[Parosmia and phantosmia: clinical update]. / Parosmie et fantosmie: mise à jour.

Olfactory disorders became known by large parts of the population since the Covid-19 pandemic. The causes of olfactory dysfunctions are manifold. Similar to other sensory impairments the disruption can be qualitative or quantitative. Quantitative olfactory disorders such as anosmia or hyposmia are well explored, whereas the knowledge on qualitative disorders such as parosmia or phantosmia is still limited. This article gives an update on the current clinical knowledge and workup of parosmia and phantosmia.

Depuis la pandémie de Covid-19, la population est davantage informée sur les troubles de l'odorat. Ils peuvent être d'origines multiples. Comme pour toute modalité sensorielle, il existe des atteintes quantitatives et qualitatives. Les troubles quantitatifs sont mieux connus et pris en charge mais les troubles qualitatifs restent méconnus. Cet article traite des troubles de l'odorat qualitatifs, notamment de la parosmie et de la fantosmie, ainsi que de leur prise en charge.

How to Manage Taste Disorders.

Purpose of the Review: This study aims to summarize the current state of the art of how taste disorders are clinically best managed. Recent Findings: Taste disorders are distressing for the concerned patients since eating and drinking become bothersome or impossible. Apart from nutritional problems, quality of life is impaired. Still, diagnosis and treatment of taste disorders are elusive, and general knowledge about taste and its affection is little within the population and the medical community. This review stresses the importance of accurate workup and diagnosis of taste disorders in order to offer an effective treatment. Yet unclear aspects of taste disorders are discussed, and interesting findings regarding the treatment of taste disorders are reviewed. A special focus is given to current pharmacological options on how to treat taste disorders. Summary: Despite impressive insights into the gustatory function and molecular logic of taste receptor cells, there is currently poor clinical knowledge on the pathophysiology of taste disorders in humans. Diagnosing, measuring, and treating gustatory disorders remain restricted to a handful of specialized smell and taste centers worldwide. Despite interesting work on potential drugs treating taste disorders, many of the reported medications lack controlled and randomized trials confirming their efficacy in taste dysfunction. Future efforts need to be focused on the treatment of taste disorders.

SARS-CoV-2 Leads to Significantly More Severe Olfactory Loss than Other Seasonal Cold Viruses.

The aim of this study was to investigate whether COVID-associated olfactory impairment differs from olfactory disorders due to other upper respiratory tract infections. We investigated the frequency of a SARS-CoV-2 infection among subjects presenting with a subjective olfactory impairment to a corona outpatient clinic between October 2020 and March 2021. Olfactory and gustatory loss were tested psychophysically, and the type of infection, SARS-CoV-2 versus 14 other common cold viruses, was assessed with nasopharyngeal swabs. Differences between the smell impairment caused by the pathogens were compared. Out of the 2120 patients, 314 reported sudden smell and/or taste loss (14%). In 68.9% of them, olfactory and in 25.6%, gustatory dysfunction could be confirmed by psychophysical testing. Of those with a psychophysically determined loss of smell, 61% were tested positive for SARS-CoV-2. SARS-CoV-2 led to a significantly more severe loss of smell and more qualitative olfactory disorders than other pathogens. Apart from rhinorrhea, shortness of breath and sore throat accompanying cold symptoms do not differ significantly between the viruses indicating the particular importance of smell loss in the differential diagnosis of seasonal colds. Multiplex-PCR in non-COVID patients revealed that only 27% of them had rhinoviruses, whereas the remainder were no further identified pathogens. Olfactory screening significantly increases diagnostic accuracy in COVID-19 patients compared to subjective assessment of olfactory loss.

Electrical stimulation of the medial orbitofrontal cortex in humans elicits pleasant olfactory perceptions.

BACKGROUND: Olfactory hallucinations can be part of epileptic seizures of orbitofrontal origin. Olfactory hallucinations, however, are rare and therefore the semiology, localization and lateralization characteristics are underdetermined. In addition, many discrepancies are found in the literature regarding olfactory processing and orbitofrontal (OF) functions and olfactory function. Particularly, the questions of laterality and affective component in coding of odors in the OF cortex remain controversial. AIMS: This study explored whether cortical electrical stimulation of the OF and mesiotemporal brain can trigger olfactory hallucinations with special focus on olfactory percepts in terms of laterality and hedonics. MATERIALS AND METHODS: Eight patients with temporal lobe epilepsy participated in the study, at the time of invasive exploration of their epilepsy. The most distal contact of the OF and anterior hippocampus depth electrodes were stimulated (50 Hz, 0.2 ms biphasic pulse; maximal stimulation 4 mA). Patients were instructed to report any kind of sensation they might experience. Intracranial depth electrodes were localized (iElectrodes): subject-specific brain mask, subcortical segmentation and cortical parcellation based on the Destrieux atlas (FreeSurfer) were superposed to the coregistered T1-weighted MRI and CT images (SPM). The center of mass of each electrode-artifact cluster determined the electrode localization. The electrode labeling was done in patient space. To obtain the electrode coordinates in Montreal Neurological Institute (MNI) space, the images obtained previously in the patient space were first segmented and normalized (SPM). Then, the localization procedure (iElectrodes) was run again with these new normalized images in MNI space. RESULTS: No hallucination was evoked by stimulation, neither of the right nor the left hippocampus (8/8 patients). Pleasant olfactory hallucinations were evoked by OF stimulation in 5/8 patients in either hemisphere. Patients named the percept as the smell of lemon or coffee for example. Among those 5 patients, electrodes were localized in the cortex of the olfactory sulcus, medial orbital sulcus or medial OF gyrus. Increasing stimulation amplitude changed the olfactory percept identification in 3 out of those 5 patients. No affective judgement or change in perceived odor intensity was reported by the patients. No hallucination was evoked by the stimulation of the white matter of the medial OF brain in 3/8 patients independently of the hemisphere stimulated. CONCLUSIONS: This study demonstrated that stimulation of the cortex of the medial OF brain and not of its white matter elicits specific pleasant olfactory hallucinations independently of the hemisphere stimulated, supporting one symmetrical olfactory processing in human.

[Widal's triad : clinical manifestations, pathophysiology and therapeutic advances]. / Syndrome de Widal : manifestations cliniques, physiopathologie et avancées thérapeutiques.

NSAID-Exacerbated respiratory disease (also known as Samter's or Widal's triad, aspirin-exacerbated respiratory disease) is characte- rized by asthma, nasal polyposis and hypersensitivity to NSAIDs. The pathogenesis of this chronic inflammation arises from an imbalance in arachidonic acid metabolism, leading to an increase in pro- inflammatory cysteinyl-leukotrienes. The treatment is based on drug management of asthma and polyps and, in advanced situations, surgical management of polyposis. Monoclonal antibodies have shown promising results in the further medical treatment of this entity.

Le syndrome de Widal (SW) (également connu sous le nom de triade de Samter, maladie respiratoire exacerbée par l'Aspirine) est une entité clinique caractérisée par la triade comprenant un asthme, une polypose nasale et une intolérance aux AINS. La physiopathologie de cette maladie, bien qu'incomplètement élucidée, est caractérisée par un déséquilibre dans le métabolisme de l'acide arachidonique (AA) en faveur de la voie des cystéinyl- leucotriènes (cysLT). Son traitement repose sur une prise en charge médicamenteuse agressive de l'asthme et des polypes et, dans des situations avancées, la prise en charge chirurgicale de la polypose. L'avènement des traitements par anticorps monoclo- naux a montré des résultats encourageants pour les alternatives thérapeutiques futures.

Chemosensory decrease in different forms of olfactory dysfunction.

The aim of this study is to investigate the effect of olfactory dysfunction (OD) on the two other chemical senses, namely gustation and the intranasal trigeminal system. Taste and trigeminal function were analyzed in a retrospective cross-sectional study of 178 participants with OD (n = 78 posttraumatic, n = 42 idiopathic, n = 27 post-infectious and n = 31 chronic rhinosinusitis (CRS) OD). All patients had been investigated for OD at our smell and taste outpatient clinic. Evaluation of olfaction was performed by means of the Sniffin' Sticks test (odor threshold, odor discrimination and odor identification), whereas gustatory function was assessed with the Taste Strips test and the intranasal trigeminal sensitivity by means of the lateralization task. The degree of olfactory impairment was found to depend on the cause of OD, but not on patients' age. Patients with posttraumatic OD showed lower olfactory function than patients with idiopathic, post-infectious and CRS OD (p = 0.01). Gustatory and trigeminal sensitivity in turn depended on age rather than the cause of olfactory dysfunction. Partial correlations between olfactory, gustatory, and trigeminal scores, with age as covariate, were significant, showing a decrease of taste and trigeminal function proportional to the OD (p < 0.05). The present data suggest that the three chemical senses are closely connected for humans underlining that in case of OD the remaining chemical senses (taste, trigeminal function) tend to decrease rather than compensate as this is seen for sensory loss in other modalities. This finding has direct clinical implications and importance when dealing with smell and taste disorders.

[The efficacy of omalizumab in the treatment of chronic rhinosinusitis with nasal polyps: a discussion of 2 refractory cases]. / Efficacité de l'omalizumab dans la polypose nasale: à propos de deux cas.

Nasal polyposis is a specific phenotype of chronic rhinosinusitis (CRS). Some cases can be managed with topical and infrequent use of systemic steroids, while many patients require surgery. Despite postoperative, regular steroid administration, recurrences may be found especially in patients suffering from Aspirin exacerbated respiratory disease (AERD), a particularly severe form of CRS with polyps, asthma and non-steroid-anti-inflammatory-drug (NSAID) intolerance. We report two cases of difficult-to-treat AERD patients following revision surgery, treated with monoclonal anti-IgE antibody (omalizumab) and successful control of the disease and symptoms. Omalizumab may be a promising alternative in selected cases of CRS with nasal polyps to avoid overuse of systemic steroids and frustrating repetition of paranasal sinus surgeries.

La rhinosinusite chronique (RSC) touche 15 % de la population et se caractérise par l'obstruction et l'écoulement nasaux pendant plus de trois mois. Les formes sévères de la RSC sont associées à la présence de polypes nasaux. Le traitement de première ligne sont des corticoïdes topiques, qui ne sont pas toujours efficaces et certains patients ont besoin de plusieurs cures de stéroïdes per os et chirurgies nasales répétitives pour stabiliser la maladie. Ce cercle vicieux s'observe souvent dans le syndrome de Widal (polypes, asthme et intolérance aux AINS). On rapporte deux cas de Widal avec interruption de cette boucle, obtenue par l'application de l'anticorps monoclonal anti-IgE omalizumab. L'omalizumab pourrait être une alternative dans certains cas de RSC pour limiter la surutilisation de stéroïdes et la répétition frustrante de chirurgie nasale.

Sleep apnea: Do not forget to inspect the throat!

Obstructive sleep apnea syndrome (OSAS) is a widespread and underdiagnosed disease. Causes are mostly related to obesity and anatomy with oro-pharyngeal narrowing. Parapharyngeal tumors are rare but can easily be treated. Careful oro-pharyngeal examination in OSAS patient is cheap, easy to perform by non-ENT specialists, quick, and avoids inadequate treatment.

[Psychophysical olfactory testing : what's new ?] / Tests psychophysiques de l'olfaction : quoi de neuf ?

Olfactory disorders are common and may lead to severe consequences on quality of life. Medical management including treatment options can be proposed to the patients. For this reason, a correct diagnosis is important. Olfactory testing is one of the cornerstones for the diagnosis of smell impairment which helps to quantify the deficit. Despite good and widespread psychophysical olfactory tests, there are still many challenges in testing olfaction. Most of the current available test may not fully account for some cultural and genetic biases. Therefore it is difficult to develop olfactory tests and standardize them across different populations. In this paper we discuss an alternative method based on « white smells ¼ which may help to overcome these issues.

Les troubles olfactifs sont fréquents et peuvent parfois entraîner des conséquences importantes pour la qualité de vie des personnes concernées. Une prise en charge médicale et des traitements peuvent être proposés pour certains patients. Les tests olfactifs sont une des pierres angulaires dans le processus diagnostique qui permettent la quantification de la perte de l'odorat. Pour améliorer ces tests, des défis sont encore à relever. Leurs résultats peuvent parfois être biaisés par des facteurs culturels ou génétiques. L'une des possibles méthodes pour contourner ces problèmes est l'utilisation d'« odeurs blanches ¼, discutée dans cet article.

Human innate lymphoid cells (ILCs): Toward a uniform immune-phenotyping.

Helper innate lymphoid cells (ILCs), the most recently identified population of the ILC family, play a fundamental role in the restoration of tissue integrity, in the protection against infiltrating pathogens as well as in tumor immune-surveillance. ILCs have been divided into three main subsets, ILC1, ILC2, and ILC3, that can be specifically activated by different signals coming either indirectly from pathogens or from other cell populations, including cancer cells. Following activation, ILCs are in turn able to promptly secrete a wide range of soluble mediators that modulate effector cell functions. The discovery and the study of these immune cells is now offering important opportunities for innovative therapies of allergic airway diseases, inflammatory disorders and might be crucial for the discovery of new targets for the therapy of cancer. It is therefore fundamental that the scientific community establishes harmonized guidelines to obtain a consensus in the identification and phenotypical and functional characterization of ILCs. © 2018 International Clinical Cytometry Society.

First report of clinical responses to immunotherapy in 3 relapsing cases of chordoma after failure of standard therapies.

Chordoma is a rare tumor of notochordal origin, currently principally treated by surgery and/or irradiation. Here, we describe the clinical outcome of 3 consecutive patients with metastatic and locally advanced chordoma, treated with different immunotherapeutic approaches. All patients presented fast growing tumors and failure of standard therapies. One was treated with a tumor-based vaccine, the 2 others with anti-PD1 antibodies, all with impressive clinical and radiological responses. We therefore propose that chordoma is an immunogenic tumor and thus that translational and clinical research is necessary to develop rationally designed immunotherapy approaches.

Warthin's tumor of the larynx: a very rare case and systematic review of the literature.

BACKGROUND: Warthin's tumor or cystadenolymphoma (CAL) is a benign salivary gland tumor occurring almost exclusively in the parotid gland. CALs of other locations are rare. CASE PRESENTATION: We report a laryngeal CAL detected in a positron emission tomography/computed tomography (PET/CT) performed for breast cancer follow-up. The tumor was successfully treated by transoral surgery. DISCUSSION: Only 14 cases of laryngeal CAL are reported worldwide. These cases confirmed our experience of an uncomplicated and mostly successful transoral resection. CONCLUSION: CALs of the larynx are very rare. They are characterized by hypermetabolism in PET/CT. The increasing use of PET/CT investigations in cancer patients could give rise to more incidental findings of CALs at unusual locations such as the larynx.

Subcutaneous sarcoidosis in a rhinoplasty scar.

The presence of a subcutaneous hard bony-like lump at the lateral nasal wall after a septorhinoplasty procedure is an unfavourable result. The reported patient developed this complication 2 years after a revision surgery, in which percutaneous osteotomies were performed. An excision biopsy of the lump took place and the histopathological analysis revealed a granulomatous gigantocellular inflammation with absence of birefringent particles on polarised lamp and negative mycobacteria culture. After additional investigations, the final diagnosis was consistent with grade 2 pulmonary sarcoidosis associated with subcutaneous sarcoidosis. No treatment was initiated. The facial symptoms resolved without any additional treatment and the pulmonary function tests have not deteriorated after 1 year of follow-up. The polymorphism of cutaneous lesions in sarcoidosis, the absence of systemic symptoms and the unrecognised entity of subcutaneous sarcoidosis in a scar illustrate the diagnostic challenge with this patient.

Rivalry of homeostatic and sensory-evoked emotions: Dehydration attenuates olfactory disgust and its neural correlates.

Neural correlates have been described for emotions evoked by states of homeostatic imbalance (e.g. thirst, hunger, and breathlessness) and for emotions induced by external sensory stimulation (such as fear and disgust). However, the neurobiological mechanisms of their interaction, when they are experienced simultaneously, are still unknown. We investigated the interaction on the neurobiological and the perceptional level using subjective ratings, serum parameters, and functional magnetic resonance imaging (fMRI) in a situation of emotional rivalry, when both a homeostatic and a sensory-evoked emotion were experienced at the same time. Twenty highly dehydrated male subjects rated a disgusting odor as significantly less repulsive when they were thirsty. On the neurobiological level, we found that this reduction in subjective disgust during thirst was accompanied by a significantly reduced neural activity in the insular cortex, a brain area known to be considerably involved in processing of disgust. Furthermore, during the experience of disgust in the satiated condition, we observed a significant functional connectivity between brain areas responding to the disgusting odor, which was absent during the stimulation in the thirsty condition. These results suggest interference of conflicting emotions: an acute homeostatic imbalance can attenuate the experience of another emotion evoked by the sensory perception of a potentially harmful external agent. This finding offers novel insights with regard to the behavioral relevance of biologically different types of emotions, indicating that some types of emotions are more imperative for behavior than others. As a general principle, this modulatory effect during the conflict of homeostatic and sensory-evoked emotions may function to safeguard survival.