Type 2 and Non-type 2 Inflammation in the Upper Airways: Cellular and Molecular Alterations in Olfactory Neuroepithelium Cell Populations.

PURPOSE OF REVIEW: Neurogenesis occurring in the olfactory epithelium is critical to continuously replace olfactory neurons to maintain olfactory function, but is impaired during chronic type 2 and non-type 2 inflammation of the upper airways. In this review, we describe the neurobiology of olfaction and the olfactory alterations in chronic rhinosinusitis with nasal polyps (type 2 inflammation) and post-viral acute rhinosinusitis (non-type 2 inflammation), highlighting the role of immune response attenuating olfactory neurogenesis as a possibly mechanism for the loss of smell in these diseases. RECENT FINDINGS: Several studies have provided relevant insights into the role of basal stem cells as direct participants in the progression of chronic inflammation identifying a functional switch away from a neuro-regenerative phenotype to one contributing to immune defense, a process that induces a deficient replacement of olfactory neurons. The interaction between olfactory stem cells and immune system might critically underlie ongoing loss of smell in type 2 and non-type 2 inflammatory upper airway diseases. In this review, we describe the neurobiology of olfaction and the olfactory alterations in type 2 and non-type 2 inflammatory upper airway diseases, highlighting the role of immune response attenuating olfactory neurogenesis, as a possibly mechanism for the lack of loss of smell recovery.

COVID-19 associated anosmia in pediatric patients: subject publications review.

OBJECTIVE: Aim: To review the publications subject to the problem of COVID-19 associated anosmia incidence in pediatric patients as well as its pathogenesis, diagnostics, treatment and recovery. The peculiarity of pediatric COVID-19 anosmia is due to children accounting for very low percentage of COVID-19 patients (comparing to one in adults), mostly with milder course of the disease. Awareness of anosmia and its proper diagnostics is crucial in children and adolescents, considering it can be the only manifestation in COVID-19 positive pediatric patients. PATIENTS AND METHODS: Materials and Methods: In order to achieve this goal a meta-analysis of information from databases followed by statistical processing and generalisation of the obtained data was carried out. CONCLUSION: Conclusions: Publications on COVID-19 anosmia in children and adolescents are less numerous than those concerning adult patients, so it is important to use every single trustworthy one. Anosmia/ageusia may be the only symptom, early identifier and the strongest predictor of COVID-19 infection in pediatric patients. Prospects for further scientific researches. Further researches regarding differential diagnostics of COVID-19 and other infections, including seasonal influenza, manifesting with both olfactory and taste dysfunction as well as anosmia diagnostics in children and adolescents with autistic spectrum and different types of mental disorders are possible.

Long-term smell loss experiences after COVID-19: A qualitative study.

OBJECTIVES: Sudden smell loss is one of the early symptoms of COVID-19. Although it is stated that the loss of smell and taste following COVID-19 improves within a few weeks, there are also cases that do not improve for a long time. The aim of this study is to reveal long-term smell loss experiences after COVID-19. METHODS: A qualitative approach was adopted. We conducted semistructured interviews with 11 participants who had smell loss for at least 3 months. Interviews were recorded, transcribed and evaluated using a thematic analysis for qualitative data. RESULTS: Nutrition and appetite, personal hygiene, threats to safety and emotional changes were the main themes created by the authors and were the areas where participant expressions focused. The participants used oral/nasal corticosteroid therapy for smell loss and received short-term olfactory training, but could not find a solution. CONCLUSIONS: Long-term smell loss problems, which were neglected during the pandemic period, should be carefully evaluated due to their negative effects. Understanding and focusing on the negative effects of loss of smell may contribute to the solution of long-term smell loss problems. PATIENT AND PUBLIC CONTRIBUTION: Eleven participants who experienced long-term loss of smell following COVID-19 contributed to the study. They enriched the study by describing the effects of their experiences. There was no other participation or contribution from the public to the research.

Sinonasal adenocarcinoma presented as a giant anterior cranial fossa mass: a case report and review of the literature.

BACKGROUND: Intestinal adenocarcinoma accounts for less than 0.1-4% of all malignancies in the region. It is common among woodworkers and leather workers. Sinonasal adenocarcinoma usually arises from the ethmoid sinus (40%) or nasal cavity (25%). Extension to nearby structures is common, but intracranial spread is very rare. These tumors are usually treated with surgery, with a reported 5-year survival rate of 59% to 80%. CASE PRESENTATION: This is a 60-year-old Black African male patient who presented with globalized headache, nasal obstruction with snoring during sleep, anosmia, change in mentation, sometimes agitation and left-side visual loss of one-year duration with worsening his above symptoms over the last one month. He couldn't smell soap bilaterally; in his left eye he could see only hand movement at nearly 30 cm. On brain magnetic resonance imaging, there was a T1 hypo- and T2 hyper-intense anterior cranial fossa mass arising from the left ethmoid sinuses and sphenoid sinuses and compressing the left optic structures, and brain computed tomography demonstrated heterogeneous hypo- to isodense mass. Complete tumor excision achieved and discharged with significant improvement and linked to oncology unit for radiotherapy. CONCLUSION: The management of these patients is multidisciplinary, involving neurosurgeons, otolaryngologists, oncologists, and maxillofacial surgeons. Surgical resection is the main treatment strategy, followed by radiotherapy, particularly intensity-modulated therapy. Chemotherapy is used in highly advanced, metastatic, and unresectable tumors.

Patterns of Olfactory Impairment Among Patients with Uncontrolled Chronic Rhinosinusitis.

OBJECTIVES: Self-reported olfactory dysfunction is an assessment component criterion for chronic rhinosinusitis (CRS) disease control of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS). No studies have objectively explored olfactory function across different psychophysical olfactory domains among patients with uncontrolled CRS. We aimed to investigate the patterns of olfactory impairment in patients with uncontrolled CRS with Sniffin' Sticks test. METHODS: A total of 79 patients with CRS were prospectively recruited and assessed for disease control based on the EPOS criteria. Sniffin' Sticks test scores, olfactory cleft computed tomography (CT) scores, olfactory cleft endoscopy scale (OCES), questionnaire of olfactory disorders-negative statements (QOD-NS), and sinonasal outcome test-22 (SNOT-22) were obtained. Multiple logistic regression was applied to explore risk factors of uncontrolled CRS. RESULTS: Twenty-six percent of patients with CRS presented with uncontrolled status. The odor threshold (OT) (p = 0.005), odor identification (OI) (p = 0.041), and thresholds-discrimination-identification (TDI) (p = 0.029) scores were significantly lower in patients with uncontrolled CRS when compared with patients with controlled CRS. Furthermore, patients with uncontrolled CRS presented with a significantly increased percentage of anosmia (p = 0.014), olfactory cleft CT score (p = 0.038), OCES (p = 0.016), QOD-NS(p = 0.008), and SNOT-22 (p < 0.001) scores than patients with controlled CRS. After adjusting for patient demographics, as for the subdomain of olfaction, only the OT score was an independent risk factor for uncontrolled CRS (odds ratio = 0.604; p = 0.030). The OT scores less than 5.950 were the best predictor of uncontrolled CRS. CONCLUSION: Patients with uncontrolled CRS demonstrated distinct patterns of olfactory impairment, and a reduced olfactory threshold was highly associated with uncontrolled CRS. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2341-2348, 2024.

Clinical characteristics of patients with Parkinson's disease with reduced 123I-metaiodobenzylguanidine uptake in the major salivary glands and heart.

BACKGROUND: Parkinson's disease (PD) shows cardiac sympathetic denervation (SD) in 123I-metaiodobezylguanidine (MIBG) scintigraphy. Recently, SD in the major salivary glands (MSG-SD) was introduced as a possible radiological feature of PD. OBJECTIVE: To identify the clinical characteristics of patients with PD with reduced MSG and cardiac MIBG uptake (dual-SD) compared with those with reduced MSG or cardiac MIBG uptake only (single-SD). METHODS: We recruited 90 patients with PD and 30 controls and evaluated their non-motor (e.g., hyposmia, autonomic dysfunction) and motor (e.g., Movement Disorder Society-Unified Parkinson's Disease Rating Scale) features. We also assessed MIBG uptake in the MSG and heart using a quantitative semi-automatic method, and compared MIBG uptakes between PD and controls. We set cut-off values for optimal sensitivity and specificity, and compared the clinical characteristics of patients with PD between dual- and single-SD groups. RESULTS: MSG and cardiac MIBG uptakes were significantly reduced in PD. Sixty-one patients had dual-SD, 25 had single-SD, and four had non-SD. In patients with PD with normal cardiac SD, 76.5% (13/17) of whom showed abnormalities only in MSG-SD. When clinical characteristics were compared between the dual-SD and single-/non-SD groups, patients in the dual-SD group were older and had more severe hyposmia and autonomic dysfunction, except motor features. Multiple logistic regression analysis identified age as an important confounder. CONCLUSIONS: Patients with PD with dual-SD have more severe non-motor features than other patients. Autonomic dysfunction might progress independently from dopaminergic degeneration. Furthermore, our findings indicate that aging is a crucial factor in PD progression.

Post-COVID-19 patients suffer from chemosensory, trigeminal, and salivary dysfunctions.

Recent literature indicates that post-COVID-19 patients suffer from a plethora of complications, including chemosensory dysfunction. However, little attention has been given to understand the interactions between chemosensory, trigeminal, and salivary dysfunctions in these patients. The aims of this study were (1) to investigate the prevalence and combinations of chemosensory, trigeminal, and salivary dysfunctions, (2) to identify the odorants/tastants that are compromised, and (3) to explore possible associations between the four dysfunctions in post-COVID-19 patients. One hundred post-COVID-19 patients and 76 healthy controls (pre-COVID-19) were included in this cross-sectional, case-controlled study. Participants' smell, taste, trigeminal, and salivary functions were assessed. The patients had a significantly higher prevalence of parosmia (80.0%), hyposmia (42.0%), anosmia (53.0%), dysgeusia (34.0%), complete ageusia (3.0%), specific ageusia (27.0%), dysesthesia (11.0%) and dry mouth (18.0%) compared to controls (0.0% for all parameters, except 27.6% for hyposmia). Complete loss of bitter taste was the most prevalent specific ageusia (66.7%) and coffee was the most common distorted smell (56.4%). Seven different combinations of dysfunction were observed in the patients, the most common being a combination of olfactory and gustatory dysfunction (48.0%). These findings indicate that post-COVID-19 patients experience a range of chemosensory, trigeminal, and salivary disturbances, occurring in various combinations.

Autoantibody profiles assessment in individuals with persistent olfactory impairment following SARS-CoV-2 infection.

BACKGROUND: Olfactory impairment, particularly hyposmia and anosmia, has emerged as a distinctive early symptom of SARS-CoV-2. Drawing on the historical association of autoimmune diseases with olfactory function, this study delves into the connections between COVID-19, autoimmunity, and persistent olfactory dysfunctions, focusing on individuals experiencing long-lasting smell disorders (3-18 months post-SARS-CoV-2 infection). METHODS: The study comprised 36 Long Covid patients with persistent olfactory dysfunctions, alongside two control groups. Olfactory functionality was assessed using the Sniffin' Sticks extended test. Non-invasive olfactory mucosa brushing and nasal secretions were processed for nasal samples, while serum samples were obtained through peripheral venous sampling. A panel of autoantibodies, including Immunocirculating Complexes, ANA, ENA, and AECA, was investigated in serum and brush supernatant samples. RESULTS: Contrary to expectations, the absence of traditional autoantibodies challenges the proposed autoimmune etiology of Long Covid-associated olfactory dysfunction. However, the presence and potential pathogenic role of AECA suggest viral cytopathic and inflammatory involvement in specific anatomical districts. One hypothesis explores the impact of inflammation and cytokine release induced by the viral infection, altering neuronal signaling and contributing to persistent hyposmia. CONCLUSION: This research contributes to our understanding of the complex relationships between autoimmunity, olfactory impairment, and COVID-19. The absence of classical autoantibodies challenges prevailing theories, while the prominence of AECA hints at unique viral-induced pathogenic mechanisms. By unraveling these complexities, this study enhances our comprehension of post-acute sequelae, offering valuable perspectives on immune-mediated responses in the aftermath of the pandemic.

Early corticosteroid treatment enhances recovery from SARS-CoV-2 induced loss of smell in hamster.

Among the numerous long COVID symptoms, olfactory dysfunction persists in ∼10 % of patients suffering from SARS-CoV-2 induced anosmia. Among the few potential therapies, corticoid treatment has been used for its anti-inflammatory effect with mixed success in patients. In this study, we explored its impact using hamster as an animal model. SARS-CoV-2 infected hamsters lose their smell abilities and this loss is correlated with damage of the olfactory epithelium and persistent presence of innate immunity cells. We started a dexamethasone treatment 2 days post infection, when olfaction was already impacted, until 11 days post infection when it started to recover. We observed an improvement of olfactory capacities in the animals treated with corticoid compared to those treated with vehicle. This recovery was not related to differences in the remaining damage to the olfactory epithelium, which was similar in both groups. This improvement was however correlated with a reduced inflammation in the olfactory epithelium with a local increase of the mature olfactory neuron population. Surprisingly, at 11 days post infection, we observed an increased and disorganized presence of immature olfactory neurons, especially in persistent inflammatory zones of the epithelium. This unusual population of immature olfactory neurons coincided with a strong increase of olfactory epithelium proliferation in both groups. Our results indicate that persistent inflammation of the olfactory epithelium following SARS-CoV-2 infection may alter the extent and speed of regeneration of the olfactory neuron population, and that corticoid treatment is effective to limit inflammation and improve olfaction recovery following SARS-CoV-2 infection.

Odor dilution sorting as a clinical test of olfactory function: normative values and reliability data.

Clinical assessment of an individual's sense of smell has gained prominence, but its resource-intensive nature necessitates the exploration of self-administered methods. In this study, a cohort of 68 patients with olfactory loss and 55 controls were assessed using a recently introduced olfactory test. This test involves sorting 2 odorants (eugenol and phenylethyl alcohol) in 5 dilutions according to odor intensity, with an average application time of 3.5 min. The sorting task score, calculated as the mean of Kendall's Tau between the assigned and true dilution orders and normalized to [0,1], identified a cutoff for anosmia at a score ≤ 0.7. This cutoff, which marks the 90th percentile of scores obtained with randomly ordered dilutions, had a balanced accuracy of 89% (78% to 97%) for detecting anosmia, comparable to traditional odor threshold assessments. Retest evaluations suggested a score difference of ±0.15 as a cutoff for clinically significant changes in olfactory function. In conclusion, the olfactory sorting test represents a simple, self-administered approach to the detection of anosmia or preserved olfactory function. With balanced accuracy similar to existing brief olfactory tests, this method offers a practical and user-friendly alternative for screening anosmia, addressing the need for resource-efficient assessments in clinical settings.

Olfaction and Mobility in Older Adults.

Importance: Decreased mobility is a hallmark of aging. Olfactory dysfunction is common in older adults and may be associated with declines in mobility. Objective: To determine whether poor olfaction was associated with faster declines in mobility in older adults. Design, Setting, and Participants: This cohort study included 2500 participants from the Health, Aging, and Body Composition Study. Participants completed the Brief Smell Identification Test during the year 3 clinical visit (1999-2000) and were followed for up to 7 years. A data analysis was conducted between January and July 2023. Exposures: Olfaction was defined as good (test score, 11-12), moderate (9-10), hyposmia (7-8), or anosmia (0-6). Main Outcomes and Measures: Mobility was measured using the 20-m usual and fast walking tests in clinical visit years 3 to 6, 8, and 10 and the 400-m fast walking test in years 4, 6, 8, and 10. Results: The primary analyses included 2500 participants (1292 women [51.7%]; 1208 men [48.3%]; 960 Black [38.4%] and 1540 White [61.6%] individuals; mean [SD] age, 75.6 [2.8] years). Multivariate-adjusted analyses showed that poor olfaction was associated with slower walking speed at baseline and a faster decline over time. Taking the 20-m usual walking test as an example, compared with participants with good olfaction, the speed at baseline was 0.027 (95% CI, 0-0.053) m/s slower for those with hyposmia and 0.034 (95% CI, 0.005-0.062) m/s slower for those with anosmia. Longitudinally, the annual decline was 0.004 (95% CI, 0.002-0.007) m/s/year faster for those with hyposmia and 0.01 (95% CI, 0.007-0.013) m/s/year faster for those with anosmia. Similar results were obtained for the 20-m and 400-m fast walking tests. Further, compared with participants with good olfaction, the odds of being unable to do the 400-m test were 2.02 (95% CI, 1.17-3.48) times higher for those with anosmia at the year 8 visit and 2.73 (95% CI, 1.40-5.35) times higher at year 10. Multiple sensitivity and subgroup analyses supported the robustness and generalizability of the findings. Conclusion and Relevance: The results of this cohort study suggest that poor olfaction is associated with a faster decline in mobility in older adults. Future studies should investigate underlying mechanisms and potential health implications.

Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

The predictive role of symptoms in COVID-19 diagnostic models: A longitudinal insight.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%-22.7%) in participants reporting loss of appetite and 31.9% (27.1%-36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms' dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.

Diagnosed and subjectively perceived long-term effects of COVID-19 infection on olfactory function assessed by supervised machine learning.

Loss of olfactory function is a typical acute coronavirus disease 2019 (COVID-19) symptom, at least in early variants of SARS-CoV2. The time that has elapsed since the emergence of COVID-19 now allows for assessing the long-term prognosis of its olfactory impact. Participants (n = 722) of whom n = 464 reported having had COVID-19 dating back with a mode of 174 days were approached in a museum as a relatively unbiased environment. Olfactory function was diagnosed by assessing odor threshold and odor identification performance. Subjects also rated their actual olfactory function on an 11-point numerical scale [0,…10]. Neither the frequency of olfactory diagnostic categories nor olfactory test scores showed any COVID-19-related effects. Olfactory diagnostic categories (anosmia, hyposmia, or normosmia) were similarly distributed among former patients and controls (0.86%, 18.97%, and 80.17% for former patients and 1.17%, 17.51%, and 81.32% for controls). Former COVID-19 patients, however, showed differences in their subjective perception of their own olfactory function. The impact of this effect was substantial enough that supervised machine learning algorithms detected past COVID-19 infections in new subjects, based on reduced self-awareness of olfactory performance and parosmia, while the diagnosed olfactory function did not contribute any relevant information in this context. Based on diagnosed olfactory function, results suggest a positive prognosis for COVID-19-related olfactory loss in the long term. Traces of former infection are found in self-perceptions of olfaction, highlighting the importance of investigating the long-term effects of COVID-19 using reliable and validated diagnostic measures in olfactory testing.

Diagnostic accuracy of the screenings Sniffin' Sticks Test (SST-12) in COVID-19 induced olfactory disorders.

Objective olfactory function can be assessed using validated olfactory tests like the Sniffin' Sticks Test (SST). However, their extensive nature makes them less suitable for clinical practice. To address this, shorter olfactory tests like the screenings Sniffin' Sticks Test (SST-12) can be used for screening purposes and reduce testing time. The SST-12 serves as a diagnostic tool for screening olfaction in cases unrelated to COVID-19. However, these screening tests are uncertain regarding their accuracy in detecting olfactory dysfunction in patients with COVID-19 as the plausible cause. We aim to determine the diagnostic accuracy of the SST-12 in adults with post-COVID-19 olfactory dysfunction. We performed a diagnostic accuracy study with data from 113 consecutive COVID-19 diagnosed patients who experienced objectified smell loss ever since. At approximately 6 months after their diagnosis, all participants underwent the SST (reference standard), part of the SST was the SST-12 (index test). Diagnostic accuracy of the SST-12 is measured as negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity. The SST-12 detected smell loss in 85 patients among 91 patients with smell loss and ruled out smell loss in 15 patients among the 22 patients without smell loss based on the reference standard. Making sensitivity 93.4% (CI 0.87-0.97), and specificity 68.2% (CI 0.48-0.85). Out of the 92 patients with a positive test result on SST-12, 85 patients had indeed smell loss (PPV 92.4% CI 0.86-0.97), and out of the 21 patients with a negative test result, 15 patients had no smell loss regarding the reference standard (NPV 71.4% CI 0.50-0.88). The findings suggest that the SST-12 holds promise as a useful tool for identifying individuals with smell loss, also in individuals with COVID-19 as cause, but it is important to have a good understanding of the interpretation of the results of the SST-12 when considering its implementation in clinical practice.

Risk stratification for phenoconversion in patients with isolated REM sleep behavior disorder. A follow-up study from Turkey. / Estratificación del riesgo de fenoconversión al parkinsonismo en pacientes con trastorno de conducta del sueño REM aislado. Estudio de seguimiento en un centro de Turquía.

INTRODUCTION: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is one of the strongest prodromal markers of alpha-synucleinopathies. We aimed to investigate non-invasive clinical and quantitative predictors of phenoconversion from iRBD to parkinsonism. PATIENTS AND METHODS: We prospectively followed-up a total of 45 patients (57.8% men) for eight years. Clinical assessments, Sniffin' Sticks Odor Identification Test, Farnsworth-Munsell 100 Hue Color Vision test, Beck Depression Inventory and Rome III Criteria for constipation were performed. Polysomnographic parameters, sleep spindles, electroencephalographic (EEG) spectral analysis, heart rate variability (HRV) were analyzed. RESULTS: Eight patients (17.8%) showed phenoconversion to parkinsonism after a mean duration of 3.2 ± 1 years. Odds ratio for predicting phenoconversion was highest for patients =60 years of age with anosmia and constipation -44.8 (4.5-445.7); kappa = 4.291-. Duration, frequency or density of sleep spindles failed to demonstrate significant correlations. In EEG spectral analysis, lower alpha power in occipital region during wakefulness and REM sleep was significantly correlated with phenoconversion. Slowing in EEG spectrum power, together with age =60 years, anosmia and constipation, resulted in the highest odds ratio -122.5 (9.7-1543.8); kappa = 3.051-. CONCLUSIONS: It is of great importance to have a world-wide perspective of phenoconversion rates from iRBD to overt neurodegeneration, since racial and geographical factors may play important modifying roles. Relatively younger age and shorter disease duration may also be confounding factors for lower rate in our study. Neurophysiological biomarkers seem to be important predictors of phenoconversion, though more research is needed to establish subtypes of iRBD with different probabilities of evolution to overt synucleinopathy.

TITLE: Estratificación del riesgo de fenoconversión al parkinsonismo en pacientes con trastorno de conducta del sueño REM aislado. Estudio de seguimiento en un centro de Turquía.Introducción. El trastorno aislado de la conducta del sueño con movimientos oculares rápidos (iRBD) es uno de los marcadores prodrómicos más potentes de las alfa-sinucleinopatías. Nuestro objetivo fue investigar los predictores clínicos y cuan­titativos no invasivos de la fenoconversión de iRBD a parkinsonismo. Pacientes y métodos. Se siguió prospectivamente a un total de 45 pacientes (57,8% hombres) durante ocho años del período de estudio. Se realizaron evaluaciones clínicas, la prueba de identificación de olores Sniffin' Sticks, la prueba Farnsworth-Munsell 100 Hue Color Vision, el inventario de depresión de Beck y los criterios de Roma III para el estreñimiento. Se analizaron parámetros polisomnográficos, husos del sueño, análisis espectral electroencefalográfico (EEG) y variabilidad de la frecuencia cardíaca. Resultados. Ocho pacientes (17,8%) mostraron fenoconversión a parkinsonismo después de una duración media de seguimiento de 3,2 ± 1 año. La odds ratio para predecir la fenoconversión fue más alta para los pacientes =60 años con anosmia y estreñimiento ­44,8 (4,5-445,7); kappa = 4,291­. La disminución de la potencia del espectro EEG, junto con la edad =60 años, la anosmia y el estreñimiento, dio como resultado el índice de odds más alto ­122,5 (9,7-1543,8); kappa = 3,051­. Conclusiones. Es de gran importancia tener una perspectiva mundial de las tasas de fenoconversión de iRBD a neurodegeneración manifiesta, ya que los factores raciales y geográficos pueden desempeñar importantes papeles modificadores. Los biomarcadores neurofisiológicos parecen ser predictores importantes de la fenoconversión, aunque se necesita más investigación para establecer subtipos de iRBD con diferentes probabilidades de evolución hacia una sinucleinopatía manifiesta.

Disparities in Olfactory Dysfunction in African Americans.

OBJECTIVES: To examine olfactory performance in African Americans (AA) and Whites by comparing individual scent scores on objective olfactory tests to assess potential racial-ethnic differences of scent detection. METHODS: Cross-sectional study of healthy participants, age 18+ years, and without sinonasal inflammatory disease from June 2021 to April 2022. Included participants self-identified as AA or White. Patients were recruited from outpatient clinics at University of Kansas Medical Center, and the local community. Two smelling tests were employed: Affordable Rapid Olfactory Measurement Array (AROMA) and Sniffin' Sticks (SST-12). Sino-Nasal Outcome Test (SNOT-22) was used for self-reported olfactory function . Pearson correlation and chi-square tests were used to detect statistical significance. RESULTS: Our sample included 102 (46 AA and 56 Whites) participants. AROMA and SST-12 scores were significantly correlated in AA (P < .01, Pearson's Rho = .642) and Whites (P < .05, Pearson's Rho = .297). Mean scores on AROMA were significantly lower for AAs: 64.2 and Whites: 75.5 (P < .01). On AROMA, AA less accurately identified the scents of Licorice, Orange, Lavender, Cinnamon, Clove, and Rosemary (P < .05). Similarly, SST-12 mean scores for AAs: 84.2 were also lower than Whites: 89.9 (P < .01). On SST-12, AA less accurately identified the scent of pineapple Based on SST-12 scoring criteria, 60.9% of AA and 30.4% of Whites were classified as hyposmic (P < .05). SNOT-22 Smell scores were equivalent for both groups. CONCLUSION: On both tests of olfaction, AA performed worse than Whites and a greater proportion of AA were considered hyposmic compared to Whites. This is a discrepancy with self-reported olfaction, which showed no difference between Whites and AA. AA performed significantly worse than their White counterparts on several scents, with possible implications regarding cultural appropriateness of scents used in olfactory testing.

Subjective Smell Disturbances in Children with Sars-Cov-2 or Other Viral Infections do not Correspond with Olfactory Test Results.

BACKGROUND: Olfactory dysfunction associated with SARS-CoV-2 infection in children has not been verified by a validated olfactory test. We aimed to determine whether these complaints are objectifiable (test-based hyposmia), how often they occur during acute SARS-CoV-2 infection compared to other upper respiratory tract infections (URTI), as well as in children recovered from COVID-19 compared to children with long COVID. METHODS: Olfactory testing (U-sniff test; hyposmia<8 points) and survey-based symptom assessments were performed in 434 children (5-17 years; 04/2021-06/2022). 186 symptom-free children served as controls. Of the children with symptoms of acute respiratory tract infection, SARS-CoV-2 PCR test results were positive in 45 and negative in 107 children (URTI group). Additionally, 96 children were recruited at least 4 weeks (17.6±15.2 weeks) after COVID-19, of whom 66 had recovered and 30 had developed long COVID. RESULTS: Compared to controls (2.7%), hyposmia frequency was increased in all other groups (11-17%, p<0.05), but no between-group differences were observed. Only 3/41 children with hyposmia reported complaints, whereas 13/16 children with complaints were normosmic, with the largest proportion being in the long-COVID group (23%, p<0.05). CONCLUSION: Questionnaires are unsuitable for assessing hyposmia frequency in children. Olfactory complaints and hyposmia are not specific for SARS-CoV-2 infection. The number of complaints in the long-COVID group could result from aversive olfactory perception, which is undetectable with the U-sniff test.

Reduced olfactory performance is associated with changed microbial diversity, oralization, and accumulation of dead biomaterial in the nasal olfactory area.

The partial or complete loss of the sense of smell, which affects about 20% of the population, impairs the quality of life in many ways. Dysosmia and anosmia are mainly caused by aging, trauma, infections, or even neurodegenerative disease. Recently, the olfactory area-a site containing the olfactory receptor cells responsible for odor perception-was shown to harbor a complex microbiome that reflects the state of olfactory function. This initially observed correlation between microbiome composition and olfactory performance needed to be confirmed using a larger study cohort and additional analyses. A total of 120 participants (middle-aged, no neurodegenerative disease) were enrolled in the study to further analyze the microbial role in human olfactory function. Olfactory performance was assessed using the Sniffin' Stick battery, and participants were grouped accordingly (normosmia: n = 93, dysosmia: n = 27). The olfactory microbiome was analyzed by 16S rRNA gene amplicon sequencing and supplemented by metatranscriptomics in a subset (Nose 2.0). Propidium monoazide (PMA) treatment was performed to distinguish between intact and non-intact microbiome components. The gastrointestinal microbiome of these participants was also characterized by amplicon sequencing and metabolomics and then correlated with food intake. Our results confirm that normosmics and dysosmics indeed possess a distinguishable olfactory microbiome. Alpha diversity (i.e., richness) was significantly increased in dysosmics, reflected by an increase in the number of specific taxa (e.g., Rickettsia, Spiroplasma, and Brachybacterium). Lower olfactory performance was associated with microbial signatures from the oral cavity and periodontitis (Fusobacterium, Porphyromonas, and Selenomonas). However, PMA treatment revealed a higher accumulation of dead microbial material in dysosmic subjects. The gastrointestinal microbiome partially overlapped with the nasal microbiome but did not show substantial variation with respect to olfactory performance, although the diet of dysosmic individuals was shifted toward a higher meat intake. Dysosmia is associated with a higher burden of dead microbial material in the olfactory area, indicating an impaired clearance mechanism. As the microbial community of dysosmics (hyposmics and anosmics) appears to be influenced by the oral microbiome, further studies should investigate the microbial oral-nasal interplay in individuals with partial or complete olfactory loss.IMPORTANCEThe loss of the sense of smell is an incisive event that is becoming increasingly common in today's world due to infections such as COVID-19. Although this loss usually recovers a few weeks after infection, in some cases, it becomes permanent-why is yet to be answered. Since this condition often represents a psychological burden in the long term, there is a need for therapeutic approaches. However, treatment options are limited or even not existing. Understanding the role of the microbiome in the impairment of olfaction may enable the prediction of olfactory disorders and/or could serve as a possible target for therapeutic interventions.

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.