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Journal of the Association For Research... Feb 2024To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.
PURPOSE
To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.
METHODS
After a systematic search and quality assessment, 31 records including 383,063 patients were selected (14 epidemiological studies and 17 genetic association studies). General information on the sample size, age, sex, tinnitus prevalence, severe tinnitus distribution, and sensorineural hearing loss was retrieved. Studies that did not include data on hearing assessment were excluded. Relative frequencies were used for qualitative variables to compare different studies and to obtain average values. Genetic variants and genes were listed and clustered according to their potential role in tinnitus development.
RESULTS
The average prevalence of tinnitus estimated from population-based studies was 26.3% for any tinnitus, and 20% of patients with tinnitus reported it as an annoying symptom. One study has reported population-specific differences in the prevalence of tinnitus, the white ancestry being the population with a higher prevalence. Genome-wide association studies have identified and replicated two common variants in the Chinese population (rs2846071; rs4149577) in the intron of TNFRSF1A, associated with noise-induced tinnitus. Moreover, gene burden analyses in sequencing data from Spanish and Swede patients with severe tinnitus have identified and replicated ANK2, AKAP9, and TSC2 genes.
CONCLUSIONS
The genetic contribution to tinnitus is starting to be revealed and it shows population-specific effects in European and Asian populations. The common allelic variants associated with tinnitus that showed replication are associated with noise-induced tinnitus. Although severe tinnitus has been associated with rare variants with large effect, their role on hearing or hyperacusis has not been established.
Topics: Humans; Tinnitus; Genome-Wide Association Study; Hearing; Hearing Loss, Sensorineural; Hyperacusis
PubMed: 38334885
DOI: 10.1007/s10162-024-00925-6 -
Journal of Clinical Medicine Jan 2024To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a...
Nine-Month Continuous Fremanezumab Prophylaxis on the Response to Triptans and Also on the Incidence of Triggers, Hypersensitivity and Prodromal Symptoms of Patients with High-Frequency Episodic Migraine.
To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a continuous 9-month fremanezumab therapy for migraine prophylaxis. We studied 63 patients with high-frequency episodic migraine (HFEM). Enrolled patients received fremanezumab for nine consecutive months before defining the response rates and being stratified into treatment responders (≥50-74% reduction in monthly headache days (MHDs)), super responders (≥75%), partial non-responders (<50%) and super non-responders (<30%). Through headache diaries, patients provided data in order to document the impact of fremanezumab on the incidence of triggers, associated symptoms followed by headache and response to triptans (the use of the migraine treatment optimization questionnaire-4 (mTOQ-4)) during the 9-month treatment period. Fremanezumab had early (after 3 monthly cycles) beneficial effects on the response to triptans in the majority of responders with relevant increases in mTOQ-4 scoring, but also in half of partial non-responders. A significant reduction in median days with migraine-associated symptoms was seen in responders after 6 months of therapy with fremanezumab, mostly for osmophobia, photophobia, phonophobia and nausea/vomiting, but partial non-responders also benefited. Likewise, the incidence of self-reported prodromal symptoms was significantly reduced in responders and was modestly diminished in partial non-responders. Triggers remained unaffected in both responders and non-responders. Fremanezumab given for at least 6-9 months may exert neuromodulatory effects in the migraine brain. These effects could result both in the inhibition of migraine chronification, but also in the diminishing of the magnitude of migraine-associated symptoms, mostly in responders and in partial non-responders.
PubMed: 38256516
DOI: 10.3390/jcm13020386 -
Medicina (Kaunas, Lithuania) Jan 2024The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion... (Review)
Review
The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort. It is important to point out that this pathology not only has a decisive impact on the quality of life of those who suffer from it but also on their families and, more generally, on society as a whole. The clinical picture of migraine is complex, with debilitating unilateral or bilateral head pain, and is often associated with characteristic symptoms such as nausea, vomiting, photophobia, and phonophobia. Hormonal, environmental, psychological, dietary, or other factors can trigger it. The present review focuses on the analysis of the physiopathological and pharmacological aspects of migraine, up to the correct dietary approach, with specific nutritional interventions aimed at modulating the symptoms. Based on the symptoms that the patient experiences, targeted and specific therapy is chosen to reduce the frequency and severity of migraine attacks. Specifically, the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine is analyzed, along with the drugs that effectively target the corresponding receptor. Particularly, CGRP receptor antagonists (gepants) are very effective drugs in the treatment of migraine, given their high diffusion in the brain. Moreover, following a ketogenic diet for only one or two months has been demonstrated to reduce migraine attacks. In this review, we highlight the diverse facets of migraine, from its physiopathological and pharmacological aspects to prevention and therapy.
Topics: Humans; Calcitonin Gene-Related Peptide; Diet, Ketogenic; Headache; Migraine Disorders; Quality of Life; Calcitonin Gene-Related Peptide Receptor Antagonists
PubMed: 38256423
DOI: 10.3390/medicina60010163 -
Frontiers in Neuroscience 2023The ongoing controversies about the neural basis of tinnitus, whether linked with central neural gain or not, may hamper efforts to develop therapies. We asked to what...
Differential cortical activation patterns: pioneering sub-classification of tinnitus with and without hyperacusis by combining audiometry, gamma oscillations, and hemodynamics.
The ongoing controversies about the neural basis of tinnitus, whether linked with central neural gain or not, may hamper efforts to develop therapies. We asked to what extent measurable audiometric characteristics of tinnitus without (T) or with co-occurrence of hyperacusis (TH) are distinguishable on the level of cortical responses. To accomplish this, electroencephalography (EEG) and concurrent functional near-infrared spectroscopy (fNIRS) were measured while patients performed an attentionally demanding auditory discrimination task using stimuli within the individual tinnitus frequency (fTin) and a reference frequency (fRef). Resting-state-fMRI-based functional connectivity (rs-fMRI-bfc) in ascending auditory nuclei (AAN), the primary auditory cortex (AC-I), and four other regions relevant for directing attention or regulating distress in temporal, parietal, and prefrontal cortex was compiled and compared to EEG and concurrent fNIRS activity in the same brain areas. We observed no group differences in pure-tone audiometry (PTA) between 10 and 16 kHz. However, the PTA threshold around the tinnitus pitch was positively correlated with the self-rated tinnitus loudness and also correlated with distress in T-groups, while TH experienced their tinnitus loudness at minimal loudness levels already with maximal suffering scores. The T-group exhibited prolonged auditory brain stem (ABR) wave I latency and reduced ABR wave V amplitudes (indicating reduced neural synchrony in the brainstem), which were associated with lower rs-fMRI-bfc between AAN and the AC-I, as observed in previous studies. In T-subjects, these features were linked with elevated spontaneous and reduced evoked gamma oscillations and with reduced deoxygenated hemoglobin (deoxy-Hb) concentrations in response to stimulation with lower frequencies in temporal cortex (Brodmann area (BA) 41, 42, 22), implying less synchronous auditory responses during active auditory discrimination of reference frequencies. In contrast, in the TH-group gamma oscillations and hemodynamic responses in temporoparietal regions were reversed during active discrimination of tinnitus frequencies. Our findings suggest that T and TH differ in auditory discrimination and memory-dependent directed attention during active discrimination at either tinnitus or reference frequencies, offering a test paradigm that may allow for more precise sub-classification of tinnitus and future improved treatment approaches.
PubMed: 38239827
DOI: 10.3389/fnins.2023.1232446 -
The American Journal of Case Reports Jan 2024BACKGROUND Superior ophthalmic vein thrombosis (SOVT) is a rare condition, with an incidence of 3 to 4 cases per million per year. SOVT can be classified according to...
BACKGROUND Superior ophthalmic vein thrombosis (SOVT) is a rare condition, with an incidence of 3 to 4 cases per million per year. SOVT can be classified according to the underlying etiology into septic or aseptic SOVT. We present a case of right SOVT in a previously healthy patient with a positive blood culture of methicillin-resistant Staphylococcus aureus (MRSA). CASE REPORT A previously healthy 38-year-old female patient presented with a 2-week history of worsening right-sided headache associated with photophobia, phonophobia, right-sided ear pain, and tinnitus. The best corrected visual acuity was 6/12 in the right eye and 6/6 in the left eye. Ophthalmic examination revealed right eye upper lid edema, proptosis, and diplopia in all gazes, mainly vertical. The fundus examination showed a raised hyperemic right optic disc with blurred margins. Laboratory investigations showed a positive blood culture of MRSA and elevated levels of inflammatory markers erythrocyte sedimentation rate and C-reactive protein. Orbital computed tomography examination showed periorbital and orbital cellulitis with superior ophthalmic vein thrombosis. The patient was treated successfully with antibiotics and anticoagulants. At 1-month follow-up, the patient was compliant with medications and reported full resolution of symptoms, with no visual acuity impairment. CONCLUSIONS SOVT is a challenging ophthalmic condition and can be present concurrent with orbital cellulitis or cavernous sinus thrombosis. Early imaging studies and proper management are important to prevent serious complications. Ophthalmologists need to be alerted of the importance of tailoring antibiotics based on the causative agent, to decrease the risk of therapeutic failure and microbial resistance.
Topics: Female; Humans; Adult; Orbital Cellulitis; Methicillin-Resistant Staphylococcus aureus; Venous Thrombosis; Eye; Anti-Bacterial Agents
PubMed: 38225808
DOI: 10.12659/AJCR.941886 -
BioRxiv : the Preprint Server For... Jan 2024Sound is jointly processed along acoustic and emotional dimensions. These dimensions can become distorted and entangled in persons with sensory disorders, producing a...
Sound is jointly processed along acoustic and emotional dimensions. These dimensions can become distorted and entangled in persons with sensory disorders, producing a spectrum of loudness hypersensitivity, phantom percepts, and - in some cases - debilitating sound aversion. Here, we looked for objective signatures of disordered hearing (DH) in the human face. Pupil dilations and micro facial movement amplitudes scaled with sound valence in neurotypical listeners but not DH participants with chronic tinnitus (phantom ringing) and sound sensitivity. In DH participants, emotionally evocative sounds elicited abnormally large pupil dilations but blunted and invariant facial reactions that jointly provided an accurate prediction of individual tinnitus and hyperacusis questionnaire handicap scores. By contrast, EEG measures of central auditory gain identified steeper neural response growth functions but no association with symptom severity. These findings highlight dysregulated affective sound processing in persons with bothersome tinnitus and sound sensitivity disorders and introduce approaches for their objective measurement.
PubMed: 38187580
DOI: 10.1101/2023.12.22.571929 -
Journal of the Association For Research... Dec 2023Tinnitus would benefit from an objective biomarker. The goal of this study is to identify plasma biomarkers of constant and chronic tinnitus among selected circulating... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Tinnitus would benefit from an objective biomarker. The goal of this study is to identify plasma biomarkers of constant and chronic tinnitus among selected circulating inflammatory proteins.
METHODS
A case-control retrospective study on 548 cases with constant tinnitus and 548 matched controls from the Swedish Tinnitus Outreach Project (STOP), whose plasma samples were examined using Olink's Inflammatory panel. Replication and meta-analysis were performed using the same method on samples from the TwinsUK cohort. Participants from LifeGene, whose blood was collected in Stockholm and Umeå, were recruited to STOP for a tinnitus subtyping study. An age and sex matching was performed at the individual level. TwinsUK participants (n = 928) were selected based on self-reported tinnitus status over 2 to 10 years. Primary outcomes include normalized levels for 96 circulating proteins, which were used as an index test. No reference standard was available in this study.
RESULTS
After adjustment for age, sex, BMI, smoking, hearing loss, and laboratory site, the top proteins identified were FGF-21, MCP4, GDNF, CXCL9, and MCP-1; however, these were no longer statistically significant after correction for multiple testing. Stratification by sex did not yield any significant associations. Similarly, associations with hearing loss or other tinnitus-related comorbidities such as stress, anxiety, depression, hyperacusis, temporomandibular joint disorders, and headache did not yield any significant associations. Analysis in the TwinsUK failed in replicating the top candidates. Meta-analysis of STOP and TwinsUK did not reveal any significant association. Using elastic net regularization, models exhibited poor predictive capacity tinnitus based on inflammatory markers [sensitivity = 0.52 (95% CI 0.47-0.57), specificity = 0.53 (0.48-0.58), positive predictive value = 0.52 (0.47-0.56), negative predictive values = 0.53 (0.49-0.58), and AUC = 0.53 (0.49-0.56)].
DISCUSSION
Our results did not identify significant associations of the selected inflammatory proteins with constant tinnitus. Future studies examining longitudinal relations among those with more severe tinnitus and using more recent expanded proteomics platforms and sampling of cerebrospinal fluid could increase the likelihood of identifying relevant molecular biomarkers.
Topics: Humans; Tinnitus; Retrospective Studies; Hearing Loss; Hyperacusis; Biomarkers
PubMed: 38079022
DOI: 10.1007/s10162-023-00920-3 -
Frontiers in Neurology 2023This study aimed to confirm the characteristics of auditory function alterations in tinnitus patients with concomitant decreased sound tolerance (ST) and provide...
This study aimed to confirm the characteristics of auditory function alterations in tinnitus patients with concomitant decreased sound tolerance (ST) and provide insights for developing tailored therapeutic approaches. A retrospective analysis was conducted on patient records from a tertiary university hospital's tinnitus clinic between March 2020 and June 2023. Demographic attributes and audiological profiles were reviewed. Patients were categorized into Group 1 if loudness discomfort level test outcomes were 77 dB or below, measured using an average of frequencies from 250 Hz to 8 kHz. The remaining patients were allocated to Group 2. Among the 434 tinnitus patients, 115 (26.5%) demonstrated decreased ST and were classified as Group 1. This group exhibited higher DPOAE amplitudes ( < 0.001), shortened latency, and decreased threshold of ABR wave V bilaterally ( < 0.05). No significant disparities were observed in gender, age, tinnitus handicap inventory, visual analog scale, and pure-tone audiometry results except subjective hyperacusis. Binary logistic regression analysis utilizing the forward conditional method revealed that the difference between groups was independently linked to DPOAE response at 7,277 Hz on the left side [B = 0.093, < 0.001, EXP(B) = 1.07, 95% CI = 1.044-1.153]. Increased DPOAE amplitude and shorter and decreased ABR wave V in tinnitus patients with decreased ST might suggest a possible association with lesions in or around the superior olivary complex or higher central auditory pathway, potentially linked to the inhibition of medial olivocochlear efferents.
PubMed: 38020634
DOI: 10.3389/fneur.2023.1273705 -
PloS One 2023Recently, the most bothersome symptom has been recommended as a co-primary endpoint in clinical trials on the acute treatment of migraine. Probable migraine is a subtype...
Recently, the most bothersome symptom has been recommended as a co-primary endpoint in clinical trials on the acute treatment of migraine. Probable migraine is a subtype of migraine that fulfills all but one criterion for migraine diagnosis. We aimed to compare the most bothersome symptom between probable migraine and migraine. This study analyzed data from a nationwide study conducted in Korea, and the most bothersome symptom was assessed by requesting the participants to select one of the four typical accompanying symptoms of migraine. Responses to acute treatment were evaluated using the migraine Treatment Optimization Questionnaire-6. Nausea was the most bothersome symptom, followed by phonophobia and vomiting in the migraine group (nausea, 61.8%; phonophobia, 25.3%; vomiting, 10.0%; and photophobia, 2.9%) and the probable migraine group (nausea, 82.2%; phonophobia, 9.5%; vomiting, 5.6%; and photophobia, 2.7%). In participants with migraine, vomiting (adjusted odds ratio = 6.513; 95% confidence interval, 1.763-24.057) and phonophobia (adjusted odds ratio = 0.437; 95% confidence interval, 0.206-0.929) were significantly associated with severe headache intensity and nausea was significantly associated with >3 headache days per 30 days (adjusted odds ratio = 0.441; 95% confidence, 0.210-0.927). Different patterns of associations were observed in probable migraine.
Topics: Humans; Photophobia; Hyperacusis; Migraine Disorders; Nausea; Vomiting; Headache; Surveys and Questionnaires; Double-Blind Method
PubMed: 38019845
DOI: 10.1371/journal.pone.0289729 -
Clinical and Experimental... Feb 2024The study aimed to assess the relationship of tinnitus with hyperacusis with cognitive impairment as indicated by the Montreal Cognitive Assessment (MoCA) tool.
OBJECTIVES
The study aimed to assess the relationship of tinnitus with hyperacusis with cognitive impairment as indicated by the Montreal Cognitive Assessment (MoCA) tool.
METHODS
This multicenter cross-sectional study included individuals with chronic tinnitus from the "Unification of Treatments and Interventions for Tinnitus Patients" (UNITI) database. Participants were recruited from four different tertiary clinical centers located in Athens and Granada (Mediterranean group), as well as Berlin and Regensburg (German group). In total, 380 individuals with a diagnosis of non-pulsatile chronic tinnitus (permanent and constant tinnitus lasting more than 6 months) and no evidence of severe cognitive impairment (MoCA score >22) were enrolled. The evaluation utilized the following tools: MoCA, Tinnitus Handicap Inventory (THI), Hyperacusis Questionnaire (GÜF), Patient Health Questionnaire (PHQ-9), and the European School for Interdisciplinary Tinnitus Research Screening Questionnaire.
RESULTS
MoCA scores differed between German and Mediterranean individuals (P<0.01), necessitating separate analyses for each group. In both cohorts, MoCA scores were significantly associated with education level, age, hearing threshold at 8 kHz, and THI. Furthermore, a significant correlation was observed between PHQ-9 scores and both THI and GÜF (P<0.01 for both Germans and those from the Mediterranean).
CONCLUSION
Our data suggest an association between tinnitus handicap, high-frequency hearing loss, and mild cognitive impairment. Additionally, PHQ-9 scores were associated with tinnitus and hyperacusis scores, independent of hearing loss thresholds.
PubMed: 37974057
DOI: 10.21053/ceo.2023.00808