Olfactory Cleft Width and Volume: Possible Risk Factors for Postinfectious Olfactory Dysfunction.

OBJECTIVES/HYPOTHESIS: Upper respiratory tract infections are a common cause of temporary and permanent olfactory dysfunction in the general population. Postviral or postinfectious olfactory loss (PIOL) develops only in rare cases. The aim of this study was to investigate the anatomical features of olfactory cleft (OC) in patients with PIOL to shed light on possible predisposing factors for PIOL. STUDY DESIGN: Retrospective study. METHODS: We retrospectively evaluated paranasal sinus computed tomography (CT) scan results of patients diagnosed with PIOL. A control group consisted of normosmic individuals who underwent paranasal sinus CT scans before septoplasty surgery. We compared the olfactory fossa depth, OC width, and volume on the CT scans of the PIOL and control groups. RESULTS: In total, 71 individuals fulfilled the study criteria (PIOL group, n = 32; control group, n = 39). There was no statistically significant difference in the olfactory fossa depth in the two groups. The OC width and volume in the PIOL group was found to be significantly increased than that in the control group (P < .001 for both). CONCLUSIONS: Patients with PIOL had increased OC width and volume than the healthy controls. An extra-wide olfactory cleft may be a predisposing factor in the pathogenesis of PIOL. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:5-9, 2021.

Loss of bacterial diversity in the sinuses is associated with lower smell discrimination scores.

Olfactory impairment affects ~ 20% of the population and has been linked to various serious disorders. Microbes in the nasal cavity play a key role in priming the physiology of the olfactory epithelium and maintaining a normal sense of smell by the host. The aim of this study was to explore the link between olfactory dysfunction and nasal bacterial communities. A total of 162 subjects were recruited for this study from a specialized olfactory dysfunction clinic and placed into one of three groups: anosmia, hyposmia or normosmia. Swabs from the nasal middle meatus were collected from each subject then processed for bacterial 16S rRNA gene sequencing. No overall differences in bacterial diversity or composition were observed between the three cohorts in this study. However, the relative abundances of Corynebacterium spp. and Streptococcus spp. were significantly (p < 0.05) different in subjects with olfactory loss. Furthermore, subjects with deficiencies in discriminating between smells (based on discrimination scores) had a lower bacterial diversity (Simpson's evenness p < 0.05). While these results are preliminary in nature, potential bacterial biomarkers for olfactory loss were identified. These findings need to be further validated and biologically tested in animal models.

Invited Review: From nose to gut - the role of the microbiome in neurological disease.

Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system (CNS) in health and disease. To date, most research has focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. We herein take the novel approach of comprehensively reviewing the roles of the microbiome across several key mucosal interfaces - the nose, mouth, lung and gut - in health and in Parkinson's disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS). This review systematically appraises the anatomical and microbiological landscape of each mucosal surface in health and disease before considering relevant mechanisms that may influence the initiation and progression of PD, AD and MS. The cumulative effects of dysbiosis from the nose to the gut may contribute significantly to neurological disease through a wide variety of mechanisms, including direct translocation of bacteria and their products, and modulation of systemic or CNS-specific immunity. This remains an understudied and exciting area for future research and may lead to the development of therapeutic targets for chronic neurological disease.

The effect of antibiotics on social aversion following early life inflammation.

Epidemiological evidence suggests that exposure to infection during early development increases the risk for neurodevelopmental disorders associated with symptoms such as a decreased desire to engage in social interactions. In animals, disruptions in social behavior can be modelled by administering bacterial mimetics such as liposaccharide (LPS). However, when evaluating social interactions in the laboratory, attention is rarely directed on the reciprocal relationship as a whole, which is important as peers may drive social withdrawal. Previously, we have shown that male adolescent rats treated neonatally (n) with LPS receive less contact from their conspecifics in a social interaction test, and that this effect is mediated through olfactory communication. In the present study, we reconfirmed this effect using a more direct social test and evaluated the hypothesis that changes in the microbiome underlie the olfactory induced social aversion. Male and female Sprague-Dawley rats were administered nLPS (50 µg/kg, i.p) or nSaline on postnatal days (P)3 and 5. On P40, adolescent nLPS treated males received less contact in a social preference test compared to nSaline treated controls, an effect not observed in females. To confirm that nLPS led male rats to elicit a scent cue, resulting in social aversion, a subset of neurotypical conspecifics underwent an anosmia procedure that disrupted their olfactory processing via olfactory neuroepithelium degeneration. This normalized the contact that they directed towards nLPS and nSaline male rats. Although 16 s rRNA sequencing failed to detect significant differences in bacterial phyla across either sex or neonatal treatment, treating male nLPS rats with an antibiotic cocktail, which induced clear changes in microbial communities, diminished the social rejection effect. Therefore, manipulation of the microbiome appears to affect social communication where there exists an underlying deficit. Moreover, our data reaffirm that social engagement is a reciprocal process and the behavior of all individuals within a dynamic interaction should be evaluated.

Intravenous olfactory test latency correlates with improvement in post-infectious olfactory dysfunction.

CONCLUSION: This cohort study showed that onset latency in the intravenous olfactory test (IVO) may help predict when olfaction in patients with post-infectious olfactory dysfunction (PIOD) improves. OBJECTIVES: To identify factors that predict the olfactory improvement period in patients with PIOD. METHODOLOGY/PRINCIPAL: All consecutive patients presenting with PIOD in 1994-2014 who were followed up for 2 years were identified retrospectively. The ability of demographic/clinical factors (age, sex, body mass index, presence/absence of allergic rhinitis, treatment/non-treatment with herbal medicines, patient dependence on herbal medicine treatment, presence/absence of diabetes mellitus, and smoking status) and olfactory test factors (response/no response and onset latency and duration in the IVO test, and detection and recognition scores on the T&T olfactory test) to predict the olfactory improvement period (defined respectively as the time from PIOD onset or olfactory testing to the first self-report of olfaction improvement) was analyzed by univariate and multivariate regression. RESULTS: Of the 187 PIOD patients, the prognostic ability of demographic/clinical factors was analyzed in 65. None predicted the olfactory improvement period. Of the 65 patients, 20 did not respond in the IVO test. In the remaining 45 patients, onset latency (but not the other olfactory test factors) was a significant prognosticator of olfactory improvement period (R2=0.24, p = 0.003).

Unilateral cacosmia: a presentation of maxillary fungal infestation.

We present a case of long-standing unilateral cacosmia in a healthy 67-year-old man due to maxillary fungal infestation. Treatment with septoplasty had been attempted 10 years prior but no further investigation or management undertaken and symptoms continued. Subsequent MRI scan revealed significant opacification of the left maxillary sinus. This was readily amenable to treatment by balloon sinuplasty. This yielded viscous grey mucus which grew Scedosporium apiospermum. The case highlights the need for careful investigation of olfactory symptoms, including blood tests to exclude systemic causes, endoscopy and imaging where indicated.

[Fungal dacryocystitis with cacosmia after penetrating keratoplasty--taxonomy and identification of pathogenic fungi based on DNA sequence analysis].

CASE: A 76-year-old woman with a history of penetrating keratoplasty had cacosmia associated with dacryocystitis. Two species of yeast-like fungi were isolated from the contents of her lacrimal sac. Each cultured fungus had a unique, distinctive odor. Althogh treated with an oral antifungal agent and washing of the nasolacrimal duct, the cacosmia was not improved. The continuous dacryocystitis with cacosmia was treated by dacryocystectomy. Two yeast-like fungi were again isolated from the contents of the lacrimal sac. Pathological examination confirmed a diagnosis of fungal dacryocystitis based on the fungal hyphae observed on the excised lacrimal sac wall. The cacosmia promptly disappeared. The fungi isolated from the contents of lacrimal sac were identified by DNA sequencing as Wickerhamomyces anamalus (Pichia anomala-Candida pelliculosa) and Galactomyces geotrichum (Geotrichum candidum). CONCLUSION: The cause of cacosmia in the present case was fungal dacryocystitis. Antibiotic eye drops and steroid eye drops for the treatment of penetrating keratoplasty can cause atypical fungal presentation in the inconsistently treated lacrimal system and can induce dacryocystitis. Careful usage and consideration is necessary in the long-term use of antibiotics and steroids following corneal transplantation.

Identification and treatment of nontuberculous Mycobacterium sinusitis.

BACKGROUND: The purpose of this study was to identify the incidence of atypical Mycobacterium identified by routine sinus cultures and review the recent literature on management. METHODS: A retrospective case series was performed in a tertiary academic hospital. A retrospective case series of all patients treated with atypical Mycobacterium rhinosinusitis from 2005 to 2010 was performed. Cases were identified from a prospective database of 676 endoscopically guided sinus cultures. RESULTS: Eight patients with atypical Mycobacterium sinusitis were identified. There were five women and three men. Median age was 63 years (range, 55-71 years). All patients had prior endoscopic sinus surgery a median of 14 months (range, 0.8-162 months) before a positive culture result. Species identified included Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium abscessus, and Mycobacterium avium complex. Chief presenting symptoms were postnasal discharge (88%), followed by decreased smell and taste (63%), and facial pain/pressure (38%). Patients were treated based on sensitivity results with long-term oral antibiotics for at least 2 months based on improvements on endoscopy. Median follow-up for patients in this study after treatment was 1.3 years (range, 0.6-4.6 years). CONCLUSION: In this study, atypical mycobacteria were identified in <1% of sinus cultures. Prolonged, culture-directed antibiotic therapy remains the mainstay of treatment when there is clinical evidence of infection. Previous endoscopic sinus surgery may represent a risk factor for colonization and subsequent infection. Further research is necessary to determine the optimal treatment duration and management to prevent disease relapse.

Cell death of olfactory receptor neurons in a rat with nasosinusitis infected artificially with Staphylococcus.

Nasosinusitis is a common cause of acquired hyposmia or anosmia. To study the apoptotic death of olfactory receptor neurons in nasosinusitis, we made an inflammation model in rat infected with Staphylococcus. The histochemical changes in olfactory epithelium were examined using antibodies against protein gene product 9.5 (PGP 9.5), single-strand DNA (ssDNA), Bcl-2 and Bax that might be involved in the apoptosis of olfactory receptor neurons. The thickness of olfactory epithelium and the number of ssDNA-labeled cells were evaluated in each post-treatment group and the results were analyzed by two-way analysis of variance (ANOVA) and post hoc tests. Hematoxylin-eosin staining showed that a severe inflammatory reaction had occurred on the infected side of the nasal cavity and sinus, but not on the non-infected side. However, apoptosis of olfactory receptor neurons occurred on both sides; the apoptosis on the non-infected side started later and behaved like a shadow curve similarly to the infected side. Repeated measures ANOVA showed significant differences of both the thickness of olfactory epithelium (P < 0.0001) and the number of ssDNA-labeled cells (P = 0.0339) in the epithelium between the infected side and non-infected side comparing treatment, time and their interactions. Bcl-2 and Bax were detected only on the infected side in the early stages. Thus, nasosinusitis induced the apoptosis of olfactory receptor neurons. However, the apoptosis occurred not only on the infected side, but also on the non-infected side with no significant inflammation. The Bcl-2/Bax family seems to play an important role in the apoptosis induced by infection, but not in the apoptosis on the non-infected side. The results suggest that mechanisms of apoptosis of olfactory receptor neurons on the infected side may differ from those on the non-infected side.