 |
|
Sudden Sensorineural Hearing Loss
Does Application of Glucocorticoids Make Sense?
Christoph Alexiou, MD;
Wolfgang Arnold, MD;
Claudius Fauser, MD;
Bruno Schratzenstaller, MD;
Bertrand Gloddek, MD;
Stefanie Fuhrmann;
Kerstin Lamm, MD
Arch Otolaryngol Head Neck Surg. 2001;127:253-258.
ABSTRACT
| |
Background Treatment of sudden sensorineural hearing loss (SSNHL) consists of administration
of blood flow–promoting drugs with or without the addition of glucocorticoids.
General guidelines based on scientific data do not currently exist.
Objective To investigate the effect of glucocorticoids on the treatment of SSNHL.
Setting Academic medical center.
Patients and Methods We retrospectively analyzed the audiograms of 603 patients with SSNHL:
301 patients (cared for between January 1, 1986, and December 31, 1991) received
intravenous blood flow–promoting drugs without glucocorticoids and 302
patients (cared for between January 1, 1992, and December 31, 1998) received
intravenous blood flow–promoting drugs with glucocorticoids (intravenous
± oral application). The age distribution of patients with SSNHL in
lower, middle, and higher frequencies was similar in both groups.
Results Patients with SSNHL in lower and middle frequencies (250-2000 Hz) who
received glucocorticoids (prednisolone-21-hydrogen-succinate) showed significantly
better recovery of hearing levels compared with those who did not receive
glucocorticoids (P<.05). There was no significant
difference at higher frequencies between the 2 groups. Patients with SSNHL
throughout all frequencies (pancochlear hearing loss) who received glucocorticoids
also had significantly better recovery of hearing levels compared with those
who received blood flow–promoting drugs alone (P<.05).
Also, patients with elevated blood sedimentation rates had better improvement
of their hearing levels after receiving glucocorticoids.
Conclusions Administration of glucocorticoids should be recommended for treatment
of patients with SSNHL. In particular, patients with SSNHL in the lower and
middle frequency range and pancochlear hearing loss have significantly better
recovery of hearing levels.
INTRODUCTION
SUDDEN SENSORINEURAL hearing loss (SSNHL) is a frequent disease and
occurs in 1 per 3000 inhabitants in the industrial world.1
It is sudden in onset, isolated, or associated with vertiginous episodes or
tinnitus. The physiopathologic mechanism of this cochlear disorder is unclear,
and a series of causative factors—including viral infection,1, 2, 3, 4 microcirculatory
disorders,5 and immunopathologic1, 6
and autoimmune factors1, 7, 8—are
considered to be possible explanations. In general, the treatment of SSNHL
is nihilistic (no therapy) or is based on the use of blood flow–promoting
drugs with or without glucocorticoids. However, general guidelines, founded
on "evidence-based medicine," are not available, although there are many individual
studies9, 10, 11, 12, 13, 14, 15
in the literature of the successful treatment of SSNHL. Furthermore, most
of these studies lack suitable control groups to prove the therapeutic effect
of the respective agent and include only small patients cohorts. The objective
of this study was to evaluate, in a retrospective analysis of 603 patients,
the therapeutic effect of glucocorticoids for the treatment of SSNHL.
MATERIALS AND METHODS
DEFINITION OF SSNHL
Sudden sensorineural hearing loss is usually unilateral and consists
of impaired hearing or deafness, which appears suddenly without a recognizable
cause. Tinnitus, pressure sensation, or vestibular disorders can also be present.
Inclusion criteria for this study were (1) hearing loss that appeared
acutely and without a recognizable cause, (2) hearing loss of more than 30
dB hearing level (dB HL) affecting 2 or more consecutive frequency levels,
(3) therapy starting within the first 7 days after onset of hearing loss,
and (4) no hearing deficiency in the affected ear in the past. Exclusion criteria
were (1) recurrent SSNHL, (2) therapy starting later than 7 days after onset
of hearing loss, (3) previous surgery in the respective ear, and (4) previously
known hearing impairment.
STUDY DESIGN
Pure-tone audiograms (before and after therapy) from 603 patients in
our hospital (Department of Otorhinolaryngology–Head and Neck Surgery,
Klinikum rechts der Isar, Technical University of Munich, Munich, Germany)
care between January 1, 1986, and December 31, 1998, with the diagnosis of
SSNHL were evaluated retrospectively. The patient collective was divided into
2 study groups: rheotherapy without glucocorticoids (Rh) and rheotherapy with
glucocorticoids (RhG).
Rh Study Group
A total of 301 patients (cared for between January 1, 1986, and December
31,1991) received Rh. These patients were given 500 mL of isotonic sodium
chloride solution intravenously daily for 14 to 16 days, which included pentoxifylline,
100 mg (Trental [1 ampoule with 5 mL = 100 mg of pentoxifylline]; Marion-Roussel,
Bad Soden, Germany), in an increasing dosage (day 1, 100 mg; day 2, 200 mg;
and day 3 and on, 300 mg), or 500 mL of hetastarch (6% HAES-steril; Fresenius-AG,
Bad Homburg, Germany) combined with vitamin B complexes (Polybion forte N
Dragees; Merck, Darmstadt, Germany), 25 mg 3 times daily.
RhG Study Group
A total of 302 patients (cared for between Janaury 1, 1992, and December
31, 1998) received RhG. During the first 3 days, these patients received a
daily intravenous dose of 500 to 1000 mg of prednisolone-21-hydrogen-succinate
(Solu-Decortin H; Merck). In some cases, eg, patients with diabetes, 250 mg
daily was given. These patients also received ranitidine, 150 mg orally (Sostril
[150-mg tablets twice daily]; Cascan/Cascapharm, Hamburg, Germany) for 4 to
5 days to protect the gastric mucosa. In selected patients, if there was no
improvement, the glucocorticoid treatment was continued orally after intravenous
therapy (the oral glucocorticoid scheme began with 100 mg of prednisolone
[Decortin H]; Merck) for 16 days, with a decreasing dosage supplemented by
ranitidine, 150 mg twice daily; 52% of patients (n = 157) were given this
additional oral therapy.
OPERATIVE INTERVENTION
Seven patients (1.2%) had complete unilateral deafness. A tympanoscopy
was performed on the affected ear in these patients to determine whether the
round window membrane of the inner ear had ruptured.
SUBJECTIVE VARIABLES
On hospital admission and discharge, patients were questioned regarding
the quality and quantity of tinnitus, pressure in the ear region, and subjective
feelings of dizziness. All these data were documented.
LABORATORY VARIABLES
On hospital admission, a blood analysis was performed that included
serum levels of sodium, potassium, glutamic oxalacetic transaminase, glutamic
pyruvic transaminase, cholinesterase, protein, C-reactive protein, and blood
coagulation variables (Quick test and partial thromboplastin time); a complete
blood cell count (hemoglobin, hematocrit, erythrocytes, and leukocytes); and
the blood sedimentation rate.
The following variables were ascertained to evaluate cochlear-vestibular
function: complete pure-tone audiogram (frequency levels, 250-8000 Hz), tympanogram,
stapedius reflex, auditory brainstem responses 10 to 14 days after the onset
of hearing loss, and electronystagmogram.
For evaluation of response to therapy, audiometric examinations (pure-tone
audiograms) were performed every 2 to 3 days during hospitalization, always
by the same examination team.
COLLECTION OF DATA AND STATISTICAL ANALYSIS
A form was developed in cooperation with the Institute for Medical Statistics
and Epidemiology, Technical University of Munich, Munich, Germany, to systematically
collect data. On this form, a short medical history and results of pure-tone
audiography, blood analyses, and the ear, nose, and throat examinations of
603 patients were recorded. Data were analyzed using the SPSS software program.16 The U test for unpaired
samples was used to compare the mean values of absolute hearing improvement
in dB HL in both study groups. The sound threshold audiograms before and after
treatment were calculated. Differences were considered statistically significant
at P<.05.
RESULTS
Onset of SSNHL was unilateral in 96% of patients and bilateral in 4%
of patients. The median ± SD time from the onset of SSNHL to the start
of therapy was 5 ± 2 days for both groups. The mean ± SD age
of Rh patients was 49 ± 16 years; 141 were women (47%) and 160 were
men (53%). The mean ± SD age of RhG patients was 47 ± 15 years;
132 were women (44%) and 170 were men (56%). In the RhG group, 157 patients
received an oral glucocorticoid scheme.
ADVERSE EFFECTS
The adverse effects listed in Table
1 were observed during therapy in both study groups.
|
|
|
|
Adverse Effects in Both Treatment Groups*
|
|
|
SUBJECTIVE VARIABLES
Tinnitus was perceived in 78% of the Rh group (234 patients) and in
82% of the RhG group (248 patients). Tinnitus improved in or was no longer
perceived by 71% of Rh patients (n = 165), with the remaining 29% (n = 69)
noting no improvement at discharge from the hospital. In the RhG group, improvement
or cessation of tinnitus was noticed in 75% of patients (n = 186), showing
no significant difference to Rh (P<.68).
AUDIOMETRIC VARIABLES
Figure 1 shows mean ±
SEM values for the Rh group of audiograms performed on hospital admission
and the threshold elevation in the pure-tone audiogram at discharge, which
were used for assessment of response to therapy. After therapy, an average
improvement in hearing was achieved in the Rh group at frequency ranges of
250, 500, and 1000 Hz of 17.6 ± 1.4 dB HL (low frequencies), at 2000
to 4000 Hz of 16.0 ± 1.2 dB HL (middle frequencies), and at 6000 to
8000 Hz of 14.2 ± 1.2 dB HL (high frequencies) (Figure 2).
|
|
|
|
Figure 1. Average values for threshold elevation
in the pure-tone audiogram in the rheotherapy without glucocorticoids group
(n = 301) before and after treatment. Error bars indicate SEM.
|
|
|
|
|
|
|
Figure 2. Average values for threshold elevation
in the pure-tone audiogram in the rheotherapy with glucocorticoids group (n
= 302) before and after treatment. Error bars indicate SEM.
|
|
|
Figure 3 shows the corresponding
data for the RhG group. Mean ± SEM improvement was 23.7 ± 1.8
dB HL at frequency levels of 250, 500, and 1000 Hz, 20.3 ± 1.6 dB HL
at 2000 to 4000 Hz, and 11.7 ± 1.0 dB HL at 6000 to 8000 Hz (Figure 3).
|
|
|
|
Figure 3. Absolute hearing gain in the pure-tone
audiogram after therapy in patients with and without use of glucocorticoids.
Asterisk indicates P<.05. Error bars indicate SEM.
|
|
|
Pure-tone audiograms were performed after completion of therapy, and
the absolute gain in hearing in dB HL for both study groups is depicted in Figure 3. The absolute hearing gain for RhG
in the low- and middle-frequency range was significantly higher than for Rh
(250 Hz, P<.05; 500 Hz, P<.01;
1000 Hz, P<.02; and 2000 Hz, P<.01). After completion of therapy, there was also a noticeably
greater hearing improvement in the RhG group in the frequency range 3000 and
4000 Hz; however, this was not significant (3000 Hz, P<.09;
and 4000 Hz, P<.4). There was no difference between
the groups at 6000 Hz (P<.65), although a greater
hearing gain was noticeable in the Rh group at 8000 Hz, which, however, was
not statistically significant (P<.13).
Pancochlear hearing loss is a severe situation inflicting all frequencies,
and patients have at least a 30-dB hearing loss. This was noted in 23% of
Rh patients (n = 68) and in 17% of RhG patients (n = 52). The absolute hearing
gain at all frequencies, defined as hearing improvement of more than 10 dB
HL over all frequency ranges (pancochlear), was 43% in the Rh group and 62%
in the RhG group (P<.05) (Figure 4).
|
|
|
|
Figure 4. Absolute hearing gain in the pure-tone
audiogram after therapy in patients with pancochlear sudden sensorineural
hearing loss. Asterisk indicates P<.05. Error bars indicate
SEM.
|
|
|
Blood sedimentation rate was obtained in 451 patients and was elevated
(>15 mm/h) in 18% (n = 80). Ninety-six percent of RhG patients improved their
HLs after receiving glucocorticoids, whereas only 74% of Rh patients did so
(Figure 5). In the remaining patients
(having no elevated blood sedimentation rate), there was no difference between
groups (Figure 5).
|
|
|
Figure 5. Left, Therapeutic results in 194
patients in the rheotherapy without glucocorticoids (Rh) group and 177 patients
in the rheotherapy with glucocorticoids (RhG) group with normal blood sedimentation
rates (BSRs) ( 15 mm/h). Right, Therapeutic results in 57 Rh patients and
23 RhG patients with elevated BSRs (>15 mm/h).
|
|
|
A tympanoscopy was performed in 7 patients (1.2%) (2 in the Rh group
and 5 in the RhG group). In 1 patient, a ruptured membrane of the round window
(perilymph fistula) was discovered; it was sealed with connective tissue and
resulted in improved hearing.
Twenty-nine percent of patients (n = 174) also reported dizziness coincident
with the onset of SSNHL. A dysfunction in the ipsilateral vestibular organ
was noted in 65% of these patients (n = 113) in an electronystagmogram. Most
of them subjectively improved; a detailed analysis of the results was not
performed.
An electrocochleogram was performed in 22 patients (12 in the Rh group
and 10 in the RhG group), during which a hydrops was found in 7 patients (1.2%).
These patients were not included in any further evaluation.
COMMENT
Glucocorticoids have cellular actions that target the genome (DNA within
the nucleus) that become evident within 1 to 2 hours and cytoplasmic effects,
mostly at very high doses, that occur after only a few minutes.17, 18(pp19-21)
Each cell contains 2 classes of corticoid receptors, type I (glucocorticoid)
and type II (mineralocorticoid) receptors, both of which are present in the
cochlear and vestibular tissues of mammals.19, 20
When cytoplasmatic glucocorticoid receptors are activated, transcription and
expression of specific genes are activated, which then inhibit the synthesis
of inflammatory mediators and cytokines, which are responsible for the anti-inflammatory
effects of glucocorticoids. Glucocorticoids also affect carbohydrate and protein
metabolism and change the physicochemical characteristics of cell membranes
by promoting their stabilization and reducing the permeability of cations
(cytoplasmic effect). Finally, glucocorticoids also regulate cellular osmolarity
by binding to type II mineralocorticoid receptors, which activate the enzyme
Na,K-ATPase.21 This enzyme is found at the
base of the external and internal hair cells, the tympanic nerve fibers, and
the spiral ganglion cells of mammals.22, 23
The activation of Na,K-ATPase by prednisolone could have positive effects
on disturbed intracellular and extracellular osmolarity, electrochemical gradients,
and neuronal activities, which are disturbed by noise-related cellular, functional
cochlear damage and autoimmune inner ear disease.15, 24, 25
Sudden sensorineural hearing loss usually occurs in healthy persons
and is a dramatic experience for the affected patient because it impairs an
important sensory perception, thus severely limiting the quality of life.
Although dysfunction of the inner ear is not life threatening, the resulting
communication problems can have drastic consequences for the individual's
professional or social life. It has been reported that use of glucocorticoids
might positively affect the expected improvement of hearing in the therapy
of SSNHL. Concerning the effect of glucocorticoids compared with placebo or
no treatment, only 4 clinical trials have been performed.9, 10, 11, 12
Mattox and Simmons12 came to the conclusion
that 20 (71%) of 28 nontreated patients recovered their hearing "completely
or at a good percentage," and 63 (72%) of 88 patients showed similar results
after glucocorticoid therapy. Wilson et al9
reported that of 52 nontreated patients, 29 regained normal hearing ability
(ie, 56%). Excluding patients with a middle-frequency hearing loss, because
spontaneous recovery was always demonstrated,9
17 (49%) of 35 nontreated patients with a low- or high-frequency hearing loss
regained their hearing ability by 3 months after onset of the affliction.9 In contrast, 11 (32%) of 34 placebo-treated patients
recovered their hearing, and 20 (61%) of 33 glucocorticoid-treated patients,
particularly those with moderate hearing loss, showed similar results.9
Moskowitz et al10 deduced that 24 (89%)
of 27 glucocorticoid-treated patients "recovered at least 50% of their hearing,"
whereas 4 (44%) of 9 patients recovered their hearing without any treatment.
Veldmann et al11 found an effective response
to glucocorticoid treatment in 6 (50%) of 12 patients, whereas only 6 (32%)
of 19 nontreated patients showed similar results.
Vischer and Arnold14 observed a similar
effect, and during that time the term "cortisone-sensitive inner ear disease"
was created. Recently, a significant hearing improvement using anti-inflammatory
substances (ie, prednisolone) in noise-induced guinea pigs was observed compared
with an untreated animal group.15 A limiting
factor for the evaluation of the effect of glucocorticoids in all of these
human studies has been the limited number of cases and, therefore, did not
include large enough control groups. Furthermore, the number of patients in
each group is too low to express recovery rates as percentages. Especially
for dividing the group into patients with hearing loss in the low, middle,
and high frequencies, the respective collectives were too small.9, 10, 11, 12
The present study demonstrates in a large number of patients (N = 603) a statistically
significant benefit with use of glucocorticoids (prednisolone) for the improvement
of frequency-specific hearing, ie, in the lower and mediocochlear levels,
compared with a control group receiving no glucocorticoids (Figure 3). The 2 study groups were comparable with respect to age
and sex and showed that sudden hearing loss more frequently affects the left
ear (53%). Furthermore, administration of glucocorticoids for sudden pancochlear
hearing deficiency revealed a significant improvement in hearing (>10 dB HL
at all frequency levels in 43% of the Rh group and 62% of the RhG group) (Figure 4).
Of special interest is the fact that all studies report spontaneous
remission in SSNHL. For example, Weinaug26
described 63 patients in whom hearing recovered completely in 68% and improved
in 89%. Because both study groups in the present investigation are comparable
regarding the number of patients, age and sex, etc, a comparable spontaneous
remission rate would be expected in both groups, meaning that the significantly
higher rate of hearing improvement in RhG can be attributed to the glucocorticoid
therapy.
It has been suggested that disorders of the microcirculation in the
cochlear region5 and changes in plasma viscosity27 impaired cochlear microcirculation due to sludging
of red blood cells, vasospasm, and endothelial swelling. A complete blood
profile was determined in all patients and did not show any significant abnormalities
in hematocrits, hemoglobin levels, leukocyte and erythrocyte counts, or serum
electrolyte levels. Blood sedimentation rates were determined in 451 patients;
18% showed elevated blood sedimentation rates (>15 mm/h), and 96% of RhG patients
had recovery of HLs compared with 74% in the Rh group (Figure 5). This underscores the thesis that inflammatory processes
may cause SSNHL and could be successfully treated with anti-inflammatory agents
such as glucocorticoids.2, 3, 4, 7, 9, 10
Mattucci and Bachoura28 described disorders
of coagulation in patients with SSNHL. In the present SSNHL study groups we
saw only a marginal change in blood coagulation status. The cumulative partial
thromboplastin time of our patients was 25.5 seconds (reference range, 26-37
seconds). The cumulative Quick value (thromboplastin time) was 99% (reference
range, 70%-120%).
Only a few patients experienced adverse effects during therapy with
glucocorticoids, such as increased blood glucose levels, elevated blood pressure,
and transient erythema (mainly in the facial area). By completion of therapy,
however, all symptoms had resolved. For increased blood glucose levels, patients
were temporarily given insulin subcutaneously (Actrapid; Novo Nordisk Pharma,
Mainz, Germany). Patients with diabetes mellitus (n = 21) received only 250
mg of prednisolone-21-hydrogen-succinate for the first 3 days and were closely
monitored for blood glucose levels. Only a few patients showed blood pressure
changes, which were probably caused by application of the rheologic agents
(500 mL of Ringer/pentoxifylline or 500 mL of 6% HAES-steril). None of our
patients had dysrhythmia. Allergic reactions, a rare adverse effect of prednisolone
therapy, occurred in only 1 RhG patient and could be controlled.29
Contraindications for glucocorticoid administration are a recent history
of a stomach ulcer, known left-sided heart insufficiency, renal insufficiency,
or an active bacterial infection. In principle, pregnancy is not a contraindication;
however, a gynecologist should always be consulted for individual cases.30
Sudden sensorineural hearing loss is an acute and often dramatic experience
for the patient that might strongly limit the quality of life. Therefore,
at the beginning of our treatment of SSNHL and according to the principles
of high-dose (pulse-dose) corticoid therapy used by other specialties (neurology,
transplantation medicine, etc), we applied similar high doses. Bührer
et al31 demonstrated in humans that after intravenous
administration of prednisolone, the concentration in cerebrospinal fluid was
only approximately one third of the corresponding plasma concentration. One
hour after intravenous application of methylprednisolone in the perilymph
of guinea pigs, Parnes et al32 measured only
one sixth of the concentration of the corresponding plasma level. Therefore,
high doses are justified to reach effective glucocorticoid levels in the perilymph
and endolymph fluid. More recent experimental studies, however, have shown
that all corticoid receptors are occupied when using approximately 300 mg
of prednisolone.18(pp109-110) However, there
are no currently available data, to our knowledge, concerning the concentration
of glucocorticoids in the perilymph after intravenous application in humans.
An ongoing study is presently being conducted at our institution. Based on
the available knowledge, we give our patients with SSNHL 500 mg of prednisolone-21-hydrogen-succinate
intravenously, combined with histamine2-receptor blockers to protect
the stomach, during the first 3 days of hospitalization.
According to our results, administration of glucocorticoids to patients
with SSNHL is highly recommended, especially for those with acute hearing
deficiencies at the lower, middle, and pancochlear sound levels. However,
the results of this retrospective analysis should be confirmed with a prospective,
randomized, multicenter study.
AUTHOR INFORMATION
Accepted for publication July 13, 2000.
We thank the Margarete Ammon Foundation, Munich, Germany, for supporting
this study and Michael Hennig, Institut für Medizinische Statistik und
Epidemeologie der Technical University of Munich(Prof A. Neiss, Director),
for statistical advice in the analysis of the data.
Preliminary results of this study were presented at the 70th annual
meeting of the German Society of Otorhinolaryngology, Head and Neck Surgery,
Aachen, Germany, May 12, 1999.
From the Department of Otorhinolaryngology–Head and Neck Surgery,
Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Corresponding author and reprints: Christoph Alexiou, MD, Klinikum
rechts der Isar, Hals-Nasen-Ohren Klinik und Poliklinik, Ismaningerstr. 22,
81675 München, Germany (e-mail: C.Alexiou{at}lrz.tu-muenchen.de).
REFERENCES
| |
1. Arnold W, ed, Ganzer U, ed. Checkliste Hals-Nasen-Ohrenheilkunde. 2nd ed. Stuttgart, Germany: Georg Thieme Verlag; 1997:157-158.
2. Schuknecht HF, Benitez J, Beekhuis J, Igarashi M, Singleton G, Ruedi L. The pathology of sudden deafness. Laryngoscope. 1962;72:1142-1157.
3. Schuknecht HF, ed. Pathology of the Ear. 2nd ed. Media, Pa: Lea & Febiger; 1993:235-242.
4. Friedmann I, ed, Arnold W, ed. Pathology of the Ear. New York, NY: Churchill Livingstone; 1993:551-567.
5. Kimura RS. Animal models of inner ear vascular disturbances. Am J Otolaryngol. 1986;7:130-139.
ISI
| PUBMED
6. Arnold W, Altermatt H, Gebbers JO, Pfaltz CR. Zur Frage der Immunpathologie des Innenohrs. Laryngol Rhinol Otol (Stuttg). 1985;64:1-8.
7. Gloddek B, Gloddek J, Arnold W. Induction of an inner ear specific autoreactive T-cell line for the
diagnostic evaluation of an autoimmune disease of the inner ear. Ann N Y Acad Sci. 1997;830:266-276.
ISI
| PUBMED
8. Arnold W. Systemic autoimmune diseases associated with hearing loss. Ann N Y Acad Sci. 1997;830:187-202.
ISI
| PUBMED
9. Wilson WR, Byl FM, Laird N. The efficacy of steroids in the treatment of idiopathic sudden hearing
loss: a double-blind clinical study. Arch Otolaryngol. 1980;106:772-776.
FREE FULL TEXT
10. Moskowitz D, Lee KJ, Smith HW. Steroid use in idiopathic sudden sensorineural hearing loss. Laryngoscope. 1984;94:664-666.
ISI
| PUBMED
11. Veldmann JE, Hanada T, Meeuwsen F. Diagnostic and therapeutic dilemmas in rapidly progressive sensorineural
hearing loss and sudden deafness. Acta Otolaryngol (Stockh). 1993;113:303-306.
PUBMED
12. Mattox DE, Simmons FB. Natural history of sudden sensorineural hearing loss. Ann Otol Rhinol Laryngol. 1977;86:463-480.
ISI
| PUBMED
13. Stokroos RJ, Albers FWJ, Tenvergert EM. Antiviral treatment of idiopathic sudden sensorineural hearing loss:
a prospective, randomized, double-blind clinical trial. Acta Otolaryngol (Stockh). 1998;118:488-495.
FULL TEXT
| PUBMED
14. Vischer M, Arnold W. Kortisonsensible innenohrschwerhörigkeit. Otorhinolaryngol Nova. 1991;1:75-79.
15. Lamm K, Arnold W. The effect of prednisolone and non-steroidal anti-inflammatory agents
on the normal and noise-damaged guinea pig inner ear. Hear Res. 1998;115:149-161.
FULL TEXT
|
ISI
| PUBMED
16. Beutel P, ed, Küffner H, ed, Schubö W, ed. SPSS 8, Statistikprogrammsystem für die Sozialwissenschaften. 3rd ed. Stuttgart, Germany: Gustav Fischer Verlag; 1980.
17. Buttgereit F, Dimmeler S, Neugebauer E, Burmester GR. Wirkungsmechanismen der hochdosierten glukokortikoidtherapie. Dtsch Med Wochenschr. 1996;121:248-254.
PUBMED
18. Kaiser H, Kley HK. Cortisontherapie. 10th ed. Stuttgart, Germany: Georg Thieme Verlag; 1997:19-21.
19. Erichsen S, Bagger-Sjöbäck D, Curtis L, Zuo J, Rarey KE, Hultcrantz M. Appearance of glucocorticoid receptors in the inner ear of the mouse
during development. Acta Otolaryngol. 1996;116:721-725.
PUBMED
20. Furuta H, Mori N, Sato C, et al. Mineralocorticoid type I receptor in the rat cochlea: mRNA identification
by polymerase chain reaction and in situ hybridization. Hear Res. 1994;78:175-180.
FULL TEXT
|
ISI
| PUBMED
21. Pitovski DZ, Drescher MJ, Kerr TP, Drescher DG. Aldosterone mediates an increase in [3H]ouabain binding
at Na,K-ATPase sites in the mammalian inner ear. Brain Res. 1993;601:273-278.
FULL TEXT
|
ISI
| PUBMED
22. Zuo J, Curtis L, Yao X, ten Cate WJF, Rarey K. Expression of Na,K-ATPase a- and b-isoforms in the neonatal rat cochlea. Acta Otolaryngol (Stockh). 1995;115:497-503.
PUBMED
23. Erichsen S, Zuo J, Curtis L, Rarey K, Hultcrantz M. Na,K-ATPase a- and b-isoforms in the developing cochlea of the mouse. Hear Res. 1996;100:143-149.
FULL TEXT
|
ISI
| PUBMED
24. Trune DR, Wobig RJ, Kempton JB, Hefeneider SH. Steroid treatment improves cochlear function in the MRL.MpJ-Fas(lpr)
autoimmune mouse. Hear Res. 1999;137:160-166.
FULL TEXT
|
ISI
| PUBMED
25. Trune DR, Wobig RJ, Kempton JB, Hefeneider SH. Steroid treatment in young MRL.MpJ-Fas(lpr) autoimmune mice prevents
cochlear dysfunction. Hear Res. 1999;137:167-173.
FULL TEXT
|
ISI
| PUBMED
26. Weinaug P. Die Spontanremission beim Hörsturz. HNO. 1984;32:346-351.
ISI
| PUBMED
27. Ciuffetti G, Scardazza A, Serafini G, Lombardini R, Manarino E, Simoncelli C. Whole blood filterability in sudden deafness. Laryngoscope. 1991;101:65-67.
ISI
| PUBMED
28. Mattucci KF, Bachoura L. Sudden hearing loss: ten years' experience. Bull N Y Acad Med. 1982;58:464-470.
ISI
| PUBMED
29. Alexiou C, Kau RJ, Luppa P, Arnold W. Allergic reactions after systemic administration of glucocorticosteroid
therapy. Arch Otolaryngol Head Neck Surg. 1998;124:1260-1264.
FREE FULL TEXT
30. Stennert E. Bell's palsy: a new concept for treatment. Arch Otorhinolaryngol. 1979;225:265-268.
FULL TEXT
| PUBMED
31. Bührer M, Frey FJ, Frey BM. Prednisolone concentrations in cerebrospinal fluid after different
prednisolone prodrugs. Br J Clin Pharmacol. 1991;31:111-113.
ISI
| PUBMED
32. Parnes LS, Sun AH, Freemann DJ. Corticosteroids pharmacokinetics in the inner ear fluids: an animal
study followed by clinical application. Laryngoscope. 1999;109:1-17.
ISI
| PUBMED
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
Archives of Otolaryngology–Head & Neck Surgery Reader's Choice: Continuing Medical Education
Arch Otolaryngol Head Neck Surg. 2001;127(3):342-343.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Idiopathic Sudden Sensorineural Hearing Loss
Rauch
NEJM 2008;359:833-840.
FULL TEXT
Glucocorticoid Receptor and Nuclear Factor-{kappa}B Interactions in Restraint Stress-Mediated Protection against Acoustic Trauma
Tahera et al.
Endocrinology 2006;147:4430-4437.
ABSTRACT
| FULL TEXT
Screening and Management of Adult Hearing Loss in Primary Care: Scientific Review
Yueh et al.
JAMA 2003;289:1976-1985.
ABSTRACT
| FULL TEXT
|
