2010 Copyright @ Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.

Corticosteroids in the Treatment of Vestibular Neuritis:

A Systematic Review and Meta-Analysis
*John K. Goudakos, *Konstantinos D. Markou, Valerie Franco-Vidal,
*Victor Vital, *Miltiadis Tsaligopoulos, and Vincent Darrouzet
*1st Department of OtorhinolaryngologyYHead and Neck Surgery, ENT Department, AHEPA University
Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; and Department of Otolaryngology and
Skull Base Surgery, Pellegrin University Hospital, University of Victor Segalen Bordeaux 2, Bordeaux, France
Objective: To systematically review and meta-analyze the
results of all randomized controlled trials comparing cortico-
steroids with placebo for the treatment of patients with vestib-
ular neuritis.
Data Sources: An electronic search was performed in
MEDLINE, EMBASE, Cochrane Library, and CENTRAL
databases, and then extensive hand-searching was performed
for the identification of relevant studies. No time and language
limitations were applied.
Study Selection: Prospective randomized controlled trials com-
paring corticosteroids with placebo for the treatment of patients
with vestibular neuritis.
Data Extraction: Odds ratios (ORs), weighted mean differ-
ences (WMD), 95% confidence intervals (CIs), and tests for
heterogeneity were reported.
Data Synthesis: Four studies were eventually identified and
systematically reviewed. Meta-analysis was feasible for 3 stu-
dies. Regarding the recovery of clinical symptoms, the propor-
tion of patients with clinical recovery at 1 month after the
initiation of therapy did not differ significantly between the cor-
ticosteroids and placebo groups (OR, 1.45; 95% CI, 0.26Y8.01;
p = 0.67). The proportion of patients with caloric complete
recovery was significantly different between the corticosteroids
and placebo groups both at 1 (OR, 12.64; 95% CI, 2.6Y61.52;
p = 0.002; heterogeneity, p = 0.53; fixed effects model) and
12 months (OR, 3.35; 95% CI, 1.45Y7.76; p = 0.005; hetero-
geneity, p = 0.03; random effects model) after the initiation of
therapy. The caloric extent of canal paresis at 12 months after
the initiation of therapy seemed to differ significantly between
patients who received corticosteroids and those who received
placebo (WMD, j12.15; 95% CI, j19.85 to j4.46; p G 0.05;
heterogeneity, p G 0.05; random effects model).
Conclusion: The present systematic review and meta-analysis,
based on the currently available evidence, suggests that corti-
costeroids improve only the caloric extent and recovery of canal
paresis of patients with vestibular neuritis. At present, clinical
recovery does not seem be better in patients receiving cor-
ticosteroids. Key Words: CorticosteroidsVMeta-analysisV
NeuritisVRandomizedVVestibular.
Otol Neurotol 31:183Y189, 2010.
Vestibular neuritis (VN) is 1 of the 3 most common
causes of peripheral vestibulopathy, with its incidence
reported to reach 3.5 per 100,000 (1,2). The symptoms
of VN includes an acute or subacute onset of sustained
rotatory vertigo, gait and postural imbalance with ten-
dency to fall, nausea, and vomiting.
The cause of the disease remains unsettled. Initially,
inflammation of the vestibular nerve and labyrinth ische-
mia had been proposed as the possible underlying cause
(3Y5). Recently, the theory of virus infection has been
postulated (2,6). Furthermore, atrophy of the vestibular
nerve and sensory epithelium, being similar to the histo-
pathological findings in herpes zoster oticus, has been
reported (7). The detection of DNA of herpes simplex
virus 1 in human vestibular ganglia, using the methods of
polymerase chain reaction, remains an additional sign of
virus involvement in the pathogenesis of VN (8Y10).
The natural course of VN is characterized by an in-
complete recovery. Clinical recovery is achieved via pro-
prioceptive and visual substitution for the unilateral
vestibular deficit combined with central vestibular com-
pensation of the imbalance in vestibular tone (11). Several
studies have reported continuous or episodic vertigo or
unsteadiness in 43 to 53% of patients (12,13). In 1993,
Okinaka et al. (14) supported that horizontal semicir-
cular canal paresis occurred in approximately 90% of
patients approximately 1 month after the onset of symp-
toms and in 80% approximately 6 months after the onset
Address correspondence and reprint requests to John K. Goudakos,
M.D., M.Sc., Otolaryngology Department, AHEPA Hospital, Aristotles
University of Thessaloniki, 54636 Thessaloniki, Greece; E-mail:
[email protected]
Otology & Neurotology
31:183Y189 2010, Otology & Neurotology, Inc.
183
2010 Copyright @ Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
of symptoms, whereas the caloric responses were normal-
ized in only 42% of them. However, it should be noted that
the vestibular impairment, deriving from the results of bed-
side and laboratory tests, does not reflect the subjective
clinical complaints and the level of incapacity (15).
Nowadays, the therapeutic choices for VN include (a)
corticosteroids, (b) antiviral therapy (acyclovir or val-
acyclovir), and (c) combination of corticosteroids and
antiviral agent. In the acute phase of VN, patients are
mostly treated by short-term vestibular suppression. The
rationale for treatment of patients with VN with cor-
ticosteroids is based on the reports of positive effects
of steroid therapy to patients experiencing acute cranial
nerves neuropathies, such as optic neuritis, facial nerve
paresis, and idiopathic hearing loss (16Y19). In addition,
the activation of glucocorticoid receptor was reported to
enhance vestibular compensation after acute peripheral
vestibular insults in various animal models (20,21).
The purpose of this systematic review was to address
the following question: Among patients with VN, is the
improvement of clinical symptoms and of the extent of
caloric paresis significantly different between patients
receiving corticosteroids and those not receiving any
drug agent (placebo group)?
PATIENTS AND METHODS
Search Strategy
A computer literature search in MEDLINE, EMBASE, the
Cochrane Library (Issue 1, 2008), and CENTRAL electronic
databases was performed by the 2 reviewers (J.G. and K.M.)
from October 10 to November 10, 2008, to identify studies that
answered the question of interest. For this purpose, the follow-
ing free-text terms were used: Bvestibular neuritis/neuronitis[
or Bidiopathic acute vestibular loss[ or Bunilateral vestibular loss[
combined with Bdrug therapy[ orBsteroids/corticosteroids/cortisone/
prednisolone/presolone/methylprednisolone/dexamethasone/
glucorticoids[or Btreatment[or Btherapy[andlimitedtoBhuman.[
In addition, extensive hand-searching of the references of all
relevant studies was performed. No time and language limita-
tions were applied.
Selection of Studies
All criteria for inclusion/exclusion of studies in the present
systematic review were specified before the literature search. In
order for a study to be eligible the following criteria should be
met: (a) The study should be a randomized controlled trial and
compare any type of corticosteroid therapy with placebo treat-
ment regardless of the route (oral or parenteral), the dose, and
the duration of administration. Vestibular sedatives should have
been administered in all patients for symptomatic relief regard-
less of the subsequent therapy with either corticosteroids or
placebo. (b) The study should include patients who started
therapy in the acute or subacute (within 3 or 5 d from the
onset of the disease, respectively) period of the disease. (c)
The follow-up protocol should include assessments of patients
clinical status at least 1 month after the onset of the disease.
The following exclusion criteria were also established: (a)
any study including patients with uncontrolled diabetes, severe
hypertension, contraindications to receive steroids, and vestib-
ular or cochlear symptoms before recruitment to the study; and
(b) any study including pregnant or breastfeeding women.
In case the published articles did not provide all the neces-
sary information for the assessment of potential eligibility, the
authors were contacted and asked to provide the missing data.
Studies Identified
The electronic search resulted in the initial identification of
157 publications. Subsequently, the titles of these articles were
examined to exclude irrelevant studies, resulting in 34 poten-
tially eligible articles. The abstracts of these articles were exam-
ined, and 14 articles that could provide data to answer the
research question of interest were identified (Fig. 1). The full
texts of these studies were examined thoroughly, resulting in
the exclusion of 10 publications.
The references of all the studies in which the full text was
retrieved were hand-searched. However, no additional studies
that could provide data to answer the research question were
identified. Eventually, 4 studies, comparing corticosteroids with
placebo agents in patients with VN, were identified (Table 1).
Eligibility of these studies for the present systematic re-
view was assessed independently by 2 of the reviewers (J.G.
and K.M.). Any disagreement was resolved unanimously by
discussion.
FIG. 1. Flow diagram for study selection.
184 J. K. GOUDAKOS ET AL.
Otology & Neurotology, Vol. 31, No. 2, 2010
2010 Copyright @ Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
Data Extraction
Data extraction was performed by 2 of the reviewers (J.G.
and K.M.). The following data were recorded from each of the
eligible studies: general characteristics (type of study, citation
data, number of patients included, and their baseline character-
istics), procedures (type of randomization, inclusion criteria,
protocol of follow-up, protocol of corticosteroid therapy or
placebo, and number of patients who dropped out of the
study), and outcome data (vestibular clinical signs, the im-
provement, or recovery of unilateral vestibular loss according
to the caloric test findings).
Outcomes
The outcome measures chosen for this systematic review and
meta-analysis were as follows: (i) Clinical recovery of patients
from vestibular symptoms at 1, 3, and 6 months after the initia-
tion of therapy. Assessment of clinical symptoms was conducted
either after the examination of patients (vertigo, spontaneous nys-
tagmus, or tendency to fall) or after the report of their subjec-
tive handicap, using specific questionnaires, such as Dizziness
Handicap Inventory (DHI). (ii) Caloric complete recovery of
unilateral vestibular loss at 1 and 12 months after the initiation
of therapy according to the findings of electronystagmogra-
phy (ENG) after caloric irrigation. The magnitude of canal pare-
sis was calculated using Jongkees formula (22). The rate of
Jongkees formula less than 25% was considered as normal, indi-
cating the complete recovery of canal paresis. (iii) And laterali-
zation in ENG caloric test 1 and 12 months after the initiation
of therapy.
Quantitative Data Synthesis
The dichotomous data results for each of the eligible studies
for meta-analysis were expressed as an odds ratio (OR) with
95% confidence intervals (CI). These results were combined for
meta-analysis using the Mantel/Haenszel model, when using
the fixed effects method, and the DerSimonian and Laird
model, when using the random effects method. When the out-
come measure of interest was a continuous variable, the differ-
ences were pooled across the studies, resulting in a weighted
mean difference (WMD) with 95% CI. The inverse variance
method and the DerSimonian and Laird model were used,
respectively, when the fixed or random effects method was
applied.
The Revman Software (The Cochrane Collaboration, 2000)
was used to combine the results for meta-analysis. Inconsis-
tency of studies (study-to-study variation) was assessed by
using the W
2
statistic (the hypothesis tested was that the studies
are all drawn from the same population, i.e., from a population
with the same effect size). A fixed effects model was used when
no heterogeneity was present, whereas a random effects model
was applied in the presence of significant heterogeneity.
Furthermore, subgroup analyses based on (i) the duration
between disease onset and therapy start, (ii) the type and dosage
of the corticosteroid that was used in corticosteroids group, and
(iii) whether the physicians that performed the assessments of
the outcomes were aware of allocated treatment were planned
to be performed.
A sensitivity analysis by excluding studies not clearly report-
ing the procedure of randomization and patient allocation was
also planned to be performed to check the stability of the
results obtained.
RESULTS
Four studies fulfilled the inclusion criteria. Character-
istics of the eligible studies are listed in Tables 1 and 2.
Systematic Review
The eligible studies were published between 1990 and
2008. Two studies used a truly randomization method
for allocation of patients to groups, and 2 studies used
quasirandomization methods. Study size ranged from 20
to 73 patients, whereas 159 patients were reviewed in total
(corticosteroids group = 78, placebo group = 81; Table 1).
Regarding the type of corticosteroid used, in 3 studies,
the patients received methylprednisolone, whereas the
patients of the remaining study received prednisone.
Details about the daily dose and the length of regimen
used in each study group are provided in Table 2.
In all the eligible studies, the follow-up procedure
included assessments of the patients for at least 1
month (Table 2). In 1 study, patients recovery was eval-
uated only at 1 month after the initiation of therapy
(23). Two studies included only long-term follow-up of
patients (24,25).
In 1 study, the researchers selected the occurrence of
vestibular clinical signs at 1 month after the initiation of
therapy as their main outcome measure (26). Recovery,
according to the findings of caloric irrigation, at 1 and
12 months after the onset of therapy was used as the
main outcome measure in 3 studies (23,24,26). Im-
provement of caloric paresis at 1 and 12 months after
TABLE 1. Demographic data of the studies included in the systematic review
Study number
Authors, publication
year, journal Design Sample size
Sample size of
steroids group
Sample size of
placebo group
RandomizationVpatient
allocation
1. Strupp et al., 2004, N Engl
J Med
Randomized 73 35 38 Computer-generated block
2. Shupak et al., 2008,
Otol Neurotol
Quasi-randomized 30 15 15 Pseudorandomization
3. Ariyasu et al., 1990, Arch
Otolaryngol Head Neck Surg
Randomized 20 10 10 NR
4. Kitahara et al., 2003,
Neurol Res
Quasi-randomized 36 18 18 Pseudorandomization
NR indicates not reported.
185 CORTICOSTEROIDS IN VESTIBULAR NEURITIS
Otology & Neurotology, Vol. 31, No. 2, 2010
2010 Copyright @ Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
the initiation of treatment was assessed in 2 studies
(24,26). The initial severity of canal paresis of patients
with VN, based on caloric findings of ENG, was reported
in 2 studies (Table 2).
Two studies supported that corticosteroids improves
the long-term recovery of peripheral vestibular function
in patients with VN (24,25). The other 2 studies reported
that therapy with corticosteroids provides earlier im-
provement, regarding the recovery of peripheral vestibular
function, but does not improve the long-term prognosis of
patients with VN (23,26).
Meta-Analysis
Of 4 studies, 3 provided relevant data for quantitative
synthesis being eligible for our meta-analysis.
Recovery of Clinical Symptoms
Only 1 study provided data regarding the clinical re-
covery, and for this reason, meta-analysis was not fea-
sible (26). In this study, the proportion of patients with
recovery of clinical symptoms (defined as lack of signs
and symptoms) at 1 month after the initiation of therapy
did not differ significantly between the corticosteroids
and placebo groups (OR, 1.45; 95% CI, 0.26Y8.01;
p = 0.67). The same was true at 3 (OR, 1.71; 95% CI,
0.40Y7.29; p = 0.47) and 6 months (OR, 1.75; 95% CI,
0.40Y7.66; p = 0.46) after the initiation of therapy.
The lack of significant difference between the corti-
costeroids and placebo groups at the first month of
assessment was also revealed based on the results of
DHI (WMD, 5.10; 95% CI, j7.52 to 17.72; p = 0.43).
Caloric Complete Recovery
The proportion of patients with caloric complete
recovery at 1 month after the initiation of therapy was
significantly different between corticosteroids group and
placebo group according to the results from 2 studies
(OR, 12.64; 95% CI, 2.6Y61.52; p = 0.002; heterogene-
ity, p = 0.53; fixed effects model; Fig. 2) (23,26).
Regarding the assessments of caloric paresis 12 months
after the initiation of therapy, the proportion of patients
with caloric compete recovery was significantly differ-
ent between the corticosteroids and placebo groups (OR,
3.35; 95% CI, 1.45Y7.76; p = 0.005; heterogeneity, p =
0.03; random effects model; Fig. 3).
When only the studies that reported a detailed analysis
of the randomization procedure and patient allocation
were analyzed, caloric complete recovery of canal pare-
sis at 12 months after the initiation of therapy differed
significantly between the corticosteroids and placebo
groups (OR, 6.35; 95% CI, 2.25Y17.39; p G 0.05).
Lateralization in ENG Caloric Test
A meta-analysis regarding the findings of lateraliza-
tion in caloric test at 1 month after the initiation of ther-
apy was not feasible because results from only 1 study
are available.
However, the lateralization in the caloric test at
12 months after the initiation of therapy seemed to differ
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186 J. K. GOUDAKOS ET AL.
Otology & Neurotology, Vol. 31, No. 2, 2010
2010 Copyright @ Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
significantly between patients who received corticoster-
oids and those who received placebo (WMD, j12.15;
95% CI, j19.85 to j4.46; p G 0.05; heterogeneity, p G
0.05; random effects model; Fig. 4).
DISCUSSION
The current systematic review and meta-analysis sup-
ports that the administration of corticosteroids to patients
with VN seems to provide benefit only to the caloric re-
covery of canal paresis and not to the recovery of clinical
symptoms.
In this systematic review and meta-analysis, the recov-
ery of vestibular signs was chosen as the main efficacy
measure because the primary goal of medical practice
remains the improvement of patients clinical symptoms.
However, only one of the eligible studies included recov-
ery of clinical symptoms (defined by lack of symptoms
and signs) of patients among their outcomes. The results
for this study do not support the presence of a benefit
from administering corticosteroids to patients with VN
compared with placebo after 1, 3, and 6 months from
presentation (26). However, as the previously mentioned
conclusion derives from the results of a single study, it
should be interpreted with caution.
It should be noted that in the aforementioned study by
Shupak et al. (26), the authors report a significant in-
crease in the Bcomplete resolution[ of patients receiving
corticosteroids 3 and 6 months after presentation com-
pared with those receiving placebo. This outcome, how-
ever, is different from the outcome Bclinical recovery[
that was used in the present meta-analysis because in
addition to the absence of clinical symptoms, it also in-
cludes a normal otoneurologic examination, DHI score
less than 6, caloric test lateralization less than 25%, and
normal ENG findings. Nevertheless, it should be stressed
that in that same study the authors report that this differ-
ence in favor of corticosteroids in complete resolution
was still not present 12 months after presentation.
It should be noted that proper evaluation of the reha-
bilitation of patients with VN requires both the assess-
ment of Bstatic[ symptoms (without head movement),
such as spontaneous nystagmus, vertigo, tendency to fall,
and Bdynamic[ dysfunction. This last dysfunction mani-
fests in the form of a retinal slip of images of the visual
scene with oscillopsia during rapid, high-frequency head
movements, walking, and running because of the insuf-
ficiency of the vestibular ocular reflex (VOR) (27,28).
Electronystagmography caloric test is one of the assess-
ment methods of VOR, indicating the improvement of
canal paresis of patients with VN.
In the present systematic review and meta-analysis,
patients who received corticosteroids had significantly
higher probability of caloric complete recovery com-
pared with those who received placebo, both at the 1st
and 12th month of assessment after the initiation of ther-
apy. The benefit from administrating corticosteroids to
FIG. 3. Odds ratio of complete recovery rate of caloric paresis 12 months after the initiation of therapy, evaluating the benefit of
administrating corticosteroids in patients with VN (p G 0.05). The measure of the effect of each study and of the meta-analysis is
represented with a square and a diamond, respectively. The vertical line representing no effect is also plotted.
FIG. 2. Odds ratio of complete recovery rate of caloric paresis 1 month after the initiation of therapy, evaluating the benefit of admin-
istrating corticosteroids in patients with VN (p G 0.05). The measure of the effect of each study and of the meta-analysis is represented with
a square and a diamond, respectively. The vertical line representing no effect is also plotted. df indicates degrees of freedom; M-H, Mantel/
Haenszel model.
187 CORTICOSTEROIDS IN VESTIBULAR NEURITIS
Otology & Neurotology, Vol. 31, No. 2, 2010
2010 Copyright @ Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
patients with VN was also revealed at the assessment of
the extent of caloric paresis 12 months after the initiation
of therapy.
A plausible explanation regarding the beneficial effect
of corticosteroids on the complete recovery of caloric
paresis might be the reduction of the swelling of the
vestibular nerve (that causes a mechanical compression
of the nerve within the temporal bone) through the anti-
inflammatory action of the corticosteroids. Moreover, in
animal experiments, corticosteroids reported to have an
effect not only on the inflammatory process but also on
the central compensation of the unilateral labyrinthine
deficit (29,30).
Considering the natural course of VN, the present sys-
tematic review confirms the previously reported lack
of correlation between recovery of clinical symptoms
and of caloric lateralization regardless of the treatment
strategy (corticosteroids or placebo) (12). Most patients
feel symptom-free 1 to 6 weeks after onset of disease, but
the functional restitution of the vestibular nerve demands
long-term central compensation.
It should be noted, however, that the results of the
present systematic review are liable to certain limitations.
Revealing the statistical significance of treatment benefit
in studies of VN requires a large number of patients
because of the variable spontaneous recovery profile of
patients. The long-term prognosis of patients with VN
was assessed mainly by the ENG caloric test, which
includes inherent limitations. The caloric test assesses
only the horizontal semicircular canal or the portion of
the superior vestibular nerve that innervates this canal.
However, approximately one-third of patients with VN
have loss of function in the inferior vestibular nerve as
well; the persistent dysfunction of which may be respon-
sible for the lack of recovery from the clinical symptoms
(31Y33). Moreover, caloric response is dependent on the
morphology of the ear, the pneumatization of mastoid
cells, and the patients alertness (34Y36). Finally, it
should be noted that the caloric test assesses only the
low-frequency VOR (up to 0.003 Hz), being unable to
evaluate the high-frequency function of the peripheral
vestibular system (37). The dynamic tone imbalance can
be assessed clinically by provoking a directional head-
shaking nystagmus or testing of the high-frequency
VOR with head-impulse test (37Y39). Thus, the reported
long-term handicap of patients with VN might be justifi-
able, despite normal ENG caloric findings (37,40).
CONCLUSION
The present systematic review and meta-analysis,
based on the currently available evidence, suggests that
corticosteroids improve only the caloric extent and re-
covery of canal paresis of patients with VN. At present,
clinical recovery does not seem to be better in patients
receiving corticosteroids. Further well-designed rando-
mized controlled trials are needed to assess with more
confidence the potential contribution of corticosteroids to
the complete resolution of VN.
Acknowledgments: The authors thank the following persons
for their support in this work: Strupp M. (Germany), Shupak A.
(Israel), Ariyasu L. (United States), and Kiatahara T. (Japan).
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