Tadashi Kitahara

Behavioral assessment and identification of a molecular marker in a salicylate-induced tinnitus in rats

Tinnitus is a non-observable phantom sensation. As such, it is a difficult condition to investigate and, to date, no effective treatment has been developed. To approach this phantom sensation, we aimed to develop a rat behavioral model of tinnitus using salicylate, an active component of aspirin known to induce tinnitus. We also aimed to establish a molecular marker of tinnitus by assessing the expression of transient receptor potential cation channel superfamily V-1 (TRPV1) in the rat auditory pathway during salicylate-induced tinnitus. Animals were trained to perform an active avoidance task: animals were conditioned by electrical footshock to move to the other side of the conditioning box when hearing a sound. Animals received a single injection of saline or salicylate (400 mg/kg i.p.) and false positive responses were measured 2 h after injection as the number of movements during a silent period. The number of responses in salicylate-treated animals was highest when the conditioned stimulus was 60 dB sound pressure level (SPL) and 16 kHz. This indicates that animals could feel tinnitus 2 h after salicylate injection, equivalent to that induced by 60 dB SPL and 16 kHz. By means of real-time PCR and western blot analysis, TRPV1 expression was significantly upregulated in spiral ganglion cells 2 h after salicylate injection and this upregulation together with the increase in the number of false positive responses was significantly suppressed by capsazepine (10 mg/kg i.p.), a specific antagonist of TRPV1. This suggests that salicylate could induce tinnitus through activation of TRPV1 in the rat auditory pathway.

Tinnitus as a prognostic factor of sudden deafness

Conclusions. The ‘tinnitus-rare’ group had a poorer prognosis for hearing than the ‘tinnitus-often’ group in all sudden sensorineural hearing loss (SSNHL), although the ‘shorter duration’ group had better prognosis than the ‘longer duration’ when restricted to SSNHL accompanied by tinnitus. This indicates that tinnitus itself may not be a sign for poor hearing prognosis but might be an essential sound for the initiation of repair of a damaged auditory system. Objectives. We examined the hearing improvement rate (HIR) and tinnitus at the onset of SSNHL to elucidate the prognostic value of tinnitus accompanying SSNHL. Patients and methods. Fifty patients with SSNHL were treated with systemic administration of steroids. Hearing recovery was determined by comparing the hearing levels before and after treatment. Tinnitus was subjectively evaluated by the tinnitus scoring questionnaire. The score for the five-step evaluation of the subjective tinnitus feelings ‘loudness’, ‘duration’ and ‘annoyance’ was obtained at the onset. Results. In terms of ‘duration’, when we divided all the cases into ‘tinnitus-rare’ group and ‘tinnitus-often’ group, HIR in the ‘tinnitus-rare’ group was significantly lower than that in ‘tinnitus-often’ group. When restricted to the ‘tinnitus-often’ group, HIR for ‘shorter duration’ was significantly higher than that for ‘longer duration’.

Endolymphatic hydrops in Meniere's disease detected by MRI after intratympanic administration of gadolinium: Comparison with sudden deafness

Abstract Conclusion: The detection rate of endolymphatic hydrops was significantly higher in patients with Menieres disease compared with those with sudden deafness, indicating that 3 T magnetic resonance imaging (MRI) with intratympanic gadolinium injection was effective in diagnosing endolymphatic hydrops. Objectives: To compare the detection rate of endolymphatic hydrops between patients with Menieres disease and sudden deafness as controls by 3 T MRI after intratympanic gadolinium injection with conventional pulse sequence such as two-dimensional fluid-attenuated inversion recovery. Methods: Ten patients with unilateral Menieres disease and eight with sudden deafness underwent inner ear MRI 24 h after intratympanic gadolinium injection. Results: The endolymphatic space was detected as a low signal intensity area, while the perilymphatic space showed high intensity by gadolinium enhancement. Due to faint enhancement, images could not be evaluated in 1 of 10 patients with Menieres disease. However, the other nine patients together with two of the eight with sudden deafness were diagnosed as having hydrops. The difference in detection rates between the two diseases was statistically significant. Two hydrops-positive cases with sudden deafness were considered to be of the secondary type of hydrops, because images were taken after partial recovery from hearing loss several months after the onset of the disease.

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 Ménières 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.

Diagnosis of the subtype and affected ear of benign paroxysmal positional vertigo using a questionnaire

Abstract Conclusion: The prediction of subtype and the affected ear of benign paroxysmal positional vertigo (BPPV) derived from the answers to our questionnaire can support the definitive diagnosis of BPPV. Objectives: We examined to what extent the diagnosis of subtype and the affected ear of BPPV judged from answers to a questionnaire agreed with the diagnosis decided by the results of the positional nystagmus test. Methods: We asked the following questions: ‘What kind of head movements induce vertigo?’ and ‘How long does the vertigo continue?’. As for the affected ear, we asked which ear was lower during stronger vertigo when induced in a supine position or during sleep. Results: The percentages of correct diagnosis speculated by the combined answers were 69% in posterior canal-type BPPV, 48% in BPPV with geotropic nystagmus, and 39% in BPPV with apogeotropic nystagmus. The percentage of correct diagnoses of the affected ear was more than 80%.

Changes in caloric responses after temporal bone surgery with posterior tympanotomy

OBJECTIVEnTo elucidate the role of facial recess bony plate in the thermal transmission route from external auditory canal to lateral semicircular canal during caloric stimulation test, we performed the test on patients before and after removal of the plate, i.e. posterior tympanotomy. In the present study, we adopted facial nerve decompression (FND) as posterior tympanotomy without surgery-induced inner ear damages and cochlear implantation (CI) as posterior tympanotomy with surgery-induced inner ear damages.nnnMETHODSnBetween 1999 and 2003, we performed FND on 19 patients with unilateral facial nerve paresis due to Bells palsy (n=7), Ramsay-Hunt syndrome (n=7) or facial nerve trauma (n=5) at Osaka Rosai Hospital. We also performed CI on 34 patients with bilateral deafness at Osaka University Hospital. To examine effects of FND or CI on caloric responses in vestibular periphery, caloric stimulation (30 degrees C cold water and 44 degrees C hot water) with ENG was performed twice, just before and 6 months after surgery in each subject. The caloric-induced nystagmus was recorded by using ENG under dark and open-eyes situation to calculate the maximum slow phase eye velocity.nnnRESULTSnIn cases of FND (n=19), there were significant decreases between pre- and post-operative 30 degrees C responses (t-test: p=0.049<0.05). There were no significant differences between pre- and post-operative 44 degrees C responses (t-test: p=0.467>0.05). In cases of CI (n=34), there were significant changes between pre and post-operative responses in both temperatures (t-test: p<0.0001 in 30 degrees C; p=0.011<0.05 in 44 degrees C).nnnCONCLUSIONnThe insertion of electrodes during CI did some damages to vestibular peripheral function and reduced both hot and cold caloric responses according to the results of CI. However, the procedure during posterior tympanotomy could also decrease caloric responses especially in cold stimulation according to the results of FND. Therefore, we should consider the effect of structural change in temporal bone on the thermal transmission in case of evaluation of vestibular peripheral function by using caloric stimulation test.

Benign paroxysmal positional vertigo showing sequential translations of four types of nystagmus.

OBJECTIVEnWe report a case of benign paroxysmal positional vertigo (BPPV) showing sequential translation of four types of nystagmus and discuss its pathophysiology.nnnMETHODSnThe case was 65-year-old female. We analyzed her nystagmus three-dimensionally.nnnRESULTSnAt the first visit, she showed vertical-torsio nystagmus of the posterior canal type of BPPV (P-BPPV) and subsequently showed recently reported geotropic nystagmus with a long time constant. Two weeks later, she showed apogeotropic nystagmus of the horizontal canal type of BPPV (AH-BPPV) and subsequently a geotropic nystagmus with a short time constant of the horizontal canal type of BPPV (GH-BPPV).nnnCONCLUSIONSnThree kind of nystagmus, namely P-BPPV, AH-BPPV and GH-BPPV can be explained by the otoconial debris hypothesis of the same ear. Finally, the recently reported geotropic nystagmus with a long time constant may be explained by a reversible lesion such as the denatured cupula or utricular imbalance of the same ear.

Low-tone air-bone gaps after endolymphatic sac surgery

OBJECTIVESnWe detected chronic low-tone air-bone gaps (LTABGs) in some patients with Menieres disease after endolymphatic sac surgery. The aim of the present study was to elucidate the mechanism of LTABGs after endolymphatic sac surgery.nnnMETHODSnWe investigated 50 patients with Menieres disease, who underwent surgery more than two years prior. LTABGs were defined as the three-tone-average=20dB formulated by (a+b+c)/3, where a, b, and c are ABGs at 0.25, 0.5, and 1kHz, respectively (ABG ±). The intra-operative finding was focused on identifying operculum (OPC ±).nnnRESULTSnThe ratio of post-operative ABG(+) was 50.0% (25/50). The ratio of intra-operative OPC(+) was 72.0% (36/50). The surgery results were as follows: the ratio of complete vertigo suppression (VS(+)) was 84.0% (42/50), air-conduction hearing gain (aHG(+)) was 40% (20/50), bone-conduction hearing gain (bHG(+)) was 64% (32/50), and speech discrimination gain (SDG(+)) was 28% (14/50). The post-operative ABG(+) was commonly observed in patients with intra-operative OPC(+) (chi-square test, p=0.013). aHG(+) and SDG(+) results were related to the post-operative ABG(+) (chi-square test, p=0.021 and p=0.0018, respectively).nnnCONCLUSIONSnThese data suggest that intra-operative OPC(+) may be causative for post-operative ABG(+), resulting in post-operative aHG(+) and SDG(+). Thus, as enlarged vestibular aqueduct syndrome and superior semicircular canal deficiency syndrome exhibit LTABGs due to the third mobile inner ear window, endolymphatic sac surgery with adequate endolymphatic sac decompression and exposure to high doses of steroids, might induce LTABGs and the beneficial results of endolymphatic sac surgery.

Implication of substance P neuronal system in the amygdala as a possible mechanism for hypergravity-induced motion sickness.

We previously reported that motion sickness was prevented in rats with amygdala lesion and that provocative motion stimuli increased the number of Fos-positive neurons in the amygdala, suggesting that the amygdala is one of the neural substrates involved in the development of motion sickness. NK-1 receptors in the brain stem and amygdala are thought to play an important role in emesis and affective disorders, respectively. In the present study, to elucidate a role of substance P neuronal system and NK-1 receptors in the brain stem and amygdala in the development of motion sickness, we measured changes in gene expression of NK-1 receptors and preprotachykinin, a precursor of substance P, using quantitative real-time PCR methods in solitary tract nucleus and amygdala in rats after provocative motion stimuli induced by 2G hypergravity load. Effects of systemic administration of CP-99,994, an antagonist for NK-1 receptors, on hypergravity-induced motion sickness were also examined using pica behavior, eating non-nutritive substances such as kaolin, as an index of motion sickness in rats. Hypergravity-induced motion sickness was inhibited by CP-99,994 with a dose-dependent and enantioselective manner. Preprotachykinin mRNA expression was increased in basolateral nucleus of amygdala and solitary tract nucleus after hypergravity load for 3h, whereas NK-1 receptor mRNA expression was not changed by hypergravity in amygdala and solitary tract nucleus. Present results suggest that 2G hypergravity load activated the substance P neuronal system in amygdala as well as in the brain stem and this activation would be related to the development of motion sickness.

3D analysis of spontaneous upbeat nystagmus in a patient with astrocytoma in cerebellum

AIMSnWe report the case of a 58-year-old female patient who consulted our Department complaining of positional vertigo and showing spontaneous upbeat nystagmus (UBN) in darkness.nnnMETHODnWe analyzed her UBN three-dimensionally. The MRI scan revealed the astrocytoma in the left cerebellum involving the cerebellar vermis.nnnRESULTnThree-dimensional analysis showed a spontaneous UBN rotating around the intra-aural axis in the pitch plane.nnnCONCLUSIONnSince the cerebellar vermis is known to plays an inhibitory role on the central vertical vestibule-ocular reflex (VOR), the present results suggest that the spontaneous UBN in darkness observed in this patient was induced by an imbalance of central vertical VOR tone.