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PubMed1980

[On the central-nervous localization of the anosmia-ageusia-syndrome (author's transl)].

After head-injury about 50% of our own patients show combined lesion of the senses of smell and taste. The discussion of the localization of the responsible defect is not closed. The results of a chemosensory test battery indicate that the thalamic nucleus ventroposteromedialis belongs to the damaged area. This nucleus is in contact with the gustatory tract, with mechanoreceptive impulses out of the upper airways, and with olfactory sensations.

Ageusia↗
PubMed1995

[Diagnostic methods in the assessment of anosmia in neurologic diseases].

Several important neurological diseases can impair the sense of smell. In the past the substances generally used for testing were not well defined, and the testing procedures did not follow the rules of psychophysical test procedures. Therefore, in this paper standardized new methods of testing the olfactory system are presented. Based on published data, the University of Pennsylvania Smell Identification Test is the most suitable test for screening purposes. More detailed information can be obtained when using the Connecticut Chemosensory Clinical Research Center's Odor Identification Test that includes the possibility of determining the olfactory threshold. Additionally, a new method that combines the testing of olfactory threshold, odor discrimination and odor identification with the recording of specific olfactory-evoked potentials is described. The latter test is especially useful when objective neurophysiological data are requested.

Cerebral Cortex↗
PubMed2002

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.

Adolescent↗
PubMed1987

Loss of sense of smell in adult, hypothyroid mice.

Adult hypothyroid humans can lose their sense of smell. The present study was designed to investigate whether anosmia follows hypothyroidism in mice. If so, this would provide an animal model in which to study the mechanism for this effect. Adult mice were made hypothyroid with propylthiouracil (PTU) in their drinking water. Their sense of smell was tested before and after treatment by measuring the amount of time they spent sniffing food vs water odours, after a 24-h fast. Thyroid function was assessed histologically or by radioimmunoassay of blood serum for free thyroxine or free triiodothyronine. In Expt. 1 mice treated for 50 days with PTU were hypothyroid and anosmic. Control, euthyroid mice maintained their sense of smell, as did PTU-treated mice which also received daily thyroxine injections. PTU-induced anosmia was reversible: 50 days after removal of treatment previously anosmic mice were euthyroid and had regained their sense of smell (Expt. 3). It was possible that hypothyroidism induced non-specific effects which indirectly affected the olfactory function tests. However, short-term treatment with PTU caused severe hypothyroidism but no anosmia (Expt. 2). Additionally, non-specific effects of hypothyroidism were examined in open-field activity tests after short- and long-term hypothyroidism: euthyroid and hypothyroid animals were similarly active (Expts. 1 and 2). We conclude that chronic hypothyroidism produces anosmia in mice, as it does in humans. This anosmia is prevented by daily injections of thyroxine, and the sense of smell can recover to normal once thyroid function is restored.

Animals↗
PubMed2006

The clinical significance of electrophysiological measures of olfactory function.

AIM: To establish the detectability of olfactory event-related potentials (OERP) in relation to the results from psychophysical tests of olfactory function. METHODS: Fifty-nine men and 64 women (aged 19-89 years) participated all of whom presented themselves to a specialized "Smell and Taste Clinic" because of chemosensory complaints. Their olfactory function was assessed by means of psychophysical tests, e.g., assessment of odor threshold, odor discrimination, and odor identification, which were combined in a composite "Threshold Discrimination Identification" score ("TDI score"). OERP were obtained in response to the olfactory stimulant phenyl ethyl alcohol; their presence/absence was judged by a trained observer. Using logistic regression the TDI score was calculated in relation to the subjects' olfactory function at which the probability of the presence of OERP became greater than chance. RESULTS: Based on psychophysical tests, 40 subjects were diagnosed with functional anosmia, 40 with hyposmia, and 43 subjects scored within the normal range. Causes of hyposmia and anosmia included congenital anosmia, Parkinson's disease, head trauma, infections of the upper respiratory tract, and sinunasal disease. A TDI score of 22.6 equivalent to "pronounced hyposmia" was identified as the turning point at which the probability of detection of OERP was higher than 50%. Its 95% confidence interval of 16.1-27.8 well reflected the range of hyposmia, i.e., was above significant loss of olfactory function (functional anosmia, TDI score<15.5) and below normal olfactory function (TDI score>30.5). CONCLUSION: The present results indicate that the probability to detect an OERP becomes greater than 50% within a range of olfactory function that separates functional anosmia from normosmia. Presence of OERP clearly signifies presence of olfactory function while this is not always the other way around with absence of OERP.

Adult↗
PubMed1985

Antigonadal actions of olfactory and light deprivation. II. Effects of pinealectomy or melatonin injections in olfactory bulb deafferented or bulbectomized male rats.

Since olfactory bulb deafferentation (peripheral anosmia) potentiates the antigonadal effects of light deprivation, we studied a) the pineal involvement in this action and b) whether peripheral anosmia might increase the response to melatonin injections. Four-week-old male rats were used in two experimental series. The first included rats in which blindness + peripheral anosmia was associated with either pinealectomy or sham pinealectomy. In the second series, intact, olfactory bulb deafferented and bulbectomized rats received daily injections of either melatonin (50 micrograms) or the vehicle alone. In both experiments animals were killed at 10 weeks of age. The reduction in the weight of accessory sexual glands and prostates, as well as in the serum testosterone levels, induced by blindness + peripheral anosmia was fully prevented by pinealectomy, whereas body and pituitary weight reduction induced by the dual sensory deprivation were only partially prevented. Melatonin produced no effects in intact animals whereas in rats with either peripheral anosmia or bulbectomy it reduced the weight of body, accessory sexual glands, and prostates. Serum testosterone levels were not modified in any case with melatonin treatment.

Animals↗
PubMed1984

Hansen's disease and olfaction.

The sense of smell was assessed in a group of 50 leprosy patients. It was found that 40% of the patients showed a mild to complete impairment of the smell sense (anosmia) which was related to the systemic clinical state and to the severity of nasal lesions. Possible reasons for anosmia in leprosy patients are discussed. It has been observed that anosmia may be the presenting feature of leprosy. Most leprosy patients are not aware of olfactory disturbances, and anosmia may be missed unless specifically looked for. It is emphasized that leprosy should be considered an important cause of anosmia, at least in endemic areas, and in an anosmic patient leprosy should be always excluded.

Adult↗
PubMed2001

Idiopathic gonadotrophin deficiency: genetic questions addressed through phenotypic characterization.

OBJECTIVE: The association of idiopathic hypogonadotrophic hypogonadism (IHH) with congenital olfactory deficit defines Kallmann's syndrome (KS). Although a small proportion of IHH patients have been found to harbour defined genetic lesions, the genetic basis of most IHH cases remains to be elucidated. Genes currently recognized to be involved comprise KAL (associated with X-linked-KS), the GnRH receptor (associated with resistance to GnRH therapy), DAX 1 (associated with adrenohypoplasia congenita) and three loci also associated with obesity, leptin (OB), leptin receptor (DB) and prohormone convertase (PC1). Because of the rarity of the condition and the observation that patients are almost universally infertile without assistance, familial transmission of IHH is encountered infrequently and pedigrees tend to be small. This has constrained the ability of conventional linkage studies to identify other candidate loci for genetic IHH. We hypothesized that a systematic clinical evaluation of a large patient sample might provide new insights into the genetics of this rare disorder. Specifically, we wished to examine the following propositions. First, whether normosmic (nIHH) and anosmic (KS) forms of IHH were likely to be genetically discrete entities, on the basis of quantitative olfactory testing, analysis of autosomal pedigrees and the prevalence of developmental defects such as cryptorchidism and cleft palate. Second, whether mirror movements and/or unilateral renal agenesis were specific phenotypic markers for X-linked-KS. DESIGN AND PATIENTS: We conducted a clinical study of 170 male and 45 female IHH patients attending the endocrinology departments of three London University teaching hospitals. Approximately 80% of data were obtained from case records and 20% collected prospectively. Parameters assessed included olfaction, testicular volume, family history of hypogonadism, anosmia or pubertal delay, and history or presence of testicular maldescent, neurological, renal or craniofacial anomalies. Where possible, the clinical information was correlated with published data on genetic analysis of the KAL locus. RESULTS: Olfactory acuity was bimodally distributed with no evidence for a spectrum of olfactory deficit. Testicular volume, a marker of integrated gonadotrophin secretion, did not differ significantly between anosmic and normosmic patients, at 2.0 ml and 2.2 ml, respectively. Nevertheless, the prevalence of cryptorchidism was nearly three times greater in anosmic (70.3%, of which 75.0% bilateral) than in normosmic (23.2%, of which 43.8% bilateral) patients. Individuals with nIHH, eugonadal isolated anosmia and/or KS were observed to coexist within 6/13 autosomal IHH pedigrees. On three occasions, fertility treatment given to an IHH patient had resulted in the condition being transmitted to the resulting offspring. Mirror movements and unilateral renal agenesis were observed in 24/98 and 9/87 IHH patients, respectively, all of whom were identifiable as X-KS males on the basis of pedigree analysis and/or defective KAL coding sequence. Abnormalities of eye movement and unilateral sensorineural deafness were observed in 10/21 and 6/111 KS patients, respectively, but not in nIHH patients. DISCUSSION: Patients with IHH are almost invariably either anosmic (KS) or normosmic (nIHH), rather than exhibiting intermediate degrees of olfactory deficit. Moreover, the prevalence of cryptorchidism is nearly three times greater in KS than in nIHH despite comparable testicular volumes, suggesting a primary defect of testicular descent in KS independent of gonadotrophin deficiency. Disorders of eye movement and hearing appear only to occur in association with KS. Taken together, these findings indicate a clear phenotypic separation between KS and nIHH. However, pedigree studies suggest that autosomal KS is an heterogeneous condition, with incomplete phenotypic penetrance within pedigrees, and that some cases of autosomal KS, nIHH and even isolated anosmia are likely to have a common genetic basis. The prevalences of anosmia, mirror movements and unilateral renal agenesis among X-KS men are estimated to be 100, 85 and 31%, respectively. In sporadic IHH, mirror movements and unilateral renal agenesis are 100% specific phenotypic markers of de novo X-KS. By comparison, only 7/10 X-KS families harboured KAL coding defects. Clinical ascertainment, using mirror movements, renal agenesis and ichthyosis as X-KS-specific phenotypic markers, suggested that de novo X-KS was unlikely to comprise more than 11% of sporadic cases. The majority of sporadic KS cases are therefore presumed to have an autosomal basis and, hence, the preponderance of affected KS males over females remains unexplained, though reduced penetrance in women would be a possibility.

Adolescent↗
PubMed1999

Proposed classification scheme for quantitative olfactory function alterations.

Given the need for a clinical classification for daily patient examinations to refer to each type of quantitative alteration in the sense of smell, we have created a topographic classification of such alterations, establishing groups to distinguish among patients with decreased or total loss of olfaction. Because the classification is based on the diagnosis of the different causes of anosmia, it implicitly includes etiologic and topographic considerations. We have established 3 main groups on the basis of the site of the causal lesion: conduction, sensorineural, and mixed anosmias. In addition, within the sensorineural anosmias, we distinguish between the epithelial, retroepithelial, and central anosmias.

Adolescent↗