A double-blinded, randomized controlled clinical trial of hydrogen inhalation therapy for idiopathic sudden sensorineural hearing loss.

Background: Hydrogen (H2) has been reported to be effective in reducing hearing loss due to several causes in animal studies. However, no study has examined the effectiveness of H2 in treating hearing loss in humans. Thus, we investigated whether H2 is effective for the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL). Materials and methods: We conducted a double-blind randomized controlled trial at six hospitals between June 2019 and March 2022. The study protocol and trial registration have been published in the Japan Registry of Clinical Trials (jRCT, No. jRCTs06119004). We randomly assigned patients with ISSNHL to receive either H2 (H2 group) or air as a placebo (control group) through inhalation combined with the administration of systemic glucocorticoids and prostaglandin E1. The primary outcome was the hearing threshold and changes in hearing threshold 3 months after therapy. In contrast, the secondary outcomes included the proportion of patients with a good prognosis (complete recovery or marked improvement). Results: Sixty-five patients with ISSNHL (31 and 34 in the H2 and control groups, respectively) were included in this study. The hearing threshold 3 months after treatment was not significantly different between the groups; 39.0 decibels (dB) (95% confidence interval [CI]: 28.7-49.3) and 49.5 dB (95% CI: 40.3-58.7) in the H2 and control groups, respectively. In contrast, the changes in hearing threshold 3 months after treatment was 32.7 dB (95% CI: 24.2-41.3) and 24.2 dB (95% CI: 18.1-30.3) in the H2 and control groups, respectively. Consequently, the changes in hearing threshold were significantly better in the H2 group than in the control group (P = 0.048). However, no adverse effects due to the inhalation of H2 gas have been reported. Conclusion: This is the first study to investigate the efficacy of H2 for the treatment of ISSNHL in humans. The results suggest that H2 therapy may be effective for ISSNHL treatment. Clinical trial registration: [https://jrct.niph.go.jp/re/reports/detail/10442], identifier [jRCTs06119004].

Multifocal hyperfunctioning thyroid carcinoma without metastases.

Hyperthyroidism due to thyroid carcinoma is rare, and most cases are caused by hyperfunctioning metastatic thyroid carcinoma rather than primary carcinoma. Among primary hyperfunctioning thyroid carcinoma, multifocal thyroid carcinoma is exceedingly rare, with the only one case being reported in the literature. Here, we describe the case of a 62-year-old woman with multifocal functioning thyroid carcinoma. Technetium-99m (99m Tc) scintigraphic imaging showed four hot areas in the thyroid gland. Histopathological examination of all four nodules revealed papillary carcinoma, corresponding to hot areas in the 99m Tc scintigram. DNA sequencing of the thyrotropin receptor (TSH-R) gene from all nodules revealed no mutation, indicating that activation of TSH-R was unlikely in the pathophysiogenesis of hyperfunctioning thyroid carcinoma in the present case.

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 Bell's palsy, excluding zoster sine herpete. STUDY DESIGN: Prospective, multicenter, randomized placebo-controlled study. SETTING: Six academic tertiary referral centers. PATIENTS: Ultimately, 221 patients with Bell's palsy who were treated within 7 days of the onset. Serological and polymerase chain reaction examinations were performed to distinguish Bell's 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 Bell's 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 Bell's palsy cases based on an etiologic background.

Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation of herpes simplex virus type 1.

CONCLUSION: Although both T-cell subsets are essential for inhibiting HSV-1 reactivation in the GG, CD4 + T cells play a more important role in host defense against virus replication. OBJECTIVE: To elucidate the host immunological factors that participate in herpes simplex virus type 1 (HSV-1) reactivation in the geniculate ganglia (GG) and lead to facial paralysis, we developed a mouse model of facial paralysis that involved the reactivation of HSV-1 following general immune suppression. MATERIAL AND METHODS: Eight weeks after recovery from primary facial paralysis caused by inoculating the auricle with HSV-1 the auricle was scratched and mice (n = 69) were given an i.p. injection of either anti-CD4 (n = 46) or anti-CD8 (n = 23) monoclonal antibody to deplete specific T-lymphocyte subsets. Following this reactivation procedure, the rate of recurrent facial paralysis was compared between the two models. The GG were examined histopathologically and using polymerase chain reaction to detect HSV-1 DNA. RESULTS: Facial paralysis developed in 42% of mice in the anti-CD4 model and in 13% in the anti-CD8 model. HSV-1 DNA was detected in 50% of the mice in both models. Histopathologically, neurons were destroyed in parts of the GG and numerous virus particles were seen in the surviving neurons.

Efficacy of early treatment of Bell's palsy with oral acyclovir and prednisolone.

OBJECTIVE: To investigate the therapeutic effects of acyclovir and prednisolone in relation to the timing of treatment in Bell's palsy. STUDY DESIGN: This was a retrospective study of 480 Bell's palsy patients who were treated with oral acyclovir and prednisolone (94 cases) or prednisolone alone (386 cases). PATIENTS: Patients met the after criteria: (1) severe or complete Bell's palsy with a score lower than 20 on the 40-point Yanagihara facial score and (2) treatment started within 7 days after onset. The patients were treated with oral prednisolone (60-40 mg/day) with or without oral acyclovir (2,000 mg/day). MAIN OUTCOME MEASURE: Rate of recovery, which was defined as a facial score of 36 or more, and the absence of contracture with synkinesis. RESULTS: The overall recovery rate of patients treated with acyclovir and prednisolone was 95.7 percent, which was better than that of patients treated with prednisolone alone (88.6%). The recovery rate in patients who began the combined therapy within 3 days of the onset of palsy was 100 percent and early treatment resulted in early remission. In contrast, the recovery rate in patients who started the combined therapy more than 4 days after onset was 86.2 percent. CONCLUSION: These results suggest that early diagnosis and treatment within 3 days of the onset of paralysis are necessary for maximal efficacy of combined acyclovir and prednisolone therapy for Bell's palsy.

Swelling of the intratemporal facial nerve in Ramsay Hunt syndrome.

Although Ramsay Hunt syndrome is one of the most important diseases causing peripheral facial palsy, the detailed pathology of the disease in the intratemporal facial nerve remains unclear. The purpose of this study was to increase knowledge of the pathogenesis of the syndrome by means of surgical findings. Between April 1976 and March 1997 we performed subtotal decompression of the facial nerve in 74 patients with severe Ramsay Hunt syndrome. The grade of nerve swelling was assessed using a microscope and recorded in a standardized form. The relationships between nerve swelling, the timing of surgery and the swelling of each segment were analyzed. Pronounced neural swelling, involving the geniculate ganglion and the horizontal segment, was consistent finding in the acute phase. Although the incidence of pronounced swelling of the horizontal segment gradually declined with time after onset, in most cases nerve swelling persisted even beyond the 16th week after onset. These data suggest that diffuse viral neuritis occurs throughout the intratemporal facial nerve. We assume that the viral inflammatory swelling involving the geniculate ganglion and horizontal segment is mostly responsible for the acute facial palsy in the acute phase.

Primary endobronchial Burkitt's lymphoma in a child: a case report.

Primary endobronchial tumors are rare in children and often are misdiagnosed, resulting in a delay of appropriate treatment. Here, we present a case of 4-year-old girl with primary endobronchial lymphoma who presented with persistent pneumonia despite medical treatment. Her chest radiograph showed left atelectasis, and a bronchial foreign body was initially suspected. Bronchoscopic examination demonstrated a granulomatous tumor occupying the left main bronchus. Localized Burkitt's lymphoma in the left trachea was diagnosed histopathologically. This case emphasizes the consideration of endobronchial tumor and bronchoscopy in children who show persistent atelectasis or recurrent pneumonia.

Resection of peripheral branches of the posterior nasal nerve compared to conventional posterior neurectomy in severe allergic rhinitis.

OBJECTIVE: Transnasal resection of the posterior nasal nerve (TRPN) is the surgical procedure for drug therapy-resistant, intractable allergic rhinitis (AR). Submucous inferior turbinectomy also improves nasal symptoms in severe AR. Surgical injury to this peripheral nerve fibre may be the major cause of the decrease in allergic symptoms. During submucous turbinectomy, we have identified the peripheral branches of the posterior nasal nerve in the inferior turbinate and resected them (SRPN). The aim of this study was to evaluate the therapeutic effects of turbinoplasty with SRPN in severe AR. METHODS: Improvements in subjective symptoms were compared between 13 patients who underwent SRPN with turbinoplasty (Group 1) and 11 who underwent TRPN combined with turbinoplasty and SRPN (Group 2) by retrospective chart review. Pre- and postoperative sneezing, rhinorrhea, and nasal obstruction were evaluated with questionnaires. Postoperative complications and drug therapy before and after surgery were investigated. RESULTS: All symptoms improved postoperatively in both groups, with no significant differences in the improvements in nasal symptom scores between the groups. CONCLUSIONS: SRPN combined with submucosal turbinectomy was shown to be a safe, useful, and efficient approach to patients with AR unresponsive to medical therapy. Although this is a short-term study, the results of this study suggest that SRPN represents one of the treatment options for intractable AR.

Facial synkinesis after experimental compression of the facial nerve comparing intratemporal and extratemporal lesions.

OBJECTIVES/HYPOTHESIS: The anatomical configuration of the facial nerve differs greatly between the intratemporal and extratemporal portions. The purpose of this study was to investigate the incidence of facial synkinesis and misdirection on clamping the facial nerve at the intratemporal or extratemporal portion of the facial nerve in guinea pigs. STUDY DESIGN: Experimental study. METHODS: In 16 guinea pigs, the facial nerve was clamped with microsurgical needle forceps at either the extratemporal (group A) or intratemporal (group B) segment. Facial nerve function was evaluated 1 week postoperatively using electroneurography (ENoG), and the incidence of facial synkinesis was evaluated 15 weeks postoperatively using an evoked blink reflex test. Fifteen weeks postoperatively, two retrograde fluorescent tracers (Dil [1-1'-dioctodecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate] and True Blue) were injected into the facial muscles to observe reorganization of the facial nucleus. RESULTS: No significant difference in the ENoG threshold was observed between groups A and B. In group A, none of the animals developed facial synkinesis and the somatotopic organization of the facial nucleus was not disturbed. In contrast, synkinesis occurred and the somatotopic organization was disturbed in group B. CONCLUSIONS: A lack of funicular structure within the intratemporal facial nerve increases the possibility of misdirected regenerating axons and synkinesis.

Bilateral spontaneous cerebrospinal fluid otorrhea.

We present a rare case of bilateral cerebrospinal fluid (CSF) otorrhea via multiple bony defects in the left tegmen and a single defect with the herniated brain tissue on the right side. Initially, the patient complained of left hearing loss and fullness and was diagnosed with serous otitis media. After myringotomy, the pulsating watery discharge suggested CSF otorrhea. Five months after surgical repair of the left side, right-side CSF leakage occurred. The right side was repaired surgically, and the patient recovered without incident. From our findings and a review of the literature, we postulate that bilateral CSF otorrhea resulted mainly from the thinness of the tegmen because of well-pneumatized mastoid air cells and the weakness of the dura after chronic inflammatory changes. In case of spontaneous CSF otorrhea, the roof of tegmen should be assessed bilaterally with care using radiologic examinations so as not to overlook a subclinical condition on the contralateral side.

Demyelination associated with HSV-1-induced facial paralysis.

In 1995, we developed an animal model of transient homolateral facial nerve paralysis by inoculating Herpes simplex virus type 1 (HSV-1) into the auricle of mice. This study examined the mechanism of facial nerve paralysis in this model histopathologically. Using the immunofluorescence technique with anti-HSV-1 antibody, the time course of viral spread and the site of viral replication were investigated over the entire course of the facial nerve. Furthermore, viral replication and nerve degeneration at the site of viral replication were observed by electron microscopy. On the 7th day after inoculation, facial paralysis was observed in more than 60% of mice. Immunofluorescence study revealed HSV-1 in the geniculate ganglion, the descending root, and the facial nucleus at this stage. On the 9th day, the descending root in the sections stained with osmium looked pale, because prominent demyelination had occurred in this region; electron micrographs showed many degenerated oligodendrocytes and large naked axons. In contrast, the facial nucleus neurons showed no remarkable degeneration, despite HSV-1 particles in their cytoplasm. From these findings, we concluded that facial nerve paralysis in this model is caused mainly by facial nerve demyelination in the descending root.