Hisamitsu Hayashi

Subclinical deviation of the subjective visual vertical in patients affected by a primary headache

Conclusion. Our results suggest that patients with migraine or tension-type headache have subclinical deviations of the subjective visual vertical, which may be associated with their subjective imbalance Objectives. Patients affected by migraine or tension-type headache often complain of unsteadiness. However, they rarely show a clinical significance in the objective examinations of their equilibrium. We investigated the equilibrium functions in patients affected by migraine or tension-type headache Subjects and methods. We investigated the neurotological findings of 17 patients with migraine, 20 patients with tension-type headaches, and 16 patients without headache. All patients in this study experienced vertigo or dizziness before they underwent the examination; however, they never had vertigo attacks for more than 1 month before the examination. All patients in this study were tested during headache-free intervals Results. There was no significant difference in the hearing levels of pure tone audiometry, the canal palsy percentage of bithermal caloric test, and the body sway in posturography among the three groups (p>0.05, Mann-Whitney U test). The average values in absolute deviations of subjective visual vertical (SVV) in patients with tension-type headache (1.3±1.1°) and patients with migraine (1.5±1.2°) were significantly larger in comparison with those of patients without headache (0.6±0.4) (p<0.05, Mann-Whitney U test). Intra-individual varaiances of the SVV in patients with primary headache were significantly larger than those in patients without headache (p<0.05, Mann-Whitney U test).

Tracing Sox10-expressing cells elucidates the dynamic development of the mouse inner ear.

The inner ear is constituted by complicated cochlear and vestibular compartments, which are derived from the otic vesicle, an embryonic structure of ectodermal origin. Although the inner ear development has been analyzed using various techniques, the developmental events have not been fully elucidated because of the intricate structure. We previously developed a Sox10-IRES-Venus mouse designed to express green fluorescent protein under the control of the Sox10 promoter. In the present study, we showed that the Sox10-IRES-Venus mouse enabled the non-destructive visualization and understanding of the morphogenesis during the development of the inner ear. The expression of the transcription factor Sox10 was first observed in the invaginating otic placodal epithelium, and continued to be expressed in the mature inner ear epithelium except for the hair cells and mesenchymal cells. We found that Sox10 was expressed in immature hair cells in the developing inner ear, suggesting that hair cells were generated from the Sox10-expressing prosensory cells. Furthermore, we demonstrated that scattered Sox10-expressing cells existed around the developing inner ear, some of which differentiated into pigmented melanocytes in the stria vascularis, suggesting that they were neural crest cells. Further analyzing the Sox10-IRES-Venus mice would provide important information to better understand the development of the inner ear.

The association of the plasma vasopressin level during attacks with a prognosis of Meniere's disease.

Abstract An elevation of the plasma arginine vasopressin (AVP) level has frequently been observed in Menieres disease patients. However, little is known regarding the mechanism behind this elevation. The plasma AVP levels in acute phase were determined in 21 Menieres disease patients and 16 patients with other types of vertigo. The plasma AVP levels of Menieres disease patients in the acute phase were significantly higher than in those of other vertigo patients (p < 0.01). In Menieres disease patients with abnormally high levels of AVP (more than 3.5 pg/ml) in the acute phase, 36% of patients were resistant to conservative treatments for frequent vertigo attacks for the follow-up period of at least 2years. A significant correlation was observed between the plasma AVP in the acute phase and the highest hearing threshold level at a frequency of 1kHz for the follow-up period of at least 1 year (r=0.45, p < 0.05). These results suggest that the elevation in plasma AVP level in the acute phase is associated with the prognosis of Menieres disease. Sumario La elevación del nivel plasmático de vasopresina arginina (AVP) ha sido frecuentemente observado en los pacientes con enfermedad de Meniere. Sin embargo, se sabe poco de los mecanismos detrás de esta elevación. Se determinaron los niveles plasmáticos de AVP durante la fase aguda en 21 paciente con enfermedad de Meniere y en 16 pacientes con otro tipo de vértigo. Los niveles plasmáticos de AVP en los pacientes en la fase aguda de la enfermedad de Meniere fueron significativamente más elevados que aquellos con otro tipo de vértigo (p < 0.01). De los pacientes con enfermedad de Meniere y niveles anormalmente elevados de AVP (más de 5.5 pg/ml) durante la fase aguda, 36% de ellos fueron resistentes al tratamiento conservador para los ataques frecuentes de vértigo en un periodo de seguimiento de hasta 2 años. Se observó una correlación significativa entre el nivel plasmático de AVP en la fase aguda y el umbral más elevado en la frecuencia de 1kHz durante el periodo de seguimiento de un año (r = 0.45, p < 0.05). Estos resultados sugieren que la elevación plasmática de AVP en la fase aguda está asociada con el pronóstico de la enfermedad de Meniere.

Effect of lyophilized powder made from enzymolyzed honeybee larvae on tinnitus-related symptoms, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones.

Objectives: Tinnitus interferes with sleep and concentration which is associated with depression; however, no drug has been effective in treating tinnitus. Our purpose is to evaluate our hypothesis that the treatment with lyophilized powder of enzymolyzed honeybee larvae as a complementary medicine may provide a therapeutic effect on tinnitus-related symptoms. Design: Sixty tinnitus sufferers participated in a randomized double-blind placebo-controlled trial using the lyophilized powder of enzymolyzed honeybee larvae or a placebo. The Tinnitus Handicap Inventory, a visual analog scale to rate the severity of tinnitus, hearing levels, and hypothalamus–pituitary–adrenal axis-related hormones drawn early in the morning were measured upon entry into the study and after 12 wk of follow-up. Results: The lyophilized powder of enzymolyzed honeybee larvae was not superior to placebo with regard to the total score on the Tinnitus Handicap Inventory and the visual analog scale. However, subjects in the honeybee larvae group showed significant improvements in some items about depression associated with tinnitus, whereas subjects in the placebo group showed no improvement in any items. The honeybee larvae group showed significant improvements in the hearing levels at 2 and 4 kHz in the audiogram of the better ear. The intervention of the lyophilized powder of enzymolyzed honeybee larvae was associated with lower serum cortisol levels, serum prolactin levels, and cortisol/dehydroepiandrosterone sulfate ratios. The ratios in the placebo group significantly were increased. Conclusions: Our results suggest that the lyophilized powder of enzymolyzed honeybee larvae represents an effective complementary medicine to alleviate depression associated with tinnitus by regulating the activity of the hypothalamus–pituitary–adrenal axis.

The association between impaired perception of verticality and cerebral white matter lesions in the elderly patients with orthostatic hypotension.

BACKGROUND The morbidity of orthostatic hypotension (OH) increases with aging and the elderly often complain of dizziness associated with OH, which is implicated in white matter lesions (WMLs) on MRI. However little is known how WMLs are contributed to the development of dizziness in elderly patients. OBJECTIVE We evaluated the involvement of cerebral WMLs in the vertical perception in the elderly with OH. METHODS This study consisted of 71 dizzy patients who underwent the examinations including the Schellong orthostatic test and subjective visual vertical (SVV) test. RESULTS The male patients aged <65 years with OH (1.9 ± 0.9°) showed a significantly higher magnitude of variance of SVV, which reflects an impaired vertical perception, in comparison with the male patients aged <65 years without OH and the male patients aged < 65 years with OH (1.0 ± 0.4°, 0.9 ± 0.4°, p < 0.05). The variance of SVV significantly correlated with the volume of WMLs in both sides on MRI in the male, but not female patients (p < 0.01). CONCLUSIONS Our results suggest that severe WMLs in the elderly with OH are involved in impaired perception of verticality, resulting in inducing subjective dizziness.

The relevance of hypothalamus-pituitary-adrenocortical axis-related hormones to the cochlear symptoms in Ménière's disease

Abstract Objective: To investigate the association of the HPA (hypothalamus-pituitary-adrenocortical) axis-related hormones with the progression of cochlear symptoms in patients with Ménières disease. Design: Clinical assessments (Tinnitus Handicap Inventory: THI, visual analog scale to rate the degree of the tinnitus: VAS, hearing levels in pure-tone audiometry) were conducted upon entry into the study (baseline) and at 12 weeks follow-up (week 12). Blood sampling to measure HPA axis-related hormones took place between 9:00 and 10:00 a.m. at baseline and at 12 weeks follow-up. Study samples: This study consisted of 20 unilateral Ménières disease patients and 21 patients with other diseases with unilateral sensorineural hearing loss and tinnitus. Results: A significant deterioration of the hearing level at high frequency range, especially at 2 kHz, was found during the 12 weeks follow-up in the Ménières disease group (p < 0.05). The average hearing levels significantly correlated with the serum cortisol level at baseline and week 12 in the Ménières disease group, especially regarding the high frequency levels (p < 0.01). Conclusions: Our results suggest that the cortisol levels influence the endolymphatic homeostasis resulting in a deterioration of hearing at high frequency with upstaging of Ménières disease. Sumario Objetivo: Investigar la asociación de hormonas relacionadas con el eje hipotálamo-pituitario-adrenocortical (HPA), con la progresión de síntomas cocleares en pacientes con enfermedad de Ménière. Diseño: Se llevaron a cabo evaluaciones clínicas (Cuestionario de desventaja por acúfeno, THI; Escala análoga visual para clasificar el grado del acúfeno: VAS; y niveles de audición con audiometría por tonos puros) al iniciarse el estudio (línea basal) y a 12 semanas de seguimiento (semana 12). Se tomó muestra de sangre para medir las hormonas relacionadas con el eje HPA entre las 9:00 y las 10:00 de la mañana en la linea basal y en la semana 12 del seguimiento. Muestras de estudio: Este estudio comprendióa 20 pacientes con enfermedad de Ménière unilateral y 21 pacientes con otras enfermedades con pérdida auditiva neurosensorial unilateral y acufeno. Resultados: Se encontró un deterioro significativo de los niveles auditivos en el rango de las frecuencias altas, especialmente en 2 kHz, durante las 12 semanas de seguimiento en el grupo de enfermos de Ménière (p > 0.05). Los niveles promedio de audición correlacionaron significativamente con el nivel de cortisol sérico en la línea basal y en la semana 12 en el grupo con enfermedad de Ménière, especialmente en relación con los niveles en las frecuencias altas (p > 0.01). Conclusiones: Nuestros resultados sugieren que los niveles de cortisol sérico ejercen influencia en la homeostasis endolinfática, lo que determina un deterioro de la audición en laa frecuencias altas y que hacen eclipsable a la enfermedad de Ménière.

The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling

Endogenous electric fields (EFs) are required for the physiological control of the central nervous system development. Application of the direct current EFs to neural stem cells has been studied for the possibility of stem cell transplantation as one of the therapies for brain injury. EFs generated within the nervous system are often associated with action potentials and synaptic activity, apparently resulting in a pulsed current in nature. The aim of this study is to investigate the effect of pulsed EF, which can reduce the cytotoxicity, on the migration of human neural progenitor cells (hNPCs). We applied the mono-directional pulsed EF with a strength of 250mV/mm to hNPCs for 6h. The migration distance of the hNPCs exposed to pulsed EF was significantly greater compared with the control not exposed to the EF. Pulsed EFs, however, had less of an effect on the migration of the differentiated hNPCs. There was no significant change in the survival of hNPCs after exposure to the pulsed EF. To investigate the role of Ca2+ signaling in electrotactic migration of hNPCs, pharmacological inhibition of Ca2+ channels in the EF-exposed cells revealed that the electrotactic migration of hNPCs exposed to Ca2+ channel blockers was significantly lower compared to the control group. The findings suggest that the pulsed EF induced migration of hNPCs is partly influenced by intracellular Ca2+ signaling.

Molecular organization and fine structure of the human tectorial membrane: is it replenished?

Auditory sensitivity and frequency resolution depend on the physical properties of the basilar membrane in combination with outer hair cell-based amplification in the cochlea. The physiological role of the tectorial membrane (TM) in hair cell transduction has been controversial for decades. New insights into the TM structure and function have been gained from studies of targeted gene disruption. Several missense mutations in genes regulating the human TM structure have been described with phenotypic expressions. Here, we portray the remarkable gradient structure and molecular organization of the human TM. Ultrastructural analysis and confocal immunohistochemistry were performed in freshly fixed human cochleae obtained during surgery. Based on these findings and recent literature, we discuss the role of human TMs in hair cell activation. Moreover, the outcome proposes that the α-tectorin-positive amorphous layer of the human TM is replenished and partly undergoes regeneration during life.

Involvement of platelet-derived growth factor receptor-β in maintenance of mesenchyme and sensory epithelium of the neonatal mouse inner ear

Platelet-derived growth factor receptor (PDGFR) signaling has been demonstrated to play a pivotal role in early embryonic development. Although the expression of PDGF in the inner ear has been studied by RT-PCR, how PDGFR is involved there remains largely unclear. In the current study, we used the antagonistic anti-PDGFR-beta antibody, APB5, to investigate the role of PDGFR-beta in the neonatal mouse inner ear. PDGFR-beta was detected immunohistochemically in the mesenchymal tissue adjacent to the sensory epithelium of the inner ear, and a ligand for PDGFR-beta was detected around the sensory epithelium. To determine whether this expression plays a functional role, we injected APB5 into neonates to block the function of PDGFR-beta. Mesenchymal tissue defects and abnormal capillaries with irregular shapes, especially in the cochlear lateral wall, were detected in APB5-treated mice. The results of a TUNEL assay revealed that not only the adjacent mesenchymal cells but also the sensory epithelial cells underwent cell death. These results indicate that PDGFR-beta signals are required for the survival of the capillary and mesenchymal cells in the neonatal mouse inner ear and also indirectly implicate these signals in the survival of the sensory epithelium.