Clinical assessment of retronasal olfactory function

OBJECTIVES: To develop a test kit for the simple assessment of retronasal olfactory function and to compare orthonasal and retronasal olfactory function in healthy subjects and patients with olfactory disorders. DESIGN AND PATIENTS: We tested 230 individuals with normosmia, hyposmia, and anosmia using grocery-available powders. Initially, 30 different substances were investigated. Subjects identified each substance using a list with 4 verbal items (forced choice). After preliminary experiments, 20 items were selected according to the degree to which they were identified by normosmic and anosmic subjects. Orthonasal olfactory function was assessed psychophysically using "sniffin' sticks," which includes tests for odor identification, discrimination, and butanol odor thresholds. In addition, anosmia was confirmed electrophysiologically by means of olfactory-evoked potentials. RESULTS: In healthy subjects, there was a test-retest reliability correlation of r(27) = 0.76 for retronasal olfactory function, which is similar to other odor identification tests. Retronasal testing in normosmic subjects allowed for the discrimination of sex-related differences, with women scoring higher than men (P =.007), and the identification of a slight decrease with age (r(120) = -0.20; P =.03). Orthonasal and retronasal identification of odors was found to correlate (r(86) = 0.78; P<.001). Retronasal testing allowed for the discrimination between normosmia, hyposmia, and anosmia (P<.001). In addition, retronasal performance of anosmic patients appeared to improve with duration of anosmia (P =.03). No difference was found between patients with anosmia of different origin. CONCLUSION: Results of the present investigation indicate that the assessment of retronasal olfactory function is possible using oral stimulus presentation.     

Olfactory neuroblastoma associated with Kallman's syndrome.

Kallman's syndrome is an unusual clinical entity that includes anosmia and hypogonadotropic hypogonadism. We present a patient in whom an olfactory neuroblastoma was discovered during evaluation of his Kallman's syndrome. While other craniofacial abnormalities have been associated with this condition, to our knowledge this is the first report of its association with olfactory neuroblastoma.     

Retro- and orthonasal olfactory function in relation to olfactory bulb volume in patients with hypogonadotrophic hypogonadism

Introduction

Idiopathic hypogonadotrophic hypogonadism with an olfactory deficit is defined as Kallmann syndrome and is distinct from normosmic idiopathic hypogonadotrophic hypogonadism.

Comparison of diagnostic findings using different olfactory test methods

OBJECTIVE: To quantify discrepancies in the diagnosis of olfactory function that might exist when comparing results obtained from centers using different methods of olfactory testing. STUDY DESIGN: Prospective study of 50 healthy adult volunteers and 25 adult patients with olfactory complaints. METHODS: Two test methods, the Connecticut Chemosensory Clinical Research Center (CCCRC) test widely used in the United States, and the Jet Stream Olfactometer (JSO) test used in Japan, were used to measure and categorize the diagnostic level of olfactory function (normosmia, mild hyposmia, moderate hyposmia, severe hyposmia, anosmia). Olfactory function was measured separately for each nostril. RESULTS: There was a significant correlation (rs = 0.788, P < .01, n = 150 nostrils) between diagnostic categories assigned by the CCCRC and JSO test methods. Diagnostic categories were identical for 66.7% of the nostrils tested, and in only 7.3% of the cases did the results differ by more than one category. For the anosmic and normosmic categories, test results were in agreement 91.7% of the time, whereas for the hyposmic categories (mild, moderate, and severe) results were in agreement only 22.2% of the time. CONCLUSIONS: Our results demonstrate that when comparing clinical or research data obtained from centers using different olfactory test methods, subjects with diagnoses of anosmia or normosmia may be more reliably compared than those with different levels of hyposmia.     

Hazardous events associated with impaired olfactory function

OBJECTIVE: To evaluate the risk of olfactory-related hazardous events in patients with impaired olfactory function. DESIGN: Retrospective cohort study. SETTING: A university-based clinic for smell and taste disorders. PATIENTS: A total of 445 patients who underwent olfactory testing between 1983 and 2001. INTERVENTIONS: Patient interview, olfactory testing. MAIN OUTCOME MEASURES: (1) Frequency of olfactory-related hazardous events including cooking incidents (ie, burning pots or pans), undetected fires, undetected gas leaks, and ingestion of spoiled foods or toxic substances; (2) level of olfactory function (anosmia; severe, moderate, or mild hyposmia; or normosmia) as determined by olfactory testing. RESULTS: Olfactory testing revealed that 76% of patients had some degree of impairment; 30% had complete anosmia. Thirty-seven percent of patients with olfactory impairment but only 19% of patients without impairment experienced at least 1 olfactory-related hazardous event. Of the hazardous events reported by impaired patients, cooking-related incidents were most common, representing 45%, with ingestion of spoiled food (25%), inability to detect a gas leak (23%), and inability to smell a fire (7%) reported less frequently. There was a significant correlation between frequency of hazardous events and degree of olfactory impairment (Cochran-Armitage trend test, P<.001): at least 1 hazardous event was reported by 45.2% of patients with anosmia, 34.1% with severe hyposmia, 32.8% with moderate hyposmia, 24.2% with mild hyposmia, and 19.0% of patients with with normal olfaction by testing. CONCLUSION: Patients with impaired olfactory function are more likely to experience olfactory-related hazardous events than those with normal olfactory function.     

外伤后失嗅患者的嗅觉事件相关电位和MRI评估

目的 探讨嗅觉事件相关电位(olfactory event related potentials,OERP)和嗅觉通路MRI对外伤后失嗅的评估价值.方法 回顾性分析24例外伤后失嗅患者的临床资料.所有患者均行详细的病史采集、全面体检、T&T嗅觉检查、鼻内镜检查、OERP测试、颅脑CT和嗅觉通路MRI检查.结果 主观嗅觉测试:双侧完全失嗅20例;单侧完全失嗅,对侧嗅觉减退2例;单侧完全失嗅,对侧嗅觉正常2例.OERP测试:双侧最大嗅刺激均不能引出OERP者20例,单侧最大嗅刺激不能引出OERP者4例;单侧能引出OERP者4例,其中2例能正常引出,另2例OERP幅值下降且潜伏期延长.氨气刺激均能引出鼻内三叉神经化学感受事件相关电位.嗅路MRI检查:嗅球损伤24例次(100%),额叶直回损伤22例次(91.7%),额叶眶回损伤16例次(67%),远端嗅束和颞叶损伤各2例次(8%).结论 OERP能对外伤后嗅觉进行定性和定量的客观整体评估;嗅路MRI能对外伤后失嗅的损伤部位、程度进行客观、精确的评估.两者结合能对嗅觉功能进行全面、客观评价.     

先天性失嗅患者的临床研究

目的总结先天性失嗅的分类、临床表现以及影像学特点。方法回顾性分析2004年8月-2006年9月收治的8例先天性失嗅病例的临床资料。4例为伴有其他异常的先天性失嗅患者，其中卡尔曼综合征（Kallmann syndrome）3例，鼻腔鼻窦发育异常1例；另外4例为孤立性失嗅。8例患者均行详细的病史采集、全面体检、T＆T嗅觉检查、嗅觉事件相关电位测试、鼻内镜检查和鼻窦CT检查。7例行嗅觉通路MRI和性激素检测，2例行嗅黏膜活组织检查。结果8例患者自幼均未闻到过任何气味。除1例鼻腔鼻窦发育异常外，其余7例耳鼻咽喉科常规检查以及鼻内镜检查未见异常。主观嗅觉测试均为完全失嗅。嗅觉事件相关电位测试显示最大嗅刺激引不出嗅觉事件相关电位。CT检查显示1例鼻腔鼻窦未发育，其余7例未见异常。MRI检查：6例均为嗅球、嗅束缺失，嗅沟缺失或部分变浅；1例双侧嗅球发育差。内分泌检查：3例青春期后外生殖器以及男性第二性征发育不良，血清睾酮、雌二醇、促黄体生成素以及促卵泡生成素水平低于正常。其余4例性激素检测正常。嗅黏膜活检：1例未见嗅上皮典型结构；另1例为鳞状上皮组织伴慢性炎性病变。结论先天性失嗅诊断应依据病史、专科体检、嗅觉测试、鼻窦cT以及嗅路MRI检查结果。嗅路MRI对诊断有重要价值。     

Can we smell without an olfactory bulb?

BACKGROUND: Lack of an olfactory bulb (OB) is typically associated with anosmia. METHODS: We present a patient with subnormal olfactory function in whom the OB could not be detected with magnetic resonance imaging (MRI). RESULTS: Olfactory function was evaluated on two occasions. Orthonasal olfactory function was assessed with the "Sniffin' Sticks" test providing a score equivalent to hyposmia. Retronasal olfactory function was studied with "smell powders" indicating a decreased, but not absence of, olfactory function. Importantly, chemosensory event-related potentials were clearly present in response to olfactory and trigeminal stimuli. CONCLUSION: This indicates that olfactory function may be present in some subjects even when an OB can not be detected with MRI.     

Testing olfaction in a clinical setting

Assessment of olfactory functioning at the CCCRC entails a threshold test and an odor identification test that contains eight everyday items. A performance average on the two tests yields a composite score on a scale from 0 (anosmia) to 7 (normosmia). The performance of normal volunteers is stable over most of an individual's life span, but decreases for persons over the age of 65 years. Approximately half the patients with olfactory complaints display anosmia, and the other half have hyposmia. The distribution of scores, however, varies with etiologic category, emplified by the fact that patients with nasal/sinus disease display anosmia more frequently than hyposmia. The tests can determine cause (e.g., improvement of score with corticosteroid treatment in cases of nasal/sinus disease) and can also assess degree of improvement with treatment, such as sinus operation.     

Simple assessment of olfaction in patients with chronic rhinosinusitis

Conclusion: The brief-smell identification test (B-SIT) can substitute for the butanol threshold test (BTT) in screening of anosmia and postoperative assessment of olfactory outcomes in patients with chronic rhinosinusitis (CRS). A time-effective test battery composed of B-SIT and the visual analog scale (VAS) can be implemented for simple olfactory assessment in any otolaryngology clinic. Objectives: Anosmia is a distinct clinical entity requiring special attention. Unpredictable olfactory outcomes after surgery make preoperative assessment more important. We compared the results of the BTT, B-SIT, and VAS to investigate whether B-SIT or VAS can substitute for BTT in screening of anosmia and postoperative follow-up. Methods: We collected data on 68 CRS patients who had bilateral CRS and underwent endoscopic sinus surgery. Olfactory performance was graded using the BTT: normosmia, hyposmia, or anosmia. VAS and B-SIT were also performed. All tests were repeated 6 months after surgery. Postoperative improvement was defined by an increase of the BTT score ≥ 2. Results: The B-SIT and VAS scores of the anomics were significantly lower than those of the normosmics. B-SIT discriminated anosmia with high specificity. Within the improvement group, postoperative increase of B-SIT/VAS score showed significance. However, neither the B-SIT nor the VAS differentiated between no change and deterioration of olfaction.     

Screening of olfactory function using odourized markers

BACKGROUND: The goal of our study was to create a psychophysical test for the screening of olfactory function on the basis of commercially available odourized markers (OM). There are six coloured markers in one package filled with different odourants at suprathreshold levels. In order to identify the best approach, we investigated five different variations of the technique. MATERIALS AND METHODS: Olfaction was investigated in 189 subjects. Healthy participants as well as patients suffering from olfactory disorders were tested. Initially subjects were tested by one of five methods using OM. Finally, the "Sniffin' Sticks" test (butanol odour threshold, odour identification) was performed. RESULTS: Correlation of the OM screening test and the "Sniffin' Sticks" ranged from 0.49 to 0.93 indicating that variations of the technique strongly influence the results of testing. The best technique for evaluating olfactory function included spontaneous naming of odours and odour identification from a list of four distractors. The sensitivity of this method was sufficient to determine anosmia. CONCLUSIONS: The odourized markers screening test can be used to screen for anosmia in the general population. However, the precise quantification of olfactory function is not possible, because of the relatively small amount of odours.     

Objective test of smell with cognitive potentials

BACKGROUND: An objective smelling test is indicated for a reliable assessment of olfactory disorders. Usually olfactory evoked potentials (OEP) are registered. But the technique of this measurement is complicated and the generation of the OEP depends on the respiration of the subject. Alternatively, the contingent negative variation (CNV) can be used in the diagnosis of anosmia and parosmia, requiring only a simple olfactory stimulator. SUBJECTS AND METHOD: OEP and CNV were derived from 25 adults with normal smelling and from 16 patients with anosmia after head injury. First, the "direct" CNV was registered when the subjects expected a tone following a smell stimulus after 1.5 s. Using two different odors in a random order, the tone only followed one of them, so the "selective" CNV was scored. RESULTS: In both tests a distinct CNV was found in 21 and 23 normal smelling subjects, respectively. OEPs were absent in 4.3 % of this control group. No patient with anosmia showed an OEP or a CNV. The amplitudes of the "selective" CNV are significantly higher than those of the "direct" CNV. No gender dependency was found. CONCLUSION: The results show that an objective olfactometry can be realized by registration of CNV. Contrary to the measurement of OEP which depend on the physical parameters of olfactory stimuli, CNV correlates well with the cognitive identification of odor.     

The influence of olfactory loss on dietary behaviors

OBJECTIVES: To assess dietary behavior and possible changes in food selection in patients with smell loss. PATIENTS AND METHODS: A total of 176 patients (114 women and 62 men) age 17 to 86 years were classified into three diagnostic groups (normosmia, n = 12; hyposmia, n = 75; functional anosmia, n = 89) according to their olfactory test scores obtained with "Sniffin' Sticks." Group differences in food intake and dietary behaviors were investigated with a specifically designed questionnaire providing a dietary alterations score (DAS). RESULTS: Numerous dietary changes were reported, e.g., 29% of all patients reported that they eat less since the onset of olfactory dysfunction, 39% use more spices with their food, 47% go out to eat at restaurants less frequently, 37% eat less sweets, and 48% drink less sweet beverages. Subjects with weight gain or weight loss scored higher on the DAS scale than subjects who did not report changes in weight. Similarly, DAS scale changes were more pronounced in subjects with a gradual onset of olfactory loss compared to subjects with a sudden loss of olfaction. Finally, a change of taste preferences toward savory and salty foods was observed across all patients enrolled in the present study. CONCLUSIONS: Patients with olfactory loss report alterations of dietary behaviors. Numerous factors appear to impact the results of olfactory loss in terms of changes in diet.     

Clinical significance of olfactory event-related potentials related to orthonasal and retronasal olfactory testing

OBJECTIVE: The purpose of this study was to evaluate the likelihood of recording olfactory event-related potentials (OERPs) in patients with an olfactory dysfunction and to correlate the electrophysiological responses to orthonasal and retronasal olfactory testing. DESIGN/MATERIALS AND METHODS: This was a prospective study of 65 patients with different origins of their olfactory loss. Orthonasal olfactory function was assessed with the "Sniffin' Sticks" test (orthonasal score; maximal score 48) and retronasal olfactory function with odorized powders presented intraorally (retronasal score; maximal score 20). The OERPs were obtained after presentation of 2-phenyl ethyl alcohol, the selected olfactory stimulus. Causes of olfactory dysfunction included postinfectious olfactory loss (n = 15), head trauma (n = 26), nasal polyposis (n = 15), and mixed causes (idiopathic, toxic, drug induced) (n = 9). RESULTS: Based on orthonasal testing, 32 and 33 patients were diagnosed with anosmia and hyposmia, respectively. Twenty-two patients from the hyposmic group demonstrated reliable OERPs. No OERPs were recorded in the anosmic group. Prevalence of OERPs in a cohort of patients with olfactory dysfunction was 33.8% (22 of 65). Median score (expressed as the percentage of the maximal score that could be obtained theoretically) in which OERPs were recorded was 50% (24 of 48) with orthonasal testing and 80% (16 of 20) with retronasal testing. CONCLUSIONS: Patients with olfactory dysfunction usually demonstrate OERPs in one third of the cases. When olfactory dysfunction is in the range that separates normosmic subjects from anosmic patients, patients may have identifiable OERPs. Interpretation of both orthonasal and retronasal psychophysical olfactory testing should be supported by the recording of OERPs in a clinical setting.     

Clinical significance of results from olfactory testing

BACKGROUND: Although widely used in healthy subjects and patients with olfactory loss, the significance of changes of scores from validated olfactory tests is unknown. AIM AND METHODS: The aim of the present study was to relate the self-assigned changes of olfactory function in terms of "better," "unchanged," and "worse" in patients with smell disorders with the results from olfactory testing by means of a validated test set. Olfactory function of 83 anosmic or hyposmic patients (40 women, 43 men; age 12-84 yr) was tested on two occasions (mean interval 136 days, minimum 7 days, maximum 6.7 yr). Olfactory function was assessed using a validated technique ("Sniffin' Sticks"). This test consists of three subtests, one for odor threshold (T), odor discrimination (D), and odor identification (I), with possible results ranging up to 16 points each. From the sum of the results from the three subtests a composite "TDI" score was obtained. RESULTS: Forty-four patients indicated an improvement of olfactory function, whereas 39 patients reported no change. No subject reported deterioration of olfactory sensitivity. Subjects assigned to group BETTER had higher TDI scores in the second olfactory tests than subjects assigned to the group UNCHANGED, both in absolute terms and as compared with the first olfactory test (effect "test occasion" by "self-assessed improvement," P < .001). There was no significant difference between groups with respect to age and sex (P = .99 and .84, respectively). Logistic regression showed that more than 60% of the subjects reported an improvement of olfactory sensitivity when the TDI score increased by 5.5 points. CONCLUSION: We show that there is a statistically significant relation between measured and perceived improvement of olfactory function in patients who first presented with the diagnosis of anosmia or hyposmia. The results indicate that improved olfactory function in patients with olfactory deficiency is perceived as such in everyday life and is quantitatively related to an improvement in the composite TDI score of the "Sniffin' Sticks" olfactory test battery. This is the basis for the application of a specific therapy for olfactory loss because of a possible gain in quality of life for the patients.     

Magnetic resonance imaging findings in the evaluation of traumatic anosmia

OBJECTIVES: Head trauma is a common cause of anosmia, but diagnosis is typically late, owing to more life-threatening sequelae of the injury. Herein, we describe our workup for a case of traumatic anosmia and the magnetic resonance imaging (MRI) findings both at the time of injury and at the 18-month follow-up. METHODS: We present a case report and a review of the literature. RESULTS: A 33-year-old woman presented to our institution with a chief complaint of loss of smell and taste following an occipital blow to her head that occurred when she was hit by a car while riding a bicycle. We present the findings of MRI performed at the time of the injury and at the 18-month follow-up. We describe the clinical progression of her disease, from symptoms of parosmic and phantosmic episodes accompanied by dysgeusia to total anosmia at the 18-month follow-up. CONCLUSIONS: We advocate the use of MRI, coupled with otolaryngology consultation and formal olfactory testing, in the diagnosis, management, and counseling of patients with anosmia sustained from head injury.     

Kallmann's syndrome and chemosensory evoked potentials

Summary Kallmann's syndrome is generally assessed by history and subjective tests of olfactory function. In this study three patients suffering from Kallmann's syndrome were investigated with more objective techniques, including the recording of chemosensory evoked potentials (CSEPs). After testing olfactory function by means of a simple odor identification test, anosmia was confirmed in only one patient, since the other two patients were able to distinguish between several odorants. However, investigations in which CSEPs were employed indicated that all three patients had complete loss of their olfaction as well as hypersensitivity of the trigeminal nerve. These findings prove the usefulness of CSEPs in clinical investigations of the sense of smell. Offprint requests to: T. Hummel     

Intranasal zinc and anosmia: the zinc-induced anosmia syndrome

OBJECTIVE: Commercial preparations of intranasal zinc gluconate gel are marketed as a remedy for the common cold. However, intranasal zinc has been reported as a cause of anosmia in humans and animals. Seventeen patients presenting with anosmia after the use of intranasal zinc gluconate are described. METHODS: The authors conducted a retrospective case series of patients presenting to a nasal dysfunction clinic and conducted complete history and physical examination on all patients, including nasal endoscopy. All patients underwent detailed odor threshold and identification testing. RESULTS: Threshold and identification testing revealed impaired olfaction in all patients. Inflammatory and traumatic causes of anosmia were excluded based on history, physical examination, and imaging. All patients diagnosed with zinc-induced anosmia or hyposmia reported sniffing deeply when applying the gel. This was followed by an immediate sensation of burning lasting minutes to hours. Loss of sense of smell was then perceived within 48 hours. Seven of 17 patients never developed symptoms of an upper respiratory infection. CONCLUSIONS: The zinc-induced anosmia syndrome, characterized by squirt, sniff, burn, and anosmia, occurs after the exposure of olfactory epithelium to zinc cation. It can be distinguished from postviral anosmia based on history.     

Anosmia after intranasal zinc gluconate use

BACKGROUND: Zinc is an essential mineral. Beneficial zinc absorption takes place via enteral, parenteral, or cutaneous routes. However, direct application to the olfactory epithelium has been reported to cause loss of smell. Recently, intranasal zinc gluconate has been recommended as a treatment for the common cold. Severe posttreatment hyposmia and anosmia have been observed. METHODS: The case report of a typical patient is presented and analyzed in detail, followed by a series of patients with severe hyposmia or anosmia after the use of intranasal zinc gluconate. RESULTS: Although interindividual variation in drug response and drug effect is apparent, the severe hyposmia or anosmia appears to be long lasting or permanent in some cases. The mechanism of olfactory loss is thought to be the direct action of the divalent zinc ion on the olfactory receptor cell. CONCLUSIONS: Zinc ions are toxic to olfactory epithelium. Reports of severe hyposmia with parosmia or anosmia have occurred after intranasal use of zinc gluconate.     

Severe chemotherapy-induced parosmia

BACKGROUND: Smell and taste disorders are among the side effects of chemo- and radiotherapy. Although direct radionecrosis of the salivary glands and the taste buds might explain the chemosensory problems after radiotherapy, the olfactory and gustatory complaints seen after chemotherapy remain unexplained. The patients reporting olfactory symptoms rarely complain about qualitative olfactory disorders such as parosmia or phantosmia. Quantitative olfactory loss such as anosmia and hyposmia seem to be more frequent. METHODS: We present the case of a 63-year-old woman with chemotherapy-induced parosmia leading to severe nutrition and appetite problems resulting in a life-threatening weight loss. RESULTS: With the aid of a simple nose clip the parosmia could be abolished and oral food intake became possible again. Parosmia resolved gradually over an observation period of 9 months, in parallel to an increase of olfactory sensitivity. The patient progressively gained appetite and weight. CONCLUSION: Parosmia can occur as a severe and potentially life-threatening complication of chemotherapy. This rare presentation of parosmia illustrates the importance of olfactory testing with an adequate recognition of the underlying problem and a consecutive treatment.