Endolymphatic sac tumor with overexpression of V2 receptor mRNA and inner ear hydrops.

CONCLUSION: We reported previously that hyperactivation of vasopressin type-2 receptor (V2R)-mediated signaling in the endolymphatic sac could affect endolymphatic fluid metabolism, resulting in the pathogenesis of endolymphatic hydrops. Taken together with the present endolymphatic sac tumor (ELST) study, it is suggested that disorder of V2R signaling in the endolymphatic sac for any reason could be involved in the pathogenesis of endolymphatic hydrops. Although it is due to tumor genesis in ELST, it is idiopathic in nature in Meniere's disease. OBJECTIVE: We encountered two cases of ELST showing Meniere's disease-like symptoms. Both cases were suspected of having endolymphatic hydrops using neuro-otological examinations. To clarify the histopathological diagnosis of ELST and the molecular pathogenesis of endolymphatic hydrops, we performed histopathological and molecular biological examinations of the endolymphatic sac. METHODS: ELSTs in two rare cases were removed completely through the transmastoidal approach. V2R mRNA expression was examined using real-time PCR. RESULTS: The first case was diagnosed as inflammatory granulation adjacent to the endolymphatic sac, i.e. pseudo-ELST, and the second case was diagnosed as papillary adenoma of ELST. V2R mRNA expression was up-regulated in the endolymphatic sac of both cases as seen in Meniere's disease compared with controls.

Plasma vasopressin and V2 receptor in the endolymphatic sac in patients with delayed endolymphatic hydrops.

OBJECTIVE: There are some kinds of sicknesses provoked by inadequate adaptation to physical and/or psychogenic stress in daily life. Delayed endolymphatic hydrops (DEH) is an inner ear disease like Ménière's disease (MD) characterized by episodic vertigo in the setting of preexisting unilateral deafness that especially occurs in civilized people with a stressful lifestyle. Its otopathologic finding was demonstrated to be inner ear endolymphatic hydrops through a temporal bone study in 1976, as in the case with MD in 1938. To elucidate the relationship between stress and the inner ear, we examined the plasma antidiuretic stress hormone vasopressin (pAVP) and its type 2 receptor (V2R) expression in the endolymphatic sac in patients with DEH. STUDY DESIGN: A prospective molecular biological study. METHODS: Between 1998 and 2007, we enrolled 20 patients with ipsilateral DEH to examine their pAVP during remission from vertigo attacks. Plasma vasopressin was also examined in 87 patients with unilateral MD and 30 control patients with chronic otitis media. Using the real-time polymerase chain reaction method with tissue samples obtained during surgery, we examined V2R mRNA expression in the endolymphatic sac in 6 patients with ipsilateral DEH, 9 patients with unilateral MD, and 6 control patients with acoustic neuroma. RESULTS: Plasma vasopressin (1.5 times versus controls; unpaired t test, p = 0.140) and V2R mRNA expression in the endolymphatic sac (35.8 times versus controls; unpaired t test, p = 0.002) were higher in patients with DEH compared with those with acoustic neuroma. There were no significant differences in pAVP or V2R expression in the endolymphatic sac between DEH and MD. Patients with DEH showed a significantly negative correlation between pAVP and V2R (Pearson test, r = -0.92, p = 0.009) as in those with MD (Pearson test, r = -0.68, p = 0.043). CONCLUSION: Civilized people are frequently exposed to stress in their daily life, and pAVP can easily become elevated at any time. Therefore, a negative feedback system between pAVP and V2R in the endolymphatic sac may function for inner ear fluid homeostasis against stress-induced increases in pAVP. For the pathogenesis of endolymphatic hydrops resulting in vertigo attacks in patients with DEH as well as MD, pAVP may represent a matter of consequence, but V2R overexpression in the endolymphatic sac could be much more essential as a basis for these diseases.

Vestibular type of Mondini anomalies with BPPV and Meniere's disease-like symptoms.

An extremely rare case with labyrinthine anomaly with normal hearing was demonstrated. This case firstly showed transient positioning vertigo like benign paroxysmal positional vertigo (BPPV) and subsequently episodic vertigo like Meniere's disease. A 55-year-old male attended our hospital, complaining of transient but persistent positioning vertigo in 2004. The apogeotropic positioning nystagmus was observed in spine position. In 2005, he came to feel episodic vertigo continuously for more than 30min like Meniere's disease. We examined CT scan and 3D-MRI, indicating the hypoplastic lateral semicircular canal (L-SCC) fused together with enlarged vestibule on the left side. We finally diagnosed this case as Mondini anomaly on the left side. The imaging analysis is the most useful for differential diagnosis of Mondini anomalies, because symptoms in these patients are actually various due to the individual inner ear condition. The mechanism of generation of BPPV-like vertigo: the otolith in deformed utricle might be transferred into the fused space with vestibule and L-SCC, resulting in the irrigation of the hypoplastic cupula. The mechanism of generation of Meniere's disease-like vertigo: neuro-otologic findings with furosemide test implied endolymphatic hydrops on the left side. Meniere's disease-like episodic vertigo could be due to subsequently generated endolymphatic hydrops.

Changes in mitochondrial uncoupling protein expression in the rat vestibular nerve after labyrinthectomy.

In the present study, to elucidate the role of mitochondrial uncoupling proteins (UCPs) in inner ear, we examined quantitative changes in the mRNA expression in vestibular ganglion (VG) after unilateral labyrinthectomy (UL) in rats. Using real-time PCR methods, UCP2, 3 and 4 mRNA expressions in the ipsilateral VG were significantly up-regulated with the maximum increase at the post-operative 1 day and all but UCP2 returned to the control level 1 week after UL. UCP2 mRNA expression was significantly up-regulated even 4 weeks after UL. Only UCP2 mRNA expression in the contralateral VG was gradually up-regulated between 1 and 4 weeks after UL. According to previous reports, UCP2 and 3 as well as UCP1 were thermogenic in yeast and brain UCP2 was suggested to modulate pre- and post-synaptic events by axonal thermogenesis. It was also reported that UCP1, 2 and 3 responses to superoxide application were an antioxidant protective mechanism. These findings suggest that mitochondrial UCPs could play both a neuro-protective role against oxidative damage and a thermal signaling role for neuro-modulation in vestibular nerve.