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.

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.