Utility of laboratory testing in autoimmune inner ear disease.

OBJECTIVES: To assess the utility of various laboratory tests used to diagnose autoimmune inner ear disease. STUDY DESIGN: Retrospective study of 82 patients evaluated at the University of Washington Otology Clinic from 1996 through 1998 with review of clinical history, laboratory tests, audiograms, response to therapy, and final diagnoses. METHODS: Charts were reviewed for presenting history and initial workup including test results for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Clq binding assay, anticardiolipin antibody (aCL), antineutrophil cytoplasmic antibody (ANCA), microhemagglutinin assay for Treponema pallidum (microhemagglutination assay), Lyme disease titers, and the Western blot for heat shock protein 70 (hsp 70). RESULTS: The Western blot for hsp 70 is the best test for predicting corticosteroid responsiveness. The sensitivity was low at 42%, although the specificity was 90%, and the positive predictive value of this test was excellent at 91%. The ESR was as good as the CRP in detecting acute-phase reactants. The other, more specific tests in the laboratory panel (aCL, ANCA, MHA, and Lyme disease titers) did not detect any new cases of autoimmune disease in addition to those which were already identified by an abnormal ESR. CONCLUSIONS: A diagnostic test panel for autoimmune inner ear disease should include an ESR and the Western blot for hsp70. More specific laboratory testing for systemic disease is warranted when the ESR is elevated. In patients with a positive Western blot, a trial of corticosteroid therapy can be given with good conviction because the test is quite specific. However, many people who are Western blot negative may also respond to corticosteroid therapy because the test lacks sensitivity.

Refined mastoid reconstruction with the pedicled postauricular perichondrial flap.

Successful canal wall reconstruction after open cavity surgery may be compromised by both immediate (graft dehiscence and infection) or delayed (graft retraction, absorption, and extrusion) complications. Many of the healing problems following canal wall reconstruction are related to incomplete soft tissue coverage of the graft and limited blood supply. Under these conditions, we sought to increase graft viability with a broad-based perichondrial flap developed from the posterior surface of the auricle. The flap was used over a period of 3 years at a tertiary referral center in 36 cases of canal wall reconstruction in conjunction with composite grafts of cartilage and perichondrium. The patients ranged in age from 12 to 63 years and in all cases had undergone a canal down tympanomastoidectomy that was reconstructed either primarily or secondarily. The canal wall was successfully reconstructed in 35 of 36 ears. These results demonstrate a reduction in our dehiscence rate from 10 to 3% since the introduction of the perichondrial flap. With the perichondrial flap, we were consistently able to achieve better soft tissue coverage of the composite cartilage graft, eliminate lateral graft dehiscence, and encourage reepithelization of the canal. By implication, we believe this flap provides a source of nutritional support for the free cartilage graft as well as the overlying skin.

Magnetic resonance imaging of intratemporal facial nerve lesions in the animal model.

The facial nerve is often injured in head trauma. Computed tomography (CT) is the diagnostic study most frequently used to evaluate temporal bone fractures, but it does not demonstrate all soft tissues well. Recently, magnetic resonance imaging (MRI) has been used to evaluate certain soft tissues, including cranial nerves. Experience with MRI evaluation of temporal bone trauma is limited and consists primarily of anecdotal reports. This study assesses the accuracy of MRI in evaluating experimentally induced acute intratemporal facial nerve lesions. The tympanic segments of the right facial nerve in nine rabbits were contused, and MRI scans were performed without and with gadolinium-diethyl-triamine-pentaacetic acid (Gd-DTPA) at varying intervals after surgery. MRI with Gd-DTPA accurately identified the lesion site in eight of nine subjects. Gd-DTPA-enhanced MRI appears to be useful in the evaluation of traumatic facial nerve injuries.

Ototoxicity of topical otomicrobial agents.

Topical antimicrobial solutions are used commonly for prevention or treatment of purulent otorrhea even though most solutions contain ototoxic agents. This study compares the cochlear and middle ear toxicity of cortisporin otic solution (COS), 0.3% gentamicin ophthalmic solution (GOS), benzalkonium chloride (0.026% and 0.05%), and 1.0% Ofloxacin, a new quinolone antibiotic. Saline 0.9% was used as a control. The agent was instilled daily for 7 days into the bulla of juvenile guinea pigs. The animals were sacrificed on the 14th day. The organ of Corti was examined using surface preparation light microscopy and scanning electron microscopy. The tympanic membrane (TM) and adjacent middle ear mucosa were examined with light microscopy. The average cochlear hair cell damage was 66% for COS, 6.5% for GOS, and 1% for Ofloxacin, benzalkonium and saline. COS and benzalkonium 0.05% produced moderate mucosal thickening and inflammation. However, this was not statistically different from the mild mucosal thickening produced by saline, GOS, Ofloxacin and 0.026% benzalkonium. There was statistically significant mild to moderate thickening of the TM for all agents compared to the saline control.

Composite autograft "shield" reconstruction of remnant tympanic membranes.

The authors present their combined experience with large cartilage-perichondrial composite grafts used to reconstruct total tympanic membrane perforations in 294 ears. Patients chosen for this procedure had failed earlier tympanoplasty surgery or were identified as poor candidates for conventional facial tympanoplasty because of the perforation size. Successful perforation closure was achieved in 97% of ears with chronic otitis media characterized by absence of the tympanic membrane, including portions of the anterior annular ligament. Hearing results in general were good, considering the advanced stage of the disease, which required the use of alloplastic ossicular prostheses (PORP and TORP) in 76% of ears. Hearing improvement was maximal at 2000 Hz regardless of the method of ossicular reconstruction. Closure of the air-bone gap at this frequency to within 10 dB was achieved in 87% of type I tympanoplasties, 73% of type III (PORP), and 70% of type III (TORP) tympanoplasties. Although cartilage autografts have also been promoted to reverse tympanic membrane atelectasis, the authors believe that the above preoperative conditions are strong indications for this grafting technique, which is described in detail.

Effect of perilymphatic fistulas on evoked otoacoustic emissions in the guinea pig.

Round window perilymphatic fistulas were surgically created in 20 guinea pigs. Distortion product otoacoustic emissions (DPOAEs) at 2fl - f2 were recorded prior to and immediately following laceration of the round window. The stimuli were equal level sinusoids (f1 < f2) with f2 ranging from 2 to 10 kHz, a fixed f2:f1 ratio of 1.25, and stimulus levels (L2 = L1) ranging from 20 to 80 dB SPL. After an 18-day survival period, emission measurements were repeated, and fluorescein was infused into the cerebrospinal fluid to verify patency or closure of the fistula. Nine animals demonstrated patent fistulas, whereas 11 had closed fistulas. There was a statistically significant reduction in DPOAE amplitude after an acute fistula across all stimulus levels (p < .001). At 18 days the DPOAE amplitudes in animals with healed fistulas could not be differentiated from controls, whereas DPOAE amplitudes in animals with patent fistulas were statistically different from controls (p < .05). The results suggest that evoked otoacoustic emissions may be useful in detecting perilymphatic fistulas.

Current concepts in hair cell regeneration.

Hair cell regeneration following various mechanical or chemical insults to the inner ear has become the subject of intense scientific research. This article details current concepts relating to this topic, including descriptions of the hair cell precursor population, the ultrastructural properties of the newly regenerated hair cells, and regeneration of hair cells on the vestibular epithelium. Numerous photomicrographs supplement the text.

Morphological correlates of functional recovery in the chicken inner ear after gentamycin treatment.

Newly hatched chickens were allowed to survive 6, 10, 15, and 20 weeks after 10 days of gentamycin sulfate treatment. Ultrastructural studies of hair cells and nerve terminals in the auditory receptor organ, the basilar papilla, were carried out with transmission and scanning electron microscopes. Attention was paid to absolute sensory cell (hair cell) numbers, stereocilia maturity and orientation, and reinnervation within a band 100 micron wide centered 1,100 microns from the basal end of the avian cochlea. Sensory cell numbers were equivalent to those of untreated control animals within the study area in the earliest survival group. Both immature and mature appearing hair cells were identified throughout the recovery period. However, the ratio of mature to immature hair cells gradually increased to exceed 95% at 20 weeks. Stereocilia bundle reorientation also occurred throughout the study period. Orientation was often abnormal at 6 weeks, but by 20 weeks more than 95% of the regenerated hair cells were aligned within normal limits established in the control ears. Hair cell differentiation occurring at 10-15 weeks was associated with degeneration of the afferent nerve receptor complexes commonly observed in 6 week survivors. These complexes were replaced by one or two small bouton shaped efferent terminals per cell. At 20 weeks, two or three chalice shaped vesiculated terminals were observed per cell in both the gentamycin treated and control ears. On the basis of these observations normal physiological activity would be predicted at 20 weeks following gentamycin treatment, at which time sensory cell repopulation, maturation, reorientation, and innervation approximates the normal anatomical condition.

Electrical evaluation of the facial nerve in acoustic neuroma patients: preliminary comparison between transcranial magnetic coil stimulation and electroneurography.

Subclinical involvement of the facial nerve by acoustic neuromas may be identified preoperatively using conventional electroneurography (ENoG). The clinical application of extratemporal stimulation distal to the stylomastoid foramen is limited in these cases by the more proximal site of the lesion. Transcranial magnetic coil stimulation (MCS) is a noninvasive means by which the facial nerve is stimulated at the level of the motor cortex or the brain stem, before it enters the internal auditory canal. Topographically such an assessment may have more diagnostic relevance than other forms of electrical stimulation in acoustic neuroma patients. To test this theory the facial nerves of 20 patients with acoustic neuromas were stimulated using ENoG and MCS preoperatively and 1 week postoperatively. Stimulation parameters were comparable and included threshold and suprathreshold levels of stimulation while compound action potential amplitudes and early and late response latencies were monitored. Facial nerve function was assessed clinically using the Stennert grading system. All the patients had clinically normal facial nerve function preoperatively. Normative data suggested a close correlation between threshold and suprathreshold amplitudes generated by both ENoG and MCS. To the contrary, in the pathologic ears there was a higher incidence of stimulus response abnormality determined by MCS than by ENoG. A comparison of these data, tumor size, and postoperative results promotes further evaluation of MCS as a prognostic index in acoustic neuroma patients.

[Electrophysiologic evaluation of the facial nerve in patients with acoustic neuromas. Preliminary results of a comparative study between conventional electroneurography and transcranial magnetic pulse stimulation]. / Elektrophysiologische Beurteilung des Nervus facialis bei Patienten mit Akustikusneurinomen. Vorläufige Ergebnisse einer vergleichenden Untersuchung zwischen konventioneller Elektroneurographie und transkranieller Magnetspulenstimulation.

Subclinical invasion of the facial nerve by acoustic neuromas may be identified preoperatively using conventional electroneurography (ENOG). The clinical application of extratemporal stimulation distal to the stylomastoid foramen is limited in these cases because of the more proximal site of the lesion. Transcranial magnetic coil stimulation (MCS) is a non-invasive means by which the facial nerve is stimulated at the level of the motor cortex or the brain stem before it enters the internal auditory canal. Topographically such an assessment may have more diagnostic relevance than other forms of electrical stimulation in acoustic neuroma patients. To test this theory the facial nerves of 20 patients with an acoustic neuroma were stimulated using ENOG and MCS before and 1 week after operation. Stimulation parameters were comparable and included threshold, double-threshold and supra-threshold levels of stimulation while compound action potential amplitudes and early and late response latencies were monitored. All the patients had clinically normal facial nerve function preoperatively. Using ENOG 65% of the patients showed amplitude reduction on the tumour side, whereas 70% of these patients had a reduction of amplitude to MCS. Combining both techniques, 88% of the patients had a significant amplitude reduction on the neuroma side. Comparison of the preoperative threshold measurements of both techniques showed that there was a significantly higher incidence of detection of lesions on the diseased side in neuromas larger than 2 cm by the use of MCS.

Visual impairment and cognitive dysfunction in Alzheimer's disease.

OBJECTIVE: To determine whether impaired visual acuity is associated with dementia and cognitive dysfunction in older adults. DESIGN: Paired case-control comparisons of the relative frequencies of visual impairment in demented cases and nondemented controls. Cohort analyses of correlation between visual acuity and cognitive functioning in demented cases. SETTING: Internal medicine clinics at two academically affiliated medical centers. PARTICIPANTS: Eighty-seven consecutively selected patients greater than or equal to 65 years of age with mild-to-moderate, clinically diagnosed Alzheimer's disease (cases) and 87 nondemented controls matched to the cases by age, sex, and education. MEASUREMENTS AND MAIN RESULTS: The prevalence of visual impairment was higher in cases than in controls [unadjusted odds ratio for near-vision impairment = 2.7 (95% CI = 1.4, 5.2); unadjusted odds ratio for far-vision impairment = 2.1 (95% CI = 1.02, 4.3); odds ratios adjusted for family history of dementia, depression, number of medications, and hearing loss were 2.5 (95% CI = 1.1, 10.5) for near-vision impairment and 1.9 (95% CI = 0.8, 4.6) for far-vision impairment]. When further stratified by quartiles of visual acuity, no statistically significant "dose-response" relationship between vision impairment and dementia risk was observed. Among cases, the degree of visual impairment was significantly correlated with the severity of cognitive dysfunction for both near and far vision (adjusted ps less than 0.001). CONCLUSIONS: Visual impairment is associated with both an increased risk and an increased clinical severity of Alzheimer's disease, but the increased risk may not be consistent with a progressive dose-response relationship. Further studies are needed to determine whether visual impairment unmasks and exacerbates the symptoms of dementia or is a marker of disease severity.

Management of middle third facial fractures.

In the management of fractures of the middle third of the face, it should be apparent to the surgeon that the more sophisticated fixation techniques carry increased liability, and their incorrect and imprecise application mandates identification and correction of any contributing factors if malunion is to be avoided. A less sophisticated stabilization technique that, by convention, generally is reliable, less complicated, less expensive, and less intimidating may be preferred. Given the complexity and diversity of midfacial injuries and the variety of available fixation and stabilization techniques, it is unlikely that any one method precisely suits every situation.

Ultrastructural observations on regenerating hair cells in the chick basilar papilla.

This experiment was designed to investigate cellular and subcellular maturational changes in regenerated immature sensory cells and support cells of the chick basilar papilla following gentamycin treatment. Scanning and transmission electron microscopy were used. The experimental animals received one subcutaneous injection of gentamycin sulfate daily (50 mg/kg) for five or 10 days. The animals receiving five days of injection were sacrificed the following day. The remaining animals were allowed to survive either seven or 28 days before sacrifice and preparation for electron microscopy. The initial lesion consisted of total degeneration of hair cells within 500 microns of the proximal tip providing the opportunity to study a 'pure' population of regenerating sensory cells. Sensory cell regeneration could be identified by one day after terminating gentamycin treatment. Early in development sensory cell precursors were morphologically very similar to supporting cells. A density gradient, based on cytoplasmic staining characteristics, was established which increased from cells displaying low density at the base of the supporting cell layer to high density cells at the luminal surface. These changes in density were equated to increase in number of and types of cytoplasmic organelles. In contrast to the empty appearing cytoplasm of the support cell, the cytoplasm of the hair cell precursor contained numerous mitochondria, clusters of ribosomes, and vesicles. As the cell approached the surface, mitochondria became more numerous as did smooth and coarse endoplasmic reticulum and Golgi apparatus. This gradient suggested that determination of the cellular phenotype occurred at the level of the basal membrane followed by migration to the surface, during which time differentiation was characterized by an increase in number and complexity of cellular organelles. Luminal surface modifications occurred as soon as the cell erupted. The development of stereocilia, rootlet, cuticular plate and cellular polarization followed the normal embryogenetic pattern. At 28 days, stereocilia organization was still incomplete as was the orientation of the bundle. To the extent that proper orientation of hair cells or bundles is necessary for normal transduction, mature function at 28 days would not be anticipated. Innervation of the presumptive hair cell precursors could be observed one day after treatment, early in the course of hair cell differentiation. Synaptogenesis followed the normal embryogenetic sequence; however, afferent and efferent nerve terminals remained immature appearing at 28 days. This observation may have physiological implications manifested by delay of hearing

Possible precursors of regenerated hair cells in the avian cochlea following acoustic trauma.

Hair cell regeneration following acoustic trauma to the avian cochlea has been documented using DNA labeling with tritiated thymidine. The goal of this study was to identify potential precursor cell populations for regenerating hair cells. Chicks were exposed in pairs to a 1500 Hz pure tone at 120 dBSPL for 18 h. The animals received repeated injections of 3H-thymidine over a survival period of 6, 15, or 24 h, 3 days or 30 days after the completion of noise exposure. One cochlea from each animal was processed for autoradiography and the other for scanning electron microscopy. Labeled, regenerated hair cells were present by 3 days after exposure and recovery from injury was nearly complete by 30 days. Examination of animals in short survival groups suggest that two precursor populations may exist. For inferior sensory epithelial damage, cuboidal or hyaline epithelial cells appear to serve as the precursor cell population for the regeneration of both hair cells and supporting cells. With isolated superior damage, however, supporting cells may be the precursor population.

Relationship of hearing impairment to dementia and cognitive dysfunction in older adults.

We conducted a case-control study in 100 cases who had Alzheimer's-type dementia and 100 age-, sex-, and education-matched, nondemented controls to evaluate the hypothesis that hearing impairment contributes to cognitive dysfunction in older adults. The prevalence of a hearing loss of 30 dB or greater was significantly higher in cases than in controls (odds ratio, 2.0; 95% confidence interval, 1.2 to 3.4), even when adjusted for potentially confounding variables. In addition, we observed a dose-response relationship in which greater hearing loss was associated with a higher adjusted relative odds of having dementia. Hearing loss was also significantly and independently correlated with the severity of cognitive dysfunction, as measured by the Mini-Mental State Examination, in nondemented as well as demented patients. These results demonstrate an association between hearing impairment and dementia and lend support to the hypothesis that hearing impairment contributes to cognitive dysfunction in older adults.

Validity and reliability of auditory screening tests in demented and non-demented older adults.

The validity and reliability of auditory screening tests were evaluated in 34 demented and 31 non-demented elderly outpatients. In reference to an audiometric gold standard (40-dB HL hearing loss in speech frequencies), 512-Hz and 1024-Hz tuning forks, finger rub, and whispered voice tests performed well (ROC curve areas = 0.82 to 0.94). Simultaneously high (greater than 0.80) sensitivities and specificities were achievable for all these tests in demented patients. In non-demented patients, however, only the whispered voice test achieved simultaneously high specificity and sensitivity. The most accurate rule for air conduction screening audiometry was the inability to hear greater than or equal to two of four 40-dB HL speech frequencies (sensitivity = 1.0, specificity = 0.75 in non-demented patients; sensitivity = 0.97, specificity = 0.74 in demented patients). Interobserver/test-retest reliability was generally high for tuning forks, finger rub, and whispered voice tests (range of intraclass correlation coefficients = 0.38 to 0.90), and was somewhat higher in demented than in non-demented patients. These results suggest that some of the simple, traditional methods of auditory screening may have considerable validity and reliability in demented and non-demented older adults.

Intraocular pressure as an index of ocular injury in orbital fractures.

An improved method of screening for ocular injuries in patients sustaining orbital fractures is proposed. We performed a retrospective study of 107 patients who sustained orbital fractures. Intraocular pressures were measured on presentation in 17 patients and were found to be elevated on the side of the injury in eight patients, five (63%) of whom had significant ocular injury. No patient with normal intraocular pressure was found to have an ocular injury. In a prospective study, the intraocular pressures of 30 patients sustaining orbital fractures were measured. Twelve patients (40%) had normal (less than 22 mm Hg) and bilaterally symmetric (less than 3 mm Hg difference) intraocular pressures. One (8%) of these patients sustained ocular injury. In contrast, 18 patients (60%) had either an elevated intraocular pressure (greater than 22 mm Hg) or a difference between eyes of greater than or equal to 3 mm Hg. Eleven (61%) of these patients were found to have sustained an ocular injury. We conclude that intraocular hypertension or significant interocular pressure differences should alert the physician to a potential ocular injury.

Chronic perilymphatic fistula: experimental model in the guinea pig.

Chronic perilymphatic fistulas were created in guinea pig cochleas using silicone rubber tubing placed into the scala tympani through the round window. Fistula patency was determined by fluorescein perfusion into cerebral spinal fluid. Fistula were found to be patent in 6 of 6 animals at 7 days and 8 of 13 animals at 28 days. Analysis of ABRs revealed threshold increases of 10 to 15 dB across all frequencies at 1 hour and 7 days. However, thresholds returned to pre-fistula levels by 28 days. Animals with acute fistulas (simple laceration of the round window) had similar threshold increases at 1 hour; however, recovery to baseline levels occurred by day 7. Control animals with intact round windows did not have threshold shifts. Scanning electron microscopy revealed hair cell loss localized to the apical and basal turns of the cochlea. The morphologic changes observed occurred acutely (within 7 days) and were not progressive, despite the presence of a fistula. Hair cell loss or degeneration did not correlate with hearing loss.

The effect of cochleostomy on the development of endolymphatic hydrops--morphologic changes in the rabbit cochlea.

The present study was designed to examine the effects of cochleostomy on the development of endolymphatic hydrops in the rabbit. Fistulization of the cochlear partition and simultaneous obstruction of the endolymphatic duct was performed in one group of animals (n = 13). Rabbits in two other groups underwent either cochleostomy (n = 6) or endolymphatic duct obstruction (n = 6) alone. Animals were terminated at 1-, 4-, and 6-week intervals and the cochleas were examined with the light microscope to document the presence or absence of hydrops, or were evaluated with the scanning electron microscope to assess sensory-cell damage. Hydrops was observed in 67% of the animals in the combined duct-obstruction/cochleostomy group, in 100% of the duct-obstruction alone group, and in 0% of the cochleostomy alone group. Widespread sensory-cell degeneration was observed with the scanning electron microscope in the combined and the cochleostomy alone groups.