Papillary carcinoma in thyroglossal duct cyst: Two case reports and review of the literature.

The thyroglossal duct cyst is one of the more common congenital anterior neck masses. In rare cases, carcinoma has been detected within one of these cysts on histopathologic analysis of resected tissue. Since the incidence of thyroglossal duct cyst carcinoma is low, the appropriate management of the thyroid gland proper is not algorithmic. We present 2 cases of papillary thyroid carcinoma that were discovered in a thyroglossal duct cyst, and we describe the diagnostic and therapeutic measures taken in each case. Particular attention is paid to two points: (1) fine-needle aspiration biopsy may not be sufficient to rule out carcinoma and (2) removal of the thyroid gland may be advisable in selected situations.

A rare case of splenic marginal zone B-cell lymphoma mimicking relapsing polychondritis of the ear.

Relapsing polychondritis (RPC) is a poorly understood phenomenon associated with cartilaginous inflammation of the ear, nose, tracheobronchial tree, and peripheral joints. Many cases of RPC respond to anti-inflammatories and resolve with no further complications. However, RPC has also been linked to more insidious conditions such as malignancies, autoimmune disorders, vasculitis, or underlying infections. Given the spectrum of associated disorders, patients with RPC may need to be monitored for more insidious underlying conditions. In this case, we report a unique case of bilateral auricular inflammation and nasal inflammation mimicking RPC as the only presenting symptom of splenic marginal zone B-cell lymphoma and we survey related cases in the literature.

A new mutation of the Atoh1 gene in mice with normal life span allows analysis of inner ear and cerebellar phenotype in aging.

Atoh1 is a transcription factor that regulates neural development in multiple tissues and is conserved among species. Prior mouse models of Atoh1, though effective and important in the evolution of our understanding of the gene, have been limited by perinatal lethality. Here we describe a novel point mutation of Atoh1 (designated Atoh1(trhl) ) underlying a phenotype of trembling gait and hearing loss. Histology revealed inner ear hair cell loss and cerebellar atrophy. Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emission (DPOAE) showed functional abnormalities in the ear. Normal lifespan and fecundity of Atoh1(trhl) mice provide a complementary model to facilitate elucidation of ATOH1 function in hearing,central nervous system and cancer biology.

Sound sensitivity of the saccule for low frequencies in healthy adults.

Approximately 80 years ago John Tait speculated about a possible auditory role for the otolith organs in humans those days, there was no direct evidence for that idea. This time is for us to review and research. Then, the objective of our study was to investigate saccular hearing in healthy adults. We selected twenty healthy controls and twenty-four dizzy cases. Assessment comprised of audiologic evaluations, cervical vestibular evoked myogenic potentials (cVEMPs), and recognition of spoken phonemes in white noise (Rsp in wn). In the case group (a total of 48 ears), the cVEMPs abnormalities were all unilateral (24 affected ears and 24 contralateral unaffected ears). Affected ears with decreased vestibular excitability as detected by abnormal cVEMPs had decreased Rsp in wn (mean = 60.78 ± 8.33), whereas both unaffected (mean = 96.24 ± 2.4) and control ears (mean = 96.24 ± 2.4) presented normal results. The correlation between RSP in wn and p13 latencies was significant (P < 0.05, r = -0.551). The peak-to-peak amplitudes showed significant correlation to RSP in wn (P < 0.05, r = 0.307). The correlation between RSP in wn and the latencies of n23 was significant (P < 0.05, r = -0.493). We concluded in presence of severe competing noise, saccule has a facilitating role for cochlea and can improve to detection of loud low-frequencies.

Metastasis of untreated head and neck cancer to percutaneous gastrostomy tube exit sites.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) has become a mainstay in providing enteral access for patients with obstructive head and neck tumors. PEG tube placement is considered safe and complications are infrequent. METHODS: A comprehensive review of the literature in MEDLINE (1962-2011) was performed. We report herein 3 new cases. RESULTS: The literature search revealed 43 previous cases. The interval between PEG placement and diagnosis of metastasis ranged from 1 to 24 months. CONCLUSIONS: Metastatic cancer should be considered in patients with head and neck cancer that have persistent, unexplained skin changes at PEG site, anemia, or guaiac positive stools without a clear etiology. The direct implantation of tumor cells through instrumentation is the most likely explanation, although hematogenous and/or lymphatic seeding is also a possibility. Our review of the literature and clinical experience indicate that the "pull" technique of PEG placement may directly implant tumor cells at the gastrostomy site.

Vestibular hearing and speech processing.

Vestibular hearing in human is evoked as a result of the auditory sensitivity of the saccule to low-frequency high-intensity tone. The objective was to investigate the relationship between vestibular hearing using cervical vestibular-evoked myogenic potentials (cVEMPs) and speech processing via word recognition scores in white noise (WRSs in wn). Intervention comprised of audiologic examinations, cVEMPs, and WRS in wn. All healthy subjects had detectable cVEMPs (safe vestibular hearing). WRSs in wn were obtained for them (66.9 ± 9.3% in the right ears and 67.5 ± 11.8% in the left ears). Dizzy patients in the affected ears, had the cVEMPs abnormalities (insecure vestibular hearing) and decreased the WRS in wn (51.4 ± 3.8% in the right ears and 52.2 ± 3.5% in the left ears). The comparison of the cVEMPs between the subjects revealed significant differences (P < 0.05). Therefore, the vestibular hearing can improve the speech processing in the competing noisy conditions.

Temporal features of spectral integration in the inferior colliculus: effects of stimulus duration and rise time.

This report examines temporal features of facilitation and suppression that underlie spectrally integrative responses to complex vocal signals. Auditory responses were recorded from 160 neurons in the inferior colliculus (IC) of awake mustached bats. Sixty-two neurons showed combination-sensitive facilitation: responses to best frequency (BF) signals were facilitated by well-timed signals at least an octave lower in frequency, in the range 16-31 kHz. Temporal features and strength of facilitation were generally unaffected by changes in duration of facilitating signals from 4 to 31 ms. Changes in stimulus rise time from 0.5 to 5.0 ms had little effect on facilitatory strength. These results suggest that low frequency facilitating inputs to high BF neurons have phasic-on temporal patterns and are responsive to stimulus rise times over the tested range. We also recorded from 98 neurons showing low-frequency (11-32 kHz) suppression of higher BF responses. Effects of changing duration were related to the frequency of suppressive signals. Signals<23 kHz usually evoked suppression sustained throughout signal duration. This and other features of such suppression are consistent with a cochlear origin that results in masking of responses to higher, near-BF signal frequencies. Signals in the 23- to 30-kHz range-frequencies in the first sonar harmonic-generally evoked phasic suppression of BF responses. This may result from neural inhibitory interactions within and below IC. In many neurons, we observed two or more forms of the spectral interactions described here. Thus IC neurons display temporally and spectrally complex responses to sound that result from multiple spectral interactions at different levels of the ascending auditory pathway.

Vestibular evoked myogenic potentials in normal mice and Phex mice with spontaneous endolymphatic hydrops.

OBJECTIVE AND BACKGROUND: Vestibular evoked myogenic potentials (VEMPs) have been recorded from the neck musculature and the cervical spinal cord in humans and a limited number of laboratory animals in response to loud sound. However, the mouse VEMP has yet to be described. Evaluation of the sacculocollic pathway via VEMPs in mice can set the stage for future evaluations of mutant mice that now play an important role in research regarding human auditory and vestibular dysfunction. MATERIALS AND METHODS: Sound-evoked potentials were recorded from the neck extensor muscles and the cervical spinal cord in normal adult mice and in circling Phex(Hyp-Duk/y) mice with known vestibular abnormalities, including endolymphatic hydrops (ELH). RESULTS: Biphasic potentials were recorded from all normal animals. The mean threshold of the VEMP response in normal adult mice was 60 dB normal hearing level with a mean peak latency of 6.25 +/- 0.46 and 7.95 +/- 0.42 milliseconds for p1 and n1 peaks, respectively. At the maximum sound intensity used (100 dB normal hearing level), 4 of 5 Phex mice did not exhibit VEMP responses, and 1 showed an elevated threshold, but normal response, with regard to peak latency and amplitude. The histologic findings in all of these Phex mice were consistent with distended membranous labyrinth, displaced Reissner membrane, ganglion cell loss, and ELH. CONCLUSION: This is the first report of VEMP recordings in mice and the first report of abnormal VEMPs in a mouse model with ELH. The characteristics of these potentials such as higher response threshold in comparison to auditory brainstem response, myogenic nature of the response, and latency correlation with the cervical recording (accessory nerve nucleus) were similar to those of VEMPs in humans, guinea pigs, cats, and rats, suggesting that the mouse may be used as an animal model in the study of VEMPs. The simplicity and reliability of these recordings make the VEMP a uniquely informative test for assessing vestibular function, and these results suggest that they may be informative in mice with various mutations. However, further investigation is necessary.

Protection against aminoglycoside-induced ototoxicity by regulated AAV vector-mediated GDNF gene transfer into the cochlea.

Since standard aminoglycoside treatment progressively causes hearing disturbance with hair cell degeneration, systemic use of the drugs is limited. Adeno-associated virus (AAV)-based vectors have been of great interest because they mediate stable transgene expression in a variety of postmitotic cells with minimal toxicity. In this study, we investigated the effects of regulated AAV1-mediated glial cell line-derived neurotrophic factor (GDNF) expression in the cochlea on aminoglycoside-induced damage. AAV1-based vectors encoding GDNF or vectors encoding GDNF with an rtTA2s-S2 Tet-on regulation system were directly microinjected into the rat cochleae through the round window at 5 x 10(10) genome copies/body. Seven days after the virus injection, a dose of 333 mg/kg of kanamycin was subcutaneously given twice daily for 12 consecutive days. GDNF expression in the cochlea was confirmed and successfully modulated by the Tet-on system. Monitoring of the auditory brain stem response revealed an improvement of cochlear function after GDNF transduction over the frequencies tested. Damaged spiral ganglion cells and hair cells were significantly reduced by GDNF expression. Our results suggest that AAV1-mediated expression of GDNF using a regulated expression system in the cochlea is a promising strategy to protect the cochlea from aminoglycoside-induced damage.

Protection Against Aminoglycoside-induced Ototoxicity by Regulated AAV Vector-mediated GDNF Gene Transfer Into the Cochlea.

Since standard aminoglycoside treatment progressively causes hearing disturbance with hair cell degeneration, systemic use of the drugs is limited. Adeno-associated virus (AAV)-based vectors have been of great interest because they mediate stable transgene expression in a variety of postmitotic cells with minimal toxicity. In this study, we investigated the effects of regulated AAV1-mediated glial cell line-derived neurotrophic factor (GDNF) expression in the cochlea on aminoglycoside-induced damage. AAV1-based vectors encoding GDNF or vectors encoding GDNF with an rtTA2s-S2 Tet-on regulation system were directly microinjected into the rat cochleae through the round window at 5 × 1010 genome copies/body. Seven days after the virus injection, a dose of 333 mg/kg of kanamycin was subcutaneously given twice daily for 12 consecutive days. GDNF expression in the cochlea was confirmed and successfully modulated by the Tet-on system. Monitoring of the auditory brain stem response revealed an improvement of cochlear function after GDNF transduction over the frequencies tested. Damaged spiral ganglion cells and hair cells were significantly reduced by GDNF expression. Our results suggest that AAV1-mediated expression of GDNF using a regulated expression system in the cochlea is a promising strategy to protect the cochlea from aminoglycoside-induced damage.

Specific and efficient transduction of Cochlear inner hair cells with recombinant adeno-associated virus type 3 vector.

Recombinant adeno-associated virus (AAV) vectors are of interest for cochlear gene therapy because of their ability to mediate the efficient transfer and long-term stable expression of therapeutic genes in a wide variety of postmitotic tissues with minimal vector-related cytotoxicity. In the present study, seven AAV serotypes (AAV1-5, 7, 8) were used to construct vectors. The expression of EGFP by the chicken beta-actin promoter associated with the cytomegalovirus immediate-early enhancer in cochlear cells showed that each of these serotypes successfully targets distinct cochlear cell types. In contrast to the other serotypes, the AAV3 vector specifically transduced cochlear inner hair cells with high efficiency in vivo, while the AAV1, 2, 5, 7, and 8 vectors also transduced these and other cell types, including spiral ganglion and spiral ligament cells. There was no loss of cochlear function with respect to evoked auditory brain-stem responses over the range of frequencies tested after the injection of AAV vectors. These findings are of value for further molecular studies of cochlear inner hair cells and for gene replacement strategies to correct recessive genetic hearing loss due to monogenic mutations in these cells.

Vestibular-evoked myogenic potentials in infancy and early childhood.

OBJECTIVE: Hearing impairment and the often concurrent loss of vestibular function, which is rarely assessed in infants, can both impair sensory integration critical to the development of normal motor coordination. This study demonstrates, for the first time, that vestibular function in infants can be noninvasively assessed using vestibular-evoked myogenic potentials (VEMPs). Our intentions were to demonstrate that VEMPs can be reliably recorded from neonates and to compare neonatal VEMPs with those obtained from normal adults. STUDY DESIGN: Prospective cohort study. METHODS: Myogenic evoked potentials induced by air- and bone-conducted auditory stimuli were recorded from the sternocleidomastoid muscles of 12 normal neonates and 12 neonates with various clinical findings. These included infants with bilateral atresia of the external auditory canals, Treacher-Collins syndrome, and neonates who failed universal neonatal screening. RESULTS: With the exception of one patient with hearing loss, reproducible biphasic VEMPs were recorded from the sternocleidomastoid muscle of all the infants using loud, short tone-burst sounds. CONCLUSIONS: The VEMP has characteristics that differentiate it from the postauricular response and the Jaw reflex. The VEMPs were dominant on the side ipsilateral to the stimulated ear. The overall morphology of the neonatal VEMP is quite similar to that of adults. The major neonatal differences are a shorter latency of the n23 peak and higher amplitude variability. Our results suggest that recording of the VEMP in neonates with various audio-vestibular problems provides useful information about vestibular function in this population and may provide information that leads to better care and rehabilitation for neonates at risk of developmental and motor system delay.

Sacculo-collic pathway dysfunction accompanying auditory neuropathy.

CONCLUSIONS: In a patient with bilateral auditory neuropathy (AN), the vestibular-evoked myogenic potential (VEMP) was probably absent because of a neuropathy involving the inferior vestibular nerve and/or its end organ, the saccule. Our result can therefore be interpreted as a concomitant unilateral sacculo-collic neuropathy. We suggest the use of more precise terms to characterize AN patients with involvement of different parts of the inner ear and its innervations. We encourage detailed vestibular assessment in patients with AN in order to assess the co-existence of any symptomatic or asymptomatic vestibular disorder. Information such as that provided in this report will be valuable for clinicians caring for this group of patients. OBJECTIVE: AN is a disorder characterized by the absence or severe impairment of auditory brainstem responses in the presence of normal cochlear outer hair cell function as revealed by otoacoustic emissions (OAEs) and/or electrocochleography (ECoG). A variety of processes and etiologies are thought to be involved in its pathophysiology. In most literature reports the auditory profile of patients with AN is discussed. However, the extent of vestibular involvement, especially that involving the saccule, is not known. We performed vestibular tests to assess the status of the saccule in a patient with AN. MATERIAL AND METHODS: One patient with AN was studied. The patient was a right-handed 21-year-old female with chief complaints of hearing loss and speech perception difficulty. RESULTS: The auditory test results were consistent with the diagnosis of AN, i.e. absent auditory brainstem responses, moderate hearing loss, an inappropriately profound speech discrimination score and the presence of OAEs and measurable cochlear microphonics on ECoG. On neurological examination, gait and balance tests were normal. Ice-water caloric testing induced a sensation of dizziness in both ears. Short tone-burst VEMPs showed no response on left-ear stimulation and a biphasic response with normal latency and amplitude on right-ear stimulation.

Time-intensity trading in bilateral congenital aural atresia patients.

In an effort to examine the rules by which information of bilaterally applied bone-conducted signals arising from interaural time differences (ITD) and interaural intensity differences (IID) is combined, data were measured for continuous 500 Hz narrow band noise at 65-70 dB HL in 11 patients with bilateral congenital aural atresia. Time-intensity trading functions were obtained by shifting the sound image towards one side using ITD, and shifting back to a centered sound image by varying the IID in the same ear (auditory midline task). ITD values were varied from -600 to +600 micros at 200 micros steps, where negative values indicate delays to the right ear. The results indicate that time-intensity trading is present in patients with bilateral aural atresia. The gross response properties of time-intensity trading in response to bone-conducted signals were comparable in patients with bilateral aural atresia and normal-hearing subjects, though there was a larger inter-subject variability and higher discrimination thresholds across IIDs in the atresia group. These results suggest that the mature auditory brainstem has a potential to employ binaural cues later in life, although to a restricted degree. A binaural fitting of a bone-conducted hearing aid might optimize binaural hearing and improve sound lateralization, and we recommend now systematically bilateral fitting in aural atresia patients.

Vestibular-evoked myogenic potentials in three patients with large vestibular aqueduct.

An enlarged vestibular aqueduct (LVA) is a common congenital inner ear anomaly responsible for some unusual vestibular and audiological symptoms. Most of the cases show bilateral early onset and progressive hearing loss in children. The gross appearance on CT scan of the inner ear is generally normal. However, precise measurements of the inner ear components reveal abnormal dimensions, which may account for the accompanying auditory and vestibular dysfunction. Despite extensive studies on hearing and the vestibular apparatus, saccular function is not studied. To our knowledge this is the first report of saccular malfunction in three patients with LVA by means of vestibular evoked myogenic potentials. Conventional audiograms revealed bilateral severe sensorineural hearing loss in two patients and mixed type hearing loss in one patient. Two of the patients complained about vertigo and dizziness but vestibular assessments of the patients showed normal results. The diagnosis had been made by high-resolution CT scans and MR images of the skull that showed LVA in the absence of other anomalies. The VEMP threshold measured from the ear with LVA in two patients with unilateral enlargement of the vestibular aqueduct was 75-80 dB nHL whereas the threshold from normal ears was 95 dB nHL. The third patient with mixed type hearing loss and bilateral LVA had VEMP responses despite a big air-bone gap in the low frequency range. The VEMP in this patient was greater in amplitude and lower in threshold in the operated ear (the patient had a tympanoplasty which did not improve her hearing). These findings and results of other patients with Tullio phenomenon and superior semicircular canal dehiscence, who also showed lower VEMP threshold, confirmed the theory of a 'third window' that allows volume and pressure displacements, and thus larger deflection of the vestibular sensors, which would cause the vestibular organ to be more responsive to sound and pressure changes.

Negamycin restores dystrophin expression in skeletal and cardiac muscles of mdx mice.

The ability of aminoglycoside antibiotics to promote read-through of nonsense mutations has attracted interest in these drugs as potential therapeutic agents in genetic diseases. However, the toxicity of aminoglycoside antibiotics may result in severe side effects during long-term treatment. In this paper, we report that negamycin, a dipeptide antibiotic, also restores dystrophin expression in skeletal and cardiac muscles of the mdx mouse, an animal model of Duchenne muscular dystrophy (DMD) with a nonsense mutation in the dystrophin gene, and in cultured mdx myotubes. Dystrophin expression was confirmed by immunohistochemistry and immunoblotting. We also compared the toxicity of negamycin and gentamicin, and found negamycin to be less toxic. Furthermore, we demonstrate that negamycin binds to a partial sequence of the eukaryotic rRNA-decoding A-site. We conclude that negamycin is a promising new therapeutic candidate for DMD and other genetic diseases caused by nonsense mutations.

Binaural interaction of bone-conducted auditory brainstem responses in children with congenital atresia of the external auditory canal.

Bilateral bone-conducted auditory brainstem responses (BC-ABRs) were recorded in children with atresia of the external auditory canal bilaterally (AECB) in order to compare the response characteristics to normal hearing adults. The binaural interaction component (BIC) of the ABR occurs when the sum of the monaural-evoked ABR amplitudes are different in amplitude when compared to the binaural-evoked ABR amplitude. Previous electrophysiological work from our lab has shown that children with AECB lateralize bone-conducted (BC) sound. Furthermore, we have found in normal-hearing adults that BICs exist using BC clicks. In adults, BC-BIC occurred in the latency region corresponding to waves IV-VI, whereas for children with AECB corresponding peak latencies occurred earlier. Same as normal-hearing adults, BC-ABR IV-V complex peak amplitudes for sum of the BC-monaural right and BC-monaural left ears were different from binaural response amplitude. Individual peak latencies were similar in children with AECB when compared to normal-hearing adults except for shorter latencies for BIC. These results indicate that: (1) BC-BI is present in children with AECB as well as normal-hearing adults; (2) the gross response properties of BIC are similar in children with AECB and normal-hearing adults; (3) fitting of a bilateral BC hearing aid might be a feasible method to optimize binaural hearing and sound lateralization.

Distortion evoked otoacoustic emission using GSI 70 analyzer for neonatal screening.

OBJECTIVE: Following the recommendation of the United State National Institute of Health Consensus Conference in 1993, otoacoustic emissions (OAE) are now used internationally for hearing screening. The GSI 70 OAE screener provides the means for carrying out OAE recordings within a short period of time and includes an automatic evaluation of results. The aim of this study was to determine the reliability of recordings in comparison with available standards in brainstem audiometry. METHOD: OAE recorded in 29 hearing-impaired suspected infants and young children (aged 1 months-7 years old) in order to compare the result of the GSI 70 screener with the result of ABR. This study was conducted in the outpatient clinic of the Tokyo University Hospital. RESULT: Our study showed that the GSI 70 screener has higher false negative rate compared with ABR results (P<0.01). Consequently, an OAE measuring method, is also provides high sensitivity and easy to use. However, there was no trend toward increased refer rates with increased age. CONCLUSION: Our findings show that the GSI 70 screener can meet the demands of systematic hearing screening in infants and young children, although there is a tendency to miss cochlear impaired cases.

The otolithic organ as a receptor of vestibular hearing revealed by vestibular-evoked myogenic potentials in patients with inner ear anomalies.

The human vestibule has preserved an ancestral sound sensitivity and it has been suggested that a reflex could originate from this property underlying cervical muscle micro-contractions secondary to strong acoustic stimulation. Previous studies have established that an early component of loud sound-evoked myogenic potentials from the sternocleidomastoid muscle originate in the vestibule. This is based on findings that the response can still be obtained from patients with complete loss of cochlear and vestibular (semi-circular canal) function. Our data confirm, in a more direct way, a saccular origin of this short-latency acoustic response and verifies that a saccular acoustic response persists in the human ear. The contribution of this response to the perception of loud sounds is discussed. It is concluded that vestibular response to sound might be used to assist in the rehabilitation of deafness.