Audiovestibular Manifestations in Patients with Primary Raynaud's Phenomenon and Raynaud's Phenomenon Secondary to Systemic Sclerosis.

OBJECTIVES: To address the prevalence of audiovestibular disorders in patients with primary Raynaud's Phenomenon (RP). A series of patients with primary RP and secondary RP in the context of systemic sclerosis (SSc) were compared with healthy controls. METHODS: A prospective multicenter observational cross-sectional study was conducted in several Otolaryngology and Rheumatology Divisions of tertiary referral hospitals, recruiting 57 patients with RP and 57 age- and gender-matched controls. Twenty patients were classified as primary RP when unrelated to any other conditions and 37 patients who met the 2013 ACR/EULAR classification criteria for SSc were classified as having secondary RP associated with SSc. Audiometric and vestibular testing (vHIT), clinical sensory integration and balance testing (CTSIB), and Computerized Dynamic Posturography (CDP) were performed. RESULTS: As significant differences were found in the age of the two study groups, primary and secondary RP, no comparisons were made between both groups of RP but only with their control groups. No sensorineural hearing loss (SNHL) was recorded in any of our patients with primary RP and no differences were found in the voice audiometry tests with respect to controls. Four of 37 (10.8%) secondary RP patients presented SNHL. Those with SNHL were 7.03 times more likely to have a secondary RP than controls (p < 0.001). The audiometric curve revealed high-frequency hearing loss in 4 patients with RP secondary to SSc, and statistically significant differences were achieved when RP secondary was compared to controls in vHIT gain, caloric test, CTSIB, and CDP. CONCLUSIONS: Unlike patients with RP secondary to SSc, patients with primary RP do not show audiovestibular abnormalities. Regarding audiovestibular manifestations, primary RP can be considered a different condition than secondary RP.

Update on consensus on diagnosis and treatment of idiopathic sudden sensorineural hearing loss. / Actualización del consenso sobre el diagnóstico y tratamiento de la sordera súbita idiopática.

INTRODUCTION: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a sudden, unexplained unilateral hearing loss. OBJECTIVES: To update the Spanish Consensus on the diagnosis, treatment and follow-up of ISSNHL. MATERIAL AND METHODS: After a systematic review of the literature from 1966 to March 2018, on MESH terms «(acute or sudden) hearing loss or deafness¼, a third update was performed, including 1508 relevant papers. RESULTS: Regarding diagnosis, 11ISSNHL is clinically suspected, the following diagnostic tests are mandatory: otoscopy, acumetry, tonal audiometry, speech audiometry, and tympanometry, to discount conductive causes. After clinical diagnosis has been established, and before treatment is started, a full analysis should be performed. An MRI should then be requested, ideally performed during the first 15 days after diagnosis, to discount specific causes and to help to understand the physiopathological mechanisms in each case. Although treatment is very controversial, due to its effect on quality of life after ISSNHL and the few rare adverse effects associated with short-term steroid treatment, this consensus recommends that all patients should be treated with steroids, orally and/or intratympanically, depending on each patient. In the event of failure of systemic steroids, intratympanic rescue is also recommended. Follow-up should be at day 7, and after 12 months. CONCLUSION: By consensus, results after treatment should be reported as absolute decibels recovered in pure tonal audiometry and as improvement in speech audiometry.

Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere's Disease.

Meniere's disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case-control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661-2.627); p = 1.39 × 10-09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10-11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD.

Clinical Subgroups in Bilateral Meniere Disease.

Meniere disease (MD) is a heterogeneous clinical condition characterized by sensorineural hearing loss, episodic vestibular symptoms, and tinnitus associated with several comorbidities, such as migraine or autoimmune disorders (AD). The frequency of bilateral involvement may range from 5 to 50%, and it depends on the duration of the disease. We have performed a two-step cluster analysis in 398 patients with bilateral MD (BMD) to identify the best predictors to define clinical subgroups with a potential different etiology to improve the phenotyping of BMD and to develop new treatments. We have defined five clinical variants in BMD. Group 1 is the most frequently found, includes 46% of patients, and is defined by metachronic hearing loss without migraine and without AD. Group 2 is found in 17% of patients, and it is defined by synchronic hearing loss without migraine or AD. Group 3, with 13% of patients, is characterized by familial MD, while group 4, that includes 12% of patients, is associated by the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by AD. This approach can be helpful in selecting patients for genetic and clinical research. However, further studies will be required to improve the phenotyping in these clinical variants for a better understanding of the diverse etiological factors contributing to BMD.

Sordera súbita: encuesta nacional en España / Sudden hearing loss: National survey in Spain

Introducción: El objetivo de nuestro estudio es identificar las actitudes diagnósticas y terapéuticas que se llevan a cabo en los diferentes servicios de otorrinolaringología (tanto del ámbito privado como público) en España con respecto a la sordera súbita. Esto permitirá establecer una base que ayude a generar un nuevo consenso a nivel nacional, unificando criterios para el tratamiento, diagnóstico y seguimiento de esta patología. Material y métodos: Se realizó una encuesta anónima por Internet, dirigida a otorrinolaringólogos españoles a nivel nacional (n = 2.029 especialistas afiliados a la SEORL), recopilando en 33 preguntas diferentes aspectos en relación a los criterios diagnósticos, pruebas complementarias, pautas de tratamiento y factores pronósticos en la sordera súbita, según los diferentes protocolos instaurados y experiencia de los participantes en la encuesta. Resultados: Participaron 293 otorrinolaringólogos españoles de forma anónima (14% del total). Respecto a criterios diagnósticos, destaca el requerimiento de confirmar una hipoacusia neurosensorial (91,1%), de inicio en menos de tres días (75%) y afectación de tres frecuencias consecutivas (76,4%). Más de la mitad de los participantes solicitan resonancia magnética de CAI/APC (68,7%), y el 88,2% utiliza contraste con gadolinio en esta prueba. El factor pronóstico que se consideró con mayor frecuencia en la encuesta fue la demora hasta inicio del tratamiento con un 84,8%. Respecto al tratamiento empleado en casos primarios, la gran mayoría de los encuestados (99,7%) coinciden en la administración de corticoides. La vía oral es la más utilizada (66%), seguida de la administración intravenosa (29,6%), e intratimpánica (1,4%). El 92% no han tenido complicaciones mayores con el tratamiento corticoide sistémico. La vía intratimpánica es empleada en un 70% como rescate en fracasos. Conclusiones: En España, existe actualmente una importante disparidad en el uso de los medios diagnósticos en la sordera súbita y un mayor acuerdo en el uso de corticoides como su tratamiento. Sería necesario implementar medidas que permitan un mejor abordaje, homogéneo y consensuado de esta patología (AU)

Introduction: The objective of our study was to identify the diagnostic and therapeutic approaches in the different ENT Departments of Spain with respect to sudden deafness. We wanted to establish a basis to help to create a new nation-wide consensus, unifying treatment, diagnostic and follow-up criteria for this disease. Methods: We carried out an anonymous Internet survey, addressing Spanish ENT doctors nation-wide (n = 2,029), gathering in 33 questions different aspects about diagnostic criteria, additional tests, treatment procedures and prognostic factors in sudden deafness, according to the different protocols and experience of the participants in the survey. Results: A total of 293 Spanish ENT doctors (14%) took part anonymously. In relation to diagnostic criteria, is the most noteworthy was the requisite of a confirmed neurosensorial loss (91.1%) followed by "initiated in less than three days" (75%) and 3 consecutive frequencies affected (76.4%). More than half of the participants requested an MRI of the IAC/CPA (68.7%) and 88.2% used gadolinium in this test. The prognostic factor most frequently considered was delay in commencement of treatment onset (84.8%). As far as treatment of primary cases, most of the responders agreed on the use of corticosteroids (99.7%). Oral administration was the most widely used (66%), followed by intravenous (29.6%) and intratympanic (1.4%) administration. Ninety-two percent had not had any major complications with systemic steroids. Intratympanic treatments were used by 70% of responders for rescue in failure. Conclusions: In Spain there is currently a significant disparity of concepts regarding the diagnosis of sudden deafness, and more agreement as to using steroids as their treatment. This highlights the need to implement measures to promote a better approach, which would be homogeneous and consensual, to this condition (AU)

Sudden hearing loss: National survey in Spain.

INTRODUCTION: The objective of our study was to identify the diagnostic and therapeutic approaches in the different ENT Departments of Spain with respect to sudden deafness. We wanted to establish a basis to help to create a new nation-wide consensus, unifying treatment, diagnostic and follow-up criteria for this disease. METHODS: We carried out an anonymous Internet survey, addressing Spanish ENT doctors nation-wide (n=2,029), gathering in 33 questions different aspects about diagnostic criteria, additional tests, treatment procedures and prognostic factors in sudden deafness, according to the different protocols and experience of the participants in the survey. RESULTS: A total of 293 Spanish ENT doctors (14%) took part anonymously. In relation to diagnostic criteria, is the most noteworthy was the requisite of a confirmed neurosensorial loss (91.1%) followed by "initiated in less than three days" (75%) and 3 consecutive frequencies affected (76.4%). More than half of the participants requested an MRI of the IAC/CPA (68.7%) and 88.2% used gadolinium in this test. The prognostic factor most frequently considered was delay in commencement of treatment onset (84.8%). As far as treatment of primary cases, most of the responders agreed on the use of corticosteroids (99.7%). Oral administration was the most widely used (66%), followed by intravenous (29.6%) and intratympanic (1.4%) administration. Ninety-two percent had not had any major complications with systemic steroids. Intratympanic treatments were used by 70% of responders for rescue in failure. CONCLUSIONS: In Spain there is currently a significant disparity of concepts regarding the diagnosis of sudden deafness, and more agreement as to using steroids as their treatment. This highlights the need to implement measures to promote a better approach, which would be homogeneous and consensual, to this condition.

Mutations of the gene encoding otogelin are a cause of autosomal-recessive nonsyndromic moderate hearing impairment.

Already 40 genes have been identified for autosomal-recessive nonsyndromic hearing impairment (arNSHI); however, many more genes are still to be identified. In a Dutch family segregating arNSHI, homozygosity mapping revealed a 2.4 Mb homozygous region on chromosome 11 in p15.1-15.2, which partially overlapped with the previously described DFNB18 locus. However, no putative pathogenic variants were found in USH1C, the gene mutated in DFNB18 hearing impairment. The homozygous region contained 12 additional annotated genes including OTOG, the gene encoding otogelin, a component of the tectorial membrane. It is thought that otogelin contributes to the stability and strength of this membrane through interaction or stabilization of its constituent fibers. The murine orthologous gene was already known to cause hearing loss when defective. Analysis of OTOG in the Dutch family revealed a homozygous 1 bp deletion, c.5508delC, which leads to a shift in the reading frame and a premature stop codon, p.Ala1838ProfsX31. Further screening of 60 unrelated probands from Spanish arNSHI families detected compound heterozygous OTOG mutations in one family, c.6347C>T (p.Pro2116Leu) and c. 6559C>T (p.Arg2187X). The missense mutation p.Pro2116Leu affects a highly conserved residue in the fourth von Willebrand factor type D domain of otogelin. The subjects with OTOG mutations have a moderate hearing impairment, which can be associated with vestibular dysfunction. The flat to shallow "U" or slightly downsloping shaped audiograms closely resembled audiograms of individuals with recessive mutations in the gene encoding α-tectorin, another component of the tectorial membrane. This distinctive phenotype may represent a clue to orientate the molecular diagnosis.

Síndrome de Ramsay Hunt: nuestra experiencia / Ramsay Hunt syndrome: our experience

Introducción: El síndrome de Ramsay Hunt (SRH) es causado por el virus Varicela-Zoster (VVZ) y está caracterizado clínicamente por erupciones cutáneas a nivel auricular, parálisis facial periférica (PFP), y afectación cócleo-vestibular. Objetivo: Analizar la evolución clínica de los síntomas más frecuentes del SRH y valorar la evolución de los mismos en un período superior a los 6 meses. Métodos: Estudio retrospectivo y descriptivo que incluye a todos los pacientes que acudieron al servicio de urgencias con el diagnóstico de SRH entre enero de 1995 y diciembre de 2004, y que fueron controlados por un período superior a los 6 meses. Resultados: Total de 54 pacientes. Rango de edad: 16 y 74 años, media de 49 años. El 7,5% de los pacientes debutaron con PFP seguido de síntomas cócleo-vestibulares mientras que el 20,2% presentaron de forma concomitante ambos síntomas. El 72,4% presentó clínica cócleo-vestibular previa a la PFP. La otodinia se presentó en un 83% en las primeras 48h. La hipoacusia fue referida en el 26% de los enfermos, acúfenos en un 7% y síntomas vestibulares en 84% de los casos. Conclusión: La recuperación de la PFP se relaciona con el grado de afectación inicial. Las manifestaciones cócleo-vestibulares son más frecuentes en pacientes con un mayor grado de afectación del nervio facial. La hipoacusia suele presentar una evolución tórpida. Los síntomas vestibulares tienen una buena respuesta clínica. La hipoacusia puede pasar inadvertida en estos pacientes y debe ser siempre confirmada con las pruebas complementarias (AU)

Introduction: Ramsay Hunt syndrome (RHS) is a disease caused by the Varicella Zoster virus and characterised by skin rash, peripheral facial palsy and otologic symptoms. Objective: This was an epidemiological study on the incidence and prognosis of this syndrome. Methods: A retrospective study was carried out on the patients diagnosed with RHS who were seen in the emergency room between January 1995 and December 2004, and were followed up for more than 6 months. Results: Of the 54 patients included in this study, 7.5% had facial palsy as their first symptom, followed by otologic signs (20.2% had both simultaneously); 72.5% presented otologic signs before facial palsy. Hypoacusis was reported in 26% of the patients, but was objectively present in all of them. The level of facial palsy determined the prognosis. Conclusion: In this syndrome, the prognosis of facial palsy depends on the initial symptoms and clinical findings. Otologic symptoms occur more frequently in patients having a greater degree of facial nerve affectation. Vestibular symptoms have a good prognosis. Hypoacusis is much more frequent than reported; as it may go unnoticed in these patients, it should always be confirmed by complementary tests (AU)

[Ramsay Hunt syndrome: our experience]. / Síndrome de Ramsay Hunt: nuestra experiencia.

INTRODUCTION: Ramsay Hunt syndrome (RHS) is a disease caused by the Varicella Zoster virus and characterised by skin rash, peripheral facial palsy and otologic symptoms. OBJECTIVE: This was an epidemiological study on the incidence and prognosis of this syndrome. METHODS: A retrospective study was carried out on the patients diagnosed with RHS who were seen in the emergency room between January 1995 and December 2004, and were followed up for more than 6 months. RESULTS: Of the 54 patients included in this study, 7.5% had facial palsy as their first symptom, followed by otologic signs (20.2% had both simultaneously); 72.5% presented otologic signs before facial palsy. Hypoacusis was reported in 26% of the patients, but was objectively present in all of them. The level of facial palsy determined the prognosis. CONCLUSION: In this syndrome, the prognosis of facial palsy depends on the initial symptoms and clinical findings. Otologic symptoms occur more frequently in patients having a greater degree of facial nerve affectation. Vestibular symptoms have a good prognosis. Hypoacusis is much more frequent than reported; as it may go unnoticed in these patients, it should always be confirmed by complementary tests.

Tumor de saco endolinfático como causa infrecuente de síndrome de Ménière / Endolymphatic sac tumour as an infrequent cause of Ménière's syndrome

Los tumores del saco endolinfático son tumores raros. Se han clasificado como adenocarcinomas de grado bajo de malignidad y hasta la fecha no se ha documentado metástasis. Presentamos a una paciente con enfermedad de Von Hippel-Lindau y síndrome de Ménière con un tumor de saco endolinfático. El diagnóstico y tratamiento precoz son esenciales para conservar la audición, por lo que se recomienda, ante una clínica sugestiva, realizar un seguimiento durante años (AU)

Endolymphatic sac tumours are uncommon. They have been classified as adenocarcinomas with a low degree of malignancy and no metastases have yet been documented. We report on a female patient with Von Hippel-Lindau disease and Ménière's syndrome suffering from an endolymphatic sac tumour. Diagnosis and early treatment are essential to preserve hearing, so long-term monitoring is recommended when this clinical combination is encountered (AU)

[Endolymphatic sac tumour as an infrequent cause of Ménière's syndrome]. / Tumor de saco endolinfático como causa infrecuente de síndrome de Ménière.

Endolymphatic sac tumours are uncommon. They have been classified as adenocarcinomas with a low degree of malignancy and no metastases have yet been documented. We report on a female patient with Von Hippel-Lindau disease and Ménière's syndrome suffering from an endolymphatic sac tumour. Diagnosis and early treatment are essential to preserve hearing, so long-term monitoring is recommended when this clinical combination is encountered.