Since olfactory disorders or even total olfactory loss are far less of a handicap than blindness or deafness for the person concerned, there have not been many attempts to estimate the percentage of people with olfactory problems. Initial surveys were done with questionnaires and rapid smell tests. They revealed that approximately 1-3% of the population has an olfactory problem [117, 118]. Since most of the decrease in olfactory function, like any other sensory function, is due to aging , this high incidence was not so astonishing in an aging society with an increasing mean age. In these first attempts to evaluate the epidemiology of olfactory problems, olfactory function was tested rather rudimentarily. Consecutive studies yielded much higher percentages of the population concerned by olfactory dysfunctions . Importantly, olfactory disorders seem to affect more younger people than previously thought and most anosmic or hypos-mic subjects either do not realize that they have an olfactory disorder or are simply not sufficiently handicapped to consult a physician [121, 122]. Current consensus is that approximately 5 percent of the general population suffer from anosmia, unrelated to chronic nasal problems. Although the highest incidence is found in the age group above 65 years, anosmia is astonishingly frequent in subjects between 45 and 65 years of age. Results are similar for the distribution of hyposmia, with a mean percentage of approximately 20% of the general population exhibiting mild or moderate smell dysfunction [120-122]. Recent studies underlined the potential alteration of quality of life consecutive to olfactory impairment [123-125]. Although not all patients with olfactory impairment seek medical help due to decreased quality of life, some may experience hazardous events in daily life like eating spoiled food or undetected smoke or gas leaks .
Several reports have been published on the frequency of the diverse origins of olfactory dysfunction. A recent survey conducted in Austria, Switzerland and Germany  revealed that approximately 50% of patients with olfactory dysfunction seen in ENT clinics are due to sinunasal problems. Further frequent causes of olfactory dysfunction are related to traumatic and post-URTI events.
Olfactory Loss Following Infections of the Upper Respiratory
As mentioned above, epidemiological questions surrounding olfactory disorders within the general population have only recently been addressed. Previous contributions to the epidemiology of olfactory loss included retrospective analyses of specialized ''Smell and Taste Centers'' on their respective data bases [128-130]. With some minor differences, these reports show similar findings about the main causes of olfactory disorders. Apart from posttraumatic and sinunasal origin, post-URTI olfactory loss is among the major causes of olfactory dysfunction.
The patient's history typically starts with a cold, during which he loses his sense of smell. Not particularly bothered during the cold, the patient becomes suspicious about the smell loss when, one or two months after all sinunasal symptoms have abated, normal olfactory function does not return. This is usually the moment when the patient seeks medical advice, either from their general practitioner or from an ENT specialist. Unfortunately, very few studies focused on the epidemiology and prognostic outcome of post-URTI olfactory disorders [131-134]. Currently, no good data indicate which agent in such upper tract respiratory infections (URTI) leads to olfactory lesions. It is not even clear whether toxicity originates from a virus or bacteria, or from the immune response directed against olfactory neuroepithelium. Some authors claim that viral rather than bacterial infections are responsible for olfactory disturbances, and observe a higher incidence of dysosmias after spring and summer URTI . Furthermore, women above 45 years of age seem to be affected at a higher percentage than men [132, 135, 136] - which brings up the potential olfactory protective effect of estrogens . Nevertheless, the effect of estrogen on olfactory function remains an open debate [122, 138].
Clinically, it is important to know, and to inform patients with post-URTI olfactory anosmia or hyposmia, about the possibility of parosmia. Parosmia (also termed troposmia), the unpleasant distortion of odorous sensations, tends to occur two to three month after the URTI, although it appears sometimes to occur directly after the URTI. The real frequency of parosmia is probably higher than previously believed, in particular because patients do not always mention it to their physician [139, 140]. According to our clinical experience, up to 25% of subjects with URTI olfactory dysfunction experience parosmia or phantosmia.
Posttraumatic olfactory disorders represent approximately 20% of the patients seen in ''Smell and Taste Clinics'' . Most posttraumatic olfactory dysfunctions are said to occur after occipital trauma, although no clear data on olfactory dysfunctions after lateral impacts exist. The current explanation is that ''coup-contre-coup'' lesions or tearing of the filae olfac-toriae leads to anosmia or hyposmia. Although the entity of posttraumatic olfactory loss had already been described by the end of the last century it has, like most olfactory disorders received little systematic attention . This might also be due to the modest olfactory complaints of severely poly-traumatized patients during their hospitalization. Olfactory loss seems to correlate with the severity of the trauma [142-145], although several authors pointed out the fact that there is considerable individual variability in terms of the vulnerability of olfactory structures [145, 146]. Thus, even minor trauma can lead to anosmia whereas severe brain injuries may not alter olfaction. Probably, the injured parts of the olfactory system are most often the filae olfactoriae which cross the cribriform plate. However, central structures such as the orbitofrontal cortex and gyrus rectus have also been found to be affected after head trauma . Similar to post-URTI olfactory impairment, these patients are prone to develop parosmia and phantosmia several months after the trauma. Clinical experience shows that most patients with posttraumatic olfactory disturbance typically become aware of the alteration after some delay. It is usually several weeks after the injury, when the major health problems have resolved and patients are discharged from the hospital, that they begin to complain of taste or smell loss. This is probably due to increased attention to olfaction once the general health status improves.
The third large group of patients who seek counseling for olfactory problems are patients suffering from concomitant sinunasal problems. Approximately 20% of all patients in smell and taste consultations have lost or impaired olfactory function due to a nasal problem . Nasal polyposis has been known for a long time to decrease olfactory abilities due to the mechanical obstruction of nasal cavity restricting the airflow to the olfactory cleft [77, 129, 147-151]. During the last two decades, as a result of better olfactory tests, mild olfactory impairments could also be identified in other groups of patients with sinunasal diseases such as allergic and uncomplicated chronic rhinosinusitis [77, 152, 153]. In contrast to posttrau-matic and post-URTI olfactory dysfunctions, these patients rarely exhibit parosmia or phantosmia.
Olfactory loss is common in patients with idiopathic Parkinson's disease (IPD) [154-156]. While a decreased sniff volume seems to contribute to the diminution of olfactory function , electrophysiological recordings in response to passive olfactory stimulation clearly established the presence of olfactory impairment in IPD [158, 159]. This olfactory deficit is so reliable that it can be used as a marker of IPD . In other words; if a patient with normal olfactory function presents with IPD symptoms the diagnosis should be re-investigated [160, 161]. It can also be assumed that olfactory loss precedes the onset of motor symptoms by 4-6 years [162, 163] so that IPD may be the reason for ''idiopathic olfactory loss'' in some patients. Ol factory loss is also observed regularly in Alzheimer's disease, but at a much lower frequency and is less pronounced in multiple system atrophy, Huntington's disease, and motor neuron disease . Little or no olfactory deficit is seen in cortico-basal degeneration, progressive supranuclear palsy, or essential tremor [161, 164].
According to the retrospective epidemiological studies of Taste and Smell Clinics, the diagnosis of idiopathic - unknown - origin of smell impairment accounts for almost 20% of the cases, with the sampling bias discussed above. This seems simply to reflect the poor understanding of factors interfering with olfaction. With further insight and research this percentage should logically decrease. A considerable number of these idiopathic causes might be due to sinunasal disease, post URTI dysosmias following an almost undetected URTI, or neurodegenerative diseases .
Less Frequent Causes
Diabetes is probably one of the best investigated endocrine diseases concerning olfactory disorders [121, 166-168]. Most studies reveal slight olfactory deficiencies in diabetic patients especially at threshold levels indicating a peripheral patho-mechanism compatible with a possible diabetic micro-angiopathy or peripheral polyneuropathy. However, olfactory impairment in diabetes is relatively mild. Two recent studies conducted with identification tests in large study samples did not find that diabetic patients exhibit a decreased ability to identify odors compared to healthy controls [121, 122]. Several other endocrine diseases such as hypothyroidism [169, 170], adre-nocortical insufficiency (Addison's disease)  or pseudohypoparathyr-oidism , have been reported to cause olfactory disorders. Many endocrine diseases have been reported to cause hyposmia but rarely lead to anosmia.
Epileptic patients have been repeatedly tested with all possible olfactory testing modalities, and the general findings were that epileptic patients perform similar to controls with regard to odor thresholds [173, 174]. In contrast, more centrally believed tasks such as odor identification, discrimination or memory tests revealed that epileptic patients have olfactory impairments predominating on the side of the epileptic focus [74, 174-176].
Furthermore, olfactory evoked potentials have been shown to be altered in epileptic patients . This latter study showed increased latencies in olfactory ERP ipsilateral to the epileptic lesion. These latencies were even longer when the lesion was right-sided. Taken together the data indicate that decreased olfactory function in epileptic patients is primarily due to centrally altered olfactory structures whereby the temporal lobe is the main lesion site. Studies on olfactory function in patients with frontal epileptic lesions, however, are lacking.
Long lists of general pathologies causing olfactory disorders can be found in most reviews and textbooks of smell and taste disorders [172, 178]. Nevertheless, only few studies on specific pathologies have been conducted, sometimes on small sample sizes using unreliable olfactory tests, and sometimes with contradictory outcomes. Besides the above mentioned endocrine diseases, metabolic disorders such as kidney  and liver [122, 179, 180] affections have been associated with decreased olfactory function. Olfactory disturbances in those patients are especially interesting, since they are discussed as a potential cause of malnutrition with a more general impact on the patients' health .
Anosmia may occur after general anesthesia during the course of surgical interventions not necessarily associated with nasal surgery [122, 182]. Further research should clarify whether surgery under general anesthesia presents a risk of anosmia. For surgical interventions in the sinu-nasal region, anosmia as complication has been estimated to occur in 1% of the cases  although this risk has probably been overestimated as indicated by the results of two large studies [184, 185].
Numerous toxins have been implicated as causes of olfactory disorders . Nevertheless, this information has been mainly accumulated on the basis of case reports. Knowledge about drugs inducing smell and taste disorders is also mainly based on case reports, but several major groups of drugs have been identified as likely to cause problems. Among these, cardiovascular drugs , anti-hypertensive drugs [188, 189], and antibiotics [172, 190] are the most frequently mentioned. Usually, the chemosensory side effects disappear when the medication is discontinued.
Currently we distinguish between congenital anosmia occurring as an isolated defect or occurring within the context of a syndrome . Isolated congenital anosmia seems to occur more often than previously believed. Apart from the typical patient history of no odor memories, only MR imaging leads to a more definitive diagnosis [192, 193]. In the frontal imaging planes just tangential to the eye bulbs, hypoplastic or aplastic olfactory bulbs can be visualized. This plane also allows an evaluation of the olfactory sulcus which is flattened if the olfactory bulb is absent or aplastic. This is a useful indicator of congenital anosmia, especially since the bulb is not always easy to identify. Among cases of congenital anosmia as part of a syndrome, the Kallmann-Syndrom  is the disorder in which it is most frequently encountered. This is an anosmia associated with hypogonado-tropic hypogonadism clinically characterized by infertility and anosmia, where infertility can be reversed by substitution of gonadotropins .
Congenital anosmia is typically discovered during early puberty. It is a matter of speculation whether olfaction starts to be more important in this period compared to younger years.
Although this distinction is a matter of debate, the discrimination between qualitative and quantitative olfactory disorder have proven helpful in clinical practice. This distinction is mainly based on the patient's history and psychophysical test results.
Normosmia/Hyposmia/Anosmia: Normosmia is the subjectively perceived normal olfactory function, usually defined as the ability to detect the great majority of tested odors in a given olfactory test. Hyposmia means the decrease of this olfactory function and anosmia the total loss of any olfactory function. Beside total anosmia, specific anosmias have been described, where only certain odors are not perceived and most odors are smelt normally . The term functional anosmia was chosen since many subjects with severe olfactory loss appear to be able to still perceive a few single odors. Nevertheless, those rare and weak olfactory impressions are too poor to be of any help to these patients in daily life.
The term ''qualitative olfactory disorder'' reflects the qualitatively changed perception of odorous sensation. They are frequently, but not necessarily, associated with quantitative olfactory disorders.
Parosmia describes the distorted perception of smells in presence of an odor source. In other words, parosmias are triggered by odors. This is a symptom occurring particularly often in post-URTI or posttraumatic olfactory disorders. Mostly odors are distorted into unpleasant odors (although some exceptions seem to exist: TH, personal communication). For example, to parosmic patients, coffee smells like burnt plastic. The exact explanation of the molecular modifications leading to parosmia is as yet unknown. Even the site of parosmia generation (olfactory epithelium, olfactory bulb, or other central-nervous olfactory structures) is not clear. Important clinically, is the observation that most parosmic impressions tend to diminish over months and finally disappear after years.
Phantosmia describes the distorted perception of smells in the absence of an odor source. Most often, phantosmias occur after trauma or URTI and consist of unpleasant odors occurring without being elicited through environmental odor sources. Phantosmias are rarely triggered but menstruation- and stress-related phantosmias have been reported . Similar to parosmia, there is no exact explanation as yet of the molecular modifications leading to phantosmia; also, the site of its generation remains unclear. Phantosmias also have a tendency to disappear over the course of years.
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