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  • Updated 06.22.2023
  • Released 10.13.2022
  • Expires For CME 06.22.2026

Disorders of olfaction

Introduction

Overview

Patients and clinicians frequently overlook disorders of olfaction, but they can worsen quality of life, distort taste, lessen appetite, augment depressive disorders and sometimes paranoia, and can also pose a safety risk. When patients report alterations in the quality of olfaction in response to an odorant (ie, parosmias), the perceptions are almost universally unpleasant, a condition referred to as aliosmia (the perception of unpleasant odors from nominally pleasant odorants). Disorders of olfaction are particularly common with synucleinopathies, aging, and COVID-19. This article reviews the range of olfactory symptoms, categorizes disorders of olfaction, prognosis, and complications of these disorders, and reviews disease pathogenesis, diagnosis, and management.

Key points

• Patients with olfactory symptoms generally report diminution or absence of olfactory sensation (hyposmia or anosmia, respectively) and forms of distorted olfaction (parosmia).

• Except in unusual circumstances, hyperosmia is a subjective sensation of hyperacuteness of olfaction.

• There is no evidence that pregnant women or migraineurs experience an objective increase in olfactory sensitivity.

• When patients report alterations in the quality of olfaction in response to an odorant (ie, parosmias), the perceptions are almost universally unpleasant, a condition referred to as aliosmia (the perception of unpleasant odors from nominally pleasant odorants).

• Aliosmias may involve the perception of fecal or rotten smells (cacosmia) or chemical or burned smells (torquosmia).

• Complaints of impaired “taste” are often a symptom of olfactory dysfunction because much of the flavor of a meal derives from olfactory stimulation. Indeed, the complex sensory experience of “flavor” during the consumption of foods and drinks cannot be constructed simply from combinations of the basic taste qualities (sweet, salty, sour, bitter, and umami/savory).

• Chemosensory deficit may be the first symptom (a "sentinel symptom") in patients with COVID-19, but there is wide variation in the proportion of cases in which this is reported to occur.

• Most patients with COVID-19-related chemosensory dysfunction do not present associated nasal congestion or rhinorrhea.

• Presbyosmia (literally “elderly olfaction” or “old age olfaction”) is the gradual loss of olfactory abilities that occurs in most people as they grow older.

• Clinically significant olfactory loss is common in the elderly but frequently unrecognized, partly because deficits typically accumulate gradually over decades. Indeed, self-reported olfactory impairment significantly underestimates prevalence rates obtained by olfactory testing.

• Olfactory deficits involving odor detection, identification, and discrimination are present in more than 90% of patients with early-stage Parkinson disease.

• In dementia with Lewy bodies, as in Parkinson disease, olfactory dysfunction is nearly universal, develops early (before any movement or cognitive disorder), and is often severe.

Historical note and terminology

Printed medical illustrations began in 1490, and by the beginning of the 16th century, they included representations of afferent connections from the special sensory organs to the brain (115). These were typically part of highly schematic diagrams of brain function representing the medieval cell doctrine. Three “cells” or ventricles were usually assigned functions of sensory integration and imagination, cognition, and memory (116). Indeed, many early 16th-century woodcuts of the medieval cell doctrine show presumptive connections between the organs subserving the special senses, either with the most anterior cell or ventricle of the brain or with a specific portion of it--the sensus communis (ie, sensory commune or common sense, a structure Aristotle had postulated is responsible for monitoring and integrating the panoply of sensations from which unified conscious experience arises) (115; 116; 117). A representation of the olfactory bulbs is incorporated into many of these woodcuts, beginning with an illustration by German physician, philosopher, and theologian Magnus Hundt (Parthenopolitanus, 1449-1519) in 1501 in his Antropologium, which showed central projections of the two olfactory bulbs joining in the meshwork of the rete mirabile (117; 118). German physician and anatomist Johann Eichmann, known as Johannes Dryander (1500-1560), modified Hundt’s figure for his own monograph in 1537 but retained the representation of the olfactory bulbs (117; 118).

In 1503, German Carthusian humanist writer Gregor Reisch (c 1467-1525) published an influential and highly copied woodcut in his Margarita philosophica, showing connections from the olfactory bulbs overlying the bridge of the nose to the sensus communis in the anterior cell or ventricle (117). In the following centuries, numerous authors derived similar figures from Reisch’s original schematic illustration of the medieval cell doctrine, including Brunschwig (1512, 1525), Głogowczyk (1514), Romberch/Host (1520), Leporeus/Le Lièvre (1520, 1523), and several others (117).

Similar representations were provided by Peyligk (1518) and Eck (1520) (117).

These stereotyped 16th-century schematic images typically located the olfactory receptors (depicted as small circular or oval objects resembling tiny eyeglasses) across the bridge of the nose and at exactly the anatomic level of the olfactory bulbs. Such images linked the olfactory bulbs to olfaction before the advent of more realistic images beginning in the mid-16th century.

Observational anatomy was largely lost from the time of Galen in the second century, and it became regimented and dogmatized with the scholasticism of the Middle Ages until a few anatomists began to seriously challenge Galen beginning in the 16th century. Most notably, Flemish anatomist Andreas Vesalius (1514-1564) provided much greater realism with the publication of his de Humani corporis fabrica (1543); however, Vesalius’ image did not, in fact, show clear bulb-like enlargements but rather an optic tract and bulb of roughly uniform thickness.

Even after Vesalius championed a return to observational anatomy, the medieval cell doctrine and its associated representation of the olfactory pathways persisted well into the 19th century, even if it gradually moved to the fringes of medical thought (117). These included, for example, Venetian humanist Lodovico Dolce's (1508/1510-1568) and Basque Franciscan Bernardus de Lavinheta's (died c 1530) edition of a much earlier work by Bernardus de Lavinheta Ramón Lull (Raimundus Lullius, c 1235-1316) in 1612 (117). One of the last of these representations was published in 1835 by British physician and phrenologist John Elliotson MD FRS (1791-1868) (117).

Many of the histological features of the olfactory epithelium, the olfactory sensory nerves, the passage of olfactory nerves from the olfactory epithelium through the cribriform plate, the synapse of these bipolar neurons in the glomeruli of the olfactory bulb, and further circuits within the olfactory bulb were elaborated remarkably well in the late 19th century and early 20th century by Italian histologist Camilo Golgi (1843-1926) and his upstart nemesis, the Spanish histologist Santiago Ramón y Cajal (1852-1934) along with Cajal's disciples Tomás Blanes Viale (1878-1900) and Fernando de Castro (1896-1918) (74; 167; 168; 169; 170; 13; 152; 125; 39; 40; 41; 42; 136; 113; 119; 132; 195; 38; 66; 149; 179; 57).

The greatness of these early histologists can be appreciated by comparing the drawings of histological preparations from the late 19th century with modern photomicrographs of histological and immunohistological preparations.