Smell Impairment Research Articles

Neurological complications caused by SARS-CoV-2.

SUMMARYSARS-CoV-2 can not only cause respiratory symptoms but also lead to neurological complications. Research has shown that more than 30% of SARS-CoV-2 patients present neurologic symptoms during COVID-19 (A. Pezzini and A. Padovani, Nat Rev Neurol 16:636-644, 2020, https://doi.org/10.1038/s41582-020-0398-3). Increasing evidence suggests that SARS-CoV-2 can invade both the central nervous system (CNS) (M.S. Xydakis, M.W. Albers, E.H. Holbrook, et al. Lancet Neurol 20: 753-761, 2021 https://doi.org/10.1016/S1474-4422(21)00182-4 ) and the peripheral nervous system (PNS) (M.N. Soares, M. Eggelbusch, E. Naddaf, et al. J Cachexia Sarcopenia Muscle 13:11-22, 2022, https://doi.org/10.1002/jcsm.12896), resulting in a variety of neurological disorders. This review summarized the CNS complications caused by SARS-CoV-2 infection, including encephalopathy, neurodegenerative diseases, and delirium. Additionally, some PNS disorders such as skeletal muscle damage and inflammation, anosmia, smell or taste impairment, myasthenia gravis, Guillain-Barré syndrome, ICU-acquired weakness, and post-acute sequelae of COVID-19 were described. Furthermore, the mechanisms underlying SARS-CoV-2-induced neurological disorders were also discussed, including entering the brain through retrograde neuronal or hematogenous routes, disrupting the normal function of the CNS through cytokine storms, inducing cerebral ischemia or hypoxia, thus leading to neurological complications. Moreover, an overview of long-COVID-19 symptoms is provided, along with some recommendations for care and therapeutic approaches of COVID-19 patients experiencing neurological complications.

The long-term effect of COVID-19 infection on olfaction and taste; a prospective analysis

PurposeTo estimate long-term prognosis of chemosensory dysfunctions among patients recovering from COVID-19 disease.MethodsBetween April 2020 and July 2022, we conducted a prospective, observational study enrolling 48 patients who experienced smell and/or taste dysfunction during the acute-phase of COVID-19. Patients were evaluated for chemosensory function up to 24 months after disease onset.ResultsDuring the acute-phase of COVID-19, 80% of patients reported anosmia, 15% hyposmia, 63% ageusia, and 33% hypogeusia. At two years’ follow-up, 53% still experienced smell impairment, and 42% suffered from taste impairment. Moreover, 63% of patients who reported parosmia remained with olfactory disturbance. Interestingly, we found a negative correlation between visual analogue scale scores for smell and taste impairments during the acute-phase of COVID-19 and the likelihood of long-term recovery.ConclusionOur study sheds light on the natural history and long-term follow-up of chemosensory dysfunction in patients recovering from COVID-19 disease. Most patients who initially suffered from smell and/or taste disturbance did not reach full recovery after 2 years follow-up. The severity of impairment may serve as a prognostic indicator for full recovery.

Prevalence of smell and taste dysfunction in different clinical severity groups of COVID-19 patients

BACKGROUND: Studies on the long-term prevalence of smell and taste impairment concerned with severe disease in the acute phase of COVID-19 are limited. The aim of our study was to assess and compare psychophysical testing and self-reported smell and taste disturbances and recovery between three patient groups suffering from critical, severe, or mild COVID-19 in a follow-up at six-months after the acute phase. METHODOLOGY: The prospective controlled study of 227 participants comprised 72 intensive-care-unit-treated (ICU-treated), 53 pulmonology- or infectious-diseases-ward-treated (WARD-treated), and 48 home-isolated patients (HOME) with preceding COVID-19, and 54 individuals with no history of COVID-19 (CONTROL). All participants visited a follow-up clinic for a sense-of-smell screening and underwent Magnetic Resonance Imaging (MRI) of the brain, olfactory bulbs and sinonasal area at six months after acute disease. Before the follow-up visit, the participants received a questionnaire concerning smell and taste function. We sent a supplementary questionnaire including questions about phantosmia and parosmia and taste recovery at a median of 502.5 days after the acute phase. RESULTS: We found no statistically significant differences between the groups in the incidence of smell and taste dysfunction, recovery, or the occurrence of parosmia or phantosmia. There were no statistically significant differences in semi-objective smell performance across the different study groups and controls. The olfactory bulb volume was normal in all patients and controls. Mucosal thickening in paranasal sinuses was rare. CONCLUSIONS: We found no difference in a six-month follow-up in the subjective or semi-objective senses of smell and taste between three severity groups of COVID-19 and controls.

Validity and Reliability of the Malay Questionnaire for Olfactory Disorders.

Olfactory disorders (OD) are an umbrella term for a diverse group of smell problems. Numerous tests and questionnaires have been formulated to identify and test the severity of smell impairment, which is not readily available or translated for the Malaysian population. This study aimed to translate the Questionnaire for Olfactory Disorders (QOD) and validate and test the reliability of the Malay Questionnaire for Olfactory Disorders (mQOD). This cross-sectional study was conducted in two tertiary centres. A forward and backward translation was conducted for the QOD. The translated questionnaire was distributed to subjects with self-reported smell disorders on days 1 and 7. Internal consistency was analysed using Cronbach's alpha and test-retest reliability was tested with an intraclass correlation coefficient. Confirmatory factor analysis was performed to test construct validity. A total of 375 participants were recruited, 52 dropped out and 323 completed the questionnaire a second time. The Cronbach's alpha coefficient was 0.537 for parosmia (P), 0.892 for life quality (LQ), 0.637 for sincerity (S) and 0.865 for visual analogue score (VAS). The intraclass correlation coefficient (ICC) for domain scores was > 0.9, while the ICC for all items was good to excellent. A three-factor model for mQOD showed an acceptable fit with indices chi-square value (CMIN)/degree of freedom (DF) = 3.332, Tucker-Lewis fit index (TLI) = 0.923, comparative fit index (CFI) = 0.939, root mean square error of approximation (RMSEA) = 0.079 and standardised root mean square residual (SRMR) = 0.0574. The mQOD is a valid and reliable tool for assessing OD in patients.

Cytokine profile of nasal polyps and clinical characteristics of patients with polypous rhinosinisitis at different degree of therapeutic control and disease severity

The issues of recurrencies in chronic rhinosinusitis with nasal polyps (CRSwNP) still remain unresolved. Therefore, detection patients with uncontrolled clinical course of CRSwNP is required.The aim of the present study was to assess cytokine profile in nasal polyps as well as clinical characteristics of patients with CRSwNP at varying levels of therapeutic control.The study included 99 patients with chronic rhinosinusitis. The contents of interferon IFNγ, interleukin IL- 1β, IL-4, IL-5, IL-13, tumor necrosis factor TNFα, transforming growth factors TGF-β1, TGF-β2, TGF-β3 were measured in polyp tissue samples by means of multiplex analysis. The patients were treated according to a stepwise СRSwNP therapeutic algorithm [9]. Following observation for 5 years, all patients were divided into groups, as based on medical control degree. Group 1 included patients with mild CRSwNP, who mainly received stage I and II treatment for the entire observation period. Group 2 was presented by moderate- severity CRSwNP, with stage II or III therapy according to the referred algorithm. Group 3 included the patients with severe CRSwNP who received one or more stage IV courses. The patients underwent repeated SNOT-22 questionnaire, endoscopic examination, clinical assessment. In case of bronchial asthma (BA), ACQ-7 was repeated. Initial cytokine profile of nasal polyps was analyzed by the mentioned clinical groups.Results:After 5 years of observations in group 1 (mild CRSwNP), we found a minimal decrease in quality of life (SNOT-22), severity of nasal congestion, or smell impairment. Bronchial asthma duration in these patients was significantly lower compared to group 3, the patients had better asthma control level. Cytokine profile of nasal polyps was characterized by the highest IL-4 concentration, average values IL-1β, TNFα, IFNγ and minimal TGF-β1 values.In group 2 (moderate CRSwNP), we noted more pronouced impairment of smell, nasal congestion and quality of life. Bronchial asthma was less controlled than in group 1. The maximal concentrations of IFNγ, IL-1β, TNFα, IL-5, TGF-β1, TGF-β2 were registered.In group 3 with poor CRSwNP control, the highest SNOT-22 scores, severity of difficulty in nasal breathing, impaired sense of smell were revealed. Duration of bronchial asthma was longer, with lowest levels of medical control. In nasal polyps, minimal levels of IFNγ, IL-1β, TNFα, IL-4, IL-5, TGF-β2, TGF-β3 were noted.Treatment of patients depending on the clinical phenotypes of CRSwNP in the presence/absence of allergic rhinitis or bronchial asthma may improve control and reduce incidence of relapses in CRSwNP.

Predictive factors of involuntary weight loss in patients with smell and taste disorders.

Chemosensory dysfunction (olfaction, taste, and trigeminal) affects quality of life, potentially impacting eating behaviors. We investigated which factors are associated with weight loss in patients with smell and taste disorders. Retrospective study of consecutive adult patients seen in the smell and taste clinic during a 10-year period. Patients were asked about smell, flavor and taste impairment. Psychophysically, smell was assessed with Sniffin' Sticks, flavor with a retronasal test, and taste with Taste Strips. A total of 554 patients (313 females) were included with a median age of 51 years (IQR 23). Seventy-six (13.7%) reported involuntary weight loss (median 6 kg, IQR 6) due to chemosensory disorders. The odds of losing weight were 2.1 times higher when patients reported subjective changes in flavor perception. Parosmia was a significant predictor of weight loss. Patients with symptoms lasting longer than two years were less likely to present with weight loss. Post-traumatic chemosensory dysfunction was a significant predictor of losing weight. On psychophysical testing, the probability of a patient losing weight increased by 8% for every 1-unit reduction in Taste Strips score. Factors associated with weight loss were self-reported changes in flavor perception, parosmia, duration of symptoms for less than two years, head injury, and psychophysically measured low Taste Strips score. These data help to identify patients at risk of weight loss from smell or taste impairment.

Effectiveness of dupilumab versus endoscopic sinus surgery for the treatment of type-2 chronic rhinosinusitis with nasal polyps: a preliminary report.

Historically managed with intranasal corticosteroids (INCS) and endoscopic sinus surgery (ESS), type-2 Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) treatment was revolutionized by the introduction of dupilumab but universally accepted guidelines are still lacking. Patients treated at our University Hospital for type-2 CRSwNP were enrolled. Demographic data were collected, as well as laboratory (eosinophils, total IgE), endoscopic [nasal polyps score (NPS), modified Lund-Kennedy score (mLKS)], radiological [Lund-Mackay score (LMS) at CT scan], SNOT-22, and olfactory [Sniffin' Sticks identification test (SSIT)] features. Patients were treated with dupilumab or ESS and re-evaluated after 3 and 12 months. At 3 and 12 months, patients undergoing ESS achieved a higher reduction of NPS and mLKS, while patients receiving dupilumab experienced a higher improvement at SNOT-22 and SSIT with a greater positive variation in the prevalence of anosmia (-57.7% vs -42.9%) and normosmia (+ 37.8 vs + 28.5%). Mean mLKS and LMS were quite similar. Results were independent of clinical features known to contribute to CRSwNP severity, except for patients with ≥ 2 prior ESS who had a significantly lower smell improvement. ESS and dupilumab were effective at reducing CRSwNP inflammatory burning. CRSwNP smell impairment cannot be attributed only to olfactory cleft obstruction and other mechanisms may be involved. Dupilumab acts systemically with poor correlation with NPS. As of today, dupilumab appears to be more suitable for elderly patients with anesthesiological contraindications and/or several previous surgeries, while ESS may represent the first-line choice in surgery-naive patients.

Prevalence of Persisting and New Symptoms Following Recovery from COVID-19 in the Jordanian Population.

Many patients do not have a clear idea about the recovery from COVID-19 infection. This study focuses on the prevalence of persistent symptoms of COVID-19 infection as well as new symptoms that appear after recovery, and it aids in determining the relationships between these symptoms and a variety of variables. An online observational study was conducted between April and June 2022. It consisted of a self-administered web-based questionnaire conducted using social media platforms. Inclusion criteria were residency in Jordan, being 18 years of age or older, having recovered from COVID-19 for at least 90 days, and giving consent to participate. Participants whose infection was not confirmed by a positive PCR were excluded. The most common persistent symptoms were loss of smell (34.7%), fatigue (34.6%), loss of taste (29.5%), myalgia (26.3%), and headache (25.9%), while the most common newly appearing symptoms after recovery were smell hallucinations (15.8%), fatigue (15.5%), taste hallucinations (14.9%), and focus impairment (12.9%) and smell impairment (12.8%). The symptoms persisted more in females, non-smokers, and those who needed medical care sor oxygesnation and with increased infection duration. The study about persistent and new symptoms after COVID-19 among Jordanians found a greater prevalence of symptoms related to the sense of smell. There is no association between persistent and new symptoms after COVID-19 recovery with comorbidities or oxygen therapy during illness. We recommend studying the effect of COVID-19 mutants and vaccination on the persistence of symptoms after recovery.

Neurological Manifestations in Hospitalized Geriatric Patients With COVID-19 at King Abdulaziz Medical City in Jeddah, Western Region, Saudi Arabia From 2020 to 2021: A Cross-Sectional Study.

Introduction COVID-19 involvement in the nervous system has been reported in many cases.Viral neuroinvasion has multiple routes of entry.Neurological manifestations of COVID-19 can be divided into ones of the central nervous system (CNS), such as headache, dizziness, altered mental status, ataxia, and seizure, and of theperipheral nervous system (PNS), including ageusia, anosmia, acute illness demyelinating polyneuropathy, and neuralgia. Aim and objectives This study aims to observe and report the neurological manifestations in geriatric patients who were diagnosed with COVID-19 at KAMC-J and report the duration of admission to the in-patient and ICU wards. Methods This was a cross-sectional study conducted on admitted geriatric patients with PCR-confirmed COVID-19 from April 1, 2020 to June 30, 2021 at KAMC-J. Using Raosoft®, the sample size was estimated with a CI of 95% and a 36.4%prevalence of neurological symptoms in COVID-19 patients to be 289. Convenience sampling was used, and the data were collected from BESTCare EMRs. IBMSPSSStatistics for Windows, Version 20 (Released 2011) was used for descriptive and inferential statistical analysis. Results In this study, a total of 290 patients' data were collected, 161 (55.5%) of which were males. In addition, the median age was 71 (Q1-Q3: 65-78) years; furthermore, the median body mass index (BMI) was 30(Q1-Q3: 25-34) kg/m2. In descending order, the most prevalent comorbidities were hypertension (HTN) (70.3%), diabetes mellitus (DM) (68.6%), cardiac disease (42.1%), chronic kidney disease(26.6%), neurological disease (23.6%), cancer malignancy (13.1%), and finally chronic respiratory disease (11.4%).Regarding typical COVID-19 manifestations, 181 patients claimed to have experienced cough(62.4%), dyspnea by 164 (56.7%), fever by 154 (53.5%), fatigue by 93 (32.3%), a reading of anoxia by 68 (23.4%), abdominal pain by 58 (20.0%), diarrhea by 56 (19.4%), and finally throat pain by 19 (6.6%). Manifestations and pathologies of the CNS included headache (25.4%), dizziness (21.5%), impaired consciousness (17.2%), delirium (6.6%), ischemic stroke (4.1%), focal cranial nerve dysfunction(2.8%), seizure (2.8%), intracerebral hemorrhage (ICH) (0.3%), and ataxia (0.3%). Moreover, pathologies of the PNS manifested as taste impairment in 46 patients (15.9%), smell impairment in 33 (11.4%), nerve pain in 7 (24%), visual impairment in 5 (1.7%), Bell's palsy in 2 (0.7%), and Guillain-Barre syndrome in 1 (0.3%). Moreover, the majority of patients who developed an ischemic stroke or ICH, or required admission to the ICU had either DM or HTN. In addition, 17 (25.4%) of the 67 patients admitted to the ICU developed impaired consciousness. All-cause mortality in our study was 31 (10.71%) cases. Conclusion Neurological manifestations of COVID-19 are common and can result in serious complications if not detected and managed early, especially in the elderly. These complications are mostly seen in severely ill patients and may be the only symptoms in COVID-19 patients. In addition,patients' clinical conditions could deteriorate rapidly and result in significant morbidity and mortality. Therefore, a high index of suspicion is required among healthcare providers when dealing with such cases. Moreover, we recommend systematically collecting data on the short- and long-term neurological complications of COVID-19 globally and documenting the functional long-term outcomes after these complications.

Vitamin D and smell impairment, routine histology for unilateral tonsillar enlargement, and a machine learning model for predicting the three-year survival status of patients with hypopharyngeal squamous cell carcinoma.

Vitamin D and smell impairment, routine histology for unilateral tonsillar enlargement, and a machine learning model for predicting the three-year survival status of patients with hypopharyngeal squamous cell carcinoma.

Camera-based visual feedback learning aid for recovering sense of smell and taste in COVID-19 survivors: a proof-of-concept study.

A significant proportion of people report persistent COVID-19-related anosmia, hyposmia or parosmia, often accompanied with ageusia, hypogeusia or dysgeusia. Here, we present a proof-of-concept study that assessed the feasibility and acceptability of a new Camera-Based Visual Feedback Learning Aid (CVFLA) and explored its potential to restore or improve persistent COVID-19-related smell and/or taste impairment. Fifteen adult participants with persistent smell and/or taste impairment were randomly allocated to 7-, 14-, or 21-days baseline of symptom monitoring before receiving the intervention in up to 10 sessions (length and frequency determined by participant's preference and progress) using a specialised CVFLA apparatus (patent no. 10186160). Smell and taste were assessed pre- and post-intervention subjectively, and also objectively using the ODOFIN Taste Strips and Sniffin Sticks. Participant feedback about their experience of receiving CVFLA was obtained via a semi-structured interview conducted by someone not involved in delivering the intervention. The intervention was extremely well received, with no dropouts related to the intervention. There was also a significant improvement in smell and taste from pre- to post-CVFLA intervention (mean number of sessions = 7.46, SD = 2.55; total duration = 389.96 min, SD = 150.93) both in subjective and objective measures. All participants, except one, reported experiencing some improvement from the 2nd or 3rd session. This new CVFLA intervention shows promise in improving COVID-19 related impairment in smell and taste with a very high level of acceptability. Further studies with larger samples are required to confirm its potential in restoring, improving or correcting smell and/or taste impairment in relevant clinical and non-clinical groups.

Anosmia and dysgeusia associated with COVID-19 infection among patients visiting a tertiary hospital at Kaski, Nepal

Introduction: A number of studies have shown that anosmia and dysgeusia present as symptoms of COVID-19. These symptoms can appear with sudden onset following COVID-19 infection. The objective of the study was to observe epidemiological and clinical profile of COVID-19 patients who had experienced anosmia and dysgeusia. Methods: A cross-sectional study was carried out in Ear, Nose and Throat outpatient department of Pokhara Academy of Health Sciences over a period of two months, from February 2022 to March 2022. Patients visiting the outpatient department were enquiredabout the COVID-19 infection status in the past and symptoms related to taste and smell impairment were asked about. Results: Out of total 198 patients, 141 (71%) had experienced impairment of taste and smell, either one or both, while the rest did not develop such features after testing positive for COVID-19 virus. Conclusions: Anosmia and dysgeusia were common features in COVID-19 infection.

Recovery from olfactory and gustatory dysfunction following COVID-19 acquired during Omicron BA.1 wave in Italy

BackgroundDespite alterations in the sense of smell and taste have dominated the symptoms of SARS-CoV-2 infection, the prevalence and the severity of self-reporting COVID-19 associated olfactory and gustatory dysfunction has dropped significantly with the advent of the Omicron BA.1 subvariant. However, data on the evolution of Omicron-related chemosensory impairment are still lacking. ObjectiveThe aim of the present study was to estimate the prevalence and the recovery rate of self-reported chemosensory dysfunction 6-month after SARS-CoV-2 infection acquired during the predominance of the Omicron BA.1 subvariant in Italy. MethodsProspective observational study based on the sino-nasal outcome tool 22 (SNOT-22), item “sense of smell or taste” and additional outcomes conducted in University hospitals and tertiary referral centers in Italy. ResultsOf 338 patients with mild-to-moderate COVID-19 completing the baseline survey, 294 (87.0 %) responded to the 6-month follow-up interview. Among them, 101 (34.4 %) and 4 (1.4 %) reported an altered sense of smell or taste at baseline and at 6 months, respectively. Among the 101 patients with COVID-19-associated smell or taste dysfunction during the acute phase of the disease, 97 (96.0 %) reported complete resolution at 6 months. The duration of smell or taste impairment was significantly shorter in vaccinated patients (p = 0.007). ConclusionsCompared with that observed in subjects infected during the first wave of the pandemic, the recovery rate from chemosensory dysfunctions reported in the present series of patients infected during the predominance of the Omicron BA.1 subvariant was more favorable with a shorter duration being positively influenced by vaccination.

COVID-19-Related Long-Term Taste Impairment: Symptom Length, Related Taste, Smell Disturbances, and Sample Characteristics.

The COVID-19 infection triggered in some patients a prolongedreduction in the perception of bothgustatory and olfactory senses (ageusia and anosmia).These symptomscould be manifested during the first days after the contagion, acting as predictors of COVID-19 infection, and additionally, they could be the only symptoms manifested at all.Clinical resolution of anosmia and ageusia was expected to occur within a few weeks, yet in some cases, patients began to demonstrate COVID-19-related long-term taste impairment(CRLTTI), a condition that can persist for longer than two months, contradicting initial evidence. Objectives: The authors' aimed to describe the characteristics of the sample of 31 participants with COVID-19-related long-term taste impairment, and their capacity to quantify taste and rate their smell perception. Material and Methods: Participants were submitted to a taste evaluation of four hyper-concentrated tastes perceived by the tongue (0-10), self-reported their smell (0-10), and answered a semi-structured questionnaire. Results: Different tastes seemed to be affected differently by COVID-19, despite the lack of statistical relevance observed in this study. Dysgeusia was only expressed in bitter, sweet, and acidic tastes. The mean age observed was 40.2 (SD 12.06) years, with women representing 71% of the sample. Taste impairment persisted for an average period of 10.8 months (SD 5.7). Self-reported smell impairment was reported by the majority of participants with taste impairment. Non-vaccinated people represented 80.6% of the sample. Conclusions: COVID-19 infection could trigger taste and smell disturbances that lasted as long as 24 months. CRLTTI seems not to affect the four main taste perceptions (hyper-concentrated) equally. Women represented the majority of the sample, with an average age of 40 years (SD 12.06). Previous diseases, medication use, and behavioral aspects seem not to be linked to CRLTTI development.

Smell Dysfunction in Patients with Primary Sjögren's Syndrome: Impact on Quality of Life.

Patients with primary Sjögren's syndrome (pSS) often report smell and taste disturbances. However, the correlation between smell impairment and mucosal dryness is not well understood. The objectives of this study were to investigate the following: (1) the prevalence of smell hypofunction in patients with SS; (2) the impact of smell hypofunction on their quality of life (QoL); (3) whether the patients' smell is correlated with xerostomia; and (4) whether the patients' smell is affected by taste hypofunction, disease duration, age, smoking or self-reported neuropathy. An ethically approved cross-sectional study was conducted on 65 female patients with SS and 62 sex-matched healthy controls. Their smell was assessed using the University of Pennsylvania Smell Identification Test. Their taste acuity was assessed using the Taste Strips Test. A visual analogue scale was used for the self-assessment of smell and taste functions. Xerostomia was assessed by the salivary flow rate, clinical oral dryness score and the Xerostomia Inventory. The patients' QoL and mental health well-being were assessed using validated questionnaires. In the SS group, the patients' smell function was impaired in 27/65 patients compared with the controls (15/62, p < 0.05), and it did not correlate with the severity of xerostomia, taste acuity (r = 0.05, p = 0.6) or self-reported nasal dryness (r = -0.02, p = 0.7). In the patients' group, smell hypofunction was not correlated with disease duration (β = 0.1, 95% CI = -0.07-0.1) or smoking (β = -0.02, 95% CI = -8-7). Age was not correlated with the smell function in the patients' group (β = -0.1, p = 0.5) but was correlated significantly with smell in the healthy participants' group (β = -0.3, p = 0.02). Neuropathy affected 81.2% of the patients' group. Their QoL and mental health well-being were not affected by smell hypofunction. Smell hypofunction appears to be a clinical manifestation in patients with SS, but it does not seem to be associated with the severity of mucosal dryness or with taste disturbance.

Restoration of Adult Neurogenesis by Intranasal Administration of Gangliosides GD3 and GM1 in The Olfactory Bulb of A53T Alpha-Synuclein-Expressing Parkinson's-Disease Model Mice.

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the body and mind of millions of people in the world. As PD progresses, bradykinesia, rigidity, and tremor worsen. These motor symptoms are associated with the neurodegeneration of dopaminergic neurons in the substantia nigra. PD is also associated with non-motor symptoms, including loss of smell (hyposmia), sleep disturbances, depression, anxiety, and cognitive impairment. This broad spectrum of non-motor symptoms is in part due to olfactory and hippocampal dysfunctions. These non-motor functions are suggested to be linked with adult neurogenesis. We have reported that ganglioside GD3 is required to maintain the neural stem cell (NSC) pool in the subventricular zone (SVZ) of the lateral ventricles and the subgranular layer of the dentate gyrus (DG) in the hippocampus. In this study, we used nasal infusion of GD3 to restore impaired neurogenesis in A53T alpha-synuclein-expressing mice (A53T mice). Intriguingly, intranasal GD3 administration rescued the number of bromodeoxyuridine + (BrdU +)/Sox2 + NSCs in the SVZ. Furthermore, the administration of gangliosides GD3 and GM1 increases doublecortin (DCX)-expressing immature neurons in the olfactory bulb, and nasal ganglioside administration recovered the neuronal populations in the periglomerular layer of A53T mice. Given the relevance of decreased ganglioside on olfactory impairment, we discovered that GD3 has an essential role in olfactory functions. Our results demonstrated that intranasal GD3 infusion restored the self-renewal ability of the NSCs, and intranasal GM1 infusion promoted neurogenesis in the adult brain. Using a combination of GD3 and GM1 has the potential to slow down disease progression and rescue dysfunctional neurons in neurodegenerative brains.

Measuring Nasal Patency and the Sense of Smell in CRSwNP Patients Treated with Dupilumab.

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the most severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with dupilumab in different rhinological units were followed up at 1, 3, 6 and 12 months from the first administration and were considered for this study. At baseline (T0) and at each follow-up, patients underwent nasal endoscopy and completed the sinonasal outcome test (SNOT)-22, a visual analogue scale (VAS) for smell/nasal obstruction, peak nasal inspiratory flow (PNIF) and the Sniffin' Sticks identification test (SSIT). The aim of the present study was to evaluate the effects of dupilumab in patients with severe uncontrolled CRSwNP on recovering nasal obstruction and smell impairment. Moreover, the method between PNIF and SSIT with the highest correlation with patients' response to dupilumab was evaluated. One hundred forty-seven patients were included. All parameters improved during treatment (p < 0.001). At T0, no correlations were found between PNIF and nasal symptoms. Nevertheless, during the following evaluations significant correlations between PNIF changes and both nasal symptoms and NPS were observed (p < 0.05). At T0, SSIT did not correlate with SNOT-22. Similarly to PNIF, during the follow-up SSIT changes significantly correlated with nasal symptom and NPS (p < 0.05). Comparing PNIF and SSIT correlations with SNOT-22 and NPS, PNIF showed a higher correlation with both. Dupilumab improves nasal obstruction and the sense of smell. PNIF and SSIT are effective tools in monitoring patients' response to dupilumab.

The relation between subjective cognitive complaints in patients after COVID-19 and the smell impairment related to the disease

The relation between subjective cognitive complaints in patients after COVID-19 and the smell impairment related to the disease

Electrophysiological evidence of subclinical trigeminal dysfunction in patients with COVID-19 and smell impairment: A pilot study.

BackgroundSmell and taste disturbances are among the most frequent neurological symptoms in patients with COVID-19. A concomitant impairment of the trigeminal nerve has been suggested in subjects with olfactory dysfunction, although it has not been confirmed with objective measurement techniques. In this study, we explored the trigeminal function and its correlations with clinical features in COVID-19 patients with impaired smell perception using electrophysiological testing.MethodsWe enrolled 16 consecutive patients with mild COVID-19 and smell impairment and 14 healthy controls (HCs). Olfactory and gustatory symptoms were assessed with self-reported questionnaires. Electrophysiological evaluation of the masseter inhibitory reflex (MIR) and blink reflex (BR) was carried out to test the trigeminal function and its connections within the brainstem.ResultsMasseter inhibitory reflex (MIR) analysis revealed higher latency of ipsilateral and contralateral early silent period in patients when compared with HCs. No significant differences between groups were detected as regards the duration of the early and late silent period. However, several patients showed a prolonged duration of the early silent period. BR evaluation disclosed only an increased amplitude of early components in patients.ConclusionsPatients with COVID-19 and smell impairment show a subclinical trigeminal nerve impairment. Trigeminal alterations mainly involve the oligosynaptic pathway, as a result of either direct viral damage or secondary neuroinflammation of the peripheral trigeminal fibers, whereas the polysynaptic ponto-medullary circuits seem to be spared. The prolonged duration of the early silent period and the increased amplitude of early BR response might reflect a compensatory upregulation of the trigeminal function as a consequence of the olfactory dysfunction.

Cross-sectional analysis of clinical aspects in patients with long-COVID and post-COVID syndrome.

ObjectiveRegarding pathogenesis, clinical manifestations, at-risk individuals, and diagnostic methods for stratifying patients for therapeutic approaches, our understanding of post-COVID syndrome is limited. Here, we set out to assess sociodemographic and clinical aspects in patients with the long-COVID and post-COVID syndrome.MethodsWe performed a cross-sectional analysis of patients presenting at our specialized university hospital outpatient clinic. We assessed patients' clinical presentation, fatigue, symptoms of depression and anxiety, and impairment of smell.ResultsA total of 101 patients were included (73.3% female), of whom 78.2% had a mild course of COVID-19. At presentation, 93.1% suffered from fatigue, 82.2% from impaired concentration, and 79.2% from impaired memory, 53.5% had impaired sleep. The most common secondary diagnosis found in our cohort was thyroid disease. Fatigue analysis showed that 81.3% of female and 58.8% of male patients had severe combined fatigue. Female gender was an independent risk factor for severe fatigue (severe cognitive fatigue OR = 8.045, p = 0.010; severe motor fatigue OR = 7.698, p = 0.013). Males suffered from more depressive symptoms, which correlated positively with the duration of symptom onset. 70.3% of patients with anamnestic smell impairment had hyposmia, and 18.9% were anosmic.InterpretationMost long-COVID patients suffered from severe fatigue, with the female sex as an independent risk factor. Fatigue was not associated with symptoms of depression or anxiety. Patients with long-COVID symptoms should receive an interdisciplinary diagnostic and therapeutic approach depending on the clinical presentation.