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[Olfactory disorders and general pathology. Analysis and review of the literature].

INTRODUCTION: Disturbances of the sense of smell have been documented in many general pathologies. The actual etiology of such impairments is often difficult to determine. The aim of the authors is to review the literature on olfactory disorders in general diseases. CURRENT KNOWLEDGE AND KEY POINTS: Acute and chronic liver disorders are frequently associated with hyposmia, which can be improved by vitamin A intake. Renal insufficiency could induce hyposmia according to the severity of the renal disease. Olfactory disorders seem to regress after transplantation but not after dialysis. Patients with AIDS--especially neurological forms--often present with taste and smell impairments. Smell alteration can also be noted in hypothyroidism and pseudohypoparathyroidism. In addition, taste and smell impairments have been described in patients with adrenal insufficiency or Cushing's disease. Subsequent to glucocorticoid therapy, adrenal insufficiency can induce regressive olfactory hypersensitivity. Olfactory impairments in diabetic patients can be associated with diabetic macrovascular manifestations due to ischemic alterations in the olfactory neuroepithelium. Impairment of the sense of smell has been described in many systemic diseases such as Horton's arteritis and Sjögren's syndrome. FUTURE PROSPECTS AND PROJECTS: Olfactory disorders should be investigated in patients presenting one of the above-mentioned diseases.

Acquired Immunodeficiency Syndrome↗

Chemosensory function and dysfunction.

Taste and smell are fundamental sensory systems essential in nutrition and food selection, for the hedonic and sensory experience of food, for efficient metabolism, and, in general, for the maintenance of a good quality of life. The gustatory and olfactory systems demonstrate a diversity of transduction mechanisms, and during the last decade, considerable progress has been made toward our understanding of the basic mechanisms of taste and smell. Understanding normal chemosensory function helps clarify the molecular events that underlie taste and smell disorders. At least 2,000,000 Americans suffer from chemosensory disorders--a number that is likely to grow as the aging segment of the population increases. Smell disorders are more frequent than taste disturbances, due to the vulnerability and anatomical distinctiveness of the olfactory system, and because a decline in olfactory function is part of the normal aging process. Common gustatory and olfactory complaints are due to a number of medications, to upper respiratory infections, to nasal and paranasal sinus diseases, and to damage to peripheral nerves supplying taste and smell. Most chemosensory complaints have an identifiable cause. Although diagnosis of taste and smell disorders has improved considerably over the last two decades, treatment of these disorders is still limited to conditions with discernible and reversible causes. Future research is needed for a better understanding of chemosensory mechanisms, establishing improved diagnostic procedures, and disseminating knowledge on chemosensory disorders among practitioners and the general public.

Aging↗

[Olfactory dysfunction. Epidemiology, pathophsiological classification, diagnosis and therapy].

The present manuscript is the result of a collaborative effort within the framework of the Working Group of Olfactology and Gustology of the German Society for ENT, Head and Neck Surgery. It provides a comprehensive overview about the current views on the epidemiology, terminology, diagnostics, and therapy of olfactory dysfunction, and aims to offer a framework for the standardized procedures for the diagnosis and therapy of olfactory disorders.

Algorithms↗

[Remarks on the systematization and terminology of smell and taste disorders].

Based on the experience of the Olfactogustometry Laboratories in Halle and in Poznan, a proposal of clinical terminology and systematization of smell and taste disorders has been presented. Individual interpretation of the data from anamnesis in relation to the findings of the olfactogustometric investigations were stressed as indispensable.

Humans↗

Olfactory event-related potentials in normal subjects and patients with smell disorders.

We developed a device to record olfactory event-related potentials (OERP) from the human scalp. Methyl-cyclopentenolone was used as the odorant element. A total of 50 stimuli were delivered. Each stimulus lasted 0.5 sec and was delivered once every three inspirations. Normal OERPs were obtained with this device. The positive peak latencies were approximately 350 msec (P1) and 700 msec (P2), respectively. OERPs were also recorded in 40 patients with smell disorders. A positive response at about 300-400 msec was recorded in 7 patients (all females, 15-59 years old). The other 33 patients showed no response. The high potential area of this positive peak was located in the centro-occipital region of the scalp. The latency and the high potential area of this peak were similar to P1 recorded in normal subjects. The source of this peak was considered identical to that of P1. This may be a response to the trigeminal nerve during odor administration. P2 was not recorded in the patients with smell disorders. P2 may therefore be a response to the olfactory nerve.

Adolescent↗

Impaired sense of smell in patients with nasal surgery.

The aim of the study was to determine the incidence of olfactory disorders before and following nasal and paranasal sinus surgery. It was a prospective observational study. Over a 6-month period, all patients who had been listed for nasal and paranasal sinus surgery underwent preoperative and postoperative evaluation of their sense of smell. A questionnaire and the 'Smell Diskettes Test' were used to assess olfaction. One hundred and eighty-four patients were studied. Preoperatively, 19 patients (10.3%) had an impaired sense of smell (8.1% before septoplasty, 6.1% before rhinoplasty and 17.1% before endoscopic sinus surgery). Only 16 (84%) of these patients were aware of their impaired sense of smell. Following surgery, four patients (2.5%) who were normal preoperatively developed impaired olfaction on questioning, and this was supported by testing it. In the subgroup that had a septoplasty, no patient developed hyposmia compared to one patient (2.6%) after rhinoplasty and one patient (3%) after endoscopic sinus surgery. No patient developed anosmia. Preoperatively, 10.3% of patients had an altered sense of smell, making it desirable that this is documented in order to avoid postoperative claims that this was caused by surgery. It also helps to audit the results of surgery.

Female↗

[Semiology and etiology of anosmia: apropos of 306 patients].

Chemosensory dysfunction is relatively common. This article describes a series of 306 patients who presented with anosmia. We divided olfactory disorders into those associated with interruption of the transport of stimulus and those associated with damage to either peripheral or central nervous system structures. Nasal and paranasal sinus disease (transport interruption) was found to be causative in 67% of patients presenting with anosmia. These patients are generally 45 years old, the loss of olfaction is progressive and associated with additional nasal symptoms. Upper respiratory infection was found to be causative in 18% of patients. They are generally older, with a mean age of 58 years and are predominantly female (78%). The loss of smell is sudden and anosmia is often accompanied by troublesome parosmias (50%). CT-scan is necessary for the evaluation of a smell dysfunction.

Adult↗

[Disorders of olfactory function in penetrating head injuries sustained during war].

Olfactory function was estimated in the group of 37 patients with the penetrating war head injury. In 4 (10.8%) patients mutual anosmia was found. In comparison to healthy volunteers the injured showed worse performance on the level of the tested olfactory parameters. In 9 (24.3%) patients the offered smells were sensed as very unpleasant. The subgroup of patients from Glasgow Coma Scale (GSC) < or = 8 showed the highest degree of olfactive disfunction. The patients with complicated penetrating head injury were less successful at the level of all olfactive qualities comparing to those without injury complications. The localization of the focal penetrating wound, regardless of the kind of a weapon causing the brain injury, was not significantly correlated with the results of olfactometry in distinction from hemisphere lateralization of the lesion. The recovery of the retested was minimal.

Adult↗

Brain gamma-aminobutyric acid levels are decreased in patients with phantageusia and phantosmia demonstrated by magnetic resonance spectroscopy.

BACKGROUND: Olfactory and gustatory hallucinations (phantosmias and phantageusias, respectively) are sensory distortions that commonly follow losses of olfactory and gustatory acuity (hyposmia and hypogeusia, respectively). The biochemical basis of these hallucinations is unclear. Functional magnetic resonance imaging has been used previously to demonstrate widespread and robust central nervous system (CNS) activation to memories of these sensory distortions in patients with these symptoms. In this study, possible CNS mechanisms responsible for these distortions were evaluated using magnetic resonance spectroscopy, because this technique has been used to measure various CNS metabolites in patients with neurologic disorders. METHODS: Forty-seven subjects were studied: 28 normal volunteers (13 men and 15 women) and 19 patients (8 men and 11 women) with persistent oral global phantageusia and/or birhinal phantosmia studied before any treatment. Four patients (1 man and 3 women) were studied before and after pharmacologic treatment that reduced the severity of their sensory distortions. All subjects were studied in a Signa 1.5-T magnetic resonance scanner with a quadrature head coil using a modified standard 2-dimensional J-point resolved excitation in the steady state (PRESS) sequence by which gamma-aminobutyric acid (GABA), glutamic acid, choline, N-acetylaspartate, and creatine (Cre) were measured in various CNS regions. Results were expressed using Cre as a denominator to determine ratios for each measurement. Differences were defined between normal subjects and patients before treatment and in patients before and after successful pharmacologic treatment. RESULTS: Before treatment, GABA levels in several CNS regions were lower in patients than in normal volunteers and were the only biochemical changes found; significantly lowered GABA levels were found in the cingulate, right and left insula, and left amygdala. No differences between patients and normal volunteers were found in any of the metabolites in the posterior occipital region. After treatment that inhibited sensory distortions, CNS GABA levels increased in the cingulate, insula, and amygdala but significantly only in the left insula and in the right and left amygdala. After this successful treatment, no change in any biochemical parameter was found in the posterior occipital region. CONCLUSIONS: These results indicate that decreased brain GABA levels can serve as biochemical markers of phantageusia and/or phantosmia in patients with these distortions and are the first biochemical changes in the CNS that reflect these sensory changes. After successful treatment of these distortions, CNS GABA levels increased to levels at or near normal, consistent with functional remission of these symptoms. These results substantiate a role for CNS GABA in the generation and inhibition of these sensory hallucinations. Although the underlying biochemical mechanism(s) for the generation of these decreased GABA levels are complex, because similar types of sensory hallucinations occur as auras or prodromata of epileptic seizure and migraine activity, these results suggest that there may be common biochemical changes among these disorders.

Adult↗

Allergic rhinitis, olfactory disorders and secretory IgA.

The authors point out the possible relationship between the biochemical and immunological components of nasal mucus in subjects affected by allergic rhinitis and/or olfactory disorders. Fifty seven subjects (33 F, 24 M) aged between 19 and 73 years, (median age 65 SD 14.60) were studied. Twenty seven of them were normosmic affected by allergic rhinitis and taken as control group, (14 were positive to allergometric tests and/or RAST, while the other 13 were negative), 30 were dysosmic, and subdivided into parosmic (n = 6), anosmic (n = 15) and hyposmic (n = 9) (only one was negative both to allergometric tests and to RAST). In all patients we assessed: nasal mucus (it was analysed for: mucus quantity, pH, protein concentration, K+ concentration and the SIgA antibodies, tested both by radian immunodiffusion and by ELISA), allergometric tests, PRIST, RAST, anterior rhinomanometry, evoked olfactory potential. As regard to allergometric tests, we have no observed statistically significant differences between the control and the dysosmic group, although all the dysosmic patients (except one) were positive both to allergometric tests and to RAST. Total (PRIST) and specific (RAST) IgE values (except for the anosmic subjects who had IgE values moderately higher) were similar to the results obtained by allergometric tests. As regards to nasal secretion quantity, it was reduced (p: n.s.), like the pH (p: n.s.), in the parosmic subjects. On the other hand, proteins concentration of nasal secretion was lowered in hyposmic (p: n.s.) and anosmic (p = 0.05) subjects, while there were no differences between parosmic subjects and control group. The values of SIgA in controls and hyposmic subjects were not too different and similar to those observed by other authors; however they were slightly increased in controls affected by allergic rhinitis with positivity both to RAST and/or allergometric tests (p: n.s.), while they were reduced in the parosmic and significantly in the anosmic patients (p < 0.01). On the basis of that data, the authors conclude that, (though related to a limited case reports) being the secretory IgA values inversely proportional to the gravity of olfactory pathology, a their protective role (if the anatomic-functional substratum is efficient), in the pathologies examined, can be easily hypothesized. Besides, that data highlight that their concentration is slightly decreased in those patients affected by allergic rhinitis, without olfactory disorders (p: n.s.).

Adolescent↗

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.

"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."

Adolescent↗

[Olfactory disorders in Alzheimer's disease and in Parkinson's disease. Review of the literature].

Olfactory disorders in Alzheimer's disease and Parkinson's disease have been the topic of a large body of work over the last decades. Work devoted to olfactory disorders in Alzheimer's disease includes over 300 papers providing clinical and fundamental data. Anatomy studies in Alzheimer's disease have demonstrated a specific concentration of lesions in peripheral and central olfactory structures (senile plaques, neurofibrillary degeneration) as well as lesions in layers II and III of the entorhinal cortex. These neuropathological findings led to the development of the hypothesis that olfactory disorders in Alzheimer's disease would result from a toxic process. Observed olfactory deficits involve both identification and recognition of odors and detection thresholds. Nevertheless, patients with Alzheimer's disease rarely consult for sensorial deficits as the other signs of the disease predominate. Neuropathology data on the olfactory system are much more sparse in Parkinson's disease. Lewy bodies suggestive of Parkinson's disease have been observed in the olfactory bulb and pathways, but, unlike Alzheimer's disease, the olfactory disorders appear to be stable, changing little over time, as opposed to the evolution of neurological symptoms and cognition impairment. Clinicians should be aware that olfactory disorders are an integral part of Alzheimer's disease and Parkinson's disease. Screening for sensorial impairment however is a secondary objective in the context of these neurodegenerative diseases.

Alzheimer Disease↗

Definitive localization of X-linked Kallman syndrome (hypogonadotropic hypogonadism and anosmia) to Xp22.3: close linkage to the hypervariable repeat sequence CRI-S232.

Kallmann syndrome is a genetically heterogeneous disease characterized by hypogonadotropic hypogonadism and anosmia. Six families in which the disorder followed an X-linked inheritance were investigated by linkage analysis. Diagnostic criteria were uniformly applied and included tests for hypogonadotropic hypogonadism and anosmia. Close linkage was found by using the hypervariable repeated sequence CRI-S232 (DXS278) previously mapped to Xp22.3. At a maximum lod score of 6.5, the recombination fraction was calculated as .03. Of 30 fully informative meioses, one recombination between the disease locus and the loci recognized by probe CRI-S232 was observed. When an independent approach is used, these results confirm the X-linked Kallmann syndrome assignment previously made by deletion mapping, and allow definitive localization of the syndrome assignment previously made by deletion mapping, and allow definitive localization of the syndrome to the Xp22.3 region. This opens the way to carrier detection and to the identification of a gene responsible for this disorder.

Chromosome Mapping↗

[A pragmatic assessment of sense of smell].

A new clinical odour test was developed and validated in a clinical trial including 50 healthy volunteers as well as 35 patients suffering from smell disorders. The aromas were incorporated in an inert gas under disclosure from oxygen, avoiding impairment caused by oxidative transformation. Conventional smell test by Elsberg bottles was used as standard. The spray test proved to be equally effective in discriminating subjects suffering from smell disorders as the standard procedure. Moreover the spray test is feasible and long term constance of the substances is guaranteed.

Aerosols↗

A re-evaluation of the classification of olfactory epithelia in patients with olfactory disorders.

We have previously demonstrated that human olfactory epithelia can be classified into five grades according to the degree of degeneration present in patients with various kinds of olfactory disorders. In practice, however, the occurrence of additional types of cell changes in other kinds of olfactory disorders and findings with immunohistochemical techniques have led us to re-evaluate our previous classification. In the present study, changes in olfactory epithelia from ten patients with various kinds of olfactory disorders are discussed and a revised classification is proposed. Microvillar and differentiating cells were also evaluated in the epithelium studied.

Adult↗

[Gustatory disorders during multiple sclerosis relapse].

Gustatory dysfunction is a known but uncommon element in the course of multiple sclerosis. Gustatory dysfunction has been described during the chronic progressive phase and during the relapse phase. We report five patients with clinically definite multiple sclerosis who developed transient gustatory disorders during the relapse phase of their disease. Agueusia occurred as one of the first symptoms in three patients, revealing the disease. Symptoms generally improved with remission or corticosteroid administration. These disorders are due to demyelinating lesions of the gustatory pathways in the thalamus or brainstem. MRI studies were not performed during the relapse phase and no clinical neuroimaging correlations could be established. Agueusia may be accompanied by olfactory dysfunction which is due to plaque demyelinization of the olfactory pathways, particularly in the temporal and inferior frontal lobes. Taste anomalies can also be observed in other diseases, including systemic diseases such as sarcoidosis or Sjogrën's syndrome. Drug-induced gustatory disorders are also reported.

Adult↗

Olfactory identification ability in anorexia nervosa.

OBJECTIVE: The hypothesis tested was that patients with severe eating disorders would demonstrate olfactory identification deficits as a result of zinc deficiency or malnutrition. METHOD: The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 27 hospitalized female patients with anorexia nervosa and 50 normal control female subjects. For a subgroup of patients, serum zinc levels and body mass indices were obtained at pre- and post-nutritional repletion phases. RESULTS: UPSIT scores for patients with eating disorders were equivalent to normal control subjects in spite of the fact that the patients were nutritionally compromised as determined by body mass index. Serum zinc levels were not significantly different at pre- and post-nutritional repletion. CONCLUSIONS: In contrast to patients with schizophrenia, patients with severe eating disorders have intact olfactory function. This finding suggests that transient metabolic or nutritional disturbances alone cannot account for previously reported olfactory deficits.

Adolescent↗

[Toxic anosmia and rhinitis due to occupational solvent exposure].

A patient's case report documents the development of anosmia and rhinitis caused by occupational exposure to organic solvents, including tetrahydrofuran, cyclohexanone, acetone and other ketones. Physicians should inquire about possible mucosal irritation or prenarcotic symptoms during exposure. If an occupational disease is assumed, notification must be sent to the Institution for Statutory Accident Insurance and Prevention (Berufsgenossenschaft). Some diseases, for example olfactory disorders due to chemical mixtures, are not included in the German list of occupational diseases. In this case, a special law (Sozialgesetzbuch VII) regulates compensation.

Adult↗