(BQ) Part 2 book “Smell and taste disorders” has contents: Non-neurodegenerative disorders of olfaction, non-neurodegenerative disorders of gustation, neurodegenerative chemosensory disorders, assessment, treatment, and medicolegal aspects of chemosensory disorders.
Chapter Non-neurodegenerative Disorders of Olfaction Chemosensory disorders are common in the general population Olfactory impairment, which is more prevalent than taste dysfunction, affects 1–2% of people below the age of 65 years and more than 50% in those above this age (Doty et al., 1984; Hoffman et al., 1998; Murphy et al., 2002) Of 750 consecutive patients presenting to the University of Pennsylvania Smell and Taste Center with chemosensory complaints, 68% reported decreased quality of life, 46% changes in appetite or body weight, and 56% adverse influences on daily living or psychological well-being (Deems et al., 1991) In another study of 445 such patients, at least one significant hazardous event (e.g., food poisoning or failure to detect fire or leaking natural gas) was reported by 45.2% of those with anosmia (total loss of smell ability), 34.1% of those with severe hyposmia (lowered smell function), 32.8% of those with moderate hyposmia, 24.2% of those with mild hyposmia, and 19.0% of those with normal olfactory function It is particularly noteworthy that a number of longitudinal studies have found mortality risk to be much higher in older non-demented persons with smell identification deficits than in those with a normal sense of smell (Wilson et al., 2010; Gopinath et al., 2012; Pinto et al., 2014; Devanand et al., 2015) In the most definitive of these studies, the increased risk of death progressively increased as olfactory dysfunction increased over a four-year period (Devanand et al., 2015) Participants with the lowest UPSIT scores had a 45% mortality rate over this time, as compared to an 18% mortality rate in those with the highest UPSIT scores A recurrent confusion in the minds of patients and many of their medical advisors is the fact that individuals with smell impairment complain regularly of loss of taste This can lead to unnecessary evaluations such as extensive gastrointestinal investigations, and reflects a lack of understanding of the important role olfaction plays in producing food flavor When we ingest food, there is taste appreciation from taste buds over the tongue and pharynx but, simultaneously, odorants released from food escape into the retropharyngeal space and enter the nasal cavity where they stimulate the olfactory receptor cells (Burdach & Doty, 1987) Thus, any food entering the mouth will evoke a sensation of both taste and smell, unless it is an odorless tastant that evokes only sweet, sour, salt, bitter, or umami taste perceptions Sensations such as chocolate, meat sauce, strawberry, cola, lime, walnut, and lemon are mediated principally by smell, not taste Only on rare occasions will a patient suffer impairment of both smell and taste Gustatory problems, per se, can be ascertained in many cases by asking patients if they can still detect the sweetness of sugar, the sourness of grapefruit, or the saltiness of potato chips, although these questions are surprisingly insensitive when compared to objective testing (Soter et al., 2008) This chapter deals with smell problems of relevance to the clinician and describes, from the chemosensory perspective, the major non-neurodegenerative diseases influenced by such 182 15:42:05 06 Non-neurodegenerative Disorders of Olfaction 183 disorders, including head injury, tumor, infection and inflammation, endocrine disease, epilepsy, and multiple sclerosis Non-neurodegenerative taste disorders are similarly reviewed in Chapter 6, and neurodegenerative diseases, such as Alzheimer’s, Parkinson’s disease, and related syndromes, are discussed in Chapter Classification of Types of Olfactory Disorders Olfactory disorders can be classified according to their behavioral or psychological manifestations The most common terms used in such classification are defined and described as follows: Anosmia Anosmia has two meanings; some use it literally to describe total loss of smell, others just to describe some impairment which may be complete or partial or related to just one odor Similar confusion is mirrored by other neurological words, such as aphasia and dysphasia, alexia and dyslexia, etc Specific anosmia refers to the inability to detect one or a few related odorants while still being able to detect other odors in a normal fashion Patients with specific anosmias generally not recognize their problem and not present clinically with concerns, unlike patients with general anosmia Most specific anosmics actually can smell the substance to which they are anosmic if it is presented at high enough concentrations; in such cases the term specific hyposmia is preferred Agnosia Olfactory agnosia occurs when a cognitively normal individual loses the ability to recognize an odor, yet maintains the ability to perceive and distinguish it from other odors in a normal fashion Extremely few cases of olfactory agnosia have been identified, which is surprising in view of the well-recognized forms of agnosia in the visual and auditory spheres In one case report, agnosia was described in a 53-year-old male patient with predominantly right inferior temporal lobe atrophy (presumably degenerative) in association with prosopagnosia, i.e., agnosia for familiar faces This results usually from disorder of the fusiform gyrus which is also located on the undersurface of the temporal lobe (Mendez & Ghajarnia, 2001) Also described in another case report is a patient with ipsilateral olfactory agnosia (with normal olfactory thresholds) associated with complex partial seizures localized to the right medial temporal lobe (Lehrner et al., 1997) The prediction that patients with semantic dementia (SD) would have difficulty in naming smells in the presence of normal discrimination was confirmed in a study of eight patients with SD, as described in more detail in Chapter (Luzzi et al., 2007) Hyposmia Hyposmia refers to decreased sensitivity to odors Like anosmia, such decrements can exist on one or both sides of the nose Since hyposmia is classically associated with a raised threshold, the term microsmia has been introduced to denote decreased function as measured by odor identification tests, although odor identification and threshold tests are, in general, highly correlated (Doty, 1995) Unilateral microsmia is regularly overlooked in clinical practice – a point of considerable relevance, for example, in diagnosis of an olfactory groove meningioma (which is often one-sided) Temporary hyposmia can occur as a result of accelerated or prolonged adaptation, as in cases of chronic exposure to some workplace chemicals like acrylates or hydrogen sulfide (Schwartz et al., 1989) 15:42:05 06 184 Smell and Taste Disorders Hyperosmia This is defined as enhanced sensitivity to one or more odors Although hyperosmia is usually assumed to reflect atypically low olfactory thresholds, many who report this condition show no such alterations In some cases, hyperosmia is associated with hyper-reactivity rather than a true change in sensitivity Hyper-reactivity can reflect a liberal response criterion, i.e., greater willingness to report the presence of an odor or simply an emotional response to a smell in the absence of any change in sensitivity to that odor Although rarely reported in humans, the concept of hyperosmia now has a more scientific footing as a result of gene knockout experiments Mice with gene-targeted deletion of the Kv 1.3 channel had a 1,000- to 10,000fold lower threshold for detection of odors, and increased ability to discriminate between odorants in comparison with their normal littermates, earning the title of “supersmeller” mice (Fadool et al., 2004) According to Menashe et al (2007), hypersensitivity to the odor isovaleric acid (sweaty socks smell) may relate to polymorphisms in the human olfactory receptor gene, OR11H7P Dysosmia This refers to any form of distorted smell perception, sometimes termed parosmia and, when it has a fetid character, cacosmia Dysosmias can be either stimulated or unstimulated, i.e., appear in the presence or the absence of an identifiable odor The latter type of dysosmia is often termed phantosmia or olfactory hallucination Phantosmias can be experienced by both healthy and sick people Thus, medical students who spend long periods in the dissecting room may continue to experience the smell of formalin or phenol several hours after they have left the area and may have temporary decrements in olfactory function (Hisamitsu et al., 2011) Traditional teaching holds that most hallucinations, including the olfactory variety, indicate organic disease within the uncinate region that make up the aura of a complex partial epileptic attack In fact, most dysosmias reflect degeneration or attempts at regeneration in the olfactory neuroepithelium Moreover, lesions of the orbitofrontal cortex, an olfactory association area, may also produce olfactory illusions, hallucinations, autonomic signs, or gestural automatisms as part of a seizure complex (Chabolla, 2002) Phantosmias that decrease in frequency or intensity over time probably indicate changes within the olfactory epithelium, whereas those that progressively increase in frequency or intensity likely reflect central nervous system (CNS) anomalies similar to the kindling phenomenon induced in animals In the latter context, anticonvulsant medication (e.g., phenytoin, gabapentin, pregabalin) may minimize progressive neural damage associated with some centrally mediated dysosmic sensations, although good evidence for this is presently lacking Conditions Affecting Olfactory Function As indicated in Table 5.1 and Figure 5.1, numerous relatively common diseases may compromise the sense of smell, sometimes permanently These range from the simple cold to extremely debilitating neurodegenerative diseases Such disturbances may reflect peripheral influences, such as blockage of airflow to the receptors or damage to the olfactory epithelium, whereas others involve central mechanisms, e.g., tumors that compromise the olfactory bulbs or higher-order structures Systemic factors, such as metabolic changes that generally influence olfactory functioning, can also be involved 15:42:05 06 Non-neurodegenerative Disorders of Olfaction 185 Table 5.1 List of main categories of disease associated with smell disturbance with typical examples Neurodegenerative causes are given separately in Chapter Disease Examples Local nasal Polyps; allergic rhinitis; sinus disease Infection Common cold; influenza; herpes encephalitis; leprosy; AIDS Prion disease Fungi, e.g., aspergillosis, mucormycosis; Paget’s disease Head injury Usually severe posterior or lateral impact; superficial siderosis Epilepsy Olfactory aura Complex partial seizure Migraine Before, during, or after an attack Immunologic diseases Multiple sclerosis; Narcolepsy; Sjögren’s syndrome; Myasthenia gravis; Wegener’s granulomatosis, Churg-Strauss syndrome Tumors and inflammatory disease Nasopharyngeal carcinoma; olfactory groove meningioma or neuroblastoma; Paraneoplastic, e.g., small cell lung carcinoma Endocrine and metabolic Diabetes; Cushing & Klinefelter’s syndromes; Kallman’s syndrome; septo-optic dysplasia; Addison’s disease; hypoparathyroidism; pseudohypoparathyroidism Wilson’s disease; liver and kidney disease Rare genetic disorders Refsum’s syndrome; Bardet-Biedel syndrome; Aniridia type 2; Kartagener syndrome; DiGeorge syndrome; Wolfram syndrome Psychiatric Depression; Korsakoff syndrome; malingering; hysteria; olfactory reference syndrome Miscellaneous Radiotherapy; pregnancy; medication; toxins; idiopathic intracranial hypertension Neurodegenerative See Chapter Unfortunately, a given disturbance cannot always be connected with a peripheral, central, or systemic cause Although total loss of smell is classically associated with peripheral causes, it can result from damage anywhere in the olfactory pathway Thus, in addition to damage to the olfactory epithelium (as in toxic exposures, chronic rhinosinusitis, or upper respiratory infections), a disturbance can reflect injury to axons of the receptor cells or sectors of the olfactory bulb (as in head trauma-related shearing of the olfactory filaments), or disorders of the olfactory cortex (as in multiple sclerosis) Similarly, dysosmia can be attributed to peripheral, central, systemic, or a combination of these causes Usually dysosmia is accompanied by lessening of olfaction, regardless of its locus As mentioned earlier, threshold disorders that are characteristically attributed to peripheral sectors of the olfactory pathway may, in fact, signify central dysfunction; conversely, problems with smell identification not automatically indicate a more centrally mediated etiology With these caveats, and purely as a general rule, complete lack of smell early in the course of disease is more likely to be caused by a peripheral than central lesion due, in part, to the direct exposure of the olfactory epithelium to the environment and to the considerable redundancy in central olfactory areas Impairment of smell that is continuous is more likely to be neurogenic in origin, whereas fluctuating microsmia with intermittent recovery often points to inflammatory pathology/ obstruction within the nose or sinuses 15:42:05 06 186 Smell and Taste Disorders Complaints Test Results 2.8% 8.7%