Hidenori Ozeki

Endothelin-1 regulates the dorsoventral branchial arch patterning in mice.

Endothelin-1 (ET-1), a 21-amino acid peptide secreted by the epithelium and core mesenchyme in the branchial arches as well as vascular endothelium, is involved in craniofacial and cardiovascular development through endothelin receptor type-A (EdnrA) expressed in the neural crest-derived ectomesenchyme. Here we show that ET-1(-/-) mutant mice exhibit a homeotic-like transformation of the lower jaw to an upper jaw. Most of the maxillary arch-derived components are duplicated and replaced mandibular arch-derived structures, resulting in a mirror image of the upper and lower jaws in the ET-1(-/-) mutant. As for hyoid arch-derivatives, the ventral structures are severely affected in comparison to the dorsal ones in the ET-1(-/-) mutant. Correspondingly, the expression of Dlx5 and Dlx6, Distalless-related homeobox genes determining the ventral identity of the anterior branchial arches, and of the mandibular marker gene Pitx1 is significantly downregulated in the ET-1(-/-) mutant, whereas the expression of Dlx2 and the maxillary marker gene Prx2 is unaffected or rather upregulated. These findings indicate that the ET-1/EdnrA signaling may contribute to the dorsoventral axis patterning of the branchial arch system as a mediator of the regional intercellular interactions.

Galvanic-evoked myogenic responses in patients with an absence of click-evoked vestibulo-collic reflexes

OBJECTIVES To show that galvanic-evoked responses on the sternocleidomastoid muscle (SCM) are useful for differentiating labyrinthine lesions from retro-labyrinthine lesions in patients with an absence of click-evoked vestibulo-collic reflexes. METHODS We studied the average responses in the unrectified electromyographic (EMG) activities of the SCM to galvanic stimulation (3mA, 1ms). The cathodal electrode was on the mastoid, and the anodal electrode was on the forehead. Twenty-two healthy subjects and 28 patients with vestibular disorders were studied. All of the 28 patients showed the unilateral absence of vestibulo-collic reflexes evoked by 95dBnHL clicks on the affected side. RESULTS In healthy subjects mastoid-forehead galvanic stimulation produced a positive-negative biphasic EMG response at short latency on the SCM ipsilateral to the cathodal electrode. All patients with labyrinthine lesions showed biphasic EMG responses even in the affected side. In contrast, almost all patients with retro-labyrinthine lesions (16/18) showed no response or a decreased response on the affected side. CONCLUSIONS These results suggest that galvanic-evoked myogenic responses on the SCM may be useful in the differential diagnosis of labyrinthine lesions from retro-labyrinthine lesions in patients with an absence of vestibulo-collic reflexes evoked by clicks.

The site of lesion in “vestibular neuritis”: Study by galvanic VEMP

Vestibular neuritis (VN) is characterized by isolated vertigo without other neurologic signs or symptoms.1 Patients show unilateral peripheral vestibular dysfunction mainly in the superior vestibular nerve region,2 although some patients also have dysfunction in the inferior vestibular nerve region.1,3⇓ Although VN supposedly involves the vestibular nerve, insufficient evidence is available concerning the VN lesion site. It is known that some patients with VN have benign paroxysmal positional vertigo (BPPV) following severe vertigo attacks.1 These patients would be expected to have some lesions in the labyrinth because BPPV is caused by floating debris in the semicircular canal.4 Recently, it was reported that short-duration galvanic stimulation could evoke vestibulocollic reflexes in the sternocleidomastoid muscle (SCM)5-7⇓⇓ (galvanic vestibular evoked myogenic potentials [VEMP]). It has also been reported that these reflexes are useful for differentiating labyrinthine lesions from nerve lesions in patients with an absence of VEMP by click (click VEMP).6 We postulated that galvanic VEMP could indicate the site …

Vestibular Evoked MyogenicPotentials in Patients with Bilateral Profound Hearing Loss

We report vestibular evoked myogenic potentials (VEMPs) in 3 patients with bilateral profound hearing loss in order to confirm that they are not of cochlear origin. All of the 3 patients (31-year-old man, 67-year-old man and 47-year-old woman) had bilateral profound hearing loss. They were diagnosed as having congenital hearing loss, bilateral Ménière’s disease and inner ear syphilis. Their pure-tone hearing ranged from 81 dB HL to nearly total hearing loss. Stimulation by click (95 dB nHL) evoked biphasic myogenic responses (p13–n23) on the sternocleidomastoid muscle ipsilateral to the stimulated ear. The ear in which the stimulation did not evoke biphasic myogenic responses did not have a caloric response either. These results suggested that VEMPs are not likely of cochlear origin but of vestibular origin.

Laterality of vestibular evoked myogenic potentials

To clarify the laterality of acoustically evoked vestibulocollic reflexes with a short latency (vestibular evoked myogenic potentials, VEMPs), responses on the bilateral sternocleidomastoid muscles (SCMs) to unilateral acoustic stimulation were studied. Twenty-one healthy volunteers were enrolled. Surface electrodes were placed on the upper half of each SCM (active) and on the lateral end of the upper sternum (reference). Clicks and 500-Hz tone-bursts (95 dB nHL) were used. All subjects showed positive-negative biphasic responses on the ipsilateral SCM by clicks and tone-bursts. Click-stimulation of 41 of the 42 ears did not evoke any response on the contralateral SCM. However, in one ear, positive-negative biphasic responses were evoked on the contralateral SCM. Recordings on the contralateral SCM by tonebursts showed no response in 32 ears, small positive-nega-tive biphasic responses in four ears, and small negative-positive biphasic responses in six ears. These findings show that VEMPs are ipsilateral-dominant, basically consistent with the hypothesis that they are of saccular origin. Sumario Para aclarar la lateralidad de los reflejos vestíbulo-colicu-lares de latencia corta evocados acústicamente (potenciales miogénicos evocados vestibulares - VEMP) se estudiaron las respuestas de ambos músculos esternocleidomastoideos (SCM) a la estimulación acústica unilateral. Se involucró a un grupo de veintiún voluntarios sanos. Se colocaron electrodos de superficie en la parte superior de cada SCM (activos) y en el extremo lateral y superior del esternón (referencia). Se utilizaron clicks y bursts tonales de 500 Hz (a 95 dB nHL). La estimulación por click en 41 de los 42 oídos no produjo ninguna respuesta en el SCM contralateral. Sin embargo, en un oído, se evocaron respuestas bifásicas positivo-negativas en el SCM contralateral. Los registros con bursts tonales en el SCM contralateral no mostraron respuestas en 32 oídos, una pequen˜a respuesta bifásica positivo-negativa en cuatro oídos, y una pequen˜a respuesta bifásica nega-tivo-positiva en seis oídos. Estos hallazgos muestran que los VEMP son dominantes ipsilateralmente, por lo que son consistentes con la hipótesis de que tienen un origen sacular.

Vestibular drop attack secondary to Meniere's disease results from unstable otolithic function

Conclusion. The otolithic organs of patients with vestibular drop attack (VDA) secondary to Menieres disease were damaged but the damage was not complete. In other words, the otolithic functions of patients with VDA were unstable. Objective. To evaluate otolithic function using vestibular evoked myogenic potential (VEMP) in patients with VDA secondary to Menieres disease. Patients and methods. Clinical records of three patients with VDA secondary to Menieres disease were reviewed with special reference to VEMP testing. Results. The three patients were classified as stage II or III Menieres disease. A long-term follow-up of VEMP in two patients showed reversible changes of VEMP reflexes, and VEMP testing with glycerol administration in two patients revealed the recovery of VEMP responses after taking glycerol, and the existence of saccular endolymphatic hydrops.

Development and regeneration of hair cells

The vertebrate inner ear is derived from the otic placode and undergoes a complicated series of morphogenetic processes to differentiate into an elaborate structure harboring mechanosensory epithelia featuring hair cells, the mechanoreceptors of hearing and balance. Recently, the principal mechanisms producing hair cells and the key molecules involved in their fate determination and differentiation have been gradually unveiled. The in-depth understanding of hair cell development is consequently providing clues to strategies for mammalian hair cell regeneration. Among them, the identification and characterization of progenitor cells for the hair cell lineage, which is just emerging, is of particular interest. Herein, we review the molecular mechanisms of inner ear development with particular focus on perspectives for hair cell regeneration.

Effect of stimulation repetition rate on galvanic-evoked vestibulo-collic reflexes

Conclusion Taking examination time and patient compliance into consideration, we propose that 5 Hz is the optimal stimulation rate of galvanic vestibular-evoked myogenic potentials for clinical use. Objectives To evaluate the influence of stimulation repetition rate on galvanic-evoked vestibulo-collic reflexes and to propose the optimal stimulation rate for clinical use. Material and methods Both ears of 30 healthy adults were tested at 5 different galvanic stimulation rates (1, 3, 5, 7 and 9 Hz) in a random order. Results Responses were evident in all 60 ears only at 5 Hz; some ears showed no response at the other frequencies. The relative amplitudes in individual ears were higher at 1, 3 and 5 Hz than at 7 and 9 Hz. Comparison of the latencies of p13g and n23g showed no significant difference among the five stimulation rates.

Establishment of mice expressing EGFP in the placode-derived inner ear sensory cell lineage and FACS-array analysis focused on the regional specificity of the otocyst.

In this study, we established a novel enhanced green fluorescent protein (EGFP) reporter mouse line that enables the visualization of the placode‐derived inner ear sensory cell lineage. EGFP was initially expressed in the otic placode and throughout its differentiation process into the inner ear sensory patches. At embryonic day 10.5 (E10.5), EGFP was expressed in the ventral and dorsomedial region of the otocyst. These regions could mainly give rise to the cochlea, including the organ of Corti, and the saccule, including the macula and the endolymphatic duct. The region could also give rise to cells that will develop as either prosensory cells or statoacoustic ganglion neuroblasts. By using this line and fluorescence‐activated cell sorting (FACS)‐array technology, we developed a new gene expression profile of the regional specificity of the otocyst. EGFP‐positive regions include the Otx1‐positive region, which could be clearly distinguished from EGFP‐negative regions. The signal log ratio of microarray data showed high efficiency in predicting the genes expressed mainly in the ventral and/or dorsomedial otocyst and the data could be mined to uncover many novel genes involved in inner ear morphogenesis and cell fate regulation. Additionally, these data suggest that some novel genes enriched in EGFP‐positive regions may be potentially involved in human congenital sensorineural hearing loss. This reporter line could play important roles in the use of animal models for detailed analysis of the differentiation process into the sensory patches and the identification of regional‐specific gene networks and novel gene functions in the developing inner ear. J. Comp. Neurol. 518:4702–4722, 2010.

Neuro-otological findings at the acute stage of vertigo in migraine associated vertigo: a report of 2 cases.

Although many patients with both episodic vertigo and migraine have been reported, we have few opportunities to observe pathological nystagmus during an attack in these patients. We report herein on two cases with migraine associated vertigo (MAV) in which neuro-otological findings could be observed at the acute stage of vertigo. The first patient was a 46-year-old woman, with migraine without aura. She visited our clinic complaining of an episodic dizzy feeling with a migrainous headache and phonophobia. On the first examination, she did not show nystagmus or disequilibrium. Four months later, she had further acute vertigo attacks, during which she showed right beating spontaneous nystagmus lasting for 3 hours. Her vertigo attack and headache are currently well-controlled with lomerizine. The second case was a 47-year-old woman who visited our clinic complaining of vertigo accompanied by a migrainous headache and left tinnitus. On the first examination, there were no remarkable findings except for 35% canal paresis of the left ear on caloric testing. Later, she showed direction fixed spontaneous nystagmus during a vertigo attack lasting for a few days. This patients vertigo attack and headache have also been well-controlled with lomerizine. These cases showed that patients with MAV could have acute asymmetrical disorders of the vestibular system. The lesion site was considered to be in the peripheral vestibular system at least in the second case. However, the actual pathophysiology of MAV remains unclear.