Vascular Factors in Patients with Midlife Sensorineural Hearing Loss and the Progression to Mild Cognitive Impairment.

Background and Objectives: Midlife hearing loss (HL) has been considered as a major modifiable risk factor for a later-life progression to dementia. Our aim was to detect a link between precocious sensorineural hearing loss (SNHL) and mild cognitive impairment (MCI) and their association to putative risk factors for a common pathology. Materials and methods: In this study, a retrospective case-control study was carried out. A total of 112 patients were enrolled as following: 81 patients with bilateral SNHL and 31 subjects with normal hearing, whose ages ranged from 50 to 65 years. Both groups performed pure tone audiometry, a tinnitus handicap inventory (THI), Mini-Mental State examination (MMSE), and the Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS-A and HADS-D). Results: The mean age was 58 ± 5.2 in SNHL patients and 53.2 ± 4.8 in the control group. The mean pure tone average in the SNHL group was 40.2 ± 18.7 dB HL on the right side and 41.2 ± 17.2 dB HL on the left side, while in the control group it was 12.5 ± 2.8 dB HL on right side and 12.4 ± 3.1 dB HL on left side. About 64% of patients with SNHL exhibited comorbidities, and the most common condition was hypertension. Altered MoCA test scores were significantly related to the pure tone averages in patients with SNHL compared to the control group (p = 0.0004), while the differences in the HADS-A and HADS-D were not significant. Furthermore, a significant correlation was observed in SNHL patients between an altered MoCA test and hypercholesterolemia (p = 0.043). Conclusions: Hearing impairment and screening tests to detect MCI should be considered in the midlife in order to carry out strategies to prevent the progression to dementia. Hypertension and hypercholesterolemia are two risk factors in the development of endothelial dysfunction, oxidative stress, and vascular inflammation, and may represent the common pathology linking the inner ear and brain damage.

Does Hearing Loss in the Elderly Individuals Conform to Impairment of Specific Cognitive Domains?

BACKGROUND: It is well known that age-related hearing loss (ARHL) is strongly associated with dementia. Different hypotheses have been considered to explain this link, including sensorial deprivation, the reduction in cognitive reserve, and the presence of shared pathological pathways (microvascular damage of the brain). AIMS: We carried out a study of the audiological and neuropsychological characteristics of a sample of hearing impaired but cognitively healthy individuals (HIH). The aim of our study was to carefully outline the neuropsychological profile of the patients in order to verify whether hearing loss correlated with deficits in specific cognitive domains. RESULTS: Episodic memory is affected by the presence of hearing loss, while semantic competences, syntactic, and grammar skills seem not to be affected. Furthermore, some audiological features linked to the intelligibility of spoken words can predict the presence of executive dysfunction; the same does not apply to memory impairment. CONCLUSION: In HIH, executive functions are widely employed in maintaining an acceptable level of comprehension of spoken language; consequently, other cognitive domains and instrumental abilities in HIH are not properly supported. Thus, it is arguable that programs of hearing rehabilitation for HIH could restore the allocation of attentional resources to the functioning of other cognitive domains.

Clinical Evolution of Acute Vestibular Syndrome: Longitudinal Retrospective Analysis of Epidemiological Data and Prognostic Factors for Recovery.

We evaluated the clinical features of patients admitted to the ED with acute vertigo, verifying symptoms after one month and one year to establish epidemiological factors and predictors of resolution. We reviewed 233 records of patients admitted to ED for acute vertigo (125 F and 85 M, mean age 56.12 years). We analyzed the correlation between time of resolution (at one month and one year) and symptoms duration (subjective and/or objective vertigo, instability, cervical pain, audiological, neurological, and neurovegetative symptoms), comorbidities, and therapies, the result of the clinical and instrumental vestibular examination. Resolution of acute vertigo occurred in 81.1%, while persistence of vertigo one year after ED access was reported in 18.8%. There were 135 patients who recovered in one month. The presence of instability, auditory and neurovegetative symptoms, and neck pain represents a significant factor for recovery within one year. Age over 65 and a history of hypertension are associated with a worst recovery. Patients with spontaneous Nystagmus or positive HIT showed a significant difference in symptoms recovery within one month and one year. Presence of positional Nystagmus represents a positive prognostic factor. Our findings emphasize the importance of clinical evaluation of the acute vertigo, helping the clinicians to define central or peripheral diagnosis and predict the resolution of vertigo.

Hearing Impairment and Neuroimaging Results in Mitochondrial Diseases.

Mitochondrial diseases (MDs) are heterogeneous genetic disorders characterized by mitochondrial DNA (mtDNA) defects, involving tissues highly dependent on oxidative metabolism: the inner ear, brain, eye, skeletal muscle, and heart. We describe adult patients with genetically defined MDs, characterizing hearing function and neuroimaging results. We enrolled 34 patients (mean age: 50.02 ± 15 years, range: 18-75 years; 20 females and 14 males) classified in four groups: MELAS, MIDD, PEO, and Encephalopathy/Polyneuropathy. Audiological evaluations included psychoacoustical tests (pure-tone and speech audiometry), electrophysiological tests (Auditory Brainstem Responses, ABRs), and Impedenzometry. Neuroimaging evaluations considered global MRI abnormalities or structural brain changes. In total, 19/34 patients carried the m.3243A > G mutation (6 affected by MELAS, 12 affected by MIDD, and 1 affected by PEO); 11 had an mtDNA deletion (all affected by PEO); 3 had nuclear genes associated with MDs (POLG1 and OPA1); and 1 patient had an mtDNA deletion without an identified nuclear gene defect (affected by PEO). Sensory neural, bilateral, and symmetrical hearing loss was present in 25 patients (73.5%) to different degrees: 9 mild, 9 moderate, 5 severe, and 2 profound. The severe/profound and mild hearing losses were associated with pantonal and high-frequency audiograms, respectively. Instead, moderate hearing losses were associated with both high-frequency (five cases) and pantonal (five cases) audiogram shapes. In addition, 21/25 patients showed a cochlear site of lesion (84%), and 4/25 (16%) showed a retrocochlear site. We found global MRI abnormalities or structural brain changes in 26/30 subjects (86.6%): 21 had white matter abnormalities, 15 had cortical atrophy, 10 had subcortical atrophy, 8 had basal nuclei involvement or cerebellar atrophy, 4 had stroke-like lesions or laminar necrosis, and 1 had cysts or vacuolated lesions. We concluded that genetic alterations are associated with different clinical presentations for both auditory function and neuroradiological findings. There is no fixed relationship between genotype and phenotype for the clinical conditions analyzed.

Vestibular evoked myogenic potentials in children affected by myelomeningocele.

PURPOSE: The aim of the present study is to establish if the vestibular evoked myogenic potentials (VEMPs) could be used as a clinical test for the evaluation of vestibular function in children affected by myelomeningocele (MMC). MATERIALS AND METHODS: Fifteen children, aged between 3 and 17 years, who had been affected by MMC were investigated. Data obtained from these children were compared with normal data from healthy children of the same age. Electromyographic activity of sternocleidomastoid muscle was recorded, while children were laid supine and asked to raise their head off the bed in order to activate their neck flexors bilaterally. The saccular receptors were acoustically stimulated with a logon of 500 Hz at an intensity of 130 dB peSPL presented monaurally through earphones. In each recording, we analyzed latencies and amplitudes of the p13-and n23 waves and the amplitude ratio between the two ears. RESULTS: VEMPs were detected to be normal in 13 patients. In particular, the mean p13 and mean n23 latencies were 15.7 (±1.4) and 21.7 (±1.1) ms, respectively; the mean amplitude value was 84.7 (±36.6), while the mean amplitude ratio was 17.4 (±12). A comparison of latencies and amplitude ratios between the children and healthy control group did not reveal any significant difference. On the contrary, a comparison of amplitude values between the two groups showed significant differences. CONCLUSION: In conclusion, vestibulocollic reflex is normal in patients affected by MMC, and VEMPs could represent a valid and noninvasive technique eligible to investigate the vestibular functions in these children.

A Nasal Complication of Nasopharyngeal Swab for Reverse Transcription Polymerase Chain Reaction (RT-PCR) Detection of SARS-CoV-2 mRNA.

Nasopharyngeal (NP) and oropharyngeal (OP) specimens in the detection of the SARS-Cov-2 RNA are considered to have the highest diagnostic sensitivity and they have been recommended by the World Health Organization as the most reliable test. However, collecting NP specimens require specialized operators and adequate technique. We describe an intranasal breaking of the nasopharyngeal swab for anatomical reasons needing a surgical removing. We conclude that a safely procedure needs possibly a check for septal deviations or other causes of nasal obstruction.

Trafficking and postsecretory events responsible for the formation of secreted human salivary peptides: a proteomics approach.

To elucidate the localization of post-translational modifications of different classes of human salivary proteins and peptides (acidic and basic proline-rich proteins (PRPs), Histatins, Statherin, P-B peptide, and "S type" Cystatins) a comparative reversed phase HPLC-ESI-MS analysis on intact proteins of enriched granule preparations from parotid and submandibular glands as well as parotid, submandibular/sublingual (Sm/Sl), and whole saliva was performed. The main results of this study indicate the following. (i) Phosphorylation of all salivary peptides, sulfation of Histatin 1, proteolytic cleavages of acidic and precursor basic PRPs occur before granule storage. (ii) In agreement with previous studies, basic PRPs are secreted by the parotid gland only, whereas all isoforms of acidic PRPs (aPRPs) are secreted by both parotid and Sm/Sl glands. (iii) Phosphorylation levels of aPRPs, Histatin 1, and Statherin are higher in the parotid gland, whereas the extent of cleavage of aPRP is higher in Sm/Sl glands. (iv) O-Sulfation of tyrosines of Histatin 1 is a post-translational modification specific for the submandibular gland. (v) The concentration of Histatin 3, Histatin 5, and Histatin 6, but not Histatin 1, is higher in parotid saliva. (vi) Histatin 3 is submitted to the first proteolytic cleavage (generating Histatins 6 and 5) during granule maturation, and it occurs to the same relative extent in both glands. (vii) The proteolytic cleavages of Histatin 5 and 6, generating a cascade of Histatin 3 fragments, take place after granule secretion and are more extensive in parotid secretion. (viii) Basic PRPs are cleaved in the oral cavity by unknown peptidases, generating various small proline-rich peptides. (ix) C-terminal removal from Statherin is more extensive in parotid saliva. (x) P-B peptide is secreted by both glands, and its relative quantity is higher in submandibular/sublingual secretion. (xi) In agreement with previous studies, S type Cystatins are mainly the product of Sm/Sl glands.

Correlation between GJB2 mutations and audiological deficits: personal experience.

Mutations in GJB2 gene are the most common cause of genetic deafness. More than 100 mutations have been described. The aim of this work is to describe the personal experience in genetic hearing loss, investigating the audiological and genetical characteristics of Cx26 deafness and correlating genotype and phenotype. We performed audiological and genetical evaluation in 154 patients affected by non-syndromic deafness of different degree. All patients showed a bilateral symmetrical sensorineural hearing loss. From the genetical analysis 127 probands resulted as negatives while 27 as positives (51.8% homozygous for 35 delG, 14.8% compound heterozygosis and 33.3% single mutation); 7.5% of patients had a mild deafness, 37% moderate, 33.3% severe and 22.2% profound. The c.35 delG mutation was detected in 66.6% of patients. Three mutations were found in compound heterozygosis with 35 delG, six different single mutations already described, and a new mutation S138G were also found. Correlation between genotype and phenotype confirmed the high variability of hearing loss.

Vestibular evoked myogenic potentials in children.

OBJECTIVE: The aim of this work is to establish if the vestibular evoked myogenic potentials (VEMPs) could be used as a clinical test of vestibular function in children. MATERIALS AND METHODS: Forty normal hearing children, aged between 3 and 15 years, and classified in preschool and scholar group, have been investigated in order to study normal development of vestibular potentials and to define fundamental parameters of VEMPs, establishing normal data of latencies and amplitude ratio. Electromyographic activity of sternocleidomastoid muscle was recorded while children were laid supine on a bed and asked to raise their head off of the bed in order to activate their neck flexors bilaterally. The saccular receptors were acoustically stimulated with a logon of 500Hz at an intensity of 130dB peSPL presented monaurally through earphones. In each recording, we analysed latencies and amplitudes of the p13 and n23 waves and the amplitude ratio between the two ears. RESULTS: VEMPs were normally detected in all subjects. In preschool group mean p13 and mean n23 latencies were, respectively, 16.13 (+/-2.12)ms and 21.17 (+/-2.77)ms; mean amplitude ratio was 28.49 (+/-18.10). In scholar group mean p13 and n23 were respectively 16.14 (+/-3.48)ms and 21.78 (+/-3.39)ms, while mean amplitude ratio 20.44 (+/-13.24). Comparison of latencies and amplitude ratio between the children groups and control adult group did not showed any significant differences. CONCLUSION: In conclusion, VEMPs could represent a valid and non-invasive technique able to investigate vestibular function in children and, in particular, vestibulo collic reflex.

Audiologic Assessment in Adults With Down Syndrome.

Increased life expectancy in persons with Down syndrome (DS) is associated with premature age-related changes. The aim of this study was to assess auditory function in adults with DS and to evaluate the prevalence of hearing loss in this population. Audiometric tests were performed in 72 adults with DS (mean age 37.3±10.1 years, 51.4% females). Air conduction pure tone average (PTA) thresholds at frequencies 0.5-1-2-4 kHz were calculated to assess hearing function. Hearing loss was present if the PTA threshold was > 20 dB hearing level. Higher frequencies of 4 and 8 kHz were also assessed. Hearing loss was shown in 47 (65.3%) participants. The prevalence of hearing loss increased with age, ranging from 42.86% in the 20-29 years group to 90.91% in the 50-59 years group. High frequencies (4 and 8 kHz) were more often impaired than other frequencies used to measure PTA. Thus, the study concluded hearing loss is common in adults with DS and shows a pattern compatible with precocious aging of the hearing system. Auditory evaluation is strongly recommended in adults with DS.

Expression of vascular endothelial growth factor and its receptors in the cochlea of various experimental animals.

CONCLUSION: The results of this study indicate that vascular endothelial growth factor (VEGF) may be an important regulator of the vascular network of the inner ear and suggest that the VEGF signalling pathway may play a role in pathophysiologic conditions. OBJECTIVE: In order to clarify the role of vascular growth factor in the modulation of the vascular network of the cochlea, we studied the expression of VEGF and its receptors-fms-like tyrosine kinase (Flt-1) and foetal liver kinase (Flk-1)-in the inner ear of 3-month-old rodents of different species: C57BL/6J mice, Wistar albino rats and Hartley albino guinea pigs. MATERIAL AND METHODS: Qualitative immunohistochemical studies were performed by using specific antibodies to VEGF and its receptors on paraffin sections of the cochlea. The expression levels of VEGF and its receptors were quantified by means of Western blot analysis of cochlea protein extracts. RESULTS: We demonstrated that VEGF and its receptors are expressed in the cochlea and described their distribution in the inner ear. In particular, VEGF and Flt-1 are present at the level of the modiolus, spiral ganglion, spiral ligament, basilar membrane, supporting cells, outer and inner hair cells and stria vascularis. Flk-1 was less strongly expressed in the cochlea and was not detected in the organ of Corti.

VEMPs and dynamic posturography after intratympanic gentamycin in Menière's disease.

In this study, we investigated whether vestibular evoked myogenic potentials (VEMPs) and dynamic posturography (DP) are useful in the evaluation of the vestibular function in patients affected by active monoaural Menière's disease (MD) treated with intratympanic gentamycin. Twelve subjects affected by monoaural MD were treated with weekly intratympanic injections of 0.5 ml of gentamycin at a concentration of 20 mg/ml. VEMPs were used to test saccular function, while postural control was analyzed by DP. The results obtained with these two techniques were compared with those obtained by using bithermal caloric test. The mean follow-up was 15.3 months (6--28 months). Therapy resulted in complete absence of the caloric response in six subjects (50) and in caloric test-induced asymmetry in the remaining individuals, ranging from 83 to 27. At follow-up, eleven patients (91.6%) were free of vertigo, while one patient had two vertigo spells 9 months after treatment. Before treatment, VEMPs were present in the affected ear of eleven patients. After treatment VEMPs were absent in all the patients. At the end of follow-up, reappearance of VEMPs was observed in two patients, with no changes in latency values and amplitude ratio. DP demonstrated a reduction of the Composite Score (CS) one week after therapy, with a prevalent reduction of the vestibular component. After 6 months, there was an improvement of the CS and, in particular, of the vestibular component. The present study demonstrates that bithermal caloric test and VEMPs allow for the functional evaluation of both the horizontal semicircular canal and the sacculus, suggesting that these techniques might be used together to monitor the efficacy of intratympanic gentamycin therapy. In addition, our data indicate that DP might provide important information on compensation phenomena and show that intratympanic gentamycin can improve postural control in MD patients.

A case-control study on proinflammatory genetic polymorphisms on sudden sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: Sudden sensorineural hearing loss (SSNHL) is strictly related to inner ear vascular injuries and recently to some atherosclerotic risk factors. The pathogenic role of inflammatory molecules in atherosclerosis is well established. However, there is little knowledge about the potential role of inflammatory cytokines and adhesion molecules on SSNHL etiology. STUDY DESIGN: The aim of this study was to evaluate the role of proinflammatory genetic polymorphisms of the MCP-1 (CCL2), E-selectin, and interleukin (IL)-6 gene in SSNHL patients. METHODS: We evaluated the frequency and distribution of selected single nucleotide polymorphisms of the MCP-1 (CCL2), E-selectin, and IL-6 gene in 87 SSNHL patients and 107 healthy controls. RESULTS: Our results did not show significant difference between the compared groups for MCP-1 and E-selectin genes, whereas a significant difference was reported for the IL-6 gene (P < .0001). CONCLUSIONS: The main finding of our study is that the 174G/G polymorphism (with a wider distribution of wt/wt genotype in SSNHL patients than in the healthy controls) of the IL-6 gene is significantly associated with the risk of SSNHL, which is consistent with a previous finding on serum levels of IL-6 in SSNHL. It is possible that the variant acts as a triggering agent of different lipidemia-related phenotypes. Both the -174G/G polymorphism and elevated IL-6 levels in SSNHL patients could suggest that IL-6 plays a role in the inner ear involvement by atherosclerotic inflammatory events.

Pathogenesis of presbycusis in animal models: a review.

Presbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal models.

Modifications in nasal function and nitric oxide serum level in type 1 diabetes.

OBJECTIVE: In this study, we evaluated the modifications of nasal function in type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]) by active anterior rhinomanometry (AAR) to understand if involvement of the nasal nervous system and microcirculation could be detected in nasal mucosa. METHOD: We studied 35 nonsmoking IDDM patients without diabetic complications, nasal pathology, or septal deviation. We measured serum levels of nitric oxide (NO) and nasal airway in three conditions: basal, supine, and after decongestion (phenylephrine hydrochloride 0.25 mg spray) by means of rhinomanometry, determining inspiratory total resistance and nasal airflow. The rhinomanometric results of the IDDM patients were compared with those of control normal subjects. In the IDDM patients, neuropathy was evaluated according to standardized procedures, including the vibration perception threshold test, cardiovascular autonomic tests, conduction velocity test, and fundoscopic examination. RESULTS: The NO serum level was significantly higher in IDDM patients (12.5 +/- 3.8) compared with normal controls (4.8 +/- 1.4). The AAR results showed that in IDDM patients, inspiratory total resistance in the basal (0.82 +/- 0.4 Pa/cm3) and supine (0.94 +/- 0.7 Pa/cm3) positions and after decongestion (0.59 +/- 0.2 Pa/cm3) were increased compared with the control group in three conditions (basal, 0.52 +/- 0.2 Pa/cm3; supine, 0.58 +/- 0.3 Pa/cm3; after decongestion, 0.48 +/- 0.2 Pa/cm3). After decongestion, there was a greater decrease in nasal resistance in diabetic patients than in normal subjects. CONCLUSION: Nasal function is involved in IDDM, rhinomanometry can also be considered an important test in the evaluation of this involvement in patients without other signs of diabetic neuropathy, and an increase in NO could partially explain these alterations.