Olfactory sensory evaluation in new-born children of women infected with COVID-19 during pregnancy

Introduction: In adults, olfactory loss is one of the earliest and most frequent acute clinical manifestations of SARS-CoV-2 infection. The number of children infected with SARS-CoV-2 is relatively small, perhaps due to the lower expression of Angiotensin Converting Enzyme 2 (ACE2) in children compared to adults. Little is known about foetal impairment in mothers infected with SARS-CoV-2. Objective: The goal of the present study is to develop and validate a behavioural evaluative scale of olfactory perception in healthy new-borns and to apply this scale to new-born children of women infected with COVID-19 during pregnancy comparing to new-born children of women without COVID-19 infection history. Methods: This is a retrospective comparative analytical cohort study of 300 new-borns exposed and unexposed to COVID-19 during pregnancy. The data collection will follow the experimental procedure in a previous study that explored odours of the maternal breastmilk, vanilla (sweet) and distilled water (neutral). A coffee smell was implemented as an addition to this previous study in order to include the acid/bitterness category to the categories of stimuli. Discussion: It is feasible to argue the hypothesis of the involvement of the foetus' olfactory bulb during intrauterine life as one of the indelible pathophysiological manifestations to the clinical diagnosis of COVID-19 with neurosensory olfactory deficit in foetuses and new-borns affected by intrauterine infection. This study aims to investigate if new-born children of women infected with COVID-19 during pregnancy have olfactory sensory changes. The clinical trial was registered in the Brazilian Registry of Clinical Trials (ReBEC- RBR-65qxs2).

Olfaction in patients with Parkinson’s disease: a new threshold test analysis through turning points trajectories

Olfactory deficit is a widely documented non-motor symptom in Parkinson’s disease (PD). Abnormal turning points trajectories through olfactory threshold testing have been recently reported in patients with olfactory dysfunction, who seem to adapt faster to olfactory stimuli, but data on PD patients are lacking. The aim of this study is to perform olfactory threshold test and explore the turning points trajectories in PD patients in comparison to normal controls. We recruited 59 PD patients without dementia, and no conditions that could influence evaluation of olfaction and cognition. Sixty healthy subjects served as controls. Patients and controls underwent a comprehensive olfactory evaluation with the Sniffin’ Sticks extended test assessing threshold, discrimination and identification and a full neuropsychological evaluation. Besides, threshold test data were analyzed examining all the turning points trajectories. PD patients showed a different olfactory threshold test pattern, i.e., faster olfactory adaptation, than controls with no effect of age. Normosmic PD patients showed different olfactory threshold test pattern, i.e., better threshold score, than normosmic controls. Visuospatial dysfunction was the only factor that significantly influenced this pattern. Olfactory threshold trajectories suggested a possible adaptation phenomenon in PD patients. Our data offered some new insights on normosmic PD patients, which appear to be a subset with a specific psychophysical profile. The analysis of the turning points trajectories, through an olfactory threshold test, could offer additional information on olfactory function in PD patients. Future larger studies should confirm these preliminary findings.

Ageing and Olfactory Dysfunction in Trisomy 21: A Systematic Review

Purpose: The olfactory system is particularly vulnerable in an ageing brain, both anatomically and functionally, and these brain changes are more pronounced among individuals with trisomy 21. Furthermore, the age of the system starts to deteriorate, and the mechanism involved is unclear in an individual with trisomy 21. Therefore, the present review aims to summarise the available information related to this topic and to suggest questions still unanswered which can be a subject of further research. Methods: A systematic literature search of trisomy 21 and olfactory dysfunction was conducted using PubMed/MEDLINE and Scopus electronic database following PRISMA guidelines. References and citations were checked in the Google Scholar database. Reports were extracted for information on demographics and psychophysical evaluation. Then, the reports were systematically reviewed based on the effects of ageing on the three olfactory domains: threshold, discrimination, and identification. Results: Participants with trisomy 21 show an early onset of olfactory impairment, and the age effect of the olfactory deficit is fully expressed at age > 30 years old. The three olfactory domains, threshold, discrimination, and identification, are suggested to be impaired in trisomy 21 participants with age > 30 years old. Conclusions: Olfactory dysfunction in an individual with trisomy 21 commences at a relatively young age and affects the three olfactory domains. A challenge for the future is to quantitatively establish the olfactory function of an individual with trisomy 21 at all ages with more detailed measurements to further understand the pathophysiology of this brain deterioration.

A Comprehensive Phenotype of Non-motor Impairments and Distribution of Alpha-Synuclein Deposition in Parkinsonism-Induced Mice by a Combination Injection of MPTP and Probenecid

Parkinson’s disease (PD) is characterized by non-motor symptoms as well as motor deficits. The non-motor symptoms rarely appear individually and occur simultaneously with motor deficits or independently. However, a comprehensive research on the non-motor symptoms using an experimental model of PD remains poorly understood. The aim of the current study is to establish a chronic mouse model of PD mimicking the comprehensive non-motor symptoms of human PD by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid (MPTP/p). The non-motor and motor symptoms were evaluated by performing buried food, short-term olfactory memory, hot plate, open field, tail suspension, Y maze, novel object recognition, bead expulsion, one-h stool collection, rotarod, rearing, catalepsy, and akinesia tests after 10 injections of MPTP/p into mice. The expression levels of α-synuclein, glial fibrillary acidic protein (GFAP), tyrosine hydroxylase (TH) or DJ-1 were analyzed by Western blotting or immunostaining. MPTP/p-treated mice achieved to reproduce the key features of non-motor symptoms including olfactory deficit, thermal hyperalgesia, anxiety, depression, cognitive decline, and gastrointestinal dysfunction in addition to motor deficits. The MPTP/p-treated mice also showed the high levels of α-synuclein and low levels of TH and DJ-1 in striatum, substantia nigra, olfactory bulb, hippocampus, amygdala, prefrontal cortex, locus coeruleus, or colon. In addition, the expression levels of phosphorylated-α-synuclein and GFAP were elevated in the striatum and substantia nigra in the MPTP/p-treated mice. Taken together, our study clarifies that the chronic MPTP/p-treated mice have a variety of non-motor dysfunctions as well as motor abnormalities by α-synuclein overexpression and dopaminergic depletion. Therefore, the study of comprehensive phenotypes of non-motor symptoms in one PD model would advance in-depth understandings of neuropathological alternations and contribute to future strategies for PD treatment.

Anti-COVID-19 efficacy of ivermectin in the golden hamster

The devastating coronavirus disease 2019 (COVID-19) pandemic, due to SARS-CoV-2, has caused more than 47 million confirmed cases and more than 1.2 million human deaths around the globe1, and most of the severe cases of COVID-19 in humans are associated with neurological symptoms such as anosmia and ageusia, and uncontrolled inflammatory immune response2–5. Among therapeutic options6–8, the use of the anti-parasitic drug ivermectin (IVM), has been proposed, given its possible anti-SARS-CoV-2 activity9. Ivermectin is a positive allosteric modulator of the α-7 nicotinic acetylcholine receptor10, which has been suggested to represent a target for the control of Covid-19 infection11, with a potential immunomodulatory activity12. We assessed the effects of IVM in SARS-CoV-2-intranasally-inoculated golden Syrian hamsters. Even though ivermectin had no effect on viral load, SARS-Cov-2-associated pathology was greatly attenuated. IVM had a sex-dependent and compartmentalized immunomodulatory effect, preventing clinical deterioration and reducing olfactory deficit in infected animals. Importantly, ivermectin dramatically reduced the Il-6/Il-10 ratio in lung tissue, which likely accounts for the more favorable clinical presentation in treated animals. Our data support IVM as a promising anti-COVID-19 drug candidate.

Systematic evaluation of olfaction in patients with hereditary cystic kidney diseases/renal ciliopathies

BackgroundHereditary cystic kidney diseases such as nephronophthisis, polycystic kidney disease and Bardet-Biedl syndrome (BBS) are caused by a dysfunction of primary cilia. Cilia are involved in a variety of cellular functions and perceptions, with one of them being the sense of smell. Hyposmia is a typical feature found in patients with BBS. However, reports of olfactory dysfunction in other cystic kidney diseases are sparse. Here we provide a systematic survey on olfaction in a large cohort of patients displaying genetically determined renal ciliopathies.MethodsWe performed a match-controlled systematic olfactory evaluation in a group of 75 patients with a defined genetic background using age adapted and validated odour identification tests.ResultsTest results revealed a significant olfactory deficit in patients carrying TMEM67 variants (n=4), while all other genetic disorders causing nephronophthisis (n=25) or polycystic kidney disease (n=18) were not associated with an impaired sense of smell. Also in patients with BBS, olfactory performance was depending on the underlying molecular defect. While defects in the BBS1 gene (n=9) had no impact on the sense of smell, all other BBS gene disorders (n=19) were associated with significant hyposmia. Noteworthy, there was no correlation of the olfactory deficit with the level of renal impairment.ConclusionHyposmia is a part of the clinical spectrum of BBS and of other renal ciliopathies. Depending on the genetic background, clinicians should be aware of this subtle and so far underappreciated symptom when clinically assessing patients with BBS or TMEM67 gene variants.