今日の臨床サポート

後天性難聴(薬剤性難聴、ウイルス感染による難聴)

著者: 中島務 一宮医療療育センター

監修: 森山寛 東京慈恵会医科大学附属病院

著者校正/監修レビュー済:2019/09/20
参考ガイドライン:
厚生労働科学研究費補助金難治性疾患克服研究事業:急性高度難聴に関する調査研究平成23年度 総括・分担研究報告書(24年3月)、ムンプス難聴診断基準(案)
患者向け説明資料

概要・推奨   

  1. アミノ配糖体抗菌薬、シスプラチンによる難聴では、グルタチオンや抗酸化薬の投与を行う場合がある(推奨度2)
  1. 抗癌薬であるシスプラチンを投与するとき、耳毒性の予防のために抗酸化薬やグルタチオンを事前に投与することは、現時点では推奨されない(推奨度3)
  1. 母親が妊娠中、耳毒性となる薬物投与を受けたとき、新生児の聴覚スクリーニングは強く推奨される(推奨度1)
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
中島務 : 特に申告事項無し[2021年]
監修:森山寛 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い文献ふくめて加筆修正おこなった。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 後天性難聴とは、突発性難聴、外リンパ瘻、メニエール病、騒音性難聴、機能性難聴、聴神経腫瘍、中枢性循環障害(前下小脳動脈領域)、薬剤やウイルス感染症により、後天的に難聴が起きることである。この項目では主に、薬剤やウイルス感染症について扱う。
  1. 薬剤性難聴の原因となる薬剤として抗菌薬、抗癌薬、ループ利尿薬など種々ある。リストを表に示す。(表<図表>
  1. 抗生物質のうちアミノ配糖体系抗生物質は、結核の治療にも用いられており不可逆性の感音難聴を来す。
  1. アミノ配糖体系抗生物質による難聴の感受性には、ミトコンドリア遺伝子による母系遺伝が関与する。
  1. 抗癌薬として白金製剤のシスプラチンが広く用いられているが、難聴、耳鳴の訴えに注意する。
  1. ウイルス感染による後天性難聴としてムンプス難聴、帯状疱疹ウイルスによるハント症候群(ラムゼイハント症候群)がよく知られている。
  1. ムンプス難聴は、高度難聴で有効な治療法はないので、予防としてムンプスワクチンの接種が勧められる。
 

a:アミノ配糖体系抗菌薬による難聴進行パターン
b:ムンプス難聴の聴力図

出典

img1:  著者提供
 
 
 
  1. ムンプス予防接種は、難聴予防のため推奨される(推奨度1)
  1. ムンプス(おたふくかぜ)の罹患により高度な感音難聴を来すことがある。多くは一側性であるが、両側性のときもある。現在、日本では、ムンプス予防接種率の低下からムンプス難聴発症数の増加が危惧され、ムンプス予防接種が推奨されている[1][2][3]。一側性の難聴があり、ムンプス未罹患である場合は、ムンプスの予防接種が強く推奨される。
 
問診・診察のポイント  
 
問診:
  1. 難聴の有無、その経緯

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Yoshiyuki Kawashima, Kazushige Ihara, Mieko Nakamura, Tsutomu Nakashima, Satoshi Fukuda, Ken Kitamura
雑誌名: Auris Nasus Larynx. 2005 Jun;32(2):125-8. doi: 10.1016/j.anl.2005.01.009. Epub 2005 Apr 7.
Abstract/Text In Japan, mumps vaccination is optional and the mumps were increased accompanied with prevalent waves according to the Infections Agents Surveillance Report (IASR). The aim of this study was to clarify that there was relevance for increase of mumps epidemic and mumps deafness. The Acute Profound Deafness Research Committee of the Japanese Ministry of Health and Welfare (reorganized to the Ministry of Health, Labour and Welfare in 2001) conducted a nationwide epidemiological survey to determine the number of patients treated for mumps deafness in 1987, 1993 and 2001. Based on its findings, the annual numbers of mumps deafness cases was estimated to be 300 in 1987, 400 in 1993 and 650 in 2001, which correlated with the overall incidence of mumps in those years. Because the majority of cases exhibited severe or profound sensorineural hearing loss that usually did not recover, rapid improvement of mumps vaccine coverage is strongly recommended.

PMID 15917168  Auris Nasus Larynx. 2005 Jun;32(2):125-8. doi: 10.1016/・・・
著者: Tsutomu Nakashima, Taku Hattori, Michihiko Sone, Kiyomitsu Asahi, Naoko Matsuda, Masaaki Teranishi, Tadao Yoshida, Ken Kato, Eisuke Sato
雑誌名: Otol Neurotol. 2012 Feb;33(2):165-8. doi: 10.1097/MAO.0b013e318241c0db.
Abstract/Text OBJECTIVE: The effect of cochlear blood flow (CBF) on speech perception ability in cochlear implant (CI) users has not been reported. We investigated various factors influencing speech perception including CBF in CI users.
PATIENTS: Eighty-two patients who received CI surgery at an academic hospital.
METHODS: CBF was measured during CI surgery using laser Doppler flowmetry. The speech perception level was measured after a sufficient interval after CI surgery. Multivariate analysis was used to evaluate the influences of age, duration of deafness, sex, cause of deafness, and CBF on the speech perception level.
RESULTS: CBF decreased significantly with age but was not related to the speech perception level. In patients with congenital hearing loss, the speech perception level was significantly worse in children who received a CI at 3 years of age than in those who received a CI at 2 years of age or younger. Duration of deafness before CI surgery had deteriorative effects on the speech perception level.
CONCLUSION: CBF may be associated with progression of hearing loss. However, measuring CBF during CI surgery is not useful for predicting postoperative speech perception.

PMID 22215456  Otol Neurotol. 2012 Feb;33(2):165-8. doi: 10.1097/MAO.0・・・
著者: P R Donald, E Doherty, F J Van Zyl
雑誌名: Cent Afr J Med. 1991 Aug;37(8):268-71.
Abstract/Text The risk of deafness developing in the unborn child following the use of streptomycin (SM) during pregnancy remains uncertain. We have followed up 30 children whose mothers received SM during pregnancy. One child (3pc), whose mother received SM during the first trimester of pregnancy, had profound unilateral hearing loss which could possibly be ascribed to SM. This child had however, in addition, features of congenital hypotonia and a unilateral single crease. Two further children had conductive deafness which could not be due to SM, associated with serious otitis media. Although the risk to the foetus of hearing loss following the use of SM during pregnancy appears relatively low it should, where possible, be avoided during the first trimester of pregnancy.

PMID 1807803  Cent Afr J Med. 1991 Aug;37(8):268-71.
著者: Tsutomu Nakashima, Taku Hattori, Michihiko Sone, Eisuke Sato, Mitsuo Tominaga, Makoto Sugiura
雑誌名: Ann Otol Rhinol Laryngol. 2004 Jun;113(6):426-30.
Abstract/Text We measured cochlear blood flow (CBF) in 55 patients who received cochlear implants, using a laser-Doppler probe placed over the site of drilling in the cochlear bony wall. The subjects included 29 patients with congenital deafness of unknown cause, 8 with idiopathic progressive sensorineural hearing loss, 4 with postmeningitic deafness, 3 with Waardenburg's syndrome, 3 with congenital cytomegalovirus infection, and 8 whose deafness had other causes. There was a wide range of CBF values in patients with congenital deafness of unknown cause. In the patients with idiopathic progressive sensorineural hearing loss, the CBF was significantly lower in patients more than 40 years old. Intracochlear calcification following meningitis appears to be associated with a reduced CBF.

PMID 15224823  Ann Otol Rhinol Laryngol. 2004 Jun;113(6):426-30.
著者: S Caluwaerts, K VAN Calsteren, L Mertens, L Lagae, P Moerman, M Hanssens, K Wuyts, I Vergote, F Amant
雑誌名: Int J Gynecol Cancer. 2006 Mar-Apr;16(2):905-8. doi: 10.1111/j.1525-1438.2006.00223.x.
Abstract/Text Although cervical carcinoma is among the most frequently encountered malignancies during pregnancy, only four cases of neoadjuvant chemotherapy during pregnancy have been reported. A 28-year-old A0P1G2M0 was diagnosed at 15 weeks with stage Ib1 invasive squamous cervical cancer. Because she strongly desired the continuation of this pregnancy, after extensive counseling she was treated with 75 mg/m(2) cisplatin every 10 days starting at 17 weeks. After six cycles, clinically and radiologically stable disease with normalization of the squamous cell carcinoma tumor marker was obtained. An elective cesarean delivery followed by radical hysterectomy and lymphadenectomy was performed at 32 weeks gestation. The pathology report revealed a moderately differentiated squamous cell carcinoma of 3.5 cm, and all 33 lymph nodes were free of disease. Neonatal examination of the baby could not reveal any abnormalities, and this was confirmed at 6 months. The use of neoadjuvant chemotherapy enabled us to continue this pregnancy until the fetus was viable. Cisplatin did not influence the short-term outcome, but only a long-term follow-up will inform us on its safety during pregnancy.

PMID 16681782  Int J Gynecol Cancer. 2006 Mar-Apr;16(2):905-8. doi: 10・・・
著者: L Elit, A Bocking, C Kenyon, R Natale
雑誌名: Gynecol Oncol. 1999 Jan;72(1):123-7. doi: 10.1006/gyno.1998.5190.
Abstract/Text OBJECTIVE: The use of chemotherapeutic drugs in pregnancy is a rare occurrence. Experience and results need to be shared.
METHOD: At 23 weeks gestational age, a patient was diagnosed with an endodermal sinus tumor of the ovary. She received one course of postoperative bleomycin, cisplatin, and etoposide. One week later, the patient was investigated for increasing abdominal pain and the fetus was noted to have ventriculomegaly.
RESULTS: The baby was delivered, and the patient was surgically staged and completed chemotherapy. Although the patient is alive and well 16 months after delivery, the infant has developed significant ventriculomegaly with cerebral atrophy.
CONCLUSION: The etiology of this infant's significant cerebral atrophy is not clear. Tumor-specific, perioperative, or drug-related events must be considered.

Copyright 1999 Academic Press.
PMID 9889045  Gynecol Oncol. 1999 Jan;72(1):123-7. doi: 10.1006/gyno.・・・
著者: Olivier Mir, Paul Berveiller, Stanislas Ropert, François Goffinet, François Goldwasser
雑誌名: Cancer. 2008 Dec 1;113(11):3069-74. doi: 10.1002/cncr.23935.
Abstract/Text The incidence of cancer during pregnancy is increasing given the trend for women to postpone childbearing. Knowledge of the potential toxicity and teratogenicity of chemotherapy agents is crucial for patient counseling. Platinum derivatives are active against various malignancies that occur more frequently during pregnancy: melanoma, cervical and ovarian cancers, and lung cancer. The authors of this article performed a systematic review of reports documenting the use of platinum derivatives during pregnancy in the English literature from 1977 through January 2008. Forty-three pregnancies were described: 36 patients received cisplatin, 6 patients received carboplatin, and 1 patient received both drugs. Two fetal malformations occurred after in utero exposure to cisplatin, but the causative link between cisplatin administration and these malformations remains speculative. However, either detectable cisplatin levels or platinum-DNA adducts were observed in neonates who were exposed to platinum derivatives during the third trimester, providing evidence for a late-onset transplacental transfer of these drugs. The administration of platinum derivatives, although feasible during the second and third trimesters of pregnancy, raises concern regarding the transplacental transfer of these drugs in late pregnancy and has unknown short- and long-term effects.

(c) 2008 American Cancer Society
PMID 18985677  Cancer. 2008 Dec 1;113(11):3069-74. doi: 10.1002/cncr.2・・・
著者: Shuai Hao, Xuejun Jiang, Aihui Yan, Bo Yang
雑誌名: Arch Toxicol. 2011 Jan;85(1):19-25. doi: 10.1007/s00204-010-0543-7. Epub 2010 Apr 16.
Abstract/Text The objective of this study was to evaluate the role of apoptosis in the development of the newborn cochlear structures and hearing loss caused by prenatal cis-diaminedichloroplatinum (cisplatin) exposure. Pregnant albino guinea pigs were intraperitoneally injected with 1.5 mg/kg body weight cisplatin once a day for seven consecutive days at gestational day (GD) 51 to GD 57. At postnatal day (PND) 14, pups were examined in the distortion product otoacoustic emission (DPOAE) task. The temporal bones were then removed and immunohistochemically stained for caspase 3, using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Cisplatin used during pregnancy could induce hearing loss in newborn and cochlear hair cell apoptosis. In conclusion, apoptosis may play an important role in the development of hearing impairment, caused by perinatal cisplatin exposure.

PMID 20396870  Arch Toxicol. 2011 Jan;85(1):19-25. doi: 10.1007/s00204・・・
著者: American Academy of Pediatrics, Joint Committee on Infant Hearing
雑誌名: Pediatrics. 2007 Oct;120(4):898-921. doi: 10.1542/peds.2007-2333.
Abstract/Text
PMID 17908777  Pediatrics. 2007 Oct;120(4):898-921. doi: 10.1542/peds.・・・
著者: Hironao Otake, Makoto Sugiura, Shinji Naganawa, Tsutomu Nakashima
雑誌名: Int J Pediatr Otorhinolaryngol. 2006 Dec;70(12):2115-7. doi: 10.1016/j.ijporl.2006.07.025. Epub 2006 Sep 15.
Abstract/Text A 6-year-old boy suffered acute profound right side deafness after his classmates had mumps. Although his salivary glands were not swollen, he had high levels of anti-mumps IgM and IgG antibodies. The three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) procedure applied to magnetic resonance imaging (MRI) showed high signals in the right cochlea and vestibule. This indicated hemorrhage or a high concentration of protein in the right inner ear. This is the first case demonstrating a high 3D-FLAIR MRI signal of the inner ear in a patient with mumps deafness. Our findings suggest that 3D-FLAIR MRI may help to identify and define labyrinthitis in mumps deafness.

PMID 16978711  Int J Pediatr Otorhinolaryngol. 2006 Dec;70(12):2115-7.・・・
著者: Makoto Sugiura, Shinji Naganawa, Seiichi Nakata, Sawako Kojima, Tsutomu Nakashima
雑誌名: Acta Otolaryngol. 2007 May;127(5):547-9. doi: 10.1080/00016480600801399.
Abstract/Text Three-dimensional, fluid-attenuated inversion recovery (3D-FLAIR) of magnetic resonance imaging (MRI) has recently been developed to detect hemorrhage or high concentrations of protein. We present a patient with Ramsay Hunt syndrome, in whom high signals in the cochlear and vestibular apparatus were identified with 3D-FLAIR. The high signal areas in 3D-FLAIR were not detected by T1- and T2-weighted MRI in this case. This is the first report of high concentrations of protein in the inner ear in Ramsay Hunt syndrome using 3D-FLAIR, and suggests that high concentrations of protein in the inner ear are associated with hearing deterioration in some patients with Ramsay Hunt syndrome. 3D-FLAIR could be a useful diagnostic tool in the early stages of Ramsay Hunt syndrome.

PMID 17453483  Acta Otolaryngol. 2007 May;127(5):547-9. doi: 10.1080/0・・・
著者: Seiichi Nakata, Terukazu Mizuno, Shinji Naganawa, Makoto Sugiura, Tadao Yoshida, Masaaki Teranishi, Michihiko Sone, Tsutomu Nakashima
雑誌名: Acta Otolaryngol. 2010 May;130(5):632-6. doi: 10.3109/00016480903338123.
Abstract/Text CONCLUSION: Among patients with facial nerve paralysis, significant difference was observed on three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI) between those with and without audio-vestibular disturbance. This MRI technique may contribute to elucidation of the pathology of Ramsay Hunt syndrome and Bell's palsy.
OBJECTIVE: To evaluate the 3D-FLAIR MRI findings in patients who have facial nerve paralysis with and without audio-vestibular disturbance.
METHODS: 3D-FLAIR MRI was performed with and without gadolinium enhancement in 15 patients (5 men and 10 women) with unilateral facial nerve paralysis: 3 patients with Ramsay Hunt syndrome, 3 patients having facial nerve paralysis with hearing loss or vertigo without vesicles, and 9 patients with Bell's palsy.
RESULTS: Five of the six patients with audio-vestibular disturbance showed high signals in the inner ear on precontrast 3D-FLAIR. In comparison, among nine patients with Bell's palsy, only one patient showed high signals in the inner ear on precontrast 3D-FLAIR (p < 0.05).

PMID 19916898  Acta Otolaryngol. 2010 May;130(5):632-6. doi: 10.3109/0・・・
著者: Michihiko Sone, Terukazu Mizuno, Shinji Naganawa, Tsutomu Nakashima
雑誌名: Acta Otolaryngol. 2009 Mar;129(3):239-43. doi: 10.1080/00016480802226163.
Abstract/Text CONCLUSION: 3D-FLAIR imaging is sensitive to inflammatory inner ear disturbances and may be a useful method in investigating the severity of inner ear disturbance in cases of inflammation-induced SNHL.
OBJECTIVE: To evaluate the usefulness of the three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) sequence in investigating different etiology of inner ear disturbances in cases with inflammation-induced acute sensorineural hearing loss (SNHL).
PATIENTS AND METHODS: Five cases with inflammation-induced acute SNHL by different conditions are included in this study: acute meningitis, acute otitis media, and Wegener granulomatosis. Imaging analysis was performed using a three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) sequence, and correlation between clinical symptoms and FLAIR abnormalities was evaluated.
RESULTS: In the affected ears in all cases, 3D-FLAIR revealed high pre-contrast signal and increased signal in the cochlea after the administration of gadolinium. Enhancement was still observed in the inner ear after several months with continuing nystagmus in those cases induced by meningitis and severe otitis media. In a case with Wegener granulomatosis, increased signal in the post-contrast images was stronger on the side of the cochlea with the worse hearing level.

PMID 18720058  Acta Otolaryngol. 2009 Mar;129(3):239-43. doi: 10.1080/・・・
著者: Tadao Yoshida, Makoto Sugiura, Shinji Naganawa, Masaaki Teranishi, Seiichi Nakata, Tsutomu Nakashima
雑誌名: Laryngoscope. 2008 Aug;118(8):1433-7. doi: 10.1097/MLG.0b013e318172ef85.
Abstract/Text OBJECTIVES/HYPOTHESIS: Three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) has recently been developed to detect high concentrations of protein or hemorrhage. We have previously reported that 50% of patients with sudden sensorineural hearing loss (SNHL) show high signals in the affected inner ear on 3D-FLAIR MRI. However, the relationship between 3D-FLAIR findings and hearing prognosis is unclear. Our objective was to evaluate the relationship between the results of 3D-FLAIR MRI at 3 Tesla and prognosis in sudden SNHL.
STUDY DESIGN AND METHODS: We used 3D-FLAIR at 3 Tesla with and without gadolinium enhancement to evaluate the pathologic conditions in the inner ears of 48 patients with sudden SNHL.
RESULTS: Thirty-one of 48 patients with sudden SNHL showed high signals in the affected inner ear on precontrast 3D-FLAIR. Hearing improvement in patients with high signals in the affected inner ear on precontrast 3D-FLAIR (25 +/- 19 dB) was significantly worse than that in patients with no signal (45 +/- 27 dB; P < .05). Our analysis suggests that high signals in the affected inner ear on precontrast 3D-FLAIR MRI is a new prognostic factor for sudden SNHL.
CONCLUSIONS: 3D-FLAIR findings show that high signals in the cochlea on precontrast 3D-FLAIR are related to a poor hearing prognosis. These signals may reflect minor hemorrhage or an increased concentration of protein in the inner ear, which has passed through blood vessels with increased permeability or has originated in disrupted cells in the inner ear.

PMID 18475208  Laryngoscope. 2008 Aug;118(8):1433-7. doi: 10.1097/MLG.・・・
著者: S L Garetz, R A Altschuler, J Schacht
雑誌名: Hear Res. 1994 Jun 15;77(1-2):81-7.
Abstract/Text The effect of glutathione co-therapy on the expression of gentamicin ototoxicity was tested in pigmented guinea pigs. The first group of animals was injected with gentamicin (100 mg/kg body weight/day) for two weeks followed by 10 weeks of rest. A second group received glutathione by gastric gavage immediately prior to each gentamicin injection. Two groups of controls were treated either with saline injections or glutathione gavage alone. Auditory brainstem responses, taken at 2-week intervals, revealed a progressive gentamicin-induced hearing loss reaching a 30 to 40 dB threshold shift at 2 kHz, approximately 60 dB at 8 kHz and 80 dB at 18 kHz. Glutathione co-therapy slowed the progression of hearing loss and significantly attenuated the final threshold shifts by 20 to 40 dB. Morphological evaluation confirmed hair cell loss after gentamicin treatment and protection by glutathione. Drug serum levels were assayed at 2 and 7 days of treatment. There were no differences between the gentamicin (mean = 183 micrograms/ml; range, 90 to 300) and the gentamicin/glutathione group (mean = 164 micrograms/ml; range, 80 to 320). Antimicrobial activity of gentamicin was tested against Staphylococcus aureus and Pseudomonas aeruginosa. A 30-fold molar excess of glutathione did not influence the efficacy of gentamicin. These studies suggest that glutathione protects against ototoxicity by interfering with the cytotoxic mechanism.

PMID 7928740  Hear Res. 1994 Jun 15;77(1-2):81-7.
著者: R Ravi, S M Somani, L P Rybak
雑誌名: Pharmacol Toxicol. 1995 Jun;76(6):386-94.
Abstract/Text The dose and duration limiting toxic effects of cisplatin are ototoxicity and nephrotoxicity. While several studies have attempted to shed some light on the causes of nephrotoxicity, the reasons for ototoxicity induced by cisplatin are poorly understood. Therefore, this investigation was undertaken to delineate the potential mechanisms underlying cisplatin ototoxicity. The role of glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde levels, and antioxidant enzyme activities [superoxide dismutase, catalase, GSH peroxidase, and GSH reductase] were examined in cochlear toxicity following an acute dose of cisplatin. Male Wistar rats were treated with various doses of cisplatin. Pretreatment auditory brain stem evoked responses (ABR) were performed and then post-treatment ABRs and endocochlear potentials were also performed after three days. Acute cochlear toxicity (ototoxicity) was evidenced as elevated hearing thresholds and prolonged wave I latencies in response to various stimuli (clicks and tone bursts at 2, 8, 16 and 32 kHz) on ABRs. The endocochlear potentials were reduced (50% control) in cisplatin-treated rats as compared to control animals. The rats were sacrificed and cochleae isolated. The GSH, GSSG and malondialdehyde levels, and antioxidant enzyme activities were determined. Cisplatin ototoxicity correlated with a decrease in cochlear GSH [0.45 +/- 0.012 nmol/mg] after cisplatin administration compared to 0.95-012 nmol/mg in control cochleae (P < 0.05). Superoxide dismutase, catalase activities and malondialdehyde levels were significantly increased in the cochleae of cisplatin injected rats. Cochlear GSH-peroxidase and GSH reductase activity significantly decreased after cisplatin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 7479581  Pharmacol Toxicol. 1995 Jun;76(6):386-94.
著者: S H Sha, J Schacht
雑誌名: Hear Res. 2000 Apr;142(1-2):34-40.
Abstract/Text We have recently suggested antioxidant therapy against aminoglycoside-induced hearing loss based on the hypothesis of a redox-active aminoglycoside-iron complex causing ototoxicity. The present study compares seven antioxidants and iron chelators for their ability to attenuate gentamicin-induced free radical generation in vitro and ototoxicity in guinea pig in vivo. Free radical formation by gentamicin was measured by chemiluminescence detection both in a non-enzymatic system in vitro and in cell culture. Deferoxamine, 2,3-dihydroxybenzoate, or salicylic acid suppressed gentamicin-induced luminescence in both tests. This indicated the usefulness of the assay as a screen for potential protectants since these agents had previously been shown to attenuate gentamicin-induced ototoxicity in vivo. Histidine and D-methionine, amino acids with chelating and antioxidant properties, also suppressed gentamicin-mediated luminosity both in vitro and in cell culture. In contrast, the metal chelators succimer (2, 3-dimercaptosuccinic acid (DMSA)) and trientine (N, N'-bis[2-aminoethyl]-1,2 ethanediamine) promoted free radical formation and were excluded from further studies. Histidine and D-methionine were then administered to guinea pigs receiving concurrent treatment with gentamicin (120 mg/kgx19 days). Threshold shifts induced by gentamicin were significantly attenuated by twice-daily injections of D-methionine. Once-daily injections of histidine or D-methionine were less effective, pointing to the importance of pharmacokinetics in antioxidant protection in vivo. The study presents a simple screening system for agents with the potential to attenuate gentamicin-induced hearing loss. It also supports the hypothesis of free radical formation as an underlying cause of gentamicin ototoxicity.

PMID 10748326  Hear Res. 2000 Apr;142(1-2):34-40.
著者: Anna Rita Fetoni, Bruno Sergi, Aldo Ferraresi, Gaetano Paludetti, Diana Troiani
雑誌名: Int J Audiol. 2004 Mar;43(3):166-71.
Abstract/Text Gentamicin, acting as an iron chelator, activates membrane lipid peroxidation (MPL) and induces free radical formation, as observed in vitro and in vivo. Antioxidants, such as alpha-tocopherol, are able to suppress MLP, thus attenuating tissue damage. The present study was designed to investigate the possible protective effects of alpha-tocopherol on gentamicin ototoxicity. The study was carried out on albino guinea pigs (250-350 g). The animals were divided into four groups: group A (n = 4), injected with corn oil daily at a dose of 100 mg/kg body weight intramuscularly (IM); group B (n = 10), treated with corn oil at a dose of 100 mg/kg body weight and gentamicin base at a dose of 100 mg/kg body weight (IM); group C (n = 10). treated with gentamicin alone at a dose of 100 mg/kg body weight (IM); and group D (n = 10), treated with gentamicin at the same dose plus alpha-tocopherol acetate at dose of 100 mg/kg body weight (IM). Electrocochleographic recordings were made from an implanted round-window electrode. All animals were treated for 14 days. The compound action potentials (CAPs) were measured at 2-16 kHz at days 0, 10, 14 and 18 after treatment. Changes in cochlear function were characterized as CAP threshold shifts. Morphological changes were analysed by scanning electron microscopy. Gentamicin induced progressive high-frequency hearing loss of 50-60 dB SPL. alpha-Tocopherol co-therapy slowed the progression of hearing loss. The significant loss of outer hair cells (OHCs) in the cochlear basal turn in gentamicin-treated animals was not observed in the cochleas of animals protected with alpha-tocopherol. This study supports the hypothesis that alpha-tocopherol interferes with gentamicin-induced free radical formation, and suggests that this drug may be useful in protecting OHC function from aminoglycoside ototoxicity, thus reducing hearing loss.

PMID 15198381  Int J Audiol. 2004 Mar;43(3):166-71.
著者: Chisato Fujimoto, Tatsuya Yamasoba
雑誌名: Antioxidants (Basel). 2019 Apr 24;8(4). doi: 10.3390/antiox8040109. Epub 2019 Apr 24.
Abstract/Text Mitochondrial dysfunction is associated with the etiologies of sensorineural hearing loss, such as age-related hearing loss, noise- and ototoxic drug-induced hearing loss, as well as hearing loss due to mitochondrial gene mutation. Mitochondria are the main sources of reactive oxygen species (ROS) and ROS-induced oxidative stress is involved in cochlear damage. Moreover, the release of ROS causes further damage to mitochondrial components. Antioxidants are thought to counteract the deleterious effects of ROS and thus, may be effective for the treatment of oxidative stress-related diseases. The administration of mitochondria-targeted antioxidants is one of the drug delivery systems targeted to mitochondria. Mitochondria-targeted antioxidants are expected to help in the prevention and/or treatment of diseases associated with mitochondrial dysfunction. Of the various mitochondria-targeted antioxidants, the protective effects of MitoQ and SkQR1 against ototoxicity have been previously evaluated in animal models and/or mouse auditory cell lines. MitoQ protects against both gentamicin- and cisplatin-induced ototoxicity. SkQR1 also provides auditory protective effects against gentamicin-induced ototoxicity. On the other hand, decreasing effect of MitoQ on gentamicin-induced cell apoptosis in auditory cell lines has been controversial. No clinical studies have been reported for otoprotection using mitochondrial-targeted antioxidants. High-quality clinical trials are required to reveal the therapeutic effect of mitochondria-targeted antioxidants in terms of otoprotection in patients.

PMID 31022870  Antioxidants (Basel). 2019 Apr 24;8(4). doi: 10.3390/an・・・
著者: K A Pussegoda
雑誌名: Clin Genet. 2010 Jul;78(1):33-5. doi: 10.1111/j.1399-0004.2010.01414_2.x.
Abstract/Text
PMID 20597921  Clin Genet. 2010 Jul;78(1):33-5. doi: 10.1111/j.1399-00・・・
著者: J Lautermann, B Song, J McLaren, J Schacht
雑誌名: Hear Res. 1995 Aug;88(1-2):47-53.
Abstract/Text This study demonstrates that cisplatin ototoxicity depends on dietary factors and correlates with decreased levels of cochlear glutathione and serum albumin. After 12 days of injections, cisplatin (1 mg/kg body weight, s.c.) caused a small hearing loss in guinea pigs fed a regular, full-protein diet (9 +/- 6 dB at 8 kHz and 10 +/- 9 dB at 18 kHz) but a significantly higher hearing loss in animals on a low-protein diet (23 +/- 17 dB at 8 kHz and 32 +/- 23 dB at 18 kHz). Animals on the low-protein diet gained significantly less weight than those on the regular diet, and cisplatin treatment lowered the weight gain in both groups. The low-protein diet also significantly reduced cochlear glutathione levels from 180 +/- 50 to 90 +/- 21 nmol/mg protein and serum albumin from 2.32 +/- 0.04 to 1.75 +/- 0.06 g/dl. Cisplatin treatment tended to decrease glutathione and serum albumin in animals on a full-protein diet but not on the low-protein diet. Renal function was assessed by measuring blood urea nitrogen (BUN) and serum creatinine. While BUN and creatinine values indicated some cisplatin-induced nephrotoxicity, there was no correlation with the severity of ototoxicity. Furthermore, serum platinum levels did not differ between animals on either diet, ruling out a potential influence of altered pharmacokinetics on ototoxicity. These results suggest that the metabolic state of the animal is a risk factor for cisplatin ototoxicity.

PMID 8576002  Hear Res. 1995 Aug;88(1-2):47-53.
著者: S Murakami, N Hato, J Horiuchi, N Honda, K Gyo, N Yanagihara
雑誌名: Ann Neurol. 1997 Mar;41(3):353-7. doi: 10.1002/ana.410410310.
Abstract/Text Although the antiviral agent acyclovir is currently used for the treatment of Ramsay Hunt syndrome, its effects on facial nerve and hearing recovery remain controversial. We retrospectively analyzed the effects of acyclovir-prednisone treatment in 80 Ramsay Hunt patients. Of 28 patients for whom treatment was begun within 3 days of the onset of facial paralysis, the recovery from paralysis was complete in 21 (75%). By comparison, of 23 patients for whom treatment was begun more than 7 days after onset, recovery from facial paralysis was complete in only 7 (30%). A significant difference in facial nerve recovery was found between these groups. Early administration of acyclovir-prednisone was proved to reduce nerve degeneration by nerve excitability testing. Hearing recovery also tended to be better in patients with early treatment. There was no significant difference in facial nerve outcome between intravenous and oral acyclovir treatment.

PMID 9066356  Ann Neurol. 1997 Mar;41(3):353-7. doi: 10.1002/ana.4104・・・
著者: M Kinishi, M Amatsu, M Mohri, M Saito, T Hasegawa, S Hasegawa
雑誌名: Auris Nasus Larynx. 2001 Aug;28(3):223-6.
Abstract/Text OBJECTIVE: Although the antiviral agent, acyclovir, is currently employed for the treatment in Ramsay Hunt syndrome, the benefit of acyclovir on facial nerve is still unknown and remains controversial. This study was designed to evaluate the effect of acyclovir in facial nerve recovery in Ramsay Hunt syndrome.
METHODS: To evaluate drug effect on facial nerve function, evaluation of the facial voluntary movement and nerve excitability testing were performed. We have used an infusion therapy of acyclovir in combination with a high dose of steroid (AS), which was started within 7 days of onset of facial nerve palsy in 91 patients with Ramsay Hunt syndrome. The results were compared with those of 47 patients whose therapy was steroid alone started within 7 days of onset.
RESULTS: Out of 91 patients treated with AS, nerve exitability was good in 68 (75%), while it was poor in 17 and absent in six. Of 47 patients treated with steroid alone, nerve exitability was good in 25 (53%), while it was poor in 11 and absent in 11. There was statistically significant difference between AS and steroid therapy in the posttreatment degree of nerve function. Complete recovery to grade I in facial voluntary movement was attained in 82 of 91 patients (90%) in the AS therapy, while out of 47 patients treated with steroid alone complete recovery to grade I was attained in only 30 (64%). A statistically significant difference in the recovery rate of facial nerve function was induced between AS and steroid therapy.
CONCLUSION: The AS therapy was proved to keep good degree of nerve function indicated with nerve excitability testing and improve recovery rate of facial nerve in Ramsay Hunt syndrome. Based on this study, we now believe that the AS therapy is an advisable treatment modality to improve the recovery rate of facial nerve function in Ramsay Hunt syndrome.

PMID 11489365  Auris Nasus Larynx. 2001 Aug;28(3):223-6.
著者: C J Sweeney, D H Gilden
雑誌名: J Neurol Neurosurg Psychiatry. 2001 Aug;71(2):149-54.
Abstract/Text The strict definition of the Ramsay Hunt syndrome is peripheral facial nerve palsy accompanied by an erythematous vesicular rash on the ear (zoster oticus) or in the mouth. J Ramsay Hunt, who described various clinical presentations of facial paralysis and rash, also recognised other frequent symptoms and signs such as tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. He explained these eighth nerve features by the close proximity of the geniculate ganglion to the vestibulocochlear nerve within the bony facial canal. Hunt's analysis of clinical variations of the syndrome now bearing his name led to his recognition of the general somatic sensory function of the facial nerve and his defining of the geniculate zone of the ear. It is now known that varicella zoster virus (VZV) causes Ramsay Hunt syndrome. Compared with Bell's palsy (facial paralysis without rash), patients with Ramsay Hunt syndrome often have more severe paralysis at onset and are less likely to recover completely. Studies suggest that treatment with prednisone and acyclovir may improve outcome, although a prospective randomised treatment trial remains to be undertaken. In the only prospective study of patients with Ramsay Hunt syndrome, 14% developed vesicles after the onset of facial weakness. Thus, Ramsay Hunt syndrome may initially be indistinguishable from Bell's palsy. Further, Bell's palsy is significantly associated with herpes simplex virus (HSV) infection. In the light of the known safety and effectiveness of antiviral drugs against VZV or HSV, consideration should be given to early treatment of all patients with Ramsay Hunt syndrome or Bell's palsy with a 7-10 day course of famciclovir (500 mg, three times daily) or acyclovir (800 mg, five times daily), as well as oral prednisone (60 mg daily for 3-5 days). Finally, some patients develop peripheral facial paralysis without ear or mouth rash, associated with either a fourfold rise in antibody to VZV or the presence of VZV DNA in auricular skin, blood mononuclear cells, middle ear fluid, or saliva. This indicates that a proportion of patients with "Bell's palsy" have Ramsay Hunt syndrome zoster sine herpete. Treatment of these patients with acyclovir and prednisone within 7 days of onset has been shown to improve the outcome of recovery from facial palsy.

PMID 11459884  J Neurol Neurosurg Psychiatry. 2001 Aug;71(2):149-54.
著者: G Nigro, H Scholz, U Bartmann
雑誌名: J Pediatr. 1994 Feb;124(2):318-22.
Abstract/Text The efficacy of two regimens of ganciclovir therapy was evaluated in 12 infants with symptomatic congenital cytomegalovirus (CMV) infection. Virologic investigations included culture from urine, saliva, and cerebrospinal fluid, detection of CMV DNA by polymerase chain reaction, and detection of CMV class-specific antibodies (IgG, IgA, IgM) by enzyme immunoassays. Six infants were given ganciclovir, 5 mg/kg twice daily for 2 weeks (group 1); the other six infants were given 7.5 mg/kg twice daily for 2 weeks and 10 mg/kg three times weekly for 3 months (group 2). In group 1 the CMV cultures of specimens from three infants became sterile; two of these infants also had negative results on CMV DNA studies; results of culture and CMV DNA study were still positive after ganciclovir therapy in the remaining three infants. Subsequently, normal outcome was observed in only two patients. In group 2, all infants had negative CMV-culture and CMV DNA results; clinical improvement was evident in five infants, one of whom had later development of mild psychomotor retardation. In another infant, severe psychomotor retardation and hearing loss developed after transient improvement developed. These preliminary data indicate that a ganciclovir regimen including a higher dose and more prolonged therapy might be more effective in infants with symptomatic congenital CMV infection.

PMID 8301446  J Pediatr. 1994 Feb;124(2):318-22.
著者: Marian G Michaels, David P Greenberg, Diane L Sabo, Ellen R Wald
雑誌名: Pediatr Infect Dis J. 2003 Jun;22(6):504-9. doi: 10.1097/01.inf.0000069767.43169.2d.
Abstract/Text BACKGROUND: Congenital cytomegalovirus (CMV) infection affects approximately 1% of live births in the US. Ten percent of these infants have symptoms at birth and another 10 to 15% acquire hearing loss or developmental problems. Congenital CMV is the most common cause of nonhereditary sensorineural hearing loss in children, and progressive hearing loss is common. To arrest the natural progression of congenital CMV, children referred to our center were treated with a prolonged course of ganciclovir.
METHODS: Medical records of children with congenital CMV who were treated with ganciclovir were reviewed to tabulate their presenting symptoms, duration of treatment, audiologic and developmental assessments and complications.
RESULTS: We treated nine children with symptomatic CMV with iv ganciclovir at a median age of 10 days (range, 3 days to 11 months). Findings at diagnosis included microcephaly (five of nine); petechiae (five of nine); thrombocytopenia (seven of nine); and intracranial calcifications (six of eight). Hearing loss was noted before therapy in five of nine. The median duration of iv and subsequent oral ganciclovir was 1 year and 0.83 year, respectively. Median follow-up was 2 years (range, 1 to 7 years). No child had progression of hearing loss; improvement occurred in two. Seven children had at least one complication of ganciclovir therapy: central venous catheter/site infection (six); catheter malfunction (three); and neutropenia (one).
CONCLUSION: Of nine children none treated with ganciclovir for congenital CMV had detectable progressive hearing loss. Complications associated with iv therapy occurred frequently. Currently available oral analogues of ganciclovir may facilitate earlier and more prolonged therapy for children with symptomatic congenital CMV and should be subjected to randomized controlled trials.

PMID 12799506  Pediatr Infect Dis J. 2003 Jun;22(6):504-9. doi: 10.109・・・
著者: Naoko Tanaka-Kitajima, Naomi Sugaya, Takeshi Futatani, Hirokazu Kanegane, Chizuko Suzuki, Makoto Oshiro, Masahiro Hayakawa, Masahide Futamura, Tsuneo Morishima, Hiroshi Kimura
雑誌名: Pediatr Infect Dis J. 2005 Sep;24(9):782-5.
Abstract/Text BACKGROUND: Congenital cytomegalovirus (CMV) infection is common, and its morbidity rate is high. Ganciclovir (GCV) treatment has been used for congenital CMV infection, but there are few reports on viral loads associated with GCV therapy.
METHODS: A real-time PCR assay was used to monitor viral load in 6 cases of symptomatic CMV infection that received GCV therapy. Initially GCV was given at a dose of 5-12 mg/kg/d for 2-7 weeks. In 2 cases, additional doses were given as symptoms returned.
RESULTS: After GCV administration, active signs of chorioretinitis, thrombocytopenia and anemia disappeared or improved in all cases. During GCV therapy, viral loads decreased while patients improved clinically and increased again when GCV therapy was stopped. Although CMV DNA continued to be detectable for a long period, clinical findings did not always worsen. In 2 cases, an improvement of hearing loss was observed.
CONCLUSION: GCV therapy transiently suppresses the CMV concentrations. Subsequent increases of viral titers do not appear to be correlated with the clinical course or neurologic outcome.

PMID 16148844  Pediatr Infect Dis J. 2005 Sep;24(9):782-5.
著者: E P Acosta, R C Brundage, J R King, P J Sánchez, S Sood, V Agrawal, J Homans, R F Jacobs, D Lang, J R Romero, J Griffin, G Cloud, R Whitley, D W Kimberlin, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group
雑誌名: Clin Pharmacol Ther. 2007 Jun;81(6):867-72. doi: 10.1038/sj.clpt.6100150. Epub 2007 Mar 28.
Abstract/Text Cytomegalovirus (CMV) is the most common viral congenital infection, producing both sensorineural hearing loss and mental retardation. Our objective was to assess the population pharmacokinetics of a research-grade oral valganciclovir solution in neonates with symptomatic congenital CMV disease. Twenty-four neonates received 6 weeks of antiviral therapy. Ganciclovir and valganciclovir were measured by liquid chromatography/tandem mass spectroscopy. NONMEM version VI beta was used for population analyses. All profiles were consistent with a one-compartment model. Postnatal age, body surface area, and gender did not improve the model fit after body weight was taken into account. The typical value of clearance (l/h), distribution volume (l), and bioavailability of ganciclovir were 0.146 x body weight (WT)(1.68), 1.15 x WT, and 53.6%, respectively. Although these results cannot be extrapolated to extemporaneously compounded valganciclovir preparations, they provide the foundation on which a commercial-grade valganciclovir oral solution may be a viable option for administration to neonates.

PMID 17392728  Clin Pharmacol Ther. 2007 Jun;81(6):867-72. doi: 10.103・・・
著者: David W Kimberlin, Edward P Acosta, Pablo J Sánchez, Sunil Sood, Vish Agrawal, James Homans, Richard F Jacobs, David Lang, Jose R Romero, Jill Griffin, Gretchen A Cloud, Fred D Lakeman, Richard J Whitley, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group
雑誌名: J Infect Dis. 2008 Mar 15;197(6):836-45. doi: 10.1086/528376.
Abstract/Text BACKGROUND: Intravenous ganciclovir administered for 6 weeks improves hearing outcomes in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system.
METHODS: Twenty-four subjects received antiviral therapy for 6 weeks. Serial pharmacokinetic assessments were performed after administration of valganciclovir oral solution and of intravenous ganciclovir.
RESULTS: On the basis of a previous pharmacokinetic study of the use of intravenous ganciclovir in this population, a target AUC12 (area under the concentration-time curve over a 12-h period) of 27 mg x h/L was defined. The median dose of oral valganciclovir administered in the present trial was 16 mg/kg, which produced a geometric mean AUC12 of 27.4 mg x h/L. The bioavailability of valganciclovir was 41.1%. Of the 18 subjects who had detectable CMV in whole blood at baseline or during therapy, 11 had <4 log viral DNA copies/mL at baseline, and 7 had > or =4 log viral DNA copies/mL at baseline; subjects who started the study with the higher viral burden experienced greater decreases in viral load but did not clear virus during the 42-day course of therapy. Neutropenia of grade 3 or 4 developed in 38% of subjects.
CONCLUSIONS: In neonates with symptomatic congenital CMV disease, valganciclovir oral solution provides plasma concentrations of ganciclovir comparable to those achieved with administration of intravenous ganciclovir. The results of the present study cannot be extrapolated to extemporaneously compounded liquid formulations of valganciclovir.

PMID 18279073  J Infect Dis. 2008 Mar 15;197(6):836-45. doi: 10.1086/5・・・
著者: Jayne M Ramirez Inscoe, Thomas P Nikolopoulos
雑誌名: Otol Neurotol. 2004 Jul;25(4):479-82.
Abstract/Text BACKGROUND: Concerns have been expressed with regard to suitability for cochlear implantation of children deafened by cytomegalovirus because of possible coexisting central disorders/learning difficulties. The aim of the current study was to assess speech perception and intelligibility of speech produced by children deafened by cytomegalovirus and compare their progress with that of congenitally deaf children after cochlear implantation.
METHODS: The study assessed 16 implanted children who were deafened by cytomegalovirus, using the Iowa Closed Sentence Test and Speech Intelligibility Rating. The results were compared with those of a group of 131 children who had undergone implantation who were congenitally deaf but did not have cytomegalovirus as the cause of deafness. The mean age at implantation was 3.9 years for the cytomegalovirus group (median, 3.5 years) and 4.1 years (median, 4 years) for the congenitally deaf children. They all received the Nucleus multichannel cochlear implant system. The follow-up period ranged from 1 to 5 years after implantation for both groups.
RESULTS: After cochlear implantation, the intelligibility of speech produced by children deafened by cytomegalovirus had a wide range, varying from unintelligible speech to connected speech intelligible to all listeners. Relative to the median score for the control group at the last evaluation interval, 3 of the 16 children with cytomegalovirus (19%) performed better, 8 children (50%) performed more poorly, and 5 (31%) performed the same. The difference between the two groups was not statistically significant (p > 0.05). With regard to speech perception Iowa Sentence Test (Level B), relative to the median score for the control group at the last evaluation interval, 5 of the 16 children with cytomegalovirus (31%) performed better, 3 children (19%) performed more poorly, and 8 (50%) performed the same. The difference between the two groups was not statistically significant (p > 0.05). With regard to Level A and relative to the median score for the control group at the last evaluation interval, 1 of the 16 children with cytomegalovirus (6%) performed better, 6 children (38%) performed more poorly, and 9 (56%) performed the same. The difference between the two groups was statistically significant (p = 0.04).
CONCLUSION: The results of the current study showed that cytomegalovirus alone, as a cause of deafness, is not a contraindication for cochlear implantation. Parents should be informed about the wide range of linguistic outcomes after implantation and that these children may need more specific or intensive rehabilitation. Although additional problems are common and outcomes may, on average, be poorer, cochlear implantation can provide useful auditory input to these children. Further research is needed to identify factors associated with cytomegalovirus that may influence the outcomes.

PMID 15241225  Otol Neurotol. 2004 Jul;25(4):479-82.
著者: Daniel J Lee, Lawrence Lustig, Margaret Sampson, Jill Chinnici, John K Niparko
雑誌名: Otolaryngol Head Neck Surg. 2005 Dec;133(6):900-5. doi: 10.1016/j.otohns.2005.08.013.
Abstract/Text OBJECTIVE: Human cytomegalovirus (CMV) is a commonly recognized viral cause of perinatal sensorineural hearing loss. CMV-infected infants are also at risk for developmental neurological deficits. This retrospective study assesses the impact of CMV-induced deafness on pediatric cochlear implant outcomes.
STUDY DESIGN AND SETTING: Thirteen patients from the Johns Hopkins pediatric cochlear implant database were identified with CMV-related deafness. A retrospective review of the medical records of the Johns Hopkins Hospital was performed.
RESULTS: The mean age at implantation was 5.6 years. Follow-up audiometric data ranged from 6 to 48 months postoperatively. Mean speech perception scores were 4.5 (out of 6) following implantation.
CONCLUSION: We have shown that cochlear implants can provide useful speech comprehension to patients with CMV-related deafness. Speech recognition scores were within the range established by our overall pediatric implant population.
SIGNIFICANCE: This observation underscores the importance of a multidisciplinary rehabilitation program following implantation in these patients at risk for cognitive delay.

PMID 16360511  Otolaryngol Head Neck Surg. 2005 Dec;133(6):900-5. doi:・・・
著者: Satoshi Iwasaki, Hiroshi Nakanishi, Kiyoshi Misawa, Toru Tanigawa, Kunihiro Mizuta
雑誌名: Audiol Neurootol. 2009;14(3):146-52. doi: 10.1159/000171476. Epub 2008 Nov 13.
Abstract/Text OBJECTIVE: To evaluate the development of speech perception and auditory skills after cochlear implantation in deaf children with asymptomatic congenital cytomegalovirus (CMV) infection diagnosed based on the presence of CMV DNA in the neonatal urine.
STUDY DESIGN: A prospective study of congenital CMV infection was done between 1996 and 2003. Of 18 children diagnosed with congenital CMV infection, 2 deaf children with asymptomatic CMV infections received cochlear implantation.
RESULTS: The 2 deaf children who received cochlear implantation had delayed-onset, progressive sensorineural hearing loss on follow-up audiometric examinations administered at 29 and 39 months of age. After cochlear implantation, their Infant-Toddler Meaningful Auditory Integration Scale scores increased consistently during 36 months of follow-up; these results were similar to those of 5 congenitally deaf children without CMV infection who had cochlear implantation.
CONCLUSIONS: Cochlear implantation was effective for improving the development of speech perception and auditory skills in deaf children with asymptomatic congenital CMV infection. There was no significant difference in the development of useful auditory integration between our general pediatric cochlear implant population without CMV infection and those with asymptomatic CMV infection.

Copyright 2008 S. Karger AG, Basel.
PMID 19005248  Audiol Neurootol. 2009;14(3):146-52. doi: 10.1159/00017・・・
著者: Haruo Yoshida, Yukihiko Kanda, Haruo Takahashi, Ikue Miyamoto, Tomomi Yamamoto, Hidetaka Kumagami
雑誌名: Otol Neurotol. 2009 Sep;30(6):725-30. doi: 10.1097/MAO.0b013e3181b1212e.
Abstract/Text OBJECTIVE: To assess the impact of cochlear implantation (CI) on children with cytomegalovirus (CMV)-induced deafness.
STUDY DESIGN: Retrospective chart review.
PATIENTS: Four children with congenital CMV-related deafness (CMV group) and 17 children with congenital deafness without CMV infection as the cause of deafness (non-CMV group). The age at CI ranged from 2.0 to 3.3 years (mean, 2.6 yr) in the CMV group and from 1.8 to 3.6 years (mean, 2.6 yr) in the non-CMV group. Their follow-up period ranged from 3.0 to 4.3 years (mean, 3.3 yr) in the CMV group and from 1.6 to 4.3 years (mean, 3.3 yr) in the non-CMV group.
METHODS: Evaluation and comparison of preoperative and postoperative hearing levels, motor, social, and language development, Infant-Toddler Meaningful Auditory Integration Scale, and Enjoji Scale of Infant Analytical Development between the 2 groups.
RESULTS: Within 12 months after CI, the mean score of both language perception and production was poorer in the CMV group than in the non-CMV group, and the difference in the language production was statistically significant. However, 12 months after CI, the language perception and production showed good progress at levels similar to that of the non-CMV group.
CONCLUSION: Long-term results of the language perception and production after CI was satisfactory in Japanese children with congenital CMV-related deafness compared with in subjects deafened by other causes. CMV alone, as a cause of deafness, is not likely a contraindication for CI.

PMID 19638941  Otol Neurotol. 2009 Sep;30(6):725-30. doi: 10.1097/MAO.・・・
著者: Andrea Ciorba, Roberto Bovo, Patrizia Trevisi, Chiara Bianchini, Rosa Arboretti, Alessandro Martini
雑誌名: Eur Arch Otorhinolaryngol. 2009 Oct;266(10):1539-46. doi: 10.1007/s00405-009-0944-5. Epub 2009 Mar 13.
Abstract/Text The aim of the study was to characterize the audiological consequences of congenital cytomegalovirus infection (CMV) and to evaluate the outcome of rehabilitation with hearing aids and/or cochlear implant (CI), associated with an adequate speech-language therapy. A retrospective review of data was made from a total of 16 infants, affected by severe to profound hearing loss from congenital CMV infection, referred to a tertiary audiological center for rehabilitation. Audiological evaluation was performed using behavioral audiometry, auditory brainstem responses (ABR) and/or electrocochleography (ECochG). Of the 16 children (median age at diagnosis of hearing loss: 21.33 +/- 0.7 months) with CMV hearing loss, 14 were affected by profound bilateral hearing loss and received a CI, while 2 were affected by bilateral severe hearing loss and received hearing aids. Cochlear implants can provide useful speech comprehension to patients with CMV-related deafness, even if language development is lower when compared to a group of Connexin (Cx) 26+ cochlear-implanted children (eight subjects), matched for age. Congenital CMV infection still represents a serious clinical condition, as well as an important cause of hearing loss in children. More studies have claimed to identify the pathophysiological mechanisms of damage and thus to ensure a better therapeutic approach. Nonetheless, in cases of CMV-deafened babies, the overall outcome of cochlear implantation is good.

PMID 19283400  Eur Arch Otorhinolaryngol. 2009 Oct;266(10):1539-46. do・・・
著者: Vikas Malik, Iain A Bruce, Stephen J Broomfield, Lisa Henderson, Kevin M J Green, Richard T Ramsden
雑誌名: Laryngoscope. 2011 Aug;121(8):1780-4. doi: 10.1002/lary.21818.
Abstract/Text OBJECTIVES/HYPOTHESIS: Congenital cytomegalovirus (cCMV) infection is a common cause of sensorineural hearing loss (SNHL). The incidence of SNHL is higher in symptomatic cCMV infants and is usually identified early. By contrast, the incidence of SNHL is lower in children with asymptomatic cCMV, and the hearing loss can be delayed in onset and progressive. The objective was to compare the outcome of cochlear implantation in children deafened by cCMV with a control group of children with implants who do not have the condition.
STUDY DESIGN: Retrospective review of case notes and data base.
METHODS: Retrospective review of 14 children with asymptomatic cCMV who underwent cochlear implantation. Their outcome measures were compared with those of a matched population by using standard assessment tools.
RESULTS: In the study group, the Modified Categories of Auditory Performance (M-CAP) score (range, 1-7) ranged from 2 to 7 (mean, 4.2). In the control group, the M-CAP ranged from 5 to 7 (mean, 6.0). In the study group, the Manchester Spoken Language Development Scale (MSLDS) score (range, 1-10) ranged from 1 to 9 (mean, 5.4). In the control group, the MSLDS ranged from 3 to 10 (mean, 8.1).
CONCLUSIONS: Children with asymptomatic deafness caused by cCMV benefit from cochlear implantation but perform less well than a comparable group of children with implants who do not have cCMV. There is a range of performance in the cCMV group that may relate to the degree of motor or cognitive disabilities.

Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.
PMID 21792969  Laryngoscope. 2011 Aug;121(8):1780-4. doi: 10.1002/lary・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから