Medical Thesis Fan - auditory neuropathy.doc

Auditory neuropathy (auditory neuropathy, AN) is increasingly being recognized in recent years, a kind of special clinical manifestation of hearing impairment, its diagnosis and treatment are different from the normal sensorineural hearing loss. Worthington et al 1 in 1980 reported 4 cases, they have can be measured by pure-tone hearing thresholds, but was absent auditory brainstem response (auditory brainstem response, ABR). Since then, scholars have reported similar cases 2,3, where Kraus et al 3 first noted that the speech recognition rate of these patients disproportionately lower than the pure tone threshold, then further found that these patients evoked potentials and cochlear microphonic otoacoustic emissions were normal. 1993, Berlin et al 4 first found in 2 patients evoked otoacoustic emission suppression of the disappeared, and proposed a -type afferent neuron disease concept. 1996, Starr et al 5 for the first time named auditory neuropathy in 1998, Doyle et al 6 reported eight cases of children with auditory neuropathy. Such lesions show also attracted the concern of Chinese scholars, GU Rui et al 7 in 1992 reported 16 cases of central low-tone sensorineural hearing loss, according to hearing the results of electrophysiological examination should be consistent with auditory neuropathy in some patients diagnosis; 1999 Leung Fung, and so on 8 reported 17 cases. Clinical features A lower incidence of auditory neuropathy, and many childhood years of onset. 1999, Rance et al 9 In 5199 cases of neonatal period are risk factors for hearing impairment in infants and young children and adolescents ABR abnormalities detected in 109 cases, of which 12 cases was absent ABR, but the microphonic potential of the normal, that is, auditory neuropathy In this group of high-risk infants and young children, the incidence rate of about 0.23%. Starr et al 5 reported 10 cases of adult patients were sporadic cases, although the doctor when the patients age spans, but they are from the infant and young child or adolescent onset. The incidence of auditory neuropathy no gender differences. 1. History: Most patients complained of ears could not hear voices, there are different degrees of verbal communication difficulties, a small number of cases associated with tinnitus, and many childhood years of onset. There was no ototoxicity and noise exposure history, may have a family history of deafness. 2. Pure-tone and speech audiometry: auditory neuropathy in patients with pure-tone audiometry showed mild to moderate sensorineural hearing loss and showed marked individual differences. Audiogram mainly be based on the rise in low-frequency loss of type, it can be for the decline mainly to high-frequency loss of type, can also flat curve, but the low-tone sensorineural deafness more, Soliman et al 10 and GU Rui et al 7 reported a group of patients, respectively, their pure-tone hearing thresholds are dominated by low-frequency loss. Speech Hearing difference is an important feature of auditory neuropathy, in patients with speech recognition rate is often disproportionately lower than the pure tone hearing thresholds, Starr et al 11 and Zeng et al 12 speculated that speech recognition ability is poor and the non-synchronization of auditory nerve discharge related. Rance et al 9 is considered to be central to the hearing to reach a higher-bit signal distortion caused by speech. 3. ABR: ABR auditory neuropathy was absent response is one of the most important features. ABR non-response reasons include: no neural activity; nerve conduction block; auditory nerve fibers of non-synchronized or synchronized discharge discharge damage 1. Patients with auditory neuropathy may exist from the quantitative measurement of hearing, that there is a certain degree of nerve impulses pass point of view, the first three kinds of cases is likely. Myelinated nerve fibers caused by the non-synchronized discharge of the most common reason is that demyelination. 4. Evoked otoacoustic emissions and contralateral suppression: This refers primarily to transient evoked otoacoustic emissions (transient evoked otoacoustic emission, TEOAE) and distortion product otoacoustic emissions (distortion production otoacoustic emission, DPOAE), auditory neuropathy in patients, even if the the performance of pure-tone hearing threshold was severe sensorineural hearing loss, evoked otoacoustic emissions can still be normal or mild changes, while microphonic potential also were normal, which is to listen to another important feature of the neuropathy. Normal evoked otoacoustic emissions contralateral suppression exists in the test plus a certain intensity to the right ear of white noise, TEOAE amplitude of a general decline in 2 4 dB 4, but in listening to this contralateral suppression in patients with neuropathy phenomenon disappears. Berlin et al 4 compares an auditory neuropathy patients and normal sensorineural hearing loss in patients with contralateral TEOAE suppression results, although the two almost identical pure-tone hearing thresholds, but the phenomenon of contralateral suppression in patients with auditory neuropathy disappeared. Berlin suggested as a possible explanation: -type auditory afferent fibers of non-synchronous discharge not excited contralateral suppression of otoacoustic emissions; rely solely on auditory afferent fibers of type to maintain certain frequency zone of normal pure-tone hearing threshold; primary auditory neurons synchronized discharge heard by the auditory system, regulation, which came system dysfunction is the starting factor in the disease. Since white noise does not make the auditory pathway neurons synchronized discharge, indicating otoacoustic emissions contralateral suppression reflex arc of the excitement does not require synchronization of auditory afferent discharge. With auditory neuropathy patients have enough to stimulate the introduction of sound, under the phenomenon of contralateral suppression disappeared, suggesting that the brain stem auditory pathways or auditory system, there spread disease, the first three kinds of possibilities and can not be easily ruled out. Also note that may occur secondary otoacoustic emission was absent, so necessary, simultaneous detection of otoacoustic emissions and microphonic potentials 13. 5. Medium-and long latency response: auditory neuropathy patients, the long-latency response has obvious individual differences, Starr et al 5 reported that about half of the adult cases, may elicit, it may be due to the long latency response test does not strictly require the synchronization of neuronal discharge. 6. Acoustic impedance tests: auditory neuropathy in patients with tympanogram Jun Cheng A type, suggesting that middle ear function was normal; stapedial reflex was absent. Berlin et al 4 two cases of sensorineural hearing loss in patients with comparison, they have almost the same pure tone hearing threshold, are for the 2 kHz at normal, but auditory neuropathy in patients with stapedial reflex was absent, its control may be to bring out while the general understanding, which should be at least at 2 kHz can be derived. With the contralateral suppression of otoacoustic emissions is similar to the excitement of stapedial reflex does not depend on the synchronization of auditory afferent fibers emissions, auditory nerve disease Have some hearing in the case of incoming signals is still stapedial reflex was absent, suggesting that brain stem auditory pathways of disease. Lesion Lesion of auditory neuropathy has not been established. Since the ABR waves are within the auditory nerve fibers from the cochlear place, Starr et al 5 According to the ABR was absent in patients with auditory neuropathy lesions may occur in response to speculation the remote part of the auditory nerve, including the inner hair cells, spiral ganglion cells, 2 synaptic connections between the cochlea and auditory nerve fibers. Harrison et al 14 the use of Kappa injury Chinchilla (chinchilla) suits the hair cells of cochlea hair cells, the basic characteristics of non-involvement in order to establish an animal model of auditory neuropathy. He used pure-tone-induced hypothalamic threshold of single-cell electrical response on behalf of pure-tone hearing thresholds will be compared with the ABR was found disproportionately higher than the ABR threshold of pure tone thresholds. Auditory neuropathy in patients with pure-tone hearing thresholds and ABR similar inconsistencies. However, the model leads, after all, ABR waveform, inconsistent with auditory neuropathy, but it can explain just having inner hair cell damage sufficient to explain all manifestations of auditory neuropathy. -type spiral ganglion cells and inner hair cell junction characteristics of the anatomical structure is conducive to neuronal synchronization of discharge 11. Whether auditory neuropathy exists in the cell junction structure due to the destruction of Er Shi neurons lost time locking (time lock), which led to ABR was absent and the speech the possibility of hearing loss? In addition, the synaptic connections between the two lesions, from the theoretical analysis, the same can produce the performance of auditory neuropathy. Inner hair cells, neurotransmitter synthesis and release of the non-synchronization will inevitably lead to nerve impulse discharge of non-synchronization. Outer hair cells are necessary to produce hearing, but its relationship with the inner hair cells, and the connected type afferent fiber function are still not clear, so it is the role of auditory neuropathy is also difficult to determine. Although the evoked otoacoustic emission and microphonic potential prompted mechanical activity of outer hair cells and occurrence of micro-receptor potential function was normal, but not Be able to exclude others, such as neurotransmitter synthesis, release, outer hair cells and ganglion cells in type abnormal synaptic connections. But these are the lack of appropriate detection means. Starr et al 5 reported 10 cases of adult cases, 8 cases of hearing impairment in after a few years with varying degrees of peripheral neuropathy performance; it was reported 15-17 with hereditary motor and sensory neuropathy of the family, some members of the the performance of auditory neuropathy occurs, suggesting that lesions involving the auditory nerve. Described above with auditory neuropathy may be a systemic neuropathy in the auditory system performance. Rance et al 9 reported 12 cases of children with auditory neuropathy were not found in the performance of peripheral nerve involvement may be the need for a process of disease development. In addition, according to the clinical manifestations of auditory neuropathy there exists an obvious individual differences in the characteristics preclude the simultaneous existence of two or more lesions two possibilities. Some parts of the lesion for all patients with auditory neuropathy are common, while others in different parts of the lesion was specific to patients. Etiology and pathology Auditory neuropathy is a functional diagnosis, has not yet determined its cause. Because auditory neuropathy is more than period of infantile and juvenile onset, so patients with neonatal period and early childhood diseases that have arisen aroused great attention. Possible causes are now considered: genetic diseases such as Charcot - Marie - Tooth syndrome (including the Hereditary motor and sensory neuropathy type and ), and Ferid reich ataxia; autoimmune diseases such as Guillain - Barre syndrome; infectious diseases such as measles, meningitis; metabolic diseases such as toxic substances neonatal hyperbilirubinemia; a variety of reasons, such as hyaline membrane disease, pneumonia caused by hypoxia; no obvious incentive. Among these with neonatal hyperbilirubinemia is particularly eye-catching, Rance et al 9 survey of 12 cases of children with auditory neuropathy, there have been six cases of neonatal hyperbilirubinemia, serum bilirubin concentration of more than 350 mol / L, another Berlin et al 18 reported five cases of children with auditory neuropathy, have also appeared in neonatal hyperbilirubinemia. Hyperbilirubinemia in children can be expressed in both ABR threshold increases the reaction can also be expressed as - -wave latency was prolonged, suggesting that bilirubin may affect both peripheral and central auditory systems. Gunn rat is an excellent An acute animal model of hyperbilirubinemia. Hyperbilirubinemia in Gunn rats showed ABR abnormalities, microphonic potential normal, cochlear nucleus and the trapezoid body and cell size were significantly reduced 19,20. But damage the auditory system bilirubin cause there are still many unresolved issues, such as bilirubin can damage the auditory nerve fibers? Is acting on Schwann cells, or axon? Internally, the outer hair cells and spiral ganglion cells, whether there is injury? Cochlear supporting cells and blood vessels on the role of how the pattern? Bilirubin on the auditory system and to what extent the damage will have to listen to the performance of neuropathy? Some patients with hearing impairment in auditory neuropathy after several years (average 10 years) appears the performance of peripheral neuropathy is the disease at another incomprehensible. The cause of auditory neuropathy may result in addition to genetic and autoimmune diseases, other risk factors are within a short time can be controlled, such as the high choline hyperlipidemia, hypoxia, infection, etc., then why do they want to, after a few years Peripheral neuropathy was caused by it? There are two possible explanations: the exception of certain genetic and autoimmune diseases have involving the auditory nerve and peripheral nerves, the other auditory neuropathy and peripheral neuropathy no correlation occurred in the same patient is purely coincidental; auditory system of the above-mentioned risk factors more sensitive and more rapid disease development. Exactly how to interpret the information to be related to the further accumulation. Due to lack of corresponding parts of the biopsy, so right little is known about pathological changes of auditory neuropathy. The auditory nerve fibers in the currently considered the possibility of non-uniform demyelinating larger, it is based: the auditory nerve fibers can explain the non-uniform demyelinating ABR was absent, and speech audiometry disproportionately lower than the pure-tone audiometry; patients accompanied by the performance of peripheral neuropathy, and demyelination as the pathological changes in the basis of all; certain to demyelination as the main pathological features of peripheral neuropathy involving the auditory nerve, there may be the performance of auditory neuropathy 15-17; some of the original central -onset demyelinating diseases such as multiple sclerosis involving the auditory pathway, there may be similar to the performance of auditory neuropathy. Starr et al 5 reported 10 cases of adult cases, 8 cases after several years in the hearing impairment of varying degrees of the performance of peripheral nerve involvement, of which 3 cases are Charcot-Marie-Tooth syndrome, and the other five cases only peripheral nerve conduction velocity, and tendon reflex abnormalities. Charcot-Marie-Tooth syndrome, the pathological changes of demyelination as the major manifestations of nerve, nerve conduction velocity is decreased and the tendon reflexes diminish the performance of nerve demyelination. However, Pareyson et al 21 reported on 81 cases and 21 cases of demyelinating axonal peripheral neuropathy a total of 102 patients ABR studies, in which 44 patients with abnormal, mainly to extend the incubation period for the wave , - interval prolongation , a small number of - interval prolongation and found no reaction to the phenomenon was absent. If the auditory neuropathy is only the performance of the auditory nerve fiber demyelination, then this peripheral neuropathy with demyelinating lesions involving the auditory nerve What is the difference? Why are there different ABR performance? The auditory nerve fiber demyelination to what extent the party was absent ABR, and to what extent is only caused by the extension of ABR wave latency? The auditory nerve demyelination is due to Schwann cells degrade myelin components, or due to Schwann cell death caused by, or a combination of the two? Because Schwann cells are stable cells and they can repair damage by proliferation, if the demyelination of Schwann cell death is caused by irreversible auditory neuropathy in the existence of a mechanism to inhibit the regeneration of Schwann cells? Treatment The current lack of auditory neuropathy is still a very effective drug treatment, for the suitability of wearing hearing aids and cochlear implants remaining controversial. Starr et al 5 that the wearing of hearing aids to improve hearing in patients with auditory neuropathy unhelpful, and in some cases even generate negative results. Rance et al 9 reports were much more positive, in 15 cases of children wearing hearing aids in use in seven cases no improvement after one year, another eight cases of children with speech recognition and general auditory response to a significant improvement, which in children with auditory neuropathy for at least show that there is improved by wearing hearing aids, speech recognition techniques possible. Therefore, Rance is recommended for all acts of abnormal auditory threshold in children with peripheral neuropathy should wear a hearing aid, but is applicable to adults,