关于听性稳态反应的若干问题

刺激速率为70～110 Hz的听性稳态反应（auditory steady-state response,ASSR）统称为80 Hz ASSR.因为它在婴幼儿能够可靠地引出而引起了听力学界的广泛关注.80 Hz ASSR的特点是高刺激速率、频域内分析结果、反应客观判定,并且能够同时分析记录多个刺激信号所诱发的反应.目前正常听力或感音神经性聋成人、婴幼儿的80Hz ASSR的研究表明其有一定的临床应用价值，本文就听力师和耳科医师关心的ASSR的频率特异性、多个刺激声之间的干扰以及骨导ASSR的研究做一回顾和总结。     

听性稳态反应在新生儿听力评估中的应用

目的 探讨听性稳态反应(auditory steady-state responses,ASSR)在新生儿听力评估中的准确性及应用价值.方法 对30例(60耳)畸变产物耳声发射(distortion product otoacoustic emission,DPOAE)正常的新生儿和45例(78耳)DPOAE异常的新生儿进行ASSR与听性脑干反应(auditory brainstem response audiome-try,ABR)测试,比较ASSR与ABR阈值差异有无统计学意义,并进行两者反应阈的相关性分析.结果 ①DPOAE正常组:ASSR 250 Hz反应阈与ABR阈值差异有统计学意义(P＜0.05),ASSR平均阈值及4 000 Hz反应阈与ABR阈值差异无统计学意义(P＞0.05),ASSR的250、500、1 000 Hz反应阈与ABR阈值相关性不明显,但2 000、4 000 Hz反应阈与ABR阈值有明显的相关性;②DPOAE异常组:ASSR的250～4 000 Hz阈值及平均阈值与ABR阈值差异均无统计学意义(P＞0.05).ASSR各频率反应阈与ABR阈值均有显著的相关性.结论 ASSR可以比较准确地评估听力筛查正常新生儿的平均听阈和中、高频听阈以及听力筛查未通过新生儿的各频率听阈.     

听性稳态反应应用于婴幼儿听力评估的现状

刺激速率为70～110 Hz的听性稳态反应(auditory steady-state response, ASSR)(亦称为80 Hz)最近倍受听力学工作者特别是小儿听力学工作者的关注,设备制造商也正在推销其产品.本文回顾了ASSR的技术、应用基础,并总结了其应用于婴幼儿听力评估的现状.文中斜体字为基本原则.详细的ASSR方法学、正常值以及一些ASSR研究结果请参阅Picton(2003)的综述.ASSR并不是一个新发现的听觉反应,1960年Geisler就从人类头颅上记录到了该反应;以后研究者又记录到了短声、正弦调制波以及方波调制波所诱发的反应.Galambos等在1981年发表的有关40 Hz事件相关电位将ASSR引入听力领域.不同刺激速率的ASSR的产生部位是不同的,40 Hz的ASSR产生于皮层和脑干,而80 Hz的ASSR主要来源于脑干,而且很有可能它就是ABR的波Ⅴ,只是与ABR的刺激和记录方法不同而已.ASSR的重要特征之一就是在频域内分析的方法,通过计算位相相关性或刺激速率值处的信噪比,再根据统计学分析来判定反应的引出与否,这种客观性使ASSR显著优于ABR.ASSR的刺激信号最早是象ABR一样的短纯音信号,以后主要用调幅调制声,有时也加入10%～20%的调频调制,目前大多数设备都采用这一信号,最近一种新ASSR设备的缺省设置是5～8 ms的短音.ASSR的另一个重要特征是能够同时记录多个刺激声信号所产生的反应,这种多频刺激的方法能够同时记录双耳八个频率(每耳四个频率)的反应.研究证明只要各个信号的频率相距一个倍频程以上,强度在75 dB SPL以下,多个刺激声之间的干扰就很小或没有.不对称型的听力图、不同频率所产生的反应幅度的不同以及多频刺激方式所导致的各个频率反应幅度整体的下降延长了这种方法的测试时间,使其不如理想中的那么省时,但仍比单一刺激方式快2～3倍.80 Hz ASSR通常采用的是正弦调幅调制纯音,因为其特有的频率特异性而被认为是优于短纯音ABR的一个方面,但是声信号的频率特异性只是其中的一方面,还应考虑到耳蜗基底膜的部位特异性以及神经反应的特异性.研究证明ASSR的频率特异性与短纯音ABR是非常接近的.ASSR技术以飞快的速度发展,十年前还没有商用的设备,五年前只有两家,而目前至少有六种不同的设备.随着设备的增加,各个设备之间标准化的问题突显出来.有些设备有很浑厚的研究背景,而有些则没有,使用者应该根据设备的性能及临床资料而加以选择.关于80 Hz ASSR与行为听力测试相关性的研究很多,多为感音神经性聋成人或较大儿童,结果表明至少在该人群中ASSR的阈值能够很好地预测行为听力阈值.许多ABR与ASSR的比较研究声称ASSR比ABR能够更好地评估残余听力,也就是当受试者听力损失很重、ABR不能引出时,仍能够引出ASSR.尽管这一现象客观存在,但是还有一些其他需要考虑的影响因素,如:①所比较的信号在某一特定频率上的能量是不相等的,众所周知短声的能量分布频率范围很宽,其最大输出强度较ASSR信号小;②ASSR在高强度会有伪迹或非听性反应;③ASSR的长时强声刺激会导致耳蜗损害.因此需慎重对待这一问题.目前还没有关于传导性聋或混合性聋气导ASSR的研究,模拟传导性聋的研究表明气导ASSR阈值远高于行为听阈,而且ASSR骨气导差过大.骨导ASSR的研究显示听力正常婴幼儿各个频率的ASSR的阈值与成人显著不同.正常听力婴幼儿的短纯音ABR阈值以及诊断标准已经确立,而ASSR在这一方面的研究则显得不足,而且不同研究所采用的刺激(单频与多频)及记录(不同信噪比、噪声标准以及记录时间)方法不同,使这一形势更加恶化.综合不同调幅调制纯音ASSR的研究结果,正常听力婴幼儿在500、1 000、2 000及4 000 Hz的平均阈值分别为41、43、35和32 dB HL,如果转换为dB SPL则与短纯音ABR非常相似.如果以均值的90%～95%为可信区间,取二倍标准差,则诊断标准在500 Hz为60 dB HL,1 000、2 000及4 000 Hz为50 dB HL.关于感音神经性聋儿童ASSR的研究有很多,这种研究比较理想的方法应该将婴幼儿的ASSR阈值与行为听阈或短纯音ABR阈值相比较.遗憾的是多数研究都是短声ABR与ASSR的比较.总结以上工作发现,首先样本数量还很少,其次多数有方法学的缺陷,加之不同研究所采用的刺激和记录方法不同,临床资料就更加减少.最后还没有不同类型听力损失的婴幼儿ASSR的研究.总而言之,尽管ASSR在婴幼儿听力评估方面很有前途,但目前单独以此作为听力诊断的电生理方法还为时过早,还必须结合短纯音ABR,因为只有短纯音ABR才具有充足的基础、临床研究和明确的诊断标准,因而也是目前婴幼儿听力诊断电生理方法的金标准.根据上述回顾,ASSR在婴幼儿听力诊断的现状总结如下:①新的刺激及记录方法通常都没有经过同行审阅的临床科研为依据,特别是缺乏听力障碍婴幼儿的数据;②不同设备采用不同的刺激和记录方法,且缺少专业人员的评估;③不同的方法或设备层出不穷,缺乏标准化;④刺激声信号的校准问题以及ASSR与行为听力之间的关系问题还没有解决,各种设备采用不同的刺激和记录方法更加恶化了这一状况;⑤极重度聋者的ABR和ASSR的关系还有待于进一步研究;⑥听力损失儿童的ASSR与行为听力测试的关系的研究还很少,而且现有的大多数研究没有能够将ASSR与听力诊断的金标准--行为听力和/或短纯音ABR进行比较;⑦六个月以下婴幼儿的ASSR 研究还很少;⑧传导性聋或混合性聋成人和婴幼儿的研究还很少;⑨成人的骨导ASSR研究很少,还没有婴幼儿骨导ASSR的研究报道,也没有病理状态下成人或婴幼儿的骨导ASSR研究(极重度聋除外).如果上述问题得不到解决,ASSR技术就不能称为成熟.因为对于一个结果,无法准确地判定该阈值是正常还是升高.短纯音ABR的研究虽然尚需完善,但它已有非常多的研究背景和临床数据,能够提供气导和骨导听阈,是当前婴幼儿(特别是6个月以下儿童)听阈确定的首选方法.因此目前ASSR还需与短纯音ABR或行为听力测试结合使用. 80 Hz ASSR除了用于阈值的评估外,也可以用于阈上功能的评估,如单词识别或助听器效果的预估.结果 表明在正常或异常听力成人以言语调制声为信号,其识别阈与ASSR有显著相关性,它反映了较低水平的听觉处理能力.     

ABR、40Hz-AERP和ASSR与主观纯音听阈测定的相关性研究

目的分析听性脑干反应(ABR)、40 Hz听觉相关电位(40 Hz-AERP)、多频稳态听觉诱发电位(ASSR)电反应阈与纯音测听各频率主观听阈的相关性。方法运用纯音测听、ABR、40 Hz-AERP、ASSR为一组测试组合,对55例(84耳)患者进行检测,分析ABR、40 Hz-AERP(500 Hz、1 kHz)、ASSR(500 Hz、1 kHz、2 kHz、4 kHz)客观电反应阈与纯音测听500 Hz、1 kHz、2k Hz、4 kHz的主观听阈的差值及相关性。结果 ABR与纯音测听2 kHz+4 kHz均值的相关系数最高,为0.829。40 Hz-AERP的500 Hz、1 kHz电反应阈与纯音测听500 Hz、1 kHz听阈的相关系数分别为0.507和0.667。ASSR 500 Hz、1 kHz、2 kHz、4 kHz的电反应阈与纯音相应频率听阈的相关系数分别为0.507、0.715、0.793和0.816。以上相关性均有统计学意义(P0.01)。84耳纯音测听听阈均值为39.8±22.9 dB HL, ABR、ASSR电反应阈均值分别为41.1±18.0 dB nHL和42.4±22.9 dB nHL,40 Hz-AERP/500Hz和1 kHz均值分别为39.5±18.0dB nHL和40.2±19.4 dB nHL。结论 ABR、40 Hz-AERP、ASSR电反应阈与纯音测听各频率主观听阈显著相关,测试结果准确可靠。测试组合可以推断听力曲线的形态,对不能主动配合完成主观测听的婴幼儿及伪聋患者的听力学的辅助诊断非常有价值。     

成人频率特异性chirp听性稳态反应与纯音听阈测试的相关性研究

目的采用chirp信号作为声刺激进行听性稳态反应(auditory steady-state response,ASSR)测试,观察chirp-ASSR反应阈值与纯音听阈的相关性,探讨chirp-ASSR客观听力检测在成人临床听力评估中的价值。方法研究对象包括正常成人组(年龄20～60岁,共计151耳)和感音神经性听力损失组(年龄22～82岁,共计83耳)。在500Hz、1000Hz、2000Hz和4000Hz处进行Chirp-ASSR和纯音听阈测试,并对结果进行统计学分析。结果 0.5～4kHz频率听力正常组Chirp-ASSR反应阈与纯音听阈的相关系数r分别为0.19、0.43、0.58、068;0.5-4.0kHz频率感音神经性听力障碍者的相关系数r分别为0.68、0.84、0.87、0.84;校正后0.5～4kHz各听力组预估听力阈值与纯音听阈的差值较校正前明显缩小。结论在0.5～4.0kHz频率,Chirp-ASSR反应阈与纯音听阈之间存在明显的相关性,在听力损失组中两者的相关性更加显著,而在500Hz处两者的相关性较其它频率低。Chirp-ASSR在客观听力评价中有较好的准确率。     

大鼠弥漫性脑损伤后内耳听觉脑干反应和40Hz听觉相关电位及多频稳态反应与血红素加氧酶-1的相关性研究

目的探讨血红素加氧酶-1(heme oxygenase,HO-1)在弥漫性脑损伤(diffuse brain injury,DBI)大鼠耳蜗的表达,分析听觉脑干反应(auditory brainstem response,ABR)、4 0 Hz听觉相关电位(4 0 Hzauditory event related potential,4 0 Hz AERP)和多频稳态反应(auditory steady-state response,ASSR)与HO-1表达的相关性。方法建立DBI大鼠模型并随机分为5组,即正常对照组、外伤1、2、3、4周组,每组3 0只大鼠。采用ABR、4 0 Hz AERP、ASSR测定,光镜、免疫组织化学及扫描电镜观察各组动物HO-1表达及ABR、40Hz AERP、ASSR的变化。结果对照组大鼠耳蜗HO-1无表达,外伤后各组内耳HO-1表达有明显变化(P<0.01)。外伤后各组ABR、40Hz AERP、ASSR阈值之间比较有明显差别(P<0.05)。外伤各组内耳HO-1表达与ABR、40Hz AERP、ASSR阈值变化具有相关性(P<0.05)。结论大鼠DBI对内耳HO-1表达及听功能均有不同程度的影响,ABR、40 Hz AERP、ASSR阈值变化可能与HO-1表达有关。     

单频和多频刺激骨导听性稳态反应的比较

目的测试听力正常青年人单频及多频刺激骨导听性稳态反应(BC-ASSR)阈值,比较两者是否有差异。方法选取听力正常青年人28例(56耳),进行骨导ASSR及纯音听阈测试,记录0.5、1、2、4kHz单频刺激及多频刺激的BC-ASSR反应阈及纯音听阈,比较两种刺激方式所得结果。结果在0.5、1、2、4kHz频率单频刺激骨导的ASSR反应阈分别为53、47、53、51dB SPL,多频刺激骨导ASSR反应阈分别为59、54、63、61dB SPL,两者间有高度显著性差异(P<0.01),且高频处的差异相对较大。结论BC-ASSR测试时,单频刺激和多频刺激方法所得听阈值存在一定的差异,且高频处的差异相对较大,因而临床应用测试时宜采用单频刺激方式。     

正常听力青年志愿者听觉稳态反应的测试研究

目前,对于听阈的客观测试,人们多采用耳声发射、ABR、40 Hz听觉相关电位(40 Hz auditory event-related potential,40 Hz AERP)等,但都有各自的缺陷.多频听觉稳态反应(multiple auditory steady-state responses,MASSR)多简称听觉稳态反应(auditory steady-state responses,ASSR),具有频率特异性,整个反应结果由电脑自动判读,具有客观性.     

一组健听成人的听觉稳态诱发反应研究

目的探讨正常听觉稳态诱发反应(auditory steady-state response,ASSR)阈值与纯音测听阈值的关系及睡眠对ASSR测试结果的影响．明确ASSR的临床应用价值。方法本实验中,24名健听人(48耳),以74～95 Hz的调制频率诱发睡眠状态下500～4000 Hz单频听觉稳态诱发反应。与纯音测听阈值相比较。将5名健听人(10耳)清醒状态与睡眠状态的ASSR阈值进行比较。结果500,1000,2000．4000 Hz ASSR听阈与纯音测听阈值的差值分别为20．6±6．2．16．4±4．9,16．8±6．5．16．3±7．2 dB。清醒状态较睡眠状态的ASSR阈值平均升高20 dB。结论70～110 HZ ASSR可以用于预测纯音听阈,受试者须处于睡眠状态。     

成人感音神经性聋的听觉稳态反应反应阈与纯音听阈

目的探讨成人感音神经性聋的听觉稳态反应（auditory steady-state responses,ASSR）反应阈与纯音听阈的关系。方法选择中国医科大学附属一院耳鼻咽喉科门诊感音神经性聋的成人患者,分别进行纯音听力测试、ASSR检查,比较ASSR在0.5、1、2、4 kHz频率处的反应阈与纯音听阈的相关性及按听力损失程度比较两者的差值。结果 ASSR反应阈与纯音听阈在各频率处的相关系数分别为0.840、0.905、0.886、0.924;随着感音神经性听力损失的加重二者的差值明显缩小。随着频率的增加,两者的差值明显缩小。结论成人感音神经性聋ASSR反应阈与纯音听阈有显著相关性,随着听力损失的加重,ASSR反应阈愈接近纯音听阈,ASSR作为成人感音神经性聋听力定量诊断的客观方法有很大的临床应用价值。     

The expression of vascular endothelial growth factor (VEGF) and VEGF‐C in early laryngeal cancer: relationship with radioresistance

The expression of vascular endothelial growth factor (VEGF) and VEGF‐C in early laryngeal cancer: relationship with radioresistance Angiogenesis is essential for tumour growth and invasion. Vascular endothelial growth factor (VEGF) is a prime mediator of tumour angiogenesis. VEGF‐C is a closely related protein that effects lymphatic endothelial cells and may be important in the process of lymphatic metastasis. The purpose of this study was to evaluate the expression of these cytokines in patients with T1 and T2a glottic, squamous cell carcinoma, in comparison with normal epithelial control tissue, to ascertain any association with radioresistance. Twenty‐two tumours treated by radiotherapy (13 radiosensitive, nine radioresistant) and seven normal control tissues were studied. The minimum follow‐up was 2 years after radiotherapy. Expression of VEGF and VEGF‐C was evaluated by immunohistochemistry of formalin‐fixed, paraffin‐embedded biopsy specimens. Analysis was carried out using a quantitative computer image analyser. Both VEGF and VEGF‐C were detectable in tumour and normal control specimens. There was increased expression in tumour specimens of both VEGF (P = 0.03) and VEGF‐C (P < 0.001). In addition, the expression of VEGF‐C was associated with tumours of higher histological grade (P = 0.021). There was, however, no difference in VEGF and VEGF‐C expression between radioresistant and radiosensitive tumours. The expression of VEGF and VEGF‐C is increased in early laryngeal squamous cell carcinoma (SCC). However, measuring the expression of these proteins cannot predict radioresistance in this tumour group.     

Treatment of Maxillary Sinus Carcinoma: Clinical Results Using the Kitasato Modality

The conventional therapeutic regimen for maxillary sinus carcinoma consists of dissection of the maxilla, full-dose irradiation and extensive chemotherapy. However, the results obtained with this treatment are often poor. Even when patients recover, their quality of life is significantly reduced as a result of deformity of facial structures and swallowing and articulation dysfunctions. A retrospective analysis of 68 patients with maxillary sinus carcinoma treated with the Kitasato modality between 1975 and 1999 was conducted. All patients underwent pergingival maxillary sinus surgery combined with pre- and postoperative irradiation therapy with standardized total doses of 16 Gy; the postoperative irradiation was given in combination with regional intra-arterial infusion chemotherapy administered via the superficial temporal artery. All visible tumor lesions were removed where possible in order to preserve or facilitate cellular immunity after surgery. The cumulative 5-year survival rates were 85.7% for Stage II patients, 88.1% for Stage III, 76.6% for Stage IVA and 75.0% for Stage IVB.     

Tongue Base Reduction with Temperature-controlled Radiofrequency Volumetric Tissue Reduction for Treatment of Obstructive Sleep Apnea Syndrome

In recent years a considerable effort has been made to establish the use of different surgical techniques for the treatment of obstructive sleep apnea syndrome (OSAS). Nevertheless, treatment of hypopharyngeal obstruction due to tongue base hypertrophy remains in many ways an unsolved problem. The aim of this study was to evaluate the safety and efficacy of tongue base reduction with temperature-controlled radiofrequency volumetric tissue reduction in the treatment of OSAS. Twenty patients with OSAS and tongue base hypertrophy were treated with radiofrequency tissue ablation. An intensified treatment protocol was used, delivering 2,800 J per treatment session under local anesthesia. Two nights of polysomnography testing were performed before and after treatment. Daytime sleepiness, snoring and postoperative morbidity were assessed using questionnaires. Mean respiratory disturbance index (RDI) was reduced from 32.1 to 24.9/h after a mean of 3.4 treatment sessions. Six patients (33%) were cured after the procedure (reduction in RDI of &#83 50% and a postoperative RDI of <15/h) and ten (55%) showed an improvement of >20% in their RDI. Daytime sleepiness and snoring improved significantly. Peri- and postoperative morbidity was low; one severe complication occurred (tongue base abscess). We were able to achieve similar cure and responder rates to those reported in a recently published pilot study but with a reduced number of treatment sessions. We believe that this technique may improve patient acceptance and have beneficial cost implications.     

Cervical Reflex Induced by Click Stimuli in Cats

We studied click-evoked potentials in the anterior horn of the spinal cord in 17 cats. A concentric needle electrode was inserted into the anterior horn of the spinal cord at levels C3-C6. Potentials evoked with 105 dB SPL clicks were recorded with a peak latency of 4.89-5.10 ms only at the C3 level. These responses were observed 45-60 dB SPL above the auditory brainstem response (ABR) threshold, and no potentials were evoked by stimulation of the contralateral ear. Average was performed 100 times with changes in stimulation frequency of 1-20 Hz. The amplitude of the potentials decreased with increasing stimulus frequency, but there were no changes in ABRs. The responses disappeared after destruction of the medial vestibulospinal tract at the obex level, but ABRs were still recorded. The spinal nucleus of the accessory nerves was located in the anterior horn of the spinal cord at levels C1-C6, and the sternocleidomastoid muscle motoneurons were found at levels C1-C3. The click-evoked potentials recorded in this study reflect responses of the spinal nucleus of accessory nerves through the vestibulospinal tract to click stimulation. The responses have the same characteristics as vestibular-evoked myogenic potentials that can be recorded using surface electrodes over the sternocleidomastoid muscles of humans.     

Lack of significant estrogen and progesterone receptor expression in nasal telangiectasias in hereditary hemorrhagic telangiectasia: an immunohistochemical analysis

Obstructive sleep apnea syndrome (OSAS) is characterized by snoring and apnea during sleep leading to decreased oxygen saturation and disturbed sleep, excessive daytime sleepiness and neuropsychological disturbances. This study investigates cognitive neuropsychological abilities in a group of 53 OSAS patients before and after treatment with uvulopalatopharyngoplasty. General intellectual ability, verbal learning and memory as well as executive functioning were measured at baseline and 6 months postoperatively. After surgery there were significant improvements in verbal learning and memory (mean change - 39, SD 57.3, p <0.001), recall (mean change - 24.3, SD 39.3, p <0.001) and executive functioning (as assessed by percentage of errors on the Wisconsin Card Sorting Test; mean change-9.1, SD 15.7, p <0.001). These improvements were in accordance with improvements in the degree of sleep apnea, the oxygen desaturation index (mean change -9.7, SD 15.9, p <0.001) and arterial minimum oxygen saturation (mean change 4.5%, SD 10.2%, p <0.01). Surgical treatment seems to improve verbal learning, memory and recall and executive functions in parallel with better oxygenation in OSAS.     

Measurement of chemosensory function

Although hundreds of thousands of patients seek medical help annually for disorders of taste and smell, relatively few medical practitioners quantitatively test their patients' chemosensory function, taking their complaints at face value. This is clearly not the approach paid to patients complaining of visual, hearing, or balance problems. Accurate chemosensory testing is essential to establish the nature, degree, and veracity of a patient's complaint, as well as to aid in counseling and in monitoring the effectiveness of treatment strategies and decisions. In many cases, patients perseverate on chemosensory loss that objective assessment demonstrates has resolved. In other cases, patients are malingering. Olfactory testing is critical for not only establishing the validity and degree of the chemosensory dysfunction, but for helping patients place their dysfunction into perspective relative to the function of their peer group. It is well established, for example, that olfactory dysfunction is the rule, rather than the exception, in members of the older population. Moreover, it is now apparent that such dysfunction can be an early sign of neurodegenerative diseases such as Alzheimer's and Parkinson's. Importantly, older anosmics are three times more likely to die over the course of an ensuring five-year period than their normosmic peers, a situation that may be averted in some cases by appropriate nutritional and safety counseling. This review provides the clinician, as well as the academic and industrial researcher, with an overview of the available means for accurately assessing smell and taste function, including up-to-date information and normative data for advances in this field.