intracranial hypertension or only benign intra- cranial hypertension, headache and/or dizziness with pyramidal liberation. Moderately ill patients were those who ...
Rev. Insí. Med. trap. São Paula 30 (5):387-389, setembro-outubro,
1988
NEUROCYSTICERCOSIS: TREATMENT WITH ALBENDAZOLE A N D DEXTROCHLOROPHENIRAMINE (PRELIMINARY REPORT).
, 2
121
Svellana AGAPEJEV"», Domingos Alves MEIRA"', Benedito BARRAV I E R A \ Jussara Marcondes M A C H A D O , Paulo Câmara Marques PEREIRA' ', Rinaldo Pôncio MENDES»' ', Amélia KAMEGASAW A'-" & Paulo Roberlo CURI'2
2
11
KEY W O R D S : N e u r o c y s t i c e r c o s i s : Treatment.
Albendazole;
The clinical variability of n e u r o c y s t i c e r c o s i s is d u e t o a series of f a c t o r s s u c h as n u m b e r , l o c a t i o n , f o r m , d i m e n s i o n s a n d s t a g e of d e v e l o p m e n t of t h e p a r a s i t e , t h e n a t u r e of its a c t i o n o n t h e o r g a n i s m a n d t h e individual immunological r e s p o n s e of the h o s u . 4 , 6 . T h u s , d i a g n o s i s is v e r y d i f f i c u l t , especially in n o t highly e n d e m i c a r e a s or in r e g i o n s w e r e l a b o r a t o r y s u p p o r t is l a c k i n g . A n o t h e r i m p o r t a n t f e a t u r e t o be c o n s i d e r e d in t h e a p p r o a c h t o n e u r o c y s t i c e r c o s i s is t h e lack of an a l t e r n a t i v e p r o g r a m of a n t i p a r a s i t i c t r e a t m e n t . T h e h i g h c o a s t of t r e a t m e n t w i t h praziquantel and the s i d e e f f e c t s ' of c o r t i c o s t e r o i d s a r e f a c t o r s t h a t h a v e led to t h e s e a r c h for n e w t r e a t m e n t p r o g r a m s . 5
A l b e n d a z o l e , a d r u g b e l o n g i n g to the b e n z i m i d a z o l e g r o u p , is c h a r a c t e r i z e d by high t h e r a p e u t i c indices as a p o l y v a l e n t a n t i h e l m i n t i c agent * a n d w i t h efficacy in p a t i e n t s with h y d a t i c c y s t s . D e x t r o c h l o r o p h e n i r a m i n e is a p o t e n t a n t i - h i s t a m i n i c w i t h good p e n e t r a t i o n in t h e c e n t r a l n e r v o u s s y s t e m w h i c h acts on cerebral h i s t a m i n e r e c e p t o r s by a competitive mechanism . 1
7
2
T h e o b j e c t i v e of t h e p r e s e n t r e s e a r c h w a s t o e v a l u a t e for t h e first t i m e t h e t h e r a p e u t i c
Dextrochloropheniramine;
a c t i o n o f a l b e n d a z o l e in c o m b i n a t i o n w i t h d e x t r o c h l o r o p h e n i r a m i n e in p a t i e n t s w i t h cysticercosis. Fourty patients were treated on the Infectious a n d Parasitic Diseases a n d on the N e u r o l o g y w a r d of the University H o s p i t a l , F a c u l t y o f M e d i c i n e of B o t u c a t u , U N E S P , f r o m S e p t e m b e r 1984 t o D e c e m b e r 1987. T h r e e clinical t r e a t m e n t g r o u p s w e r e f o r m e d : Group 1: 10 t o 15 m g / k g / d a y of a l b e n d a z o l e by o r a l r o u t e in t w o series o f 28 days each; G r o u p 11: 15 t o 25 m g / k g / d a y , in t h r e e series of 21 d a y s e a c h ; G r o u p I I I : 15 t o 30 m g / k g / d a y , in t w o series o f 21 a n d 30 d a y s . All o f t h e p a t i e n t s in the three g r o u p s also received u n i n t e r r u p t e d l y 18 mg/day dextrochloropheniramine administered orally, during and 4 to 6 m o n t h s after the end of t r e a t m e n t . All p a t i e n t s w e r e e v a l u a t e d b y c l i n i c a l examination and laboratory tests, during a n d i m m e d i a t e l l y a f t e r , as well as 5 t o 2 0 m o n t h s a f t e r t h e e n d o f t r e a t m e n t . All p o t e n t i a l l y fertile w o m e n w e r e s u b m i t t e d t o p r e g n a n c y tests before and during t r e a t m e n t with a l b e n d a z o l e . T h e ethical n o r m s of Helsinki
(1) D e p a r t m e n t of Neurology and Psychiatry, Faculty of Medicine of Botucatu ( U N E S P ) , Botucatu, São P a u l o , Brazil.. (2) D e p a r t m e n t of Infectious and Parasitic Diseases, Dermatology and Radiology, Faculty of Medicine of Botucatu ( U N E S P ) , Botucatu, São P a u l o , Brazil. (3) Department of O p h t h a l m o l o g y and Otorhinolaryngology, Faculty of Medicine of Botucatu ( U N E S P ) , Botucatu, São P a u l o , Brazil. (4) Statistician, Faculty of Medicine of Botucatu ( U N E S P ) , Botucatu, São P a u l o , Brazil. Address for correspondence: D r a . Svetlana Agapejev. D e p a r t a m e n t o de Neurologia e Psiquiatria da Faculdade de Medicina de Botucatu ( U N E S P ) . C E P 18610, Botucatu, S P , Brasil.
A G A P E J E V , S.; M E 1 R A , D . A . ; B A R R A V I E R A , B . ; M A C H A D O , J . M . ; P E R E I R A , P . C . M . ; M E N D E S , R . P . ; K A M E G A S A W A , A . & C U R 1 , P . R . — Neurocyslicercosis: Ireatmenl with a l b e n d a z o l e a n d d e x t r o c h l o r o p h e n i r a m i n e . (Preliminary report). Rev. Inst. Med. Irop.
São Paulo, 30(5):387-389, 1988.
Treaty w e r e strictly o b e y e d for all o f the participants in t h e three g r o u p s . T h e f o l l o w i n g parameters were used t o evaluate t h e treatment s c h e d u l e u s e d :
Clinical:
remission
of
clinical
manifestations, as indicated by the d i s a p p e a r a n c e o f s y m p t o m s , by t h e i m p r o v e o f the neurological examination and o f the quality o f life. T h e latter w a s a l s o e v a l u a t e d quantitatively by attributing scores t o t h e different t y p e s , as f o l l o w s : d e a t h = 0; great l i m i t a t i o n s = 1; m e d i u m limitations = 2 ; small limitations = 3 and n o r m a l life = 4 . Laboratory tests: realized t o detect s o m e side effects o f t h e drug: c o m p l e t e h e m o g r a m ; measurements of blood glucose, amino transferase, bilirubins, p r o t e i n s , m u c o p r o t e i n s , uric a c i d ; u r e a , c r e a t i n i n e a n d e l e c t r o l y t e s ( C a *, N a * a n d K + )- Fecal p a r a s i t o l o g y a n d urinalysis were a l s o included in the p r o t o c o l . Cerebrospinal fluid (CSF): n o r m a l i z a t i o n or at least i m p r o v e o f the C S F analysis by the realization o f tests for the presence o f anticysticercum a n t i b o d i e s , g l u c o s e , protein a n d chloride m e a s u r e m e n t s , cellularity a n d protein e l e c t r o p h o r e s i s . P u n c t u r e s were p e r f o r m e d at the s u b o c c i p i t a l levels in all p a t i e n t s . Tomography (CT): decrease o f t h e n u m b e r a n d / o r size o f c y s t s , e d e m a , h y d r o c e p h a l u s a n d the increase or a p p e a r a n c e o f t h e n u m b e r o f calcifications. P a t i e n t s were a l s o further classified as h a v i n g the b e n i g n , m o d e r a t e or serious f o r m o f the d i s e a s e . B e n i g n cases were c o n s i d e r e d t o be those patients w h o did not present h y d r o c e p h a l u s , alterations in c o n s c i e n c e , or localizing n e u r o l o g i c a l signs a n d w h o had n o intracranial h y p e r t e n s i o n o r o n l y benign intracranial hypertension, headache and/or dizziness with p y r a m i d a l liberation. M o d e r a t e l y ill patients were t h o s e w h o presented c o n v u l s i v e seizures o f difficult c o n t r o l , w h o progressed t o +
a c o n d i t i o n o f " s t a t u s e p i l e p t i c u s " o r w h o had localizing n e u r o l o g i c a l s i g n s , meningitis or m e n i n g o e n c e p h a l i t i s . Serious cases were t h o s e o f patients presenting h y d r o c e p h a l u s or serious intracranial h y p e r t e n s i o n , or d i s t u r b a n c e s o f c o n s c i e n c e a s s o c i a t e d or n o t with localizing n e u r o l o g i c a l s i g n s . A m o n g these were t w o patients with m u l t i p l e r a c e m o s e cysticercosis. T h e results are s h o w e d in table 1. O f the 4 0 patients with neurocysticercosis treated with a l b e n d a z o l e , 3 2 ( 8 0 . 0 % ) i m p r o v e d , whereas 4 ( 1 0 . 0 % ) r e m a i n e d u n c h a n g e d , and 4 ( 1 0 . 0 % ) d i e d . O f t h e four patients w h o died, two had racemose cysticercosis. The t o m o g r a p h i c alterations were o b s e r v e d after an average o f 6 m o n t h s after the e n d o f treatment in 23 o f the 4 0 patients (Figure 1). T h e best results in terms o f n e u r o l o g i c a l m a n i f e s t a t i o n s were o b s e r v e d in patients with benign a n d m o d e r a t e forms o f cysticercosis, i.e. t h o s e patients w h o s h o w e d epileptic s y n d r o m , benign intracranial h y p e r t e n s i o n , h e a d a c h e a n d / o r dizziness with pyramidal l i b e r a t i o n , m e n i n g i t i s or m e n i n g o e n c e p h a l i t i s . T h e results reported b y the various a u t h o r s w h o used praziquantel in t h e treatment o f cysticercosis are n o t uniform'.3.». It s h o u l d be p o i n t e d o u t that n e u r o c y s t i c e r c o s i s is frequent in the rural z o n e in Brazil, where it mainly attacks low socioeconomic-level individuals w h o have difficulty in acquiring this drug b e c a u s e o f its high c o s t . The combination of albendazole and d e x t r o c h l o r o p h e n i r a m i n e s e e m s t o represent a valuable alternative treatment option. We e m p h a s i z e that each c a s e s h o u l d be analyzed individually in terms o f surgical p r o c e d u r e s , symptom-relieving medication a n d specific c h e m o t h e r a p y , a n d the possibility o f relapses are high for patients w h o c o n t i n u e t o live under the s a m e precarious h y g i e n e c o n d i t i o n s .
TABLE 1 Percentage of satisfactory results from neurological manifestation, quality o f life CT scan a n d CSF analysis, according t o t h e t r e a t m e n t groups.
Group I G r o u p II G r o u p III
Patients (N?)
Neurological manifestation
Quality of life
CT scan
CSF
8 13 19
50.0% 83.3% 94.7%
62.5% 75.0% 94.7%
71.4% 71.4% 77.8%
41.1% 54.9% 60.3%
ACAPEJEV, S.; MEIRA, D.A.; BARRA VIERA, B.; MACHADO, J.M.; PEREIRA, P.C.M.; CURI, P.R. — Neurocyslicercosis: treatment with albendazole and dextrochloropheniramine. São Paulo, 30(5):387-389, 1988.
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M U R A D , F. — Goodman and Oilman's. The p h a r m a cological basis of therapeutics. 7 ed. New York, Mac Millan, 1980. 1839 p . INTERNATIONAL SYMPOSIUM O F CYSTICERC O S I S . J. bras. Med., 45 (suppl. M a y ) : l - 1 0 1 , 1982. M O R R I S , D . L . ; D Y K E S , P . W . ; M A R R I N E R , S.; B O G A N , J.; B U R R O W S , F . ; S K E E N E - S M I T H , H . & C L A R K S O N , M . J . — Albendazole: objective evidence of response in h u m a n hydatid disease. J. Amer. med. Ass., 253:2053-2057, 1985. PENE, P.; M O J O N , M.; GARIN, J.P.; C O U L A N D , J . P . & R O S S I G N O L , J . F . — Albendazole: a new b r o a d - s p e c t r u m antihelmintic. Double-blind multicen¬ ter clinical trial. Amer. J. trop. Med. H y g . , 31:263-266, 1982. ROBLES, C ; SEDANO, A.M.; VARGAST E N T O R I , N . & G A L I N D O - V I R G E N , S. — Longterm results of praziquantel therapy in neurocysticercosis. J. Neurosurg., 66:359-363, 1987. l h
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6. 7.
r d
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8.
9.
Recebido p a r a publicação em 2 0 / 3 / 1 9 8 8 .
