Kiyofumi Gyo

Valacyclovir and prednisolone treatment for Bell's palsy: a multicenter, randomized, placebo-controlled study.

Objective: To investigate the effects of valacyclovir and prednisolone in comparison with those of placebo and prednisolone for the treatment of Bells palsy, excluding zoster sine herpete. Study Design: Prospective, multicenter, randomized placebo-controlled study. Setting: Six academic tertiary referral centers. Patients: Ultimately, 221 patients with Bells palsy who were treated within 7 days of the onset. Serological and polymerase chain reaction examinations were performed to distinguish Bells palsy from zoster sine herpete. Intervention: The patients were treated with either valacyclovir (dosage, 1,000 mg/d for 5 days) plus prednisolone (VP [n = 114]) or placebo plus prednisolone (PP [n = 107]) administered orally. Main Outcome Measure: Recovery from the palsy was defined as a score higher than 36 using Yanagihara 40-point scoring system without facial contracture or synkinesis. The patients were followed up until complete recovery occurred or for more than 6 months in cases with a poor prognosis. Results: The overall rate of patient recovery among those treated with VP (96.5%) was significantly better (p < 0.05) than the rate among those treated with PP (89.7%). The rate of patient recovery was also analyzed by classifying the initial severity of facial palsy. In cases of complete or severe palsy, the rates of patients treated with VP and PP who recovered were 95.7% (n = 92) and 86.6% (n = 82), respectively; the recovery rate for treatment with VP was significantly better than that with PP (p < 0.05). Conclusion: The valacyclovir and prednisolone therapy was more effective in treating Bells palsy, excluding zoster sine herpete, than the conventional prednisolone therapy. To our knowledge, this is the first controlled study of an antiviral agent in the treatment of a sufficient number of Bells palsy cases based on an etiologic background.

Measurement of the Ossicular Vibration Ratio in Human Temporal Bones by Use of a Video Measuring System

Vibration modes of the ossicles and the lever function were studied in human cadaver temporal bones with an intact cochlea. After placing tiny steel spheres on the ossicles, ossicular vibration to a sound stimulus was measured by observing the displacements of the spheres under a microscope with strobe illumination by means of a video measuring system. The lever ratio varied from 1.9 at 0.6 kHz (minimum) to a peak of 6 near 2 kHz. This relatively high lever ratio at higher frequencies was considered to be caused by a shift of the malleus-incus rotation axis secondary to the loading of the cochlear fluid on the ossicular system. Dependence of the lever ratio on frequency indicated that the rotation axis of the ossicles was not fixed, but variable according to frequency due to a relative increase in the translational movements of the rotation axis of the malleus and incus with frequency.

Efficacy of early treatment of Bell's palsy with oral acyclovir and prednisolone

Objective To investigate the therapeutic effects of acyclovir and prednisolone in relation to the timing of treatment in Bells palsy. Study Design This was a retrospective study of 480 Bells palsy patients who were treated with oral acyclovir and prednisolone (94 cases) or prednisolone alone (386 cases). Patients Patients met the after criteria: (1) severe or complete Bells palsy with a score lower than 20 on the 40-point Yanagihara facial score and (2) treatment started within 7 days after onset. The patients were treated with oral prednisolone (60–40 mg/day) with or without oral acyclovir (2,000 mg/day). Main Outcome Measure Rate of recovery, which was defined as a facial score of 36 or more, and the absence of contracture with synkinesis. Results The overall recovery rate of patients treated with acyclovir and prednisolone was 95.7 percent, which was better than that of patients treated with prednisolone alone (88.6%). The recovery rate in patients who began the combined therapy within 3 days of the onset of palsy was 100 percent and early treatment resulted in early remission. In contrast, the recovery rate in patients who started the combined therapy more than 4 days after onset was 86.2 percent. Conclusion These results suggest that early diagnosis and treatment within 3 days of the onset of paralysis are necessary for maximal efficacy of combined acyclovir and prednisolone therapy for Bells palsy.

Ramsay Hunt syndrome in children

In a retrospective study, 52 children were diagnosed with Ramsay Hunt syndrome. The facial palsy was milder and complete recovery of the function was achieved in 78.6% of patients. Associated cranial neuropathies were less common in children than in adults. The timing of vesicle appearance tended to be delayed in children. In preschool children, Ramsay Hunt syndrome was rare, although the frequency has recently increased. The syndrome is relatively common in older children. This study suggested that vaccination can prevent or reduce the occurrence of Ramsay Hunt syndrome. Ann Neurol 2000;48:254–256

Efflux of glutamate into the perilymph of the cochlea following transient ischemia in the gerbil

Using a microdialysis technique followed by an enzyme cycling analysis, we measured changes in the glutamate levels in the perilymph of gerbil cochleae before, during and after transient ischemic insult. The basal glutamate level in perilymph was 0.35 +/- 0.22 pmol/microl. An almost immediate and continuous rise in the level of glutamate occurred after the ischemic insult, which advanced even further after recirculation; the average concentration was higher than 40 pmol/microl 55 min after recirculation. The compound action potentials (CAP) monitoring the auditory function totally disappeared after ischemic insult. However, CAP reappeared after recirculation; the threshold for acoustic stimulation was higher than that observed at the pre-ischemic state.

Varicella-Zoster Virus Distribution in Ramsay Hunt Syndrome Revealed by Polymerase Chain Reaction

The pathogenesis of facial nerve paralysis and vestibulo-cochlear dysfunction of Ramsay Hunt syndrome remains unclear as varicella-zoster virus (VZV) has not been demonstrated in the lesions. Using the polymerase chain reaction, we detected VZV genomes not only in the vesicles on the auricles or oral cavity but also in the facial nerve sheath, middle ear mucosa and cerebrospinal fluid from patients with Ramsay Hunt syndrome. The VZV genome was undetectable in the same kinds of clinical samples obtained from control patients with facial nerve paralysis of other etiologies. The results indicated that VZV spreads widely in the neural components, mucocutaneous tissue and cerebrospinal fluid. The present study will facilitate better understanding of the pathogenesis of facial nerve paralysis, vertigo, hearing impairment and other cranial nerve dysfunction of Ramsay Hunt syndrome.

Insulin-like growth factor 1 treatment via hydrogels rescues cochlear hair cells from ischemic injury

This study was designed to investigate the protective effects of recombinant human insulin-like growth factor 1 (rhIGF1), applied locally via a hydrogel, against ischemic damage of the cochleae in gerbils. A hydrogel was immersed in rhIGF1 or saline and was applied on the round window membrane 30 min after the ischemia. Local rhIGF1 treatment significantly reduced the elevation of auditory brain responses thresholds at a frequency of 8 kHz on days 1, 4, and 7 after ischemia. A histological analysis revealed increased survival of inner hair cells in the animals treated with rhIGF1 via the hydrogel 7 days after ischemia. These findings showed that local rhIGF1 application using a hydrogel has the potential to protect the cochleae from ischemic injury.

Effect of single-drug treatment on idiopathic sudden sensorineural hearing loss

OBJECTIVES In order to evaluate the effect of a medical administration for the sudden deafness patients, single-drug treatment for idiopathic sudden sensorineural hearing loss (ISSHL) was assessed at multi-centers participating in the Acute Severe Hearing Loss Study Group sponsored by the Ministry of Health, Labor and Welfare of Japan. METHODS The subjects consisted of ISSHL patients who were (1) 20 years of age or older, (2) diagnosed within 2 weeks after the onset of hearing loss, (3) showing a mean hearing level of 40-90 dB at five frequencies from 250 to 4000 Hz, (4) previously untreated, and (5) with normal for age in hearing of the opposite ear. The drugs used in this study were ATP, alprostadil, hydrocortisone and amidotrizoate, which were administered intravenously, and beraprost sodium and betamethasone, which were given orally. Two drugs were assigned to each center, one of which was selected according to the code hidden in envelopes and administered for 1 week. The treatment after the single-drug administration was conducted at the discretion of each center. The hearing gain and recovery rate at 1 week after the initiation of single-drug treatment and at 1 month or over when the hearing level was fixed, were evaluated based on the criteria for hearing recovery prepared by the Acute Severe Hearing Loss Study Group. RESULTS There was no statistically significant difference in the recovery rate among drugs either at 1 week after the initiation of single-drug treatment or at the time of fixed hearing level. At the time when the hearing level was fixed, a statistically significant difference in the complete recovery rate was detected only between amidotrizoate and beraprost sodium. CONCLUSION From these results, we could not find any specific drugs recommended for ISSNHL. In evaluating the effect of the drugs, however, several problems in the clinical trial for ISSHL should be considered.

Hearing loss and glutamate efflux in the perilymph following transient hindbrain ischemia in gerbils

The mechanism underlying ischemia‐induced hearing loss was studied in gerbils with transient hindbrain ischemia. Occlusion of the vertebral arteries caused an increase in the concentration of glutamate in the perilymph and elevated the compound action potential (CAP) threshold to 24.6 dB at 5 minutes. the CAP threshold subsequently recovered on reperfusion, gradually reaching 8.3 dB 120 minutes after reperfusion. Under electron microscopy, afferent dendrites of the cochlear nerve in contact with inner hair cells exhibited abnormal swelling 5 minutes after ischemia/reperfusion. These morphological changes were not observed in cochleas treated with an alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA)/kainate‐type glutamate receptor antagonist, 6‐7‐dinitroquinoxaline‐2,3‐dione (DNQX), before hindbrain ischemia; an N‐methyl‐D‐aspartate (NMDA)‐type receptor antagonist, D‐2‐amino‐5‐phosphonopentanoate (D‐AP5), was ineffective. Moreover, the histopathological alterations noted 5 minutes after reperfusion were spontaneously ameliorated 120 minutes after ischemia/reperfusion. These findings suggest that the ischemia‐induced increase in extracellular glutamate concentration with subsequent activation of AMPA/kainate receptors is responsible for neurite degeneration and hearing loss in the early stages following transient hindbrain ischemia. J. Comp. Neurol. 418:217–226, 2000.

Effect of Middle Ear Pressure Change on Middle Ear Mechanics

The effect of graded variations in middle ear pressure on ossicular vibration was measured in 15 normal human temporal bone specimens. The displacement amplitude of the umbo and stapes head was measured at 16 frequencies between 0.2 kHz and 3.5 kHz at a constant sound pressure of 134 dB SPL at the tympanic membrane (TM) using a non-contacting video measuring system. Both negative and positive pressures decreased umbo and stapes vibration at low frequencies and slightly increased the vibration at higher frequencies. The effects were greater for negative pressure than for positive pressure. The change in stapes vibration was less than that of the umbo at low frequencies, but increased at higher frequencies. In some temporal bones, a small positive pressure produced improvement in stapes vibration at all frequencies. These effects were thought to be primarily due to an increased stiffness of the TM and a damping of ossicular vibration, due to stretching of the ossicular suspensory ligaments and the annular ligament of the footplate.