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loss without EVA from 1998 to 2010. Patients included in the
study were required to meet the following criteria: 1) diagnosis of
EVA was consistent with the previously published and well-
established criteria;
9,11
2) a complete audiometric assessment
was performed and at least 3 months of audiometric follow-up
data were available; and 3) genetic testing (
GJB2, SLC26A4
)
was performed if offered at our institution at the time of the
hearing loss evaluation (Fig. 1). Exclusion criteria included
temporal bone dysmorphology that would prevent measure-
ments, aural atresia, known syndromic hearing loss, documented
ototoxicity, or a history of temporal bone fractures, meningitis,
hydrocephalus with a shunt, autoimmune inner ear disease, or
auditory neuropathy. Demographic data, audiometric data,
temporal bone measurements, and genetic test results were
obtained for study patients. This study was approved by the
institutional review board and was in compliance with Health
Insurance Portability and Accountability Act of 1996 regulations.
Audiometric Data
A pure tone average (PTA) for each ear was derived by
averaging the audiometric findings at 500, 1,000, 2,000, and
4,000 Hz at the initial and most recent audiometric evaluation. A
PTA for each ear was also derived for the high frequencies (high-
frequency PTA [HFPTA]) by averaging the audiometric findings
at 4,000, 6,000, and 8,000 Hz. An additional subanalysis was
performed on the individual 250-Hz pure tone frequency.
Progressive hearing loss was defined as a 10 dB or greater
increase in PTA over a follow-up period of at least 3 months.
Patients with an initial PTA 90 dB were eliminated from fur-
ther analysis with regard to progressive SNHL. Progressive
hearing loss was evaluated as absolute change in PTA values as
well as a rate of change in PTA (in decibel loss per year), which
takes into account the time between audiologic visits. When
reporting PTA values for patients with asymmetric bilateral
hearing loss, the better-hearing ear was used for describing the
hearing phenotype for that patient. The levels of hearing loss
were defined within the following framework: mild loss (20–39
dB), moderate loss (40–54 dB), moderately severe loss (55–69
dB), severe loss (70–89 dB), and profound loss (
>
90 dB).
Temporal Bone CT Analysis
Measurement of the various structures of the temporal
bone seen on CT scans was carried out according to a previously
published algorithm.
9,11
All patients in the study had CT scans
available for review. Briefly, the width of the aqueduct was meas-
ured at both the operculum (a line perpendicular to the posterior
surface of the petrous pyramid going to the most lateral or pos-
terolateral pixel in the medial wall of the operculum) and at the
midpoint between the coronal plane of the operculum and the
coronal plane of the posterior wall of the crus commune or upper
vestibule. The vestibular aqueduct was considered enlarged
when its width exceeded the 95th percentile of normal temporal
bones at either the operculum or the midpoint (1.9 mm and 0.9
mm, respectively; Fig. 2). All measurements were performed by
two neuroradiologists (
C
.
B
. and
M
.
H
.). When there was a discrep-
ancy between the measurements performed by these two
physicians, the mean of the two measurements was used.
Methodology for
GJB2
,
GJB6, MTRNR1
, and
SLC26A4
Genetic Testing
Genomic DNA was isolated from blood and buccal swab
tissues using the Puregene DNA purification Kit (Gentra Sys-
tems, Minneapolis, MN) or the Roche MagNA Pure Compact
system (Roche Diagnostics Corporation, Indianapolis, IN)
according to the manufacturers’ instructions. Coding exons and
at least 50 base pairs of the adjacent intronic regions of the
GJB2
(NC_000013 and NM_86849), MTRNR1 (NC_001807) and
SLC26A
(NC_000007.13 and NM_000441) genes were amplified
by polymerase chain reaction (PCR), followed by bidirectional
sequencing using the BigDye Terminator Cycle Sequencing Kit
(Applied Biosystems by Life Technologies, Foster City, CA).
Fig. 1. Flow diagram of enlarged
vestibular aqueduct (EVA) study
population. *HL
¼
hearing loss; **HF
¼
high frequency. [Color figure can
be viewed in the online issue, which
is available at wileyonlinelibrary.
com.]
Laryngoscope 123: June 2013
Greinwald et al.: Unilateral Enlarged Vestibular Aqueduct
134