Conclusions
Lesion-side laterality of the labyrinth in ISSNHL can be identified on
4-hour delayed-enhanced 3D-FLAIR MR images. The extent of enhancement in
the labyrinth is associated with clinical findings such as impaired
audio-vestibular function, and also with the prognosis of ISSNHL.
Keywords : Idiopathic sudden sensorineural hearing loss, 4-hour
delayed 3D FLAIR MRI, Audio-vestibular function, Prognosis.
Level of Evidence ; 4
Key Points
1. Sudden sensorineural hearing loss (SSNHL) is an emergent disease and
significance of 4-hour delayed-enhanced 3D-FLAIR MR imaging for
diagnosis or prognostic factor has not been studied thoroughly.
2. This retrospective study of the 76 patients with ISSNHL aimed to
investigate correlation between 4‐hour delayed enhanced 3D-FLAIR MRI and
audio-vestibular function.
3. Lesion–side labyrinth lesions can be identified by 4hr delayed
3D-FLAIR MRI in patients with idiopathic sudden sensorineural hearing
loss.
4. The extent of labyrinthine enhancement on 4hr delayed 3D-FLAIR MRI is
related to the results of hearing and vestibular function tests.
5. As the extent of labyrinthine enhancement on 4hr delayed 3D-Flair MRI
increased, vertigo became more common, and the sum of the vestibular
function tests increased significantly.
Introduction
Idiopathic sudden sensorineural hearing loss (ISSNHL) is defined as
sensorineural hearing loss that occurs suddenly with no clear cause, and
involves hearing loss ≥ 30 dB at ≥ 3 consecutive frequencies in pure
tone audiometry within 3 days from the onset of the symptom.(1) Although
many underlying causes have been suggested such as vascular
insufficiency, viral infection, auditory nerve tumors, ototoxic drugs,
trauma, autoimmune diseases, and congenital anomalies, the exact cause
and mechanism have not been elucidated. (2, 3) ISSNHL is frequently
accompanied by ear fullness, tinnitus, and vertigo. Since vertigo is a
subjective symptom related to the functioning of the inner ear, patients
are generally given vestibular function tests. Once the video-head
impulse test (vHIT) had been developed, all the vestibular end organs,
including the three semicircular canals (SCCs), could be evaluated.(4)
Steroids are widely used as standard treatment worldwide because of
their effectiveness in restoring hearing; they are generally given
orally or in combination with intratympanic administration of
dexamethasone.(5, 6) Rapid diagnosis and treatment are required because
if treatment is delayed, the prognosis may be affected, and the quality
of life of the patient may decrease.(3)
It is crucial to divide patients with sensorineural hearing loss into
cochlear and retro‐cochlea pathologies. There are various hearing tests,
notably the auditory brainstem response (ABR), for differentiating
retro‐cochlea pathologies. With the development of radiological
examination, magnetic resonance imaging has come to be used to diagnose
retro‐cochlear lesion-induced hearing losses, such as those due to
auditory nerve tumors. Currently magnetic resonance imaging is
recognized as an accurate test for identifying retro‐cochlea pathologies
rather than for detecting pathological changes of the lesion side inner
ear.(7, 8) However, recent studies emphasize the usefulness of 4‐hour
delayed‐enhanced 3.0 Tesla (3T) 3D‐FLAIR MR images with double-dose
intravenous gadolinium (Gd) for prognosis of ISSNHL and have suggested
that focal contrast enhancements in the inner ear are due to breakdown
of the blood-labyrinth barrier.(9, 10) Various MRI protocols have been
introduced to identify subtle changes in the inner ear from the contrast
enhancement period. There is a recent report that 4-hour delayed
enhanced images can identify efficiently neuroinflammatory conditions in
the inner ear. In contrast, 10-minute delayed enhanced images may be
better at identifying non-neuroinflammatory findings.(11) Therefore, the
aim of this study was to investigate the correlation between focal
enhancement of the affected inner ear on 4‐hour delayed‐enhanced 3D
FLAIR MRI and audio-vestibular function in ISSNHL, and to analyze its
utility for prognosis.
Materials and methods
Study populations and subjects
A total of 323 patients with unilateral hearing loss visited our
hospital from June 2016 to November 2020. The diagnostic criterion for
idiopathic sudden hearing loss was sensorineural hearing loss ≥ 30 dB at
≥ 3 consecutive frequencies in pure tone audiometry without apparent
cause within 3 days from the onset of the symptom. Patients with
conductive hearing loss of ≥10 dB and hearing loss due to trauma or
retro-cochlear pathologies were excluded from the analysis. 76 patients
were eventually diagnosed with ISSHL and completed the study protocol;
their medical records were retrospectively analyzed following STROBE
guidelines, and all were treated with high-dose oral steroid for 5 days.
If their hearing improved, the dose was gradually reduced over 7 days.
If there was no improvement in hearing, the steroid dose was reduced,
and intratympanic steroid was injected 4 times over 2 weeks. The study
was reviewed and approved by the Institutional Review Board of “Blinded
for review” (IRB FILE No: 2021-10-008).
Audio - vestibular tests
Audiologic and vestibular function tests, including the video–head
impulse test (vHIT), cervical vestibular-evoked myogenic potential test
(cVEMP), ocular vestibular-evoked myogenic potential test (oVEMP), and
caloric test, were performed for diagnosis and evaluation. A single
senior audiologist performed the tests. For all three semicircular
canals, high-frequency vestibulo-ocular reflex (VOR) gains were measured
by vHIT using an ICS Impulse (GN Otometrics, Taastrup, Denmark).
VOR-gain abnormality was defined as VOR-gain <0.8 for
horizontal canals or <0.7 for vertical canals.(12) The cVEMP
testing saccule and the oVEMP testing utricle were used to evaluate
otolith function, employing an auditory evoked potential system, the
Biologic Navigator Pro (Biologic System Corp., IL). If the response was
absent or the P1-N1 amplitude differed by
>30% on the two
sides, it was considered abnormal.(13) The horizontal canals were
evaluated with the caloric test using a Visual Eyes 4-channel
VNGTM (Micromedical Technologies, Illinois,USA) or an
ICS Chartr 200 (GN Otometrics, Denmark). According to Jongnkee’s
formula, if the canal paresis (CP) value was ≥30%, it was defined as
abnormal.(14) Also, the vestibular function test was recalculated by
summing the scores on each test including vHIT, o-cVEMP and the caloric
test, and by defining normal as 0 and abnormal as 1 for each test.
Pure tone audiometry was performed at first visit and 3 months after the
end of treatment to assess hearing recovery. The average hearing
threshold was calculated by the hexadecimal method of 500, 1000, 2000,
and 4000 Hz, and hearing recovery was evaluated according to the AAO-HNS
hearing classification. Complete recovery was defined as hearing
improvement with a difference of less than 10dB from the unaffected
side, partial recovery as the hearing threshold improved by 10dB or
more, and no recovery as the hearing threshold improved by less than
10dB.
3D‐FLAIR MRI
4‐hour delayed‐enhanced 3D‐FLAIR MRI using double‐dose IV gadolinium was
performed in all cases before treatment was started. All scans involved
3 Tesla MRI (Achieva 3T; Philips Healthcare, Best, The Netherlands)
using a receive‐only 32‐channel phased array coil. 3D-FLAIR imaging was
performed before and after intravenous administration of a double dose
of Gd–DTPA at 0.2 mmol/kg. Contrast-enhanced 3D-FLAIR was initiated 4
hours after Gd administration. Two head and neck radiologists evaluated
the MR images visually and recorded them separately as positive or
negative in terms of lesion-side laterality. The extent of enhancement
in the inner ear was also assessed. Lesion-side laterality was defined
when the MR image of the inner ear structure including cochlea,
vestibule and semicircular canals showed obvious contrast enhancement
and clear asymmetry compared to the unaffected ear (Figure 1). In our
study, the extent of enhancement in the inner ear was classified as E0,
E1 or E2. E0 was defined as the absence of lesion-side laterality; E1 as
focal enhancement of the cochlea only, on the lesion side, and E2 as
enhancement of the cochlea and other inner ear structures including
vestibule and/or semicircular canals (Figure 2).
Statistics
Statistical analysis was performed using SPSS version 19.0 (IBM Corp.,
Armonk, NY, USA). Continuous variables were expressed as mean ± standard
deviation, and categorical variables as frequencies and ratios.
Independent t-tests and one-way ANOVA were used for comparisons of
continuous variables, and Pearson’s chi-square test for categorical
variables. P values <0.05 were considered statistically
significant.
Results
Demographics
Of the total of 76 patients, 30 (39.5%) were male, and the mean age was
53.0 (±14.3) years. In terms of underlying disease, 20 patients (26.3%)
had hypertension, 22 (28.9%) diabetes mellitus, and 5 (6.6%)
cardiovascular or cerebrovascular disease. The affected ear was on the
right in 24 cases (31.6%), and there was no case where both sides were
affected. The mean time to start treatment after symptom onset was
4.7±10.5 days. At the time of admission, average hearing was 72.1(±9.3)
dB on pure tone audiometry. Associated symptoms included vertigo (23,
30.3%), tinnitus (49, 64.5%), and ear fullness (52, 68.4%). Fifteen
patients (19.7%) received only high-dose oral steroid therapy; since no
hearing recovery was detected in the remaining 61 patients (80.3%)
after administration of oral steroids, intratympanic steroid injection
was added to the treatment. No patients received only intratympanic
steroid. Thirty-six (47.4%) patients recovered their hearing completely
according to AAO-HNS guidelines, 19 (25%) recovered their hearing
partially, and 21 (27.6%) patients showed no improvement in hearing.
Factors associated with hearing recovery
Based on the AAO-HNS hearing classification, the patients were
classified into three groups: complete, partial, and no hearing
recovery. Table 1 compares certain characteristics of these groups. A
history of cardiac or cranial vascular disease was significantly
associated with recovery rate (P=0.024). Also, patients with normal
oVEMP (P=0.006), high posterior semicircular canal gain in vHIT
(P=0.006), a low initial hearing threshold (P=0.000) and better speech
discrimination (P=0.008) had a better hearing prognosis.
Lesion-side laterality on 3D‐FLAIR MRI
All 76 patients underwent 4‐hour delayed‐enhanced 3D‐FLAIR MRI, and 31
(40.8%) had an obviously asymmetric enhancement of the inner ear
structures. In all the latter cases, the asymmetry was in the affected
ear. A comparison of clinical parameters according to presence or
absence of lesion-side laterality is presented in Table 2. The recovery
rate of patients with lesion-side inner ear enhancements was
significantly lower than that of patients without such enhancement
(P=0.028).
Extent of the enhancement in the labyrinth on 3D‐FLAIR MRI
According to the extent of enhancement in the inner ear we divided the
patients into groups E0, E1 and E2, corresponding to absence of
lesion-side laterality, focal enhancement of cochlea only and
enhancement of cochlea and other inner ear structures, respectively.
Table 3 shows the associations between clinical parameters and extent of
inner ear enhancement. There was no difference in sex, age, or
comorbidity between these groups. Initial hearing in the three groups
was 68.93±23.14dB in E0, 72.79±25.17dB in E1, and 82.67±24.73 in E2,
with no statistically significant difference between them. Speech
discrimination was 48.21±40.41, 32.44±39.57 29.82±42.42, respectively,
in the three groups, again with no statistically significant difference
between them. Furthermore, the results of the vestibular function tests
were not related to the extent of inner ear enhancement. However, as the
extent of enhancement of the inner ear increased, vertigo became more
frequent (P=0.011) and lateral canal gain declined or became abnormal
(P=0.030, P=0.020).
Vestibular function test SUM scores
All patients underwent vestibular function tests including vHIT, a
caloric test, oVEMP and cVEMP. Each test was scored as 0 for normal and
1 for abnormal. After summing the results of different combinations of
tests, the resulting groups were compared in terms of the extent of
inner ear enhancement. Table 4 shows that, for all the combinations of
VHT tests (except oVEMP+cVEMP ) the extent of abnormality of the test
results increased significantly as the extent of lateral hyperintensity
increased.
Discussion
We have studied the relationship between 4hr delayed 3D FLAIR MRI
findings and audio-vestibular function in patients with idiopathic
sudden sensorineural hearing loss (ISSNHL). Our results can be
summarized as follows; (1) of 76 patients, 31 (40.4%) showed focal
enhancement in the affected inner ear and the patients had a
significantly lower hearing recovery rate than those without focal
enhancement. (2) Hearing recovery was better when the initial hearing
threshold was higher. (3) The lower the PSCC gain in vHIT, the poorer
the hearing recovery rate. (4) While the individual vestibular function
test results were not significantly correlated with the extent of
enhancement in the labyrinth, the sum of the vestibular function
tests was significantly correlated with the extent of enhancement.
ISSNHL is a medical emergency that lasts for several hours to several
days without any specific cause, and its etiology has not been
elucidated. Many factors are associated with the etiology and treatment
of the disease, and for this reason we needed to evaluate a variety of
aspects of the patients.
3D FLAIR MRI, which we used as a
diagnostic tool for evaluating inner ear structure, is a routine type of
brain MR imaging. It yields an image of the lesion restricted by water
signal suggesting local hemorrhage and concentrated protein material due
to an increase in permeability.(10) Additionally, after gadolinium
injection, if there is breakdown of the blood labyrinth barrier (BLB) in
the affected ear, the MRI identifies any contrast enhancement in the
labyrinth. The breakdown of the blood labyrinth barrier (BLB) causes
disruption of inner ear homeostasis and damages the inner ear structure.
It can be associated with many pathological conditions such as
infections, inflammation, hypoxia, and noise exposure, which resemble
the causes of ISSNHL. Hence, focal enhancement and high-intensity
signals on 3D-FLAIR images after injection of gadolinium are important
findings in indicating various pathologic conditions of the inner
ear.(15) 3D FLAIR MRI is also emerging as a clinical indicator of the
prognosis of the disease after treatment, not only as a way to detect
retro‐cochlear lesion-induced hearing loss such as that due to auditory
nerve tumors. There have been several studies of the usefulness of 3D
FLAIR images in ISSNHL. In one study, a comparison was made between
cases showing focal enhancement of the cochlear base only of the
affected inner ear, those with enhancement of the whole inner ear
including semicircular canals, and those with no inner ear
enhancement.(16) It demonstrated that the greater the contrast
enhancement in the labyrinth, the poorer the hearing prognosis..
In this study, we examined the correlation between the results of 4hr
delayed 3D-Flair MRI with double-dose intravenous Gd and
auditory-vestibular function in patients with ISSNHL, and assessed the
value of 3D-Flair MRI as a prognostic factor. The percentage of patients
with lesion-side laterality was 40.4%, which was similar to that in
previous studies, and cases with lesion-side laterality had a
significantly lower hearing recovery rate than those without laterality.
Blood-labyrinth barrier breakdown, which affects inner ear homeostasis
and structure, is thought to influence the prognosis for hearing
recovery. One previous study of the relationship between the degree of
hearing loss before treatment and hearing recovery after treatment
reported that the prognosis was good when the average hearing threshold
was below 45 dB between 500 and 2000 Hz.(17) Another study demonstrated
that the greater the initial hearing loss, the poorer the prognosis.
(18) We confirmed the latter finding, with a statistically significant
difference in recovery between the two groups. Another report suggested
that abnormal vHIT gain in the posterior SCC is a specific predictor of
incomplete hearing recovery in ISSNHL,(19) and we confirmed that the
lower the PSCC gain in vHIT the poorer the hearing recovery after
treatment. Furthermore, it has been reported that unilateral vestibular
enhancement on 3D FLAIR MRI is not only associated with hearing
prognosis but also with abnormal findings in vestibular function
tests.(20) We were unable to confirm a significant association between
the results of the individual vestibular function tests and the extent
of lateral hyperintensity. However, we found that as the extent of
labyrinthine enhancement on 4hr delayed 3D-Flair MRI increased, vertigo
became more common, and the sum of the vestibular function tests
increased significantly.
The limitations of this study are that it was a retrospective study also
that the vestibular function of the patients could not be compared after
treatment because the vestibular function tests were not repeated, since
the vestibular function of the patients generally adjusted over time. In
addition, two head and neck radiologists read the FLAIR MR images and
there may have been subtle differences in the way they interpreted the
images as there were no objective guidelines for radiologic
interpretation. A prospective study with more cases and a maximum
interval between the onset of ISSNHL and the beginning of treatment
would be desirable, and would allow more accurate assessment of the
clinical value of 4hr delayed 3D FLAIR MRI.
Despite these limitations, this report is noteworthy in that it
discusses the relationship between 4hr delayed 3D FLAIR MRI, the
prognosis of hearing after treatment and the results of vestibular
function tests in ISSNHL. Although the results do not point to a change
in treatment, they may be useful for developing a unified MR imaging
protocol, and for making treatment decisions in the clinic.
Conclusions
In conclusion, we have shown that lesion–side labyrinth lesions can be
identified by 4hr delayed 3D FLAIR MRI in patients with idiopathic
sudden sensorineural hearing loss, and that the extent of labyrinthine
enhancement is related to the results of hearing and vestibular function
tests and prognosis of the disease.
Conflicts of interest
None of the authors have any conflicts of interest.
References
1. Whitaker S. Idiopathic sudden hearing loss. The American journal of
otology. 1980;1(3):180-3.
2. Simmons FB. Theory of membrane breaks in sudden hearing loss.
Archives of Otolaryngology. 1968;88(1):41-8.
3. Chau JK, Lin JR, Atashband S, Irvine RA, Westerberg BD. Systematic
review of the evidence for the etiology of adult sudden sensorineural
hearing loss. The Laryngoscope. 2010;120(5):1011-21.
4. Halmagyi G, Chen L, MacDougall HG, Weber KP, McGarvie LA, Curthoys
IS. The video head impulse test. Frontiers in neurology. 2017;8:258.
5. Kakehata S, Sasaki A, Oji K, Futai K, Ota S, Makinae K, et al.
Comparison of intratympanic and intravenous dexamethasone treatment on
sudden sensorineural hearing loss with diabetes. Otology & Neurotology.
2006;27(5):604-8.
6. Wilson WR, Byl FM, Laird N. The efficacy of steroids in the treatment
of idiopathic sudden hearing loss: a double-blind clinical study.
Archives of otolaryngology. 1980;106(12):772-6.
7. Robson A, Leighton S, Anslow P, Milford C. MRI as a single screening
procedure for acoustic neuroma: a cost effective protocol. Journal of
the Royal Society of Medicine. 1993;86(8):455.
8. Welling DB, Glasscock III ME, Woods CI, Jackson CG. Acoustic neuroma:
a cost-effective approach. Otolaryngology—Head and Neck Surgery.
1990;103(3):364-70.
9. Yoshida T, Sugiura M, Naganawa S, Teranishi M, Nakata S, Nakashima T.
Three‐dimensional fluid‐attenuated inversion recovery magnetic resonance
imaging findings and prognosis in sudden sensorineural hearing loss. The
Laryngoscope. 2008;118(8):1433-7.
10. Sugiura M, Naganawa S, Teranishi M, Nakashima T. Three‐dimensional
fluid‐attenuated inversion recovery magnetic resonance imaging findings
in patients with sudden sensorineural hearing loss. The Laryngoscope.
2006;116(8):1451-4.
11. Kim T, Park D, Lee Y, Lee J, Lee S, Chung J, et al. Comparison of
inner ear contrast enhancement among patients with unilateral inner ear
symptoms in MR images obtained 10 minutes and 4 hours after gadolinium
injection. American Journal of Neuroradiology. 2015;36(12):2367-72.
12. McGarvie LA, MacDougall HG, Halmagyi GM, Burgess AM, Weber KP,
Curthoys IS. The video head impulse test (vHIT) of semicircular canal
function–age-dependent normative values of VOR gain in healthy
subjects. Frontiers in neurology. 2015;6:154.
13. Rosengren SM, Colebatch JG, Young AS, Govender S, Welgampola MS.
Vestibular evoked myogenic potentials in practice: methods, pitfalls and
clinical applications. Clinical neurophysiology practice. 2019;4:47-68.
14. Jongkees L. Value of the caloric test of the labyrinth. Archives of
Otolaryngology. 1948;48(4):402-17.
15. Naganawa S, Komada T, Fukatsu H, Ishigaki T, Takizawa O. Observation
of contrast enhancement in the cochlear fluid space of healthy subjects
using a 3D-FLAIR sequence at 3 Tesla. European radiology.
2006;16(3):733-7.
16. Byun H, Chung JH, Lee SH, Park CW, Park DW, Kim TY. The clinical
value of 4‐hour delayed‐enhanced 3D‐FLAIR MR images in sudden hearing
loss. Clinical Otolaryngology. 2019;44(3):336-42.
17. JL S. Vasodilator therapy in sensory-neural hearing loss. The
Laryngoscope. 1960;70:885-914.
18. Byl Jr FM. Sudden hearing loss: eight years’ experience and
suggested prognostic table. The Laryngoscope. 1984;94(5):647-61.
19. Byun H, Chung JH, Lee SH. Clinical implications of posterior
semicircular canal function in idiopathic sudden sensorineural hearing
loss. Scientific reports. 2020;10(1):1-8.
20. Ryu IS, Yoon TH, Ahn JH, Kang WS, Choi BS, Lee JH, et al.
Three-dimensional fluid-attenuated inversion recovery magnetic resonance
imaging in sudden sensorineural hearing loss: correlations with
audiologic and vestibular testing. Otology & Neurotology.
2011;32(8):1205-9.