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This article reviews the importance of the round-window membrane in exposing the labyrinth to or protecting it from the toxic effects of otitis media. Only in the last decades have the middle ear and the inner ear been recognized as valid and important immunocompetent structures [1]. The purpose of this article is to review the interrelations between the middle ear and the inner ear in otitis media and the role of bacteria, bacterial products, and inflammatory mediators as toxic agents acting through the roundwindow membrane. The middle-ear space is lined by a mucous membrane that in turn is covered by a layer of mucin (mucus) through which microorganisms must pass before they reach the mucosa itself (Table 1).
Once the microorganisms have reached the epithelial surface of the mucous membrane, they must overcome the rapidly dividing mucosal cells and the superficial specific mucosal immune system [4].
If bacteria are able to overcome the mucus and epithelial layers of the mucosa, they must meet with both nonspecific and specific defense systems in the lamina propria. Once bacteria overcome the defense mechanisms of the middle-ear mucosa, damage to the inner ear can occur. The conditions caused in the middle ear by bacteria - acute otitis media, chronic suppurative otitis media, and middle-ear effusion - now are accepted as representing different phases in the spectrum of the same pathological continuum of otitis media [11]. Bacteria that cause acute otitis media are predominantly aerobic, particularly Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis [13- 15]. Also related to inner-ear damage caused by otitis media is the role of inflammatory mediators. Round-window membrane anatomy and structural studies disclose three basic layers: an outer epithelium, a middle core of connective tissue, and an inner epithelium (Figs.
The acoustic neuroma, also known as vestibular schwannoma,or an acoustic neuroma, is a nonmalignant tumor of the 8th cranial nerve (see Figure 1). In spite of the usual origin of acoustics in the vestibular nerve (Roosli et al 2012), vertigo (spinning) is not common, occurring in only about 20% of persons with acoustic neuroma. Facial sensory disturbances occur only in large tumors (about 50% of those greater than 2 cm in size).
Acoustic neuroma occurs in two forms: a sporadic form and a form associated with an inherited syndrome. Figure 2: MRI scan of the brain showing an acoustic neuroma (the white spot on the left side of the picture).
Electronystagmography (ENG testing) is frequently abnormal, and about 50% of all tumors are associated with unilateral loss of calorics. Although it is relatively costly compared to audiometry or ABR, the optimal test for excluding an acoustic neuroma is a gadolinium enhanced T1 MRI (Figure 3). Acoustic neuromas range in size up to 4 cm.A The smallest, the intracanalicular acoustic, is measured in millimeters. If surgery is eventually required, surgical complications in this situation, such as severe facial nerve weakness, are nearly 100%. In January 2008, a visit to the National Library of Medicine’s search engine, PubMed, revealed more than 5409 research articles referring to acoustic neuroma published since 1949 with 150 published in the last year.
The American Hearing Research Foundation is a non-profit foundation that funds research into hearing loss and balance disorders related to the inner ear and is also committed to educating the public about these health issues.
Watch our award-winning video on hearing aids and the most recent advancements in hearing aid technology.
Download our Guide to Better Hearing to review what you need to know about the process of improving your hearing. Schedule a no-obligation appointment with one of our highly trained professionals to start your journey to better hearing. What if you could touch a single point of your ear and make your craving for food, nicotine, alcohol or anything else disappear? Many people have chosen auriculotherapy as their treatment of choice for eliminating addicting behaviours including alcohol and drug abuse, attention deficit disorder, obsessive-compulsive disorder, and even gambling. Auricoltherapy is very similiar to ear acupuncture but instead of needles, a microcurrent stimulator is place on reflex points on the outer ear that then send a message to the brain based on the location of the stimulation. You can learn how to indentify the reflex points on the outer ear and their therapeutic effect on the body and do-it-yourself at home! Characteristics of the immune system in the human middle ear and middle-ear mechanisms against bacteria are explained. One of the first and most important studies pertaining to the immunological aspects of the middle ear, published in 1974 [2], concerned the role of the secretory immune system in the middle ear and otitis media. In this article, we emphasize the importance of continued investigations into the facilitative or protective contributions of the round-window membrane in inner-ear toxicity in the several forms of otitis media.
Within the mucin are found substances that can either kill the bacteria or inhibit their growth: lysozyme, lactoferrin, and lactoperoxidase [4]. This specific defense system depends on the secretory antibodies, mainly secretory immunoglobulin A (IgA). The first system is made up of a complement system, phagocytes (macrophages and polymorphonuclear neutrophils), and transferrin.
Pathological events can be caused by a direct effect of the bacteria itself: Bacterial penetration of all three layers of the round-window membrane was demonstrated experimentally and resulted in bacteria entering into cochlear turns and neuronal pathways, causing nerve degeneration and edema and hemorrhage of the stria vascularis [8]. Experimentally, the same pattern of otitis media pathological changes were observed in the round-window membrane and in the mucoperiosteum of the middle ear.
Even middle-ear effusion, often considered to be or described as a sterile condition, is now accepted as containing bacteria and bacterial products in a high percentage of cases [16,l7], and the predominant microorganisms are the same as those in acute otitis media [18,19]. Mediators are biochemical components produced by epithelial cells, infiltrating inflammatory cells, and endothelial cells, which mediate inflammatory reactions in a sequential manner [20].
Only after drilling the lateral edge of the round window niche is the round window membrane clearly visible. Photomicrograph of the normal human round-window membrane, which consists of an outer low cuboidal epithelium (left side of the image) , a middle core of connective tissue, and an inner simple epithelium (right side of the image). Most commonly, it arises from the covering cells (Schwann cells) of the inferior vestibular nerve (Roosli et al 2012).
NF2 is rare; there are only several thousand affected individuals in the entire United States, corresponding to about 1 in 40,000 individuals.
On MRI, acoustic neuromas are frequently uniformly enhanced, dense, and expand the internal auditory meatus. Acoustic neuroma caused by neurofibromatosis type II (NF 2) should be suspected in young patients and those with a family history of neural tumors. Gamma knife stereotactic radiosurgery has become more prevalent recently as it has been demonstrated to be safe and effective in the control of acoustic neuromas (Likhterov, 2007).

This occurs because the facial nerve often becomes “fused” to the tumor after the gamma knife procedure. This might occur if an acoustic tumor is present in the only hearing ear, or after surgery to remove bilateral acoustic neuromas.
In spite of this concentration of effort by the medical community, acoustic neuroma remains a disorder that cannot be prevented and is often diagnosed after it is too late to save hearing. Ruckenstein, MJ Bigelow DC, The efficacy of corticosteriods in restoring hearing in patients undergoing conservative management of acoustic neuromas.
Comparison between intraoperative observations and electromyographic monitoting data for facial nerve outcome after vestibular schwannoma surgery. Causes of unilateral sensorineural hearing loss screened by high-resolution fast spin echo magnetic resonance imaging: review of 1070 consecutive cases.
Outcome analysis of acoustic neuroma management: a comparison of microsurgery and stereotactic radiosurgery. Pain subsequent to resection of acoustic neuromas via suboccipital and translabyrinthine approaches. Retrospective study of postcraniotomy headaches in suboccipital approach: diagnosis and management. What if by touching a part of your ear you could lower blood pressure or reduce fever, inflammation or swelling? The role of bacteria and bacterial products in inner-ear damage is detailed, and related pathological events are described. The concept that the inner ear is capable of mounting an immune response dates back only to the 1980s [3]. Sialic acid-containing oligosaccharides of the mucin form another defense mechanism and appear to act as mucin receptors for the bacteria, preventing their adherence to the epithelial wall, thus modulating bacterial colonization [5].
This system depends on B cells derived from mucosa-associated lymphoid tissue (MALT), which consists of lymphoepithelial structures, such as those constituting Waldeyer's pharyngeal ring [6]. Bacterial products also were important: Instillation of a suspension of Escherichia coli endotoxin into the round-window niche in rats demonstrated an inner-ear disturbance using a frequency-specific auditory brain stem response technique [9].
These changes could account for modifications of permeability, rendering the membrane an easy pathway from the middle to the inner ear [12]. In chronic otitis media, the most common isolate is Pseudomonas aeruginosa, and other isolates include such aerobic organisms as Staphylococcus aureus, S.
Besides bacterial infections, endotoxins, exotoxins, and other bacterial products, inflammatory mediators could be involved in the development of sensorineural hearing loss, the more frequent complication attributable to interaction between the middle ear and the inner ear [21]. Initially, round-window membrane alterations induced by otitis media were thought to be restricted to or predominantly centered in the outer epithelium, but subsequent ultrastructural studies demonstrated that the three layers participate in the resorption and secretion of substances to and from the inner ear [30].
For easy identification of the membrane for the image, the membrane was disrupted, and the lumen of scala tympani then is clearly visible.
The entire membrane might participate in the inner-ear defense mechanism , but structural changes in otitis media were confined mainly to the inner epithelium and connective ti ssue layers. Characteristics of secretory immune system in human middle ear: Implications in otitis media. Binding between outer membrane proteins of nontypeable Haemophilus influenzae and human nasopharyngeal mucin.
Bacteriology of acute otitis media in a cohort of Finnish children followed for the first two years of life. Bacteriological findings and persistence of middle ear effusion in otitis media with effusion. Effect of prostaglandin, leukotriene, and arachidonic acid on experimental otitis media with effusion in chinchillas.
Effect of exogenous arachidonic acid metabolites applied on round window membrane on hearing and their levels in the perilymph. Cytokine profiles in a rat model of otitis media with effusion caused by eustachian tube obstruction with and without Streptococcus pneumoniae infection. Clinical aspects of round window membrane permeability under normal and pathological conditions.
Acoustic neuromas comprise about 6% of all intracranial tumors, about 30% of brainstem tumors, and about 85% of tumors in the region of the cerebellopontine angle.
A high-frequency sensorineural pattern is the most common type, occurring in approximately two-thirds of patients. Unsteadiness is much more prevalent than vertigo, andA approximately 70% of patients with large tumors have this symptom.
A fast spin-echo T2 variant of MRI is very sensitive to acoustics, and in some clinical settings, can be done fairly inexpensively. Tumors are staged by a combination of their location and size: An intracanalicular tumor is small and in the internal auditory canal (IAC). There are several other tumors that can occur in the same region of the brain [the cerebellopontine angle (CPA)] as acoustic neuromas. Gamma knife does not generally make tumors go away — Figure 3 is actually that of a patient who had gamma knife surgery several years prior.
Belal (2001) reported that cochlear implantation is possible only if there is an intact cochlear nerve (as shown by a positive response to promontory stimulation), and if the implantation is done at the time of acoustic tumor removal, before the cochlea ossifies (turns to bone). At the American Hearing Research Foundation (AHRF), we have funded basic research on acoustic neuroma in the past, and are very interested in funding additional research on acoustic neuroma in the future. A comparison of direct eighth nerve monitoring and auditory brainstem response in hearing preservation surgery for vestibular schwannoma. Intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation for preservation of facial nerve function in patients with large acoustic neuroma. Irradiation of cochlear structures during vestibular schwannoma radiosurgery and associated hearing outcome.
Facial nerve monitoring paramaters as a predictor of postoperative facial nerve outcomes after vestibular schwannoma resection. Medical history, cigarette smoking and risk of acoustic neuroma: an international case-control study. Hearing preservation following fractionated stereotactic radiotherapy for vestibular schwannomas: prognostic implications of cochlear dose.
The hypothetical role of inflammatory mediators in bacteriainduced inner-ear toxicity is particularly emphasized. Ciliary function is also important because it promotes drainage of mucus and secretions or pus from the middle-ear cavity through the eustachian tube.

These MALT-induced B cells migrate through lymph and blood to target such tissues as the middle-ear mucosa, where they differentiate after extravasation to IgA-producing plasma cells. However, a large field of knowledge remains to be elucidated about the extent to which these roundwindow otitis media-induced alterations influence the permeability of the membrane [31]. In the remaining third, the next most common observation is hearing loss at low frequency (which would be more typical of Meniere’s disease). Facial twitching, also known as facial synkinesis or hemifacial spasm, occurs in about 10% of patients. Some small studies have found an association of acoustic neuromas with cellular phone use or prolonged exposure to loud noises, but other studies do not find this link (Christensen et al 2004, Edwards et al 2006, Edwards et al 2007, Hardell et al 2003, Lonn et al 2004, Myung et al 2009, Schlehofer et al 2007, Schoemaker et al 2007). It has been estimated that 5% of persons with sensorineural hearing loss have acoustics (Daniels et al 2000), but this estimate is suspect as it would imply a much higher prevalence of acoustic neuromas than are commonly accepted.
If an MRI cannot be done, an air-CT scan should be obtained in high-risk individuals, particularly if the ABR is suggestive of an acoustic neuroma.
Instead, gamma knife radiation shrinks the tumor and prevents future growth in most patients.
The risk of hearing loss correlates with the radiation dose to the cochlea (Thomas, 2007; Massager, 2007).
Those who opt not to have surgery will likely need to have periodic imaging studies to determine if it is still safe to leave the tumor without treatment. We are particularly interested in projects that might lead to early detection (prior to onset of hearing loss). Effects of vestibulo-ocular reflex exercises on vestibular compensation after vestibular schwannoma surgery. Environmental risk factors for sporadic acoustic neuroma (Interphone Study Group, Germany).
Clinical conditions causing these events are detailed, and the most frequently involved microorganisms are mentioned. The round-window membrane is permeable to many substances, including inflammatory mediators, and many studies have shown that these mediators can affect inner-ear function, as seen in auditory brainstem response, cochlear microphonics, otoacoustic emissions, and cochlear blood flow studies [20]. An equally important consideration is that at least part of the response to inflammation is protective [20].
Only about 10 tumors are newly diagnosed each year per million persons in the United States, corresponding to between 2,000 and 3,000 new cases each year. There is not hard evidence supporting a link between environmental factors and acoustic neuromas. Less conservative incidence estimates for acoustic neuroma in asymmetrical hearing loss are reported at 2.5% (Suzuki et al 2010). Delayed facial weakness, and facial numbness also occur in roughly one-third of patients after gamma knife. Management options for cerebrospinal fluid leak after vestibular schwannoma surgery and introduction of an innovative treatment.
Conservative management, gamma-knife radiosurgery, and microsurgery for acoustic neurinomas: a systematic review of outcome and risk of three therapeutic options.
The core principles of this therapy is that every point of the outer ear corresponds to, and is associated with, a specific part of the human anatomy. Finally, roundwindow membrane macroscopic and microscopic anatomy is discussed, and considerations about the exact role of membrane inflammation - protection versus damage of the inner earare expressed.
The exact role of inflammatory consequences of otitis media in protection of versus damage to the inner ear has yet to be determined. In patients with hearing asymmetry, it is believed that only about 1 in 1,000 has acoustic neuroma (source: National Institutes of Health).
When abnormal with a progressively worsening pattern, audiometry usually leads to further testing such as ABR (auditory brainstem response) and gadolinium enhanced MRI (magnetic resonance imaging), which establishes the diagnosis. Some tumors cause hydrocephalus by obstructing cerebrospinal fluid (CSF) drainage pathways in the 4th ventricle. The recurrence rate of the tumor is about 3% after surgery, and 14% after gamma knife, but of course, this figure will vary with the surgeon and the gamma knife protocol. Hydrocephalus has been reported to occur in between 3 and 12.8% (Noren et al, Pollock et al). Train time as quantitative electromyographic paramater for facial nerve function in patients undergoing surgery for vestibular schwannoma. Preservation of facial nerve function after postoperative vasoactive treatment in vestibular schwannoma surgery.
Bacterial products generated by some of these microorganisms and involved in deleterious inner-ear effects were mentioned by Hellstrom et al.
The comprehension of these mechanisms is of fundamental importance to the development of measures to counteract inner-ear consequences of otitis media, particularly sensorineural hearing loss and tinnitus. Acoustic neuromas are sometimes identified in asymptomatic patients on radiological exams for other reasons, and may be identified in up to 0.02% incidentally (Lin et al, 2005). However, because acoustic neuroma is a rare condition, sudden hearing loss attributable to an acoustic tumor occurs in only 1 to 5% of patients with sudden hearing loss as there are many more common causes (Nosrati-Zarenoe et al 2010, Suzuki et al 2010).
Dysequilibrium is reported 8 to 31% of the time, a figure analogous to surgical management. A new technique, called summated ABR, which is essentially several ABRs compared over time, may provide better sensitivity. Tinnitus is very common in acoustic neuroma, and is usually unilateral and confined to the affected ear. Radiation to the head increases the risk of future tumors of the brain and skull, but this risk is thought to be small.
Radiation damage can also occur in the surrounding tissues, including nerves that control the face and tongue.
A five year follow-up study of 317 patients who underwent gamma knife radiosurgery found a five- and ten-year progression-free survival rates of 93% and 92% with minimal complications.

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