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.

[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.

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.

Diagnostic value of biopsies in identifying cytoplasmic antineutrophil cytoplasmic antibody-negative localized Wegener's granulomatosis presenting primarily with sinonasal disease.

BACKGROUND: A substantial proportion of Wegener's disease (WG) patients present with localized disease of the upper airways, i.e., sinonasal and other ear/nose/throat (ENT) symptoms. Because of the oligosymptomatic presentation a timely diagnosis of this potentially fatal disease is challenging. This study evaluates diagnostic peculiarities between WG in its localized and generalized form of the disease. METHODS: Retrospective analysis was performed of 82 patients with suspected WG manifesting in the ENT region between 1989 and 2009. Comparison was performed of the clinical and laboratory results between patients with localized (n = 15) and generalized stage (n = 16) as well as non-WG patients (n = 50). RESULTS: ENT signs and symptoms were subtle, especially in the population presenting with localized disease. Therapy refractory rhinosinusitis or serous otitis media were the most frequent presentations of WG. In testing for localized WG, mucosal biopsy had the highest sensitivity (53%) compared with cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCAs) with a lower sensitivity (47%) but highest specificity (96%) and highest positive predictive value (PPV; 78% versus 73%). Patients with generalized WG typically revealed a pathological urine sediment, hemoptysis, or rheumatological symptoms. In the generalized stage, c-ANCA had the highest sensitivity (81%), specificity (96% versus 95%), and highest PPV (87%). CONCLUSION: Timely diagnosis and treatment of localized WG limited to the ENT region remains problematic. Even with adequate therapy, nearly one-half of patients with sinonasal localization suffer from relapse, at least 1 in 10 will progress to generalized disease, and up to two-thirds may develop permanent tissue damage. Unfortunately, the diagnostic usefulness of c-ANCA is significantly reduced at this early stage compared with cases with generalized disease (p = 0.04). Hence, the relative diagnostic value of mucosal biopsy increases especially for the significant proportion of c-ANCA(-) localized WG patients (47%). Sinonasal tissue sampling represents a cornerstone for diagnosis, which unlike c-ANCA testing can be repeated in short intervals and is associated with low morbidity.

Orbital involvement in Pott's puffy tumor: a systematic review of published cases.

BACKGROUND: Pott's puffy tumor (PPT) is a frontal subperiosteal abscess associated with underlying frontal bone osteomyelitis. It represents a well-known source of sinogenic intracranial infection, but the orbital complications related to this entity are rarely reported. The goal of this study was to characterize the orbital involvement in PPT. METHODS: We performed a systematic review through a Medline search (1950-2010). The authors reviewed all cases of PPT, selecting those explicitly describing orbital complications associated with PPT. RESULTS: We screened 139 articles, of which 93 reported cases of PPT. Of these, 35 articles described a total of 42 cases presenting simultaneous orbital complications. Eyelid and/or periorbital edema was the most common finding in patients with orbital involvement, and preseptal cellulitis is by far the most prevalent orbital complication in PPT. Postseptal involvement (orbital cellulitis, subperiosteal abscess of the orbit, and orbital abscess) is much rarer. Although treatment of the classic PPT is surgical, only a minority of patients with orbital infection required orbital drainage. Most reported patients made a full recovery, without permanent sequelae. CONCLUSION: Orbital infections are possible in patients with PPT. In contrast to surgical treatment of the frontal subperiosteal abscess, the orbital complications can be treated conservatively most of the time. Early diagnosis and aggressive therapy of the underling PPT are essential to avoid severe local or systemic complications.

Recovery from long-lasting post-tonsillectomy dysgeusia.

Transient post-tonsillectomy taste dysgeusia (PTD) is a common complaint. Long-lasting PTD is less frequent but has significant consequences on patients' quality of life, with some cases leading to medicolegal issues. Treatment options and knowledge about mechanisms and factors favoring PTD are limited. PTD may result from direct surgical injury, tongue compression, inflammatory processes or side effects of local anesthetics. Some authors also claim that dietary zinc deficiency plays a role in the development of PTD. Although this latter cause had not yet received a lot of attention, we report a case of a female patient who reported a 4-year PTD and recovered within 2 months after oral intake of zinc sulfate. This clinical observation, together with recent findings on significant improvement of taste disorders after zinc treatments for other causes, opens again the question of what extent zinc deficiency plays a role in PTD.

Chemosensory function in Wegener's granulomatosis: a preliminary report.

Despite the fact that Wegener's granulomatosis affects the nasal and paranasal cavities and the cranial nerves regularly, chemosensory impairments have not been reported. The objective of this study is to test the three chemosensory systems, olfaction, taste, and intranasal trigeminal function in Wegener disease patients. We tested olfactory, gustatory, and intranasal trigeminal function in nine patients (5 women, 4 men, mean age 57 years) with confirmed Wegener's granulomatosis. Olfaction was tested with the Sniffin'Sticks, gustatory function with the "Taste strips" and intranasal trigeminal function with a lateralization task. One patient had anosmia (11%), four patients had hyposmia (44%) and four patients were normosmic (45%). Gustatory testing function showed pathological taste strip results in five patients (55%) and normal results in three patients (33%). One patient did not undergo taste testing. Intranasal trigeminal function was lowered in five patients (56%) and normal in four patients (44%). Neither previous nasal surgery status nor endoscopic status was associated to a higher frequency in pathological scores for any of the three chemical senses. In conclusion, these preliminary results suggest a consistent affection in chemosensory functions in Wegener's granulomatosis patients.

Postoperative/posttraumatic gustatory dysfunction.

Clinical taste testing in humans is far from being routinely performed in ear, nose and throat (ENT) clinics. Consequently, most reports on posttraumatic and postoperative taste disorders are case reports and mainly consist of qualitative (e.g. dysgeusia, metallic taste) taste changes after either head injury or ENT surgery. Since quantitative taste deficiencies (ageusia, hypogeusia) often go unnoticed by the patients, the real incidence of ageusia and hypogeusia after head trauma and various surgical procedures remains largely unknown. This lack of reliable clinical data is partly due to the lack of easy, reproducible and rapid clinical taste testing devices. The present chapter tries to resume the current knowledge on postoperative and posttraumatic taste disorders. Despite the sparse literature, the chapter focuses on those ENT surgical procedures where at least some prospective and systematic studies on gustatory dysfunction exist. Accordingly, taste disorders after middle ear surgery, tonsillectomy and dental interventions are largely discussed.

Mechanical obstruction of the olfactory cleft reveals differences between orthonasal and retronasal olfactory functions.

Following up on recent observations in patients with nasal polyposis (NP), the present study aimed to investigate whether a mechanical obstruction of the anterior olfactory cleft (OC) would produce differential effects on orthonasal and retronasal olfactory functions. To this end, we studied 33 healthy subjects in a randomized trial. Sponges with high content of saline were either placed in the OC or on the respiratory epithelium, such that this was blinded to both subject and observer. The results indicated that orthonasal (P = 0.04) but not retronasal (P = 0.15) olfactory identification ability was lower when the OC was blocked. This confirms the idea that differences between orthonasal and retronasal olfactory functions, as observed in NP patients, are, at least to some degree, due to mechanical obstruction of the anterior portion of the OC. The present data also suggest that mechanical obstruction is a means to induce reversible hyposmia void of side effects which can be performed in a blinded fashion. This might become a valuable model of hyposmia for future investigations.