Download Enlarged vestibular aqueduct: Review of controversial aspects

The Laryngoscope
C 2011 The American Laryngological,
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Rhinological and Otological Society, Inc.
Contemporary Review
Enlarged Vestibular Aqueduct: Review of Controversial Aspects
Quinton Gopen, MD; Guangwei Zhou, MD, ScD; Kenneth Whittemore, MD; Margaret Kenna, MD, MPH
Objectives: To review the controversial aspects of the enlarged vestibular aqueduct syndrome.
Study Design: Contemporary review.
Methods: A literature search using the terms ‘‘enlarged vestibular aqueduct and large vestibular aqueduct’’ were used
to generate the articles for review in this article.
Results: The enlarged vestibular aqueduct is a condition causing variable auditory and vestibular dysfunction. Although
it has been 32 years since Valvasorri and Clemis recognized the clinical importance of the enlarged vestibular aqueduct, many
controversial aspects of the diagnosis remain. The topics reviewed in this discussion are as follows: size criteria for radiographic
diagnosis, precipitating factors for hearing loss, corticosteroid treatment and sac surgery, conductive component to hearing
loss, natural progression of hearing loss, correlations between aqueduct size and hearing loss, genetics, vestibular symptoms,
and theories regarding mechanisms behind the symptoms.
Conclusion: The enlarged vestibular aqueduct remains a controversial entity with variable presentation, progression,
and prognosis.
Key Words: Cranial base, otology, pediatric ears/otology, vestibular.
Level of Evidence: 2a.
Laryngoscope, 121:1971–1978, 2011
INTRODUCTION
The vestibular aqueduct is a temporal bone structure
that runs from the vestibule to the posterior cranial fossa.
It contains the endolymphatic duct, which terminates at
the endolymphatic sac within the bony operculum. Both
auditory and vestibular dysfunction have been associated
with enlargement of the vestibular aqueduct. The
enlarged vestibular aqueduct was first discovered by
Mondini in 1791, during a temporal bone dissection.1
Mondini described a specific cochlear malformation of
incomplete cochlear partition (hypoplastic modiolus),
short cochlear duct with flat cochlea, auditory and vestibular organs that were immature, a dilated vestibule,
semicircular canals that were wide, small, or missing,
an endolymphatic sac that was bulbous, and a large
vestibular aqueduct. Instead of its usual 2.5 turns, the
cochlea had 1.5 turns with an absent interscalar septum
From the Division of Head and Neck Surgery (Q.G.), U.C.L.A.
Medical Center, Los Angeles, California, U.S.A.; Department of
Otolaryngology and Communication Enhancement (G.Z., K.W., M.K.),
Children’s Hospital Boston, Harvard Medical School, Boston,
Masschausetts, U.S.A.
Editor’s Note: This Manuscript was accepted for publication May
10, 2011.
The authors have no financial disclosures for this article.
The authors have no conflicts of interest to disclose.
Send correspondence to Dr. Quinton Gopen, Division of Head and
Neck Surgery, U.C.L.A. Medical Center, 200 Medical Plaza, Suite 550,
Los Angeles, CA 90095. E-mail: [email protected]
DOI: 10.1002/lary.22083
Laryngoscope 121: September 2011
between the middle and apical turn. Embryologically, this
corresponds to arrest in development during the seventh
week of gestation.
Valvassori first reported Meniere’s like symptoms in
the presence of an enlarged vestibular aqueduct in
1969.2 Valvasori and Clemis3 are credited with recognizing the clinical relationship between enlarged vestibular
aqueducts and hearing loss in 1978 when they identified
enlargement of the vestibular aqueduct in 50 cases out
of 3,700 tomograms, or 1.4%. Of these 50 cases, most
had congenital hearing loss and many had vestibular
symptoms. The enlarged vestibular aqueducts in their
study measured from 1.5– 8.0 mm in diameter. They
considered a measurement greater than 1.5 mm in anterior–posterior diameter as abnormally enlarged. Sixty
percent had other structural anomalies, including an
enlarged vestibule (14), an enlarged vestibule and semicircular canals (7), an enlarged vestibule and
hypoplastic cochlea (4), and hypoplastic cochlea (4). In
addition, the authors suspected many others had abnormalities below the level of resolution of the tomograms.
In their series, the enlarged vestibular aqueducts were
2:1 bilateral to unilateral and 3:2 female to male. The
enlarged vestibular aqueduct remains the most common
inner ear anomaly found on radiographic evaluation of
children with hearing loss.4
The enlarged vestibular aqueduct syndrome is associated with Pendred’s syndrome and with mutations in
the SLC26A4 (PDS) gene. This gene encodes for pendrin,
Gopen et al.: Enlarged Vestibular Aqueduct: Controversies
1971
an important protein involved in the cellular transport
of chloride, iodine, and bicarbonate anions. Mutations in
SLC26A4 can cause Pendred’s syndrome as well as nonsyndromic recessive deafness (DFNB4). Enlarged
vestibular aqueducts have also been associated with distal renal tubular acidosis,5,6 Waardenburg’s syndrome,7
X-linked congenital mixed deafness,8,9 branchio-oto-renal
syndrome,10,11 otofaciocervical syndrome,12 and Noonan’s
syndrome.13,14
Since its initial discovery in 1791, many controversial aspects about the condition remain. This review
attempts to summarize our current understanding of
enlarged vestibular aqueduct syndrome as well as these
controversial aspects.
neural hearing loss and found a range of 0–1.8 mm at
the midpoint and a range of 0–3.4 mm at the operculum.
They found that 95% of vestibular aqueducts were less
than 0.9 mm at the midpoint and 1.9 mm at the operculum. They used these figures to support 0.9-mm
midpoint and 1.9-mm operculum diameters as the
threshold for the diagnosis of enlarged vestibular aqueduct. Again, however, this is an arbitrary supposition. In
fact, this study can be interpreted in exactly the opposite
way: specifically, that 5% of normal scans will have
vestibular aqueducts that are greater than the Cincinnati criteria and be classified incorrectly. This further
supports the notion of confirmatory functional testing
whenever possible.
METHODS
Precipitating Factors for Hearing Loss
For this review, a literature search using pubmed was conducted using the key words ‘‘large vestibular aqueduct’’ and
‘‘enlarged vestibular aqueduct.’’ The search was limited to publications in English. Additional articles were also obtained from
the references in any included studies.
DISCUSSION
Radiographic Size Criteria for Diagnosis
The initial size criterion for the diagnosis of an
enlarged vestibular aqueduct was put forth by Valvassori and Clemis3 in their landmark paper in 1978. In
this report, the bony vestibular aqueduct was considered
enlarged if it was greater than 1.5 mm at the midpoint
of its course from the vestibule to the posterior cranial
fossa. Jackler15 used the criteria for diagnosis of an
enlarged vestibular aqueduct if the diameter was greater
than 2 mm at its midpoint. Other investigators also
used 2 mm at the aqueduct’s midpoint, including Arcand
and Levenson.16,17 Okumura18 defined the aqueduct as
enlarged if it was greater than 4 mm at the operculum
or if the distance between the vestibule and traceable
part of the vestibular aqueduct nearest the vestibule was
short, specifically less than 1 mm. Wilson’s19 definition
compared the aqueduct to the posterior semicircular
canal, and considered it enlarged if the diameter of the
aqueduct at its midpoint was twice the diameter of the
posterior semicircular canal. Most recently, the Cincinnati group advocated the criteria for enlargement be
revised down to 0.9 mm at the midpoint or 1.9 mm at the
operculum. Their rationale was based on a large series of
patients without other identifiable causes for hearing
loss.20 They used this study as evidence that ‘‘borderline’’
patients without another explanation for their hearing
loss do, in fact, have symptomatic enlarged vestibular
aqueducts. In 2009, Dewan21 reviewed 130 cochlear
implant candidates and found that 16% had enlarged
vestibular aqueducts based on the Valvasori criteria but
45% had enlarged vestibular aqueducts based on the Cincinnati criteria. This resulted in 70 ears that had
previously unexplained hearing loss to subsequently be
classified as having an enlarged vestibular aqueduct.
In an attempt to define the spectrum of size for
normal vestibular aqueducts, Vijayaserkaran et al.22 in
2007 reviewed 73 CT scans of children without sensoriLaryngoscope 121: September 2011
1972
Many investigators have noted that a small but significant fraction of enlarged vestibular aqueduct
patients lose some or all of their hearing with certain
events. The most widely reported precipitating event is
head trauma, representing a small percentage in many
series of patients with enlarged vestibular aqueducts
(see Table I). The head trauma need not be severe. In
addition to head trauma, some investigators have also
linked barotrauma (including Valsalva), upper respiratory tract infections, high fevers, noise trauma, and
physical exercise to hearing loss. For head trauma, by
far the most commonly reported precipitator, the incidence was as high as 80% in one small study, but has a
wide range of incidence in different reports.23 Table I
shows the different series with the incidence found in
each patient population and the etiology reported.
The natural history of the acute trauma induced
hearing loss is quite variable, with some patients having
full recovery while other patients have persistent hearing loss without improvement. This has significant
implications for patient counseling. Some investigators
recommend restricting activities, especially contact
sports, to limit the risk of hearing loss associated with
head trauma.34 Although upper respiratory tract infections and high fevers are somewhat unavoidable, head
trauma can be minimized by avoiding contact sports and
barotrauma can be minimized by avoiding activities that
might provoke a change in hearing, such as scuba diving, sneezing with the nose pinched closed, straining
when going to the bathroom, weight lifting, and other
similar activities. The discussion becomes even more
complex when the enlarged vestibular aqueduct is bilateral, a common occurrence.
Type of Hearing Loss
The type of hearing loss in enlarged vestibular
aqueduct syndrome remains a point of significant controversy. All three types of hearing loss (sensorineural,
mixed, and conductive) have been reported in the condition. Pure conductive hearing loss is by far the least
common type in all studies reported. Although some
investigators describe sensorineural hearing loss in the
majority of patients, some believe that nearly all
patients with enlarged vestibular aqueduct have an air
Gopen et al.: Enlarged Vestibular Aqueduct: Controversies
TABLE I.
Review of Series Reporting Precipitating Factors Resulting in
Hearing Loss in Enlarged Vestibular Aqueduct Patients.
Study
17
Levenson
Year
Patients
in Series
(Total)
1989
12
Patients with
Loss from
an Event (%)
Etiology
4/12 (25)
head trauma
1/12 (8.3)
valsalva
1/12 (8.3)
2/17 (11.8)
barotrauma
head trauma
Jackler15
1989
17
Arcand16
1991
33
1/33 (3.0)
head trauma
Okumura18
1995
13
7/13 (53.8)
Dahlen24
1997
21
2/21 (9.5)
head trauma, URI,
or exercise
head trauma
Antonelli25
1998
26
3/26 (11.5)
valsalva
3/26 (11.5)
‘‘sometimes
occurred’’
head trauma
head trauma
Govaerts26
1999
10
Harker23
1999
5
4/5 (80.0)
head trauma
Mamikoglu27
Madden7
2000
2003
1
77
case report
3/77 (3.9)
head trauma
head trauma
Lin28
2005
16
3/16 (18.8)
head trauma
4/16 (25.0)
5/17 (29.4)
URI
head trauma or
other ‘‘triggering
event’’
URI
Berrettini6
2005
17
Colvin29
2006
27
Steinbach30
2006
1
Grimmer31
2007
32
1/27 (3.7)
1/27 (3.7)
exercise
7/27 (25.9)
N/A
head trauma
noise trauma
2/32 (6.3)
barotrauma
3/32 (9.4)
6/32 (18.8)
high fevers
head trauma
Ma32
2009
23
5/23 (21.7)
head trauma
Atkin33
2009
20
3/20 (15.0)
head trauma
quently, a patient could have an enlarged vestibular
aqueduct with an air bone gap but without sensorineural
hearing loss and would not be enrolled in many of the
studies above, resulting in a selection bias against conductive hearing loss patients.
Different size entrance criteria between studies as
to what defines enlarged vestibular aqueduct may also
play a role. In addition, some patients with enlarged vestibular aqueduct progress to profound hearing loss,
making testing of bone conduction difficult or impossible.
Such patients may not show an air bone gap when the
ear becomes deaf, but would have demonstrated air bone
gaps if tested earlier in the course of the condition.
Hearing Loss Progression over Time
This is certainly one of the most controversial
aspects of the disorder. The spectrum of enlarged vestibular aqueduct hearing loss ranges from complete
deafness in early childhood to stable hearing well into
adult life. As the condition was identified just over 30
years ago, many patients older than that were not diagnosed with the condition. Furthermore, submillimeter
CT and magnetic resonance (MR) imaging are now routinely used, but were not readily available in the 1970s.
This certainly skews the population toward younger
patients. As time goes forward, many of the major centers should have long-term data such that patients with
the condition can be followed later in life yielding better
long-term statistics. Currently, there is no valid method
to predict what a patient’s hearing will be in the years
to come. To date, no study has associated either gender
or bilaterality with hearing loss progression.
Table III summarizes the studies that categorize
the hearing loss into stable, fluctuating, and progressive.
Some studies divide the categories into stable and not
TABLE II.
Series Reporting Hearing Loss by Type.
35–37
bone gap, particularly at the lower frequencies.
Part
of the explanation for discrepancies between studies
may be improper or incomplete audiometric testing.37
Specifically, many children are examined using ABR
testing, which poses some difficulties in the assessment
of the lowest frequencies with bone conduction and may
lead to an overestimation of sensorineural hearing loss
instead of mixed hearing loss in many cases. Furthermore, many cases have bilateral severe hearing loss,
creating a masking dilemma that further confounds
results.
Table II summarizes the major studies reporting the
type of hearing loss. Certainly numerous confounding factors make the data analysis difficult and varied. Some of
the studies suffer from selection bias. Specifically, the
study by Antonelli25 required sensorineural hearing loss
as a criteria for obtaining a computed tomography (CT)
scan and entrance into their study. Similarly, Arjmand41
required sensorineural hearing loss as a criteria for
enrollment in study. Patients with enlarged vestibular
aqueducts can have suprathreshold bone conduction
responses, particularly at lower frequencies. ConseLaryngoscope 121: September 2011
Patients Ears
SNHL
(%)
Mixed CHL
Normal
(%)
(%) Hearing (%)
Study
Year
Valvassori38
1983
160
15
0
1
Emmett39
Jackler15
1985
1989
26
17
47 77
33 73
17
27
0
0
6
0
Antonelli25
? 83.75
1998
26
48 27
73
0
0
1999
Govaerts26
Nakashima36 2000
10
15
18 10
28 0
90
100
0
0
0
0
Sato35
Madden7
2002
2003
13
77
24 0
144 72
100
28*
0
0
0
Lai40
2004
12
24 87.5
12.5
0
0
Arjmand41
Berrettini6
2004
2005
19
17
26 85
32 37
12
63*
0
3
0
Colvin29
2006
27
50 20
80*
Zhou37
Reyes42
2008
2009
54
32
82 20
64 68.7
74
31.3
6
0
0
0
King43
2010
?
90 67
28
4
1
0
*Represents combined mixed hearing loss and conductive hearing
loss (not delineated seprately in these studies).
SNHL ¼ sensorineural hearing loss.
Gopen et al.: Enlarged Vestibular Aqueduct: Controversies
1973
TABLE III.
Hearing Loss—Progression Over Time.
Study
Year
Patients
Valvassori
1983
15
?
40
0
Emmet39
Jackler15
1985
1989
24
17
48
33
83
35
17*
12
53
2 days to 12 years
7.3
Levenson17
1989
12
22
27
46
27
4.2
Arcand16
Okumura18
1991
1995
13
13
20
23
54
39
46*
61*
Zalzal4
1995
15
26
64
36*
Antonelli25
Madden7
1998
2003
26
77
42
144
24
51
40
28
36
21
2.3
?
Arjmand41
2004
?
?
50
33
17
?
Lai40
Baerrettini6
2004
2005
12
17
24
32
67
30
33*
29
41
?
?
Colvin29
2006
27
50
30
33
37
9.7
Madden20
Grimmer31
2007
2008
71
32
119
?
50
16
22
29
28
55
1.2
3.6
Reyes42
2009
32
64
47
21
32
9.5
Atkin33
King43
2009
2010
20
83
37
143
50
26
50*
37
30
?
3.7
38
Ears
Stable
Fluctuating
Progressive
60
f/u Years Mean
3
4.0
1.4
3.8
*Represents combined fluctuating and progressive hearing loss (not delineated separately in these studies).
stable (combining fluctuating and progressive; see Table
III). If mean follow-up was not provided but the range of
follow-up was provided it is reported. If no mention of
follow-up is given in the study, it is demarcated by a ‘‘?.’’
Again, the studies are confounded by different
entrance criteria for each category. For example, how
are patients that are deaf at their first visit categorized?
In some ways they can be considered stable, as the hearing is not changing over time. Another interpretation
would be they are progressive and just at the end stage
of progression. What defines stable hearing? Some studies show a gradual hearing loss of around 4 dB per year,
such that small changes in hearing may be classified as
stable by some and progressive by others. This might
help explain the wide ranges reported. For example,
‘‘stable’’ hearing was as high as 83% and as low as 16%.
The three longer term studies had somewhat similar
results. Reyes with a 9.5-year mean follow-up found 47%
of the ears were stable42 and Colvin with a 9.7-year mean
follow up found 30% of the ears to be stable.29 Jackler,15
with a 7.3-year mean follow-up had 35% of the ears stable.
Certainly long-term follow-up is needed to sort out these
differences with a more consistent categorization between
centers. This notion is supported by the Zalzal study when
groups were divided into less than 2 years and greater
than 2 years, with a significant increase in the incidence
of progression within the longer term group.4
Steroid Treatment
The idea that corticosteroid therapy could benefit
patients with an enlarged vestibular aqueduct stemmed
from patients who had a sudden sensorineural hearing
loss. Corticosteroids are often used to treat idiopathic
sudden sensorineural hearing loss.44,45 Grimmer46 studLaryngoscope 121: September 2011
1974
ied the use of steroids in enlarged vestibular aqueduct
patients retrospectively in a small cohort of 12 patients.
He noted hearing improvement in four of five patients
treated with corticosteroids but a lack of hearing
improvement in six of seven patients that were not
treated with steroids. He determined a prospective study
with approximately 20 to 45 patients in each group
would be required to prove statistical significance.
Lin and coworkers,28 in 2005, studied 16 children
retrospectively with enlarged vestibular aqueducts and
defined successful treatment if the hearing thresholds
improved by 10 dB at two frequencies. Seven children over
4.5 years had 13 episodes of hearing loss, with an 85%
improvement rate. No control group was used in this
study. This is quite problematic, as the natural history of
the disease is known to have a high incidence of spontaneous recovery after fluctuations in hearing.
To date, there have been no prospective trials of either systemic or intratympanic corticosteroid use in
enlarged vestibular aqueduct patients who have fluctuating or progressive hearing loss.
Endolymphatic Sac Surgery
Endolymphatic sac surgery has been attempted to
improve or even stabilize hearing in patients with
enlarged vestibular aqueducts. In 1989, Jackler15
reviewed this very supposition and concluded that endolymphatic sac shunt surgery is contraindicated in the
disorder after four of seven patients he operated on had
a significant early decline in hearing thresholds on postoperative follow-up evaluation. Welling,46 in 1999, had
similar results, performing endolymphatic sac occlusion
on 10 patients, with 9 patients having some degree of
additional haring loss after the procedure.
Gopen et al.: Enlarged Vestibular Aqueduct: Controversies
The only study with favorable results was done by
Wilson,19 in 1997, when he reported a series of endolymphatic sac obliterations on seven children. He reported
six of seven patients maintained stable hearing on longterm follow-up, between 6 months and 6 years. One
patient had continued progression of their hearing loss,
and no control groups were used in this small study.
EVA Size Correlations with Hearing Loss
There is some discrepancy as to whether the magnitude of the enlarged vestibular aqueduct plays a role in
hearing loss severity or progression. Several studies
have reviewed this topic with mixed results. Antonelli25
found the amount of enlargement and morphology of the
vestibular aqueduct correlated highly with the severity
of hearing loss, but that the degree of modiolar deficiency did not correlate with hearing loss. Madden7
found a correlation between vestibular aqueduct size at
the operculum and progressive loss. Lai40 showed the
midpoint diameter and the diameter at the operculum of
the enlarged vestibular aqueduct correlated with the frequency and severity of hearing loss fluctuations, but did
not correlate with the progression of hearing.
In contrast, most studies have not shown correlation
between hearing loss and sac or duct size.4,6,17,24,29,47–49
Naganawa,50 in 2000, used 1.5 T T2-weighted MR sequences to quantify the volume of the vestibular aqueduct and
sac, the area of the modiolus, the diameter of the duct and
sac, and the signal intensity of the endolymphatic sac,
and did not show any significant correlation with the
degree of hearing loss.
SLC26a4 (PDS) Gentotype Correlates
with Hearing Loss and Enlarged
Vestibular Aqueduct
In 1896, Vaughn Pendred,51 in the Lancet,
described two Irish sisters with goiter and hearing loss.
In 1927, Brain52 described it as having autosomal recessive inheritance. In 1960, Fraser et al.,53 using the
perchlorate discharge test, recognized the variability in
the thyroid function in patients with Pendred syndrome.
Then, several investigators, including Sheffield et al.
(1996),54 Gausden et al. (1997),55 and Coucke et al.
(1997)56 linked the region for the PDS gene to 7q31. In
1997, Everett et al.57 identified PDS, also called
SLC26A4, as the gene causing Pendred syndrome. Abe
et al. (1999)58 noted patients with EVA and fluctuating
sensorineural hearing loss had localization of the gene to
7q31, a region containing the Pendred syndrome gene.
Finally, in 1999, Usami et al.59 found that mutations in
the PDS gene were associated with the presence of both
syndromic (Pendred syndrome) and nonsyndromic
(DFNB4) enlarged vestibular aqueducts.
Some studies have correlated SLC26A4 mutations
with a worse prognosis for hearing. In 2006, Albert60
reported that biallelic mutations in SLC26A4 in nonsyndromic patients had more severe hearing loss and a
higher likelihood of fluctuations when compared to
enlarged vestibular aqueduct patients without SLC26A
mutations. Another study by King,43 in 2009, correlated
Laryngoscope 121: September 2011
a worse hearing prognosis with identification of the
SLC26A4 genotype in patients with enlarged vestibular
aqueducts. King did not find any correlation between
cochlear anomalies and hearing loss. Madden20 found a
correlation between SLC26A4 mutations with wider
aqueducts at the midpoint and more severe hearing loss.
In opposition, however, both Reyes42 and Jonard61
recently have published studies that show no correlation
between SLC26A4 gene mutations and hearing loss.
Vestibular Symptoms
Certainly, vestibular dysfunction has been correlated with the diagnosis of an enlarged vestibular
aqueduct. Several case reports of children and adults
with enlarged vestibular aqueducts and symptoms of
vestibular dysfunction can be found.62–65 The vestibular
symptoms are typically dysequilibrium or epidosic vertigo attacks of variable length. Younger children may
present with motor delays such as delayed ambulation
and poor coordination.
Interestingly, some of the reported series evaluating
the frequency of vestibular dysfunction, either based on
symptoms or abnormal testing, have revealed a wide disparity of results. The incidence of vestibular symptoms
ranged from 0% to 100%, but this likely represents selection criteria bias for inclusion within each study.
Comparison of these studies is difficult due to differences in age, variable lengths of follow-up, and different
inclusion criteria. Okumura18 stated that their study
identified a higher incidence of vestibular symptoms due
to a longer period of follow-up with a mean duration of
11 years. Grimmer’s47 study also found no statistical differences when comparing adult and pediatric rates of
vestibular dysfunction. Many of the studies report vestibular symptoms but only performed selected vestibular
testing. These studies are summarized in Table IV.
Some of the inherent difficulties in establishing a
frequency for vestibular symptoms in any study are the
assessment of pediatric patients. Most studies have a
majority of pediatric patients, some of whom are too
young to report vestibular symptoms. Furthermore,
pediatric patients are much more resilient in general to
vestibular symptoms than adult patients, and may not
report dysequilibrium or even milder forms of vertigo. If
a child has severe vestibular loss from the condition in
the perinatal period or early during development, they
may display few vestibular symptoms later in life, as
they will have compensated through development.
Hypothesis for Etiology of Hearing Loss in
Enlarged Vestibular Aqueduct Patients
Many different theories as to how the enlarged vestibular aqueduct leads to hearing loss have been
proposed. Some feel that the enlarged vestibular aqueduct is an epiphenomenon, with the true pathology
being undetected at a molecular level. However, the
theories proposed to date are listed below:
1. Back pressure/damaging pressure wave theories:
Early on, Valvasori,3 and more recently Riley66 both
Gopen et al.: Enlarged Vestibular Aqueduct: Controversies
1975
TABLE IV.
Vestibular Symptoms and Testing.
Study
Year
3
Patients
Vestibular
Symptoms
Vestibular Testing
Valvassori
1978
50
10%*
100% patients (6 patients tested) markedly decreased or absent
vestibular functions tests
Valvassori38
1983
160
4%
vestibular function tests absent or markedly reduced in 80% of
patients
Emmett39
1985
26
12%
ENG reduced in 53% of patients rotational chair with
low-frequency phase lag 100% of patients and 57% of
patients had directional preponderance
Jackler15
1989
17
29%
ENG in 2 patients one with direction changing nystagmus and
normal ENG the other with no response but had no vestibular
symptoms
Schessel83
Okumura18
1992
1995
3
4
100%
100%
reduced calorics 67% of patients
reduced calorics 100% of patients
Okumura84
1996
8
80%
none reported
Antonelli25
Yetiser85
1998
1999
30
10
43%
30%
none reported
90% of patients with ENG reduced or no response
Nakashima36
2000
15
33%
VEMP with increased amplitude at reduced threshold in 92%
of patients, absent in 8% of patients
Oh86
2001
3
100%
1 patient: ENG normal, rotational chair testing normal
1 patient: no testing done
1 patient: ENG normal but rotational chair testing with decreased
gain and increased phase lead
Naganawa78
2002
7
14%
no testing reported
Madden7
Sheykholeslami82
2003
2004
77
3
4%
67%
no testing reported
ENG normal (1 patient), VEMP present 2 out of 2 patients tested
Berrettini6
2005
17
47%
ENG reduced in 87% of patients
Grimmer47
Merchant81
2007
2007
15
5
47%
0%
no testing reported
no testing reported
Zhou87
2010
25
20%
VEMP with increased amplitude and reduced threshold in 88%
of patients, absent in 12% of patients
VEMP ¼ vestibular evoked myogenic potential testing; ENG ¼ electronystagmonography testing.
*In this study, the reported incidence of vestibular symptoms is 10%, but the author goes on to state that ‘‘vestibular complaints of inconsequential
magnitude could be elicited from many patients.’’
proposed that the conductive component of the hearing loss can be explained by a back pressure of perilymphatic and endolymphatic fluid. Theoretically, this
results in decreased stapes mobility. As evidence, they
site an increased rate of perilymphatic gushers and
oozers encountered when the inner ear is opened,
either during stapedotomy or cochleostomy.26,30,67–73
However, this can also be explained by a higher incidence of concurrent cochlear modiolar deficiencies
seen in patients with enlarged vestibular aqueducts.
Furthermore, acoustic reflexes remain intact, a finding inconsistent with stapes fixation in cases of
enlarged vestibular aqueduct. This theory does not
explain the high incidence of sensorineural hearing
loss as well.
In a related line of thinking, Lemmerling50 theorized that the enlarged vestibular aqueduct allows for
greater pressure shifts generated from the intracranial space to cross through the enlarged vestibular
aqueduct and damage the inner ear. This could
explain why during head trauma or Valsalva hearing
loss is seen at a high rate. Okamoto,74 in a similar
argument, proposes that elevated pressures damage
the hair cells.
Laryngoscope 121: September 2011
1976
2. Electrolyte imbalance theory: Jackler15 proposed that
the endolyphatic sac may be dysfunctional in terms of
its physiologic role in inner ear hemostasis. The
enlarged and dysfunctional endolyphatic sac results
in electrolyte derangement or toxic biproducts that
damage the inner ear. He theorized that large
volumes of endolymph introduced from the enlarged
system might overwhelm the ion pump mechanism
of the stria vascularis. As evidence, he sites the
Gussen75 temporal bone study, which demonstrates
that the histologic structure of the sac and duct in
enlarged vestibular aqueduct cases is clearly abnormal, with thin-walled cyst-like changes in the endolyphatic sac architecture and flattened epithelium
along the endolymphatic duct. Other investigators
have supported this theory as well.17,76
3. Hyperosmolar fluid reflux theory: A somewhat similar
theory to the electrolyte imbalance theory, Schucknecht77 along with Levenson17 and Okamoto74 theorize that the endolymphatic sac fluid, which is known
to contain hyperosmolar fluid, can reflux more easily
through the enlarged endolymphatic sac and duct and
enter the inner ear resulting in damage to the inner
ear structures. Arguing against this theory is an MRI
Gopen et al.: Enlarged Vestibular Aqueduct: Controversies
study that found endolymphatic sac volume and
intensity vary dynamically and independently of
hearing in cases of enlarged vestibular aqueduct.
Presumably, intensity of the endolymphatic duct and
sac is correlated with hyperosmolarity. However, this
study included only two patients!78
4. Stapes fixation: Shirazi76 published an article on a
patient who underwent a middle ear exploration for
mixed hearing loss and identified the stapes bone as
fixed. Attempted stapedotomy was aborted due to a
perilymphatic gusher, and postoperative imaging
demonstrated an enlarged vestibular aqueduct.76 This
is a single case report. Talbot79 presents four patients
with X-linked congenital mixed hearing loss, enlarged
vestibular aqueduct, and fixed stapes footplate. Three
of the four underwent stapes surgery with intraoperative findings of a perilymphatic gusher. However,
these three patients had other inner ear anomalies,
including cochlear base hypoplasia, absent modiolus,
and enlarged internal auditory canals. In contrast,
Govaerts26 explored three ears with enlarged vestibular aqueducts and found normal ossicular mobility
but absent round window reflexes. Mamikoglu27
reports exploring a child with enlarged vestibular
aqueduct and finding an intact, mobile ossicular
chain. Also, Nakashima36 found that acoustic reflexes
persist in cases of enlarged vestibular aqueduct,
inconsistent with stapes fixation.
5. Ossicular discontinuity theory: Nakashima36 suggests
air bone gaps seen in some cases are due to ossicular
discontinuity based on the results of their study
showing the resonant frequency of patients with
enlarged vestibular aqueducts was low compared to
patients with otosclerosis. They site a temporal bone
study demonstrating a 38% incidence of ossicular
deformities in enlarged vestibular aqueduct cases.80
6. Third-window lesion: Third-window lesions are any
abnormal opening into the inner ear excluding the
normal oval window (first window) and round window
(second window). The abnormal opening in the bony
labyrinth changes the compliance of the system and
results in sound energy being shunted out of the cochlea. Furthermore, the decrease in compliance of the
system allows for an enhancement in bone conduction,
resulting in the characteristic mixed hearing loss seen
in many cases. It can also explain the supranormal
bone conduction responses seen in some patients.81
Vestibular evoked myogenic potential testing in other
third-window lesions, such as superior or posterior
semicircular canal dehiscence, results in a similar
characteristic response as in enlarged vestibular aqueducts, specifically an elevated amplitude of response at
a reduced volume of sound.82 This theory does not,
however, explain the deterioration seen in many
patients over time.
CONCLUSIONS
The enlarged vestibular aqueduct remains a common cause of hearing loss in the pediatric population.
Although it can be classified as a third window lesion,
Laryngoscope 121: September 2011
many questions about its mechanism of action and differences between patients remain a mystery. Little
useful prognostic information can be given to families in
specific cases, and rehabilitative efforts with hearing
aids or cochlear implantation remain the mainstays of
treatment. Corticosteroid treatment for sudden hearing
loss remains controversial but has little direct evidence
demonstrating any benefit. Endolymphatic sac decompression and oblitteration have not been shown to be
beneficial and have even been correlated with worsening
of symptoms in most investigations.
BIBLIOGRAPHY
1. Mondini C. Anatomica surdi nati sectio. De Bononiensi Scientarium
et Artium Instituto atque Academia Commenarii. Banoniae 1791:7:419.
2. Valvassori G, Naunton R, Lindsay J. Inner ear anomalies: clinical and histopathological considerations. Ann Otol Rhinol Laryngol 1989;78:
929–938.
3. Valvasori G, Clemis J. The large vestibular aqueduct syndrome. Laryngoscope 1978;88:723–728.
4. Zalzal G, Sharon T, Vezina L, Bjornsti P, Grundfast K. Enlarged vestibular
aqueduct and sensorineural hearing loss in childhood.Arch Otolaryngol
Head Neck Surg 1995;121:23–28.
5. Karet F, Finberg K, Nelson R, et al. Mutations in the gene encoding B1
subunit of HþATPase cause renal tubular acidosis with sensorineural
deafness. Nat Genet 1999;21:84–90.
6. Berrettini S, Forli F, Fausto B. Large vestibular aqueduct syndrome:
audiological, radiological, clinical and genetic features. Am J Otolaryngol 2005;26:363–371.
7. Madden C, Halsted M, Benton C, Greinwald J, Choo D. Enlarged vestibular aqueduct syndrome in the pediatric population. Otol Neurotol 2003;
24:625–632.
8. Talbot J, Wilson D. Computed tomographic diagnosis of X-linked congenital mixed deafness, fixation of the stapedial footplate and perilymphatic
gusher. Am J Otol 1994;15:177–182.
9. Arellano B, Pera A, Ramirez-Camacho R, et al. Pendred’s syndrome and
non-syndromic DFNB4 deafness associated with the homozygous T410M
mutation in the SLC26A4 gene in siblings. Clin Gen 2005;67:438–440.
10. Ceruti S, Stinckens C, Cremers C, Casselman J. Temporal bone anomalies
in the BOR syndrome: detailed computed tomographic and magnetic
resonance imaging findings. Otol Neurotol 2003;23:200–207.
11. Stinckens C, Standaert L, Casselman J, Huygen P, Kumar S, Van de Wallen J, Cremers C. The presence of a widened vestibular aqueduct and
progressive sensorineural hearing loss in the Branchio-Oto-Renal syndrome. A family study. Int J Pediatr Otolaryngol 2001;29:163–172.
12. Megarbane A, Chouery E, Rassi S, Delague V. A new autosomal recessive
oto-facial syndrome with midline malformations. Am J Med Genet 2005;
123:398–401.
13. Miura M, Sando I, Orita Y, Hirsch B. Temporal bone histopathological
study of Noonan syndrome. Int J Pediatr Otorhinolaryngol 2001;60:
73–82.
14. Gonzalez-Garcia J, Ibanez A, Ramirez Camacho R, Rodriguez A, Garcia
Berrocal J, Trinidad A. Enlarged vestiubular aqueduct: looking for genotypic–phenotypic correlations. Eur Arch Otorhinolaryngol 2006;263:
971–976.
15. Jackler R, De La Cruz A. The large vestibular aqueduct syndrome. Laryngoscope 1989;99:1238–1243.
16. Arcand P, Desrosiers M, Dube J, Abela A. The large vestibular aqueduct
syndrome and sensorineural hearing loss in the pediatric population.
J Otolaryngol 1991;20:247–250.
17. Levenson M, Parisier S, Jacobs M, Edelstein D. The large vestibular aqueduct syndrome in chilren. Arch Otolaryngol Head Neck Surg 1989;115:
54–58.
18. Okumura T, Takahashi H, Honjo I, Takagi A, Mitamura K. Sensorineural
hearing loss in patients with large vestibular aqueduct. Laryngoscope
1995;105:289–294.
19. Wilson D, Hodgson R, Talbot J. Endolymphatic sac obliteration for large
vestibular aqueduct syndrome. Am J Otol 1997;18:101–106.
20. Madden C, Halsted M, Meinzen-Derr J. The influence of mutations in the
SLC26A4 gene on temporal bone in a population with enlarged vestibular aqueduct. Arch Otolaryngol Head Neck Surg 2007;133:162–168.
21. Dewan K, Wippold F, Lieu J. Enlarged vestibular aqueduct in pediatric
sensorineural hearing loss. Otolaryngol Head Neck Surg 2009;140:
552–558.
22. Vijayasekaran S, Halsted M, Boston M, Meinzen-Derr J, Bardo D,
Greinwald J, Benton C. When is the vestibular aqueduct enlarged? A
statistical analysis of the normative distribution of vestibular aqueduct
size. AJNR 2007;28:1133–1138.
23. Harker L, Vanderheiden S, Veazey D, Gentile N, McCleary E. Multichannel cochlear implantation in children with large vestibular aqueduct
syndrome. Ann Otol Rhinol Laryngol 1999;108:39–43.
Gopen et al.: Enlarged Vestibular Aqueduct: Controversies
1977
24. Dahlen R, Harnsberger R, Gray S, Shelton C, Allen R, Parkin J, Scalzo D.
Overlapping thin-section fast spin-echo MR of the large vestibular aqueduct syndrome. AJNR 1997;18:67–75.
25. Antonelli P, Nall A, Lemmerling M, Mancuso A, Kubilis P. Hearing loss
with cochlear modiolar defects and large vestibular aqueducts. Am J
Otol 1998;19:306–312.
26. Govaerts P, Casselman J, Daemers K, De Ceulaer G, Somers T, Offeciers
F. Audiological findings in large vestibular aqueduct syndrome. Int J
Pediatr Otorhinolaryngol 1999;51:157–164.
27. Mamikoglu B, Bentz B, Wiet R. Large vestibular aqueduct syndrome presenting with mixed hearing loss and an intact mobile ossicular chain.
Otorhinolaryngologia 2000;10:204–206.
28. Lin C, Lin S, Kao C, Wu J. The remediation of hearing deterioration in
children with large vestibular aqueduct syndrome. Auris Nasus Larynx
2005;32:99–105.
29. Colvin I, Beale T, Harrop-Griffiths H. Long-term follow-up of hearing loss
in children and young adults with enlarged vestibular aqueducts: relationship to radiologic findings and pendred syndrome diagnosis. Laryngoscope 2006;116:2027–2036.
30. Steinbach S, Brockmeier S, Kiefer B. The large vestibular aqueduct—case
report and review of the literature. Acta Otolaryngol 2006;126:788–795.
31. Grimmer J, Hedlund G, Park A. Steroid treatment of hearing loss in
enlarged vestibular aqueduct anomaly. Int J Pediatr Otorhinolaryngol
2008;72:1711–1715.
32. Ma X, Yang Y, Xia M, Li D, Xu A. Computed tomography findings in large
vestibular aqueduct syndrome. Acta Otolaryngol 2009;139:700–708.
33. Atkin J, Grimmer J, Hedlund G, Park A. Cochlear abnormalities associated with enlarged vestibular aqueduct anomaly. Int J Pediatr Otorhinolaryngol 2009;73:1682–1685.
34. Nowak K, Messner A. Isolated large vestibular aqueduct syndrome in a
family. Ann Otol Rhinol Laryngol 2000;109:40–44.
35. Sato E, Nakashima T, Lilly D, et al. Tympanometric findings in patients
with enlarged vestibular aqueducts. Laryngoscope 2002;112:1642–1646.
36. Nakashima T, Ueda H, Furuhashi A, Sato E, Asahi K, Naganawa S,
Beppu R. Air bone gap and resonant frequency in large vestibular aqueduct syndrome. Am J Otol 2000;21:671–674.
37. Zhou G, Gopen Q, Kenna M. Delineating the hearing loss in children with
enlarged vestibular aqueduct. Laryngoscope 2008;118:2062–2066.
38. Valvassori G. The large vestibular aqueduct and associated anomalies of
the iner ear. Otolaryngol Clin North Am 1983;16:95–101.
39. Emmet J. Large vestibular aqueduct syndrome. Am J Otol 1985;6:
387–415.
40. Lai C, Shiao A. Chronological changes of hearing in pediatric patients
with large vestibular aqueduct syndrome. Laryngoscope 2004;114:
832–838.
41. Arjmand E, Webber A. Audiometric findings in children with a large vestibular aqueduct. Arch Otolaryngol Head Neck Surg 2004;130:
1169–1174.
42. Reyes S, Wang G, Ouyang X. Mutation analysis of SLC26A4 in mainland
Chinese patients with enlarged vestibular aqueduct. Otolaryngol Head
Neck Surg 2009;141:502–508.
43. King K, Choi B, Zalewski C, et al. SLC26A4 genotype, but not cochlear
radiologic structure, is correlated with hearing loss in ears with an
enlarged vestibular aqueduct. Laryngoscope 2010;120:384–389.
44. Jeyakumar A, Francis D, Doerr T. Treatment of idiopathic sudden sensorineural hearing loss. Acta Otolaryngol 2006;126:709–713.
45. Chen C, Halpin C, Rauch S. Oral steroid treatment of sudden sensorineural hearing loss: a ten year retrospective analysis. Otol Neurotol 2003;
24:728–733.
46. Welling C, Slater P, Martyn M, et al. Sensorineural hearing loss after
occlusion of the enlarged vestibular aqueduct. Am J Otol 1999;20:
338–343.
47. Grimmer J, Hedlund G. Vestibular symptoms in children with enlarged
vestibular aqueduct anomaly. Int J Pediatr Otorhinolaryngol 2007;71:
275–282.
48. Pryor S, Madeo A, Reynolds C, et al. SLC26A4/PDS genotype–phenotype
correlation in hearing loss with enlargement of the vestibular aqueduct
(EVA): evidence that Pendred syndrome and non-syndromic EVA are
distinct clinical and genetic entities. J Med Genet 2005;42:159–165.
49. Lemmerling M, Mancuso A, Antonelli P, Kubilis P. Normal modiolus: CT
appearance in patients with a large vestibular aqueduct. Radiology
1997;204:213–219.
50. Naganawa S, Koshikawa T, Iwayama E, et al. MR imaging of the enlarged
endolymphatic duct and sac syndrome by use of a 3D fast asymmetric
spin-echo sequence: volume and signal intensity measurement of the
endolymphatic duct and sac and area measurement of the cochlear modiolus. AJNR 2000;21:1664–1669.
51. Pendred V. Deaf-mutism and goitre. Lancet 1896;2:532.
52. Brain W. Heredity in simple goitre. QJ Med 1927.20:303–319.
53. Fraser G, Morgans M, Trotter W. The syndrome of sporadic goitre and congenital deafness. QJ Med 1960;29:279–295.
54. Sheffield V, Kraiem Z, Beck J, et al. Pendred syndrome maps to chromosome 7q21–34 and is caused by an intrinsic defect in thyroid iodine
organification. Nat Genet 1996;12:424–426.
55. Gausden E, Coyle B, Armour J, et al. Pendred syndrome: evidence for
genetic homogeneity and further refinement of linkage. J Med Genet
1997;34:126–129.
Laryngoscope 121: September 2011
1978
56. Coucke P, Van Camp G, Demirhan O, et al. The gene for Pendred syndrome is located between D7S501 and D7S692 in a 1.7-cM region on
chromosome 7q. Genomics 1997;40:48–54.
57. 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.
58. 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.
59. 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.
60. Albert S, Blons H, Jonard L, et al. SLC26A4 gene is frequently involved in
nonsyndromic hearing impairment with enlarged vestibular aqueduct in
Caucasian populations. Eur J Hum Genet 2006;114:773–779.
61. Jonard L, Niasme-Grare M, Bonnet C, et al. Screening of SLC26A4,
FOXI1 and KCNJ10 genes in unilateral hearing impairment with ipsilateral enlarged vestibular aqueduct. Int J Pediatr Otorhinolaryngol
2010;74:1049–1053.
62. Hill J, Freint A, Mafee M. Enlargement of the vestibular aqueduct. Am J
Otolaryngol 1984;5:411–444.
63. Walsh R, Ashford C, Chavda S, Proops D. Large vestibular aqueduct syndrome. ORL J Otorhinolaryngol Relat Spec 1999;61:41–44.
64. Griffith A, Arts A, Downs C, Innis J, Shepard N, Sheldon S, Gebarski S.
Familial large vestibular aqueduct syndrome. Laryngoscope 1996;106:
960–965.
65. Ramirez-Camacho R, Ramon Garcia Berrocal J, Arellano B, Trinidad A.
Familial isolated unilateral large vestibular aqueduct syndrome. ORL J
Otorhinolaryngol Relat Spec 2003;65:45–48.
66. Riley L, Stokroos R, Manni J. The large vestibular aqueduct syndrome as
a cause for sudden deafness in children. Otorhinolaryngol Nova 1998;8:
230–234.
67. Au G, Gibson W. Cochlear implantation in children with large vestibular
aqueduct syndrome. Am J Otol 1999;20:183–186.
68. Fahy C, Carney A, Nikolopoulos N, Ludman C, Gibbin K. Cochlear
implantation in children with large vestibular aqueduct syndrome and
a review of the syndrome. Int J Pediatr Otorhinolaryngol 2001;59:
207–215.
69. Aschendorff A, Marangos N, Laszig R. Large vestibular aqueduct syndrome and its implication for cochlear implant surgery. Am J Otol 1997;
18:S57.
70. Miyamoto R, Bichey B, Wynne M, Kirk K. Cochlear implantation with
large vestibular aqueduct syndrome. Laryngoscope 2002;112:1178–1182.
71. Bent J, Chute P, Parisier S. Cochlear implantation in children with
enlarged vestibular aqueducts. Laryngoscope 1999;109:1019–1022.
72. Temple R, Ramsden R, Axon P, Saeed S. The large vestibular aqueduct
syndrome: the role of cochlear implantation in its management. Clin
Otolaryngol Allied Sci 1999;24:301–306.
73. Lee K, Lee J, Isaacson B, et al. Cochlear implantation in children with
enlarged vestibular aqueduct. Laryngoscope 2010;120:1675–1681.
74. Okamoto K, Ito J, Furusawa T, Sakai K, Horikawa S, Tokiguchi S. MRI of
enlarged endolymphatic sacs in the large vestibular aqueduct syndrome.
Neuroradiology 1998;40:167–172.
75. Gussen R. Histological evidence of specialized microcirculation of the endolymphatic sac. Arch Otorhinolaryngol 1980;228L:7–16.
76. Shirazi A, Fenton J, Fagan P. Large vestibular aqueduct syndrome and
stapes fixation. J Laryngol Otol 1994;108:989–990.
77. Schuknecht H, Richter E. Apical lesions of the cochlea in idiopathic endolymphatic hydrops and other disorders: pathophysiological implications.
ORL 1980;42:46–76.
78. Naganawa S, Koshikawa T, Fukatsu H, Ishigaki T, Nakashima T. Serial
MR imaging studies in enlarged endolymphatic duct and sac syndrome.
Eur Radiol 2002;12:S114–S117.
79. Talbot J, Wilson D. Computed tomographic diagnosis of X-linked congenital deafness, fixation of the stapedial footplate, and perilymphatic
gusher. Am J Otol 1994;15:177–182.
80. Hirai S, Cureoglu S, Schachern P, et al. Large vestibular aqueduct syndrome: a human temporal bone study. Laryngoscope 2006;116:2007–2011.
81. Merchant S, Nakajima H, Halpin C, et al. Clinical investigation and mechanism of air-bone gaps in large vestibular aqueduct syndrome. Ann Otol
Rhinol Laryngol 2007;116:532–541.
82. Sheykholeslami K, Schmerber S, Habiby M, Kaga K. Vestibular-evoked
myogenic potentials in three patients with large vestibular aqueduct.
Hear Res 2004;190:161–168.
83. Schessel D, Nedzelski J. Presentation of large vestibular aqueduct syndrome to a dizziness unit. J Otolaryngol 1992;21:265–269.
84. Okumura T, Takahashi H, Honjo I, Takagi A, Azato R. Magnetic resonance
imaging of patients with large vestibular aqueducts. Eur Arch Otorhinolaryngol 1996;253:425–428.
85. Yetsier S, Kertmen M, Ozkaptan Y. Vestibular disturbance in patients
with large vestibular aqueduct syndrome (LVAS). Acta Otolaryngol
1999;119:641–646.
86. Oh A, Ishiyama A, Baloh R. Vertigo and the enlarged vestibular aqueduct
syndrome. J Neurol 2001;248:971–944.
87. Zhou G, Gopen Q. Characteristics of vestibular evoked myogenic potentials
in children with enlarged vestibular aqueduct. Laryngoscope 2010;121:
220–225.
Gopen et al.: Enlarged Vestibular Aqueduct: Controversies