CARDIAC INVOLVEMENT IN HUMAN RABIES CASE REPORT

CARDIAC INVOLVEMENT IN HUMAN RABIES

CASE REPORT

Carlos Floriano de MORAIS (1) and Raimunda Violante Campos de ASSIS (2)

S U M M A R Y

A case of human rabies with cardiac involvement and viral inclusion bodies

in the heart is presented. The Negri bodies were found in the Schwann cells of

the right epicardial atrium, with secondary mononuclear cells inflammation. In

the myocardium, an interstitial edema, proliferation of Anitschkov and rare

mo-nonuclear inflammatory cells were seen. There was no relevant cardiovascular

signs or symptoms. The rarity of histological descriptions of Negri bodies in the

heart is stressed, as well as the importance of cardiac involvement as a

poten-tial complication for cases with life prolonged by intensive care units, or in

the end-stages of the disease.

I N T R O D U C T I O N

Clinical and/or pathological heart

involve-ment in human rabies has been already

report-ed in few cases (revisreport-ed by WARRELLM). The

cause of death was not the cardiac lesions, but

encephalitis; however, probably they play an

important role in the end-stages of the disease,

or in cases with a more prolonged evolution in

intensive care units which may prolong life up

to 133 days (ABAUJO et al.

; BHATT et al.2;

CHEETHAN & HART

_{; EMMONS et}

alJ;

RU-BIN et al.w; W A R R E L L " ) . Furthermore,

the-re athe-re descriptions of human rabies cases with

recovery, stressing the importance of

occasio-nal complications and their future prevention

(HATTWICK et al.*).

Among the cases showing myocarditis, just

one had Negri bodies in the heart; the viral

inclusion bodies were in a parasympathetic

cardiac neuron, associated with inflammatory

cells (ARAUJO et al.i).

This paper reports another case of human

rabies with cardiac involvement and the

pre-sence of viral inclusion bodies in the atrial

ner-vous branches.

CASE DESCRIPTION

AJVLS., a 12 years-old white boy who came

from Araguari, Minas Gerais State (M.G.),

Bra-zil. Six days before admission he had a

sud-den episode of fever, malaise and psychomotor

agitation treated symptomatically, without

im-provement. Two days after appeared

dyspha-gia with refusal of fluids and food. He was

first admitted in Hospital of the University of

Uberlândia, M.G., where the clinical diagnosis

of rabies was established. The cerebrospinal

fluid examination demonstrated 100 cells, with

absolute predominance of mononuclear cells.

The clinical picture persisted together with

in-tense excitation, psychic and behavioral

distur-bances, hydrophobia and aerophobia. In this

occasion, six days after the first symptom, he

was transferred to the "Hospital das Clínicas"

of the São Paulo University, Medical School.

From the Department of Pathology, São Paulo University Medical School, São Paulo Brazil (1) Resident in Pathology

T h e pulse w a s 7 0 / m i n . a n d m e a n b l o o d pressu

re 7x6 c m H g ; t h e r e w a s e x c e s s i v e s a l i v a t i o n and d e h y d r a t i o n . T h e n e u r o l o g i c a l e x a m i n a t i o n d e m o n * t r u l e d s o m n o l e n c e , p s y c h i c c o n f u s i o n , b l u r r e d v o i c e , d y s a r t h r i a , stiff n e c k and gene iiilisrcl ( i o n i c m o v i m e n l s at the least stlmulM

l i o n ; n o m o t o r d e f i c i t s c o u l d b e f o u n d . T h e r e w a s n o c a r d i o v a s c u l a r a b n o r m a l i t i e s besides t h e h y p o t e n s i o n .

In t h e next 4H h o u r s the disease p r o g r e s s e d t o t o t a l a r e f l e x i a . p r o b a b l y w i t h b r a i n s t e m

d a m a g e , i n f e r r e d by the a p p e a r i n g of a p n e a , and death. T h e f a m i l y i n f o r m e d that t h e pa tient used t o g o t o a f a r m in w h o s e house li-v e d b a t s ; he h a d a l s o b e e n b i t t e n by a d o g t w o m o n t h s e a r l i e r , w i t h o u t i n f o r m a t i o n o n n e i t h e r

t h e a n i m a l health c o n d i t i o n n o r t h e Injury site.

At a u t o p s y , f r a g m e n t s of c e r e b e l l u m w e r e

used both f o r r a b i e s v i r u s d e m o n s t r a t i o n ,

t h r o u g h s p e c i f i c i m m u n o f l u o r e s c e n t • I n s t i t u t o

P a s t e u r of S ã o P a u l o * a n d b i o l o g i c a l assay in

m i c e w i t h p o s i t i v e results.

T h e b r a i n w e i g h e d 1 574 g. w a s e d e m a t o u s a n d c o n g e s t e d w i t h f l a t t e n e d a n d b r o a d c o n v o lutions in t h e right f r o n t a l s i d e a p e r f o r a t i n g lesion w a s s e e n , due t o t r e p a n a t i o n for

intra-cranial p r e s s u r e c o n t r o l . T h e m i c r o s c o p i c a l study s h o w e d a m o d e r a t e d e g r e e of m o n o n u c l e a r i n f l a m m a t o r y c e l l s a r o u n d vessels and ne-c r o t i ne-c o r d e g e n e r a t i n g n e u r o n s , t o g e t h e r w i t h

.1 f e w n e u t r o p h i l s . M a n y of these n e u r o n s h a d c y t o p l a s m a t i c N e g r i b o d i e s ( F i g . 1 ) . Such al-t e r a al-t i o n s w e r e m o r e inal-tense in b r a i n s al-t e m , ba-sal ganglia a n d h y p o t h a l a m u s . T h e m e n i n g e s w e r e g r o s s l y w h i t i s h and t h e h i s t o p a t h o l o g t c a l e x a m i n a t i o n s h o w e d an intense n e u t r o p h i l i c

in-f l a m m a t o r y r e s p o n s e , m a i n l y a r o u n d t h e trepa-n a t i o trepa-n area.

d e l ( P i g . 3 ) . I n the c y t o p l a s m of S c h w a n n cells N e g r i b o d i e s c o u l d b e f o u n d ( P i g . 4 ) . I n t h e a d r e n a l m e d u l l a a n i n t e n s e m o n o n u c l e a r cell i n f l a m m a t o r y r e s p o n s e w a s a l s o f o u n d ,

w i t h o u t n e c r o s i s o r v i r a l Inclusion b o d i e s .

D I S C I S S I O N

T h e r e a r e f e w c l t n i c o - p a l h o l n g l c a ) r e p o r t s

of c a r d i a c i n v o l v e m e n t i n the c o u r s e o f h u m a n T h e heart a n d o t h e r o r g a n s w e r e g r o s s l y

n o r m a l . I n t h e m y o c a r d i a l i n t e r s t t t i u m a

mo-d e r a t e mo-d e g r e e o f e mo-d e m a , h y p e r p l a s i a o f A n l t s

c e l l s , f e w m o n o n u c l e a r i n f l a m m a t o r y

cells, a b s e n c e of c a r d i a c f i b e r n e c r o s i s and ;i

few n e u t r o p h i l s w e r e seen ( F i g . 2 » . A r o u n d the

right a t r i a l p a r a s y m p a t h e t i c n e r v o u s b r a n c h e s

m o n o n u c l e a r c e l l s w e r e n u m e r o u s a n d the g a n

mi-rabies in p a t i e n t s w i t h o u t p r e v i o u s h e a r t

di-sease* I A R A U J O e t al. ' : C H E E T H A N Sc H A R T1

:

R O S S & A R M E N T R O U T ' : R O U X et

al.*',

R E L L

T h e ineidence ot h i s t o p a t h o l o g i c a l lesions is v a r i a b l e ; A R A U J O et a l . ' round focal

h u m a n cases, d e m o n s t r a t e d c a r d i a c

involve-m e n t i n all. H o w e v e r , f r o involve-m t h e involve-m i c r o s c o p i c s t a n d p o i n t , ( h e lesions c o n s i s t e d of a v a r i a b l e a s s o c i a t i o n of d e g e n e r a t i v e , c o n g e s t i v e a n d in-f l a m m a t o r y a l t e r a t i o n s in-f r e q u e n t l y m i l d and in-f o c a l . A d i a g n o s i s o f m y o c a r d i t i s c o u l d not

al-w a y s b e d o n e .

In s o m e s e r i e s t h e r a b i e s v i r u s w e r e

iso-l a t e d in the h e a r t o r w a s seen in e p i c a r d i a iso-l nerv o u s cells, a l l o w i n g the e t i o l o g y of t h e m y o c a r -d i a l l e s i o n s t o be a s c e r t a i n e -d ( A R A U J O et a l .1

; D U E 8 A S et a l . ' ; R O U X et al.*; W A R R E L L et

I n m a n y reported cases t h e r e w e r e , besi-d e s t h e p a t h o l o g i c a l a l t e r a t i o n s , c a r besi-d i o v a s c u l a r s i g n s and s y m p t o m s a n d p u l m o n a r y c o m p l i c a -t i o n s such a s : h y p o -t e n s i o n ( C H E E T H A N A H A R T R O S S & A R M E N T R O U T * ) . c a r d i a c a r

r h y t m l a a I C H E E T H A N & H A R T1

; M I L L E R & N A T H A N S O N7

; R O S S & A R M E N T R O U T *; R O U X e t al.*) a n d inespecific e l e t r o c a r d l o g r a -p h i c a l t e r a t i o n s ( R O S S &am-p; A R M E N T R O U T » ; W A R R E L L " ) .

I n this case, besides t h e h y p o t e n s i o n , no o t h e r c l i n i c a l a l t e r a t i o n s w e r e o b s e r v e d . H o w e v e r , a n I n f l a m m a t o r y r e s p o n s e a r o u n d atrial n e r v o u s b r a n d i e s , a s s o c i a t e d w i t h m y o c a r d i a l interstitial a l t e r a t i o n s w a s f o u n d . I f t h e patient

had s u r v i v e d f o r a l o n g e r p e r i o d t h e s e l e s i o n s w o u l d p r o b a b l y h a v e b e c a m e w o r s e and a s t r a i g h f o r w a r d p i c t u r e of m y o c a r d i t i s c o u l d pos-s i b l y b e pos-seen. T h e m i c r o pos-s c o p i c c a r d i a c p i c t u r e w a s c o n s i d e r e d due t o the r a b i e s v i r u s

becau-s e o f t h e p r e becau-s e n c e o f N e g r i b o d i e becau-s in the h e a r t ; h o w e v e r it w a s not d i s c a r d e d the p o s s i b i l i t y that, at least p a r t i a l l y , t h e interstitial a l t e r a t i o n s w e r e r e a c t i v e t o t h e acute m e n i n g i t i s .

T h e d a t a p r e s e n t e d r e i n f o r c e t h e p r e v i o u s o b s e r v a t i o n s o n t h e e t i o l o g y of m y o c a r d i t i s i o r o f t h e h i s t o p a t h o l o g i c a l a l t e r a t i o n s ) in t h e

c o u r s e o f h u m a n rabies a n d the r a r i t y o f pa-t h o l o g i c a l r e p o r pa-t s d e s c r i b i n g N e g r i b o d i e s i n the h e a r t .

O n the o t h e r hand, t h e finding of N e g r i bo-d i e s i n the h e a r t a n bo-d the i n f l a m m a t o r y respon-se in the a d r e n a l m e d u l l a are e v i d e n c e s f o r t h e d i s s e m i n a t i o n b y centrifugal p a s s i v e t r a n s p o r t

of rabies g e n o m e i n a x o p l a s m of p e r i p h e r a l n e r v e s f r o m the c e n t r a l n e r v o u s s y s t e m ( M I L L E R

&i N A T H A N S O N T ) .

R E S U M O

Comprometimento cardíaco na raiva humana Relato de caso

O s A u t o r e s d e s c r e v e m u m c a s o h u m a n o d e

prometimento cardíaco. No entanto, ao

exa-me microscópico do coração, à necropsia, foi

evidenciado infiltrado inflamatório ao redor de

ramúsculos nervosos do epicardio do átrio

di-reito, ao lado de corpúsculos de Negri intra-ci¬

toplasmáticos nas células de Schwann. No

miocárdio foi verificado edema intersticial, rea¬

tividade das células pertencentes ao sistema

monocítico-fagocitário e raras células

inflama-tórias mononuclear es. É salientada a raridade

de descrições semelhantes, bem como a

impor-tância do envolvimento cardíaco como

poten-cial complicação para os casos submetidos a

tratamento intensivo e, portanto, com evolução

mais prolongada, ou nos estágios finais da

doença.

ACKNOWLEDGEMENTS

The Authors thank Dr. Thales de Brito for

the orientation and text review and Ms. Ivany

Tavares da Silva for the photographic work.

REFERENCES

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