Neuroimaging the Development of Olfactory Function in a Woman With No Olfactory Bulbs.

This case report describes a woman with lifelong anosmia in her 20s who presented with the acquisition of unpleasant olfactory phantoms.

Olfactory training with four and eight odors: comparison with clinical testing and olfactory bulb volumetrics.

PURPOSE: Post-infectious olfactory dysfunction (PIOD) is one of the most common causes of olfactory impairment but has limited treatment options. Recently, olfactory training (OT) has been considered an effective treatment method; however, several questions have arisen regarding its optimal scheme. The aim of this study was to assess whether an OT scheme with 8 odors is more effective than the classic OT scheme with 4 odors by comparing psychophysical test results and olfactory bulb (OB) volumetrics. METHODS: In this prospective cohort study, 72 patients with PIOD were included. The patients followed either the classic 4-odor OT scheme (COT; n = 34 patients) or an extended 8-odor scheme (EOT; n = 38 patients) for 16 weeks. All patients underwent olfactory testing with a Sniffin'Sticks battery test at 0, 8, and 16 weeks. Of the patients, 38 underwent brain magnetic resonance imaging for OB volumetric assessment before and after treatment. RESULTS: The comparison of the olfactory test results did not show any significant difference between the two study groups, in agreement with the OB volumetrics. The convex OB showed better test results than the non-convex OB, with significantly better improvement after treatment regardless of OT type. The EOT group presented significantly better adherence than the COT group. CONCLUSION: The number of odors did not appear to play a significant role in the effect of the OT. However, the training scheme with more than four odors showed better adherence among the patients in a long-term treatment plan. The shape of the OB may have prognostic value in clinical assessment and warrants further investigation.

[Olfactory function and olfactory bulbs in patients with Kallmann syndrome].

BACKGROUND: The majority of Kallmann patients have anosmia or hyposmia. This is how the disease is diagnosed. Some of them don't have such complaints but olfactory dysfunction is diagnosed via olfactometry. Nowadays there is the lack of information about correlation between olfactometry results and subjective complaints. Correlation between olfactory bulbs size and olfactory dysfunction has been little studied. AIM: To explore olfactory bulb size and olfactory function in patients with congenital isolated hypogonadotropic hypogonadism. To correlate olfactory bulb sizes and smell test scores. MATERIALS AND METHODS: Single-centre comparative study. 34 patients were included. The main group consisted of 19 patients with hypogonadotropic (15 -with Kallmann syndrome, 4 - with normosmic hypogonadism). Olfactory bulbs MRI were provided to all the patients, olfactory test (Sniffin' Sticks Test) and molecular-genetic studies were provided in all patients with hypogonadism. Control group consisted of 15 patients who were provided with orbits MRI. Olfactory bulbs were evaluated additionally in them. RESULTS: Normal size of olfactory bulbs were only in 1 patient with hypogonadism. Olfactory bulbs height and width were significantly smaller in patients with hypogonadism in comparison with control group (p<0.01). Height median of right bulb was 1.0 mm [0.2; 1.8] in patients from the main group vs. 3.0 [2.5; 3.2] in controls, width median of right bulb was 1.0 mm [0.2; 1.9] in patients from the main group vs. 2.5 [2.0; 3.0] in controls. Height median of left bulb was 0.8 mm [0.0; 1.2] in patients from the main group vs. 3.0 [2.7; 3.2] in controls, width median of left bulb was 0.8 mm [0.0; 1.2] in patients from the main group vs. 2.5 [2.0; 3.0] in controls. Correlation has been established between left bulb height (r=0.59) and width (r=0.67) and olfactometry results (p<0.05). 4 patients had no anosmia complaints but had olfactory dysfunction according to Sniffin' Sticks Tests. CONCLUSION: Olfactometry was able to diagnose olfactory dysfunction in 78.5% (i.e. in 15 out of 19 patients with congenital isolated hypogonadotropic hypogonadism. However, anosmia complaints had only 11 out of 19 patients. It is the first results of olfactory bulb sizes in patients with hypogonadotropic hypogonadism in Russia. Uni - or bilateral hypoor aplasia were diagnosed in 94.7% patients with hypogonadism regardless of olfactory dysfunction. Bilateral olfactory bulbs hypoplasia were the most common MRI-finding (36.8%). Unilateral hypoor aplasia was diagnosed in 31.6% patients.

Deficits in peripheric and central olfactory measurements in smokers: evaluated by cranial MRI.

OBJECTIVES: Cigarette smoking remains a serious health problem all over the world. We investigated the peripheral and central olfactory pathways in young male smokers to determine whether there is a relationship between the amount of cigarettes smoked and duration of smoking and the dimensions of the olfactory areas. METHODS: In this retrospective study, cranial Magnetic Resonance Imaging (MRI) images of adult male smokers aged ≤ 40 years (n = 51) and 50 healthy male adults were analyzed. The olfactory bulbus (OB) volumes and olfactory sulcus (OS) depths, insular gyrus, and corpus amygdala areas were measured via cranial MRI. In the smoker group, the number of cigarettes smoked and duration of smoking were noted and the Brinkmann index was calculated. RESULTS: OB volume, OS depth, and the insular gyrus areas of the smokers were lower than in the control group (p < 0.05). There were no differences between the groups in terms of the corpus amygdala measurements (p > 0.05). No significant correlations were found between the number of cigarettes smoked daily, smoking duration, and the Brinkmann index and the peripheral and central olfactory measurements in our study (p > 0.05). CONCLUSIONS: In smokers, OB volumes, the OS, and the central areas decrease bilaterally, regardless of smoking duration and number of cigarettes smoked daily. This could be related to inflammatory mediators that may be harmful to the olfactory neuroepithelium, gray matter atrophy in the brain, or endothelial damage related to smoking and its effects on blood support to the brain and olfactory regions.

Magnetic Resonance Imaging as a Diagnostic and Research Tool in Patients with Olfactory Dysfunction: A Systematic Review.

BACKGROUND: Patients with acquired, idiopathic olfactory dysfunction (OD) commonly undergo magnetic resonance imaging (MRI) evaluation to rule out intracranial pathologies. This practice is highly debated given the expense of MRI relative to the probability of detecting a treatable lesion. This, combined with the increasing use of MRI in research to investigate the mechanisms underlying OD, provided the impetus for this comprehensive review. OBJECTIVE: The purpose of this systematic review was to both assess the utility of MRI in diagnosis of idiopathic OD and to describe MRI findings among mixed OD etiologies to better understand its role as a research tool in this patient population. METHODS: A literature search of PubMed, Embase, Cochrane, Web of Science, and Scopus for studies with original MRI data for patients with OD was completed. Studies exclusively investigating patients with neurocognitive deficits or those studying traumatic or congenital etiologies of OD were excluded. RESULTS: From 1758 candidate articles, 33 studies were included. Four studies reviewed patients with idiopathic OD for structural pathologies on MRI, of which 17 of 372 (4.6%) patients had a potential central cause identified, and 3 (0.8%) had an olfactory meningioma or olfactory neuroblastoma. Fourteen studies (42.4%) reported significant correlation between olfactory bulb volume and olfactory outcomes, and 6 studies (18.8%) reported gray matter volume reduction, specifically in the orbitofrontal cortex, anterior cingulate cortex, insular cortex, parahippocampal, and piriform cortex areas, in patients with mixed OD etiologies. Functional MRI studies reported reduced brain activation and functional connectivity in olfactory network areas. CONCLUSION: MRI uncommonly detects intracranial pathology in patients with idiopathic OD. Among patients with mixed OD etiologies, reduced olfactory bulb and gray matter volume are the most common abnormal findings on MRI. Further research is required to better understand the role of MRI and its cost-effectiveness in patients with acquired, idiopathic OD.

[Prognostic value of olfactory bulb volume in patients with post-viral olfactory dysfunction].

Objective:The purpose of this study was to compare the olfactory function examination results of patients with post-viral olfactory dysfunction（PVOD） in different prognostic groups and analyze prognostic factors, especially the influence of olfactory bulb volume（OBV） on prognosis, so as to provide objective basis for clinical diagnosis and treatment. Methods:After approval by the hospital ethics committee, the patients with PVOD admitted to Beijing Anzhen Hospital's outpatient department from January 2019 to December 2019 were followed up for at least 1 year. These patients completed the Sniffin' Sticks test and MRI examination of the olfactory pathway before treatment. According to the results of the Sniffin' Sticks test after 1 year follow-up（threshold-discrimination-identification（TDI） score of the patients was increased at least 6 points）, the patients were divided into two groups as the improvement group and the non-improvement group. The prognostic factors of PVOD patients were preliminarily determined by comparing the differences of various factors and the results of olfactory function examination between the two groups. Results:In this study, 47 patients with PVOD were included, with the smell improvement rate was 53.2%. Compared with the improvement group, the patients in the non-improvement group had longer duration, poorer initial olfactory function, higher olfactory threshold, and poorer olfactory discrimination and recognition ability（All P<0.01）. There was no statistical difference in terms of gender, age, allergic rhinitis and smoking between the two groups（All P>0.05）.The OBV of the non-improvement group was （59.48±23.92） mm³, which was significantly lower than that in the improvement group（[92.77±14.35]mm³, P<0.001）. Multiple logistic regression analysis showed that prognostic factors included course of disease（OR 0.677, 95%CI 0.461-0.993, P=0.046）, initial T value（OR 263.806, 95%CI 1.028-67 675.884, P=0.049） and OBV（OR 1.160, 95%CI 1.002-1.343, P=0.047）. The area under the receiver operating characteristic curve（ROC curve） of OBV was 0.888（0.797-0.979, P<0.001）. The correct diagnostic index of OBV≥78.50 mm³was used to determine the prognosis of olfactory function, with a specificity of 0.818 and a sensitivity of 0.840. The ROC curve analysis showed that the area under the ROC curve of duration was 0.822（0.703-0.940, P<0.001）. The correct diagnostic index of the duration ≤6 months was used to determine the prognosis of olfactory function, with a specificity of 0.727 and a sensitivity of 0.800. The area of T score was 0.793（0.662-0.924, P=0.001）. T score ≥1.25 was used as the correct diagnostic index to determine the prognosis of olfactory function. The specificity and sensitivity were 0.818 and 0.680, respectively. Conclusion:The prognosis of olfactory function in PVOD patients is related to the course of disease, the degree of olfactory loss and OBV. Those with no improvement in olfactory function have a longer disease course, aggravated olfactory damage and reduced OBV than those with improved olfactory function. The factors of Duration ≤6 months, T value ≥1.25 and OBV≥78.50 mm³suggested better prognosis, and the results of objective olfactory examination have greater value in evaluating the prognosis of olfactory function.

Effect of olfactory bulb atrophy on the success of olfactory training.

PURPOSE: To evaluate the success of olfactory training in patients with olfactory loss and olfactory bulb (OB) atrophy detected on magnetic resonance imaging (MRI) and other characteristics. METHODS: This study included 48 patients with olfactory loss who underwent a nasal endoscopic examination and MRI before olfactory training. The Korean Version of the Sniffin' Sticks Test was performed before and after training. The olfactory training success was defined as an improvement of more than 6 points in the Threshold-Discrimination-Identification (TDI) score. Patient characteristics and OB atrophy pre-training were compared between successful and unsuccessful groups. RESULTS: The etiology of olfactory loss included respiratory viral infection in 30 (62.5%), trauma in 10 (20.8%), and idiopathic loss in 8 (16.7%) patients. Twenty-three (47.9%) of 48 patients exhibited successful olfactory training. Etiology, age, gender, and symptom duration were not different between unsuccessful and successful groups. Pre-training discrimination, identification, and TDI scores were significantly different between unsuccessful and successful groups (P < 0.05). Success rate of patients with bilateral OB atrophy was significantly lower than that of patients with unilateral OB atrophy and normal morphology (P = 0.006). OB height was significantly lower in the unsuccessful group than in the successful group (P < 0.05). Bilateral OB atrophy was an independent risk factor for failure of olfactory training according to the multivariate analysis. CONCLUSION: Olfactory loss patients with bilateral OB atrophy may not be able to improve olfactory function after olfactory training.

Cortical Atrophy, White Matter Lesions, and Bulb Configuration in Patients with Idiopathic Olfactory Loss and Other Causes of Olfactory Loss.

INTRODUCTION: While magnetic resonance imaging (MRI) is not included in the current guidelines for diagnosing olfactory disorders in the most recent position paper on olfactory dysfunction, both 1.5T and 3T MRI are commonly used in the diagnostic workup of many patients with olfactory loss. Often, MRI is used to rule out intracranial tumours, but other useful information may be obtained from MRI scans in these patients. The potential of MRI in olfactory loss depends on sufficient knowledge of structural changes in different aetiologies of olfactory loss. We present common clinical MRI findings in olfactory loss and evaluate the usefulness of structural integrity scores in differentiating between aetiologies. METHODS: In this study, we investigated if white matter hyperintensities (WMHs, measured by Fazekas score), global cortical atrophy (GCA), and medial temporal lobe atrophy (MTA) are more common in patients with idiopathic olfactory loss than in patients with acquired olfactory loss due to other aetiologies. Furthermore, we compared olfactory bulb (OB) configurations in different olfactory loss aetiologies. RESULTS: In 88 patients with olfactory loss, WMHs, GCA, and MTA were not more significant findings on MRI in idiopathic olfactory loss (n = 51) compared with other causes of acquired olfactory loss (Fazekas score p = 0.2977; GCA score p = 0.6748; MTA score p = 0.7851). Bulb configurations differed in patients suffering from post-traumatic olfactory loss and may aid in identifying the underlying aetiology in patients where trauma is among the suspected causes of olfactory loss. CONCLUSION: We recommend that structural MRI with an OB sequence is included in the diagnostic evaluation of olfactory loss with suspected congenital and post-traumatic aetiology and should be considered in idiopathic olfactory loss with suspected central aetiology (e.g., tumour).

In vivo magnetic resonance imaging evidence of olfactory bulbs changes in a newborn with congenital Citomegalovirus: a case report.

BACKGROUND: Citomegalovirus (CMV) infects approximately 1% of live newborns. About 10% of the infants affected by congenital CMV infection are symptomatic at birth and up to 60% of these infants will develop permanent neurological disabilities. Depending on gestational age (GA) at the time of infection, the involvement of central nervous system (CNS) can lead to malformations of cortical development, calcifications, periventricular white matter lesions and cysts, ventriculomegaly and cerebellar hypoplasia. CASE PRESENTATION: We report the MRI findings in a Caucasian female born at 32 weeks of post-menstrual age with post-birth diagnosis of congenital CMV infection showing an unusual and peculiar marked T2 hyperintensity of the inner part of olfactory bulbs in addition to the CMV related diffuse brain involvement. Despite the known extensively described fetal and neonatal Magnetic Resonance Imaging (MRI) findings in CMV infected fetuses and newborns, any in vivo MRI depiction of olfactory system damage have never been reported so far. Nevertheless, in murine studies CMV is known to infect the placenta during pregnancy showing particular tropism for neural stem cells of the olfactory system and previous neuropathologic study on CMV infected human fetal brains from 23 to 28 weeks of GA reported damage in the olfactory bulbs (OB) consisting in disseminated cytomegalic cells, inflammation, necrosis and neuronal and radial glial cell loss. Therefore, we assume an OB involvement and damage in congenital CMV infection. CONCLUSION: To our knowledge this is the first in vivo MRI evidence of OB damage in a newborn with congenital CMV infection that may give new insights on CMV infection.

Evaluation of the olfactory bulb volume and morphology in patients with coronavirus disease 2019: can differences create predisposition to anosmia?

SUMMARY OBJECTIVE: This study aimed to investigate whether the volume and morphology of the olfactory bulb are effective in the occurrence of anosmia in patients after COVID-19 infection. METHODS: The olfactory bulbus volume was calculated by examining the brain magnetic resonance imaging of cases with positive (+) COVID-19 polymerase chain reaction test with and without anosmia. Evaluated magnetic resonance imaging images were the scans of patients before they were infected with COVID-19. The olfactory bulbus and olfactory nerve morphology of these patients were examined. The brain magnetic resonance imaging of 59 patients with anosmia and 64 controls without anosmia was evaluated. The olfactory bulb volumes of both groups were calculated. The olfactory bulb morphology and olfactory nerve types were examined and compared between the two groups. RESULTS: The left and right olfactory bulb volumes were calculated for the anosmia group and control group as 47.8±15/49.3±14.3 and 50.5±9.9/50.9±9.6, respectively. There was no statistically significant difference between the two groups. When the olfactory bulb morphology was compared between the two groups, it was observed that types D and R were dominant in the anosmia group (p<0.05). Concerning olfactory nerve morphology, type N was significantly more common in the control group (p<0.05). CONCLUSIONS: According to our results, the olfactory bulb volume does not affect the development of anosmia after COVID-19. However, it is striking that the bulb morphology significantly differs between the patients with and without anosmia. It is clear that the evaluation of COVID-19-associated smell disorders requires studies with a larger number of patients and a clinicoradiological approach.

Evaluation of the Neuroanatomical Basis of Olfactory Dysfunction in the General Population.

Importance: Olfactory dysfunction is a prodromal manifestation of many neurodegenerative disorders, including Alzheimer and Parkinson disease. However, its neuroanatomical basis is largely unknown. Objective: To assess the association between olfactory brain structures and olfactory function in adults 30 years or older and to examine the extent to which olfactory bulb volume (OBV) mediates the association between central olfactory structures and olfactory function. Design, Setting, and Participants: This cross-sectional study analyzed baseline data from the first 639 participants with brain magnetic resonance imaging (MRI) in the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Participants were enrolled between March 7, 2016, and October 31, 2017, and underwent brain MRI and olfactory assessment. Data were analyzed from March 1, 2018, to June 30, 2021. Exposure: Volumetric measures were derived from 3-T MRI T1-weighted brain scans, and OBV was manually segmented on T2-weighted images. The mean volumetric brain measures from the right and left sides were calculated, adjusted by head size, and normalized to all participants. Main Outcomes and Measures: Performance on the 12-item smell identification test (SIT-12) was used as a proxy for olfactory function. Results: A total of 541 participants with complete data on MRI-derived measures and SIT-12 scores were included. This population had a mean (SD) age of 53.6 (13.1) years and comprised 306 women (56.6%). Increasing age (difference in SIT-12 score, -0.04; 95% CI, -0.05 to -0.03), male sex (-0.26; 95% CI, -0.54 to 0.02), and nasal congestion (-0.28; 95% CI, -0.66 to 0.09) were associated with worse olfactory function (SIT-12 scores). Conversely, larger OBV was associated with better olfactory function (difference in SIT-12 score, 0.46; 95% CI, 0.29-0.64). Larger volumes of amygdala (difference in OBV, 0.12; 95% CI, 0.01-0.24), hippocampus (0.16; 95% CI, 0.04-0.28), insular cortex (0.12; 95% CI, 0.01-0.24), and medial orbitofrontal cortex (0.10; 95% CI, 0.00-0.20) were associated with larger OBV. Larger volumes of amygdala (volume × age interaction effect, 0.17; 95% CI, 0.03-0.30), parahippocampal cortex (0.17; 95% CI, 0.03-0.31), and hippocampus (0.21; 95% CI, 0.08-0.35) were associated with better olfactory function only in older age groups. The age-modified association between volumes of central olfactory structures and olfactory function was largely mediated through OBV. Conclusions and Relevance: This cross-sectional study found that olfactory bulb volume was independently associated with odor identification function and was a robust mediator of the age-dependent association between volumes of central olfactory structures and olfactory function. Thus, neurodegeneration-associated olfactory dysfunction may primarily originate from the pathology of peripheral olfactory structures, suggesting that OBV may serve as a preclinical marker for the identification of individuals who are at an increased risk of neurodegenerative diseases.

[Study on the clinical characteristics of isolated congenital anosmia].

Objective: To retrospectively analysely the electrophysiological and imaging features of isolated congenital anosmia (ICA) and to assess the clinical phenotypic characteristics and classification of ICA. Methods: Clinical data of 30 ICA patients in Beijing Anzhen Hospital from 2012 to 2019 was retrospectively reviewed, including 13 males and 17 females, aged (35±19) years. The control group consisted of 30 healthy people from medical examination center, including 13 males and 17 females, aged (39±14) years. The clinical characteristics of ICA were analyzed using Sniffin' Sticks test, olfactory event-related potentials (oERPs), trigeminal event-related potentials (tERP) and olfactory pathway MRI. SPSS 17.0 software was used to compare the difference of olfactory function between the two groups. The correlation between olfactory bulb, olfactory sulcus structure and age was observed, and the clinical phenotype characteristics of ICA patients were analyzed. Results: The subjective olfactory function was completely lost in ICA patients. oERP was absent in all of the ICA patients, but showed normal N1 and P2 waves in controls. tERP could be evoked in 63.3% (19/30) of ICA patients, and signals in these patients showed higher amplitude in the N1 ((-10.33±6.93) µV vs (-5.11±2.71) µV, t=-10.113, P<0.01) and P2 ((+17.25±8.51) µV vs (+7.31±3.46) µV, t=5.443, P<0.01) waves than that of the controls. Olfactory bulbs were aplastic in 80.0% (24/30) of patients and hypoplastic in 20.0% (6/30) of patients. Fifty-six point seven percent (17/30) of patients had bilateral olfactory sulcus deletion while 43.3% (13/30) had dysplasia, and all of the patients exhibited a depth of olfactory sulcus less than 8 mm. Both the structure of olfactory bulbs and olfactory sulcus were not associated with age for ICA patients (r value was -0.174 and 0.325, respectively, all P>0.05). Conclusions: ICA patients show neurophysiologic deficits and some anatomic differences compared with healthy controls. The absence of oERP combining with a depth of olfactory sulcus less than 8 mm is the important indicator for clinical diagnosis of ICA. The structure of olfactory bulb may be a critical factor for clinical classification of ICA.

Olfactory bulb enlargement in neurofibromatosis type 1: report of a novel finding.

Neurofibromatosis type 1 (NF1) is a genetic autosomal dominant disease caused by mutation of the protein neurofibromin, a regulator of cell growth. The most frequent intracranial findings are unidentified bright objects (UBOs), thickening of the corpus callosum, sphenoid wing dysplasia, cerebral vasculopathy, optic and non-optic pilocytic astrocytomas, and plexiform neurofibromas. We report two cases of NF1 patients with asymptomatic olfactory bulbs (OBs) enlargement depicted with Magnetic Resonance Imaging (MRI). To the best of our knowledge, this finding has not been reported in the scientific literature so far. We hypothesize that olfactory bulbs enlargement may have a pathogenetic nature like that of the UBOs as in one of our patients there was spontaneous regression during follow-up. The olfactory bulbs enlargement expands the broad neuroradiological spectrum of finding of NF1. More reports are required to better understand incidence, pathogenesis, and clinical behavior of olfactory bulbs enlargement in NF1 patients.

Olfactory neurocytoma as a unique cause of chronic SIADH.

A 32-year-old man was found to have a nasal mass on DOTATATE positron emission tomography (PET) scan to investigate the cause of his syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient presented 6 years earlier with malignant hypertension followed by a second emergency admission for hyponatraemia. Multiple scans and blood tests over 6 years yielded no cause for his SIADH. Nasendoscopy was unremarkable. A PET scan prompted endoscopic sinus surgery which resulted in the resection of a mass in the anterior hiatus semilunaris. The histological findings were fitting with a diagnosis of a neurocytic-type tumour favouring an olfactory neurocytoma. Following resection, the patient remains well and is cured of his SIADH. An olfactory neurocytoma although rare should be considered as a benign differential for a mass in the nasal space. This case demonstrates how an olfactory neurocytoma can present as a cause of SIADH.

COVID-19-induced anosmia associated with olfactory bulb atrophy.

As the global COVID-19 pandemic evolves, our knowledge of the respiratory and non-respiratory symptoms continues to grow. One such symptom, anosmia, may be a neurologic marker of coronavirus infection and the initial presentation of infected patients. Because this symptom is not routinely investigated by imaging, there is conflicting literature on neuroimaging abnormalities related to COVID-19-related anosmia. We present a novel case of COVID-19 anosmia with definitive olfactory bulb atrophy compared with pre-COVID imaging. The patient had prior MR imaging related to a history of prolactinoma that provided baseline volumes of her olfactory bulbs. After a positive diagnosis of COVID-19 and approximately 2 months duration of anosmia, an MRI was performed that showed clear interval olfactory bulb atrophy. This diagnostic finding is of prognostic importance and indicates that the olfactory entry point to the brain should be further investigated to improve our understanding of COVID infectious pathophysiology.

Olfactory Cleft Measurements and COVID-19-Related Anosmia.

OBJECTIVE: This study aimed to investigate the differences in olfactory cleft (OC) morphology in coronavirus disease 2019 (COVID-19) anosmia compared to control subjects and postviral anosmia related to infection other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). STUDY DESIGN: Prospective. SETTING: This study comprises 91 cases, including 24 cases with anosmia due to SARS-CoV-2, 38 patients with olfactory dysfunction (OD) due to viral infection other than SARS-CoV-2, and a control group of 29 normosmic cases. METHODS: All cases had paranasal sinus computed tomography (CT), and cases with OD had magnetic resonance imaging (MRI) dedicated to the olfactory nerve. The OC width and volumes were measured on CT, and T2-weighted signal intensity (SI), olfactory bulb volumes, and olfactory sulcus depths were assessed on MRI. RESULTS: This study showed 3 major findings: the right and left OC widths were significantly wider in anosmic patients due to SARS-CoV-2 (group 1) or OD due to non-SARS-CoV-2 viral infection (group 2) when compared to healthy controls. OC volumes were significantly higher in group 1 or 2 than in healthy controls, and T2 SI of OC area was higher in groups 1 and 2 than in healthy controls. There was no significant difference in olfactory bulb volumes and olfactory sulcus depths on MRI among groups 1 and 2. CONCLUSION: In this study, patients with COVID-19 anosmia had higher OC widths and volumes compared to control subjects. In addition, there was higher T2 SI of the olfactory bulb in COVID-19 anosmia compared to control subjects, suggesting underlying inflammatory changes. There was a significant negative correlation between these morphological findings and threshold discrimination identification scores. LEVEL OF EVIDENCE: Level 4.

Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia.

BACKGROUND: Olfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated. CASE REPORT: This report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2. CONCLUSION: The biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.

Diagnostic Accuracy of MRI-Based Morphometric Parameters for Detecting Olfactory Nerve Dysfunction.

BACKGROUND AND PURPOSE: Although olfactory dysfunction is a common cranial nerve disorder, there are no simple objective morphometric criteria to assess olfactory dysfunction. The aim of this study was to evaluate the diagnostic performance of MR imaging morphometric parameters for detecting olfactory dysfunction. MATERIALS AND METHODS: This prospective study enrolled patients from those presenting with olfactory symptoms who underwent both an olfactory function test and MR imaging. Controls without olfactory dysfunction were recruited during the preoperative work-up for pituitary adenoma. Two independent neuroradiologists measured the olfactory bulb in 3D and assessed olfactory bulb concavity on MR imaging while blinded to the clinical data. Diagnostic performance was assessed using receiver operating characteristic curve analysis. RESULTS: Sixty-four patients and 34 controls were enrolled. The patients were significantly older than the controls (mean age, 57.8 ± 11.9 years versus 47.1 ± 12.1 years; P < .001). Before age adjustment, the olfactory bulb height was the only olfactory bulb parameter showing a significant difference between patients and controls (1.6 ± 0.3 mm versus 2.0 ± 0.3 mm, P < .001). After age adjustment, all parameters and olfactory bulb concavity showed significant intergroup differences, with the olfactory bulb height having the highest area under the curve (0.85). Olfactory bulb height was confirmed to be the only significant parameter showing a difference in the detection of olfactory dysfunction in 22 pairs after matching for age and sex (area under the curve = 0.87, P < .001). Intraclass correlation coefficients revealed moderate-to-excellent degrees of inter- and intrareader agreement. CONCLUSIONS: MR imaging morphometric analysis can differentiate patients with olfactory dysfunction, with the olfactory bulb height having the highest diagnostic performance for detecting olfactory dysfunction irrespective of age.

A novel heterozygous intron mutation in SEMA7A causing kallmann syndrome in a female.

Kallmann syndrome (KS) is a rare inherited disorder, which has significantly genotypic and phenotypic heterogeneity. KS is clinically characterized by the combination of hypogonadotropic hypogonadism and hypo/anosmia. At present, there is no relevant report that intron mutation in SEMA7A gene helps induce KS. A 17-year-old Chinese female (46, XX) came to our department due to primary amenorrhea, who actually had hyposmia since her childhood. Hypogonadotropic hypogonadism was then detected. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were remarkably low. And estradiol level was extremely low. The laboratory test results were consistent with KS. A heterozygous point mutation of intron 13 in SEMA7A (NM_003612.3:c.1640-3C > A) was identified. The patient received the treatment of pulsatile gonadotropin-releasing hormone (GnRH) pump, which could imitate physiological ovarian stimulation, thus resulting in mature follicle and a peak of LH. The patient was injected subcutaneously every 90 min with a dose of 10 µg per pulse, which had bona efficacy. She acquired menarche at about 43 days after the treatment. We firstly report a case of KS caused by a novel mutation site in the intron of SEMA7A gene. We mainly provide insight into the clinical manifestations, genetic diagnosis and treatment of KS.

Olfactory bulb and olfactory tract abnormalities in acrocallosal syndrome and Greig cephalopolysyndactyly syndrome.

We describe association of olfactory bulb and olfactory tract abnormalities in a child with acrocallosal syndrome caused by kinesin family membrane 7 (KIF7) mutation in sonic hedgehog pathway. The child also had fontanellar bone in the anterior fontanelle, short sagittal suture, sagittal synostosis, hippocampal malrotation and Joubert malformation. Fontanellar bone has been described in GLI3 mutation and mutant mice models but has not been reported in KIF7 mutation. We briefly review the role of sonic hedgehog pathway and its components KIF7 and GLI3 in forebrain and olfactory system development and also describe olfactory system abnormality in a child with GLI3 mutation.