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PubMed2003

Intratympanic therapies for sensorineural hearing loss and vertigo.

The theory behind intratympanic therapy is that by instilling small amounts (0.5 cc) of medications into the middle ear, absorption into the inner ear occurs though the round window. The medicines exert their effects on the cochlear and vestibular end organs. The benefits of these therapies include: control of systemic side effects, and the ability to treat the patients in the clinic or outpatient setting with encouraging results. The purpose of this paper is to explain the potential role of intratympanic therapy in treating specific inner ear disorders.

Anti-Bacterial Agents↗
PubMed2005

Cochlear hair cell loss in single-dose versus continuous round window administration of gentamicin.

CONCLUSIONS: Gentamicin-induced cochlear hair cell loss depends on local middle ear administration kinetics and the total drug dose. Single-dose gentamicin instillation in the middle ear is associated with a high variation in hair cell loss. OBJECTIVE: To compare the effects of single-dose and continuous round window administration of gentamicin on cochlear hair cell loss in a guinea pig model. MATERIAL AND METHODS: Two methods for drug administration to the inner ear were used. In groups of five animals, a total dose of 0.8 or 3.2 mg of gentamicin was either instilled as a single dose directly into the round window niche or administered continuously over a 1-week period using a pump-catheter system. Continuous administration was achieved by means of a posterior tympanotomy and subcutaneous placement of an osmotic pump fitted with a catheter. The tip of the catheter was fixed in the round window niche. One group of five animals served as controls and received a saline infusion. The animals were sacrificed after 1 week and hair cell loss was determined microscopically after dissection and phalloidin labelling of the basilar membrane and organ of Corti. RESULTS: Quantitation of cochlear hair cell loss revealed a dose-dependent effect of gentamicin. With both treatment modalities the higher dose induced a higher percentage of hair cell loss. There was inner and outer hair cell loss in all four groups that received gentamicin. With the single-dose instillation, hair cell loss was distributed irregularly from the round window membrane towards the cochlear apex, whereas continuous administration induced hair cell loss close to the round window membrane. Single-dose instillation induced greater hair cell loss than continuous administration at the same dose. The inter-individual variation in hair cell loss was highest following single-dose instillation.

Administration, Topical↗
PubMedDate not supplied

Microfissure between the round window niche and posterior canal ampulla.

The microfissure between the round window niche and the posterior canal ampulla was examined in fetal, child, and adult human temporal bones. The communication which was filled with mesenchymal tissue and blood vessels extending from the middle ear, was observed between the round window niche and the posterior canal ampulla in 10 to 15-week human fetuses. The mesenchymal tissue in the communication was replaced by cartilage with advancing age of the fetus. No communication was observed at birth. From newborn to 12 months of age, no microfissure was observed. After one year of age, the microfissure was first observed and the frequency of the observation increased with increasing age of the patient. After six years of age, the microfissure was observed bilaterally in 100% of cases studied. The microfissure has its origin from the communication between the round window niche and the posterior canal ampulla in fetal life, and is a normal developmental and anatomical structure, and not a pathological finding.

Adolescent↗
PubMed1989

Computer-aided three-dimensional reconstruction and measurement of the round window and its membrane.

This study was performed to clarify the complex three-dimensional shape of the round window and its membrane, and to measure these structures by using the computer-aided three-dimensional reconstruction method we developed. The equipment used included a personal computer, a high-resolution, 14-inch color monitor, and a digitizer. Materials consisted of five normal temporal bones obtained from five individuals with negative otologic histories who had been 5 months and 14, 15, 18, and 59 years old at death. Round window membranes were found to be convex to the middle ear side when viewed in the coronal plane, but to be concave when viewed in the sagittal plane; thus the membrane in most cases seemed to be shaped like a saddle, tapered toward the vestibular end. The average maximal diameter, sagittal length, horizontal width, and surface area of the round window were 2.32 +/- 0.19 mm, 2.08 +/- 0.22 mm, 1.76 +/- 0.10 mm, and 2.70 +/- 0.43 mm2, respectively. The average surface area of the round window membrane was 2.98 +/- 0.43 mm2.

Adolescent↗
PubMed1991

On the pathomechanism of cochlear dysfunction in experimental perilymph fistulas.

The mechanism leading to hearing impairment in perilymph fistulas was investigated in guinea pigs with perforated round window membranes (RWM) by analyzing alterations of inner ear fluid pressure, changes of auditory function following manipulations to get presumed air bubbles out of the cochlea ("positional audiometry"), and temporal bone sections. The instantaneous loss of normal positive inner ear fluid pressure after RWM perforation had no immediate effect on auditory function. Inner ear pressure was restored 4 days following RWM perforation. "Positional audiometry" was negative in guinea pigs with perforated RWM. All ears in which auditory thresholds had increased had additional iatrogenic lesions at the spiral lamina. Fistulas in the RWM per se do not affect auditory thresholds. The question of the surgical repair of fistulas was not directly addressed; it only can be concluded that there are no direct sequelae of an isolated fistula which induce auditory impairment and which could be prevented by surgical repair of the fistula.

Acoustic Stimulation↗
PubMed1981

Traumatic rupture of the eardrum with round window fistula.

Traumatic perilymphatic round window fistula may manifest itself with minimal cochleovestibular symptoms. Its association with tympanic membrane perforation secondary to ear washing has previously never been published. The rapid complete recuperation of cochleovestibular function after a conservative obliteration of the round window niche with fat and a myringoplasty, leads us to suggest early surgical intervention when there is evidence or high suspicion of perilymphatic fistula with a traumatic membrane perforation.

Cochlea↗
PubMedDate not supplied

The round window membrane: otological observations.

The membrane of the round window serves as a barrier between the middle and inner ear and has a well-established role in cochlear physiology. It is important in many otological conditions: otitis media, otosclerosis, trauma, sequelae to drugs reaching the middle ear, tumors, congenital dysplasia, sudden deafness. We here describe the first electron microscopic findings in round window membranes from adult humans, and various conditions in reference to these findings. Since surgical lesions are made in this membrane during cochlear implantation, and by some otologists in treating vertigo, preliminary findings of a lesioning experiment in animals are presented. Interestingly, early healing resulted from a mesothelial cellular reaction in the adjacent scala tympani, with formation of clots, while in the middle ear the epithelial cellular layer sealed the edges of the perforation, leading to formation of an indentation ("pocket"). Subsequently, the middle layer of the membrane contributed to healing.

Adult↗
PubMed2004

Direct measurement flow resistance of cochlear aqueduct in guinea pigs.

OBJECTIVE: The cochlear aqueduct connects the scala tympani to the subarachnoid space and is the main pressure equalization canal for the inner ear. Increases in inner ear volume and pressure are thought to cause clinical symptoms such as vertigo, tinnitus and fluctuating hearing loss. In this study the flow resistance of the cochlear aqueduct was determined and its relation with inner ear pressure was studied. MATERIAL AND METHODS: Inner ear pressure was measured in the scala tympani through the round window using a micropipette. Through a second micropipette, artificial perilymph was infused into, or withdrawn from, the scala tympani at various constant rates. From the infusion rate and the change in perilymphatic pressure during infusion the flow resistance of the cochlear aqueduct was calculated. RESULTS: The flow resistance was found not to be constant but to depend on the position of the round window membrane and possibly on the magnitude and direction of fluid flow through the aqueduct. Measured flow resistance values were in the range 11-45 Pa s/nl. For very small flow values the flow resistance averaged over 6 animals was 21 Pa s/nl. CONCLUSIONS: The flow resistance of the cochlear aqueduct is not a constant value. The cochlear aqueduct is a canal with dynamic properties and may play a role in the complicated process of inner ear pressure regulation.

Animals↗
PubMed1994

Differential sensitivity to rotation measured on potentials evoked by electrical stimulation of the guinea-pig ear.

Responses to electrical stimulation of the ear applied between round-window and vertex electrodes were recorded in awake guinea-pigs from the same electrodes or from separate vertex/mastoid subdermal needle electrodes. They were averaged during opposite phases of sinusoidal rotation or before and after constant velocity rotation. In both cases the responses were subtracted from each other and yielded differential per- or post-rotatory "electrovestibular" responses. For comparison, responses were also recorded in the same animals and conditions of electrical stimulation during silence and during silence and during presentation of a broad-band noise. The difference yielded "electroacoustic" responses. In round-window records, electrovestibular and electroacoustic responses presented typical compound nerve action potential patterns. Electrovestibular responses could be recorded for head angular velocities as low as 3 degrees sec-1 at 0.1 Hz. Response amplitude showed a logarithmic relation to head velocity. Changes in amplitude, as a function of time after rotation, were comparable to those reported for vestibular nerve fibre responses. In vertex/mastoid records, electroacoustic responses presented a sequence of peaks similar to the click-evoked auditory brain-stem responses, and electrovestibular responses presented two peaks, presumably representing contributions of central vestibular structures. Such "electrovestibulography" permits the study of an individual ear and makes available to the investigator a large range of vestibular stimulation conditions.

Animals↗
PubMed1978

Rupture of the round window membrane.

The mechanism of development of rupture of the round window membrane appears to be an increase in pressure in the cerebrospinal fluid transmitted to the inner ear via the cochlear aqueduct. Two cases of rupture of the round window membrane in divers are described in detail. One diver had ruptures of both round window membranes following difficulty in autoinflating when diving, and the other had a rupture of one round window membrane, having presented with acute prostating vertigo and normal hearing. Surgical repair restored the hearing in the former case and preserved normal hearing in the latter. The similarity between ruptures of the round window membrane and poststapedectomy fistula is emphasized, and it is suggested that spontaneous healing of ruptures may well occur. A case history supporting this hypothesis is presented. The technique of repair of ruptures of the round window membrane is described as well as postoperative management. Normal nasal function in divers is essential if inner ear barotrauma and ruptures of the round window membranes are to be avoided.

Adult↗
PubMed2003

Interrelations between the middle and inner ear in otitis media.

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. Characteristics of the immune system in the human middle ear and middle-ear mechanisms against bacteria are explained. The role of bacteria and bacterial products in inner-ear damage is detailed, and related pathological events are described. The hypothetical role of inflammatory mediators in bacteria-induced inner-ear toxicity is particularly emphasized. Clinical conditions causing these events are detailed, and the most frequently involved microorganisms are mentioned. Finally, round-window membrane macroscopic and microscopic anatomy is discussed, and considerations about the exact role of membrane inflammation--protection versus damage of the inner ear--are expressed.

Bacterial Toxins↗
PubMed1981

The round window membrane following application of staphylococcal exotoxin: an electron microscopic study.

The round window membrane has been considered as a pathway for the passage of toxic substances from the middle ear cavity to the vestibular labyrinth in cases of otitis media. To determine the role of the round window membrane in this passage, chinchillas were given intrabullar inoculations with staphylococcal exotoxin and the round window membranes were examined electron microscopically. We observed cytoplasmic vacuolization, intercellular edema, cellular and nuclear swelling of the surface epithelia and polymorphonuclear leukocyte (PMN) infiltration of the fibrous layer. Light microscopic observation of the labyrinth revealed PMN infiltration of the most basal portion of the scala tympani. These findings demonstrate a chemotactic effect of the toxin for PMNs and support the concept of the round window membrane as an important avenue of entry.

Animals↗
PubMed2006

Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration.

Before new drugs for the treatment of inner ear disorders can be studied in controlled clinical trials, it is important that their pharmacokinetics be established in inner ear fluids. Microdialysis allows drug levels to be measured in perilymph without the volume disturbances and potential cerebrospinal fluid contamination associated with fluid sampling. The aims of this study were to show: (i) that despite low recovery rates from miniature dialysis probes, significant amounts of drug are removed from small fluid compartments, (ii) that dialysis sampling artifacts can be accounted for using computer simulations and (iii) that microdialysis allows quantification of the entry rates through the round window membrane (RWM) into scala tympani (ST). Initial experiments used microdialysis probes in small compartments in vitro containing sodium fluorescein. Stable concentrations were observed in large compartments (1000 microl) but significant concentration declines were observed in smaller compartments (100, 10 and 5.6 microl) comparable to the size of the inner ear. Computer simulations of these experiments closely approximated the experimental data. In in vivo experiments, sodium fluorescein 10 mg/ml and dexamethasone-dihydrogen-phosphate disodium salt 8 mg/ml were simultaneously applied to the RWM of guinea pigs. Perilymph concentration in the basal turn of ST was monitored using microdialysis. The fluorescein concentration reached after 200 min application (585+/-527 microg/ml) was approximately twice that of dexamethasone phosphate (291+/-369 microg/ml). Substantial variation in concentrations was found between animals by approximately a factor of 34 for fluorescein and at least 41 for dexamethasone phosphate. This is, to a large extent, thought to be the result of the RWM permeability varying in different animals. It was not caused by substance analysis variations, because two different analytic methods were used and the concentration ratio between the two substances remained nearly constant across the experiments and because differences were apparent for the repeated samples obtained in each animal. Interpretation of the results using computer simulations allowed RWM permeability to be quantified. It also demonstrated, however, that cochlear clearance values could not be reliably obtained with microdialysis because of the significant contribution of dialysis to clearance. The observed interanimal variation, e.g., in RWM permeability, is likely to be clinically relevant to the local application of drugs in patients.

Animals↗
PubMed1990

Role of middle ear endotoxin in inner ear inflammatory response and hydrops: long-term study.

The permeability of the round window membrane for Salmonella typhimurium-derived endotoxin was examined with use of a total of 33 chinchillas. One milligram of each endotoxin was instilled into the tympanic cavities via the superior bullae. The endotoxin activities in middle ear effusions (MEEs), perilymph, and sera were determined by limulus amebocyte lysate assay. Endotoxin was detected in perilymph on the inoculated side by 12 hours after endotoxin instillation and persisted for up to 3 weeks. Endotoxin level peaked at 24 to 48 hours postinstillation, and it steadily declined afterward. This result suggests that the maximum penetration occurred during the active inflammatory stage. Histologic evidence demonstrated remarkable pathologic changes in the inner ear, including bleeding and inflammatory cell recruitment, mostly in the perilymphatic spaces (eg, scalae tympani, scalae vestibuli, spiral ligament), strial swelling, and sensory cell degeneration. This result suggests that endotoxin present in the middle ear can permeate the round window membrane, causing inner ear tissue damage in this animal model.

Animals↗
PubMed1988

Surgery of the round window.

Tympanotomy is routinely performed in our institution to control the round window membrane for patients with recurrent sudden deafness, with Meniere-like attacks, and those with Meniere's disease. In a large number of these patients, especially those with vertigo, perilymph fistula has been diagnosed. Most patients are free of attacks after the fistula has been closed, and in those with a short history of illness, hearing can become normal. In the future, closure of the round window membrane should be considered an important procedure in the treatment of inner ear dysfunctions.

Barotrauma↗
PubMed1989

Round window membrane permeability. An in vitro model.

The round window membrane of the mongolian gerbil was dissected out, together with its bony niche. The preparation was mounted between two glass chambers representing the middle ear cavity and the perilymphatic space respectively. Passage through the round window membrane did not occur within 3 h when testing high-density lipoprotein with a molecular weight 115-350 kD. Horse-radish peroxidase, with a molecular weight of 48 kD, passed the round window membrane at a mean rate of 6 micrograms/h when the concentration of the protein was 10 g/l in the middle ear chamber. The present in vitro model is considered to be free from leakage artifacts between the chambers. Passage rates for different substances through the round window membrane can be calculated under controlled conditions using this type of in vitro model.

Albumins↗
PubMed1986

Diagnosis and treatment of perilymph fistulas without hearing loss.

In 1978, I reported on the diagnostic criteria and therapy based on the treatment of 34 cases of perilymph fistula. Of that group, 20 patients had no hearing loss associated with the fistula. Since that time, an additional 30 cases of fistula--15 without hearing loss--have been seen and treated operatively. The 30 significant variables of history and physical findings identified in the first study were statistically reviewed, along with a new finding that seems highly significant. Twenty-three of the 26 new cases so evaluated had a positive "eyes-closed turning test" (staggering when turning to the side of the lesion after walking with eyes closed). A further finding has been the presence of an abnormally placed round window membrane, in most cases involving the round window. The total operative population of fistulas, both those with and without hearing loss, is reviewed to identify the operative technique best suited for each window and the graft material most likely to succeed. Perichondrium is the choice tissue for graft material, except for very small fistulas at the annular ligament. The graft must be held firmly in place, with either a prosthesis or appropriate packing, carefully avoiding adhesions between the round window and the tympanic membrane.

Adolescent↗