Subjective versus Psychophysical Measures of Chemosensory Alterations following COVID-19.

INTRODUCTION: Olfactory dysfunction is a common symptom of COVID-19. However, subjective perception of olfactory function does not always correlate well with more objective measures. This study seeks to clarify associations between subjective and psychophysical measures of olfaction and gustation in patients with subjective chemosensory dysfunction following COVID-19. METHODS: Adults with persistent COVID-19-associated chemosensory disturbance were recruited for a prospective, longitudinal cohort study at a tertiary care institution. Participants provided subjective measures of olfactory and gustatory function and underwent psychophysical assessment using Sniffin' Sticks olfactory and Monell gustatory tests. RESULTS: Data analysis (n = 65) showed a statistically significant association between subjective and psychophysical measures of olfaction (p < 0.001). For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.11 (95% CI: 0.06, 0.16; p < 0.001) point increase in TDI score while adjusting for age at baseline assessment, sex, and follow-up time. For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.04 (95% CI: 0.02, 0.06; p < 0.001) point and 0.05 (95% CI: 0.03, 0.07; p < 0.001) point increase in discrimination and identification scores, respectively, when adjusting for age at baseline assessment, sex, and follow-up time. CONCLUSION: Subjective olfaction shows a mild to moderate association with psychophysical measures, but it fails to comprehensively assess persistent COVID-19-associated chemosensory deficits. The lack of significant association between subjective olfaction and threshold limits the utility of subjective olfaction in tracking recovery. These findings support the push for more widespread psychophysical chemosensory testing.

Vocal Cord Paralysis in Pediatric Chiari Malformation: A Systematic Review and Meta-analysis.

OBJECTIVE: Arnold-Chiari Malformation is one possible cause of congenital vocal cord paralysis (VCP). The natural history of VCP in children with Chiari malformation has previously been limited to small case studies. This systematic review seeks to better characterize the prognostic factors that may predict symptom severity and resolution of congenital VCP in children with Arnold-Chiari malformation. We hypothesized that the onset of stridor or VCP at a younger age would be associated with a poorer prognosis and earlier intervention with posterior fossa decompression would be associated with better outcomes. DATA SOURCES: PubMed, Web of Science, Cochrane Library, and bibliographic review. REVIEW METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Database search yielded 866 articles. Study abstracts were reviewed by 2 independent examiners. One hundred and seventy-six studies underwent full-text review. The following were extracted: age at onset of stridor or VCP, Chiari malformation type, laryngoscopy findings, type and timing of neurosurgical intervention, and tracheostomy history. Statistical analyses utilized χ2 tests. RESULTS: Younger age at symptom onset showed statistically significant associations with decreased likelihood for symptom resolution and tracheostomy decannulation. The shorter time interval from symptom onset to neurosurgical intervention was not significantly associated with better outcomes. CONCLUSION: This meta-analysis suggests poorer prognosis in those with earlier-onset symptoms, reinforcing prior case series findings. Additional prospective studies are needed to elucidate the natural history and utility of early intervention in children with vocal cord paralysis secondary to Chiari malformation.

B-cell Lymphoblastic Lymphoma Presenting as a Sinonasal Mass: A Case Report.

B-cell lymphoblastic lymphoma (B-LBL) is an abnormal proliferation of lymphocyte precursor cells located primarily outside of the bone marrow and peripheral blood, typically in the mediastinum or other lymph nodes. It is often a disease of childhood that presents with lymphadenopathy, fatigue, pallor, bone pain, and weight loss with laboratory findings of anemia and thrombocytopenia. Initial presentations prompted by head and neck manifestations are exceedingly rare. A five-year-old girl with no significant past medical history presented with right facial swelling and mild proptosis on ophthalmologic evaluation. She was referred to a tertiary care facility by her local otolaryngologist for further management after computed tomographic imaging revealed right maxillary sinus opacification and erosion of the anterior maxillary bone. Her symptoms were initially responsive to prednisone and amoxicillin-clavulanate, and only right unilateral nasal discharge persisted with a near-complete resolution of other sinonasal symptoms. Notably, laboratory values, including complete blood count, were within normal limits. Given concern for the etiology of the bony erosion, the patient presented for a second opinion, where imaging and biopsy resulted in flow cytometry findings consistent with B-ALL/LBL. After a bone marrow biopsy, the ultimate diagnosis was Murphy's stage III B-cell lymphoblastic lymphoma. Malignant neoplasms of the sinonasal region are rare in children, where primary sinonasal B-LBL is a unique occurrence. Clinical features of sinonasal B-LBL in the paranasal sinuses may masquerade as pathologies such as acute sinusitis, orbital cellulitis, and benign tumors or polyps that can lead to a confounding diagnosis. In this case presentation, an initial response to steroids and antibiotics should not provide false reassurance when other features and signs, such as maxillary bone erosion, may suggest the presence of malignancy.

Associations between olfactory dysfunction and cognition: a scoping review.

INTRODUCTION: Strong evidence suggests that olfactory dysfunction (OD) can predict additional neurocognitive decline in neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. However, research exploring olfaction and cognition in younger populations is limited. The aim of this review is to evaluate cognitive changes among non-elderly adults with non-COVID-19-related OD. METHODS: We performed a structured comprehensive literature search of PubMed, Ovid Embase, Web of Science, and Cochrane Library in developing this scoping review. The primary outcome of interest was the association between OD and cognitive functioning in adults less than 60 years of age. RESULTS: We identified 2878 studies for title and abstract review, with 167 undergoing full text review, and 54 selected for data extraction. Of these, 34 studies reported on populations of individuals restricted to the ages of 18-60, whereas the remaining 20 studies included a more heterogeneous population with the majority of individuals in this target age range in addition to some above the age of 60. The etiologies for smell loss among the included studies were neuropsychiatric disorders (37%), idiopathic cause (25%), type 2 diabetes (7%), trauma (5%), infection (4%), intellectual disability (4%), and other (18%). Some studies reported numerous associations and at times mixed, resulting in a total number of associations greater than the included number of 54 studies. Overall, 21/54 studies demonstrated a positive association between olfaction and cognition, 7/54 demonstrated no association, 25/54 reported mixed results, and only 1/54 demonstrated a negative association. CONCLUSION: Most studies demonstrate a positive correlation between OD and cognition, but the data are mixed with associations less robust in this young adult population compared to elderly adults. Despite the heterogeneity in study populations and outcomes, this scoping review serves as a starting point for further investigation on this topic. Notably, as many studies in this review involved disorders that may have confounding effects on both olfaction and cognition, future research should control for these confounders and incorporate non-elderly individuals with non-psychiatric causes of smell loss.

Hampshire Sheep as a Large-Animal Model for Cochlear Implantation.

BACKGROUND: Sheep have been proposed as a large-animal model for studying cochlear implantation. However, prior sheep studies report that the facial nerve (FN) obscures the round window membrane (RWM), requiring FN sacrifice or a retrofacial opening to access the middle-ear cavity posterior to the FN for cochlear implantation. We investigated surgical access to the RWM in Hampshire sheep compared to Suffolk-Dorset sheep and the feasibility of Hampshire sheep for cochlear implantation via a facial recess approach. METHODS: Sixteen temporal bones from cadaveric sheep heads (ten Hampshire and six Suffolk-Dorset) were dissected to gain surgical access to the RWM via an extended facial recess approach. RWM visibility was graded using St. Thomas' Hospital (STH) classification. Cochlear implant (CI) electrode array insertion was performed in two Hampshire specimens. Micro-CT scans were obtained for each temporal bone, with confirmation of appropriate electrode array placement and segmentation of the inner ear structures. RESULTS: Visibility of the RWM on average was 83% in Hampshire specimens and 59% in Suffolk-Dorset specimens (p = 0.0262). Hampshire RWM visibility was Type I (100% visibility) for three specimens and Type IIa (> 50% visibility) for seven specimens. Suffolk-Dorset RWM visibility was Type IIa for four specimens and Type IIb (< 50% visibility) for two specimens. FN appeared to course more anterolaterally in Suffolk-Dorset specimens. Micro-CT confirmed appropriate CI electrode array placement in the scala tympani without apparent basilar membrane rupture. CONCLUSIONS: Hampshire sheep appear to be a suitable large-animal model for CI electrode insertion via an extended facial recess approach without sacrificing the FN. In this small sample, Hampshire specimens had improved RWM visibility compared to Suffolk-Dorset. Thus, Hampshire sheep may be superior to other breeds for ease of cochlear implantation, with FN and facial recess anatomy more similar to humans.

Surgical and medical management of chronic rhinosinusitis in pediatric cystic fibrosis patients: Impact on olfactory symptoms.

BACKGROUND AND PURPOSE: Olfactory dysfunction (OD) commonly occurs in patients with sinonasal dysfunction, but the prevalence and severity of olfactory issues in adolescents with cystic fibrosis (AwCF) is unclear. OD may contribute to dietary deficiencies and exacerbate nutritional challenges. We sought to review literature on the effectiveness of medical and surgical management of sinonasal symptoms in AwCF and the associated impact on olfactory function. METHODS: We performed a systematic literature search of PubMed, Embase, Web of Science, and Ebsco CINAHL from 1980 to 2022 per PRISMA-ScR protocols to conduct a scoping review in an effort to compile data on study design, patient demographics, clinical characteristics and outcomes, along with risk of bias. RESULTS: Of 368 abstracts, 3 articles exclusively evaluated AwCF for a total of 34 patients. Two studies evaluated endoscopic sinus surgery (ESS) and dornase alfa. An additional 6 articles were included for mixed pediatric and adult CF populations totaling 313 patients. Interventions included ESS, elexacaftor-tezacaftor-ivacaftor (ETI), ivacaftor, saline, dornase alfa, hyaluronic acid, and hyaluronic acid-tobramycin combination. Outcome measures included subjective assessment of OD using non-validated (4/9) and validated (4/9) surveys, and psychophysical (1/9) smell testing. Studies evaluating ESS, FESS, dornase alfa, ivacaftor, and both hypertonic and isotonic saline reported statistically significant improvement in OD, whereas ETI failed to improve OD despite improvement in other quality of life measures. CONCLUSIONS: There is limited data regarding the impact of medical and surgical interventions on olfaction for AwCF. Assessment of olfaction was often limited to subjective and qualitative self-report. We suggest that tracking of olfactory outcomes with psychophysical testing is critical in this population with dietary challenges and weight management issues.

Accessing the Eustachian tube: Conventional nasal spray vs. exhalation delivery system and the impact of targeted endoscopic sinus surgery on topical distribution patterns.

BACKGROUND: Eustachian tube dysfunction (ETD) may occur distinct from, or in conjunction with, chronic rhinosinusitis (CRS+ETD). Intranasal corticosteroid sprays are often prescribed for ETD, although ET distribution may be limited. To date, no anatomic studies compare nasopharynx (NP) distribution between conventional nasal sprays (NS) and exhalation delivery systems (EDS) after surgery. This study utilizes a cadaver model to examine topical NP delivery using EDS vs. NS before and after targeted endoscopic sinus surgery (ESS). METHODS: Sixteen sinonasal cavities were administered fluorescein solution via NS and EDS before and after maxillary antrostomy and anterior ethmoidectomy, followed by nasal endoscopy of the NP and ET orifice. Seven blinded experts submitted staining ratings of endoscopy images on a 0- to 3-point scale, with ratings averaged for analysis. RESULTS: Interrater reliability was excellent (intraclass correlation, 0.956). EDS was associated with significantly greater NP staining vs. NS in a pooled cohort of nonsurgical and ESS specimens (1.19 ± 0.81 vs. 0.78 ± 1.06; p = 0.043). Using a logistic regression model, EDS significantly outperformed NS in nonsurgical (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.21-10.09; p = 0.021) and post-ESS (OR, 9.00; 95% CI, 1.95-41.5; p = 0.005) specimens, with the greatest relative staining observed for EDS after targeted ESS (OR, 18.99; 95% CI, 3.44-104.85; p = 0.001). CONCLUSIONS: EDS is more effective than NS in topical delivery to the NP and ET orifices in cadavers. Targeted ESS may facilitate greater NP penetration by EDS compared with NS, with possible synergism after ESS for augmented delivery. These findings suggest a role for EDS delivery methods for ETD management and in CRS+ETD patients undergoing sinus surgery.

Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment: A longitudinal cohort study.

Objectives: Persistent olfactory dysfunction (OD) following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID. Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function. Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery. Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell. This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD. Methods: We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin' Sticks extended test at baseline and 1-year time points. Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available. Results: Baseline olfactory evaluation was completed by 122 participants, 53 of whom completed the 1-year follow-up assessment. Among participants presenting with perceived OD, 74.5% had confirmed psychophysical OD at baseline, with 55.1% at 1-year follow-up. Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points. The total threshold, discrimination, and identification (TDI) score improved by +3.25 points in the cohort with psychophysical OD (p = 0.0005), with this improvement largely attributable to an increase in median threshold scores (+2.75 points; p = 0.0004). Conclusions: OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19, with many demonstrating lingering deficits at 1-year. Improvements in threshold, but not discrimination or identification, most significantly mediate improvement of total TDI score at follow-up.

Delivering Therapy to the Olfactory Cleft: A Comparison of the Various Methods of Administering Topical Nasal Medications.

Background and objective Chronic rhinosinusitis (CRS) is an inflammatory condition affecting the nasal mucosa, and it causes olfactory dysfunction (OD) in up to 78.2% of patients. Corticosteroids are the mainstay of treatment to shrink nasal polyposis, reduce inflammation, and improve olfactory function. While many delivery methods for topical nasal corticosteroids exist, there is scarce data on the efficacy of the various medication delivery methods to the olfactory cleft (OC). In light of this, this study aimed to compare the following delivery methods to the OC: conventional nasal spray (NS), nasal drops in the Kaiteki position (KP), and exhalation delivery system (EDS). Methods We evaluated 16 sinonasal cavities from eight cadaver specimens in this study. Each sinonasal cavity was administered fluorescein dye solution via NS, KP, and EDS. Following administration, nasal endoscopy was employed to capture staining patterns in the OC. OC staining was rated with scores ranging from 0 (no staining) to 3 (heavy staining) after each administration of dye solution. Mean OC staining ratings were calculated and compared using the Kruskal-Wallis rank sum test and the Wilcoxon signed-rank test. Results The mean OC staining score for the different delivery methods was as follows - NS: 1.095 ± 1.008, EDS: 0.670 ± 0.674, and KP: 2.038 ± 1.097. Nasal drops in the KP had a significantly higher staining score compared to NS (p=0.041) and EDS (p=0.003). However, there was no significant difference in staining scores between NS and EDS. Conclusions Nasal drops in the KP are more effective at reaching the OC than NS or EDS and should be considered as a first-line modality for administering topical medications when treating OD.

Sheep as a Large-Animal Model for Otology Research: Temporal Bone Extraction and Transmastoid Facial Recess Surgical Approach.

PURPOSE: Sheep are used as a large-animal model for otology research and can be used to study implantable hearing devices. However, a method for temporal bone extraction in sheep, which enables various experiments, has not been described, and literature on middle ear access is limited. We describe a method for temporal bone extraction and an extended facial recess surgical approach to the middle ear in sheep. METHODS: Ten temporal bones from five Hampshire sheep head cadavers were extracted using an oscillating saw. After craniotomy and removal of the brain, a coronal cut was made at the posterior aspect of the orbit followed by a midsagittal cut of the occipital bone and disarticulation of the atlanto-occipital joint. Temporal bones were surgically prepared with an extended facial recess approach. Micro-CT scans of each temporal bone were obtained, and anatomic dimensions were measured. RESULTS: Temporal bone extraction was successful in 10/10 temporal bones. Extended facial recess approach exposed the malleus, incus, stapes, and round window while preserving the facial nerve, with the following surgical considerations: minimally pneumatized mastoid; tegmen (superior limit of mastoid cavity) is low-lying and sits below temporal artery; chorda tympani sacrificed to optimize middle ear exposure; incus buttress does not obscure view of middle ear. Distance between the superior aspect of external auditory canal and tegmen was 2.7 (SD 0.9) mm. CONCLUSION: We identified anatomic landmarks for temporal bone extraction and describe an extended facial recess approach in sheep that exposes the ossicles and round window. This approach is feasible for studying implantable hearing devices.

Olfaction and neurocognition after COVID-19: a scoping review.

Introduction: COVID-19 induces both acute and chronic neurological changes. Existing evidence suggests that chemosensory changes, particularly olfactory loss, may reflect central neurological dysfunction in neurodegenerative diseases and mark progression from mild cognitive impairment to Alzheimer's. This scoping review summarizes the available literature to evaluate the relationship between neurocognition and olfaction in young to middle-aged adults with minimal comorbidities following COVID-19 infection. Methods: A literature search of PubMed, Ovid Embase, Web of Science, and Cochrane Library was conducted. Studies underwent title/abstract and full text screening by two reviewers, with a third reviewer resolving any conflicts. Remaining studies underwent data extraction. Results: Seventeen studies were eligible for data extraction after the review process, where 12 studies found significantly poorer cognition in those suffering from olfactory dysfunction, four studies showed no association between cognition and olfaction, and one study reported lower anosmia prevalence among patients with cognitive impairment. Conclusion: The majority of studies in this review find that olfactory dysfunction is associated with poorer cognition. More rigorous studies are needed to further elucidate the relationship between olfaction and cognition after COVID-19.

BMI Increases in Individuals with COVID-19-Associated Olfactory Dysfunction.

(1) Background: Reports suggest COVID-19-associated olfactory dysfunction (OD) may result in alterations in dietary behaviors and perceived weight change, but few studies using psychophysical evaluation of post-COVID-19-associated chemosensory dysfunction and body mass index (BMI) exist. The purpose of this study is to assess the impact of both quantitative and qualitative features of COVID-19-associated OD on BMI; (2) Methods: Recruitment of thirty-one participants with self-reported OD in the form of quantitative loss with and without qualitative features. Surveys with questions specific to qualitative olfactory function, Sniffin' Sticks tests, and BMI measures were completed at two visits, one year apart. Group differences were assessed with Wilcoxon signed-rank tests and the Holm-Bonferroni method; (3) Results: Individuals with persistent quantitative OD (n = 15) and self-reported parosmia (n = 19) showed statistically significant increases in BMI after 1 year (p = 0.004, adjusted α = 0.0125; p = 0.011, adjusted α = 0.0167). Controls with transient quantitative OD (n = 16) and participants without self-reported parosmia (n = 12) showed no statistically significant changes in BMI over the same time period (p = 0.079, adjusted α = 0.05; p = 0.028, adjusted α = 0.025); (4) Conclusions: This study shows an association between COVID-19-associated OD and BMI, suggesting olfaction may play a role in altering dietary habits and nutrition in this population. Larger study cohorts are needed to further evaluate this relationship.

Beyond aroma: A scoping review on the impact of chronic rhinosinusitis on retronasal olfaction.

Background: Retronasal olfaction (RNO) refers to the perception of odorants inhaled through the mouth and carried through the nasopharynx to olfactory receptors within the olfactory cleft, enabling the perception of flavor. Although orthonasal olfactory dysfunction in chronic rhinosinusitis (CRS) has been widely described, the impact of CRS on RNO is less clear. In this study, we systematically review available literature to provide an update on RNO in the setting of CRS. Methods: We systematically searched PubMed, Ovid Embase, Web of Science, and the Cochrane Library for studies examining RNO in patients with documented CRS. The primary outcome of interest was objective psychophysical measurement of olfaction, including characterization of RNO. Results: We identified 404 unique references that underwent title and abstract review by two independent reviewers, with 52 articles undergoing full-text review, where 10 relevant studies underwent data extraction. Although outcome measures varied, all included studies demonstrated diminished RNO in patients with CRS. Of six studies evaluating the relationship between retronasal and orthonasal olfactory test scores in CRS patients two out of six (33%) demonstrated a correlation between both forms of olfaction and CRS, and two out of six studies (33%) found significantly lower orthonasal olfactory test scores compared to retronasal olfactory test scores. Two of three found significant improvement in RNO with treatment of underlying CRS. Of three studies examining patient reported outcome measures (PROMs) in CRS, two found significant associations between retronasal olfactory test scores and PROMs. Conclusions: Based on the current literature, CRS patients appear to have diminished RNO, which may be associated with orthonasal olfactory dysfunction and decreased quality of life in this population. Higher level of evidence studies are required to further elucidate these relationships and the impact of medical and surgical CRS management on RNO.