A Case of Fungal Maxillary Sinusitis Extending to the Contralateral Side Through the Nasal Septum.

Fungal rhinosinusitis (FRS) presents as various phenotypes ranging from asymptomatic colonization to life-threatening infections. Here, we report an atypical case of FRS of the left maxillary sinus that extended to the contralateral maxillary sinus through the nasal septum. An 80-year-old woman with a history of osteoporosis was referred to our hospital for further management of headaches and chronic rhinosinusitis. Computed tomography (CT) of the sinus revealed a mass lesion with calcification in the left maxillary sinus, extending to the contralateral maxillary sinus through the nasal septum. T1-weighted and T2-weighted magnetic resonance imaging revealed a mass lesion with low-intensity signals. Endoscopic sinus surgery was performed for the diagnosis and treatment. Histopathological examination revealed fungal elements in the caseous material of the left maxillary sinus. However, no tissue-invasive fungal forms were found. Additionally, eosinophilic mucin was not observed. Based on these findings, the patient was diagnosed with fungus ball (FB). To the best of our knowledge, there are no reports of a FB extending contralaterally through the nasal septum. This report serves as a reminder that FB can extend into contralateral paranasal sinuses through the nasal septum and the possibility that osteoporosis is a cause of extensive bone destruction.

Improvement of eosinophilic chronic rhinosinusitis after infection with severe acute respiratory syndrome corona virus 2 during dupilumab therapy: A case report.

Eosinophilic chronic rhinosinusitis (ECRS) is an intractable type 2 inflammatory disease of the paranasal sinuses that persists even after endoscopic sinus surgery (ESS) and systemic corticosteroid therapy. Dupilumab, a monoclonal antibody against the shared receptor components of interleukin (IL)-4 and IL-13, is a novel and effective treatment option for ECRS. Herein, an atypical case of ECRS that improved after infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) during dupilumab therapy is reported. A 40-year-old man with a history of ESS for ECRS visited our hospital with complaints of nasal congestion and dysosmia. Nasal endoscopy revealed bilateral nasal polyps occupying the nasal cavity. Computed tomography (CT) revealed a soft tissue density lesion filling all sinuses on both sides. Based on these findings, ECRS recurrence was confirmed; however, 3 years of subsequent corticosteroid therapy did not improve disease activity. Accordingly, dupilumab therapy was initiated, although 6 months of therapy resulted in only slight improvement in ECRS. Eight months after the initiation of dupilumab therapy, the patient was infected with SARS-CoV-2; thereafter, he noticed an improvement in smell. Nasal endoscopy and sinus CT revealed a marked reduction in nasal polyps and soft tissue density lesions of the sinuses, respectively. With continued dupilumab therapy, no re-exacerbation of ECRS was confirmed at the 6-month follow-up from SARS-CoV-2 infection. Currently, there are no reports describing the impact of SARS-CoV-2 infection on ECRS. As such, careful follow-up and accumulation of cases are necessary.

A Case of Mumps Presenting With Unilateral Submandibular Sialadenitis and Laryngeal Edema.

Mumps is a viral infection that primarily affects the parotid glands. Here, we report an atypical case of mumps presenting with unilateral submandibular sialadenitis and laryngeal edema. A 20-year-old woman with unremarkable medical history was referred to our hospital for the management of left submandibular sialadenitis. Laryngeal endoscopy revealed laryngeal edema. Contrast-enhanced computed tomography of the neck revealed swelling of the left submandibular gland with surrounding fluid density and increased density of the cervical subcutaneous adipose tissue. A few days later, both anti-mumps immunoglobulin M (IgM) and IgG antibodies were positive, and she was diagnosed with mumps. To date, there have been no reports of unilateral submandibular gland mumps complicated by laryngeal edema. It is important to keep in mind that the involvement of the submandibular gland in cases of mumps is probably a risk factor for laryngeal edema.

Case report: Unilateral transnasal endoscopic marsupialization of nasopalatine duct cyst.

Nasopalatine duct cyst (NPDC) is the most common type of non-odontogenic cysts of the jaw. It has been treated with complete surgical resection using a sublabial or palatine approach. However, complete removal of the cyst can be accompanied by postoperative complications including oronasal fistula. Recently, endoscopic marsupialization for the disease has been advocated, but there are still few reports regarding the surgery. Herein, we report a case of NPDC that was treated with unilateral transnasal endoscopic marsupialization. A 43-year-old man with no relevant previous medical history was referred to our hospital for the treatment of lesion occupying the right nasal cavity. A computerized tomography scan of the sinus revealed an egg-shaped lesion with a well-defined border centered on the lower half of the nasal cavity and hard palate. Based on the site of the lesion, it was considered to be NPDC. Transnasal endoscopic marsupialization was performed to diagnose and improve nasal obstruction. Histopathological examination revealed stratified squamous epithelium without atypia, which was consistent with NPDC. Although the patient noticed paresthesia of the right upper incisor area, symptoms improved 3 months after surgery. Written informed consent was obtained from the patient for the publication of any potentially identifiable images or data included in this article. Transnasal endoscopic marsupialization for NPDC is minimally invasive and useful; however, it is necessary to build evidence for an appropriate excision range based on the position and size of the lesion.

Prolonged and extended impacts of SARS-CoV-2 on the olfactory neurocircuit.

The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.

Immunological status of the olfactory bulb in a murine model of Toll-like receptor 3-mediated upper respiratory tract inflammation.

BACKGROUND: Postviral olfactory dysfunction (PVOD) following a viral upper respiratory tract infection (URI) is one of the most common causes of olfactory disorders, often lasting for over a year. To date, the molecular pathology of PVOD has not been elucidated. METHODS: A murine model of Toll-like receptor 3 (TLR3)-mediated upper respiratory tract inflammation was used to investigate the impact of URIs on the olfactory system. Inflammation was induced via the intranasal administration of polyinosinic-polycytidylic acid (poly(I:C), a TLR3 ligand) to the right nostril for 3 days. Peripheral olfactory sensory neurons (OSNs), immune cells in the olfactory mucosa, and glial cells in the olfactory bulb (OB) were analyzed histologically. Proinflammatory cytokines in the nasal tissue and OB were evaluated using the quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: In the treated mice, OSNs were markedly reduced in the olfactory mucosa, and T cell and neutrophil infiltration therein was observed 1 day after the end of poly(I:C) administration. Moreover, there was a considerable increase in microglial cells and slight increase in activated astrocytes in the OB. In addition, qPCR and ELISA revealed the elevated expression of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma both in the OB and nasal tissue. CONCLUSIONS: Taken together, the decreased peripheral OSNs, OB microgliosis, and elevated proinflammatory cytokines suggest that immunological changes in the OB may be involved in the pathogenesis of PVOD.

A murine model of eosinophilic chronic rhinosinusitis using the topical application of a vitamin D3 analog.

BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease, characterized by eosinophilic infiltration, T-helper type 2 (Th2-type) response, and olfactory dysfunction. A master regulator of Th2-type inflammation, thymic stromal lymphopoietin (TSLP), is important for basophil activation. TSLP-elicited basophils are a key factor in the pathogenesis of ECRS. METHODS: In order to elucidate the mechanisms of ECRS in humans, we aimed to establish a murine model of ECRS based on TSLP production in response to the topical application of MC903 (a vitamin D3 analog) and the subsequent TSLP-induced basophil activation. Histological analyses were performed to assess immune cell infiltration into the nasal mucosa and to explore the impact of eosinophilic inflammation on the olfactory epithelium. The status of Th2-type inflammation was evaluated by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). RESULTS: Eosinophils, basophils, and M2 macrophages increased significantly in the nasal mucosa of the mice treated with MC903 and ovalbumin (OVA), compared to those treated with OVA alone or the controls. Quantitative real-time PCR and ELISA revealed elevated expression of interleukin (IL)-4, IL-5, IL-13, TSLP, the chemokine CCL11, and CCL24 in the nasal mucosa of the ECRS mice. In parallel, thinned olfactory epithelium and decreased mature olfactory sensory neurons were observed in the ECRS mice. CONCLUSIONS: Our model of ECRS displayed Th2-type inflammation in the sinonasal region, including both eosinophil infiltration and basophil infiltration. Additionally, olfactory epithelium turned out to be affected by eosinophilic inflammation. These features are consistent with the characteristics of the human ECRS.

Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa.

The effects of caloric restriction (CR) on cell dynamics and gene expression in the mouse olfactory neuroepithelium are evaluated. Eight-week-old male C57BL/6 mice were fed either control pellets (104 kcal/week) or CR pellets (67 kcal/week). The cytoarchitecture of the olfactory neuroepithelium in the uninjured condition and its regeneration after injury by an olfactotoxic chemical, methimazole, were compared between mice fed with the control and CR diets. In the uninjured condition, there were significantly fewer olfactory marker protein (OMP)-positive olfactory receptor neurons and Ki67-positive proliferating basal cells at 3 months in the CR group than in the control group. The number of Ki67-positive basal cells increased after methimazole-induced mucosal injury in both the control and the CR groups, but the increase was less robust in the CR group. The recovery of the neuroepithelium at 2 months after methimazole administration was less complete in the CR group than in the control group. These histological changes were region-specific. The decrease in the OMP-positive neurons was prominent in the anterior region of the olfactory mucosa. Gene expression analysis using a DNA microarray and quantitative real-time polymerase chain reaction demonstrated that the expression levels of two inflammatory cytokines, interleukin-6 and chemokine ligand 1, were elevated in the olfactory mucosa of the CR group compared with the control group. These findings suggest that CR may be disadvantageous to the maintenance of the olfactory neuroepithelium, especially when it is injured.

Repetitive Sinus-Related Symptoms May Accelerate the Progression of Chronic Maxillary Atelectasis.

Chronic maxillary atelectasis (CMA) is characterized by a progressive decrease in maxillary sinus volume. The factors that promote the stage progression of CMA remain poorly understood. Here, we describe the time course of anatomical changes in a 40-year-old woman with stage II CMA that progressed to stage III disease. She did not show stage progression until she started to develop repetitive sinus-related symptoms. The stage progression was characterized by ocular symptoms. The repetitive inflammatory episodes may have increased the negative pressure in the affected sinus and weakened the bone walls, thereby promoting stage progression. Thus, a history of repetitive sinus-related symptoms may be a risk factor for stage progression in CMA.

Facial nerve paralysis associated with temporal bone masses.

OBJECTIVE: To investigate the clinical and electrophysiological features of facial nerve paralysis (FNP) due to benign temporal bone masses (TBMs) and elucidate its differences as compared with Bell's palsy. METHODS: FNP assessed by the House-Brackmann (HB) grading system and by electroneurography (ENoG) were compared retrospectively. RESULTS: We reviewed 914 patient records and identified 31 patients with FNP due to benign TBMs. Moderate FNP (HB Grades II-IV) was dominant for facial nerve schwannoma (FNS) (n=15), whereas severe FNP (Grades V and VI) was dominant for cholesteatomas (n=8) and hemangiomas (n=3). The average ENoG value was 19.8% for FNS, 15.6% for cholesteatoma, and 0% for hemangioma. Analysis of the correlation between HB grade and ENoG value for FNP due to TBMs and Bell's palsy revealed that given the same ENoG value, the corresponding HB grade was better for FNS, followed by cholesteatoma, and worst in Bell's palsy. CONCLUSIONS: Facial nerve damage caused by benign TBMs could depend on the underlying pathology. Facial movement and ENoG values did not correlate when comparing TBMs and Bell's palsy. When the HB grade is found to be unexpectedly better than the ENoG value, TBMs should be included in the differential diagnosis.

Longer latency of sensory response to intravenous odor injection predicts olfactory neural disorder.

A near loss of smell may result from conductive and/or neural olfactory disorders. However, an olfactory test to selectively detect neural disorders has not been established. We investigated whether onset latency of sensory response to intravenous odor injection can detect neural disorders in humans and mice. We showed that longer preoperative onset latency of odor recognition to intravenous odor in patients with chronic rhinosinusitis predicted worse recovery of olfactory symptoms following sinus surgery. The onset latency of the olfactory sensory neuron (OSN) response to intravenous odor using synaptopHluorin signals from OSN axon terminals was delayed in mice with reduced numbers of OSNs (neural disorder) but not with increased mucus or blocked orthonasal pathways (conductive disorders). Moreover, the increase in onset latency correlated with the decrease in mature OSN numbers. Longer onset latency to intravenous odor injection is a useful biomarker for presence and severity of olfactory disorders with neural etiology.

Denervation of nasal mucosa induced by posterior nasal neurectomy suppresses nasal secretion, not hypersensitivity, in an allergic rhinitis rat model.

The posterior nasal nerve is the dominant source of the parasympathetic, sympathetic, and sensory fibers that innervate the nasal respiratory mucosa. Therefore, a posterior nasal neurectomy (PNN) is thought to induce denervation of the nasal mucosa and relieve the nasal symptoms of allergic rhinitis. However, the underlying mechanisms and therapeutic action of PNN remain unknown. To investigate the impact of PNN-induced denervation of the nasal mucosa on allergic rhinitis, we developed a rat model of PNN and examined the effects of PNN on allergic rhinitis in ovalbumin-sensitized rats. This rat model of PNN was characterized by the depletion of nerve fibers, choline acetyltransferase, and neuropeptides (eg, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and neuropeptide Y) in the nasal respiratory mucosa. These animals exhibited nasal gland and goblet cell hypertrophy in the septal mucosa and atrophy of the submucosal gland in the lateral nasal wall, as well as reduced nasal secretion due to deficient acetylcholine synthesis. In an ovalbumin-sensitized model of allergic rhinitis, PNN also induced the depletion of nerve fibers, choline acetyltransferase, and neuropeptides in the nasal mucosa and suppressed nasal secretion. However, PNN did not affect mucosal thickening, eosinophil and mast cell infiltration, interleukin-4 and interferon-γ mRNA expression, and allergic symptoms (ie, sneezing and nasal scratching). These results suggest that the peripheral nerves and corresponding neuropeptides regulate nasal secretion, but not hypersensitivity, in allergic rhinitis, and that allergic rhinitis-related mucosal reactions occur in a highly denervated mucosa after PNN. Posterior nasal neurectomy may be a therapeutic option for the treatment of hyperrhinorrhea, but not allergic rhinitis hypersensitivity.

T-cell phenotypes in chronic rhinosinusitis with nasal polyps in Japanese patients.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is characterized by local inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis, and non-eosinophilic chronic rhinosinusitis. The objective of this study was to investigate the expression of key transcription factors for Treg and Th1/Th2/Th17 cells, in relation to the mRNA expression of representative cytokines in these two subtypes of chronic rhinosinusitis with nasal polyps. METHODS: The expression of forkhead box P3 (FOXP3), T-box transcription factor (T-bet), GATA3, retinoid acid-related orphan receptor C (RORc), the suppressive cytokines TGF-ß1 and IL-10, and Th1/Th2/Th17 cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-17) were analyzed by means of RT-PCR in eosinophilic polyps. Eosinophilic polyps were defined as having an eosinophil count of more than 50 per microscopic field (×400 magnification) using five fields located in the subepithelial area of the polyps, while the non-eosinophilic polyps and controls did not fulfill this criteria. The numbers of T cells, CD4+ T cells, CD8+ T cells and Treg were histologically counted using sections that were immunostained for CD3, CD4, CD8, and FOXP3, respectively. RESULTS: In eosinophilic polyps, we observed significantly fewer CD4+ T cells and CD8+ T cells, and lower GATA3, RORc and IL-10 mRNA expression, but a significantly higher IL-5, and IL-13 mRNA expression compared with controls, whereas FOXP3 and T-bet mRNA expression were not significantly different compared with controls. In non-eosinophilic polyps, FOXP3, IL-10, IL-17A, TGFß1 and IFNγ mRNA expression was significantly higher compared with controls, whereas IL-4, 5 and 13 expression was not significantly different from controls. CONCLUSION: We showed a reduction of GATA3 and RORc mRNA, low Treg-related cytokines and elevated Th2 cytokine levels in eosinophilic chronic rhinosinusitis, whereas we demonstrated the upregulation of Treg cells and increases of Th1 and Th17 cytokines in non-eosinophilic chronic rhinosinusitis in the Japanese population. The different mRNA expression profiles of Treg and Th1/Th2/Th17 signature transcription factors and cytokines between eosinophilic chronic rhinosinusitis and non-eosinophilic chronic rhinosinusitis suggests heterogeneity in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Distortion-product otoacoustic emission tests evaluate cochlear function and differentiate cochlear and vestibular schwannoma.

OBJECTIVES: (1) To investigate cochlear function in patients with acoustic neuroma by distortion-product otoacoustic emission tests and (2) to evaluate the utility of this method for identifying the nerve origin of acoustic neuroma. STUDY DESIGN: Diagnostic test assessment. SETTING: Community hospital. METHODS: The study included 196 patients with unilateral acoustic neuroma who were surgically treated in our hospital between April 2008 and March 2011. In all patients, pure-tone audiometry and distortion-product otoacoustic emission tests were conducted before surgery, and tumor size was measured on magnetic resonance imaging. RESULTS: Superior vestibular schwannoma (n = 112), inferior vestibular schwannoma (n = 80), and cochlear schwannoma (n = 4) were observed. Positive results of distortion-product otoacoustic emission tests were observed in 11 patients with superior vestibular schwannoma, 14 with inferior vestibular schwannoma, and 3 with cochlear schwannoma. They were predictive of cochlear schwannoma, with 75.0% sensitivity (95% confidence interval [CI], 30.6-95.4) and 87.0% specificity (95% CI, 86.1-87.4). Retrocochlear hearing loss was detected in 5 patients with inferior vestibular schwannoma and 1 with cochlear schwannoma. It was also predictive of cochlear schwannoma. This criterion showed 25.0% sensitivity (95% CI, 4.7-66.1) and 97.4% specificity (95% CI, 97.0-98.3). CONCLUSION: Percentages of patients with positive results on distortion-product otoacoustic emission tests and those with retrocochlear hearing loss differed by nerve origin. Distortion-product otoacoustic emission tests can be of some assistance in differentiating cochlear and vestibular schwannoma.

Cephalic tetanus presenting as acute vertigo with bilateral vestibulopathy.

Cephalic tetanus is a rare form of tetanus, defined by paralysis of more than one cranial nerve. The seventh cranial nerve is the most frequently involved. We report a 58-year-old man with cephalic tetanus and bilateral vestibulopathy. The patient's initial symptoms were rotatory vertigo and hypertension. He then developed trismus and cranial nerve palsies of the fifth and seventh nerves. The caloric test and vestibular evoked mygenic potentials in response to air-conducted clicks revealed absent responses on both sides, although audiometry and auditory brainstem responses were normal in both ears. To the best of our knowledge, this is the first report of involvement of the eighth cranial nerve in cephalic tetanus.

Dislocation of stapes with footplate fracture caused by indirect trauma.

We report the first case of isolated stapedial dislocation caused by indirect head trauma, and present imaging and surgical findings in the case of a 25-year-old woman who suffered hearing loss and dizziness after head trauma caused by a traffic accident. The pure tone average was 60 dB, with an air-bone gap of 50 dB. The stapedial reflex was positive with the probe on the affected ear. Computed tomography scans revealed a longitudinal fracture of the temporal bone and a dislocated stapedial superstructure in the tympanic cavity, adhering to the tympanic membrane. During surgery, it was found that the stapes was broken at the base of the posterior crus and at the anterior one third of the footplate and that the stapedial superstructure was dislocated outward and downward, with the anterior one third of the footplate adhering to the tympanic membrane. The stapedial tendon was connected to the superstructure. Ossicular chain reconstruction was performed with success. In the present case, two mechanisms may have acted together: 1) an increase in perilymphatic pressure that caused the footplate to fracture, and 2) a distorting force that broke the posterior crus, disconnecting the incudostapedial joint, and finally dislocating the stapedial superstructure together with the anterior part of the footplate.

Utility of elastography for differential diagnosis of benign and malignant thyroid nodules.

OBJECTIVE: 1) To classify the appearance of thyroid nodules displayed on ultrasound elastography; 2) to explore the sensitivity and specificity of this examination for differentiating benign and malignant nodules, with histopathologic analysis as the reference standard; and 3) to evaluate its utility for avoiding unnecessary procedures. STUDY DESIGN: Diagnostic test assessment. SETTING: Community hospital. SUBJECTS AND METHODS: Forty-seven thyroid nodules in 44 consecutive patients were examined with ultrasound elastography. The images we obtained were classified into four patterns. In addition, the mean strain index of the thyroid nodule and that of the sternocleidomastoid muscle were measured, and the nodule-to-muscle strain ratio was calculated. As the reference findings, the presence or absence of calcification, irregular margins, and hypoechogenicity of the thyroid nodules were examined using B-mode ultrasound. RESULTS: Elastography patterns 3 and 4 were predictive of malignancy, with 73 percent sensitivity (95% confidence interval [CI]: 39%-94%) and 64 percent specificity (95% CI: 46%-79%). Additionally, all nodules without calcification and those that presented with patterns 1 or 2 were benign. A strain ratio greater than 1.5 was set as the predictor of thyroid malignancy. This criterion showed 90 percent sensitivity (95% CI: 59%-100%) and 50 percent specificity (95% CI: 33%-67%). CONCLUSION: Although elastography can assist in the differential diagnosis of thyroid nodules, its diagnostic performance is not ideal at present. Further improvements in the technique and the diagnostic criteria are necessary for this examination to provide a useful contribution to diagnosis.