Case Report: Preservation of Otolithic Function After Triple Semicircular Canal Occlusion in a Patient With Intractable Ménière Disease

Operative measures are considered when medical treatment fails to control vertigo in patients with intractable Ménière disease. The present report discusses a case in which triple semicircular canal occlusion was performed in a 30-year-old female patient who responded poorly to previously performed endolymphatic sac surgery. Her vestibular and auditory functions were evaluated both before and after surgery. Class A control of vertigo was achieved during the 76-month postoperative follow-up period. Ocular and cervical vestibular evoked myogenic potentials could be elicited before and after surgery. This case suggests that relatively long-term preservation of otolithic function can be achieved following triple semicircular canal occlusion, highlighting its potential as an alternative treatment for patients with Ménière disease.

DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease

Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed on MD. Here we performed whole-genome bisulfite sequencing in 14 MD patients and six healthy controls, with the aim of identifying an MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (n= 9545), several of them in hearing loss genes, such as PCDH15, ADGRV1 and CDH23. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including two UMR in an inter CpG island in the PHB gene. We suggest that the DNA methylation signature allows distinguishing between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.

DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease

Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed in MD. Here we performed whole genome bisulfite sequencing in 14 MD patients and 6 healthy controls, with the aim of identifying a MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (N= 9,545), several of them in hearing loss genes such as PCDH15, ADGRV1 and CDH23. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including 2 UMR in an inter CpG island in the PHB gene. We suggest that the DNA methylation signature allows to distinguish between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.

Clinical and Cytokine Profile in Patients with Early and Late Onset Meniere Disease

Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profiles in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early-onset MD (EOMD, <35 years old), and 39 with late-onset MD (LOMD, >50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL,1 and IL-1β were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1β were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p = 0.004) and a higher prevalence of migraine than LOMD (p = 0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3, and CXCL4 were different between patients with MD or migraine and controls.

Clinical and Cytokine Profile in Patients with Early and Late Onset Meniere Disease

Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profile in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early onset MD (EOMD, &lt;35 years old), and 39 with late onset MD (LOMD, &gt; 50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL1 and IL-1&beta; were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1&beta; were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p=0.004) and a higher prevalence of migraine than LOMD (p=0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3 and CXCL4 were different between patients with MD or migraine and controls.

The relationship between clinical characteristics and magnetic resonance imaging results of Ménière disease: a prospective study

Ménière disease (MD) is an idiopathic inner ear disorder, and endolymphatic hydrops (EH) being considered to be its pathological basis. Currently, there is no gold standard for diagnosing MD. Previous study has reported visualized EH using MRI by intratympanic gadolinium-based contrast media (GBCM) administration (IT-Gd) in patients with MD, and this technique was gradually established for MD diagnosis. However, few studies reported their diagnostic sensitivity and specificity in clinical application. This prospective study aimed at investigating the clinical characteristics and magnetic resonance imaging (MRI) results of patients with MD, and analyzing the relationship between clinical results and MRI findings in MD patients. Our study shows that the diagnostic sensitivity and specificity of MRI were 79.2% and 80.7% respectively. Moreover, there was no significant correlation between hearing levels and cochlear grading scores, nor vestibular grading scores. The duration of disease was not significantly associated with cochlear or vestibular grading scores. These findings suggest that IT-Gd MRI offers reliable radiological diagnostic criteria for MD.