Masaru Aoyagi

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.

Optimal modulation frequency for amplitude-modulation following response in young children during sleep

In young children, there appears to be no advantage to recording steady-state response (SSR) at a stimulus rate of 40 Hz. To determine the optimal modulation frequency in auditory SSR evoked by sinusoidally amplitude-modulated (SAM) tones (amplitude-modulation following response: AMFR) in children during sleep and compare response patterns of AMFR at different modulation frequencies while awake with those during sleep, AMFR was examined in 10 adults with normal hearing while awake and during sleep and in 10 young children with normal hearing during sleep. The stimulus was a 1000 Hz, 50 dBnHL SAM tone with a modulation depth of 95%. Modulation frequency was varied from 20 to 200 Hz in 20 Hz steps. Response was determined by phase spectral analysis and the S/N ratio calculated by spectral amplitude at the modulation frequency and noise level around the modulation frequency using fast Fourier transform. Although AMFR was clearly evoked only by a modulation frequency of 40 Hz in adults while awake, AMFRs at modulation frequencies of 80 and 100 Hz were detected during sleep, in addition to 40 Hz AMFR. In children, 40 Hz AMFR was difficult to detect, but response could be clearly detected at higher modulation rates, especially at modulation frequencies of 80 and 100 Hz, compared with response in adults during sleep. Modulation frequencies from 80 to 100 Hz would thus appear optimal for detecting AMFR during sleep in children.

Reliability of 80-Hz Amplitude- Modulation-Following Response Detected by Phase Coherence

The reliability and frequency specificity of the 80-Hz amplitude-modulation-following response (80-Hz AMFR) during sleep detected by phase coherence as a measure of the hearing threshold was evaluated in 169 affected ears of 125 children with hearing impairment. The 80-Hz AMFR at a carrier frequency of 1000 Hz was monitored in all 169 ears and the auditory brainstem response (ABR) elicited by 1000-Hz tone pips was evaluated in 93 ears. Both responses were examined during sleep, and the thresholds were compared with the behavioral hearing threshold, which was determined by standard pure-tone audiometry or play audiometry. In 24 ears of 22 children with various patterns of audiogram, the 80-Hz AMFR was examined at different carrier frequencies, and the threshold pattern was compared with the pure-tone audiogram to investigate the frequency specificity of 80-Hz AMFR. The mean and standard deviation of the difference between the 80-Hz AMFR at a carrier frequency of 1000 Hz and pure-tone thresholds of 1000 Hz was 3.8 and 12.9 dB, and that between the ABR and pure-tone thresholds was 6.8 and 14.1 dB, respectively. The threshold patterns of 80-Hz AMFR clearly followed the corresponding audiogram patterns in all types of hearing impairment. The measurement of 80-Hz AMFR thus appears to be accurate in hearing assessment and to have good frequency specificity in children during sleep.

Pure-tone threshold prediction by 80-Hz amplitude-modulation following response.

The usefulness of 80-Hz amplitude-modulation following response (AMFR) detected by phase spectral analysis to predict the hearing threshold during sleep was evaluated in 20 normal adults, 8 normal children and 37 children with hearing impairment. The onset effect of tonal stimulus on 80-Hz steady state response was studied in normal adults during sleep and a threshold of 80-Hz AMFR detected by phase spectral analysis was compared with that of ABR elicited by tone pips in children during sleep. Although 80-Hz AMFR is not appropriate for the assessment of hearing in adults, it appears useful for evaluating hearing in young children during sleep. Hearing prediction by 80-Hz AMFR appears to be more accurate than that by ABR elicited with tone pips. The onset effect of stimulus on 80-Hz AMFR with modulation depth of 95% was less than 80-Hz SSR evoked by clicks.

Reactivation of Herpes Simplex Virus Type 1 and Varicella‐Zoster Virus and Therapeutic Effects of Combination Therapy With Prednisolone and Valacyclovir in Patients With Bell's Palsy

Objectives: To determine whether reactivation of herpes simplex virus (HSV) type 1 or varicella‐zoster virus (VZV) is the main cause of Bells palsy and whether antiviral drugs bring about recovery from Bells palsy.

Nuclear localization of diacylglycerol kinase ζ in neurons

Diacylglycerol kinase (DGK) is involved in intracellular signal transduction as a regulator of levels of diacylglycerol which leads to protein kinase C activation. Previous studies have revealed that DGK consists of a family of isozymes in mammalian species and that most if not all of them show abundant expression in the central nervous system, suggesting the importance of this enzyme in neuronal function. Among the isozymes, DGKζ (previously also known as DGK‐IV for the rat clone) has unique structural features, such as four ankyrin‐like repeats and a nuclear localization signal (NLS), and shows intense mRNA expression in neurons of the olfactory bulb, hippocampus and cerebral and cerebellar cortices (Goto, K. & Kondo, H. (1996), Proc. Natl Acad. Sci. USA, 93, 11196–11201). However, previous studies have given conflicting results about whether or not DGKζ localizes to the nucleus in these cells. In this study, we have used immunohistochemistry with specific antibodies in brain tissues and cDNA transfection into primary cultured neurons to address this question. We have shown that, while DGKζ is primarily a nuclear protein in neurons, it can also be cytoplasmic in some conditions, and the subcellular location depends not only on the cell type but also on the developmental state or growth conditions of the cell. In addition, we have used deletion mutants to show that nuclear transport of DGKζ depends on a cooperative interaction between the NLS and the C‐terminal region including ankyrin repeats in a manner which suggests that the NLS is a cryptic site whose exposure is regulated by the C‐terminal region. Together, these results support the hypothesis that the localization of DGKζ may be regulated by differential expression of these various proteins which interact with its C‐terminal region.

Short-Term Outcome and Prognosis of Acute Low-Tone Sensorineural Hearing Loss by Administration of Steroid

Acute low-tone hearing loss (ALHL) is a typical type of hearing loss in Ménière’s disease and thought to be caused by endolymphatic hydrops in the inner ear. We treated 40 patients with ALHL by administration of the steroid and the early outcome and prognosis of the hearing level was retrospectively evaluated. The prognosis was generally determined within 7–10 days after administration of steroid. High-dose steroid cured some patients who failed to recover with low-dose steroid therapy. Our results showed that steroid is one of the effective therapies for ALHL and supported that etiology of ALHL involves an immune response.

Facial Nerve Enhancement in Gd-MRI in Patients with Bell's palsy

The diagnostic value of a contrast enhanced MRI in patients with Bells palsy was investigated. It was a characteristic finding that the internal acoustic meatal segment of the facial nerve was enhanced only on the affected side. The signal intensity ratio of the geniculate ganglion and the tympanic segment was significantly higher on the affected side than on the normal side. The severity of the facial palsy and the results of physiological examinations showed no relation to the results of MRI scans. Gd enhanced MRI thus appears to provide some useful findings for estimating the affected region of Bells palsy, whereas it is not considered to be valuable in the diagnosis of severity.

Frequency specificity of amplitude-modulation following response detected by phase spectral analysis

To investigate the frequency specificity of steady-state responses elicited with a sinusoidally amplitude-modulated tone (amplitude-modulation-following response, AMFR), AMFR at different carrier frequencies were examined in 15 subjects with normal hearing, 12 patients with abrupt high-frequency hearing loss, 5 patients with low-frequency hearing loss and 1 patient with mid-frequency hearing loss. The stimulus was a sinusoidally amplitude-modulated tone with a modulation frequency of 40 Hz and modulation depth of 95%. Carrier frequencies were from 250 to 4000 Hz in normal subjects and from 250 to 8,000 Hz in hearing-impaired subjects. Fridmans phase spectral analysis was conducted for automatic detection of response. The thresholds of AMFR were distributed within 30 dB nHL at all carrier frequencies in normal subjects. In the hearing-impaired subjects, AMFR thresholds were between 0 and 25 dB above the behavioral threshold at all carrier frequencies. The threshold patterns of AMFR detected by phase spectral analysis very closely resembled the corresponding audiogram patterns in all types of hearing impairment. AMFR is thus shown to have a very good frequency specificity.

Effects and mechanism of OK-432 therapy in various neck cystic lesions

Abstract Conclusion: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of benign neck cysts. In OK-432 therapy, inflammatory cytokines may play important roles in shrinkage of the cystic spaces. Objective: The aim of this study was to evaluate the outcome and mechanism of action of OK-432 therapy in benign neck cysts. Methods: We tried OK-432 therapy in 83 patients with benign neck cysts between April 1997 and August 2009. We aspirated as much of the fluid content of each cystic lesion as possible, and then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. We evaluated the mechanism of action of OK-432 in 43 of the patients. The intracystic fluid in the cysts was aspirated before and after OK-432 therapy, and cytokine production in each aspirate was analyzed by ELISA. Results: Disappearance of the lesion was observed in 63 of 83 patients (76%). Marked reduction was observed in 13 of the 83 patients (16%). Partial reduction was observed in two patients (2%) and no response was seen in five (6%). Local discomfort at the injection site and low-grade fever were side effects observed in half of the patients, but such problems resolved within a few days. No local scarring or deformity of the injected sites occurred in any patient. We performed OK-432 therapy on an outpatient basis without hospitalization. Levels of various cytokines, including tumor necrosis factor, interleukin-8, interleukin-6, interferon gamma, and vascular endothelial growth factor, were significantly elevated in each aspirate after OK-42 therapy.