MOTOR UNIT INVOLVEMENT IN HUMAN
ACUTE CHAGAS' DISEASE
O. R. BENAVENTE — O. LEDESMA PATIÑO — L. BAEZ PEÑA — H. LUGONES E. KALALA — C. RIBAS MENECLIER — O. GENOVESE — R. E. P. SICA
S U M M A R Y — T h i r t y f i v e p a t i e n t s w i t h a c u t e C h a g a s ' d i s e a s e w h o d e m o n s t r a t e d p a r a s i t a e m i a at t h e t i m e o f t h e i n v e s t i g a t i o n w e r e s u b m i t t e d t o a d e t a i l e d e l e c t r o m y o g r a p h i c a l s t u d y . W i t h t h e i r m u s c l e s a t r e s t , 12 p a t i e n t s s h o w e d f i b r i l l a t i o n p o t e n t i a l s a n d / o r p o s i t i v e s h a r p w a v e s . O n v o l i t i o n a l c o n t r a c t i o n , 7 h a d s h o r t d u r a t i o n m o t o r u n i t p o t e n t i a l s ( M U P s ) a n d l o w p o l y p h a s i c M U P s . O n m o t o r a n d s e n s o r y n e r v e f i b e r s c o n d u c t i o n s t u d i e s , 20 d i s c l o s e d v a l u e s b e l o w t h e l o w e r c o n t r o l l i m i t w i t h i n o n e o r m o r e n e r v e s . F i n a l l y , 12 p a t i e n t s p r o d u c e d a m u s c l e , d e c r e m e n t a l r e s p o n s e o n n e r v e s u p r a m a x i m a l r e p e t i t i v e s t i m u l a t i o n . T h e f i n d i n g s s i g n a l t h a t p r i m a r y m u s c l e i n v o l v e m e n t , n e u r o p a t h y a n d i m p a i r e m e n t o f t h e n e u r o m u s c u l a r t r a n s m i s s i o n , e i t h e r i s o l a t e d o r c o m b i n e d , m a y b e f o u n d i n t h e a c u t e s t a g e o f h u m a n C h a g a s ' d i s e a s e .
Compromiso de la unidad motora en la fase aguda de la enfermedad de Chagas humana.
R E S Ú M E N — T r e i n t a y c i n c o p a c i e n t e s c o n el d i a g n ó s t i c o d e e n f e r m e d a d d e C h a g a s e n s u e t a p a a g u d a , t o d o s c o n p a r a s i t e m i a p o s i t i v a e n e l m o m e n t o d e l a i n v e s t i g a c i ó n , f u e r o n s o m e t i d o s a e s t u d i o e l e c t r o m i o g r á f i c o p o r t é c n i c a s c o n v e n c i o n a l e s . E n r e p o s o , 12 d e e l l o s m o s t r a r o n f i b r i l a c i o n e s y / o p o t e n c i a l e s p o s i t i v o s . D u r a n t e l a c o n t r a c c i ó n v o l u n t a r i a , e n 7 p a c i e n t e s l o s p o t e n c i a l e s d e u n i d a d m o t o r a e r a n b i f á s i c o s d e c o r t a d u r a c i ó n y p o l i f á s i c o s d e b a j a a m p l i t u d . E n 20 s e e n c o n t r ó d i s m i n u c i ó n d e l a v e l o c i d a d d e c o n d u c c i ó n m o t o r a y / o s e n s i t i v a e n u n o o m a s d e l o s n e r v i o s e x p l o r a d o s . F i n a l m e n t e , 12 p a c i e n t e s m o s t r a r o n c a i d a d e la a m p l i t u d d e l p o t e n c i a l m u s c u l a r e v o c a d o p o r e s t í m u l o n e r v i o s o r e p e t i t i v o s u p r a m á x i m o . L o s h a l l a z g o s h e c h o s s e ñ a l a n q u e d u r a n t e l a f a s e a g u d a d e l a e n f e r m e d a d de, C h a g a s e n e l h o m b r e p u e d e p r o d u c i r s e a l t e r a c i ó n p r i m a r i a d e l m ú s c u l o , n e u r o p a t í a y c o m p r o m i s o d e la t r a n s m i s i ó n n e u r o m u s c u l a r , e n f o r m a a i s l a d a o c o m b i n a d a s e n t r e s i .
In the past years, the involvement of the peripheral nervous system has been extensively reported in chronic human Chagas' disease 9-u and, more recently, the same type of lesion could be demonstrated in chronic experimental models 4,8. However, only few attempts have been done looking for the eventual damage of the peripheral nervous system in the acute stage of the human d i s e a s e2
. Some experimental data obtained from the mouse support the possibility of a very early injury of the peripheral nerve 5, besides the well-known myositis 6, shortly after the inoculation of the animal.
The aim of the present study, has been to make a first approach searching for
the involvement of the peripheral nervous system in patients affected by acute Chagas' disease who live in an endemic area. A previous and limited account of these findings has been published elsewhere 1.
C e n t r o d e E n f e r m e d a d d e C h a g a s y P a t o l o g í a R e g i o n a l , H o s p i t a l I n d e p e n d e n c i a , S a n t i a g o d e l E s t e r o ; D e p a r t a m e n t o d e M e d i c i n a , O r i e n t a c i ó n N e u r o l o g í a , F a c u l t a d d e M e d i c i n a , U n i -v e r s i d a d d e B u e n o s A i r e s ; D i -v i s i ó n N e u r o l o g í a , H o s p i t a l R a m o s M e j í a , B u e n o s A i r e s .
284 Arq Neuro-Psiquiat (Sâo Paulo) 47(3) 1989
M A T E R I A L , A N D M E T H O D S
T h e whole study was carried out at Santiago del Estero Province, Argentina, where the disease is endemic.
Subjects — Altogether 35 patients were explored. Their ages ranged between 3 and 22 years. Nineteen were females and 16 males. Thirty-three of them lived in rural areas, while j u s t two unhabited within the town. T h e diagnosis w a s done at the 'Centro de Chagas y Patologia Regional de Santiago del Estero'. A l l them had positive parasitaemia at the time of the investigation, while only 29 of the studied subjects showed also positive sera tests (immunofluorescence and haemagglutination).
Their clinical initial manifestations were eye-lymph node complex (33 patients), localized swelling at the site of the Triatoma infestans bite (one patient) and widespread subcutaneous oedema (one patient). F r o m this study were rejected all those patients who m a y have other causes able to induce nervous or muscle damage. T h e time elapsed between the, appearance of the first sign or symptom related to the disease and the observation of the patient varied between 5 and 30 days, with a mean of 1 3 . 3 4 ±5 . 6 days. Controls — A n a g e matched group of 25 subjects selected from the same area, without parasitaemia, with negative serum tests, and in good health conditions at the time of the study were employed as controls.
Techniques — Patients and controls were submited to the following procedures: a. Electromyographical investigation: Conventional electromyographical (emg) studies, with coaxial needle electrodes, were performed in deltoid, abductor pollicis brevis, quadriceps, tibialis anterior and extensor digitorum brevis muscles. In every case, with the patient resting, a search w a s made for spontaneous activity, namely fibrillation potentials and positive sharp waves. Thereafter, the subject was instructed to weakly voluntary contract muscles and the characteristics of the motor unit potentials ( M U P s ) were analized on the screen of a storage oscilloscope. Finally, the subject produced a full contraction and the pattern of M U P s recruitment was observed. b. Nerve conduction studies: Conventional maximal motor conduction velocities were studied at the median, ulnar and deep peroneal nerves. Also, conventional sensory conduction velocity was explored, with surface electrodes, at the median nerve b y stimulating the I l l r d digit and recording the sensory action potential at the wrist. W h e n performing this investigation, the skin overlying the studied nerve w a s warmed up and the ambient temperature was mantained at about 2 8 ° C . c. State of the neuromuscular transmission: Supramaximal ulnar nerve repetitive stimulation at 3, 5 and 10 H z , through trains of 2 seconds each, was delivered at the wrist. T h e responses were obtained at the hypothenar muscles with surface electrodes. T h e amplitudes of the 3rd, 6th and 10th muscle potentials were refered to the first, as percentage.
R E S U L T S
W i t h the muscles at rest, 12 out of 34 patients explored (35%) disclosed fibrillations and/or positive sharp waves in, at the least, one of the investigated muscles. On full voluntary muscle contraction, all the patients tested (nr=34) showed a normal interference pattern. W i t h weaker effort, 7 of them had biphasic short duration M U P s and low amplitude polyphasic M U P s . T w o out of these 7 patients had also fibrillation potentials when their muscles were at rest.
Figure 1 shows the results obtained in 35 patients who underwent nerve conduction studies. T w e n t y two of them showed some nerve involvement. T h e commonest was the slowness of the sensory fibers of the median nerve (14 out of 33 patients studied, 42.4%) followed by the involvement of the motor median nerve (8 out of 21, 38%) and of the ulnar nerve (6 out of 31, 19.3%) and, finally, of the deep peroneal nerve (5 out of 31, 16.1%). T h e
most frequent type of peripheral nerve damage was the slowness of an isolated nerve (63.6% of the patients). T w o nerves were, affected in 18% of the patients, 3 in 13.6% and 4 only in 4.5% of them.
Seven patients who showed neuropathy disclosed also spontaneous activity (31.8%) and
4 associated neuropathy with an emg of the primary muscle involvement type (18.1%). Twelve out of 33 patients explored (36.3%) disclosed a décrémentai muscle response, larger than
15% ( o ) of the amplitude of the first potential, on repetitive nerve stimulation. Six of the 12 patients with this abnormal response showed also neuropathy. T h r e e had neuropathy
plus signs of primary muscle involvement, while the remaining three patients had no other associated abnormality.
It was observed that there was a positive relationship between the timing of the
Motor unit in acute Chagas' disease 285
detected in 37% of the patients within the first 10 days post-infection (pi) ; in 71.4% of
them in the second 10 days pi; in 66% in the last 10 days (r—0.61). Signs of primary muscle involvement were found in 12.5%, 19% and 33% of the patients within equal periods ( r = 0 . 9 6 ) and, finally, décrémentai responses to repetitive nerve stimulation were observed in 12.5%, 33.3% and 66% of them also in similar time periods (r—0.98).
W h e n electrophysiological findings were compared with laboratory tests results, it was observed that out of the 6 patients w h o showed negative serological tests (17%), 4 had neuropathy. One of them had also signs of primary muscle involvement, other spontaneous muscle activity, and a third subject involvement of the neuromuscular transmission.
C O M M E N T S
As a whole, the findings in this study point out to the motor unit as one of the target structures which are damaged during the acute stage of the infection in humans. The different components of the motor unit seem to be involved almost simultaneously leading to an electrophysiological complex picture where signs of dener-vation coexist with signs of primary muscle involvement. T h e combination of both pathologies could be found in some patients, while in others the predominance of one of them was observed. This situation resembles quite closely the findings of Losavio et alJ and Jones et al.5 in their mouse experimental model where, either electrophy-siologically or anatomically, a similar behaviour was detected at early post-infection stages. Those authors suggested that this was due to vasculitis, and consequent ischa-emic processes, which could be found at the nerve trunk and muscle levels. Despite the lack of anatomical evidence, one is tempted to attribute the human findings to a similar mechanism.
A second point to be discussed is the cause of the damage. At present it is hard to give an adequate answer. Nevertheless, it seems likely that the parasitaemia, which was present in every patient, may play a significant role.
The abnormalities found seem to be time-dependent, because they involved an increasing number of subjects when the time of infection was more prolonged, a feature which could mean progressive damage of the structures involved.
Despite of the electrophysiological evidences, none of the patients had clinical signs or symptoms of peripheral nerve or muscle involvement. This may be related to the amount of damage imposed by the infection which has to be mild enough as not to produce clinical manifestations.
Acknowledgement — T h i s i n v e s t i g a t i o n r e c e i v e d f i n a n c i a l S u p p o r t f r o m t h e U N D P / W o r l d B a n k / W H O S p e c i a l P r o g r a m m e f o r R e s e a r c h a n d T r a i n i n g i n T r o p i e a l D i s e a s e s .
R E F E R E N C E S
1. B e n a v e n t e O R , L e d e s m a P a t i ñ o O , L u g o n e s H , K a l a l o E , M a r t e l e u r A , S i c a R E P — C o m p r o m i s o d e l s i s t e m a n e r v i o s o p e r i f é r i c o e n l a fase a g u d a d e la e n f e r m e d a d d e C h a g a s h u m a n a : e s t u d i o e l e c t r o m i o g r á f i c o . M e d i c i n a ( B u e n o s A i r e s ) 46 : 645, 1986.
2. D e F a r i a C R , M e l o - S o u z a S E , R a s s i A , L i m a A F — E v i d ê n c i a s e l e t r o m i o g r á f i c a s d e d e s n e r v a ç ã o m o t o r a e m p a c i e n t e s n a f a s e a g u d a d a d o e n ç a d e C h a g a s . R e v G o i a n a M e d 25 : 153, 1979.
3. D e s m e d t J, B o r e s t e i n S — D i a g n o s i s o f m y a s t h e n i a g r a v i s b y n e r v e s t i m u l a t i o n . A n n N Y A c a d S c i 274 : 174, 1976.
4. G o n z a l e z - C a p p a S M , S a n z O P , M u l l e r L , M o l i n a H , F e r n a n d e z J, R i m o l d i M T , S i c a R E P — P e r i p h e r a l n e r v o u s s y s t e m d a m a g e i n e x p e r i m e n t a l c h r o n i c C h a g a s ' d i s e a s e . A m J T r o p M e d H y g 36 : 41, 1987.
5. J o n e s M , C e l e n t a n o A , L o s a v i o A , S a n z O P , M u c h n i k S, G o n z a l e z - C a p p a S M , S i c a R E P C h a g a s c r ó n i c o e x p e r i m e n t a l : e s t u d i o h i s t o l ó g i c o d e n e r v i o y m ú s c u l o . M e d i c i n a ( B u e n o s A i r e s ) 46 : 583, 1986.
6. L a g u e n s R P , C a b e z a M e c k e r t P , B a s o m b r i o M A , C h a m b o G J , C o s s i o P M , A r a n á R M , G e l p i R — I n f e c c i ó n c r ó n i c a d e l r a t ó n c o n T r y p a n o s o m a C r u z i . M o d e l o e x p e r i m e n t a l d e e n f e r m e d a d d e C h a g a s . M e d i c i n a 40 ( S u p l 1) :33, 1980.
7. L o s a v i o A , S a n z O P , C e l e n t a n o A , J o n e s M , G o n z a l e z - C a p p a S M , S i c a R E P , M u c h n i k S — C h a g a s c r ó n i c o e x p e r i m e n t a l : c a p a c i d a d r e i n e r v a t o r i a y a l t e r a c i ó n en la t r a n s m i s i ó n n e u r o m u s c u l a r . M e d i c i n a ( B u e n o s A i r e s ) 46 : 582, 1986.
8. S a i d G, J o s k o w i c z M , B a r r e i r a A A , E i s e n H — N e u r o p a t h y a s s o c i a t e d w i t h e x p e r i m e n t a l C h a g a s d i s e a s e . A n n N e u r o l 18 : 676, 1985.
9. S a n z O P , S i c a R E P , B a s s o S, F u m o T — C o m p r o m i s o d e l s i s t e m a n e r v i o s o p e r i f é r i c o en la e n f e r m e d a d d e C h a g a s c r ó n i c a . M e d i c i n a ( B u e n o s A i r e s ) 40 ( S u p l . 1) : 231, 1980. 10. S i c a R E P , F i l i p i n i D , P a n i z z a M , F u m o T , B a s s o S, L a z a r i J, M o l i n a H — I n v o l v e m e n t
o f t h e p e r i p h e r a l s e n s o r y n e r v o u s s y s t e m in h u m a n c h r o n i c C h a g a s d i s e a s e . M e d i c i n a ( B u e n o s A i r e s ) 46 : 662, 1986.
