Low-Molecular-Weight Hyaluronic Acid Contributes to Noise-Induced Cochlear Inflammation.

INTRODUCTION: Our previous work indicated that the activation of the Toll-like receptor (TLR) 4 signaling pathway contributed to noise-induced cochlear inflammation. Previous studies have reported that low-molecular-weight hyaluronic acid (LMW-HA) accumulates during aseptic trauma and promotes inflammation by activating the TLR4 signaling pathway. We hypothesized that LMW-HA or enzymes synthesizing or degrading HA might be involved in noise-induced cochlear inflammation. METHODS: The present study included two arms. The first arm was the noise exposure study, in which TLR4, proinflammatory cytokines, HA, hyaluronic acid synthases (HASs), and hyaluronidases (HYALs) in the cochlea as well as auditory brainstem response (ABR) thresholds were measured before and after noise exposure. The second arm was analysis of HA delivery-induced reactions, in which control solution, high-molecular-weight HA (HMW-HA), or LMW-HA was delivered into the cochlea by cochleostomy or intratympanic injection. Then, the ABR threshold and cochlear inflammation were measured. RESULTS: After noise exposure, the expression of TLR4, proinflammatory cytokines, HAS1, and HAS3 in the cochlea significantly increased over the 3rd to 7th day post-noise exposure (PE3, PE7). The expression of HYAL2 and HYAL3 dramatically decreased immediately after noise exposure, gradually increased thereafter to levels significantly greater than the preexposure level on PE3, and then rapidly returned to the preexposure level on PE7. The expression of HA, HAS2, and HYAL1 in the cochlea remained unchanged after exposure. After cochleostomy or intratympanic injection, both the hearing threshold shifts and the expression of TLR4, TNF-α, and IL-1ß in the cochleae of the LMW-HA group were obviously greater than those of the control group and HMW-HA group. The expression of proinflammatory cytokines in the LMW-HA and control groups on the 7th day (D7) after cochleostomy tended to increase compared to that on the 3rd day (D3), whereas levels in the HMW-HA group tended to decrease on D7 compared to D3. CONCLUSION: HAS1, HAS3, HYAL2, and HYAL3 in the cochlea are involved in acoustic trauma-induced cochlear inflammation through the potential proinflammatory function of LMW-HA.

Consensus on intratympanic drug delivery for Menière's disease.

PURPOSE: Intratympanic (IT) drug delivery receives attention due to its effectivity in treatment for Menière's disease (MD). Due to the release of the consensuses and new evidence on IT drug delivery for MD have been published, the review with a view to supplementing the details of IT treatment of MD is indispensable. METHODS: The literatures on IT injection for MD treatment over the last two decades are retrieved, International consensus (ICON) on treatment of Menière's disease (2018), Clinical Practice Guideline (2020) and European Position statement on Diagnosis and Treatment of Meniere's Disease (2018) are taken into account for reference, and follow advice from experts from Europe, USA and China. RESULTS: Experts agree on the following: (1) The effectiveness of IT methylprednisolone (ITM) on vertigo control seems to be somewhat better than that of IT dexamethasone (ITD), and ITM can restore hearing in some cases. (2) Due to the ototoxicity of aminoglycosides, the application of intratympanic gentamicin (ITG) in MD patients with good hearing is conservative. However, some studies suggest that ITG with low doses has no significant effect on hearing, which needs to be further proved by clinical studies with high levels of evidence. (3) Currently, generally accepted treatment endpoint of ITG is no vertigo attack in a 12-month period or a vestibular loss in objective tests in the affected ear. CONCLUSION: More studies with high level of evidence are needed to evaluate the drug type, efficacy, and therapeutic endpoint of IT therapy for MD.

High-quality imaging of endolymphatic hydrops acquired in 7 minutes using sensitive hT2W-3D-FLAIR reconstructed with magnitude and zero-filled interpolation.

BACKGROUND: It is still challenging to detect endolymphatic hydrops (EH) in patients with Meniere's disease (MD) using MRI. The aim of the present study was to optimize a sensitive technique generating strong contrast enhancement from minimum gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) while reliably detecting EH in the inner ear, including the apex. MATERIALS AND METHODS: All imaging was performed using a 3.0 T MR system 24 h after intratympanic injection of low-dose Gd-DTPA. Heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed with magnitude and zero-filled interpolation (hT2W-FLAIR-ZFI) was optimized and validated in phantom studies and compared with medium inversion time inversion recovery imaging with magnitude reconstruction (MIIRMR). The following parameters were used in hT2W-FLAIR-ZFI: repetition time 14,000 ms, echo time 663 ms, inversion time 2900 ms, flip angle 120°, echo train length 271, and field of view 166 × 196 mm2. RESULTS: MRI obtained using hT2W-FLAIR-MZFI yielded high-quality images with sharper and smoother borders between the endolymph and perilymph and a higher signal intensity ratio and more homogenous perilymph enhancement than those generated with MIIRMR (p < 0.01). There were predominantly grade II EHs in the cochleae and grade III EHs in the vestibule in definite MD. EH was detected in the apex of 11/16 ipsilateral ears, 3/16 contralateral ears in unilateral definite MD and 3/6 ears in bilateral MD. CONCLUSIONS: The novel hT2W-FLAIR-MZFI technique is sensitive and demonstrates strong and homogenous enhancement by minimum Gd-DTPA in the inner ear, including the apex, and yields high-quality images with sharp borders between the endolymph and perilymph.

Vestibular drop attacks in Ménière's disease and its association with migraine.

PURPOSE: We explored the association of vestibular drop attacks (VDA) with or without migraine in patients with Ménière's disease (MD) and compared with patients classified as vestibular migraine (VM). METHOD: The study involved a cross-sectional survey design. Data were collected from 401 members of Finnish Ménière Federation who experienced VDA. RESULTS: In the sample of 401 patients with VDA who did not experience headache, VM was diagnosed among 16.4% participants and migraine not associated with vertigo was experienced among 25.2% of the participants. Severity of postural instability, ability to move, and ability to stand up from chair differed among VDA baseline, VDA migraine and VM patient groups. Syncope associated with VDA was noticed more frequently in VM group. In terms of neurological complaints, except for visual problems, all other symptoms differed significantly between three patient groups. The health-related quality of life also differed between groups with VM group having the worse scores. CONCLUSIONS: The current study suggests that migraine is common in MD patients who experience VDA. We observed no definite complaint that could be ascertained to VM. The coexistence of migraine increased the impact of complaints associated with VDA.

Menière's disease.

Menière's disease causes paroxysmal rotatory vertigo, due to endolymphatic hydrops, an accumulation of endolymph in the endolymphatic space of the labyrinth. Its major symptoms are attacks of rotatory vertigo lasting minutes to hours, with unilateral hearing loss, tinnitus and aural fullness. As the disease progresses, attacks happen less often, but hearing loss and tinnitus gradually become permanent. Neuro-otological complications may develop, such as benign paroxysmal positional vertigo, vestibular drop attacks and bilateral vestibulopathy. The diagnosis of Menière's disease is based on the typical clinical picture and typical findings on the audiogram. Furthermore, it is now possible to diagnose it by MR of the inner ear. Long-term management has several steps, including diet, diuretics, intratympanic injection of corticosteroid or gentamicin and surgery (endolymphatic sac surgery, grommet insertion, surgical labyrinthectomy).

Relational quality, illness interference, and partner support in Ménière's disease.

OBJECTIVE: The current study aimed to better understand how patients and their significant others (SOs) cope with Menière's disease (MD). DESIGN: The study used a cross-sectional design and the data were collected using questionnaires. STUDY SAMPLE: Seventy-five dyads in which one person had MD. RESULTS: SOs of patients with MD not only experienced activity and participation restrictions but also had positive experiences. In relational quality, the SOs reported uncertainty of their future, limited visits in noisy places, limited activities as walking, watching TV, and participating in social life. The illness interference correlated with the patients' complaints, and most significant was the problem of imbalance. The quality of life was significantly reduced in patients with MD, and the illness interference in terms of quality of life was correlated with the SOs in items related to mood and anxiety. The stress related conditions of the SOs were correlated with two positive items (e.g. alleviating the stress factor). The SOs could also identify one positive item (i.e., improved relationship). CONCLUSIONS: Perceptions of MD as interfering in couples' lives influence dyadic coping in unique ways. The current study identified that dyadic coping has both positive aspects and limitations as a consequence of their partner's MD.

Internet-based peer support for Ménière's disease: a summary of web-based data collection, impact evaluation, and user evaluation.

OBJECTIVE: This paper presents a summary of web-based data collection, impact evaluation, and user evaluations of an Internet-based peer support program for Ménière's disease (MD). DESIGN: The program is written in html-form. The data are stored in a MySQL database and uses machine learning in the diagnosis of MD. The program works interactively with the user and assesses the participant's disorder profile in various dimensions (i.e., symptoms, impact, personal traits, and positive attitude). The inference engine uses a database to compare the impact with 50 referents, and provides regular feedback to the user. Data were analysed using descriptive statistics and regression analysis. STUDY SAMPLE: The impact evaluation was based on 740 cases and the user evaluation on a sample of 75 cases of MD respectively. RESULTS: The web-based system was useful in data collection and impact evaluation of people with MD. Among those with a recent onset of MD, 78% rated the program as useful or very useful, whereas those with chronic MD rated the program 55%. CONCLUSIONS: We suggest that a web-based data collection and impact evaluation for peer support can be helpful while formulating the rehabilitation goals of building the self-confidence needed for coping and increasing social participation.

Novel endosomolytic peptides for enhancing gene delivery in nanoparticles.

Trapping in the endosomes is currently believed to represent the main barrier for transfection. Peptides, which allow endosomal escape have been demonstrated to overcome this barrier, similarly to the entry of viruses. However, the design principles of such endosomolytic peptides remain unclear. We characterized three analogs derived from membrane disrupting antimicrobial peptides (AMP), viz. LL-37, melittin, and bombolitin V, with glutamic acid substituting for all basic residues. These analogs are pH-sensitive and cause negligible membrane permeabilization and insignificant cytotoxicity at pH7.4. However, at pH5.0, prevailing in endosomes, membrane binding and hemolysis of human erythrocytes become evident. We first condensed the emerald green fluorescent protein (emGFP) containing plasmid by protamine, yielding 115 nm diameter soluble nanoplexes. For coating of the nanoplex surface with a lipid bilayer we introduced a hydrophobic tether, stearyl-octa-arginine (SR8). The indicated peptides were dissolved in methanol and combined with lipid mixtures in chloroform, followed by drying at RT under a nitrogen flow. The dry residues were hydrated with nanoplexes in Hepes, pH7.4 yielding after a 30 min incubation at RT,rather monodisperse nanoparticles having an average diameter of 150-300 nm, measured by DLS and cryo-TEM. Studies with cell cultures showed the above peptides to yield expression levels comparable to those obtained using Lipofectamine 2000. However, unlike the polydisperse aggregates formed upon mixing Lipofectamine 2000 and plasmid, the procedure described yields soluble, and reasonably monodisperse nanoparticles, which can be expected to be suitable for gene delivery in vivo, using intravenous injection.

Calcium Metabolism Profile in Rat Inner Ear Indicated by MRI After Tympanic Medial Wall Administration of Manganese Chloride.

OBJECTIVES: To evaluate the efficacy of the novel method for the targeted delivery of Mn(++) to the inner ear and monitor calcium metabolism activity in the inner ear. MATERIALS AND METHODS: Dynamic signal changes of Mn(++) in the rat inner ear were followed using T1-weighted magnetic resonance imaging (MRI) after administration of 2.5 µl MnCl2(500 mM) to the medial wall of the middle ear cavity. RESULTS: Mn(++) passed through both the oval and round windows and distributed in the perilymphatic compartments, where it formed bright sharp lines along the fluid-cellular borders 12 minutes post administration and entered the endolymph sufficiently after 45 minutes. After 6 hours, the distribution of Mn(++) shifted from a fluid-dominant pattern to a cell-dominant pattern. Mn(++) concentrated in the area of the basilar membrane, periphery process, and soma of the spiral ganglion on day 2; became more distinguishable on day 4; declined on day 8; and remained detectable for 16 days post administration. CONCLUSIONS: The novel targeted delivery method efficiently introduced Mn(++) into the inner ear. The dynamic distribution pattern of Mn(++) in the inner ear shown by MRI indicates that this method can be used to monitor calcium metabolism activity in the inner ear.

Micro CT visualization of silver nanoparticles in the middle and inner ear of rat and transportation pathway after transtympanic injection.

BACKGROUND: Silver nanoparticles (Ag NPs) displayed strong activities in anti-bacterial, anti-viral, and anti-fungal studies and were reportedly efficient in treating otitis media. Information on distribution of AgNPs in different compartments of the ear is lacking. OBJECTIVE: To detect distribution of Ag NPs in the middle and inner ear and transportation pathways after transtympanic injection. METHODS: Contrast effect of Ag NPs in the micro CT imaging was assessed in a phantom. AgNPs at various concentrations (1.85 mM, 37.1 mM, and 370.7 mM) were administered to rat middle ear using transtympanic injection and cadaver heads were imaged using micro CT at several time points. RESULTS: The lowest concentration of Ag NPs that could be visualized using micro CT was 37.1 mM. No difference was observed between the solvents, deionized H2O and saline. Ag NPs at 37.1 mM were visible in the middle ear on 7 d post-administration. Ag NPs at 370.7 mM generated signals in the middle ear, ossicular chain, round window membrane, oval window, scala tympani, and Eustachian tube for both 4 h and 24 h time points. A gradient distribution of Ag NPs from the middle ear to the inner ear was detected. The pathways for Ag NPs to be transported from the middle ear into the inner ear are round and oval windows. CONCLUSION: This study provided the imaging evidence that Ag NPs are able to access the inner ear in a dose-dependent manner after intratympanic administration, which is relevant to design the delivery concentration in the future clinic application in order to avoid adverse inner ear effect.

Imaging Optimization of Temporal Bones With Cochlear Implant Using a High-resolution Cone Beam CT and the Corresponding Effective Dose.

OBJECTIVE: To evaluate the impact of tube voltage, tube current, pulse number, and magnification factor on the image quality of a novel experimental set-up and the corresponding radiation. MATERIALS AND METHODS: Six human temporal bones with cochlear implant were imaged using various tube voltages, tube currents, pulse numbers, and magnification. The effect of radiation was evaluated using a metaloxide semiconductor field-effect transistor (MOSFET) dosimeter device on an anthropomorphic RANDO RAN102 male head phantom. A copper and aluminum combination filter was used for hardware filtration. RESULTS: Overall, 900 frames, 11 mA, and 88 kV provided the best image quality. In temporal bones imaged with the optimized parameters, the cochlea, osseous spiral lamina, modiolus, stapes, round window niche, and oval window landmarks were demonstrated with anatomic structures still fully assessable in all parts and acceptable image quality. The most dominant contributor to the effective dose was bone marrow (36%-37 %) followed by brain (34%-36%), remainder tissues (12%), extra-thoracic airways (7%), and oral mucosa (5%). CONCLUSIONS: By increasing the number of frames, the image quality of the inner ear details obtained using the novel cone-beam computed tomography improved.

Enhanced oval window and blocked round window passages for middle-inner ear transportation of gadolinium in guinea pigs with a perforated round window membrane.

To elucidate the communication between the middle and inner ear, and the fluid dynamics of the inner ear with the perilymphatic fistula (PLF) of the round window membrane (RWM). The PLF of the RWM was created in nine guinea pigs. Gadolinium diethylenetriamine pentaacetic acid bismethylamide (Gd-DTPA-BMA) was delivered into the middle ear and followed in the inner ear using a 4.7 Tesla MRI. Pressure was delivered to the external ear canal of PLF ear in an attempt to enhance the inner ear uptake of Gd-DTPA-BMA. The immediate loading of Gd-DTPA-BMA in the scala tympani of the basal turn was ablated by the outflow of perilymph through the leaking RWM while the oval window passage for Gd-DTPA-BMA was enhanced. There was more Gd-DTPA-BMA distribution in the scala tympani than in the scala vestibuli in the second turn of the PLF cochlea (within 20 min). Signal in the vestibulum and scala vestibuli of the basal turn and rest part of PLF cochlea was greater than that of the control cochlea with intact RWM within 30 min. Pressure applied to the external ear canal tended to enhance the loading of Gd-DTPA-BMA in the perilymphatic scalae of the PLF cochlea. The enhanced oval window passage of Gd-DTPA-BMA was proven by the distorted distribution in the inner ear with PLF. The radial communication of cochlear perilymph was supported by the Gd-DTPA-BMA gradient among the perilymphatic scalae. Applying positive pressure to the external ear canal caused backflow of perilymph into the cochlea which has a potential of transmitting microbes from the middle ear into the inner ear.

Hyaluronan up-regulation is linked to renal dysfunction and hearing loss induced by silver nanoparticles.

Increased application of silver nanoparticles (AgNPs) has raised concerns on their potential adverse effects on human health. However, the precise toxicological mechanisms are not known in detail. The current study hypothesized that AgNPs induced glycosaminoglycan accumulation in the basement membrane that associated with the up-regulation of its component hyaluronic acid, known as a hydrophilic molecule of binding and retaining water, and caused toxicities in the kidney and cochlea. Rats administered AgNPs through either intravenous or intratympanic injection were observed at different time points after exposure. The concentrations of creatinine and urea in the serum were elevated remarkably, and proteins leaked into the urine were increased. A significant hearing loss over a broad range of frequencies was indicated. AgNP exposure induced glycosaminoglycan accumulation and hyaluronic acid up-regulation in the basement membrane. Abundant apoptotic cell death was demonstrated in the AgNP-exposed organs. Our results suggested that glycosaminoglycan accumulation associated with the up-regulation of hyaluronic acid was involved in the toxicities of kidney and cochlea caused by AgNPs.

Attitudes of significant others of people with Ménière's disease vary from coping to victimization.

OBJECTIVE: To explore the impact, reactions and coping methods of the significant others (SOs) of people with Ménière's disease (MD). DESIGN: SOs of people with MD were asked to answer open-ended questions reporting the 'life effects' and 'positive experiences' they have had as a result of the partner's condition. The replies to the 'life effects' question was categorized using the WHO-ICF framework. The responses of 'life effects' from this study and the 'positive experiences' reported in a recent study ( Manchaiah et al, 2013 ) were evaluated with K-means clustering analysis. STUDY SAMPLE: Eighty-eight SOs (42 male, 42 female, and four did not state gender). RESULTS: While the SOs mainly listed their own problems, a significant number of responses related to the problems of their partner. Personal perspectives tended to focus on the consequences of their partner's condition, whereas in perspectives of their partner they focussed on his/her symptoms. Further, replies from 81 SOs were used in evaluation of responses and were classified into four categories: constrained life attitude; disease burden attitude; care and support attitude; and social isolation attitude. CONCLUSIONS: The results of this study support the importance of including the SO of people with MD in the rehabilitation process.

Positive experiences associated with acquired hearing loss, Ménière's disease, and tinnitus: a review.

OBJECTIVE: It is common to study and understand how various illness and disorders result in negative consequences. However, positive experiences have been reported in a range of disabling conditions including multiple sclerosis, heart disease, physical and sensory disabilities. This paper presents a literature review of studies that have explored positive experiences associated with acquired hearing loss, Ménière's disease, and tinnitus. DESIGN: A review of the peer reviewed scientific literature. STUDY SAMPLE: A comprehensive search strategy identified 15 articles after applying inclusion criteria. RESULTS: A range of positive experiences have been reported by patients with hearing and balance disorders and by their significant others. Associations between demographic variables (e.g. age, gender), audiological variables (e.g. severity of the condition, duration) and the reported positive experiences are low. In Ménière's disease, self-reported positive experiences can predict the impact of the condition. However, this phenomenon has not yet been demonstrated in relation to hearing loss and tinnitus. CONCLUSIONS: Positive experiences associated with audio-vestibular disorders have been demonstrated. Further research is needed on the long-term benefits of the encouragement of such experiences and positive attitudes in persons with hearing loss, tinnitus, and imbalance.

Aural fullness in Ménière's disease.

OBJECTIVE: Aural fullness in Ménière's disease and the predisposing and consequential factors were investigated and possible consequences of aural fullness on participation activity were explored. METHODS: 726 subjects of the Finnish Ménière Association replied to a questionnaire focusing on symptoms of Ménière's disease, sense of coherence, attitude, participation restriction, and general health-related quality of life (EQ-5D). In the analysis, the severity of the disease was controlled. RESULTS: 68% of the subjects had aural fullness and in 37% it was moderate or strong. Aural fullness was rated as the worst problem by 4.4% of the subjects. Females reported more aural fullness than males. Tinnitus, hyperacusis and balance problems were significant predictors of aural fullness. Aural fullness was associated with reduced quality of life and complaints such as vertigo attacks, balance problems and hearing loss. Analysis based on participation restriction indicated that severe aural fullness leads to social isolation. CONCLUSIONS: Largely, psychological factors and personal traits modify problems experienced by aural fullness. Relaxation was the only statistically significant method that alleviated aural fullness.

Toxicity of silver nanoparticle in rat ear and BALB/c 3T3 cell line.

BACKGROUND: Silver nanoparticles (AgNPs) displayed strong activities in anti-bacterial, anti-viral, and anti-fungal studies and was reportedly efficient in treating otitis media .The potential impact of AgNPs on the inner ear was missing. OBJECTIVE: Attempted to evaluate the potential toxicity of AgNPs in the inner ear, middle ear, and external ear canal after transtympanic injection in rats. RESULTS: In in vitro studies, the IC50 for AgNPs in neutral red uptake assay was lower than that in NAD(P)H-dependent cellular oxidoreductase enzyme assay (WST-1) and higher than that in total cellular ATP and nuclear membrane integrity (propidium iodide) assessments. In in vivo experiments, magnetic resonance imaging (MRI) showed that significant changes in the permeability of biological barriers occurred in the middle ear mucosa, the skin of the external ear canal, and the inner ear at 5 h post-transtympanic injection of AgNPs at concentrations ranging from 20 µg/ml to 4000 µg/ml. The alterations in permeability showed a dosage-response relationship, and were reversible. The auditory brainstem response showed that 4000 µg/ml AgNPs induced hearing loss with partial recovery at 7 d, whereas 20 µg/ml caused reversible hearing loss. The functional change in auditory system was in line with the histology results. In general, the BALB/c 3T3 cell line is more than 1000 times more sensitive than the in vivo studies. Impairment of the mitochondrial function was indicated to be the mechanism of toxicity of AgNPs. CONCLUSION: These results suggest that AgNPs caused significant, dose-dependent changes in the permeability of biological barriers in the middle ear mucosa, the skin of the external ear canal, and the inner ear. In general, the BALB/c 3T3 cell line is more than 1000 times more sensitive than the in vivo studies. The rat ear model might be expended to other engineered nanomaterials in nanotoxicology study.

Postural control in restless legs syndrome with medication intervention using pramipexole.

Central dopamine regulation is involved in postural control and in the pathophysiology of restless legs syndrome (RLS) and Parkinson's disease (PD). Postural control abnormalities have been detected in PD, but there are no earlier studies with regard to RLS and postural control. Computerized force platform posturography was applied to measure the shift and the velocity (CPFV) of center point of forces (CPF) with eyes open (EO) and eyes closed (EC) in controls (n = 12) and prior and after a single day intervention with pramipexole in RLS subjects (n = 12). CPFV (EO) was significantly lower in the RLS group (p < 0.05) than in controls. After pramipexole intake, the difference disappeared and the subjective symptom severity diminished. Pramipexole did not significantly influence CPFV (EC) or CPF shift direction. Subjects with RLS used extensively visual mechanisms to control vestibule-spinal reflexes to improve or compensate the postural stability. Further research is needed to clarify altered feedback in the central nervous system and involvement of dopamine and vision in the postural control in RLS.

Association of Head Injury, Neck Injury or Acoustic Trauma on Phenotype of Ménière's Disease.

The aim of the present study was to investigate adverse effects of head injury, neck trauma, and chronic noise exposure on the complaint profile in people with Ménière's disease (MD). The study used a retrospective design. Register data of 912 patients with MD from the Finnish Ménière Federation database were studied. The data comprised case histories of traumatic brain injury (TBI), neck trauma and occupational noise exposure, MD specific complaints, impact related questions, and the E-Qol health-related quality of life instrument. TBI was classified based on mild, moderate, and severe categories of transient loss of consciousness (TLoC). The mean age of the participants was 60.2 years, the mean duration of the disease was 12.6 years, and 78.7% were females. Logistic regression analysis, linear correlation, and pairwise comparisons were used in evaluating the associations. 19.2% of the participants with MD had a history of TBI. The phenotype of participants with TBI was associated with frequent vestibular drop attacks (VDA), presyncope, headache-associated vertigo, and a reduction in the E-QoL. Logistic regression analysis explained the variability of mild TBI in 6.8%. A history of neck trauma was present in 10.8% of the participants. Neck trauma associated with vertigo (NTwV) was seen in 47 and not associated with vertigo in 52 participants. The phenotype of NTwV was associated with balance problems, VDA, physical strain-induced vertigo, and hyperacusia. Logistic regression analysis explained 8.7% of the variability of the complaint profile. Occupational noise exposure was recorded in 25.4% of the participants and correlated with the greater impact of tinnitus, hyperacusis, and hearing loss. Neither the frequency, duration, or severity of vertigo or nausea were significantly different between the baseline group and the TBI, NTwV, or noise-exposure groups. The results indicate that TBI and NTwV are common among MD patients and may cause a confounder effect.