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Pro Otology
Balkan Journal of Otology & Neuro-Otology, Vol. 4, No 1:49—53 © 2004
All rights reserved. Published by Pro Otology Association
Our Experience with Immune Modulator - Inosine Pranobex (Isoprinosine) in the Treatment of Sudden Sensorineural Hearing Loss of Suspected Viral Origin
Roumen Benchev, Zlatina Zhelyazkova
Clinic of Otorhinolaryngology, Medical Institute, Ministry of Interior, Sofia, Bulgaria
ABSTRACT
Objective: The purpose of this study was to observe the effectiveness of immune modulator –Inosine Pranobex (Isoprinosine) in the treatment of sudden sensorineural hearing loss of suspected viral origin.
Study design: The study design was a retrospective analysis.
Setting: This study was performed in the Clinic of Otorhinolaryngology in the Medical Institute of Ministry of Interior, Sofia.
Patients: The study included 28 patients with sudden hearing loss of suspected viral origin, divided randomly into two groups.
Intervention: The first group of 14 patients was treated with corticosteroids and vasodilators. The second group of 14 patients was treated with corticosteroids, vasodilators and immune modulator - Isoprinosine.
Main Outcome Measures: The patients passed precise otorhinolaryngological examination, pure tone audiometry, speech audiometry, stapedial reflex testing, ABR, CT scan, hematological testing –complete blood count (CBC) and sedimentation rate, biochemistry and serologic testing for syphilis. The patients with vertigo passed observation for nystagmus, static and kinetic tests, posturography and electronystagmography (ENG).
Results: We compared the two groups before and after the treatment regarding mean hearing level at each frequency, speech reception threshold improvement, and tinnitus and balance complaints. 4 patients recovered totally, 19 patients improved their hearing with 20 dB and 5 patients showed no improvement. The second group of patients, cured with Isoprinosine recovered in shorter time.
Conclusions: Administration of a combination of corticosteroids, vasodilators and immune-modulator should be recommended for treatment of patients with sudden sensorineural hearing loss.
Key words: Sudden sensorineural hearing loss, Isoprinosine, Corticosteroids, Vasodilators.
Pro Otology 1:49—53, 2004
INTRODUCTION
Sudden sensorineural hearing loss is defined as 30 dB or more sensorineural hearing loss over at least three contiguous audiometric frequencies occurring within 3 days or less. The phylogenetically newer portion of the inner ear, which includes the cochlea and saccule, is relatively more susceptible to various agents than the pars superior. Besides, it is known the intolerance of the cochlea to ischemia. Sudden hearing loss may be idiopathic but also significant differential diagnoses must be considered. In etiologic courses may be included the following purposes: neoplastic as: acoustic neurinoma, myeloma, meningeal carcinomatosis; traumatic as: perilymphatic fistula, tempore bone fracture, otologic surgery, noise exposure; pressure changes in the inner ear fluids as: scuba diving, sneezing, performing Valsava maneuver; haematological disorders as: leukemia, macroglubolinemia, polycytemia, sickle cell anemia; infectious diseases such as: syphilis, meningitis; neurological diseases as: multiple sclerosis, migraine, strokes involving the anteroinferior cerebellar artery circulation; autoimmune disorders as: ulcerative colitis, polyarteritis nodosa, rheumatoid arthritis, lupus erytematosus, scleroderma, Cogan’s syndrome, Wegener’s granulomatosis, autoimmune inner ear disease (1-4). The patients, included in our study, did not have in their history any of these well-established courses or mentioned upper diseases. Etiology of the sudden sensorineural hearing loss includes as well viral, vascular and viral-vascular combination. Patients in our study reported antecedent history of upper respiratory infection within a month or less of onset of the hearing loss. The viruses of mumps, measles, herpes simplex, herpes zoster, adenoviruses and influenza deserve particular attention in view of their clearly demonstrated etiologic role in sudden sensineural hearing loss. Shuknecht et al. (1962) described the findings in four cases of sudden sensineural hearing loss in which the pathologic changes closely resembled what had been found in viral endolymphatic labyrinthitis of mumps, measles and prenatal rubeolla (5). The cutaneus lesions associated with herpes zoster infections make this form of viral neurinitis and ganglionitis relatively easy to diagnose clinically and to relate etiologically the sudden sensorineural loss to the virus (6).
The vascular courses include vasospasm, thrombosis, embolism, hemorrhage, hypercoaguability and rheologic abnormalities. Experimental studies have shown that the ganglion cells are the most sensitive to ischemia, while the pathologic data indicates that the organ of Corti, stria vascularis and tectorial membrane are the predominant structures affected in cases of sudden sensineural hearing loss (7). The findings in animal models of hearing loss of vascular origin are of extensive cochlear fibrosis and ossification.
The viral-vascular combination theory suggests that a viral infection initiates a hypercoagulable state secondary to the effect of viruses on the vascular system. One of the mechanism by which hearing loss develops is through changes in cellular immunity. Rapidly progressive bilateral sensorineural hearing loss shows autoimmune etiology. Additional evidence of that type of etiology is indicated by the fact that patients had substantial hearing improvement with mono steroid treatment.
The therapy that has been proven to be effective in the treatment of sudden sensorineural hearing loss is the etiologic based one. We used a combination of medicines, according to the viral-vascular etiologic theory (8-10).
| Table 1. The scheme of therapy administered to the both of the patients groups. |
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PATIENTS AND METHODS
28 patients of either gender (24 male and 4 female), aged between 12 and 47 years with sudden hearing loss were enrolled in the study. 8 patients noted their hearing loss upon first awakening in the morning, 2 patients – after stress situation, 18 patients had in their history a viral upper respiratory infection as 2 patients were in contact with varicella – infected persons, 1 woman was with rubeolla and 15 patients had in their history symptoms of influenza. The hearing loss developed over the course of an hour, a day or three days. 18 patients had unilateral hearing loss and 10 patients – bilateral. The amount of hearing loss involved different parts of hearing frequency range. The entire examined group had tinnitus, which preceded the hearing loss by several hours with usually a roaring quality. 12 patients had mild and transient vertigo. 10 patients had aural fullness.
All the patients were questioned about previous otologic disease and surgery; ototoxic drug use; trauma, diving, flying, intense noise exposure; diabetes mellitus, autoimmune disorders – inflammatory, non-infectious diseases; multiple sclerosis, cerebrovascular accidents. Ophthalmologic, neurological and rheumatologic consultations were carried out to rule out systemic vasculitic diseases. The otorhinolaryngologic examination included otoscopy, anterior rhinoscopy and pharyngoscopy. The ear examination showed normal otoscopic structures. The audiometric patterns from the pure tone audiometry were variable with mild to profound hearing losses. There was positive stapedial reflex of impedancemetry. Auditory brainstem response testing was normal. CT scan examination was normal. Diagnostic lab tests help in the evaluation of hematological and autoimmune diseases. The complete blood count showed elevated sedimentation rate in 22 patients. Serum glucose and urinalysis were normal. Serologic testing for syphilis was negative. The patients with vertigo passed observation for nystagmus, static and kinetic tests, posturography and ENG.
The patients were divided in two groups: A. Patients, treated by corticosteroids and vasodilators. Methylprednisolon was administrated in the beginning at a dose of 1 mg/kg/day (60-80 mg/day) in a single morning dose intravenous for 6 days, followed by a tapering schedule. Cavinton was administrated 10 mg to 40 mg intravenous for 14 days. B. Patients treated by the same course of corticosteroids and vasodilators and in addition immune-modulator – Isoprinosine – 3g per day (3x2 tabl.) for a period of 5 days. (Table 1).
| Table 2. The scheme of therapy administered to the both of the patients groups. |
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RESULTS
All the studied patients had sudden sensorineural hearing loss. Pure tone audiometry before treatment showed different types of audiograms as follows:
a) 10 patients had unilateral sensorineural hearing loss of down sloping type (FIG. 1);
b) 6 patients had unilateral midfrequency sensorineural hearing loss of flat type (FIG. 2);
c) 2 patients had unilateral sensorineural hearing loss of upsloping type (FIG. 3);
d) 7 patients had bilateral sensorineural hearing loss of flat type (FIG. 4);
e) 2 patients had bilateral sensorineural hearing loss of upsloping type (FIG. 5);
f) 1 patient had bilateral sensorineural hearing loss of down sloping type (FIG. 6).
Speech audiometry showed two types of discrimination scores:
a) 22 patients with better discrimination score;
b) 6 patients with poor discrimination score.
Pure tone audiometry was performed weekly during the first 14 days of the treatment, 4 weeks after the onset of the disease and 2 months later.
After 14 days of the treatment in the Clinic of Otorhinolaryngology and 2 weeks more at home, the results were as following in Table 2.
We compared the two groups before and after treatment regarding mean hearing level at each frequency, speech reception threshold improvement, and tinnitus and balance complaints. 4 patients recovered totally, 19 patients improved their hearing with 20 dB and 5 patients showed no improvement. The second group of patients, cured with Isoprinosine recovered in shorter time.
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DISCUSSION
Sudden sensorineural hearing loss should be considered an otologic emergency. It is one of the most controversial-unsolved mysteries in Otolaryngology. The treatment of sensorineural hearing loss often proves to be frustrating to the clinician as, in the majority of cases, the etiology is unknown and the underlying disease process is irreversible. Otorhinolaryngologists make efforts to treat the sudden sensorineural hearing loss according to the established etiologic courses as viral, vascular or viral-vascular combination (11-15). Support for a viral theory is the antecedent history of a viral upper respiratory infection and epidemic of viral diseases, such as parainfluenza, mumps, varicella, rubeola, and adenovirus infections. Histological analyses of temporal bones from patients who suffered from sudden sensorineural hearing loss displayed atrophy of the organ of Corti, stria vascularis and tectorial membrane. These changes are similar to those seen in cases of viral labyrinthitis (7). Haemaglutination and slaging of blood may occur when virus particles attach to erythrocytes. The pathologic changes were consistent with vascular embarrassment of the inner ear. In the histological findings the organ of Corti was absent throughout the cochlea; the stria vascularis was atrophic throughout. The spiral ganglion cells were considerably decreased in the basal turn and somewhat decreased in the apical turn. Commonly in viral inflammation, extravasation of blood results in micropetechiae. The vascular endothelium is invaded and inclusion bodies may be seen in the endothelial cells in viral diseases. The capillary endothelium is often swollen and may proliferate. These changes narrow the lumen of the capillaries and reduce blood flow. There is, however, overall hyperemia at the site of inflammation and total effective blood flow may not be altered. Infiltration of lymphocytes, plasma cells, macrophages and polymorphonuclear leukocytes occurs. Perivascular spaces then fill with edema fluid. Necrosis of neuroepithelium may occur and is indicated by hyperchromatism, fragmentation and lysis of nuclei (5). The most common route of access of viral particles to the inner ear is a viremia in the early phase of viral illness in which virions are deposited within the membranous cochlea. That is why we use antiviral medications and especially immune stimulator. Isoprinosine was used to support the mechanism of immune answer to the foreign agent – the virions and to reduce the damage of the cochlea structures. Isoprinosine improves cochlear oxygenation and circulation. Medications like Acyclovir may be unhelpful when the cause is a virus that is not in the herpes family, that’s why Isoprinosine is favored. The corticosteroids, as well, have an anti-inflammatory effect on the organ of Corti and the microvasculature. The length of their usage should be increased and gradually tapered.
It is not surprising that the cochleovestibular blood supply may be affected by circulatory disorders such as embolic phenomenon, thrombosis, vasospasm and hypercoagulable or high viscosity states resulting in sudden sensorineural hearing loss. The vascular etiologic theory is favored because of the sudden nature of the onset of hearing loss. The underlying pathophysiology can be explained by the occurrence of sudden anoxic injury to the cochlea. Effects of anoxia result in changes in the cochlea microphonics with loss of the action potential. Despite restoration of the cochlea blood flow, loss of endocochlear potentials may be irreversible after 30 minutes (4). The cochlea is extraordinarily intolerant of blood disruptions. The arterial supply to the cochlea is such that the basal turn is fed first by the main cochlear artery with the cochlear apex fed last. The findings in animal models of hearing loss of vascular origin prove extensive cochlear fibrosis and ossification. Vasodilators promote blood flow and reverse vasospasm.
The viral-vascular combination theory suggests that a viral infection initiates a hypercoagulable state secondary to the effect of viruses on the vascular system. Viruses are able to attach to red cells and cause haemaglutination. Oedema of the capillary endothelia and hypercoagulation occur. So the combination of immune-mediator (Isoprinosine), corticosteroid (Methylprednisolon) and vasodilator (Cavinton) proved to be effective in treatment of sudden sensorineural hearing loss. The degree of hearing loss is considered the most important prognostic factor. Hearing recovery in profound losses tends to occur in the low tones, which correlates with involvement at the apex of the cochlea rather than the basal end. Patients with upsloping audiogram or midfrequency losses recover better. Patients with flat type audiogram improved their hearing with 20 dB. Some of the patients with downsloping type audiogram recover worse. Patients with good hearing capability at 8 kHz recover better. Patients with measurable speech discrimination scores on presentation uniformly improved with treatment, even if their pure tone-average was profound. Presence of vertigo is associated with more severe losses and represents a greater insult to the labyrinth and those patients recover worse. Application of combination of steroid, vasodilator and immunostimulater significantly improves the recovery outcomes in cases of sudden sensorineural hearing loss.
CONCLUSIONS
Administration of a combination therapy of corticosteroids, vasodilators and immune-modulator should be recommended for treatment of patients with sudden sensorineural hearing loss of suspected viral origin. This type of treatment result in earlier hearing recovery and less extensive cochlear destruction compared to steroids and vasodilators. The recovery is significantly related, as well, to onset of hearing loss and audiogram type. Treatment aimed at the possible etiologic agent might be beneficial only in the very early phase of the hearing loss.
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