No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Sudden Sensorineural Hearing Loss: Does Application of Glucocorticoids Make Sense?
Abstract
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.
To investigate the effect of glucocorticoids on the treatment of SSNHL.
Academic medical center.
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.
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.
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.
... CSs are recommended for the treatment of ISSNHL. Several studies showed the benefit of CS use for the treatment of sudden HL [10][11][12] , although some meta-analyses do not support that [13] . Only a few clinical studies compared the efficacy of glucocorticoids and placebo, but the question of spontaneous recovery remains open because of small sample sizes and limited methodological validity [7,10,[14][15][16] . ...
... Several studies showed the benefit of CS use for the treatment of sudden HL [10][11][12] , although some meta-analyses do not support that [13] . Only a few clinical studies compared the efficacy of glucocorticoids and placebo, but the question of spontaneous recovery remains open because of small sample sizes and limited methodological validity [7,10,[14][15][16] . Data on the dose of systemic and IT CSs are inconclusive. ...
... Our study confirms that the hearing thresholds at low frequencies improved better than at high frequencies [10,18,24,31,32] . Age did not have a statistically significant influence on the hearing outcome, which is consistent with the results of other studies [6,33] . ...
Objective: To investigate the efficacy of prompt concomitant corticosteroid treatment with a single application of high-concentration intratympanic (IT) dexamethasone and tapered low-dose systemic methylprednisolone of an idiopathic sudden sensorineural hearing loss (ISSNHL).
Materials and Methods: Between September 2017 and September 2019, 86 adult patients met the criteria for the diagnosis of ISSNHL at baseline evaluation. The patients received immediate concomitant treatment with single high-concentration (24 mg/mL) IT dexamethasone and low-dose (48 mg) oral methylprednisolone for 1 week followed by tapered doses. Improvement in pure-tone average (PTA) and word recognition score (WRS) was determined after 1 and 6 months.
Results: A total of 63 patients met the requirements for the analysis. PTA improved in 71% and WRS improved in 59% of patients with ISSNHL. PTA and WRS were statistically significantly different at different time points during the intervention (p<0.0005). Hearing improved in all measured frequencies from 125 to 8000 Hz until the second follow-up. In 65.4% of patients with tinnitus, the WRS has improved compared with 27.3% without tinnitus (p<0.05). In 69.2% of patients without vertigo, the WRS has improved compared with 41.7% with vertigo (p<0.05).
Conclusion: Prompt concomitant single high-concentration IT and low-dose systemic corticosteroid treatment is efficient in recovering hearing loss and speech discrimination in ISSNHL. Tinnitus positively predicts hearing outcome. Vertigo negatively predicts speech discrimination recovery.
... The rationale for the treatment of ISSHL using high doses of systemic glucocorticoids is based on retrospective cohort studies. Alexiou et al. (2001) retrospectively analyzed the audiograms of 603 patients with ISSHL, with 301 patients (1986)(1987)(1988)(1989)(1990)(1991) receiving no glucocorticoid and 302 patients (1992-1998) receiving high dose i.v. glucocorticoids (prednisolone) and showed a benefit for patients receiving high-dose prednisolone [1]. ...
... Alexiou et al. (2001) retrospectively analyzed the audiograms of 603 patients with ISSHL, with 301 patients (1986)(1987)(1988)(1989)(1990)(1991) receiving no glucocorticoid and 302 patients (1992-1998) receiving high dose i.v. glucocorticoids (prednisolone) and showed a benefit for patients receiving high-dose prednisolone [1]. Egli Gallo et al. (2013) retrospectively evaluated the effectiveness of systemic high-dose dexamethasone therapy (administered orally) and demonstrated a significantly better improvement of hearing compared with a historical control using the clinic's earlier treatment regimen (standard prednisone; [11]). ...
Background
Systemic glucocorticosteroids (“steroids”) are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids without evidence from randomized controlled trials (RCTs) and refers solely to retrospective cohort studies. This RCT aims to assess the efficacy (improvement in hearing) and safety (especially systemic side effects) of high-dose steroids versus standard of care (standard dose systemic steroids) for the treatment of unilateral ISSHL, when given as a primary therapy.
Methods
The study is designed as a multicenter (approximately 40 centers), randomized, triple-blind, three-armed, parallel group, clinical trial with 312 adult patients. The interventions consist of 5 days of 250 mg/day intravenous prednisolone (intervention 1) + oral placebo, or 5 days of 40 mg/day oral dexamethasone (intervention 2) + intravenous placebo. The control intervention consists of 60 mg oral prednisolone for 5 days followed by five tapering doses + intravenous placebo. The primary efficacy endpoint is the change in hearing threshold in the three most affected contiguous frequencies between 0.25 and 8 kHz 1 month after ISSHL. Secondary endpoints include further measures of hearing improvement including speech audiometry, tinnitus, quality of life, blood pressure, and altered glucose tolerance.
Discussion
There is an unmet medical need for an effective medical therapy of ISSHL. Although sensorineural hearing impairment can be partially compensated by hearing aids or cochlear implants (CI), generic hearing is better than using hearing aids or CIs. Since adverse effects of a short course of high-dose systemic corticosteroids have not been documented with good evidence, the trial will improve knowledge on possible side effects in the different treatment arms with a focus on hyperglycemia and hypertension.
Trial registration
EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) Nr. 2015-002602-36; Sponsor code: KKSH-127.
... dexamethasone) [15]. The mechanism of action is complex, and little is known about the glucocorticoid effects in the inner ear: it could have effects on intra-and extra-cellular osmolarity, neural activity and electrochemical gradients [16]. ...
... This type of application is based on the fact that microcirculation of the cochlea could be impaired by changes in the viscosity of the plasma, vasospasm, the sludging of red blood cells, etc. However, previously in SSNHL, no significant abnormality was found in blood cell count or in electrolyte levels [16]. ...
Background: Ménière’s disease is characterised by episodic rotational vertigo, sensorineural hearing loss, tinnitus, and vegetative symptoms.
Objectives: The aim of our study is to follow-up the effects of the intratympanic steroid treatment of hearing loss in MD.
Material and methods: A group of 105 clinically diagnosed MD patients were enrolled in this investigation. Long-term follow-up was carried out, and pure tone speech audiometry results of the subjects before and after application of steroid were contrasted. Statistical analysis was carried out using the IBM SPSS V24 software.
Results: Based on the audiograms in this population, all stages of hearing loss were presented (from slight to profound). In most of the cases (68.6%), after intratympanic dexamethasone treatment, stagnation in the hearing profile was achieved. Moreover, there was a smaller group demonstrating hearing improvement after the treatment (12.4%). According to logistic regression [p = .001; Odds ratio: 2.75 (95% CI 1.068–4.442,)], there was a strong correlation between hearing improvement and dexamethasone treatment (all patients were treated with intratympanic dexamethasone, while improvement without steroid treatment could never be attained).
Conclusions and significance: Intratympanically administered dexamethasone is a potent agent to prevent the progression of hearing loss in MD.
... beobachteten eine Erholung des Hörvermögens bei der Hälfte der 12 mit Prednison behandelten Patienten im Gegensatz zu 6 von 19 Patienten (32 %), bei denen eine Erholung ohne Therapie beobachtet wurde [14]. Die bisher umfangreichste kontrollierte Studie zur Wirksamkeit von Glukokortikoiden stammt von Alexiou et al. (2001). Im Rahmen einer retrospektiven Kohortenstudie (siehe Kap. ...
... Im Rahmen einer retrospektiven Kohortenstudie (siehe Kap. 5.1.2) fanden die Autoren, dass die Therapie mit Prednisolon zusätzlich zu einer intravenösen rheologischen Therapie mit einer signifikant besseren Hörerholung im Frequenzbereich £ 2000 Hz einhergeht oder wenn der Hörverlust pancochleär war [15]. ...
Für Therapie und Rehabilitation bei Hörstörungen stehen vielfältige Möglichkeiten zur Verfügung. Dazu zählen medikamentöse, akustische, elektrische, chirurgische, radiologische, verhaltensmedizinisch orientierte und so genannte „alternative“ Strategien.
Auffällig ist jedoch die weite Spanne zwischen viel versprechenden tierexperimentellen Ergebnissen bis hin zur Regeneration und Stammzelltransplantation einerseits und der Mangel an klinischen Studien mit hohem Evidenzniveau selbst bei seit Jahrzehnten etablierten Therapieverfahren andererseits. In dieser Übersicht werden zum einen der gegenwärtige Stand und die Vielfalt der konservativen Therapiemöglichkeiten und Therapieversuche bei Hörstörungen dargestellt. Dabei soll die Übersicht und Kommentierung durchgeführter klinischer Studien dem Leser ein eigenes Urteil über die Wirksamkeit verschiedener, insbesondere medikamentöser Behandlungen und damit die Entscheidungshilfe bei der Therapie erleichtern. Zum anderen wird ein Ausblick auf zukünftige Therapiestrategien, insbesondere auch der lokalen Medikamentapplikation an das Innenohr, gegeben.
... However, Alexiou et al. and Egli Gallo et al. have shown that high-dose systemic steroid therapy is superior to conventional systemic corticosteroid therapy [37]. ...
Background
Numerous infections can result in neurological symptoms, including anosmia, facial paralysis, and abrupt sensorineural hearing loss (SSNHL). During the earlier SARS pandemic, coronaviruses were linked to a loss of smell and taste due to brain damage.
Purpose
To clinically detect corticosteroid treatment effectiveness in SSNHL post-COVID-19 infection and to detect the factors that affect the prognosis for these patients for better diagnosis and earlier management.
Subjects and method
Subjects included 20 subjects diagnosed by PCR as COVID-19 virus positive, complaining of sudden onset hearing loss post viral infection in different durations. All subjects had basic audiological evaluation done pre-treatment and repeated after 1 week, 2 weeks, and 1 month after treatment with methylprednisolone 21-acetate tablets.
Results
Onset of hearing loss post-COVID infection ranged from 1 to 3 months. As regards the improvement recognized with treatment course, thirteen patients (65%) of all twenty patients showed complete improvement at 1 month after starting treatment, and seven patients (35%) showed no improvement even after 1 month.
Conclusion
SSNHL has been widely recognized in the context of COVID-19 to date. Early corticosteroid therapy could help in the recovery of hearing, especially if the beginning of therapy was early in the first 2 weeks.
... The least statistically significant improvement was observed for a frequency of 8000 Hz in Air Conduction. This dependence seems to be in line with worse treatment results as far as the descending curves in PTA observed in current medical reports are concerned [6,12,13]. In the examined group, the statistical analysis of results confirmed statistically significant differences in the end results of treatment related to steroid therapy. ...
Oral, intravenous, or intratympanic steroid therapy (ST) are commonly applied methods of pharmacotherapy in Sudden Sensorineural Hearing Loss (SSNHL). There are vast discrepancies on the recommended initial dose and the duration of ST in medical reports. The aim of the research is a retrospective comparison of patients’ examination results with different therapeutical strategies. The medical records of 218 patients treated for SSNHL at the Military Institute of Medicine were subjected to retrospective analysis by comparison of the results of pure tone audiometry prior to and after treatment with steroid therapy (first-dose delay, mass of first dose, duration of treatment). Postponement of implementation of ST to 5 days resulted in a significant improvement of hearing across all frequencies. The implementation of ST sequentially in periods (5th–10th day; >10th day) resulted in a statistically insignificant improvement of hearing in the following frequencies: 250 Hz, 1000 Hz, 1500 Hz, 2000 Hz, 3000 Hz, 4000 Hz. There was a statistical improvement of hearing within all frequencies analyzed for the initial dose of prednisone above 50 mg. For an initial dose below 50 mg, in 4000 Hz, the improvement of hearing was statistically insignificant. The research demonstrated a significant influence of steroid therapy on treatment results in patients with Sudden Sensorineural Hearing Loss.
... Mora et al. reported positive outcomes of an intravenous tissue plasminogen activator therapy [18]; Miller et al. showed that neurotrophins could enhance spiral ganglion cell survival after inner ear hair cell loss [19] and Lalwani et al. described the benefits of the introduction of an adeno-associated virus into the cochlea of a guinea pig [20]. However, as a corticosteroid therapy has been mainly effective in stopping, decreasing or correcting an auditory impairment in numerous other etiologies of hearing loss [21][22][23][24], a steroid therapy has also been encouraged in the field of surgical inner ear interventions. ...
Protecting tissues from excessive inflammation by glucocorticoids results in an effective blockade of inflammation; however, it does not instigate processes of inflammatory resolution or tissue repair. Moreover, glucocorticoids have side effects such as a susceptibility to infections. In otolaryngology—specifically, within the inner ear—surgical and non-surgical pathologies include cochlear implantation, stapes surgery, perilymph fistulas and Meniere’s disease. For these, steroids are indicated in order to prevent excessive inflammation that might lead to hearing and vestibular failure. Unless tissue homeostasis is restored, the compromised tissue is at risk of a functional loss. α1-Antitrypsin (AAT) is a circulating inflammation-modulating molecule that rises during the molecular signs of a tissue injury; it manipulates inflammation towards an inflammatory resolution and advances tissue repair. Lifelong infusions of AAT are currently indicated for genetic AAT deficiencies and are safe. In the present review, we discuss the advantages and downfalls of glucocorticoid treatments across several surgical inner ear injuries alongside evidence of the beneficial attributes of treatments with AAT. Collectively, the present knowledge places AAT treatments, wither independent or in combination with glucocorticoids, as adding focus on tissue repair in the context of unmet medical needs in otolaryngology.
... The exact pathophysiology of tinnitus is not fully understood, and studies describe many factors that may be involved, including the use of medication [43,44]. However, no reports have been found that describe the occurrence of tinnitus after the use of GCs. ...
Background:
Intranasal corticosteroids are one of the cornerstone treatment options for allergic rhinitis and chronic sinusitis complaints. Safety information in the summary of product characteristics may not be representative for observations in daily clinical practice. The Netherlands Pharmacovigilance Center (Lareb) collects post-marketing safety information, using spontaneous reporting systems.
Objective:
Our objective was to analyse reports of adverse drug reactions associated with intranasal corticosteroids reported in the Dutch spontaneous reporting database of the Netherlands Pharmacovigilance Center Lareb to obtain insight into real-world safety data.
Methods:
We retrospectively examined all adverse drug reactions of intranasal corticosteroids reported to the Netherlands Pharmacovigilance Center Lareb, entered into the database from 1991 until 1 July, 2020.
Results:
In total, 2263 adverse drug reactions after intranasal corticosteroid use were reported in 1258 individuals. Headache (n = 143), epistaxis (n = 124) and anosmia (n = 57) were reported most frequently. Nasal septum perforation (reporting odds ratio 463.2; 95% confidence interval: 186.7-1149.7) had the highest reporting odds ratio, followed by nasal mucosal disorder (reporting odds ratio 104.5; 95% confidence interval 36.3-301.3) and hyposmia (reporting odds ratio 90.8; 95% confidence interval 45.1-182.7). Moreover, 101 (4.5%) reports were classified as serious by Lareb, including reports of Cushing's syndrome, adrenal cortical hypofunction and growth retardation.
Conclusions:
Many side effects are consistent with the safety information in the summary of product characteristics of intranasal corticosteroids. Several serious (systemic) side effects are reported and it is important to realise that intranasal corticosteroids may contribute to the development. Healthcare providers and patients should be aware of the potential (individual) adverse drug reactions of intranasal corticosteroids. This information could help in discussing treatment options.
... Corticosteroids as an initial therapy to patients may be offered within 2 weeks of the onset of symptoms and intratympanic steroids may be administrated when patients have incomplete recovery from sudden sensorineural hearing loss between 2 and 6 weeks after onset of symptoms of SSNHL [37]. Administration of glucocorticoids should be recommended for treatment of patients with SSNHL, especially in patients with SSNHL in the lower and middle frequency range, and those with pancochlear hearing loss have significantly better recovery of hearing levels [38]. According to the prospective randomized controlled clinical trial, where three different steroid therapies were assessed (oral steroid for 10 days in comparison with the intratympanic dexamethasone administration and in comparison with oral and intratympanic administration simultaneously), the conclusion was that all three treatment protocols resulted in the similar recovery rates [39]. ...
Abstract: (1) Background: A retrospective clinical study was conducted to compare the effectiveness of different pharmacological and non-pharmacological regimens for treating sudden sensorineural hearing loss (SSNHL). (2) Methods: Adult patients (n = 130) diagnosed with sudden sensorineural hearing loss (SSNHL) and hospitalized between 2015 and 2020 were enrolled in this study. Depending on the treatment regimen applied, patients were divided into five groups. Inclusion criteria were as follows: (i) hearing loss of sudden onset; (ii) hearing loss of at least 30 dB at three consecutive frequencies; (iii) unilateral hearing loss; (iv) age above 18 years. Exclusion criteria were as follows: (i) no follow-up audiogram; (ii) bilateral hearing loss; (iii) recognized alternative diagnosis such as tumor, disorder of inner ear fluids, infection or inflammation, autoimmune disease, malformation, hematological disease, dialysis-dependent renal failure, postdural puncture syndrome, gene-related syndrome, mitochondrial disease; and (iv) age below 18 years. (3) Results: Complete recovery was found in 14% of patients (18/130) and marked improvement was found in 6% (8/130), giving an overall success rate of 20%. The best results were obtained in the second group (i.e., patients given intratympanic glucocorticoid + prolonged orally administered glucocorticoid) where the success rate was 28%. In general, the older the patient, the smaller the improvement in hearing, a correlation that was statistically significant. (4) Conclusions: In treating SSNHL, the highest rate of hearing recovery—28%—was in the group of patients given intratympanic corticoid plus prolonged treatment with orally administered glucocorticoid.
Keywords: sudden sensorineural hearing loss; dexamethasone; prednisone
... In the clinic, sudden sensorineural hearing loss is treated with anti-inflammatory glucocorticoids [30]. For some patients, this treatment correlates with hearing restoration [31,32]; however, there are also reports of individuals who recover spontaneously [33]. ...
Most adults who acquire hearing loss find it to be a disability that is poorly corrected by current prosthetics. This gap drives current research in cochlear mechanosensory hair cell regeneration and in hearing restoration. Birds and fish can spontaneously regenerate lost hair cells through a process that has become better defined in the last few years. Findings from these studies have informed new research on hair cell regeneration in the mammalian cochlea. Hair cell regeneration is one part of the greater problem of hearing restoration, as hearing loss can stem from a myriad of causes. This review discusses these issues and recent findings, and places them in the greater social context of need and community.
... Similar results were obtained in a recent RCT including 67 patients treated for 14 days (Study group: 500 mg IV methylprednisolone daily for three days followed by 1 mg/kg/day of oral prednisolone for 11 days; Control group: 1 mg/kg/day oral prednisolone for 14 days) (Eftekharian and Amizadeh, 2016). However, there is some evidence from retrospective studies regarding treatment advantage for high dose systemic steroids therapy (Alexiou et al., 2001;Egli Gallo et al., 2013). Niedermeyer et al. showed that the level of cortisol in human perilymph was significantly higher after 250 mg intravenous prednisolone compared to 125 mg dose. ...
Sudden sensorineural hearing loss (SSNHL) is an enigmatic entity, with obscure pathophysiology and debatable efficacy of the treatment agents used. An underlying cause is identified in only 10–15% of cases. The management of the remaining patients, classified as ‘idiopathic’, is empirical, and is conventionally with systemic steroids, vasodilator therapy, rheological agents, and antioxidants, to list a few amongst the host of the agents employed for the treatment. The availability of conflicting outcomes and lack of conclusive evidence has resulted in the propagation of consensus-based treatment protocols. In the present review, we discuss the various controversial issues and newer developments in the management of idiopathic SSNHL. The current review aims to present a narrative outlook of the updated evidence base available from PUBMED, augmented with relevant designated publications.
... Glucocorticoids, however, are known for their potential and severe side effects in many organ systems (13)(14)(15). As a result, use of the steroids is contraindicated in patients with certain systemic conditions, such as insulin-dependent or poorly controlled diabetes, labile hypertension, tuberculosis, and peptic ulcer disease (16,17). Furthermore, simultaneous administration of steroids and diuretics (combination treatment) may induce unwanted drug interactions that affect sodium and water metabolism. ...
Objective:
Acute low-frequency hearing loss (ALHL) is typically treated with combination therapy, including steroids and diuretics. To avoid unnecessary use of steroids we proposed a method of sequential administration using these two drugs, and compared the efficacy of our protocol with that of existing combination treatments.
Methods:
A prospective, randomized, open-label, single-blind, noninferiority clinical trial was conducted to investigate whether the effectiveness of sequential treatment is noninferior to that of combination treatment for ALHL. Ninety-two patients with ALHL received either steroids and diuretics simultaneously for 2 weeks (combination group), or diuretics for 2 weeks followed by steroids for another 2 weeks if they did not respond to diuretic treatment (sequential group). The primary outcome measure was a change in mean hearing threshold at three frequencies (125, 250, and 500 Hz) at 4 weeks after treatment.
Results:
The mean hearing threshold of the low frequencies improved 20.0 and 17.2 dB in the combination and the sequential group, respectively. The 95% lower confidence interval was -8.0 dB and noninferiority was established at p < 0.05. At 4 weeks after treatment, the complete recovery rate was 80.5 and 82.9% in the combination and sequential groups, respectively.
Conclusion:
This is the first study on ALHL treatment following the establishment of Consolidated Standards of Reporting Trials (CONSORT). The sequential treatment is not inferior to combination treatment for ALHL, and therefore may be a better treatment guideline for ALHL considering that patients receive less steroid exposure and smaller restrictions in diuretic use compared with steroids.
... The rational basis for the treatment of idiopathic sudden sensorineural hearing loss (ISSHL) with systemic highdose steroids are retrospective cohort studies. Alexiou et al. analyzed the audiograms of 603 patients with sudden hearing loss; 301 of them (from 1986 to 1991) did not receive steroids and 302 patients (from 1992 to 1998) were treated with high-dose intravenously administered steroids (prednisolone) [82]. A treatment advantage was observed in the group of patients who underwent highdose steroid therapy. ...
This article reviews recent aspects of diagnostics, differential diagnostics, and evidence in systemic and local therapy of idiopathic sudden sensorineural hearing loss (ISSHL). Since a number of disorders can be accompanied by sudden hearing loss, a meaningful and targeted diagnostic strategy is of utmost importance. An important differential diagnosis of sudden hearing loss are intralabyrinthine schwannomas (ILS). The incidence of ILS is probably significantly underestimated. This may be due to the lack of awareness or lack of explicit search for an intralabyrinthine tumor on MRI or an inappropriate MRI technique for the evaluation of sudden hearing loss (“head MRI” instead of “temporal bone MRI” with too high slice thicknesses). Therefore, the request to the radiologist should specifically include the question for (or exclusion of) an ILS. With special MRI techniques, it is possibly today to visualize an endolymphatic hydrops. The evidence in the therapy of ISSHL is – with respect to the quality and not quantity of studies – unsatisfying. The value of systemically (low dose) or intratympanically applied corticosteroids in the primary treatment of ISSHL is still unclear. In order to investigate the efficacy and safety of high dose corticosteroids as primary therapy for ISSHL, a national, multicenter, three-armed, randomized, triple-blind controlled clinical trial is currently performed in Germany (http://hodokort-studie.hno.org/). After insufficient recovery of the threshold with systemic therapy of ISSHL, intratympanic corticosteroid therapy appears to be associated with a significantly higher chance of an improved hearing threshold than no therapy or placebo. Both, hearing gain and final hearing threshold, however, appear to be independent from the onset of secondary therapy. Based on currently available data from clinical studies, no recommendation can be made with respect to the type of corticosteroid and specifics of the intratympanic application protocol.
... Corticosteroids might cause anti-inflammatory and metabolic effects, and alter the immune response [15]. With prolonged use of systemic steroids, significant adverse reactions such as abnormal liver function, gastrointestinal trouble, avascular necrosis, epistaxis, acne, and gluteal abscess can occur [9,16]. ...
Background and Objectives
Viral and vascular disorders are considered to be a major cause of idiopathic sudden sensorineural hearing loss (ISSNHL). Lipoprostaglandin E1 (lipo-PGE1) has vasodilating activity and has been used to treat ISSNHL. The purpose of this study was to determine the specific therapeutic effects of lipo-PGE1 and compare them to other treatment modalities for ISSNHL.
Subjects and Methods
The study group had 1,052 patients diagnosed with ISSNHL. All were treated with steroid, carbogen inhalation, stellate ganglion block (SGB), or PGE1. The CP group (steroid, carbogen inhalation, and PGE1 injection; 288 patients) was treated with lipo-PGE1 and carbogen inhalation, the CS group (steroid, carbogen inhalation, and stellate ganglion block; 232 patients) with steroid, carbogen inhalation, and SGB, the C group (steroid and carbogen inhalation; 284 patients) with steroid and carbogen, and the control group (steroid only; 248 patients) with steroid only. Patients in the groups receiving lipo-PGE1 received a continuous infusion of 10 µL lipo-PGE1.
Results
The overall recovery rate after treatment was 52.2%, and recovery rates by group were 67.7% in the CP group, 54.3% in the CS group, 52.1% in the C group, and 32.2% in the control group. Therefore, the therapeutic results in groups treated with lipo-PGE1 were better than results in other groups. The difference was statistically significant.
Conclusions
The study results suggested that the CP group received effective treatment modalities for ISSNHL. The combined therapy of lipo-PGE1 with carbogen inhalation in patients with ISSNHL was more beneficial than other treatment modalities.
... Conlin and Parnes (27,28) de aynı şekilde steroidin etkili tedavi olduğunu gösterecek geçerli kontrollü randomize çalışmanın olmadığı ve AİK'da altın standart tedavi olamayacağı sonucuna varmıştır. Ayrıca kortikosteroidlerin sistemik kullanımı gastrik ülser, bilinen kalp yetersizliği, renal yetersizlik anamnezi ve aktif bakteriyel enfeksiyonu olanlarda kontrendikedir (29) . Hem sistemik kullanımdaki steroid yan etkileri hem de daha yüksek perilenf konsantrasyonu oluşturması nedeniyle intratimpanik steroid tedaviler düşünülmüştür. ...
... 7 Steroids are known to act in the inner ear and have been effectively used in viral, syphilitic, autoimmune, endolymphatic (Meniere's disease) and other causes of hearing loss. 8,9 Other pharmacological agents like antivirals, thrombolytics, vasoactive substances, vasodilators, hyperbaric oxygen therapy, carbogen inhalation therapy also have been tried. ...
p class="abstract"> Background: To assess the clinical and audiometric profile in patients presenting with sudden sensorineural hearing loss (SSNHL).The study also aimed to find out any possible etiology of SSNHL, prognostic factors and effectiveness of treatment. Prospective, open label, randomized study conducted in department of ENT at the Ram Lal eye and ENT hospital attached to Government medical college, Amritsar, Punjab, India.
Methods: 50 patients of either sex aged between 18 to 50 years suffering from unilateral or bilateral onset SSNHL included in the study on the basis of predetermined clinical criteria. The hearing assessments of patients were done before and after the treatment with tuning fork tests, pure-tone and impedance audiometry.
Results: Most of the patients of SSNHL presented with unknown etiology. Steroid treatment gave a statistically significant improvement in pure tone averages. Maximum improvement is observed in patients who started treatment within one month of developing SSNHL. Post-treatment outcomes were not influenced by age of the patient and type of the pure tone audiometry graph. The presence of vertigo and diabetes are bad prognostic factors for hearing outcome in SSNHL.
Conclusions: Most of the cases of sudden sensorineural hearing loss have unknown etiology. Patients with associated DM and vertigo are having poor recovery of hearing. Early starting of treatment gives maximum improvement of hearing. </p
... Es importante mencionar que hasta un 10% de los pacientes experimentan un empeoramiento de su audición en el tiempo, a pesar de la instauración del (19,20) tratamiento adecuado . ...
Acute bacterial meningitis is an infectious emergency as it can lead to serious sequelae or even death. The presentation of this condition with sudden deafness and ataxia is rare. We present the case of a 14-year old female adolescent, who presented with vestibular ataxia and sudden deafness and was subsequently diagnosed with bacterial meningitis due to serogroup C meningococcus. She was treated with corticosteroids and pentoxifylline, in addition to antibiotics, for the baseline infection. Hearing recovery was not adequate; she persisted with severe deafness, unilateral hearing loss and persistent and disabling vestibular ataxia.
... [4,5] With an unclear mechanism, a series of causative factors-including microcirculatory disorders, upper respiratory tract infections, autoimmune disorders, and barotrauma have been reported. [4,[6][7][8] Different causative factors make different damage to the functioning of the cochlea or/and internal auditory meatus, and patients will have different levels of syndromes. Many researchers have been aware of this and put forward the necessity to classify SSHL into definite types initially. ...
Sudden sensorineural hearing loss (SSHL) is an otological emergency defined as a rapid hearing loss, seriously affects patient's social life. To data, no study has reported the treatment by acupuncture alone in the acute phase. In this report, Acupuncture and Moxibustion therapy of excitation-focus transfer is outlined.
The patient was a 26-year-old young woman who had an SSHL coupled with ear fullness. The patient had no past medical history, but she had undergone variable emotions and had a history of excessive noise exposure. The patient refused to receive any medicine especially steroids and hyperbaric oxygen therapy. She just only received acupuncture treatment.
Her symptoms and outcome measurements were improved every week and completely recovered after the last week.
Even though the article presents a single case and is based on self-reports, there are very clear trends on how patients with SSHL responded to acupuncture treatments.
... Insbesondere im Falle nichtkommerzieller, wissenschaftsinitiierter Studien (wie der in diesem Artikel vorgestellten Abb. 1 In der "global burden of disease"-WHO-Liste stehen Hörbehinderungen an 15. Stelle und an 2. Stelle in Bezug auf "Lebensjahre mit Behinderung". ...
Systemic steroids are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids for primary therapy of ISSHL, without evidence from randomized controlled trials (RCTs). The rationale for the treatment of ISSHL using high dose steroids is only based on retrospective cohort studies.
This article describes the planning and initiation of a multicenter, national, randomized, controlled clinical trial entitled Efficacy and safety of high dose glucocorticosteroid treatment for idiopathic sudden sensorineural hearing loss – a three-armed, randomized, triple-blind, multicenter trial (HODOKORT). This clinical trial aims to compare standard dose with two types of high-dose steroids for primary systemic therapy with respect to their efficacy in improving hearing, and thus communication ability, in patients with idiopathic sudden sensorineural hearing loss.
This study is funded by the „Clinical Trials with High Patient Relevance“ research program in the health research framework of the German Federal Ministry of Education and Research. It is one of two studies by the German Study Center of Clinical Trials of the German Society of Otorhinolaryngology, Head and Neck Surgery (DSZ-HNO). Planning and initiation was done in cooperation with the DSZ-HNO, the Coordination Center of Clinical Trials of the Martin-Luther-University Halle-Wittenberg, and the Study Center of the University Hospital Freiburg.
... In a recent double blind prospective study, Cinamon et al. 14 suggested that prednisolone 1 mg/kg/day had no therapeutic advantage over a placebo (BEL Ib). However, Alexiou et al. 15 performed a retrospective study in 2001 concerning the use of 500-1000 mg of prednisolone for three days, and found that glucocorticoids should be recommended for the treatment of SSHL, particularly for patients with hearing loss in the lower and middle frequencies (BEL Ib). ...
This update on the latest studies and management policies for patients suffering from sudden sensorineural hearing loss (SSHL) represents a cooperative effort of Belgian ENT surgeons from various corners of the country. SSHL has an incidence ranging from 5 to 20 cases per 100,000 persons per year, and is a relative medical emergency, as only 30% to 65% of the patients recover spontaneously.1-3 Nowadays, treatment varies a great deal between countries and hospitals. The various etiologies and therapeutic modalities are reviewed, and evidence levels are indicated. Finally, diagnostic and therapeutic organigrams are proposed along with a Belgian therapeutic cocktail in view of conducting a large Belgian study on the management of SSHL.
... Although vertigo is considered a poor prognostic factor [1] , we did not notice any difference on hearing gain if vertigo was present. Chin-Saeng Cho's research on prognostic factors showed no direct effect of vertigo on hearing improvement but found close correlations between vertigo and initial hearing level, which also predicts the prognosis of the disease [26] . The age and sex of the patient did not influence treatment outcome. ...
OBJECTIVE: Idiopathic sudden sensorineural hearing loss (ISSNHL) or sudden deafness is considered an otologic emergency. In spite of numerous investigations, its cause and treatment remain uncertain. Vascular hypothesis is one of the accepted etiologic theories, and vasodilator agents have been used to treat this medical condition. MATERIALS and METHODS: We conducted a retrospective study in which we have compared the efficiency of two vasoactive/vasodilative agents-pentoxifylline and betahistine-separately and together for treatment of sudden deafness in 59 patients. Methylprednisolone was used in all three groups. Hearing threshold (HT) was measured, and pure tone average (PTA) was calculated on admission, after 1 week, and after 3 months. RESULTS: Hearing improvement was noticed in 33 out of 59 patients (56%) at the second follow-up with a mean PTA improvement of 20 dB. The best recovery rate was seen in the pentoxifylline + steroid group (69%) versus the pentoxifylline + betahistine + steroid group (55%) and betahistine + steroid group (48%). There was no statistically significant difference in treatment outcome (p=0.433) between all three groups. Methylprednisolone dosage was 32, 48, or 64 mg/day. The amount of steroid given was not statistically significant for recovery of hearing loss (HL) (p=0.418). CONCLUSION: The pentoxifylline with methylprednisolone group achieved the best results. In that group, 67% of patients improved at the first follow-up versus 69% after 3 months. Statistically, there was no significant difference in treatment outcome between all three groups (p=0.433). Greater PTA improvement was seen at higher doses of steroid. The amount of steroid given was not found to have a statistically significant influence on hearing recovery (p=0.418).
... Several glucocorticoids have been used alone or in combination to treat patients with sudden idiopathic hearing loss (231)(232)(233)(234). In general, these treatments appear to be more effective in immune-mediated hearing loss (235). ...
Hearing loss due to aging, hereditary factors, noise exposure, ototoxic drugs and infection is a major healthcare problem. While the causative agents of hearing loss are diverse, many share common sequelae involving oxidative stress, generation of reactive oxygen and nitrogen species, depletion of antioxidant enzymes and signaling pathways leading to apoptosis or necrosis. During the past decades, a host of new strategies for preventing hearing loss have been evaluated. Animal studies have identified a variety of exogenous antioxidants or compounds that enhance antioxidant defenses, providing significant protection. An alternative therapeutic approach involves the use of small molecules to suppress downstream signaling pathways involved in apoptosis. Since many insults lead to inflammation, a third approach has focused on antiinflammatory drugs, some of which suppress the immune system. Finally, growth factors and neurotrophic factors represent a new method to protect and promote the survival of hair cells and neurons in the inner ear. While a great deal is now known about the efficacy of individual compounds, future efforts might benefit from a multifactorial approach involving therapeutic "cocktails" that optimize the degree of protection against age-related hearing loss and other ototraumatic insults. Copyright © 2011 Prous Science, S.A.U. or its licensors. All rights reserved.
... Response rates to systemic steroids range between 49 and 89 percent. [14,15] Emergence of SHL is presumably attributed to inflammatory processes in the inner ear due to various etiologies as viral infection and ischemia and steroids have been used with their conceivably effectiveness in breaking or reversing this inflammatory cascade. However as is known, systemic steroid administration cannot overcome blood-brain barrier efficiently and thus its adequate levels in CSF and bone tissue cannot be sustained. ...
... These include autoimmune and allergic diseases, other types of inflammatory conditions, tumors, and as a substitutive therapy in Cushing's syndrome and some types of adrenal gland insufficiency. For inner ear disorders, glucocorticoid therapy is used for the treatment of Meniere's disease, tinnitus, acoustic trauma, sudden hearing loss and autoimmune inner ear disorders (McCabe, 1979;Moskowitz et al., 1984;Alexiou et al., 2001;. Unfortunately, the beneficial effect of glucocorticoid therapy on hearing lasts only during treatment and disappears upon tapering the therapy (Harris et al., 2003;Doyle et al., 2004). ...
... La historia natural de la SS es variable, debido a que las causas son múltiples. Algunos pacientes se recuperan completamente sin intervención médica, habitualmente durante los tres primeros días (recuperación espontánea) y, generalmente, no acuden al médico [93][94][95] . ...
Idiopathic sudden sensorineural hearing loss is an unexplained unilateral hearing loss with onset over a period of less than 72 hours, without other known otological diseases.We present a consensus on the diagnosis, treatment and follow-up of this disease, designed by AMORL, after a systematic review of the literature from 1966 to June 2010.Diagnosis of sudden sensorineural hearing loss is based on mandatory otoscopy, acoumetry, tonal audiometry, speech audiometry, and tympanometry. After clinical diagnosis is settled, and before treatment is started, a full analysis should be done and an MRI should be requested later.Treatment is based on systemic corticosteroids (orally in most cases), helped by intratympanic doses as rescue after treatment failures.Follow-up should be done at day 7, with tonal and speech audiometries, and regularly at 15, 30, and 90 days after start of therapy, and after 12 months.By consensus, results after treatment should be reported as absolute dBs recovered in pure tonal audiometry, as improvement in the recovery rate in unilateral cases, and as improvement in speech audiometry.ResumenLa sordera súbita idiopática es aquella hipoacusia neurosensorial de inicio súbito, en menos de 72 horas, sin otros antecedentes otológicos previos.Presentamos un consenso sobre el diagnóstico, tratamiento y seguimiento de la sordera súbita, surgido desde la Asociación Madrileña de ORL.Mediante revisión sistemática de la literatura sobre sordera súbita, desde 1966 hasta junio de 2010, sobre los términos MESH “(acute or sudden) hearing loss”, llegando a las siguientes sugerencias: en cuanto al diagnóstico, ante una sospecha clínica de sordera súbita, las pruebas diagnósticas que se consideran necesarias son: otoscopia, acumetría, audiometría tonal, audiometría verbal y timpanograma.Una vez hecho el diagnóstico clínico de sordera súbita, antes de comenzar el tratamiento, se solicitará una batería analítica, debiendo completarse más tarde el estudio con RM de oído interno.Se recomienda que el tratamiento de la sordera súbita esté basado fundamentalmente en los corticoides sistémicos, generalmente por vía oral, apoyados en los corticoides intratimpánicos como rescate.Respecto al seguimiento, se realizará un control a la semana del inicio del mismo, incluyendo audiometría tonal y verbal, y a los 15, 30 y 90 días del diagnóstico, y 12 meses después.Como consenso, el resultado de los tratamientos aplicados debería presentarse, tanto en cuanto a la cantidad de dBs recuperados en el umbral auditivo tonal como siguiendo la tasa de recuperación en los casos unilaterales, así como con parámetros de audiometría verbal.
... La historia natural de la SS es variable, debido a que las causas son múltiples. Algunos pacientes se recuperan completamente sin intervención médica, habitualmente durante los tres primeros días (recuperación espontánea) y, generalmente, no acuden al médico [93][94][95] . ...
Idiopathic sudden sensorineural hearing loss is an unexplained unilateral hearing loss with onset over a period of less than 72hours, without other known otological diseases.We present a consensus on the diagnosis, treatment and follow-up of this disease, designed by AMORL, after a systematic review of the literature from 1966 to June 2010.Diagnosis of sudden sensorineural hearing loss is based on mandatory otoscopy, acoumetry, tonal audiometry, speech audiometry, and tympanometry. After clinical diagnosis is settled, and before treatment is started, a full analysis should be done and an MRI should be requested later.Treatment is based on systemic corticosteroids (orally in most cases), helped by intratympanic doses as rescue after treatment failures.Follow-up should be done at day 7, with tonal and speech audiometries, and regularly at 15, 30, and 90 days after start of therapy, and after 12 months.By consensus, results after treatment should be reported as absolute dBs recovered in pure tonal audiometry, as improvement in the recovery rate in unilateral cases, and as improvement in speech audiometry.
Objective:
To determine the efficacy of long-term high-dose intratympanic dexamethasone in protecting the hearing capacity of cancer patients undergoing cisplatin-based ototoxic treatment.
Design:
A randomized controlled phase IIIB clinical trial to evaluate the efficacy of dexamethasone in protecting against hearing loss in patients undergoing cisplatin treatment. The subjects participating in the clinical trial were patients with a neoplastic disease whose treatment protocol included cisplatin. The average dose of cisplatin was 444.87 mg (SD 235.2 mg). Treatment consisted of intratympanically administering dexamethasone via a passive diffusion device called Microwick (8 mg/24 h dose) from the start of treatment with cisplatin to 3 weeks after the last cycle. Patients were administered the medication to one ear, and the contralateral ear was used as the control. The treated ears were randomly chosen using a computer system (randomization). The hearing threshold was evaluated using pure tone audiometry before each cisplatin cycle.
Results:
Thirty-four patients were recruited over a 2-year period at a reference tertiary hospital, of whom 11 were excluded. Forty-six ears were analyzed (23 treated and 23 control ears). When treatment was completed, the audiometric analysis showed a higher hearing threshold in the study group than in the control group. Differences were statistically significant at frequencies of 500, 1000, and 6000 Hz: 4.9 dB (1.1 to 8.7), 5.5 dB (0.8 to 10.3), and 16 dB (3.2 to 28.7), respectively, (p < 0.05, 95% confidence interval), but were not clinically significant according to the ASHA hearing loss criteria. Both 8.69% infection complications during treatment and 34.8% permanent perforation at 6 mo were detected after device removal.
Conclusions:
Long-term high-dose intratympanic dexamethasone treatment did not prevent cisplatin-induced hearing loss.
Background:
In recent years, the incidence of sudden deafness has gradually increased, with a very limited understanding of the etiology and the pathogenesis. Glucocorticoids are the first choice for the treatment, but some hormoneresistant patients are not sensitive to glucocorticoid therapy. The pathogenesis is not yet known. In this study, we aim to construct HEI-OC1 cell line stably overexpressing glucocorticoid receptor beta (GRβ), and identify its exact role in the cases of glucocorticoid-resistant sudden deafness.
Method:
We used the endotoxin lipopolysaccharide-stimulated cochlear hair cells (HEI-OC1) to investigate the relationship of inflammation factor IL-2, TNF alpha, and SRp30c with the high expression GRβ. We build a stable GRβ high expression HEI-OC1 cell line and clarified its effects on the therapeutic effect from Dexamethasone. MTT assay, colony formation assay, CCK-8 assay, Western blot, and RT-qPCR were utilized for the characterizations.
Results:
Dexamethasone reduced LPS-induced inflammatory response in HEI-OC1 cells (p<0.05), detected by MTT assay. Dexamethasone could protect HEI-OC1 cells, but its protective effect was weakened due to the transfection of SRp30c overexpression plasmid (p<0.05). The transfection of SRp30c over-expression plasmid in HEI-OC1 cells could elevate the expressions of GRβ (p<0.05).
Conclusion:
We clarified the mechanisms of high expression of GRβ in glucocorticoid-resistant sudden sensorineural hearing loss, and proved that the inhibition of SRp30c may act as a new treatment way of glucocorticoid-resistant sudden sensorineural hearing loss.
Glucocorticoid (GC) is a steroid hormone secreted from the adrenal cortex in response to stress, which acts by binding to cytoplasmic glucocorticoid receptors (GRs). Dexamethasone (DEX) is a synthetic GC exhibiting immunosuppressive effects in both human and rodent models of hearing loss. While clinical evidence has shown the effectiveness of DEX for treatment of various inner ear diseases, its mechanisms of action and the optimal timing of treatment are not well understood. In the present study, intergroup comparisons were conducted based on the time point of treatment with DEX: (1) pretreatment; (2) posttreatment; and (3) pre&post-noise. The pre&post DEX treatment group showed a significant improvement in threshold shift at 1 day post-noise exposure as compared to the TTS (transient threshold shift)-only group at 8 and 16 kHz. Both TTS and PTS (permanent threshold shift) significantly reduced cochlear GR mRNA expression and increased serum corticosterone and cochlear inflammatory cytokines. The pre&post DEX treatment group showed a significant decrease in serum corticosterone level as compared to other DEX treatment groups and TTS-treated group at 3 days after acoustic trauma. Our results suggest that the timing of DEX administration differentially modulates systemic steroid levels, GR expression and cochlear cytokine expression.
Contexte. La prise en charge correcte des urgences est loin d’être organisée et évaluée dans notre pays. Cette enquête préliminaire décrit l’organisation de ce service aux Cliniques Universitaires de Kinshasa (CUK).Méthodes. Etude prospective et descriptive du fonctionnement des urgences du service de médecine interne(MISU) aux CUK, période du 15 janvier au 15 février 2011. Le cadre, le personnel, le plateau technique, la fréquentation et l’organisation du travail ont été étudiés, pour évaluer la qualité de la prise en
charge des patients.
Résultats. Le MISU a accueilli 58,1% des admissions totales aux urgences. Ce service est sous-équipé, et son personnel non qualifié en gestion des urgences.La prise en charge des patients n’est pas codifiée et les procédures ne sont pas uniformisées. Une médiane de 15 consultations/j a été calculée, et les délais sont encore trop longs pour plusieurs prestations (soins endéans 1h, 31,3% des patients ; transfusions au-delà de 3h ; 71,4% des sujets). Les résultats des analyses sanguines ont été disponibles, après des délais médians de 4 h 10 et de 5 h 01’, pour les explorations d’imagerie.
Conclusion. Le MISU affiche de nombreuses défaillances structurelles et fonctionnelles, susceptibles d’affecter la qualité de la prise en charge. Cette enquête illustre les besoins urgents de la promotion de la formation du personnel en gestion des urgences. La formalisation des procédures administratives et des soins et le renforcement du plateau technique, s’imposent également comme des exigences incontournables, dans l’amélioration du service à la communauté.
Background
Sudden sensorineural hearing loss (SSHL) is a disease, which severely affects the patient’s social and relational life. The underlying pathomechanisms have not been finally clarified yet and outcome is not predictable.
Methods
We conducted a retrospective study in order to identify parameters that influence hearing recovery. The data base contains results of basic otoneurological tests and clinical parameters of 198 patients with idiopathic SSHL of at least 60 dB in at least four frequencies, diagnosed and treated at the University Hospital of Münster, Germany, between 1999 and 2015. Hearing recovery was measured by pure tone audiometry.
Results
Multivariate linear and logistic regression analyses indicate that the chance as well as the magnitude of hearing recovery is higher for patients with normal caloric testing than for patients with pathological caloric testing. However, for the subgroup of patients who attained a hearing recovery, the caloric testing result was not found to influence the magnitude. Instead, the magnitude was noticeably lower for patients within this subgroup who had a previous hearing loss. Furthermore, we found indications that the magnitude is higher for men than for women and that receiving a high-dose steroid therapy is associated with a higher chance and magnitude of a hearing recovery.
Conclusions
We conclude that SSHL associated with disorders of the vestibular system or previous hearing loss represent special sub-entities of SSHL that may be caused by unique pathophysiological mechanisms and are associated with worse outcome. Furthermore, our data support the importance of elevated dosage of steroids in SSHL therapy.
Heilung bzw. Linderung von Symptomen einer Erkrankung oder Prävention von Erkrankungen unter Abwägung von Nutzen und Risiko des jeweils vorgesehenen Arzneimittels
Background
High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AimTo develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined. Materials and methodsA series of experiments with different impulse noise exposures were performed. Permanent hearing loss and hair cell density were assessed 14 days after exposure. Hearing and hair cell preservation were investigated as a function of the glucocorticoid dose. ResultsAfter impulse noise exposure, local application to the round window of the cochlea of high-dose prednisolone (25 mg/ml) or methylprednisolone (12.5 mg/ml) resulted in a statistically significant reduction in hearing loss compared with the control group. Conclusion
The local application of high doses of the drugs to the round window of the cochlea appears to be an effective treatment for acute noise trauma.
BACKGROUND
High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma.
AIM
To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined.
MATERIALS AND METHODS
A series of experiments with different impulse noise exposures was performed. Permanent hearing loss and hair cell density were assessed 14 days after exposure. Hearing and hair cell preservation were investigated as a function of glucocorticoid dose.
RESULTS
After impulse noise exposure, local application of high-dose prednisolone (25 mg/ml) or methylprednisolone (12.5 mg/ml) to the round window of the cochlea resulted in a statistically significant reduction in hearing loss compared to the control group.
CONCLUSION
Local application of high doses of the drugs to the round window of the cochlea appears to be an effective treatment for acute noise trauma.
Sudden Sensorineural Hearing Loss (SSHL) was commonly seen in middle aged people. Tinnitus was reported by 87.2% of the patients, and dizziness or vertigo were reported by 48.5%. The most common concomitant disorder of SSHL was hyperlipidemia.
A retrospective register study with SSHL was performed in Xi'an, China, from 2000-2009.
Of 617 inpatients, the right ear was affected in 267 cases, the left ears in 282 cases, and both ears in 68 cases. The most common age of patients was 41-50 years. There were 20.4% SSHL patients with hypertension, coronary artery disease, or diabetes, and 49.6% patients with hyperlipidemia. Auditory Brainstem Responses (ABR) were performed in 460 patients (504 ears) before treatment, and the ABR threshold of 56.4% ears was > 90 dB. The constituent ratio of patients with an ABR threshold over 90 dB was greater in the vertigo group than the other group. CT and/or MRI scans were available in 277 cases, of which 40 cases (14.4%) were abnormal.
Hypothesis: Intratympanically injected dexamethasone 21-phosphate is converted to its active form dexamethasone in the inner ear and follows the distribution of the glucocorticoid receptor. Background: Although dexamethasone is routinely delivered intratympanically for hearing loss, we know little of its inner ear pharmacokinetics. Dexamethasone 21-phosphate is the pharmaceutical compound available for injection, but it must be converted to its biologically active form (dexamethasone) to bind to the glucocorticoid receptor. Therefore, the current study was conducted to determine the time course of dexamethasone 21-phosphate movement from the middle ear into the inner ear, its conversion to dexamethasone, and the distribution of both forms relative to the glucocorticoid receptor. Methods: BALB/c mice were injected intratympanically with the prodrug dexamethasone 21-phosphate and inner ears collected at postinjection times ranging from 5 minutes to 7 days. Ears were immunohistochemically stained for dexamethasone 21-phosphate, dexamethasone, and the glucocorticoid receptor. Results: Both forms of dexamethasone were seen in the inner ear within 15 minutes, reaching their highest staining intensity at 1 hour. Neither drug was seen after 24 hours. The strongest staining occurred in the spiral ligament, organ of Corti, spiral ganglion, and vestibular sensory epithelia. Distribution of the drug paralleled locations of the glucocorticoid receptor except in the stria vascularis marginal cells, which stained heavily for the receptor but not the drug. Conclusion: Dexamethasone rapidly travels from the middle ear into the inner ear and converts to its active form. The drug distribution follows that of the glucocorticoid receptor. However, it probably has little impact on ear tissues after 24 hours.
In the majority of cases, tinnitus derives primarily peripherally, from damage to hair cells in the inner ear; suffering and annoyance, however, are caused by central cortical processing and functional networks of cerebral plasticity. Therefore, new therapeutic approaches aim to influence these structures; whether it be directly by magnetic radiation, or via direct or indirect electrical stimulation. However, these methods can only be efficient if they can integrate and rehabilitate the existing hearing loss. Effective habituation therapies consist of hearing therapy, rehabilitation of hearing loss by hearing aids and psychosomatic stabilisation. In this review, different therapeutic approaches are described and valuated.
Intratympanic steroids (ITSs) are recommended for treatment of sudden sensorineural hearing loss (SSNHL). On the other hand, the dosage, frequency and duration of the intratympanic therapy are still not clear. We aimed to evaluate the efficacy of low-dose intratympanic steroid (ITS) treatment of SSNHL.
Seventy patients (ears) treated for SSNHL were involved in the study. The patients were divided into four groups: the systemic steroid, combined, intratympanic initial (ITSi) and intratympanic salvage (ITSs). The demographic data, accompanying symptoms, treatment onset duration, the treatment protocol, and pre- and post-treatment pure tone audiometry results were recorded.
The mean treatment onset was 60 days in the ITSs group, which is statistically later than the other groups (p<0.001). The treatment response was assessed based on Siegel's criteria. Hearing recovery was statistically higher in the combined group than the systemic steroid group (p=0.042). 87.5% of the ITSi group showed full recovery, which is a statistically significantly higher difference than the other groups (p<0.001). In the salvage treatment group, the use of low-dose ITS was observed to be inadequate for the treatment (p<0.001). The post-treatment pure tone average gains in dB were analyzed at 500, 1000, 2000, and 4000Hz and the recovery determined for each of the four groups was found to be statistically significant (p<0.001 to p<0.031).
The ITS administration as the initial treatment for mild to moderate hearing loss is adequate while low dose of dexamethasone used as a salvage treatment is inadequate. The use of low-dose ITS in the combined treatment may increase the hearing gain.
Copyright © 2015. Published by Elsevier Ireland Ltd.
Unilateral sensorineural hearing loss (SNHL) affects people at any age, can present as an acute and/or progressive process, and can range from mild to profound. Although the great majority of cases have an unknown cause, the known causes of unilateral SNHL need to be excluded including neoplasms, stroke, demyelinating and autoimmune diseases, infection, perilymphatic fistula, and Ménière's disease. The majority of individuals with idiopathic sudden SNHL will recover complete or partial hearing. However, there is a small subset of patients who remain with unilateral hearing impairment, which can result in communication difficulties. The goal of this article is to present the etiology and medical management of unilateral SNHL in the adult population.
A randomized placebo-controlled study has demonstrated no effect of prednisolone in customary dosage on idiopathic sudden sensorineural hearing loss (ISSNHL). The aim of the present paper is to analyse a larger patient group by meta-analysis of data from the RCT together with a corresponding material drawn from the Swedish national database for ISSNHL. Data from 192 patients, 18-80 years with ISSNHL, were available. All had an acute hearing loss of at least 30 dB measured as PTA in the three most affected contiguous frequencies. All patients had been enrolled within one week after onset and evaluated by audiograms after 3 months. 45/99 (RCT) and 54/99 (the database) had been treated with prednisolone in tapering doses from 60 mg daily and 42/93 with placebo (RCT) or 51/93 with no treatment (the database). Primary outcome was the mean hearing improvement on day 90 for the different groups. A mean difference of >10 dB improvement was required to demonstrate a treatment effect for prednisolone compared to placebo/no treatment. No significant difference was seen between the prednisolone group and placebo/no treatment (p = 0.06). Total recovery was 38 % in prednisolone group, 40 % in the placebo and 14 % in the no treatment group. Vertigo at the onset of hearing loss and age at onset had an equal negative prognostic value in all groups and signs of inflammation had a positive effect. Prednisolone in customary dosage does not influence recovery after ISSNHL.
Noise at the working environment is highly affecting the human health, especially in mining. Continuity of this noise causes hearing loss of miners. In this study, hearing loss based on noise is researched by audiometry and otoacoustic emission on casual staff of TKİ-ELİ coal mines. The difference of this method is taking the otoacoustic emission measurements before audiometry measurements. In 2007, audiometry and otoacoustic emission measurements were made on 639 miners at Ege Lignite Enterprises. It is determined that conductive hearing loss had seen at 32 miners and sensorineural hearing loss had seen at 83 miners. It was decided to dispatch 9 miners to Occupational Diseases Hospital after making tests to these 83 miners at Soma State Hospital. It is revealed that these 9 miners shouldn’t be allowed to work at loud environment according to the first report of Occupational Diseases Hospital. The detection of the possible and occupational disease group hearing loss has become very easy with this method.
La «sordera brusca» es una entidad clínica idiopática. Aislada o asociada a vértigos, su mecanismo sigue siendo desconocido. Es probable que agrupe diferentes afecciones: infecciones víricas, bloqueos microcirculatorios, procesos autoinmunitarios y rotura de tímpano. Los diagnósticos diferenciales fundamentales son el neurinoma del acústico y las disecciones arteriales vertebrobasilares, que pueden cursar con sordera aguda. Los principales elementos del pronóstico son: la profundidad de la hipoacusia, el tipo de curva audiométrica (ascendente, plana o descendente) y la presencia de vértigos. Resulta difícil demostrar la eficacia de los tratamientos debido a la frecuencia de las regresiones espontáneas precoces. En general, se asocian corticoides y tratamientos vasculares, aunque en algunos casos se proponen otros tratamientos como carbógeno, antivíricos, etc. Las sorderas fluctuantes constituyen una nosología mal establecida. Algunas evolucionan hacia sordera profunda, a veces bilateral. La causa más frecuente es la enfermedad de Ménière, con vértigos paroxísticos desde su inicio, o de forma secundaria después de un plazo de 6 meses. Cuando son bilaterales, hay que pensar en la sífilis, las malformaciones cocleares y enfermedades autoinmunitarias. A menudo, la causa permanece desconocida y su tratamiento sigue siendo incierto.
Idiopathic sudden hearing loss may be isolated or associated with vertiginous symptoms. The pathophysiologic mechanism is unclear. Probably it represents the common end point of numerous and various pathologic processes: viral infection, microcirculatory disorders, autoimmune disorders, intralabyrinthine membrane ruptures. Acoustic neuromas and vertebrobasilar dissection are rare cause of sudden hearing loss but should be considered in the differential diagnosis. The treatment is nihilistic (no therapy) or based on the use of blood flow promoting drugs with steroids. A number of other treatments have been advocated including antiviral drugs and carbogen. The principal factor that makes the analysis of treatment efficacy difficult is the high rate of early spontaneous resolution. Principal prognosis factors are: the severity of the loss, flat or downsloping audiograms, and the presence of vertigo that all must be taken into account when trying to ascertain the benefit of any treatment. Fluctuating sensorineural hearing loss is a poorly defined clinical entity with the potential for progressive serious hearing impairment. While the aetiology includes syphilis, cochlear malformations, autoimmune and perilymphatic fistulas, the most common origin is Meniere disease. In the early stage, episodic vertigo may be absent but appears within 6 months. Very often, the origin remains unknown. Any specific treatment may be advised.
Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) remains one of the major unsolved otologic emergencies. It is characterized by the onset of an unilateral sensorineural hearing loss developing within 24 hours, and averaging on pure tone audiogram at least 30 dB HL for three subsequent octave steps, with no marked vestibular symptoms and no identifiable cause. ISSHL is a syndrome covering several heterogeneous entities resulting from different pathogenetic mechanisms. At this time, the audiogram is the unique tool which may help clinicians to identify these entities and provide a classification based on 5 types of hearing loss. Numerous experimental and clinical studies have investigated the mechanisms by which infectious, ischemic, mechanic or immunologic insults may induce cochlear dysfunction. However, extrapolation to humans and rationale therapeutic approaches to ISSHL remain uncertain. SSHL being a diagnosis of exclusion, retrocochlear and neurologic etiologies should be eliminated. No argument allows to consider ISSHL a therapeutic emergency. More precisely, the experimental data presently available on cochlear physiology suggests that a treatment could have some chance to be effective if undertaken within minutes following the onset of ISSHL, a condition never encountered in daily practice. Conversely, it is not justifiable to impute the absence of hearing recovery to a delay in therapy. The various therapeutic strategies currently recommended are highly empirical and should be questionned in terms of cost-effectiveness, the most common being high-dose corticosteroids.
New investigation tests are required for improving our approach to ISSHL.
Purpose. – Sudden idiopathic deafness is a sensorineural hearing loss with no recognized causes at the time of onset. The impairment site is usually localized in the cochlea, but some cases of retrocochlear lesions (e.g., cerebellopontine angle tumors, degenerative neural diseases, neuraxial ischemic lesions) can induce sensorineural deafness. The medical management of patients presenting with sudden deafness aims at detecting a causal mechanism, and at administering emergency therapeutic drugs. The diagnosis of idiopathic sudden deafness can be definitely made when no causes are found. Usually, the impairing mechanism involves the cochlea. The pathophysiology of this sensorineural alteration is still unknown. It is most likely that several mechanisms are associated together, their common point being an impairment to the feedback loop of the organ of Corti.Current knowledge and key points. – It is very likely that reactivation of neurotropic viruses and/or cochlear ischemia are frequent etiologies. Whatever the cause, the treatment is to be administered urgently, and consists of a high-dose corticotherapy at the least. Other treatments have never really proven to be effective. It is secondarily checked that no retrocochlear pathological processes, such as a cerebellopontine angle tumor, is present, in particular in young people.Future prospects and projects. – One of the current objectives is to determine when cochlear ischemia is involved, in a mini-invasive manner, such as with laser Doppler flowmetry, so that the treatment can be optimized. From a therapeutic point of view, early acoustic protection has been proven to be effective in cases of cochlear ischemia in small laboratory animals. Its efficacy in case of sudden deafness, non-exclusive of other causes than ischemia, is being assessed in a multicentric project.
Der plotzliche Horsturz ist eine akut auftretende Horminderung im Sinne einer Schallempfindungsschwerhorigkeit, welche meist einseitig und ohne erkennbare Ursache ist. Liegt ein Horsturzverdacht vor, was aufgrund von Otoskopiebefund und Stimmgabelversuch festgestellt werden kann, soll der Patient wegen der moglichen weitreichenden Konsequenzen rasch einer HNO-spezialarztlichen Untersuchung zugefuhrt werden. Nach der Erstbeurteilung mittels Ohrmikroskopie und Audiogramm kann eine weiterfuhrende Diagnostik notwendig sein. Findet sich keine Ursache, spricht man vom idiopathischen Horsturz. Dieser kann in Anlehnung an die verschiedenen Theorien seiner Entstehung polypragmatisch behandelt werden. Es kommen hierbei vor allem entzundungshemmende, antivirale und durchblutungsfordernde Medikamente zum Einsatz. Dabei muss die hohe Spontanheilungsrate und der immer noch ausstehende Beweis einer tatsachlichen Wirksamkeit aller bisher eingesetzten Therapieformen berucksichtigt werden.
Obwohl die Ursache eines Hörsturzes im Einzelfall nicht klinisch diagnostisch gesichert werden kann, besteht mittlerweile großer Konsens darüber, dass mehrere unterschiedliche pathogenetische Prinzipien zu dem Symptom akute Innenohrschwerhörigkeit führen können. Ausgangspunkt für die Einschätzung, welcher Pathomechanismus einem Hörsturz zugrunde liegt, ist die Form des Audiogramms und das Ausmaß des Hörverlustes. Basierend auf der Vorstellung, dass der Hörsturz keine einheitliche Ätiologie aufweist, existieren dementsprechend auch eine Reihe unterschiedlicher Therapieformen, deren Wirkung zumindest teilweise in klinischen Studien belegt ist. Welche Therapie im Einzelfall zweckmäßigerweise eingesetzt wird, ist abhängig von der Audiogrammform, aber auch von der subjektiven Einschätzung des behandelnden Arztes zur vermuteten Ursache eines Hörsturzes. Im Folgenden werden fünf unterschiedliche Hörverluste und deren vermutete Pathogenese beschrieben. Zugeordnet sind unterschiedliche Therapieprinzipien deren Wirkungsweise erläutert wird.
Up to date: Therapy of Sudden Hearing Loss
Sudden sensorineural hearing loss is thought to be of different origin. Disturbances of microcirculation, autoimmune pathology and viral infection are among the most likely causes. The shape of the puretone audiogram can be a useful clue to its origin. Following is a description of five different forms of sudden hearing loss, its suspected pathogenesis and different therapeutic strategies recommended for the treatment of sudden hearing loss.
Expression of mineralocorticoid type I receptor (MR) gene in the rat cochlea was determined using molecular biological techniques. We synthesized complementary DNA (cDNA) from rat cochlear total RNA and then amplified MR cDNA fragments by polymerase chain reaction (PCR). The amplified cDNA fragments were subcloned into an expression vector and the nucleotide sequence was analyzed to confirm the expression of mRNA encoding MR in the cochlea. We then synthesized digoxigenin-labeled riboprobes with this cloned DNA template and examined the localization of MR mRNA in the cochlea by in situ hybridization. The amino acid sequence of MR cDNA expressed in the cochlea was identical to that of the MR first cloned in the rat hippocampus. In situ hybridization showed the expression of MR mRNA in marginal cells of the stria vascularis, suggesting that aldosterone may regulate microhomeostasis of the endolymph, presumably by modulating Na, K-ATPase activity. Intense MR signal was also identified in spiral ganglion cells, the function of which remains to be determined.
Immunohistochemistry was used to investigate the presence of Na,K-ATPase α- and β-subunits isoforms (α1, (α2, α3β1and β2) in the cochlea of the mouse at different ages between embryological day (E) 19 and postnatal day (P)+30. α1 was mainly found in the stria vascularis and in the spiral ligament; it increased steadily from p+4. These data correlates well with the morphological and electrophysiological maturation of the cochlea. α3 predominated in the spiral ganglia and the cochlear nerve. This finding is well in accordance with reports that α3 seems to be associated with the nervous system. The β-subunit was found mainly in those tissues where staining of the α-subunit also was seen. Both subunits were localized in tissue regions where fluid regulation is expected to play an important role. For some isoforms, the expression pattern of Na,K-ATPase during development in the mouse is different from that in the rat. The expression of Na,K-ATPase and that of glucocorticoid receptors during development in the inner ear of the mouse show a similar pattern, which may indicate that glucocorticoid receptors could be involved in regulating the expression of Na,K-ATPase.
(Auto)immunologisch bedingte Erkrankungen besitzen eindeutige Kriterien und lassen sich danach klar definieren. Ausgehend von einer Synopsis der vorliegenden Ergebnisse der Immunologie, der immunologischen Innenohrforschung und aus klinischen Berichten zur Frage immunpathologischer Prozesse am Innenohr, wird versucht herauszufinden, ob wir bereits in der Lage sind, bestimmten Formen von Innenohrschwerhörigkeiten einen (Auto)immunpathomechanismus zu unterstellen.
Bei den zur Zeit anerkannten Autoimmunerkrankungen werden bisher keine Funktionsstörungen des Innenohres beschrieben. Auf der anderen Seite gelingt es bei manchen Patienten mit unklarer Innenohrschwerhörigkeit, im indirekten Immunfluoreszenz-Test Serumantikörper gegen menschliches Innenohrgewebe nachzuweisen. Solange hierbei ein immunpathologischer Prozeß noch nicht erwiesen ist, sollte nur von „Erkrankungen mit Autoimmunmarkern” gesprochen werden.
Indessen geht die tierexperimentelle Provokation von Antikörpern gegen Innenohrgewebe mit morphologischen und funktionellen Veränderungen am Innenohr einher. Der menschliche Saccus endolymphaticus gibt sekretorisches IgA in die Endolymphe ab, das Epithel enthält (intraepitheliale) Lymphozyten und der Saccus ist von Lymphozyten, Plasmazellen (IgA, IgG) und Makrophagen umgeben. Damit verfügt das Innenohr sehr wahrscheinlich über ein eigenes Immunsystem, das möglicherweise sogar unabhängig vom systemischen Immunsystem wirken kann. So könnten Antigene, die einerseits aus dem Mittelohr in die perisacculäre Region oder andererseits in die Endolymphe gelangen, im Bereich des Saccus endolymphaticus lokale Immunreaktionen auslösen. Damit wären auch (auto-)immun-pathologische Prozesse möglich, die sich nur auf das Innenohr beschränken und daher schwer nachweisbar sind.
Summary
Immunologically mediated tissue lesions or functional disturbances can result from immune responses either to foreign antigens or autoantigenic constituents. Before a disease or a functional disorder can be called an (auto)immune disease, it must be established that immunological processes are involved in its etiology and/or pathogenesis. After reviewing the available data on immunology and on research on immunobiology of the inner ear, as well as clinical observations on disorders of the inner ear of possibly immunological origin, an attempt is made to determine whether (auto)immu-nopathology can be assumed in some patients with sensineural hearing loss.
In patients with disorders presently recognized as autoimmune diseases, no hearing loss has been described so far. However, serum antibodies can be found via the indirect immunofluorescence method in some patients having functional disorders of the inner ear. These serum antibodies interact with normal human inner ear tissue. However, as long as immunopathological mechanisms have not been confirmed, these disorders should merely be called “diseases with autoimmune markers.”
It has been shown in animal experiments that the production of autoantibodies against inner ear components is associated with morphological and functional changes of the inner ear.
The human endolymphatic sac releases secretory IgA into the lumen. Its epithelium contains (intraepithelial) lymphocytes, whereas lymphocytes, plasma cells (IgA, IgG) and macrophages occur in the perisaccular region. In this manner, the inner ear has its own immune system, which can possibly react independently of the systemic immune system. Antigenic material, which might gain access from the middle ear to the perisaccular tissue or to the endolymph, could initiate a local immune response at the site of the endolymphatic sac, so that (auto)immunological processes could then be limited to the inner ear and would be difficult to detect.
Na+,K+-ATPase has been implicated in the maintenance of high [K+], low [Na+] in endolymph of the inner ear, ionic properties condered to support transduction by the receptor cells6. In exocrine ion-transporting epithelia, Na+,K+-ATPase activity is modulated by aldosterone mineralocorticoid hormone31. In the present study, the effect of alteratio of serum aldosterone levels on Na+, K+-ATPase in ion-transporting regions of the mammalian inner ear was investigated. A high Na+/low K+ diet offered ad libitum for 5 days was utilized to significantly decrease serum aldosterone in male Hartley guinea pigs compared to controls. An injection of aldosterone (10 μg/100 g b.wt.) 21 h prior to sacrifice resulted in significant elevation of serum aldosterone over that obtained with the high Na+/low K+ diet. Binding of [3H]ouabain, a specific inhibitor of Na+,K+-ATPase, was significantly elevated in microdissected lateral wall of the basal turn of the cochlea and in the ampulla of the semicircular canal, for aldosterone-injected vs. vehicle-injected animals. Serum [Na+] and [Cl−] were elevated in animals on the high Na+/low K+ diet and unaltered by administration of exogenous aldosterone. The enhancement of ouabain binding in inner ear tissues observed in aldosterone-injected animals, therefore, did not appear to reflect an alteration of serum electrolytes per se. The results of these experiments are consistent with the hypothesis that aldosterone increases the number of Na+,K+-ATPase sites in ion-transporting epithelia of the mammalian cochlea and semicircular canal.
Es wird über vorläufige Ergebnisse einer Infusionsbehandlung berichtet, die sich von bisher gebräuchlichen konservativen Therapieformen einer-seits durch deutlich höhere Kortison-Dosen und andererseits durch die Kombination dieser antiphlogistischen Maßnahme mit einer rheologischen Behandlung, bestehend aus niedermolekularem Dextran und Pentoxifyllin, unterscheiden.
Bei mehr als der Hälfte der so therapierten Patienten kam es bereits unter der 10-tägigen Behandlung zu einer klinisch und elektromyografisch nachweisbaren Besserung. Der Prozentsatz an kompletten Heilungen lag bei Beurteilung rein klinischer Kriterien um 7–10% und bei Einbeziehung neurophysiologischer Parameter um 0–18% höher als bei anderen Therapiemethoden. Verglichen mit der Spontanheilungsquote wurden 20% mehr vollständige Ausheilungen erzielt.
Angesichts dieser Resultate scheint weder die Dekompressions-Operation noch ein therapeutischer Nihilismus länger gerechtfertigt.
The concentration-time curves of prednisolone in cerebrospinal fluid (CSF) and plasma were measured following an equimolar i.v. bolus dose of prednisolone phosphate (five patients) and prednisolone phthalate (four patients). Independent of the prodrug administered, the value of the AUC (0.360 min) in CSF was more than three times lower than the corresponding value in plasma. The AUCs of unbound prednisolone in plasma were higher after prednisolone phosphate, than after prednisolone phthalate (68.1 +/- 15.7 vs 19.0 +/- 5.2 micrograms ml-1 min, P less than 0.001). Similarly, the AUCs of prednisolone were higher in the CSF after prednisolone phosphate, than after prednisolone phthalate (17.6 +/- 2.8 vs 3.3 +/- 1.0 micrograms ml-1 min, P less than 0.0001). The results indicate that the concentrations of prednisolone in CSF are much lower than the unbound concentrations in plasma and that therapeutic inequivalence should be expected when the two prodrugs are given in equimolar doses.
Animal models of vascular disorders are identified or developed for the evaluation of functional deficits and morphologic alterations. This information will serve a useful purpose for a better understanding of sudden deafness, Meniere's disease, and presbycusis. The study of microcirculation of the inner ear vessels reveals that their responses to various stimuli, such as anoxia, sympathetic nerve stimulation, hypothermia, and drugs, are different from those of the middle ear vessels. In sudden occlusion of the major vascular supply to the inner ear, the cochlea is found to be more vulnerable than the vestibular labyrinth; outer and inner hair cells and stria vascularis are most often affected. Animal models for Meniere's disease are also described, and the importance of vascularity at the endolymphatic duct and sac is discussed from an etiologic viewpoint. In presbycusis, animal models show sensory cell and spiral ganglion cell atrophies in different locations than in human cochleas, and the relationship between these atrophies and vascular impairments is not clear at the present time.
Sera from 76 patients with a clinical diagnosis of idiopathic rapidly progressive sensorineural hearing loss (SNHL) (n = 15), sudden deafness (n = 31) and with other etiologies of their hearing loss (n = 30) were analysed by western blot assay. Seventy-three percent of the cases with rapidly progressive SNHL had cross-reacting antibodies (27, 45, 50, 68 kD). The overall response to immunoprogressive therapy was effective in only 50% of cases. Sixty-five percent of the patients with sudden deafness also had cross-reacting antibodies (27, 45, 50, 80 kD). In these cases steroid therapy was more effective in re-establishing the hearing than no treatment, regardless of the western blot outcome. Spontaneous recovery occurred in approx. 50% of cases, but only in those with a positive assay. The antigenic epitopes detected with immunoblotting were not cochlea specific; they were also found in protein extracts of other organs (cranial nerves, kidney, brain).
CBA mice were sacrificed at different ages of developments at embryonic day 13 (E13), E14, E16, E19, E20 and postnatal day 1 (P1), P2, P3, P4, P6, P8, P10, P14, P16, P18, P20 and P30. The temporal bones were quickly removed and deep frozen in order to prepare cryosections for immunohistochemical staining with polyclonal antibodies against glucocorticoid receptors. The avidin-biotin, ABC-method was used to visualize binding. Both the vestibular and the cochlear regions of the inner ear were analysed. A faint staining of the crista ampullaris, the utricle and the cochlear duct was seen at E19; and staining became clearly visible at P1. A decrease in labelling was found at day 2-5 post partum whereafter an increased staining was again noticed until postnatal day 14 when an adult pattern was observed. The appearance of glucocorticoid receptors in the inner ear during development does not follow a linear curve. Further, the labelling pattern may indicate an impact of glucocorticoid receptors on the embryologic maturation itself as well as a functional role in the adult ear.
The effect of anti-inflammatory agents, such as the synthetic glucocorticoid prednisolone, diclofenac sodium, and histamine H1-receptor antagonist, was studied in unexposed and noise-exposed (broad-band noise, bandwidth 1-12 kHz, 106 dB SPL, 30 min) guinea pigs. The results were compared with the results obtained from no treatment and with isotonic saline (placebo) therapy. The cochlear blood flow (CoBF) and the partial oxygen pressure in the perilymph (PL-pO2) were continuously and simultaneously recorded over a period of 210 min. In addition, cochlear microphonics (CMs), compound action potentials of the auditory nerve (CAPs), and auditory brain stem responses (ABRs) were registered. Noise-induced hearing loss paralleled a decrease of PL-pO2. Both were found to occur before evidence of reduced CoBF. PL-pO2 and CoBF progressively declined post-exposure, while CMs, CAPs, and ABRs did not further deteriorate nor showed signs of recovery up to 180 min after cessation of noise. Treatment started 60 min post-exposure, or after 90 min without manipulation and was then further studied for 120 min. In the unexposed animals, diclofenac sodium and prednisolone induced a significant decline of PL-pO2, while CoBF, CMs, CAPs, and ABRs revealed no change. Isotonic saline did not influence the measured parameters. After infusion of the histamine H1-receptor antagonist, a significant decrease of CoBF together with blood pressure and CMs was observed, while PL-pO2, CAPs, and ABRs showed no change. In the noise-exposed animals, diclofenac sodium induced partial restoration of CM and CAP amplitudes and full restoration of ABRs. Following a high dose of prednisolone (25 mg), partial restoration of CMs and full restoration of CAPs and ABRs were registered. This effect was significantly less pronounced following a low dose of prednisolone (2.5 mg). Restoration of CMs, CAPs, and ABRs was immediate (i.e. 50 min after infusion) and remained stable for another 60 min until the end of the recording period. The histamine H1-receptor antagonist and isotonic saline did not influence CMs, CAPs, and ABRs. None of the applied drugs resulted in relief of progressive noise-induced cochlear hypoxia and post-traumatic ischemia. These findings indicate direct cellular effects of prednisolone and diclofenac sodium in the cochlea taking into account no blood flow and oxygenation. The possible mechanisms involved are discussed.
Different patterns of sensorineural hearing loss with a potential improvement in auditory function following immunosuppressive therapy might be caused by an isolated autoimmune disease of the inner ear. Because of the lack of well-defined detection methods to identify autoimmune processes within the inner ear and the fact that the human inner ear is one of the few organs of the body not amenable to diagnostic biopsy, there has been great interest in developing animal models. Previous studies found evidence that this entity might be cellular mediated. By heterologeous immunization of inbred Lewis rats with inner-ear tissue, an autoreactive inner-ear-specific T-cell line was established. After passive transfer of these cells, a labyrinthitis was induced in recipient animals. The experimental design can serve as an animal model for a cellular-mediated autoimmune disease of the inner ear. Further studies have to split the cochlear proteins and to identify the protein with the strongest autoimmunological potency. After biotechnical production of this protein, a clinical test to diagnose an autoimmune disease of the inner ear in man should be possible.
A subclinical viral labyrinthitis has been postulated in the literature to elicit Idiopathic Sudden Sensorineural Hearing Loss. An etiological role for the herpes virus family is assumed. Corticosteroids possess a limited beneficial effect on hearing recovery in ISSHL. In this study, the therapeutic value of the antiherpetic drug aciclovir (Zovirax) on hearing recovery in 44 ISSHL patients receiving prednisolone is evaluated in a multicentre clinical trial. The study is designed prospectively, randomized, double-blind and placebo-controlled. Subjective parameters include hearing recovery, a pressure sensation on the affected ear, disequilibrium or vertigo and tinnitus. Audiometric parameters include pure tone and speech audiometry. A one-year follow up is obtained. Both the pressure sensation and disequilibrium or vertigo have a good prognosis, but tinnitus, occurring in most patients, has a poor prognosis. Hearing recovery prognosis depends on the severity of initial hearing loss, and not on vestibular involvement. No beneficial effect from combining aciclovir with prednisolone can be established in ISSHL.
To describe patients who developed allergic reactions (ie, erythema on their face and body, itching, flushing, drop in blood pressure, respiratory distress, and cold sweats) immediately after intravenous injection of prednisolone hemisuccinate (SoluDecortin H, E Merck, Darmstadt, Germany).
Academic medical center.
Three of 4 patients had a positive reaction to an intracutaneous test with prednisolone hemisuccinate (SoluDecortin H) but no reaction to the additive sodium succinate. The results of the prick test were negative for all patients. Although no specific IgE antibodies were detected in the serum of these patients, allergic reaction was noted in 3 cases, since standardized techniques to detect antibodies in the serum for hydrocortisone acetate (ie, prednisolone) are lacking. One female patient had a cross-reaction to prednisolone and dexamethasone (Fortecortin, E Merck, Darmstadt, Germany). A renewed application of prednisolone hemisuccinate was well tolerated by all patients when histamine1 and histamine2 receptors were blocked with the use of cimetidine hydrochloride, 200 mg twice per day (1-0-1 ampules, Tagamet, SmithKline Beecham Pharmaceuticals, Philadelphia, Pa) and dimethindene maleate, 4 mg twice per day (1-0-1 ampules, Fenistil, Novartis, Munich, Germany); calcium was given for membrane stabilization.
Allergic reactions to glucocorticoid therapy are only occasionally mentioned in the literature. These reactions appear more often when glucocorticoids are applied topically and may lead to dangerous complications in patients if administered systemically. Therefore, when allergic reactions result from glucocorticoid therapy, (immediate-type reactions should be suspect), consider corticosteroid allergy as a differential diagnosis.
Autoimmune disease (e.g., Cogan syndrome) and other inflammatory inner ear diseases may ravage the labyrinth if not treated aggressively with antiinflammatory medication. Corticosteroids are the mainstay of treatment, yet, partly because of the existence of the blood-labyrinthine barrier, the ideal drug, dose, and route of administration are currently unknown.
In the present study, we established cochlear fluid pharmacokinetic profiles of hydrocortisone, methylprednisolone, and dexamethasone in the guinea pig following oral, intravenous, and topical (intratympanic) administration. High-performance liquid chromatography was used to determine the drug concentrations, and comparisons were made with simultaneous pharmacokinetic profiles from blood and cerebrospinal fluid.
Our findings demonstrated a much higher penetration of all three drugs into the cochlear fluids following topical application as compared with systemic administration, with methylprednisolone showing the best profile.
The results suggested that intratympanic administration of corticosteroids might be more efficacious while avoiding high blood levels and therefore the deleterious side effects of systemic use. CLINICAL APPLICATION: Thirty-seven patients with various inner ear disorders causing sensorineural hearing loss were subsequently treated using intratympanic corticosteroids, 20 with dexamethasone, and 17 with methlyprednisolone. Patients with immune-mediated hearing losses showed the best results, with notable improvement also seen in several cases of a "sudden deafness." No benefit was seen in patients with cochlear hydrops or those with sudden deterioration of a preexisting hearing loss. Three patients developed a transient otitis media related to the treatments, easily controlled with antibiotics. There were no cases of treatment-induced hearing loss and no permanent tympanic membrane perforations.
Overall injection of intratympanic corticosteroids for the treatment of hearing loss in inner ear disorders appears to be both safe and highly effective for certain disorders. The concept of this technique is supported by animal experimental data. The findings from the present study warrant further clinical application and experimental investigation.
Corticosteroid therapy reverses clinical autoimmune sensorineural hearing loss, although little is known of how steroids restore normal auditory function. If suppression of systemic autoimmune processes underlies hearing restoration, then preventing autoimmune symptoms from developing should prevent cochlear dysfunction. MRL. MpJ-Fas(lpr) autoimmune mice were used to test this potential mechanism by initiating oral prednisolone treatment at 6 weeks of age, prior to autoimmune disease and hearing loss onset. The steroid treatment group was given prednisolone in their drinking water, while untreated controls were given tap water. Treatment continued for 7 months with periodic evaluations of cochlear function with auditory brainstem response (ABR) audiometry. Autoimmune mice given the steroid lived longer and did not develop levels of serum immune complexes seen in their untreated controls. Also, their ABR thresholds remained near normal throughout the 7 months of treatment, while untreated controls showed progressive threshold elevations typical for autoimmune disease. This correlation of suppressed systemic autoimmune activity and maintenance of normal cochlear function identifies one potential mechanism for autoimmune hearing loss and hearing restoration with steroid therapy. The autoimmune mouse should serve as a valuable model for future studies of the cochlear mechanisms responsive to steroid treatment in autoimmune hearing loss.
Corticosteroid therapy is used to reverse autoimmune sensorineural hearing loss, although little is known of the mechanism by which this occurs. This has been due to the lack of a suitable animal model with spontaneous hearing loss that is steroid responsive. The present study examined the effects of prednisolone treatment on auditory thresholds in the MRL.MpJ-Fas(lpr) autoimmune mouse to determine its suitability as such a model. Autoimmune mice at 3.5-4. 5 months of age were evaluated by pure-tone auditory brainstem response (ABR) to establish threshold elevations due to the disease. The steroid treatment group was then given prednisolone in their drinking water for 2.5 months, while untreated controls were given tap water. Significantly more steroid treated mice survived to the time of post-treatment ABR evaluation. Half of the steroid treated ears demonstrated either improvement or no change in cochlear function compared to only 25% in the untreated controls. Overall, cochlear thresholds in the untreated controls increased by 14.7 dB, whereas no significant threshold increase was seen in the steroid treated group (4.3 dB) over the treatment period. No qualitative anatomical differences were seen in the ears of those mice surviving to the end of the study. These findings establish the autoimmune mouse as a model for studies of steroid responsive mechanisms within the ear. This could apply to autoimmune sensorineural hearing loss, as well as any hearing disorder for which steroid therapy is recommended.