Assessment of Olfaction and Gustation
Summary
Smell disorders occur frequently. In general, 5 to 6% of the population exhibit functional anosmia. Typically, interviews are insufficient to properly assess patients’ symptoms. Structured diagnostic procedures are required to quantify olfactory function. Among diagnostic measures, simple psychophysical instruments are most important, but electrophysiological procedures are widely established as well. In addition, both imaging methods—e.g., volumetric assessment of the olfactory bulb or functional magnetic resonance imaging with gustatory or olfactory stimulation—and immunohistochemical evaluation of biopsy material are available.
Why Assess the Chemical Senses?
Approximately 5% of the population are unable to smell and roughly 20% above the age of 50 years are suffering from significant smell loss,1 with the main causes being sinonasal disorders2 or age dependent impairment of olfaction.3,4
To evaluate smell disorders, they need first to be quantified. A patient history is important but insufficient because of the discrepancy between self-described and quantified olfactory function in the majority of patients.5 A similar situation exists with respect to gustatory function.6 Interestingly, it has been shown that self-description of olfactory performance does not reflect olfactory function per se, but rather nasal airflow! Only if the patient′s focus is directed toward their actual olfactory acuity (e.g., by means of a smell test) does rating of their own olfactory sensibility become more accurate.5 Therefore, assessment of chemosensory performance is indispensable.
Note
Self-ratings of olfaction and gustation correlate poorly with quantified test results. Smell and taste function need to be assessed properly; subjective estimates are of limited value.
Psychophysical methods to evaluate the sense of smell are widely used. Approximately 200 psychophysical testing methods are available but only the most important will be introduced here: First, because many tests are basically very similar and, second, because most of them are unvalidated (see ref. 7). The majority currently assess orthonasal olfaction (with odors entering the nose by sniffing) rather than retronasal olfaction (in which odors reach the nose during eating and drinking). However, significant differences between processing olfactory stimuli from the two pathways have been established,8,9 which are also present on a clinical level.10
Psychophysical tests are based upon interviewing patients and rely upon their cooperation. In cases of insufficient ability to cooperate (e.g., in children or patients with cognitive impairment) or lack of motivation to accomplish the test (e.g., if the aim of the test is to yield an expert medical opinion), findings may be difficult to evaluate. Here, different procedures may be helpful, particularly ones based upon electrophysiological methods, such as recording of olfactory event-related potentials (see below). These procedures, granting a higher degree of objectivity, are technically more demanding than psychophysical tests, and require the investigator′s expertise. Owing to their expense, they are primarily used in legal contexts where medical evidence is required. Furthermore, biopsies from the olfactory mucosa, and imaging methods, both structural and functional, yield additional ways of evaluating olfaction or prognosis of smell disorders. However, the practical value of these tools on an intra-individual level has yet to be clarified.
Of course, prior to applying a test or starting an examination, the patient′s history has to be ascertained. A detailed introduction to establishing the history of smell and taste disorders may be found in the Guidelines of the German ENT Society (compare with ref. 11).
Tests of Olfaction
Psychophysical Assessment of Orthonasal Olfaction
Short Tests
Several tests are based upon odor naming, because of the ease and comprehensibility of this approach.12 However, as most of these tools include verbal components, one has to consider the influence of cognition and language on these tests. Short screening tests are able to differentiate between normosmia and hyposmia/anosmia. Their advantage is their short duration; their disadvantage is their comparatively poor validity with respect to detailed results, which renders the short tests unsuitable for medicolegal contexts and—at least on an individual basis—evaluation of the course of therapy.
Cross-Cultural Smell Identification Test
The “Cross-Cultural Smell Identification Test” (CCSIT) is a short test requiring the patient to identify odors from lists of four identifiers.13 In a multiple forced-choice procedure, 12 odors are tested. Microencapsulated odors are attached to paper, and may be released by rubbing the paper with a pencil. The test has a long shelf-life and is well validated. It may be performed by patients unassisted.
Sniffin’ Sticks Screening
The “Sniffin’ Sticks,” too, allow screening of olfactory function, analogous to the CCSIT. Odors are released from small cylinders with capped points, similar to felt pens. The screening procedure is an identification test and may be performed with either 12 pens14 or 16 pens in an extended version.15 The test is well validated and, unlike the CCSIT, may be used repeatedly. Depending on the frequency of application, the pens’ shelf-life may be a year or longer. Patients may perform the test by themselves.16
Note
Several well-validated, inexpensive, easy, and quick tests are available for olfactory screening.
European Test of Olfactory Capabilities
The “European Test of Olfactory Capabilities”17 is based upon 12 odors ( Fig. 6.1a ) in small glass bottles. Two procedures are performed: The first task is to identify one out of four bottles containing an odorant, which then has to be identified from a four-item list in multiple choice mode.
Zürcher Riechtest
The “Zürcher Riechtest”18 includes eight odors on so-called smell disks; odors have to be identified from three items. The disks are reusable and may be applied by patients unassisted. The test has been validated in a relatively small sample.
Identification Tests with Very Few Odors
Among the identification tests using very few odors are those from the UPSIT family (“University of Pennsylvania Smell Identification Tests”), namely, the “Pocket-Smell-Test” and another tool, both based upon three odors.19 The “Sniffin’ Sticks” family, too, includes short versions with three20 and five21 odors, which distinguish normosmic patients from anosmic patients with high specificity at very low scores, occasionally failing, however, to identify an anosmic patient. These tests are primarily useful in contexts requiring a global estimate rather than a detailed olfactory assessment.
Another very simple tool is the “Alcohol-Sniff-Test.”22 The sachet of a disposable, prepackaged alcohol swab is opened and the pad is slowly moved toward the nose; the distance from which the smell is perceived yields a diagnostic clue with respect to olfactory function.
Note
Humans are typically poor at correctly identifying odors. Basically, this can only be achieved if a list of items to choose from is available. Thus, the mere presentation of a tin of ground coffee or a flask of perfume is, at best, a fragranceassisted interview, and cannot be considered a smell test.
Psychophysical Tests Assessing Olfaction in a More Extensive Manner
In recent years, both standardized and validated psychophysical tests have been developed to investigate olfactory function in a detailed fashion. Several aspects are assessed, such as perception thresholds of one or more odorants; the ability to discriminate between odors and to identify them; olfactory memory; and the rating of suprathreshold odor concentrations.
University of Pennsylvania Smell Identification Tests
Exclusively an odor identification test, the UPSIT consists of forty microencapsulated odorants embedded in paper, which are released by rubbing (“scratch and sniff,” see Fig. 6.1b ), and identified in multiple forced-choice mode from item lists.23 Although this disposable tool is the most frequently applied smell identification test worldwide, the original version is somewhat regionally restricted because of intercultural differences in familiarity of odors (e.g., root beer, wintergreen). However, UPSIT versions are available today that have been adapted to a number of languages (www.sensonics.com).
Sniffin’ Sticks
“Sniffin’ Sticks” permit a more detailed evaluation of the sense of smell24–26 ( Fig. 6.1c ). They are reusable. The whole test is divided into a threshold, a discrimination, and an identification part, with the last two being suprathreshold tests. The test battery is based upon the notion that different tests assess different dimensions of olfaction.27,28 In this concept, it is assumed that threshold tests rather reflect peripheral aspects of the olfactory system, as opposed to more advanced, complex processing levels represented in identification and discrimination tasks. However, an absolutely clear-cut separation of these functions cannot be achieved by specific olfactory tests (see ref. 29), as discriminating and memory processes do play an important role in threshold testing, and, conversely, odor intensity is correlated with the activity of olfactory receptor neurons (ORNs).30
Threshold testing with Sniffin’ Sticks yields the concentration above which an odor is perceived. Olfactory sensitivity may be tested with n-butanol or phenylethyl alcohol. During this test, patients wear a blindfold to conceal the pens’ labels. Concentrations of the odor solutions represent a geometric series, starting at a concentration of 4%, and progressing in a total of 16 steps with a dilution ratio of 1:2 at each step.
Patients are presented with triplets of Sniffin’ Sticks. Each triplet consists of one odorous pen and two pens containing an odorless solvent. The sequence of presentation within triplets is random. Patients are required to identify the smelling pen in each triplet. Starting at a low concentration, and continuing with increasing concentrations as long as no correct response is obtained, the first “turning point” is reached when the odorous pen is identified in two succeeding triplets (indicating that the threshold has been passed). At any turning point, the direction of concentration changes is reversed from decreasing to increasing or vice versa, and presentation thus continues until the next failure or success, respectively. The procedure is completed at the seventh turning point, and the mean of the last four turning points is established as the threshold. A similar test, based upon odor flasks, is available in conjunction with the UPSIT. Other methods of odor threshold detection are used (for example, refs. 31–37), but at least some of them appear to be less suitable than Sniffin’ Sticks in clinical contexts.36
The nonverbal discrimination test of the Sniffin’ Sticks battery tests the ability to discriminate between odors. Again, patients are blindfolded, and triplets are presented, in this case with suprathreshold concentrations in all pens. In each triplet, two items contain the same odorant, whereas the third one is different, and is required to be detected. Patients are presented with each pen only once. Altogether, 16 triplets are used; the number of correctly identified items represents the discrimination score. This test appears to be strongly affected by cognitive abilities.28
Identification is tested as in the UPSIT procedure, with Sniffin’ Sticks used rather than microencapsulated odors, and the number of items typically being 16 or 32.26 Odor identification is influenced by numerous factors (e.g., cognitive abilities, verbal skills, number of items in the multiple choice list, or similarity of these items, etc.).38,39
After completion of the entire test battery, the sum of the scores from all three subtests is calculated (Threshold + Discrimination + Identification = TDI score). A TDI score difference of six and above indicates a clinically significant change.40 For computer assisted test procedure and documentation, free software may be downloaded from: http://www.tu-dresden.de/medkhno/riechen_schmecken/download.htm
Note
Olfactory threshold, discrimination, and identification tests tap into different portions of olfactory function.
Connecticut Chemosensory Clinical Research Center Test
The test developed by the Connecticut Chemosensory Clinical Research Center (CCCRC-Test 32) is available in two parts ( Fig. 6.1d ). The threshold is assessed for butanol. Starting at a very low concentration, increasing odorant concentrations are presented, along with a nonodorous sample; patients are asked to identify the sample containing the odorant. The threshold is represented by the concentration that is correctly identified in three to five consecutive trials. In the identification task, patients are presented with eight odorants that have to be identified from a 16-item list. Scores of both subtests are combined to a single score.
Note
Clinically, testing is almost exclusively performed for both nostrils together; monorhinal testing is frequently omitted. This procedure misses lateralized differences in olfactory function (which are frequent; see ref. 41). Such differences may be indicative of lateralized brain lesions (e.g., olfactory meningioma). They may also contain information on the prognosis of the olfactory loss.42
T&T Test
The Japanese T&T Test (the name refers to the developers of the test, Professor SF Takagi and Professor B Toyoda43) is based upon five odors (β-phenylethyl alcohol, methyl cyclopentenolone, isovaleric acid, γ-undecalactone, scatole) in eight concentrations ( Fig. 6.1e ). Presenting samples in increasing concentrations, first the perception threshold (the concentration at which the odor is first perceived), and then the identification threshold (the concentration at which the odor is correctly recognized), is established.
All extensive tests permit differentiation among normosmia, hyposmia, and anosmia ( Table 6.1 ). By way of commercial availability and standardized application in several centers, comparability of various investigations could be accomplished.
Note
Forced-choice procedures are indispensable to avoid patients deciding on the “no smell” option, as this is easy and tempting and will be chosen by several patients, irrespective of whether anything was perceived or not. Only if these patients are requested to concentrate on the presented stimuli using forced-choice tasks, may they realize their perceptive abilities—which often come as a surprise to the patients themselves!
Psychophysical Assessment of Retronasal Olfaction
Retronasal olfaction represents the perception of smell during eating and drinking ( Fig. 6.2a ). As retronasal olfaction occurs virtually exclusively in the context of food and drink intake, it is mostly mistaken for taste perception. This explains why ~60% of patients suffering from only smell disorders complain about loss of smell and taste.44 Therefore, at least some cursory taste test (sweet, bitter, sour, and salty), ought to be performed along with a smell test in any patient presenting with a taste problem. Frequently, exclusive olfactory disorders are found in these cases, without any impairment of taste function.44
To our knowledge, the first clinical test of retronasal olfaction was introduced by Güttich,45 who believed he had found the ideal tool to expose malingerers in medicolegal investigations. The basic idea was that anosmic people would be unable to perceive the “taste” of liquid odorants applied to the mouth (e.g., “cherry in rum”). If an alleged anosmic could still identify the “taste” of the solutions, this would indicate odor perception. The test is, however, unstructured and thus unreliable.46
In spite of impaired orthonasal olfaction, some patients are able to identify retronasally presented odors.47 Aside from that, in disorders such as nasal polyposis or hyperplastic tonsils, discrepancies between ortho- and retronasal olfaction occur. In addition, in a small group of patients, ortho nasal smelling was found to be selectively affected, whereas retronasal olfaction was still intact.48
The Aachen “rhinotest” 49 is a screening test of retronasal smell identification, using six odorous sprays applied to the mouth. Individuals are required to select odor quality from a list of six identifiers (flowery, disgusting, fruity, raisiny, stinging, spicy). This reusable test has a long shelf-life and can be applied by the patients themselves.
In a test developed in Japan, odorants such as prosultiamine (smell of garlic) are administered intravenously 50 and the latency at which the odor is perceived (if at all) is assessed. This test is based on the pulmonary exhalation of the odorant.
Another test of retronasal olfaction is the standardized “taste powder” tool47 ( Fig. 6.2b ). So-called taste powders (20 pulverized food and spice samples, e.g., cinnamon) are applied to the mouth and identified by patients from lists of four items. This relatively simple test may be easily performed anywhere with powders purchased from a grocery. It is suitable to validate complaints of complete olfactory loss with (nearly) unimpaired gustation and vice versa.48 Recently, another test of retronasal sensitivity has been introduced,51 which is based on aromatized sorbitol candies.
Note
Ortho- and retronasal olfaction may be selectively affected. Therefore, separate testing of both pathways is worthwhile.
Electrophysiological Procedures to Assess Olfaction
Olfactory Event-related Potentials
Electroencephalography (EEG)-based olfactory event-related potentials (ERP) 52,53 is a method to validate smell disorders quantitatively. It has become a routine technique in many countries. Prerequisites of the stimulating device (olfactometer), apart from precise duration, concentration, and steep rise of the chemical stimuli, are constant flow, temperature, and humidity of the air stream ( Fig. 6.3 ).
Stimulus durations of 200 milliseconds at intervals of 30 to 40 seconds are recommended, with an airflow of 7 to 8 L/min (but see also ref. 54). Typically, 16 to 80 stimuli (optimally 80) are used to calculate an average ERP.55 An essential requirement of olfactory ERP is a sufficiently steep rising edge of the stimuli. At the olfactometer′s outlet, air temperature should approximate body temperature, and air humidity should be 70 to 80%. Chemical stimulation must not be accompanied by any mechanical, thermal, or acoustic phenomena, as these are likely to elicit evoked responses that interfere with the olfactory response.53 Olfactory ERPs have been shown to be generated in areas of the brain including the amygdala, the insula, and the orbitofrontal cortex.56
Only “pure” olfactory stimulants such as hydrogen sulfide (“rotten eggs”), vanillin, or phenylethyl alcohol (“rose fragrance”) should be used to elicit olfactory ERPs. In addition, a trigeminal stimulant should be applied separately for control purposes (e.g., odorless carbon dioxide). For clinical evaluation of smell disorders, olfactory ERPs should be obtained from at least three recording positions, with the patient′s eyes open. The main ERP recordings are a negative deflection at latencies between 200 and 700 milliseconds, and a positive peak at latencies between 300 and 800 milliseconds. In cases in which olfactory ERPs are obtained, it can be assumed that olfactory function is present.55,57,58 This is of particular significance in contexts where expert medical opinions are required.53
Related posts:
The Human Vomeronasal System
Clinical Disorders of the Trigeminal System
Sinonasal Olfactory Disorders
Functional Anatomy of the Olfactory System II: Central Relays, Pathways, and their Function
Miscellaneous Causes of Olfactory Dysfunction
Functional Anatomy of the Olfactory System I: From the Nasal Cavity to the Olfactory Bulb
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