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A key concern of both the patient and physician is whether treatment is available that will eliminate or quell a given chemosensory disturbance. In cases where obvious oral, nasal, or intracranial pathology is involved, rational straightforward approaches to treatment are often available. In cases where damage to the sensory pathways is secondary to chronic inflammatory disease, trauma, viral invasion, toxic exposure, or unknown causes, the direction for therapy is more challenging. Indeed, many chemosensory disorders, if present for any period of time, cannot be reversed, while others spontaneously remit without any therapeutic intervention. This review assesses the strengths and weaknesses of more than two dozen approaches to treatment that have been suggested for a wide range of taste and smell disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Information on the dynamics of molecules following olfactory dysfunction remains essential for understanding the molecular events involved in the pathological process of olfactory dysfunction. This study for the first time demonstrates a method based on the combination of in vivo microdialysis with high performance liquid chromatography (HPLC) and electrochemical detection (ECD) for the measurement of the dynamics of norepinephrine (NE) in the olfactory bulbs of Sprague-Dawley rats following olfactory dysfunction induced by brain ischemia and its responses toward dexamethasone treatment. The method possesses a high spatial resolution and benefits from in vivo microdialysis and high selectivity and is thus capable of measuring NE in the olfactory bulb of rats. With this method, the basal level of NE in the olfactory bulb was evaluated to be ca. 235 ± 25 nM (n = 6). This level was found to increase by 260 ± 90% at a time point of 240 min after brain ischemia with bilateral ligation of both common carotid arteries. The increase was found to be suppressed upon the treatment of the animals with 0.2% dexamethasone in the olfactory bulb. These results suggest that NE is involved in the pathological process of ischemia-induced olfactory dysfunction and this information is useful to further understand the molecular events involved in olfactory dysfunction.

Detonation of explosive devices creates blast waves, which can injure brains even in the absence of external injuries. Among these, blast-induced mild traumatic brain injury (bmTBI) is increasing in military populations, such as in the wars in Afghanistan, Iraq, and Syria. Although the clinical presentation of bmTBI is not precisely defined, it is frequently associated with psycho-neurological deficits and usually manifests in the form of poly-trauma including psychiatric morbidity and cognitive disruption. Although the underlying mechanisms of bmTBI are largely unknown, some studies suggested that bmTBI is associated with blood-brain barrier disruption, oxidative stress, and edema in the brain. The present study investigated the effects of novel antioxidant, molecular hydrogen gas, on bmTBI using a laboratory-scale shock tube model in mice. Hydrogen gas has a strong prospect for clinical use due to easy preparation, low-cost, and no side effects. The administration of hydrogen gas significantly attenuated the behavioral deficits observed in our bmTBI model, suggesting that hydrogen application might be a strong therapeutic method for treatment of bmTBI.

We report the case of a 27-year-old female who presented with a peculiar story of anosmia fluctuating in a circadian manner. Olfactory function appeared an hour after breakfast, was normal during daytime, and disappeared in the early evening. Imaging confirmed chronic rhinosinusitis (CRS). Initial systemic, followed by topical steroid treatment, rapidly and sustainably reversed this condition. The olfactory fluctuation paralleled the endogenous steroid production. This suggests that slight congestion changes in a chronically inflamed nasal mucosa may have been sufficient to induce this circadian anosmia. The importance of identifying fluctuation of olfactory function as a sign of CRS is emphasized and discussed. Laryngoscope, 128:1537-1539, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective Hyposmia is a sensorial disorder in which patients have a reduced sense of smell. However, there are no effective regimens for the management of this disorder. Therefore, the aim of this study is to evaluate the therapeutic effect of intranasal insulin on olfactory recovery in patients with hyposmia. Study Design This is a double-blinded, randomized controlled trial. Setting Intervention. Subjects and Methods This study was administered on 38 patients with hyposmia according to the inclusion and exclusion criteria. Patients were randomly divided into 2 parallel groups. The intervention and placebo groups underwent endoscopic placement of intranasal insulin gel foam (40 IU) and saline-soaked gel foam into the olfactory cleft, respectively. The procedure was performed twice a week for 4 weeks with butanol threshold testing initially and 4 weeks after treatment. Results The Connecticut Chemosensory Clinical Research Center score in the intervention group was significantly higher compared to that of the placebo group after 4 weeks ( P = .01). Moreover, no adverse effects were reported in both groups. Conclusion Our findings indicated that intranasal insulin (40 IU) administration may trigger the improvement in the olfactory sense and also appears to be free of significant adverse events in this small cohort. However, due to limited research regarding this topic, further studies using a larger population are required.

Objective: In this study, we aimed to functionally and morphologically demonstrate the effectiveness of platelet-rich plasma (PRP) on anosmia in a mouse model of anosmia., Study Design: Animal study., Methods: A total of 16 male mice were included. When selecting the mice, the food-finding test (FFT) was used to make sure that the animals could smell, and anosmia was induced by administration of intraperitoneal 3-methylindole. The mice were randomly divided into two groups of eight (groups A and B). After 1 week, topical PRP was administered to the mice in group A and topical saline was administered to the mice in group B. The FFT was again administered at 7, 14, and 21 days. The mice were sacrificed on day 21, the olfactory neuroepithelium was histopathologically examined, and the epithelial damage scores and epithelial thickness were measured., Results: After topical administration of PRP and saline, the difference in the average FFT values of the groups was statistically significant at 7, 14, and 21 days (P < 0,005). During the histopathological examination, the epithelial damage score was statistically significantly lower in the PRP group (P = 0.001) than in the saline group, and epithelial thickness was statistically significantly greater in the PRP group compared to the saline group (P = 0.003)., Conclusion: We showed that PRP administration has a curative effect on olfactory functions in an anosmia-induced mice model. However, there is a need for further research before PRP can be considered for use in patients with anosmia in clinical practice., Level of Evidence: NA. Laryngoscope, 128:E157-E162, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Children who are born preterm are at risk for encephalopathy of prematurity, a leading cause of cerebral palsy, cognitive delay and behavioral disorders. Current interventions are limited and none have been shown to reverse cognitive and behavioral impairments, a primary determinant of poor quality of life for these children. Moreover, the mechanisms of perinatal brain injury that result in functional deficits and imaging abnormalities in the mature brain are poorly defined, limiting the potential to target interventions to those who may benefit most. To determine whether impairments are reversible after a prenatal insult, we investigated a spectrum of functional deficits and diffusion tensor imaging (DTI) abnormalities in young adult animals. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) would induce multiple functional deficits concomitant with reduced microstructural white and gray matter integrity, and tested whether these abnormalities could be ameliorated using postnatal erythropoietin (EPO), an emerging neurorestorative intervention. On embryonic day 18 uterine arteries were transiently occluded for 60min via laparotomy. Shams underwent anesthesia and laparotomy for 60min. Pups were born and TSHI pups were randomized to receive EPO or vehicle via intraperitoneal injection on postnatal days 1 to 5. Gait, social interaction, olfaction and open field testing was performed from postnatal day 25-35 before brains underwent ex vivo DTI to measure fractional anisotropy, axial diffusivity and radial diffusivity. Prenatal TSHI injury causes hyperactivity, impaired gait and poor social interaction in young adult rats that mimic the spectrum of deficits observed in children born preterm. Collectively, these data show for the first time in a model of encephalopathy of prematurity that postnatal EPO treatment mitigates impairments in social interaction, in addition to gait deficits. EPO also normalizes TSHI-induced microstructural abnormalities in fractional anisotropy and radial diffusivity in multiple regions, consistent with improved structural integrity and recovery of myelination. Taken together, these results show behavioral and memory deficits from perinatal brain injury are reversible. Furthermore, resolution of DTI abnormalities may predict responsiveness to emerging interventions, and serve as a biomarker of CNS injury and recovery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Previous research has suggested that sodium citrate improves hyposmia by decreasing mucus calcium levels in the nose. This study aimed to confirm or refute this effect in a single application and assess potential side-effects., Design: Study design was a randomised double-blind controlled trial of sodium citrate nasal spray (intervention) vs sterile water (control). Fifty-five patients with non-conductive olfactory loss were randomised to receive the intervention or placebo., Setting: Tertiary care clinic., Main Outcome Measures: The primary outcome measure was improvement in measured olfactory thresholds for phenyl ethyl alcohol (PEA) over 2 hours. Other outcome measures assessed were improvement in olfactory thresholds in 1-butanol, eucalyptol and acetic acid; number of responders with a clinically relevant response in each arm; and adverse effects., Results: A significant effect was seen in the intervention arm for PEA and for 1-butanol and eucalyptol when compared to the control arm (P<.05); 32% of the intervention arm responded in terms of improved sensitivity towards some of the odours. Minor adverse effects noted included sore throat, nasal paraesthesia, slight rhinorrhoea and itching. The duration of effect of the citrate is transient, peaking at 30-60 minutes after application., Conclusions: Sodium citrate yields some potential as a treatment for non-conductive olfactory loss; however, these findings require corroboration in further clinical trials looking at longer term regular use of the spray as a viable therapeutic option for patients where it would be applied at frequent intervals such as before mealtimes., (© 2017 John Wiley & Sons Ltd.)

Patients with CKD suffer from food aversion, anorexia, and malnutrition. Although olfaction has a significant role in determining food flavor, our understanding of olfactory impairment and of the olfaction-nutrition axis in patients with kidney disease is limited. We quantified odor identification, odor threshold, and subjective odor perception in a cohort ( n =161) comprising 36 participants with CKD, 100 participants with ESRD, and 25 controls. We investigated olfaction-nutrition associations in these participants and examined a novel intervention to improve olfaction in ESRD. The mean odor identification score was lower in patients with CKD (75.6%±13.1%; P =0.02) and ESRD (66.8%±15.1%; P <0.001) than in controls (83.6%±11.4%). Patients with ESRD exhibited higher odor threshold than the remaining participants exhibited. All groups had similar scores for subjective smell assessment. In multivariable adjusted analyses, kidney disease associated with increased odds of odor identification deficits (odds ratio, 4.80; 95% confidence interval, 1.94 to 11.89). A reduction in odor identification score was associated with higher subjective global assessment score and lower serum total cholesterol, LDL cholesterol, and albumin concentrations. We found no associations between odor threshold and nutritional parameters. In a proof of concept, 6-week, open-label clinical trial, intranasal theophylline (an epithelial membrane transport and proton secretion activator) increased odor identification score in five out of seven (71%) patients with ESRD. In conclusion, patients with kidney disease have olfactory deficits that may influence their nutritional status. Our preliminary results regarding olfactory improvement using intranasal theophylline warrant confirmation in a randomized controlled trial., (Copyright © 2017 by the American Society of Nephrology.)

Objective: To observe the effect of ginkgo biloba extraction combined with glucocorticoids on postviral olfactory dysfunction. Method: Forty-two patients were diagnosed as postviral olfactory dysfunction. All patients underwent olfactory test, including T&T test and Sniffin Sticks test before and after treatment. The treatment lasted up to 3 months based on effectiveness. The results of olfactory test were recorded every month. Result: Twenty patients received the treatment with prednisone acetate. T&T test showed that the effective and improvement rate of the treatment with prednisone acetate were 25.00%(5/20) and 45.00%(9/20),respectively; Sniffin Sticks test showed that the effective and improvement rate of the treatment were 20.00%(4/20)and 50.00%(10/20),respectively. Twenty-two patients received the treatment combined with extract of ginkgo biloba. T&T test showed that the effective and improvement rate of the treatment with prednisone acetate were 31.82%(7/22)and 50.00%(11/22),respectively; through Sniffin Sticks test showed that the effective and improvement rate of the treatment were 27.27%(6/22)and 54.55%(12/22),respectively. Conclusion: Olfactory function in patients with postviral olfactory dysfunction was improved with two therapy. There was no significant difference on effect between the two therapeutic groups, but the effect of combination of extract of ginkgo biloba was better than the effect of prednisone acetate. Prolong duration of treatment is help for the recovery of the olfaction., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: Olfactory dysfunction is one of the comorbidities associated with allergic rhinitis (AR) and AR is one of the common causes of olfactory problems. We aimed to evaluate by the Sniffin' Sticks test the effects on olfactory functions of nasal steroids and leukotriene antagonists used for allergic rhinitis., Methods: Thirty patients with seasonal rhinitis were included in this study. Patients were randomly divided into three groups of 10 patients; group 1 received montelukast sodium and mometasone furoate (MF) therapy, group 2 received only montelukast, and group 3 only MF. Patients' olfactory functions were determined using the Sniffin' Sticks olfactory test before and after a month treatment., Results: Threshold, discrimination, identification, and the sum of threshold, discrimination, and identification (TDI) values were not significantly different among the groups before treatment. For Group 1 and Group 3 patients, there were statistically significant differences in threshold, discrimination, identification, and TDI values before and after treatment (P<0.05) (Wilcoxon signed ranks analysis). For Group 2 patients, the before and after treatment values of threshold, discrimination, identification, and TDI showed no significant difference (P>0.05)., Conclusion: According to the findings of our study, MF is superior to montelukast in improving olfactory function. Although montelukast has been shown to be effective against AR symptoms, its effect on olfactory function was not demonstrated in this study., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Vitamin A plays a decisive role in the regeneration of olfactory receptor neurons. In this retrospective study we investigated the effectiveness of topical vitamin A in patients with post-infectious and posttraumatic smell disorders. Retrospective cohort. A total of 170 patients (age range 18-70 years, mean age 52 years) participated. Forty-six patients were treated with smell training only. The remaining 124 patients received smell training and topical vitamin A. Olfactory function was assessed using the Sniffin' Sticks test kit, a validated technique to measure odor thresholds, discrimination and identification. The duration of olfactory training was 12 weeks. In patients receiving vitamin A, this was applied topically (head back position) at a dose of 10,000 IU/day for 8 weeks. Follow-up testing was performed approximately 10 months after the first assessment. Thirty-seven per cent of all post-infectious patients treated with vitamin A exhibited clinical improvement, whereas only 23% improved in controls. Using a Chi-square test, this was a significant result (χ 2  = 7.06, df = 2, p = 0.03). In addition, when comparing change in score after treatment, olfactory training + vitamin A produced significantly greater improvement compared with training alone, in discrimination score for all patients (1.4 points, p = 0.008), and in threshold and discrimination in the post-infectious group (1.6 points, p = 0.01 and 1.4 points, p = 0.04, respectively). Intranasal vitamin A at a dose of 10,000 IU per day for 2 months may be useful in the treatment of post-infectious olfactory loss. Further work with prospective, placebo-controlled studies is required to confirm these findings.

Objectives: Free calcium plays an integral role in peripheral olfactory processing, including feedback inhibition. It has therefore been suggested that reduction of intranasal free calcium with buffer solutions such as sodium citrate may improve olfactory function in patients with smell impairment. Several previous studies have supported this hypothesis, particularly in post-infectious olfactory loss. We therefore aimed to determine whether treatment with intranasal sodium citrate improves olfactory function in patients with post-infectious impairment., Design: Prospective, single-blind, placebo-controlled trial., Setting: Interdisciplinary Smell and Taste Clinic, TU Dresden (tertiary referral centre)., Participants: Forty-nine adult participants with post-infectious olfactory impairment (M : F = 11 : 38, mean age 58.71 ± 11.03 years)., Main Outcome Measures: Olfactory function (odour threshold and identification) before and after treatment as determined using "Sniffin' Sticks". Patients were treated monorhinally with 1 mL sodium citrate solution. The contralateral nasal cavity was treated with 1 mL physiological sodium chloride solution, which acted as internal control. Clinical improvement was assumed where threshold or identification score increased by ≥2.5 or 3 points, respectively, or ≥5.5 points together., Results: We demonstrated a statistically significant improvement in composite threshold + identification scores following treatment with sodium citrate, compared with placebo. This was true for all patients (mean improvement 0.87 ± 2.68 points, P = 0.04), and on subgroup analysis in those with hyposmia (mean improvement 1.15 ± 2.37 points, P = 0.02). However, the effect size did not reach clinical significance., Conclusions: Further basic and clinical work is required to fully delineate the effect of intranasal sodium citrate in the treatment of post-infectious olfactory loss., (© 2016 John Wiley & Sons Ltd.)

Purpose: We previously demonstrated the presence of sonic hedgehog (Shh) in nasal mucus in normal subjects and in patients with smell loss (hyposmia). Nasal mucus Shh levels were found significantly diminished in untreated hyposmic patients of multiple etiologies. Since treatment with oral theophylline has been previously associated with improvement in smell function we wished to study if such treatment increased nasal mucus Shh as well as improved smell function in patients with hyposmia., Methods: Forty-four patients with hyposmia of several etiologies were evaluated for changes in hyposmia by subjective measurements of smell, taste and flavor perception and by olfactometry. Measurements of nasal mucus Shh were made in relationship to each set of sensory measurements. Patients were treated with oral theophylline at doses of 200-800mg for periods of 2-10months with sensory function, nasal mucus Shh and serum theophylline levels evaluated at these time intervals. Nasal mucus Shh measurements were made with a sensitive spectrophotometric ELISA assay and theophylline with a fluorometric assay., Results: There was consistent, significant improvement in subjective responses in smell, taste and flavor perception and in olfactometry associated with increased nasal mucus Shh and serum theophylline after theophylline treatment., Conclusions: Improvement in smell function and in nasal mucus Shh was positively correlated in a dose-response relationship after treatment with oral theophylline. Results are consistent with a successful role for theophylline in improvement of smell function in hyposmic patients of multiple etiologies associated with increased nasal mucus Shh which can act as a biochemical marker for smell function., (Copyright © 2016. Published by Elsevier Inc.)

Limited olfactory improvement after topical steroid therapy in chronic rhinosinusitis (CRS) patients might result from restricted drug access to the olfactory cleft. The aim of our study was to investigate the difference between two methods to topically administer steroids with respect to olfaction: (1) conventional nasal spray and (2) a device using pressure and vibration to distribute steroid aerosol endonasally. A prospective study was performed in patients with olfactory impairment due to chronic rhinosinusitis with and without nasal polyps. While the first group used the conventional dexamethasone nasal spray, the second group used the device over a period of 12 days. Olfactory testing was done at 0, 2, and 8 weeks using Sniffin' Sticks test. A significant olfactory improvement was found after 2 weeks of treatment with either steroid (p = 0.005). However, there was no significant difference between the different methods of steroid application. There is a significant olfactory improvement in CRS patients following topical dexamethasone therapy, but no obvious superiority of one of the two ways to administer the steroid.

Acute rhinosinusitis (ARS) is defined as an inflammation of the mucosa of the nose and paranasal sinuses and affects 1-5 % of general population in Europe. Sinonasal diseases represent the main cause of smell alterations in adult patients and lead to mucosal congestion, increased quantity and density of secretions and altered mucociliary transport. For this reason the odorous molecules contained in the inspired air, cannot interact with the olfactory epithelium. Medical therapy of ARS has to reduce the severity and duration of symptoms and prevent complications. Recent studies have shown that Sodium hyaluronate modulate inflammation and has a reparative effect on the nasal mucosa. 48 patients affected by acute rhinosinusitis proven by CT scan, were enrolled. They were submitted to nasal endoscopy, olfactometric and mucociliary transport evaluation (MCTt), Visual Analogue Scale Questionnaire (VAS) at T0, after 14-18 days (T1) and after 30-35 days (T2). The patients were randomized into two treatment groups, A and B, and were treated for 30 days; each group was composed of 24 subjects. All patients received Levofloxacin (500 mg for 10 days) and Prednisone (50 mg for 8 days, 25 mg for 4 days and 12, 5 mg for 4 days). Moreover, Group A received twice a day for 30 days high molecular weight Sodium Hyaluronate (3 %) plus saline solution (3 mL sodium chloride-NaCl-0.9 %) using a nebulizer ampoule for nasal douche. Group B received twice a day for 30 days saline solution (6 mL sodium chloride-NaCl-0.9 %) using a nebulizer ampoule for nasal douche. At T1 Group A shown lower values in MCTt and threshold score was significantly higher than in Group B. VAS showed statistically significant differences between the two groups, in particular for smell, nasal obstruction and for nasal discharge. At T2 Group A MCTt was significantly lower than in Group B; odour threshold improved in both groups but in Group A was still significantly higher than in Group B. No statistical differences between two groups regarding odour discrimination and odour identification were confirmed at T1 and T2. VASy score showed statistically significant differences between the two groups only for nasal discharge.

Background: Anticholinergic challenge can induce odor identification impairment that indicates Alzheimer's disease pathology., Objective: To determine if decline in odor identification ability with anticholinergic challenge can predict improvement with donepezil, a cholinesterase inhibitor (ChEI), in patients with mild cognitive impairment (MCI)., Methods: At baseline, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge. Donepezil was started at 5 mg daily, increased to 10 mg daily if tolerated, and then the dose was kept constant for 52 weeks. Main outcomes were change in Selective Reminding Test (SRT) total immediate recall and ADAS-Cog total score from baseline to 26 and 52 weeks., Results: In 37 participants, mean age 70.4 (SD 9.8) y, greater atropine-induced decrease in UPSIT score at baseline was associated with greater improvement in SRT total recall score from baseline to 26 and 52 weeks (p < 0.03). This effect remained after adjusting for time, age, education, gender, APOE ɛ4 status, and baseline cognitive score (p < 0.05). Decrease in UPSIT score was associated with global improvement (CIBIC-plus) over 52 weeks (p < 0.02). After excluding patients with congential anosmia, increase in UPSIT score from 0 to 8 weeks showed a trend-level association with improvement on the ADAS-Cog (p = 0.07)., Conclusions: Anticholinergic challenge-induced odor identification decline was associated with cognitive improvement, and short-term improvement in odor identification tended to predict longer term cognitive improvement. These simple inexpensive strategies have the potential to improve selection of patients with MCI for ChEI treatment.

Background: Loss of olfaction can cause noticeable reduction in general quality of life. Only a small portion of patients with olfactory loss respond to current medications. Thus, development of novel therapeutic strategies seems to be necessary. Looking into traditional medical knowledge can be of great value in addressing useful remedies. Traditional Persian Medicine (TPM) has been practiced in Persia for more than 2000 years. Avicenna is the most eminent Persian physician., Objective: To survey Avicenna's views on etiology and management of olfactory loss and to search for relevant modern pharmacological data., Methods: Avicenna's views on etiology and management (including suggested medicinal plants) of olfactory loss were obtained from "Canon of Medicine". In addition, a detailed search in ScienceDirect, PubMed, Scopus and Google Scholar databases was performed to elucidate relevant pharmacological actions and mechanisms of the plants and their major compounds with special focus on neuroprotective activity., Results: Acorus calamus L., Allium cepa L., Allium sativum L., Aloe spp., Cinnamomum cassia (L.) J.Presl, Lavandula stoechas L., Mentha longifolia (L.) L., Nigella sativa L., Peganum harmala L., Piper nigrum L. and Zingiber officinale Roscoe were found to be the most emphatic plants for the treatment of olfactory loss. Pharmacological studies revealed biological activities including neuroprotective, anti-inflammatory, free radical scavenging activities and promoting endogenous antioxidant capacity for these plants and their major components., Conclusion: regarding the lack of effective treatments for recruiting normal smell in many cases, treatments suggested by Avicenna worth entering pharmacologic experiments and clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Chronic rhinosinusitis (CRS) has significant impacts upon productivity, economic metrics, and medication usage; however, factors that are associated with these economic outcomes are unknown., Methods: We evaluated olfactory dysfunction in 221 patients with CRS using the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) and the 40-item Smell Identification Test (SIT) and assessed whether an association existed between these olfactory metrics and healthcare utilization, productivity, and medication usage over the preceding 90 days., Results: After adjusting for CRS-associated comorbidities, objective measures of disease, demographics, and CRS-specific quality of life (QOL), patients with lower QOD-NS scores (worse patient-reported olfaction) had more missed days of normal productivity and employment, worse productivity levels, more hours of missed employment due to physician visits, more time caring for sinuses, greater distance traveled to medical appointment, more days of oral steroid use, and higher odds of being on disability insurance. Clinical olfaction, as measured by SIT, was associated with greater distance traveled to medical appointment and higher odds of being on disability insurance, but did not correlate with other productivity measures., Conclusion: Impaired olfactory-specific QOL is associated with significantly worse economic and productivity metrics and increased medication usage even after adjusting for CRS-specific comorbidities, objective measures of disease, demographics, and severity of CRS-specific QOL. Future studies are warranted to determine if targeting the impaired olfactory-specific QOL noted in patients with CRS results in improved productivity and economic outcomes., (© 2016 ARS-AAOA, LLC.)

Background & Objective: Down syndrome, a genetic condition caused by triplication of chromosome 21, is characterized by widespread neurogenesis reduction and cognitive impairment. Unlike other brain functions, smell is not impaired at early life stages and olfactory deterioration begins to appear in adulthood. Similarly to individuals with Down syndrome, in the Ts65Dn mouse model of Down syndrome smell function is normal at early life stages. Smell impairment only appears in adulthood associated with a reduction in the number of new granule neurons migrated to the olfactory bulb from the subventricular zone. Based on evidence that lithium positively impacts neurogenesis, the goal of current study was to establish whether treatment with lithium restores olfactory bulb neurogenesis and olfactory performance in middle-aged Ts65Dn mice., Method: Euploid and Ts65Dn mice aged 13 months were treated with lithium chow or control chow for one month. Before the end of treatment, mice were injected with BrdU, in order to label proliferating cells. Results showed that in Ts65Dn mice lithium treatment restored the number of neural precursor cells in the subventricular zone of the lateral ventricle, rostral migratory stream and olfactory bulb. This effect was accompanied by restoration of olfactory performance. Unlike in olfactory neurogenic regions, treatment had no neurogenesis-enhancing effect on the subgranular zone of the hippocampal dentate gyrus, indicating that lithium has no generalized positive effect on the brain., Conclusion: Results suggest that lithium may have a positive impact in brain disorders that, similarly to Down syndrome, are characterized by olfactory decline and neurogenesis impairment in the subventricular zone., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Conclusion: Twice-daily topical corticosteroid treatment using a squirt system was beneficial in maintaining improvements in olfactory dysfunction which had been achieved by oral steroid treatment., Objectives: Some patients suffering from olfactory dysfunction respond well to corticosteroids. However, maintaining these improvements is challenging. The aim of this study was to evaluate the maintenance effect of twice-daily topical steroid treatment using a squirt system., Methods: Twenty-two anosmic patients with an increase in odor threshold, discrimination, and identification (TDI) scores in Sniffin' Sticks tests by more than six points after 1-week of oral steroid treatment were enrolled. All the patients used a squirt system to apply topical corticosteroids and were followed up at 1, 3, and 6 months., Results: Nineteen, 16, and 10 patients were followed-up at 1, 3, and 6 months after treatment, respectively. All the patients had significant visual analog scale scores improvements compared to pre-treatment. The mean improvements in TDI scores were 9.80 (p < 0.001), 11.58 (p = 0.001), and 13.87 (p = 0.005) after 1, 3, and 6 months of treatment, respectively. The self-rated and objective olfactory function scores were maintained with steroid squirt therapy without significant decline, even in the patients who were followed up for 6 months.

Background: Calcium plays an integral role in olfactory signal transduction, including feedback inhibition. Sodium citrate acts as a calcium sequestrant and when applied intranasally, reduces free calcium available for feedback inhibition, which should theoretically improve olfaction. We aimed to investigate the utility of intranasal sodium citrate in improving the olfactory function of hyposmic patients, by performing this prospective placebo controlled, single-blind trial., Methodology: Monorhinal olfactory testing for odour identification and threshold was performed in hyposmic patients using Sniffin Sticks, before and after treatment. Treatment consisted of one-off sodium citrate solution application to the olfactory cleft. Sodium chloride solution was applied to the contralateral olfactory cleft, which therefore acted as placebo control. Patients were blinded to the side of sodium citrate application, and side of treatment was randomized between patients., Results: 57 patients participated, aged 22-79. Causes of hyposmia included: post-viral (7); posttraumatic (10); sinonasal disease (30) and idiopathic (10). Compared with placebo, there was significant improvement in the identification scores of participants with post-viral hyposmia, following sodium citrate treatment. No significant change in olfactory function occurred for either identification or threshold in any other aetiological subgroup., Conclusions: Intranasal sodium citrate may be of benefit to patients with post-viral hyposmia.

Smell and taste are known to be influenced by thyroid function changes. However, many hypothyroid patients and physicians are unaware of their dysosmia and dysgeusia. The present study was performed to shed more light on the relation between hypothyroidism and olfactory loss. 32 primary hypothyroid patients and 31 controls enrolled in the prospective randomized interventional study. Newly diagnosed Primary hypothyroid patients were treated with L-thyroxine for 3-6 months. The control group was selected on the basis of the biochemical evidence of a normal thyroid function. Psychophysiological olfactory testing was performed using odor dispensers similar to felt-tip pens ("Sniffin' Sticks", Burghart, Wedel, Germany). Taste function tests were made using "Taste Strips" (Burghart, Wedel, Germany) which are basically tastant adsorbed filter paper strip. Smell identification, threshold, discrimination, TDI scores, bitter and sweet taste scores were significantly lower in untreated hypothyroid patients compared to controls (12.31±1.09 vs. 14.03±1.05, p<0.001; 7.09±1.15 vs. 8.89±1.12, p<0.001; 11.47±0.95 vs. 13.06±0.85, p<0.001; 30.90±2.70 vs. 35.89±2.07, p<0.001; 4.88±1.6 vs. 6.64±0.96, p<0.001; and 5.5±2.22 vs. 6.58±1.28, p=0.021) respectively. Comparison of scores at the third month of treatment and before treatment of hypothyroid patients revealed significant improvement in smell and taste functions in terms of identification, threshold, discrimination, TDI scores, bitter, sweet and salty tastes (12.31±1.09 vs. 13.84±1.22, p<0.001; 7.09±1.15 vs. 8.02±1.16, p<0.001; 11.47±0.95 vs. 12.41±1.21, p<0.001; 30.90±2.70 vs. 34.27±3.25, p<0.001; 4.88±1.6 vs. 6.06±1.4, p<0.001; 5.5±2.22 vs. 6.38±1.28, p<0.001; and 6.12±2.32 vs. 6.62±1.48, p=0.044) respectively. On correlation analysis, there was a negative correlation between TPO-Ab levels and discrimination, identification and TDI scores (r=-0.409, p=0.02; r=-0.424, p=0.016; r=-0.532, p=0.002), and also between Tg-Ab levels and identification, TDI, and bitter scores (r=-0.423, p=0.016; r=-0.468, p=0.007; r=-0.409, p=0.02) respectively. Primary hypothyroidism was found to have a negative effect on smell and taste. RAI treatment was found to be most destructive on smell and taste compared to surgical and autoimmune hypothyroidism. Treatment of hypothyroidism was positively correlated with an improvement of both senses. Thus, the future workup of patients with smell/taste loss should include investigations for thyroid functions., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Smell function has been initiated with theophylline treatment in 63% of patients with Type II congenital smell loss. Based upon a systematic evaluation of the protein components of nasal mucus we have demonstrated that interactions among four chemical moieties in nasal mucus may play significant roles in this initiation. Prior to treatment three of these moieties, cAMP, cGMP and sonic hedgehog (Shh), were significantly decreased in concentration whereas one of these moieties, TNFalpha, was increased in concentration. The mechanism(s) responsible for initiation of smell function in these patients, not immediately apparent, may depend upon understanding interactions among these moieties., Methods: Measurements of cAMP, cGMP, Shh and TNFalpha in nasal mucus by specific spectrophotometric immunoassays before and after treatment with theophylline., Results: Before theophylline treatment cAMP, cGMP and Shh in nasal mucus, which act as growth factors to support olfactory receptor function, were significantly decreased below normal levels whereas TNFalpha which acts as a "death factor" to inhibit olfactory receptor function was significantly increased above normal. After theophylline treatment cAMP, cGMP and Shh increased significantly whereas TNFalpha decreased significantly., Conclusions: These results indicate that there are specific biochemical changes associated with smell loss in patients with Type II congenital smell loss and that correction of these biochemical changes are associated with initiation of smell function in these patients. Understanding these relationships play an important role in understanding receptor action in smell function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The purpose of this study was to investigate the potential effects of caffeine in patients with olfactory loss. The suggested mechanisms of action consist in the non-selective blocking of adenosine receptors as well as inhibition of the phospodiesterase. Olfactory function was tested twice in 76 hyposmic patients either because of URTI or because of sinunasal causes. For definition of hyposmia and for later assessment of phenyl ethyl alcohol odor threshold, and odor discrimination the Sniffin Sticks data test was used. Using a double-blinded design, the participants were divided into two groups: one received a cup of espresso with caffeine (65 mg/cup), the other a cup of espresso without caffeine (placebo). Before and approximately 45 min after espresso consumption olfactory function was assessed. Across all participants, in comparison to placebo there was no significant effect of caffeine on olfactory function, regardless whether it was caused by an acute infection of the upper respiratory tract or sinunasal disease. These results indicate that-under the current conditions-the phosphodiesterase-inhibitor/adenosine-receptor agonist caffeine has little or no short-term effect on olfactory function in patients with olfactory loss.

The olfactory system is a unique part of the mammalian nervous system due to its capacity for neurogenesis and the replacement of degenerating receptor neurons. Cigarette smoking is a major cause of olfactory dysfunction. However, the mechanisms by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs) remain unclear. Here, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. Administration of methimazole caused detachment of the olfactory epithelium from the basement membrane and induced olfactory dysfunction, thus enabling us to analyze the process of ORN regeneration. We found that intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of ORNs and olfaction following ORN injury. Defective ORN recovery in CSS-treated mice was not associated with any change in the number of SOX2(+) ORN progenitor cells in the basal layer of the OE, but was associated with impaired recovery of GAP43(+) immature ORNs. In the nasal mucosa, mRNA expression levels of neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-5, glial cell-derived neurotrophic factor, and insulin-like growth factor-1 (IGF-1) were increased following OE injury, whereas CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of ORN recovery following injury. These results suggest that CSS impairs regeneration of ORNs by suppressing the development of immature ORNs from ORN progenitors, at least partly by reducing IGF-1 in the nasal mucosa.

Parosmia has been described in neurological disorders, including temporal epilepsy. We reported a case of parosmia associated with unilateral hyposmia and mesial temporal sclerosis. We assessed the olfactory function by using Sniffin' sticks test and olfactory event-related potentials (OERPs). The findings of unilateral deficit of identification associated with parosmia only in the side ipsilateral to mesial temporal sclerosis area, that involves temporal olfactory regions responsible for higher level of smell processing, suggest a central genesis of olfactory disorders. The administration of levetiracetam restored olfactory function, OERP N1-P2 amplitude, and mesial temporal sclerosis-related electroencephalographic findings.

Background: Postviral olfactory dysfunction (PVOD) is the most common cause of olfactory dysfunction. Several treatments have been presented in the literature. The objective of this study is to systematically review the existing literature on the effectiveness of pharmacologic treatments for PVOD., Methods: We performed a literature search of PubMed, Ovid, and ScienceDirect from 1966 to 2014. Inclusion criteria included English-language articles containing original data on pharmacologic treatment of PVOD with ≥5 subjects, measurable outcomes, and readily available treatments. Data was collected regarding study design, subject demographic information, clinical outcomes, and level of evidence. Two investigators reviewed all articles independently., Results: Of 445 abstracts identified, 8 articles were included, yielding 563 patients. Treatments investigated included oral corticosteroids, local injections of corticosteroids, zinc sulfate, alpha lipoic acid, caroverine, vitamin A, Ginkgo biloba, and minocycline. Outcome measures were determined by symptom scores and objective olfactory test methods-the most common being Sniffin' Sticks. Improvement was noted in subjects receiving oral corticosteroid therapy, local injections of corticosteroid, alpha lipoic acid, and caroverine, whereas vitamin A, zinc sulfate, Ginkgo biloba, and minocycline groups did not show significant improvement., Conclusion: The majority of therapies investigated that show benefit in treating PVOD are of poor quality. Although caroverine therapy showed benefit and is a level 1b study, etiologies of olfactory dysfunction other than PVOD were included as well, which clouds the results. Overall, there is no strong evidence for any pharmacologic treatment of PVOD in the literature., (© 2016 ARS-AAOA, LLC.)

Objective: To determine the effect of a soluble human tumor necrosis factor alpha (TNF-α) receptor blocker (etanercept) on an inducible olfactory inflammation (IOI) mouse model., Study Design: An in vivo study using a transgenic mouse model., Setting: Research laboratory., Subjects and Methods: To study the impact of chronic inflammation on the olfactory system, a transgenic mouse model of chronic rhinosinusitis-associated olfactory loss was utilized (IOI mouse), expressing TNF-α in a temporally controlled fashion within the olfactory epithelium. In one group of mice (n = 4), etanercept was injected intraperitoneally (100 μg/dose, 3 times/week) concurrent with a 2-week period of TNF-α expression. A second group of mice (n = 2) underwent induction of TNF-α expression for 8 weeks, with etanercept treatment administered during the final 2 weeks of inflammation. Olfactory function was assayed by elecro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Each group was compared with an equal-number control group., Results: Compared with nontreated IOI mice, etanercept-treated IOI mice showed significantly improved EOG responses after 2 weeks (P < .001). After 8 weeks of induced inflammation, there was massive loss of olfactory epithelium and no EOG response in nontreated IOI mice. However, in etanercept-treated mice, regeneration of olfactory epithelium was observed., Conclusion: Concomitant administration of etanercept in IOI mice results in interruption of TNF-α-induced olfactory loss and induction of neuroepithelial regeneration. This demonstrates that etanercept has potential utility as a tool for elucidating the role of TNF-α in other olfactory inflammation models., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Background: Patients with congenital smell loss (hyposmia) are born without a sense of smell. They comprise two types. Type I patients have genetic abnormalities manifested by brain, gonadal and other somatic abnormalities. Type II patients have neither a family history of smell loss nor any somatic abnormalities. No systematic attempts to initiate smell function in Type II patients have been reported., Methods: Smell function was measured in 19 Type II congenital smell loss patients by both subjective responses and by olfactometry using measurements of detection and recognition thresholds, magnitude estimation and hedonics in response to four odors (pyridine, nitrobenzene, thiophene and amyl acetate) before and after treatment with oral theophylline, 200-800mg daily for periods of 2-36months with evaluation of smell function and serum theophylline measured at intervals of 2-6months., Results: In 12 of the 19 Type II patients (63%) smell function was initiated for the first time and was quantitated by both subjective responses and by olfactometry. Initiation of smell function occurred after treatment with 200-800mg of oral theophylline for periods of 2-19months., Interpretation: This is the first systematic demonstration of initiation of smell in patients who were born without smell function. Oral theophylline presumably acts to increase both olfactory receptor growth, development and perpetuation and brain plasticity which enables them to recognize olfactory signals with initiation of olfactory function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Systemic treatment with corticosteroids shows therapeutic effects, few patients benefit from intranasal topical drug application, probably due to limited access of the drug to the olfactory epithelium. The aim of the present study was to investigate how drops distribute within the nasal cavity when the "Kaiteki" position is performed. Thirteen healthy volunteers participated. Subjects were lying on the side with the head tilted and the chin turned upward. Blue liquid was used to visualize the intranasal distribution of the nasal drops. The investigation was carried out using photo documentation thorough nasal endoscopy; the intranasal distribution of the dye was judged by two independent observers in both a decongested state and a natural state where no decongestants had been used. With regard to the main criterion of this study, using the "Kaiteki" position, nasal drops reached the olfactory cleft in 96 % of the decongested cases and 75 % of the cases who had not been decongested. However, this difference was not statistically different. Because the "Kaiteki" maneuver is not too difficult to perform, it is more likely that topical steroids can be helpful in cases of olfactory loss.

Background: Smell and taste disorders, sicca symptoms, can be detected in patients with head and neck cancer. The purpose of this study was to assess the utility of local liposomal application in the treatment of patients with head and neck cancers., Methods: Ninety-eight patients with head and neck cancer were included in this study. The groups were defined as: group 1 = only surgery; group 2 = surgery + adjuvant radiochemotherapy; and group 3 = primarily radiochemotherapy. All patients had finished cancer treatment and received liposomal sprays for the nose and mouth for 2 months (LipoNasal, LipoSaliva; Optima Pharmaceutical GmbH, Germany) and suffered from taste and smell disorders. We performed tests with "Sniffin' Sticks," "Taste Strips," and a xerostomia questionnaire before and after treatment., Results: After application of liposomes, patients demonstrated a statistically significant increase in smell and taste, and reduced xerostomia., Conclusion: Our results demonstrate that using nonpharmaceutical liposomal sprays improve smell, taste, and symptoms of xerostomia in patients with head and neck cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1232-E1237, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: The application of intranasal insulin in healthy humans has been linked to improved memory function, reduced food intake, and increased olfactory thresholds. There has also been some correlation between the morbidities associated with central nervous system (CNS) insulin resistance, such as type II diabetes mellitus, Alzheimer's disease, obesity, and impaired odour recognition. Given that impaired odour recognition is an important component of olfactory performance, mechanisms that govern these effects may account for impaired olfactory functions in anosmic patients., Methodology: Ten patients with post-infectious olfactory loss received intranasal administration of 40 IU insulin or a placebo solution, as well as olfactory performance tests before and after administration., Results: When administered insulin, patients exhibited an immediate performance improvement with regard to olfactory sensitivity and olfactory intensity ratings. In addition, more odours were correctly identified. Furthermore, an improvement in the odour identification task was detected in patients with higher body mass index., Conclusion: Results of this pilot study shed light on the link between cerebral insulin level and an impaired sense of smell. This research line might provide a better understanding of olfactory loss in relation to eating and dietary behavior, and could offer opportunities to develop faster therapeutic intervention for patients with olfactory dysfunction.

The effects of rasagiline on olfaction in animal studies are convincing. However, apart from various anecdotal patient reports, they could not be reproduced in prospective studies in humans. Cross-sectional data of large patient groups are still missing. The aim of this study was therefore to determine the olfactory function in a broad heterogeneous Parkinson's disease (PD) population with and without rasagiline intake. In this single-center, cross-sectional study 224 PD patients with and without rasagiline (1 mg/day) participated. Seventy-four of them received rasagiline as mono, or adjunct therapy. One-hundred fifty patients were untreated or received PD medication other than rasagiline. Comprehensive olfactory testing was performed for phenyl-ethyl alcohol odor thresholds, odor discrimination, and odor identification. Olfactory function did not differ between the two treatment groups with disease duration up to 29 years. Rasagiline-treated patients with disease duration of less than 8 years, however, presented with significant better odor discrimination abilities compared to PD patients without rasagiline treatment. This effect was no longer evident in patients with longer disease duration and proofed to be independent of age, sex, and medication. Our results may suggest that rasagiline treatment has a positive effect on the processing of olfactory information in early PD.

Parkinson disease (PD) is a neurodegenerative disorder characterized by massive loss of midbrain dopaminergic neurons. Whereas onset of motor impairments reflects a rather advanced stage of the disorder, hyposmia often marks the beginning of the disease. Little is known about the role of the nigro-striatal system in olfaction under physiological conditions and the anatomical basis of hyposmia in PD. Yet, the early occurrence of olfactory dysfunction implies that pathogens such as environmental toxins could incite the disease via the olfactory system. In the present study, we demonstrate a dopaminergic innervation from neurons in the substantia nigra to the olfactory bulb by axonal tracing studies. Injection of two dopaminergic neurotoxins-1-methyl-4-phenylpyridinium and 6-hydroxydopamine-into the olfactory bulb induced a decrease in the number of dopaminergic neurons in the substantia nigra. In turn, ablation of the nigral projection led to impaired olfactory perception. Hyposmia following dopaminergic deafferentation was reversed by treatment with the D1/D2/D3 dopamine receptor agonist rotigotine. Hence, we demonstrate for the first time the existence of a direct dopaminergic projection into the olfactory bulb and identify its origin in the substantia nigra in rats. These observations may provide a neuroanatomical basis for invasion of environmental toxins into the basal ganglia and for hyposmia as frequent symptom in PD.

Levodopa (L-DOPA) is used as the most effective drug available for the symptomatic treatment of Parkinson's disease (PD). However, long-term treatment of L-DOPA frequently causes complications, including abnormal involuntary movements such as dyskinesia and response fluctuations in PD patients. In the present work, we investigated whether hydroxysafflor yellow A (HSYA) ameliorates L-DOPA-induced dyskinesia and motor fluctuations in the 6-hydroxydopamine-lesioned rat model of PD. Valid PD rats were treated daily with vehicle, HSYA alone, L-DOPA, or a combination of HSYA plus L-DOPA for 21days, respectively. L-DOPA (8mg/kg) and benserazide (15mg/kg) were treated intraperitoneally. HSYA was administrated intraperitoneally at a dose of 10mg/kg. The abnormal involuntary movements and rotational behavior were evaluated. The expression of the dopamine D3 receptor in the striatum was also assayed. The results demonstrated that daily administration of L-DOPA to PD rats for 21days induced a steady expression of dyskinesia. Coadministration of HSYA with L-DOPA significantly ameliorated L-DOPA-induced dyskinesia. The combination treatment also prevented the shortening of the motor response duration that defines wearing off motor fluctuations. HSYA also inhibited the increase of expression of the dopamine D3 receptor in the striatum. These findings demonstrated that HSYA provided anti-dyskinetic relief against L-DOPA in a preclinical model of PD via regulating the expression of the dopamine D3 receptor. The combination of L-DOPA and HSYA also reduced the likelihood of wearing off development, and may thus support the utility of such compounds for the improved treatment of PD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The clinical characteristics of 16 patients with congenital anosmia were examined retrospectively. MRI (magnetic resonance imaging) was used to assess the morphological changes in the olfactory bulbs and olfactory sulci according to the method of P. Rombaux (2009). Congenital anosmia was divided into two forms: syndromic forms in association with a syndrome, and isolated forms without evidence of other defects. Only three patients (19%) in our series had syndromic forms of congenital anosmia, such as the Kallmann syndrome. Most cases (13 patients, 81%) had isolated congenital anosmia. Psychophysical testing of the olfactory function included T&T olfactometry and the intravenous Alinamin test, which are widely used in Japan. In T&T olfactometry, detection and recognition thresholds for the five odorants are used to assign a diagnostic category representing the level of olfactory function. Most cases (14 patients, 88%) showed off-scale results on T&T olfactometry, and the Alinamin test resulted in no response in all 11 patients who underwent the test. Abnormal MRI findings of the olfactory bulbs and sulci were detected in 15 of 16 patients (94%). Olfactory bulbs were bilaterally absent in nine patients (56%), and two patients (13%) had unilateral olfactory bulbs. Four patients (25%) had bilateral hypoplastic olfactory bulbs, and only one patient had normal olfactory bulbs (6%). The olfactory sulcus was unilaterally absent in one patient (6%), and nine patients (56%) had bilaterally hypoplastic olfactory sulci. Two patients (13%) had a unilateral normal olfactory sulcus and hypoplastic olfactory sulcus. Three patients (19%) had normal olfactory sulci. Quantitative analysis showed that the volume of olfactory bulbs varied from 0 mm3 to 63.5 mm3, with a mean volume of 10.20 ± 18 mm3, and the mean depth of the olfactory sulcus varied from 0 mm to 12.22 mm, with a mean length of 4.85 ± 4.1 mm. Currently, there is no effective treatment for congenital anosmia. However, diagnosis of congenital anosmia is important, as its presence can lead to dangerous situations. Careful examination for hypogonadism is also required in people with anosmia. MRI examinations of the olfactory bulbs and sulci were useful for the diagnosis of congenital anosmia.

Objectives: To study the effects of zinc and steroid in the treatment of traumatic anosmia., Study Design: A prospective, randomized study., Setting: Academic medical center., Subjects and Methods: Patients with a clear history of loss of smell after head injury and whose thresholds were -1 measured by the phenyl ethyl alcohol threshold test were included in this study from January 2010 to May 2013. They were randomly divided into 4 groups. Patients in group 1 were treated with zinc gluconate for a month and high-dose prednisolone with tapering for 2 weeks. Those in group 2 took only zinc gluconate, and those in group 3 took only prednisolone. Patients in group 4 did not take any medicine. All patients were followed up by phenyl ethyl alcohol threshold testing, and magnetic resonance imaging was performed to measure the volume of olfactory bulbs., Results: Thirty-nine patients in group 1, 35 in group 2, 34 in group 3, and 37 in group 4 completed the study. The recovery of olfactory function was observed in 11 patients (28.2%) in group 1, in 9 (25.7%) in group 2, in 4 (11.8%) in group 3, and in 1 (2.7%) in group 4. The recovery rates of olfactory function of groups 1 and 2 were significantly higher than the recovery rate of group 4. The volume of olfactory bulbs was not significantly different between those with and without improved olfactory function., Conclusion: Our results show that zinc gluconate has a promising effect in treating traumatic anosmia., (© American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.)

Background: Olfactory dysfunction is deemed to be a significant contributor to poor quality of life in chronic rhinosinusitis (CRS)., Objective: To assess and to compare the effectiveness of three modalities of corticosteroids administration in patients with CRS., Study Design: A prospective randomized controlled study, Methods: Thirty patients with CRS were randomized in three groups depending on the route of corticosteroids administration: 16 days by oral route (Medrol (Pfizer, Belgique), 32 mg/8 days -16 mg/4 days-8 mg/4 days); nasal spray (Rhinocort (AstraZeneca, Belgique), 2 × 2 × 64 µg/nostril); or sonic nebulization (Pulmicort (AstraZeneca, Belgique), 2 × 1 mg/4 mL) (Sonic nebulizer, AOHBOX-NL11SN, DTF, France). Olfactory function was assessed using orthonasal threshold discrimination identification and retronasal psychophysical olfactory tests (RNT) before and after the treatment. Same intranasal modalities were previously tested for in vitro airways scintigraphic deposition., Results: In vitro differences in drug deposition pattern between both intranasal modalities were demonstrated. Threshold discrimination identification and RNT were similar between three groups at baseline. Threshold discrimination identification improved by 5.5, 5.8, and -1.1 for sonic nebulization, oral, and nasal spray groups, respectively (P = 0.010). This improvement was clinically relevant for oral and nebulized administration. It was similar between oral and nebulized administration but significantly higher than nasal spray administration. Retronasal psychophysical olfactory tests improved similarly for the three groups (P = 0.231) CONCLUSION: Effectiveness of sonic nebulized and oral administration is demonstrated on orthonasal olfactory. The clinical benefit is better than with nasal spray., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Olfaction plays an important role in mammalian social behavior. Olfactory deficits are common in schizophrenia and correlate with negative symptoms and low social drive. Despite their prominence and possible clinical relevance, little is understood about the pathological mechanisms underlying olfactory deficits in schizophrenia and there are currently no effective treatments for these deficits. The prosocial neuropeptide oxytocin may affect the olfactory system when administered intranasally to humans and there is growing interest in its therapeutic potential in schizophrenia., Methods: To examine this model, we administered 40IU of oxytocin and placebo intranasally to 31 patients with a schizophrenia spectrum illness and 34 age-matched healthy control participants in a randomized, double-blind, placebo-controlled, cross-over study. On each test day, participants completed an olfactory detection threshold test for two different odors: (1) lyral, a synthetic fragrance compound for which patients with schizophrenia have specific olfactory detection threshold deficits, possibly related to decreased cyclic adenosine 3',5'-monophosphate (cAMP) signaling; and (2) anise, a compound for which olfactory detection thresholds change with menstrual cycle phase in women., Results: On the placebo test day, patients with schizophrenia did not significantly differ from healthy controls in detection of either odor. We found that oxytocin administration significantly and selectively improved olfactory detection thresholds for lyral but not for anise in patients with schizophrenia. In contrast, oxytocin had no effect on detection of either odor in healthy controls., Discussion: Our data indicate that oxytocin administration may ameliorate olfactory deficits in schizophrenia and suggest the effects of intranasal oxytocin may extend to influencing the olfactory system. Given that oxytocin has been found to increase cAMP signaling in vitro a possible mechanism for these effects is discussed., (Published by Elsevier Ltd.)

Background: Chronic rhinosinusitis (CRS) has been defined as inflammation of the paranasal sinuses lasting at least 12 weeks with corresponding 2 or more "cardinal symptoms" that include: (1) nasal obstruction; (2) thick nasal discharge; (3) facial pain/pressure; and (4) reduction or loss of sense of smell. Although prior studies have investigated symptoms of CRS after sinus surgery, none have compared the outcomes of these specific symptoms to ongoing medical therapy., Methods: Patients with CRS were prospectively enrolled into a multi-institutional, comparative effectiveness, cohort study. Subjects elected either continued medical management or endoscopic sinus surgery (ESS). Baseline characteristics and objective clinical findings were collected. Cardinal symptoms of CRS were operationalized by 4 questions on the 22-item Sino-Nasal Outcome Test (SNOT-22). Symptom improvement was evaluated in subjects with at least 6-month follow-up., Results: A total of 342 subjects were enrolled, with 69 (20.2%) electing continued medical management, whereas 273 (79.8%) elected ESS. Subjects electing surgical therapy were more likely to have a higher baseline aggregate SNOT-22 score (44.3 (18.9) vs 53.6 (18.8); p < 0.001). All subjects improved across all cardinal symptoms; however, subjects undergoing ESS were significantly more likely (p ≤ 0.013) to experience improvement in thick nasal discharge (odds ratio [OR] = 4.36), facial pain/pressure (OR = 3.56), and blockage/congestion of nose (OR = 2.76). Subjects with nasal polyposis were significantly more likely to report complete resolution of smell/taste following ESS compare to medical management (23.8% vs 4.0%; p = 0.026)., Conclusion: Across a large population, surgical management is more effective at resolving the cardinal symptoms of CRS than ongoing medical management with the exception of sense of smell/taste., (© 2014 ARS-AAOA, LLC.)

The aim of our study was to analyze olfactory function in patients with idiopathic inflammatory myopathies (IIM). We performed a case-control study on 60 IIM patients (48 females and 12 males) and 60 healthy controls (HC) recruited by the best friend method, matched for age, sex and lifestyle. Olfactory function was analyzed by "Sniffin' sticks test" and expressed through a score (TDI), indicating normosmia (TDI > 30), hyposmia (TDI 15-30) and anosmia (TDI < 15). Mood was investigated by Beck depression inventory (BDI) test. Statistic was performed using SPSS package. Mean ± SD TDI was significantly reduced in patients versus HC (26.8 ± 5.2 vs. 31.4 ± 3.5, p < 0.001). Anosmia was detected in two patients (3.3 %) and no HC, hyposmia in 41 patients and 14 HC (68.3 vs. 23.3 %, p < 0.0001) and normosmia in 17 patients and 48 HC (28.3 vs. 76.6 %, p < 0.0001). In the multivariate analysis carried out in the pool population of patients and HC, low TDI score was associated with age ≥50 years (p < 0.0001), disease status (p < 0.0001) and high BDI (p = 0.007). When adjusting for BDI, disease status was still associated with low TDI (p = 0.037). In IIM, TDI was lower in subjects aged ≥50 years (p = 0.008) and in patients who were taking corticosteroids (p < 0.0001). In the multivariate analysis carried out in IIM patients, low TDI was associated with age ≥50 years (p = 0.001) and prednisone intake (p < 0.0001). The olfactory function is impaired in IIM patients. An underlying immune-mediated mechanism is conceivable, yet a possible interference due to age, steroid intake and depression should be considered.

Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder with cognitive, psychiatric, motor, neuroendocrine and peripheral dysfunctions. Symptom onset and progression can be closely modeled in HD transgenic mice, which facilitate the search for therapeutics and environmental modulators. In the first investigation of chronic stress in HD, we have previously shown that administering a moderate dose of the stress hormone, corticosterone (CORT) had no effect on short-term memory in wildtype (WT) mice but accelerated the onset of the impairment in male R6/1 HD mice. We now extend this investigation to ethological dysfunctions in HD, which we hypothesized to be more susceptible to CORT treatment compared to the same functions in WT littermates. Both genotypes consumed similar doses of CORT dissolved in drinking water across 6-14 weeks of age and were assessed for olfactory sensitivity, nest-building, saccharin preference as well as vocal responses to sociosexual stimuli. In female HD and WT mice, olfactory sensitivity and saccharin preference were reduced by 2 and 4 weeks of CORT, respectively. In males, there was no effect of CORT on saccharin preference, however the number of vocalizations to a female mouse was transiently increased by CORT-drinking, regardless of genotype. Nest-building was severely impaired in HD mice at an early age, but was unaffected by CORT. Our results suggest that the presence of the HD mutation had no bearing on CORT-induced effects at this dose, suggesting that even moderately elevated stress hormone levels can impair ethological behaviors in both the HD and healthy brain., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: Allergic rhinitis (AR), a chronic inflammatory disorder of the nasal mucosa, affects approximately 20% of the world's population and often causes olfactory dysfunction. Conventional treatments cannot cure it, but only alleviate and control the symptoms. Systemic immunotherapy (SIT) is the only curative treatment for AR, but its positive effect on olfactory function has not been quantitatively demonstrated. We measured the olfactory function in patients using a "Sniffin' Sticks" test and analyzed the effects of subcutaneous SIT., Methods: The study included 12 patients (aged 13-44 years) who were eligible to receive subcutaneous SIT to treat AR between 2010 and 2012 in the Department of Otolaryngology, Sisli Etfal Training and Research Hospital. A 3-step Sniffin' Sticks test was performed before and 18 months after subcutaneous SIT. The data collected before and after treatment were compared for each patient., Results: The average scores for smell test parameters increased after treatment. Although improvements in the mean threshold, mean discrimination, and mean total scores were not significant, the mean identification score was significantly improved after treatment (P < 0.05). Age, sex, and smoking were not significantly related to the changes in the parameters., Conclusions: Subcutaneous SIT improved the olfactory performance in AR patients. Additional studies with larger patient populations and longer follow-up periods are needed to establish subcutaneous SIT as an effective treatment for olfactory disorders in these patients.