Galvanic vestibular stimulation-induced activation of C1 neurons in medulla oblongata protects against acute lung injury.

Autonomic nerves, including the sympathetic and parasympathetic nerves, control the immune system along with their physiological functions. On the peripheral side, the interaction between the splenic sympathetic nerves and immune cells is important for the anti-inflammatory effects. However, the central mechanism underlying these anti-inflammatory effects remains unclear. C1 neurons respond to stressors and subsequently determine the outflow of the autonomic nervous system. We have previously shown that C1 neurons protect against acute kidney injury and found a signaling connection between peripheral vestibular organs and C1 neurons. Thus, we hypothesized that hypergravity load or galvanic vestibular stimulation (GVS) might protect against acute lung injury. We showed that C1 neurons are histologically and functionally activated by stimulating the peripheral vestibular organs. Protection against acute lung injury that was induced by a 2 G load disappeared due to vestibular lesions or the deletion of C1 neurons. This GVS-induced protective effect was also eliminated by the deletion of the C1 neurons. Furthermore, GVS increased splenic sympathetic nerve activity in conscious mice, and splenic sympathetic denervation abolished the GVS-induced protection against acute lung injury. Therefore, the activated pathway between C1 neurons and splenic sympathetic nerves is indispensable for GVS-induced protection against acute lung injury.

Repeated activation of C1 neurons in medulla oblongata decreases anti-inflammatory effect via the hypofunction of the adrenal gland adrenergic response.

The immune system is known to be controlled by the autonomic nervous system including sympathetic and parasympathetic (vagus) nerves. C1 neurons in the medulla oblongata, which participate in the control of the autonomic nervous system, are responders to stressors and regulate the immune system. Short-term activation of C1 neurons suppresses inflammation, while the effect of a long-term activation of these neurons on the inflammatory reflex is unclear. We, herein, demonstrate that the coactivation of both the splenic sympathetic nerves and the adrenal gland adrenergic response are indispensable for the prognosis of acute lung injury. The chemogenetic activation of C1 neurons increased plasma catecholamine including adrenaline and noradrenaline levels. The deletion of catecholaminergic cells using local injections of viral vector in the adrenal gland abolished the protective effect against acute lung injury when the C1 neurons were stimulated by either chemogenetic or optogenetic tools. Furthermore, repeated activation of C1 neurons using chemogenetic tool inhibited the adrenal response without affecting the plasma noradrenaline levels, eliminated the protective effect against acute lung injury. This was rescued by the isoprenaline administration. We concluded that the maintenance of an adrenergic response via C1 neurons in the adrenal gland is a prerequisite for the delivery of an effective anti-inflammatory response.

Cervical Vestibular Evoked Myogenic Potentials That Are Absent at 500 Hz But Present at 1000 Hz Are Characteristic of Endolymphatic Hydrops-Related Disease.

OBJECTIVES: It remains unclear whether the dominance of 1000 Hz responses over responses at 500 Hz in cervical vestibular evoked myogenic potentials (cVEMPs) are characteristic of endolymphatic hydrops (EH), due to the presence of patients with absent responses at both frequencies. The purpose of the present study is to examine whether the dominant cVEMP responses at 1000 Hz over 500 Hz are characteristic findings of EH-related diseases among patients who show various cVEMP findings. DESIGN: We retrospectively reviewed the medical records of 470 consecutive patients who underwent cVEMP testing with short-tone bursts at both 500 Hz and 1000 Hz. We categorized the cVEMP responses of these 470 patients into the following five groups: (group 1) present responses at both frequencies bilaterally, (group 2) present responses at 500 Hz but absent at 1000 Hz on at least one side, (group 3) absent responses at 500 Hz but present at 1000 Hz on at least one side, (group 4) absent responses at both frequencies on one side and present at both frequencies on the other side, and (group 5) absent responses at both frequencies bilaterally. We compared the proportion of EH-related diseases between each group and the other four groups and then investigated any increased or decreased disease incidence in each group. RESULTS: In group 3, the proportion of EH-related disease was significantly higher (p < 0.01), and the incidence of an EH-related disease was greatly increased (standard residual value > 3). CONCLUSIONS: cVEMPs that are absent at 500 Hz and present at 1000 Hz may be characteristic of EH-related disease.

Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa.

The effects of caloric restriction (CR) on cell dynamics and gene expression in the mouse olfactory neuroepithelium are evaluated. Eight-week-old male C57BL/6 mice were fed either control pellets (104 kcal/week) or CR pellets (67 kcal/week). The cytoarchitecture of the olfactory neuroepithelium in the uninjured condition and its regeneration after injury by an olfactotoxic chemical, methimazole, were compared between mice fed with the control and CR diets. In the uninjured condition, there were significantly fewer olfactory marker protein (OMP)-positive olfactory receptor neurons and Ki67-positive proliferating basal cells at 3 months in the CR group than in the control group. The number of Ki67-positive basal cells increased after methimazole-induced mucosal injury in both the control and the CR groups, but the increase was less robust in the CR group. The recovery of the neuroepithelium at 2 months after methimazole administration was less complete in the CR group than in the control group. These histological changes were region-specific. The decrease in the OMP-positive neurons was prominent in the anterior region of the olfactory mucosa. Gene expression analysis using a DNA microarray and quantitative real-time polymerase chain reaction demonstrated that the expression levels of two inflammatory cytokines, interleukin-6 and chemokine ligand 1, were elevated in the olfactory mucosa of the CR group compared with the control group. These findings suggest that CR may be disadvantageous to the maintenance of the olfactory neuroepithelium, especially when it is injured.

The adhesion molecule cadherin 11 is essential for acquisition of normal hearing ability through middle ear development in the mouse.

Cadherin 11 (Cdh11), a member of the cadherin adhesion molecule family, is expressed in various regions of the brain as well as the head and ear. To gain further insights into the roles of Cdh11 in the development of the ear, we performed behavioral tests using Cdh11 knockout (KO) mice. KO mice showed reduced acoustic startle responses and increased thresholds for auditory brainstem responses, indicating moderate hearing loss. The auditory bulla volume and ratio of air-filled to non-air-filled space in the middle ear cavity were reduced in KO mice, potentially causing conductive hearing loss. Furthermore, residual mesenchymal and inflammatory cells were observed in the middle ear cavity of KO mice. Cdh11 was expressed in developing mesenchymal cells just before the start of cavitation, indicating that Cdh11 may be directly involved in middle ear cavitation. Since the auditory bulla is derived from the neural crest, the regulation of neural crest-derived cells by Cdh11 may be responsible for structural development. This mutant mouse may be a promising animal model for elucidating the causes of conductive hearing loss and otitis media.

Macrophage recruitment, but not interleukin 1 beta activation, enhances noise-induced hearing damage.

It has been suggested that macrophages or inflammatory monocytes participate in the pathology of noise-induced hearing loss (NIHL), but it is unclear how extensively these cells contribute to the development of temporary and/or permanent NIHL. To address this question, we used clodronate liposomes to deplete macrophages and monocytes. After clodronate liposome injection, mice were exposed to 4-kHz octave band noise at 121 dB for 4 h. Compared to vehicle-injected controls, clodronate-treated mice exhibited significantly reduced permanent threshold shifts at 4 and 8 kHz and significantly smaller outer hair cell losses in the lower-apical cochlear turn. Following noise exposure, the stria vascularis had significantly more cells expressing the macrophage-specific protein F4/80, and this effect was significantly suppressed by clodronate treatment. These F4/80-positive cells expressed interleukin 1 beta (IL-1ß), which noise exposure activated. However, IL-1ß deficient mice did not exhibit significant resistance to intense noise when compared to wild-type mice. These findings suggest that macrophages that enter the cochlea after noise exposure are involved in NIHL, whereas IL-1ß inhibition does not reverse this cochlear damage. Therefore, macrophages may be a promising therapeutic target in human sensorineural hearing losses such as NIHL.

Denervation of nasal mucosa induced by posterior nasal neurectomy suppresses nasal secretion, not hypersensitivity, in an allergic rhinitis rat model.

The posterior nasal nerve is the dominant source of the parasympathetic, sympathetic, and sensory fibers that innervate the nasal respiratory mucosa. Therefore, a posterior nasal neurectomy (PNN) is thought to induce denervation of the nasal mucosa and relieve the nasal symptoms of allergic rhinitis. However, the underlying mechanisms and therapeutic action of PNN remain unknown. To investigate the impact of PNN-induced denervation of the nasal mucosa on allergic rhinitis, we developed a rat model of PNN and examined the effects of PNN on allergic rhinitis in ovalbumin-sensitized rats. This rat model of PNN was characterized by the depletion of nerve fibers, choline acetyltransferase, and neuropeptides (eg, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and neuropeptide Y) in the nasal respiratory mucosa. These animals exhibited nasal gland and goblet cell hypertrophy in the septal mucosa and atrophy of the submucosal gland in the lateral nasal wall, as well as reduced nasal secretion due to deficient acetylcholine synthesis. In an ovalbumin-sensitized model of allergic rhinitis, PNN also induced the depletion of nerve fibers, choline acetyltransferase, and neuropeptides in the nasal mucosa and suppressed nasal secretion. However, PNN did not affect mucosal thickening, eosinophil and mast cell infiltration, interleukin-4 and interferon-γ mRNA expression, and allergic symptoms (ie, sneezing and nasal scratching). These results suggest that the peripheral nerves and corresponding neuropeptides regulate nasal secretion, but not hypersensitivity, in allergic rhinitis, and that allergic rhinitis-related mucosal reactions occur in a highly denervated mucosa after PNN. Posterior nasal neurectomy may be a therapeutic option for the treatment of hyperrhinorrhea, but not allergic rhinitis hypersensitivity.

Human Papillomavirus 16 Physical Status and the TP53 Codon 72 Polymorphism in Japanese HPV-Positive Oropharyngeal Cancer Patients.

BACKGROUND: In human papillomavirus (HPV)-induced carcinogenesis, the arginine (Arg) allele of the TP53 codon 72 polymorphism binds more efficiently to the HPV E6 oncoprotein than the proline (Pro) allele. We investigated the physical status of HPV-16 DNA and the TP53 codon 72 polymorphism in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Tumor samples from 70 p16-positive OPSCC patients were tested for HPV-16 physical status by examining the E2 and E6 open reading frames. The TP53 codon 72 polymorphism was screened by direct sequencing. RESULTS: Of 70 patients, 53 were E6 positive, 29 had integrated forms of HPV-16 DNA, and 24 had mixed or episomal forms. Furthermore, 44 carried the Arg/Arg or Arg/Pro genotype, 3 carried the Pro/Pro genotype, and in 6 patients we were unable to obtain sequencing data. CONCLUSIONS: HPV-16 physical status was heterogeneous in our OPSCC patients. Most OPSCC patients had the TP53 Arg/Arg or Arg/Pro genotype.

Prognostic value of p16 expression irrespective of human papillomavirus status in patients with oropharyngeal carcinoma.

OBJECTIVE: In a previous study, we reported the value of p16 expression and alcohol consumption in oropharyngeal carcinoma in Japan. We now report the clinical significance of human papillomavirus status and p16 expression in oropharyngeal carcinoma in Japan. METHODS: Over a 9-year period, a retrospective case comparison study of the pathology database was conducted at the University of Tokyo to identify tumor samples of oropharyngeal carcinoma. We performed immunohistochemistry for the p16 protein, in situ hybridization for human papillomavirus-deoxyribonucleic acid and polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 in oropharyngeal carcinoma in Japanese patients. We evaluated the human papillomavirus status in patients with oropharyngeal carcinoma to determine its prevalence and association with prognosis. We defined human papillomavirus(+) and human papillomavirus(-) oropharyngeal carcinoma cohorts as those with and without polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 or in situ hybridization-human papillomavirus. RESULTS: In oropharyngeal carcinoma, the prevalences of p16(+)human papillomavirus(+), p16(+)human papillomavirus(-), p16(-)human papillomavirus(+) and p16(-)human papillomavirus(-) were 32% (48/150), 7% (10/150), 2% (3/150) and 59% (89/150), respectively. Low tobacco and alcohol consumption, tonsil or base of tongue localization, but not age, were associated with p16(+)human papillomavirus(+). Low alcohol consumption was associated with p16(+)human papillomavirus(-). There was a significant difference in overall survival between p16(+)human papillomavirus(-) and p16(-)human papillomavirus(-) (P = 0.03). In multivariate Cox regression models, p16 was the independent prognostic factor, regardless of human papillomavirus status. CONCLUSION: p16 expression was a reliable prognostic biomarker regardless of human papillomavirus status.

Clinical characteristics of patients with abnormal ocular/cervical vestibular evoked myogenic potentials in the presence of normal caloric responses.

OBJECTIVE: To investigate the clinical features and vestibular symptoms of patients with abnormal ocular vestibular evoked myogenic potentials (oVEMPs) and/or cervical VEMPs (cVEMPs) in the presence of normal caloric responses. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. METHODS: One thousand five hundred twenty-one consecutive patients with balance problems who underwent the caloric, cVEMP, and oVEMP tests were included, and patients who showed abnormal oVEMPs and/or cVEMPs in the presence of normal caloric responses were selected. Clinical characteristics, diagnoses, and vestibular symptoms of the patients were analyzed. RESULTS: Of the 1521 patients, 227 (15%) were found to have abnormal oVEMPs and/or cVEMP responses with normal caloric responses. Benign paroxysmal positional vertigo (BBPV), Meniere's disease, and vestibular migraine were the common diagnoses of these patients. Eighty-one patients (36%) could not be diagnosed with a recognizable disease. Multiple episodes of spinning vertigo with a duration of seconds to hours were their most common vestibular symptoms. CONCLUSION: BPPV, Meniere's disease, and vestibular migraine are the most frequent diagnoses showing abnormal oVEMP and/or cVEMPs without canal paresis. Apart from these clinical entities, a portion of undiagnosed patients with multiple episodes of vertigo might have a disease that involves the otolith organs only.

Idiopathic latent vestibulopathy: a clinical entity as a cause of chronic postural instability.

The objective of this study is to describe a new clinical entity of idiopathic latent vestibulopathy (ILV), in which patients have unilateral or bilateral vestibulopathy combined with unsteadiness but without episodic vertigo, auditory disturbance, or a medical history suggesting the presence of vestibulopathy. A retrospective study of 1,233 consecutive new outpatients was conducted. Two-legged stance tasks were performed by 11 patients identified as having ILV in four conditions: eyes open with and without foam rubber, and eyes closed with and without foam rubber. We examined six parameters: the velocity of movement of the center of pressure (COP) with eyes closed/foam rubber, the envelopment area traced by the movement of the COP with eyes closed/foam rubber, Romberg's ratio of velocity and area with foam rubber, and the foam ratios of velocity and area with eyes closed. Multiple regression analyses were performed in order to explore the relationship between the presence of ILV and the six parameters recorded during foam posturography, while adjusting for the subjects' gender and age. The presence of ILV had a significantly positive relationship with the values of 4 of the 6 parameters. Even though six patients showed only unilateral vestibulopathy, their median value in all 6 parameters was greater than that of healthy controls. ILV could be a clinical entity accountable for postural instability.

Developmental changes in the protective effect of exogenous brain-derived neurotrophic factor and neurotrophin-3 against ototoxic drugs in cultured rat vestibular ganglion neurons.

We examine developmental changes in the responsiveness of rat vestibular ganglion neurons (VGNs) to two neurotrophic factors (NTFs), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and investigate the protective effects of these NTFs against ototoxic drugs during postnatal development in dissociated cultures. VGNs were obtained from rats on postnatal days (P) 1, 3, 7 and 14. BDNF facilitated neuronal survival as well as neurite sprouting of VGNs obtained from younger rats (P1 and P3), whereas these effects were not observed in older rats (P7 and P14). BDNF was also effective in facilitating neurite extension in VGNs at each of the postnatal ages. NT-3 also facilitated neuronal survival and neurite extension of VGNs from younger rats but these effects were significantly smaller than those of BDNF (p < 0.05). The protective effects of BDNF and NT-3 against ototoxic drugs, gentamicin and cisplatin, were also age-dependent: they were effective for neuronal survival, neurite sprouting and neurite extension in VGNs from younger rats, whereas these effects tended to disappear in VGNs from older rats. Analysis of the changes in the expression of the receptors of NTFs revealed that expression of TrkB and TrkC proteins and their mRNA did not change during the developmental period, whereas expression of p75(NTR) protein was down-regulated together with that of p75(NTR) mRNA during the developmental period. Developmental changes in the responsiveness to exogenous NTFs in VGNs, which is not caused by the changes of their receptors but probably caused by changes in the intracellular signaling pathways, should be taken into consideration in the prevention of neuronal degeneration caused by ototoxic drugs.

Premature senescence is regulated by crosstalk among TFEB, the autophagy lysosomal pathway and ROS derived from damaged mitochondria in NaAsO2-exposed auditory cells.

Age-related hearing loss (ARHL) is one of the most prevalent types of sensory decline in a superaging society. Although various studies have focused on the effect of oxidative stress on the inner ear as an inducer of ARHL, there are no effective preventive approaches for ARHL. Recent studies have suggested that oxidative stress-induced DNA damage responses (oxidative DDRs) drive cochlear cell senescence and contribute to accelerated ARHL, and autophagy could function as a defense mechanism against cellular senescence in auditory cells. However, the underlying mechanism remains unclear. Sodium arsenite (NaAsO2) is a unique oxidative stress inducer associated with reactive oxygen species (ROS) that causes high-tone hearing loss similar to ARHL. Transcription factor EB (TFEB) functions as a master regulator of the autophagy‒lysosome pathway (ALP), which is a potential target during aging and the pathogenesis of various age-related diseases. Here, we focused on the function of TFEB and the impact of intracellular ROS as a potential target for ARHL treatment in a NaAsO2-induced auditory premature senescence model. Our results suggested that short exposure to NaAsO2 leads to DNA damage, lysosomal damage and mitochondrial damage in auditory cells, triggering temporary signals for TFEB transport into the nucleus and, as a result, causing insufficient autophagic flux and declines in lysosomal function and biogenesis and mitochondrial quality. Then, intracellular ROS derived from damaged mitochondria play a role as a second messenger to induce premature senescence in auditory cells. These findings suggest that TFEB activation via transport into the nucleus contributes to anti-senescence activity in auditory cells and represents a new therapeutic target for ARHL. We have revealed the potential function of TFEB as a master regulator of the induction of oxidative stress-induced premature senescence and the senescence-associated secretion phenotype (SASP) in auditory cells, which regulates ALP and controls mitochondrial quality through ROS production.

The effect of a first-generation H1-antihistamine on postural control: a preliminary study in healthy volunteers.

First-generation H1-antihistamines are known to cause fatigue and drowsiness, due to their poor receptor selectivity and their high penetration rate of the blood-brain barrier. However, little is known about the effects of first-generation H1-antihistamines on postural stability. The purpose of this study was to evaluate the effects of d-chlorpheniramine on postural stability using posturography with and without foam rubber. A double-blind study with three parallel groups was conducted. Twenty-seven healthy young volunteers (mean age 21.9 years) were recruited and orally administered d-chlorpheniramine, 2 or 4 mg, or placebo. Postural sway was measured every hour up to 8 h after administration. Two-legged stance tasks were performed by each subject in four conditions: eyes open or eyes closed and with or without foam rubber. Inter-group comparisons showed that the group receiving 4-mg d-chlorpheniramine showed significantly larger sway in the eyes open with foam rubber condition (visual and vestibular information available, somatosensory information reduced). Inter-subject analysis in the 4-mg d-chlorpheniramine group showed that the effect of d-chlorpheniramine on postural control was variable. Our results suggest that among the three main sensory systems responsible for postural control (visual, vestibular, and somatosensory), d-chlorpheniramine may have a larger effect on the visual and/or vestibular systems in susceptible individuals.

Effect of vestibular dysfunction on the development of gross motor function in children with profound hearing loss.

OBJECTIVE: To evaluate the function of the superior and inferior vestibular nerve systems in children with profound sensorineural hearing loss, and to assess the influence of dysfunction of each vestibular nerve system on the development of gross motor function. STUDY DESIGN: Retrospective study. SETTING: A tertiary referral center. METHODS: Eighty-nine children (age range: 20-97 months) with profound sensorineural hearing loss who were due to undergo cochlear implant surgery were recruited. Function of the superior vestibular nerve system was evaluated by the damped rotation test and the caloric test, whereas functions of the inferior vestibular nerve systems were evaluated by the vestibular evoked myogenic potential (VEMP) test. Gross motor development was assessed using the age of acquisition of head control and independent walking. RESULTS: Among the children able to complete the vestibular function tests, abnormalities were found in 20% (16 of 84 children) in the damped rotation test, 41% (31 of 75 children) in the caloric test and 42% (26 of 62 children) in the VEMP test. Children who showed abnormal responses in the vestibular function tests showed significantly delayed acquisition of head control (p < 0.05) and independent walking (p < 0.05) in comparison with children with normal responses. The children who showed abnormal responses in all 3 vestibular tests showed the greatest delay in acquisition of gross motor function in comparison with the other groups. CONCLUSIONS: Children with profound hearing loss tend to have dysfunction in the superior as well as the inferior vestibular nerve systems. Both the superior and inferior vestibular nerve systems are important for the development of gross motor function in children.

Diagnostic usefulness of multifrequency tympanometry for Ménière's disease.

Multifrequency tympanometry (MFT) is the measurement of the impedance of the middle ear transmission system at a wide range of frequencies from 200 Hz to 2 kHz. A potential use of MFT as a new diagnostic tool for detecting endolymphatic hydrops has recently been reported. However, its clinical usefulness for diagnosing Ménière's disease (MD) remains unclear. To evaluate the clinical usefulness of MFT as a new qualitative and diagnostic test for MD, we performed MFT in 70 patients with unilateral or bilateral MD and in 29 normal control subjects. The width of double peaks in the admittance tympanograms (Y width) at 2 kHz and the resonance frequency (RF) were analyzed, and receiver operating characteristic (ROC) curves were constructed. The Y width in MD-affected ears was significantly greater than that in control ears (p < 0.001). The RF in MD-affected ears was significantly lower than that in control ears (p < 0.01). Neither the Y width nor RF had a significant relationship with hearing levels or the results of caloric and vestibular myogenic potential testings. The area under the ROC curve was 0.71 for the Y width and 0.66 for the RF. At the optimal cutoff points, the sensitivity and specificity of the Y width were 47.3 and 86.8%, respectively, and those of the RF were 41.3 and 84.2%, respectively. These results indicated that MFT is significantly associated with the presence of MD, but its diagnostic accuracy is only modest. MFT is a simple, noninvasive test, which should be considered as a complementary test in the diagnosis of MD.

Oral Administration of TrkB Agonist, 7, 8-Dihydroxyflavone Regenerates Hair Cells and Restores Function after Gentamicin-Induced Vestibular Injury in Guinea Pig.

The causes of vestibular dysfunction include the loss of hair cells (HCs), synapses beneath the HCs, and nerve fibers. 7, 8-dihydroxyflavone (DHF) mimics the physiological functions of brain-derived neurotrophic factor. We investigated the effects of the orally-administered DHF in the guinea pig crista ampullaris after gentamicin (GM)-induced injury. Twenty animals treated with GM received daily administration of DHF or saline for 14 or 28 days (DHF (+) or DHF (-) group; N = 5, each). At 14 days after GM treatment, almost all of the HCs had disappeared in both groups. At 28 days, the HCs number in DHF (+) and DHF (-) groups was 74% and 49%, respectively, compared to GM-untreated control. In the ampullary nerves, neurofilament 200 positive rate in the DHF (+) group was 91% at 28 days, which was significantly higher than 42% in DHF (-). On day 28, the synaptic connections observed between C-terminal-binding protein 2-positive and postsynaptic density protein-95-positive puncta were restored, and caloric response was significantly improved in DHF (+) group (canal paresis: 57.4% in DHF (+) and 100% in DHF (-)). Taken together, the oral administration of DHF may be a novel therapeutic approach for treating vestibular dysfunction in humans.

The effect of self-management vestibular rehabilitation on persistent postural-perceptual dizziness.

Objective: To investigate the effects of self-management vestibular rehabilitation (VR) on the subjective symptoms of dizziness and postural stability in persistent postural-perceptual dizziness (PPPD). Study design: Retrospective case review. Methods: The medical records of 30 patients newly diagnosed with PPPD based on the Bárány Society's diagnostic criteria were reviewed. Nineteen patients (4 males and 15 females; age range 27-84 years, mean age ± standard deviation 57.4 ± 14.2 years) who was newly instructed to self-management VR were included and instructed to perform self-management VR for 2 months. Results: One patient did not visit the outpatient clinic again, and in the remaining 18 patients, 4 (22%) discontinued VR at their own discretion. In the 12 patients who completed 2 months of VR (67%), there was a significant improvement in Niigata PPPD Questionnaire (NPQ) and Dizziness Handicap Inventory (DHI) scores after VR compared to those before VR (p < .05). However, the mean velocity of center of pressure (COP) movement (velocity) and the envelopment area traced by COP movement (area), as well as the Romberg ratio and foam ratio of velocity and area, did not differ significantly after VR when compared to those before VR (p > .05). Conclusions: For PPPD, self-management VR improved subjective symptoms of dizziness, but not stability of standing posture. It is necessary to improve patients' adherence to the treatment. Level of evidence: 4.

Inter-day and intra-day variations in effective intensity of noisy galvanic vestibular stimulation to improve postural stability in bilateral vestibulopathy.

BACKGROUND: The reproducibility of the effective intensity of noisy galvanic vestibular stimulation (nGVS) to improve postural stability is not well known. OBJECTIVE: We aimed to investigate inter-day and intra-day variations in effective intensity in patients with bilateral vestibulopathy (BVP). METHODS: Thirteen BVP patients were measured for center-of-pressure movements in the standing posture at five time points: morning of the first test day, morning and evening of the second test day, and morning and evening of the third test day. The mean velocity, the envelopment area, and the root mean square were measured in the eyes-closed condition for 30 s during nGVS application ranging from 0 to 1000µA. The effective intensity was defined as the intensity at which all the three parameters measured during the stimulation were simultaneously smaller than the values at baseline (0µA). RESULTS: Seven of the 13 patients had a common effective intensity throughout the three test days. Six patients on the second test day and five patients on the third test day had no common effective intensity between morning and evening. CONCLUSIONS: The effective intensity of nGVS changes depending on the time during the day as well as between the days.

Analysis of postural stability using foam posturography in patients with persistent postural-perceptual dizziness.

BACKGROUND/OBJECTIVE: Persistent postural-perceptual dizziness (PPPD) is worsened in a standing posture, or by body movement, or visual stimulation. We aimed to evaluate postural stability in PPPD patients using foam posturography and to investigate the dependence on visual and somatosensory input in the standing posture. METHODS: Foam posturography was performed on 53 PPPD patients, and data from the PPPD patients were compared with the data from an age- and sex-matched healthy controls. The PPPD patients were divided into four groups based on the findings of vestibular function tests and the effect of vestibular function on posturographic data was examined. RESULTS: Romberg's ratios were significantly higher in PPPD patients than in controls. The median Romberg's ratios in PPPD patients with normal vestibular function were also higher than those in controls. However, foam ratio was significantly lower in PPPD patients than in controls. The median foam ratios in PPPD patients with vestibular dysfunction were also lower than those in controls. CONCLUSIONS: In a standing posture, PPPD patients may be more dependent on visual input and less dependent on somatosensory input than healthy subjects. Higher dependence on visual and lower dependence on somatosensory input in PPPD may be a feature unaffected by vestibular function.