SUDDEN SENSORINEURAL HEARING LOSS
A case rep o rt su p p o rt in g t h e im m u n o lo g ic t h eo ry
Ant onio Luiz dos Sant os Werneck
1, Luiz Carlos do Amaral Gurgel
2,
Laurinda M oura de M ello
3, Gabriella Queiroz de Albuquerque
4ABSTRACT - Sud d en sensorineural hearing loss (SSNHL) is one of the autoim m une d iseases of the inner ear (AIED), w hich is characterized b y a hearing loss of ab ove 30 d ecib els in at least three contig uous aud iom etric freq uencies over a tim e course of 72 hours or shorter. Its cause can b e found in only 10% to 15% of p atients. Histop atholog ic find ing s have rep orted retrog rad e neuronal d eg eneration and atrop hy of Corti’s org an and of the vascular stria. This p ap er d escrib es a case of a m id d le-ag ed fem ale p atient und erg oing a treatm ent for hyp erthyroid ism w ho d evelop ed b ilateral SSNHL. The p atient w as treated w ith m ethylp red nilisone (1m g /kg / d ay) for three d ays w ith consid erab le hearing im p rovem ent. This treatm ent w as follow ed b y lung and kid ney tub erculosis. The im m une m echanism of this entity and the p ossib ility of interconnected p articip ation of the antig en typ e, of an autoim m une d isease and of b acterial infection are d iscussed .
KEY WORDS: sudden sensorineural hearing loss, autoim m une disease, autoim m une thyroid disease, tuberculosis.
Surdez neurosensorial súbita: relato de um caso clínico corroborando a teoria auto-imune
RESUMO - A su rd ez n eu ro sen so ria l a g u d a (SNSA) é u m a d a s d o en ça s a u t o -im u n es d o o u vid o in t ern o caracterizad a p ela p erd a d a aud ição acim a d e 30 d ecib éis, em p elo m enos 3 freq üências aud iom étricas contíg uas, no p eríod o m áxim o d e 3 d ias. Sua causa só é d efinid a em 10 a 15% d os p acientes. Achad os histopatológicos dem onstram degeneração neuronal retrógrada e atrofia do órgão de Corti e da estria vascular. Relatam os o caso d e um a p aciente d e m éd ia id ad e em tratam ento d e hip ertireoid ism o q ue ap resentou SNSA b ilateral. A p aciente foi tratad a com m etil-p red nisilona (1m g /kg /d ia) d urante três d ias evoluind o p ara um a m elhora consid erável d a aud ição. Este tratam ento foi seg uid o d e tub erculose p ulm onar e renal. Discute-se o m ecanism o im unológ ico d esta entid ad e, e a p ossib ilid ad e d e p articip ação cruzad a d o tip o antíg eno, d oença autoim une e infecção b acteriana.
PALAVRAS-CHAVE: surdez neurosensorial aguda, doença auto-imune, doença auto-imune da tireóide, tuberculose.
Serviço d e Clín ica Méd ica d o Ho sp it al Cen t ral d o In st it u t o d e Assist ên cia ao s Servid o res d o Est ad o d o Rio d e Jan eiro (IASERJ; Rio d e Jan eiro RJ, Brasil; 1Ch efe d o Serviço d e Neu ro lo g ia; 2Ch efe d o Serviço d e Clín ica Méd ica; 3Méd ica d o Serviço d e Clín ica Méd ica; 4Méd ica
Resid en t e d o Serviço d e Clín ica Méd ica.
Received 28 Ap ril 2003, received in fin al fo rm 16 Ju ly 2003. Accep t ed 20 Au g u st 2003.
Dr. Ant onio Luiz dos Sant os Werneck - Rua João de Barros 137/601 - 22441-100 Rio de Janeiro RJ - Brasil.
In 1923, Du ke1 su g g est ed fo r t h e first t im e t h at
su d d en d eafn ess co u ld b e relat ed t o so m e allerg ic p h en o m en o n . In 1979, McCab e2 list ed a g ro u p o f
d iseases w h ich h e d en o m in at ed au t o im m u n e in n er ea r d isea ses (AIED). Am o n g t h ese w ere in clu d ed su d d en sen so rin eu ral h earin g lo ss (SSNHL), su d d en d ea fn ess a n d Mén ière’s d isea se. Sa t isfa ct o ry resp o n se o f SSNHL t o co rt ico st ero id s resp erm it t ed it s in -clusion in this group . The cochlear channel is situated in t h e m em b ran o u s lab yrin t h o f t h e in n er ear. Th e a u d it o ry sp ira l o rg a n is lo ca t e d in t h e co ch le a r ch an n el an d it is fo rm ed b y ciliat ed n eu ro ep it h elial cells an d d iverse variet ies o f su p p o rt in g cells. Th e p en et rat io n o f t h e so u n d in t o t h e in n er ear reach es
Co rt i’s o rg a n via t h e en d o lym p h o f t h e co ch lea r channel up to the hair cells. This stim ulus is conveyed b y n erve fib ers sit u at ed at t h e b ase o f t h e h air cells u p t o t h e sp iral g an g lio n n eu ro n s, w h ere t h ere are ab out 30,000 afferent neurons. AIED is characterized by retrograde neuronal degeneration, endolym phatic edem a, proliferation of fibrous tissue, com pression of perilym phatic spaces, in addition to the atrophy of Corti’s organ and of the vascular stria3. These findings
suggest the existence of a sim ultaneous inflam m atory and ischem ic vascular process in the inner ear.
w it h in a p erio d ran g in g fro m t h ree h o u rs t o t h ree d ays4. Th e est im at ed yearly in cid en ce o f SSNHL is 5
to 20 cases 100,000 p ersons5. Its cause b eing know n
in o n ly 10-15% o f t h e cases6. Tab le 1 list s t h e m ajo r
nervous system and cochlear causes of SSNHL. Young fem ale ad u lt s are p referab ly affect ed , an d t h e d iag -n o sis is b ased o -n cli-n ical crit eria a-n d o -n g o o d res-p o n se t o co rt ico st ero id s. Nu m ero u s at t em res-p t s h ave b een m ad e t o d evelo p assays t o d et ect seru m m ar-kers t h at m ay h elp t o co n firm t h e d iag n o sis, w h ich include: erytrocyte sedim entation rate, eletrophoresis o f im m u n o g lo b u lin s, co m p lem en t s (C3, C4, CH50, C1q ), anticollagen antib od ies, rheum atoid factor, im -m u n o p h e n o t yp e o f ly-m p h o cyt e s (CD4 + , CD8 + , CD4+ /CD8+ ), West ern -Blo t fo r p ro t ein -70 sen sit ive to heat shock, antiviral antib od ies and PCR, b acterial t est s an d t est s fo r fu n g i.
A ca se o f SSNHL is d e scrib e d w it h p a rt icu la r a sp e ct s n o t ye t re fe rre d in t h e lit e ra t u re , w h ich su p p o rt s t h e im m u n o lo g ic t h eo ry.
CASE
A w o m an , b o rn in Au st in /RJ, Brazil, 52 years o ld w as h o sp it alized o n Au g u st 8t h 2002, p resen t in g w eig h t lo ss
(14 kg in t h ree m o n t h s), an o rexia, ast h en ia an d severe an em ia (h em at o crit : 19%). Th e p at ien t h ad u n d erw en t a t reat m en t fo r h yp ert h yro id ism fo r at least fo u r years, w it h t h e u se o f 200m g /d ay o f p ro p ylt h io u racil fo r ab o u t eig h t m o n t h s. Aft er eig h t d ays o f h o sp it alizat io n , t h e p at ien t p resen t ed co u g h in g w it h m u co id exp ect o rat io n , d ysp n ea an d co n st an t fever d u rin g t h ree d ays (averag e 39-40 d e-g rees). In t h is p h a se w e h a ve o p t ed fo r a n in crea se in t h e
d o sag e o f p ro p ylt h io u racil t o 600m g /d ay, as t h ere w ere h ig h ra t e s o f T3 (2 . 8 5 n g /m l), T4 (1 7 . 4 8 n g /d l) a n d TSH< 0.01 n IU/m l. Scin t ig rap h y o f t h e t h yro id sh o w ed a m o d era t e in crea se o f t h e vo lu m e o f t h e g la n d , esp ecia lly in t h e rig h t lo b e, w it h d iffu se a n d h et ero g en eo u s eco t ex-ture. Physical exam ination show ed : thinness, p aleness and d ehyd rated p atient; b ilateral and sym m etrical exop htalm ia with lid lag; increased thyroid volum e with irregular surface an d h ard en ed co n sist en ce. Search fo r acid -fast , an t i-HTL VI/II-Elisa a n d in d ica t o rs fo r h e p a t it is B a n d C w e re neg ative. Protein electrop horesis w ithout anom alous frac-t io n s; n o n -reag en frac-t ANF; co m p lem en frac-t CH50, C3 an d C4, n o rm al; n eg at ive LE cells; ferrit in : 20n g /m l, t o t al t ran s-ferrin: 200m g /m l; iron linkag e cap acity: 250.3; reticulocyte co u n t 1IU/m l; CEA: 3n g /m l; an t ig en s Ca 19-9: 13 IU/m l an d CA 125:11IU/m l.
Aro u n d eleven d ays aft er h o sp it alizat io n , t h e p at ien t p resen t ed su d d en , b ila t era l h ea rin g lo ss. Th e resu lt s o f o t o rh in o laryn g o lo g ical exam s w ere n o rm al, w it h t h e ex-cep t io n o f d eafn ess. Au d io m et ry (Fig 1) sh o w ed sen so ri-neural hearing loss from intense to severe, with an ab sence o f resp o n se in 8 KHz in b o t h ears. In t h e left ear, aerial co n veyan ce w as o f 61.6 d B, an d o f 63.3 d B in t h e rig h t ear. Bo n e co n veyan ce w as at 51.6 in t h e left ear, w h ile in t h e rig h t ear it w as o f 56.6 d B. S.R.T. w as o f 60 d B in t h e left ear an d o f 70 d B in t h e rig h t ear. Th ere w as a d iscrim i-n at io i-n o f 28% w it h 100d B ii-n t h e left year, co m p ared w it h 36% an d 100 d B in t h e rig h t ear. Tym p an o m et ry d em o n s-t ras-t ed a cu rve o f s-t h e “A” b ilas-t eral s-t yp e, w is-t h an a b sen ce o f t h e co n t ralat eral st ap ed ial reflex in b o t h ears. Th ere w as n o resp o n se t o t h e in t erru p t io n o f p ro p ylt h io u racil fo r six d ays. Met h ylp red n ilo so n e w as t h en ad m in ist ered at 1m g / kg /d ay t o t h e p at ien t fo r t h ree d ays, fo llo w ed b y 60 m g /
Table 1. Causes of sudden sensorineural hearing loss.
Nervous system causes
1 Perip h eral: m en in g it is, sarco id o sis, Gu illain -Barré, Vo g t -Ko yan ag i-Harad a, aco u st ic n eu rin o m a, m et ast asis in t h e cereb ello -p o n t ile an g le, au t o im m u n e n eu ro p at h y, p aran eo p last ic n eu ro p at h y.
2 Cen t ral: m u lt ip le sclero sis, cereb ro vascu lar d iso rd ers, en cep h alit is.
3 Cen t ral an d /o r p erip h eral: m ig rain e
Cochlear causes
1 In fect io n s: viru s, mycoplasma pneumoniae, syp h ilis, Lym e d isease.
2 Au t o im m u n e d iseases: Co g an ’s syn d ro m e, relap sin g p o lych o n d rit is, co llag en d iseases, Beh cet ’s d isease, u veit is, u lcerat ive co lit is, g lo m eru lo n ep h rit is, m yast h en ia g ravis, AIDS.
3 Trau m at ic: b rain t rau m a, m id d le ear d eco m p ressio n d isease, o t o lo g ic su rg ery, lym p h at ic fist u la, Mén ière’s d isease.
4 Met ab o lic: ren al in su fficien cy, d iab et es m ellit u s, h yp o an d h yp ert h yro id ism .
5 Vascu lar: cereb ro vascu lar d isease, leu kem ia, m yelo m a, eryt h ro p at h ies.
d ay fo r 6 d ays an d 30 m g /d ay fo r eig h t d ays. Ten d ays a ft er t h e in t ro d u ct io n o f t h is sch em e t h ere w a s co m p let e su b ject ive reg ressio n o f d ea fn ess.
Approxim ately 20 days later the patient presented fever a n d d ry co u g h . Th o ra cic X-ra y sh o w ed d iffu se fo cu ses in b o t h lu n g s, in d icat ive o f m iliary t u b ercu lo sis. Blo o d t est sh o w ed : crea t in in e - 1.9 m g /d l a n d u rea - 121 m g /d l. Therap eutic evid ence confirm ed the d iag nosis of lung and kid n ey t u b ercu lo sis.
DISCUSSION
Mag u ch i et al.7 h ave rep o rt ed o n e case o f h yp
ert h yro id ism asso ciaert ed ert o SSNHL in a 36year o ld w o -m an treated w ith p rop ylthiouracil, w here a d ecrease o f t h e co m p lem en t level, o f t h e h ig h levels o f M im m unog lob ulin and of the antineutrop hil cytop las-m ic an t ib o d y (ANCA) react ive t o las-m yelo p ero xid ase (MPOANCA) co u ld b e d em o n st rat ed . Th ere w as an am elioration of deafness after the withdrawal of pro-pylthiouracil. Until then, no case of SSNHL associated w it h MPOANCA h ad b een rep o rt ed , w h ich led t h e authors to sug g est that m icrovascular d isease m ig ht b e relat ed t o SSNHL p at h o p h ysio lo g y. Fo n g et al.8
rep o rt ed p o lyart h rit is, leu ko cyt o sis, h ep at o t o xicit y, n o rm o cyt ic n o rm o ch ro m ic an em ia, h ig h fever, cu t a-neous vasculitis and SSNHL in one p atient using p ro-p ylt h io u racil, evo lvin g t o co m ro-p let e rem issio n aft er it s w it h d raw al.
In t h e assessm en t o f t h e case d escrib ed , w e h ave in it ially t h o u g h t o f o t o t o xic seco n d ary effect relat ed to the use of p rop ylthiouracil, since there are rep orts o f ad verse react io n s in 1 t o 5% o f t h e p at ien t s w h o h ave u sed t h is su b st an ce. Ho w ever, t h ere w as n o resp o n se t o t h e in t erru p t io n o f m ed icat io n , t h e p
a-t ien a-t b ein g asym p a-t o m aa-t ic o n ly afa-t er u sin g m ea-t h yl-p red nilosone (1g /d ay) for three d ays. We b elieve this t reat m en t facilit at ed t h e o ccu rren ce o f m iliary t u -b ercu lo sis.
Several st u d ies asso ciat e viral in fect io n , vascu lit is an d im m u n o lo g ical fact o rs t o m o d els o f exp erim en -t al lab iryn -t h i-t is in SSNHL9,10. Th e p resen ce o f in
fec-t io n s b y h erp esviru s is afec-t fec-t rib u fec-t ed fec-t o ab o u fec-t 70% o f the cases11. In such cases, the infection by virus would
provoke som e type of vascular functional disturbance w h ich w o u ld b e fo llo w ed b y a relevan t im m u n o lo -g ical resp o n se in sid e t h e in n er ear. Th e co n seq u en ce w o u ld b e t h e p ro d u ct io n o f b o n e-fib er m at rix, resp o n sib le fo r irreversib le co ch lear lesio n an d ret ro -grad e neuronal d egeneration. These alterations have been described in diverse autoim m une diseases, such as m yast h en ia g ravis, syst em ic lu p u s erit h em at o su s (SLE), Guillain-Barré, Vog t-Koyanag i-Harad a, Graves’ d ise a se , We g e n e r’s g ra n u lo m a t o sis a n d Co g a n ’s syn d ro m e9,12-14. It seem s p o ssib le t h at h yp ert h yro
i-d ism m ay have som e p articip ation in the im m unop a-t h o g en y o f SSNHL. Ia-t is kn o w n a-t h aa-t p o lym o rp h ism is one of the characteristics of the HLA m olecules, being som e of its p ep tid es d ep end ent on ind ivid ual alleles. Autoim m une d iseases such as hyp erthyroid ism , m ya-stenia gravis, and LSE suffer the influence of inherited alleles cap ab le o f p layin g a p art in t h e fo rm at io n o f som e type of self-antigen. It is also possible to ascribe so m e vascu lar p art icip at io n t o t h e p h ysio p at h o lo g y o f SSNHL. So m e case rep o rt s asso ciat ed m ig rain e with fluctuating lowfreq uency hearing loss and sud -den, unilateral hearing loss15. Studies carried out with
p at ien t s w it h au t o im m u n e d iseases o f t h e SLE an d p eriarteritis nod osa (PAN) typ es have show n the p re-sence of cochlear fibrosis and ossification of the inner ear, fin d in g s w h ich are ch aract erist ic o f vascu lar d i-sease16. At ro p h y o f Co rt i’s o rg an an d o f t h e vascu lar
st ria, o ssificat io n o f t h e in n er ear, d eg en erat io n o f t h e vascu lar elast ic m em b ran e w it h o r w it h o u t as-sociated vasculitis and , still, retrog rad e neuronal d e-g e n e ra t io n h a ve a lso b e e n re p o rt e d1 6 ,1 7. Th e se
fin d in g s su g g est t h e exist en ce o f a sim u lt an eit y b et w een t h e in flam m at o ry p ro cess an d t h e isch em ic in -vo lvem en t in t h e SSNHL.
Th e p resen ce o f an t ien d o t h elial an t ib o d ies in p a-t ien a-t s w ia-t h SSNHL in d icaa-t es a-t h e p ara-t icip aa-t io n o f se-ro lo g ic m arkers o f vascu lit is, alt h o u g h so m e st u d ies w it h an t in u clear an t ib o d ies, rh eu m at o id fact o r, an -t im t o ch o n d rial an -t ib o d ies, sm o o -t h an -t fib er, an -t i-sarco lem m a, an t ilam in in e an d an t ico llag en II h ave b een co n t ro versial. Besid es t h at , SSNHL m ay b e t h e in it ia l m a n ifest a t io n o f Sjö g ren ’s syn d ro m e, SLE,
We g e n e r’s g ra n u lo m a t o sis, PAN a n d Co g a n ’s synd rom e18,19.
The existence of autoantib od ies ag ainst inner ear an t ig en s im p lies an au t o im m u n e p at h o g en esis o f SSNHL. Analysis throug h im m unolog ical assay of the West ern -Blo t t yp e d em o n st rat ed t h e p resen ce o f a self-an t ib o d y an t i-68Kd in t h e p at ien t s’ seru m w it h SSNHL20. Th e exist en ce o f a co n n ect io n b et w een t h e
an t ig en 68 kilo d alt o n w it h p ro t ein -70 sen sit ive t o heat shock (HSP-70) has already been observed20. This
p ro t ein t h at act s in cellu lar p ro t ect io n is p resen t in t h e b lo o d vessel, in Co rt i’s o rg an an d in t h e b rain . Boulassel et al.21 carried out a study on self-antibodies
ag ain st p ro t ein s o f t h e in n er ear in an im al m o d els w h ich h ave b een fo u n d in p at ien t s w it h AIED. It h as b een d em o n st rat ed t h at p ro t ein s o f 30, 42 an d 68 kilo d alt o n are p art o f t h e p erip h ery o f t h e m ain p ro -t ein o f PO m yelin , an d o f -t h e b e-t a-ac-t in ic p ro -t ein . PO p rotein ap p ears exclusively in the Schw ann’s cells o f t h e p erip h eral n ervo u s syst em , in t h e sp iral g an g lio n an d in Co rt i’s o rg an , w h ereas b et aact in ic p ro -tein m ay b e o b served in th e m ech an ic-sen so rial cells o f t h e ciliary su p p o rt . Bet a-act in ic p ro t ein h as b een o b served w it h it s m o d ified co m p o sit io n in p at ien t s w it h d eafn ess an d p erip h eral vest ib u lar syn d ro m e. Su ch d e-st ru ct u rin g m ay resu lt in d isin t eg rat io n o f structural cells of the inner ear w hich are resp onsib le fo r t h e t ran sfo rm at io n o f m ech an ic in t o elect ro ch e-m ical st ie-m u li. Th u s, o n e can also b elieve t h at an t i-b o d ies ag ain st i-b et a-act in ic p ro t ein m ay lead t o ves-tib ular-aud itory d isturb ances. Otherwise, anti-PO an-tib od ies have b een rep orted in p atients affected with Gu illain -Barré 22. Hyp o acu sis sym p t o m h as b een
re-p orted in these re-p atients although no antib od ies aga-in st PO an d b et a-act aga-in ic p ro t eaga-in s h ave b een fo u n d .
It is im p o rt an t t o p o in t o u t t h e p art icip at io n o f corticosteroid s in em ergency therap eutics. Recep tors o f co rt ico st ero id s in co ch lear an d vest ib u lar t issu es o f an im al m o d els h ave b een id en tified23, w hich have
led t o t h e t reat m en t o f AIED w it h in t ra-t ym p an ic o r system ic corticosteroids. High levels of C3, C3bc, C4e, C1q h ave b een rep o rt ed in p at ien t s w it h SSNHL24,
w h ich m ay id en t ify p at ien t s t h at resp o n d t o an t i-in flam m at o ry d ru g s o f t h e co rt ico st ero id t yp e. Th e m ain act io n o f co rt ico st ero id s in SSNHL w o u ld b e t h e b lo ckag e in t h e p ro d u ct io n o f an t ib o d ies, o f in -t erleu kyn s (IL, IL-2, IL-3, IL-4&l-t; IL-5, IL-6, IL), o f TNF-Alfa an d o f g am m a-in t erfero n an d t h e red u ct io n o f t h e lym p h o p ro liferat ive p ro cess9. In sp it e o f im m u
-n o lo g ical i-n vest ig at io -n b ei-n g cap ab le o f accu rat ely id entifying p atients w ith SSNHL, cand id ates to corti-co t h erap y, t em p o ral clin ic crit eria an d au d io m et ry
are t h e m ain p at t ern s t o b e o b served in t h e im m e-d iat e t reat m en t o f t h is en t it y.
We h ave n o t fo u n d an y referen ce t o a p o ssib le association b etw een SSNHL and m iliary tub erculosis. It seem s p o ssib le t h at t h e o ccu rren ce o f an im m u -n o lo g ical resp o -n se i-n t h e e-n d o lym p h at ic saccu lu s p ro vo ked b y t h e p resen ce o f t h e Ko ch ’s b acillu s, so far clin ically lat en t , m ig h t h ave t rig g ered so m e t yp e o f au t o im m u n e resp o n se. Alt erat io n s h ave b een re-p o rt ed in T cell su b re-p o re-p u la t io n s in re-p a t ien t s w it h SSNHL associated to infection b y Mycop lasm a p neu-m o n iae o r viru s, w h en it w as o b served an in crease in t h e m em o ry T cells (CD4CD5RO) an d a d ecrease o f n aive T cells (CD4CD45RA)14. It is p o ssib le t h at a
b act erial ag en t m ig h t p ro vo ke su fficien t an t ig en ic st im u lu s t o t ran sfo rm n aive T cells in t o m em o ry T cells. The activation of the then latent m icroorganism would stim ulate the p resence of m em ory T-cells with the conseq uential autoim m une resp onse in the inner ear. Th e resu lt o f t h is im m u n o lo g ical in flam m at o ry response would be the degeneration of Corti’s organ, o f t h e b lo o d vessel an d t h e sp iral g an g lio n .
It is also kn o w n t h at t h e an t ib o d ies t h at react ag ain st an t ig en s o f in n er ear m ay ap p ear in in t er-co n n ect ed react io n w it h b act erial o r viral in fect io n s, o r in t h e even t o f t issu lar d est ru ct io n . Ext ract s t aken fro m t h e in n er ear o f an im al m o d els w it h p ro t ein s of various m olecular sizes (14 to 200 kilod alton) have react ed p o sit ively t o West ern -Blo t w h en co n fro n t ed w it h t h e seru m fro m p at ien t s w it h SSNHL 21.
In su m m ary, t h e im m u n e m ech an ism s t h at are o p erat ive in t h e g en esis o f SSNHL are n o t fu lly u n -d erstoo-d . The case rep orte-d sug g ests a link b etw een b act erial in fect io n , h yp ert h yro id ism an d au t o im m u n e react io n s t o t h e ab n o rm al exp ressio n o f au t o an -t ig en s o n in n er ear cells.
REFERENCES
1. Duke WW. Ménière’s syndrome caused by allergy. JAMA 1923;81:2179-2181. 2. McCabe BF. Autoimmune sensorineural hearing loss. Ann Otol Rhinol
Laryngol 1979;88:585-589.
3. Schuknecht H. Ear patho lo gy in auto immune d isease. A d v Oto Rhinolaryngol 1991;45:50-70.
4. Wilson WR, Byl FM, Laird N. The efficacy of steroids in the treatment of idiopathic sudden hearing loss. A double-blind clinical study. Arch Otorhinolaryngol 1980;106:772-776
5. Byl FMJr. Sudden hearing loss: eigth years’ experience and suggested prognosis table. Larynngoscope 1984:94:647-661.
6. Mattox DE, Lyles CA. Idiopathic sudden sensorineural hearing loss. Am J Otol 1999;20:587-595.
7. Maguchi S, Sato shi F, Chid a E, Terayama Y. Myelo pero xid ase-antineutrophil cytoplasmic antibody-associated sensorineural hearing loss. Auris Nasus Larynx 2001;28 (Suppl 1); S103-S106.
8. Fong PC, Pun KK, Tai YT, Yeung RT. Propylthiouracil hypersensivity with circumstantial evidence for drug-induced reversible sensorineural deafness. Horm Res 1991;35:132-136.
10. Oldstone MBA. Virus-induced autoimmunity: molecular mimicry as a route to autoimmune disease. J Autoimmune 1989;(Suppl 2):S187-S194. 11. Wilson WR. The relationship of the herpesvirus family to sudden hearing lo ss: a pro spective clinical stud y and literature review . Laryngoscope 1986;96:870-877.
12. A mmar-Kho dia A . A uto immune deafness and myasthenia. Rev Laryngol Otol Rhino (Bord). 1991;112:161-163.
13. Bicknell JM, Ho lland JV. Neuro lo gic manifestatio ns o f Co gan´s syndrome. Neurology 1978;28:278-280.
14. García Berrocal JR, Ramírez-Camacho R, Portero F, Vargas JA. Role of viral and M ycoplasma pneumoniae infectio n in id io pathic sud d en sensorineural hearing loss. Acta Otolaryngol (Stockh ) 2000;120:835-839. 15. Lee H, Whitman GT, Lim JG, et al. Hearing symptoms in migrainous
infarction. Arch Neurol 2003;60:113-116.
16. Yoon TH, Paparella MM, Schaschern PA. Systemic vasculitis: a tempo-ral bone histopathologic study. Laryngoscope 1989;99:600-609. 17. Yoon TH, Paparella MM, Schaschern PA, Alleva M. Histopathology of
sudden hearing loss. Laryngoscope 1990:1990;100:707-715.
18. Lunardi C, Bason C, Leandri M, et al. Autoantibodies to inner ear and endothelial antigens in Cogan´s syndrome. Lancet 2002;360:915-921. 19. Harris JP, Sharp PA. Inner ear autoantibodies in patients with rapidly
progressive sensorineural hearing loss. Laryngoscope 1990;100:516-524. 20. Billings PB, Keithley EM, Harris JP. Evidence linking the 68 kilodalton antigen identified in progressive sensorineural hearing loss patient sera with heat shock protein 70. Ann Otol Rhino Laryngol 1995;104:181-188.
21. Bo ulassel MR, Deggo uji N , To masi JP, Gersd o rff M. Inner ear autoantibodies and their targets in patients with autoimmune inner ear diseases. Arch Otolaryngol 2001;121:28-34.
22. Ben-Joulloun-Dellagi S, Dellagi K, Burger D, et al. Chidhood peripheral neuropathy w ith autoantibodies to myelin glycoprotein PO. A nn Neurol 1992;32:700-702.
23. Rarey KE, Curtis LM. Receptors for glucocorticoids in the human inner ear. Otolaryngol Head Neck Surg 1996;115:38-41.
