OTOLOGY SEMINAR
Enlarged Vestibular Aqueduct Syndrome (EVA syndrome)
R3 陳泓里
2003/2/19
1. Definition:
early-onset, progressed or fluctuated sensorineural hearing loss
detection of enlarged vestibular aqueduct by temporal bone image
“Large endolymphatic duct and sac syndrome”
2. Anatomy and Physiology:
Vestibular aqueduct(VA):
a bony canal from medial wall of vestibule to the outer opening in the
posterior aspect of petrous pyramid
Endolymphatic duct(ED) :
proximally from union of saccular and utricular ducts
course parallels the common crus of SSC, PSC in VA
Endolymphatic sac(ES):
partially within the bony niche of posterior surface of petrous bone, partially
within the posterior fossa dura layers
tall epithelium with rugosity → regulating the volume, pressure and ionic
composition of endolymph
3. Embryology:
VA derives from a medial diverticulum of otocyst during 5th week of gestation.
Inner ear structures attained its adult proportion in the midterm while
VA has a straight course parallel the commom crus of PSC and SSC.
VA became elongated while ED and ES are pulled downward as growth
of posterior cranial vault in late prenatal and postnatal life
VA acquires its normal adult shape as “ inverted J”.
Short limb ( isthmus): 3~5 mm, parallels the commom crus
Long limb: 3.5~11mm, normal 0.4~1.0 mm in width
4. Diagnostic criteria in image:
Polytomography by lateral projection:Valvassori and Clemis(1968)
Temporal bone high resolution CT (Swartz 1985) or MRI in axial view:
A-P diameter >1.5 mm by midpoint of postisthmic segment
Half way between common crus and external aperture
4. History review:
1791~ Carlo Mondini: autopsy of a boy born to be deaf
Enlarged VA is frequent in “Mondini Dysplasia”
1960~ Study of VA by polytomography in Meniere’s disease.
1978
1985
Valvassori and Clemis(1968), Schuknecht(1972)
Valvassori and Clemis ( laryngoscope)
Large vestibular aqueduct associated with SNHL
50/3700 patients (1.5%) by polytomography
Female, bilateral predominance, most with other inner anomaly:
enlarged vestibule or SCCs, hypoplastic cochlea…..
→ Arrest of inner development in embryo,
Emmett
47/ 5368 ears, audiometric and vestibular function evaluation
→ a distinct clinical entity, possibly a variant of Mondini deformity
HRCT consistent with tomography
5. Epidemiology
Most common inner ear anomaly demonstrated in modern image
Incidence: Valvassori and Clemis(1978) :1.5% , Emmett(1985) :1 %
Levenson(1989): 0.64%
Would be rarer in general population
Female predominance (56%), Bilateral predominance(72~81%)
60%~88% associated with other inner anomaly: enlarged vestibule or
SCC(50~63%), hypoplastic cochlea(16~28%).
6. Pathophysiology of SNHL in EVA syndrome:
Valvassori and Clemis (1978): arrest of inner development in embryo?
Gussen(1985): pressure with the dilated ED & ES and erosion of VA
Levenson(1989): hyperosmotic and hyperproteineous sac contents refluxed into
cochlea
Okamoto(1998):higher intensity of ES and ED by CT and spin-echo MRI than
CSF → protein rich, hyperosmolar endolymph in sac
Belenky(1993): round window anomaly in EVA → perilymphatic fistula
7. Clinical presentation:
Progressive and early-onset SNHL, Fluctuated SNHL
Preceding insult (minor head trauma, airplane flight)
Delayed speech
Nonspecific and mild aural and vestibular symptoms
7.Genetics, inheritance and association with Pendred syndrome
Pedigree analysis: Tong(1997) 39% family occurrence (13/33)
Heterogeneity in inheritance: AR, incomplete AD, multifactorial ?
Molecular genetics of hereditary hearing loss
EVA in syndromic hearing loss ( Pendred , Branchiootorenal syndrome)
Pendred syndrome: most common syndromic hereditary hearing loss
10% of hereditary hearing loss
PDS gene (7q31) with AR inheritance
goiter, iodine organization defect, hypothyroidism,SNHL
EVA, cochlear or vestibular dysplasia
Cremers(1998) Phelps(1998): 100% PDS with EVA by imaging
Abe(1999):localize gene responsible for EVA to 7q31( PDS)
different mutations with different phenotype
→ syndromic Pendred syndrome and nonsyndromic EVA
Everett(1997),Coyle(1998),Van Hauwe(1998),Usami(1999):
Identification of >30 mutation points: missence, frameshift
Reardon(2000):
41/57(72%) of EVA diagnosed as Pendred syndrome
EVA is the most likely presentation of Pendred’s syndrome
Pendrin: 5kb sulfate transporters, expressed in thyroid tissue
↓Sulphation of thyroglobulin, ↓ iodine organization
The role of Pendrin in cochlear development ?
Hypothyroidism impair inner ear development in embryo?
Direct effect of Pendrin in cochlear development
8. Evaluation and diagnosis:
History taking: FH, preceding insult, prenatal insult
Physical examination
Audiometry:
Pure tone: moderate to profound, downward sloping SNHL
Speech audiometry: SRT, Discrimination score
Vestibular function evaluation: peripheral vestibulopathy
Image study:
Polytomography: poor resolution and high radiation exposure
Temporal bone HRCT: VA and other inner ear bony structures
High-resolution MR: membranous labyrinth, including ED and ES
* For Pendred syndrome:
Perchlorate dischage test: 10~80% discharge
Thyroid function test: subclinical hypothyroidism
Mutation analysis of PDS gene
Management recommendation:
Early detection:
congenital or early-onset sensorineural deafness  imaging study
No medical or surgical therapy recommended in progressive SNHL
Family and patient’s education and warning to prevent head trauma
Auditory rehabilitation with hearing aid fitting: as early as possible
Experience in surgical intervention:
Endolymphatic sac occlusion:
block the reflux and pressure gradients detrimental to the inner ear
Intraluminal: Wilson(1997)  hearing stablization in 6/7 ears
Intraluminal & extraluminal: Welling(1999):
significant postoperative loss of hearing and not recommended
Endolymphatic subarachnoid shunt
Emmett(1985): no improvement in 4 patients
Jacker and De la Cruz(1989): 4/7 with postoperative hearing drop
Cochlear implant : Bent (1999):
10 patients of EVA undergo CI, 7/8 gained good speech recognization.
Postlingual hearing loss is good candidates for CI.
Cochleotomy gusher does not prevent successful implantation.
Reference
1.
Valvassori G, Clemis J: The large vestibular aqueduct syndrome. Laryngoscope 1978,
88:723-748.
2.
Cremers W, Bolder C, Admiraal R, et al.: Progressive sensorineural hearing loss and a
widened vestibular aqueduct in pendred syndrome. Arch Otolaryngol Head Neck Surg 1998,
124:501-505
3.
Emmett J: The large vestibular aqueduct syndrome. Am J Otol 1985, 6:387-403.
4.
Arcand P, Desrosiers M, Dube J, et al.: The large vestibular aqueduct syndrome and
sensorineural hearing loss in the pediatric population. J Otolaryngol 1991, 20:247-250.
5.
Belenky W, Madgy D, Leider J, et al.: The enlarged vestibular aqueduct syndrome. Ear
Nose Throat J 1993, 72:746-751.
6.
Jackler R, De La Cruz A: The large vestibular aqueduct syndrome. Laryngoscope 1989,
99:1238-1243.
7.
Levenson M, Prasier S, Jacobs M, et al.: The large vestibular aqueduct syndrome in children.
Arch Otolaryngol Head Neck Surg 1989, 115:54-58.
8.
Zalzal G, Tomaski S, Vezina L, et al.: Enlarged vestibular aqueduct and sensorineural hearing
loss in childhood. Arch Otolaryngol Head Neck Surg 1995, 121:23-28.
9.
Okamoto K, Ito J, Furusawa T, et al.: MRI of enlarged endolymphatic sacs in the large
vestibular aqueduct syndrome. Neuroradiology 1998, 40:167-172.
10. Gussen R: The endolymphatic sac in Mondini disorder. Arch Otorhinolaryngol 1985,
242:71-76.
11. Tong K, Harnsberger H, Dahlen R, et al.: Large vestibular aqueduct syndrome: a genetic
disease? AJR Am J Roentgenol 1997, 168:1097-1101.
12. Everett L, Glaser B, Beck J, et al.: Pendred syndrome is caused by mutations in a putative
sulphate transporter gene (PDS). Nat Genet 1997, 17:411-422.
13. Cremers C, Admiraal R, Huygen P, et al.: Progressive hearing loss, hypoplasia of the cochlea
and widened vestibular aqueducts are very common features in pendred's syndrome. Int J
Pediatr Otorhinolaryngol 1998, 45:113-123.
14. Phelps P, Coffey R, Trembath R, et al.: Radiological malformations of the ear in pendred
syndrome. Clin Radiol 1998, 53:268-273.
15. Abe S, Usami S, Hoover D, et al.: Fluctuating sensorineural hearing loss associated with
enlarged vestibular aqueduct maps to 7q31, the region containing the pendred gene. Am J
Med Genet 1999, 82:322-328.
16. Usami S, Abe S, Weston M, et al.: Non-syndromic hearing loss associated with enlarged
vestibular aqueduct is caused by PDS mutations. Hum Genet 1999, 104:188-192. This paper
discusses the specific mutations found within the PDS gene responsible for EVA.
17. Reardon W, O'Mahoney C, Trembath R, et al.: Enlarged vestibular aqueduct: a radiologic
marker of pendred syndrome, and mutation of the PDS gene. Q J Med 2000, 93:99-104. This
paper discusses the critical role of PDS mutation in the generation of EVA and suggests a
new definition for Pendred syndrome.
18. Hirsch B, Weissman J, Curtin H, et al.: Magnetic resonace imaging of the large vestibular
aqueduct. Arch Otolaryngol Head Neck Surg 1992, 118:1124-1127.
19. Wilson D, Hodgson R, Talbot J: Endolymphatic sac obliteration for the large vestibular
aqueduct syndrome. Am J Otol 1997, 87:101-106.
20. Welling D, Martyn M, Miles B, et al.: Endolymphatic sac occlusion for the enlarged
vestibular aqueduct syndrome. Am J Otol 1998, 19:145-151.
21. Welling D, Slater P, Martyn M, et al.: Sensorineural hearing loss after occlusion of the
enlarged vestibular aqueduct. Am J Otol 1999, 20:338-343.
22. Bent J, Chute P, Parisier S: Cochlear implantation in children with the enlarged vestibular
aqueduct syndrome. Laryngoscope 1999, 109:1019-1022.
23. Lasak J, Welling D: The enlarged vestibular aqueduct syndrome. Current Opinion in
Otolaryngol Head Neck Surg 2000,8:380-383