Antibody deposition in the stria vascularis of the MRL-Fas(lpr) mouse.

The MRL-Fas(lpr) mouse, a model of multisystemic, organ non-specific autoimmune disease, has been proposed as a model of immune-mediated inner ear disease. Preliminary studies indicate that it develops cochlear pathology focused in the stria vascularis including intracellular edema and degeneration which develops in the absence of an inflammatory infiltrate but in the presence of antibody deposition. It was thus hypothesized that the antibodies found in the stria were mediating a direct pathologic effect on this structure, without recruiting classical inflammatory mediators. It was further hypothesized that the antibodies deposited within the stria would be derived from the non-complement fixing isotypes and subclasses, which are known to be able to mediate direct pathologic effects on target tissues. This study utilized immunohistologic techniques to identify the antibody isotypes and subclasses deposited within the stria vascularis of the MRL-Fas(lpr) mouse. Results indicate that all antibody isotypes and subclasses can be identified within the stria vascularis in the absence of complement. Thus, antibody deposition was not restricted to non-complement fixing antibodies. While it is possible that antibodies are mediating direct pathologic effects within the stria, the non-specific nature of the antibody deposition may indicate that these antibodies are not responsible for the observed pathology. Rather, other mechanisms, such as metabolic and genetic etiologies, must also be considered.

Ultrastructural pathology in the stria vascularis of the MRL-Fasl(lpr) mouse.

The MRL-Fas(lpr) mouse, a model of multisystemic, organ nonspecific autoimmune disease, has been proposed as a model of immune-mediated inner ear disease. A preliminary study employing light microscopy indicated that it develops cochlear pathology that appeared most striking in the stria vascularis, where cells underwent edema and degeneration. However, other structures, including the inner and outer hair cells and the supporting cells, also appeared to display pathology. The current study analyzed cochlear ultrastructure using transmission electron microscopy to better delineate the cochlear lesions found in these animals. MRL-Fas(lpr) animals were allowed to develop systemic disease (20 weeks old) and then had auditory brainstem response (ABR) thresholds determined. Animals were then killed and their cochleas prepared for electron microscopy. Age-matched MRL-+/+ and BALB/c mice served as controls. Results indicated that MRL-Fas(lpr) mice demonstrated elevated ABR thresholds. In contrast to a preliminary report, the cochlear pathology was observed exclusively in the stria vascularis, where cells demonstrated hydropic degeneration. Strial capillary structure was normal as were the rest of the cellular cochlear constituents. No inflammatory infiltrate was noted. These studies confirm that the MRL-Fas(lpr) mouse develops cochlear abnormalities focused in the stria vascularis. Whether the mechanism of the cellular degeneration involves autoimmune, genetic, or uremic processes has yet to be determined.

Therapeutic efficacy of the Epley canalith repositioning maneuver.

OBJECTIVES/HYPOTHESES: The hypotheses of the current study are as follows: 1) That if the Epley canalith repositioning maneuver is an effective treatment for benign positional vertigo (BPV), relief from the vertigo should occur virtually immediately after the performance of the maneuver; 2) that the Epley canalith repositioning maneuver does provide almost immediate relief in BPV and should be the established treatment of choice for this disorder in both primary and tertiary care settings; and 3) that residual symptoms of lightheadedness and imbalance do persist after the resolution of the vertigo. The distinction of these symptoms from the vertigo is required for the accurate evaluation of the efficacy of positional maneuvers. STUDY DESIGN: Prospective cohort study in a tertiary care balance center. METHODS: Eighty-six patients (95 cases) with a history and physical examination consistent with active BPV were entered in the study. Patients were treated with a modified Epley canalith repositioning maneuver. A modified 360 degrees roll was used to treat those patients with horizontal canal BPV. Patients were provided with a preprinted diary in which they were to circle the answer most relevant to their symptoms for 14 days after the maneuver. Patients were then re-evaluated in the office at 2 weeks after the maneuver. RESULTS: The mean duration of the BPV before treatment was 9 weeks. Seventy-four percent of cases that were treated with one or two canalith repositioning maneuvers had a resolution of vertigo as a direct result of the maneuver. A resolution attributable to the first intervention was obtained in 70% of cases within 48 hours of the maneuver. An additional 14% of cases that were treated had a resolution of vertigo; however, it is not possible to say that these patients definitely benefited from the canalith repositioning maneuver. Only 4% of cases (three patients) manifested BPV that persisted after four treatments. Residual symptoms of lightheadedness or imbalance, or both, were frequent (47% of cases) but rarely required formal intervention with vestibular rehabilitation physical therapy. CONCLUSIONS: The Epley canalith repositioning maneuver results in a resolution of vertigo in the majority of patients (70% of cases) immediately after one treatment. It is safe and requires no special equipment or investigations. It should be established as the treatment of choice for BPV in both primary and tertiary care settings.

An accurate, cost-effective approach for diagnosing retrocochlear lesions utilizing the T2-weighted, fast-spin echo magnetic resonance imaging scan.

Recent data indicate that the auditory brainstem response (ABR) fails to identify a significant number of retrocochlear lesions. Although the magnetic resonance imaging (MRI) scan with paramagnetic enhancement is highly accurate at detecting these lesions, it is time consuming and expensive. We report on our prospective evaluation of a cohort of 155 patients who underwent T2-weighted, fast-spin echo MRI scans designed to screen for retrocochlear lesions. This imaging technique is rapidly performed and provides superb visualization of the relevant anatomic structures at a global cost of $475. Four tumors were identified with this technique. Cost analysis indicates that supplanting ABR with this limited MRI may well represent a cost-effective approach for evaluating patients with suspected retrocochlear lesions.

Effects of immunosuppression on the development of cochlear disease in the MRL-Fas(lpr) mouse.

OBJECTIVES: The MRL-Fas(lpr) mouse, an animal that spontaneously develops multisystemic autoimmune disease, has been proposed as model of immune-mediated inner ear disease. Previous studies revealed that this mouse manifested elevated auditory brainstem response thresholds, hydropic degeneration of strial cells, and antibody deposition within strial capillaries. As the etiology of the observed strial disease may be immune, genetic, or uremic, a study was designed to attempt to delineate between these possible etiologic factors. STUDY DESIGN: Prospective, controlled animal study. METHODS: Dexamethasone, which is known to suppress autoantibody production and glomerulonephritis in these animals, was administered systemically on a daily basis to experimental animals, beginning at 6 weeks of age. Control animals received no treatment. Animals were allowed to age, with control animals predictably manifesting systemic disease at 20 weeks of age, at which point all animals were sacrificed. RESULTS: Animals receiving dexamethasone treatment manifested a significant reduction in serum immunoglobulin levels, lymphoid hyperplasia, and a significant improvement in the level of renal function. However, morphologic analysis revealed a persistence of strial disease despite the elimination of strial antibody deposition. CONCLUSION: The results of this experiment support the hypothesis that genetic mechanisms may be responsible for the observed strial disease. Further studies are under way to confirm these findings.

Ototoxic effects of supradose cisplatin with sodium thiosulfate neutralization in patients with head and neck cancer.

OBJECTIVE: To assess the incidence and magnitude of ototoxicity in patients undergoing an experimental targeted chemoradiation protocol incorporating extremely high-dose intra-arterial cisplatin therapy with systemic sodium thiosulfate neutralization for the treatment of advanced carcinomas of the head and neck. DESIGN: Inception cohort study. SETTING: University-based, tertiary care referral center for advanced head and neck malignant disease. PATIENTS: The first 70 patients with advanced carcinomas of the head and neck consecutively entered in the protocol. INTERVENTION: Patients received up to 4 weekly courses of intra-arterial cisplatin (150 mg/m2 per infusion), together with systemic sodium thiosulfate and external beam radiation (68-70 Gy). Audiometric analysis was performed before the initiation of therapy, and subsequent to the second and fourth cisplatin infusions. MAIN OUTCOME MEASURES: Audiometric thresholds. Ototoxicity was defined as an increase in pure-tone threshold of 15 dB at 1 frequency or 10 dB at 3 frequencies, between 250 and 4000 Hz. RESULTS: The incidence of ototoxicity was 25% at 150 mg/m2, 50% at 300 mg/m2, 64% at 450 mg/m2, and 60% at 600 mg/m2. Hearing at frequencies of 2000 Hz or less was minimally or not affected. Previous hearing loss did not appear to affect the incidence of ototoxicity. A plateau of hearing loss at 60-dB hearing level, as noted by other authors, was not observed. There were no cases of debilitating tinnitus or of vestibular loss. CONCLUSIONS: Ototoxicity did occur but was largely confirmed to the higher frequencies. Hearing losses resulting from this chemoradiation protocol were not sufficiently severe to alter its application.

The Basic Symptom Inventory-53 and its use in the management of patients with psychogenic dizziness.

OBJECTIVE: To identify an accurate psychological screening questionnaire to assist in the management of patients with psychogenic dizziness. STUDY DESIGN: Patients referred to the Balance Center of the University of Pennsylvania with a presumptive diagnosis of psychogenic dizziness based on neurotologic assessment were administered a Basic Symptom Inventory-53 (BSI-53) psychological screening questionnaire and were referred for psychiatric assessment. Neither the patients nor the psychiatrist were aware of the results of the BSI-53. The results of the neurotologic assessment, the BSI-53, and the psychiatric assessment were then compared for their degree of association. RESULTS: Strong associations were demonstrated between the results of the BSI-53 questionnaire and the results of the neurotologic and psychiatric assessments. CONCLUSIONS: The BSI-53 is an easily administered, objective, and accurate tool useful in identifying the presence of psychopathology in patients thought to have psychogenic dizziness. It is recommended as a valuable addition to the battery of tests performed when evaluating the dizzy patient.

Strial dysfunction in the MRL-Fas mouse.

The MRL-Fas(lpr) mouse, a model of multisystemic autoimmune disease, has been proposed as a potential model of autoimmune inner ear disease. Cochlear pathology, consisting of hydropic degeneration of the stria vascularis, has been documented to occur coincident with the establishment of systemic disease in this animal. Because the cochlear pathology is restricted to the stria, this study was designed to evaluate whether the endocochlear potential (EP) would be diminished in these animals because of a loss in strial Na, K-ATPase. Experimental (MRL-Fas(lpr)) mice, with established systemic disease, had auditory brain stem response thresholds and EPs recorded. MRL-+/+ mice served as controls. Animals were then euthanized, and their cochleas were processed for immunohistologic assay for the alpha1 and beta2 subunits of Na,K-ATPase. Density of staining was evaluated by use of quantitative means with densitometry image analysis of digitized images. MRL-Fas(lpr) mice revealed significant elevations in auditory brain stem response thresholds and reductions in EPs but no reductions in Na,K-ATPase levels, as evidenced by immunohistochemical assay. The reduction of EP likely occurs as a result of cellular degeneration within the stria vascularis and likely results from an abrogation of the strial perilymph/endolymph barrier and not from a reduction in strial Na, K-ATPase levels.

Management of far advanced otosclerosis in the era of cochlear implantation.

OBJECTIVE: To evaluate issues pertaining to cochlear implantation in patients with far advanced cochlear otosclerosis. STUDY DESIGN: Prospective cohort. SETTING: Tertiary care referral center. PATIENTS: Eight adult patients (18 years of age or older) referred for management of profound hearing loss, the cause of which was determined to be otosclerosis. INTERVENTION: Cochlear implantation with multichannel cochlear implant device. MAIN OUTCOME MEASURES: Benefit from cochlear implant as measured by CID sentence scores, incidence and management of facial nerve stimulation, and technical issues pertaining to cochlear implantation in this patient population. RESULTS: All patients demonstrated significant improvement in auditory function as measured by performance on CID sentence scores and ability to engage in telephone conversation. Facial nerve stimulation was present in two of eight patients and was managed with deactivation of the stimulating electrodes. Ossification in the basal turn of the cochlea, detected on preoperative computed tomography, necessitated placement of the electrode into the scala vestibuli in two patients and use of a thinner electrode (Nucleus 24) in a third patient. CONCLUSION: Patients with profound hearing loss secondary to otosclerosis derive excellent benefits from cochlear implantation. Surgical implantation may be complicated by ossification of the cochlea, which can be detected on preoperative computed tomography. Electrode activation may be complicated by facial nerve stimulation, which can be addressed with programming strategies.

Tinnitus suppression in patients with cochlear implants.

OBJECTIVE: To determine the degree of tinnitus suppression provided by currently available multichannel cochlear implants and to determine factors that can influence this process. STUDY DESIGN: Prospective cohort. SETTING: Tertiary-care referral center. PATIENTS: Thirty-eight adult patients (18 years of age or older) with severe-to-profound hearing loss and tinnitus who met criteria for cochlear implantation. INTERVENTION: Cochlear implantation with a multichannel cochlear implant device. MAIN OUTCOME MEASURES: Patients rated the intensity of their tinnitus using a semiquantitative scale before and after cochlear implantation. These data were analyzed to determine the significance of the reduction of tinnitus after implantation. Tinnitus levels after implantation were also analyzed to determine whether the level of speech recognition, patient gender, or the implant type influenced the degree of tinnitus reduction. RESULTS: Statistical analysis revealed a significant reduction in tinnitus intensity in patients using cochlear implants, with 35 of 38 patients (92%) experiencing a reduction in tinnitus intensity. All multichannel implants studied afforded similar degrees of tinnitus suppression. The degree of tinnitus reduction was not correlated with speech recognition, as measured by CID Everyday Sentence scores. Female patients had significantly greater degrees of tinnitus before implantation, but both male and female patients demonstrated similar levels of tinnitus after implantation. No patient experienced greater levels of tinnitus after implantation. CONCLUSION: All currently available multichannel cochlear implant devices provide effective and similar levels of tinnitus suppression when activated. Exacerbation of tinnitus as a result of cochlear implantation does not represent a significant risk. The mechanisms by which cochlear implants exert tinnitus suppression are, as yet, unclear.

Na,K-ATPase in the cochlear lateral wall of human temporal bones with endolymphatic hydrops.

Meniere's disease has traditionally been thought to arise from a disruption in longitudinal endolymphatic flow. This view has been brought into question by recent experimental studies that have focused attention on derangements of cochlear fluid and electrolyte homeostatic mechanisms in Meniere's disease, including abnormalities in Na,K-ATPase enzymes found in the cochlear lateral wall. The current study examined the immunohistochemical labeling pattern of the major ion-transporting enzyme of the stria vascularis, Na,K-ATPase, in archival sections of hydropic and nonhydropic human temporal bones for increased density of label that could indicate overproduction of fluid. The results showed good labeling of the stria vascularis in the celloidin sections. The hydropic ears tended to have darker label, but the difference was not statistically significant. The findings are consistent with normal functioning of the stria vascularis in cases of Meniere's disease.

Vertigo and dysequilibrium with associated hearing loss.

There are numerous disorders that can present with hearing loss and vertigo or dysequilibrium. The combination of vertigo and imbalance associated with hearing loss are symptoms suggestive of a peripheral vestibular disorder. This article summarizes presentation, diagnosis, and treatment of the various common and rare peripheral vestibular disorders that can present with these symptoms.

Balance function testing: a rational approach.

Recent advances in the area of balance function testing have left clinicians with a wide variety of diagnostic tests that provide insights into the function of the balance system. Laboratory tests used to evaluate the balance system include electronystagmography, rotational chair, and dynamic posturography. This article summarizes the currently available balance function testing protocols. A cost-effective and rational protocol for the application of these tests is provided.

The MRL-lpr/lpr mouse: a potential model of autoimmune inner ear disease.

Most attempts at developing a model of autoimmune inner ear disease have focused on the immunization of healthy animals with cochlear tissue. We have chosen an alternate route of studying this entity utilizing the MRL-lpr/lpr (Lupus) mouse, an animal known to spontaneously develop multisystemic, organ nonspecific autoimmune disease. We report on the auditory pathology found in animals at early stages of this systemic disease. At the onset of clinical signs of illness (cachexia, weight loss, lethargy) animals were sacrificed and their cochleas and kidney prepared for morphologic analysis. Significant pathology was seen in the MRL/lpr animals involving the basal and middle turns of the cochlea which could not be correlated with the presence or degree of glomerulonephritis. Findings included outer and inner haircell degeneration, strial edema and degeneration, and an acellular infiltrate in the tunnel of Corti. Cochlear pathology was not found in control animals. Thus, at early stages of systemic disease, MRL/lpr mice manifest significant cochlear pathology not seen in control animals. The implications of these results with regard to the pathogenesis of these lesions as well as their clinical relevance are discussed.

A practical approach to dizziness. Questions to bring vertigo and other causes into focus.

Evaluation of a patient presenting with dizziness begins with and largely depends on the patient's history. The diagnosis often can be accurately determined in a primary care setting when a stepwise algorithmic approach is used. The first step is getting a detailed account of precisely what the patient means by "dizziness." This helps determine whether the cause is vertigo or another condition, such as orthostatic hypotension. Establishing whether the vertigo is central or peripheral in origin and, if peripheral, how long episodes last further focuses the investigation. Certain clues on physical examination and appropriate use of diagnostic tests help support the diagnosis. Referral should be contemplated when significant central disease is suspected and when vertigo of peripheral origin is persistent or atypical.

Hearing loss. A plan for individualized management.

Because some cases of hearing loss demand urgent attention, an approach to patients with hearing loss should be adopted in the primary care setting that allows for systematic institution of an individualized and appropriate treatment plan. Workup is enhanced by categorizing the hearing loss as acute or chronic and conductive or sensorineural. The Rinne and Weber tuning fork tests are the most important tools in distinguishing between conductive and sensorineural hearing loss. The patient history and otologic examination also provide diagnostic clues. Treatment depends on the cause and the type of hearing loss.

Evaluating facial paralysis. Expensive diagnostic tests are often unnecessary.

In most cases, the cause of facial paralysis can be determined on the basis of the clinical evaluation, and expensive diagnostic tests can be avoided. Because Bell's palsy is not always the cause, physicians need to be able to identify critical findings on history and physical examination that indicate an alternative diagnosis. Once identified, these findings can lead to a specific and directed evaluation.

Motion sickness. Helping patients tolerate the ups and downs.

The sensory conflict theory provides a useful framework for understanding motion sickness. Few modifications of this model have been proposed since its publication. The weak link in the study of motion sickness has been the failure to delineate the anatomic structures that correspond to the model's components. Effective pharmacotherapy is available for treatment of motion sickness. The choice should be based on the need to provide prophylaxis for or treatment of symptoms and on the side effect profile of the drug.