The clınıcal profıle of nonmotor fluctuatıons ın parkınson's dısease patıents

THE CLINICAL PROFILE OF NONMOTOR FLUCTUATIONS

IN PARKINSON'S DISEASE PATIENTS

D ile k İnce G ü n a l, M .D .* / K erim N urichalich i, M .D .* / Neşe Tuncer, M .D .*

N u ral B ek iro ğ lu , P h.D .** / Sevinç A k ta n , M .D .*

* D e p a rtm e n t o f n e u ro lo g y , S c h o o l o f M e d ic in e , M a rm a ra U n ive rsity, Is ta n b u l, Turkey.

** D e p a rtm e n t o f B io s ta tis tic s , S c h o o l o f M e d ic in e , M a rm a ra U n iv e rs ity , Is ta n b u l, Turkey.

ABSTRACT

O b j e c t i v e : R e c e n tly d e s c r ib e d n o n m o to r flu c tu a tio n s m a y c a u s e d is a b ility in P a rk in s o n 's d is e a s e p a tie n ts . T h e s e flu c tu a t io n s a re g e n e ra lly g ro u p e d a s s e n s o ry , a u to n o m ic a n d c o g n itiv e /p s y c h ia tric . T h e c lin ic a l s p e c tru m a n d fre q u e n c y o f th e s e s y m p to m s a m o n g p a tie n ts w ith flu c tu a tin g P a r k in s o n 's d is e a s e a re u n k n o w n .

M e t h o d s : W e s tu d ie d th e c o r r e la tio n o f n o n m o to r flu c tu a tio n s w ith m o to r s y m p to m s a n d d e te rm in e d th e e ffe c t o f a g e a t d is e a s e o n s e t, d u ra tio n o f d is e a s e , d o s a g e a n d d u ra tio n o f le v o d o p a tr e a tm e n t to th e o c c u r r e n c e o f n o n m o to r flu c tu a tio n s .

R e s u lt s : T h e s ta tis tic a l a n a ly s is s h o w e d a p o s itiv e c o rre la tio n o f all a b o v e c rite r ia w ith s e n s o ry a n d a u to n o m ic flu c tu a tio n s . W h e re a s , c o g n itiv e -p s y c h ia tric flu c tu a tio n s w e re fo u n d to b e o n ly c o rre la te d w ith th e d u ra tio n o f le v o d o p a u s a g e . T h e n o n m o to r flu c tu a tio n s in c lu d e d in th e s tu d y w e re o b s e rv e d d u rin g "o n " p e rio d a s w e ll a s "o ff" a n d "e n d d o s e o ff" p e rio d s .

C o n c lu s i o n : T h e v a r ia b ilit y o f n o n m o to r flu c tu a tio n s in c lin ic a l p r e s e n ta tio n a n d c o a p p e a ra n c e o f th e s e flu c tu a tio n s w ith d iffe re n t ty p e s o f m o to r flu c tu a tio n s w e re c o n s id e re d a s th e e ffe c t o f o th e r n e u ro tra n s m itte r s y s te m s

a c tin g s y n c ro n o u s ly w ith d o p a m in e . In th is s tu d y , w e d e te r m in e d th e h ig h r is k fa c to r s fo r n o n m o to r f lu c tu a t io n s in p a tie n ts w ith P a rk in s o n ’s d is e a s e .

K ey W ords:

P a rk in s o n 's d is e a s e , N o n m o to r, flu c tu a tio n s , D o p a m in e , L e v o d o p a

INTRODUCTION

A c tu a lly a ll p a tie n ts w ith P a rk in s o n 's d is e a s e (P D ) e x p e r ie n c e m o to r f lu c tu a t io n s u s u a lly r e la te d to c h r o n ic le v o d o p a t h e r a p y in p r o g r e s s io n o f d is e a s e . T h e s e flu c tu a t io n s c o n s titu d e th e g re a te s t p ro b le m d u rin g th e lo n g te r m m a n a g e m e n t o f th e p a tie n ts ( 1 ) . It is e s tim a te d th a t a p p r o x im a te ly 1 0 % o f all p a tie n ts tr e a te d w ith le v o d o p a w ill d e v e lo p m o to r flu c tu a tio n s p e r y e a r, s o th a t 5 0 % a re a ffe c te d a fte r fiv e y e a rs o f s u s ta in e d le v o d o p a th e ra p y (2 ). R e c e n tly , in a d d itio n to m o to r flu c tu a t io n s , n o n m o to r flu c tu a tio n s h a v e b e e n d e s c rib e d a s s e n s o ry , a u to n o m ic a n d c o g n itiv e /p s y c h ia tr ic f l u c t u a t io n s ^ ) . In o u r s tu d y w e p la n n e d to e s tim a te th e n o n m o to r s y m p to m s a n d th e n flu c tu a tio n s in th e s e s y m p to m s . T h e a g e at d is e a s e o n s e t, d u ra tio n o f d is e a s e , d o s a g e a n d d u ra tio n o f le v o d o p a u s a g e w e re d e te r m in e d a n d th e c o rre la tio n b e tw e e n th e s e p a ra m e te rs a n d n o n m o to r flu c tu a tio n s w e re s tu d ie d .

Nonmotor fluctuations in Parkinson’s disease patients

M e t h o d s : D u rin g s ix m o n th s p e rio d (N o v e m b e r 1 9 9 8 - A p ril 1 9 9 9 ) w e e v a lu a te d 8 5 c o n s e c u tiv e P D p a tie n ts . T h e e th ic a l a p p ro v a l o f th e s tu d y w a s g ra n te d b y th e u n iv e rs ity e th ic a l c o m m itte e a n d th e in fo r m e d c o n c e n t w a s g iv e n . T h e s y m p to m s w e re c la s s ifie d in s e n s o ry , a u to n o m ic a n d c o g n itiv e / p s y c h ia t r ic g r o u p s b y q u e s tio n n a ire a s d e s c rib e d in ta b le I. If th e s y m p to m s w e re p o s itiv e , th e p a tie n t w a s a s k e d to d e s c rib e th e c o rre la tio n o f th e s e s y m p to m s w ith m o to r s y m p to m s (o n , o ff s ta te s , d y s k in e s ia , e n d -d o s e o ff, p re d o s e ). W e d e te rm in e d th e a g e a t d is e a s e o n s e t, d u ra tio n o f th e d is e a s e , d o s a g e a n d d u ra tio n o f le v o d o p a u s a g e o f th e p a tie n ts . T h e U n ifie d P a rk in s o n 's d is e a s e ra tin g s c a le s (U P D R S ) a n d H o e h n a n d Y a h r (H & Y ) s c a le s of th e p a tie n ts w e re e v a lu a te d . T h e p a tie n ts w e re a ls o e v a lu a te d b y m in im e n ta l s ta tu s s c a le to e x c lu d e th e c o g n itiv e d e c lin e in te rfe rin g w ith in te rv ie w p e rfo rm a n c e .

T a b l e I. T h e n o n m o to r sy m p to m s a n d relation with m otor flu c tu a tio n s w e re s tu d ie d a c c o rd in g to this q u e stio n n a ire .

Noncorrelated

with motor fluctuations "On" "Otf "End dose off "Predose'

Sensory Symptoms: 1. Pain 2. Paresthesls 3. Akathisia 4. Restless leg Autonomic symptoms: 1. Pallor of skin 2. Drooling

3. Difficulty with swallowing 4. Excessive gas with frequent burbing 5. Bloating (excessive fullness) 6. Episodic spasm of the anus 7 Shodness of breath 8. Excessive sweating 9. Flushing or chilling 10. Frequent urination 11. Orthostatic hypotension Cognitive/psychiatric symptoms: 1. Hallucinations 2. Moaning or screaming 3. Elevated mood 4. Depressed mood 5. Panic attack

S t a t is t ic s : T h e n o n m o to r flu c tu a tio n s c la s s ifie d a s s e n s o ry , a u to n o m ic a n d c o g n itiv e /p s y c h ia tric w e r e s tu d ie d s t a t is t ic a lly to d e te r m in e th e c o rre la tio n w ith a g e a t d is e a s e o n s e t (y e a r), d u ra tio n o f d is e a s e a n d le v o d o p a u s a g e (y e a r)

b y t te s t. F o r le v o d o p a d o s e s (m g /d a y ), chi s q u a re te s t w a s u s e d . H & Y a n d U P D R S s c a le s o f th e p a tie n ts w ith n o n m o to r flu c tu a tio n s a n d w ith o u t flu c tu a tio n s w e re s tu d ie d s ta tis tic a lly b y t te s t. P < 0 .0 5 w a s c o n s id e r e d s ta tis tic a lly s ig n ific a n t. P a tie n ts a n d R e s u lt s : T h e 8 5 p a tie n ts in c lu d e d in th e s tu d y c s is te d o f 5 0 m a le a n d 3 5 fe m a le . T h e m e a n a g e o f th e p a tie n ts w a s 6 6 .1 9 ± 9 .3 5 (3 8 -8 5 ). T h e a g e a t d is e a s e o n s e t, d u ra tio n of d is e a s e , d o s a g e a n d d u ra tio n o f le v o d o p a u s a g e a n d s c a le s w e re g iv e n in ta b le II. T h e m in im e n ta l s ta tu s s c a le s o f all p a tie n ts w e re o v e r 2 5 /3 0 .

T a b l e II. D e m o g ra p h ic c h a ra c te riz a tio n of th e p a tie n ts with P a rk in so n 's d is e a s e in this study.

Mean Range Age 66 (38-85) Age of disease onset 62 (31-83) Disease duration (year) 5 (0.5-33) Duration of levodopa usage (yr) 3 (0.5-25) Levodopa dose/day (mgr) 500 (62.5-750) H&Y 2.16 (1-5) UPDRS 40.49 (5-122) H&Y: Hoehn and Yahr scale

UPDRS: Unified Parkinson’s Disease Rating Scale

S e v e n ty tw o o f 8 5 p a tie n ts (8 4 .7 % ) h a d m o to r flu c tu a tio n s . A ll o f th e s e p a tie n ts e x p e rie n c e d o n e o r m o re n o n m o to r s y m p to m s . T h e flu c tu a tio n s o f th e s e n o n m o to r s y m p to m s a n d re la tio n w ith m o to r flu c tu a tio n s w e re s tu d ie d b y c la s s ify in g s y m p to m s in to s e n s o ry , a u to n o m ic , c o g n itiv e / p s y c h ia t r ic s in c e th e c o e x is te n c e o f d iffe r e n t n o n m o to r s y m p to m s in th e s a m e p a tie n t w o u ld c a u s e c o n flic ts in s ta tis tic a l e v a lu a tio n .

S e n s o r y f l u c t u a t io n s : F ifty n in e o f 72 p a tie n ts (6 9 .4 % ) h a d s e n s o r y s y m p to m s . T h e s e s y m p to m s w e re c o r r e la te d w ith m o to r flu c tu a tio n s in 2 8 p a tie n ts (3 8 .8 % ) a n d c a lle d s e n s o ry flu c tu a tio n s . R e g a rd in g th e s e n s o ry flu c tu a tio n s , 8 8 .8 8 % w a s d u rin g "o ff" p e rio d , 1 1 .1 1 % w a s d u rin g " e n d -d o s e o ff" p e rio d . W e fo u n d a s ta t is t ic a lly s ig n ific a n t d iffe r e n c e b e tw e e n p a tie n ts w ith s e n s o ry flu c tu a tio n s a n d w ith o u t s e n s o ry flu c tu a tio n s in th e a s p e c t o f a g e o f d is e a s e o n s e t, d u r a tio n o f d is e a s e , th e d u r a tio n o f le v o d o p a u s a g e a n d d o s a g e . (p < 0 .0 0 5 , p < 0 .0 5 , p < 0 .0 5 , p < 0 .0 5 re s p e c tiv e ly ).

Dilek Ince Gunal, et aI

T h e s e n s o ry flu c tu a tio n s w e re s ig n ific a n tly h ig h in th e p a tie n ts w ith e a rly a g e o f d is e a s e o n s e t, lo n g d is e a s e d u ra tio n , h ig h le v o d o p a d o s a g e a n d lo n g d u ra tio n o f le v o d o p a u s a g e . T h e re s u lts w e re s h o w n in ta b le III.

A u t o n o m i c f l u c t u a t i o n s : S ix ty o n e o f 72 p a tie n ts (8 4 .7 % ) h a d a u to n o m ic s y m p to m s . O n ly 2 9 .1 6 % (21 p a tie n ts ) to ld c o rre la tio n w ith m o to r flu c tu a tio n s . T h e s e a u to n o m ic flu c tu a tio n s w e re p re s e n t d u rin g "o ff" p e rio d in 7 5 % o f th e p a tie n ts , d u rin g "o n " p e ro id in 2 5 .8 % o f th e p a tie n ts , d u rin g "e n d -d o s e o ff" p e rio d in 1 5 % a n d d u rin g " p r e d o s e " p e rio d in 1 5 % . S e v e n p a tie n ts re p o rte d to h a v e m o re th a n o n e a u to n o m ic s y m p to m . F o r th e a u to n o m ic flu c tu a tio n s s im ila r to s e n s o ry flu c tu a tio n s , th e e a rly a g e o f d is e a s e o n s e t, lo n g d is e a s e d u ra tio n , h ig h le v o d o p a d o s a g e a n d lo n g d u ra tio n o f le v o d o p a u s a g e w e re th e ris k fa c to rs (p < 0 .0 5 , p < 0 .0 5 , p < 0 .0 5 , p < 0 .0 5 re s p e c tiv e ly ). T h e re s u lts w e re s h o w n in ta b le III. C o g n it iv e a n d p s y c h i a t r i c f l u c t u a t io n s : T h irty fo u r o f 7 2 p a tie n ts (4 7 .2 % ) h a d c o g n itiv e /p s y c h ia tric s y m p to m s a n d 11 (1 5 .2 7 % ) o f th e p a tie n ts h a d c o rre la te d th e ir s y m p to m s w ith m o to r f lu c tu a t io n s . T h e s e c o g n itiv e / p s y c h ia tric flu c tu a tio n s w e re d u rin g "o ff" p e rio d in 8 1 .8 1 % o f th e p a tie n ts , d u rin g "o n " p e rio d in 1 8 .1 8 % o f th e p a tie n ts . W e d id n o t fin d a s ta t is t ic a lly s ig n if ic a n t d iffe r e n c e b e tw e e n p a tie n ts w ith c o g n itiv e /p s y c h ia tr ic flu c tu a tio n s a n d w ith o u t th e s e flu c tu a tio n s in th e a s p e c t o f a g e a t d is e a s e o n s e t, d u ra tio n o f d is e a s e a n d le v o d o p a u s a g e . H o w e v e r , le v o d o p a d o s e b e tw e e n p a tie n ts w ith c o g n itiv e / p s y c h ia t r ic flu c tu a tio n s a n d w ith o u t flu c tu a tio n s s h o w e d a s ta tis tic a lly s ig n ific a n t d iffe r e n c e (p < 0 .0 5 ). T h e h ig h le v o d o p a d o s a g e w a s fo u n d to b e c o rre la te d w ith th e o c c u r r e n c e o f c o g n itiv e / p s y c h ia t r ic flu c tu a tio n s ( ta b le III).

H & Y a n d U P D R S re s u lts o f th e p a tie n ts w ith n o n m o to r flu c tu a tio n s a n d w ith o u t flu c tu a tio n s w e re c o m p a re d s ta tis tic a lly a n d b o th s c a le s w e re s ig n ific a n tly h ig h in n o n m o to r flu c tu a tin g p a tie n ts (p < 0 .0 5 ). T h e d is e a s e p ro g re s s io n h a s in c r e a s e d th e o c c u r r e n c e o f n o n m o to r flu c tu a tio n s .

T a b l e III. T able sh o w s correlation of d is e a s e related p a ra m e te rs with th e o c c u rre n c e of n o n m o to r fluctuations. Age at disease onset Disease duration

(year) Duration of levodopa usage (year) Levodopa dose mg/d The patients with sensory fluctuations 54.78±11.14” 8.75±7.64* 6.10±5.63* 564.9±177.2* The patients without sensorv fluctuations 62.17±9.61 5.34±3.96 3.37±3.44 458.75±183.68 The patients with autonomic fluctuations 54.95±10.46* 9.16±6.68* 6.54±6.10* 571 4± 191.9* The patients without autonomic fluctuations 61.31±10.32 5.57±5 3.43±3.35 465,9±178.74 The patients with cogn/psyhiatric fluctuations 60.27±12.18 10.27±8.51 4.7±3.34 650±129.1 * The patients without coo/nsvhiatric fluctuations " p<0.05 ** p<0.005 59.66±10.50 5.89±4.92 4.28±4.65 475.74± 185.9

Nonmotor fluctuations in Parkinson's disease patients

DISCUSSION

T h e m o s t c o m m o n flu c tu a tio n s s e e n in PD p a tie n ts c o n s is t o f c h a n g e s in m o to r fu n c tio n s p re s u m a b ly a s s o c ia te d w ith a lte ra tio n s in th e c o n c e n tr a tio n a n d e ffic a c y o f s tr ia ta l d o p a m in e rg ic a c tiv ity . T h e s e m o to r flu c tu a tio n s m a y re s u lt in d e g re e s o f d is a b ility a t le a s t e q u a l to th a t c a u s e d b y th e d is e a s e its e lf(2 ). N e w ly d e s c r ib e d n o n m o to r flu c tu a tio n s a re th o u g h t to b e fre q u e n t a n d c a n b e g ro u p e d a s s e n s o ry , a u to n o m ic a n d c o g n itiv e /p s y c h ia tric f lu c t u a t io n s ^ ) . T h e c lin ic a l s p e c tr u m a n d fr e q u e n c y o f th e s e n o n m o to r s y m p to m s a m o n g p a tie n ts w ith flu c tu a tin g P D p a tie n ts a re u n k n o w n . H ille n e t a l(3 ) s tu d ie d th e n a tu r e a n d o c c u r r e n c e o f n o n m o to r flu c tu a tio n s in 1 3 0 c o n s e c u tiv e P D p a tie n ts . T h e y e m p h a s iz e d th e re c o g n itio n o f th e s e s y m p to m s a s "o ff" p h e n o m e n a . In o u r s tu d y g ro u p , th e s e n s o ry flu c tu a tio n s w e re p re s e n t d u rin g "o ff" a n d "e n d d o s e o ff" p e rio d s . W h e re a s th e a u to n o m ic flu c tu a tio n s w e re d e te rm in e d d u rin g "o n " a n d "p re d o s e " p e rio d s a s w e ll a s "o ff" p e rio d . T h e s e fin d in g s w e re c o n s id e re d th a t n o n m o to r flu c tu a tio n s c o u ld n o t b e d e s c rib e d a s "o ff" p h e n o m e n a . " O n " a n d " p r e d o s e " p e rio d flu c tu a tio n s a n d u n re s p o n s iv e n e s s o f s o m e o f th e n o n m o to r f lu c tu a t io n s to d o p a m in e r g ic tr e a tm e n t s tra te g ie s m ig h t in d ic a te th e e ffe c t o f o th e r n e u r o tr a n s m itte r s y s te m s o n to th e n o n m o to r flu c tu a tio n s .

T h e c o rre la tio n b e tw e e n n o n m o to r flu c tu a tio n s a n d d is e a s e r e la te d p a ra m e te rs w e re e v a lu a te d in o u r s tu d y to d e te rm in e th e p a tie n t g ro u p s h a v in g h ig h ris k fo r n o n m o to r flu c tu a tio n s . O u r s ta tis tic a l a n a ly s is s h o w e d th a t n o n m o to r s e n s o ry flu c tu a tio n s w e re m o s tly p re s e n t in p a tie n ts w ith e a rly a g e of d is e a s e o n s e t a s w e ll a s th e p a tie n t w ith lo n g d is e a s e d u ra tio n a n d lo n g d u ra tio n o f le v o d o p a u s a g e . T h e d o s a g e o f le v o d o p a u s e d w a s fo u n d s ta tis tic a lly h ig h in th e s e p a tie n ts .

A u to n o m ic s y m p to m s w e re q u ite fre q u e n t in o u r p a tie n ts (8 4 .7 % ) b u t, o n ly 3 3 % o f th e p a tie n ts ' c o m p la in ts w e re c o r r e la te d w ith m o to r flu c tu a tio n s . A lth o u g h s e n s o ry flu c tu a tio n s w e re m o s tly s e e n d u r in g " o ff" o r “ e n d - d o s e o f f ” p e rio d s , a u to n o m ic flu c tu a tio n s w e re re p o rte d

d u rin g “o ff” (7 5 % ), “o n ” (2 5 ,8 % ) a n d “p re d o s e ” p e rio d s (1 5 % ). T h e a u to n o m ic flu c tu a tio n s m o s tly s e e n d u rin g “o ff” p e rio d w e re in c re a s e d s a liv a tio n , a b d o m in a l b lo a tin g , s w e a tin g , fa c ia l flu s h in g a n d o r th o s ta tic h y p o te n s io n . T h e p a tie n ts w ith a u to n o m ic flu c tu a tio n s h a d th e s im ila r c lin ic a l c h a ra c te ris tic s w ith th e p a tie n ts h a v in g s e n s o ry flu c tu a tio n s . T h e e a rly a g e of d is e a s e o n s e t, lo n g d is e a s e d u ra tio n a n d le v o d o p a u s a g e , h ig h le v o d o p a d o s e s w e re fo u n d to b e im p o rta n t in th e o c c u rre n c e of a u to n o m ic flu c tu a tio n s . In G o e tz (4 ) a n d L a n g s to n (5 ) s tu d ie s a b o u t a u to n o m ic d y s fu n c tio n in P D , it w a s re p o rte d th a t a u to n o m ic d y s fu n c tio n c o u ld n o t b e e x p la in e d o n ly b y n ig ra l d e g e n e ra tio n .

F lu c tu a tin g c o g n itiv e a n d p s y c h ia tric s y m p to m s w e re fr e q u e n tly re p o rte d in P D (6 ). T w o th ird s of p a tie n ts re c e iv in g c h ro n ic le v o d o p a tre a tm e n t e x p e r ie n c e flu c tu a t io n s in m o o d (1 ). A n y c o m b in a tio n o f d e p re s s io n , a n x ie ty (7 ), p a n ic (8 ), irrita b ility o r a p a th y d u rin g "o ff" p e rio d s h a s b e e n re p o rte d . D e lis (9 ) fo u n d a m o d e ra te d e c lin e in of n e u ro p s y c h o lo g ic a l te s ts d u rin g "o ff" p e rio d . In o u r p a tie n ts lik e o th e r re p o rts in th e lite ra tu re , w e o b s e rv e d a m o o d d e c lin e d u rin g w o rs e n in g p e rio d o f th e m o to r s y m p to m s . T h e s e flu c tu a tio n s o f m o o d in P D p a tie n ts h a v e b e e n th o u g h t to b e a p h e n o m e n o n re la te d w ith m o to r flu c tu a tio n s ra th e r th a n a re a c tiv e p h e n o m e n o n to th e m o to r d is a b ility . H o w e v e r, in la te r re p o rts m o o d flu c tu a tio n s s e e n in P D p a tie n ts h a v e b e e n s tu d ie d e x te n s iv e lly a n d d e p re s s iv e m o o d h a s b e e n s h o w n a ls o d u rin g " d y s k in e s ia " p e rio d o th e r th a n "o ff" p e rio d (9 ,1 0 ). T h is d a ta s u p p o rts th e im p o r ta n c e o f m o to r d is a b ilit y a n d re a c tiv e p ro c e s s h y p o th e s is a b o u t m o o d flu c tu a tio n s . In o u r s tu d y , th e p a tie n ts w ith c o g n itiv e /p s y c h ia tric flu c tu a t io n s d id n o t s h o w a n y s ta tis tic a lly s ig n ific a n t d iffe r e n c e b e tw e e n n o n flu c tu a tin g p a tie n ts in th e a s p e c t o f th e a g e o f d is e a s e o n s e t, th e d u ra tio n o f d is e a s e o r le v o d o p a u s a g e , b u t th e le v o d o p a d o s a g e w a s s ig n ific a n tly h ig h in flu c tu a tin g p a tie n ts . T h e p o s itiv e c o rr e la tio n fo u n d b e tw e e n th e le v o d o p a d o s e a n d c o g n itiv e /p s y c h ia tric flu c tu a tio n s m ig h t b e th e d ire c t e ffe c t o f le v o d o p a . W e c o u ld n o t e x p la in w h y th e d u ra tio n o f le v o d o p a u s a g e w a s n o t c o rre la te d w ith c o g n itiv e /p s y c h ia tric flu c tu a tio n s s in c e w e e x c lu d e d th e c o g n itiv e d e c lin e o f th e p a tie n ts in te rfe rin g w ith in te rv ie w p e rfo rm a n c e b y m in im e n ta l s ta te e x a m in a tio n . T h e la c k of

Dilek ince Günal, et al

c o rre la tio n fo u n d b e tw e e n th e a g e o f d is e a s e o n s e t, th e d u ra tio n o f d is e a s e o r le v o d o p a u s a g e m ig h t in d ic a te th a t th e c o g n itiv e / p s y c h ia t r ic flu c tu a tio n s p ro g re s s in a d iffe re n t m a n n e r th a n s e n s o ry a n d a u to n o m ic flu c tu a tio n s .

N e w ly d e s c rib e d n o n m o to r flu c tu a tio n s a re n o t c le a rly e x p la in e d in th e ir m e c h a n is m o f a c tio n . S o m e a u th o rs b la m e o th e r n e u ro tra n s m itte rs flu c tu a tin g s y n c ro n o u s ly w ith d o p a m in e s in c e a v a r ie ty o f f lu c tu a t in g s y m p to m s h a v e b e e n re p o r te d (1 1 ,1 2 ). O u r s tu d y re s u lts s u p p o rt th e h y p o th e s is o f o th e r n e u ro tra n s m itte rs flu c tu a tin g s y n c ro n o u s ly w ith d o p a m in e . W e th o u g h t th a t to c la r ify th e e x a c t m e c h a n is m s u n d e r ly in g in n o n m o to r flu c tu a tio n s , th e s tu d ie s in c lu d in g la rg e s a m p le s w ith m o re h o m o g e n o u s p a tie n t g ro u p s a re n e e d e d .

REFERENCES

1. Q u in n HP. C la s s ific a tio n o f f lu c t u a t io n s in p a t ie n ts w ith P a r k in s o n s d is e a s e , n e u r o lo g y 1 9 8 8 ;5 1 ( s u p p l 2 ), 2 5 - 2 9 . 2 . P o e w e W fl. C l in i c a l a s p e c t s o f m o t o r f lu c t u a t io n s in p a t ie n t s w ith P a r k in s o n s d is e a s e , n e u r o lo g y 19 9 4 ; 4 4 ( s u p p l 6 ):6 -9 . 5 . f l il le n ME, S a g e J l. n o n m o t o r f lu c t u a t io n s in p a t ie n ts w ith P a r k in s o n s d is e a s e , n e u r o lo g y 1 9 9 6 ,4 7 : 1 1 8 0 - 1 1 8 3 . 4. Q o e tz CG , L u tg e J , T a n n e r CM. A u t o n o m ic d y s f u n c t io n in P a r k in s o n s d is e a s e , n e u r o lo g y 1 9 9 6 ;3 6 : 7 3 - 7 5 . 5 . L a n g s to n J W , P o r n o LS. H y p o th a la m u s in P a r k in s o n s d is e a s e . A n n n e u r o l 1 9 7 8 ; 3 : 1 2 9 - 1 3 3 . 6. O la n o w CW , H o lle r WC. A n a lg o r it m f o r th e m a n a g e m e n t o f P a r k in s o n s d is e a s e . T r e a t m e n t g u id e lin e s . n e u r o lo g y 19 8 8 ; 5 0 ( s u p p l 3 ) :2 3 - 3 0 . 7. R o u th LC , B la c k J L , A h ls h o g JE . P a r k in s o n s d is e a s e c o m p lic a t e d w ith a n x ie ty . M a y o C lin P ro c 1 9 8 7 ;6 2 : 7 3 3 - 7 3 5 . 8 . V a s q u e z A, J im e n e z EJ, G a rc ia -R u iz P. P a n ic a tta c k s in P a r k in s o n s d is e a s e . A c ta n e u r o l S c a n d 1 9 9 3 ;8 7 : 1 4 - 1 8 . 9. D e lis D, D ir e n f e ld L, A le x a n d e r MP, K a p la n E. C o g n itiv e f lu c t u a t io n s a s s o c ia te d w ith o n - o f f p h e n o m e n o n in P a r k i n s o n s d is e a s e , n e u r o lo g y 19 8 2 ; 3 2 : 1 0 4 9 - 10 5 2 . 10. S ie m e r s ER, S h e k h a r A, Q u a id H, D ic k s o n H. A n x ie t y a n d m o t o r p e r f o r m a n c e in P a r k in s o n s d is e a s e . M o v D is o r d 1 9 9 3 ;8 :5 0 1 - 5 0 6 . 1 1 . n is s e n b a u m H, Q u in n HP, B r o w n RG, T o o n e B, G o th a m A M , M a rs d e n CD. M o o d s w in g s a s s o c ia te d w ith t h e " o n - o f f p h e n o m e n o n in P a r k in s o n s d is e a s e . P s y c h o l M e d 1 9 8 7 ;1 7 : 8 9 9 - 9 0 4 . 12. S a g e J l, M a rk M H. B a s ic m e c h a n is m o f m o t o r f lu c t u a t io n s , n e u r o lo g y 1 9 9 4 ; 4 4 ( s u p p l 6 ) : 10- 14.

URUN BİLGİSİ

F o rm ü l: Her yumuşak kapsül 60 mg Alverin sitrat 300 mg Simetikon içerir. F a rm a ko lo jik Ö ze llikle ri: Meteospasmyl yumuşak kapsül, iki etken maddeden oluşmuş bir üründür. Alverin, papaverine benzer etki ile müskülotropik karakterde antispazmodik özellik gösteren bir maddedir. Alverin'in spazmolitik etkisi, papaverinden daha fazla, yan etkisi ise papaverinden üç kat daha az bulunmuştur. Atropine benzer etki göstermediğinden mide asidi üzerine bir etkisi yoktur. Alverin ile yapılan farmakokinetik çalışmalarda, serum konsantrasyonları oldukça düşük düzeyde bulunmuştur. (2.5 ng/ml'nin altında). Bu sonuç, alverinin resorbe olmadığı veya simetikon ile birlikte alındığında, karaciğerde önemli oranda ilk geçişte eliminasyon etkisine uğradığını düşündürmektedir. Bu sonuçlar, alverinin etkisini lokal olarak gösterdiğini desteklemektedir. Simetikon, fizyolojik olarak inert bir maddedir. Oral yolla alındıktan sonra herhangi bir metabolizasyona uğramadan dışkıyla atılır. Simetikon,

aktive edilmiş dimetikon olup, güçlü gaz giderici özelliğe sahiptir. Gastrointestinal sistemdeki gaz kabarcıklarının yüzey gerilimlerini değiştirerek, onların biraraya gelm esini ve fizyolojik yollardan (geğirme, yellenme gibi) kolayca atılm alarını sağlar. E ndikasyonları: Karın ağrısı, spazm, şişkinlik, ishal ve/veya kabızlık ile seyreden irritabl (spastik) kolon sendromu, fonksiyonel sindirim bozuklukları ve sindirim kanalında aşırı gazın yarattığı ağrılı durum ların tedavisinde endikedir. K o n tre nd ikasyo n ları: İçerdiği maddelere karşı aşırı hassasiyeti olan kişilerde kullanımı kontrendikedir. U yarılar/Ö nlem ler: Gebelik ve süt verme döneminde kullanılması önerilmez. Yan E tkiler/A dvers E tkiler: Alverin, papaverine benzer etki gösterdiğinden, papaverin kullanılması sırasında karşılaşılan yüz ve boyunda kızarma, bulantı, baş ağrısı, hafif uyuşukluk hali, alerjik cilt döküntüleri gibi yan etkiler görülebilir. K u lla n ım Ş e kli ve D ozu: M eteospasm yl yum uşak kapsül, doktor tarafından başka bir şekilde önerilmediği taktirde; belirtilen endikasyonlarda, günde 2-3 kez yemeklerden önce bir kapsül alınır. A m b a la j: 20 yumuşak kapsül içeren blister ambalaj. R u h sa t T a rih i ve No.: 0 9 .0 7 . 1996-99/61 R uhsat S a h ib i: Ali Raif İlaç San. A Ş. İm al Y eri: Mayoly Spindler (Fransa) Reçete ile satılır. Daha geniş bilgi için firmamızı arayınız.

Ocak 2000 P.S.F. 1.909.650.-TL. M A Y O L Y SPİNDLER J0P A L İ R A İF İL A Ç S A N . A Ş .

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