SENSORY AND MOTOR NERVE CONDUCTION VELOCITY
IN LONG-TERM DIPHENYLHYDANTOIN THERAPY
JOSÉ H . XAVIER DE CASTRO; MARIO L . ACOSTA;
ROBERTO E . P . SICA; N E L L Y GUERCIO
Since Merrit and Putnam (1938)
8introduced the diphenylhydantoin
( D P H ) in the treatment of epilepsy, it has been used largely as the main
drug in many forms of the disease.
Several attempts have been made to demonstrate its action on the
peri-pheral nerve, but the obtained results are controversial. K o r e y
6first, and
Morrell, Bradley and Ptashne
< Jafter, gave experimental evidence of D P H
toxic effect on the nerve. Histologically Guercio, Sica, Taratuto and Poch
: idemonstrated a demyelinating effect on the peripheral nerve of men which
was correlated with prolonged administration of the drug.
Brumlik and M o r e t t i
2failed to demonstrate any abnormality in motor
or sensory nerve conduction velocity in patients under D P H therapy; however
H o p f
5found slowing of slowly motor conduction nerve fibres, while
others
3.
7found a slowing of the maximum nerve motor conduction velocity,
which suggest that the fastest fibres in the nerve are damaged as well.
We now wish to report our findings in epileptic patients under D P H
therapy. The background of this investigation was to estimate the motor
and sensory conduction velocities in the median nerve, in an attempt to
elucidate further the effect of D P H on peripheral nerve.
M A T E R I A L A N D M E T H O D
E l e v e n e p i l e p t i c p a t i e n t s , 5 m a l e s and 6 f e m a l e s , a g e d b e t w e e n 17 and 52 y e a r s , w e r e s u b m i t t e d f o r e l e c t r o p h y s i o l o g i c a l i n v e s t i g a t i o n . A l l o f t h e m w e r e u n d e r D P H t h e r a p y m a i n l y , h o w e v e r o t h e r a n t i c o n v u l s i v a n t d r u g s w e r e e m p l o y e d . T h e l e n g t h o f t r e a t m e n t v a r i e d b e t w e e n 3 and 18 y e a r s . O t h e r causes o f n e u r o p a t h y , such as d i a b e t e s , u r e m i a , a l c o h o l i c i n t o x i c a t i o n w e r e e x c l u d e d .
T w e n t y subjects, 5 m a l e s and 15 f e m a l e s , a g e d b e t w e e n 19 and 46 y e a r s , in g o o d h e a l t h a t t h e t i m e o f t h e e x p e r i e n c e and w i t h o u t h i s t o r y o f a n y n e u r o l o g i c a l disorder, w e r e e m p l o y e d as c o n t r o l s f o r m e d i a n n e r v e s e n s o r y c o n d u c t i o n v e l o c i t y .
F o u r t e e n subjects, 4 m a l e s a n d 10 f e m a l e s , a g e d b e t w e e n 18 and 53 y e a r s , in g o o d h e a l t h and w i t h o u t h i s t o r y o f n e u r o l o g i c a l d i s t u r b a n c e , a c t e d as c o n t r o l s for m e d i a n n e r v e m a x i m u m m o t o r c o n d u c t i o n v e l o c i t y .
T h e r e c o r d i n g e l e c t r o d e w a s a s i l v e r foil 2 c m l o n g a n d 0 . 5 c m w i d e c o v e r e d w i t h a f e l t p a d s o a c k e d in s a l i n e s o l u t i o n a t t a c h e d t o t h e skin p r e v i o u s l y p r e p a r e d w i t h e l e c t r o d e j e l l y , o f t h e m e d i a l a s p e c t o f t h e w r i s t , o v e r t h e m e d i a n n e r v e ( F i g . 1 ) . T h e r e f e r e n c e e l e c t r o d e w a s s i m i l a r t o t h e r e c o r d i n g o n e a n d w a s f i x e d t o t h e skin o f t h e m e d i a l a s p e c t o f t h e w r i s t 2 c m p r o x i m a l t o t h e r e c o r d i n g o n e < F i g . 1 ) .
T h e e a r t h e l e c t r o d e w a s a s i l v e r f o i l 5 c m l o n g , 0,5 c m w i d e , c o a t e d w i t h e l e c t r o d e j e l l y a n d a t t a c h e d t o t h e m e d i a l a s p e c t o f t h e w r i s t , w h i c h h a d b e e n p r e p a r e d w i t h e l e c t r o d e j e l l y p r e v i o u s l y , by a p l a s t i c b a n d b e t w e e n t h e r e c o r d i n g e l e c t r o d e and t h e s t i m u l a t i n g c a t h o d e ( F i g . 1 ) .
A D I S A c o a x i a l n e e d l e e l e c t r o d e , t y p e 9013K0031, w a s i n s e r t e d in t h e a b d u c t o r p o l l i c i s b r e v i s m u s c l e for r e c o r d i n g m o t o r c o n d u c t i o n v e l o c i t y .
first p h a l a n x o f t h e 2nd and 3rd f i n g e r s ( F i g . 1 ) , w i t h t h e c a t h o d e p r o x i m a l . P r e -v i o u s l y , t h e skin o f t h e p h a l a n x w a s p r e p a r e d w i t h e l e c t r o d e j e l l y .
F o r m o t o r c o n d u c t i o n v e l o c i t y , t h e s t i m u l a t i n g e l e c t r o d e s w e r e a p a i r o f c h l o r i d e s i l v e r s c r e w s , w h i c h w e r e c o v e r e d by f e l t p a d s s o a c k e d in s a l i n e .
experimental procedure — N e r v e sensory c o n d u c t i o n v e l o c i t y : o n c e t h e e l e c t r o d e s w e r e a t t a c h e d t o t h e skin, t h e s u b j e c t w a s e n c o u r a g e d t o r e l a x , t h e n t h e s t i m u l u s i n t e n s i t y w a s i n c r e a s e d p r o g r e s s i v e l y u n t i l t h e first e v o k e d p o t e n t i a l o f t h e m e d i a n n e r v e c o u l d be seen. T h e v a l u e o f t h e s t i m u l u s i n t e n s i t y , in v o l t s , a t t h i s m o m e n t , w a s r e g a r d e d as t h r e s h o l d . T h e n , t h e s t i m u l u s i n t e n s i t y w a s i n c r e a s e d a g a i n until t h e m a x i m a l a m p l i t u d e o f t h e e v o k e d m e d i a n n e r v e p o t e n t i a l w a s o b s e r v e d , t h e n t h e s t i m u l u s i n t e n s i t y w a s m a d e s u p r a m a x i m a l by 10 V and 10 s u c c e s i v e r e c o r d s w e r e o b t a i n e d .
T h e s t i m u l i w e r e s q u a r e pulses, 0 . 5 m s e c d u r a t i o n , d e l i v e r e d f r o m a M u l t i s t i m s t i m u l a t o r , t y p e 13G04, a t a r a n g e o f a b o u t o n e e v e r y 2 o r 3 seconds.
T h e p o t e n t i a l s w e r e d i s p l a y e d on t h e s c r e e n o f a 3 c h a n n e l s D I S A e l e c t r o m y o g r a p h , t y p e 13A69, and a l l o f t h e m w e r e p h o t o g r a p h e d . T h e m e a s u r e m e n t s w e r e m a d e on t h e prints.
M a x i m u m m o t o r n e r v e c o n d u c t i o n v e l o c i t y w a s m e a s u r e d f o l l o w i n g t h e t e c h n i q u e d e s c r i b e d by H o d e s , L a r r a b e e and G e r m a n \
T h e a m b i e n t t e m p e r a t u r e w a s m a i n t a i n e d in all t h e e x p e r i e n c e o v e r 2 53
C .
Treatment of the results — T e n r e c o r d s o f s e n s o r y n e r v e c o n d u c t i o n v e l o c i t y w e r e o b t a i n e d in e a c h s u b j e c t , t h e r e s u l t s w e r e p o o l e d a n d t h e m e a n a n d t h e s t a n d a r d d e v i a t i o n o f e a c h o n e w a s c a l c u l a t e d . T h r o u g h o u t t h e t e x t m e a n s a r e g i v e n w i t h t h e i r s t a n d a r d d e v i a t i o n . D i f f e r e n c e b e t w e e n m e a n s w a s c a l c u l a t e d u s i n g t h e " S t u d e n t " t test. C o r r e l a t i o n s w e r e e s t i m a t e d by t h e P e a r s o n c o r r e l a t i o n c o e f f i -c i e n t ( r ) .
R E S U L T S
F i g u r e 2 s h o w s t h e i n d i v i d u a l v a l u e s o f m a x i m u m m o t o r c o n d u c t i o n v e l o c i t y o b t a i n e d in p a t i e n t s and c o n t r o l s . E i g h t p a t i e n t s ( 7 2 . 5 % ) w e r e b e l o w t h e l o w e r l i m i t o f t h e c o n t r o l g r o u p , s h o w i n g a s l o w i n g o f t h e f a s t e s t c o n d u c t i n g m o t o r n e r v e fibres. F u r t h e r m o r e , t h e m e a n m o t o r c o n d u c t i o n v e l o c i t y o f t h e w h o l e p a t i e n t s g r o u p w a s s i g n i f i c a n t l y d i f f e r e n t f r o m t h e c o n t r o l g r o u p ( T a b l e 1 ) . A p p a r e n t l y t h e s l o w i n g o f c o n d u c t i o n v e l o c i t y in t h e m o t o r f i b r e s w a s n e g a t i v e l y c o r r e l a t e d w i t h t h e l e n g t h o f t r e a t m e n t ( r = - 0 . 7 4 ; P < 0 . 0 1 ) , but not w i t h t h e d a y l y e m p l o y e d dosis ( r = 0 . 3 8 ; P > 0 . 1 ) .
F i g u r e 3 s h o w s t h e i n d i v i d u a l v a l u e s o f n e r v e s e n s o r y c o n d u c t i o n v e l o c i t y , o b t a i n e d in e a c h s u b j e c t . I t c a n be seen t h a t 8 p a t i e n t s ( 7 2 . 5 % ) a r e b e l o w t h e l o w e r l i m i t o f t h e c o n t r o l p o p u l a t i o n . T h e m e a n v a l u e o f p a t i e n t s g r o u p w a s s i g n i f i c a n t l y s m a l l e r t h a n t h e c o n t r o l g r o u p ( T a b l e 1 ) . T h e c o n d u c t i o n v e l o c i t y o f t h e sensory f i b r e s is p o s i t i v e l y c o r r e l a t e d w i t h t h e c o n d u c t i o n v e l o c i t y o f t h e f a s t e s t m o t o r n e r v e f i b r e s ( r = 0 . 8 7 ; P < 0 . 0 0 1 ) a n d n e g a t i v e l y c o r r e l a t e d w i t h t h e l e n g t h o f t r e a t m e n t ( r - - 0 . 7 6 ; p < 0 . 0 1 ) b u t n o t w i t h t h e d a y l y dosis ( r =- 0 . 2 5 ; P > 0 . 1 ) . A s it can be e x p e c t e d f r o m the a b o v e results, t h e m e a n s e n s o r y l a t e n c y in p a t i e n t s g r o u p w a s s i g n i f i c a n t l y l a r g e r t h a n t h e c o n t r o l g r o u p ( T a b l e 1 ) .
On t h e o t h e r h a n d , t h e m e a n t h r e s h o l d f o r sensory c o n d u c t i n g f i b r e s w a s , as w e l l , s i g n i f i c a n t l y d i f f e r e n t f r o m t h e c o n t r o l p o p u l a t i o n ( T a b l e l ) , in spite t h a t a l l t h e v a l u e s , e x c e p t 2, were- in t h e c o n t r o l r a n g e and w a s n o t c o r r e l a t e d w i t h t h e s l o w i n g o f sensory c o n d u c t i o n v e l o c i t y ( r = 0 . 2 0 ; P > 0 . 1 ) .
D I S C U S S I O N
Slowing of the fastest nerve motor fibre has been demonstrated
pre-viously by several a u t h o r s
1.
3.
5'
7in D P H treated patients. The present
results show that the damage of the motor axons seems to be correlated
with the length of theatment, but not with the dayly employed dose. Similar
results have been obtained with the sensory nerve conduction velocity,
allowing us to assume that D P H has not a selective effect on motor or
sensory fibres and that the drug needs to be acting on the nerve for long
periods, at least when it is administrated at therapeutical doses, to produce
damage on it.
Another fact is the tendency to increase the sensory nerve fibre threshold
in patients group which accounts for a further abnormality of the fibre.
The lack of significant difference in the mean amplitude of the sensory
evoked potentials between the affected and control groups, could signify that
most of the sensory axons are not really destroyed, but disturbed in some
way to become slower.
S U M M A R Y
R E S U M O
Velocidade de condução sensitiva e motora no tratamento prolongado
com a difenilidantoina
Para avaliar as velocidades de condução sensitiva e motora no nervo
mediano, foram utilizados 11 pacientes epilépticos submetidos a tratamento
prolongado com a difenilidantoina, administrada em doses terapêuticas. Os
resultados obtidos foram correlacionados com grupos controles. Estes
resulta-dos mostraram significativa diminuição das velocidades de condução
sensi-tiva e motora, que estavam relacionadas com o tempo de tratamento e não
com a dose diária empregada. Conclui-se que a D P H , em administração
prolongada, altera a condutibilidade motora e sensitiva nos nervos periféricos.
R E F E R E N C E S
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