The use of basic fibroblast growth factor to treat intractable Bell's palsy administered via transcanal endoscopic ear surgery.

PURPOSE: Facial nerve decompression surgery is an invasive procedure which has hitherto been the main option for patients with severe intractable Bell's palsy which is resistant to drug treatment. We have developed a new salvage treatment for such patients by using minimally invasive transcanal endoscopic ear surgery (TEES) to deliver the biological regenerative agent, basic fibroblast growth factor (bFGF), to the damaged facial nerve. MATERIALS AND METHODS: An endoscopic salvage treatment group was studied prospectively and was made up of severe intractable Bell's palsy patients who did not respond to high dose steroid treatment and had an ENoG value of 5 % or less. This surgery group was retrospectively compared to a similar control group who had received high dose steroid only. RESULTS: Complete recovery to House-Brackmann (HB) Grade I was achieved by 44.8 % of the endoscopic salvage treatment group which was significantly higher than the 21.2 % of the control group at one-year follow up. Patients with an ENoG value of 1 % to 5 % exhibited a significantly higher complete recovery rate of 71.4 % in the endoscopic salvage treatment group than the 28.6 % of the control group. In addition, no complications were observed including hearing loss. CONCLUSIONS: bFGF delivered via TEES shows considerable promise as a new salvage treatment of severe intractable Bell's palsy that is resistant to high dose steroid treatment without the risks presented by facial nerve decompression surgery.

Effect of Phosphorylation of CM2 Protein on Influenza C Virus Replication.

CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication. Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined. In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed. No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s). Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants was inhibited in comparison with that in cells infected with wild-type VLPs. The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus. Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus. These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins. In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication. However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication. This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.

Open-type cholesteatoma is the predictive factor for residual disease in congenital cholesteatoma treated with TEES.

OBJECTIVE: To determine the predictive factors for residual disease occurring after surgical removal of congenital cholesteatomas and whether these predictive factors differ between microscopic ear surgery (MES) using data from the literature and transcanal endoscopic ear surgery (TEES) using data from our own institution. METHODS: Twenty-three patients with a congenital cholesteatoma who underwent surgical treatment at Yamagata University Hospital between December 2011 and December 2017 were retrospectively investigated. We divide TEES into three different approaches: non-powered TEES, powered TEES and dual MES/TEES. Main outcome measures were Potsic stage, closed or open congenital cholesteatoma type, TEES surgical approach, appearance of residual disease, tympanoplasty type and hearing outcome. RESULTS: A logistic regression analysis was conducted on the Potsic stage, closed or open type, TEES surgical approach and age to obtain the odds ratio for residual disease. The chance of residual disease significantly increased in the presence of an open-type congenital cholesteatoma (odds ratio: 30.82; 95 % confidence interval: 1.456-652.3; p = 0.0277), but not for any of the other factors including Potsic stage. The timing of the confirmation of residual disease after ossicular chain reconstruction was analyzed using a Kaplan-Meier analysis. The residual disease rate was significantly higher with an open-type congenital cholesteatoma (log-rank test, p < 0.05). In addition, all residual disease occurred within three years after surgery. CONCLUSIONS: Our results showed that an open-type congenital cholesteatoma is the strongest predictive factor for residual disease when removing a congenital cholesteatoma by TEES.

Clinical course of five patients definitively diagnosed with idiopathic perilymphatic fistula treated with transcanal endoscopic ear surgery.

Objectives: An idiopathic perilymphatic fistula (PLF) can be difficult to diagnose because patients present with sudden sensorineural hearing loss (SSHL) and/or vestibular symptoms without any preceding events. In such cases, we currently test for cochlin-tomoprotein (CTP) to confirm the diagnosis of idiopathic PLF because CTP is only detected in the perilymph. In this study, we report the clinical course of five patients definitively diagnosed with idiopathic PLF who underwent PLF repair surgery using transcanal endoscopic ear surgery (TEES). Patients and methods: Five patients were initially treated with intratympanic dexamethasone for SSHL, at which time a CTP test was also performed (preoperative CTP test). Due to refractory hearing loss and/or fluctuating disequilibrium, PLF repair surgery using TEES was performed to seal the oval and round windows using connective tissue and fibrin glue. These patients were diagnosed with definite idiopathic PLF based on pre- or intra-operative CTP test results (negative, < 0.4 ng/mL; intermediate, 0.4-< 0.8 ng/mL; and positive, > 0.8 ng/mL). We evaluated pre- and intra-operative CTP values, intraoperative surgical findings via a magnified endoscopic view, and pre- and post-operative changes in averaged hearing level and vestibular symptoms. Results: Pre- and intra-operative CTP values were positive and intermediate in three patients, positive and negative in one patient, and negative and positive in one patient. None of the patients had intraoperative findings consistent with a fistula between the inner and middle ears or leakage of perilymph. Only two patients showed a slight postoperative recovery in hearing. Four patients complained of disequilibrium preoperatively, of whom two had resolution of disequilibrium postoperatively. Conclusion: A positive CTP test confirms PLF in patients without obvious intraoperative findings. The CTP test is considered more sensitive than endoscopic fistula confirmation. We consider that CTP test results are important indicators to decide the surgical indication for idiopathic PLF repair surgery. In our experience with the five cases, two of them showed improvements in both hearing and vestibular symptoms.

Benefits of High-Dose Corticosteroid and Antiviral Agent Combination Therapy in the Treatment of House-Brackman Grade VI Ramsay Hunt Syndrome.

OBJECTIVE: Few large-scale investigations have been conducted on treatment of House-Brackmann grade VI (HB grade VI) Ramsay Hunt syndrome (RHS) patients. We compared recovery rates among patients receiving a normal-dose corticosteroid (prednisolone [PSL] 60 mg/d) or high-dose corticosteroid (PSL 200 mg/d), both with or without an antiviral agents. Recovery rates were also examined based on the order of presentation of herpetic vesicles versus facial palsy. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: A total of 128 patients with HB grade VI RHS were treated in our department between 1995 and 2017. These patients were divided into four treatment groups based on corticosteroid dosage and use of an antiviral agent. METHODS: We assessed treatment outcomes for HB grade VI patients together with logistic regression analysis to investigate factors that can impact treatment outcomes, that is, sex, age, days to start of treatment, PSL dosage, and antiviral agent administration. RESULTS: Recovery rates were best in the high-dose corticosteroid group with an antiviral agent (71.1%) in comparison with the normal-dose corticosteroid group with an antiviral agent (60.0%) or high-dose corticosteroid alone (57.1%). Significant factors for treatment outcomes were high-dose corticosteroid administration and early initiation of treatment. A better recovery rate was also found when the herpetic vesicles appeared before facial palsy. CONCLUSION: We showed that a combination of a high-dose corticosteroid and antiviral agent produced the best outcomes for patients with HB grade VI RHS. However, our results were not statistically significant because of small sample size.

Facial nerve and chorda tympani schwannomas: Case series, and advantages of using non-rigid registration of post-enhanced 3D-T1 Turbo Field Echo and CT images (TURFECT) in their diagnosis and surgical treatment.

OBJECTIVE: Facial nerve schwannomas (FNSs) and chorda tympani schwannomas are very rare. Diagnosis of these tumors is sometimes difficult, and treatment consensus has not yet been reached. We report here a series of cases of FNS and chorda tympani schwannoma and highlight the usefulness of our newly developed technique of non-rigid registration of post-enhanced 3D-T1 Turbo Field Echo and CT images (TURFECT) in their diagnosis and treatment. METHODS: MRI images were adjusted with the corresponding CT images in terms of angle and position in order to index the anatomical structures. The well-enhanced T1-Gd+ lesions of tumors having good blood flow show up as bright red after color mapping. RESULTS: Between 2014 and 2018, five patients were diagnosed with schwannomas in the temporal bone: three with FNS and two with chorda tympani schwannoma. Gd-enhanced MRI showed only a high-intensity mass, and we could not detect the relationship between tumor-like mass and bone (including the ossicles) by MRI only. In contrast, TURFECT was very useful for diagnosing the precise location, allowing us to decide on an endoscopic surgical plan in some of our cases. An endoscope enabled visualization of the medial wall of the tympanic cavity and the status of the tumors, thus we could successfully perform transcanal endoscopic biopsy and resections. CONCLUSION: TURFECT can be very useful for diagnosis of FNSs and chorda tympani schwannomas and for deciding surgical treatments such as a transcanal endoscopic approach.

The effect of the cytoplasmic tail of influenza C virus CM2 protein on its biochemical properties and intracellular processing.

CM2 is an integral membrane protein encoded by the influenza C virus M gene. To examine the effects of the cytoplasmic tail of CM2 on its biochemical properties, deletion and substitution mutations were introduced into CM2 cytoplasmic tail at residues 47-115, and the expressed CM2 mutants were investigated. Although the cytoplasmic tail is not essential for the oligomerization of CM2, it may affect the degree of oligomerization. The residues 47-48, 67-69, 73-90 and 113-115 were all required for the proper expression of CM2. Pulse-chase experiments suggest that residues 47-48, 67-69, 73-75 and 79-87 stabilize CM2, thereby affecting CM2 expression. The C-terminal region at residues 61-115 is not essential for CM2 transport to the cell surface, and a 14-amino-acid, but not an 11-amino-acid, cytoplasmic tail is sufficient for the cell surface expression of CM2. These results suggest that either certain amino acid sequences or the length of the CM2 cytoplasmic tail are necessary for the proper conformational maturation, stability, expression level and intracellular transport of CM2.