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PubMed1999

[Screening of olfaction with smell diskettes].

BACKGROUND: Aim of the study was the development of a new screening test of olfaction with reusable diskettes as odorant applicators. METHODS: A screening test of olfaction was designed using 8 diskettes containing different odorants. The diskettes can be opened to release the odor and are closed after testing. The test was designed as a triple forced multiple choice test using a questionnaire, resulting in a score from 0 to 8 correct answers. Ninety-one volunteers with a normal sense of smell and 13 patients with subjective hyposmia or anosmia were tested to validate the developed test. The same volunteers were also tested with the sniffin' sticks test, another screening test of olfaction that is already validated. After testing, the volunteers were asked to compare the two tests. RESULTS: Among the 91 volunteers with normal sense of smell, 10 achieved a score of 7, and 81 a score of 8 in the smell disk test. The 13 patients with hyposmia or anosmia achieved a score between 0 and 5. Based on the test design, there is a probability of 99.74% that a person who achieves a score of 7 or 8 will have normal olfaction. In the sniffin' sticks test, 85 volunteers with normal sense of smell achieved a score in the normal range for this test (6-8) whereas 6 volunteers were below with a score of 4 or 5. The 13 patients with hyposmia or anosmia scored between 0 and 6. The smell disk test was preferred by 86 persons, the sniffin' sticks test by 5, and 12 assessed both tests as equal. CONCLUSIONS: The developed screening test is reliable for identifying patients with a normal sense of smell, and it can distinguish them from patients with hyposmia and anosmia. The diskettes proved to be reliable and comfortable applicators for odorants in clinical practice.

Adolescent↗
PubMed1985

Heterogeneity of Kallmann's syndrome.

Kallmann's syndrome is a rare condition defined as a combination of hypogonadotropic hypogonadism and anosmia. The present study shows two genealogical tables. In the first family six male members in four generations had Kallmann's syndrome. All carrier females seemed to have normal fertility and normal olfactory function. X-linked recessive or - less probable - dominant sex linked inheritance was considered to be most probable. Renal malformation was discovered in one and was excluded in two affected members. In the second family only one affected female was discovered. She had a monozygotic twin sister with normal pubertal development, but also total anosmia. Four individuals with anosmia alone were found in this family, but no further cases of hypogonadism. The possibility of an acquired hypothalamic insufficiency on the basis of hereditary anosmia is discussed.

Adolescent↗
PubMed1994

Chemical senses.

In the last decade, studies using approaches from molecular biology have substantially advanced our understanding of the early events in olfaction and taste. The many odorants that we can recognize may well interact with many distinct receptor proteins. Of the four taste qualities that we recognize, studies on salty and sour suggest that these tastes involve ion channels in the membrane of receptor cells while sweets and bitters bind to receptor proteins. Some volatiles (pheromones) play special roles in reproductive behavior via the vomeronasal organ (VNO) and the accessory olfactory system. Initial belief that humans lack a VNO has been questioned recently, thus raising the fascinating possibility of human pheromones. The roles that taste and smell play in the world of the newborn are very different. Acceptance of sweet and rejection of bitter appear to be hard-wired while the affect associated with odors depends much more on experience. Genetic variation may produce total losses (Kallman's syndrome produces anosmia and familial dysautonomia produces ageusia) or losses specific to certain stimuli. The best known of the specific anosmias is that for androstenone, which has no smell to some, a urinous smell to others, and a smell like sandalwood to still others. Analogous to the specific anosmias, some individuals are unable to taste PROP while others, supertasters, perceive PROP to be exceedingly bitter. Clinical studies reveal pathologies responsible for total or partial losses. The olfactory system, dependent on one cranial nerve, is more vulnerable than taste, and total anosmia is a relatively common clinical problem. Three cranial nerves carry taste and two of those nerves inhibit one another such that damage to one disinhibits the other and preserves over-all taste function. Total ageusia is very rare. Throughout these studies we see that taste and olfaction have different properties and often different functions (e.g. odor and reproduction). Yet taste and smell can also be integrated to determine what does or does not enter the body. In Adrian's words, "we are dealing with the sense organs which signal the quality of the air we breathe and that of the food and drink we propose to swallow."

Ageusia↗
PubMed2004

[GnRH deficiency: new insights from genetics].

The acquisition of a sexually dimorphic phenotype is a critical event in mammalian development. Hypogonadotropic hypogonadism (HH) results from impaired secretion of GnRH. The patients display with delayed puberty, micropenis and cryptorchidism in the male reflecting gonadotropin insufficiency, and amenorrhea in the female. Kallmann's syndrome (KS) is defined by the association of HH and anosmia or hyposmia (absent smelling sense). Segregation analysis in familial cases has demonstrated diverse inheritance patterns, suggesting the existence of several genes regulating GnRH secretion. The X-linked form of the disease was associated with a genetic defect in the KALI gene located on the Xp22.3 region. KAL1 gene encodes an extracellular matrix glycoprotein anosmin-1, which facilitates neuronal growth and migration. Abnormalities in the migratory processes of the GnRH neurons with the olfactory neurons explain the association of HH with anosmia. Recently, mutations in the FGF recepteur 1 (FGFR1) gene were found in KS with autosomal dominant mode of inheritance. The role of FGFR1 in the function of reproduction requires further investigation. Besides HH with anosmia, there are isolated HH (IHH). No human GnRH mutations have been reported although hypogonadal mice due to a GnRH gene deletion exist. In patients with idiopathic HH and without anosmia an increasing number of GnRH receptor (GnRHR) mutations have been described which represent about 50% of familial cases. The clinical features are highly variable and there is a good relationship between genotype and phenotype. A complete loss of function is associated with the most severe phenotype with resistance to pulsatile GnRH treatment, absence of puberty and cryptorchidism in the male. In contrast, milder loss of function mutations causes incomplete failure of pubertal development. The preponderant role of GnRH in the secretion of LH by the gonadotrophs explains the difference of the phenotype between male and female with partial GnRH resistance. Affected females can have spontaneous telarche and normal breast development while affected males exhibit no pubertal development but normal testis volume, a feature described as "fertile-eunuch". High-dose pulsatile GnRH has been used to induce ovulation. Another gene, called GPR54, responsible for idiopathic HH has been recently described by segregation analysis in two different consanguineous families. The GPR54 gene is an orphan receptor, and its putative ligand is the product of the KISS-1 gene, called metastine. Their roles in the function of reproduction are still unknown.

Amino Acid Sequence↗
PubMed1995

[Posturographic registration of body sway after odor stimulation].

The methods of "reflex olfactometry" are rarely able to detect simulated anosmia because of the lack of reproducible correlations between stimulus and intensity of reaction. Interactions between the olfactory and vestibulospinal systems have not yet been investigated. Thirty persons with normosmia and 21 patients with anosmia were studied using a posturographic platform. Only in subjects with normosmia were body sway increases statistically significant in an anterior-posterior direction after the application of an olfactory nerve stimulant. Stimulations of the trigeminal nerve cause both in subjects with normosmia, and anosmia an increase in body sway occurred in a sagittal and lateral direction. The recording of vestibulospinal reactions during platform posturography after application of an olfactory stimulations enables quantification of body sway. These responses can also be useful in differentiating real from stimulated anosmia.

Acetates↗
PubMed1997

Olfactory dysfunction in patients with head trauma.

BACKGROUND: The ability to smell is commonly altered by head trauma (HT). However, the nature, prevalence, prognosis, and etiology of such alterations are poorly understood. OBJECTIVES: To quantitatively determine the degree of olfactory function in patients with HT-related chemosensory complaints and to examine the influences of age, sex, HT severity, time since HT, and other variables on such function. Also, to use quantitative magnetic resonance imaging (MRI) to establish whether and to what degree damage to the olfactory bulbs and tracts, frontal lobes, and temporal lobes occurs. PATIENTS AND METHODS: Two hundred sixty-eight patients with HT from the University of Pennsylvania Smell and Taste Center, Philadelphia, were administered a quantitative odor identification test, a depression inventory, and a medical history questionnaire; 66 were retested after individual test-retest periods ranging from 1 month to 13 years. The volume of olfactory-related brain structures was determined in 15 patients and 15 controls using MRI. RESULTS: One hundred seventy-nine patients (66.8%) had anosmia, 55 (20.5%) had microsmia, and 34 (12.7%) had normosmia. Frontal impacts produced less dysfunction than back or side impacts. Of the 66 retested patients, 24 (36%) improved slightly, 30 (45%) had no change, and 12 (18%) worsened; only 3 patients, none of whom initially had anosmia, regained normal olfactory function. Trauma severity was related to olfactory test scores in patients with microsmia. Parosmia prevalence decreased from 41.1% to 15.4% over an 8-year posttrauma period. Olfactory bulb and tract volumes of male, but not female, patients with HT were greatly reduced relative to volumes of controls. CONCLUSIONS: Patients complaining of HT-related olfactory dysfunction typically have anosmia and rarely regain normal olfactory ability, parosmia prevalence decreases over time in such patients, and damage to olfaction-related brain structures can be observed in most such patients using an appropriate MRI protocol.

Adult↗
PubMed2004

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.

Accidents, Home↗
PubMed1987

Estimating frequency of Kallmann syndrome among hypogonadic and among anosmic patients.

The frequency of Kallmann syndrome (hypogonadotropic hypogonadism and anosmia, HHA) was estimated in patients presenting with hypogonadism and patients with anosmia. Of 791 hypogonadal males 19 had HHA. The frequency of HHA was about 1:25 (n = 8/189) in outpatients questioned about their sense of smell, about 1:50 (n = 11/579) in patients whose blood samples were sent to us for chromosome analysis, and about 1:30 (n = 19/605) in males with hypogonadism and 46,XY chromosomes. The relation of patients with HHA to those with Klinefelter syndrome was 1:10 (n = 19/186). From 24 patients presenting with anosmia we found 1 hitherto undiagnosed case of HHA. The mean age at diagnosis was 24.8 and 24.9 years in our cases and cases from literature, respectively. These data provide evidence that Kallmann syndrome is not infrequent and that most patients remain undiagnosed until the third decade of life. Earlier diagnosis is emphasized by questioning each hypogonadal patient about his sense of smell because therapeutic success seems to be age dependent.

Adolescent↗
PubMed2003

Olfaction in neurodegenerative disorder.

There has been an increase of interest in olfactory dysfunction since it was realised that anosmia was a common feature of idiopathic Parkinson's disease (PD) and Alzheimer-type dementia (AD). It is an intriguing possibility that the first sign of a disorder hitherto regarded as one of movement or cognition may be that of disturbed smell sense. In this review of PD, parkinsonian syndromes, essential tremor, AD, motor neurone disease (MND) and Huntington's chorea (HC) the following observations are made: 1). olfactory dysfunction is frequent and often severe in PD and AD; 2). normal smell identification in PD is rare and should prompt review of diagnosis unless the patient is female with tremor-dominant disease; 3). anosmia in suspected progressive supranuclear palsy and corticobasal degeneration is atypical and should likewise provoke diagnostic review; 4). hyposmia is an early feature of PD and AD and may precede motor and cognitive signs respectively; 5). subjects with anosmia and one ApoE-4 allele have an approximate 5-fold increased risk of later AD; 6). impaired smell sense is seen in some patients at 50% risk of parkinsonism; 7). smell testing in HC and MND where abnormality may be found, is not likely to be of clinical value; and 8). biopsy of olfactory nasal neurons shows non-specific changes in PD and AD and at present will not aid diagnosis.

Apolipoprotein E4↗
PubMed1985

Axillary 5 alpha-androst-16-en-3-one in men and women: relationships with olfactory acuity to odorous 16-androstenes.

Axillary 5 alpha-androst-16-en-3-one (5 alpha-androstenone) levels were found to be significantly higher in men than in women but do not vary between left and right axillae, are not related to age, handedness or degree of hirsutism (in women) nor to anosmia to this steroid. In men (but not in women), levels are related linearly to axillary cholesterol concentrations but not to squalene. Olfactory thresholds for 5 alpha-androstenone varied widely, the lowest recorded being 0.2 ppb, but there was no difference in thresholds between men and women. Women (70%) found the smell 'repellant' but anosmia did not differ greatly between men and women (9-20%). Anosmia to the smell of 5 alpha-androst-16-en-3 alpha-ol was most marked in women (90%) rather than in men (45%). Axillary 5 alpha-androstenone values were generally consistent with the 'musky' or 'strong' smells of male axillary extracts, compared with the 'sweet' smell of those from female subjects.

Adolescent↗
PubMed1986

Effect of bilateral transection of the lateral olfactory tract on the male-induced implantation failure (the Bruce effect) in mice.

Bilateral transection of the lateral olfactory tract (LOT) at the rostral level induced anosmia in female mice; by contrast, sectioning of the LOT at more caudal levels failed to induce anosmia in females. Transection of the LOT at all the levels inhibited the alien male-induced implantation failure in newly inseminated mice (the Bruce effect). Sham-operated as well as intact females exhibited a high rate of implantation failure following alien male exposure. The results suggest that the inhibition of the Bruce effect in LOT-transected females is not due to anosmia induced by the operation procedure, but due to interruption of the primary olfactory bulb projections to the posterior parts of the olfactory cortex. Our results rule out the involvement of the nervus terminalis in the Bruce effect. The present report lends support to the involvement of the accessory olfactory system in the transmission of the pheromonal stimulus involved in the male-induced implantation failure.

Animals↗
PubMed1995

Olfactory bulbectomy temporarily impairs Morris maze performance: an ACTH(4-9) analog accellerates return of function.

Rats with a bilateral lesion of the olfactory bulb are permanently anosmic. However, this lesion also produces nonspecific behavioral effects that recover over time. In this study olfactory bulb-lesioned animals are given a spatial orientation task--the Morris maze--which supposedly relies on visual and not olfactory cues. In exp. 1 this assumption was verified by subjecting animals with peripherally induced anosmia to the Morris maze (olfactory neurons in the nasal mucosae were destroyed by flushing the nose with ZnSO4). Anosmia did not affect the acquisition rate of the animals. In exp. 2 anosmia was produced by a central lesion to the bulbus olfactorius. Two weeks after lesioning the Morris maze performance is severely impaired. Interestingly, chronic administration (10 micrograms/48 h/rat, during these 14 days, SC) of the ACTH(4-9) analog ORG 2766 diminished the impairment in performance. In exp. 3 olfactory bulb-lesioned animals were allowed 6 wk to recover before Morris maze testing began, to investigate if spontaneous recovery of performance occurred. No difference was seen in the acquisition performance of lesioned animals when compared to sham animals at this timepoint. The effect of the peptide is discussed in the context of an acceleration of the recovery of nonspecific consequences of brain lesioning.

Adrenocorticotropic Hormone↗
PubMed2004

Anesthesia affects olfaction and chemosensory event-related potentials.

OBJECTIVE: Olfactory and trigeminal systems interact and contribute to the perception of odorants. This study was aimed at investigating the effect of local anesthesia on olfaction. METHODS: One percent of tetracaine on a cotton swab was applied intranasally at three different locations in 20 volunteers and 4% of lidocaine was applied to the olfactory cleft in a head-down position. Before and after anesthesia, self-assessment, psychometric testing and olfactory event-related potentials [OERPs, using H(2)S and phenyl ethyl alcohol (PEA)], and chemosomatosensory event-related potentials (CSSERPs, using CO(2)) were examined. RESULTS: Anesthesia at all four locations significantly lowered the perceived self-assessment of olfaction, while using the cotton swab only anesthesia in the middle meatus elevated threshold (P = 0.020), lowered discrimination (P = 0.015), and prolonged OERP (PEA, P = 0.008; H(2)S, P = 0.016), as well as CSSERPs latencies (CO(2), P = 0.020). However, complete temporary anosmia was only achieved after applying 4% lidocaine into the olfactory cleft. CONCLUSIONS: Intranasal anesthesia applied with a swab reduced self-assessment of olfaction but was unable to produce anosmia. Psychometric test results were concordant with changes in chemosensory event-related potentials. SIGNIFICANCE: Temporary anosmia is technically difficult to achieve but could be demonstrated for the first time using local anesthesia. Even though anesthesia influences self-assessment, measurable olfactory function can remain unchanged.

Administration, Intranasal↗
PubMed2001

[Normal sense of smell in Kallmann syndrome. A case report].

BACKGROUND: Kallmann's syndrome (KS) was first mentioned in 1944 as an association of anosmia and hypogonadotropic hypogonadism. Causes are multiple genetic defects the most common of which is the x-linked KS appearing mostly in men. However, autosomal dominant and autosomal recessive forms have also been described. PATIENT: We present a case of KS with normosmia (male, 39 years of age). All symptoms of hypogonadotropic hypogonadism were present. RESULTS: Psychophysical olfactory testing revealed left-sided anosmia with right-sided normosmia which was confirmed by electrophysiological measures of olfactory function. Magnetic resonance imaging indicated aplasia of the left olfactory tract and bulb, whereas the right-sided structures appeared to be normal. CONCLUSIONS: As indicated in this case with lateralized anosmia and contralateral normosmia, overall olfactory function strongly depends on the "best" nostril. Therefore, in many clinical situations, lateralized olfactory testing appears to be extremely important.

Adult↗
PubMed2002

[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.

Adult↗
PubMed1999

[Special characteristics of expert assessment of olfactory and taste disorders].

BACKGROUND: The number of medical expert opinions dealing with smell and taste disorders has continuously increased in recent years. However, an overview of the specific problems and results of those expert opinions has not been published until now. INDIVIDUALS AND METHODS: Olfaction was assessed by multiple subjective tests in 145 individuals with chemosensory dysfunction caused by trauma or occupational and environmental exposures. Additionally, a gustatory test, nasal endoscopy, anterior rhinomanometry, and radiography of the paranasal sinuses were performed. Malignering was diagnosed on a trial of multiple symptoms. Retronasal olfaction was tested using the Güttich gustatory olfaction test. RESULTS: Most of the medical expert opinions have been ordered by professional associations (42%) and insurance companies (28%). Compensation for olfactory dysfunction was claimed after trauma (64%), occupational exposure (23%) rhinosurgical procedures (8%), and laryngectomy (5%). Anosmia or hyposmia was claimed by 66% and 24% of all individuals, respectively. According to the results of the chemosensory tests, 41% of patients suffered from anosmia and 40% had hyposmia. Malignering was registered in 14%. CONCLUSIONS: The study shows that the "characteristic case" is a male in the late fourties, complaining of anosmia initially noticed after an occipital or frontobasal head trauma. The assessment of olfactory deficits related to toxic or chemical occupational exposure is difficult when a latency between the occupational exposure and the onset of chemosensory dysfunction is present. Moreover, interactions between the occupational exposure and nicotine or alcohol abuse must be taken into consideration. Claims for medical liability arose in 3% of the study group after septoplasty and sinus surgery.

Adolescent↗
PubMed2002

Linking olfaction with nausea and vomiting of pregnancy, recurrent abortion, hyperemesis gravidarum, and migraine headache.

OBJECTIVE: The experience of women was sought about nausea and vomiting, its relation to olfaction, its occurrence among pregnant women with anosmia, and the potential association of hyperemesis gravidarum and migraine headache. METHODS: We performed a community-based study with a physician/patient-directed questionnaire, and a retrospective analysis of hospital records. RESULTS: Nearly all women (n = 163 parous women) experience nausea (98%) and vomiting (97%). The highest frequency causes of nausea and vomiting were "food poisoning" (65%), "flu" (58%), pregnancy (54%), and offensive odors (52%); vomiting occurred as frequently as nausea for the first 2 causes, and one half as often for the latter causes. Most women reported that the pain experienced during vomiting exceeded that of parturition. Among 9 women with hypogonadotropic anosmia with advanced reproductive technology-induced pregnancies, 2 experienced nausea and vomiting, one from "food poisoning." Among 37 women with migraine headache, 10 (27%) had experienced hyperemesis gravidarum, and among 16 who experienced hyperemesis gravidarum, 5 (37%) had migraine headaches. CONCLUSIONS: The frequency of nausea and vomiting, caused most often by nonpregnancy-related triggers, is high among women. In a small sample of women with congenital anosmia, nausea and vomiting of pregnancy occurred in only 1 pregnancy, suggesting that olfaction is a highly selected trigger for nausea and vomiting of pregnancy. The shared nausea and vomiting experience of hyperemesis gravidarum and migraine headache among women suggests a common mechanism, possibly based on allelic variations within the DRD2 (dopaminergic receptor) gene. Because olfactory receptors, odor types, and MHC antigens are closely integrated, and because olfactory stimuli often incite episodes of pregnancy, nausea, and vomiting, hyperemesis gravidarum, and migraine headache, these genes and their products invite further scrutiny. The pregnancy-conserving effect of PNV and the MHC antigen overlap in couples with recurrent abortion are important clues possibly relating olfaction, MHC antigens, and reproductive success or failure.

Abortion, Habitual↗
PubMed1996

Case report: olfactory function in a fertile eunuch with Kallmann syndrome.

The olfactory and gonadal dysfunction in Kallmann syndrome share a common embryologic pathophysiology. To characterize further the linkage between the hypogonadotropic hypogonadism and anosmia, the authors performed a detailed evaluation of olfactory function in a patient with Kallman Syndrome having the rare variant of partial gonadotropin deficiency (fertile eunuch). The subject was seen initially at age 16 years because of delayed puberty. He received testosterone replacement therapy and subsequently completed pubertal development. As an adult, while untreated, he had subnormal levels of serum testosterone, low gonadotropins, and normal response to luteinizing hormone- releasing hormone. He also had impotence that was reversible with testosterone therapy, and a normal sperm count. Despite the mild degree of hypogonadism, olfactory function was completely absent, and the response to nasal trigeminal stimulants was markedly attenuated. Complete anosmia may therefore be associated with gonadotropin deficiency that is only partial; the presence of anosmia does not predict the need for gonadotropin therapy to attain fertility.

Adolescent↗