Study of cochlear microphonic potentials in auditory neuropathy

Introduction Auditory Neuropathy/Dyssynchrony is a disorder characterized by the presence of Otoacoustic Emissions and Cochlear Microphonic Potentials, an absence or severe alteration of Brainstem Evoked Auditory Potential, auditory thresholds incompatible with speech thresholds and altered acoustic reflexes. The study of the Cochlear Microphonic Potential appears to be the most important tool for an accurate diagnosis of this pathology. Objective Determine the characteristics of the Cochlear Microphonic in Auditory Neuropathy/Dyssynchrony using an integrative review. Methods Bibliographic survey of Pubmed and Bireme platforms and MedLine, LILACS and SciELO data banks, with standardized searches up to July 2014, using keywords. Criteria were established for the selection and assessment of the scientific studies surveyed, considering the following aspects: author, year/place, degree of recommendation/level of scientific evidence, objective, sample, age range, mean age, tests, results and conclusion. Results Of the 1959 articles found, 1914 were excluded for the title, 20 for the abstract, 9 for the text of the article, 2 for being repeated and 14 were selected for the study. Conclusion The presence of the Cochlear Microphonic is a determining finding in the differential diagnosis of Auditory Neuropathy/Dyssynchrony. The protocol for the determination of Cochlear Microphonic must include the use of insert earphones, reverse polarity and blocking the stimulus tube to eliminate electrical artifact interference. The amplitude of the Cochlear Microphonic in Auditory Neuropathy/Dyssynchrony shows no significant difference from that of normal individuals. The duration of the Cochlear Microphonic is longer in individuals with Auditory Neuropathy/Dyssynchrony.


Introduction
The term auditory neuropathy (AN) was first used in 1996 to define a group of individuals with auditory symptoms, who had in common normal cochlear function despite having abnormal cochlear nerve function. Moreover, they experienced difficulty in understanding speech especially in noisy environments, although in some cases they responded to sound stimuli. 1 Today the most common denomination is auditory neuropathy/dyssynchrony (AN/AD).
In general findings reveal the absence or severe abnormality of the Auditory Brainstem Response (ABR) with preservation of the otoacoustic emissions (OAE) and/or the Cochlear Microphonic (CM), indicating disordered function of the auditory nerve with normal function of the cochlear hair cells (HC). 1 ---4 It is often difficult to determine exactly the onset of AN/AD, but the disease can occur at all ages. 4 Its prevalence has been estimated at 11% in a group of 109 hearing-impaired children who failed the newborn hearing screening (NHS) and ABR. 5 Another study reports a similar prevalence of 8.44% in 379 children evaluated with ABR alteration. 4 The CM is a potential generated from the outer hair cells (OHC) and inner hair cells (IHC) of the cochlea and its absence is consistent with alterations in the function of these cells. 2,6 It is an electrical activity that precedes the synapses of the HC with the auditory nerve and, therefore, when recorded, it appears before wave I on ABR and maintains its latency even when the stimulus intensity is decreased. 5 There are still no available data regarding CM parameters in individuals with normal hearing or with hearing loss. However, recording the CM attracted renewed interest after the identification of the AN/AD, 1 as the association between the cochlea and an acoustic stimulation has been used in the differential diagnosis of AN/AD, once the presence of CM can be used as evidence of OHC integrity. 7 The literature recommends that tests of cochlear function, particularly CM, become part of the NHS (Newborn Hearing Screening) protocol in all children with absent or altered ABR, facilitating the diagnosis of AN/AD. 5 The aim of the study is to verify the characteristics of cochlear microphonism in Auditory Neuropathy/Dyssynchrony through an integrative review.

Methods
The methodological process characterized the present study as an integrative review, to gather data from studies that help the understanding of the subject in a systematic and orderly manner, thus helping to acquire further knowledge on Cochlear Microphonic characteristics in Auditory Neuropathy/Dyssynchrony.
The integrative review was carried out from electronic searches in Pubmed and Bireme platforms and in the following databases: MedLine, LILACS and SciELO ---Regional. The data search was started and concluded in July 2014. Studies published in English, Spanish or Portuguese were selected for the analysis. There was no restriction regarding the year of publication, i.e. studies published up to July 2014 were analyzed, and subsequently, the articles were selected according to inclusion and exclusion criteria.
The search strategy was performed by crossing the descriptors (DeCS and MeSH), as well as the free terms, which are terms not found in MeSH and MeSH, but that are relevant to the search. The descriptors used to locate the studies were Cochlear Microphonic and Cochlear Microphonic Potential and the free terms used were Auditory Neuropathy and Auditory Dyssynchrony.

Search strategy
The search strategy was directed by a specific question: ''What are the characteristics of the Cochlear Microphonic in Auditory Neuropathy/Dyssynchrony?''. Aiming to identify the relevant articles with the proposed question, a search strategy was developed, using the descriptors in groups, with at least two keywords.

Inclusion criteria
Articles with the following characteristics were included: original article, case report or literature review including as research subjects individuals diagnosed with auditory neuropathy.

Exclusion criteria
The articles that did not describe the findings of audiological assessment in individuals with AN/AD were excluded from this review.

Study identification, selection and inclusion
The study was independently carried out by two researchers and the points of conflict were discussed at specific meetings. After applying the search strategy containing the defined descriptors, article selection was performed in three stages: 1. Identification and reading of titles in different electronic databases. Articles that clearly did not meet any of the inclusion criteria of this study were excluded. 2. Reading of summaries of the studies selected at the first stage. Similarly, we excluded articles that clearly did not meet any of the pre-established inclusion criteria. 3. All studies that were not excluded in these first two stages were read in full for the selection of those that would be included in this review.
All studies used met the inclusion criteria defined in the beginning of the methodological protocol of this study, aiming to answer the question that guided this integrative review. The main data of each article were fully collected and entered into a Microsoft Office Excel 2011 program database.
For better presentation of the results, it was decided to consider the following variables of the selected articles: author, year/location, type of study, grade of recommendation/level of scientific evidence, objective, sample, age range, mean age in years, tests performed, results and conclusion.
As for the level of scientific evidence, the classification used was that of Oxford Center for Evidence-Based Medicine. 8

Results
According to the performed search, 1959 articles were found in the electronic searches. According to the inclusion and exclusion criteria defined in the method and after eliminating the repeated references found in more than one database, 14 articles were selected.
In the MedLine database, via PubMed, after employing the keywords and free terms, 1959 articles were found, of which 1913 were excluded after reading the title, 44 abstracts were read and 25 articles were selected for reading in full. Of these 25, two were repeated articles and nine were excluded. In the LILACS and MEDLINE databases via Bireme, no articles were found for this search. Tw o articles were found in the SciELO database; one was excluded after reading the title and the other was excluded after being read in full.
The following flow chart (Fig. 1) is a synthesis of the article selection process for the integrative review. Table 1 is a synthesis with the characteristics of the studies included in the integrative review.

Discussion
Due to the recent increase in the number of studies on AN, this review shows that most studies were published between 1996 and 2014. All selected articles associated AN with the Artigos repetidos = 2 Excluídos pela leitura do resumo = 20 Figure 1 Flowchart of articles identified, excluded and included in the integrative review.
MC recording through two specific tests, ABR and the Ecog, using invasive or non-invasive methods, in addition to other tests to assess auditory function. There was greater investment in research in this area in the late 90s, when AN was described. 1 Since then, studies have sought to explain the location of the lesion, risk factors, prevalence and more accurate diagnostic tests in AN.
Regarding location, the literature indicates a broad possibility, as the lesion may occur in several structures or in more than one at the same time, such as the IHC, auditory nerve fibers, or in their synapses. 9 Another study suggests that there is an abnormality in the auditory system, located in the VIII nerve, ganglion neurons, in the IHC, between their synapses or a combination of them. 1 Risk factors are usually associated to neonatal problems such as prematurity, low birth weight, anoxia, hypoxia, hyperbilirubinemia, need for mechanical ventilation and intracranial hemorrhage, 10 as well as genetic and mitochondrial disorders 11 and a family history of hearing disorders. 3,12 According to the studies shown in this review, the prevalence of AN in children and young individuals with severe to profound hearing loss was 13.4% 9 and 1.2% in individuals with SNHL. 13 The prevalence has also been described in children with risk criteria for AN as 1 in 433 (0.23%) and in the group of children with permanent hearing deficit, it was 1 in 9 (11.01%). 5 Another study indicates a prevalence of 8.44% in a group of 379 children with ABR alteration. 4 There is an agreement in the reviewed literature regarding examination findings in patients with neuropathy, who have present OAE and CM, absent or very altered ABR and absent acoustical reflexes. 9,10,12---23 In audiometry, the described pattern is permanent or fluctuating hearing loss of varying degrees, with flat or ascending audiometric configurations, 12,17 in addition to difficulties in speech perception, especially in the presence of noise. 9,10,12,14---17,22,23 The OAE are present, but they may disappear with time. 16 The results of objective electrophysiological tests such as presence of TOAE, absent or very altered ABR and presence of CM have emerged as the first diagnostic tool for AN in infants. 4,24 Additionally, patients with AN have an alteration in OAE suppression effect caused by the efferent auditory pathways. 25 The absence of OAE suppression suggests that the olivocochlear efferent function is altered. 24 Considering the findings of the auditory function tests, the presence of CM becomes the determinant finding in the differential diagnosis of AN. 16 The protocol used to record the CM by ECoG or ABR should always reverse the stimulus polarities to confirm the recording inversion and, therefore, confirm CM. 13,16,17,19,22 Furthermore, the use of insert earphones is important to allow the blocking of the plastic tube, indispensable to confirm the biological response, discarding the presence of electrical signal artifact. 13,17,20 Insert earphones should always be used in the ABR to allow stimulus artifacts to be separated from cochlear potentials. 2 Another study also confirmed the CM response by closing the stimulus tube to prevent the acoustic signal from reaching the ear canal, eliminating the artifacts. 5 Some studies have reported the use of Ecog as a diagnostic test for AN. But there are reports suggesting that the Transtympanic Electrocochleography (EcogT) is the gold standard tool to evaluate CM, 9,16,17 because Ecog allows a more detailed analysis of cochlear function in relation to ABR. 9,17 However, promontory recordings are considered more sensitive than the ear canal and that results in a better signal-to-noise ratio, as the CM comes first from the basal portions of the cochlea, with a negligible contribution of the apical regions. 7 In one of the reviewed studies, no significant difference was found between the amplitude of the CM in normal hearing individuals and those with AN. The maximum amplitudes of CM for almost all patients were around 0.6 ms after the stimulus. 13 The literature reports that CM in patients with AN are especially prominent and persist for several milliseconds after a transient stimulus. 2,24 Another study reported that the mean amplitudes of the CM was 0.4 ms in patients with AN, significantly higher than in individuals with normal hearing. 24 The duration of the CM was longer in the group with AN than in the group with normal hearing. 13,16 In patients with AN in the ABR, the CM appears wide and can exhibit a duration of up to 4 ---6 ms, and may be mistaken for electrical activity of the brain stem; however it does not change with decreasing intensity, but with the reversed stimulus polarity. 25 In general, the assessed literature agrees on the location, risk factors and clinical findings of AN and reports that its differential diagnosis is confirmed based on the CM recording, because even at an advanced state of AN, CM remains present.
This review includes studies that describe the tests most commonly used to describe the characteristics of Cochlear Microphonism in Auditory Neuropathy/Dyssynchrony. For that purpose, several types of studies were selected, which may seem like a limitation, but on the other hand, they may have different perspectives on the subject, always taking into account the previously defined selection criteria.

Conclusion
Based on the studies included in this literature review, we conclude that: The presence of the CM is a crucial finding in the differential diagnosis of AN. The CM recording protocol must include the use of insert earphones and reverse polarity and the stimulus blocking to prevent electrical artifact interference. The amplitude of CM in AN showed no significant difference when compared with the amplitude of CM in individuals with normal hearing. The duration of CM is longer in individuals with AN.