RESUMO
This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.
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Perda Auditiva , Neuroma Acústico , Perilinfa , Proteoma , Humanos , Neuroma Acústico/líquido cefalorraquidiano , Neuroma Acústico/metabolismo , Neuroma Acústico/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Perilinfa/metabolismo , Perda Auditiva/líquido cefalorraquidiano , Adulto , Idoso , Líquido Cefalorraquidiano/metabolismo , Audiometria de Tons PurosRESUMO
We report a case of a woman presenting with unilateral right profound hearing loss accompanied by vertigo secondary to barotrauma-induced perilymph fistula during recreational skydiving. Video head impulse test demonstrated a reduced gain in both the right horizontal and right anterior semicircular canals accompanied by frequently gathered overt corrective saccades. High-resolution computed tomography revealed an enlarged vestibular aqueduct on the affected side, a predisposing factor for the development of perilymph fistula. An exploratory tympanotomy was performed during which a perilymph leak was visualized at the round window niche. Temporal fascia patches enforced by absorbable gelatin sponges were applied to both round and oval windows. During post-surgery follow-up, the patient remained free of vestibular symptoms. An audiogram displayed mild improvement in the right ear speech reception threshold, although her hearing remained non-serviceable. The video head impulse test showed a favorable dynamic with a stepwise return to normal gain values in all semicircular canals and the disappearance of overt corrective saccades. This is the first case in which video head impulse test was employed as a valuable diagnostic tool for the evaluation and post-surgery follow-up of vestibular function in a barotrauma-induced perilymph fistula. The demonstration of an enlarged vestibular aqueduct on high-resolution computed tomography and the risk of perilymph fistula recurrence are discussed.
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Barotrauma , Fístula , Doenças Vestibulares , Humanos , Feminino , Perilinfa , Teste do Impulso da Cabeça , Doenças Vestibulares/complicações , Barotrauma/complicações , Osso Temporal , Fístula/diagnóstico por imagem , Fístula/etiologia , Fístula/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The use of intratympanic (IT) steroids has drastically increased over the past 10-15 years to manage many otological pathologies. OBJECTIVES: This study aimed to compare the concentrations of prednisolone and prednisolone sodium succinate (SS) in the plasma and inner ear perilymph of participants who underwent cochlear implantation 24 h after IT injection. MATERIALS AND METHODS: It was a prospective comparative randomized study. Twenty participants received an IT injection of prednisolone SS â¼24 h before the cochlear implantation. The other five participants received an IT saline injection and represented the control group. Perilymph and blood were sampled during the cochlear implantation surgery. RESULTS: Both prednisolone and prednisolone SS were still present in perilymph â¼24 h after the IT administration. Only prednisolone was present in the blood plasma of seven participants (35%). CONCLUSION: IT injection of prednisolone SS resulted in high perilymph concentrations of prednisolone and prednisolone SS, which could stay in the perilymph for at least 24 h. Using a mini-endoscope during the IT injection may effectively detect barriers infront of the round window membrane, increasing the drug concentration in the inner ear. SIGNIFICANCE: IT injection is an effective method for delivering prednisolone to the inner ear.
Assuntos
Implante Coclear , Orelha Interna , Humanos , Perilinfa , Injeção Intratimpânica , Estudos Prospectivos , Prednisolona , PlasmaRESUMO
Objective:To investigate the relationship between imaging characteristics and intraoperative perilymph gusher in patients with Mondini inner ear malformation in cochlear implantation, in order to provide basis and clinical guidance for predicting of intraoperative perilymph gusher before cochlear implantation. Methods:According to Sennaroglu's classification method, children with severe sensorineural hearing loss screened from January 2020 to December 2021 were divided into Mondini group, simple enlarged vestibular aqueduct group and normal inner ear group according to inclusion criteria strictly. The images of temporal bone HRCT and inner ear MRI were post-processed, some relative indicators were measured, including cochlear height and width of vestibular aqueduct, etc., and the gusher situation during cochlear implantation was recorded. The mean value of each indicator among the three groups were compared respectively, and the differences of each indicator between the gusher group and the non-gusher group were analyzed. Results:There were statistically significant differences in cochlear height, length of cochlear bottom turn, width of cochlear aperture, vestibular length and vestibular width among the Mondini groupï¼24 casesï¼, simple EVA groupï¼15 casesï¼ and normal inner ear groupï¼28 casesï¼. The incidence of gusher of Mondini group in cochlear implantation was 30.77%ï¼8/26ï¼. The outer diameter of the VAï¼[3.10±0.74]mmï¼ and the middle width of the VAï¼[1.90±0.68] mmï¼ in the gusher group were wider than those in the non-gusher group, and the difference was statistically significant. The incidence of intraoperative gusher in patients with EVA was 20.00%ï¼3/15ï¼, and there was statistically significant difference in the length of endolymph sac between gusher group and non-gusher groupï¼P<0.05ï¼. Conclusion:The causes of intraoperative perilymph gusher in patients with Mondini inner ear malformation are complex. The enlarged vestibular aqueduct may be one of the anatomical basis. Whether it can be used to guide the preoperative assessment of the risk of intraoperative perilymph gusher need to be further confirmed by a large sample of clinical research from multiple centers in the future.
Assuntos
Implante Coclear , Perda Auditiva Neurossensorial , Aqueduto Vestibular , Vestíbulo do Labirinto , Criança , Humanos , Perilinfa , Perda Auditiva Neurossensorial/cirurgia , Aqueduto Vestibular/anormalidades , Implante Coclear/métodos , Estudos RetrospectivosRESUMO
INTRODUCTION: Sensorineural hearing losses (SNHLs) are a significant public health issue, and the hearing loss field is desperately in need of effective therapy. Pathophysiological mechanisms are not yet clearly understood in the absence of validated methods to assess the inner ear content. Proteomic and metabolomic analysis of perilymph is opening new research perspectives for SNHLs. We aimed to demonstrate the feasibility of an innovative mass spectrometry (MS) strategy using porous silicon chips (PSCs) to investigate the low molecular weight (LMW) protein and metabolite content of human perilymph. Our second objective was to stratify perilymph samples according to their MS profiles and compare these results with clinical data. MATERIAL AND METHODS: Perilymph samples obtained during cochlear implant surgery from patients with SNHLs were retrieved from a validated biobank. To focus on LMW entities, we used a PSC enrichment protocol before MALDI-ToF MS analysis. PSCs were used as a LMW molecular preanalytical stabilizer and amplifier. Patients' clinical data and SNHL characteristics were retrieved retrospectively from medical charts. RESULTS: We successfully acquired and compared 59 exploitable MS profiles out of 71 perilymph samples. There was a good correlation between duplicates. Comparing both ears from the same patient, we found good reproducibility even when there was a one-year interval between samplings. We identified three distinct groups when comparing the samples' metabolomic profiles and four homogeneous groups comparing their LMW proteome profiles. Clinical data analysis suggested that some groups shared clinical or preanalytical characteristics. CONCLUSION: This proof-of-concept study confirms that LMW proteome and metabolome content of perilymph can be analyzed with PSCs. Based on protein profiles, we managed to stratify perilymp samples according to their molecular composition. These results must be confirmed with a larger population, and sampling methods require improvement, but this approach seems promising. In the future, this approach may pave the way for companion test strategies to precisely diagnose and define potential molecular targets for audioprotective therapies.
Assuntos
Perda Auditiva Neurossensorial , Silício , Perda Auditiva Neurossensorial/metabolismo , Humanos , Perilinfa/metabolismo , Porosidade , Proteoma/análise , Proteoma/metabolismo , Proteômica , Reprodutibilidade dos Testes , Estudos Retrospectivos , Silício/análise , Silício/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Intratympanically applied treatments are of increasing interest to the otologic community to treat sudden sensorineural hearing loss or vestibular disorders but also to deliver gene therapy agents, or biologics to the inner ear. Further diversion from the middle ear and perilymph to blood circulation and cerebrospinal fluid via the cochlear aqueduct are one of the limiting factors and so far not understood well enough. In this study, intratympanically applied triamcinolone acetonide was determined in cerebrospinal fluid. Additionally, perilymph was sampled through the round window membrane as well as at the lateral semicircular canal to determine drug levels. Of the twenty-one included patients, triamcinolone acetonide was quantifiable in cerebrospinal fluid in 43% at very low levels (range 0 ng/ml-6.2 ng/ml) which did not correlate with perilymph levels. Drug levels at the two different perilymph sampling sites were within a range of 13.5 ng/ml to 1180.0 ng/ml. Results suggest an equal distribution of triamcinolone acetonide to semicircular canals, which might support the use of triamcinolone acetonide as a treatment option for vestibular pathologies such as Menièrés disease. On the other hand, the distribution to cerebrospinal fluid might be limiting current approaches in gene therapy where a central distribution is unwanted.
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Líquido Cefalorraquidiano/metabolismo , Glucocorticoides/administração & dosagem , Neuroma Acústico/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Feminino , Humanos , Injeção Intratimpânica , Masculino , Pessoa de Meia-Idade , Perilinfa/metabolismoRESUMO
As noise-induced hearing loss (NIHL) is a leading cause of occupational diseases, there is an urgent need for the development of preventive and therapeutic interventions. To avoid user-compliance-based problems occurring with conventional protection devices, the pharmacological prevention is currently in the focus of hearing research. Noise exposure leads to an increase in reactive oxygen species (ROS) in the cochlea. This way antioxidant agents are a promising option for pharmacological interventions. Previous animal studies reported preventive as well as therapeutic effects of Insulin-like growth factor 1 (IGF-1) in the context of NIHL. Unfortunately, in patients the time point of the noise trauma cannot always be predicted, and additive effects may occur. Therefore, continuous prevention seems to be beneficial. The present study aimed to investigate the preventive potential of continuous administration of low concentrations of IGF-1 to the inner ear in an animal model of NIHL. Guinea pigs were unilaterally implanted with an osmotic minipump. One week after surgery they received noise trauma, inducing a temporary threshold shift. Continuous IGF-1 delivery lasted for seven more days. It did not lead to significantly improved hearing thresholds compared to control animals. Quite the contrary, there is a hint for a higher noise susceptibility. Nevertheless, changes in the perilymph proteome indicate a reduced damage and better repair mechanisms through the IGF-1 treatment. Thus, future studies should investigate delivery methods enabling continuous prevention but reducing the risk of an overdosage.
Assuntos
Perda Auditiva Provocada por Ruído , Fator de Crescimento Insulin-Like I , Animais , Cobaias , Limiar Auditivo , Cóclea/metabolismo , Audição , Perda Auditiva Provocada por Ruído/prevenção & controle , Perda Auditiva Provocada por Ruído/terapia , Fator de Crescimento Insulin-Like I/uso terapêutico , Perilinfa , SinapsesRESUMO
Stapediovestibular dislocation is a rare disorder as a result of traumatic injury to the structures in the middle ear. We described a case of a 60-year-old female with stapediovestibular dislocation with associated perilymph fistula. She presented with symptoms including hearing loss, vertigo, and tinnitus after a penetrating injury by an ear pick. After 4 months of conservative management, her symptoms failed to improve. Therefore, she underwent surgery which resolved completely her vestibular symptoms and her hearing loss had partially improved. The restoration of the stapes to its normal anatomical position coupled with ossiculoplasty and closure of the tympanic membrane are effective in patients with stapediovestibular dislocation.
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Perda Auditiva , Cirurgia do Estribo , Feminino , Humanos , Bigorna , Pessoa de Meia-Idade , Perilinfa , Estribo , Vertigem/diagnósticoRESUMO
Evaluation of hearing loss patients using clinical audiometry has been unable to give a definitive cellular or molecular diagnosis, hampering the development of treatments of sensorineural hearing loss. However, biopsy of inner ear tissue without losing residual hearing function for pathologic diagnosis is extremely challenging. In a clinical setting, perilymph can be accessed, potentially allowing the development of fluid based diagnostic tests. Recent approaches to improving inner ear diagnostics have been focusing on the evaluation of the proteomic or miRNA profiles of perilymph. Inspired by recent characterization and classification of many neurodegenerative diseases using exosomes which not only are produced in locally in diseased tissue but are transported beyond the blood brain barrier, we demonstrate the isolation of human inner ear specific exosomes using a novel ultrasensitive immunomagnetic nano pom-poms capture-release approach. Using perilymph samples harvested from surgical procedures, we were able to isolate exosomes from sensorineural hearing loss patients in only 2-5 µL of perilymph. By isolating sensory hair cell derived exosomes through their expression level of myosin VIIa, we for the first-time sample material from hair cells in the living human inner ear. This work sets up the first demonstration of immunomagnetic capture-release nano pom-pom isolated exosomes for liquid biopsy diagnosis of sensorineural hearing loss. With the ability to isolate exosomes derived from different cell types for molecular characterization, this method also can be developed for analyzing exosomal biomarkers from more accessible patient tissue fluids such as plasma.
Assuntos
Exossomos/patologia , Células Ciliadas Auditivas/patologia , Perda Auditiva Neurossensorial/diagnóstico , Perilinfa/citologia , Adulto , Audiometria , Fracionamento Celular , Estudos de Viabilidade , Feminino , Células Ciliadas Auditivas/citologia , Perda Auditiva Neurossensorial/patologia , Humanos , Separação Imunomagnética , Biópsia Líquida/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Non-contrast FLAIR revealed increased signal within the inner ear in patients with vestibular schwannoma, which is generally assumed to occur in the perilymph; however, the majority of previous studies did not differentiate between the endolymph and perilymph. Therefore, endolymph signal changes have not yet been investigated in detail. The purpose of the present study was three-fold: (1) to assess perilymph signal changes in patients with vestibular schwannoma on heavily T2-weighted (T2W) 3D FLAIR, also termed positive perilymphatic images (PPI), (2) to evaluate signal and morphological changes in the endolymph on PPI, and (3) to establish whether vertigo correlates with the signal intensity ratios (SIR) of the vestibular perilymph or vestibular endolymphatic hydrops. METHODS: Forty-two patients with unilateral vestibular schwannoma were retrospectively recruited. We semi-quantitatively and qualitatively evaluated the perilymph signal intensity on the affected and unaffected sides. We also quantitatively examined the signal intensity of the vestibular perilymph and assessed the relationship between vertigo and the SIR of the vestibular perilymph on the affected side. We semi-quantitatively or qualitatively evaluated the endolymph, and investigated whether vestibular hydrops correlated with vertigo. RESULTS: The perilymph on the affected side showed abnormal signal more frequently (signal intensity grade: overall mean 1.45 vs. 0.02; comparison of signal intensity: overall mean 36 vs. 0 cases) and in more parts (the entire inner ear vs. the basal turn of the cochlea and vestibule) than that on the unaffected side. No significant difference was observed in the SIR of the vestibular perilymph with and without vertigo (5.54 vs. 5.51, p = 0.18). The endolymph of the vestibule and semicircular canals showed the following characteristic features: no visualization (n = 4), signal change (n = 1), or vestibular hydrops (n = 10). A correlation was not observed between vestibular hydrops and vertigo (p = 1.000). CONCLUSIONS: PPI may provide useful information on signal and morphological changes in the endolymph of patients with vestibular schwannoma. Further research is warranted to clarify the relationship between vertigo and the MR features of the inner ear.
Assuntos
Endolinfa/diagnóstico por imagem , Hidropisia Endolinfática/diagnóstico por imagem , Imageamento por Ressonância Magnética , Neuroma Acústico/diagnóstico por imagem , Perilinfa/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Endolinfa/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/patologia , Neuroma Acústico/fisiopatologia , Perilinfa/fisiologia , Estudos Retrospectivos , Vertigem/etiologiaRESUMO
Hearing loss is a common disability affecting the world's population today. While several studies have shown that inner ear gene therapy can be successfully applied to mouse models of hereditary hearing loss to improve hearing, most of these studies rely on inner ear gene delivery in the neonatal age, when mouse inner ear has not fully developed. However, the human inner ear is fully developed at birth. Therefore, in order for inner ear gene therapy to be successfully applied in patients with hearing loss, one must demonstrate that gene delivery can be safely and reliably performed in the mature mammalian inner ear. In this study, we examine the steps involved in posterior semicircular canal gene delivery in the adult mouse inner ear. We find that the duration of perilymphatic leakage and injection rate have a significant effect on the post-surgical hearing outcome. Our results show that although AAV2.7m8 has a lower hair cell transduction rate in adult mice compared to neonatal mice at equivalent viral load, AAV2.7m8 is capable of transducing the adult mouse inner and outer hair cells with high efficiency in a dose-dependent manner.
Assuntos
Dependovirus/metabolismo , Terapia Genética/métodos , Células Ciliadas Auditivas/metabolismo , Canais Semicirculares/cirurgia , Animais , Dependovirus/genética , Técnicas de Transferência de Genes , Terapia Genética/efeitos adversos , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Perda Auditiva , Camundongos Endogâmicos CBA , PerilinfaRESUMO
Importance: The use of intratympanically applied steroids is of increasing interest. Consequently, research has focused on finding an ideal drug that diffuses through the round window membrane and can be retained in the perilymph. Objective: To compare levels of triamcinolone acetonide (TAC) in perilymph and plasma after intratympanic injection. Design, Setting, and Participants: This randomized clinical trial included 40 patients receiving cochlear implants at a single tertiary care center in Vienna, Austria. Patients were randomized to 1 of 4 treatment groups receiving 1 of 2 intratympanic doses of TAC (10 mg/mL or 40 mg/mL) at 1 of 2 approximate time points (24 hours or 1 hour) before sampling the perilymph. Inclusion was carried out between November 2017 and January 2020, and data were analyzed in December 2020. Interventions: All patients underwent intratympanic injection of TAC. During cochlear implantation, perilymph and plasma were sampled for further analysis. Main Outcomes and Measures: Levels of TAC measured in perilymph and plasma. Results: Among the 37 patients (median [range] age, 57 [26-88] years; 18 [49%] men) included in the analysis, TAC was present at a median (range) level of 796.0 (46.4-7706.7) ng/mL. In the majority of patients (n = 29; 78%), no drug was detectable in the plasma after intratympanic injection. Levels above the limit of detection were less than 2.5 ng/mL. The 1-factorial analysis of variance model showed lower TAC levels in the group that received TAC, 10 mg/mL, 24 hours before surgery (median, 271 ng/mL) compared with the group that received TAC, 10 mg/mL, 1 hour before surgery (median, 2877 ng/mL), as well as in comparison with the groups receiving TAC, 40 mg/mL, 24 hours before surgery (median, 2150 ng/mL) and 1 hour before surgery (median, 939 ng/mL). The 2-factorial analysis of variance model showed lower TAC levels in the group receiving TAC, 10 mg/mL, 24 hours before surgery than the group receiving TAC, 10 mg/mL, 1 hour before surgery, and higher TAC levels in the group receiving TAC, 40 mg/mL, 24 hours before surgery compared with the group receiving TAC, 10 mg/mL, 24 hours before surgery. Patients with thickening of the middle ear had statistically significantly higher plasma levels (median, 1.4 ng/mL vs 0 ng/mL) and lower perilymph levels (median, 213.1 ng/mL vs 904 ng/mL) than individuals with unremarkable middle ear mucosa. Conclusions and Relevance: In this randomized clinical trial, TAC was shown to be a promising drug for intratympanic therapies, with similar levels in perilymph 1 hour and 24 hours after injection (distinctly in the groups receiving the 40 mg/mL dose). There was also minimal dissemination to the plasma, especially in patients with unremarkable middle ear mucosa. Trial Registration: ClinicalTrials.gov Identifier: NCT03248856.
Assuntos
Anti-Inflamatórios/farmacocinética , Implante Coclear , Perilinfa/química , Cuidados Pré-Operatórios/métodos , Triancinolona Acetonida/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/metabolismo , Esquema de Medicação , Feminino , Humanos , Injeção Intratimpânica , Masculino , Pessoa de Meia-Idade , Triancinolona Acetonida/administração & dosagem , Triancinolona Acetonida/metabolismo , Adulto JovemRESUMO
HYPOTHESIS: MicroRNAs predicted to regulate neurotrophin signaling can be found in human perilymph. BACKGROUND: Animal and human temporal bone studies suggest that spiral ganglion health can affect cochlear implant (CI) outcomes. Neurotrophins have been identified as a key factor in the maintenance of spiral ganglion health. Changes in miRNAs may regulate neurotrophin signaling and may reflect neurotrophin expression levels. METHODS: Perilymph sampling was carried out in 18 patients undergoing cochlear implantation or stapedotomy. Expression of miRNAs in perilymph was evaluated using an Agilent miRNA gene chip. Using ingenuity pathway analysis (IPA) software, miRNAs targeting neurotrophin signaling pathway genes present in a cochlear cDNA library were annotated. Expression levels of miRNAs in perilymph were correlated to the patients' preoperative pure-tone average. RESULTS: Expression of mRNAs coding for neurotrophins and their receptors were identified in tissue obtained from normal human cochlea during skull base surgery. We identified miRNAs predicted to regulate these signaling cascades, including miR-1207-5p, miR-4651, miR-103-3p, miR-100-5p, miR-221-3p, miR-200-3p. There was a correlation between poor preoperative hearing and lower expression of miR-1207 (predicted to regulate NTR3) and miR-4651 (predicted to regulate NTR2). Additionally, miR-3960, miR-4481, and miR-675 showed significant differences in expression level when comparing mild and profound hearing loss patients. CONCLUSIONS: Expression of some miRNAs that are predicted to regulate neurotrophin signaling in the perilymph of cochlear implant patients vary with the patient's level of residual hearing. These miRNAs may serve as biomarkers for changes in neurotrophin signaling.
Assuntos
Implante Coclear , Implantes Cocleares , MicroRNAs , Fatores de Crescimento Neural/metabolismo , Audição , Humanos , MicroRNAs/genética , Perilinfa/metabolismo , Transdução de SinaisRESUMO
Intratympanic (IT) steroid therapy is a mainstay treatment for sudden sensorineural hearing loss (SSNHL) for both initial therapy and salvage therapy. We report a rare case of iatrogenic perilymphatic fistula that resulted from trauma during an IT steroid injection for SSNHL. We discuss the diagnosis and treatment in the current case and compare it with previous reports from the literature. Laryngoscope, 131:2088-2090, 2021.
Assuntos
Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/tratamento farmacológico , Canais Semicirculares/patologia , Esteroides/efeitos adversos , Idoso de 80 Anos ou mais , Audiometria de Tons Puros/métodos , Feminino , Fístula/etiologia , Humanos , Doença Iatrogênica , Injeção Intratimpânica , Perilinfa , Terapia de Salvação , Canais Semicirculares/lesões , Cirurgia do Estribo/efeitos adversos , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Resultado do Tratamento , Vertigem/diagnóstico , Vertigem/etiologia , Doenças Vestibulares/complicaçõesRESUMO
Patients with residual hearing can benefit from cochlear implantation. However, insertion can damage cochlear structures and generate oxidative stress harmful to auditory cells. The antioxidant N-acetyl-L-cysteine (NAC) is a precursor of glutathione (GSH), a powerful endogenous antioxidant. NAC local delivery to the inner ear appeared promising to prevent damage after cochlear implantation in animals. NAC-loaded liposomal gel was specifically designed for transtympanic injection, performed both 3 days before and on the day of surgery. Hearing thresholds were recorded over 30 days in implanted guinea pigs with and without NAC. NAC, GSH, and their degradation products, N,N'-diacetyl-L-cystine (DiNAC) and oxidized glutathione (GSSG) were simultaneously quantified in the perilymph over 15 days in non-implanted guinea pigs. For the first time, endogenous concentrations of GSH and GSSG were determined in the perilymph. Although NAC-loaded liposomal gel sustained NAC release in the perilymph over 15 days, it induced hearing loss in both implanted and non-implanted groups with no perilymphatic GSH increase. Under physiological conditions, NAC appeared poorly stable within liposomes. As DiNAC was quantified at concentrations which were twice as high as NAC in the perilymph, it was hypothesized that DiNAC could be responsible for the adverse effects on hearing.
Assuntos
Implante Coclear , Acetilcisteína , Animais , Cóclea , Cobaias , Humanos , Lipossomos , PerilinfaRESUMO
Traumatic perilymphatic fistula (PLF) is an uncommon cause of acute vestibular symptoms and hearing loss following head injury in children. We describe the management of 3 pediatric patients with traumatic PLF using an endoscopic ear surgery (EES) approach. Three pediatric patients with traumatic PLF underwent repair via an EES approach between August and October 2018. Patients included a 14-year-old female (oval window), a 13-year-old male (round window), and a 10-month-old male (oval and round window). Ossicular chain injury was identified and repaired in 2 patients. The 10-month-old patient required a second-stage surgery that included lumbar drain placement and a post-auricular, endoscopic-assisted approach due to an especially brisk leak. All patients had complete resolution of vestibular symptoms post-operatively with no recurrence at a mean follow-up of 8.3 months. Traumatic PLF can be safely and effectively diagnosed and managed via an EES approach in children, though an endoscopic-assisted approach may be necessary in select cases due to factors such as patient age and leak severity.
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Fístula , Doenças Vestibulares , Adolescente , Feminino , Humanos , Lactente , Masculino , Perilinfa , Janela da CócleaRESUMO
La fístula perilinfática de causa traumática es una patología poco habitual. En general, es causada por lápices, hisopos, hebillas de pelo y fósforos.Dentro de los síntomas más frecuentes, los pacientes pueden presentar hipoacusia y vértigo. Su diagnóstico requiere un examen físico completo que incluya otomicroscopía, audiometría ytomografía computada de ambos peñascos. El tratamiento depende de la sintomatología del paciente. En general, en un principio, es conservador, pero puede llegar a requerir cirugía. Se presenta un caso clínico de un niño de 6 años con fístula perilinfática secundaria a un traumatismo del oído izquierdo por un hisopo, que requirió tratamiento quirúrgico
Traumatic perilymphatic fistula is an unusual pathology. Generally caused by pencils, swabs, hair buckles, and matches. Among the most frequent symptoms, patients can present hearing loss and vertigo.Diagnosis requires a complete physical examination that includes otomicroscopy, audiometry and computed tomography of both boulders. Treatment depends on the patient's symptoms. In general, it is conservative at first, but may require surgery.We present a clinical case of a 6-year-old boy with perilymphatic fistula secondary to left ear trauma due to swab, which required surgical treatment
Assuntos
Humanos , Masculino , Criança , Perilinfa , Fístula/diagnóstico por imagem , Ferimentos e Lesões , Orelha Média , Fístula/cirurgiaRESUMO
Traumatic perilymphatic fistula is an unusual pathology. Generally caused by pencils, swabs, hair buckles, and matches. Among the most frequent symptoms, patients can present hearing loss and vertigo. Diagnosis requires a complete physical examination that includes otomicroscopy, audiometry and computed tomography of both boulders. Treatment depends on the patient's symptoms. In general, it is conservative at first, but may require surgery. We present a clinical case of a 6-year-old boy with perilymphatic fistula secondary to left ear trauma due to swab, which required surgical treatment.
La fístula perilinfática de causa traumática es una patología poco habitual. En general, es causada por lápices, hisopos, hebillas de pelo y fósforos. Dentro de los síntomas más frecuentes, los pacientes pueden presentar hipoacusia y vértigo. Su diagnóstico requiere un examen físico completo que incluya otomicroscopía, audiometría y tomografía computada de ambos peñascos. El tratamiento depende de la sintomatología del paciente. En general, en un principio, es conservador, pero puede llegar a requerir cirugía. Se presenta un caso clínico de un niño de 6 años con fístula perilinfática secundaria a un traumatismo del oído izquierdo por un hisopo, que requirió tratamiento quirúrgico.