13 years of age with a diagnosis of acute bacterial meningitis. All the patients were examined daily by the same group of neurologists, using a standardized ...
PROGNOSIS OF BACTERIAL MENINGITIS IN CHILDREN IRENIO GOMES*, AILTON MELO**, RITA LUCENA***, MARCO HELENO CUNHA -NASCIMENTO****, ADRIANA FERREIRA****, JULIETA GÓES****, ISMARA BARRETO****, NEILA JONES****, VERÔNICA GASPARI****, EMILIA KATIANE EMBIRUÇU****, MARIELZA VEIGA*
A B S T R A C T - We studied the incidence and prognosis of acute neurologic complications in 281 children under 13 years of age with a diagnosis of acute bacterial meningitis. All the patients were examined daily by the same group of neurologists, using a standardized neurological examination. Patients with signs of encephalic lesions, unsatisfactory response to antibiotics or decreased level of consciousness were submitted to brain computer tomography. The overall lethality rate was 20.3% and cases whose causative agent was identified presented a higher lethality rate (23.7%) than those in which the agent was not found. The most important neurological abnormalities were meningeal signs (88.3%) followed by decreased consciousness (47.7%), irritability (35.2%), seizures (22.4%), fontanel bulging (20.6%) and cranial nerve palsy (14.2%). Seizures, cranial nerve palsy and the absence of meningeal signs were related to higher rates of lethality. Diminished consciousness, seizures, subdural effusion, abscess and hydrocephalus were the most important complications, respectively. We can conclude that acute bacterial meningitis continues to be an important health problem in developing countries and that public health measures will be necessary to minimize the impact of sequelae and reduce the mortality rate in children with that pathology. KEY W O R D S : pyogenic meningitis, bacterial meningitis, septicemia, meningitis in children.
Prognóstico de meningite bacteriana em crianças RESUMO - Para estudar os fatores prognósticos e incidência de complicações em meningite bacteriana, 281 crianças (idade abaixo de 13 anos) com quadro clínico e do LCR compatíveis com esse diagnóstico foram acompanhadas, durante o internamente), através de ficha de avaliação padrão. Aquelas que apresentaram sinais de lesão encefálica, resposta inadequada ao tratamento ou diminuição do nível de consciência, com Glasgow < 7, foram submetidas a tomografia computadorizada de crânio. A taxa de letalidade global foi 20,3%, sendo maior quando o agente etiológico foi identificado (23,7%). As alterações neurológicas mais encontradas foram: irritação meníngea, diminuição do nível de consciência, convulsões, irritabilidade, abaulamento de fontanela e comprometimento de nervos cranianos. Convulsões, comprometimento de nervos cranianos e ausência de irritação meníngea foram associados a maior Ietalidade. Complicações neurológicas ocorreram em 5 8 % , sendo as mais frequentes diminuição do nível de consciência (47,7%), convulsões (22,4%), coleção subdural (3,2%), abscesso(2,5%) e hidrocefalia(2,5%). Observamos que meningite bacteriana continua sendo problema de saúde publica em países em desenvolvimento e que medidas para redução da morbidade e mortalidade desta doença são necessárias. PALAVRAS-CHAVE: meningite piogênica, meningite bacteriana, septicemia, meningite em crianças.
A l t h o u g h t h e u s e of antibiotics h a s d r a m a t i c a l l y c h a n g e d t h e mortality of patients with p y o g e n i c 6,7
m e n i n g i t i s , m a n a g e m e n t of n e u r o l o g i c a l c o m p l i c a t i o n s r e m a i n s as a significant p r o b l e m . Fatalities m a y o c c u r in s p i t e of a p p r o p r i a t e t r e a t m e n t a n d m a y b e r e l a t e d t o c e r e b r a l e d e m a , v a s c u l i t i s ,
Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia (UFBA), Salvador; * D o c e n t e do S e r v i ç o de N e u r o l o g i a ; * * C h e f e do S e r v i ç o d e N e u r o l o g i a ; * * * P ó s - g r a d u a n d a de Neuropsicofarmacologia; ****Estagiário do Serviço de Neurologia. This paper was partially presented at the Fifth Meeting of the European Neurological Society. Aceite: 11-abril-1996. Dr. Ailton Melo - Faculdade de Medicina UFBA - Av. Reitor Miguel Calmon, s/n - 40110-100 Salvador BA Brasil. FAX 5571 3580592.
91
t h r o m b o p h l e b i t i s " o r a l t e r a t i o n s of c e r e b r a l v a s c u l a r flow, as h a s b e e n d e s c r i b e d in l a b o r a t o r y a n i m a l s . M o s t of t h e clinical r e p o r t s o n c o m p l i c a t i o n s a n d m o r t a l i t y in bacterial m e n i n g i t i s h a v e b e e n d o n e in d e v e l o p e d c o u n t r i e s " " . In S o u t h A m e r i c a a n d Africa, d e s p i t e a c o n t i n u e d h i g h i n c i d e n c e of m e n i n g i t i s , there are few reports a n a l y z i n g aspects of neurological m o r b i d i t y in c h i l d r e n w i t h a d i a g n o s i s of p y o g e n i c m e n i n g i t i s . 9,11
6
8
1 4
13
F o r this p a p e r , w e p e r f o r m e d a p r o s p e c t i v e s t u d y in 2 8 1 c h i l d r e n u n d e r 13 y e a r s of a g e , in a n infectious d i s e a s e hospital in S a l v a d o r ( N o r t h e a s t e r n B r a z i l ) , in o r d e r to d e t e r m i n a t e a c u t e n e u r o l o g i c c o m p l i c a t i o n s in c h i l d r e n w i t h p y o g e n i c m e n i n g i t i s .
METHODS The Hospital Couto Maia, a large reference hospital for the treatment of infectious diseases, located in Salvador - Bahia, Northeastern Brazil, provides healthcare services to virtually all suspected cases of community meningitis in Salvador, excluding neonatal patients. From April to December 1993, we studied 281 patients under 13 years of age who fulfilled one of the following diagnostic criteria for pyogenic meningitis: 1, positive cerebral spinal fluid (CSF) culture for pyogenic bacteria; 2, presence of Gram-negative diplococci in CSF; 3, positive blood cultures for Neisseriae meningitidis with CSF cell count over 4 cells/mm ; 4, CSF cell count of 1000 or more cells/mm3 with more than 50% being neutrophils; 5. visualization of Gram stained bacteria in CSF. It was established that the first three criteria would identify the causative agent. Infants with a congenital or acquired abnormality of the central nervous system(CNS), a prosthetic device inserted into the CNS or previous episodes of bacterial meningitis were excluded. 3
On admission every patient underwent anamnesis and a standardized neurologic examination. Subsequently, patients were given follow up exams in hospital wards. A CT scanning was performed in patients who presented: signs of encephalic lesions, a diminished level of consciousness, less than 7 on the Glasgow coma scale, an unsatisfactory response to the proper therapeutic treatment. All information was recorded in questionaries filled out by the examiners and entered in a computer file created in Fox Pro version 2.5. The data were analyzed with the help of a statistical software program, EPIINFO version 5.01b. Five children were removed to other health care unities and the lethality was calculated with a total of 276 patients.
RESULTS T h e r e w e r e 158 ( 5 6 . 2 % ) m a l e s a n d 123 ( 4 3 . 8 % ) f e m a l e s . E t i o l o g i c a g e n t s w e r e i d e n t i f i e d in 2 0 8 ( 7 4 % ) c a s e s w i t h a p r e d o m i n a n c e of H. influenzae, a n d S.pneumoniae
( T a b l e 1). H. influenzae
f o l l o w e d , r e s p e c t i v e l y , b y N.
meningitidis
w a s t h e p r i m a r y c a u s a t i v e a g e n t in c h i l d r e n four y e a r s of
a g e o r y o u n g e r . A f t e r that a g e g r o u p , N. meningitides
w a s t h e p r i m a r y e t i o l o g i c a g e n t . S.
pneumoniae
w a s t h e s e c o n d in i m p o r t a n c e o n l y after t h e a g e of n i n e . O t h e r a g e n t s like Citrobactersp.,S.
aureus.
and Klebsiella
sp. o c c u r r e d less f r e q u e n t l y ( 3 . 2 % ) . T h e e t i o l o g i c d i s t r i b u t i o n in c h i l d r e n a g e d 2
m o n t h s o r y o u n g e r w a s v e r y u n u s u a l d u e t o t h e l o w n u m b e r of c a s e s in this a g e g r o u p .
T h e o v e r a l l lethality r a t e w a s 2 0 . 3 % . T h e r a t e w a s h i g h e r a m o n g c a s e s w i t h identified a g e n t s (23.7%) than a m o n g cases with unidentified agents (10.1%). T h e m o s t f r e q u e n t clinical a l t e r a t i o n s w e r e fever (97.1 % ) , v o m i t i n g ( 7 7 . 2 % ) a n d s o m n o l e n c e ( 5 0 . 2 % ) . R e s p i r a t o r y i n f e c t i o n s ( 2 4 . 2 % ) , otitis ( 7 . 5 % ) a n d o t a l g i a ( 6 . 4 % ) w e r e the m o s t i m p o r t a n t p r e d i s p o s i n g f a c t o r s . P r e v i o u s u s e of a n t i b i o t i c s w a s p r e s e n t in 1 7 . 4 % of p a t i e n t s . S o m n o l e n c e , f e v e r a n d o t a l g i a w e r e p r e d o m i n a t i n g in o u r c a s e s . N o n e of t h e s e c l i n i c a l a l t e r a t i o n s h a d a n y r e l a t i o n s h i p w i t h i n c r e a s e d lethality. T h e most important neurologic findings were meningeal signs (88.3%), diminished c o n s c i o u s n e s s ( 4 7 . 7 % ) , irritability ( 3 5 . 2 % ) , s e i z u r e s ( 2 2 . 4 % ) , f o n t a n e l b u l g i n g ( 2 0 . 6 % ) a n d c r a n i a l nerve palsy (14.2%). S e i z u r e s , c r a n i a l n e r v e p a l s y a n d a n a b s e n c e of m e n i n g e a l s i g n s w e r e r e l a t e d t o a h i g h e r mortality rate (Table 2). T h e o v e r a l l c o m p l i c a t i o n r a t e w a s 5 8 % ( T a b l e 3) w i t h t h e m o s t c o m m o n b e i n g : l o w e r e d c o n s c i o u s n e s s ( 4 7 . 7 % ) ; seizures ( 2 2 . 4 % ) ; subdural effusion ( 3 . 2 % ) ; brain abscess (2.5%); hydrocephalus (2.5%). Leukoencephalopathy (1.4%), stroke (1.1%), cortical atrophy (0.4%) and e n c e p h a l i t i s ( 0 . 4 % ) w e r e less frequent. In g e n e r a l t h e c o m p l i c a t i o n s p r e d o m i n a t e d in c h i l d r e n u n d e r
o n e y e a r o f a g e ( 7 1 % ) . S u b d u r a l effusions a n d h y d r o c e p h a l u s p r e d o m i n a t e d in y o u n g e r c h i l d r e n a n d a b s c e s s o c c u r r e d m a i n l y after four y e a r s of a g e . S. pneumoniae f o l l o w e d b y H. influenzae
w a s the e t i o l o g i c a g e n t r e l a t e d t o t h e h i g h e s t c o m p l i c a t i o n r a t e ( 7 8 . 8 % ) , ( 6 4 % ) , u n i n d e n t i f i e d a g e n t s ( 5 6 . 2 % ) a n d N. meningitidis
(40.3%). Other
a g e n t s , a s a g r o u p , h a d a h i g h r a t e of c o m p l i c a t i o n s , b u t the n u m b e r of c a s e s is n o t significant. T h e c o m p l i c a t i o n s in TV. meningitidis
p a t i e n t s w e r e l i m i t e d to r e d u c e d c o n s c i o u s n e s s a n d s e i z u r e s . M o s t
a b s c e s s a n d s u b d u r a l effusions o c c u r r e d in cases with unidentified a g e n t s w h i l e h y d r o c e p h a l u s o c u r r e d m a i n l y in c a s e s w h o s e a g e n t s w e r e H. influenzae
and S. pneumoniae
(Table 4).
DISCUSSION In this s t u d y w e p r o v i d e e v i d e n c e that p y o g e n i c m e n i n g i t i s c o n t i n u e s to b e o n e of t h e m o s t i m p o r t a n t c a u s e s of n e u r o l o g i c a l s e q u e l a a n d m o r t a l i t y in c h i l d r e n of B a h i a , as h a s b e e n p r e v i o u s l y d e s c r i b e d b y o t h e r a u t h o r s ' . W e also s h o w e d that m o r e t h a n half of the 2 8 1 patients s t u d i e d d e v e l o p e d neurological complications during the acute phase of disease and these findings were m o r e frequents in c h i l d r e n a g e d o n e y e a r o r less. T h e m a i n p r e d i c t i v e factors of lethality w e r e altered c o n s c i o u s n e s s a n d s e i z u r e s . T h e s e clinical s i g n s w e r e m o s t r e l a t e d to s u b d u r a l effusion, h y d r o c e p h a l u s a n d b r a i n a b s c e s s . In a p r o s p e c t i v e clinical s t u d y u t i l i z i n g an a d u l t p o p u l a t i o n , t h e m o s t i m p o r t a n t a c u t e n e u r o l o g i c a l c o m p l i c a t i o n d u r i n g b a c t e r i a l m e n i n g i t i s w a s r e l a t e d to c e r e b r a l e d e m a a n d c e r e b r o v a s c u l a r i n v o l v e m e n t w h i c h 9
w e r e d i a g n o s e d u s i n g c e r e b r a l a n g i o g r a p h y a n d C T s c a n . A l t h o u g h it w a s n o t p o s s i b l e t o p e r f o r m a n g i o g r a p h i e s s y s t e m a t i c a l l y , o u r clinical e x p e r i e n c e l e a d u s to b e l i e v e that c e r e b r a l infarct is l e s s i m p o r t a n t in c h i l d r e n t h a n in a d u l t s . A s w e h a v e d e s c r i b e d in o u r r e p o r t , o n l y t h r e e p a t i e n t s h a d s t r o k e . A n o t h e r l i m i t a t i o n of o u r s t u d y is that l o n g t e r m f o l l o w u p w e r e p o s s i b l e in o n l y a few p a t i e n t s , d u e t o t h e c h a r a c t e r i s t i c s of o u r h o s p i t a l . S u b d u r a l effusion a n d h y d r o c e p h a l u s w e r e m o r e c o m u m in p a t i e n t s u n d e r o n e y e a r o f a g e . B r a i n a b s c e s s e s o c c u r r e d in s e v e n p a t i e n t s ; five p a t i e n t s w e r e o v e r four y e a r s of a g e , o n e p a t i e n t w e r e 8 m o n t h s o l d a n d t h e o t h e r 9 m o n t h s o l d . W e w e r e n o t a b l e t o find a n y r e a s o n a b l e e x p l a n a t i o n for the frequency of s u b d u r a l effusion in c h i l d r e n w i t h m e n i n g i t i s . In o u r o p i n i o n , insufficient d r a i n a g e of C S F , v i a t h e a r a c h n o i d villi c e l l s , a c o m m o n c o m p l i c a t i o n in c a s e s of b a c t e r i a l m e n i n g i t i s
1 1 1 4
, is
m o r e p r e v a l e n t in c h i l d r e n , w h i c h favors t h e d e v e l o p m e n t of s u b d u r a l c o l l e c t i o n s . In c h i l d r e n , m a i n l y
in t h o s e u n d e r o n e y e a r of a g e , a d i a g n o s i s of C N S c o m p l i c a t i o n s is o b t a i n e d o n l y if t h e r e is an e x p e r i e n c e d t e a m f o l l o w i n g t h e p a t i e n t s d a y after day. W e o b s e r v e d that t h e m a j o r i t y of C N S c o m p l i c a t i o n s o c c u r r e d w i t h i n t h e first d a y s of a d m i s s i o n a n d , for all a g e g r o u p s , S. pneumoniae w a s related to the highest lethality and complication rates. H o w e v e r , this observation m a y b e u n d e r s t i m a t e d b e c a u s e w e d i d n o t h a v e t h e o p p o r t u n i t y to r e c o r d h e a r i n g i m p a i r m e n t in o u r g r o u p of p a t i e n t s , w h i c h h a s b e e n s h o w n t o b e o n e o f t h e m o s t i m p o r t a n t s e q u e l a in c a s e s of m e n i n g i t i s , m a i n l y in p a t i e n t s w i t h S. pneumoniae m e n i n g i t i s . N. meningitidis was related to fewer sequela and a l o w e r m o r t a l i t y rate, as s h o w n in T a b l e 4 . In s o m e patients s u b d u r a l effusion a n d / o r a b s c e s s o c c u p i e d g r e a t e x t e n s i o n s of t h e b r a i n . H o w e v e r , s u r g i c a l p r o c e d u r e s w e r e n o t n e c e s s a r y in a n y b u t t w o of o u r p a t i e n t s w i t h b r a i n a b s c e s s . O n e p a t i e n t d i e d five d a y s after surgery. S. aureus a c c o u n t e d for 5 ( 1 . 8 % ) o f t h e c a s e s of b a c t e r i a l m e n i n g i t i s in o u r p o p u l a t i o n , b u t , c o n t r a r y t o o t h e r p u b l i c a t i o n s , o n l y t w o p a t i e n t s ( 4 0 . 0 % ) d i e d . O f t h e p a t i e n t s w i t h S. aureus m e n i n g i t i s , o n e h a d a soft t i s s u e a b s c e s s a n d a n o t h e r h a d e n d o c a r d i t i s d u e to r h e u m a t i c fever. 12
T h e m o s t i m p o r t a n t p r e d i c t i v e factors for d e a t h w e r e s e i z u r e s , cranial n e r v e palsies a n d a b s e n c e of m e n i n g e a l s i g n s . W e b e l i e v e that s e i z u r e s c o u l d b e r e l a t e d t o c o r t i c a l h y p o x i a a n d / o r i s c h e m i a , u s u a l l y o b s e r v e d in p a t i e n t s w i t h b a c t e r i a l m e n i n g i t i s , a s d e s c r i b e d e l s e w h e r e . 6
A l t h o u g h w e c o u l d not find statistical significance to associate d e c r e a s e d c o n s c i o u s n e s s level to i n c r e a s e d lethality, there is an i m p o r t a n t t e n d e n c y to establish this a s s o c i a t i o n in o u r g r o u p of patients. A r e t r o s p e c t i v e study, c a r r i e d o u t at t h e s a m e h o s p i t a l f r o m 1 9 7 3 t o 1 9 8 2 ' , a n a l y z e d 4 1 0 0 a d m i s s i o n s for m e n i n g i t i s . O f t h e s e c a s e s , c h i l d r e n u n d e r 15 y e a r s o f a g e a c c o u n t e d for 7 9 % . T h i s s t u d y r e v e a l e d a n o v e r a l l c a s e fatality r a t e of 3 3 % , w i t h 5 0 % of d e a t h s o c c u r r i n g w i t h i n 4 8 h o u r s of a d m i s s i o n . A l t h o u g h t h e a u t h o r s o b s e r v e d that t h e o v e r a l l c a s e fatality r a t e w a s l o w e s t in p a t i e n t s f r o m 2 to 15 y e a r s of a g e , t h e r e w a s a l o w e r m o r t a l i t y rate in all t h e a g e g r o u p s w h e n w e c o m p a r e d b o t h p o p u l a t i o n s . H o w e v e r , a majority of patients c o n t i n u e s to d i e w i t h i n 4 8 h o u r s of h o s p i t a l i z a t i o n . It is p o s s i b l e that b e t t e r m a n a g e m e n t of t h e c o m p l i c a t i o n s a n d t h e e a r l i e r u s e of p r o p e r a n t i b i o t i c s c o u l d b e r e l a t e d t o t h e d e c r e a s e d m o r t a l i t y r a t e o b s e r v e d in o u r c a s e s . In trial s t u d i e s in c h i l d r e n w i t h b a c t e r i a l m e n i n g i t i s , d e x a m e t h a s o n e h a s b e e n s h o w n to r e d u c e m e n i n g e a l i n f l a m m a t i o n a n d i m p r o v e t h e o u t c o m e of disease - - ' . C o r t i c o s t e r o i d s h a v e b e e n utilized s y s t e m a t i c a l l y a s a n a d d i t i o n a l t h e r a p y i n c h i l d r e n w i t h b a c t e r i a l m e n i n g i t i s a d m i t t e d to o u r h o s p i t a l . H o w e v e r , at the p r e s e n t t i m e , it is n o t p o s s i b l e t o e s t a b l i s h t h e t r u e i m p a c t of c o r t i c o s t e r o i d s in o u r p o p u l a t i o n . 4
5
7
8
REFERENCES 1. Bryan JP, Silva HR, Tavares A, Rocha H, Scheld W M . Etiology and mortality of bacterial meningitis in Northeastern Brazil. Rev Inf Dis 1990;12:128-135. 2. Cadoz M, Denis F, Diop Mar I. Etude épidémiologique des cas de méningites purulentes hospitalises à Dakar pendant la décennie 1970-79. Bull Organis Mond Santé 1981;59:575-584. 3 . Ferreira A, N a s c i m e n t o M H C , G o m e s 1, M e l o A. N e u r o l o g i c c o m p l i c a t i o n s in bacterial m e n i n g i t i s . J Neurol 1995;242:(Suppl):S-115. 4. Geiman BJ, Smith AL. Dexamethasone and bacterial meningitis: a metanalysis of randomized controllled trials. West J Med 1992;157:27-31. 5. Girgis NI, Farid Z, Mikhail IA, Ferrag I, Sultan Y, Kilpatrick ME. Dexamethasone treatment for bacterial meningitis in children and adults. Pediatr Infect Dis J 1989;8:848-851. 6. Herson VC, Todd JK. Prediction of morbidity in H. influenzae meningitis. Pediatrics 1977;59:35-39. 7. Lebel M H , Freij BJ, Syrogiannopoulos G A et al. Dexamethasone therapy for bacterial meningitis: results of two double blind placebo controlled trials. N Engl J Med 1988;319:964-971. 8. Odio CM, Faingezcht I, Paris M et al. The beneficial effects of early dexametasone administration in infants and children with bacterial meningitis. N Eng J Med 1991 ;324:1525-1531. 9. Pfister HW, Borasie GD, Dirnagl U, Bauer M, Einhaupl KM. Cerebrovascular complications of bacterial meningitis in adults. Neurology 1992;42:1497-1504. 10. PfisterHW, Feiden W, Einhaupl KM. Spectrum of complications during bacterial meningitis in adults: results of a prospective clinical study. Arch Neurol 1993;50:575-581. 11. Quagliarello V, Scheld WM. Bacterial meningitis: pathogenesis, pathophysiology and progress. N Engl J Med 1992;327:864-872. 12. Schlesinger LS, Ross SC, Schaberg DR. Staphylococcus aureus meningitis: a broad based epidemiologic study. Medicine 1987;66:148-156. 13. Spanos A, Harrel FE, Durack DT. Differential diagnosis of acute meningitis: an analysis of the predictive value of initial observations. J A M A 1989;2700-2707. 14. Tunkel AR, Wispelwey B, Scheld M. Bacterial meningitis: recent advances in pathophysiology and treatment. Ann Intern Med 1990;112:610-623.
