11

Disorders of Smell and Taste

The sensations of smell (olfaction) and taste (gustation) receptor cells, which number between 6 and 10 million in
are suitably considered together. Physiologically, these each nasal cavity; sustentacular or supporting cells, which
modalities share the singular attribute of responding maintain the electrolyte (particularly potassium) levels in
primarily to chemical stimuli; that is, the end organs the extracellular milieu; and basal cells, which are stem
that mediate olfaction and gustation are chemoreceptors. cells and the source of both the olfactory and sustentacular
Also, taste and smell are interdependent clinically, as the cells during regeneration. The olfactory cells are actually
appreciation of the flavor of food and drink depends to bipolar neurons. Each of these cells has a peripheral pro-
a large extent on its aroma, and an abnormality of one cess (the olfactory rod) from which project 10 to 30 fine
of these senses is frequently misinterpreted as an abnor- hairs, or cilia. These hair-like processes, which lack motil-
mality of the other. In comparison to sight and hearing, ity, are the sites of olfactory receptors.
taste and smell play a less critical role in the life of the The central processes of these cells, or olfactory fila,
individual. However, chemical stimuli in communication are very fine (0.2 mm in diameter) unmyelinated fibers that
between humans are probably very important for some converge to form small fascicles enwrapped by Schwann
functions that have not been fully explored. Pheromones cells that pass through openings in the cribriform plate of
(pherein, “to carry”; hormon, “exciting”), that is, odor- the ethmoid bone into the olfactory bulb (Fig. 11-1). Col-
ants exuded from the body, as well as perfumes, play a lectively, the central processes of the olfactory receptor
part in sexual attraction; noxious body odors may repel. cells constitute the first cranial (olfactory) nerve. Notably,
In certain vertebrates the olfactory system is remark- this is the only site in the body where neurons are in direct
ably well developed, rivaling the sensitivity of the visual contact with the external environment. The epithelial sur-
system. Though humans were thought to be capable of face is covered by a layer of mucus, which is secreted by
discriminating as many as 10,000 different odorants based tubuloalveolar cells (Bowman glands) and within which
on work by Reed and others, recent experimental studies there are immunoglobulins A and M, lactoferrin, and
by Bushdid and colleagues have shown that this may be a lysoenzyme as well as odorant-binding proteins. These
vast underestimation. molecules are thought to prevent the intracranial entry of
Disorders of taste and smell can be persistently pathogens via the olfactory pathway (Kimmelman).
unpleasant, but only rarely is the loss of either of these In the olfactory bulb, the receptor-cell axons synapse
modalities a serious handicap. Nevertheless, as all foods with granule cells and mitral cells (so-called because
and inhalants pass through the mouth and nose, these they are triangular, like a bishop’s miter), the dendrites
two senses serve to detect noxious odors (e.g., smoke) and of which form brush-like terminals or olfactory glomeruli
to avoid tainted food and potential poisons. The loss of (see Fig. 11-1). Smaller tufted cells in the olfactory bulb
these senses could then have serious consequences. Also, also contribute dendrites to the glomerulus. Approxi-
because a loss of taste and smell may signify a number of mately 15,000 olfactory cell axons converge on a single
intracranial, neurodegenerative, and systemic disorders, glomerulus. This high degree of convergence is thought
they assume clinical importance. to account for an integration of afferent information. The
mitral and tufted cells are excitatory; the granule cells—
along with centrifugal fibers from the olfactory nuclei,
OLFACTORY SENSE locus ceruleus, and piriform cortex—inhibit mitral cell
activity. Presumably, interaction between these excitatory
Anatomic and Physiologic Considerations and inhibitory neurons provides the basis for the special
physiologic aspects of olfaction.
Nerve fibers subserving the sense of smell have their cells The axons of the mitral and tufted cells form the
of origin in the mucous membrane of the upper and poste- olfactory tract, which courses along the olfactory groove
rior parts of the nasal cavity (superior turbinates and nasal of the cribriform plate to the cerebrum. Within the olfac-
septum). The entire olfactory mucosa covers an area of tory tract and posterior to the olfactory bulbs are groups
about 2.5 cm2 and contains three cell types: the olfactory of cells that constitute the anterior olfactory nucleus

240

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 Chapter 11 Disorders of Smell and Taste 241

Amygdaloid
nucleus

Anterior olfactory nucleus

Interior
granule
cell
Anterior
perforated
space

Olfactory Anterior commissure

Septal area
bipolar cell
Cell of anterior Medial olfactory stria
olfactory nucleus
Internal Intermediate
granule olfactory
cell striae
Mitral
cell

Olfactory Lateral
glomerulus olfactory stria
Olfactory bulb
Olfactory
neuron Olfactory tract
Gyrus rectus Primary
Medial olfactory stria olfactory
Nasal mucous Anterior commissure cortex
membrane Lateral olfactory stria
Diagonal band
Anterior perforated
Lamina terminalis substance

Figure 11-1.  Diagram illustrating the relationships between the olfactory receptors in the nasal mucosa and neurons in the olfactory bulb and
tract. Cells of the anterior olfactory nucleus are found in scattered groups caudal to the olfactory bulb. Cells of the anterior olfactory nucleus make
immediate connections with the olfactory tract. They project centrally via the medial olfactory stria and to contralateral olfactory structures via
the anterior commissure. Inset: diagram of the olfactory structures on the inferior surface of the brain (see text for details).

(see Fig. 11-1). Dendrites of these cells synapse with fibers and the medial dorsal nucleus of the thalamus; the amyg-
of the olfactory tract, while their axons project to the olfac- daloid nuclei connect with the hypothalamus and septal
tory nucleus and bulb of the opposite side; these neurons nuclei. The role of these latter structures in olfaction is not
are thought to function as a reinforcing mechanism for well understood, but presumably they subserve reflexes
olfactory impulses. related to eating and sexual function. As with all sensory
Posteriorly, the olfactory tract divides into medial and systems, feedback regulation occurs at every point in the
lateral olfactory striae. The medial stria contains fibers afferent olfactory pathway.
from the anterior olfactory nucleus; these pass to the In quiet breathing, little of the air entering the nostril
opposite side via the anterior commissure. Fibers in the reaches the olfactory mucosa; sniffing carries the air into
lateral stria originate in the olfactory bulb, give off collater- the olfactory crypt, which contains the olfactory receptors.
als to the anterior perforated substance, and terminate in To be perceived as an odor, an inhaled substance must be
the nuclei of the amygdaloid complex and the prepiriform volatile—that is, spread in the air as very small particles—
area (also referred to as the lateral olfactory gyrus). The and soluble in water. Molecules provoking the same odor
latter represents the primary olfactory cortex, which in seem to be related by their shape more than by their
humans occupies a restricted area on the anterior aspect chemical quality. When a jet of scented vapor is directed
of the parahippocampal gyrus and uncus (area 34 of Brod- to the sensory epithelium, as by sniffing, a slow negative
mann; see Figs. 21-1 and 21-2). Thus olfactory impulses potential shift called the electroolfactogram (EOG) can be
reach the cerebral cortex without a relay through the thala- recorded from an electrode placed on the mucosa. The
mus; in this respect also, olfaction is unique among sen- conductance changes that underlie this receptor potential
sory systems. From the prepiriform cortex, fibers project to are induced by molecules of odorous material dissolved in
the neighboring entorhinal cortex (area 28 of Brodmann) the mucus overlying the receptor.

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 242 Part 2 CARDINAL MANIFESTATIONS OF NEUROLOGIC DISEASE

The transduction of odorant stimuli to electrical sig- odorant receptor. In this way, each of the glomeruli is attuned
nals is mediated in part by a guanosine triphosphate to a distinct type of odorant stimulus. Presumably, this
(GTP)-dependent adenylyl cyclase (“G protein”). Like encoding is preserved in the olfactory cortex.
other cyclic adenosine monophosphate (AMP) pathways, Something is to be learned from a second, distinct
this one utilizes the same intracellular second messen- olfactory system in many animals (the vomeronasal olfac-
ger, which opens a voltage-gated calcium channel in the tory system or organ of Jacobson), in which the repertoire
receptor. There follow conformational changes in trans- of olfactory receptors is much more limited than in their
membrane receptor proteins and a series of intracellular main olfactory system. This functionally and anatomically
biochemical events that generate axon potentials. distinct olfactory tissue is attuned to pheromones and
Intensity of olfactory sensation is determined by the thereby importantly influences menstrual, reproductive,
frequency of firing of afferent neurons. The quality of the ingestive, and defensive behavior (see review of Wysocki
odor is thought to be provided by “cross-fiber” activation and Meredith). The vomeronasal receptors employ differ-
and integration, as described earlier, because the indi- ent signaling mechanisms than other olfactory receptors
vidual receptor cells are responsive to a wide variety of and project to the hypothalamus and amygdala via a dis-
odorants and exhibit different types of responses to stimu- tinct accessory olfactory bulb.
lants—excitatory, inhibitory, and on–off responses have
been obtained. The olfactory potential can be eliminated Clinical Manifestations of Olfactory Lesions
by destroying the olfactory receptor surface or the olfac-
tory filaments. The loss of EOG occurs 8 to 16 days after Disturbances of olfaction may be subdivided into four
severance of the nerve; the receptor cells disappear, but groups, as follows:
the sustentacular (Sertoli) cells are not altered. As a result Quantitative abnormalities: loss or reduction of the
1. 
of division of the basal cells of the olfactory epithelium, sense of smell (anosmia, hyposmia) or, rarely, increased
the olfactory receptor cells are constantly dying and being olfactory acuity (hyperosmia)
replaced by new ones. In this respect, the chemorecep- Qualitative abnormalities: distortions or illusions of
2. 
tors, both for smell and for taste, constitute one of the few smell (dysosmia or parosmia)
examples of neuronal regeneration in humans. Olfactory hallucinations and delusions caused by tem-
3. 
The trigeminal system also participates in chemesthe- poral lobe disorders or psychiatric disease
sis through undifferentiated receptors in the nasal mucosa. Higher-order loss of olfactory discrimination (olfactory
4. 
These receptors have little discriminatory ability but a agnosia)
great sensitivity to irritant stimuli. The trigeminal afferents
also release neuropeptides that result in hypersecretion of Anosmia, or Loss of the Sense of Smell (Table 11-1)
mucus, local edema, and sneezing. Finally, stimulation of
the olfactory pathway at cortical sites of the temporal lobe This is the most frequent clinical abnormality of olfaction
may also induce olfactory experiences. and, if unilateral, usually is not recognized by the patient.
The olfactory system adapts quickly to a sensory Unilateral anosmia can sometimes be demonstrated in
stimulus, and for sensation to be sustained, there must the hysterical patient on the side of anesthesia, blindness,
be repeated stimulation. The olfactory sense differs from or deafness. Bilateral anosmia, on the other hand, is a
other senses in yet another way. It is common experi- common complaint, and the patient is usually convinced
ence that an aroma can restore long-forgotten memories that the sense of taste has been lost as well (ageusia).
of complex experiences. That olfactory and emotional
stimuli are strongly linked is not surprising in view of their Table 11-1
common roots in the limbic system. Yet, paradoxically, the
ability to recall an odor is negligible in comparison with MAIN CAUSES OF ANOSMIA
the ability to recall sounds and sights. As Vladimir Nabo- Nasal
kov has remarked, “Memory can restore to life everything  Smoking
except smells.” It is also interesting that dreams do not  Chronic rhinitis (allergic, atrophic, cocaine, infectious—
  herpes, influenza)
embody olfactory experiences.   Overuse of nasal vasoconstrictors
The remarkable evolutionary role of olfactory recep- Olfactory epithelium
tors can be appreciated by the fact that about 2 percent   Head injury with tearing of olfactory filaments
of the human genome exists to express unique odorant   Cranial surgery
receptors (over 400 distinct functional genes). The wide   Subarachnoid hemorrhage, meningitis
 Toxic (organic solvents, certain antibiotics—aminoglycosides,
diversity of these transmembrane proteins permits subtle   tetracyclines, corticosteroids, methotrexate, opiates, l-dopa)
differentiation of thousands of different odorant mol-  Metabolic (thiamine deficiency, adrenal and thyroid
ecules, as delineated by Young and Trask and the genetic   deficiency, cirrhosis, renal failure, menses)
basis for which Buck and Axel were awarded a Nobel Prize.   Wegener granulomatosis
 Compressive and infiltrative lesions (craniopharyngioma,
This specificity for molecules is encoded neuroanatomi-   meningioma, aneurysm, meningoencephalocele)
cally. Different odorant molecules activate specific olfactory Central
receptors. Each olfactory neuron expresses only one allele   Degenerative diseases (Parkinson, Alzheimer, Huntington)
of one receptor gene. Moreover, each olfactory glomerulus   Temporal lobe epilepsy
receives inputs from neurons expressing only one type of Malingering and hysteria

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 Chapter 11 Disorders of Smell and Taste 243

This calls attention to the fact that taste depends largely prevent olfactory stimuli from reaching the receptor cells.
on the volatile particles in foods and beverages, which Heavy smoking is the most frequent cause of this type of
reach  the olfactory receptors through the nasopharynx, hyposmia in practice. Chronic atrophic rhinitis; sinusitis
and that the perception of flavor is a combination of of allergic, vasomotor, or infective types; nasal polyposis;
smell, taste, and tactile sensation. This can be proved by and overuse of topical vasoconstrictors are other common
demonstrating that patients with anosmia but without a causes. Biopsies of the olfactory mucosa in cases of allergic
complaint of ageusia are able to distinguish the elemen- rhinitis have shown that the sensory epithelial cells are still
tary taste sensations on the tongue (sweet, sour, bitter, and present, but their cilia are deformed and shortened and
salty). The olfactory defect can be verified readily enough are buried under other mucosal cells. Influenza, herpes
by presenting a series of nonirritating olfactory stimuli simplex, and hepatitis virus infections may be followed
(vanilla, peanut butter, coffee, tobacco) and asking the by hyposmia or anosmia caused by destruction of recep-
patient to sniff once and identify them. If the odors can tor cells; if the basal cells are also destroyed, this may be
be detected and described, even if they cannot be named, permanent. These cells may also be affected as a result of
it may be assumed that the olfactory nerves are relatively atrophic rhinitis and local radiation therapy or by a rare
intact (humans can distinguish many more odors than type of tumor (esthesioneuroblastoma) that originates in
they can identify by name). If they cannot be detected, the olfactory epithelium. There is also a group of uncom-
there is an olfactory defect. Ammonia and similar pungent mon diseases in which the primary receptor neurons are
substances are unsuitable stimuli because they do not test congenitally absent or hypoplastic and lack cilia. One of
the sense of smell but have a primary irritating effect on these is the Kallmann syndrome of congenital anosmia
the mucosal-free nerve endings of the trigeminal nerves. and hypogonadotropic hypogonadism. A similar disorder
The value of testing smell in one nostril at a time occurs in Turner syndrome and in albinism because of an
has been questioned, for example by Welge-Luessen and ill-defined congenital structural defect.
colleagues, who studied olfactory groove meningiomas. Anosmia that follows head injury is most often a result
They found, contrary to expectations, that this test was not of tearing of the delicate filaments of the receptor cells as
sensitive to the presence of a unilateral lesion, ostensibly they pass through the cribriform plate, especially if the
because of mixing of air in the nasopharynx as well as injury is severe enough to cause fracture. The damage
crossing of medial olfactory stria fibers as described ear- may be unilateral or bilateral. With closed head injury,
lier. Nonetheless, other experience suggests that rapidly complete anosmia is relatively infrequent (6 percent of
sniffing through one nostril does briefly allow segregation Sumner’s series of 584 cases), but lesser degrees are com-
of each side of the nasal cavities and can detect unilateral mon in our experience. Some recovery of olfaction occurs
lesions. in about one-third of cases over a period of several days
A more elaborate scratch-and-sniff test has been to months. Beyond 6 to 12 months, recovery is negligible.
developed and standardized by Doty and colleagues (Uni- Cranial surgery, subarachnoid hemorrhage, and chronic
versity of Pennsylvania Smell Identification Test). In this meningeal inflammation may have similar effects.
test the patient attempts to identify 40 microencapsulated In some of the cases of traumatic anosmia, there is
odorants, and olfactory performance is compared with also a loss of taste (ageusia). Ferrier, who first described
that of age- and sex-matched normal individuals. Unique traumatic ageusia in 1876, noted that there was always
features of this test are a means for detecting malingering anosmia as well—an observation subsequently corrobo-
and amenability to self-administration. Air-dilution olfac- rated by Sumner. Often, the ageusia also clears within a few
tory detection is an even more refined way of determin- weeks. A bilateral traumatic lesion near the frontal opercu-
ing thresholds of sensation and of demonstrating normal lum and paralimbic region, where olfactory and gustatory
olfactory perception in the absence of odor identification. receptive zones are in close proximity, would best explain
The use of olfactory evoked potentials is being investigated this concurrence, but this has not been proven. As stated
in some electrophysiology laboratories, but their reli- earlier, the interruption of olfactory filaments alone would
ability is uncertain. These last two refined techniques are explain a reduction in the ability to perceive the subtleties
essentially research tools and are not used in neurologic of specific flavors, but does not explain ageusia.
practice. Olfactory acuity varies throughout the menstrual
The loss of smell usually falls into one of three catego- cycle, possibly through a imputed vomeronasal system
ries: nasal (in which odorants do not reach the olfactory in humans, and may be disordered during pregnancy as
receptors), olfactory neuroepithelial (caused by destruc- well. Nutritional and metabolic disorders such as thia-
tion of receptors or their axon filaments), and central mine deficiency (Wernicke disease), vitamin A deficiency,
(olfactory pathway lesions). adrenal and perhaps thyroid insufficiency, cirrhosis, and
Viewed from another perspective, in an analysis of chronic renal failure may give rise to anosmia, all as a
4,000 cases of anosmia from specialized clinics, Hendriks result of sensorineural dysfunction. A large number of
found that the three most common diagnoses were viral toxic agents—the more common ones being organic sol-
infection of the upper respiratory tracts (the largest group), vents (benzene), metals including platinum-containing
nasal or paranasal sinus disease, and head injury. chemotherapies, dusts, cocaine, corticosteroids, metho-
Regarding the nasal diseases responsible for bilateral trexate, aminoglycoside antibiotics, tetracyclines, opiates,
hyposmia or anosmia, the most frequent are those in and l-dopa—can damage the olfactory epithelium (Doty
which hypertrophy and hyperemia of the nasal mucosa et al). Alcoholics with Korsakoff psychosis also have a

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 244 Part 2 CARDINAL MANIFESTATIONS OF NEUROLOGIC DISEASE

defect in odor discrimination (Mair et al). In this disorder, unduly sensitive to odors, but for the most part there is
anosmia is presumably caused by degeneration of neurons no proof of an actual change in their threshold of percep-
in the higher-order olfactory systems involving the medial tion of odors. Interestingly, Menashe and colleagues have
thalamic nuclei. linked enhanced sensitivity to the odorant isovaleric acid
Anosmia has been found in some patients with tem- to single nucleotide polymorphism (SNP) variants of the
poral lobe epilepsy and particularly in such patients who olfactory receptor gene OR11H7P, and more associations
had been subjected to anterior temporal lobectomy. In of this kind may be elucidated.
these conditions, Andy and coworkers have found impair-
ment in discriminating the quality of odors and in match-
Olfaction in neurodegenerative disease  Hyman and
colleagues have emphasized the many earlier observations
ing odors with test objects seen or felt.
of an early neuronal degeneration in the olfactory region
As with other sensory modalities, olfaction (and taste)
of the hippocampus in cases of Alzheimer, Lewy body, and
is diminished with aging (presbyosmia). The receptor cell
Parkinson disease. Moreover, a large proportion of patients
population is depleted, and if the loss is regional, neuro-
with other degenerative diseases of the brain have anosmia
epithelium is slowly replaced with respiratory epithelium
or hyposmia. A number of theories have been proposed to
(which is normally present in the nasal cavity and serves
explain the initial loss of smell, the most relevant of which
to filter, humidify, and warm incoming air). Neurons of
is based on the finding that the earliest neuropathologic
the olfactory bulb may also be reduced as part of the aging
changes of many neurodegenerative processes begin in
process.
olfactory structures and then appears serially in neighboring
Bilateral anosmia has been a manifestation of malin-
structures, only later reaching the parts of the brain that
gering, now that it has been recognized as a compensable
produce the characteristic neurologic features of these
disability. The fact that true anosmics will complain inor-
diseases. The implication from these findings, originating
dinately of a loss of taste (but show normal taste sensation)
with Braak and Braak, has been that Lewy bodies in
may help to separate them from malingerers. If it were to
particular are caused by a pathogen that enters through
be perfected, testing of olfactory evoked potentials would
the peripheral olfactory system and proceeds centrally
be of use here.
through the medial temporal lobe (see Chap. 38 for further
The nasal epithelium or the olfactory nerves them-
details). Prions have been suggested as a candidate agent
selves may be affected in Wegener granulomatosis and
because of their ability to alter protein folding and to
by craniopharyngioma, respectively. A meningioma of
transfer this property in a sequentially topographic manner.
the olfactory groove may implicate the olfactory bulb
The studies relating to olfaction in Parkinson disease have
and tract and may extend posteriorly to involve the optic
been reviewed by Doty, Braak and colleagues, Quinn et al,
nerve, sometimes with optic atrophy; if combined with
and Benarroch. It should be emphasized to patients,
papilledema on the opposite side, these abnormalities are
however, that the reverse is not the case; that is, the majority
known as the Foster Kennedy syndrome (see Chap. 12). A
of individuals with hyposmia do not have a generalized
large aneurysm of the anterior cerebral or anterior com-
neurodegenerative disease.
municating artery may produce a similar constellation.
With tumors confined to one side, the anosmia may be
strictly unilateral, in which case it will not be reported by Dysosmia or Parosmia
the patient but will be found on examination. The limita- These terms refer to distortions of odor perception where
tions of testing each side of the nose separately have been an odor is present. Parosmia may occur with local nasopha-
mentioned earlier. These defects in the sense of smell are ryngeal conditions such as infection of the nasal sinuses
attributable to lesions of either the receptor cells and their and upper respiratory infections. In some instances, the
axons or the olfactory bulbs, and current test methods do abnormal tissue itself may be the source of unpleasant
not distinguish between lesions in these two localities. In odors; in others, where partial injuries of the olfactory
some cases of increased intracranial pressure, olfactory bulbs have occurred, parosmia is in the nature of an olfac-
sense has been impaired without evidence of lesions in the tory illusion. Parosmia may also be a troublesome symp-
olfactory bulbs. tom in persons with depressive and psychotic illnesses,
The term specific anosmia has been applied to an who may report that every article of food has an extremely
unusual olfactory phenomenon in which a person with unpleasant odor (cacosmia). Sensations of disagreeable
normal olfactory acuity for most substances encounters a taste are often associated (cacogeusia). Nothing is known
particular compound or class of compounds that is odor- of the basis of this state; there is usually no loss of discrimi-
less to him, although obvious to others. In a sense, this is native sensation.
a condition of “smell blindness,” analogous to color blind- The treatment of parosmia is difficult. The use of neu-
ness. The basis of this disorder is unclear although there roleptic or antiepileptic drugs has yielded unpredictable
is evidence that specific anosmia for musky and urinifer- results. Claims for the efficacy of zinc and vitamins have
ous odors is inherited as an autosomal recessive trait (see not been verified (and there is a risk that zinc administra-
Amoore). tion may interfere with the absorption of copper). Some
Whether a true hyperosmia exists is a matter of con- reports indicate that repeated anesthetization of the nasal
jecture, but it is so frequently reported by migraineurs mucosa reduces or abolishes the parosmic disturbance. In
that the problem seems worthy of attention. Anxious, many cases, the disorder subsides spontaneously. Minor
highly introspective individuals may complain of being degrees of parosmia are not necessarily abnormal, for

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 Chapter 11 Disorders of Smell and Taste 245

unpleasant odors have a way of lingering for several hours Korsakoff psychosis; this impairment is not attributable
and of being reawakened by other olfactory stimuli, as to reduced olfactory acuity or to failure of learning and
every pathologist knows. memory (Mair et al). As indicated previously, the olfac-
tory disorder in the alcoholic Korsakoff patient is most
Olfactory Hallucinations likely caused by lesions in the medial dorsal nucleus of the
The report of an odor without stimulus, olfactory halluci- thalamus; several observations in animals indicate that
nation, is always of central origin. The patient perceives an this nucleus and its connections with the orbitofrontal
odor that no one else can detect (phantosmia). Most often cortex give rise to deficits in odor discrimination (Mair
this a manifestation of temporal lobe seizures (“uncinate et al, Slotnick and Kaneko). Eichenbaum and associates
fits”), in which circumstances the olfactory hallucinations demonstrated a similar impairment of olfactory capacities
are brief and accompanied or followed by an alteration of in a patient who had undergone extensive bilateral medial
consciousness and other manifestations of epilepsy (see temporal lobe resections. The operation was believed to
Chap. 15 on epilepsy). have eliminated a substantial portion of the olfactory affer-
If the patient is convinced of the presence of what is ents to the frontal cortex and thalamus, although there was
in fact a hallucination and also gives it personal origin, the no anatomic verification of this. In patients with stereotac-
symptom assumes the status of a delusion (a fixed false tic or surgical amygdalotomies, Andy and coworkers noted
belief). The combination of olfactory hallucinations and a similar reduction in odor discrimination. Thus it appears
delusions of this type signifies a psychiatric illness. Zilstorff that both portions of the higher olfactory pathways (medial
wrote informatively on this subject. There is often a com- temporal lobes, and medial dorsal nuclei) are necessary
plaint of a large array of odors, most of them noxious and for the discrimination and identification of odors.
seemingly emanating from the patient (intrinsic hallucina-
tions); in others, they are attributed to an external source
(extrinsic hallucinations). Both types vary in intensity and GUSTATORY SENSE
are remarkable with respect to their persistence. They may
be combined with gustatory hallucinations. According to
Anatomic and Physiologic Considerations
Pryse-Phillips, who took note of the psychiatric illness in
a series of 137 patients with olfactory hallucinations, most The sensory receptors for taste (taste buds) are distributed
were associated with endogenous depression or schizo- over the surface of the tongue and, in smaller numbers,
phrenia. In schizophrenia, the olfactory stimulus is usually over the soft palate, pharynx, larynx, and esophagus.
interpreted as arising externally, and as being induced Mainly they are located in the epithelium along the lateral
by someone for the purpose of upsetting the patient. In surfaces of the circumvallate and foliate papillae and to a
depression, the perception is of the stimulus being intrinsic. lesser extent on the surface of the fungiform papillae. The
The patient may go to great lengths to rid himself of the taste buds are round or oval structures, each composed
perceived odor, the usual ones being excessive washing of up to 200 vertically oriented receptor cells arranged
and use of deodorants; the condition may lead to social like the staves of a barrel. The superficial portion of the
withdrawal. There is reason to believe that the amygdaloid bud is marked by a small opening, the taste pore or pit,
group of nuclei is the source of the hallucinations, as ste- which opens onto the mucosal surface. The tips of the
reotactic lesions here have reportedly ameliorated both the sensory cells project through the pore as a number of fili-
olfactory hallucinations and the psychiatric disorder (see form microvilli (“taste hairs”). Fine, unmyelinated sensory
Chitanondh). fibers penetrate the base of the taste bud and synapse
Olfactory hallucinations and delusions may occur in directly with the sensory taste cells, which have no axons.
conjunction with Alzheimer dementia, but one should also The taste receptors are activated by chemical sub-
consider the possibility of a late-life depression. stances in solution and transmit their activity along the
sensory nerves to the brainstem. There are four primary
Loss of Olfactory Discrimination (Olfactory Agnosia) and readily tested taste sensations that have been long
Finally, one must consider a disorder in which the primary known: salty, sweet, bitter, and sour; recently a fifth, umami,
perceptual aspects of olfaction (detection of odors, adap- signifying a savory taste—the taste of glutamate, aspartate,
tation to odors, and recognition of different intensities of and certain ribonucleotides—has been added. The full
the same odor) are intact, but the capacity to distinguish range of taste sensations is much broader, consisting of com-
between odors and their recognition by quality is impaired binations of these elementary gustatory sensations. Older
or lost. In the writings on this subject, this deficit is usually notions of a “tongue map,” which implied the existence of
referred to as a disorder of olfactory discrimination. In specific areas subserving one or another taste, are incor-
dealing with other sense modalities, however, the inabil- rect. Any one taste receptor is capable of responding to a
ity to identify and name a perceived sensation would be number of sapid substances but each is preferentially sen-
called an agnosia. To recognize this deficit requires special sitive to one substance. In other words, the receptors are
testing, such as matching to sample, the identification and only relatively specific. The sensitivity of these receptors is
naming of a variety of scents, and determining whether remarkable: as little as 0.05 mg/dL of quinine sulfate will
two odors are identical or different. arouse a bitter taste when applied to the base of the tongue.
Such an alteration of olfactory function has been A G-protein transduction system (gustducin), similar
shown to characterize patients with the alcoholic form of to the one for olfaction, has been found to be operative

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 246 Part 2 CARDINAL MANIFESTATIONS OF NEUROLOGIC DISEASE

in signaling taste sensations in the tongue receptors. A nerve. The presence of this alternative pathway probably
discussion of this system can be found in the commentary accounts for reported instances of unilateral taste loss that
by Brand. have followed section of the root of the trigeminal nerve
The receptor cells of the taste buds have a brief life and instances in which no loss of taste has occurred with
cycle (about 10 days), being replaced constantly by mitotic section of the chorda tympani.
division of adjacent basal epithelial cells. The number of The second sensory neuron for taste has been dif-
taste buds, not large to begin with (approximately 10,000), ficult to identify. Neurons from the gustatory segment
is gradually reduced with age; also, changes occur in the of the nucleus solitarius project to adjacent nuclei (e.g.,
taste cell membranes, with impaired function of ion chan- dorsal motor nucleus of the vagus, ambiguus, salivato-
nels and receptors (Mistretta). Gustatory (and olfactory) rius superior and inferior, trigeminal, and facial nerves),
acuity diminishes with age (everything begins to taste and which serve viscerovisceral and viscerosomatic reflex
smell the same). According to Schiffman, taste thresholds functions, but those concerned with the conscious rec-
for salt, sweeteners, and amino acids are 2 to 2.5 times ognition of taste are currently considered to form an
higher in the elderly than in the young. The reduction in ascending pathway to a pontine parabrachial nucleus.
the acuity of taste and smell with aging may lead to a dis- From the latter, two ascending pathways have been traced
tortion of food habits (e.g., excessive use of salt and other (in animals). One is the solitariothalamic lemniscus to
condiments) and contribute to the anorexia and weight the ventroposteromedial nucleus of the thalamus. A sec-
loss of elderly persons. ond passes to the ventral parts of the forebrain, to parts of
Richter has explored the biologic role of taste in nor- the hypothalamus (which probably influences autonomic
mal nutrition. Animals made deficient in sodium, calcium, function), and to other basal forebrain limbic areas in
certain vitamins, proteins, etc., will automatically select or near the uncus of the temporal lobe. Other ascend-
the correct foods, on the basis of their taste, to compensate ing fibers lie near the medial lemniscus and are both
for their deficiency. Interesting genetic polymorphisms in crossed and uncrossed. Experiments in animals indicate
the receptor for sweet substances in rats have been found that taste impulses from the thalamus project to the
to underlie differences in the proclivity to ingest sweet tongue–face area of the postrolandic sensory cortex. This
substances, and a similar system has been proposed in is probably the end station of gustatory projections in
humans (Chaudhari and Kinnamon). humans as well, insofar as gustatory hallucinations have
been produced by electrical stimulation of the parietal
Neural Innervation of the Tongue and/or rolandic opercula (Hausser-Hauw and Bancaud).
Penfield and Faulk evoked distinct taste sensations by
Sensory impulses for taste arise from several sites in the
stimulating the anterior insula.
oropharynx and are transmitted to the medulla via several
cranial nerves (V, VII, IX, and X). The main pathway arises
on the anterior two-thirds of the tongue; these taste fibers Clinical Manifestations of Disorders of Taste
first run in the lingual nerve (a major branch of the man-
dibular segment of the trigeminal [V] cranial nerve). After
Testing of Taste Sensation
coursing within the lingual nerve for a short distance, the Unilateral gustatory impairment can be identified by with-
taste fibers diverge to enter the chorda tympani (a branch drawing the tongue with a gauze sponge and using a moist-
of the facial [VII] nerve); thence they pass through the pars ened applicator to place a few crystals of salt, sugar, lemon
intermedia and geniculate ganglion of the seventh nerve to (sour), and quinine (bitter) on discrete parts of the tongue;
the rostral part of the nucleus of the tractus solitarius in the the tongue is then wiped clean and the subject is asked
posterolateral medulla, where all taste afferents converge to report what was sensed. One use of such testing is to
(see the following text and Fig. 44-3). corroborate the existence of Bell palsy by comparing taste
From the posterior one-third of the tongue, soft palate, sensation on each side of the anterior tongue (see Chap.
and palatal arches, the sensory taste fibers are conveyed 44). A stimulus that has been used as a surrogate for sour
via the glossopharyngeal (IX) nerve and ganglion nodo- sensation is a low-voltage direct current, the electrodes of
sum to the nucleus of the tractus solitarius. Taste fibers which can be accurately placed on the tongue surface. If the
from the extreme dorsal part of the tongue and the few that taste loss is bilateral, mouthwashes with a dilute solution of
arise from taste buds on the pharynx and larynx run in the sucrose, sodium chloride, citric acid, and quinine may be
vagus (X) nerve. The gustatory nucleus is situated in the used. After swishing, the test fluid is spit out and the mouth
rostral and lateral parts of the nucleus tractus solitarius, rinsed with water. The patient indicates whether a taste was
which receive the special afferent (taste) fibers from the detected and then is asked to try to identify it. Special types
facial and glossopharyngeal nerves. Probably both sides of of apparatus (electrogustometers) have been devised for
the tongue are represented in this nucleus. the measurement of taste intensity and for determining the
Fibers from the palatal taste buds pass through the detection and recognition thresholds of taste and olfactory
pterygopalatine ganglion and adjacent to greater super- stimuli (Krarup; Henkin et al), but these are beyond the
ficial petrosal nerve fibers, joining the facial nerve at needs of the usual clinical examination.
the level of the geniculate ganglion, and proceed to the
nucleus of the tractus solitarius (see Fig. 44-3). Possibly, Ageusia, or Loss of the Sense of Taste (Table 11-2)
some taste fibers from the tongue may also reach the Apart from the loss of taste sensation that accompanies
brainstem via the mandibular division of the trigeminal normal aging, smoking is probably the most common

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 Chapter 11 Disorders of Smell and Taste 247

Table 11-2 Malnutrition because of neoplasm or radiation therapy

may also cause ageusia. Some patients with certain can-
MAIN CAUSES OF AGEUSIA cers remark on a reduced perception for bitter foods, and
Bell palsy some who have been radiated for breast cancer or sublin-
Diabetes mellitus gual or oropharyngeal tumors find sour foods intolerable.
Malnutrition (zinc deficiency) and hypovitaminosis (A, B2, B12) The loss of taste from radiation of the oropharynx is usu-
Sjögren syndrome
Infections (gingivitis, oral thrush, influenza, HIV)
ally recovered within a few weeks or months; the reduced
Lead or copper toxicity turnover of taste buds caused by radiation therapy usually
Exposure to organic solvents, certain antibiotics, methotrexate, recovers.
l-dopa, and zinc depleters/chelators An interesting syndrome of idiopathic hypogeusia—in
Radiation exposure which decreased taste acuity is associated with dysgeusia,
Degenerative disease (Parkinson)
hyposmia, and dysosmia—has been described by Henkin,
Schechter and colleagues. Food has an unpleasant taste
and aroma, to the point of being revolting (cacogeusia and
cause of impairment of taste sensation. Extreme drying cacosmia); the persistence of these symptoms may lead to
of the tongue from any cause may lead to temporary loss a loss of weight, anxiety, and depression.
or reduction of the sense of taste (ageusia or hypogeusia), Unilateral lesions of the medulla oblongata have not
as saliva is essential for normal taste function. Saliva been reported to cause ageusia, perhaps because the
acts as a solvent for chemical substances in food and for nucleus of the tractus solitarius is outside the zone of
conveying them to taste receptors. Dryness of the mouth infarction or because there is representation from both
(xerostomia) from inadequate saliva, as occurs in Sjögren sides of the tongue in each nucleus. Unilateral thalamic
syndrome; hyperviscosity of saliva, as in cystic fibrosis; and parietal lobe lesions, however, have both been associ-
irradiation of head and neck; and pandysautonomia ated with contralateral impairment of taste sensation in
all interfere with taste. Also, in familial dysautonomia rare cases.
(Riley-Day syndrome), the number of circumvallate and As indicated previously, a gustatory aura occasionally
fungiform papillae is reduced, accounting for a dimin- marks the beginning of a seizure originating in the fronto-
ished ability to taste sweet and salty foods. If unilateral, parietal (supra-sylvian) cortex or in the uncal region. Gus-
ageusia is seldom the source of complaint. Taste is fre- tatory hallucinations are much less frequent than olfactory
quently lost over the anterior two-thirds of one side of ones. Nevertheless, gustatory sensations were reported in
the tongue in cases of mundane Bell palsy, as indicated 30 of 718 cases of intractable epilepsy (Hausser-Hauw and
previously and in Chap. 44. Bancaud). During surgery, these investigators produced
A permanent decrease in the acuity of taste and an aura of disagreeable taste by electrical stimulation of
smell (hypogeusia and hyposmia), sometimes asso- the parietal and frontal opercula, and also by stimulation
ciated with perversions of these sensory functions of the hippocampus and amygdala (uncinate seizures). In
(dysgeusia and dysosmia), may follow influenza-like their view, the low-threshold seizure focus for taste in the
illnesses. These abnormalities have been associated temporal lobe is secondary to functional disorganization
with pathologic changes in the taste buds as well as in of the opercular gustatory cortex by the seizure. Gustatory
the nasal mucous membranes. In a group of 143 patients hallucinations were more frequent with right hemisphere
who presented with hypogeusia and hyposmia, 87 were lesions, and in half of the cases the gustatory aura was fol-
of this postinfluenza type, as determined by Henkin and lowed by a convulsion.
colleagues; the remainder developed their symptoms Zinc supplements are contained in over-the-counter
in association with scleroderma, acute hepatitis, viral and complementary medical products aimed at improving
encephalitis, myxedema, adrenal insufficiency, malig- smell and appetite and for the treatment of incipient colds.
nancy, deficiency of vitamins B and A, and the admin- We have had no opportunity to confirm the often-cited
istration of a wide variety of drugs. Also, according to benefits of zinc on any of these conditions, and the sup-
Schiffman, more than 250 drugs have been implicated porting evidence is sparse; however, the continued admin-
in the alteration of taste sensation, making it necessary istration of zinc in high doses has been associated with the
to consider virtually all drugs as a cause of taste loss. development of copper deficiency and a myeloneuropathy
Lipid-lowering drugs, antihistamines, antimicrobials, (see Chaps. 38 and 42).
antineoplastics, bronchodilators, antidepressants, and
antiepileptics are the main offenders, but little is known Burning mouth syndrome  Another poorly defined
about the mechanisms by which drugs induce these disorder is the burning mouth syndrome, which occurs
effects. More obvious is altered taste because of nasally mainly in postmenopausal women and is characterized by
and orally administered inhalant drugs, including the persistent, severe intraoral pain (particularly of the tongue).
“triptans” for migraine and a variety of antiallergy and We have seen what we believe to be fragmentary forms of
antiasthmatic medications. the syndrome in which pain and burning are isolated to
Distortions of taste and loss of taste are sources of the alveolar ridge or gingival mucosa. The oral mucosa
complaint in patients with certain local malignant tumors. appears normal and some patients may report a diminution
Oropharyngeal tumors may, of course, abolish taste by of taste sensation. A small number of such patients prove
invading the chorda tympani and lingual nerves or the to have diabetes, Sjögren syndrome, or vitamins B2 or B12
skull base foramina through which these nerves pass. deficiency (causing glossitis), but in most no systemic

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 248 Part 2 CARDINAL MANIFESTATIONS OF NEUROLOGIC DISEASE

illness or local abnormality can be found. Many such or ganglionopathy (see Chap. 43). Clonazepam may be
patients that we have encountered appeared to have a useful, and capsaicin has been tried with uncertain results.
depressive illness, but they responded only inconsistently to This disorder and others in which burning is a prominent
administration of antidepressants. A few patients have this feature is commented on in Chap. 7.
oral complaint as a component of a small fiber neuropathy

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