Cortical activation during a pitch discrimination task in tinnitus patients and controls--an fMRI study.

Chronic subjective tinnitus has been associated with aberrant activation of cortical areas involved in the perception of auditory information. This leads to the hypothesis that neural correlates of altered auditory perception may be found in tinnitus patients using functional magnetic resonance imaging. To study brain activation patterns due to acoustic stimulation in a pitch discrimination task, 6 tinnitus patients and 6 age-matched controls were investigated. Tones were presented binaurally at 5 beeps/s with three different frequencies in a block design. Using Statistical Parametrical Mapping, we found activation of secondary auditory areas in both groups. Furthermore, controls showed activation of the right-hemispheric anterior insula, whereas the middle frontal gyrus, putamen and left-hemispheric insula were activated in tinnitus patients. In the between-group analysis, activation of the caudate nucleus, superior frontal gyrus (Brodmann area 8) and cingular cortex was more pronounced in patients than in controls suggesting the perception of auditory inputs in a more emotional context in our patient group compared to controls.

Otologic manifestations of relapsing polychondritis. Review of literature and report of nine cases.

OBJECTIVE: Relapsing polychondritis (RP) is an episodic disease most likely of autoimmune etiology, characterized by recurrent inflammation of cartilaginous structures. METHODS: Retrospective case study at two tertiary referral centers with presentation of nine patients with otologic involvement of RP, review of the spectrum of otologic disorders seen, and treatment. RESULTS: The clinical course of otologic manifestations of RP was highly variable and ranged from mild to moderate. In 6/9 patients there was an association with other autoimmune disorders. In addition to recurrent auricular chondritis, which was present in 8/9 patients, our patients had otitis externa, chronic myringitis, Eustachian tube dysfunction, conductive hearing loss, sensorineural hearing loss, and tinnitus. All patients had their diagnosis of RP made on the basis of their otologic involvement and the response to systemic corticosteroids. CONCLUSION: The diagnosis of RP is primarily clinical, but laboratory studies and biopsy may contribute as well. Once the diagnosis is suspected, the otolaryngologist should consider consultation with a rheumatologist to assist in the management of additional systemic manifestations.

Anomalies of the ear in the Pierre Robin triad.

OBJECTIVES: The Pierre Robin triad (PRT) consists of micrognathia-retrognathia, glossoptosis, and an oval or cleft palate. The goal of this study was to identify patterns of similarity to and differences from the two previous temporal bone studies of the PRT. METHODS: Seven children with the PRT (ages, 45 minutes to 2 years; gestational ages, 41 to 43 weeks) were studied. Thirteen temporal bones were decalcified, sectioned at a thickness of 20 microm, and studied by light microscopy. RESULTS: Our study demonstrated multiple architectural anomalies involving the entire ear, including abnormal auricles, and anomalies of the ossicles, including abnormal stapes footplates (6/13). All children showed signs of middle ear infection (12/13). Anomalies of the inner ear included aplasia of the lateral semicircular canals (5/13), a large vestibular aqueduct (2/13), and unusually large otoconia (1/13). In the mastoid process there were islands of cartilage in the expected position of Reichert's cartilage (9/13) and dehiscence of the fallopian canal (11/13). Loss of cochlear hair cells was seen in children who had antemortem hypoxia. CONCLUSIONS: Although the PRT is caused by various genes, most anomalies can be traced to the development of the first and second branchial arches.

Fixation of the stapes footplate in children: a clinical and temporal bone histopathologic study.

OBJECTIVE: To clarify the anatomic characteristics, cause, and surgical outcomes relating to fixation of the stapes footplate in children. STUDY DESIGN: Retrospective case review and four-center histopathologic study of temporal bones. SETTING: Tertiary referral center. PATIENTS: We reviewed charts and histologic specimens from 12 children, aged 7 to 13 years, who underwent surgery for footplate fixation. We also studied stapes footplates in 288 temporal bones from 181 children ranging from newborn (20-44 weeks of gestation) to 13 years of age. MAIN OUTCOME MEASURE: Anomalies of the stapes footplate in children. RESULTS: The average age of diagnosis of hearing loss was 6.6 years. Criteria for a diagnosis of otosclerosis were progression of a conductive hearing loss and an intraoperative finding of fixation of the anterior stapediovestibular joint in five patients. In contrast, a nonhomogeneous, thickened, fixed footplate and the absence of an annular ligament were indicators of congenital fixation in six children. In one child, there was neither new bone from the otic capsule nor any obvious otosclerotic foci. In the temporal bone study, 17 of 181 (9.4%) children had anomalies of the stapes footplates, with ankylosis in 4 (2.2%). In two subjects (1.1%), there was an otosclerotic focus not in contact with the stapes footplate. CONCLUSION: Children younger than 6 years with various congenital anomalies are more likely to have congenital footplate fixation, which will present intraoperatively as a thickened footplate with a partial or absent annular ligament. Children older than 6 years with progressive conductive hearing loss are more likely to have otosclerosis, which presents as fixation of the anterior stapediovestibular joint. The difference in surgical outcomes is probably related to different degrees of footplate abnormality.

The deafness of Ludwig van Beethoven: an immunopathy.

OBJECTIVE: To analyze and discuss the deafness of Ludwig van Beethoven (1770-1827) and to offer a logical theory for its etiology. METHOD: The study will carefully review the composer's symptoms as described in his letters to friends and acquaintances and also will review a large body of source material, particularly publications by his contemporaries, some of which were generously loaned by Beethoven-Haus, Bonn, Germany, where necessary translations were made directly from the original German. We will also study publications on Inflammatory Bowel Disease (IBD) and its associated extraintestinal manifestations and personal discussions with experienced gastroenterologists. RESULTS: Beethoven's abdominal symptoms that began in his teens are highly suggestive of IBD, which we believe to be a correct diagnosis. IBD is an umbrella term that includes a number of named entities such as ulcerative colitis and Crohn's Disease. IBD is now considered to be a problem of immune regulation with extra intestinal manifestations that include sensorineural hearing loss and primary sclerosing cholangitis (PSC). PSC eventually causes cirrhosis and failure of the liver. A diagnosis of IBD therefore provides a single entity that explains most of the composer's symptoms and was finally the cause of his death. Our conclusion is that Beethoven's sensorineural hearing loss was an immunopathy associated with IBD.

Autoimmune-mediated sympathetic hearing loss: a case report.

BACKGROUND: Damage to one inner ear is occasionally followed by contralateral sensorineural hearing loss. This has been defined as sympathetic hearing loss. HYPOTHESIS: It is hypothesized that autoimmunity can play a role in the pathogenesis of sympathetic hearing loss. METHODS: A male patient who developed right-sided sympathetic hearing loss at 20 years of age, 11 years after deafness of the left ear caused by a temporal bone fracture, is described. The patient's serum was analyzed for the presence of autoantibodies against inner ear tissues by immunocytochemistry and Western blotting using rat inner ear tissues. The patient's serum was tested specifically for antibodies against heat shock protein 70 by immunodot blot. The presence of autoantibodies known to play a role in systemic autoimmune disease was also examined. RESULTS: Immunocytochemistry on rat temporal bone sections demonstrated autoantibodies in the patient's serum specifically targeted against cochlear outer hair cells. No reactivity of the patient's serum was observed with control tissues including kidney, brain, and liver. Western blotting using homogenized rat cochlear tissues showed that the patient's serum reacted with a 25- and 27-kDa protein. No reactivity was observed with heat shock protein 70 in the immunodot blot analysis. The patient's serum did not contain autoantibodies against antinuclear antibodies, double-stranded DNA, antineutrophil cytoplasmic antibodies, basement membrane, reticulin, intestinal mucosa, muscle, collagen, or mitochondria. CONCLUSION: Observations indicate that this patient suffered sympathetic hearing loss caused by organospecific autoimmunity directed to cochlear outer hair cells.

Antiphospholipid antibodies in patients with sensorineural hearing loss.

Sensorineural hearing loss can be associated with autoimmune diseases and the presence of antiphospholipid antibodies. Sixty patients (mean age 47 years, range 18-76 years) with sudden sensorineural hearing loss were studied with audiograms, stapedial thresholds, otoacoustic emissions, positional and caloric testing. The serologic testing included antibodies against phosphatidylserine and beta(2)-glycoprotein. Additionally, a group of 34 patients (mean age 65 years, range 31-81 years) with normal tension glaucoma was examined because in a previous study these patients were reported to have elevated concentrations of antiphospholipid antibodies with a coincidence of progressive sensorineural hearing loss. The baseline for antiphospholipid antibody levels was established in a control group of 40 healthy blood donors. In 12 of the 60 patients with sudden sensorineural hearing loss, levels of antiphospholipid antibodies were elevated. Antiphosphatidylserine IgM antibodies were significantly lower compared to controls and patients with the combination of hearing loss and normal tension glaucoma (Fisher's exact two-sided test, P < 0.01). Our data suggest that antibodies against beta2-glycoprotein seem to coincidence with an acute event, such as sudden sensorineural hearing loss, whereas antibodies against phosphatidylserine IgG are detectable in the prolonged sequel, such as in patients with progressive sensorineural hearing loss and normal tension glaucoma.

3-D reconstruction of the vestibular endorgans in pediatric temporal bones.

We investigated the vestibular endorgans in three children using 3-D reconstructions from histological sections. The right temporal bone of a newborn child without peripheral vestibular pathology was used as reference model and the temporal bones from a child with Goldenhar syndrome and a child with Pierre Robin sequence with known peripheral vestibular pathology were studied. All five temporal bones were prepared by the celloidin technique and sectioned at 20 microm. Each available section was digitized with a slide scanner. The imaging data were layered anatomically correctly and rendered in a 3-D software. With this technique all vestibular endorgans were reconstructed and measured. The standard deviations in distances ranged between 0.5 and 1.2% and in angles between 0.1 and 2.9 degrees. Both maculae were curved in the longitudinal and transverse axes which described a curve of approximately 35 degrees. The angles between the semicircular ducts varied between 97 and 110 degrees. The pathological models demonstrated a distorted configuration of the semicircular canals and differed substantially from the reference model in most of the measured distances and angles. The method presented is capable of generating 3-D models of the vestibular system from histological sections with an acceptable precision without previously inserted reference marks. Archival celloidin sections are widely available and will be an important resource in understanding the detailed 3-D geometry of the vestibular system which has not yet been accomplished.

Ante mortem ruptures of the endolymphatic membranes in children: real finding or artifact?

We undertook this study to determine whether or not ante mortem ruptures of the endolymphatic membranes occurred naturally in the infantile labyrinth, what were the most frequent locations and to assess the statistical correlation of an earlier finding of bulging of Reissner's membrane in pediatric temporal bones. We examined 128 temporal bones from 80 children between the ages of newborn to 12 years with an average age of 15.4 months. All temporal bones were prepared by the celloidin technique and studied by light microscopy. The endolymphatic membranes of the cochlear duct, saccule, utricle and semicircular ducts were examined for ruptures. A rupture of the saccule and utricle was considered to be an ante mortem event if its edges were rolled and bound with fine adhesions and could be identified in adjacent sections. Ante mortem ruptures were seen in 11.1% of the specimens and occurred in 2.4% in Reissner's membrane, in 6.3% in the saccular membrane and in 2.4% in the utricular membrane. In these specimens, the histopathological changes included atrophy of the stria vascularis and collapse of the organ of Corti, which provided further evidence of an ante mortem event. Infants with extralabyrinthine congenital anomalies or children who were treated with chemotherapy were more likely to develop ruptures of the endolymphatic membranes if they also received aminoglycosides.

The incidence and distribution of cupular deposits in the pediatric vestibular labyrinth.

OBJECTIVES: Deposits of basophilic material on the cupulae of the semicircular ducts have been described in adult human temporal bones, and such deposits have been implicated in the clinical phenomenon of benign paroxysmal positional vertigo (BPPV). Although relatively rare, BPPV has been reported to occur in children. The goal of this study was to evaluate the occurrence of cupular deposits in pediatric material. STUDY DESIGN: Basic science, two-center histopathologic temporal bone study. METHODS: We examined 186 temporal bones from 121 individuals between the ages of newborn and 10 years. The average age was 14.7 months. All temporal bones were acquired at autopsy, embedded in celloidin, and sectioned for light microscopic study. The cupulae of the semicircular ducts were identified and any deposits found were graded according to their size and position on the cupula. RESULTS: A total of 276 cupulae were identified, and in 35 (12.7%) of these a basophilic deposit was found. In many cases the deposits contained recognizable otoconial crystals. Most deposits were small and they were almost equally distributed between the three semicircular ducts. However, the lateral and posterior cupulae were somewhat more involved than the superior cupula. Our data showed that cupular deposits are less frequently found in the pediatric labyrinth, compared with adults as reported in previous studies. CONCLUSIONS: The lower occurrence in children versus adults suggests that the deposits may be a phenomenon of the aging vestibular labyrinth.