Late metastasis of breast adenocarcinoma into internal auditory canal and cerebellopontine angle: case report

A case of metastasis of breast adenocarcinoma into the internal auditory canal (IAC) and cerebellopontine angle (CPA) is presented, which appeared 16 years after primary tumor had been treated by surgery and radiation therapy. The 66-year old patient was considered cured from the primary disease, when she started with a rapidly developing hearing loss and intermittent facial palsy. Magnetic resonance image (MRI) displayed an intra- and extracanalicular tumor mass, which radiologically resembled a vestibular schwannoma. Surgery was performed and histopathological studies showed an adenocarcinoma compatible with breast origin. Metastasis is a rare occurrence within the IAC and CPA. Clinical history of severe facial palsy will rise suspicion of malignant tumor in spite of the radiological findings.     

Acute auditory agnosia as the presenting hearing disorder in MELAS

MELAS is commonly associated with peripheral hearing loss. Auditory agnosia is a rare cortical auditory impairment, usually due to bilateral temporal damage. We document, for the first time, auditory agnosia as the presenting hearing disorder in MELAS. A young woman with MELAS (A3243G mtDNA mutation) suffered from acute cortical hearing damage following a single stroke-like episode, in the absence of previous hearing deficits. Audiometric testing showed marked central hearing impairment and very mild sensorineural hearing loss. MRI documented bilateral, acute lesions to superior temporal regions. Neuropsychological tests demonstrated auditory agnosia without aphasia. Our data and a review of published reports show that cortical auditory disorders are relatively frequent in MELAS, probably due to the strikingly high incidence of bilateral and symmetric damage following stroke-like episodes. Acute auditory agnosia can be the presenting hearing deficit in MELAS and, conversely, MELAS should be suspected in young adults with sudden hearing loss.     

Cavernous haemangioma of the internal auditory canal: a case report.

We report a patient with a cavernous haemangioma of the internal auditory canal (IAC). A 47-year-old man presented with a left profound hearing loss and a left facial palsy that had progressed over 5 years. With a preoperative diagnosis of acoustic or facial nerve neurinoma, the tumour was removed totally by a translabyrinthine approach. Intraoperatively, the tumour appeared red; it compressed the facial and cochlear nerves, and adhered to the vestibular nerve. The tumour was diagnosed as a cavernous haemangioma upon histologic and immunohistochemical examination. No recurrence of tumour occurred, but hearing loss and left facial palsy persisted. Although cavernous haemangiomas of the IAC is found in small size less than 10 mm, they often cause severe hearing loss and facial palsy. Our patient had no improvement of facial palsy, but many reports describe recovery of facial nerve function.     

Plasticity of auditory cortex associated with sensorineural hearing loss in adult C57BL/6J mice

The representation of frequency was mapped in the primary auditory cortex (AI) of C57BL/6J (C57) mice during young adulthood (1.5–2 months) when hearing is optimal, and at 3, 6, and 12 months of age, a period during which progressive, high frequency, sensorineural hearing loss occurs in this strain. Maps were also obtained from CBA/CaJ mice which retain good hearing as they age. In AI of young adult C57 mice, and CBA mice, characteristic frequencies (CFs) of multiple-unit clusters were easily identified with extracellular recordings, and a general tonotopic organization was observed from dorsal (high frequency) to ventral and caudal (low frequency). In individual cases there appeared to be deviations from the above tonotopic organization, despite the fact that inbred mice are genetically invariant. As progressive loss of high frequency sensitivity ensued peripherally, a substantially increased representation of middle frequencies was observed in AI. There was no apparent change in the surface area of the auditory cortex despite the elimination of high frequencies, and virtually the entire auditory cortex became devoted to the middle frequencies (especially 10–13 kHz) for which sensitivity remained high. Similar age-related changes were not observed in normal-hearing CBA mice. These findings indicate that plasticity in the representation of frequency in AI is associated with high frequency hearing loss in C57 mice. © 1993 Wiley-Liss, Inc.     

Round window membrane delivery of L-methionine provides protection from cisplatin ototoxicity without compromising chemotherapeutic efficacy

Cisplatin (cis-diamminedichloroplatinum(II) (CDDP)) is a widely used, highly effective, oncolytic agent that has serious ototoxic side-effects. To test the effectiveness of local delivery, of L-methionine (L-Met) as an otoprotective agent against CDDP ototoxicity, we used a rat model of a highly metastatic breast cancer tumor, i.e. Fisher 344 rats implanted with MTLn3 breast cancer cells. Four experimental groups were evaluated--I: untreated; II: CDDP-treated (three dosages); III: systemically-delivered L-Met + CDDP-treated; IV: locally delivered L-Met + CDDP-treated. The integrity of the outer hair cells (OHCs) was determined using scanning electron microscopy (SEM); hearing was assessed by recording auditory brainstem responses (ABRs) at multiple frequencies. The chemotherapeutic effectiveness of CDDP was quantified by measuring changes in tumor mass and the presence of tumor metastasis. L-Met provided otoprotection of the OHCs against CDDP toxicity in the cochleae of rats following either systemic (III) or local (IV) administration. The ABRs were unchanged in each of the L-Met protection Groups (III and IV) and in the untreated animals of Group I. Treatment with CDDP only (II) induced significant hearing losses at both 16 and 18 kHz when compared to ABRs of untreated rats(I). CDDP was effective in controlling the MTLn3 initiated breast cancer tumors in the CDDP-treated (II) and the local L-Met protection, CDDP-treated (IV) Groups. In contrast, the tumors in the systemic L-Met protection, CDDP-treated Group (III) were not controlled by the CDDP treatment regime. This study demonstrates that local delivery of L-Met to the scala tympani of the cochlea via the round window membrane (IV) provides effective protection against CDDP ototoxicity without compromising its ability to control a highly metastatic form of cancer.     

Cortical auditory evoked potentials in unsuccessful cochlear implant users

In some cochlear implant users, success is not achieved in spite of optimal clinical factors (including age at implantation, duration of rehabilitation and post-implant hearing level), which may be attributed to disorders at higher levels of the auditory pathway. We used cortical auditory evoked potentials to investigate the ability to perceive and discriminate auditory stimuli in 10 unsuccessful implant users aged 8–10 years (CI) and 10 healthy age-matched controls with normal hearing (NH). Pure tones (1 and 2 kHz) and double consonant-vowel syllables were applied. The stimuli were presented in an oddball paradigm that required the subjects to react consciously. The latencies and amplitudes of the P1, N1, P2, N2 and P3 waves were analyzed, in addition to reaction times and number of responses. Significant differences in the average response times and number of responses were observed between the CI and NH groups. The latencies also indicate that the CI group took longer to perceive and discriminate between tonal and speech auditory stimuli than the NH group.     

精神分裂症幻听患者初级听觉皮质的脑磁图研究

目的 探讨在不同频率纯音刺激下男性精神分裂症幻听患者初级听觉皮质的脑磁图(MEG)定位.方法 对均为右利手的10例男性精神分裂症幻听患者(研究组)和11名男性健康受试者(对照组),分别给予频率为0.5,2,4,8 kHz的纯音刺激,强度90 dB,持续200ms,刺激声间隔1 s.用脑磁图设备记录刺激后产生的听觉诱发磁场,并将MEG资料叠加到核磁共振成像以获得磁源性影像.结果 (1)对照组初级听觉皮质均定位于双侧颞横回;与对照组比较,研究组右侧初级听觉皮质位置更靠近颞横回外部,左侧明显偏向颞上回后外下部(P<0.05).(2)在分别给予2 kHz和4kHz纯音刺激时,研究组大脑双侧M100潜伏期[2 kHz:左(97±16)ms,右(97±10)ms,4 kHz:左(93±13)ms,右(99±14)ms]均短于对照组[2 kHz:左(121±15)ms,右(113±6)ms,4 kHz:左(113±13)ms,右(114±6)ms](均P<0.01),而波幅[2 kHz:左(89±10)fT,右(118±37)fT,4 kHz:左(81±9)fT,右(108±14)fT]高于对照组[2 kHz:左(73±12)fT,右(79±13)fT,4 kHz:左(69±14)fT,右(81±20)fT](均P<0.05～0.01).结论 男性精神分裂症幻听患者的初级听觉皮质位置与正常人不同,其M100波幅高,潜伏期短,这些功能及解剖结构的异常可能是精神分裂症幻听产生的病理生理机制之一.     

Clinical and surgical considerations for cerebellopontine angle meningiomas

We retrospectively reviewed 24 patients with cerebellopontine angle (CPA) meningioma from our institution to describe the clinical and surgical significance of extensions into the internal auditory canal (IAC). Of these patients, 62% had invasion of the IAC, which was associated with high rates of unilateral hearing loss at presentation (67% versus [vs.] 22%, p < 0.05). A retrosigmoid approach was used in 22/24 patients, of whom 13 had an IAC extension. In five patients, IAC drilling was needed to achieve a more complete resection and 20 patients of the 22 (91%) had improved or stable hearing postoperatively, and one patient had permanent facial paralysis. Cranial nerve IX and X were the most common complications (17% and 33% respectively), and were almost exclusively associated with resection of tumor extensions into the jugular foramen (p < 0.01). We conclude that CPA meningiomas can be removed with excellent rates of hearing and facial nerve preservation. Caution must be used when attempting to resect tumor extensions into the jugular foramen given the high rates of lower CN complications.     

Effects of a zinc-deficient diet on hearing in CBA mice

This study investigated the effect of a zinc-deficient diet on the hearing in CBA mice and aimed to verify whether this hearing change is reversible by supplementation of zinc afterwards. We assessed hearing through an auditory brainstem response (ABR) with tone burst stimulation in 4, 8, 16, and 32 kHz and distortion product otoacoustic emissions in 5.6, 8, 11.3, and 16 kHz every week. The ABR threshold started to increase after 4 weeks on a zinc-deficient diet. The difference in the threshold between control and zinc-deficient animals became greater over time and plateaued at about 6 weeks. The ABR threshold differences between control and zinc-deficient mice were greater at higher frequencies. Four weeks of normal diet, following 8 weeks of a zinc-deficient diet, restored the ABR threshold to normal at all measured frequencies. Zinc-deficient mice did not show any distortion product otoacoustic emission threshold change at all frequencies. This finding suggests that a zinc-deficient diet increased the ABR threshold in CBA mice and a zinc-adequate diet restored the ABR threshold to normal.     

Rapid increases of gamma power in the auditory cortex following noise trauma in humans

Tinnitus is an auditory perception in the absence of any external sound source. It has been suggested that tinnitus is related to enhanced synchronization of neuronal activity in the auditory cortex. Usually a hearing damage can be identified suggesting auditory deprivation to central auditory regions to be fundamental for neurophysiological processes related to tinnitus. Until now, human research has been conducted on patients with chronic tinnitus (>6 months). However, neuronal activity accompanying auditory deprivation and putatively tinnitus may not remain constant over time, making it difficult to directly relate outcomes of current animal studies (acute tinnitus) to chronic tinnitus in humans, and vice versa. We investigated 14 amateur rock musicians who frequently reported a short-term tinnitus immediately after band practice. Magnetoencephalographic resting-state recordings, audiometry and tinnitus testing were performed at two separate occasions: with and without previous exposure to loud music. Analyses revealed that transient tinnitus was accompanied by temporary hearing loss in both ears and increased gamma activity in the right auditory cortex in 13 out of 14 cases. Additionally, tinnitus frequency was strongly correlated to hearing loss. Analogous to animal studies, our results show for the first time in humans that noise trauma leads rapidly to increased neuronal synchrony in the auditory cortex. Importantly, the strongly right-lateralized effect implies that it does not reflect tinnitus percept per se. This could rather have been triggered by greater discontinuities of hearing loss at high frequencies that were particularly pronounced in the left ear.     

Enhanced activation of the auditory cortex in patients with inner-ear hearing impairment: a magnetoencephalographic study.

OBJECTIVE: Injury of peripheral auditory organ often induces abnormality of loudness sensation such as loudness recruitment. However, objective evaluation of this phenomenon has rarely been performed. To elucidate this abnormal loudness sensation, cortical mechanisms were investigated by recording auditory evoked magnetic fields (AEFs). METHODS: We recorded AEFs in 8 patients suffering from inner-ear hearing impairment with loudness recruitment and in 14 healthy hearing controls using a 122-channel whole-head neuromagnetometer. Tone bursts of 1 kHz were presented monaurally at 4 different intensities (40, 50, 60, 70 dB HL) with a constant interstimulus interval of 1 s. RESULTS: In both groups, the 100 ms response (N100m) increased in amplitude and decreased in latency as a function of stimulus intensity in both hemispheres. Concerning the source strength, increment of dipole moment of N100m was more rapid according to the stimulus intensity in patients compared with that in healthy subjects. Source strength of N100m was enhanced at high stimulus intensity in patients, and its ratio to healthy subjects was 1.08 at 50 dB, 1.69 at 60 dB and 2.04 at 70 dB. CONCLUSIONS: In patients with inner-ear hearing impairment, enhanced activation of the auditory cortex was observed, and may help explain loudness recruitment.     

Caspase inhibitor facilitates recovery of hearing by protecting the cochlear lateral wall from acute cochlear mitochondrial dysfunction

We recently showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) causes hearing loss mainly due to degeneration of cochlear lateral-wall fibrocytes. In the present study, we analyzed the effect of the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (Z-VAD-FMK) on 3-NP-induced hearing loss in a model showing temporary threshold shifts at low frequencies and permanent threshold shifts at high frequencies. The model rats received an intraperitoneal injection of either Z-VAD-FMK or vehicle for 3 days starting 1 day prior to 3-NP treatment. One day after the administration of 3-NP, the auditory brain-stem response (ABR) threshold at 20 kHz was elevated to 70 dB in the Z-VAD-FMK group and to 85 dB in controls. The Z-VAD-FMK group completely recovered to the preoperative level within 14 days, whereas in the controls, the ABR threshold remained elevated at 50 dB even 28 days after the administration of 3-NP. Treatment with Z-VAD-FMK also improved recovery of hearing at 8 kHz but did not change recovery at 40 kHz. Histological examination demonstrated that treatment with Z-VAD-FMK inhibited progressive degeneration of the lateral-wall fibrocytes in the cochlear basal turn, as well as apoptosis of these fibrocytes. These results clearly indicate that caspase-dependent apoptosis of fibrocytes in the cochlear lateral wall plays an important role in hearing loss in the present animal model. Moreover, the results of the present study suggest that systemic administration of a caspase inhibitor may be an effective therapy for sensorineural hearing loss caused by acute energy failure such as that observed in cochlear ischemia.     

Frequency representation in the auditory midbrain and forebrain of a marsupial, the northern native cat (Dasyurus hallucatus)

The representation of sound frequency was examined in the auditory cortex and inferior colliculus of anaesthetized marsupial native cats (Dasyurus hallucatus) using microelectrode mapping techniques. The tonotopic organizations of these two auditory regions are grossly similar to those described in brush-tailed possums and in Eutheria. There appears to exist a biased representation of high frequencies (greater than 10kHz) in native cats and a paucity of frequencies below 1 kHz. Unit threshold audiograms indicate minimum thresholds between 7 and 12kHz and high thresholds above 30kHz.     

Long-term follow-up of auditory agnosia as a sequel of herpes encephalitis in a child

We report a pediatric patient with auditory agnosia as a sequel of herpes encephalitis. His early development was completely normal. He uttered three words at 12 months old. Disease onset was 1 year and 2 months of age. He was discharged from the hospital seemingly with no sequel; however, he could not recover his intelligible words even at age 2 years. He was diagnosed as having auditory agnosia caused by bilateral temporal lobe injury. We began to train him at once, individually and intensively. Adult patients with pure auditory agnosia followed by two episodes of temporal lobe infarction have impairment in central hearing but not inner language. Therefore, they can communicate by reading and writing. Moreover, impairment in hearing is not always severe and is often transient. However, despite long-term (more than 15 years) energetic education and almost normal intellectual ability (Performance IQ of Wechsler Intelligence Scale for Children-Revised was 91), our patient's language ability was extremely poor. Cerebral plasticity could not work fully on our patient, whose bilateral temporal lobe was severely injured in early childhood. The establishment of a systematic training method in such patients is an urgent objective in this field.     

Frequency representation in auditory cortex of the common marmoset (Callithrix jacchus jacchus)

The location and characteristics of the primary auditory cortex of the common marmoset, Callithrix jacchus jacchus, were determined in five anesthetized male adult animals by mapping the responses of cortical units and unit clusters to pure tone stimuli presented to the contralateral ear. The primary auditory cortex lies largely ventral to the lateral sulcus, the only major fissure on the lateral cortex of this smooth-brained primate, but in some animals it may extend significantly down the ventral bank of this sulcus. Responses are distributed such that low best frequencies are found rostroventrally whereas high best frequencies occur caudally. The disposition of frequency-band contours is fan-shaped, with contours separating low-frequency octaves nearly parallel to the lateral sulcus and high-frequency (greater than 8 kHz) contours perpendicular to that sulcus. Best frequencies range from 0.6 to 30 kHz across the primary field, but there is a disproportionate representation of the three octaves between 2 and 16 kHz. The most sensitive thresholds (as low as -2 dB SPL) are found between 7 and 9 kHz. The primary auditory cortex is similar in cytoarchitecture to that reported for the cat, showing a blurring of lamination in the middle layers (II-IV) and a preponderance of small cells in these merged layers, giving a highly granular appearance. The accessibility of the cochlear representation on the gyral surface makes the marmoset an attractive animal for studies of primate auditory cortex.     

Redefining the tonotopic core of rat auditory cortex: physiological evidence for a posterior field

Previous physiological studies have identified a tonotopically organized primary auditory cortical field (AI) in the rat. Some of this prior research suggests that the rat, like other mammals, may have additional fields surrounding AI. We, therefore, recorded in the Sprague-Dawley rat extracellular responses of single neurons throughout AI, and continued posteriorly to verify the existence of a posterior field (P) and to compare the neuronal properties in the two regions. Acoustic stimuli, including tones, bandpass noise, broadband noise, and temporally modulated stimuli, were delivered dichotically via sealed systems. Consistent with previous findings, AI was characterized by an anterior-to-posterior tonotopic progression from high to low frequencies (ranging from >40 kHz to <1 kHz). A frequency reversal at the posterior border of AI marked entry into a second core tonotopic region, P, with progressively higher frequencies encountered further posteriorly, up to a point (approximately 8 kHz) where cells were no longer tone responsive. Nevertheless, bandpass noise was an effective stimulus in P, enabling characterization of cells up to 15 kHz. Compared with AI, the frequency tuning of response areas was relatively broader in P, the response latency was often longer and more variable, and the response magnitude was more commonly a nonmonotonic function of stimulus level. In both fields, most neurons were binaurally influenced. The presence of multiple auditory cortical fields in the rat is consistent with auditory cortical organization in other mammals. Moreover, the response properties of P relative to AI in the rat also resemble those found in other mammals. Finally, the physiological data suggest that core auditory cortex (temporal area TE1) is composed not only of AI as previously thought, but also of at least two other subdivisions, P and an anterior field (A). Furthermore, our physiological characterization of TE1 reveals that it is larger than suggested by previous anatomical characterizations.     

Long-term monaural auditory deprivation and bilateral cochlear implants

Long-term binaural auditory deprivation is associated with poorer speech recognition outcomes after cochlear implantation, even for postlingual hearing loss. It is, however, unknown to what extent the outcomes of implantation are related to the peripheral changes occurring monaurally or to changes at a higher level in the auditory system related to binaural deafness. This retrospective study aimed to unravel peripheral and central contributions to cochlear implantation outcomes by comparing outcomes obtained in individual ears for adults with long-term monaural auditory deprivation (i.e. unilateral use of hearing aid) who received bilateral cochlear implants. Results showed that similar outcomes can be obtained with the implant placed in the auditory-deprived or in the aided ear. This suggests that the peripheral changes related to monaural auditory deprivation have little effect on outcomes of cochlear implantation.     

Vinpocetine prevents 4-aminopyridine-induced changes in the EEG, the auditory brainstem responses and hearing

OBJECTIVE: The purpose of the present study was to investigate if the sodium channel blocker and memory enhancer, vinpocetine, was capable to overcome the epileptic cortical activity, the abnormalities in the later waves of the auditory brainstem responses (ABRs) and the hearing loss induced by 4-AP at a convulsing dose in the guinea pig in vivo. METHODS: EEG and ABR recordings before and at specific times within 2h after the injection of 4-AP (2 mg/kg, i.p.) were taken in animals pre-injected i.p. with vehicle or with vinpocetine (2 mg/kg) 1 h before 4-AP. The amplitude and latency of the ABR waves induced by a monoaural stimulus of high intensity (100 dB nHL) at 4 and 8 kHz pure tone frequencies and the ABR threshold were determined in the animals exposed to the different experimental conditions. RESULTS: Vinpocetine inhibited the EEG changes induced by 4-AP for the ictal and post-ictal periods as well as the alterations in amplitude and latency of P3 and P4 and the increase in the ABR threshold induced by 4-AP. CONCLUSIONS: Vinpocetine prevents the retro-cochlear alterations and the hearing decline that accompany the epileptic cortical activity. SIGNIFICANCE: Vinpocetine could be a promising alternative for the treatment of epilepsy.     

Development of contralateral and ipsilateral frequency representations in ferret primary auditory cortex

Little is known about the maturation of functional maps in the primary auditory cortex (A1) after the onset of sensory experience. We used intrinsic signal imaging to examine the development of the tonotopic organization of ferret A1 with respect to contralateral and ipsilateral tone stimulation. Sound-evoked responses were recorded as early as postnatal day (P) 33, a few days after hearing onset. From P36 onwards, pure tone stimuli evoked restricted, tonotopically organized patches of activity. There was an age-dependent increase in the cortical area representing each octave, with a disproportionate expansion of cortical territory representing frequencies > 4 kHz after P60. Similar tonotopic maps were observed following stimulation of the contralateral and ipsilateral ears. During the first few weeks following hearing onset, no differences were found in the area of cortical activation or in the magnitude of the optical responses evoked by stimulation of each ear. In older animals, however, contralateral stimuli evoked stronger responses and activated a larger A1 area than ipsilateral stimuli. Our findings indicate that neither the tonotopic organization nor the representation of inputs from each ear reach maturity until approximately 1 month after hearing onset. These results have important implications for cortical signal processing in juvenile animals.     

Fat graft-assisted internal auditory canal closure after retrosigmoid transmeatal resection of acoustic neuroma: Technique for prevention of cerebrospinal fluid leakage

The retrosigmoid transmeatal approach remains an important strategy in the surgical management of acoustic neuromas. Gross total resection of acoustic neuromas requires removal of tumor within the cerebellopontine angle as well as tumor involving the internal auditory canal (IAC). Drilling into the petrous bone of the IAC can expose petrous air cells, which can potentially result in a fistulous tract to the nasopharynx manifesting as cerebrospinal fluid (CSF) rhinorrhea. We describe our method of IAC closure using autologous fat graft and assessed the rates of postoperative CSF leakage. We performed a retrospective study of 24 consecutive patients who underwent retrosigmoid transmeatal resection of acoustic neuroma who underwent our method of fat graft-assisted IAC closure. We assessed rates of postoperative CSF leak (incisional leak, rhinorrhea, or otorrhea), pseudomeningocele formation, and occurrence of meningitis. Twenty-four patients (10 males, 14 females) with a mean age of 47 years (range 18–84) underwent fat graft-assisted IAC closure. No lumbar drains were used postoperatively. There were no instances of postoperative CSF leak (incisional leak, rhinorrhea, or otorrhea), pseudomeningocele formation, or occurrence of meningitis. There were no graft site complications. Our results demonstrate that autologous fat grafts provide a safe and effective method of IAC defect closure to prevent postoperative CSF leakage after acoustic tumor removal via a retrosigmoid transmeatal approach. The surgical technique and operative nuances are described.