以耳聲傳射評估聽力正常的耳鳴病患

Tinnitus sufferers with normal hearing: assessment with otoacoustic emissions

徐愫儀(Su-Yi Hsu)

指導教授 ： 許權振

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2006年)

https://doi.org/10.6342/NTU.2006.02608

摘要

耳鳴（tinnitus）一詞源自於拉丁文tinnire，用於醫學上指的是沒有外界音聲的刺激但病人卻有聽覺感受的情形。
耳鳴是臨床上很常見的問題，瑞典和英國的統計報告顯示，約莫有10-14%的成人有耳鳴的症狀，而大約有0.5-1%的成人因為耳鳴而影響到正常生活。耳鳴雖然常與聽障合併發生，但是聽力正常的人也會發生耳鳴。根據Swedish population study的統計，聽力正常者有19%終日為耳鳴所擾；而British national study也指出，7%的成人有自發性耳鳴，但聽力檢查卻正常。
聽覺系統中從外聽道至中樞神經任一處的病變都可能導致耳鳴的發生，但自發性耳鳴的病理生理學至今仍不十分清楚。根據以往的文獻指出，主觀性耳鳴可以用一些精神性聽覺方法（psychoacoustic methods）做客觀性的評估，而所得結果通常有很高的測試再測試信度，由此推測耳鳴的形成應該是基於一個固定的病理生理機轉。
耳鳴至今仍舊是ㄧ門複雜難解的學問而且有其無法突破之治療瓶頸，而既然耳鳴的來源可能來自於聽覺系統中週邊至中樞的任一環節，於是各派說法及研究應運而生，試圖找出能有效評估耳鳴的客觀工具並藉以釐清耳鳴產生的最根本機轉，以期能應用在目前仍陷於瓶頸的耳鳴臨床治療上。
Møller等人（1992）曾針對19名藥物治療無效的耳鳴病患施以第八對腦神經的顯微血管減壓手術，並在手術過程中對第八對腦神經複合動作電位（compound action potential，CAP）及聽性腦幹誘發電位（brainstem auditory evoked potential，BAEP）進行監測，將結果與對照組資料作比較分析，由於BAEP第V波的潛值在耳鳴患者有較為短縮的情形，Møller等人推測耳鳴的問題似乎出在上橄欖複合體（superior olivary complex）。
在許多研究中，聽力正常的耳鳴病患被發現有聽覺皮質改組（cortical reorganization）的情形，而這改變和幻肢痛（phantom limb pain）病人大腦皮質的變化相似，所以耳鳴可以說是ㄧ種幻聽現象（auditory phantom phenomenon）。
近30年來聽覺生理學與聽力學最重要的進展之ㄧ便是耳蝸機械性活動（cochlear mechanical process）的發現與應用。耳聲傳射（otoacoustic emissions；OAEs）產生於耳蝸外毛細胞，藉由檢測耳聲傳射可以直接反映外毛細胞的健全與否，也可間接反映出調控耳蝸之神經系統功能是否異常，其中又以上橄欖複合體發出的內側橄欖核耳蝸神經束（medial olivocochlear bundle；MOC bundle）最為重要。曾有不少研究指出耳鳴和耳蝸機械性活動的改變有關。Veuillet（1992）及Chéry-Croze（1993）分別以耳聲傳射對耳鳴病患的內側橄欖核耳蝸神經束功能進行評估，發現此類病人的內側橄欖核耳蝸神經束功能有低下的情形；1996年Attias針對噪音誘發耳鳴的正常聽力患者進行研究分析，推論此類病人的聽覺傳出神經系統有功能障礙；Ceranic在1998年的報告中也指出，20名頭部外傷後聽力未受損卻發生耳鳴的病人有較強的耳聲傳射反應而且內側橄欖核耳蝸神經束功能明顯低下。
本研究的假說是：耳鳴的發生是因為上橄欖複合體及內側橄欖核耳蝸神經束功能出現障礙，導致了耳蝸機械性活動、耳蝸之神經輸出及聽神經複合動作電位的改變，並續而發生大腦聽覺中樞重組的情形，於是產生了耳鳴的聴幻覺現象。
研究個案條件的純化及同質化有助於致病機轉的釐清，而在耳鳴研究中的可能干擾因素包括有年齡、性別、健康狀況、聽力閾值及耳鳴持續時間等，這些影響因子都必須被控制。於是我們計劃對聽力正常且無其他病史的耳鳴患者進行研究，藉以免除所有可能的干擾因素。
本研究的目的是希望藉由聽力正常之耳鳴患者的耳聲傳射分析，証實耳聲傳射檢查在耳鳴臨床評估上之價值，並期盼能有助於瞭解耳鳴的形成機轉或來源，進而提昇耳鳴之臨床治療。

研究材料及方法

本研究收集聽力正常卻有單側或雙側持續性耳鳴之病例為實驗組，正常聽力且無耳鳴之志願者為對照組。每個耳鳴患者均接受耳鳴音調及響度分析，藉此將主觀的耳鳴症狀予以客觀量化。所有實驗組及對照組個體應接受之檢查有耳鏡檢查、純音聽力檢查、鼓室圖及靜態應力檢查、鐙骨肌反射檢查、聽性腦幹反應檢查、耳聲傳射檢查（包括自發性耳聲傳射檢查、短暫音誘發耳聲傳射檢查、變頻耳聲傳射檢查），及耳聲傳射對側音聲抑制測試（contralateral acoustic suppression test of OAEs）。將所有個案的資料分為三組，分別為耳鳴患者患側耳、耳鳴患者健側耳、以及對照組正常耳，藉由統計方法比較分析三組耳朵的各項檢查結果。

結果

三組耳朵各頻率平均聽力閾值、自發性耳聲傳射、短暫音誘發耳聲傳射值無統計學上之差異；但耳鳴病人患側耳及健側耳的變頻耳聲傳射值與對照組正常耳比較，均在某些頻率區有明顯低落的情形，而且有明顯較高比例在部份頻率區呈現顯著下降或上升，這代表在耳蝸中這些頻率區外毛細胞機械性活動的改變，不管是減弱或增強，確實存在於耳鳴病人的患側耳及健側耳。然而，以音調比對所測得的耳鳴頻率卻大多落在變頻耳聲傳射強度減弱或增強的頻率區之外，以這樣的結果來看，單純的耳蝸機制並無法完整解釋耳鳴的發生。
短暫音誘發耳聲傳射對側抑制檢測平均抑制值在三組耳朵無統計學上之差異；但在耳鳴患者健側耳以及對照組正常耳可發現給予對側耳噪音刺激後之短暫音誘發耳聲傳射值有統計學上有意義之降低，而耳鳴病人患側耳之短暫音誘發耳聲傳射值在給予對側耳噪音刺激前後的改變並無統計學上之意義。就變頻耳聲傳射的對側抑制檢測結果來看，耳鳴病人患側耳與健側耳兩組的對側抑制檢測平均抑制值在各頻率區無顯著之差異，但若分別與對照組正常耳比較，均在某些頻率區有明顯低落的情形。所以，依據以上耳聲傳射對側抑制檢測的結果推論，耳鳴病人的內側橄欖核耳蝸神經束有功能不彰的情形。
最後，針對各組耳朵的聽性腦幹反應檢查結果加以比較，發現耳鳴病人患側耳第III波及第V波的潛值和對照組正常耳相比有延長的情形，但兩組的III-V波潛時間隔差並無差異，依此推測，耳鳴患者患側耳同側的橋腦尾端區可能有問題。

結論

由以上的研究分析來看，變頻耳聲傳射檢查似乎較自發性耳聲傳射檢查或短暫音誘發耳聲傳射檢查更能早期偵測到耳鳴病人耳蝸機械性活動的改變；而利用變頻耳聲傳射檢查及短暫音誘發耳聲傳射檢查所作的對側抑制檢測均反應出耳鳴病人其調控耳蝸之中樞輸出神經的功能障礙，所以耳聲傳射檢查在耳鳴臨床評估上應有其應用價值。
在耳聲傳射對側抑制檢測中，我們觀察到耳鳴患者內側上橄欖核發出的內側橄欖核耳蝸神經束可能有功能障礙，而聽性腦幹反應檢查結果亦顯示耳鳴患側耳同側橋腦尾端區域可能有機能障礙，這些證據暗示：耳鳴的發生來源或許在於上橄欖核所在的橋腦尾端區域，而後續是以如何的機轉造成耳蝸機械活動的改變以及耳鳴的發生有待往後更多的研究加以釐清。

關鍵字

耳鳴 ； 耳聲傳射 ； 內側橄欖核耳蝸神經束

並列摘要

Background
Tinnitus (from Latin tinnire, which means to ring or to tinkle) describes an auditory perception experienced in the absence of any evident external stimulus.
Overall, 10-14% of adults have prolonged spontaneous tinnitus or have tinnitus ‘always’ or ‘often’. In 0.5-1%, tinnitus has a severe effect on quality of life or on ability to lead a normal life. Hearing impairment is commonly associated with tinnitus, but it is not exceptional for tinnitus to occur in patients with normal hearing. In a Swedish population study, 19% of subjects with subjective normal hearing said they suffered from tinnitus "always", and the British national study found that 7% of adults were annoyed by prolonged spontaneous tinnitus but did not have difficulty hearing. (Axelsson-1989; Vesterager-1997)
The conditions in which tinnitus occurs are legion, but the pathophysiology of tinnitus remains obscure. The source of ‘tinnitogenic’ activity could be any level of the auditory system. Purely subjective tinnitus can be evaluated by psychoacoustic methods. Most of these psychoacoustic features have a high test-retest reliability, which proves that subjective tinnitus is based on some constant pathophysiological process (Hoke-1989).
The complexity of the changes in the nervous system associated with tinnitus may explain why it is so resistant to treatment. In view of the great number of individuals
(0.5-1%) who are unable to lead a normal life and the ineffectiveness of current tinnitus therapy (Lockwood-2002) it is highly desirable that some method be devised to objectively assess the existence of tinnitus.
Møller et al had ever recorded the compound action potentials (CAPs) directly from the exposed intracranial portion of the eighth nerve in 19 patients undergoing microvascular decompression of the eighth nerve for intractable tinnitus. In the study, brainstem auditory evoked responses (BAEPs) in response to click sounds were also recorded during the operation. According the analyses of results, it may be assumed that the abnormalities in the latencies of peak V of BAEPs in the patients with tinnitus are a result of abnormalities in the superior olivary complex (SOC). (Møller-1992)
In pervious studies, auditory cortical reorganization was demonstrated in normal hearing tinnitus (Hoke-1989; Mühlnickel-1998; Andersson-2000). Similarities between the data and the previous demonstrations that phantom limb pain is highly correlated with somatosensory cortical reorganization suggest that tinnitus may be an auditory phantom phenomenon (Mühlnickel-1998).
The discovery of otoacoustic emissions, energy emitted by the outer hair cells (OHCs) in cochlea and recordable as acoustic vibrations in external auditory canal (Kemp-1978), was important for both theoretical and practical reasons. As otoacoustic emissions are invariably associated with functioning outer hair cells, their presence is a reliable indicator of cochlear structural integrity, and their absence may indicate a cochlear lesions. Besides being an expression of the cochlear structural status, otoacoustic emissions may also give an indication of functional integrity of the mechanisms which control the cochlea. The olivocochlear efferent system is a part of that regulatory complex, and its medial division, widely known as the medial olivocochlear (MOC) system, seems to be of particular importance in the modulation of cochlear activity.
It has been suggested that tinnitus may be related to cochlear mechanical activity (Kemp-1981; O-Uchi-1988; Plinkert-1990; Norton-1990; Mckee-1992; Chéry-Croze-1994). Less effectiveness of MOC system had been revealed in tinnitus also (Veuillet-1992; Chéry-Croze-1993; Attias-1996; Ceranic-1998).
Our proposed hypothesis is that dysfunction of MOC system in tinnitus alters the cochlear mechanical process, cochlear neural output and compound action potential of auditory nerve, and then the consequent cortical reorganization triggers the phantom perception of tinnitus.
A better comprehension of the mechanisms underlying a symptom will probably come from exhaustive exploration of simplified cases. A more precise evaluation of the medial olivocochlear efferent activity in tinnitus patients requires a homogenous population. Factors including age, gender, general health, hearing threshold, duration of tinnitus suffering, clearly must be controlled for.
Our study tried to explore the dysfunction level of the auditory system in the patients who suffer from annoying tinnitus with normal or nearly normal hearing by assessment with otoacoustic emissions. By this study, we will show the potential value of otoacoustic emissions in the assessment of tinnitus. This information may contribute to a better understanding of the origin and mechanisms underlying tinnitus.

Materials and methods

We collected patients complain of unilateral or bilateral tinnitus. All patients included in the study should have normal or nearly normal hearing. Normal subjects without auditory complaints were introduced to be the control group. Pitch matching test and loudness-balance test were carried out on tinnitus sufferers for objectifying tinnitus. All subjects underwent a protocol which includes an interview to obtain relevant information, otoscopy, standard pure tone audiometry, tympanometry, static compliance measurement, acoustic reflex test, auditory brainstem response survey, otoacoustic emissions examination (including SOAEs, TEOAEs, DPOAEs), and olivocochlear suppression test. Then we compared the results in tinnitus-disease ears, tinnitus-health ears and control-normal ears.
An effort was made to match the age and gender proportion of the tinnitus to those of control subjects. Informed consent was obtained from all subjects.

Results and Discussion

Although there were no significantly statistical differences in the thresholds of pure tone audiometry, prevalence of SOAEs and TEOAE responses between three ear groups, averaged DPOAE levels of tinnitus-disease and tinnitus-health ears were significantly decreased over limited frequency range in comparison with those of control-normal group. Furthermore, higher percentage in tinnitus-disease and tinnitus-health ears were noted to have significant decreases or increases on DPOAE amplitude over a limited frequency range. But, in the present study, the pitch-matched tinnitus frequency was out of the frequency range in numbers of the cases. It is suggested that changes of cochlear dynamic properties exist in tinnitus, but simplex cochlear mechanism can not explain the tinnitogenesis.
Significantly reduction of TEOAE responses under contralateral acoustic stimulation was observed in both tinnitus-health and control-normal groups, but not in tinnitus-disease ears. In comparison with control-normal group, the averaged central efferent suppression on DPOAEs of tinnitus-disease and tinnitus-health ears were significantly decreased over limited frequency range. Deducible connection between dysfunction of descending auditory pathway and tinnitus could be made logically.
At last, inspection of the records of ABR showed significant prolonged latencies of peak III and V in the tinnitus-disease group compared with the control-normal group, although the values of IPL III-V were not statistically different from each other. Caudal pontine lesion ipsilateral to tinnitus affected ear was implied and may be the source of tinnitogenic activity.

Conclusions

This study has shown the potential value of otoacoustic emissions in the assessment of tinnitus. The dysfunction of descending auditory pathway caudal to SOC (medial olivocochlear efferents, MOC system) maybe play the leading role in the tinnitogenesis.

並列關鍵字

tinnitus ； otoacoustic emissions ； medial olivocochlear bundle

參考文獻

Abdala C, Sininger YS, Starr A. Distortion product otoacoustic emission suppression

Achor LJ, Starr A. Auditory brainstem responses in the cat. I. Intracranial and extracranial recording. Electroencephalogr Clin Neurophysiol 1980a;48(2):154-173.

Achor LJ, Starr A. Auditory brainstem responses in the cat. II.Effects of lesions. Electroencephalogr Clin Neurophysiol 1980b;48(2):174-190.

Andersson G, Lyttkens L, Hirvelä C, Furmark T, Tillfors M, Fredrikson M. Regional cerebral blood flow during tinnitus: a PET case study with lidocaine and auditory stimulation. Acta Otolaryngol 2000;120(8):967-972.

Arnold W, Bartenstein P, Oestreicher E, Römer W, Schwaiger M. Focal metabolic activation in the predominant left auditory cortex in patients suffering from tinnitus: a PET study with (18F) deoxyglucose. ORL J Otorhinolaryngol Relat Spec 1996;58(4):195-199.