High Test-Retest Reliability of the Extended Version of the "Sniffin' Sticks” Test

The "Sniffin' Sticks” test kit is a validated and commonly used tool for assessment of olfactory function in subjects with normal sense of smell and in individuals with smell loss. That test incorporates subtests for odor threshold, discrimination, and identification. To gain higher subtest reproducibility, tests on odor discrimination and odor identification were extended using 32 instead of the usually applied 16 single trials each. In developing the extended Sniffin' Sticks test, a number of preliminary experiments were performed in 46 healthy, normosmic individuals 1) to evaluate intensity and familiarity of the additionally selected odors, 2) to select distractors for the discrimination and identification test, and 3) to evaluate the test-retest reliability of each subtest. Furthermore, the extended test was applied to 126 patients with olfactory loss and 71 normosmic individuals. Follow-up investigation could be performed in 69 controls within an average interval of 4 days. Results revealed significant differences between patients and healthy subjects. Estimated intensity and familiarity of the newly selected 16 items of the discrimination test did not differ significantly from the 16 standard items. Test-retest reliability was found to be r = 0.80 (odor discrimination), r = 0.88 (odor identification), and r = 0.92 (odor threshold). In conclusion, the extended test kit allows a precise evaluation of olfactory function, especially when different olfactory tasks are assessed using individual subtests. Furthermore, the high test-retest reliability of both the 16 and the 32-item tests allows the evaluation of even relatively small changes of olfactory function over time by means of either tes

Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors with a strong hereditary background and a large genetic heterogeneity. Identification of the underlying genetic cause is crucial for the management of patients and their families as it aids differentiation between hereditary and sporadic cases. To improve diagnostics and clinical management we tailored an enrichment based comprehensive multi-gene next generation sequencing panel applicable to both analyses of tumor tissue and blood samples. We applied this panel to tumor samples and compared its performance to our current routine diagnostic approach. Routine diagnostic sequencing of 11 PPGL susceptibility genes was applied to blood samples of 65 unselected PPGL patients at a single center in Dresden, Germany. Predisposing germline mutations were identified in 19 (29.2%) patients. Analyses of 28 PPGL tumor tissues using the dedicated PPGL panel revealed pathogenic or likely pathogenic variants in known PPGL susceptibility genes in 21 (75%) cases, including mutations in IDH2, ATRX and HRAS. These mutations suggest sporadic tumor development. Our results imply a diagnostic benefit from extended molecular tumor testing of PPGLs and consequent improvement of patient management. The approach is promising for determination of prognostic biomarkers that support therapeutic decision-making.Acknowledgments: We thank the patients and their families who have made this research possible. We want to thank JacquesW. Lenders for his support. We further thank Alexander Krüger, Lydia Rossow and Franziska Stübner for technical support as well as Katharina Langton and Uwe Siemon for their assistance in patient administration.S

Olfactory testing in clinical settings - is there additional benefit from unilateral testing?

In clinical settings, olfactory testing is usually performed bilaterally; thus, unilateral olfactory loss may go unnoticed. The aims of this study were to evaluate 1) whether patients presenting with self-reported olfactory disorders demonstrate significant side differences in odour perception, depending on the prevalance of measured unilateral disorder, and 2) to evaluate the existing testing procedure. In 518 patients presenting with olfactory disorders, olfactory testing was performed using the "Sniffin' Sticks" test battery (consisting of a threshold, discrimination, and odour identification test) examining each nostril separately. According to the history and results from the clinical examination, olfactory disorders were classified as related to trauma, sinunasal disease, upper respiratory tract infection (URTI), tumour, congenital, idiopathic, and other. A difference of three or more points in one of the subtests or six or more points in the composite olfactory test score was considered a side difference. In almost one quarter of all presenting patients (23.4%), a side difference was detected. To not to miss lateralized disorders, we recommend testing each nostril separately. Depending on the presence or absence of a significant difference, testing then can be continued birhinally or separately for each nostril

Unilateral Choanal Atresia : Indications of Long-Term Olfactory Deficits and Volumetric Brain Changes Postsurgically

Background: Very few studies have investigated whether unilateral choanal atresia is associated with permanent olfactory deficits. Objective: This study aimed to evaluate the olfactory performance of patients with unilateral choanal atresia postsurgically. Methods: Three patients with unilateral atresia were examined in terms of olfactory performance with the Sniffin Sticks test (odor identification, threshold, and discrimination), size of the olfactory bulb, and volumetric brain changes. Results: All patients demonstrated significantly lower olfactory performance in terms of odor threshold on the same side with the choanal atresia. Grey matter reductions were found ipsilaterally in the hippocampus. Conclusions: This pilot study indicates that persistent olfactory deficits and volumetric brain changes are present in patients with unilateral choanal atresia.Funding Agencies|Alexander von Humboldt FoundationAlexander von Humboldt Foundation</p

The impact and prospect of traumatic brain injury on olfactory function: a cross-sectional and prospective study

Traumatic brain injury (TBI) can cause olfactory loss. The aim of this cross-sectional and prospective study was to determine the prevalence of olfactory loss among 110 patients with TBI within 3 months after the trauma. In 81 patients ("cross-sectional"-group), olfactory function could be measured using the validated "Sniffin' Sticks" test for odor threshold and odor identification. In addition, the prospective change of olfactory function was studied in 36 patients ("follow-up"-group) by means of a validated odor threshold, discrimination and identification test. Olfactory function was significantly better in patients with TBI I° compared to individuals with TBI II° and III°. Clinically significant improvement of olfactory function was found in 36 % of the patients, most frequently during the first 6 months after the injury, in a median follow-up interval of 21 months. TBI I° has in general no major effect on olfaction. In contrast, patients with TBI II° and III° exhibit smell loss in 57 %. Chances for olfactory recovery were highest within the first 6 months after the trauma

Expression and distribution of the intermediate filament protein nestin and other stem cell related molecules in the human olfactory epithelium

The olfactory epithelium (OE) is unique inregenerating throughout life and thus is an attractivetarget for examining neurogenesis. The nestin proteinwas shown to be expressed in the OE of rodents and issuggested to be essentially involved in the process ofregeneration. Here we report the expression anddistribution of nestin in the human OE at RNA andprotein level. Moreover, we analysed the expressionprofiles in dependence on age and olfactory capacity.After sinus surgery, biopsies were taken from theolfactory epithelium of 16 patients aged 20-80 yearswith documented differences in their olfactory function.Our studies revealed that nestin is constantly detectablein the apical protuberances of sustentacular cells withinthe human OE of healthy adults. Its expression is notdependent on age, but rather appears to be related to theolfactory function, as a comparison with specimensobtained from patients suffering either from persistentanosmia or hyposmia suggests. Particularly, in thecourse of dystrophy, often accompanied with impairedolfaction, nestin expression was occasionally decreased.Contrarily, the expression of the p75-NGFR protein, amarker for human OE basal cells, was not altered,indicating that at least in the tested samples olfactoryimpairment is not connected with abnormalities at thebasal cell level. These observations emphasize anessential role of nestin for the process of regeneration,and also highlight this factor as a candidate marker forsustentacular cells in the human olfactory epitheliu

Expression and distribution of the intermediate filament protein nestin and other stem cell related molecules in the human olfactory epithelium

The original publication is available at http://pubs.acs.org/page/jnprdf/Smoke plays an intriguing role in promoting the germination of seeds of many species following a fire. Recently, a bicyclic compound containing a condensed butenolide moiety, 3-methyl-2H-furo[2,3-c]pyran-2-one (1), was reported as a potent germination promoter from plant-derived smoke. In this study, a related butenolide, 3,4,5-trimethylfuran- 2(5H)-one (2), which inhibits germination and significantly reduces the effect of 1 when applied simultaneously, was also isolated from plant-derived smoke. The interaction of these compounds with opposing actions on seed germination may have important ecological implications in a post-fire environment and could be useful molecules for understanding the events involved in breaking seed dormancy and promoting seed germination