La pathophysiologie de la maladie de Ménière au niveau du sac endolymphatique : une étude immunohistochimique de l’aquaporine-2, le récepteur de Vasopressine V2R, NKCC2 et TRPV4

Objectifs: La pathophysiologie de la maladie de Ménière (MM) demeure mal comprise. Nous avons identifié dans la littérature un groupe de protéines exprimées sur le sac endolymphatique (SEL) et impliquées dans la régulation du volume endolymphatique : l’Aquaporine-2 (AQP2), le récepteur V2R de vasopressine (AVP), le Co-transporteur de Sodium Potassium et Chlorure type 2 (NKCC2) et le canal TRP type V4 (TRPV4). Notre objectif est de déterminer si leur expression sur le SEL est altérée dans la MM, pour améliorer notre compréhension de la physiologie de l’hydrops endolymphatique. Méthodes: Recrutement des cas de MM et schwannomes vestibulaires (SV) comme contrôles, le jour de leurs chirurgies respectives. Prélèvement de biopsies de SEL et sang pour AVP. L’immunohistochimie pour AQP2, V2R, NKCC2 et TRPV4 fut effectuée, et les lames scannées pour analyse digitale de densité d’expression par un logiciel spécialisé (VIS par Visiopharm®). Résultats: Total de 27 cas MM et 23 contrôles. Les scores générés par le logiciel représentent la densité d’expression totale et relative des protéines, exclusivement sur l’épithélium du SEL. Les scores d’AQP2 sont élevés de façon significative dans la MM comparée aux contrôles (p = 0.018). Nous ne rapportons aucune variation significative pour AVP, V2R, NKCC2 et TRPV4. Conclusion: Cette étude originale évalue l’expression simultanée de AQP2, V2R, NKCC2 et TRPV4 sur le SEL dans la MM, avec un groupe contrôle (SV). Nos résultats démontrent une augmentation isolée de l’AQP2 dans la MM. Nous proposons une surexpression constitutive de cette dernière, indépendante de son axe de régulation (AVP-V2R). Une mutation somatique au niveau des séquences régulatrices pourrait justifier nos observations.Objectives: Endolymphatic sac (ELS) pathophysiology in Ménière’s Disease (MD) remains poorly understood. We identified from the literature a group of proteins expressed on the ELS and involved in endolymph volume regulation: Aquaporin-2 (AQP2), vasopressin receptor V2R, Sodium Potassium Chloride Cotransporter type 2 (NKCC2) and TRP channel type V4 (TRPV4). Our objective was to determine whether their ELS expression was altered in MD, to better understand the pathophysiology of endolymphatic hydrops. Methods: Patients with definite MD undergoing endolymphatic duct blockage surgery were recruited, as well as controls undergoing surgery for vestibular schwannomas (VS). ELS biopsies and blood samples for plasma Arginine Vasopressin (AVP) were obtained. Immunohistochemistry for AQP2, V2R, NKCC2 and TRPV4 was performed. Slides were scanned digitally for highly sensitive pixel density analysis by specialized software (VIS by Visiopharm®). Results: 27 definite MD patients and 23 VS controls were included. Global scores generated by the software represent total and relative protein expression density of 3 staining intensity levels, exclusively on ELS epithelium. AQP2 expression density was significantly elevated in MD compared to VS (p = 0.018). There was no significant difference in plasma AVP, V2R, NKCC2 and TRPV4 expression. Conclusion: This original study evaluates simultaneous in-situ expression of AQP2, V2R, NKCC2 and TRPV4 on the human ELS in MD, with a VS control group. Our results show only AQP2 up regulation on the ELS of MD patients. We suggest a constitutively increased expression of AQP2 in MD, independent of its regulatory axis (AVP-V2R). Acquired regulator sequence mutations could support this model

Eustachian tube symptoms are frequent in chronic rhinosinusitis and respond well to endoscopic sinus surgery

BACKGROUND: Symptoms of Eustachian tube (ET) dysfunction are seldom assessed in patients with chronic rhinosinusitis (CRS). The Sino-Nasal Outcome Test (SNOT-22) quality-of-life tool includes two questions that specifically screen for symptoms of ET dysfunction (Ear Fullness; Ear Pain). OBJECTIVE: The purpose of this study was to determine the extent to which these ET symptoms were present in patients with CRS, and whether these symptoms respond to endoscopic sinus surgery (ESS). METHODOLOGY: SNOT-22 data collected prospectively at time of recruitment into IRB-approved clinical trials or case-control studies in CRS was pooled to provide a cross section of the frequency and severity of ET dysfunction. When applicable to the trials, the SNOT-22 was repeated at least 3 months following ESS. RESULTS: Five trials rendering 131 patients were available for assessment. The control group comprised of 251 participants from two case-control studies. Ear Fullness of equal/greather than 1 was reported in 80/131 CRS patients compared to 45/251 control patients. Ear Pain of equal/greather than 1 was reported in 39/131 CRS patients compared to 33/251 control patients. Following ESS, mean Ear Fullness and Ear Pain scores decreased to 1.17 and 0.73, respectively. CONCLUSION: Symptoms suggestive of ET dysfunction are frequent in CRS, and for most patients the symptoms will decrease post-ESS to a level comparable with a non-CRS population. Patients whose ET symptoms do not respond to ESS may represent a target population for emerging therapeutic options for ET dysfunction

Hearing Outcomes Following Endolymphatic Duct Blockage Surgery and Factors Associated with Improved Audition at Two Years Follow-Up

Objective: To evaluate hearing outcomes at 2 years post endolymphatic duct blockage (EDB) surgery, with an analysis of factors that may predict hearing improvement. Study Design: Retrospective comparative study. Setting: Tertiary care center. Subjects: Definite Ménière’s Disease (MD) patients undergoing EDB for refractory disease. Methods: Chart review was conducted to assign cases to one of the three hearing outcome groups (deteriorated, stable, and improved). All cases that met our inclusion criteria were selected. Preoperative data collected were audiograms, bithermal caloric tests, preoperative vertigo episodes, history of previous ear surgery for Ménière, intratympanic steroid injections (ITS) and intraoperative endolymphatic sac (ELS) tear or opening. Postoperative data collected at 24 months were audiograms, vertigo episodes and bithermal caloric testing. Results: Preoperative vertigo episodes, caloric paresis and history of surgery, ITS injections or ELS integrity, as well as postoperative vertigo class distribution and caloric paresis changes were not different between our groups. Preoperative word recognition score (WRS) was lowest in the improved hearing group (p = 0.032). The persistence of tinnitus at 2 years postoperatively was associated with deteriorated hearing (p = 0.033). Conclusions: There are no strong predictors of hearing improvement on presentation pre-EDB, but low preoperative WRS may be the best estimator available. Therefore, ablative interventions should be considered very carefully in patients presenting with low WRS, as they may benefit more from EDB; there is a fair chance of a good hearing outcome with EDB surgery. Persistence of tinnitus can reflect deteriorating audition. Vertigo control and hearing preservation are independent outcomes of EDB surgery, making it desirable as an early intervention for refractory MD cases

Staphylococcus aureus on Sinus Culture Is Associated With Recurrence of Chronic Rhinosinusitis After Endoscopic Sinus Surgery

Objectives: Identify whether identification of S. aureus on conventional culture is a predictor of success or failure after ESS followed by budesonide nasal irrigations (BUD) in chronic rhinosinusitis (CRS) patients at high risk of recurrence.Methodology: Prospective clinical trial including 116 patients from a tertiary care center at high-risk of disease recurrence following ESS+BUD. Blood samples, microbial swabs, and SNSS/SNOT-22 were taken on the day of surgery (Visit-1) and 4 months postoperatively (Visit-2). Outcomes were evaluated using symptoms and mucosal status as assessed by the Lund-Kennedy endoscopic score.Results: Seventy-five patients (69.4%) attained SNOT-22 MCID or higher. (Mean = 33.4, range 9–75). Objective documentation of recurrence of disease, as defined by combined endoscopic/symptomatic criteria, was noted in 58/116 patients (50%). Revision surgery was associated with a significantly higher rate of disease recurrence (60.0 vs. 28.0%; p < 0.001). Culture for Staphylococcus aureus was associated with disease recurrence, preoperatively and at 4 months post-surgery (p = 0.020; p < 0.001). This was restricted to post-operative cultures in the revision group (10.0 vs. 48.8%; p < 0.001). Other factors associated with poor outcome included intolerance to non-steroidal anti-inflammatory drugs (NSAID) (p = 0.036). Significantly higher Lund-Kennedy scores in the recurrence groups despite similar symptom intensity, emphasizing the importance of considering objective outcome in addition to patient-reported ones.Conclusion: Patients undergoing revision ESS are at high risk of disease recurrence, even when budesonide irrigations are used post operatively. Presence of S. aureus on culture pre-operatively or at 4 months post-ESS is associated with a negative outcome. This suggests that S. aureus negatively influences outcome, possibly via a number of mechanisms, including interactions with the (i) immune system, (ii) regeneration and repair of the sinus epithelium, or (iii) via interference with the sinus microbiome. This suggests that S. aureus may be a simple and inexpensive biomarker for disease severity and indicates a clear need to better appreciate S. aureus on how it contributes mechanistically to disease development and persistence in order to develop targeted therapeutic strategies