Search Results (239)

Background: Congenital anosmia (CA) is a rare condition characterized by a lifelong inability to perceive odors, which significantly affects daily life and may be linked to broader neurodevelopmental alterations. This study aimed to investigate structural brain differences in patients with CA using MRI, focusing on gray matter (GM) and white matter (WM) changes and their implications for neurodevelopment. Methods: This retrospective study included 28 patients with CA and 28 age- and gender-matched healthy controls. Patients with CA were diagnosed at a single medical center between 1 January 2001 and 30 August 2024. Controls were randomly selected from an imaging database and had no history of olfactory dysfunction. Brain Magnetic Resonance Imaging (MRI)was analyzed using volumetric analysis in SPM12.GM and WM volumes were quantified across 11 anatomical brain regions based on theWFU_PickAtlas toolbox, including frontal, temporal, parietal, occipital, limbic, sub-lobar, cerebellum (anterior/posterior), midbrain, the pons, and the frontal–temporal junction. Left–right hemispheric comparisons were also conducted. Results: Patients with CA exhibited significantly smaller GM volumes compared to healthy controls (560.6 ± 114.7 cc vs. 693.7 ± 96.3 cc, p < 0.001) but larger WM volumes (554.2 ± 75.4 cc vs. 491.1 ± 79.7 cc, p = 0.015). Regionally, GM reductions were observed in the frontal (131.9 ± 33.7 cc vs. 173.7 ± 27.0 cc, p < 0.001), temporal (81.1 ± 18.4 cc vs. 96.5 ± 14.1 cc, p = 0.001), parietal (52.4 ± 15.2 cc vs. 77.2 ± 12.4 cc, p < 0.001), sub-lobar (57.8 ± 9.7 cc vs. 68.2 ± 10.2 cc, p = 0.001), occipital (39.1 ± 13.0 cc vs. 57.8 ± 8.9 cc, p < 0.001), and midbrain (2.0 ± 0.5 cc vs. 2.3 ± 0.4 cc, p = 0.006) regions. Meanwhile, WM increases were notable in the frontal(152.0 ± 19.9 cc vs. 139.2 ± 24.0 cc, p = 0.027), temporal (71.5 ± 11.5 cc vs. 60.8 ± 9.5 cc, p = 0.001), parietal (75.8 ± 12.4 cc vs. 61.9 ± 11.5 cc, p < 0.001), and occipital (58.7 ± 10.3 cc vs. 41.9 ± 7.9 cc, p < 0.001) lobes. A separate analysis of the left and right hemispheres revealed similar patterns of reduced GM and increased WM volumes in patients with CA across both sides. An exception was noted in the right cerebellum-posterior, where patients with CA showed significantly greater WM volume (5.625 ± 1.667 cc vs. 4.666 ± 1.583 cc, p = 0.026). Conclusions: This study demonstrates widespread structural brain differences in individuals with CA, including reduced GM and increased WM volumes across multiple cortical and sub-lobar regions. These findings suggest that congenital olfactory deprivation may impact brain maturation beyond primary olfactory pathways, potentially reflecting altered synaptic pruning and increased myelination during early neurodevelopment. The involvement of the cerebellum further implies potential adaptations beyond motor functions. These structural differences may serve as potential neuroimaging markers for monitoring CA-associated cognitive or emotional comorbidities. Full article

Kallmann syndrome (KS) is a form of hypogonadotropic hypogonadism (HH) characterized by gonadotropin-releasing hormone (GnRH) deficiency and anosmia due to defective neuronal migration. While traditionally considered irreversible, cases of spontaneous improvement of HH have been reported, suggesting residual GnRH neuronal function in some individuals. We present a case of a 29-year-old man with KS who exhibited spontaneous recovery of endogenous testosterone production following the cessation of long-term androgen therapy without the use of alternative hormonal agents. After ceasing testosterone therapy for several months, the patient’s total testosterone levels normalized (407–424 ng/dL), accompanied by increased secondary sexual characteristics, stable gonadotropin levels, and normal testicular volume. Persistent anosmia was noted, suggesting that restoration of reproductive endocrine function can occur independently of olfactory recovery. Genetic testing identified heterozygous mutations in PCSK1 and HS6ST1, genes implicated in GnRH regulation and KS pathogenesis. This case highlights the potential role of genetic variation in spontaneous HH improvement and underscores the need for individualized management strategies, including periodic reassessment of gonadal function and fertility potential. Further research is needed to elucidate the mechanisms driving spontaneous HH improvement, identify predictive biomarkers of reversibility, and explore therapeutic strategies that may promote endogenous GnRH activity in select patients with KS. Full article

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting countless individuals worldwide. PD is characterized by the onset of a marked motor symptomatology in association with several non-motor manifestations. The clinical phase of the disease is usually preceded by a long prodromal phase, devoid of overt motor symptomatology but often showing some conditions such as sleep disturbance, constipation, anosmia, and phonatory changes. To date, speech analysis appears to be a promising digital biomarker to anticipate even 10 years before the onset of clinical PD, as well serving as a useful prognostic tool for patient follow-up. That is why, the voice can be nominated as the non-invasive method to detect PD from healthy subjects (HS). Methods: Our study was based on cross-sectional study to analysis voice impairment. A dataset comprising 81 voice samples (41 from healthy individuals and 40 from PD patients) was utilized to train and evaluate common machine learning (ML) models using various types of features, including long-term (jitter, shimmer, and cepstral peak prominence (CPP)), short-term features (Mel-frequency cepstral coefficient (MFCC)), and non-standard measurements (pitch period entropy (PPE) and recurrence period density entropy (RPDE)). The study adopted multiple machine learning (ML) algorithms, including random forest (RF), K-nearest neighbors (KNN), decision tree (DT), naïve Bayes (NB), support vector machines (SVM), and logistic regression (LR). Cross-validation technique was applied to ensure the reliability of performance metrics on train and test subsets. These metrics (accuracy, recall, and precision), help determine the most effective models for distinguishing PD from healthy subjects. Result: Among all the algorithms used in this research, random forest (RF) was the best-performing model, achieving an accuracy of 82.72% with a ROC-AUC score of 89.65%. Although other models, such as support vector machine (SVM), could be considered with an accuracy of 75.29% and a ROC-AUC score of 82.63%, RF was by far the best one when evaluated across all metrics. The K-nearest neighbor (KNN) and decision tree (DT) performed the worst. Notably, by combining a comprehensive set of long-term, short-term, and non-standard acoustic features, unlike previous studies that typically focused on only a subset, our study achieved higher predictive performance, offering a more robust model for early PD detection. Conclusions: This study highlights the potential of combining advanced acoustic analysis with ML algorithms to develop non-invasive and reliable tools for early PD detection, offering substantial benefits for the healthcare sector. Full article

Background: Olfactory dysfunction (OD)—including anosmia and hyposmia—is a common and often persistent outcome of viral infections. This systematic review consolidates findings from structural and functional MRI studies to explore how COVID-19 SARS-CoV-2-induced smell loss alters the brain. Considerable heterogeneity was observed across studies, influenced by differences in methodology, population characteristics, imaging timelines, and OD classification. Methods: Following PRISMA guidelines, we conducted a systematic search of PubMed/MEDLINE, Scopus, and Web of Science to identify MRI-based studies examining COVID-19’s SARS-CoV-2 OD. Twenty-four studies were included and categorized based on imaging focus: (1) olfactory bulb (OB), (2) olfactory sulcus (OS), (3) grey and white matter changes, (4) task-based brain activation, and (5) resting-state functional connectivity. Demographic and imaging data were extracted and analyzed accordingly. Results: Structural imaging revealed consistent reductions in olfactory bulb volume (OBV) and olfactory sulcus depth (OSD), especially among individuals with OD persisting beyond three months, suggestive of inflammation and neurodegeneration in olfactory-associated regions like the orbitofrontal cortex and thalamus. Functional MRI studies showed increased connectivity in early-stage OD within regions such as the piriform and orbitofrontal cortices, possibly reflecting compensatory activity. In contrast, prolonged OD was associated with reduced activation and diminished connectivity, indicating a decline in olfactory processing capacity. Disruptions in the default mode network (DMN) and limbic areas further point to secondary cognitive and emotional effects. Diffusion tensor imaging (DTI) findings—such as decreased fractional anisotropy (FA) and increased mean diffusivity (MD)—highlight white matter microstructural compromise in individuals with long-term OD. Conclusions: COVID-19’s SARS-CoV-2 olfactory dysfunction is associated with a range of cerebral alterations that evolve with the duration and severity of smell loss. Persistent dysfunction correlates with greater neural damage, underscoring the need for longitudinal neuroimaging studies to better understand recovery dynamics and guide therapeutic strategies. Full article

Background: Although COVID-19 vaccination has been effective in reducing severe illness and mortality, its differential clinical behavior in vaccinated and unvaccinated individuals during the early stages of the pandemic—especially in settings with partial coverage and real-world conditions—remains insufficiently characterized. Objective: To assess differences in clinical presentation, comorbidity prevalence, hospitalization, and mortality between vaccinated and unvaccinated patients diagnosed with SARS-CoV-2 during the early phase of the pandemic. Methods: An analytical cross-sectional study was conducted using 4625 electronic medical records of patients diagnosed with COVID-19 in Guerrero, Mexico, between 1 January and 31 December 2021. Variables included vaccination status, age, sex, comorbidities, symptom severity, clinical outcomes, and mortality. Statistical analyses involved chi-square tests, logistic regression for hospitalization probability, and Cox proportional hazards models for mortality risk. Results: Of the patients analyzed, 31.45% had received at least one vaccine dose. Fever, headache, cough, and anosmia were more frequent among vaccinated individuals (p < 0.001). Prostration and chest pain were strongly associated with hospitalization in both groups. In unvaccinated patients, smoking (OR = 4.75), obesity (OR = 3.85), and hypertension (OR = 2.94) increased hospitalization risk. Among vaccinated patients, diabetes mellitus (OR = 3.62) and hypertension (OR = 2.88) were key predictors. Vaccination was significantly associated with lower odds of hospitalization (OR = 0.38; 95% CI: 0.26–0.55) and reduced mortality risk (HR = 0.24; 95% CI: 0.08–0.71). Conclusions: Vaccination status was a significant protective factor for both hospitalization and mortality; however, clinical symptoms and comorbidity-related risks varied, highlighting the need for individualized patient management strategies. Full article

Olfaction has been extensively studied in the yellow fever mosquito, Aedes aegypti. This species uses its sense of smell to find blood hosts and other resources, contributing to its impact as a vector for human pathogens. Two major families of protein-coding genes, the odorant receptors (Ors) and the ionotropic receptors (Irs), provide the mosquito with sensitivities to distinct classes of volatile compounds in the antennae. Individual tuning receptors in both families require co-receptors for functionality: Orco for all Ors, and Ir8a for many Irs, especially ones that are involved in carboxylic acid detection. In Drosophila melanogaster, disruptions of Orco or Ir8a impair receptor function, tuning receptor expression, and membrane localization, leading to general anosmia. We reasoned that Orco and Ir8a might also be important for coordinated chemosensory receptor expression in the antennal sensory neurons of Ae. aegypti. To test this, we performed RNAseq and differential expression analysis in wildtype versus Orco^−/− and Ir8a^−/− mutant adult female antennae. Our analyses revealed Or and Ir tuning receptors are broadly under-expressed in Orco^−/− mutants, while a subset of tuning Irs are under-expressed in Ir8a mutants. Other chemosensory and non-chemosensory genes are also dysregulated in these mutants. Furthermore, we identify differentially expressed transcription factors including homologs of the Drosophila melanogaster Mip120 gene. These data suggest a previously unknown pleiotropic role for the Orco and Ir8a co-receptors in the coordination of expression of chemosensory receptors within the antennae of Ae. aegypti by participating in a feedback loop involving amos and members of the MMB/dREAM complex. Full article

Congenital hypogonadotropic hypogonadism (CHH) is a rare and heterogeneous genetic disorder with variable penetrance caused by GnRH deficiency, leading to delayed puberty and infertility. In 50–60% of cases, CHH is associated with non-reproductive abnormalities, most commonly anosmia/hyposmia (Kallmann syndrome, KS). Over 60 genes have been implicated in CHH pathogenesis. We aimed to perform genetic screening in a cohort of 14 patients (10 males, 4 females; mean age 22 ± 7.72 years) with suspected or diagnosed HH/KS. Genetic analysis was conducted using next-generation sequencing (NGS) with a custom panel of 46 candidate genes. Variant interpretation followed ACMG standards and guidelines. Multiple tools were used to predict the structural effects of variants on tertiary protein structure, assessing their pathogenicity. Novel variants were functionally characterized by qRT-PCR on mRNA extracted from peripheral leukocytes. NGS identified nine rare variants and four novel variants in genes previously associated with normosmic isolated HH (nHH) and/or KS (FGFR1, PROK2, TAC3R, DCC, WDR11, IL17RD, DUSP6, KAL1, FGF8, IL17RD and DCC). The variant in TAC3R (p.Trp275Ter) was pathogenic; variants in ANOS1 (c.541+1G>A), IL17RD (c.1303_1304dup, p.Lys436ThrfsTer58), and TAC3R (p.Lys361Ter) were likely pathogenic. Nine variants were classified as variants of uncertain significance (VUS). Our study identified a possible genetic cause in 71% of the CHH/KS cohort, emphasizing the importance of genetic screening and functional characterization of genetic variants in patients with a phenotypically and genetically heterogeneous disorder like CHH. Full article

Background/Objectives: Primary Ciliary Dyskinesia (PCD) is a rare genetic condition characterized by compromised mucociliary clearance and chronic respiratory manifestations. Anosmia, or the loss of smell, is a lesser-known but clinically relevant symptom that can significantly impact patient safety, nutritional status, and the overall quality of life. The RSPH4A (c.921+3_921+6delAAGT) founder mutation is highly prevalent among Puerto Rican individuals with PCD and may carry distinct phenotypic implications. This study aimed to evaluate olfactory function in Puerto Rican PCD patients with this mutation using the Brief Smell Identification Test (BSIT^®) and to assess associations with age and sex. Methods: We conducted a case–control study involving 30 participants, including 15 PCD patients with genetically confirmed RSPH4A mutations and 15 age- and sex-matched healthy controls. All participants completed the BSIT, and BSIT scores were compared by diagnosis, sex, and age. Results: PCD patients had significantly lower BSIT scores than controls (p = 0.0015). When stratified by sex, both male (p = 0.0289) and female (p = 0.0178) PCD patients demonstrated significantly lower BSIT scores compared to their respective healthy counterparts. Regression analysis showed a significant inverse correlation between age and BSIT score in the PCD group (r² = 0.2873; p = 0.0395), while no such relationship was observed in controls (r² = 0.0096; p = 0.7283). Among PCD patients, age-related decline in olfactory function was more pronounced in females (r² = 0.71; p = 0.005) than in males (r² = 0.31; p = 0.25). Conclusions: These findings demonstrate that the RSPH4A founder mutation is associated with measurable olfactory impairment in PCD patients, particularly in females and with advancing age. The routine assessment of olfactory function should be considered in the clinical evaluation of patients with PCD, as anosmia may represent a key phenotypic feature and contribute to disease burden. Full article

Background: Long COVID (LC) has emerged as a significant epidemiological and public health issue, affecting patients’ health-related quality of life (HRQoL). This study explored the impact of LC on HRQoL in COVID-19 survivors in the Eastern Province of Saudi Arabia and examined the sociodemographic and clinical factors that influence HRQoL. Methods: This cross-sectional study included 1024 participants, and data were collected through face-to-face interviews using a structured questionnaire that incorporated the EQ-5D-5L tool to assess HRQoL. Sociodemographic information, acute COVID-19 symptoms, and LC symptoms were recorded. Statistical analyses included bivariate analyses and multivariable generalized linear modelling. Results: Of all participants, 63.8% reported experiencing LC symptoms, with fatigue, cough, and anosmia being the most common. Participants with LC had significantly lower HRQoL scores (mean EQ-5D-5L index score, 0.93) than those without LC (mean score, 0.98; p < 0.001). The key factors influencing lower HRQoL included a higher number of LC symptoms, older age, the presence of pneumonia during acute COVID-19, and pre-existing conditions such as anxiety and hypertension. Conclusions: LC negatively impacts HRQoL, with older age, chronic diseases, and the number of LC symptoms being strong predictors of poor outcomes. Interventions targeting rehabilitation and psychosocial support are critical for improving the long-term health outcomes of patients with LC. Full article

Neurological symptoms such as impaired smell and taste have been recognized as hallmark manifestations of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. This study investigates and quantifies microstructural changes in the white matter of the olfactory bulb and taste-related brain regions (frontal operculum, insular cortex and parietal operculum) using diffusion-weighted magnetic resonance imaging (DW-MRI). Apparent diffusion coefficient (ADC) values were measured in patients with confirmed coronavirus disease of 2019 (COVID-19) at the onset of anosmia and ageusia (24 patients, scanned between March and December 2020), 1 month post-infection (20 subjects) and 36 months post-infection (20 participants). ADC values were analyzed over time and compared to normal white matter ADC ranges (calculated retrospectively from 979 pre-pandemic patients) and to those from patients infected with the 2024 strain of SARS-CoV-2 (27 patients). The results revealed significantly elevated ADC values in the white matter of the targeted brain regions, with a peak at the time of infection, followed by a decline 1 month post-infection, and a return to near-normal levels 3 years later. In contrast, the 2024 COVID-19 variant demonstrated reduced virus-related alterations in brain microstructure compared to the 2020 strain. These findings highlight the potential of DWI as a non-invasive tool for elucidating the molecular mechanisms underlying olfactory and taste dysfunction in COVID-19 patients. Full article

Members of the California Air Resources Board (CARB) participated in the odor profile method (OPM) training program. The OPM is the flavor profile analysis (FPA) standard method applied to air samples. The FPA method is a widely used standard method in drinking water taste and odor evaluations. It was found that pre-screening of potential OPM trainees for anosmia cases was necessary. After odor characteristics were defined by odor references and standardized terminology, the trainees were able to accurately describe single odors. However, the trainees could not always simultaneously perceive all odors within a mixture. Therefore, a method to separate the odors in a mixture should be applied in the future for environmental analysis by the OPM. After a half-day training session every day for a week, a panel could be formed to accurately determine the characteristics of atmospheric odors from various facilities. With the help of an intensity scale defined by sugar solutions, the panel could also report average odor intensity values consistent with the facilities’ operation. However, a high variance of individual intensity values relative to panel average was noted. It was likely caused by the simultaneous presence of multiple odors in the air and a lack of definition of low odor intensity values by sugar solutions. Secondly, lower odor intensities were reported when sampling bags were used for the OPM analysis compared to direct sniffing at the facilities’ fenceline, apparently because of the narrow valve opening of the sampling bags. The feasibility of quick adoption of the OPM by a regulatory team as demonstrated in this study is essential for the OPM to be considered as a method to evaluate atmospheric malodors as the FPA for drinking water analysis. Full article

Background: Naso-ethmoidal schwannoma is a rare slow-growing tumor arising from the Schwann cells of the sinonasal tract. This study discusses the evolution of surgical approaches to naso-ethmoidal schwannomas with respect to tumor growth and recent advances in minimally invasive techniques. Materials and Methods: A comprehensive literature review on Embase online electronic database on benign naso-ethmoidal schwannoma was performed. Demographic, clinical, neuroradiological, pathological, and surgical factors were analyzed and discussed. Results: Twenty-five cases met the inclusion criteria. No predilection for gender was evident. The mean age at diagnosis was 40.2 years old. Nasal obstruction was the most common presenting symptom (64%), followed by headache (60%), hypo-anosmia (24%), and visual impairment (24%). Skull base and orbital involvement were registered in 64% and 16% of cases, respectively. Surgery is the unique curative treatment, with the endoscopic endonasal approach which plays the leading role (44%). Gross total resection was possible in all cases and was associated with no recurrence. The perioperative complication rate was 32% and mainly consisted of cerebrospinal fluid leakage. The mean time for treatment was 21 months. All patients were alive at last follow up. Conclusion: Surgery is the only curative treatment for naso-ethmoidal schwannomas, with the main goal to relief clinical manifestations. The endoscopic endonasal route represents the master approach for lesions confined to the midline. Transcranial and transorbital approaches play a complementary role when large intracranial extension and orbital involvement occur, respectively. Full article

Head and neck cancer affects millions worldwide. The risk factors are numerous, including smoking, alcohol consumption, and human papillomavirus to name a few. While improved preventative, diagnostic, and treatment methods have decreased mortality rates, the treatments (chemotherapy, radiotherapy, or surgery) often result in smell and/or taste impairments. These can impact quality of life during and after cancer treatment. A scoping review was performed to understand current research and future directions regarding smell and taste impairments in head and neck cancer patients. PRISMA guidelines were followed and Rayyan.ai was used to search and compile journal articles. Three databases, EBSCOhost, Google Scholar, and PubMed, were also searched. Search terms included smell, taste, dysgeusia, ageusia, hypogeusia, parosmia, anosmia, hyposmia, dysosmia, and head and neck cancer. A total of 1580 articles were found through Rayyan.ai and 8022 were found through the three databases, which were manually screened. Articles assessing patients with a different malignancy, benign tumors, pediatric populations, animal studies, abstracts, and review articles were excluded. A total of 47 articles were found using this strategy. Of those we identified, 37 articles discussed taste impairments, 12 articles discussed smell impairments, and 3 articles discussed treatments for smell and/or taste impairments. All 37 articles concluded that there was some taste alteration in head and neck cancer patients due to their treatment. However, the specific taste qualities (sweet, sour, salty, or bitter) that were impaired, whether taste function returned to baseline, and which treatments led to impairments varied. For the 12 studies that assessed smell impairments, the results also varied. Some studies found significant objective impairments in smell while others found no significant impairment. Zinc sulfate was not found to be an effective treatment option for taste impairments; however, a liposomal spray showed some potential. Future studies should aim to understand which treatments and types of head and neck cancer lead to chemosensory impairments, whether chemosensory alterations negatively impact a patient’s nutritional status, and treatments or preventative measures for smell and taste changes. Full article

Fibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism. Full article

Eosinophilic Granulomatosis with Polyangiitis (EGPA)/Churg–Strauss syndrome is a systemic vasculitis that often causes chronic nasal dysfunction, including anosmia, nasal obstruction, and sinusitis. Anosmia, affecting up to 20% of EGPA patients, has a significant negative impact on quality of life (QoL). The loss of smell disrupts daily activities, reduces enjoyment of food, and impairs social interactions, leading to feelings of isolation, depression, and anxiety. These psychosocial consequences, combined with persistent physical symptoms, contribute to a marked decline in overall well-being and are among the strongest predictors of poor QoL in EGPA patients. Early diagnosis and intervention are essential to mitigate these effects and improve patient outcomes. A multidisciplinary approach that combines pharmacological treatment, surgical options, and psychosocial support is critical to managing both the physical and emotional challenges of nasal dysfunction in EGPA. However, further research is needed to explore long-term management strategies, optimize therapeutic approaches, and better address the complex interplay between physical symptoms and QoL in EGPA patients. Full article