RESUMEN
OBJECTIVE: To assess the physiopathology of olfactory function loss (OFL) in patients with coronavirus disease 2019 (COVID-19), we evaluated the olfactory clefts (OC) on MRI during the early stage of the disease and 1 month later. METHODS: This was a prospective, monocentric, case-controlled study. Twenty severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-infected patients with OFL were included and compared to 20 age-matched healthy controls. All infected patients underwent olfactory function assessment and 3T MRI, performed both at the early stage of the disease and at the 1-month follow-up. RESULTS: At the early stage, SARS-CoV2-infected patients had a mean olfactory score of 2.8 ± 2.7 (range 0-8), and MRI displayed a complete obstruction of the OC in 19 of 20 patients. Controls had normal olfactory scores and no obstruction of the OC on MRI. At the 1 month follow-up, the olfactory score had improved to 8.3 ± 1.9 (range 4-10) in patients, and only 7 of 20 patients still had an obstruction of the OC. There was a correlation between olfactory score and obstruction of the OC (p = 0.004). CONCLUSION: OFL in SARS-CoV2-infected patients is associated with a reversible obstruction of the OC.
Asunto(s)
Anosmia/diagnóstico , Anosmia/etiología , COVID-19/complicaciones , Edema/patología , Cavidad Nasal/patología , Obstrucción Nasal/patología , Adulto , Anosmia/patología , Anosmia/fisiopatología , COVID-19/diagnóstico por imagen , COVID-19/patología , COVID-19/fisiopatología , Estudios de Casos y Controles , Edema/diagnóstico por imagen , Edema/etiología , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Cavidad Nasal/diagnóstico por imagen , Obstrucción Nasal/diagnóstico por imagen , Obstrucción Nasal/etiología , Adulto JovenRESUMEN
The aim of this study was to evaluate the postoperative consequences of chorda tympani reclining during middle ear surgery for otosclerosis. Electrogustometric taste thresholds were measured at 11 loci on the tongue and the soft palate in 14 patients before surgery, and 8 d, 1 month and (in some cases) 6 months after surgery. A significant increase in thresholds was observed on the ipsilateral side of the tongue after surgery. The extent of the deficit and the recovery time course depended on tongue locus. The tip of the tongue displayed a limited deficit, suggesting bilateral chorda tympani innervation. The edge of the tongue was less impaired than the dorsal or the lateral tip loci; it may be dually innervated by both chorda tympani and glossopharyngeal nerves in humans, as already shown in rats. Likewise for the fungiform papillae located just anterior to the circumvallate papillae. Somatosensory early complaints suggest a derepression of chorda tympani on lingual nerve signals. In a second stage, relief of complaints before electrogustometric threshold recovery suggested trigeminal compensation of the chorda tympani deficit. Relief of complaints seems to involve central integrative processes, whereas the evolution of electrogustometric threshold represents the actual recovery time course of chorda tympani peripheral sensitivity.
Asunto(s)
Nervio de la Cuerda del Tímpano/fisiopatología , Otosclerosis/cirugía , Cirugía del Estribo/efectos adversos , Trastornos del Gusto/fisiopatología , Percepción del Gusto/fisiología , Adulto , Nervio de la Cuerda del Tímpano/cirugía , Femenino , Nervio Glosofaríngeo/fisiología , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Corteza Somatosensorial/fisiología , Estadísticas no Paramétricas , Papilas Gustativas/fisiopatología , Trastornos del Gusto/etiología , Umbral GustativoAsunto(s)
Infecciones por Coronavirus , Coronavirus , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , China , Humanos , SARS-CoV-2RESUMEN
Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia. The gene underlying the X chromosome-linked form of the disease, KAL-1, consists of 14 coding exons. It encodes a glycoprotein, anosmin-1, which is involved in the embryonic migration of GnRH-synthesizing neurons and the differentiation of the olfactory bulbs. We describe herein the clinical heterogeneity in three affected brothers who carry a large deletion (exons 3-13) in KAL-1. All three had a history of hypogonadotropic hypogonadism with delayed puberty. Although brain magnetic resonance imaging showed hypoplastic olfactory bulbs in the three siblings, variable degrees of anosmia/hyposmia were shown by olfactometry. In addition, these brothers had different phenotypic anomalies, i.e. unilateral renal aplasia (siblings B and C), high-arched palate (sibling A), brachymetacarpia (sibling A), mirror movements (siblings A and B), and abnormal eye movements (sibling C). Last but not least, sibling A suffered from a severe congenital hearing impairment, a feature that had been reported in KS but had not yet been ascribed unambiguously to the X-linked form of the disease. The variable phenotype, both qualitatively and quantitatively, in this family further emphasizes the role of putative modifier genes, and/or epigenetic factors, in the expressivity of the X-linked KS.
Asunto(s)
Moléculas de Adhesión Celular/genética , Cromosomas Humanos X , Proteínas de la Matriz Extracelular , Eliminación de Gen , Ligamiento Genético , Síndrome de Kallmann/genética , Adolescente , Adulto , Estatura , Exones , Humanos , Hipogonadismo , Síndrome de Kallmann/diagnóstico , Imagen por Resonancia Magnética , Masculino , Proteínas del Tejido Nervioso/genética , Trastornos del Olfato , Bulbo Olfatorio/patología , Fenotipo , Reacción en Cadena de la Polimerasa , Pubertad Tardía , OlfatoRESUMEN
CONTEXT: Kallmann syndrome (KS) is characterized by congenital hypogonadotropic hypogonadism (CHH) and an impaired sense of smell related to defective development of the olfactory system. OBJECTIVE: The aim of the study was to use high-resolution computed tomography (CT) to detect specific abnormalities in the ethmoid bone region surrounding the olfactory bulbs in patients with KS. PATIENTS: Thirty-seven KS patients were compared to normosmic CHH (nCHH) patients (n = 15) and controls (n = 30) of similar age. DESIGN AND METHODS: We conducted a prospective study in a single referral center. Subjects underwent CT in bone windows with axial, coronal, and sagittal reconstructions centered on the olfactory fossa (OF) and cribriform plate (CP). We characterized the OF structure by measuring OF height, width, and surface area and a series of angles. The CP foramina were counted bilaterally. Olfactory bulb magnetic resonance imaging, performed in parallel, was compared with CT findings. RESULTS: OF height, width, and surface area were all significantly lower in KS patients than in nCHH patients and controls (P < .0001). KS patients also had wider angles than nCHH patients and controls (P < .0001). KS subjects with olfactory bulb agenesis on magnetic resonance imaging or who harbored KAL1 mutations had the most marked changes in OF measurements and angles. Coronal OF height distinguished KS patients from controls with the best sensitivity and specificity. The mean number of CP foramina was similar in KS, nCHH, and control subjects. CONCLUSIONS: KS is associated with specific ethmoid bone abnormalities. The preserved number of CP foramina in KS patients suggests that the integrity of olfactory structures is not mandatory for their formation during fetal development or their maintenance in adult life.
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Hueso Etmoides/anomalías , Hueso Etmoides/diagnóstico por imagen , Síndrome de Kallmann/diagnóstico por imagen , Bulbo Olfatorio/anomalías , Base del Cráneo/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Diagnóstico Diferencial , Hueso Etmoides/patología , Femenino , Humanos , Hipogonadismo/diagnóstico por imagen , Hipogonadismo/patología , Síndrome de Kallmann/patología , Imagen por Resonancia Magnética , Masculino , Trastornos del Olfato/diagnóstico por imagen , Trastornos del Olfato/patología , Bulbo Olfatorio/diagnóstico por imagen , Bulbo Olfatorio/patología , Estudios Prospectivos , Curva ROC , Reproducibilidad de los Resultados , Base del Cráneo/patología , Tomografía Computarizada por Rayos X/normas , Adulto JovenRESUMEN
Several studies indicate an essential role of the heterodimer Tas1R1-Tas1R3 for monosodium l-glutamate (MSG) detection, although others suggest alternative receptors. Human subjects show different taste sensitivities to MSG, and some are unable to detect the presence of glutamate. Our objective was to study possible relations between phenotype (sensitivity to glutamate) and genotype (polymorphisms in candidate glutamate taste receptors tas1r1, tas1r3, mGluR4, and mGluR1) at the individual level. The sensitivity was measured with a battery of tests to distinguish the effect of sodium ions from the effect of glutamate ions in MSG. A total of 142 genetically unrelated white French subjects were categorized into 27 nontasters (specific ageusia), 21 hypotasters, and 94 tasters. Reverse transcriptase polymerase chain reaction and immunohistochemistry showed expression of tas1r1, tas1r3, and alpha-gustducin in fungiform papillae in all 12 subjects tested, including subjects who presented specific ageusia for glutamate. Amplification and sequencing of cDNA and genomic DNA allowed the identification of 10 nonsynonymous single nucleotide polymorphisms (nsSNPs) in tas1r1 (n = 3), tas1r3 (n = 3), and mGluR1 (n = 4). In our sample of subjects, the frequencies of 2 nsSNPs, C329T in tas1r1 and C2269T in tas1r3, were significantly higher in nontasters than expected, whereas G1114A in tas1r1 was more frequent in tasters. These nsSNPs along with minor variants and other nsSNPs in mGluR1, including T2977C, account for only part of the interindividual variance, which indicates that other factors, possibly including additional receptors, contribute to glutamate sensitivity.
Asunto(s)
Polimorfismo de Nucleótido Simple , Receptores de Glutamato/genética , Glutamato de Sodio , Umbral Gustativo/genética , Gusto/genética , Secuencia de Bases , Femenino , Francia , Expresión Génica , Genotipo , Humanos , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple/fisiología , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Glutamato/metabolismo , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Gusto/fisiología , Papilas Gustativas , Umbral Gustativo/fisiología , Transducina/metabolismoRESUMEN
The first step in the olfactory perception is the activation by odorants of sensory neurones in the olfactory epithelium. In humans, this sensory epithelium is located at 2 narrow passages, the olfactory clefts, at the upper part of the nasal cavities. Little is known about the physiology of these clefts. We examined, in 34 patients, the impact of obstructed clefts upon detection and postlearning identification of 5 odorants. The location and extension of the obstructions were assessed using endoscopy, CT scans, and MRI. The inflammatory obstruction was usually bilateral, extending anteroposteriorly, and confined to the clefts, with no sign of obstruction or any inflammatory disease in the rest of the nasal cavities and sinuses. When tested with 5 odorants, these patients showed greatly impaired olfaction compared with a group of 73 normosmic subjects. The majority of these 34 patients had sensory deficits equivalent to that found in another group of 41 congenital anosmic patients, where inspection with MRI indicated the lack of olfactory bulbs. This study demonstrates that the olfactory clefts, in human, function as an entity that is different from other regions of the nasal cavity and is the target for local inflammatory events that are apparently not responding to corticoid and antibiotic treatments.
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Enfermedades Nasales/fisiopatología , Nariz/fisiología , Trastornos del Olfato/fisiopatología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Nariz/anatomía & histología , Enfermedades Nasales/complicaciones , Enfermedades Nasales/diagnóstico , Trastornos del Olfato/etiología , Valores de Referencia , Rinitis/fisiopatología , Olfato , Síndrome , Tomografía Computarizada por Rayos XRESUMEN
In humans, the olfactory epithelium is located in two narrow passages, the olfactory clefts, at the upper part of the nasal cavities. The olfactory epithelium is covered by a mucus layer which is essential for the function of the olfactory neurons that are directly connected with the brain through the cribriform plate. This anatomical weakness of the brain protection may be the source of infection. Little is known about the composition of this mucus in humans. Previous proteomic analyses have been performed on washes of the entire nasal cavities and therefore might better correspond to the mucus over the respiratory epithelium than to the mucus covering the olfactory epithelium. In the present study, we sampled the olfactory mucus directly from the clefts of 16 healthy adult volunteers, and 83 proteins were identified in the samples using two-dimensional gel electrophoresis, MALDI-TOF, RPLC, and Edman sequencing. Forty-three proteins were not previously observed either in nasal mucus sampled through washings, saliva, tear, or cerebrospinal fluid. In Accordance with the data in the protein databases, the most abundant proteins are secreted, whereas some others correspond to intracellular proteins covering a large range of functions: anti-inflammatory, antimicrobial, protease inhibition, antioxidant, transport, transcription, transduction, cytoskeletal, regulation, binding, and metabolism of odorant molecules. This study clearly demonstrates the complexity of the mucus covering the human olfactory epithelium, which might comprise potential markers for characterizing pathophysiological states.
Asunto(s)
Moco/química , Mucosa Olfatoria , Proteínas/análisis , Proteoma/análisis , Adulto , Animales , Cromatografía Liquida , Bases de Datos de Proteínas , Electroforesis en Gel Bidimensional , Humanos , Datos de Secuencia Molecular , Mucosa Olfatoria/anatomía & histología , Mucosa Olfatoria/química , Proteínas/genética , Análisis de Secuencia de Proteína , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Odorant-binding proteins (OBPs) are small abundant extracellular proteins belonging to the lipocalin superfamily. They are thought to participate in perireceptor events of odor detection by carrying, deactivating, and/or selecting odorant molecules. Putative human OBP genes (hOBP) have recently been described [Lacazette et al. (2000) Hum. Mol. Genet. 9, 289-301], but the presence of the corresponding proteins remained to be established in the human olfactory mucus. This paper reports the first evidence of such expression in the mucus covering the olfactory cleft, where the sensory olfactory epithelium is located. On the contrary, hOBPs were not observed in the nasal mucus covering the septum and the lower turbinate. To demonstrate the odorant binding activity of these proteins, a corresponding recombinant protein variant, hOBP(IIa)(alpha), was secreted by the yeast Pichia pastoris and thoroughly characterized. It appears as a monomer with one disulfide bond located between C59 and C151, a conservative feature of all other vertebrate OBPs. By measuring the displacement of several fluorescent probes, we show that hOBP(IIa)(alpha) is able to bind numerous odorants of diverse chemical structures, with a higher affinity for aldehydes and large fatty acids. A computed 3D model of hOBP(IIa)(alpha) is proposed and reveals that two lysyl residues of the binding pocket may account for the increased affinity for aldehydes. The relatively limited specificity of hOBP(IIa)(alpha) suggests that other human OBPs are expected to take into account the large diversity of odorant molecules.