- 學位論文
短迴旋音與機械振動刺激衍生之眼性及頸性前庭誘發肌性電位
Short tone-burst and mechanical vibration in eliciting ocular and cervical vestibular-evoked myogenic potentials
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摘要
前庭誘發肌性電位(vestibular evoked myogenic potential; VEMP)，主要用來檢測球囊頸肌反射( sacculo-collic reflex )，其反射的路徑乃藉由巨大音響刺激，經由前庭脊髓束，以肌電位形式表現於頸部肌肉上。然而，近年來新發現，前庭誘發肌性電位亦可在眼外肌上取得記錄，謂之「眼性」前庭誘發肌性電位 (ocular VEMP)，簡稱oVEMP。而在頸部肌肉上記錄的電位，則新命名為「頸性」前庭誘發肌性電位(cervical VEMP)，簡稱cVEMP。目前的研究已知，oVEMP主要用來檢測耳石眼反射(otolithic-ocular reflex)。其反射的路徑乃藉由巨大音響刺激，經由橢圓囊或球囊，進入對側的前庭眼反射，以肌電位形式表現於眼外肌上。這兩項新的電生理檢查，提供除了耳蝸與半規管外，另一條探索內耳功能的途徑。其中，cVEMP檢查目前已廣泛地在臨床上使用。而新開發的oVEMP檢查，則是本論文探討的重點。 首先，因為在記錄眼性前庭誘發肌性電位時，眼睛必須持續注視上方，為了節省檢查的時間與避免眼球疲勞，因此發展以兩耳同時音聲刺激記錄眼性前庭誘發肌性電位，來與單耳輪流音聲刺激作比較並檢視其可行性。計20名健康成人，接受眼性前庭誘發肌性電位檢查。方法乃先輪流以單耳接受音聲刺激，兩側同時記錄，以95 dB nHL，500 Hz short tone-bursts，每秒5次連續刺激，加算100次平均結果。接著以不同音聲強度刺激以求得反應之閾值。另一天再接受兩耳同時音聲刺激，兩側同時記錄，以不同音聲強度刺激求其反應之閾值。同時分析其反應率，波形的潛時與振幅。以單耳接受95 dB nHL音聲刺激時，眼性前庭誘發肌性電位會在刺激耳之對側眼球下方記錄到最大的波形，nI波潛時為11.1 ± 0.7 ms，pI波潛時為15.9 ± 1.0 ms，nI-pI振幅為6.5 ± 2.9 μV。與兩耳同時95 dB nHL音聲刺激比較，無論反應率，閾值，波形的潛時與振幅，結果發現不具統計學差異。其次，關於閾值，nI波潛時，pI波潛時或nI-pI振幅，分析單耳輪流刺激與兩耳同時刺激下的相關性，結果發現兩者間皆呈現有意義的正性相關，亦即以兩耳同時音聲刺激記錄眼性前庭誘發肌性電位可以得到與單耳輪流刺激相同的資訊，包括反應率，閾值，nI波潛時，pI波潛時或nI-pI振幅。不過，以兩耳同時音聲刺激記錄的時間只需要後者的一半，具有省時省力的可行性。 接著，因為在記錄oVEMP時，氣導音聲(air-conducted sound; ACS)並不能有效地誘發電位，然骨導振動(bone-conducted vibration; BCV)卻可輕易地誘發。因此本研究的目的，乃為發展單一刺激模式來進行oVEMP與cVEMP檢查，期望能尋找最佳刺激模式，提高臨床實用價值。計12名健康成人， 5名單側中耳炎患者(平均氣骨導差26 dB)，及10名單側梅尼爾氏症(Meniere's disease)患者均接受oVEMP及cVEMP檢查。第一天，兩耳同時接受氣導音聲刺激，兩側同時記錄oVEMP，以105 dB nHL，500 Hz short tone-bursts，每秒5次連續刺激，加算100次平均結果。接著以轉頭法輪流刺激單耳，求得cVEMP。另一天，再進行骨導振動刺激(V201 Vibrator，144 dB peak FL，0.6 ms click)，每秒5次連續刺激，加算50次平均結果，分別求得oVEMP與cVEMP。結果，以骨導振動在Fz位置刺激時，oVEMP會在兩側眼球下方記錄到最大的波形，誘發率100%，nI波潛時為8.8 ± 0.6 ms，pI波潛時為13.6 ± 1.1 ms，nI-pI振幅為18.8 ± 7.5 μV。其誘發率與波形的振幅與兩耳同時105 dB nHL音聲刺激比較，發現骨導振動明顯優於氣導音聲刺激，具統計學差異。至於cVEMP，以骨導振動在Inion位置刺激時，誘發率100%，顯著優於氣導音聲刺激；然cVEMP的振幅，兩者並無顯著差異。5名單側中耳炎病患，氣導音聲刺激皆無法誘發oVEMP與cVEMP；反之，在骨導振動刺激下，二者皆能記錄得到。10名單側梅尼爾氏症患者，無論是oVEMPs或是cVEMPs，骨導振動刺激振動的誘發率皆顯著高於氣導音聲刺激。因此，雖然氣導音聲刺激在臨床應用上有部位選擇性(site selectivity)之優點，但骨導振動的誘發率較高，能提供臨床上大量篩檢的好處。其中，Fz與Inion分別是骨導振動誘發oVEMP與cVEMP之最佳刺激部位。 進一步，由於骨導振動在誘發oVEMP的反應率明顯優於氣導音聲刺激，本研究欲探討氣導音聲和骨導振動是否刺激相同的前庭傳入神經族群(vestibular afferents population)。招募15名健康受試者，分別以105 dB nHL (127 dB SPL) 500 Hz 短迴旋音及128 dB force level (FL) 機械振動刺激誘發眼性與頸性前庭誘發肌性電位。結果發現無論是oVEMP或是cVEMP，氣導音聲均比骨導振動誘發較長的波峰潛時。至於波形的振幅，雖然在cVEMP兩種誘發模式沒有顯著差異，但是在oVEMP骨導振動刺激卻比氣導音聲刺激誘發較大的振幅，兩者有以下的關係：骨導振動刺激誘發的oVEMP振幅是氣導音聲刺激誘發oVEMP振幅的2.3 倍。足見在cVEMP方面骨導振動刺激和氣導音聲刺激可能誘發相類似的前庭傳入神經族群；但是，就oVEMP而言，骨導振動刺激比氣導音聲刺激誘發更多的前庭傳入神經族群。因此，在檢測cVEMP或是oVEMP時，應當先確認其刺激模式為何。 最後，由於內耳耳石器官的生理性刺激為線性加速度(linear acceleration)，因此直接測量機械振動所引起線性加速度的大小(magnitude)與方向(direction)為目前研究前庭誘發肌性電位的趨勢。對於氣導音聲的最佳刺激模式，目前學界已有共識；然而對於骨導振動的刺激模式，則尚未標準化。故本研究利用即時(real-time)三軸加速規計，來評估骨導振動刺激所產生的眼性前庭誘發肌性電位，以期建立骨導振動刺激之標準化。共有14名健康受試者參加本研究，接受骨導振動刺激oVEMP檢查。骨導振動刺激(V201 Vibrator)為500 Hz正弦波(sine wave)，持續時間1 ms，起始之輸入電壓為8.0伏特，接者以5 dB依次遞減，合併即時三軸加速規計(Endevco model 65-100)量測，以求得x軸(前後方向)、y軸(左右方向)、z軸(上下方向)之加速度閾值。結果所有14名受試者(100%)均出現正常之oVEMP波形。oVEMPs的三軸加速度閾值分別為0.05 ± 0.01 g (x軸)、0.16 ± 0.08 g (y軸)、及0.04 ± 0.01 g (z軸)。再者，oVEMP的振幅，均與三軸加速度的大小，呈現顯著正相關。亦即增強加速度的大小，可使前庭傳入神經更加同步化的激發(firing)，導致更加同步的誘發電位與更大的oVEMP振幅。 前庭誘發肌性電位的研究方興未艾，結合醫學工程的高科技，為神經耳科學的研究打開了一扇窗。耳石器官功能的探討，必將使得內耳疾病能被更加瞭解，可望造福眾多的暈眩患者。
並列摘要
Similar to the cervical vestibular evoked myogenic potential (cVEMP) test, which has been widely applied in clinical practice during the past decade, the recently developed ocular VEMP (oVEMP) test has been studied extensively and used to explore vestibular disorders. Both cVEMP and oVEMP tests have been used to investigate otolithic organs and their central vestibular pathways, including the ipsilateral descending sacculo-collic reflex and a crossed ascending vestibulo-ocular reflex. First of all, this study compared the oVEMPs that are elicited in response to monaural and separately, simultaneous binaural air-conducted sound (ACS) stimulations. Twenty healthy volunteers without any previous ear disorders were enrolled in this study. Each subject underwent oVEMP testing using monaural ACS stimulation (Mon-oVEMP) with different stimulus intensities. On another day, the same volunteers underwent oVEMP testing using simultaneous binaural ACS stimulation (Bin-oVEMP). With 95 dB nHL 500Hz short tone-burst ACS stimulation, the biphasic nI–pI waveforms were recorded with maximal amplitudes from the electrodes located below the eyes contralateral to the side of acoustic stimulation while the subject was gazing upward. Significant correlations were identified between Mon-oVEMPs and Bin-oVEMPs with respect to threshold, latencies and amplitude. However, no significant difference existed between Mon-oVEMPs and Bin-oVEMPs in terms of the response rate, threshold, latency or amplitude. The Bin-oVEMP test yields the same information as the Mon-oVEMP test, but the duration of recording in the former is shorter than the latter. The Bin-oVEMP test may be a more convenient screening tool for evaluating the crossed vestibulo-ocular reflex. Subsequently, the aim of this study was to determine whether bone-conducted vibration (BCV) or ACS is the optimal mode for eliciting both oVEMPs and cVEMPs. Twelve healthy volunteers, five patients with unilateral chronic otitis media, and 10 patients with unilateral Meniere disease underwent oVEMP and cVEMP tests using ACS and BCV stimulation modes in a random order. In healthy controls, BCV mode at Fz had a significantly higher response rate and larger nI-pI amplitude of oVEMPs than that of the ACS mode. In cVEMPs, a significantly higher response rate was noted in BCV mode at inion, when compared with ACS mode. However, no significant difference was noted in the p13-n23 amplitude between these two modes. In five chronic otitis media ears, absence of oVEMPs and cVEMPs in ACS mode and presence of oVEMPs and cVEMPs in BCV mode were shown. In 10 patients with Meniere disease, BCV mode elicited higher response rates of oVEMPs and cVEMPs in the pathological ears than ACS mode did. Using BCV mode, Fz and inion may be the optimal sites for eliciting oVEMPs and cVEMPs, respectively. Thus, BCV mode can be substituted for ACS mode to elicit oVEMPs and cVEMPs in the future, especially in “mass detection.” In contrast, ACS mode provides an essential clinical merit of site selectivity. Additionally, this study compared cVEMPs and oVEMPs between ACS and BCV modes to determine whether these two stimulation modes activate the same population of primary vestibular afferents. Fifteen healthy subjects underwent cVEMP and oVEMP tests using ACS stimuli at 105dB nHL and BCV stimuli at 128 dB force level (FL). The characteristic parameters of cVEMPs and oVEMPs were compared between ACS and BCV modes. The mean p13 and n23 latencies of ACS-cVEMPs were significantly longer than those of BCV-cVEMPs. Likewise, the mean nI and pI latencies for ACS-oVEMPs were also significantly longer than those for BCV-oVEMPs. There was no significant difference in the mean amplitude of cVEMPs between the ACS and BCV modes. However, comparing the oVEMP amplitude, a relationship: (Amplitude of BCV-oVEMP) = 2.3 x (Amplitude of ACS-oVEMP) was demonstrated. In short, the population of primary vestibular afferents activated by ACS and BCV stimuli is similar for cVEMPs. In contrast with oVEMPs, BCV mode activates more number of primary vestibular afferents than ACS mode does. Finally, this study combined BCV stimulation with triaxial accelerometry to correlate the acceleration magnitudes of BCV stimuli with oVEMP test results. Fourteen healthy volunteers underwent oVEMP test using BCV stimuli with simultaneous monitoring the triaxial acceleration. All subjects exhibited clear oVEMPs in response to BCV stimuli from a vibrator. The lowest acceleration magnitudes for eliciting oVEMPs along the x-, y- and z-axes were 0.05 ± 0.01 g, 0.16 ± 0.08 g, and 0.04 ± 0.01 g, respectively, exhibiting significantly higher acceleration magnitude along the y-axis than those along the x- and z-axes. In addition, significantly positive correlations were noted between the acceleration magnitude along each axis and the oVEMP amplitude. Therefore, increasing acceleration magnitude may have more synchronization of firing of vestibular afferents, resulting in more synchronized evoked potentials and greater oVEMP amplitude.
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