Food-induced stimulation of the antisecretory factor to improve symptoms in Meniere's disease: our results.

PURPOSE: Specially processed cereals (SPC) that increase endogenous antisecretory factor (AF) synthesis have been proposed to improve symptoms of Meniere's disease (MD) with controversial results. The aim of this study was to evaluate the effects of SPC in patients with definite unilateral MD and compare the results to a treatment protocol with intravenous glycerol and dexamethasone. METHODS: Thirteen patients with unilateral MD were treated with SPC and 13 patients were treated with intravenous glycerol and dexamethasone for 12 months. Audio-vestibular evaluation was performed before (T0) and at the end of the treatments (T12). The number of vertigo spells were evaluated before and after therapy and the Efficacy Index (EI) was calculated. Questionnaires for hearing loss (HHIA), tinnitus (THI) and quality of life (TFL) were administered. RESULTS: EI decreased in the SPC group in the second semester compared to the first although not significantly (p = 0.6323). There was a significant reduction for THI score in the SPC group at T12 (p = 0.0325). No significant differences were found between the two groups at T0 (p = 0.4723), while a significant difference was found at T12 (p = 0.0041). Quality of life showed an improvement in daily activities in the SPC group compared to infusion therapy group. CONCLUSION: Our study shows a reduced number of vertigo attacks and a positive effect on the discomfort generated by tinnitus and quality of life in patients with unilateral MD treated with SPC and when compared to patients treated with intravenous glycerol and dexamethasone. No effects on hearing thresholds were noted in both groups.

The Effects of Viewing Smart Devices on Static Balance, Oculomotor Function, and Dizziness in Healthy Adults.

BACKGROUND The number of people using smart devices such as smartphones (SPs) or virtual reality head-mounted displays (HMDs) is rapidly increasing. This study aimed to investigate the effects of viewing smart devices, including SPs and HMDs, on postural balance and the development of dizziness in healthy individuals. MATERIAL AND METHODS Twenty-six healthy adults underwent static balance measurements at baseline, and after 5, 10, and 20 minutes of viewing the SP and HMD display. Measurements were taken using a force plate and Wii Balance Board (WBB) and included the parameters of postural sway velocity, path length, and postural sway area. A modified Simulator Sickness Questionnaire (SSQ) evaluated oculomotor function and dizziness twice for each device, after 5 and 20 minutes of use. RESULTS Compared with baseline, the use of smart devices for 20 minutes had significantly increased effects on balance, oculomotor function, and dizziness than shorter use for 10 minutes or 5 minutes in healthy adults. Postural sway velocity and path length were significantly increased after 20 minutes of use of the HMD and SP when compared 5-minute use and baseline measurements (p<0.05). Postural sway area after 20-minute use of the HMD was significantly increased compared with the baseline and 5-minute and 10-minute use of the SP and 5-minute use of the HMD (p<0.05). The SSQ showed that dizziness was significantly increased after 20-minute use compared with 5-minute use of the HMD and SP (p<0.05). CONCLUSIONS Longer use of smart devices affected static balance, oculomotor function, and dizziness in healthy adults.

Pathogenetic Role of Endothelial Dysfunction in Idiopathic Vestibulopathy.

Comparative analysis of the groups of patients with idiopathic bilateral vestibular hypofunction and a group of vestibulopathy patients with vertebrobasilar insufficiency demonstrated identity of the basic and additional diagnostic parameters in these syndromes as well as similarity in clinical diagnostic and anamnesis data. In all cases, functional assessment of endothelium-dependent vasodilation and selected biochemical marker sICAM-1 revealed endothelial dysfunction. Drug correction of endothelial dysfunction positively affected the manifestations of major and minor features of the syndrome, which confirmed the contribution of endothelial functional disturbances to the pathogenesis of bilateral vestibular hypofunction.

Unilateral horizontal semicircular canal occlusion induces serotonin increase in medial vestibular nuclei: a study using microdialysis in vivo coupled with HPLC-ECD.

Unilateral single semicircular canal occlusion (USSCO) is an effective treatment for some cases of intractable vertigo. All patients suffer behavioural imbalance caused by surgery, and then recover with a resumption of vestibular function. However, the compensation mechanism has not been fully evaluated. Findings suggest that serotonin (5-HT) is released from nerve terminals, and plays a vital role in the plasticity of the central nervous system. In this study, we performed surgery of unilateral single semicircular canal occlusion (USSCO) on guinea pigs, and investigated the change of 5-HT by in vivo microdialysis of the medial vestibular nucleus (MVN) coupled with high-performance liquid chromatography and electrochemical detection (HPLC-ECD). A total of 12 guinea pigs were divided randomly into two groups, namely the USSCO group and the control group. Animals in the USSCO group underwent surgery of lateral horizontal semicircular canal occlusion, and those in the control group experienced the same operation but just to expose the horizontal semicircular canal without occlusion. Vestibular disturbance symptoms were observed in the case of the USSCO group, e.g. head tilting, and forced circular movements and spontaneous nystagmus at postoperative days 1 and 3. The basal level of 5-HT was determined to be 316.78 ± 16.62 nM. It elevated to 448.85 ± 24.56 nM at one day following occlusion (P = 0.001). The increase was completely abolished with the vestibular dysfunction recovery. The results showed that unilateral horizontal semicircular canal occlusion could increase the 5-HT level in MVN. 5-HT may play a significant role in the process of central vestibular compensation with residual vestibular function.

Evidence for modulation of opioidergic activity in central vestibular processing: A [(18)F] diprenorphine PET study.

Animal and functional imaging studies had identified cortical structures such as the parieto-insular vestibular cortex, the retro-insular cortex, or the anterior cingulate cortex belonging to a vestibular cortical network. Basic animal studies revealed that endorphins might be important transmitters involved in cerebral vestibular processing. The aim of the present study was therefore to analyse whether the opioid system is involved in vestibular neurotransmission of humans or not. Changes in opioid receptor availability during caloric air stimulation of the right ear were studied with [(18)F] Fluoroethyl-diprenorphine ([(18)F]FEDPN) PET scans in 10 right-handed healthy volunteers and compared to a control condition. Decrease in receptor availability to [(18)F]FEDPN during vestibular stimulation in comparison to the control condition was significant at the right posterior insular cortex and the postcentral region indicating more endogenous opioidergic binding in these regions during stimulation. These data give evidence that the opioidergic system plays a role in the right hemispheric dominance of the vestibular cortical system in right-handers.

Doubling of water intake increases daytime blood pressure and reduces vertigo in healthy subjects.

We studied the effect of increased water intake on ambulatory blood pressure (BP) in healthy individuals. Blood pressure was recorded after 2 weeks of either regular (RWI) or extra water intake (EWI, an additional 30 ml water/kg body weight per day) in 20 healthy subjects (10 males, 10 females). The extra water intake (RWI: 1.7 ± 0.59 l, EWI: 3.7 ± 0.84 l, respectively, p < 0.0001, i.e., an increase of 2 liters) induced an increase in mean arterial daytime BP from 89.0 ± 5.5 mmHg during RWI to 91.4 ± 6.4 mmHg during the EWI phase (p = 0.005), while night-time BP was unchanged by the intervention. The visual-analogue-scale (VAS, maximum score of 10) score corresponding to the statement "I often experience vertigo" was 3.1 ± 2.6 during RWI and decreased to 2.1 ± 2. 1 during EWI phase (p = 0.008). In conclusion,two liters of extra water intake for 2 weeks significantly increased daytime blood pressure and reduced a sense of vertigo in healthy individuals.

The possible contribution of angiitis to the onset of benign paroxysmal positional vertigo (BPPV).

OBJECTIVE: The aim was to evaluate the oxidative stress and the angiitis in patients with BPPV. METHOD: Patients with benign paroxysmal positional vertigo (BPPV) within 14 days of onset were analyzed. The level of diacron reactive oxygen metabolites (d-ROM) and circulating soluble vascular cell adhesion molecule 1 (VCAM-1), were evaluated. As a treatment the patients were taught to perform the Brandt-Daroff exercise at home by themselves. The prognosis of BPPV, which is measured as the time until the disappearance of positional nystagmus by a physician during the outpatient visit each week, the relation among the level of oxygen metabolites, vascular molecule and the duration until remission were analyzed. RESULTS: The patients who required longer time for the disappearance of positional nystagmus showed high d-ROM and VCAM levels, whereas those who required shorter time for remission showed lower d-ROM and VCAM levels. CONCLUSION: There is an increased expression of VCAM-1 and d-ROM confirming the existence of an angiitis and supporting the vascular involvement in BPPV. The identification of the high levels of d-ROM and VCAM-1 can open the way to selective pharmacological treatments able to correct the oxidative stress and activation of endothelial cells.

A possible mechanism of the formation of endolymphatic hydrops and its associated inner ear disorders.

The pathology of Meniere's disease (MD) is well established to be endolymphatic hydrops. However, the mechanism underlying deafness and vertigo of MD or idiopathic endolymphatic hydrops is still unknown. In order to evaluate the pathogenesis of deafness and vertigo in MD, it seems to be rational to investigate the interrelationship between hydrops and inner ear disorders using animals with experimentally-induced endolymphatic hydrops. In spite of intense efforts by many researchers, the mechanism of vertiginous attack has been unexplained, because animals with experimental hydrops usually did not show vertiginous attack. Recently, there are two reports to succeed to evoke vertiginous attack in animals with experimental hydrops. In the present paper were first surveyed past proposals about underlying mechanism of the development of hydrops and inner ear disorders associated with hydrops, and were discussed the pathogenetic mechanism of vertiginous attack in hydrops. In conclusion, abrupt development of hydrops was thought to play a pivotal role in the onset of vertiginous seizure.

Proteome of normal human perilymph and perilymph from people with disabling vertigo.

The vast majority of hearing loss, the most common sensory impairment, and vertigo, which commonly causes falls, both reflect underlying dysfunction of inner ear cells. Perilymph sampling can thus provide molecular cues to hearing and balance disorders. While such "liquid biopsy" of the inner ear is not yet in routine clinical practice, previous studies have uncovered alterations in perilymph in patients with certain types of hearing loss. However, the proteome of perilymph from patients with intact hearing has been unknown. Furthermore, no complete characterization of perilymph from patients with vestibular dysfunction has been reported. Here, using liquid-chromatography with tandem mass spectrometry, we analyzed samples of normal perilymph collected from three patients with skull base meningiomas and intact hearing. We identified 228 proteins that were common across the samples, establishing a greatly expanded proteome of the previously inferred normal human perilymph. Further comparison to perilymph obtained from three patients with vestibular dysfunction with drop attacks due to Meniere's disease showed 38 proteins with significantly differential abundance. The abundance of four protein candidates with previously unknown roles in inner ear biology was validated in murine cochleae by immunohistochemistry and in situ hybridization: AACT, HGFAC, EFEMP1, and TGFBI. Together, these results motivate future work in characterizing the normal human perilymph and identifying biomarkers of inner ear disease.

Inhibiting Histamine Signaling Ameliorates Vertigo Induced by Sleep Deprivation.

Although histamine inhibitors have been used in the motility-associated vertigo, the link between histamine and sleep deprivation (SD)-induced vertigo has not been clearly demonstrated. The histamine plasma levels were assayed in the SD volunteers before SD and 24 h after SD. Pinnacle's automated sleep deprivation system was used to establish the female C57BL/6 mice SD model. Histidine decarboxylase inhibitor 4-bromo-3-hydroxybenzoic acid (BHOA), and antihistamine diphenhydramine (DPHM) were injected intraperitoneally to test their effects on SD-induced vertigo. Rotarod tests and vestibular scores 24 and 48 h post SD were utilized to assay the vestibular function. Western blot was used to determine the expression of histidine decarboxylase (HDC) in the vestibular, and PowerChrom was utilized to quantify the concentrations of cerebrospinal fluid (CSF) histamine. SD increased plasma concentration of histamine in humans. Upregulated HDC in the vestibular and increased CSF concentration of histamine can be detected in the SD mice, indicating vestibular dysfunction which can be ameliorated by both BHOA and DPHM. Histamine signaling inhibition may ameliorate SD-induced vertigo, and histamine can be considered as a potential treatment target.

Preliminary study on the mechanism underlying the interaction of balance dysfunction and anxiety disorder.

This study aims to explore the anxiety-related behavioral changes and the concentration alterations of monoamine neurotransmitters in balance/anxiety-related nuclei of intratympanic gentamicin (GT)-induced balance disorder models. GT was administrated intratympanically in the adult male Sprague-Dawley rats to establish the vestibular impaired animal model. Rotarod was applied to test the vestibular function, and elevated plus maze and open field test were harnessed to evaluate the anxiety level. Monoamines and their metabolites were assayed by high-performance liquid chromatography. Rotarod test revealed that 6 days after GT administration, the average latency decreased significantly compared with the control group. Three days after GT administration, the travel distance and the central zone time obtained from open field and the duration of open arm stay and the times of open arm entries from elevated plus maze were apparently lower than those of the control group, whereas no significant differences were noted between 2-week group and the control group. Three days after GT administration, the concentration of norepinephrine (NE) and 5-hydroxyindoleacetic acid (5-HIAA) within medial vestibular nucleus (MVN); the concentration of NE, serotonin (5-HT), and 5-HIAA within locus coeruleus (LC); and the concentration of NE, 5-HT, 5-HIAA, and 3,4-dihydroxyphenylacetic acid within dorsal raphe nucleus (DRN) increased significantly compared with the control group. Two weeks after the administration, the concentrations of part of the neurotransmitters were lower than those of the 3-day group, indicating the rapid activation and slow deactivation of MVN-LC and MVN-DRN pathways. Vestibular impairment could lead to elevated anxiety level. The elevated anxiety levels might be attributed to increased monoamine concentrations within MVN, LC, and DRN.

Histamine H1 receptors are expressed in mouse and frog semicircular canal sensory epithelia.

Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. Their site and mechanism of action, however, are still poorly understood. To increase our knowledge of the histaminergic system in the vestibular organs, we have investigated the expression of H1 and H3 histamine receptors in the frog and mouse semicircular canal sensory epithelia. Analysis was performed by mRNA reverse transcriptase-PCR, immunoblotting and immunocytochemistry experiments. Our data show that both frog and mouse vestibular epithelia express H1 receptors. Conversely no clear evidence for H3 receptors expression was found.

Effect of blood donation on well-being of blood donors.

The demand for blood products steadily increases. Concurrently, blood donor recruitment becomes more and more difficult. This study aimed to investigate effects of blood donation on blood donors, which could be helpful for blood donor recruitment and retention. In addition to cortisol measurements in saliva, three questionnaires quantifying mood (good/bad), vigilance (awake/tired), agitation (calm/nervous), actual strain and asking for donation-related effects perceived were distributed to 110 whole blood donors (DON). Results obtained were compared with 109 control subjects (CON) lacking the blood donation experience. Overall, 216 subjects completed the questionnaires. Sixty-eight percent of DON reported at least one effect perceived with blood donation. Exclusively, positive, negative or mixed effects were described by 26.5%, 23.5% and 17.6%, respectively. Among positive effects (i.e. physical/psychological well-being, feeling satisfied, happy, proud), no significant differences were observed between males and females (P = 0.07), whereas mixed or negative effects (i.e. vertigo, dizziness, tiredness, pain) were significantly (P = 0.03; P = 0.049) more associated with females. DON showed higher levels of well-being than CON as indicated by better mood (P = 0.004), higher vigilance (P = 0.015) and relaxation (P = 0.003). The latter even increased after donation with maximum values after 15 and 30 min. Despite significantly higher initial strain scores (P = 0.008), first-time donors maintained a better mood (P = 0.025) than repeat donors. DON showed a statistically better psychological well-being than CON, although the donation experience was perceived as stressful, especially for first-time donors. The results may facilitate donor recruitment and retention as blood donation may become less frightening and perhaps even attractive.

Basilar artery angulation and vertigo due to the hemodynamic effect of dominant vertebral artery.

Vertebral arteries form the basilar artery at the pontobulbar junction. The vertebral artery may have dominancy in one of them. The branches of basilar arteries supply blood for the vestibular nuclei and its connections. Vertigo is seen generally in the upper middle aged patients. Vertigo can be observed in dolichoectasia of basilar artery such as angulation and elongation, because of the diminished blood supply and changed hemodynamic factors of vestibular nuclei and its connections. We hypothesized that angulation or elongation of basilar artery can be estimated according to the unilateral vertebral artery dominant hypertensive patients. The basilar artery can angulate from the dominant side of vertebral artery to the recessive side. These angulation and elongation can effect the hemodynamic factors in absence of growing collateral arteries. So, the vertigo attacks may occur in these patients.

Changes in cerebral activation in individuals with and without visual vertigo during optic flow: A functional near-infrared spectroscopy study.

Background and purpose: Individuals with visual vertigo (VV) describe symptoms of dizziness, disorientation, and/or impaired balance in environments with conflicting visual and vestibular information or complex visual stimuli. Physical therapists often prescribe habituation exercises using optic flow to treat these symptoms, but it is not known how individuals with VV process the visual stimuli. The primary purpose of this study was to use functional near-infrared spectroscopy (fNIRS) to determine if individuals with VV have different cerebral activation during optic flow compared with control subjects. Methods: Fifteen individuals (5 males and 10 females in each group) with VV seeking care for dizziness and 15 healthy controls (CON) stood in a virtual reality environment and viewed anterior-posterior optic flow. The support surface was either fixed or sway-referenced. Changes in cerebral activation were recorded using fNIRS during periods of optic flow relative to a stationary visual environment. Postural sway of the head and center of mass was recorded using an electromagnetic tracker. Results: Compared with CON, the VV group displayed decreased activation in the bilateral middle frontal regions when viewing optic flow while standing on a fixed platform. Despite both groups having significantly increased activation in most regions while viewing optic flow on a sway-referenced surface, the VV group did not have as much of an increase in the right middle frontal region when viewing unpredictable optic flow in comparison with the CON group. Discussion and conclusions: Individuals with VV produced a pattern of reduced middle frontal cerebral activation when viewing optic flow compared with CON. Decreased activation in the middle frontal regions of the cerebral cortex may represent an alteration in control over the normal reciprocal inhibitory visual-vestibular interaction in visually dependent individuals. Although preliminary, these findings add to a growing body of literature using functional brain imaging to explore changes in cerebral activation in individuals with complaints of dizziness, disorientation, and unsteadiness. Future studies in larger samples should explore if this decreased activation is modified following a rehabilitation regimen consisting of visual habituation exercises.

Salivary α-amylase levels in vertigo: Can it be an autonomic dysfunction?

We aim to demonstrate possible autonomic dysfunction based on salivary α-amylase measurements during and after the vertigo attacks associated with Ménière disease (MD) and benign paroxysmal positional vertigo (BPPV). Patients admitted to the emergency room with a diagnosis of vertigo attacks caused by either MD (n = 15) or BPPV (n = 9) constituted the study groups. The control group (n = 10) consisted of volunteer patients admitted to the emergency department with minor soft-tissue trauma. The first saliva samples were obtained immediately during the attacks and the second and third samples were obtained on the third and fifteenth days of the attack, respectively. In the controls, the first sample was obtained after admission to the hospital and the second sample was obtained on the third day. Salivary α-amylase levels were evaluated. The difference between salivary α-amylase levels in patients with MD and BPPV was not significant. The amylase value measured early after the BPPV attack was significantly lower than that of the controls (p = 0.008). Although not significant, an undulating pattern of salivary α-amylase levels was observed with both diseases. An autonomic imbalance could be partly demonstrated by salivary α-amylase measurement early after the attack in patients with BPPV. Therefore, amylase may be a promising marker that is worth further investigation.

Bone Metabolic Markers in the Clinical Assessment of Patients with Superior Semicircular Canal Dehiscence.

BACKGROUND: Superior semicircular canal dehiscence (SSCD) is a bony defect in the osseous shell of the petrous temporal bone. The pathophysiological association between osteoporosis and SSCD remains poorly understood. We investigated the relationship between bone metabolic markers and symptoms in patients with SSCD. METHODS: We collected patient demographics and clinical parameters for adult patients diagnosed with SSCD on high-resolution computed tomography scans. We used point-biserial correlation analysis to investigate the relationship between bone metabolic markers and symptoms in patients with SSCD. We compared clinical symptoms before and after surgical repair of SSCD through a middle fossa craniotomy using McNemar's test for paired comparisons of binary measures. RESULTS: We included a total of 99 patients (64 females and 35 males; average age 52 years; 118 surgeries). The level of serum calcium correlated with the need for a second surgery (rpb = -0.35, P = 0.001). Postoperative calcium supplementation negatively correlated with improvement in dizziness (rpb = -0.36, P = 0.01). The level of 25-hydroxyvitamin D correlated with preoperative hyperacusis (rpb = -0.98, P = 0.02) and postoperative autophony (rpb = 0.96, P = 0.04). Postoperative vitamin D supplementation positively correlated with hearing decline (rpb = 0.04, P = 0.04) The level of thyroid stimulating hormone correlated with preoperative autophony, amplification, and tinnitus (rpb = -0.71, rpb = -0.75, rpb = -0.70, all P < 0.001). CONCLUSIONS: Bone metabolic markers could be important in the clinical assessment of SSCD patients and could be potential targets for symptom management.

Mechanoreceptors in Diseased Cervical Intervertebral Disc and Vertigo.

STUDY DESIGN: We collected the samples of cervical intervertebral discs from patients with vertigo to examine the distribution and types of mechanoreceptors in diseased cervical disc. OBJECTIVE: The aim of this study was to determine whether mechanoreceptors are distributed more abundantly in cervical discs from patients with cervical spondylosis, and whether they are related to vertigo. SUMMARY OF BACKGROUND DATA: Previous limited studies have found that normal cervical intervertebral discs are supplied with mechanoreceptors that have been considered responsible for proprioceptive functions. Several clinical studies have indicated that the patients with cervical spondylosis manifested significantly impaired postural control and subjective balance disturbance. METHODS: We collected 77 samples of cervical discs from 62 cervical spondylosis patients without vertigo, 61 samples from 54 patients with vertigo, and 40 control samples from 8 cadaveric donors to investigate distribution of mechanoreceptors containing neurofilament (NF200) and S-100 protein immunoreactive nerve endings. RESULTS: The immunohistochemical investigation revealed that the most frequently encountered mechanoreceptors were the Ruffini corpuscles in all groups of cervical disc samples. They were obviously increased in the number and deeply ingrown into inner annulus fibrosus and even into nucleus pulposus in the diseased cervical discs from patients with vertigo in comparison with the discs from patients without vertigo and control discs. Only three Golgi endings were seen in the three samples from patients with vertigo. No Pacinian corpuscles were found in any samples of cervical discs. CONCLUSION: The diseased cervical discs from patients with vertigo had more abundant distribution of Ruffini corpuscles than other discs. A positive association between the increased number and ingrowth of Ruffini corpuscles in the diseased cervical disc and the incidence of vertigo in the patients with cervical spondylosis was found, which may indicate a key role of Ruffini corpuscles in the pathogenesis of vertigo of cervical origin. LEVEL OF EVIDENCE: 1.

Sleep Disturbance and Altered Expression of Circadian Clock Genes in Patients With Sudden Sensorineural Hearing Loss.

The cause of sudden sensorineural hearing loss (SSNHL) remains unclear and therefore it is often considered as idiopathic. Sleep disturbance has been linked to SSNHL and circadian rhythm disruption, but the link between circadian rhythm disruption and SSNHL has never been investigated.In this study, we surveyed the sleep quality of 38 patients with SSNHL using a simple insomnia sleep questionnaire. The expression of circadian clock genes in peripheral blood (PB) leukocytes from 38 patients with SSNHL and 71 healthy subjects was accessed using real-time quantitative reverse transcriptase-polymerase chain reaction and validated using immunocytochemical staining.We found that 61.8% of patients with SSNHL suffered from insomnia before the insult of hearing loss. Besides, significantly decreased expression of PER1, CRY1, CRY2, CLOCK, BMAL1, and CKlε was found in PB leukocytes of patients with SSNHL when compared with healthy subjects. SSNHL patients with vertigo had significantly lower expression of CRY1 and CKlε than patients without vertigo symptoms. Our results imply the association of sleep disturbance and disrupted circadian rhythm in SSNHL.