The Irritable Larynx Syndrome

7/22/2019 The Irritable Larynx Syndrome

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Journal of VoiceVol. 13, No. 3, pp. 447-455 1999 SingularPublishing Group, Inc.

The Irritable Larynx SyndromeMurray Morrison, Linda Rammag e, and A. J. Em ami

Pacific Voice Clinic, U niversity of British Co lumbia, V ancouver Gen eral Hospital,Vancouver, British Columbia, Canada

Summary: Muscular tension dysphonia, episodic laryngospasm, globus, andcough m ay be considered to be hyperfunctional laryngeal symptoms. Suggestedetiological factors for these symptom s include gastroesophageal reflux, psycho-logical problems, and/or dystonia. We propose a unifying hypothesis that in-volves neural plastic change to hrainstem laryngeal control networks throughwhich each of the abo ve etiologies, plus central nervous system viral illness, canplay a role. We suggest that controlling neurons are held in a "spasm-r eady" stateand that symptom s may be trigg ered by various stimuli. Inclusion criteria for theirritable larynx syndrome are episodic laryngospasm and/or dysphonia with orwithout globus or chronic cough; visible or palpable evidence of tension or ten-demes s in laryngeal muscles; and a definite symptom-triggering stimulus, thirty-nine patients with irritable larynx syn drom e were studied. Gastroesophag eal re-flux was felt or proven to play a major role in a large number of the group(>90%), and about one third were deemed to have psychological causative fac-tors. Viral illness seem ed quite prevalent, with one third of patients able to relatethe onset of symp toms to a viral illness that we feel might lead to central nervoussystem changes. Our proposed hypothesis includes a mechanism w hereby ac-quired plastic change to central brainstem nuclei may lead to this form o f hyper-kinetic laryngeal dysfunction. It gives structure and reason to an array of therapymeasures and suggests direction for basic research. Key Words: Muscular ten-sion dysphonia--Laryngospasm--Vocal fold dysfunction--Paradoxical vocalfold motion adductor breathing dystonia--Globus--Chronic cough--Gastroe-sophagea l re f lux~pasmodic dysphonia--Neura l p last ic i ty--CNS vira l i l l -ness~ lrritable larynx syndrom e--Environm ental sensitivity.

H y p e rk in e t i c l a ry n g e a l d y s fu n c t io n p re se n t s i n n u -me ro u s fo rms :

M u s c u l a r tension dysphonia ( M T D ) m a y m a n i -f e s t a s v o c a l f ry , c h a ra c t e r i z e d b y a n t e ro p o s t e r io r

Accepted for publication August 4, 1998.Address correspondence and reprint requests to MurrayMorrison, MD, FRCSC, Pacific Voice Clinic, University ofBritish Columbia, Vancouver General Hospital, 805 West 12thAvenue, Vancouver, V5Z 1M9, BC, Canada.This paper was presented at the 27th Sym posium of The VoiceFoundation, June 5, 1998, Philadelphia, Pennsylvania, U.S.A.

(A P) c o mp re ss io n , p h a se a sy mme t ry , l o w p i t c h , d i -p lo p h o n ia , a n d ro u g h v o ic e q u a l i t y ; l a ry n g e a l i so -me t r i c p o s tu r in g c h a ra c t e r i z e d b y A P c o mp re ss io n ,e x a g g e ra t e d p o s t e r io r g lo t t i c c h in k , l a t e ra l c o mp re s -s io n in t h e me mb ra n o u s v o c a l fo ld s , l o w p i t c h , a n dbrea th iness; or a genera l hyperadduc t ing pa t te rn char-ac te r ized by g lo t t ic (and supraglo t t ic ) compression ,adduc t io n spasms, a nd st ra ined voice qua l i ty . Voiceu se ma y b e a c c o mp a n ie d b y l a ry n g e a l p a in a n d f a -t i g u e . In so me p a t i e n t s t h e d y sp h o n ia i s a sc r ib e d top s y c h o l o g i c al c a u s e a n d t e r m e d " p s y c h o g e n i c " o r

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" func t iona l ." In o th ers i t i s a t t r ibuted to technica l , pos-tu ra l, o r be ha v io ra l m i suse . S inc e the ne u ropa tho log yc a u s i n g t h e s y m p t o m i s n o t u n d e r s to o d , o u r h u n c h e sa n d e x p e r i e n c e s o f w h a t s e e m s t o w o r k i n m o s t c a s -e s gu id e the ra py . W e o r ig ina l ly de s c r ibe d M TD 1 in1983 , a nd su bse que n t ly p re se n te d w orks on d i a gnos-t ic c r i te r ia , 2,3 pa t te rn recog ni t ion , 4 a pa thophys io log -i c a l mo de l , 5 a nd phon a to ry func t ion c ha ra c t e r i s t ic sfo r m usc l e mi su se d ysphon ia . 6,7

E p i s o d i c l a r y n g o s p a s m , v o c a l f o l d d y s f u n c t i o n ,pa ra dox ic a l voc a l fo ld mo t ion , a nd a dduc to r b re a th -ing dy s ton ia a re a l l de sc r ip t ive t e rms tha t r e l a t e to as i t ua t ion in w h ic h the g lo t t i s c lo se s dow n in suc h aw a y a s t o i nh ib i t a i rf l ow . I f one r e a ds t he p syc h ia t r i cl i t e ra tu re one w ou ld be l i ke ly t o c l a ss " voc a l fo ldd y s f u n c t i o n " a s a s o m a t o f o r m d i s o r d e r o r p o s s i b l ya n a nx ie ty d i so rde r , a nd be l i e ve tha t " spe e c h the ra -py" o r p syc ho the ra py i s m os t l i ke ly t o he lp . 8,9 R e sp i -r a to ry phys i c i a ns ma y re l a t e " pa ra dox ic a l voc a l fo ldmo t ion" to a s thm a a nd t r e a t i t as suc h w i th i nha l e d o rsys t e m ic b ronc hod i l a to r s a nd s t e ro id s . The re sp i ra to -ry l i t e ra tu re is r e p l e t e w i th a r t i c l e s d i s t i ngu i sh ing vo -c a l f o l d d y s f u n c t i o n f r o m a s t h m a b u t t e n d i n g t o l e a v ethe e t io log y as " func t iona l" . 10-13 Ne uro log ica l ly fo-c use d c l i n i c i a ns ma y de c ide tha t t he b re a th ing p rob -l e m i s a va r i a n t o f foc a l l a rynge a l dys ton ia a nd re c -o m m e n d i n t r a c o r d a l i n j e c t i o n s o f b o t u l i n u m t o x i n .O t h e r s o f u s m a y f e e l t h e l a ry n g o s p a s m i s d u e t o g a s -t r o e s o p h a g e al r e f l u x ( G E R ) a n d a r e d e t e r m i n e d t h att h e p r o b l e m w i l l r e s o l v e w i th l o n g - t e r m p r o t o n p u m pinhibi tors . 14-16 Rep orts in th e p edia t r ic l i te ra ture re -l a t e G E R t o l a r y n g o s p a s m a s w e l l a s s u d d e n i n f a n tde a th synd ro me . 17

A re the se r e a l ly fou r d i f f e re n t d i so rde r s? I f no t ,w h ic h is " re a l " ?

C hron ic c ough , t h roa t c l e a r ing , a nd the se nse o f alump in t he t h roa t (g lobus pha rynge u s) a re a l so symp-t o m s t h a t m a y b e t i e d to m u s c l e t i g h t n e s s i n t h el a rynge a l a re a . The y ha ve be e n a t t r i bu t e d to r e sp i ra -tory d isease , GE R, 18 psyc holog ica l s t ress , 19 and a l le r-g y a m o n g o t h e r th i n gs .

W h i l e t he l a rynx u sua l ly looks s t ruc tu ra l ly no rma li n p a ti e n ts w h o c o m p l a i n o f th e s e s y m p t o m s , w eh a v e b e c o m e i n c r e a s i n g l y a w a r e o f o t h e r p h y s i c a lf ind ings t ha t a re p roba b ly impor t a n t , i nc lud ing a b -n o r m a l l a r y n g e a l p o s t u r e a n d p a l p a b l e m u s c u l a r t e n-s i o n i n a n d a r o u n d t h e l a r y n x . A r o n s o n 20 descr ibed

t h is a n u m b e r o f y e a r s a g o . H a r r is a n d L i e b e r m a n 21a n d R o y a n d L e e p e r22,23 have added fur ther de ta i l ,u s i n g m a n i p u l a t i o n t e c h n i q u e s t o r e d u c e l a r y n g e a lt e n s io n a n d r e d u c e s y m p t o m s .

Some pa t i e n t s c ompla in o f va r i a n t s o f l a ryngo-spa sm o r dysphon ia , o r bo th , a nd the i r sym ptom s a ret r i gge re d by some th ing de f in i t i ve . Tr igge r s ma y in -c lude e nv i ronme n ta l s t imu l i suc h a s odo rs , a i rbo rnepa r t ic l e s , o r c he m ic a l s . Foods , r e f luxa t e , e sopha ge a ls t imu l i , o r vo i c e u se a nd /o r c ough ing ma y t r i gge rsymptoms . W he n the y a l so ha ve v i s ib l e o r pa lpa b lee v ide nc e o f l a rynge a l mu sc l e t e ns ion the y a re su f fe r -ing f rom the i rr i t ab l e l a rynx synd rom e ( ILS).

In t h i s a r t i c le w e p re se n t a su mm a ry o f c l i n i c a l in -fo rma t ion a bou t 39 c onse c u t ive pat i en t s w i th ILS , a ndp ropose a un i fy ing ne u ropa tho log ic a l hypo the s i s .

M E T H O D S A N D M A T E R I A LSThi s s tudy i s ba se d on c o l l e c t ion o f c l i n i c a l da t a

f rom p a t i e n t s a t t e nd ing the Pa c i f i c V o ic e C l in i c a t t heV a n c o u v e r G e n e r a l H o s p i t a l a n d U n i v e r s i t y o fB r i ti s h C o l u m b i a b e t w e e n S e p t e m b e r 1 99 6 a n d D e -c e mbe r 1997 . D a ta f rom a l l pa t i e n t s w ho ha d be e ng ive n the ILS l a be l du r ing th i s t ime w e re c o l l a t e d toinc lude sub je c t i de n t i t y , symptoms , phys i c a l s igns ,poss ib l e c a use s , sym ptom t r igge r s , a nd t r e a tme n t sgiven.

W e de f ine the i r r i t a b l e l a rynx synd rome a s hype r -k ine t ic l a rynge a l dy s func t ion r e su lt i ng f rom a n a sso r t-e d c o l l e c t i o n o f c a u s e s i n r e s p o n s e t o a d e f i n i t i v et r igge r ing s t imu lus .

Inc lu s ion c r i t e r ia fo r ILS d i a gnos i s a re a s fo l low s :1 . S ym ptom s a t tr i bu t a b le to l a rynge a l t e ns ion

d y s p h o n i a a n d / o r l a r y n g o s p a s m w i th o r w i thou t g lobus a nd /o r c h ron ic c ough

2 . V i s ib l e a nd pa lpa b le e v ide nc e o f te ns ion l a ryngo sc op ic la t e ra l a nd A P c on t ra c t ion pa lpa t ion : SH , TH , C T, pha rynx

3 . P re se n c e o f a se nso ry tr i gge r a i rbo rne subs t a nc e , e sopha ge a l i rr i ta n t , odo r

T h e I L S d i a g n o s i s i s e x c l u d e d i f t h e r e is a p p a r -e n t o r g a n i c l a r y n g e a l p a t h o l o g y , a n i d e n t i f i a b l en e u r o l o g i c a l d i s e a s e , o r a n i d e n t i f ia b l e p s y c h i a t r i cd i a g n o s i s .

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THE IRRITABLE LARYN X SYNDROME 449

R E S U L T S : 3 9 C O N S E C U T I V EP A T I E N T S W I T H I L S

P a t ien t s g iven the ILS d iagno s i s t end to have com -p l e x c o m b i n a t i o n s o f s y m p t o m s , s i g n s , a n d b a c k -ground fac to rs . To he lp us sor t the da ta in a m ean-i n g f u l w a y w e b e g a n b y c o n s i d e r in g g r o u p i n g s b a s e don (a ) sy m p tom com plex , (b) t r igge r ing s t im ulus , (c)e t io log ica l pos s ib i li t i e s , and (d ) t rea tm en ts p rov ided .S y m p t o m c o m p l e x g r o u p i n g s

L a r y n g o s p a s m a n d d y s p h o n i a ar e t h e 2 m a j o r I L Ss y m p t o m s , w i t h t h e f o r m e r b e i n g t h e m o s t d i s tr e ss -ing. "M inor" symptQms include globus, ch ronic cough,and peri laryngeal pain. The fol lowing f is t shows then u m b e r o f p a t i e n ts i n e a c h o f 5 s y m p t o m g r o u p i ng s( L a r y n g o s p a s m , D y s p h o n ia , G l o b u s , C o u g h , O t h e r ) .L : L a r y n g o s p a s m a l o n e ( 5)L / O : L a r y n g o s p a s m w i t h D , G , o r C ( 2 0)D : D y s p h o n i a a l o n e ( 4)

D / O : D y s p h o n i a w i t h L , G , o r C ( 6)O: Othe r (G and /or C) (4 )

I t i s no ted tha t 26 pa t i en t s had d ysph onia o r l a ryn-g o s p a s m i n c o m b i n a t i o n w i th o t h e r s y m p t o m s . S i n c ea i rw a y c o m p r o m i s e is m o r e d i s t r e s si n g t h a n v o i c el o s s , m o s t p a t i e n t s w i l l b e i n c l u d e d i n t h e l a r y n -g o s p a s m g r o u p w h e n b o t h a r e p r e s e n t. T a b le 1 s h o w sthe age and s ex dem ograp hics fo r these 39 pa t i en ts .

The p hys ica l s igns tha t s eem e d to have g rea te s t im -por tance were each g raded o n a 0 to 3 s ca le , where 0was norm al , 1 m i ld , 2 m odera te , and 3 s eve re. P os te -r io r l a ryngea l in f l am m at ion , AP suprag lo t t i c com -pres s ion , and l a te ra l g lo t t i c com pres s ion were judg edf rom v ideoendo scopic exam ina t ion . Tens ion in supra -hyoid , thyrohyo id , c r i co thyro id , and pha ryngea l con-s t r i c to r m usc le g roups was a s ses sed by pa lpa t ion .Tab le 2 shows the ave raged s eve r i ty o f each of thera ted phys ica l s igns fo r each o f the 5 sym ptom groups .

TABLE 1. T h i r t y - n i n e P a t ie n t s W i t h I L S : D e m o g r a p h i c sL L/O D D/O O Total

Total patients 5 20 4 6 4Mal e 1 2 0 2 1Female 4 18 4 4 3Age range 33-64 23-66 39-68 34-70 46-69Avg. age 50 46 52 55 55Note: L = laryngospasm; D -- dysphonia; O = other (globus/cough).

396

33

TABLE 2. A v e r a g e d P h y s i c a l S i g n S e v e r i tyL L/O D D/O O Total

Total pati ents 5 20 4 6 4 39Poster ior inflamm ation 1.6 1.1 0.7 0.8 1 1.1AP squ eez e 1.2 1.5 1.7 1.5 0.3 1.4Later al squ eeze 1.4 1.1 1.5 1.6 0.3 1.2Supra hyoid tensio n 2.2 2 2.5 2.3 1.5 2.1Thyro hyoid tensio n 2.2 2.3 2.7 2.5 1.7 2.3Cricot hyroid tensio n 2 2 2.5 2.1 1 1.9Phary ngeal tensio n 2 1.6 1.7 1.8 1 1.6Note: 0 = normal; 1 -- mild; 2 = moderate; 3 = severe.

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4 5 0 M U R R A Y M O R R I S O N E T A L

Table 3 i t emizes the t r igger ing s t imul i tha t were iden-t if i e d b y p a t i en t s i n e a c h o f th e s y m p t o m c o m p l e xg r o u p s . A i r b o r n e i r ri ta n ts a n d G E R w e r e m e n t i o n e dm o s t f r e q u e n tl y , f o l l o w e d b y p e r f u m e , f o o d s , e m o -t i o n , a n d v o i c e u s e . Th e r e w e r e n o s i g n i f ic a n t d i f f e r-e n c e s i n t r i g g e r i n c i d e n c e a m o n g t h e v a r i o u s g r o u p s .Po s s i b l e e t i o l o g i c f a c t o r s t h a t c o u l d h a v e l e d t o t h ed e v e l o p m e n t o f s y m p t o m s w e r e c o n s i d e r e d f o r e a c hg r o u p a n d t h e r e s u l t s a r e s h o wn i n Ta b l e 4 . Th e o v e r -w h e l m i n g p r e s e n c e o f G E R , p r o v e n o r h i g h l y s u s-p e c t , i s o b v i o u s . I t i s i n t e r e s t i n g t o n o t e t h a t a l m o s th a l f o f t h e p a t i e n t s we r e a b l e t o r e l a t e t h e o n s e t o fs y m p t o m s t o a we l l - r e c o g n i z e d v i r a l i l l n e s s . Of 1 7v i r a l i l l n e s s e s o n l y 5 we r e u p p e r r e s p i r a t o r y i n f e c -t i o n s . Th e r e we r e 3 f l u l i k e i l l n e s s e s , 2 h e r p e s z o s t e ri n f e c t io n s , 2 w i t h v i r a l m e n i n g i t i s , 2 E p s t e i n - Ba r r i n -f e c t i o n s , 1 Ly m e d i s e a s e , 1 ti c k - b o r n e i n f e c t io n , a n d

1 p a t ie n t w h o h a d b e e n d i a g n o s e d a s h a v i n g p o s t v i -r a l c h r o n i c f a t i g u e s y n d r o m e . Ps y c h o l o g i c a l c o n t r i b -u t o r s w e r e n e x t m o s t c o m m o n , f o l l o w e d b y m i s c e l -l a n e o u s c a u s e s t h a t i n c l u d e d a s t h m a o r it s t re a t m e n t ,e n v i r o n m e n t a l a l le r g y , a n d n e c k t o r s i o n i n j u ri e s .Ta b l e 5 l i s t s t h e t r e a t m e n t s g i v e n t o m e m b e r s o fe a c h g r o u p . Al m o s t a l l we r e t r e a t e d f o r r e f l u x wi t he i t h e r g e n e r a l l i f e s t y l e m e a s u r e s o r m e d i c a t i o n . Th i si s n o t s u r p r i s i n g , s i n c e o u r I LS h y p o t h e s i s s u p p o s e st h a t e v e n t h e " n o r m a l " a m o u n t o f r e f l u x s t i m u l a t i o nwi l l p e r p e t u a t e l a r y n g e a l h y p e r i r r i t a b i l i t y . As a m a t -t e r o f fa c t , we h a v e c o m e t o f e e l t h a t re v e r s a l o f t h ec e n t r a l n e u r a l c h a n g e s a s s o c i a t e d wi t h I LS r e q u i r e sm a x i m a l a c i d s u p p r e s si o n a n d w e t h e r ef o r e u s e p r o -t o n p u m p i n h i b i t o r s r e g u l a r l y ( o m e p r a z o l e 2 0 m gt wi c e a d a y , l a n s o p r a z o l e 3 0 m g d a i l y , o r , p a n t o p r a -z o l e 4 0 m g d a i l y ) .

T A B L E 3 . ILS Sym ptom Tr iggersL L / O D D / O O T o t a l

T o t a l p a t i e n t s 5 2 0 4 6 4 3 9P e r f u m e 0 7 1 1 1 1 0O t h e r a i r b o r n e 2 1 1 2 3 2 2 0R e f l u x 3 1 6 3 3 3 2 8F o o d s 3 7 0 0 2 1 2E m o t i o n 2 9 2 5 1 1 9V o i c e u s e 1 6 2 0 1 1 0C o u g h i n g 0 5 0 1 0 6E x e r t i o n 0 1 1 0 0 2

T A B L E 4 . I L S P o s s i b l e E t i o l o g i c F a c t o r sL L / O D D / O O T o t a l

T o t a l p a t i e n t s 5 2 0 4 6 4 3 9R e f l u x 5 1 8 3 4 3 3 3V i r u s 2 1 0 3 1 1 1 7P s y c h o g e n i c 2 5 2 5 2 1 6A s t h m a 1 5 1 1 1 9T o r s i o n i n j u r y 1 1 0 1 0 3E n v i r o m e n t a l a l l e r g y 0 4 0 1 1 6I m m u n e d i s o r d e r 0 1 0 0 1 2

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T H E I R R IT A B L E L A R Y N X S Y N D R O M E 4 51TABLE 5 . I L S T r e a t m e n t s '

L L / O D D / O O TotalTota l pa t ients 5R e f l u x p r o t o c o l 5R e f l u x r e e d s 4E x e r c i s e s 3P s y c h o t h e r a p y 0B o t o x 0M a s s a g e / m a n i p u l a t i o n 0O t h e r 1

20 4 6 4 3917 4 3 4 3319 3 3 3 3111 3 5 1 23

4 1 3 1 95 0 1 1 74 1 3 0 84 0 2 1 8

" Ex e r c i s e s " l i s t e d i n t h e t a b l e i n c l u d e v o i c e t h e r a -p y w i t h a n e m p h a s i s o n r e l a x a ti o n o f l a r y n g e a l a n da s s o c i a t e d m u s c u l a r s y s t e m s . S i n c e t h e " s n i f f ' m a x -i m a l l y s t i m u l a t es v o c a l f o l d a b d u c t i o n , m a n y o f t h ep a t i e n t s wi t h l a r y n g o s p a s m wi l l b e a s k e d t o s n i f f r e -p e a t e d l y t h r o u g h o u t t h e d a y .

F o r m a l p s y c h o t h e r a p y w a s a p a r t o f t h e t r e a tm e n tp l a n f o r o n l y 9 o f t h e 3 9 p a t ie n t s , b u t m a n y r e c e i v e di n d i r e c t p s y c h o l o g i c a l s u p p o r t a n d c o u n s e l i n g f r o mv a r i o u s m e m b e r s o f th e c l in i c al t e am . M a n y o f t h ep a t i e n t s c a m e f o l l o wi n g a s e r i e s o f u n s u c c e s s f u lt r e a t m e n t s , a n d s i m p l e r e a s s u r a n c e t h a t t h e i r d i s o r d e rw a s u n d e r s t o o d m a y h a v e b e e n t h e ra p e u ti c .

L a r y n g e a l m a n i p u l a t i o n o r m a s s a g e w a s e f f e c t i v ei n s o m e p a t i e n t s , m o r e s o i n t h o s e w i t h d y s p h o n i at h a n l a r y n g o s p a s m . T h e t e c h n i q u e u s e d w a s a c o m -b i n a t i o n o f t h o s e d e s c r i b e d b y A r o n s o n , 2 H a r r i s a n dLieberman,2~ and R oy e t a l, 22-23 wi th an em pha s i s o na c h i e v in g r e l e a s e o f te n s i o n i n t h e t h y r o h y o i d m u s -c l e r e g i o n . I f t h e f i r s t m a n i p u l a t i o n p r o v e d h e l p f u l ,t h e n i t w a s g e n e r a l l y r e p e a t e d t w o o r t h r e e t i m e swi t h i n a we e k o r t wo . Bo t u l i n u m t o x i n i n j e c t io n s s e e mt o b e l e s s e f f e c t i v e , o r n o t i n d i c a t e d , i n p a t i e n t s wi t hI L S a s c o m p a r e d w i t h t h o s e w i t h f o c a l l a r y n g e a ld y s t o n i a . F i v e o f o u r 2 5 p a t i e n ts w i t h l a r y n g o s p a s mr e c e i v e d b o t u l i n u m t o x i n i n j e c ti o n a t s o m e p o i n t i nt h e i r t re a t m e n t , b u t 2 o f th e s e u l t i m a t e l y w e n t o n t or e q u i r e t r a c h e o t o m y .H Y P O T H E S IS F O R T H E E T I O L O G Y O F T H E

I R R I T A B LE L A R Y N X S Y N D R O M EW e f e e l t h a t th e I LS d e v e l o p s i n i n d i v id u a l s a s a re -

a c t i o n to s o m e s o r t o f ce n t ra l n e r v o u s s y s t e m ( C N S )

c h a n g e t h a t l e a v e s s e n s o r i m o t o r p a t h wa y s i n a h y -p e r e x c i t a b t e s t a t e . C l i n i c a l r e v i e w m a k e s i t e v i d e n tt h a t t h e r e a r e a n u m b e r o f p o s s i b l e c a u s a t i v e fa c t o r s,a n d t h a t s e v e r a l c a n b e a c t i v e i n a n y o n e p e r s o n . Em o -t i o n a l d i st r e s s, h a b i t u a l p o s t u r a l m u s c l e m i s u s e , GER ,a n d p o s t v i ra l i l ln e s s s e e m t o b e t h e m o s t p r e v a l e n t. An u m b e r o f p o s s i b l e n e u r o p a t h o lo g i c a l p r o c e s s e s c a nb e c o n s i d e r e d i n a n e x a m i n a t i o n o f w h y t h e s e f a c -t o r s l e ad t o c h r o n i c l a r y n g e a l m o t o r s t i m u l a t i o n a n dheightened sensory i r r i t ab i l i ty .

A p r o c e s s t e r m e d n e u r a l p l a s t i c i t y m a y a l t e r c e n -t r a l n e u r o n a l c o n t r o l o f t h e l a r y n x a n d r e l a t e d s t ru c -t u r e s. Th i s i m p l i e s a c h a n g e o r a d j u s t m e n t i n t h e wa yt h a t a c e n t r a l n e u r o n r e a c t s t o a n i n c o m i n g s t i m u l u s .W h i l e t h e s e c h a n g e s a r e i m p o r t a n t f o r m e m o r y a n dl e a rn i n g , p l a s t i c i t y m a y n o t b e i n t h e b e s t i n t e r e s ts o ft h e i n d i v i d u a l a n d , i n o u r e x a m p l e , m a y c h a n g e t h ewa y t h a t l a r y n g e a l m o t o r s y s t e m s r e a c t t o s e n s a t i o n so r t h o u g h t s . Th e r e a r e s e v e r a l p r o c e s s e s b y wh i c hc e n t r al n e u r o n s m a y u n d e r g o p l a s t i c a d a p t a ti o n . I n r e -s p o n s e t o n e r v e o r t i s s u e i n j u r y , a f f e r e n t i n p u t s a r ewi t h d r a w n f r o m t h e c e n tr a l n e u ro n , wh i c h t h e n m a k e sn e w c o n n e c t i o n s b y r e s p r o u t i n g d e n d r i t e s o r r e a c t i -v a t i n g " s i l e n t " s y n a p s e s , s o t h r o u g h t h i s p r o c e s s a na f f e r e n t s t i m u l u s t h a t u s e d t o r e s u l t i n o n e r e s p o n s en o w m a y e l i c i t a d i f f e re n t o n e .

A n o t h e r m e c h a n i s m f o r c h a n g e i n c e n tr a l n e u ro n a lf u n c t i o n i s a r e s p o n s e t o r e p e a t e d n o x i o u s s t i m u l a -t io n . Co n s t a n t r e l e a s e o f n e u r o t r a n s m i t te r s a c t i v a te sp l a s t i c i t y - r e l a t e d g e n e s i n c e n t r a l n e u r o n s , s u c h a sf o s . T h e p r o b a b l e m e c h a n i s m f o r t h i s i s s h o w n i nF i g u r e 1 . W h e n t h e f i rs t n e u r o t ra n s m i t t e r s t i m u l u s a r -f i v e s a t t h e CNS n e u r o n a l c e l l wa l l , i t s e n d s a r u e s -



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4 52 M U R R A Y M O R R I S O N E T A L

N e u r a l p l a s t i c r e s p o n s e t o r e p e t i t i v e n o e i s t i m u l a t i o n. . . . . . . . . . . " ' ~ e r

F IG . 1 . S c h e m a t i c r e p re s e n t a ti o n o f th e p ro c e s s o f n e u ra l p l a s t ic i t y . Th e c e n t e r o v a l r e p -re s e n t s t h e C N S n e u ro n n u c l e u s , a n d t h e o u t e r o v a l r e p re s e n ts t h e c y t o p l a s m . R e p e t i t i v en o x i o u s s t i m u l a t i o n m a y e v e n t u a l l y l e a d to p e rm a n e n t a l t e r a t io n o f t h e c e l l g e n o m e .

s a g e t h r o u g h th e c y t o p l a s m b y w a y o f a s e c o n d m e s -s e n g e r t o t h e n u c l e u s , w h e r e i m m e d i a t e e a r l y g e n e ssuc h a s c-fos o r c-jun are i n d u c e d . C-fos t h e n m o v e sou t t o t he c y top la s m w h e r e f o s pro te in i s syn the s i z e d .T h e pro to -oncogenefos t h e n m o v e s b a c k i n to t h e n u -c l e us , w he re i t b inds w i th D N A a nd re gu la t e s t het r a nsc r ip t ion o f l a t e - re sponse ge ne s . The l a t e - re -sponse ge ne s m a y inh ib i t o r s t imu la t e ne u rona l a c t iv -i t y a nd m a y a l t e r t he c e l l phe no type . I f t he c e l l phe -no type i s a l t e re d the n the r e sponse to a no the r a f fe re n ts t imu lus ma y be d i f f e re n t t ha n i t w a s p re v ious ly .

The body o f l i t e ra tu re on c h ron ic pa in i s a he lp fu ls o u r c e o f i n f o r m a t i o n a n d u n d e r s t a n d i n g a b o u t p l a s -t i c i t y a nd i ts poss ib l e r e l a t i on to d e ve lop me n t o f 1LS .In a r e v i e w a r t i c le on the c o n t r ibu t ion o f c e n t ra l ne u r -a l p last ic i ty to pa tho logica l pa in , C ode rre e t a124 ex-a m i n e d t h e e v i d e n c e f o r w a y s t h a t c e n t r a l n e u r a lp l a s t i c i t y c a n p l a y a r o l e i n t h e d e v e l o p m e n t o fpa tho log ic a l pa in a f t e r pe r iphe ra l t i s sue da ma ge . H y-pe ra lge s i a de pe nds , i n pa r t , on c e n t ra l se ns i t iz a t ion ,a nd w h i l e i t is c r i t i c a l tha t i n i t ia l i npu t s f r om the in -j u r y r e a c h t h e C N S , t h e h y p e r a l g e s i a d o e s n o t d e -p e n d o n m a i n t e n a n c e o f i n p ut s f r o m t h e p e r i p h er a lin ju ry . P ro longe d se nso ry d i s tu rba nc e s a ssoc i a t e d

w i th t i s sue in ju ry a re be l i e ve d to r e su l t e it he r f rom are duc t ion in t he t h re sho ld o f noc i c e p to r s , r e duc e d in -h ib i to ry c on t ro l , o r i nc re a se d e xc i t a b i l i t y o f C N Sne urons invo lve d in pa in t r a nsmiss ion . The y fu r the rimp ly a c on t r ibu t ion o f C - f ibe r ne u rope p t ide s a nd e x -c i t a to ry a mino a c id (EA A ) t r a nsmi t t e r s t o nox iouss t i m u l u s - in d u c e d c h a n g e s i n C N S f u n c ti o n . T h e s el e a d t o a n i n c r e a s e i n t h e e x p r e s s i o n o f p r o t o - o n c o -g e n e s s u c h a s fo s a n d jun , w h i c h , a s d e s c r i b e da b o v e , p a r ti c i p a te i n t h e r e g u l a t i o n o f m R N A e n -c o d i n g o f d y n o r p h i n a n d e n k e p h a l i n p e p t i d e s ,w h i c h c a n i n f l u e n c e l o n g - t e r m c h a n g e s i n c e l l u l a rfunc t ion . 25

Lud low e t a 126 ha ve show n tha t d i s rup t ion o r i n ju ryo f t h e s e n s o r y f ib e r s c o m i n g f r o m t h e l a r y n x b y w a yof t he supe r io r l a rynge a l ne rve c a n re su l t i n hype r -se ns i t i v it y o f t he e f fe re n t mo to r supp ly to t he t hy -roa ry t e no id musc le s . S e nso ry a f fe re n t s e nd in t he nu -c l e us o f t he t r a c tu s so l i t a r iu s w he re se c ond-o rde rne u rons r e l a y a mo to r r e f l e x to t he nuc l e us a mb igu -us . S tudy sub je c t s w ho h a d a n e a r l i e r i n ju ry to t he su -pe r io r l a rynge a l se nso ry ne rve supp ly , w e r e found toha ve he igh te ne d mo to r r e f l e x r e sponse s t o e l e c t r i c a ls t imu la t ion o f t he supe r io r ne rve on e i t he r t he in ju re d

Journ al o f Voice, Vol. 13, No. 3 , 1999


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THE IRRITABLE LARYNX SYNDROME 453o r o p p o s i t e s id e . I n s o m e c a s e s t h e s e n s o r i m o t o r d i s -i n h i b i t i o n l e d t o t h e e m e r g e n c e o f a f o c a l d y s t o n i a -l i k e s p a s m o d i c v o i c e . I t i s f e l t t h a t d i s i n h i b it i o n m a yo c c u r a s a r e s u l t o f p r o c e s s e s s i m i l a r t o t h a t d e -s c r i b e d a b o v e f o r p a i n .Th e p e r i a q u e d u c t a l g r a y ( PAG) a r e a i n t h e b r a i n -s t e m i s in v o l v e d i n v o c a l i z a t io n . S t i m u l a t i o n o f t h ed o r s a l a n d l a te r a l re g i o n s o f t h e PAG e v o k e s v o c a l -i z a t i o n i n s o m e a n i m a l s , a n d l e s i o n s p r o d u c e d h e r ewi l l r esul t in m ut ism.27, 28 Cel l s in the c auda l a reas oft h e PAG h a v e b e e n f o u n d t o h a v e a r e la t i o n s h i p wi t hl a r y n g e a l m u s c l e a c t i v i t y . Su p r a m a x i m a l s t i m u l a t i o no f t h e i n t e rn a l b r a n c h o f t h e s u p e r i o r l a r y n g e a l n e r v ei n t h e c a t h a s b e e n s h o wn t o i n c r e a s e fos l abe l ing ind o r s o m e d i a l a n d d o r s o l a t e r a l r e g i o n s o f t h e PA G. 29Th i s e v i d e n c e s u g g e s t s t h a t n e u r o n s i n t h i s a r e a a r es t i m u l a t e d b y l a r y n g e a l s e n s o r y f i b e r s c o m i n g t o t h ePAG , p o s s i b l y v i a t h e n u c l e u s o f t h e t r ac t u s s o l i t ar i u s.

I t i s l o g i c a l t o a s s u m e t h a t CNS v i r a l i n f e c t i o n s ,herpes zos te r and o thers , can resul t in genome changest h a t a l t e r la r y n g e a l m o t o r c o n t r o l .

E m o t i o n a l c o n n e c t i o n s a f f e c t i n g t h e l a r y n x m a yw o r k t h r o u g h t h e P A G , a s i t i s w e l l k n o w n t h a t e m o -t i o n a l s t a t e s a n d d e f e n s e r e a c t i o n s r e l a t e t o PAG a c -t i v i ty ) 0 , 31 J u r g e n s 3 2 h a s p r o p o s e d t h a t t h e PAGs e r v e s a s a l i n k b e t w e e n s e n s o r y a n d m o t i v a t i o n - c o n -

t r o l li n g s t r u c tu r e s a n d t h e p e r i a m b i g u a l r e t i c u l a r f o r -m a t i o n , c o o r d i n a t i n g t h e a c t i v i t y o f t h e d i f f e r e n tp h o n a t o r y m u s c l e s . T h e s e s t u d i e s s u p p o r t t h e o b v i -o u s a s s o c i a t io n b e t w e e n i n c r ea s e d v o i c e t e n s i o n a n dp s y c h o l o g i c a l s t r e s s o r r e p r e s s e d e m o t i o n .As t h m a l i k e r e a c t i o n s i n p a r a s y m p a t h e t i c p a r t s o fl a r y n g e a l m u s c l e s y s t e m s c a n b e e x p e c t e d t o r e -s p o n d t o i r r it a ti o n i n t h e s a m e wa y a s b r o n c h i a l m u s -c l e s i n l o we r a i r wa y d i s e a s e . Th e l a r y n g e a l e f f e c tm a y p r o d u c e m u s c u l a r t e n s i o n v o i c e p r o b l e m s , c h r o n -i c c o u g h , o r l a r y n g e a l a i r wa y s p a s m r a t h e r t h a n a n" a s t h m a l i k e " e x p i r a t o r y wh e e z e . As f o r re f l u x , wek n o w t h a t t h e r e i s a d i r e c t r e f l e x r e l a t i o n s h i p b e -t w e e n s t i m u l a ti o n o f t h e l o w e r e s o p h a g u s a n d t h y -r o a r y t e n o i d m u s c l e a c t iv i t y . 33 I t a l s o s e e m s l i k e l y t ou s t h a t c h r o n i c l a r y n g e a l r e f l u x i r ri t at i o n a f f e c t s t h ePAG, wh e r e n e u r a l p l a s t i c c h a n g e r e s u l t s i n l o n g -t e r m c h a n g e s t o l a r y n g e a l f u n c t i o n .

F i g u r e 2 g r a p h i c a l ly d e m o n s t r a t e s h o w w e f e e l th el a r y n g e al C N S c o n t r o l n e t w o r k i s a f f e c t e d b y a ll t h ef a c t o r s d e s c r i b e d - - h a b i t u a l , p o s t u r a l , p s y c h o l o g i c a l ,r e f lu x , a n d v i r a l - - t o p r o d u c e a h y p e r ir r i ta b l e " s p a s m -r e a d y " s t a t e .

F i g u r e 3 r e p r e s e n t s p a s s a g e f r o m t h e " s p a s m -r e a d y " t o I L S s y m p t o m m a n i f e s t s t a t e . M u s c u l a rt o n e m o d u l a t o r s m a y b e p r e s e n t t h a t m a k e t h e s p a s m

I L S - P a t h w a y s t o C N S P l as t i c C h a n g e

/ . , o n . . \

F I G , 2 . C r e a t i o n o f a " s p a s m - r e a d y " s t a t e i n t h e C N S l a r y n g e a l c o n t r o l n e t w o r k . T h e o v a l r e-g i o n r e p re s e n ts C N S n e u r o n s t h a t m a y b e c o m e h y p e r r ea c f iv e i n r e s p o n s e t o a n u m b e r o fp r o c e s s e s .

Jo u rn a l o f Vo i ce, V o l . 1 3 , N o . 3 , 1 9 9 9


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454 M URRA Y MORR ISO N ET AL

IL S

t r i g g e r e d ~

@ - - 4 - - -[ M U S C L E P A S M ]i 1 !I D y s p h o n i a [ L a r y n ~ s p a s m I 1 G l o b u s & C o u g h I

FIG. 3. The oval area represents the CNS laryngeal control networks in a hy-pertonic but non-triggered state. Other factors, such as general anxiety or poorposture, may increase laryngeal muscle tone globally, and are termed tonemodulators. An irritant such as an airborne chemical or refluxate may triggerthe muscle spasm.

mo re e a s i ly t r i gge re d by a s e ns o ry i r r i ta n t . The s et o n e m o d u l a t o r s m a y i n c l u d e g e n e r a l p s y c h o l o g i c a ls t r a in o r po s tu ra l f a c to r s . The t r igge r i s u s ua l ly a s e n -s o ry i r r i t an t s uc h a s a c id r e f luxa te , a i rbo rn e pa r t i c le s ,o r odo rs .

S U M M A R Y A N D C O N C L U S IO N SW e be l i e ve tha t a n " i rr i t a b l e la rynx s y nd ro me " e x -

i s t s i n w h ic h hype rk ine t i c l a rynge a l dys func t ion , a sma n i fe s t by l a ryngos pa s m , dys phon ia , g lobus , a nd /o rc h ron ic c ough , i s t r i gge re d by a s e ns o ry s t imu lus . W eb e l i e v e t h a t I L S o c c u r s w h e n b r a i n s t e m l a r y n g e a lc on t ro l l i ng ne u rona l ne tw orks a re he ld in a pe rpe tu -a l hype re xc i t a b le s t a t e a nd the re fo re r e a c t i na pp ro -p r i a t e ly to s e ns o ry s t imu la t ion . W e th ink tha t t he s ec ha nge s re s u l t f rom a n a s s o r t e d c o l l e c t ion o f c a us e sinc lud ing ha b i tua l mus c le mis us e , e mo t iona l d i s -t ress , v i ra l i l lness , and chronic re f lux s t imula t ion .

R E F E R E N C E S1. Morrison MD, Rammage LA, Belisle G, Nichol H, Pullan B.

Muscular tension dysphonia. J Otolaryngol. 1983;12:302-306.

2. Morrison MD, Nichol H, Rammage LA. Diagnostic criteriain functional dysphonia. Laryngoscope. 1986;96:1-8.

3. Morrison MD, Rammage LA. Muscle misuse voice disor-ders: description and classification. Acta Otolaryngol.1993;113:428-434.

4. Morrison MD. Pattern recognition in muscle misuse voicedisorders: how I do it. J Voice. 1997;11:108-114.5. Morrison MD. A pathophysiological model for dysphonia.

In: XVI World Congress of Otorhinolaryngology Head andNeck Surgery. Bologna, Italy: Monduzzi Editore; 1997:1649-1655.

6. Rammage LA, Peppard RC, Bless DM. Aerodynamic,laryngoscopic and perceptual-acoustic characteristics ofdysphonic females with posterior glottal chink: a retrospec-tive study. J Voice. 1991;6:64-78.

7. Milenkovic R Rammage LA, Bless D. Acoustic and percep-tual characterization of vocal nodules. In: Proceedings o f theInternational Vocal Fold Conference, 1989, Stockholm,Sweden.

8. Fritz GK, Fritsch S, Hagino O. Somatoform disorders inchildren and adolescents: a review of the past 10 years. JA mAcad Child Adolesc Psychiatry. 1997;36:1329-1338.

9. American Psychiatric Association. Diagnostic and Statisti-cal Manual o f Mental Disorders. 4th ed. Washington, DC:Author.

10. Lakin RC, Metzger WJ, Haughey BH. Upper airway ob-strnction presenting as exercise-induced asthma. Chest. 1984;86:499-501.



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The Irritable Larynx Syndrome