Hilmar Gudziol

Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds

Abstract“Sniffin’ Sticks” is a test of nasal chemosensory performance that is based on penlike odor-dispensing devices. It is comprised of three tests of olfactory function: tests for odor threshold, discrimination and identification. Previous work has already established its test-retest reliability and validity in comparison to established measures of olfactory sensitivity. The results of this test are presented as a composite TDI score – i.e., the sum of results obtained for threshold, discrimination and identification measures. The present multicenter investigation aimed at providing normative values in relation to different age groups. To this end, 966 patients were investigated in 11 centers. An additional study tried to establish values for the identification of anosmic patients, with 70 anosmics investigated in five specialized centers where the presence of anosmia was confirmed by means of olfactory evoked potentials. For healthy subjects, the TDI score at the 10th percentile was 24.5 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 28.8 for ages from 36 to 55 years and 27.5 for subjects older than 55 years. While these data can be used to estimate individual olfactory abilities in relation to a subject’s age, hyposmia was defined as the 10th percentile score of 16- to 35-year-old subjects. Our latter study revealed that none of 70 anosmics reached a TDI score higher than 15. This score of 15 is regarded as the cut-off value for functional anosmia. These results provide the basis for the routine clinical evaluation of patients with olfactory disorders using “Sniffin’ Sticks.”

Anosmia Leads to a Loss of Gray Matter in Cortical Brain Areas

Chronic olfactory disorders, including the complete loss of the sense of smell (anosmia), are common. Using voxel-based morphometry (VBM) in magnetic resonance imaging (MRI), structural changes in the cerebral gray matter (GM) of a group of patients with anosmia compared with a normosmic, healthy control group were evaluated. Patients with anosmia presented a significant decrease of GM volume mainly in the nucleus accumbens with adjacent subcallosal gyrus, in the medial prefrontal cortex (MPC) including the middle and anterior cingulate cortices, and in the dorsolateral prefrontal cortex (dlPFC). These areas are part of the limbic loop of the basal ganglia and except the dlPFC secondary olfactory areas. They also play an important role in many neurological diseases. Furthermore, volume decreases in smaller areas like the piriform cortex, insular cortex, orbitofrontal cortex, hippocampus, parahippocampal gyrus, supramarginal gyrus, and cerebellum could be seen. Longer disease duration was associated with a stronger atrophy in the described areas. No local increases in the GM volume could be observed. A comparison with results of an additionally executed functional MRI study on olfaction in healthy subjects was performed to evaluate the significance of the observed atrophy areas in cerebral olfactory processing. To our knowledge, this is the first study on persisting structural changes in cortical GM volume after complete olfactory loss.

Gray and white matter reduction in hyposmic subjects — A voxel-based morphometry study

The absence of olfactory input causes structural brain remodelling in humans. Mainly, the olfactory bulb and cortical olfactory areas are involved in this process. The aim of our study was to investigate volume changes of the gray and white matter in a group of subjects with an impaired but not complete loss of olfaction (hyposmia). Magnetic resonance images of hyposmic subjects and an age- and sex-matched control group were acquired on a 3T scanner. Voxel-based morphometry (VBM) was performed using VBM8 toolbox and SPM8 in a Matlab environment. The analysis revealed significant gray matter volume loss in the insular cortex, anterior cingulate cortex, orbitofrontal cortex, cerebellum, fusiform gyrus, precuneus, middle temporal gyrus and piriform cortex. In the VBM white matter analysis areas of volume loss were found underneath the insular cortex, in the cerebellum and middle frontal gyrus. All areas of white matter atrophy were spatially connected to areas of gray matter volume loss except the middle frontal gyrus alterations. No significant gray or white matter volume increases could be observed. The pattern of gray matter alterations was similar to that known from anosmic subjects with a lower extent. To our knowledge, we report here for the first time on white matter volume alterations in patients with olfactory deficit.

VALIDATION OF THE EORTC QLQ-C30 AND EORTC QLQ-H&N35 IN PATIENTS WITH LARYNGEAL CANCER AFTER SURGERY

The aim of this study was to test the validity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Module (QLQ‐C30) and Head and Neck Module (QLQ‐H&N35) for patients who have undergone surgery due to laryngeal cancer.

Decreased Trigeminal Sensitivity in Anosmia

The present study aimed to investigate intranasal trigeminal sensitivity in a large sample of patients with anosmia due to different etiologies. We investigated the trigeminal detection threshold for formic acid in healthy controls (n = 96) and patients with anosmia due to head trauma (n = 18) or sinonasal disease (n = 54). Anosmics exhibited higher thresholds compared with normosmics (p < 0.001). In addition, thresholds were found to be higher in patients with posttraumatic anosmia compared to anosmics with sinonasal disease (p < 0.001). The data indicate that (1) loss of olfactory sensitivity in humans may be associated with a decreased sensitivity towards trigeminal stimuli and (2) alteration of intranasal trigeminal function is stronger in patients with posttraumatic anosmia compared to patients with sinonasal disease. This may have implications for the medicolegal investigation of anosmic patients where trigeminal stimuli are frequently used to assess the patient’s response bias.

Health-related and specific olfaction-related quality of life in patients with chronic functional anosmia or severe hyposmia†

To measure health‐related and olfaction‐related quality of life (QoL) in patients with permanent, severe hyposmia or functional anosmia.

Chemosensorisch evozierte Potentiale zur klinischen Diagnostik von Riechstörungen

Riechstörungen sind häufig. Zu ihrem Verständnis ist allerdings eine Intensivierung der Grundlagenforschung sowie der klinischen Forschung erforderlich. Dabei kommt den Verfahren zur objektivierenden Erfassung von Riechstörungen eine wesentliche Rolle zu. In der vorliegenden Arbeit werden Richtlinien für eine Olfaktometrie mit Hilfe evozierter Potentiale gegeben. Sie wurden von der Arbeitsgruppe “Standardisierung von Riech- und Schmeckprüfungen” der Arbeitsgemeinschaft Olfaktologie/Gustologie der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Halschirurgie entwickelt. Wir hoffen, dass durch eine Standardisierung der Olfaktometrie mit Hilfe evozierter Potentiale ein Schubeffekt gerade hinsichtlich der vergleichenden Bewertung klinischer Studien zustande kommt. Letztlich soll durch diese Standardisierung eine effektivere Arbeit in Hinsicht auf eine rationell begründete Therapie von Riechstörungen ermöglicht werden.

Gray matter alterations in parosmia.

Parosmia is a common olfactory disorder. In this condition, odors are perceived in a different quality than usual. This distorted olfactory percept is typically reported to be unpleasant. Little is known about the pathophysiology of this phenomenon. Previous studies demonstrated smaller volumes of the olfactory bulbs in patients with parosmia compared to subjects without parosmia. In order to investigate structural brain alterations in areas beyond the olfactory bulb, in the current study voxel-based morphometry was applied. A group of 22 parosmic patients was compared with control subjects matched for age- and sex, who exhibited a similar performance in olfactory tests. Performing a whole brain analysis, we found profound gray matter volume loss in the left anterior insula in parosmic patients. In an additional volume of interest analysis including primary and secondary olfactory areas, we also found volume loss in the right anterior insula, the anterior cingulate cortex, the hippocampus bilaterally, and the left medial orbitofrontal cortex. Many of these areas are critically involved in olfactory quality discrimination and odor memory. The present results indicate that reduced gray matter volume in brain regions supporting odor discrimination and memory is related to disturbed olfactory sensation in parosmia.

Position Paper on Olfactory Dysfunction

Background Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Differences in anosmic and normosmic group in bimodal odorant perception: a functional- MRI study.

So-called bimodal odorants are able to stimulate the intranasal trigeminal system at relatively low concentrations. Using them as stimuli, the current study focused on the interaction between the olfactory and trigeminal systems at a cerebral level. In the experiment, menthol was used at two concentrations, low and high, and these were delivered to two groups of subjects, a healthy control group and an anosmic group who were unable to perceive smells. A computer-controlled olfactometer based on principles of air-dilution was used to deliver the stimuli, while the brain functions were assessed by a functional magnetic resonance imaging (fMRI) technique. SPM5 was used for data analysis. The results showed that normosmic subjects exhibited activation in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), prefrontal cortex (PFC), and cerebellum. Whilst anosmic subjects activated the same area inside the anterior cingulate; moreover a cluster of activation was found in the left parahippocampal gyrus. In controls, an effect of stimulus intensity was localized between the anterior cingulated, the medial frontal gyrus and the cerebellum; such areas could not be found in anosmic subjects. These results suggest that the olfactory system modifies trigeminally mediated information causing an evident effect in the differentiation between stimulus intensities.