Exercise reduces metabolic burden while altering the immune system in aged mice.

Although several evidence has suggested the impact of exercise on the prevention of aging phenotypes, few studies have been conducted on the mechanism by which exercise alters the immune-cell profile, thereby improving metabolism in senile obesity. In this study, we confirmed that 4-week treadmill exercise sufficiently improved metabolic function, including increased lean mass and decreased fat mass, in 88-week-old mice. The expression level of the senescence marker p16 in the white adipose tissue (WAT) was decreased after 4-weeks of exercise. Exercise induced changes in the profiles of immune-cell subsets, including natural killer (NK) cells, central memory CD8+ T cells, eosinophils, and neutrophils, in the stromal vascular fraction of WAT. In addition, it has been shown through transcriptome analysis of WAT that exercise can activate pathways involved in the interaction between WAT and immune cells, in particular NK cells, in aged mice. These results suggest that exercise has a profound effect on changes in immune-cell distribution and senescent-cell scavenging in WAT of aged mice, eventually affecting overall energy metabolism toward a more youthful state.

Exercise-induced changes of gene expression in the cerebellum of aged mice.

PURPOSE: Exercise has been prescribed to the elderly based on its effect on increasing muscle strength and protein synthesis that prevent sense of balance and/or cognitive functions. However, a few molecular mechanism researches has been conducted on how the vestibular organs, cerebellum, and hippocampus, which are responsible for the deterioration and balance of spatial learning memory due to aging, are affected by exercise. METHODS: The 9-week old and 84-week old C57Bl/6 were assigned randomly to Young-Control (YC), Young-Exercise (YE), Old-Control (OC) and Old-Exercise (OE) groups for 4 -week treadmill running. A Rotarod test was used to evaluate motor coordination function. Moreover, a high-throughput whole transcript expression RNA array approach was applied to the cerebellum of aged mice to explain the novel molecular mechanism of beneficial effect of exercise. RESULTS: As results, the motor coordination function was significantly improved in exercise-aged mice. The RNA sequencing analysis showed that the expression of cerebellar genes was significantly changed by aging rather than exercise. Especially, Cers1 was up-regulated in sedentary aged mice and down-regulated in exercise aged mice. Fumonisin B1, inhibition of Cers1, mitigates neuronal cell death induced by doxorubicin. CONCLUSION: These results provide unraveling specific transcripts and understanding of the exercise-related cerebellum transcriptome in aged mice. Well-designed exercise program might prevent the motor coordination defect in aged model, which development of the exercise protocol for elderly population based on these markers.

Surgical findings to differentiate between facial nerve schwannoma and vestibular schwannoma.

OBJECTIVES: Facial nerve schwannomas may be misdiagnosed as vestibular schwannomas (VSs) if the tumor is confined to the internal auditory canal (IAC) without involvement the geniculated ganglion or labyrinthine segment of facial nerve. Because facial nerve schwannomas may be misdiagnosed as VSs, we investigated the differences between the two. METHODS: The study included 187 patients with a preoperative diagnosis of VS. Of these, six were diagnosed with facial nerve schwannomas during surgery. We reviewed the preoperative evaluations and surgical findings of facial nerve schwannomas mimicking VSs. RESULTS: No useful preoperative predictors are available for facial nerve schwannomas mimicking VSs. Facial nerve schwannomas are usually confined to the IAC. After opening the dura of the IAC, a facial nerve schwannoma can be diagnosed after identifying a normal-appearing nerve located lateral to the tumor. When this was the case, we performed facial nerve preservation surgery or decompression. CONCLUSION: Facial nerve schwannomas can be differentiated from VSs by identifying specific findings during surgery.

Mandibular condyle and infratemporal fossa reconstruction using vascularized costochondral and calvarial bone grafts.

There are some difficulties in approaching and removing the lesion in infratemporal fossa because of its anatomical location. After wide excision of tumor lesion, it is also difficult for reconstruction of mandibular condyle and cranium base on infratemporal fossa. Besides, there are some possibilities of cerebrospinal fluid leakage, intracranial infection and bone resorption. It is also challenging for functional reconstruction that allows normal mandibular movement, preventing mandibular condyle from invaginating into the skull. In this report, we present 14-month follow-up results of a patient who had undergone posterior segmental mandibulectomy including condyle and infratemporal calvarial bone and mandible reconstruction with free vascularized costochondral rib and calvarial bone graft to restoration of the temporomandibular joint area.

Functional and practical outcomes of inlay butterfly cartilage tympanoplasty.

OBJECTIVE: For tympanoplasty, the most common grafting materials are the temporalis fascia or perichondrium; however, both require incision of the canal skin, which carries a risk of morbidity and the need for postoperative care. Inlay butterfly cartilage tympanoplasty, by which the perforation edges are refreshed and a cartilage is inserted through the perforation without canal incision, makes the graft easy, and reduces operating and recovery time. We analyze the outcome of inlay butterfly cartilage tympanoplasty. MATERIALS AND METHODS: This study included 112 patients who underwent tympanoplasty from January 2011 to August 2012. Patients were divided into 2 groups: patients who underwent inlay butterfly cartilage tympanoplasty (Group I, n = 56) and patients who underwent conventional underlay tympanoplasty using the temporalis fascia (Group II, n = 56). Anatomic success was defined as an intact, repaired tympanic membrane, and functional success was defined as a significant decrease in the air-bone gap at the end of follow-up. Perioperative pain was analyzed using a visual analogue scale (VAS). Surgical success, functional success, perioperative pain, and operating time were evaluated and compared. RESULTS: The surgical success rate was 96.4% in Group I and 91.1% in Group II (p = 0.435). The mean air-bone gap decrease was 7.9 ± 2.2 dB in Group I and 8.9 ± 3.2 dB in Group II (p = 0.426). Group I showed a lower VAS score for pain (1.5 ± 1.2) and a shorter operation time (25.6 ± 8.5 min) compared with those of Group II (4.9 ± 1.7, 48.6 ± 19.5 min, respectively) (p < 0.01). CONCLUSION: Inlay butterfly cartilage tympanoplasty is compatible with the conventional underlay technique in both anatomic and functional success rates. Its simplicity, shorter operation time, and rapid recovery time could make it an attractive surgical option.

Prevalence and clinical significance of spontaneous low-frequency air-bone gaps in Ménière's disease.

OBJECTIVES: The prevalence and clinical significance of spontaneous low-frequency air-bone gaps (LFABGs) in Ménière's disease were investigated. STUDY DESIGN: A retrospective study. SETTINGS: Tertiary referral center. PATIENTS: Three hundred thirty-seven patients with definite Ménière's disease. MAIN OUTCOME MEASURES: The prevalence of LFABG in this population was calculated, and the following parameters were analyzed: 1) changes in hearing thresholds after the resolution of LFABG; 2) correlation between LFABG and electrocochleography (ECoG) results; 3) changes in the number of vertigo spells after the resolution of LFABG; 4) correlation between LFABG and canal paresis (CP) values in caloric testing; and 5) the difference in the prognoses of patients with and without LFABG. RESULTS: The prevalence of LFABG was 13.9%. Patients' hearing thresholds were significantly decreased after the resolution of LFABG (from 49.4 ± 16.8 to 38.3 ± 19.3, p = 0.044), whereas the summating potential and action potential ratio in ECoG tended to increase as LFABG increased (R = 0.09, p = 0.03). The mean number of vertigo spells was significantly reduced after the resolution of LFABG (from 2.9 to 0.5, p < 0.0001), but CP did not correlate with LFABG. The prognosis was not different for patients with and without LFABG. CONCLUSION: The number of vertigo spells and hearing thresholds were significantly higher during the period of LFABG development. Although the prognostic importance of LFABG was not significant, it likely reflects the aggravation of the endolymphatic hydrops in the cochlear and vestibular compartments and may be useful for evaluating and treating patients with Ménière's disease.

Periodic alternating nystagmus of peripheral vestibular origin.

OBJECTIVES/HYPOTHESIS: Periodic alternating nystagmus (PAN) is most commonly found either in its congenital form or after cerebellar/pontomedullary lesions. However, we identified PAN in 10 patients with peripheral vestibular disorders and will try to describe their characteristics to aid in the differential diagnosis between peripheral and central etiologies. STUDY DESIGN: Observation of a case series. METHOD: Peripheral vestibular lesions were confirmed by neurological examinations, vestibular function tests, and brain magnetic resonance imaging (MRIs). Eye movements of the patients were recorded using electronystagmography or video nystagmography for a minimum of 10 minutes to confirm the nystagmus change in direction. RESULTS: The final diagnoses of the patients included Meniere's disease (n = 3), acute labyrinthitis (n = 4), sudden sensorineural hearing loss with vertigo (n = 2), and vestibular schwannoma (n = 1). Direction-changing spontaneous horizontal nystagmus with quiescent intervals was observed in all patients under dark conditions. The nystagmus was suppressed by visual fixation; and the results of oculomotor tests were normal for saccadic and smooth pursuit eye movements and optokinetic nystagmus. All patients showed mild to complete canal paresis on a bithermal caloric test. PAN progressed into unidirectional nystagmus of the contra-lesion side in all patients within 48 hours. CONCLUSION: PAN can be observed in patients with peripheral vestibular disorders, but detecting PAN in this subpopulation is difficult because of its transitory nature. The absence of central symptoms and signs, the visual suppression of PAN, normal oculomotor tests, and transient persistence are important diagnostic clues for differentiating peripheral from central PAN. LEVEL OF EVIDENCE: 4.

Is there a deafness duration limit for cochlear implants in post-lingual deaf adults?

CONCLUSION: Patients with post-lingual deafness should not be excluded from cochlear implantation (CI) on the basis of duration of deafness. We found that the prognosis was favorable in patients who developed deafness after adolescence, even in those with extremely long-term deafness. OBJECTIVES: CI is an effective treatment for post-lingual deafness. However, it remains unclear whether CI would benefit patients with extremely long-term deafness. We evaluated the auditory performance after CI of patients who had been deaf for more than 30 years. METHODS: The study enrolled 81 adults with post-lingual deafness. Speech perception tests were performed preoperatively and 12 months postoperatively, and factors affecting the postoperative auditory performance were investigated. The subjects were divided into groups according to the duration of deafness and the postoperative speech perception scores were compared. RESULTS: A marked improvement in the open-set speech perception scores (mono/disyllabic words and sentences) after implantation was seen in all groups, and no significant difference in the improvement in speech perception scores was observed among the groups. Age at onset of deafness was closely related to the postoperative performance, and patients who had lost their hearing before adolescence performed poorly.

Change in tinnitus after treatment of vestibular schwannoma: microsurgery vs. gamma knife radiosurgery.

PURPOSE: Tinnitus is a very common symptom of vestibular schwannoma, present in 45 to 80% of patients. We evaluated changes in tinnitus after translabyrinthine microsurgery (TLM) or gamma knife radiosurgery (GKS). MATERIALS AND METHODS: Among 78 patients with vestibular schwannoma who underwent TLM or GKS at Severance Hospital from 2009-2012, 46 patients with pre- or postoperative tinnitus who agreed to participate were enrolled. Pure tone audiometry, tinnitus handicap inventory (THI), visual analogue scale (VAS) scores for loudness, awareness, and annoyance were measured before and after treatment. Changes of THI and VAS were analysed and compared according to treatment modality, tumour volume, and preoperative residual hearing. RESULTS: In the TLM group (n=27), vestibulocochlear nerves were definitely cut. There was a higher rate of tinnitus improvement in TLM group (52%) than GKS group (16%, p=0.016). The GKS group had a significantly higher rate of tinnitus worsening (74%) than TLM group (11%, p<0.001). Mean scores of THI and VAS scores significantly decreased in the TLM group in contrast to significant increases in the GKS group. Tumor volume and preoperative hearing did not affect the changes in THI or VAS. CONCLUSION: GKS can save vestibulocochlear nerve continuity but may damage the cochlea, cochlear nerve and can cause worsening tinnitus. In cases where hearing preservation is not intended, microsurgery with vestibulocochlear neurectomy during tumor removal can sometimes relieve or prevent tinnitus.

Association between vestibular schwannomas and mobile phone use.

Vestibular schwannomas (VSs) grow in the region where the energy from mobile phone use is absorbed. We examined the associations of VSs with mobile phone use. This study included 119 patients who had undergone surgical tumor removal. We used two approaches in this investigation. First, a case-control study for the association of mobile phone use and incidence of VSs was conducted. Both cases and controls were investigated with questions based on INTERPHONE guidelines. Amount of mobile phone use according to duration, daily amount, and cumulative hours were compared between two groups. We also conducted a case-case study. The location and volume of the tumors were investigated by MRI. Associations between the estimated amount of mobile phone use and tumor volume and between the laterality of phone use and tumor location were analyzed. In a case-control study, the odds ratio (OR) of tumor incidence according to mobile phone use was 0.956. In the case-case study, tumor volume and estimated cumulative hours showed a strong correlation (r(2) = 0.144, p = 0.002), and regular mobile phone users showed tumors of a markedly larger volume than those of non-regular users (p < 0.001). When the analysis was limited to regular users who had serviceable hearing, laterality showed a strong correlation with tumor side (OR = 4.5). We found that tumors may coincide with the more frequently used ear of mobile phones and tumor volume that showed strong correlation with amount of mobile phone use, thus there is a possibility that mobile phone use may affect tumor growth.

Leiomyosarcoma of the middle ear and temporal bone.

Leiomyosarcoma is a malignant tumor of smooth muscle cells that is exceedingly rare in the middle ear and temporal bone. Wide surgical resection is treatment of choice and adjuvant treatment has not proven to be of benefit. This is a report on a patient with otorrhea and rapidly growing mass on postauricualr area. A tumor that was mainly located in the middle ear and temporal bone was surgically removed and proved to be a leiomyosarcoma. The optimal surgical technique and other treatment strategy are discussed.

Mutational analysis of EYA1, SIX1 and SIX5 genes and strategies for management of hearing loss in patients with BOR/BO syndrome.

BACKGROUND: Branchio-oto-renal (BOR) or branchio-otic (BO) syndrome is one of the most common forms of autosomal dominant syndromic hearing loss. Mutations in EYA1, SIX1 and SIX5 genes have been associated with BOR syndrome. In this study, clinical and genetic analyses were performed in patients with BOR/BO syndrome focusing on auditory manifestations and rehabilitation. METHODS: The audiologic manifestations were reviewed in 10 patients with BOR/BO syndrome. The operative findings and hearing outcome were analyzed in patients who underwent middle ear surgeries. The modality and outcome of auditory rehabilitation were evaluated. Genetic analysis was performed for EYA1, SIX1, and SIX5 genes. RESULTS: All patients presented with mixed hearing loss. Five patients underwent middle ear surgeries without successful hearing gain. Cochlear implantation performed in two patients resulted in significant hearing improvement. Genetic analysis revealed four novel EYA1 mutations and a large deletion encompassing the EYA1 gene. CONCLUSIONS: Auditory rehabilitation in BOR/BO syndrome should be individually tailored keeping in mind the high failure rate after middle ear surgeries. Successful outcome can be expected with cochlear implantations in patients with BOR/BO syndrome who cannot benefit from hearing aids. The novel EYA1 mutations may add to the genotypic and phenotypic spectrum of BOR syndrome in the East Asian population.

Can the affected semicircular canal be predicted by the initial provoking position in benign paroxysmal positional vertigo?

OBJECTIVES/HYPOTHESIS: The study evaluated the relationship between the position that initially provoked vertigo and the affected semicircular canal (SCC) in patients with benign paroxysmal positional vertigo (BPPV), and aimed to predict the side affected by BPPV through history taking regarding the provoking position. STUDY DESIGN: Prospective study at a tertiary hospital. METHODS: A total of 521 patients with BPPV involving the posterior or horizontal SCCs performed questionnaires at initial visit asking to choose the initial provoking position among the 10 positions corresponding to one of the three planes (roll, pitch, or yaw). After excluding 45 patients showing signs of simultaneous multiple canal or anterior canal involvement, the frequency of the provoking positions and the correlation between the side of the provoking position and the ear affected by BPPV were analyzed. RESULTS: There were 239 patients with posterior SCC BPPV (p-BPPV) and 237 patients with horizontal SCC BPPV (h-BPPV). The waking-up position was the most common provoking position in both types of BPPV. Statistically significant correlation was demonstrated between the side of the provoking position at the onset of vertigo and the affected side by BPPV (P < .01) in patients with p-BPPV as well as h-BPPV (geotropic type [Geo]), but not in patients with h-BPPV (apogeotropic type [Apo]). CONCLUSIONS: History taking regarding the side of provoking position at the onset of vertigo may help predict the side affected by BPPV in p-BPPV and h-BPPV (Geo). When h-BPPV (Apo) is suspected, further detailed examinations using additional localization methods should be performed.

Bimodal benefits on objective and subjective outcomes for adult cochlear implant users.

BACKGROUND AND OBJECTIVES: Given that only a few studies have focused on the bimodal benefits on objective and subjective outcomes and emphasized the importance of individual data, the present study aimed to measure the bimodal benefits on the objective and subjective outcomes for adults with cochlear implant. SUBJECTS AND METHODS: Fourteen listeners with bimodal devices were tested on the localization and recognition abilities using environmental sounds, 1-talker, and 2-talker speech materials. The localization ability was measured through an 8-loudspeaker array. For the recognition measures, listeners were asked to repeat the sentences or say the environmental sounds the listeners heard. As a subjective questionnaire, three domains of Korean-version of Speech, Spatial, Qualities of Hearing scale (K-SSQ) were used to explore any relationships between objective and subjective outcomes. RESULTS: Based on the group-mean data, the bimodal hearing enhanced both localization and recognition regardless of test material. However, the inter- and intra-subject variability appeared to be large across test materials for both localization and recognition abilities. Correlation analyses revealed that the relationships were not always consistent between the objective outcomes and the subjective self-reports with bimodal devices. CONCLUSIONS: Overall, this study supports significant bimodal advantages on localization and recognition measures, yet the large individual variability in bimodal benefits should be considered carefully for the clinical assessment as well as counseling. The discrepant relations between objective and subjective results suggest that the bimodal benefits in traditional localization or recognition measures might not necessarily correspond to the self-reported subjective advantages in everyday listening environments.

Significance of the development of the inner ear third window effect after endolymphatic sac surgery in Ménière disease patients.

OBJECTIVES/HYPOTHESIS: The goal of this study was to identify the clinical significance of the low-frequency air-bone gap (LFABG) that often develops after endolymphatic sac surgery. STUDY DESIGN: Prospective study. METHODS: Sixteen patients who had been diagnosed with definite Ménière disease and underwent endolymphatic sac surgery were studied. The surgical outcome was evaluated based on the 1995 guidelines of the American Academy of Otolaryngology-Head and Neck Surgery. The number of patients who developed LFABGs (a mean air-bone gap >10 dB HL at 250, 500, and 1,000 Hz) after surgery was determined, and the significance of the LFABGs was evaluated by analyzing their relation with the surgical outcome. RESULTS: The vertigo spells of nine patients were completely controlled (class A). The number of vertigo spells was reduced by 60% to 99% in 6 patients (class B) and by 20% to 59% in 1 patient (class C). Postoperative LFABGs were observed in 13 patients. The mean LFABG of the patients in class A was significantly larger than that of the patients in classes B and C (25.0 ± 7.6 dB nHL in class A vs. 10.0. ± 7.5 dB nHL in class B and C; P = .005). CONCLUSIONS: Based on the data of the current study, we conjectured that the correlation of large LFABGs with excellent vertigo control in this study may be due to a third window phenomenon related to bony decompression of the endolymphatic sac and duct, and may serve as a favorable prognostic marker.

Genetic and epigenetic alterations of the NF2 gene in sporadic vestibular schwannomas.

BACKGROUND: Mutations in the neurofibromatosis type 2 (NF2) tumor-suppressor gene have been identified in not only NF2-related tumors but also sporadic vestibular schwannomas (VS). This study investigated the genetic and epigenetic alterations in tumors and blood from 30 Korean patients with sporadic VS and correlated these alterations with tumor behavior. METHODOLOGY/PRINCIPAL FINDINGS: NF2 gene mutations were detected using PCR and direct DNA sequencing and three highly polymorphic microsatellite DNA markers were used to assess the loss of heterozygosity (LOH) from chromosome 22. Aberrant hypermethylation of the CpG island of the NF2 gene was also analyzed. The tumor size, the clinical growth index, and the proliferative activity assessed using the Ki-67 labeling index were evaluated. We found 18 mutations in 16 cases of 30 schwannomas (53%). The mutations included eight frameshift mutations, seven nonsense mutations, one in-frame deletion, one splicing donor site, and one missense mutation. Nine patients (30%) showed allelic loss. No patient had aberrant hypermethylation of the NF2 gene and correlation between NF2 genetic alterations and tumor behavior was not observed in this study. CONCLUSIONS/SIGNIFICANCE: The molecular genetic changes in sporadic VS identified here included mutations and allelic loss, but no aberrant hypermethylation of the NF2 gene was detected. In addition, no clear genotype/phenotype correlation was identified. Therefore, it is likely that other factors contribute to tumor formation and growth.

The inhibitory effect of honokiol, a natural plant product, on vestibular schwannoma cells.

OBJECTIVES/HYPOTHESIS: As the molecular biology of vestibular schwannoma (VS) is better understood, new means of targeting the pathways involved for intervention in schwannoma cells are being developed. Honokiol, a bioactive constituent of Magnolia officinalis, has attracted attention due to its diverse biological effects. This study was conducted to determine the inhibitory effect of honokiol on schwannoma cell proliferation. METHODS: HEI 193 cells were used to investigate the growth-inhibitory effects of honokiol. Cell proliferation was assessed by MTT assays. Apoptosis was measured by flow cytometry analysis and immunofluorescence staining including Hoechst 33342 and TUNEL. Western blot analysis was used to assess the potential inhibition of extracellular signal-regulated kinase (ERK) and AKT signaling by honokiol. RESULTS: Honokiol exhibited significant antiproliferative activity in a dose-dependent manner on HEI 193 cells. Significant apoptosis was detected on schwannoma cells with 7 mg/mL(IC50) honokiol. Western blot analysis showed significant inhibition of ERK phosphorylation. CONCLUSIONS: Honokiol, a low molecular weight natural product, inhibits cell proliferation and promotes apoptosis in schwannoma cells by targeting the ERK pathway. Our data suggest that honokiol can be evaluated as a chemotherapeutic agent for VS.

Surgical management of labyrinthine fistula in chronic otitis media with cholesteatoma.

OBJECTIVE: To present the surgical outcomes of complete removal of the matrix of labyrinthine fistulas in a large series of middle ear cholesteatomas. PATIENTS AND METHODS: This is a retrospective study. We analyzed 38 of 778 patients who were operated on for cholesteatoma and were proved to have labyrinthine fistula from 1991 to 2007. For this study, a more aggressive strategy was adopted that compromised immediate total removal of the matrix, regardless of size. To evaluate the safety and efficacy of the procedure, pre and postoperative pure-tone audiometry were compared and the recurrence rate was analyzed. Relevant data from the literature using a wide array of strategies were compared with our results. RESULTS: Only two patients suffered from postoperative hearing deterioration of bone conduction of more than 10dB HL. There was no relationship between the size of labyrinthine fistulas and postoperative hearing deterioration. Recurrence of labyrinthine fistulas was not found. CONCLUSIONS: Total removal of the cholesteatoma matrix in one step is a safe and effective method for the treatment of labyrinthine fistulas.

A cupulolith repositioning maneuver in the treatment of horizontal canal cupulolithiasis.

OBJECTIVE: We evaluated outcomes and their significance of a new treatment method for horizontal canal cupulolithiasis that could be applied regardless of the side of the cupula where otoliths are attached. METHODS: Consecutive 78 patients who showed persistent apogeotropic horizontal canal positional vertigo (horizontal canal cupulolithiasis) were enrolled, and they were treated with the new cupulolith repositioning maneuver. RESULTS: Horizontal semicircular canal cupulolithiasis was alleviated in 97.4% of patients, after an average of 2.1 repetitions of the maneuver. Otoliths were suspected to be attached to the canal side of the cupula in 30 cases and the utricular side in 44 cases. CONCLUSION: The cupulolith repositioning maneuver is an effective method for treating horizontal canal cupulolithiasis. It may also provide an insight into the side of the cupula where otoliths are attached.