RESUMO
Eosinophilic chronic rhinosinusitis (ECRS) is a type 2 inflammatory disease that frequently co-occurs with bronchial asthma. The current treatment options for ECRS include endoscopic sinus surgery and oral corticosteroid therapy (OCS). However, recurrence after surgery is common, and OCS therapy may cause side effects. We present the case of a 74-year-old woman with severe asthma, ECRS, and secretory otitis media with possible eosinophilic otitis media, who experienced significant improvement in both conditions after treatment with tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) antibody. Tezepelumab treatment led to a reduction in blood and tissue eosinophil counts. It improved the nasal polyp and computed tomography scores, tympanic and hearing test results, and asthma symptoms without using OCSs. Our findings suggest that tezepelumab may be a promising option for those patients with asthma, ECRS, and secretory otitis media who do not respond well to conventional treatment because upstream of the type 2 inflammation pathway is suppressed. Further to this case report, future studies are required to confirm the long-term efficacy and safety of tezepelumab in treating ECRS and secretory otitis media due to type 2 inflammation.
RESUMO
BACKGROUND: Sublingual immunotherapy (SLIT) has become applicable to insurance for children in Japan in 2018. However, as for the efficacy of SLIT for children, objective evaluation methods have not been sufficiently investigated. SUBJECTS AND METHODS: We investigated the efficacy of SLIT as both subjective and objective evaluation in 44 children with allergic rhinitis sensitized to house dust mite who started the treatment in the summer of 2018 in our hospital. The children and their patients wrote the allergy diary every day, and in winter/spring/summer vacations, they answered Japanese allergic rhinitis quality of life standard questionnaire and were evaluated with nasal provocation test, blood test, rhinomanometry for 3 years. RESULTS: 29 (66%) of the 44 children continued SLIT for 3 years. Symptom scores, QOL scores, symptom medication scores halved in a year and the effect lasted in the second and third year. Nasal provocation test and rhinomanometry showed significant improvement. Specific IgE increased transiently and then decreased. Specific IgG4 increased annually. CONCLUSION: The present study showed a decrease in scores not only for subjective assessments but also for objective evaluation methods, the house dust nasal provocation test and the nasal airway resistance.
Assuntos
Rinite Alérgica , Imunoterapia Sublingual , Humanos , Criança , Animais , Pyroglyphidae , Qualidade de Vida , Rinite Alérgica/terapia , JapãoRESUMO
OBJECTIVE: Systemic administration of glucocorticoid steroids is the most common initial treatment for idiopathic sudden sensorineural hearing loss (ISSNHL); however, due to the prevalence of coronavirus disease, the indications for this treatment must be carefully determined. The aim of this study was to investigate the efficacy of intratympanic steroid therapy as an initial treatment for idiopathic SSNHL. METHODS: Sixty-eight patients with idiopathic ISSNHL who were treated with intravenous or intratympanic steroids were included in this study. Patients were retrospectively evaluated regarding preoperative grade, type of additional treatment, outcome of treatment, and side effects of each treatment. RESULTS: In 46 cases, patients received intravenous steroid therapy as the initial treatment, while 22 patients received intratympanic steroid therapy; 10 patients underwent salvage treatment due to inadequate improvement of symptoms. Regarding additional treatment, intravenous steroid monotherapy was used in 37 patients. The outcomes were similar after both treatments; 16 (43%) and 11 (52%) patients treated exclusively with intravenous and intratympanic steroids, respectively, were completely cured. There were no significant differences in the effects between the 2 treatments, indicating that they were almost equally effective. The side effects observed in patients treated with intravenous steroid therapy were increased blood pressure, acute gastric mucosal disorder, and insomnia. None of these side effects were observed in any of the patients treated with intratympanic steroids; however, 1 case of perforation of the tympanic membrane occurred due to the procedure. CONCLUSION: There were no significant differences in posttreatment outcomes between patients treated with either intratympanic or intravenous steroids. The therapeutic effects were comparable, and no severe side effects were observed; therefore, intratympanic steroid therapy may be considered useful as an initial treatment for ISSNHL in the context of widespread coronavirus disease.
Assuntos
COVID-19 , Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Glucocorticoides/uso terapêutico , Estudos Retrospectivos , Pandemias , Resultado do Tratamento , COVID-19/complicações , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/tratamento farmacológico , Perda Auditiva Súbita/diagnóstico , Injeção Intratimpânica , Esteroides , Dexametasona , Audiometria de Tons PurosRESUMO
Cochlear implants improve the quality of life of patients with bilateral severe sensorineural hearing loss. Normally, patients with cochlear implants can continue to use the devices for years without any complications. However, equipment failure or infection at the implant site could develop in some patients, and this might often necessitate implant replacement. Although cochlear implant replacement surgery itself is not a major risk in most cases, extensive tissue resection will be required in cases involving infection, and the insertion site of the temporal bone implant will need to be changed. We encountered a case of skin necrosis at the temporal bone implant site caused by constant external irritation from the temple of an eyeglass frame. The patient underwent cochlear implant replacement surgery involving full-thickness skin grafting from the abdomen. Thereafter, the patient's condition improved. Full-thickness skin grafting can be useful in cases of extensive skin defects encountered during cochlear implant replacement.
Assuntos
Implante Coclear , Implantes Cocleares , Perda Auditiva Neurossensorial , Humanos , Transplante de Pele , Qualidade de Vida , Perda Auditiva Neurossensorial/cirurgia , Perda Auditiva BilateralRESUMO
External auditory canal cancer is a rare disease which can be treated by surgery or chemoradiation. The most common histological type is squamous cell carcinoma, but rare types such as adenocarcinoma have been reported and are thought to be derived from the ceruminous glands. Here, we present a case of ceruminous adenocarcinoma, not otherwise specified (NOS) in the external auditory canal. A 72-year-old woman was referred to our department with discomfort due to a mass in the external ear canal. No typical symptoms of malignancy, such as pain or bleeding, were noted at the initial examination. The patient underwent a total excision under local anesthesia as a diagnostic treatment. She was diagnosed with ceruminous adenocarcinoma, NOS based on the results of immunostaining of the excised specimen, and is currently being followed up as an outpatient. Adenocarcinoma is thought to originate from the cerumen glands of the ear canal and the lack of specific symptoms may make it difficult to differentiate it from benign tumors. Although adenocarcinoma, NOS has been reported in the head and neck region, there have been no reported cases occurring in the external ear canal, and to the best of our knowledge, this is the first report.
Assuntos
Adenocarcinoma , Neoplasias Ósseas , Neoplasias da Mama , Neoplasias da Orelha , Neoplasias de Tecido Conjuntivo , Neoplasias das Glândulas Sudoríparas , Adenocarcinoma/patologia , Idoso , Neoplasias Ósseas/patologia , Neoplasias da Mama/patologia , Meato Acústico Externo/patologia , Neoplasias da Orelha/diagnóstico , Neoplasias da Orelha/patologia , Neoplasias da Orelha/cirurgia , Feminino , Humanos , Neoplasias de Tecido Conjuntivo/patologia , Neoplasias das Glândulas Sudoríparas/patologiaRESUMO
Prostate cancer (PC) is prone to bone metastases, but very rarely it can spread to soft tissues. In the head and neck region, PC can metastasize to the orbital soft tissue, causing various symptoms such as vision loss. In this report, we describe the case of a 79-year-old man with PC metastasis in the orbital apex. He presented to an ophthalmologist at our hospital with progressively worsening vision in his left eye over 3 to 4 months. He complained of a drooping eyelid in the same eye; thus, intracranial disease was suspected. Closer inspection with head computed tomography revealed a space-occupying lesion from the orbit to the posterior ethmoid sinus, and he was referred to our department. He had a history of PC, and we performed endoscopic sinus surgery for the diagnosis of malignancy, including metastasis of PC. As a result, the mass was diagnosed as PC metastasis by pathological examination. The patient began androgen blockade therapy and 3 months postoperatively, magnetic resonance imaging revealed that the extraconal orbital mass had decreased significantly. It is important to determine the metastases of PC in the paranasal region when the patient has a preexisting medical history.
Assuntos
Carcinoma , Neoplasias Orbitárias , Neoplasias da Próstata , Idoso , Androgênios , Humanos , Masculino , Neoplasias Orbitárias/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologiaRESUMO
The V-shaped arrangement of hair bundles on cochlear hair cells is critical for auditory sensing. However, regulation of hair bundle arrangements has not been fully understood. Recently, defects in hair bundle arrangement were reported in postnatal Dishevelled-associating protein (ccdc88c, alias Daple)-deficient mice. In the present study, we found that adult Daple-/- mice exhibited hearing disturbances over a broad frequency range through auditory brainstem response testing. Consistently, distorted patterns of hair bundles were detected in almost all regions, more typically in the basal region of the cochlear duct. In adult Daple-/- mice, apical microtubules were irregularly aggregated, and the number of microtubules attached to plasma membranes was decreased. Similar phenotypes were manifested upon nocodazole treatment in a wild type cochlea culture without affecting the microtubule structure of the kinocilium. These results indicate critical role of Daple in hair bundle arrangement through the orchestration of apical microtubule distribution, and thereby in hearing, especially at high frequencies.
Assuntos
Proteínas de Transporte/genética , Cóclea/patologia , Perda Auditiva/patologia , Microtúbulos/patologia , Estereocílios/patologia , Animais , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Cóclea/citologia , Cóclea/efeitos dos fármacos , Cóclea/metabolismo , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico , Técnicas de Inativação de Genes , Perda Auditiva/genética , Camundongos , Microscopia Eletrônica de Varredura , Microtúbulos/metabolismo , Nocodazol/farmacologia , Técnicas de Cultura de Órgãos , Estereocílios/metabolismoRESUMO
Cervical abscesses develop in the tissue spaces between the cervical fascia. The rapid expansion of these abscesses can lead to fatal outcomes. We describe a case of a deep cervical abscess caused by Parvimonas micra. He was referred to our department with complaints of sore throat and neck pain. Ultrasonography revealed a hypoechoic area in the cervical interfascicular space. An ultrasound-guided puncture was performed to collect pus for bacteriological examination. Subsequently, a contrast-enhanced computed tomography scan revealed a multi-focal abscess extending from the left mandible to the left side of the neck, without any mediastinal abscess. An emergency drainage and antibacterial therapies were performed, and the patient progressed well. Parvimonas micra, a gram-positive anaerobic bacterium, was detected in the pus collected before incision, and appropriate antibiotics were immediately administered. The collection of pus prior to incision and drainage aids accurate identification of the causative organism and appropriate treatment.
RESUMO
The cochlear efferent feedback system plays important roles in auditory processing, including regulation of the dynamic range of hearing, and provides protection against acoustic trauma. These functions are performed through medial olivocochlear (MOC) neurons. However, the underlying cellular and molecular mechanisms are not fully understood. The serotonin type 3A (5-HT3A) receptor is widely expressed throughout the nervous system, which suggests important roles in various neural functions. However, involvement of the 5-HT3A receptor in the MOC system remains unclear. We used mice in this study and found that the 5-HT3A receptor was expressed in MOC neurons that innervated outer hair cells in the cochlea and was involved in the activation of MOC neurons by noise exposure. 5-HT3A receptor knockout impaired MOC functions, potentiated noise-induced hearing loss, and increased loss of ribbon synapses following noise exposure. Furthermore, 5-HT3 receptor agonist treatment alleviated the noise-induced hearing loss and loss of ribbon synapses, which enhanced cochlear protection provided by the MOC system. Our findings demonstrate that the 5-HT3A receptor plays fundamental roles in the MOC system and critically contributes to protection from noise-induced hearing impairment.
Assuntos
Cóclea/fisiologia , Células Ciliadas Auditivas Externas/patologia , Perda Auditiva Provocada por Ruído/prevenção & controle , Ruído/efeitos adversos , Receptores 5-HT3 de Serotonina/fisiologia , Animais , Vias Eferentes , Perda Auditiva Provocada por Ruído/etiologia , Perda Auditiva Provocada por Ruído/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
The major symptoms of Ménière's disease are episodic vertigo, fluctuating hearing loss, and tinnitus. Direction-changing spontaneous nystagmus is a characteristic vestibular finding in Ménière's disease. In the acute stage, spontaneous nystagmus beating to the affected side (irritative nystagmus) is often observed, while paralytic nystagmus beating to the healthy side is found in the chronic stage. This direction-changing nystagmus can be reproduced in guinea pigs by increasing the potassium ion concentration in the perilymph. The objectives of the present study were to examine the effects of increasing the potassium ion concentration of the rat perilymph on hearing and nystagmus. Under isoflurane anesthesia, 22 rats received intratympanic injection of different concentrations of potassium chloride (KCl) solution or distilled water: groups 1, 2, 3, and 4 received saturated (3.4 M) KCl solution, 2 M KCl, 1 M KCl, and distilled water, respectively. The nystagmus direction and number per 15 s were monitored for 150 min. In the other 8 rats, hearing was monitored 30 min and 20 h after intratympanic injection of 2 M KCl (group 5) or distilled water (group 6) using the auditory brainstem responses. Rats in groups 1 and 2 showed spontaneous irritative nystagmus beating to the affected ear followed by paralytic nystagmus beating to the contralateral side. In group 3, irritative nystagmus occurred but paralytic nystagmus was rarely observed. Rats in group 4 showed no nystagmus. Rats in group 5 showed significant hearing impairment 30 min after KCl injection that recovered 20 h later. Control animals in group 6 showed no significant changes in hearing. The reversible hearing impairment with direction-changing spontaneous nystagmus induced by potassium injection into the tympanic cavity in rats was quite similar to that observed in acute Ménière's attacks. This rat model could be used for basic research investigating the pathophysiological mechanisms underlying Ménière's attacks.
Assuntos
Modelos Animais de Doenças , Audição/fisiologia , Doença de Meniere/induzido quimicamente , Nistagmo Patológico/induzido quimicamente , Cloreto de Potássio , Animais , Injeção Intratimpânica , Masculino , Doença de Meniere/fisiopatologia , Nistagmo Patológico/fisiopatologia , Ratos , Ratos WistarRESUMO
Cholesteatoma starts as a retraction of the tympanic membrane and expands into the middle ear, eroding the surrounding bone and causing hearing loss and other serious complications such as brain abscess and meningitis. Currently, the only effective treatment is complete surgical removal, but the recurrence rate is relatively high. In rheumatoid arthritis (RA), osteoclasts are known to be responsible for bone erosion and undergo differentiation and activation by receptor activator of NF-κB ligand (RANKL), which is secreted by synovial fibroblasts, T cells, and B cells. On the other hand, the mechanism of bone erosion in cholesteatoma is still controversial. In this study, we found that a significantly larger number of osteoclasts were observed on the eroded bone adjacent to cholesteatomas than in unaffected areas, and that fibroblasts in the cholesteatoma perimatrix expressed RANKL. We also investigated upstream transcription factors of RANKL using RNA sequencing results obtained via Ingenuity Pathways Analysis, a tool that identifies relevant targets in molecular biology systems. The concentrations of four candidate factors, namely interleukin-1ß, interleukin-6, tumor necrosis factor α, and prostaglandin E2, were increased in cholesteatomas compared with normal skin. Furthermore, interleukin-1ß was expressed in infiltrating inflammatory cells in the cholesteatoma perimatrix. This is the first report demonstrating that a larger-than-normal number of osteoclasts are present in cholesteatoma, and that the disease involves upregulation of factors related to osteoclast activation. Our study elucidates the molecular basis underlying bone erosion in cholesteatoma.
Assuntos
Osso e Ossos/patologia , Colesteatoma/patologia , Osteoclastos/fisiologia , Ligante RANK/fisiologia , Transdução de Sinais , Artrite Reumatoide/complicações , Diferenciação Celular , Humanos , Interleucina-1beta/análise , Osteoclastos/citologia , Ligante RANK/genética , RNA Mensageiro/análiseRESUMO
The sphenopalatine ganglion (SPG) is a gathering of the cell bodies of parasympathetic fibers that dominate the nasal gland, lacrimal gland and cerebral blood vessels. The SPG controls nasal secretions, tears, and the dilation of cerebral blood vessels. However, it is unclear how serotonin regulates SPG functions. In this study, we investigated the expression of genes involved in the serotonergic system in the mouse SPG. We examined the mRNA expression levels of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3A, 5-HT3B, 5-HT4, 5-HT5A, 5-HT5B, 5-HT6 and 5-HT7 receptors, as well as serotonin transporter, tryptophan hydroxylases 1 and 2, and L-amino acid decarboxylase (AADC) by RT-PCR. It revealed that the 5-HT3A and 5-HT3B ionotropic receptors and AADC were likely to be highly expressed in the SPG, as measured by RT-PCR. We next performed in situ hybridization on the SPG to examine the expression of these three genes at the cellular level after validating the specificity of each cRNA probe by northern blotting. The 5-HT3A receptor, 5-HT3B receptor, and AADC were expressed in 96.5%⯱â¯1.0%, 29.7%⯱â¯10.7%, and 57.4%⯱â¯2.9% of neuronal cell bodies in the SPG, respectively, indicating that the 5-HT3A receptor was virtually expressed in all SPG neurons. Our results on the expression of these critical serotonin system genes in the parasympathetic SPG provide insight into the pathogenetics of rhinitis, conjunctivitis and headache. Furthermore, our findings suggest that targeting the 5-HT3A receptor might have therapeutic potential in the treatment of these ailments.
Assuntos
Gânglios Parassimpáticos/metabolismo , Neurônios/metabolismo , Receptores de Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Triptofano Hidroxilase/metabolismo , Animais , Northern Blotting , Hibridização In Situ , Masculino , Camundongos , Receptores de Serotonina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Triptofano Hidroxilase/genéticaRESUMO
OBJECTIVE: This study was performed to determine whether endolymphatic sac surgery improves vestibular and cochlear endolymphatic hydrops 2 years after sac surgery and to elucidate the relationship between the degree of improvement of endolymphatic hydrops and the changes in vertigo symptoms, the hearing level, and the summating potential/action potential ratio (-SP/AP ratio) by electrocochleography (ECochG) in patients with Ménière's disease (MD). METHODS: Twenty-one patients with unilateral MD who underwent sac surgery were included in this study. All patients underwent gadolinium-enhanced magnetic resonance imaging (Gd-MRI) before and 2 years after sac surgery. We evaluated the difference in vestibular and cochlear endolymphatic hydrops between before and after surgery in both ears and compared these findings with the frequency of vertigo attacks, hearing level, and ECochG findings. RESULTS: In affected ears, the presence of vestibular endolymphatic hydrops and the frequency of vertigo attacks significantly decreased after surgery. However, affected ears showed no significant improvement in the presence of cochlear endolymphatic hydrops or the -SP/AP ratio by ECochG; there was also no significant improvement or deterioration in the hearing level. CONCLUSION: The present findings suggest that sac surgery reduces vestibular endolymphatic hydrops and prevents aggravation of cochlear endolymphatic hydrops, and these changes lead to a reduction of vertigo attacks and suppress the progression of hearing impairment associated with vertigo attacks.
Assuntos
Saco Endolinfático/cirurgia , Perda Auditiva/fisiopatologia , Doença de Meniere/cirurgia , Vertigem/fisiopatologia , Adulto , Idoso , Audiometria de Resposta Evocada , Audiometria de Tons Puros , Hidropisia Endolinfática/diagnóstico por imagem , Hidropisia Endolinfática/fisiopatologia , Hidropisia Endolinfática/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Doença de Meniere/diagnóstico por imagem , Doença de Meniere/fisiopatologia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Otológicos , Resultado do TratamentoRESUMO
We investigated fibroblast growth factor 12 (FGF12) as a transcript enriched in the inner ear by searching published cDNA library databases. FGF12 is a fibroblast growth factor homologous factor, a subset of the FGF superfamily. To date, its localisation and function in the inner ear have not been determined. Here, we show that FGF12 mRNA is localised in spiral ganglion neurons (SGNs) and the vestibular ganglion. We also show that FGF12 protein is localised in SGNs, the vestibular ganglion, and nerve fibres extending beneath hair cells. Moreover, we investigated FGF12 function in auditory and vestibular systems using Fgf12-knockout (FGF12-KO) mice generated with CRISPR/Cas9 technology. Our results show that the inner ear morphology of FGF12-KO mice is not significantly different compared with wild-type mice. However, FGF12-KO mice exhibited an increased hearing threshold, as measured by the auditory brainstem response, as well as deficits in rotarod and balance beam performance tests. These results suggest that FGF12 is necessary for normal auditory and equilibrium function.
Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Fatores de Crescimento de Fibroblastos/metabolismo , Células Ciliadas Auditivas/metabolismo , Gânglio Espiral da Cóclea/metabolismo , Nervo Vestibular/metabolismo , Animais , Sistemas CRISPR-Cas/fisiologia , Orelha Interna/metabolismo , Audição/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , RNA Mensageiro/metabolismoRESUMO
P2X2 receptors are ligand-gated cation channels activated by extracellular ATP that modulate neural transmission in various neuronal systems. Although the function and distribution of P2X2 receptors in the cochlea portion of the inner ear are well established, their physiological role in the vestibular portion is still not understood. Therefore, we investigated P2X2 receptor localization in the peripheral vestibular portion, and assessed their physiological function in vivo using P2X2 receptor knock out (P2X2-KO) mice. Histological analysis revealed that P2X2 receptors were localized on the epithelial surface of supporting and transitional cells of the vestibular end organs. To examine vestibular function in P2X2-KO mice, we conducted behavioral tests and tested the vestibulo-ocular reflex (VOR) during sinusoidal rotations. P2X2-KO mice exhibited significant motor balance impairment in the balance beam test. VOR gain in P2X2-KO mice was significantly reduced, with no decrease in the optokinetic response. In conclusion, we showed that P2X2 receptors are mainly localized in the supporting cells of the vestibular inner ear, and the loss of P2X2 receptors causes mild vestibular dysfunction. Taken together, our findings suggest that the P2X2 receptor plays a modulatory role in vestibular function.
Assuntos
Cóclea/metabolismo , Receptores Purinérgicos P2X2/deficiência , Reflexo Vestíbulo-Ocular/fisiologia , Vestíbulo do Labirinto/metabolismo , Animais , Cóclea/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Purinérgicos P2X2/análise , Vestíbulo do Labirinto/químicaRESUMO
The study of inner ear specific transcripts has revealed novel information about hereditary hearing loss and a mechanism of normal hearing. In this study, by analyzing a published cDNA library, we focused on Epiphycan (Epyc), a member of the small leucine-rich repeat proteoglycan family, whose transcript is enriched in the inner ear. Epyc mRNA was expressed abundantly and specifically in adult mice cochleae and was localized in supporting cells within the organ of Corti of both neonatal and adult mice. To examine the function of Epyc, we generated Epyc knockout (KO) mice using the CRISPR/Cas9 system. Epyc KO mice cochleae exhibited normal morphology. However, measurement of the auditory brain-stem response in Epyc KO mice revealed an elevated hearing threshold above 16 kHz frequency. This study suggests that Epyc is necessary for normal auditory function.
Assuntos
Cóclea/citologia , Cóclea/metabolismo , Audição/fisiologia , Proteoglicanos Pequenos Ricos em Leucina/genética , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteoglicanos Pequenos Ricos em Leucina/deficiência , Proteoglicanos Pequenos Ricos em Leucina/metabolismoRESUMO
Aim of this work is to establish evaluation criteria for identifying endolymphatic hydrops in the vestibule and cochlea using a magnetic resonance imaging (MRI) scanner. This is a retrospective diagnostic study. We evaluated 70 ears of 35 unilateral Ménière's disease patients. We performed 3-T MRI 4 h after intravenous gadolinium injection. Otologists manually traced the outline of vestibule, cochlea, and endolymphatic space of the vestibule and cochlea on two-dimensional fluid-attenuated inversion-recovery (2D-FLAIR) images. The traced area was measured, and rates of endolymphatic space to the vestibule and cochlea were calculated. The same otologists judged whether the low signal intensity area of the cochlea was at the edge of the cochlea. For measuring the rate of endolymphatic space to the vestibule, when the cut-off value was 30%, the presence of endolymphatic hydrops was determined with sensitivity of 87.1% and specificity of 94.3%. In contrast, the rate of endolymphatic space to the cochlea produced low accuracy. Therefore, when the presence of endolymphatic hydrops in the cochlea was judged by whether the low signal intensity area in the cochlea was at the edge of cochlea, endolymphatic hydrops could be detected with sensitivity of 91.4% and specificity of 94.3%. We were able to identify endolymphatic hydrops in the vestibule when the rate of endolymphatic space to the vestibule was greater than 30%, and could detect endolymphatic hydrops in the cochlea when a low signal intensity area was located at the edge of the cochlea in 2D-FLAIR images. Level of evidence 4.
Assuntos
Cóclea/diagnóstico por imagem , Hidropisia Endolinfática/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Vestíbulo do Labirinto/diagnóstico por imagem , Adulto , Idoso , Audiometria de Resposta Evocada , Meios de Contraste , Feminino , Gadolínio , Compostos Heterocíclicos , Humanos , Imageamento Tridimensional , Injeções Intravenosas , Masculino , Doença de Meniere/diagnóstico , Doença de Meniere/diagnóstico por imagem , Pessoa de Meia-Idade , Compostos Organometálicos , Curva ROC , Estudos RetrospectivosRESUMO
Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel expressed in sensory neurons such as those in the dorsal root and trigeminal ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat, low osmotic pressure, low pH, and phorbol derivatives such as 4α-phorbol 12,13-didecanoate (4α-PDD). We investigated the expression of TRPV4 in rat vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from VG neuron mRNA using reverse-transcription polymerase chain reaction. Furthermore, immunoblotting showed positive expression of TRPV4 protein in VG neurons. Immunohistochemistry indicated that TRPV4 was localized predominantly on the plasma membrane of VG neurons. Calcium (Ca2+) imaging of VG neurons showed that 4α-PDD and/or hypotonic stimuli caused an increase in intracellular Ca2+ concentration ([Ca2+]i) that was almost completely inhibited by ruthenium red, a selective antagonist of TRPV channels. Interestingly, a [Ca2+]i increase was evoked by both hypotonic stimuli and 4α-PDD in approximately 38% of VG neurons. These data indicate that TRPV4 is functionally expressed in VG neurons as an ion channel and that TRPV4 likely participates in VG neurons for vestibular neurotransmission as an osmoreceptor and/or mechanoreceptor.
Assuntos
Gânglios Sensitivos/metabolismo , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Canais de Cátion TRPV/genética , Nervo Vestibular/metabolismo , Animais , Cálcio/metabolismo , Gânglios Sensitivos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Forbóis/farmacologia , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Canais de Cátion TRPV/metabolismo , Nervo Vestibular/efeitos dos fármacosRESUMO
Cisplatin is a chemotherapeutic agent commonly used for the treatment of solid tumors, and its side-effects include vestibulotoxicity. Previous studies have reported cisplatin-induced vestibulotoxicity in various animal models, but no study has investigated in vivo mouse vestibular dysfunction after cisplatin. The aim of this study was to investigate cisplatin-induced vestibulotoxicity in C57BL/6J mice. Vestibular function was assessed by recording the vestibulo-ocular reflex (VOR). This was done during sinusoidal rotations in the horizontal plane at three frequencies (0.5, 1.0 and 2.5Hz). A high-resolution, high-frequency digital infra-red camera was used with eye-tracking algorithms. Cisplatin at 16mg/kg, but not 8mg/kg, decreased the VOR gain at 2.5Hz compared with the vehicle control. Following 16mg/kg cisplatin treatment, the animals showed no change in the optokinetic nystagmus response, suggesting that no major changes in visual or oculomotor functions had occurred. This mouse model may be useful for studying cisplatin-induced vestibulotoxicity and its treatment.
Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Reflexo Vestíbulo-Ocular/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Movimentos Oculares/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Nistagmo Optocinético/efeitos dos fármacos , Rotação , Testes de Função VestibularRESUMO
INTRODUCTION: A pathological nystagmus is an objective sign that a patient feels vertigo. However, there have been few opportunities to observe and record pathological nystagmus during a paroxysmal vertigo attack. Furthermore, it can be difficult to obtain cooperation in pediatric patients. We present two cases of paroxysmal vertigo in children in whom we successfully recorded and analyzed their pathological nystagmus during a vertigo attack. METHODS: Of a total sample of 4349 patients seen at our hospital for dizziness in the last decade, a retrospective analysis revealed that 68 were children (<15 years old; 1.6%). Of these 68 children, we successfully identified pathological nystagmus during paroxysmal vertigo in only two (2.9%). RESULTS: Case 1 was a 4-year-old girl. She felt vertigo the strongest when her left ear was down in the supine position. We observed and recorded her nystagmus during a vertigo attack with her mother's permission. Her positional nystagmus in the supine position was horizontal persistent apogeotropic nystagmus. Rightward nystagmus in the left-ear-down supine position was stronger than leftward nystagmus in the right-ear-down supine position. Therefore, the diagnosis was right lateral canal type of benign paroxysmal positional vertigo, of which the pathophysiology was cupulolithiasis. The other patient was an 11-year-old boy. He had a family history of migraines. His vertigo attacks occurred after onset of a severe migraine and lasted between 2 and 48 h. During an attack that we observed, he showed nystagmus, which was direction-fixed right torsional and rightward in darkness. His mother had noticed that his eyes moved abnormally and that his left eye did not shift to the left side when he looked leftward. He was old enough to clearly express his own symptoms. Other neurological examinations were normal. The diagnosis was vestibular migraine. CONCLUSIONS: We analyzed a pathological nystagmus during paroxysmal vertigo in two children. We conclude that children can be diagnosed with a combination of careful history taking and accurate examinations of a pathological nystagmus.