Correlation between genotype and phenotype with special attention to hearing in 14 Japanese cases of NF2-related schwannomatosis.

NF2-related schwannomatosis (NF2) is an autosomal dominant genetic disorder caused by variants in the NF2 gene. Approximately 50% of NF2 patients inherit pathogenic variants, and the remainder acquire de novo variants. NF2 is characterized by development of bilateral vestibular schwannomas. The genetic background of Japanese NF2 cases has not been fully investigated, and the present report performed a genetic analysis of 14 Japanese NF2 cases and examined genotype-phenotype correlations. DNA samples collected from peripheral blood were analyzed by next-generation sequencing, multiplex ligation-dependent probe amplification analysis, and in vitro electrophoresis. Ten cases had pathogenic or likely pathogenic variants in the NF2 gene, with seven truncating variants and three non-truncating variants. The age of onset in all seven cases with truncating variants was < 20 years. The age of onset significantly differed among cases with truncating NF2 variants, non-truncating NF2 variants, and no NF2 variants. However, the clinical course of tumor growth and hearing deterioration were not predicted only by germline pathogenic NF2 variants. The rate of truncating variants was higher in the present study than that of previous reports. Genotype-phenotype correlations in the age of onset were present in the analyzed Japanese NF2 cases.

Intratemporal Facial Nerve Schwannomas: A Review of 45 Cases in A Single Center.

There are no established indications for facial nerve schwannoma treatment, including surgery, radiation and follow-up observation, and it is difficult to determine treatment policy uniformly. The treatment policy was examined from each treatment course. Data of patients with facial nerve schwannomas at our hospital from 1987 to 2018 were retrospectively examined. Their age, sex, clinical symptoms, tumor localization, treatment policies and outcomes were reviewed. In total, 22 patients underwent surgery and 1 patient underwent radiotherapy; 22 patients were followed up without treatment. After total resection, there were no tumor recurrences, and most patients had grade 3 or 4 postoperative facial paralysis. After subtotal resection, tumor regrowth was observed in four patients and reoperation was required in two patients. Facial nerve function was maintained in four patients and was decreased in two patients. During follow-up, six patients showed tumor growth. Only one patient had worsening facial nerve paralysis; four patients underwent facial nerve decompression owing to facial nerve paralysis during follow-up. If the tumor compresses the brain or it is prone to growth, surgery may be indicated, and when the preoperative facial nerve function is grade ≤3, consideration should be given to preserving facial nerve function and subtotal resection should be indicated. If the preoperative facial nerve function is grade ≥3, total resection with nerve grafting is an option to prevent regrowth. If there is no brain compression or tumor growth, the follow-up is a good indication, and decompression should be considered in facial nerve paralysis cases.

Effectiveness of Hearing Aid Treatment in Patients with Chronic Tinnitus: Subscale Evaluations Using the Tinnitus Functional Index and Factor Analysis.

OBJECTIVES: The tinnitus functional index (TFI) is becoming a new international gold standard for tinnitus assessment. This study aimed to evaluate the efficacy of hearing aids for chronic tinnitus, using the Japanese version of the TFI, while focusing on its subscales. MATERIALS AND METHODS: This is a retrospective study. A total of 21 patients with chronic tinnitus were included. All participants were treated with hearing aids for at least 12 months. They answered the TFI and tinnitus handicap inventory (THI) at the first visit and 12 months later. We analyzed each TFI subscale score and the overall scores of TFI and THI. RESULTS: The overall TFI score decreased significantly after treatment (p=0.005) with moderate effect size (d=0.70). The scores of the intrusive, sense of control, sleep, and emotional subscales decreased significantly after the treatment. Large effect sizes were found in the intrusive and sense of control subscales (d=1.33 and d=1.25, respectively). CONCLUSION: Hearing aids are highly effective for improving the intrusive and sense of control subscales in patients with tinnitus. Identifying better treatments for the small effect size subscales and combining these with the use of hearing aids could achieve a higher therapeutic effect with better outcomes.

Sudden sensorineural hearing loss in patients with vestibular schwannoma.

Clinical features of sudden sensorineural hearing loss (SSNHL) associated with vestibular schwannoma (VS) are not fully understood. Determining a treatment plan and explaining it to patients requires clinicians to clearly understand the clinical features related to the tumor, including SSNHL. To identify the full range of clinical features of VS-associated SSNHL, especially recovery of hearing following multiple episodes of SSNHL and what factors predict recovery and recurrence. A multicenter retrospective chart review was conducted in seven tertiary care hospitals between April 1, 2011, and March 31, 2020. We collected and analyzed dose of administered steroid, pure-tone audiometry results, and brain MRIs of patients diagnosed with VS-associated SSNHL. Seventy-seven patients were included. They experienced 109 episodes of audiogram-confirmed SSNHL. The highest proportion of complete recoveries occurred in patients with U-shaped audiograms. The recovery rates for the first, second, and third and subsequent episodes of SSNHL were 53.5%, 28.0%, and 9.1%, respectively. Recovery rate decreased significantly with increasing number of SSNHL episodes (P =0 .0011; Cochran-Armitage test). After the first episode of SSNHL, the recurrence-free rate was 69.9% over 1 year and 57.7% over 2 years; the median recurrence time was 32 months. Logarithmic approximation revealed that there is a 25% probability that SSNHL would recur within a year. SSNHL in patients with VS is likely to recur within one year in 25% of cases. Also, recovery rate decreases as a patient experiences increasing episodes of SSNHL.

Validation and multidimensional analysis of the japanese penn acoustic neuroma quality-of-life scale.

OBJECTIVES: In the management of vestibular schwannoma (VS), patient-perceived outcomes should be given as much attention as physician-reported objective outcomes. Concomitant symptoms can be annoying for sufferers, lowering quality of life (QoL). However, it is difficult to determine the degree to which these symptoms lower QoL using only objective measures. The Penn Acoustic Neuroma Quality of Life Scale (PANQOL) is a validated disease-specific questionnaire commonly used to assess QoL in VS patients. It was developed and published in English. In this study, we translated the PANQOL questionnaire into Japanese and validated its reliability and utility. We also evaluated patient factors that could influence PANQOL scores. STUDY DESIGN: Cross-sectional study. METHODS: Seventy-two VS patients monitored conservatively were included in this study. They were assessed using the Japanese versions of PANQOL (PANQOL-J) and questionnaires about specific symptoms related to VS. The PANQOL questionnaire was translated into Japanese according to the accepted standards. The reliability and utility of the PANQOL-J questionnaire, as well as the relationship with VS-specific symptoms, were statistically analyzed. RESULTS: The mean total score was 78.7. Almost all of its domains had good internal consistency. Most PANQOL-J domains were related to those of the Short Form-36, with the exception of facial dysfunction domain. Scores of all PANQOL-J domains were comparable to scores of other questionnaires related to the VS-specific symptoms. Our analyses indicated tinnitus or facial palsy might affect the PANQOL-J total score. CONCLUSIONS: We confirmed the validity of the Japanese version of PANQOL questionnaire and its reliability and utility in the management of VS symptoms concerning facial function. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

Intraoperative Facial Nerve Monitoring Revealed the Origin of Rapidly Progressing Schwannoma in the Cerebellopontine Angle: A Case of Large Intermediate Nerve Schwannoma.

Schwannoma arising from the intermediate nerve is very rare, with only a few cases reported in the literature. Here, we report a rare case of a rapidly growing schwannoma that originated from the intermediate nerve in a 17-year-old woman. We performed tumor resection using the translabyrinthine approach with continuous intraoperative monitoring, in which the facial nerve root was used to evoke muscle action potential. The monitoring revealed the tumor origin and enabled complete surgical resection with the preservation of facial nerve motor function. The facial nerve root evoked muscle action potential-based continuous monitoring revealed the origin of the rare intermediate nerve schwannoma. Appropriate surgery using this monitoring system could spare facial nerve function even in this rare case and retain the patient's quality of life.

[Usefulness and Limitation of Thyroglobulin Measurement in Fine Needle Aspirates (FNA-Tg) for Diagnosis of Neck Lymph Node Metastasis from Thyroid Carcinoma].

BACKGROUND: Preoperative diagnosis of lymph node metastasis from thyroid carcinoma is usually confirmed by using fine needle aspiration cytology (FNAC) when thyroid carcinoma is suspected based on the clinical findings. However, the result of FNAC sometimes leads to a false negative, especially in cases of hypocellular lesions such as metastases with cystic change. Thyroglobulin measurement in fine needle aspirates (FNA-Tg) has been shown to be a useful technique to detect the protein specifically secreted by thyroid follicular cells. Elevated FNA-Tg levels in an extra-thyroidal lesion means that the lesion comprises thyroid-originated tissue, most of which suggests the metastasis from thyroid carcinoma. Thus, FNA-Tg is expected to improve the sensitivity of FNAC for the aforementioned purpose. PATIENTS AND METHODS: From 2008 to 2012, 49 extra-thyroidal lesions from 43 patients with thyroid carcinoma were examined using both FNAC and FNA-Tg, followed by surgical resection with a histopathological diagnosis. The results were retrospectively reviewed and analyzed. RESULTS: Among 49 lesions, 47 were metastatic lymph nodes from thyroid carcinoma (46 papillary carcinoma and one follicular carcinoma), one was a metastatic lymph node from submandibular gland adenocarcinoma, and one was an ectopic thyroid gland. In the 47 cases of thyroid carcinoma, the sensitivity of FNAC was 57.4% (27/47), whereas that of FNA-Tg was 76.6% (36/47). When both methods were combined, the sensitivity increased to 93.6% (44/47). Metastasis from submandibular gland adenocarcinoma was considered to be an example of a false positive from FNAC, whereas an ectopic thyroid gland was an FNA-Tg false positive. Three lesions were negative for both FNAC and FNA-Tg, although metastases were suspected by imaging studies and confirmed by histopathological diagnosis, which were consistent with examples of a false negative from both FNAC and FNA-Tg findings. CONCLUSIONS: FNAC reflects whether the lesion has malignant cells, whereas FNA-Tg reflects whether the lesion has thyroid-originated tissue that specifically secrets thyroglobulin. Therefore, FNAC and FNA-Tg are considered to be complementary to each other for the preoperative diagnosis of lymph node metastasis from thyroid carcinoma. FNA-Tg was validated to improve the preoperative diagnostic sensitivity especially when combined with FNAC, however, it is attended with the possibility of a false positive or negative finding, which requires caution in interpretation of the findings.