Migraine (MI) is the most common neurological disease, affecting with 20% of the world population. A subset of 25% of MI patients showcase concurrent vestibular symptoms, which may classify as vestibular migraine (VM). Meniere's disease (MD) is a complex inner ear disorder defined by episodes of vertigo associated with tinnitus and sensorineural hearing loss with a significant autoimmune/autoinflammatory contribution, which symptoms overlap with VM. Blood samples from 18 patients with MI (5), VM (5) and MD (8) and 6 controls were collected and compared in a case–control study. Droplet‐isolated nuclei from mononuclear cells used to generate scRNAseq and scATACseq data sets from MI, VM and MD. MI and VM have no differences in their immune transcriptome; therefore, they were considered as a single cluster for further analyses. Natural Killer (NK) cells transcriptomic data support a polarisation triggered by Type 1 innate immune cells via the release of interleukin (IL)‐12, IL‐15 and IL‐18. According to the monocyte scRNAseq data, there were two MD clusters, one inactive and one driven by monocytes. The unique pathways of the MI + VM cluster were cellular responses to metal ions, whereas MD monocyte‐driven cluster pathways showed responses to biotic stimuli. MI and MD have different immune responses. These findings support that MI and VM have a Type 1 immune lymphoid cell response, and that there are two clusters of MD patients, one inactive and one Monocyte‐driven.
Objective. Although psoriatic arthritis (PsA) is a common chronic inflammatory rheumatic disease, little is known about audiovestibular impairment in this condition. We aimed to establish whether audiovestibular manifestations were present in patients with PsA. Methods. A set of 60 consecutive patients who fulfilled the Moll and Wright criteria for PsA and 60 matched controls were studied. During the period of recruitment, individuals were excluded who had a history of cardiovascular disease, cerebrovascular complications, peripheral artery disease, renal insufficiency, syphilis, Meniere disease and other vestibular syndromes, infections involving the inner ear, barotrauma, or were in treatment with ototoxic drugs. Results. Most patients with PsA were men (63%). The mean age at the time of our study was 52.9 years and the mean age at the onset of symptoms was 33 years. Thirty-six (60%) of the 60 patients showed abnormal hearing loss in the audiogram compared to only 5 (8.3%) of the 60 controls (p < 0.001). Values of audiometric tests (pure-tone average and speech reception threshold) yielded significant differences between patients and controls (p < 0.001). The audiogram disclosed a bilateral and symmetrical sensorineural hearing loss (SNHL) in PsA with predominant pattern of high frequency SNHL in patients with PsA (46.7%) compared to controls (8.3%, p < 0.001). Patients with PsA exhibited abnormal vestibular tests more commonly than controls. A significantly increased frequency of abnormal computerized dynamic posturography with a predominant vestibular loss pattern was also observed in patients (23.3%) compared to controls (0%, p < 0.001). Conclusion. Our current study demonstrates strong evidence for inner ear damage in patients with PsA.
Meniere disease (MD) is a cochleo-vestibular syndrome defined by episodes of vertigo associated with tinnitus and sensorineural hearing loss. While MD immune response has been linked to autoinflammation and type 2 cytokines, other molecular mechanisms such as DNA methylation have an emerging yet underexplored role in MD pathophysiology.To understand the role of DNA methylation in MD, we performed whole-genome bisulphite sequencing in MD patients (n = 40) and controls (n = 13) and used differentially methylated cytosines (DMCs) to define clusters, cell types, and biochemical pathways in MD. We found three MD subclusters: Cluster 1 (40% of patients) and Cluster 3 (25%) showed DMC profiles against controls, while Cluster 2 (35%) did not. Significant DMCs from Cluster 1 and Cluster 3 versus Control analysis were annotated to 3033 and 59 unique genes, respectively. Each cluster showed a different gene enrichment; however, the KDMB4 gene had significant upregulated DNA accessibility in a complementary ATAC-seq dataset and showed significant DMCs in both Cluster 1 and Cluster 3. DNA methylation patterns in MD reveal three clusters which are reflective of an underlying difference in pathways related to cytokine stimulus, immunity T-cell, and NK-cell pathways. KDMB4 emerges as a critical MD gene which deserves further research. Key messages: We asked if DNA methylation can help understand Meniere’s Disease (MD) pathophysiology. DNA methylomes group MD patients into three distinct sub-clusters. DNA methylation in MD reflect difference in pathways related to neurons and cytokine stimulus. The data shows KDMB4 emerging as a key gene that requires further multi-modal investigation.
Background: Vestibular symptoms and objective vestibular dysfunction have been reported in patients with autoimmune and rheumatologic diseases, but available evidence remains fragmented and methodologically heterogeneous. Previous studies have often addressed audiovestibular involvement as a combined entity, limiting disease-specific interpretation of vestibular outcomes. Methods: A PRISMA 2020-based systematic review was conducted using predefined eligibility criteria targeting vestibular outcomes in autoimmune and systemic rheumatologic diseases. Observational studies reporting vestibular symptoms and/or objective vestibular test results were included. Vestibular data were extracted even when studies reported combined audiovestibular outcomes. Certainty of evidence was assessed using the GRADE approach. Results: Twenty-seven studies were included in the qualitative synthesis, comprising 14 primary observational studies and 13 reviews. Vestibular involvement was reported across multiple diseases, including systemic sclerosis, giant cell arteritis, ankylosing spondylitis, psoriatic arthritis, Behçet disease, primary Sjögren syndrome, rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, and vasculitic disorders. Objective vestibular abnormalities were most frequently identified using caloric testing, balance integration measures, videonystagmography, and video head impulse testing. Systemic sclerosis and giant cell arteritis showed more consistently reported vestibular findings, although heterogeneity in assessment methods precluded quantitative synthesis. Conclusions: Vestibular involvement occurs across autoimmune and systemic inflammatory diseases, but overall certainty of evidence remains limited. Standardized vestibular assessment and longitudinal studies are needed to better define disease-specific vestibular phenotypes.
1 November 2020 in Acta Otorrinolaringológica Española
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.