Ian S. Storper

Diagnosis and treatment of sudden-onset sensorineural hearing loss: A study of 51 patients

OBJECTIVE: The study purpose was to determine the efficacy of steroid and antiviral therapy in the management of idiopathic sudden sensorineural hearing loss (SSNHL). STUDY DESIGN AND SETTING: We conducted a retrospective study of patients presenting to an academic tertiary care center. Fifty-one patients were evaluated. All patients were placed on the same treatment protocol. RESULTS: Thirty-seven patients (73%) had recovery of hearing. Ninety-one percent of patients with vertigo and all patients with mid-frequency hearing loss and up-sloping hearing loss recovered with treatment (P < 0.05). Recovery was significantly related to age, onset of hearing loss, and audiogram type; however outcome was not significantly related to gender, vertigo, tinnitus, or laterality (P < 0.05). CONCLUSION: Our treatment protocol produced a recovery rate, which exceeds the spontaneous recovery rate. Unlike prior studies, all patients with up-sloping and mid-frequency SSNHL had recovery. In addition, vertigo did not indicate a poor prognosis. SIGNIFICANCE: Antiviral therapy and increased length of steroid treatment may play a role in the improved recovery rates.

Twenty-five years of experience with stapedectomy.

The purpose of this report is to review the outcomes of patients undergoing stapes surgery by the senior author during the past 25 years, and to compare these results with those obtained in other series.

Mutation in the COCH gene is associated with superior semicircular canal dehiscence

To the Editor: The prevalence of significant hearing loss (≥ 25 db HL) is 15-20% in young adults and rises to approximately 50% in individuals 80 years of age or older [Morton 1991]. Autosomal dominant nonsyndromic hearing loss (ADSNHL) accounts for approximately 15% of inherited hearing loss. To date, 22 genes have been implicated as causative for ADNSHL, and a further 30 loci mapped to autosomal chromosomal regions [Van Camp and Smith 2007]. ADSNHL at the DFNA9 locus is unusual amongst ADNSHL forms of deafness in that it is also associated with vestibular dysfunction. This type of hearing loss is caused by mutations in the COCH gene (chromosome 14q12), which encodes cochlin, a protein that consists of a signal peptide, an LCCL module, and two von Willebrand factor A (vWFA) domains (Table I) [de Kok et al., 1999]. Cochlin is the most highly expressed protein in the human and mouse inner ear, but its precise function remains unclear [Dessens et al., 2004; Robertson et al., 2006]. A possible role in either structural integrity or antimicrobial activity is predicted by its protein structure [Liepinsh et al., 2001] and immunohistochemistry of a temporal bone from a person with DFNA9-related deafness showing abundant aggregation of homogeneous acellular eosinophilic deposits with loss of cellularity in the cochlea and the vestibular labyrinth [Robertson et al., 2006]. Table I DFNA9-causing mutations in the COCH gene Most DFNA9-causing mutations are located within the LCCL domain, which is predicted to be involved in protein folding or a host-defense function (Table I) [Trexler et al., 2000]. The p.P51S variant that affects the LCCL module is the most frequently observed mutation in DFNA9 families [Bischoff et al., 2005; de Kok et al., 1999; Fransen et al., 2001; Fransen et al., 1999; Lemaire et al., 2003]. The identification of a large number of DFNA9 families carrying this variant has facilitated a detailed longitudinal analysis of the audiometric and vestibular impairment in 74 mutation carriers, which has shown that vestibular failure precedes and progresses more rapidly than hearing impairment [Bischoff et al., 2005]. In this study (approved by the University of Iowa Institutional Review Board), we recruited American subjects with ADNSHL and obtained DNA samples and audiograms. Audiograms were formatted for audioprofile analysis, which was conducted using the AudioGene v2.0 system [Hildebrand et al., 2008]. This system predicts the likely underlying genetic cause of hearing loss based on a number of different phenotypic parameters, including auditory thresholds, and rate of decrease in hearing relative to age and frequency. AudioGene v2.0 was trained with audiometric data from families with known deafness-causing mutations in KCNQ4 (DFNA2), DFNA5 (DFNA5), WFS1 (DFNA6/14/38), TECTA (DFNA8/12), COCH (DFNA9) and COL11A2 (DFNA13). To validate AudioGene v2.0 as a clinical and research tool, we studied a cohort of 77 families segregating presumed ADSNHL represented by audiograms from 160 individuals. Individuals from seven families were identified by AudioGene v2.0 as having a DFNA9 profile, and in six families, mutation screening of the COCH gene was completed (genomic DNA was unavailable for screening in one family). While no mutations were identified in five families, one family was found to segregate the p.P51S mutation (positive predictive value, ∼16.7%) (Figs ​(Figs1,1, ​,2).2). To our knowledge, this family is the first outside Western Europe to be reported with this mutation. However by comparing highly heterozygous short tandem repeat polymorphisms (STRPs) tightly linked to the COCH gene, we could show that this family is related to five previously reported Belgian p.P51S families [Fransen et al., 2001] (data not shown), providing further evidence of a founder effect in the Benelux region of Western Europe. Figure 1 Pedigree of the five-generation American family with nonsyndromic autosomal dominant HFSNHL, vestibular dysfunction and SSCD. Genotypes for nuceotide c.151 in the COCH gene are shown for those individuals included in the genetic analysis. Individuals ... Figure 2 The causative mutation in the COCH gene in the American family. The mutation is a heterozygous C-to-T base change in exon 3 (c.151C→T) that results in substitution of a proline residue for a serine residue at position 51 (p.P51S). The clinical presentation of all p.P51S families is very similar (Table I) [de Kok et al., 1999; Fransen et al., 2001; Fransen et al., 1999; Lemaire et al., 2003]. The hearing loss initially preferentially affects high frequencies (down-sloping) and progresses to become profound across all frequencies at a rate of ∼1.8 dB annually [Bom et al., 1999]. In a few exceptional cases, however, hearing at low frequencies declines much more rapidly, at greater than 24 dB annually [Bom et al., 1999]. In the American family, the self-reported age-of-onset of hearing loss ranged from 20 to 60 years. The hearing loss was progressive, with a general trend of initial moderate-to-severe high frequency (> 2000 Hz) hearing loss (HFSNHL) that became profound (Fig.3). In younger persons, the audioprofile was down-sloping, preserving hearing in the low and mid frequencies; with advancing age, low and mid frequency loss developed and the audioprofile flattened. Individuals IV:5 and IV:6 represent phenocopies. Figure 3 Audiograms of representative affected family members at various ages. Affected individuals initially exhibit high frequency (> 2000 Hz) mild-to-moderate SNHL (HFSNHL) that progresses to become severe-to-profound before flattening out later in ... All hearing impaired persons in this family excluding IV:5 and IV:6 also had vestibular impairment characterized by intermittent unsteadiness, particularly in the dark, and sporadic periods of dizziness. In addition, one person was diagnosed with Meniere’s-like symptoms and another with autoimmune inner ear disease requiring treatment with a diuretic and a low-salt diet. This variety of complaints is similar to that reported in other p.P51S families [Bischoff et al., 2005]. In general, p.P51S mutation carriers over 40 years of age usually have prominent vestibular symptoms however these complaints only emerge from the medical history if a targeted vestibular history is obtained. Computed tomography (CT) scanning on a number of family members revealed intact ossicles, cochleae and semicircular canals with the exception of individual V:1. This person presented at age 31 in October, 2006, for an audiogram because of the family history of hearing loss. He has no complaints and by audiometry had 10 dB thresholds bilaterally through 2 kHz, a drop to 25 dB between 3-6 kHz, and normal hearing again at 8 kHz (Fig.4A). In February, 2008, he returned with a complaint of left aural fullness and persistent otalgia (6-9 months) and underwent temporal bone CT, which revealed bilateral superior semicircular canal dehiscence (SSCD) (Fig.4B). Figure 4 Audiometry and temporal bone CT of individual V:1. A Audiogram recorded at 31 years of age showing slightly elevated hearing thresholds at high frequencies. B Coronial high-resolution CT scan of the temporal bones showing bilateral superior semicircular ... SSCD is a rare disorder. Originally described by Minor and colleagues, it is characterized by the absence of bone overlying the superior semicircular canal, which creates a third labyrinthine window (with the oval and round windows) [Minor 2000; Minor 2005]. The consequence is the loss of acoustic energy and abnormal stimulation of the vestibular system; the clinical manifestations include Valsalva- and exercise-induced vertigo, sound-induced vertigo (Tullio phenomenon), and variable conductive hearing loss [Cox et al., 2003; Mikulec et al., 2004; Minor et al., 2003]. Diagnosis requires high resolution temporal bone CT [Belden et al., 2003; Hirvonen et al., 2003]. The genetics of SSCD have not been studied, and our finding of a COCH mutation in a single patient with SSCD is noteworthy since both DFNA9-related deafness and SSCD are rare. Although it seems unlikely that SSCD is directly related to the well-documented type of vestibular impairment that is part of the DFNA9 phenotype, SSCD may be present in other DFNA9 patients. We therefore recommend high resolution temporal bone CT in patients with DFNA9-related deafness and screening of COCH in sporadic or familial cases of SSCD. This diagnostic algorithm is important because SSCD and its associated symptoms can be partially or fully corrected with surgery [Carey et al., 2007; Limb et al., 2006; Mikulec et al., 2005; Wilkinson et al., 2008]. A remarkable finding in the process of identifying DFNA9/COCH as the underlying cause of deafness in this American family was not only that a dedicated computer program, AudioGene v2.0, hinted at this possibility, but that this occurred in the course of a screening procedure for DFNA2 families [Hildebrand et al., 2008]. It is reassuring to find that AudioGene v2.0 can distinguish between the audioprofiles of genetically different types of ADNSHL, especially when both DFNA2 and DFNA9 show remarkably similar high frequency hearing loss with steeply downsloping thresholds. Admittedly, in the case of p.P51S mutation carriers genetic screening should be preferentially directed to DFNA9 and DFNA11, on the basis of the vestibular impairment findings. However, it is realistic to acknowledge the possibility that vestibular symptoms can go unnoticed. Furthermore, with other DFNA9/COCH mutations vestibular failure can be less prominent. It is not invariably penetrant and/or occurs at a more advanced age [Kemperman et al., 2005; Pauw et al., 2007a].

Giant cell tumors of the jugular foramen

PURPOSE To review the diagnosis and treatment of giant cell tumors of the jugular foramen. MATERIALS AND METHODS A typical case is reported. Symptoms, signs, and diagnostic studies are reviewed. Photomicrographs and angiographic studies showing the differences between these and glomus jugulare tumors are provided. A coherent approach to their management is presented. RESULTS These hypervascular, traditionally radioresistant tumors may cause pulsatile tinnitus, conductive hearing loss, and lower cranial nerve paresis. Angiographic studies showed a hypervascular lesion supplied by numerous small branches of the external carotid artery, making embolization difficult. Complete resection was achieved by an infratemporal fossa approach with preoperative embolization. CONCLUSION Giant cell tumors of the temporal bone may mimic glomus jugulare tumors with respect to anatomic location, cranial nerve deficits, and vascularity.

Use of glycopyrrolate in the treatment of meniere's disease

Objectives/Hypothesis: The objective of this study was to determine whether glycopyrrolate is useful as a vestibular suppressant in patients with Menieres disease. The tested hypotheses were that glycopyrrolate would decrease the perception of dizziness measured by the Dizziness Handicap Inventory in patients with Menieres disease and that placebo would cause no such decrease. Study Design: Randomized, prospective. Methods: Thirty‐seven subjects with a diagnosis of Menieres disease were administered either 2 mg of glycopyrrolate or placebo twice daily as needed for vertigo. All were also administered the regimen of 1500 mg sodium/day diet and diuretic. The following indices were examined: Dizziness Handicap Inventory, Tinnitus Handicap Inventory, Modified Somatic Perception Questionnaire, Beck Depression Inventory, hearing examination, and electronystagmography. After 4 to 6 weeks of the drug regimen, Dizziness Handicap Inventory, Tinnitus Handicap Inventory, Modified Somatic Perception Questionnaire, and Beck Depression Scale were reexamined. Paired t tests were performed to verify the significance of improvement before and after treatment. Results: Subjects who received glycopyrrolate had statistically significant reduction in Dizziness Handicap Inventory, Beck Depression Score, and Modified Somatic Perception Score. In the placebo group, no improvement in any index was found. Conclusions: The hypothesis that glycopyrrolate is a useful vestibular suppressant in patients with Menieres disease was statistically verified. Laryngoscope, 108:1442–1445, 1998

Stapedectomy in Profound Cochlear Loss

Stapedectomy can be used in certain patients with profound sensorineural hearing loss and stapes fixation to improve hearing to a level at which a hearing aid may be effective. This study reviews the outcomes of 11 patients with profound cochlear loss secondary to otosclerosis who underwent stapes surgery performed by the senior author (M.E.G.) over a 25‐year period.

ELECTROCOCHLEOGRAPHY IN RETROSIGMOID VESTIBULAR NERVE SECTION FOR INTRACTABLE VERTIGO CAUSED BY MENIERE'S DISEASE

Interest in electrocochleography has increased in recent years because of the discovery of an elevated summating potential to action potential amplitude ratio (SP/AP ratio) in patients with endolymphatic hydrops caused by Menieres disease or perilymph fistula. It was the purpose of this investigation to determine whether the intraoperative SP/AP ratio will decrease after vestibular nerve section in patients with intractable Menieres disease. Fourteen patients with medically intractable classic Menieres disease underwent retrosigmoid vestibular nerve section. Intraoperative transtympanic electrocochleography was performed with alternating click stimuli presented at 95 dB HL. In all patients the SP/AP ratio was recorded before the skin incision (“baseline” condition) and after the dura was closed (“closing” condition). Statistical analysis was applied to the recorded data. In 11 (79%) patients, the SP/AP ratio was found to be elevated above 0.30 in the baseline state. In 13 (93%) patients, the SP/AP ratio decreased more than 25% after the nerve was sectioned. These results were highly statistically significant (p < 0.001). We conclude that the SP/AP ratio does decrease in patients with Menieres disease after undergoing retrosigmoid vestibular nerve section and offer a possible explanation. (Otolaryngol Head Neck Surg 1997;116:593–6.)

Pathology quiz case 2. Chronic sclerosing sialadenitis (CSS).

A 53-YEAR-OLD WOMAN WITH PRESUMED Sjögren syndrome and a 7-year history of symmetrical, bilateral submandibular gland swelling presented with progressive, asymmetrical enlargement of the left submandibular gland. Given her prior diagnosis of Sjögren syndrome, there was concern regarding non-Hodgkin lymphoma. A review of systems revealed fatigue, keratoconjunctivitis, and xerostomia. The patient denied fever, chills, night sweats, and weight loss as well as any history of smoking or alcohol use. A recent tuberculin test was negative for purified protein derivative. The patient’s medical history was remarkable for hypothyroidism and sequelae due to her autoimmune disease, including interstitial lung disease and interstitial nephritis. Her physical examination revealed symmetrically enlarged lacrimal glands and asymmetrical left submandibular gland enlargement. Magnetic resonance images of her face and neck were notable for bilaterally enlarged lacrimal glands and bilateral submandibular gland enlargement, more on the left than the right. The left gland measured 2.8 cm in greatest dimension, without a discrete mass. An axial T1-weighted, gadolinium-enhanced magnetic resonance image with fat saturation protocol is shown in Figure 1. Fine-needle aspiration of both submandibular glands revealed varying amounts of polymorphic, chronic inflammatory cell infiltrates. The patient subsequently underwent excision of her left submandibular gland for definitive diagnosis. On histologic examination, the glandular morphological appearance of the gland was markedly distorted by dense hyalinizing fibrosis. Multifocal lymphoid aggregates with reactive germinal centers were observed (Figure 2). A patchy, variably dense infiltrate of lymphocytes and plasma cells was present both perivascularly and within acini. No lymphoepithelial lesions were noted (Figure3). Periductal fibrosis was seen in both smalland large-caliber ducts. No sialoliths or calcified concretions were seen. Increased numbers of IgG4 plasma cells were seen on immunohistochemical staining. Flow cytometry demonstrated a predominant T-cell population and polytypic B cells indicative of a reactive lymphoid infiltrate. Polymerase chain reaction–based analyses of immunoglobulin and T-cell receptor gene rearrangements showed polyclonal products. What is your diagnosis?

papillary cystadenoma of the nasal cavity

Papillary cystadenomas are benign epithelial neoplasms that occur only rarely in salivary glands. To our knowledge, this represents the only case report of a nasal cavity cystadenoma in the English literature in over 40 years. We report the management of the tumor with en bloc endoscopic resection. A 68-year-old gentleman was referred for right-sided nasal obstruction for 1 year. The patient had a history of seasonal allergies and was empirically treated for allergic rhinitis with a nasal steroid spray and oral leukotriene inhibitor by his primary medical doctor. The patient did not improve on this regimen and was referred for otolaryngologic evaluation. The patient had a 16 pack-year history of tobacco use, which he had ceased 32 years prior. His past medical history was otherwise noncontributory. The size of the mass precluded rigid endoscopic examination in the office. On flexible fiberoptic examination, a multicolored mass was noted in the right nasal cavity. The examination of the contralateral nasal cavity and nasopharynx was unremarkable. CT of the sinuses was performed (Fig 1) and was notable for a soft tissue mass in the right nasal cavity. The sinuses were well-aerated, save for small retention cysts in the left maxillary and right sphenoid sinuses. No bony destruction was noted. The patient subsequently underwent operative nasal endoscopy and excision of the nasal mass. Endoscopic evaluation of the right nasal cavity revealed a 3.5-cm, multicolored nasal mass originating from the posterior portion of the middle turbinate. This mass was excised en bloc with surrounding turbinate tissue. Frozen surgical pathology was consistent with a benign salivary neoplasm or mucocele. On permanent section (Fig 2), the mass was composed of multiple cysts, lined by oncocytic cells in a papillary pattern. On immunohistochemical staining, the cells were positive for pancytokeratin (panCK) and negative for CD34 and CD31, indicating their epithelial origin. This finding was consistent with a papillary variant of cystadenoma.