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鼓室内注射药物治疗梅尼埃病国际专家共识(全译文)

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临床耳鼻咽喉头颈外科杂志 2022年第7期36卷 487-491页

作者：李姝娜 Ilmari Pyykk?ö 张青杨军段茂利上海交通大学医学院附属新华医院耳鼻咽喉-头颈外科上海200092 上海交通大学医学院耳科学研究所上海耳鼻疾病转化医学重点实验室 Hearing and Balance Research Unit Field of OtolaryngologySchool of MedicineFaculty of Medicine and Health Technolo gyTampere UniversityTampereFinland Department of Otolaryngology-Head&.Neck Audiology and NeurotologyKarolinska University HospitalStockholmSwe den Division of Ear Nose and Throat DiseasesDepartment of Clinical ScienceIntervention and TechnologyKarolinska Institute StockholmSweden

目的:鼓室内(intratympanic,IT)注射药物治疗梅尼埃病(MD)因其疗效显著而备受关注。由于IT注射药物治疗MD的共识和新证据的发布,对IT注射药物治疗MD进行细节上的补充具有重要意义。方法:检索近二十年来有关IT注射药物治疗MD的文献,参考... 详细信息

目的:鼓室内(intratympanic,IT)注射药物治疗梅尼埃病(MD)因其疗效显著而备受关注。由于IT注射药物治疗MD的共识和新证据的发布,对IT注射药物治疗MD进行细节上的补充具有重要意义。方法:检索近二十年来有关IT注射药物治疗MD的文献,参考《梅尼埃病治疗国际共识(ICON)》(2018年),《美国梅尼埃病临床实践指南》(2020年)和《梅尼埃病诊断治疗的欧洲立场声明》(2018),并遵循来自欧洲、美国和中国的专家意见。结果:专家一致认为:①鼓室内注射甲泼尼龙(ITM)对眩晕控制的疗效优于鼓室内注射地塞米松(ITD),ITM有恢复MD患者听力的可能性。②由于氨基糖甙类药物的耳毒性,鼓室内注射庆大霉素(ITG)在听力良好MD患者中的应用持谨慎态度。但也有研究表明,小剂量ITG对听力没有显著影响,还需要高水平证据的临床研究进一步证明。③目前普遍接受的ITG治疗终点是在12个月内无眩晕发作或受累耳客观检查提示前庭功能丧失。结论:对IT注射药物治疗MD的药物类型、疗效和治疗终点还需要更多高证据水平的研究进行评价。

关键词：梅尼埃病鼓室内注射治疗糖皮质激素甲泼尼龙地塞米松氨基糖甙类药物庆大霉素

Endolymphatic hydrops in Meniere's disease secondary to otitis media and visualized by gadolinium-enhanced magnetic resonance imaging

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World Journal of Otorhinolaryngology 2013年第1期3卷 22-25页

作者： Jing Zou Ilmari Pyykk?? Hearing and Balance Research Unit Field of Oto-laryngology School of Medicine University of Tampere

Aimed to test the hypothesis that endolymphatic hydrops in Meniere's disease(MD) may be secondary to otitis media, history of a patient who developed MD as a complication of otitis media was reviewed. The inner ear was imaged using a 3.0 Tesla MR system post-intravenous injection of gadolinium-tetraazacyclododecane-tetraacetic acid(Gd-DOTA) in a standard single dosage(0.1 mmol/kg). Both t2-spc-rst-tra-iso(T2-weighted) and heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery magnetic resonance imaging [h T(2)W-3D-FLAIR] sequences were applied. As a result, in the T2-weighted images, the perilymph and endolymph, cerebrospinal fluid surrounding the eighth nerve(N8), and middle ear granulation tissue showed intense signals. In the h T(2)W-3D-FLAIR images, evident enhancement by Gd-DOTA was observed in the middle ear cavity and the perilymphatic compartments of the cochlea. Cochlear endolymphatic hydrops was implicated by the enlarged scala media in the basalturn. In general, the Gd-DOTA uptake in the vestibule was weak, and signs of vestibular endolymphatic hydrops were obvious. The N8 on the diseased side was also significantly enhanced. To conclude, endolymphatic hydrops in MD may be induced by otitis media. Cochlear endolymphatic hydrops in MD secondary to otitis media may not follow the classical pattern.

关键词： Endolymphatic hydrops Otitis media Meniere'sdisease Magnetic resonance imaging Sensorineuralhearing loss

MEFV,IRF8,ADA,PEPD,and NBAS gene variants and elevated serum cytokines in a patient with unilateral sporadic Meniere's disease and vascular congestion over the endolymphatic sac

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Journal of Otology 2022年第3期17卷 175-181页

作者： Jing Zou Zikai Zhao Guoping Zhang Qing Zhang Ilmari Pyykk?o Department of Otolaryngology-Head and Neck Surgery Changhai HospitalSecond Military Medical UniversityShanghaiChina Faculty of Information Technology and Communication Sciences Tampere UniversityTampereFinland Hearing and Balance Research Unit Field of OtolaryngologySchool of MedicineFaculty of Medicine and Health TechnologyTampere UniversityTampereFinland

The etiology and underlying mechanism of Meniere's disease(MD)development are still unknown,although inflammation and autoimmunity have been implicated as underlying mechanisms.The human endolymphatic sac(ES)has been reported to have innate and adaptive immune capacity in local immune reactions.In vivo demonstration of inflammation of the ES in patients with MD is missing in the literature.We report the case of a 47-year-old female patient diagnosed with unilateral MD with genetic variants and cytokine markers indicating inflammation and vascular congestion of the ES.Endolymphatic hydrops in the right cochlea(grade 2)and vestibulum(grade 3)were detected using MRI.She carried heterozygous variants in MEFV(c.442G>C),IRF8(c.1157G>T),ADA(c.445C>T),PEPD(c.151G>A),NBAS(c.4049T>C),CSF2RB(c.2222C>T),HPS6(c.277G>T),IL2RB(c.1109C>T),IL12RB1(c.1384G>T),IL17RC(c.260_271del GCAAGAGC TGGG),LIG1(c.746G>A),RAG1(c.650C>A),and SLX4(c.1258G>C,c.5072A>G).In the serum,the levels of granulocyte colony-stimulating factor(G-CSF),macrophage inflammatory protein 1a,and IL7 were significantly elevated,and the level of IL2Ra was reduced.Intratympanic administration of dexamethasone temporarily alleviated her hearing loss.Her vertigo was significantly relieved but remained slight after ES administration of corticosteroids.

关键词： Meniere's disease Autoinflammation Autoimmune Immune organ Endolymphatic sac

An Animal Model of Sudden Onset Sensorineural Hearing Loss with Vestibular Function Disturbances Induced By Mitochondrial Toxin

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Journal of Otology 2006年第2期1卷 86-93页

作者： pyykk ilmari Department of Otolaryngology Tampere University HospitalTeiskontie 3533520 TampereFinland (J.Z.I.P.)

Objective To establish an animal model of sudden onset sensorineural hearing loss (SSNHL) to study its mechanisms. Materials and methods The inner ear was exposed to 3-nitropropionic acid at 0.5 mol/L (3-NP (H)) and 0.3 mol/L (3-NP (L)) through the round window membrane for 30 minutes in 50 male guinea pigs. Thresholds of auditory brainstem responses(ABR) were established before the treatment and retested at 4 hours, 1 day, 3 days and 6 days following 3-NP exposure. Control animals were treated with phosphate buffered saline (PBS) and their ABRs were retested at 4 hours and 1 day after the treatment. Animals were monitored for nystagmus and postural signs of vestibular dysfunction, using a digital video camera, following the treatment procedure. Specimens were taken at 12 hours, 1 day, 3 days and 7 days following 3-NP(H) exposure and embedded in JB4 for light microscopy observation. Results ABRs were lost in all animals tested at 4 hours following 3-NP (H) exposure. The rate of complete ABR loss decreased as post-treatment test time increased. ABRs were lost in 80% (4/5) of the animals at 1 day after exposure to 3-NP (L). Spontaneous horizontal nystagmus with a fast phase away from the treated ear developed in all 3-NP (H)-treated animals and in 20 % ( 1/5) of the animals exposed to 3-NP (L), except for the one treated bilaterally. Various degree of postural disturbances consistent with unilateral vestibular dysfunction, such as spontaneous barrel rolling towards the exposure side while walking, were seen in all animals exposed to 3-NP(H) and 40% (2/5) of animals exposed to 3-NP(L), except for the one animal treated bilaterally, which showed no signs of imbalance. Both nystagmus and postural disturbances resolved in 2 days following 3-NP exposure. Histological study showed temporary edema tin the organ or Corti, Claudius cells and the inner sulcus cells 3 days after 3-NP (H) treatment. Enlargement of intercellular space in the spiral prominence was first noticed at 12 hours post-3-NP (H) exposure, progressed at d

关键词： Hearing loss vertigo mitochondrial dysfunction animal model histology

用MRI体内观测钥孔嘁血蓝素中耳免疫诱导的内淋巴积水的初步探讨

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中华耳科学杂志 2005年第3期3卷 200-203页

作者：邹静 Ilmari Pyykk? Brje BJELKE 上海第二医科大学附属新华医院耳鼻咽喉-头颈外科 Department of Otolaryngology Tampere University HospitalTampereFinland KTH and KI Nano and Microtechnology Center Department of RadiologyCenter for Surgical SciencesHuddinge University HospitalKarolinska InstitutetStockholmSweden

目的用磁共振成像方法研究中耳免疫反应诱导的动物内淋巴积水。方法将9只豚鼠分为2组,中耳免疫组(4只)和磷酸盐缓冲液(Phosphate buffered saline,PBS)对照组(5只)。先用KLH加福氏完全佐剂行四肢趾蹼免疫,2周后将KLH投放至中耳进行局部... 详细信息

目的用磁共振成像方法研究中耳免疫反应诱导的动物内淋巴积水。方法将9只豚鼠分为2组,中耳免疫组(4只)和磷酸盐缓冲液(Phosphate buffered saline,PBS)对照组(5只)。先用KLH加福氏完全佐剂行四肢趾蹼免疫,2周后将KLH投放至中耳进行局部免疫。另外5只豚鼠中耳放置PBS作为对照组。用gadolinium增强的磁共振成像观察内耳淋巴液的动态变化,用耳蜗电图评估听功能改变。结果在KLH中耳免疫的动物中,2只发生内淋巴积水,3只血迷路屏障通透性增加,2只听力损失大于10dB。结论磁共振成像可以显示KLH中耳免疫反应的耳蜗改变,内淋巴积水和血迷路屏障通透性的增加提示存在着一个“漏的迷路”,将有可能为内耳疾病的诊断提供更加精确的依据。

关键词：梅尼埃病核磁成像免疫损伤血迷路屏障中耳炎内淋巴积水免疫诱导钥孔嘁血蓝素中耳初步探讨

Dexamethasone does not affect endolymphatic hydrops(EH)in patients with Meniere's disease within 24 h,and intratympanic administration of gadolinium plus dexamethasone simplifies high-quality imaging of EH using a novel protocol of 7 min

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Journal of Otology 2022年第3期17卷 164-174页

作者： Jing Zou Zikai Zhao Hongbin Li Guoping Zhang Qing Zhang Jianping Lu Ilmari Pyykk?o Department of Otolaryngology-Head and Neck Surgery Changhai HospitalSecond Military Medical UniversityShanghaiChina Department of Radiology Changhai HospitalSecond Military Medical UniversityShanghaiChina Faculty of Information Technology and Communication Sciences Tampere UniversityTampereFinland Hearing and Balance Research Unit Field of OtolaryngologySchool of MedicineFaculty of Medicine and Health TechnologyTampere UniversityTampereFinland

Background:Intratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops(EH)using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min.The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI.Materials and methods:In an in vitro study,the potential impact of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography(HPLC)after mixing with GdDTPA.Ten patients with definite Meniere's disease(MD)were recruited to study the potential interference of dexamethasone on MRI visualization of EH,and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation(hT2FLAIR-MZFI)sequence.Results:The retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA.EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone.Excellent inner ear images were obtained from all patients,and EHs with various grades were displayed.There were significant correlations between diagnosis and cochlear EH(p<0.01,Spearman's Rho),between diagnosis and vestibular EH(p<0.01,Spearman's Rho),and between cochlear and vestibular EH(p<0.01,Spearman's Rho).The distribution of Gd-DTPA plus dexamethasone negatively correlated with the grade of vestibular EH.Injury of the endolymph-perilymph barrier was detected in one cochlea and three vestibules of 59 inner ears with MD.Conclusions:Intratympanic administration of Gd-DTPA plus d

关键词： Meniere's disease Endolymphatic hydrops MRI Contrast agent Therapeutics Topical administration

耳蜗振动创伤后血迷路屏障变化的磁共振成像表现

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中华耳科学杂志 2006年第1期4卷 61-64页

作者：邹静 Ilmari Pyykk? Pivi Sutinen Esko Toppila 上海交通大学医学院附属新华医院耳鼻咽喉-头颈外科上海200092 Department of OtolaryngologyTampere University Hospital TampereFinland Department of Physical Medicine and RehabilitationNorthern Karelian Central Hospital JoesuuFinland Department of PhysicsInstitute of Occupational Health HelsinkiFinland

目的在动物模型中探讨电钻振动诱导听力减退的机制和可能的血迷路屏障变化。方法用电磁振荡器在5只豚鼠听泡上产生可重复的振动,其振动频率为250 Hz,用复合动作电位评估其听功能,振动后3小时至4 天用4．7特斯拉磁共振成像分析其血迷路... 详细信息

目的在动物模型中探讨电钻振动诱导听力减退的机制和可能的血迷路屏障变化。方法用电磁振荡器在5只豚鼠听泡上产生可重复的振动,其振动频率为250 Hz,用复合动作电位评估其听功能,振动后3小时至4 天用4．7特斯拉磁共振成像分析其血迷路屏障变化。静脉注射T1增强剂Gadolinium-diethylenetriaminepentaacetate- bismethylamide(Gd-DTPA-BMA)作为血迷路屏障的示踪剂。结果振动诱导平均听力损失40 dB HL,在振动后立即测试的耳蜗中,其中阶摄取Gd-DTPA-BMA,提示血迷路屏障通透性增加。在振动后2天至4天的动物中,其中阶内无Gd-DTPA-BMA摄取。结论 250 Hz振动使血路屏障通透性增加是使导致听力减退的原因之一。其通透性的变化为一个可逆的过程。

关键词：动物模型对比剂钻诱导听力减退内耳屏障磁共振成像

Nanoparticle based inner ear therapy

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World Journal of Otorhinolaryngology 2013年第4期3卷 114-133页

作者： Ilmari Pyykk? Jing Zou Ya Zhang Weikai Zhang Hao Feng Paavo Kinnunen Department of Otolaryngology Hearing and Balance Research Unit University Hospital of Tampere 33520 Tampere Finland Department of Otolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Department of Orthopedics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Department of Biomedical Engineering and Computational Science Aalto University 02150 Esbo Finland

Synthetic nanoparticles can be used to carry drugs, genes, small interfering RNA(si RNA) and growth factors into the inner ear, to repair, restore and induce cellular regeneration. Nanoparticles(NPs) have been developed which are targetable to selected tissue, traceable in vivo, and equipped with controlled drug/gene release. The NPs are coated with a ‘stealth' layer, and decorated with targeting ligands, markers, transfection agents and endosomal escape peptides. As payloads, genes such as the BDNF-gene, Math1-gene and Prestin-gene have been constructed and delivered in vitro. Short-hairpin RNA has been used in vitro to silence the negative regulator of Math1, the inhibitors of differentiation and DNA binding. In order to facilitate the passage of cargo from the middle ear to the inner ear, the oval window transports gadolinium chelate more efficiently than the round window and is the key element in introducing therapeutic agents into the vestibule and cochlea. Depending upon the type of NPs, different migration and cellular internalization pathways are employed, and optimal carriers should be designed depending on the cargo. The use of NPs as drug/gene/si RNA carriers is fascinating and can also be used as an intraoperative adjunct to cochlear implantation to attract the peripheral processes of the cochlear nerve.

关键词：英文文摘医学杂志

用4.7特斯拉磁共振成像活体内观测豚鼠实验性内淋巴积水

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中华耳科学杂志 2005年第3期3卷 159-164页

作者：邹静 Ilmari Pyykk? Poul Bretlau Tomas Klason Brje Bjelke 上海第二医科大学附属新华医院耳鼻咽喉头颈外科 Department of Otolaryngology Department of Clinical NeuroscienceKarolinska InstitutetKarolinska HospitalStockholmSweden Department of OtolaryngologyTampere University HospitalTampereFinland Department of Otolaryngology-Head&Neck Surgery RigshospitaletCopenhagenDenmark MR-Center Department of Clinical NeuroscienceKarolinska InstitutetKarolinska HospitalStockholmSweden

目的探讨用4.7特斯拉试验用磁共振成像系统能否在豚鼠中检测内淋巴积水。方法20只白色或者杂色豚鼠用于该研究。5只正常豚鼠作为对照组,15只豚鼠用于制作内淋巴积水模型。9只内淋巴囊破坏组中的5只和6只内淋巴囊完整组(与乙状窦游离)动... 详细信息

目的探讨用4.7特斯拉试验用磁共振成像系统能否在豚鼠中检测内淋巴积水。方法20只白色或者杂色豚鼠用于该研究。5只正常豚鼠作为对照组,15只豚鼠用于制作内淋巴积水模型。9只内淋巴囊破坏组中的5只和6只内淋巴囊完整组(与乙状窦游离)动物采用gadolinium(Gd)-DTPA-BMA增强MRI检测内淋巴积水。结果由于Gd-DTPA-BMA主要进入鼓阶和前庭阶,耳蜗的三个阶可在所有动物中由MRI清晰显示。在内淋巴囊完整组,内淋巴囊手术后6天MRI即可检测到内淋巴积水,并且由组织学证实。在内淋巴囊破坏组中的1只动物,因内耳屏障的严重破坏而使Gd-DTPA-BMA快速漏入中阶,MRI可检测到该变化,其听力损失为60dB。结论用Gd-DTPA-BMA增强的高分辨MRI可检测出内淋巴积水,有可能对积水程度进行定量测试。在Gd-DTPA-BMA的帮助下,内耳屏障损伤或可能的膜破裂可以被检出。

关键词：动物模型耳蜗对比剂内淋巴积水磁共振成像磁共振成像系统杂色豚鼠 Gd-DTPA-BMA 实验性活体内