Smell and Taste in Health and Disel
edited by T. V. Getchell. et al.
Olfactory Dysfunction and Its Causes,450
Disorders Associated with Decreased Transport of
Odorant Molecules to the Olfactory
Neuroepithelium,453
Disorders, Agents, or Events Associated with
Damage to Olfactory Sensorineural Structures,
454
Taste Dysfunction and Its Causes,458
Chemosensory dysfunction is relatively common.
Thus, data from the National Ambulatory Medical
Care Survey suggestthat, for 1975and 1976combined,
435,000visits to physicians' offices occurred in which
a major presenting complaint was chemosensory in na-
ture (1). Importantly, the frequency of such disorders
is closely related to the age of the subject (see Chaps.
10, 11, 15, and 19), For example, while only a small
percentageof persons under the age of 65 evidence de-
creased ability to detect and identify odors, more than
half of those between the ages of 65 and 80 years and
over three-fourths of those over the age of 80 years
evidence major olfactory impairment (2). Data from a
recent worldwide National Geographic Society maga-
zine survey suggest that such age-related losses are
universal (3).
Clinical studies suggestthat upper respiratory infec-
tions, head trauma, and nasal and paranasal sinus dis-
ease are the most common recognized causes of che-
mosensory dysfunction (4-13), as shown in a recent
study of 750 consecutive patients presenting with che-
R. L. Doty: Smell and Taste Center, School of Medicine,
University of Pennsylvania, 3400 Spruce Street, Philadel-
phia, Pennsylvania 19104.
L. M. Bartoshuk: Department of Surgery (Section of oto-
laryngology), Yale University School of Medicine, 333 Ce-
dar Street, New Haven, Connecticut 06510.
J. B. Snow, Jr.: National Institute on Deafness and Other
CQJllmunication Disorders, Bethesda, Maryland 20892.
449
Raven Press, New York @ 1991.
Disorders, Agents, or Events Associated with
Decreased Transport of Taste Stimuli to the
Taste Buds, 458
Disorders, Agents, or Events Associated with
Damage to Taste Sensorineural Structures, 458
Conclusions, 460
References,460
mosensory disorders (Table 1) (4). In this study, 68%
of the patients viewed their chemosensory dysfunction
as affecting their quality of life, 46% reported that the
disorder had changed either their appetite or body
weight, and 56% reported that the problem altered
their daily living and/or psychologic well-being. Over
a quarter of the patients evidenced scores on the Beck
Depression Inventory (14) indicative of mild to severe
depression; for those with chemosensory distortions,
over one-third evidenced such scores. Such statistics
underscore the importance of chemosensory disorders
to persons who are experiencing them.
As indicated by the organization of this volume, it is
useful to divide both olfactory and gustatory disorders
into those associated with interruption of the transport
of the stimulus to the receptors (transport problems)
~nd those associated with damage to either peripheral
or central nervous system structures (sensorineural
problems). However, while the classification of disor-
ders into these components is of considerable heuristic
value in identifying the most salient aspects of each
cause, the relative contribution of these classescan be
difficult to determine in anyone case. For example,
some systemic disorders, such as those due to meta-
bolic or endocrine disturbances, can influence periph-
eral sensory structures, mucous secretion, and nasal
engorgement, in addition to central neural structures.
Nasal and paranasal sinus disease accompanied by
polyposis presumably influences both the transport of
odorant molecules to the olfactory neuroepithelium
and the functioning of the olfactory neuroepithelium
450 CHAPTER 26

TABLE 1. Etiologies, complaints, and sensory findings from 750 patients consecutively evaluated at the
University of Pennsylvania Smell and Taste Cent~-

Upper respiratory 146 3

infection/cold
Idiopathic 167 (22%) 71 96 88 3 55 71 22"
Head trauma 132 (18%) 72 60 113 7 53 46 5
Nasal and paranasal 109 (15%) 55 54 78 O 30 21 3
sinus disease
Congenital 29 ( 4%) 15 14 29 O O 1 O
Toxic chemical 18 ( 2%) 13 5 12 3 5 10 2
exposure
Oral infection 6 (.8%) 2 4 1 o O 3 2
Other infection 4 (.5%) 1 3 1 o 1 2 2
Psychiatric 4 (.5%) 2 2 1 o 2 2 1
Pregnancy related 3 (.4%) O 3 1 o 2 2 0
Seizure related 3 (.4%) 1 2 3 o 1 1 O
Sarcoidosis 2 (.3%) 0 2 1 o 1 1 1
Lupus 2 (.3%) 0 2 0 o O 2 0
Multiple chemical 2 (.3%) 0 2 0 o 2 O 0
sensitivities
Brain tumor 2 (.3%) 0 2 o O O o
Other 22 ( 3%) 10 12 2 0 6 3 o
Iatrogenic
Dental procedures 15 ( 2%) 8 7 7 2 1 10 4
Medication induced 15 ( 2%) 4 11 9 3 4 11 6
Nasal operation 8 ( 1 %) 7 1 7 3 4 0
Neurosurgery 5 (.7%) 2 3 3 O 5 2 O
Radiation therapy 4 (.5%) 1 3 3 1 1 3
Ear operation 2 (.3%) O 2 0 0 O 2 2
Other operation 4 (.5%) 2 2 3 0 1 1 1
TOTALS 750 336 414 509 23 241 257 69
From Deems et al., ref. 4.
"Note that 18 of these patients were also classified as having BMS (burning mouth syndrome; 5 men and 13 women; 3 with
olfactory loss; 1 with gustatory loss; 4 reporting dysosmia; 11 reporting dysgeusia).

itself. Similarly, head injury can influence nasal air-
flow via changes in nasal obstruction, activation of al-
lergic reactions that cause upper airway inflammation,
and displacement of bony and cartilaginous nasal
structures as well as by trauma to neuroepithelial and
central neural structures. Indeed, the relative role of
such influences can change with time since the injury
(e.g., trauma-related inflammatory reactions and he-
matomas commonly regress over time).
The primary purpose of this chapter is to provide an
overview of the major causes of smell and taste dis-
orders, so that perspective on the more specific and
detailed clinical chapters that follow can be obtained.
Salient points are highlighted and information comple-
mentary to the subsequent chapters is provided. A
secondary purpose is to impress upon the reader the
breadth of causes of chemosensory disturbances and
to stress the importance of clinical psychophysical
testing in defining the nature and extent of such dis-
orders. Emphasis is placed on recent studies and ex-
amples; no attempt has been made to provide a com-
prehensive or historical review of the literature. Since
most chemosensory disorders reflect olfactory dys-
function rather than taste dysfunction, per se, this
chapter is largely weighted by studies on the sense: of
smell. The reader is referred to the following chapters
and to other articles (4-17) for more specific informa-
tion on clinical aspects of chemosensory function.
OLFACTORY DYSFUNCTION AND ITS CAUSES
Disordered olfactory function has been associated in
the medical literature with many diseases and trau-
matic and iatrogenic events (Table 2). Unfortunately,
a number of these associations are based solely on pa-
tient reports, questionable empirical evidence, anec-
dotal observations, case studies, and a priori assump-
 CAUSES OF OLFACTORY AND GUSTATORY DISORDERS / 451

TABLE 2. Olfactory dysfunction: possible etiologic categories

Lesions of the nose/airway Neoplasms-intranasal

Structural abnormality Neuro-olfactory tumors
Deviated septum Esth esion eu roepithe Iioma
Weakness of alae nasi Esthesioneuroblastoma
Nasal polypi Esthesioneurocytoma
Allergic rhinitis Esthesioepithelioma
Seasonal Other benign or malignant nasal tumors
Perennial Conductive effect (e.g., adenocarcinoma)
Vasomotor rhinitis Perceptive effect (e.g., schwannoma, neurofibroma)
Atrophic rhinitis Nasopharyngeal tumors with extension
Chronic inflammatory rhinitis Paranasal tumors with extension
Syphilis Leukemic infiltration
Tuberculosis Neoplasms-carcinomas
Sarcoidosis Lung
Scleroma Gastrointestinal tract
Leprosy Ovary
Wegener's granulomatosis Breast
Midline granuloma Neurologic
Adenoid hypertrophy Amyotrophic lateral sclerosis
Sjogren's syndrome Familial dysautonomia
Hypertrophic rhinitis Ref sum's syndrome
Rhinitis medicamentosa Multiple sclerosis
Infections and viral Parkinson's disease
Influenza or acute viral rhinitis Progressive supranuclear palsy
Acute viral hepatitis Temporal lobe epilepsy
Bacterial rhinosinusitis Mesial temporal sclerosis (ammons horn sclerosis)
Bronchiectasis Hamartomas
Infected teeth and gums Scars/previous infarcts
Infected tonsils Myesthenia gravis
Others Retinitis pigmentosa
Fungal Vascular insufficiency and anoxia
Rickettsial Small multiple cerebrovascular accidents
Microfilarial Transient ischemic attacks
Nutritional/metabolic Subclavian steal syndrome
Vitamin deficiency Others
Vitamin A Cerebral abscess (esp. frontal or ethmoidal regions)
Vitamin B6 Meningitis
Vitamin B12 Syphilis
Trace metal deficiencies Syringomyelia
Zn Paget's disease
Cu Korsakoff's disease
Protein calorie malnutrition Hydrocephalus
Total parenteral nutrition (without adequate replacement) Migraine
Cystic fibrosis Endocrine
Abetalipoproteinemia Adrenal cortical insufficiency-Addison's disease
Chronic renal failure Congenital adrenal hyperplasia
Cirrhosis of liver Cushing's syndrome
Gout Hypothyroidism
Whipple's disease Diabetes mellitus
Neoplasms-intracranial Primary amenorrheas
Osteomas Chromatin negative gonadal dysgenesis- Turner's
Olfactory groove and cribiform plate meningiomas syndrome
Frontal lobe tumors (esp. gliomas) Hypogonadotropic hypogonadism-Kallmann's syndrome
Paraoptic chiasma tumors Hypergonadotropic hypogonadism
Pituitary tumors (esp. adenomas) Pse udohypoparathyroidi sm
Craniopharyngioma Panhypopituitarism
Suprasellar meningioma Gigantism
Aneurysms Adiposogenital dystrophy-Froelich's syndrome
Suprasellar cholesteatoma Congenital/hereditary etiologies
Temporal lobe tumors Syndrome of hypogeusia and hyposmia
Midline cranial tumors Triad of:
Parasagittal meningiomas Submucous cleft of dorsal hard palate
Tumors of the corpus callosum Facial hypoplasia
452 / CHAPTER 26

TABLE 2. Continued
Stunted growth
Phosphorus oxychloride
"Red haired disease" with pigmentary abnormality Pepper and cresol mixture
Complete and specific anosmias of genetic origin Benzene
Bronchial asthma Benzol
Multiple lentigines syndrome Butyl acetate
Orbital hypertelorism Carbon disulfide
Trauma Ethyl acetate
(Most common proposed mechanisms: 1, shearing of
Ethyl acrylate
olfactory nerves; 2, hemorrhage of the basal frontal Formaldehyde
lobes and bruising of the olfactory bulbs and tracts)
Hydrazine
Frontal fracture (esp. fronto-ethmoidal fracture) Oil of peppermint
Occipital contrecoup injury Trichloroethylene
Nasal fracture Hydrogen sulfide
Drugs Paint solvents
Adrenal steroids (chronic usage) Chlorine
Amino acid excess Benzine
Histidine Nitrous gases
Cysteine Industrial dusts (particulate)
Anesthetics, local Coke/coal
Procaine HCI Grain
Cocaine HCI Silicone dioxide
Tetracaine HCI
Spices
Anticancer agents (e.g., methotrexate) Flour
Antihistamines (e.g., chlorpheniramine maleate) Cotton
Antimicrobials
Paper
Griseofulvin Cement
Lincomycin Cadmium
Streptomycin Ashes
Tetracyclines Lead
Intranasal tyrothricin Chromium
Local neomycin Nickel
Neoarsphenamine Chalk
Antirheumatics Potash
Mercury or gold salts Iron carboxyl
D-Penicillamine Medical intervention
Antithyroids Laryngectomy
Methimazole
Rhinoplasty
Propylthiouracil Anterior craniotomy
Thiouracil Surgical interruption of olfactory tract
Hyperlipoproteinemia medications Frontal lobotomy
Clofibrate
Temporal lobotomy
Cholestyramine Paranasal sinus exenteration
Intranasal saline solutions with: Postanesthesia
Acetylcholine Radiation therapy
Acetyl, 13-methylcholine Arteriography
Menthol Influenza vaccination
Strychnine Maintenance hemodialysis
Zinc sulfate
Thyroidectomy
Opiates Hypophysectomy
Codeine
Adrenalectomy
Hydromophone HCI
Orchiectomy
Morphine Oophorectomy
Psychopharmaceuticals (e.g., psilocybin, LSD) Gastrectomy
Sympathomimetics Psychiatric
Amphetamine sulfate Schizophrenic disorders
Phenmetrazine theoclate Olfactory reference syndrome
Fenbutrazate HCI Depressive disorders
Others
Hysteria
Antipyrine Malingering
Oral ETOH Others
Local vasoconstrictors
Presbyosmia
Cimetidine
Physiologic processes
L-dopa Circadian variation
Chemical pollutants (gaseous) Menses
Sulfuric acid
Pregnancy
Hydrogen selenide
Idiopathic
From ref. 7, with modification.
 CAUSES
tions. Furthermore, even rudimentary olfactory
testing has not been performed in many of these stud-
ies. Since a number of patients are unaware of their
olfactory disorder and even a larger number mistak-
enly attribute their symptoms of flavor loss to taste
dysfunction rather than smell dysfunction (Fig. 1)
(18,19), most such associations need to be verified by
well-designed studies incorporating adequate sample
sizes and sound psychophysical procedures.
In the following sections, the major etiologic classes
associated with olfactory dysfunction are listed along
with a brief description of illustrative studies. In cases
where a given cause is described in detail elsewhere in
the volume, only a cursory description of the basic
findings is presented.
Disorders Associated with Decreased Transport of
Odorant Molecules to the Olfactory Neuroepithelium
Nasal obstruction can result from inflammatory,
neoplastic, traumatic, and developmental alterations
within the nasal cavity (20). All such processes, if they
result in bilateral restriction of airflow to the olfactory
neuroepithelium, presumably alter the ability to smell.
However, surprisingly few studies have empirically
established the degree to which such alterations are
present, and only recently have objective measures of
the influences of medical or surgical interventions
been determined for even the most common classes of
nasal airway obstruction (for review, see 21).
Complaints
2.8%
!I] Smell and Taste Loss
D Smell Loss Only
Dysosmia, Dysgeusia
or Burning Mouth
-Taste Loss Only
~ Other
FIG. 1. Distribution of total chemosensory
From Deems et al., ref. 4.
OF OLFACTORY AND GUSTATORY DISORDERS 453
Adenoid Hypertrophy
Adenoid hypertrophy can significantly influence na-
sal airflow and olfactory function in children. Ghor-
banian et al. (22) found, for example, marked preop-
erative hyposmia in a group of 28 children using a
phenylethyl alcohol (PEA) odor detection threshold
test. When tested 2 to 28 months after adenoidectomy,
20 of these children showed reductions in both nasal
airway obstruction and olfactory threshold values
(i.e., greater olfactory sensitivity). In 16 subjects who
had not received the operation, no change was ob-
served in either the nasal obstruction ratings or the de-
tection threshold values.
Nasal and Paranasal Sinus Disease
Rhinitis, polyposis, and sinusitis are accompanied
by decreased ability to smell [(23); see Chaps. 33, 34,
35, 36, and 37]. Importantly, recent quantitative stud-
ies have found considerable variability in the olfactory
function of persons with nasal and paranasal sinus dis-
ease (4) (Table 1) and have documented that medical
or surgical treatment can, in some cases, restore olfac-
tory function to normal levels (see Chaps. 33, 35, 37,
38 and 39). For example, Leonard et al. (24) assessed
the pre- and postoperative olfactory function of 25 pa-
tients who underwent unilateral or bilateral transantral
ethmoidectomy specifically for chemosensory dys-
function. Normal smell function was restored in nine
patients after surgery, whereas four evidenced mild
Test Results
~1%
[1] Smell and Taste Loss
D Smell Loss Only
-Taste Loss Only
~ No Identifiable Smell
or Taste Loss
complaints and test results (n = 750)
 454 CHAPTER 26
hyposmia, five moderate to severe hyposmia, and the
remainder no improvement. Similarly, Seiden and
Smith (25) administered the University of Pennsylva-
nia Smell Identification Test (UPSIT) (26) to five pa-
tients with nasal and paranasal sinus disease before
and after endoscopic intranasal ethmoidectomy and
antrostomy. The degree of smell loss before operation
ranged from total anosmia to moderate hyposmia
[mean UPSIT score 15.8, standard deviation (SD),
8.73]. Four to eight weeks after surgery, all five pa-
tients exhibited marked improvement in their olfactory
function (mean UPSIT score 33.4, SD 4.02).
The efficacy of corticosteroid treatment in restoring
olfactory function in patients with nasal and paranasal
sinus disease has been demonstrated in a number of
studies. These studies are reviewed in detail in Chap-
ter 35 by Mott.
Intranasal Neoplasms
Benign and malignant neoplasms can obstruct the
nasal chamber and thereby alter airflow to the olfac-
tory receptors without damaging, at least in initial
stages, the olfactory neuroepithelium (see Chaps. 35
and 38). Examples include epithelial tumors (e.g., pap-
illomas from the nasal septum, lateral nasal wall, and
paranasal sinuses and tumors that arise from the skin
of the external nose and obstruct the nasal vestibule),
mesodermal tumors (e.g., hemangiomas and pyogenic
granulomas from the nasal septum or turbinates), and
odontogenic tumors such as ameloblastomas, dermoid
tumors, and osteomas (27). To our knowledge, how-
ever, no systematic studies of olfactory function have
been performed before and after removal of such ob-
structive structures, although several authors report
the existence of anosmia in patients with such tumors
(e.g.,28).
Laryngectomy
Although there is controversy concerning the basis
'of olfactory dysfunction in laryngectomized patients,
there is little controversy about its reality. In one ques-
tionnaire study, for example, 95% of the laryngecto-
mized patients who were polled reported noticeable
loss of olfaction following this operation; however ,
half indicated that their smell returned to at least some
degree within a year of the surgery (29).
Ritter (30) hypothesized that laryngectomy-related
olfactory loss is due to the patient's inability to force
adequate amounts of air through the nose. He dem-
onstrated that odorants injected toward the olfactory
cleft of 18 laryngectomized patients were, in fact, per-
ceived to approximately the same degree as odorants
similarly injected toward the olfactory cleft of normal
subjects who held their breath during the stimulation.
'This finding led him to conclude that laryngectomy pa-
tients have an intact sense of smell that does not
change with disuse.
In contrast to this conclusion is the view proposed
by Henkin and associates (31,32) that laryngectomy
disrupts a complex neural circuit from the larynx
through the vagus nerve to central nervous system
structures associated with olfaction (e.g., the hippo-
campus). According to this view, the olfactory deficit
would be irreversible. This theory is based, in part, on
the assumption that air swallowing by laryngecto-
mized patients results in normal or near-normalamounts
of air reaching the olfactory receptors. Recent rhino-
manometric studies indicate, however, that the vol-
ume, duration, peak flow rate, and mean flow rate of
sniffs produced using the air-swallowing technique are
much lower in laryngectomized patients than in either
normal subjects or laryngectomized patients fitted
with a laryngeal bypass tube (33,34). Furthermore, the
use of larynx bypass tubes demonstrates that rela-
tively normal olfactory function is present in laryngec-
tomized patients once adequate volumes of air reach
the receptor region (35,36). Nevertheless, there is his-
tologic evidence that at least some damage may be
present in the olfactory region of laryngectomized pa-
tients (37).
Disorders, Agents, or Events Associatedwith Damage
to Olfactory Sensorinenral Structures
Viral Infections
It is well known that nasal obstruction associated
with upper respiratory infections such as the common
cold and influenza can temporarily decrease or elimi-
nate the ability to smell by blocking airflow to the ol-
factory receptor region. It is less well known, how-
ever, that viruses associated with these infections can
permanently damage the olfactory neuroepithelium
and cause anosmia or hyposmia, particularly in older
persons (4,38). In fact, the single most common cause
of hyposmia and anosmia is upper respiratory infec-
tion (4-11). It is of interest in this regard that animal
studies demonstrate that many viruses have an ad-
verse influence not only on the olfactory neuroepi-
thelium but also on the olfactory bulb, olfactory tracts,
and higher order cortical regions (see Chaps. 43 and
47).
The olfactory loss associated with viral infections is,
on average, indicative of marked hyposmia, although
considerable variability is present and a number of
subjects with this condition are anosmic. For example,
in a recent study of 192 patients with upper-respiratory
infection-related olfactory loss (4), the mean UPSIT
score was 23.2 with a SD of 9.4. In this same group,
the mean PEA detection threshold was -3.0 (Iog vol/
 CAUSES
vol in propylene glycol) with a SD of 2.2. While pro-
found, the average degree of smellloss in this group is
about the same as observed"in nasal and paranasal si-
nus disease, although not as great as that observed for
persons with head injury, as discussed in the next sec-
tion.
Head Trauma
A common cause of olfactory dysfunction is trauma
to the head. For example, 113 of 750 patients (15%)
presenting to a smell and taste center with chemosen-
sory dysfunction evidenced demonstrable decrements
in the ability to smell (4), although, as in the case of
viral infections, considerable variability in test scores
was evident [mean UPSIT score 17.8 (SO 9.7); mean
log PEA threshold value -2.3 (SO 2.2)]. Since head
trauma is reviewed in detail in Chap. 45, it will not be
further reviewed here, except to indicate that exami-
nation of large unselected series of head injury pa-
tients typically finds anosmia incidence rates on the
order of 5 to 7%.
Septoplasty, Rhinoplasty, and Turbinectomy
Most studies and case reports suggest that septo-
plasty, rhinoplasty, and turbinectomy have little or no
negative influence on the ability to smell and, in fact,
likely improve smell function (see Chaps. 33-39). Un-
fortunately, most of the major studies on this topic are
limited on methodologic grounds, as discussed in what
follows.
In 1966, Champion (39) polled 200 patients about
their ability to smell following rhinoplasty. Twenty
(10%) reported temporary anomsia lasting from 6 to 18
months after the operation and all reported regaining
normal smell function. Since, however, no empirical
olfactory testing was performed, it is unknown
whether any deficits were, in fact, present postopera-
tively. This consideration is important because, as
noted earlier in this chapter, many persons with con-
siderable smell loss are unaware of their disorder
(19,42a).
Goldwyn and Shore (40) evaluated, preoperatively
and postoperatively, the odor identification ability of
64 patients who had undergone rhinoplasty alone, 22
who had undergone rhinoplasty in combination with
submucous resection of the nasal septum, and II who
had undergone submucous resection alone. In addi-
tion, 57 controls were evaluated. Peppermint, ground
coffee, and clove served as test stimuli. Although the
findings were interpreted as supporting the notion that
none of these operations have any long-term deleteri-
ous effects on smell function, this study is flawed
methodologically. For example, the same small set of
three test stimuli were used in the preoperative and
postoperative tests (which in some cases were repeat-
OF OLFACTORY AND GUSTATORY DISORDERS /
455
edly performed), confounding practice and learning ef-
fects with any adverse effects that might have oc-
curred as a result of the operations. Because the
somewhat crude test used in this study is likely insen-
sitive to both increases in smell function from a nonan-
osmic baseline and to decreases in smell function short
of major smell loss, operation-related alterations may
have gone unnoticed.
More recently, Stevens and Stevens (35) used the
Elsberg blast injection procedure to evaluate the olfac-
tory function of 100 patients following various forms
of intranasal surgery and concluded that, in general,
the operations improved olfactory function. Of the 100
patients examined, 63 had received nasal septoplasty,
23 septorhinoplasty, 3 turbinate resection, and 10 pol-
ypectomy as the primary operation. However, 38 of
these patients also had turbinate resection, 7 polyp-
ectomy, 8 the Caldwell-Luc operation, and 4 other
types of procedures as concomitant procedures.
Therefore, defining the specific factors responsible for
the olfactory changes was difficult. The value of this
research was further compromised by the use of the
non-forced-choice Elsberg test procedure, which has
problems of reliability and validity (36,41; see Chap.
10).
In a retrospective study, Ophir et al. (42) polled 77
patients who had undergone bilateral total inferior tur-
binectomy for chronic nasal obstruction about their
ability to smell. Approximately half (51%) of these in-
dividuals claimed to be aware of a preoperative dec-
rement and, of these, 46% reported a postoperative
improvement in smell function. Subsequent to this
work, Ophir et al. (42a) established olfactory threshold
values in 24 turbinectomized patients for amyl acetate,
eugenol, citral, and camphor immediately before and
3 months following the turbinectomy. Sixteen other
patients were tested two and a half years after the op-
eration. Of the initial 24 subjects, 22 evidenced post-
operative olfactory thresholds which, on average,
were about two orders of magnitude lower than thresh-
olds measured preoperatively. None of the 16 patients
evidenced abnormal smell ability, suggesting that long-
term decrements in smell function were not associated
with the operation.
Radiation Therapy
Although the influence of ionizing irradiation of the
oral cavity on taste function is well documented (see
Chap. 48), there is little empirical information on the
influences of irradiation of the olfactory neuroepithe-
lium on the ability to smell. Nevertheless, radiation-re-
lated alterations in both odor identification and odor
detection sensitivity have been recently demonstrated
(43,44). For example, Ophir et al. (44) evaluated the
olfactory sensitivity of 12 patients before, during, and
 456 CHAPTER 26
after exposure of the olfactory neuroepithelium to ra-
diation in the course of treatment for pituitary ade-
noma or nasopharyngeal carcinoma. Decreased sensi-
tivity was found in all patients by the end of the
radiation treatment period and was still present to
some degree a month following. Although varying de-
grees of improved function were noted 3 to 6 months
after the treatment, none of the threshold values had
returned to pretreatment levels. As noted by these au-
thors, such alterations deserve more attention when
considering the disability caused by irradiation of head
and neck tumors.
Intracranial Tumors or Lesions
Intracranial tumors can alter olfactory function by
damaging or adding pressure to sectors of the central
and peripheral olfactory pathway, including structures
within the temporal lobe. Olfactory groove menin-
giomas, frontal lobe gliomas, suprasellar menin-
giomas, and sphenoidal ridge meningiomas arising
from the dura of the cribriform plate and surrounding
regions have all been associated with smell distur-
bances (5,45). In addition, olfactory dysfunction has
been reported as a result of tumors on the floor of the
third ventricle, pituitary tumors that extend above the
sella turcica, and tumors in the temporal lobe or un-
cinate convolution (5).
Despite such observations, it is of interest that intra-
cranial neoplasms are only rarely the basis of the che-
mosensory dysfunction of patients presenting to smell
and taste centers. For exampJe, in the large study by
Deems et al. (Table 1) (4), only three (0.3%) persons
complaining of chemosensory dysfunction were found
to have brain tumors. The low incidence of tumors in
such a sample presumably reflects their rarity relative
to other causes of chemosensory disturbance and the
nature of referral patterns. Thus, tumors are likely de-
tected on initial visits to specialists such as otorhino-
laryngologists and neurologists, and further referral to
.a smell and taste center for evaluation is not deemed
necessary. The reader is referred to Chap. 38 for a
more detailed discussion of this topic.
Exposure to Toxic Volatile Chemicals or Pollutants
As reviewed in detail in Chap. 49 by Cometto-Muniz
and Cain, the inhalation of a number of environmental
and industrial pollutants can lead, under some circum-
stances, to disorders associated with acute or chronic
olfactory dysfunction (Table I). Thus, in a recent case
control study of 731 employees at a chemical manufac-
turing plant (46), nonsmoking employees with a work
history in job positions in which exposure to acrylates
was common were over 6 times as likely to evidence
olfactory dysfunction than were nonsmoking employ-
'ees who had no such similar work history. Although
the physiologic basis of this phenomenon is poorly
documented, animal toxicologic studies indicate that
such acrylates, as well as a number of other airborne
chemicals, can result in marked damage to the olfac-
tory neuroepithelium, as evidenced by metaplasia to
respiratory epithelium, squamous metaplasia, loss of
olfactory neurons, hyperplasia of submucosal glandu-
lar elements, inflammation, degeneration, and focal
necrosis (46).
Considerable controversy surrounds the notion that
some individuals become hypersensitive to odors as a
result of exposure to environmental agents, particu-
larly petrochemicals. This chemical hypersensitivity
syndrome has become the subject of a number of stud-
ies and is the basis for a nontraditional popular medical
movement based upon "environmental illnesses."
However, recent data suggestthat olfactory thresholds
of persons with apparent chemical hypersensitivity do
not differ from matched normal controls, although
such persons do exhibit significantly higher nasal re-
sistances (as measured by anterior rhinomanometry),
respiration rates, and scores on the Beck Depression
Inventory (47). Whether suprathreshold measures of
olfactory function would provide psychophysical doc-
umentation for their perceived hypersensitivity is not
known.
Epilepsy
Olfactory hallucinations as a result of epileptiform
disturbances is very common, and olfactory auras are
among the most common sensory events preceding
convulsive seizure activity (48). The involvement of
limbic structures in seizure activity is well docu-
mented in animal studies (49), and the important role
of temporal lobe structures in epilepsy and in the pro-
duction of olfactory auras has long been recognized
(50-56).
Gloor et al. (50) suggest that the mesial temporal
limbic structures, rather than the temporal neocortex,
are essential for the auras, which have been variously
described as "burning oil" (56), peaches and lemons
(57), blood (58), or "something to do with animals"
(50). Chitanondh (59) reported successful treatment of
olfactory hallucinations in seven patients with seizure
disorders by stereotaxically placed amygdalotomies.
Psychiatric Disorders
Olfactory disturbances and hallucinations have been
reported in a number of psychiatric disorders, includ-
ing confusional states, depressive illnesses, chron-
ic hallucinatory psychoses, and schizophrenic syn-
dromes (5). Of particular interest are depressive
disorders, such as the olfactory reference syndrome,
in which strange smell sensations are often attributed
to environmental factors (60) (see Chap. 55).
 CAUSES
It has long been known that olfactory hallucinations
are common in schizophrenia, although less so than
visual or auditory ones (e.g.; 61). Although many early
surveys suggest that less than 5% of schizophrenics
experience olfactory disturbances and hallucinations
(5), more recent studies, particularly those based upon
prospective rather than retrospective data, indicate
that the true incidence is considerably higher, ranging
from about 10 to 39%, depending upon the population
studied (5).
Many schizophrenics evidence a decreasedability to
detect and identify odors. However, unlike such neu-
rodegenerative disorders as Alzheimer's disease (AD)
and idiopathic Parkinson's disease (PD) (see Chap.
47), the loss of olfactory function in schizophrenia is
relatively mild (62,63). For example, Hurwitz et al.
(62) report a mean UPSIT score of 33.4 (SD 5.7) for 17
neuroleptic-medicated schizophrenic patients, in con-
trast to average UPSIT score in the low 20's observed
in studies of AD and PD patients (18,19).
Neurodegenerative Diseases
It is now well documented that such neurodegener-
ative disorders as AD, idiopathic PD, and Hunting-
ton 's chorea are associated with a marked decrement
in the ability to smell (see Chap. 47). Importantly, in
the case of AD and PD, such losses occur early in the
disease process and may, in fact, be the first clinical
manifestation of the disease. As noted in detail in
Chap. 47, such olfactory dysfunction is unlikely due to
nonspecific damage within the nervous system, in that
differing degrees of olfactory loss are present among
various neurodegenerative disorders. For example,
while idiopathic PD patients evidence, on average,
UPSIT scores around 20, those with progressive su-
pranuclear palsy, a disorder that shares many of the
motor symptoms of PD, have average UPSIT scores
above 30 (64).
Neurosurgical Interventions
Alterations in the ability to smell are a common
complication of some brain operations. Although a
wide range of operations can impact on the ability to
smell, two major classes of operations are most note-
worthy in this regard: (a) operations at the base of the
brain that transect or damage the olfactory nerves or
tracts and (b) operations that impact upon temporal
lobe structures, such as those designed to eliminate
intractable epileptiform seizure activity (65,66). Re-
cently, Jones-Gotman and Zatorre (67) have shown, in
a large series of 120 patients at the Montreal Neuro-
logical Institute and Hospital, that the ability to iden-
tify odors is mildly to moderately impaired after right
or left temporal lobectomy, right or left frontallobec-
tonw, and right frontotemporal excision. Patients
OF OLFACTORY AND GUSTATORY DISORDERS 457
whose operations were confined to the left central, pa-
rietal, or posterior areas of the brain showed no sig-
nificant olfactory deficits. Importantly, the impair-
ment after frontal lobectomy was found only for those
patients whose frontal lobe removal invaded the or-
bital cortex, supporting studies that suggest a role of
the orbital cortex in higher order olfactory processing
(68).
Inherited Disorders
A number of congenital forms of olfactory dysfunc-
tion are present, ranging from the inability to detect
only one or a few compounds (see Chap. 41) to com-
plete anosmia (5,69). Congenitally related dysosmias
have been also reported (e.g., in association with epi-
leptic disturbances), although such disturbances are
rare (5).
Perhaps the most widely researched congenital an-
osmia is that associated with Kallmann's syndrome
(70). This syndrome, which likely reflects an autoso-
mal dominant mode of inheritance with incomplete ex-
pressivity, is primarily characterized by hypogonado-
tropic hypogonadism and anosmia; some individuals
also evidence midline craniofacial abnormalities,
cryptorchidism, deafness, or renal abnormalities. Al-
though several areas of the nervous system may be re-
sponsible for producing the anosmia, recent magnetic
resonance imaging studies suggest that interruption or
total absence of the olfactory sulcus is a primary de-
fining characteristic of the disorder (71).
Drugs
A number of drugs have been implicated in olfactory
dysfunction (see Chap. 54). Unfortunately, few sys-
tematic studies (e.g., double-blind ones) are available
on this topic, so many of the reported drug-related al-
terations are poorly documented; furthermore, little is
known about the sites at which such drugs exert their
influences. Thus, some systemically injected and even
topically applied drugs may influence smell function
not only by altering firing rates and Telationships
within the central nervous system but also by influ-
encing nasal vasodilatation, mucus secretion, and cell
division within the olfactory neuroepithelium (5). A re-
cent detailed review is available on this topic (72).
H emodialysis
A considerable body of literature indicates that pa-
tients evidence decreased ability to discriminate or
recognize odors following hemodialysis. In a recent
study, for example, Conrad et al. (73) administered an
olfactory recognition task and a verbal recall memory
test to dialysis subjects before and after dialysis ses-
sions as well as to controls over equivalent time pe-
458 CHAPTER 26
riods. The olfactory test scores of the patients were
significantly lower after dialysis than before dialysis.
In general, the test scores of the dialysis patients were
significantly lower than those of the normal controls.
Similar relationships were not observed for the verbal
recall memory test, suggesting that these effects were
dependent upon sensory, rather than cognitive or per-
formance, factors.
TASTE DYSFUNCTION AND ITS CAUSES
Although noticeable losses or distortions of the
sense of taste are considerably less frequent than those
observed for the sense of smell (Table I), they can be
quite debilitating when they are present. In general,
the sense of taste appears to be more resilient than the
sense of smell to the influences of age (Chap. 19), neu-
rodegenerative disorders (74,75), and head trauma (4),
partially because taste is mediated by more than one
cranial nerve and partially because of the compensa-
tion produced by inhibitory connections among the
taste nerves (see Chap. 11). Nevertheless, numerous
taste disorders are reported as a result of viral and bac-
terial infections, use of various drugs, and damage to
neural structures mediating taste. Furthermore, care-
ful regional psychophysical testing can demonstrate
regional alterations in the taste system that might oth-
erwise go unnoted.
Among the most debilitating and distressing taste
problems is that of dysgeusia (sometimes termed para-
geusia). The possible causes of this condition fall into
three general categories. First, and most common, are
chronic dysgeusias, which may reflect normal tastes
associated with substances that are actually in the
mouth, such as exudate arising from gingivitis or ab-
normal saliva. This bad taste is, of course, not a true
taste disorder, since the experience of dysgeusia in
this case is mediated by a normally functioning taste
system. The types of oral stimuli responsible for this
class of dysgeusia are discussed in Chaps. 40 and 54.
Second, some substances enter the bloodstream and
can be sensed directly by the taste system, presumably
via receptors in close proximity to blood or interstitial
fluid (75a). Third, abnormal stimulation of peripheral
or central taste structures, including that resulting
from stretching or crushing of a taste nerve, can result
in aberrant taste experiences. The association be-
tween burning mouth syndrome (abnormal perception
from the pain system) and dysgeusia is discussed in
Chap. 42.
As was the case with the sense of smell, disorders
of the sense of taste can be divided into those whose
causes seem to largely reflect disturbances in trans-
port of stimuli to the receptor membrane and to those
of sensorineural origin.
Disorders, Agents, or Events Associated with
Decreased Transport of Taste Stimuli to the Taste Buds
Although more data are needed, the available evi-
dence suggeststhat transport problems do not pose as
severe a problem in taste as in smell, since a large
number of individual taste pores must be blocked to
produce a taste problem, whereas stimulus access to
only a single cleft need be blocked to produce a smell
problem. Saliva plays complex roles in maintaining the
health of the oral cavity and in transporting taste stim-
uli to the receptors, and clinical disorders such as Sjo-
gren's syndrome, in which the salivary glands are ab-
normal, can alter taste function to some degree (see
Chap. 8). Poor oral hygiene may also reduce taste per-
ception, as discussed in Chap. 40 by Catalanotto.
Disorders, Agents, or Events Associated with Damage
to Taste Sensorineural Structures
Viral Infections
A number of studies suggest that upper respiratory
infections can alter taste function, although the mag-
nitude of the taste losses are often small. Taste loss in
the front of the tongue (76) suggests chorda tympani
nerve involvement. This nerve is particularly suscep-
tible to damage from viruses and other infective agents
since its course runs from the tongue to the brain
through the middle ear (between the malleus and in-
cus), which in turn is connected to the nasopharynx
by the eustachian tube.
An association between upper respiratory infections
and taste loss is actually not new. For example, otitis
media was reported to be associated with such loss in
the nineteenth century (77), but this observation
seems to have been lost in later literature. The high
incidence of viral infections with and without overt
otitis media makes this source of taste loss an impor-
tant area for future investigation. Infection caused by
herpes zoster is discussed in Chap. 43, and an example
of taste loss from such an infection is provided in
Chap. 11.
Tumors or Lesions Associated with the Taste Pathways
Probably the best known source of taste loss from
damage to the taste pathway is Bell's palsy. The facial
nerve is vulnerable to damage from a variety of
sources (e.g., ischemia, vasospasm, viral infection,
neoplasms). Graham (78) notes that one of the reasons
for this vulnerability is the length of the nerve in a
bony canal. Although well known, taste loss from
Bell's palsy has not been systematically evaluated
with modern psychophysical tools.
Some tumors of the peripheral taste nerves or cen-
 CAUSES
tral taste structures can cause taste loss as well as taste
dysgeusia or phantoms. A case of a salty phantom
arising from damage to the chorda tympani nerve is
described in Chap. 11. Bull (79) described metallic
sensations arising from damage to the chorda tympani
during stapedectomy, and a remarkable bitter taste
hallucination that resulted from a temporal lobe tumor
was described by EI-Deiry and McCabe (80). Chapter
43 by Esiri describes the neural lesions of the taste
system. Taste loss in these patient populations has not
been systematically evaluated, so the extent of such
losses is not known.
Head Trauma
Head trauma damages gustation as well as olfaction,
but it is apparently relatively rare and the pathophysi-
ologic mechanisms involved are usually unknown (see
Chap. 45). Such damage can be to the taste nerves or
to more central structures. Since the damage must be
extensive to override the compensatory mechanisms,
there may well be many cases of taste loss that are less
severe and go unnoticed by the patient. One interest-
ing new approach to determining the source of taste
loss in head trauma patients has been made possible
by the work of Miller and Reedy (81). They stained
human tongues temporarily with methylene blue and
photographed them with videomicroscopy (see Chap.
11). When innervation to a taste bud is intact, the taste
pore stains blue. When innervation is interrupted, the
taste pore does not stain. Thus, it is possible that pe-
ripheral damage from head trauma may be distinguish-
able from central damage by observing whether or not
taste pores stain in this manner .
Radiation Therapy
Taste loss due to both radiation therapy and che-
motherapy is well documented and reviewed in Chap.
48 by Beidler and Smith. They note that rapid cell
turnover makes the taste bud particularly vulnerable
to damage from such insults. In addition to chemosen-
sory disturbances, irradiation and chemotherapy are
associated with affective changes (i.e., conditioned
aversions) that can compromise the nutritional status
of cancer patients. This important clinical issue is dis-
cussed in Chap. 23.
Drugs
A number of drugs, especially antirheumatic and an-
tiproliferative drugs and such agents as captopril and
penicillamine, have been reported to alter the ability
to taste (see Chap. 48). The basis of such changes is
poorly understood; however, as pointed out by Schiff-
man (11), the presence of sulfhydryl groups in the mo-
lec~lar structure of the aforementioned compounds
OF OLFACTORY AND GUSTATORY DISORDERS / 459
may somehow be related. Although strong associa-
tions between dysgeusia and drugs used to treat hy-
pothyroidism have been reported (5), it is not clear to
what degreethese associations reflect the action of the
drug or the underlying disease process (see next sec-
tion and Chap. 48).
Epilepsy
Although seizures are more commonly associated
with olfactory auras than with taste auras, some gen-
uine taste symptoms have been associated with epi-
lepsy. For example, in a study of718 epileptic patients,
Hausser-Hauw and Bancaud (82) found that 4%
showed taste hallucinations. In some cases, a taste
hallucination could be induced by electrical stimula-
tion of the parietal or rolandic opercula.
Psychiatric Disorders
As in the case of olfaction, taste is reported altered
in a number of psychiatric disorders. However, few
patients with most psychiatric disorders have been
evaluated quantitatively. Exceptions include major de-
pressive disorders, where suprathreshold test intensity
is altered (see Chap. 55), and several eating disorders
(anorexia nervosa, bulimia). However, in the latter
case, the search for sensory alterations that might un-
derlie the changes in behavior have been generally un-
successful (83). Rather than affecting the sensory
properties of food, such disorders appear to affect
their hedonic properties. For example, for normal sub-
jects, eating or ingesting a sugar load decreases the
palatability of sugar. However, anorexics (84), bulim-
ics (85), and obese subjects (86) often fail to show this
effect.
There is one clearcut connection between eating dis-
orders and sensory loss. The purging behavior in bu-
limia appears to damage taste receptors on the palate
(85); however, this damage is rarely, if ever, noticed by
the patient, presumably because of the compensatory
taste mechanisms discussed in Chap. 11.
Hypothyroidism
As with the case of smell, there is evidence of an
association between thyroid disease and taste function
(see Chap. 52). The taste losses known to accompany
hypothyroidism illustrate the importance of careful
psychophysical testing. Early studies suggested that
nontasters of phenylthiocarbamide (PTC) and related
compounds showed a high incidence of thyroid dis-
ease. However, as pointed out by Mattes et al. (87),
the taste loss associated with thyroid disease might
have made these individuals only appear to be non-
tasters.
460 CHAPTER 26

Diabetes and that, in the large majority of cases, the disorders

are olfactory rather than gustatory in nature. Never-
Although there is little evidence that diabetes alters
theless, as indicated in Chap. 11, recent studies sug-
the ability to smell (5), this is not the case with taste.
gest that careful regional taste testing reveals altera-
As indicated by Settle in Chap. 53, there is evidence
tions in gustatory function that, in the past, have been
for a progressive loss of taste function beginning with
largely overlooked. The chapters that follow provide
glucose, extending to other sweeteners, salty stimuli,
considerable detail on the nature of these chemosen-
and finally to all stimuli. In his own work, Settle eval-
sory dysfunctions and point to the complexity of much
uated suprathreshold taste responses to glucose and
of this vast literature.
fructose in relatives of adult-onset diabetics and in
controls with no family history of diabetes. He identi-
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