听觉脑干反应和耳声发射在高危儿听力筛查中的应用

目的：耳声发射(OAE)和听觉脑干反应(ABR) 是新生儿听力筛查的常用方法。该研究旨在探讨畸变产物耳声发射(DPOAE) 和ABR应用于重症监护病房(NICU)高危新生儿听力筛查的差异和意义。方法：分别应用Smart-EP型听觉脑干诱发电位仪和Smart-OAE畸变产物耳声发射检查仪对600例(1 200耳)不同病因所致的高危儿同时进行DPOAE和ABR检查,将两种方法取得的检测结果进行比较。结果：在600例(1 200耳)高危新生儿中,ABR的异常率(78.6%,943/1 200耳)远高于DPOAE的未通过率(22.3%,268/1 200耳);二种检查的共同阴/阳性率分别为20.8%(241/1 200耳)和21%(252/1 200耳)。1 200耳中有493耳DPOAE和ABR的测试结果一致,占41.1%;707耳的测试结果不一致,占58.9%。DPOAE测试的假阳性率为6.0%(16/268耳),假阴性率为74.1%(691/932耳)。结论： DPOAE仅反映耳蜗功能,单独用于高危新生儿听功能筛查的价值有限。ABR检查果相对可靠,NICU高危新生儿听力筛查应先做ABR检查,ABR异常者再做OAE检查。ABR和OAE二种检测方法相互结合,方能提高高危新生儿听力筛查的准确性。     

Cisplatin ototoxicity in children: a practical grading system

A long-term follow-up study was carried out to assess ototoxicity in children who had been treated for a malignant tumour with "standard dose" cisplatin (60-100 mg/m2 per course), and were at least 2 years from stopping treatment. The median age at diagnosis was 2 years 2 months (range 1 month to 13.5 years). On the basis of hearing assessment by pure-tone audiometry, a practical grading system of hearing loss from 0 to 4 is proposed. Moderate to severe high-frequency hearing loss (grade 2-4) was found in half the children and 10 require appropriate hearing aids. The risk of developing ototoxicity increased significantly with the cumulative cisplatin dose (P = 0.027), although there was considerable individual susceptibility. Serial follow-up testing, to a median of 4 years after completion of cisplatin treatment, showed no recovery of hearing in any of these children. We suggest careful monitoring of young children by a consultant audiological physician throughout treatment with cisplatin, particularly when doses of 400 mg/m2 and over have been reached. Alternative chemotherapy should be discussed if grade 2 ototoxicity develops.     

Platinum compound-related ototoxicity in children: long-term follow-up reveals continuous worsening of hearing loss

OBJECTIVES: The purpose of this study was to evaluate the severity of hearing loss after cisplatin and/or carboplatin treatment in young children and to analyze its evolution and its relation to different therapy schedules. METHODS: One hundred twenty patients treated in the Pediatrics Department at the Institut Gustave-Roussy from 1987 to 1997 for neuroblastoma, osteosarcoma, hepatoblastoma, or germ cell tumors were analyzed. Median age at diagnosis was 2.6 (range 0-17) years. Median follow-up was 7 (1-13) years. Chemotherapy regimens contained cisplatin and/or carboplatin. Three patients also received high-dose carboplatin. Cisplatin was administered at a dose of 200 mg/m/course in 72% of cases. The median cumulative dose was 400 mg/m for cisplatin and 1,600 mg/m for carboplatin. Hearing loss of grade 2 or above, according to Brock's grading scale, was revealed with pure tone audiometry and behavioral techniques. RESULTS: Carboplatin alone was not ototoxic. Deterioration of hearing of grade 2 or above was observed in 37% of patients treated with cisplatin and 43% of patients treated with cisplatin plus carboplatin (P = NS). Fifteen percent of patients experienced grade 3 or 4 ototoxicity. Ototoxicity was most often observed after a total cisplatin dose of at least 400 mg/m. No improvement was observed with time; on the contrary, worsening or progression of hearing loss at lower frequencies was detected during follow-up. Only 5% of audiograms showed toxicity of at least grade 2 before the end of therapy; in contrast, this level was observed in 11% of early post-therapy evaluations and in 44% after more than 2 years of follow-up. CONCLUSIONS: Children treated with cisplatin at cumulative doses approaching 400 mg/m require long-term surveillance to avoid overlooking hearing deficits. Carboplatin, at a standard dose, does not appear to be a significant risk factor for ototoxicity even in patients who have already been treated with cisplatin.     

脑干听觉诱发电位与畸变产物耳声发射在听觉通路损伤患儿中的应用研究

目的　采用客观听力检测技术 ,分析听觉通路病损患儿的临床听力学特点 ,评价感音神经性聋患儿的蜗性及蜗后病变特征。方法　对感音神经性聋患儿共 310例 (5 0 0耳 ,年龄 1个月至 6岁 ,平均 2 4 2个月 )进行临床分析 ,其中中枢神经系统 (CNS)病变伴听力障碍 10 5例 (2 0 5耳 ) ,将其分为核黄疸 脑瘫组、额叶发育不良组和其他中枢性病变 3组。同年龄段对照组 6 0例 (10 4耳 )。同时检测脑干听觉诱发电位 (BAEP)和畸变产物耳声发射(DPOAE) ,对比不同组别间BAEP波V阈值及DPOAE各自的特点、同一组间不同BAEP波V阈值耳DPOAE的变化特征。结果　 (1)全组感音神经性聋患儿中有CNS病变者比例较高 (10 5例 2 0 5耳 /310例 5 0 0耳 )。 (2 )CNS病变患儿中核黄疸 脑瘫组可见严重的蜗后性听力损失 ,耳蜗功能也轻度受累 ;额叶发育不良组仅出现轻度蜗后听力损失 ;其他中枢性病变一般不累及耳蜗功能。 (3)蜗性听力损失者 ,BAEP波V阈值达 6 0nHLdB时 ,DPOAE幅值明显下降 ;达 70nHLdB以上者 ,DPOAE幅值严重下降或消失。结论　CNS病变伴感音神经性聋患儿听力障碍表现为多样性 ,临床上需联合听力专科采用不同客观听力检测技术进行综合评估 ,才能作出正确诊断。     

Hearing improvement in patients with Fabry disease treated with agalsidase alfa

AIM: To describe the nature and prevalence of hearing loss in Fabry disease, and its response to enzyme replacement therapy (ERT) with agalsidase alfa. METHODS: Fifteen male patients with Fabry disease were enrolled in a randomized, double-blind study and received placebo (n = 8) or ERT (n = 7) with agalsidase alfa for 6 months. This was followed by an open-label extension of 36 months thus far. Alongside this trial, an additional eight men and two women have so far received open-label ERT for between 6 and 30 months. Pure-tone audiometry, impedance audiometry and otoacoustic emission testing were performed at 0 (baseline), 6, 18, 30 and 42 months. RESULTS: Nine patients (36%) had bilateral and ten (40%) had unilateral high-frequency sensorineural hearing loss (SNHL). Three (12%) had unilateral middle ear effusions with conductive losses persisting beyond 6 months. Only five patients (20%) had normal hearing. The high-frequency SNHL deteriorated over the first 6 months in both placebo and active treatment groups by a median 6.3 dB (p < 0.0001, Wilcoxon matched-pairs). This hearing loss subsequently improved above baseline by 1.5 dB at 18 months (p = 0.07), by 5.0 dB at 30 months (p = 0.006) and by 4.0 dB at 42 months (p = 0.01). CONCLUSION: Significant hearing loss, usually high-frequency SNHL, is a common manifestation of Fabry disease in adults. Alpha-galactosidase A replacement therapy with agalsidase alfa appears to reverse the hearing deterioration in these patients. This improvement, however, is gradual, suggesting the need for long-term ERT.     

Electrophysiological tests of the hearing organ in Hashimoto's disease

Thyroid gland diseases resulting from an autoimmunological process may influence the hearing organ. The aim of this study was to assess peripheral and central parts of the hearing organ in children with Hashimoto's thyroiditis. Thirty children (mean age 14.9 years) with Hashimoto's thyroiditis were examined. Patients were euthyroid, and presented high blood concentration of antithyroperoxidase (ATPO) antibodies. Pure tone audiometry, tympanometry, otoacoustic emissions (DPOAEs), and brain auditory evoked potentials (BAEPs) were performed. None of the patients had any complaints about hearing acuity; pure tone audiometry, tympanometry, and DPOAEs were normal in all patients. There were considerable disturbances in auditory nerve and brainstem neural conduction in BAEPs. There was positive correlation between the blood concentration of ATPOA and the extent of the disturbances in the central part of the hearing organ. One should consider the possible presence of subclinical Hashimoto's encephalopathy affecting the central part of the auditory organ.     

Neugeborenenhörscreening

In Germany about 1-3 children in 1,000 are born with a bilateral hearing loss of >40 dB. If this damage is not discovered and therefore not treated early it mostly leads to impairment in language development. Further consequences are disruption of emotional, cognitive, intellectual and psychosocial development of the child making later access to education and professional development difficult. The average age of diagnosis of early childhood hearing loss is about 2–3 years and leads to a much too delayed initiation of therapy. After revision of the pediatric guidelines in Germany newborns will have a right to a newborn hearing screening as from January 2009. For this examination two methods are basically available: the measurement of otoacoustic emissions (OAE) and auditory brainstem response (ABR). For both methods screening devices are available. Automated measurement and analysis of the results are possible.     

不同日龄新生儿诱发性耳声发射测试

对20例正常新生儿在出生后第1～5天逐日行瞬态诱发性耳声发射(TEOAE)和畸变产物耳声发射(I)POAE)的测试。了解不同日龄新生儿畸变产物耳声发射(DPOAE)和瞬态诱发性耳声发射(TEOAE)的特征，探讨应用OAE作新生儿听力筛查的最佳时机。随新生儿日龄的增加，其TEOAE和DPOAE检出率和反应幅值逐步提高，新生儿生后第1～2天的检出率和反应幅值显著低于第3～5天，至生后第3～5天．TEOAE和DPOAE检出率接近或达到100％，反应幅值也趋于稳定。结论：应用TEOAE和DPOAE进行新生儿听力筛查时，其日龄至少应在3天或3天以上，测试TEOAE和DPOAE快速、方便，不失为普遍性新生儿听力筛查首选方法。     

Hearing loss in children with brain tumors treated with cisplatin and carboplatin-based high-dose chemotherapy with autologous bone marrow rescue

Carboplatin is less ototoxic than cisplatin, but ototoxicity may occur with carboplatin at higher doses. We evaluated hearing in children with brain tumors treated with conventional dose cisplatin followed by high-dose carboplatin. Children under 6 years of age, newly diagnosed with brain tumors, were treated after surgery with cisplatin, Etoposide, cyclophosphamide, and vincristine, followed by consolidation with carboplatin, ThioTEPA, Etoposide, and autologous bone marrow rescue. Hearing was assessed before and after consolidation, utilizing standard audiometric techniques. Seven of the 11 evaluable patients developed high-frequency sensorineural hearing loss after induction therapy. Hearing deteriorated after consolidation in five patients, with pure tone threshold shifts of up to 65 dB between 2,000 and 8,000 Hz. Of these five patients, audiological abnormalities were documented in four prior to consolidation, one received cranial irradiation after consolidation, and all five received aminoglycoside antibiotics for at least 2 weeks, with toxic drug levels in four. Three patients have subsequently required hearing aids. Significant ototoxicity is common in these patients. Ototoxicity related to consolidation therapy is likely due to the high dose of carboplatin used, prior cisplatin therapy, aminoglycosides, and, in one patient, cranial irradiation. Audiological assessment is essential in children treated with dose-intensive chemotherapy regimens containing cisplatin and carboplatin for identification and rehabilitation of ototoxicity. © 1996 Wiley-Liss, Inc.     

Ototoxicity of cisplatin in children with malignant diseases

Ten out of 20 children with malignant diseases who received cisplatin in combination with other drugs developed hearing impairment primarily at the higher and rarely also at the lower frequencies. The CDDP-ototoxicity was found to be dose-related and irreversible. Audiometric abnormalities were symmetrical and bilateral. Two patients had symptomatic hearing impairment. Ototoxicity was more severe with higher individual and higher cumulative doses. CNS-irradiation increases the ototoxic effect of CDDP. Audiometric testing at the beginning of chemotherapy and during chemotherapy is important to find out preexisting disturbances of hearing function and to recognize early developing hearing loss.     

Hearing improvement in patients with Fabry disease treated with agalsidase alfa

Aim : To describe the nature and prevalence of hearing loss in Fabry disease, and its response to enzyme replacement therapy (ERT) with agalsidase alfa. Methods : Fifteen male patients with Fabry disease were enrolled in a randomized, double-blind study and received placebo ( n = 8) or ERT ( n = 7) with agalsidase alfa for 6 months. This was followed by an open-label extension of 36 months thus far. Alongside this trial, an additional eight men and two women have so far received open-label ERT for between 6 and 30 months. Pure-tone audiometry, impedance audio-metry and otoacoustic emission testing were performed at 0 (baseline), 6, 18, 30 and 42 months. Results : Nine patients (36%) had bilateral and ten (40%) had unilateral high-frequency sensorineural hearing loss (SNHL). Three (12%) had unilateral middle ear effusions with conductive losses persisting beyond 6 months. Only five patients (20%) had normal hearing. The high-frequency SNHL deteriorated over the first 6 months in both placebo and active treatment groups by a median 6.3 dB ( p < 0.0001, Wilcoxon matched-pairs). This hearing loss subsequently improved above baseline by 1.5 dB at 18 months (p = 0.07), by 5.0 dB at 30 months ( p = 0.006) and by 4.0 dB at 42 months ( p = 0.01).
Conclusion : Significant hearing loss, usually high-frequency SNHL, is a common manifestation of Fabry disease in adults. α-Galactosidase A replacement therapy with agalsidase alfa appears to reverse the hearing deterioration in these patients. This improvement, however, is gradual, suggesting the need for long-term ERT.     

Conductive hearing loss in children with autism

Infantile autism is a serious comprehensive developmental disorder. The diagnosis of hearing loss or its exclusion, which often suggests suspected autism, is very important for early ENT, psychotherapy, and psychiatric treatment. One hundred children diagnosed with autism aged from 3 to 18 years, with a median age of 5 years, were evaluated. The control group of healthy children consisted of 100 children, aged from 3 to 18 years, with a median age of 6 years. Anamnesis and physical examination, including pediatric assessment and otoscopic examination, were carried out on children in both groups. Each child underwent bilateral otoacoustic emission examination in the 0.7, 1, 2, and 4 kHz bands and impedance audiometry examination. The data obtained were subjected to a basic statistical assessment. Chi² Pearson's test was used to compare results of tests in both groups. The absence of otoacoustic emission for the 1 and 2 kHz bands was significantly more frequent in the group of autistic children than in the control group. Furthermore, types B and C2 tympanometric curves were significantly more common in the group of autistic children than in the group of healthy children.     

Auditory and vestibular findings in Fabry disease: a study of hemizygous males and heterozygous females

AIM: This study aimed to evaluate audiological and vestibular involvement in Fabry disease and the early effects of enzyme replacement therapy with human alpha-galactosidase A. METHODS: Fourteen patients (10 males, 4 females) aged 14-57 years were studied. Each patient underwent a clinical (history of otological and vestibular aspects, otoscopy) and instrumental (pure tone and speech audiometry, impedance, auditory brainstem response and oto-acoustic emission recordings, vestibular caloric tests, electronystagmography during acceleratory stimulation, dynamic posturography) evaluation before starting enzyme replacement therapy. RESULTS: Fifty per cent of patients complained of hearing symptoms (hearing loss, tinnitus, ear fullness). Subjective hearing loss was present in six cases and in three cases it was the first reported symptom of Fabry disease. In six of the seven cases the onset and/or progression of hearing symptoms were sudden. Vertigo or dizziness was reported by four patients and in two cases was associated with hearing symptoms. Audiological evaluation showed sensorineural hearing loss in eight patients (5 males, 3 females). Hearing loss was unilateral in six cases and bilateral in the remaining two cases. The hearing loss (HL) ranged from 30 to 80 dB HL (mean, 43 dB HL) and the lesion was always cochlear. Vestibular examination showed abnormalities in four patients (bilateral weak/abolished response in three cases, side prevalence in one case), which were not related to either the audiological results or the history of vertigo/dizziness. CONCLUSION: Involvement of the inner ear is common in men and women with Fabry disease. We found a high incidence of cochlear hearing loss, which was typically unilateral and showed onset and/or progression by sudden episodes. Vascular or hydropic mechanisms could be hypothesized to explain audiological findings. Vestibular involvement had a lower incidence and showed a different pattern, thus suggesting that several pathophysiological mechanisms could play a role in determining inner ear damage in Fabry disease. Our preliminary results show that enzyme replacement therapy may stabilize hearing function; however, further follow-up is required.     

Prediction of permanent hearing loss in high-risk preterm infants at term age

The aim of this series was to assess hearing screenings; auditory brainstem responses (ABR), transient evoked otoacoustic emissions (TEOAE) and free field auditory responses (FF) for the prediction of permanent bilateral hearing loss in high-risk preterm infants at term post-conceptional age. A total of 51 preterm infants (gestational age <34 weeks, birth weight <1500 g) underwent examinations at term and hearing, speech and neurological development were followed up until a corrected age of 18 months. Significant hearing defects were verified by broader ABR examinations under sedation and by clinical ward observation including responsiveness to sounds and enhancement of hearing using an amplification device. Seven bilateral fails in ABR were found, together with nine bilateral fails in TEOAE and four fails in FF screening at term age. Six preterm infants were later confirmed to have a significant permanent bilateral hearing loss, four of whom had also cerebral palsy. Bilateral failure in ABR screening predicted hearing loss with a sensitivity of 100% and a specificity of 98%, TEOAE with a sensitivity of 50% and a specificity of 84% and in the FF examination at the levels of 50% and 98%, respectively. Conclusion Transient evoked otoacoustic emissions alone seem not to be so applicable to the neonatal screening of hearing in high-risk preterm infants as shown earlier in full-term infants, possibly because a hearing defect may be due to retrocochlear damage. Consequently, auditory brainstem response screening seems to be more suitable for very low birth weight preterm infants. Received: 21 September 1999 / Accepted: 5 January 2000     

Costs of different strategies for neonatal hearing screening: a modelling approach

OBJECTIVE: To compare the cost effectiveness of various strategies for neonatal hearing screening by estimating the cost per hearing impaired child detected. DESIGN: Cost analyses with a simulation model, including a multivariate sensitivity analysis. Comparisons of the cost per child detected were made for: screening method (automated auditory brainstem response or otoacoustic emissions); number of stages in the screening process (two or three); target disorder (bilateral hearing loss or both unilateral and bilateral loss); location (at home or at a child health clinic). SETTING: The Netherlands TARGET POPULATION: All newborn infants not admitted to neonatal intensive care units. MAIN OUTCOME MEASURE: Costs per child detected with a hearing loss of 40 dB or more in the better ear. RESULTS: Costs of a three stage screening process in child health clinics are 39.0 pounds (95% confidence interval 20.0 to 57.0) per child detected with automated auditory brainstem response compared with 25.0 (14.4 to 35.6) pounds per child detected with otoacoustic emissions. A three stage screening process not only reduces the referral rates, but is also likely to cost less than a two stage process because of the lower cost of diagnostic facilities. The extra cost (over and above a screening programme detecting bilateral losses) of detecting one child with unilateral hearing loss is 1500-4000 pounds. With the currently available information, no preference can be expressed for a screening location. CONCLUSIONS: Three stage screening with otoacoustic emissions is recommended. Whether screening at home is more cost effective than screening at a child health clinic needs further study.     

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目的探讨儿童阻塞性睡眠呼吸暂停综合征(OSAS)对耳蜗功能的影响。方法将2002年6月至2003年8月广州市儿童医院收治的26例(52耳)OSAS患儿的畸变产物耳声发射(DPOAE)的结果与28例(56耳)正常儿童DPOAE结果进行比较。结果26例OSAS患儿多导睡眠图(PSG)示最低血氧饱和度(57.91±18.61),呼吸紊乱指数(29.10±23.31),与正常儿童相比差异均有显著性意义。OSAS患儿F1～F4频率段DPOAE反应幅值与正常组比较,差异无显著性意义(P>0.05);F4～F11频率段的DPOAE反应幅值及F1～F11频率段DPOAE检出率均较正常儿童低,差异有显著性意义(P<0.05)。结论OSAS能导致患儿耳蜗功能受损,对OSAS患儿应常规做耳声发射检查,做到早诊断、早治疗。     

Hearing loss in Turner syndrome

OBJECTIVE: To address the characteristics of hearing loss in patients with Turner syndrome (TS), we evaluated hearing levels of patients with TS and analyzed causative factors. STUDY DESIGN: Thirty-three patients with TS (8 to 40 years of age) were studied through the use of audiological measurements, and causative factors were explored. RESULTS: Twenty cases (35 of 66 ears tested) showed high-frequency (8 kHz) sensory neural hearing loss (HFQ-SNHL). Fifteen cases (26 ears) and 15 cases (24 ears) of the impaired 20 cases were unresponsive to distortion-product otoacoustic emissions and transient-evoked otoacoustic emissions, respectively. HFQ-SNHL showed little relation to the history of middle ear infection and puberty, although middle ear infections were seen in 11 of the 20 cases. The hearing thresholds at high frequencies were correlated with age and body height (P < .001). The age-dependent increase in hearing thresholds in the high frequencies was more apparent in patients with TS with monosomic 45, X than in those with the mosaic type (P < .05). CONCLUSIONS: More than 60% of patients with TS had HFQ-SNHL. Because the increase in hearing threshold at high frequencies was shown to depend on karyotype and aging, regular otological examination is important for the determination of proper treatment.     

Mild impairment of neuro-otological function in early treated congenital hypothyroidism.

Pure tone audiometry, tympanometry, acoustic stapedial reflex thresholds (ASRTs), and auditory evoked brain stem responses (AEBRs) were carried out in 38 children with early treated congenital hypothyroidism aged 10-12 years, together with tests of vestibular function (electronystagraphy, rotational, and caloric tests). Sensorineural hearing loss with thresholds of greater than 15 dB was detected in 18 children (10 at 8 kHz only); only two children had more than 40 dB hearing loss, each in one ear. Raised ASRTs were found in eight children and two children had abnormal AEBRs. Of the 29 children tested, 12 had an abnormality of vestibular function. Although not significant at the 5% level, there was a tendency for the abnormalities to be more prevalent and severe in the children with more severe hypothyroidism, as judged by pretreatment plasma thyroxine. It is concluded that (i) mild abnormality of hearing is still common in children with congenital hypothyroidism despite early treatment but this is much less severe than that found before neonatal screening and (ii) mild abnormalities of vestibular function may be common in early treated congenital hypothyroidism.     

Mild impairment of neuro-otological function in early treated congenital hypothyroidism

Pure tone audiometry, tympanometry, acoustic stapedial reflex thresholds (ASRTs), and auditory evoked brain stem responses (AEBRs) were carried out in 38 children with early treated congenital hypothyroidism aged 10-12 years, together with tests of vestibular function (electronystagraphy, rotational, and caloric tests). Sensorineural hearing loss with thresholds of greater than 15 dB was detected in 18 children (10 at 8 kHz only); only two children had more than 40 dB hearing loss, each in one ear. Raised ASRTs were found in eight children and two children had abnormal AEBRs. Of the 29 children tested, 12 had an abnormality of vestibular function. Although not significant at the 5% level, there was a tendency for the abnormalities to be more prevalent and severe in the children with more severe hypothyroidism, as judged by pretreatment plasma thyroxine. It is concluded that (i) mild abnormality of hearing is still common in children with congenital hypothyroidism despite early treatment but this is much less severe than that found before neonatal screening and (ii) mild abnormalities of vestibular function may be common in early treated congenital hypothyroidism.     

Sensorineural hearing loss associated with Kawasaki disease

In five children who met the diagnostic criteria for Kawasaki Disease, sensorineural hearing loss developed in association with the acute illness. The children, aged 7 months to 13 years, had deficits ranging from mild to profound bilateral sensorineural hearing loss. There were no associated neurologic abnormalities, and immunologic investigations and magnetic resonance imaging failed to reveal a cause. Treatment regimens differed among the children, but none had high salicylate levels (greater than 20 mg/dl) or received other ototoxic medications. Antiinflammatory therapy was not obviously beneficial in any case, and four of the children have persistent hearing deficits. We conclude that auditory involvement may be a complication of Kawasaki disease; screening of clinically affected children should be considered.