) o v e r a p e rio d o f 5 5 d a y s . T h is re p o rt e m p h a s iz e s th e im p o rta n c e o f c o m b in e d a n ti-fu n g a l th e ra p y a n d s u rg ic a l re s e c tio n a s a tre a tm e n t fo r c e re b ra l a s p e rg illo m a . F u rth e rm o re , a n e a rly in itia tio n o f th e ra p y s h o u ld im p ro v e th e p ro g n o s is in s u c h c a s e s .
U N IT E R M S : A s p e rg illu s . B ra in a b s c e s s e s . A m p h o te ric in B .
IN T R O D U C T IO N
A s p e r g i l l o m a w a s t h e f i r s t m y c o t i c i n f e c t i o n d e s c r i b e d b y V i r c h o w i n 1 8 5 6 , a n d a c a s e o f A s p e r g i l l o s i s i n v o l v i n g t h e b r a i n w a s r e p o r t e d b y O p p e i n 1 8 9 7 .
Aspergillus,
a s o i l o r g a n i s m f o u n d i n w a r m , d a m p c l i m a t e s ,u s u a l l y i n f e c t s a h o s t w h o h a s s o m e u n d e r l y i n g d e b i l i t a t i n g d i s e a s e . T h e r e a r e 3 3 0 s p e c i e s o f
Aspergillus,
a l t h o u g h o n l y a f e w a r e p a t h o l o g i c a l , w i t hAspergillus
fumigatlts
t h e m o s t c o m m o m a m o n g m a n . I n f e c t i o n b y
Aspergillus
h a s r e c e n t l y b e c o m e b e i n g m o r e f r e q u e n t . T h i s i s p r o b a b l y a c o n s e q u e n c e o f t h e i n c r e a s i n g u s e o f a n t i b i o t i c s , s t e r o i d s , I c y t o t o x i c d r u g s a n d a n t i m e t a b o l i t e s . O t h e r p r e d i s p o s i n g f a c t o r s i n c l u d e : c a r d i a c s u r g e r y w i t h f u n g a lA d re s s fo r c o rre s p o n d e n c e : V a ld ir G o lJ in
R u a A p ia c a s , 3 5 1 , a p to . 1 4 1 - V ila P o m p e ia S a o P a u lo /S P - B ra s il - C E P 0 5 0 1 7 -0 2 0
e n d o c a r d i t i s ; h e p a t i c f a i l u r e ; C u s h i n g 's d i s e a s e ; a n d i m m u n o s u p p r e s s i n g d i s e a s e s .2
.3T h r o u g h t h e i n h a l a t i o n o f
t h e s p o r e s , t h e c o m m o m f o c u s o f i n f e c t i o n i s t h e l u n g ; t h e m a j o r s i t e f r o m w h i c h t h e i n f e c t i o n d e v e l o p s .
C A S E R E P O R T
A 3 8 y e a r - o l d b l a c k m a l e w a s a d m i t t e d t o t h e C e n t r a l E m e r g e n c y U n i t o f S a n t a C a s a o f S a o P a u l o M e d i c a l S c h o o l i n S a o P a u l o , S P , B r a z i l , c o m p l a i n i n g o f w e a k n e s s o n t h e l e f t s i d e o f h i s b o d y , w h i c h h a d s t a r t e d t h e d a y b e f o r e . T h e f i r s t s y m p t o m s b e g a n 1 5 d a y s b e f o r e , w i t h a c o n t i n u o u s a n d p r o g r e s s i v e t h r o b b i n g h e a d a c h e . T e n d a y s b e f o r e a d m i s s i o n t o t h e h o s p i t a l , t h e p a t i e n t n o t i c e d t h e p r e s e n c e o f t o n i c - c l o n i c m o v e m e n t s o f h i s l e f t a r m a n d l e f t l e g f o r v e r y s h o r t p e r i o d s , 2 o r 3 t i m e s a d a y . T h e d a y b e f o r e a d m i s s i o n , t h e p a t i e n t f e l t a d e c r e a s e o f l e f t s i d e
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Figure 1 - L e ft (A ). C h e st x-ra y sh o w s w e ll-d e fin e d "F u n g u s B a ll" w ith in a th ick-w a lle d rig h t u p p e r lo b e ca vity. R ig h t (B ). C o n tra st-e n h a n cst-e d , co m p u tst-e d to m o g ra p h y rst-e vst-e a ls tw o la rg st-e b ra in a b scst-e ssst-e s in th st-e rig h t p a rist-e ta l lo b st-e .
m u s c le m o v e m e n t a n d a s h ift o f th e rig h t s id e o f h is lip s .
T h e p a tie n t d id n o t h a v e fe v e r, n a u s e a o r v o m itin g d u rin g
th is p e rio d . T h e p a tie n t m e n tio n e d th a t 1 7 y e a rs b e fo re h e
h a d p u lm o n a ry tu b e rc u lo s is a n d w a s tre a te d fo r o n e y e a r.
S e v e n y e a rs la te r th e d is e a s e re la p s e d , a n d th e tre a tm e n t
w a s s ta rte d a g a in fo r th re e a d d itio n a l y e a rs . T h e p a tie n t
h a d b e e n a p a in te r a n d s a n d b la s te r fo r s ix y e a rs , u p u n til
s e v e n y e a rs b e fo re h is a d m is s io n to h o s p ita l. H e a ls o u s e d
to s m o k e 2 0 c ig a rre te s a d a y , a n d d id n o t b e lo n g to th e
A ID S ris k g ro u p s .
D u rin g th e p h y s ic a l e x a m in a tio n , th e re w e re
o b s e rv e d s ig n s o f p u lm o n a ry c o n s o lid a tio n in th e u p p e r
rig h t th o ra x . T h e n e u ro lo g ic a l e x a m in a tio n re v e a le d th e
p re s e n c e o f a c o m p le te a n d d is p ro p o rtio n a l le ft h e m ip a re s is
w ith b ra c h ia l p re d o m in a n c e . A c h e s t x -ra y s h o w e d th e
p re s e n c e o f a c a v ita ry a re a in th e rig h t u p p e r lo b e w ith a
tu m o ra l im a g e in s id e , s u g g e s tin g a " F u n g u s B a ll" . F ib ro u s
lin e s w e re a ls o o b s e rv e d in b o th th e m id d le a n d u p p e r
re g io n s w ith rig h t p le u ra l a p ic a l th ic k e n in g , a n d s h ift o f
th e tra c h e a to th e s a m e s id e (F ig .], le ft). T h e c ra n ia l x -ra y
w a s n o rm a l. A c o n tra s te d c o m p u te d to m o g ra p h y (C T ) s c a n
o f th e b ra in s h o w e d tw o e x p a n s iv e p ro c e s s e s in th e rig h t
p o s te rio r p a rie ta l re g io n . T h e le s io n p re s e n te d m a s s e ffe c t
w ith a s h ift o f th e m e d ia n lin e to th e le ft. T h e re w a s a n
im p o rta n t h y p o d e n s e a re a s u rro u n d in g th is le s io n (F ig . I ,
rig h t). A c id -fa s t b a c illu s a n d fu n g u s c o ~ ld n o t b e fo u n d
in th e s p u tu m te s ts . T h e re s u lts w e re n e g a tiv e fo r H IV
a n tib o d ie s (E L IS A ) a n d W e s te rn b lo t.
T w e n ty -fo u r h o u rs a fte r a d m is s io n , a s u rg ic a l
tre p a n a tio n w a s in d ic a te d , w ith th e d ra in a g e o f p u ru le n t
s e c re tio n s (2 0 m l) fro m th e b ra in a b s c e s s o f th e rig h t
p o s te rio r p a rie ta l re g io n . T h e b a c te rio s c o p ic e x a m w a s
p o s itiv e fo r
Aspergillus.
T re a tm e n t w ith d e x a m e th a s o n e(1 6 m g /d a y ) a n d A m p h o te ric in B in tra v e n o u s (I m g /k g / d a y ) w a s s ta rte d .
D u e to th e u s e o f h ig h d o s e s o f s te ro id s , p ro p h y la c tic
tre a tm e n t fo r tu b e rc u lo s is w a s in tro d u c e d . T h e c u ltu re o f
th e m a te ria l o b ta in e d w a s p o s itiv e
forAspergillusfumigatus
(th irtie th d a y o f c u ltu re in S a b o u ra u d 's m e d iu m ).
T h e p a tie n t re c e iv e d a n a c u m u la te d d o s a g e o f
1 5 0 0 m g o f A m p h o te ric in B d u rin g th e tim e h e s ta y e d
a t th e h o s p ita l. A c o n tro l th o ra x X -ra y a t th e e n d o f th is
tre a tm e n t s h o w e d th e d is a p p e a ra n c e o f th e " F u n g u s B a ll"
in s id e th e a p ic a l p u lm o n a ry c a v ity in th e u p p e r rig h t
lo b e (F ig . 2 , le ft). T h e C T s c a n o f th e b ra in s h o w e d
in v o lu tio n o f th e a b c e s s (F ig . 2 , rig h t).
G O L lN , V .; S P R O V IE R I, S .R .S .; C A N Q A D O , JE D ., D A N IE L , J.w . & M IM IC A , L .M .J. -A sp e rg illo sis o f th e ce n tra l n e rvo u s syste m
1276
F ig u re 2 - L e ft (A ). C h e s t x -ra y s h o w s a b s e n c e o f th e "F u n g u s B a ll". R ig h t (B ). C o m p u te d to m o g ra p y s h o w s in v o lu tio n o f b o th a b s c e s s e s , a n a re a o f d e c re a s e d d e n s ity o n ly in th e rig h t p a rie ta l lo b e , w ith o u t a s h ift o f th e m id le lin e s tru c tu re s .
O n th e f if ty - f if th d a y , th e p a tie n t w a s d is c h a r g e d a n d
p r e s c r ib e d o n ly p h e n to in , iz o n ia z id a n d r if a m p ic in .
D IS C U S S IO N
A s p e r g illo s is is in c r e a s in g in p r e v a le n c e , e s p e c ia lly
in p a ti e n ts w i th c h r o n ic r e s p i r a to r y d i s e a s e a n d
im m u n o s u p p r e s s io n . A m o n g th e im m u n o s u p p r e s s e d ,
a s p e r g iI J o s is is th e s e c o n d m o s t c o m m o n a g e n t a f te r
c a n d id ia s is a s a n o p p o r tu n is tic m y c o s is . B o th a r e
in c r e a s in g in f r e q u e n c y b e c a u s e o f th e im p r o v e d m e th o d s
o f c o n tr o llin g b a c te r ia l in f e c tio n .
T h e n a tu r a l h is to r y o f a s p e g illo m a is q u ite v a r ia b le .
L e s io n s m a y r e m a in s ta b le f o r lo n g p e r io d s o f tim e , g r o w
o r s h r in k a lo n g w ith th e s u r r o u n d in g c a v ity , o r u n d e r g o
s p o n ta n e o u s ly s is ( a b o u t 1 0 p e r c e n t o f th e c a s e s ) .
H e m o p ty s is is e n c o u n te r e d in 6 0 to 7 5 p e r c e n t o f c a s e s .
S p u tu m c u ltu r e s a r e p o s itiv e in 6 0 p e r c e n t. D ia g n o s is
r e q u ir e s a s u g g e s tiv e c h e s t r a d io g r a p h y c o m b in e d w ith
e ith e r p o s itiv e s e r u m p r e c ip itin s ( 2 0 p e r c e n t o f c a s e s ) o r a
p o s itiv e c u ltu r e o b ta in e d d ir e c tly f r o m th e c a v ita r y le s io n
( 6 0 p e r c e n t ) .
Aspergillus
m a y r e a c h th e c e n tr a l n e r v o u s s y s te m b y th r e e d if f e r e n t r o u te s . T h e f ir s t o n e is b yh e m a to g e n o u s d is s e m in a tio n f r o m a r e m o te e x tr a c r a n ia l
s ite , u s u a lly th e lu n g .4
T h e s e c o n d o n e is b y th e e x te n tio n
f r o m a c o n tig u o u s c r a n ia l f o c u s . T h is f o c u s is m o s t o f te n
th e n a s a l c a v ity a n d th e p a r a n a s a l s in u s e s f r o m w h ic h th e
f u n g u s m a y r e a c h th e in tr a c r a n ia l c a v ity b y d ir e c t
p r o p a g a tio n . T h e th ir d p o s s ib ility is b y d ir e c t in tr o d u c tio n
in to p a tie n ts w h o d e v e lo p in tr a c r a n ia l A s p e r g illo s is a f te r
n e u r o s u r g ic a l p r o c e d u r e s .
I n o u r p a tie n t, p u lm o n a r y in f e c tio n w a s s u s p e c te d ,
a lth o u g h f u n g u s in th e b r o n c h ia l s e c r e tio n w a s n o t f o u n d .
T h is s u s p ic io n w a s b a s e d o n th e r a d io lo g ic a l p ic tu r e th a t
s h o w e d a f r e e c a v ity c a u s e d b y p u lm o n a r y tu b e r c u lo s is
w ith a " F u n g u s B a ll" in s id e . T h e d ia g n o s is o f c e r e b r a l
A s p e r g illo s is , p r o b a b ly v ia a h e m a to g e n o u s r o u te , w a s
m a d e th r o u g h a n is o la tio n o f
AspergiLLus
f r o m th e b r a in a b s c e s s . B a s e d o n th e s u s p ic io n o f p u lm o n a r y in f e c tio na n d c o n f ir m a tio n o f th e c e r e b r a l A s p e r g illo m a , in tr a v e n o u s
A m p h o te r ic in B w a s in tr o d u c e d . T h e r e c o m m e n d e d
d o s a g e is 0 .5 to 1 .0 m g /k g d a ily . T h e to ta l d o s a g e s h o u ld
b e n o le s s th a n 2 .0 g r a m s , b u t th e tr e a tm e n t w a s s to p p e d
1277
after co m p letio n o f 1 .5 g d u e to clin ical an d rad io lo g ical
im p ro v em en t. A m p h o tericin B ad m in istered in trath ecally
an d /o r in trav en o u sly , an d Itraco n azo le5 an d F lu cy to zin e4
ad m in istered o rally are th e th ree fo rm s o f th erap y th at h av e
d em o n strated clin ical u sefu ln ess. In o u r rep o rted case, th e
p atien t w as treated w ith co n tin u o u s in trav en o u s
A m p h o tericin B an d cereb ral d rain ag e, w ith clin ical an d
rad io lo g ical im p ro v em en t.
RESUMO
O s a u to re s re la ta m u m c a s o ra ro d e u m h o m e m d e 3 8 a n o s , q u e d e s e n v o lv e u a b c e s s o in tra c ra n ia n o , in te re s s a n d o 0 lo b o p a rie ta l c a u s a d o p o r Aspergillus. 0 a s p e rg ilo m a c e re b ra l te v e o rig e m a tra v e s d e u m a s p e rg ilo m a p u lm o n a r e m u m p a c ie n te c o m u m a "b o la d e fu n g o " s e c u n d a ria a s e q u e la d e tu b e rc u lo s e . 0 d ia g n 6 s tic o fo i re a liz a d o a tra v e s d o is o la m e n to d o Aspergil-lus d a s e c rey3 0 d o s a b c e s s o s c e re b ra is . 0 p a c ie n te fo i tra ta d o c o m d re n a g e m d o s a b c e s s o s e A n fo te ric in a B e n d o v e n o s a . A p re s e n to u re g re s s 3 0 p ro g re s s iv a d a s im a g e n s ra d io l6 g ic a s (c e re b ra l e p u lm o n a r) n u m p e rio d o d e 5 5 d ia s . E s te re la to e n fa tiz a a im p o rtfm c ia d a te ra p ia a n tifu n g ic a a s s o c i a d a
a
d re n a g e m c iru rg ic a n o tra ta m e n to d o a s p e rg ilo m a c e re b ra l. R e s s a lta m ta m b e m a im p o rta n c ia d a te ra p ia p re c o c e n o p ro g n 6 s tic o d e s s e s c a s o s .REFERENCES
I. B o d ey G P , G lan n , A S . C en tral n erv o u s sy stem asp erg illo sis fo llo w in g stero id al th erap y fo r allerg ic
b ran ch p u lm o n ary asp erg illo sis. C h est 1 9 9 3 ;I0 3 (I):2 9 9 -3 0 I.
2 . E p stein N E . H o llin g sw eo rth R , B lack K , F arm er P .
F u n g al b rain ab scesses (asp erg illo sis/m u co rm y co sis) in
tw o im m u n o su p ressed p atien ts. S u rg N eu ral 1 9 9 1 ;3 5 (4 ):
2 8 6 -9 .
3 . S p aran o lA, G u calp R , L 1 en a IF,M o ser G F , W iern ick P H . C ereb ral in fectio n co m p licatin g sy stem ic asp erg illo sis in
acu te leu k em ia: clin ical an d raclio lo g rafic p resen tatio n .
1
N eu ro o n co l 1 9 9 2 ; 1 3 M ay ( I):9 1 -1 0 0 .
4 . P reck el M P , M ercatello A , T o g n et F , D ev au x Y , et al. C ereb ral
asp erg illo sis in im m u n o co m p ro m ised p atien ts. A n n F r
A n esth R ean im 1 9 9 1 ;IO .
5 . K reisel W , K o ch lin g G , V o n S ch illin g C , et al. T h erap y o f
in v asiv e asp erg illo sis w ith Itraco n azo le: im p ro v em en t o f
th erap eu tic efficacy b y early d iag n o sis. M y co sis 1 9 9 1 ;3 4 (9
-1 0 ):3 8 5 -9 4 .
G O L lN , V .; S P R O V IE R I, S .R .S .; C A N < ;A D O , J .E .D ., D A N IE L , J .w . & M IM IC A , L .M .J . -A s p e rg illo s is o f th e c e n tra l n e rv o u s s y s te m
