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.

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.

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.

Preceding Balance Disorders Affect Vestibular Function in Persistent Postural-Perceptual Dizziness.

Persistent postural-perceptual dizziness (PPPD) is induced by preceding conditions that cause balance disorders. To investigate the association between vestibular function and preceding balance disorders in PPPD patients, a retrospective chart review was performed. Vestibular function in 55 PPPD patients was measured using the caloric test, cervical vestibular evoked myogenic potential testing to air-conducted sound (ACS cVEMP), ocular vestibular evoked myogenic potential testing to bone-conducted vibration (BCV oVEMP), and video head impulse testing (vHIT). Patients were classified according to the type of preceding balance disorder. The age-stratified Cochran-Mantel-Haenszel (CMH) test and the exact test for the common odds ratio were conducted to evaluate the association between preceding n ≥ 4 balance disorders and present peripheral vestibular dysfunction. PPPD patients with preceding vestibular neuritis presented a significant positive association with abnormal caloric responses (p = 0.013), while those with preceding benign paroxysmal positional vertigo (BPPV) had significantly lower rates of abnormal BCV oVEMP (p = 0.003). Furthermore, patients with preceding vestibular neuritis showed lateral semicircular canal dysfunction, while those with preceding BPPV presented normal utricular functions. These results present the influence of preceding balance disorders on the vestibular function in PPPD.

Cyclin D1 controls development of cerebellar granule cell progenitors through phosphorylation and stabilization of ATOH1.

During development, neural progenitors are in proliferative and immature states; however, the molecular machinery that cooperatively controls both states remains elusive. Here, we report that cyclin D1 (CCND1) directly regulates both proliferative and immature states of cerebellar granule cell progenitors (GCPs). CCND1 not only accelerates cell cycle but also upregulates ATOH1 protein, an essential transcription factor that maintains GCPs in an immature state. In cooperation with CDK4, CCND1 directly phosphorylates S309 of ATOH1, which inhibits additional phosphorylation at S328 and consequently prevents S328 phosphorylation-dependent ATOH1 degradation. Additionally, PROX1 downregulates Ccnd1 expression by histone deacetylation of Ccnd1 promoter in GCPs, leading to cell cycle exit and differentiation. Moreover, WNT signaling upregulates PROX1 expression in GCPs. These findings suggest that WNT-PROX1-CCND1-ATOH1 signaling cascade cooperatively controls proliferative and immature states of GCPs. We revealed that the expression and phosphorylation levels of these molecules dynamically change during cerebellar development, which are suggested to determine appropriate differentiation rates from GCPs to GCs at distinct developmental stages. This study contributes to understanding the regulatory mechanism of GCPs as well as neural progenitors.

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.

Minimally important differences for subjective improvement in postural stability in patients with bilateral vestibulopathy.

OBJECTIVE: To determine minimally important differences (MIDs) for subjective improvement in postural stability after a therapeutic intervention in patients with bilateral vestibulopathy (BVP). METHODS: Thirteen BVP patients received noisy galvanic vestibular stimulation (nGVS) for 30 min and their static posture with eyes closed was monitored after the stimuli. The velocity of the center of pressure (COP) movement, the area enclosed by the COP movement, and the root mean square (RMS) of the displacement of the COP were measured for 30 s. Subjective evaluation of postural stability after nGVS was graded as worsened, slightly worsened, unchanged, slightly improved and improved in comparison with postural stability measured without nGVS. Anchor-based methods were used to estimate MIDs for subjective improvement. Velocity, area and RMS for each anchor-response group were averaged (2 sessions, each with 5 measurement periods during 3 h after the stimuli). The mean changes between the slightly improved group and unchanged group were used as estimates for MID for improvement. RESULTS: A total of 129 anchors were analyzed. Subjective evaluations numbered 83 (64%) for unchanged and 33 (26%) for slightly improved. Anchor-based methods yielded estimates for MIDs of -0.43 cm/s in velocity improvement (p < 0.01), -0.77 cm2 for area improvement (p < 0.01) and -0.23 cm for RMS improvement (p < 0.001). CONCLUSION: The present study provides the estimation of MIDs for improving postural stability in BVP patients and may be useful for interpreting whether the results from clinical trials are meaningful in future studies.

The role of SCFSkp2 and SCFß-TrCP1/2 in the cerebellar granule cell precursors.

A proper balance between proliferation and differentiation of cerebellar granule cell precursors (GCPs) is required for appropriate cerebellar morphogenesis. The Skp1-Cullin1-F-box (SCF) complex, an E3 ubiquitin ligase complex, is involved in polyubiquitination and subsequent degradation of various cell cycle regulators and transcription factors. However, it remains unknown how the SCF complex affects proliferation and differentiation of GCPs. In this study, we found that the scaffold protein Cullin1, and F-box proteins Skp2, ß-TrCP1 and ß-TrCP2 are expressed in the external granule layer (EGL). Knockdown of these molecules in the EGL showed that Cullin1, Skp2 and ß-TrCP2 enhanced differentiation of GCPs. We also observed accumulation of cyclin-dependent kinase inhibitor p27 in GCPs when treated with a Cullin1 inhibitor or proteasome inhibitor. Furthermore, knockdown of p27 rescued enhancement of differentiation by Cullin1 knockdown. These results suggest that the SCF complex is involved in the maintenance of the proliferative state of GCPs through p27 degradation. In addition, inhibition of Cullin1 activity also prevented cell proliferation and enhanced accumulation of p27 in Daoy cells, a cell line derived from the sonic hedgehog subtype of medulloblastoma. This suggested that excess degradation of p27 through the SCF complex causes overproliferation of medulloblastoma cells.

Acute bilateral vestibulopathy with simultaneous involvement of both superior and inferior vestibular nerves.

We report a case of acute vestibulopathy with the simultaneous involvement of both superior and inferior vestibular nerves on both sides. A 36-year-old female presented with dizziness, oscillopsia and a walking impairment subsequent to a high fever. Vestibular function tests including caloric testing, video head impulse testing (vHIT) and cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) were performed. In the first examination, vHIT and caloric testing showed severe impairments in all three semicircular canals in each ear, and both cVEMPs and oVEMPs were absent on both sides. During a 1-year follow-up, the gain of vHIT gradually recovered by more than 0.5 to normal. cVEMPs also recovered to normal on both sides while oVEMPs remained absent on both sides. This is the first reported case of acute bilateral vestibulopathy with simultaneous involvement of both superior and inferior vestibular nerves on both sides. Repeated evaluation of vestibular function using vHIT, cVEMPs and oVEMPs is helpful to assess the time course of recovery in patients with vestibulopathy.