Inflammation-related pathology in the olfactory epithelium: its impact on the olfactory system in psychotic disorders.

Smell deficits and neurobiological changes in the olfactory bulb (OB) and olfactory epithelium (OE) have been observed in schizophrenia and related disorders. The OE is the most peripheral olfactory system located outside the cranium, and is connected with the brain via direct neuronal projections to the OB. Nevertheless, it is unknown whether and how a disturbance of the OE affects the OB in schizophrenia and related disorders. Addressing this gap would be the first step in studying the impact of OE pathology in the disease pathophysiology in the brain. In this cross-species study, we observed that chronic, local OE inflammation with a set of upregulated genes in an inducible olfactory inflammation (IOI) mouse model led to a volume reduction, layer structure changes, and alterations of neuron functionality in the OB. Furthermore, IOI model also displayed behavioral deficits relevant to negative symptoms (avolition) in parallel to smell deficits. In first episode psychosis (FEP) patients, we observed a significant alteration in immune/inflammation-related molecular signatures in olfactory neuronal cells (ONCs) enriched from biopsied OE and a significant reduction in the OB volume, compared with those of healthy controls (HC). The increased expression of immune/inflammation-related molecules in ONCs was significantly correlated to the OB volume reduction in FEP patients, but no correlation was found in HCs. Moreover, the increased expression of human orthologues of the IOI genes in ONCs was significantly correlated with the OB volume reduction in FEP, but not in HCs. Together, our study implies a potential mechanism of the OE-OB pathology in patients with psychotic disorders (schizophrenia and related disorders). We hope that this mechanism may have a cross-disease implication, including COVID-19-elicited mental conditions that include smell deficits.

Impact of obstructive sleep apnea syndrome on olfactory and gustatory capacity.

Only a few studies have investigated olfactory function in patients with obstructive sleep apnea syndrome (OSAS) using psychophysical testing, and there is a scarcity of data regarding taste evaluation in the existing literature. The primary objectives of this study were to assess both smell and taste in patients with OSAS and to explore the correlation between the severity of symptoms and sensory perception. A total of 85 OSAS patients and a control group comprising 81 subjects were enrolled. Initial assessments included anamnesis, nasal endoscopy, and the completion of questionnaires (Epworth Sleepiness Scale, Visual Analogue Scale, Questionnaire of Olfactory Disorders, and the importance of olfaction questionnaire). The diagnosis of OSAS was confirmed by polysomnography, while nasal airflow was evaluated using rhinomanometry. Olfaction was assessed using the Sniffin' Sticks test, and the Threshold-Discrimination-Identification (TDI) score was calculated. Taste evaluation was conducted in a subgroup of participants (42 patients, 38 controls) using taste strips. The mean TDI score was 31 ±â€…5.6 for OSAS patients and 35 ±â€…4.6 for controls, indicating a significant difference (P < 0.001). Similarly, the taste score was 7 ±â€…3.0 for OSAS patients and 12.6 ±â€…3.2 for controls (P < 0.001). No correlations were observed between TDI and Apnea Hypopnea Index (AHI) (r = -0.12; P = 0.28), as well as between the taste score and AHI (r = -0.31; P = 0.22). However, a weak but significant correlation between TDI score and Epworth Sleepiness Scale was detected (r = -0.05; P = 0.002). The study revealed a significant decrease in sensory perception among patients with OSAS, though open questions persist about the pathophysiology.

Hyposmia correlates with axial signs and gait disorder in Parkinson's disease: an Italian Olfactory Identification Test study.

BACKGROUND: Olfactory dysfunction is a non-motor symptom and an important biomarker of Parkinson's disease (PD) because of its high prevalence (> 90%). Whether hyposmia correlates with motor symptoms is unclear. In the present study, we aim to investigate the relationship between olfactory impairment with both motor and non-motor features and disease variables (disease duration, stage, and severity). METHODS: One-hundred fifty-four PD patients were evaluated. Odor identification ability was tested using Italian Olfactory Identification Test (IOIT). A comprehensive spectrum of motor and non-motor features was assessed. Cognitive function was investigated through MMSE. Patients were divided into 3 different clinical phenotypes using UPDRS-III: tremor-dominant type (TDT), akinetic-rigid type (ART), and mixed type (MXT). RESULTS: Three of the 33 IOIT items were most frequently misidentified: basil (74.3%), coffee (66.9%), and mushroom (59.6%). Hyposmia was found in 93%. Hyposmic patients were older than controls (p = 0.01). Hoehn & Yahr (H&Y) score of 2 or greater was associated with higher probability of being hyposmic (OR = 5.2, p = 0.01). IOIT score did not significantly differ between TDT, ART, and MXT of analyzed PD patients. Performance to IOIT inversely correlated with age (p < 0.01), disease duration (p = 0.01), and H&Y score of 2 or higher (p < 0.01). Clinical features that associated with higher IOIT score were freezing of gait (FOG) (p < 0.001) and camptocormia (p < 0.05). CONCLUSIONS: In our cohort, IOIT scores showed a positive correlation with axial motor signs, but not with non-motor symptoms. IOIT may be a useful tool not only for supporting PD diagnosis but also for providing prognostic information about motor function.

Long-term effects of SARS-CoV-2 infection in patients with and without chemosensory disorders at disease onset: a psychophysical and magnetic resonance imaging exploratory study.

A preserved sense of smell and taste allows us to understand many environmental "messages" and results in meaningfully improvements to quality of life. With the COVID-19 pandemic, it became clear how important these senses are for social and nutritional status and catapulted this niche chemosensory research area towards widespread interest. In the current exploratory work, we assessed two groups of post-COVID-19 patients who reported having had (Group 1) or not (Group 2) a smell/taste impairment at the disease onset. The aim was to compare them using validated smell and taste tests as well as with brain magnetic resonance imaging volumetric analysis. Normative data were used for smell scores comparison and a pool of healthy subjects, recruited before the pandemic, served as controls for taste scores. The majority of patients in both groups showed an olfactory impairment, which was more severe in Group 1 (median UPSIT scores: 24.5 Group 1 vs 31.0 Group 2, p = 0.008), particularly among women (p = 0.014). No significant differences emerged comparing taste scores between Group 1 and Group 2, but dysgeusia was only present in Group 1 patients. However, for taste scores, a significant difference was found between Group 1 and controls (p = 0.005). No MRI anatomical abnormalities emerged in any patients while brain volumetric analysis suggested a significant difference among groups for the right caudate nucleus (p = 0.028), although this was not retained following Benjamini-Hochberg correction. This exploratory study could add new information in COVID-19 chemosensory long-lasting impairment and address future investigations on the post-COVID-19 patients' research.

Predictors of the Rapid Progression in Prodromal Parkinson's Disease: A Longitudinal Follow-Up Study.

INTRODUCTION: Parkinson's disease (PD) is characterized by a prodromal phase preceding the onset of classic motor symptoms. The duration and clinical manifestations of prodromal PD vary widely, indicating underlying heterogeneity within this stage. This discrepancy prompts the question of whether specific factors contribute to the divergent rates of progression in prodromal PD. METHODS: This study included prodromal PD patients from the Parkinson's progression marker initiative. They were followed up to assess the disease progression. The data collected during the follow-up period were analyzed to identify potential predictors of rapid disease progression in prodromal PD. RESULTS: In this study, 61 individuals with prodromal PD were enrolled. Among them, 43 patients presented with both RBD and hyposmia, 17 had hyposmia alone, and 1 had RBD alone at baseline. 13 (21.3%) prodromal PD participants exhibited rapid disease progression, with two of these cases advancing to non-neurological diseases. Significant differences were observed between the rapid progression group and no rapid progression group in terms of MDS-UPDRS II score and UPSIT score. Longitudinal analysis showed a significant increase in the MDS-UPDRS III score and MDS-UPDRS total score in the rapid progression group. Regression analyses identified the MDS-UPDRS II score and UPSIT score as predictors of rapid disease progression in prodromal PD. CONCLUSION: Our study findings suggest that the MDS-UPDRS II score and UPSIT score may serve as clinical markers associated with rapid disease progression. Further research and development of precise biomarkers and advanced assessment methods are needed to enhance our understanding of prodromal PD and its progression patterns.

Olfactory Loss in Rhinosinusitis: Mechanisms of Loss and Recovery.

Chronic rhinosinusitis (CRS) is a highly prevalent disease and up to 83% of CRS patients suffer from olfactory dysfunction (OD). Because OD is specifically seen in those CRS patients that present with a type 2 eosinophilic inflammation, it is believed that type 2 inflammatory mediators at the level of the olfactory epithelium are involved in the development of this olfactory loss. However, due to the difficulties in obtaining tissue from the olfactory epithelium, little is known about the true mechanisms of inflammatory OD. Thanks to the COVID-19 pandemic, interest in olfaction has been growing rapidly and several studies have been focusing on disease mechanisms of OD in inflammatory conditions. In this paper, we summarize the most recent data exploring the pathophysiological mechanisms underlying OD in CRS. We also review what is known about the potential capacity of olfactory recovery of the currently available treatments in those patients.

Intra and inter-regional functional connectivity of the human brain due to Task-Evoked fMRI Data classification through CNN & LSTM.

BACKGROUND AND PURPOSE: Olfaction is an early marker of neurodegenerative disease. Standard olfactory function is essential due to the importance of olfaction in human life. The psychophysical evaluation assesses the olfactory function commonly. It is patient-reported, and results rely on the patient's answers and collaboration. However, methodological difficulties attributed to the psychophysical evaluation of olfactory-related cerebral areas led to limited assessment of olfactory function in the human brain. MATERIALS AND METHODS: The current study utilized clustering approaches to assess olfactory function in fMRI data and used brain activity to parcellate the brain with homogeneous properties. Deep neural network architecture based on ResNet convolutional neural networks (CNN) and Long Short-Term Model (LSTM) designed to classify healthy with olfactory disorders subjects. RESULTS: The fMRI result obtained by k-means unsupervised machine learning model was within the expected outcome and similar to those found with the conn toolbox in detecting active areas. There was no significant difference between the means of subjects and every subject. Proposing a CRNN deep learning model to classify fMRI data in two different healthy and with olfactory disorders groups leads to an accuracy score of 97 %. CONCLUSIONS: The K-means unsupervised algorithm can detect the active regions in the brain and analyze olfactory function. Classification results prove the CNN-LSTM architecture using ResNet provides the best accuracy score in olfactory fMRI data. It is the first attempt conducted on olfactory fMRI data in detail until now.

[Features of olfactory impairment connected with trigeminal nerve system]. / Osobennosti narusheniya obonyaniya v aspekte sistemy troinichnogo nerva.

Data on the state of sense of smell in patients who had a new coronavirus infection caused by the SARS-CoV-2 virus are currently reduced because of the impairment of the olfactory nerve system. There are practically no results in studies of disorders in the trigeminal nerve system. OBJECTIVE: Qualitative assessment of olfactory disorders after COVID-19 according to the system of olfactory and trigeminal nerves with a targeted assessment of the functional component of olfactory disorders. MATERIAL AND METHODS: We examined 40 patients aged 19 to 66 who had a coronavirus infection. All patients underwent neurological, otorhinolaryngological examinations, olfactometry, filled out the hospital anxiety and depression scale. RESULTS: Anosmia was diagnosed in 5 (12.5%) patients, hyposmia in 21 (52.5%) patients, and normosmia in 14 (35%) patients. Formed: the 1st group - 14 patients (35%) with normogram according to olfactometry; the 2nd group - 26 patients (65%) with anosmia/hyposmia. In the 1st group, disorders of the anxiety-depressive spectrum were significantly more common. In the 2nd group, a low identification of odors was found, lying in the spectrum of fresh, sharp, unpleasant, irritating, compared with sweet and pleasant or neutral, which indicates a predominant lesion of the trigeminal system. CONCLUSION: In patients with complaints of impaired sense of smell after undergoing COVID-19, the possible functional nature of anosmia/hyposmia should be taken into account, which requires the referral of such patients to psychotherapeutic specialists, and the possible entry of olfactory disorders into the 'trigeminal' spectrum.

Incidence, clinical, risk factors and outcomes of Guillain-Barré in Covid-19.

We diagnosed 11 Guillain-Barré syndrome (GBS) cases among 71,904 COVID patients attended at 61 Spanish emergency departments (EDs) during the 2-month pandemic peak. The relative frequency of GBS among ED patients was higher in COVID (0.15‰) than non-COVID (0.02‰) patients (odds ratio [OR] = 6.30, 95% confidence interval [CI] = 3.18-12.5), as was the standardized incidence (9.44 and 0.69 cases/100,000 inhabitant-years, respectively, OR = 13.5, 95% CI = 9.87-18.4). Regarding clinical characteristics, olfactory-gustatory disorders were more frequent in COVID-GBS than non-COVID-GBS (OR = 27.59, 95% CI = 1.296-587) and COVID-non-GBS (OR = 7.875, 95% CI = 1.587-39.09) patients. Although COVID-GBS patients were more frequently admitted to intensive care, mortality was not increased versus control groups. Our results suggest SARS-CoV-2 could be another viral infection causing GBS. ANN NEUROL 2021;89:598-603.

Normal Olfactory Functional Connectivity Despite Lifelong Absence of Olfactory Experiences.

Congenital blindness is associated with atypical morphology and functional connectivity within and from visual cortical regions; changes that are hypothesized to originate from a lifelong absence of visual input and could be regarded as a general (re) organization principle of sensory cortices. Challenging this is the fact that individuals with congenital anosmia (lifelong olfactory sensory loss) display little to no morphological changes in the primary olfactory cortex. To determine whether olfactory input from birth is essential to establish and maintain normal functional connectivity in olfactory processing regions, akin to the visual system, we assessed differences in functional connectivity within the olfactory cortex between individuals with congenital anosmia (n = 33) and matched controls (n = 33). Specifically, we assessed differences in connectivity between core olfactory processing regions as well as differences in regional homogeneity and homotopic connectivity within the primary olfactory cortex. In contrast to congenital blindness, none of the analyses indicated atypical connectivity in individuals with congenital anosmia. In fact, post-hoc Bayesian analysis provided support for an absence of group differences. These results suggest that a lifelong absence of olfactory experience has a limited impact on the functional connectivity in the olfactory cortex, a finding that indicates a clear difference between sensory modalities in how sensory cortical regions develop.

Predictors of smell recovery in a nationwide prospective cohort of patients with COVID-19.

OBJECTIVE: To determine which factors (demographic, symptoms, comorbidities, and treatments) are associated with recovery of smell in patients with COVID-19 associated olfactory loss. STUDY DESIGN: Prospective, longitudinal questionnaires. SETTING: National survey. METHODS: A longitudinal web-based nationwide survey of adults with COVID-19 associated smell and taste loss was launched April 10, 2020. After completing an initial entry survey, participants received detailed follow-up questionnaires 14 days, and 1, 3 and 6 months later. RESULTS: As of June 25, 2021, 798 participants met study inclusion criteria and completed 6-month questionnaires. Of demographic characteristics only age <40 years was positively associated with smell recovery (p < .003). Of symptoms, difficulty breathing was negatively associated with smell recovery (p < .004), and nasal congestion positively associated with smell recovery (p < .03). Of pre-existing comorbidities only previous head injury (p < .017) was negatively associated with smell recovery. None of the queried medications used to treat COVID were associated with better rates of smell recovery. CONCLUSIONS: Age <40 and presence of nasal congestion at time of COVID-19 infection were predictive of improved rates of smell recovery, while difficulty breathing at time of COVID-19 infection, and prior head trauma predicted worsened rates of recovery. Further study will be required to identify potential mechanisms for the other observed associations. Such information can be used by clinicians to counsel patients suffering COVID-19 associated smell loss as to prognosis for recovery.

Persistent symptoms 1.5-6 months after COVID-19 in non-hospitalised subjects: a population-based cohort study.

This study assessed symptoms and their determinants 1.5-6 months after symptom onset in non-hospitalised subjects with confirmed COVID-19 until 1 June 2020, in a geographically defined area. We invited 938 subjects; 451 (48%) responded. They reported less symptoms after 1.5-6 months than during COVID-19; median (IQR) 0 (0-2) versus 8 (6-11), respectively (p<0.001); 53% of women and 67% of men were symptom free, while 16% reported dyspnoea, 12% loss/disturbance of smell, and 10% loss/disturbance of taste. In multivariable analysis, having persistent symptoms was associated with the number of comorbidities and number of symptoms during the acute COVID-19 phase.

COVID-19: A Global Threat to the Nervous System.

In less than 6 months, the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID-19) also involves multiple other organs, including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS-CoV-2 infection is rapidly accumulating. These may result from a variety of mechanisms, including virus-induced hyperinflammatory and hypercoagulable states, direct virus infection of the central nervous system (CNS), and postinfectious immune mediated processes. Example of COVID-19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis, and endothelialitis. In the peripheral nervous system, COVID-19 is associated with dysfunction of smell and taste, muscle injury, the Guillain-Barre syndrome, and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID-19 poses a global threat to the entire nervous system. Although our understanding of SARS-CoV-2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID-19. ANN NEUROL 2020;88:1-11 ANN NEUROL 2020;88:1-11.

Data Science-Based Analysis of Patient Subgroup Structures Suggest Effects of Rhinitis on All Chemosensory Perceptions in the Upper Airways.

Viral rhinitis contributes significantly to olfactory dysfunction, but it is unclear how many patients have other chemosensory symptoms in addition to olfactory loss. This was addressed in the present reanalysis of data previously published in Pellegrino R, Walliczek-Dworschak U, Winter G, Hull D, Hummel T. 2017. Investigation of chemosensitivity during and after an acute cold. Int Forum Allergy Rhinol. 7(2):185-191, using unsupervised and supervised machine-learning methods. Fifty-eight patients with acute rhinitis and 59 healthy controls were assessed for orthonasal and retronasal olfactory function, taste, and intranasal trigeminal sensitivity. Unsupervised analysis showed that during rhinitis, clinical scores of olfactory function, expressed as threshold, discrimination, identification (TDI) values, were trimodally distributed. Two minor modes were separated from the main mode at TDI = 30.5, which corresponds to the established limit of hyposmia. This trimodal distribution was not observed after the rhinitis subsided. Olfactory function was not significantly impaired in 40% of all rhinitis patients, whereas it was transiently impaired in 59%. For this group, supervised machine-learning algorithms could be trained with information on retronasal olfactory function, gustatory function, and trigeminal sensitivity to assign patients to subgroups based on orthonasal olfactory function with a balanced classification accuracy of 64-65%. The ability to recognize patients with olfactory loss based on retronasal olfactory function as well as gustatory function and trigeminal sensitivity suggests in turn that these modalities are affected by rhinitis. However, the only modest accuracy at which this information allowed to reproduce the olfactory diagnosis indicated they are involved in the symptomatology of rhinitis to a lesser extent compared with the orthonasal olfactory function.

Olfactory Dysfunction Predicts the Development of Depression in Older US Adults.

Neuroanatomic connections link the olfactory and limbic systems potentially explaining an association between olfactory dysfunction and depression. Some previous studies have demonstrated that olfactory dysfunction is associated with increased depressive symptoms. However, these studies were cross-sectional and unable to establish which develops first. We used longitudinal data to determine if impaired odor identification increased subsequent depressive symptoms or vice versa. We assessed olfaction and depression in the National Social Life, Health, and Aging Project, a nationally representative, 15-year longitudinal study of older US adults. Olfaction was measured using a validated odor identification test (Sniffin' Sticks). Depressive symptoms were measured using a modified version of the validated Center for Epidemiological Studies Depression Scale. Multivariable logistic regression models examined the temporal relationships between developing olfactory dysfunction and depression while accounting for demographics, disease comorbidities, alcohol use, smoking, and cognition. Older adults with olfactory dysfunction had concurrent frequent depressive symptoms (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.00-1.43). Among healthy adults at baseline, those who had olfactory dysfunction were more likely to develop frequent depressive symptoms 5 or 10 years later (OR = 2.22, 95% CI = 1.13-4.37). Conversely, those with frequent depressive symptoms at baseline were not more likely to develop olfactory dysfunction 5 or 10 years later. We show for the first time that olfactory dysfunction predicts subsequent development of depression in older US adults. These data support screening for depression in older adults with chemosensory impairment and set the stage for disentangling the relationship between olfaction and depression.

Six-Month Psychophysical Evaluation of Olfactory Dysfunction in Patients with COVID-19.

This study prospectively assessed the 6-month prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 10 patients being anosmic (6.9%) and seven being severely microsmic (4.8%). At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of the sense of smell or taste and olfactory test scores (Spearman's r = -0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had a self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of syndrome coronavirus 2 (SARS-CoV-2) infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-COV-2 infection.

Risk Factors for Olfactory and Gustatory Dysfunctions in Patients with SARS-CoV-2 Infection.

INTRODUCTION: Smell and taste loss are characteristic symptoms of SARS-CoV-2 infection. The aim of this study is to investigate the prevalence and risk factors associated with olfactory and gustatory dysfunctions in coronavirus disease (COVID-19) patients. METHODS: We conducted an observational, retrospective study on 376 patients with documented SARS-CoV-2 infection admitted to the San Gerardo Hospital in Monza, Italy, from March to July 2020. All patients answered a phone questionnaire providing information on age, sex, smoking status, and clinical characteristics. Adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated through logistic regression models including relevant covariates. RESULTS: The prevalence of olfactory and gustatory dysfunctions in COVID-19 patients was 33.5 and 35.6%, respectively. Olfactory dysfunctions were significantly directly associated with current smoking and history of allergy, the multivariable ORs being 6.53 (95% CI 1.16-36.86) for current smokers versus never smokers, and 1.89 (95% CI 1.05-3.39) for those with an allergy compared to those without any allergy. Respiratory allergy in particular was significantly associated with olfactory dysfunctions (multivariable OR 2.30, 95% CI 1.02-5.17). Significant inverse associations were observed for patients aged 60 years or more (multivariable OR 0.33, 95% CI 0.19-0.57) and hospitalization (multivariable OR 0.22, 95% CI 0.06-0.89). Considering gustatory dysfunctions, after allowance of other variables a significant direct association was found for respiratory allergies (OR 2.24, 95% CI 1.03-4.86), and an inverse association was found only for hospitalization (OR 0.21, 95% CI 0.06-0.76). CONCLUSION: Our study indicates that current smoking and history of allergy (particularly respiratory) significantly increase the risk for smell loss in COVID-19 patients; the latter is also significantly associated to taste loss. Hospitalization has an inverse association with the risk of olfactory and gustatory dysfunctions, suggesting that these may be symptoms characteristics of less severe SARS-CoV-2 infection.

Impaired olfactory neural circuit in patients with SLE at early stages.

OBJECTIVE: To investigate the changes of olfactory function and odor-induced brain activation in patients with systemic lupus erythematosus (SLE) at early stages compared with healthy controls. MATERIALS AND METHODS: Olfactory function and odor-induced brain activation in 12 SLE patients at early stages and 12 age, gender and education matched healthy controls were evaluated using olfactory behavior test and odor-induced task-functional magnetic resonance imaging (task-fMRI). RESULTS: No significant differences in olfactory behavior scores (including olfactory threshold, olfactory identification, and olfactory memory) were found in the patients with SLE at early stages compared with the healthy controls, while significantly decreased odor-induced activations in olfactory-related brain regions were observed in the patients. In the SLE group, the patients with better performance in the olfactory threshold test had significantly lower levels of anti-dsDNA antibody. CONCLUSION: The current study demonstrated that significant alterations in odor-induced brain activations occurred prior to measurable olfactory decline in SLE at early stages, which provided a new method for early diagnosis of olfactory dysfunction in SLE.

Presence of gustatory and olfactory dysfunction in the time of the COVID-19 pandemic.

BACKGROUND: The unexpected outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 49 million cases and an estimated 2,000,000 associated deaths worldwide. In Germany, there are currently more than 2,000,000 laboratory-confirmed coronavirus disease 2019 (COVID-19) cases including 51,800 deaths. However, regional differences also became apparent and with the second wave of infections, the detailed characterization of COVID-19 patients is crucial to early diagnosis and disruption of chains of infections. METHODS: Handing out detailed questionnaires to all individuals tested for COVID-19, we evaluated the clinical characteristics of negative and positive tested individuals. Expression of symptoms, symptom duration and association between predictor variables (i.e. age, gender) and a binary outcome (olfactory and gustatory dysfunction) were assessed. RESULTS: Overall, the most common symptoms among individuals who tested positive for SARS-CoV-2 were fatigue, headache, and cough. Olfactory and gustatory dysfunction were also reported by many SARS-CoV-2 negative individuals, more than 20% of SARS-CoV-2 negative tested individuals in our study reported olfactory and gustatory dysfunction. Independent of SARS-CoV-2 status, more females displayed symptoms of gustatory (29.8%, p = 0.0041) and olfactory dysfunction (22.9%, p = 0.0174) compared to men. CONCLUSIONS: Bringing early SARS-CoV-2 tests to the populations at risk must be a main focus for the upcoming months. The reliability of olfactory and gustatory dysfunction in COVID-19 negative tested individuals requires deeper investigation in the future.

α-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia: a prodromal Parkinson's disease model.

Parkinson's disease is one of the most common movement disorders and is characterized by dopaminergic cell loss and the accumulation of pathological α-synuclein, but its precise pathogenetic mechanisms remain elusive. To develop disease-modifying therapies for Parkinson's disease, an animal model that recapitulates the pathology and symptoms of the disease, especially in the prodromal stage, is indispensable. As subjects with α-synuclein gene (SNCA) multiplication as well as point mutations develop familial Parkinson's disease and a genome-wide association study in Parkinson's disease has identified SNCA as a risk gene for Parkinson's disease, the increased expression of α-synuclein is closely associated with the aetiology of Parkinson's disease. In this study we generated bacterial artificial chromosome transgenic mice harbouring SNCA and its gene expression regulatory regions in order to maintain the native expression pattern of α-synuclein. Furthermore, to enhance the pathological properties of α-synuclein, we inserted into SNCA an A53T mutation, two single-nucleotide polymorphisms identified in a genome-wide association study in Parkinson's disease and a Rep1 polymorphism, all of which are causal of familial Parkinson's disease or increase the risk of sporadic Parkinson's disease. These A53T SNCA bacterial artificial chromosome transgenic mice showed an expression pattern of human α-synuclein very similar to that of endogenous mouse α-synuclein. They expressed truncated, oligomeric and proteinase K-resistant phosphorylated forms of α-synuclein in the regions that are specifically affected in Parkinson's disease and/or dementia with Lewy bodies, including the olfactory bulb, cerebral cortex, striatum and substantia nigra. Surprisingly, these mice exhibited rapid eye movement (REM) sleep without atonia, which is a key feature of REM sleep behaviour disorder, at as early as 5 months of age. Consistent with this observation, the REM sleep-regulating neuronal populations in the lower brainstem, including the sublaterodorsal tegmental nucleus, nuclei in the ventromedial medullary reticular formation and the pedunculopontine nuclei, expressed phosphorylated α-synuclein. In addition, they also showed hyposmia at 9 months of age, which is consistent with the significant accumulation of phosphorylated α-synuclein in the olfactory bulb. The dopaminergic neurons in the substantia nigra pars compacta degenerated, and their number was decreased in an age-dependent manner by up to 17.1% at 18 months of age compared to wild-type, although the mice did not show any related locomotor dysfunction. In conclusion, we created a novel mouse model of prodromal Parkinson's disease that showed RBD-like behaviour and hyposmia without motor symptoms.