Psychological evaluation for patients with non-cured facial nerve palsy.

OBJECTIVE: The aim of the present study was to evaluate the psychological condition of patients with non-cured facial nerve palsy and to investigate whether their psychological condition is correlated with the degree of facial nerve palsy, synkinesis or quality of life. METHODS: Thirty patients with non-cured facial nerve palsy were enrolled in this study. Psychological conditions were evaluated by questionnaires including State-Trait Anxiety Inventory and Self-rating Depression Scale. RESULTS: Of the thirty patients with non-cured facial nerve palsy, 17 (56.7%) and 15 patients (50.0%) felt anxiety and depression, respectively. Although there were no significant correlations between their psychological condition and the degree of facial nerve palsy or that of sequelae, significant correlations were observed between psychological condition and the degree of QOL, especially in terms of social function. CONCLUSIONS AND SIGNIFICANCE: Disabilities associated with facial nerve palsy may be overlooked when evaluation is performed by physician-graded instruments alone. To resolve this problem, patients with non-cured facial nerve palsy should be evaluated by not only physician-graded tools but also patient-based assessment tools.

Characteristics of and Prognosis for Facial Palsy in Patients With Otitis Media With ANCA-Associated Vasculitis (OMAAV).

OBJECTIVES: The aim of the present study was to investigate the characteristics and prognosis of facial palsy in patients with otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Thirty-seven patients with OMAAV. MAIN OUTCOME MEASURES: The patients were divided into the facial palsy group and non-palsy group. The severity of and prognosis for facial palsy were evaluated using the House-Brackmann facial grading system (HB). Characteristics were compared between the facial palsy group and non-palsy group. RESULTS: Facial palsy was observed in eight patients. The last HB grade for all patients was either grade I or II after treatment with a combination of corticosteroids and immunosuppressant therapy. There were no cases in which palsy relapsed. Facial palsy in OMAAV was significantly more common in female patients, and patients with facial palsy demonstrated significantly higher rates of hypertrophic pachymeningitis than did those without facial palsy. CONCLUSIONS: Facial palsy in patients with OMAAV was detected in 21.6% and a good prognosis was obtained by use of the appropriate treatment. Facial palsy is one of the most important symptoms by which to diagnose OMAAV. When encountering the patients with intractable otitis media complicated with facial palsy, appropriate examination including ANCA titer should be performed.

Prognostic factors for duration of vertigo after stapes surgery via a time-to-event analysis.

BACKGROUND: Vertigo or dizziness after stapes surgery occurs sometimes, and it is generally temporary. However, while rare, it can be prolonged. AIMS/OBJECTIVES: To investigate the prognostic factors for duration of vertigo following stapedotomy using a time-to-event analysis. MATERIALS AND METHODS: The present study included a total of 35 primary ears (26 with otosclerosis and nine with congenital stapes fixation) from 31 patients. We assessed residual rates of nystagmus and complaints of subjective vestibular symptoms using Kaplan-Meier time-to-event methods. RESULTS: Postoperative spontaneous nystagmus was observed in 23 (65.7%) ears, and postoperative subjective vestibular symptoms were confirmed in 27 (77.1%) ears. The total mean duration of postoperative spontaneous nystagmus and subjective vestibular symptoms was 9.8 (range: 0-158) and 33.9 days (0-732), respectively. A history of stapes surgery in the opposite ear was a significant predictive factor for prolonged nystagmus and subjective vestibular symptoms (p = .0059 and p = .0146). CONCLUSIONS AND SIGNIFICANCE: For individuals with a history of stapes surgery in the opposite ear, spontaneous nystagmus and vertigo/dizziness sensations following stapedotomy may persist for a longer duration than in those without a history of stapes surgery in the opposite ear.

Usefulness of the Video Head Impulse Test for the Evaluation of Vestibular Function in Patients With Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVES: To investigate usefulness of the video Head Impulse Test (vHIT) as a method for evaluating semicircular canal function in patients with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Fourteen patients with OMAAV underwent vestibular examination. MAIN OUTCOME MEASURES: The gain in vestibulo-ocular reflex (VOR) and the presence of catch-up saccade were examined for each semicircular canal. RESULTS: Seven (50.0%) of the 14 patients felt subjective symptoms of disequilibrium. Dysfunction in at least one semicircular canal was detected in all ears of the OMAAV patients evaluated by vHIT. Dysfunction in posterior semicircular canal was detected more frequently than that in the anterior or horizontal canal. There were no significant correlations between the gain in VOR and hearing loss. CONCLUSIONS: vHIT is thought to be the most suitable method for evaluating semicircular canal function in patients with OMAAV as vHIT is not influenced by middle ear pathology and was able to evaluate vertical canal function including the posterior canal.

Analysis of semicircular canal function as evaluated by video Head Impulse Test in patients with vestibular schwannoma.

OBJECTIVE: The aim of the present study was to investigate the factors influencing semicircular canal function as evaluated by video Head Impulse Test (vHIT) in patients with vestibular schwannoma. METHODS: Twenty-four patients with untreated vestibular schwannoma underwent vHIT examination. The correlations between semicircular canal function and factors including age, tumor size, disease duration and hearing loss were evaluated. RESULTS: The functions of all three semicircular canals on the affected side evaluated by vHIT were significantly lower than those on the unaffected side. Although there were no significant correlations between semicircular canal function and age, tumor size or disease duration, a negative significant correlation between vestibulo-ocular reflex (VOR) gain as evaluated by vHIT and hearing loss was observed. CONCLUSIONS: From the results of the relationship between hearing loss and VOR gain, the damage to the audio and vestibular systems in patients with VS may be correlated. As it has been suggested that tumor size was not a significant factor in the VOR gain evaluated by vHIT, multifactorial causes rather than the simple compression of the vestibular nerves alone may be related to the dysfunction of the semicircular canals in patients with vestibular schwannoma.

Evaluation of Semicircular Canal Function by Video Head Impulse Test in Patients With Facial Nerve Schwannoma.

OBJECTIVES: The aim of the present study was to evaluate semicircular canal function by video Head Impulse Test (vHIT) in patients with facial nerve schwannoma (FNS). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Seven patients with FNS underwent vHIT examination. MAIN OUTCOME MEASURES: The gain in vestibulo-ocular reflex and the presence of catch-up saccade were examined for the semicircular canals including the vertical canals. RESULTS: Dysfunction of the semicircular canals was detected by vHIT in three of seven cases. Nystagmus beating toward the non-affected side was observed in all three cases with semicircular canal dysfunction. Dysfunction was observed in a case with no direct compression of the vestibular nerve or semicircular canals by FNS. CONCLUSIONS: Semicircular canal function in patients with FNS could be evaluated by vHIT. vHIT has two advantages for the evaluation of vestibular function in patients with FNS. First, vHIT could be used for the patients in whom a tumor exists in the external auditory canal or middle ear, unlike caloric testing. Second, as vHIT could evaluate all three canals, impaired vestibular nerves could be speculated from vHIT results when a tumor exists in internal auditory canal. vHIT should be performed in patients with FNS, especially before surgery, to evaluate vestibular function.

Evaluation of Vertical Semicircular Canal Function in Patients With Vestibular Schwannoma.

OBJECTIVES:: The aim of this study was to investigate vertical semicircular canal function in patients with vestibular schwannoma (VS) by video head impulse test (vHIT). METHODS:: Fifteen patients with VS who had not received any treatment, including surgery or stereotactic radiotherapy, before vHIT examination were enrolled. Vestibulo-ocular reflex gain and catch-up saccade in vHIT were evaluated. RESULTS:: Dysfunction of anterior and posterior semicircular canals was detected by vHIT in 26.7% and 60.0%, respectively. Six patients (40.0%) demonstrated abnormalities referable to both vestibular nerve divisions. Abnormalities referable to the superior vestibular nerve were identified in 3 patients (20.0%), while 3 patients (20.0%) demonstrated a pattern indicative of inferior vestibular nerve involvement. Anterior semicircular canal vHIT produced fewer abnormalities than did either horizontal or posterior semicircular canal vHIT. CONCLUSIONS:: Dysfunction of the semicircular canals, including the vertical canals, in patients with VS was detected by vHIT. The anterior semicircular canal was less frequently involved than the horizontal or posterior semicircular canal. The examination of the vertical canals by vHIT is useful in the evaluation of vestibular function in patients with VS.

Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma.

: TRIM29 (tripartite motif-containing protein 29) is a TRIM family protein that has been implicated in breast, colorectal, and pancreatic cancers. However, its role in stratified squamous epithelial cells and tumors has not been elucidated. Here, we investigate the expression of TRIM29 in cutaneous head and neck squamous cell carcinomas (SCC) and its functions in the tumorigenesis of such cancers. TRIM29 expression was lower in malignant SCC lesions than in adjacent normal epithelial tissue or benign tumors. Lower expression of TRIM29 was associated with higher SCC invasiveness. Primary tumors of cutaneous SCC showed aberrant hypermethylation of TRIM29. Depletion of TRIM29 increased cancer cell migration and invasion; conversely, overexpression of TRIM29 suppressed these. Comprehensive proteomics and immunoprecipitation analyses identified keratins and keratin-interacting protein FAM83H as TRIM29 interactors. Knockdown of TRIM29 led to ectopic keratin localization of keratinocytes. In primary tumors, lower TRIM29 expression correlated with the altered expression of keratins. Our findings reveal an unexpected role for TRIM29 in regulating the distribution of keratins, as well as in the migration and invasion of SCC. They also suggest that the TRIM29-keratin axis could serve as a diagnostic and prognostic marker in stratified epithelial tumors and may provide a target for SCC therapeutics. SIGNIFICANCE: These findings identify TRIM29 as a novel diagnostic and prognostic marker in stratified epithelial tissues.

Notch1 regulates invasion and metastasis of head and neck squamous cell carcinoma by inducing EMT through c-Myc.

OBJECTIVE: As 50% of patients of head and neck squamous carcinoma (HNSCC) exhibit poor prognosis, the identification of new therapeutic targets is required. Recently, there have been several reports about the correlation between Notch1 and HNSCC, but the precise mechanism is still obscure. Therefore, in this study, we examined the involvement of Notch1 in HNSCC by using HNSCC cell lines and surgical specimens. METHODS: To investigate the role of Notch1 in HNSCC, we examined the effect of Notch inhibitor DAPT on cell growth, invasion, and tumorigenicity using five HNSCC cell lines in vitro and in vivo. We further examined that the correlation with Notch expression and clinical prognostic factors was evaluated by using 101 HNSCC surgical specimens. RESULTS: DAPT reduced the nuclear expression of Notch and c-Myc and repressed cell growth, EMT-dependent cell invasion in vitro, and tumorigenicity in vivo. An overexpression of Myc enhanced EMT with an increase of Snail and vimentin together with decreased levels of E-cadherin in HSC3 cells. Finally, we discovered that Notch expression was well correlated with MIB-1 index and lymph node metastases. CONCLUSION: We discovered that Notch1 was strongly correlated with HNSCC growth, invasion, and metastases. Therefore, Notch1 might be a new therapeutic target and a predictive marker of proliferation and metastasis of HNSCC.

Orphan Nuclear Receptor NR4A1 Binds a Novel Protein Interaction Site on Anti-apoptotic B Cell Lymphoma Gene 2 Family Proteins.

B cell lymphoma gene 2 (Bcl-2) family proteins are key regulators of programmed cell death and important targets for drug discovery. Pro-apoptotic and anti-apoptotic Bcl-2 family proteins reciprocally modulate their activities in large part through protein interactions involving a motif known as BH3 (Bcl-2 homology 3). Nur77 is an orphan member of the nuclear receptor family that lacks a BH3 domain but nevertheless binds certain anti-apoptotic Bcl-2 family proteins (Bcl-2, Bfl-1, and Bcl-B), modulating their effects on apoptosis and autophagy. We used a combination of NMR spectroscopy-based methods, mutagenesis, and functional studies to define the interaction site of a Nur77 peptide on anti-apoptotic Bcl-2 family proteins and reveal a novel interaction surface. Nur77 binds adjacent to the BH3 peptide-binding crevice, suggesting the possibility of cross-talk between these discrete binding sites. Mutagenesis of residues lining the identified interaction site on Bcl-B negated the interaction with Nur77 protein in cells and prevented Nur77-mediated modulation of apoptosis and autophagy. The findings establish a new protein interaction site with the potential to modulate the apoptosis and autophagy mechanisms governed by Bcl-2 family proteins.

CRKL plays a pivotal role in tumorigenesis of head and neck squamous cell carcinoma through the regulation of cell adhesion.

The signaling adapter protein CRK is an indispensable molecule involved in regulating the malignant potential of human cancers. CRK-like (CRKL) is a hematopoietic cell-dominant homologue of CRK that is reported to be phosphorylated by BCR-ABL tyrosine kinase in chronic myelogenous leukemia patients, but its biological function in non-hematopoietic tumors remains unclear. In this study, we explored the tumorigenic role of CRKL in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Immunoprecipitation analysis of HNSCC cell line, HSC-3 cells, showed that the dominant binding partner for C3G was CRKL, not CRK. To clarify the molecular function of CRKL, we established lentiviral shRNA-mediated CRKL-knockdown HNSCC cell lines. In CRKL-knockdown HSC-3 and HSC-4 cells, cell growth and motility were diminished compared to control cells. Cell adhesion assays showed that cell attachment onto both fibronectin- and collagen-coated dishes was significantly suppressed in CRKL-knockdown HSC-3 cells, while no significant change was observed for poly-l-lysine-coated dishes. Immunofluorescence staining revealed that focal adhesion was reduced in CRKL-knockdown HSC-3 cells. With a pulldown assay, CRKL-knockdown HSC-3 cells showed decreased amounts of active Rap1 compared to control cells. Moreover, in an in vivo assay, tumor formation of CRKL-knockdown HSC-3 cells in nude mice was significantly abrogated. Our results indicate that CRKL regulates HNSCC-cell growth, motility, and integrin-dependent cell adhesion, suggesting that CRKL plays a principal role in HNSCC tumorigenicity.