There are a number of medical journal articles available from The National Library of Medicine (copies can be ordered from them for a fee; if you live near another medical or university library, they might have these articles as well). Some of the articles that intrigued me the most follow (not all of them have to do with anosmia; some simply examine interesting facets of olfaction).
Feldmesser E, Bercovich D, Avidan N, et al. Mutations in olfactory signal
transduction genes are not a major cause of human congenital general anosmia.
Chem Senses 2007;32(1):21-30.
Anosmia affects the western world population, mostly the elderly, reaching
to 5% in subjects over the age of 45 years and strongly lowering their quality
of life. A smaller minority (about 0.01%) is born without a sense of smell,
afflicted with congenital general anosmia (CGA). No causative genes for human
CGA have been identified yet, except for some syndromic cases such as Kallman
syndrome. In mice, however, deletion of any of the 3 main olfactory transduction
components (guanidine triphosphate binding protein, adenylyl cyclase, and the
cyclic adenosine monophosphate-gated channel) causes profound reduction of physiological
responses to odorants. In an attempt to identify human CGA-related mutations,
we performed whole-genome linkage analysis in affected families, but no significant
linkage signals were observed, probably due to the small size of families analyzed.
We further carried out direct mutation screening in the 3 main olfactory transduction
genes in 64 unrelated anosmic individuals. No potentially causative mutations
were identified, indicating that transduction gene variations underlie human
CGA rarely and that mutations in other genes have to be identified. The screened
genes were found to be under purifying selection, suggesting that they play
a crucial functional role not only in olfaction but also potentially in additional
pathways.
Frasnelli J, Schuster B, Hummel T. Subjects with congenital anosmia have
larger peripheral but similar central trigeminal responses. Cereb Cortex 2007;17(2):370-7.
Most odorants not only stimulate olfactory receptor neurons but also activate
the intranasal trigeminal nerve. The simultaneous activation of the olfactory
and the trigeminal system leads to an interaction in the brain. Therefore, assessment
of the trigeminal impact of odorants may be difficult in subjects with a normal
sense of smell. To obtain a deeper insight into both, mechanisms of changes
in trigeminal sensitivity in anosmic patients and interactions between the olfactory/trigeminal
systems in healthy subjects, 21 patients with isolated congenital anosmia (ICA)
were investigated in this series of explorative, hypothesis-generating experiments
and compared with 35 healthy controls. Trigeminal sensitivity was measured by
psychophysical (lateralization task, intensity ratings) and electrophysiological
(trigeminal event-related potential, negative mucosal potential) means. ICA
patients were found to have higher peripheral activation than controls. On central
levels, however, similar responsiveness to trigeminal stimuli was found in ICA
patients when compared with healthy subjects. The results of the study are discussed
by proposing a model of mixed sensory adaptation/compensation in the interactions
between olfactory and the trigeminal system.
Gudziol V, Hummel C, Negoias S, et al. Lateralized differences in olfactory
function. Laryngoscope 2007;117(5):808-11.
BACKGROUND: Birhinal testing of odor identification will not allow the
detection of unilateral olfactory loss. The aim of the presented study was to
evaluate side differences of odor identification in large groups of healthy
subjects and in patients with nasal symptoms. PARTICIPANTS AND METHOD: Self-assessment
of olfactory function and evaluation of olfactory function by means of a validated
test were performed in 479 healthy subjects, in 765 patients with chronic rhinosinusitis
(CRS), and in 53 patients with a tumor. A 12-item odor identification test (“Sniffin’
Sticks”) was used to evaluate olfactory function separately for each nostril.
RESULTS: Fifteen percent of the healthy subjects demonstrated side differences
in the identification of at least 3 out of 12 odors. Healthy elderly subjects
showed larger side differences in identification of odor than younger ones;
a general difference between odor identification with the right or left nostril
was not found. Both CRS patients and patients with a tumor had larger side differences
than healthy subjects. Only 20% of the patients with a tumor complained about
impaired olfactory sensitivity, but more than 75% of them showed deficits in
olfactory tests. CONCLUSION: Side differences of odor identification of 25%
or greater should give reason for further investigation. Future studies are
needed to investigate whether side differences in healthy subjects are a predicator
of a higher risk for general olfactory loss.
Kobayashi M, Reiter ER, DiNardo LJ, Costanzo RM. A new clinical olfactory
function test: cross-cultural influence. Arch Otolaryngol Head Neck Surg 2007;133(4):331-6.
OBJECTIVE: To investigate whether a new clinical olfactory test, the Odor
Stick Identification Test for Japanese (OSIT-J), can be used to assess olfactory
function cross-culturally in a US patient population. DESIGN: Cross-sectional
prospective study. SETTING: A university medical center otolaryngology clinic.
PATIENTS: Fifty US patients presenting with complaints of olfactory dysfunction
from December 2004 to January 2006. INTERVENTIONS: Olfactory testing and patient
interview. MAIN OUTCOME MEASURES: Comparison of test results obtained with the
OSIT-J, the Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory
function test, and patients’ self-reported level of olfactory function.
Patients’ opinions regarding the 2 test methods were also recorded. RESULTS:
The mean +/- SD time required to administer the OSIT-J (8 +/- 1 minutes) was
shorter than that required for the standard CCCRC test (21 +/- 6 minutes). Significant
Spearman rank correlations were found between the OSIT-J and CCCRC test scores
(r(s) = 0.80, P<.001, n = 50), and patients’ self-reported level of
olfactory function (r(s) = 0.73, P<.001, n = 50). Although 3 of the 13 odors
used in the OSIT-J were not familiar to US subjects, patients reported that
the OSIT-J was easier, more interesting, and the odors used more pleasant than
the CCCRC test. CONCLUSIONS: Olfactory function tests developed in different
countries should be evaluated to determine if a cross-cultural bias exists among
test odorants. Although a cultural bias was detected for a few odorants, this
study demonstrates that a modified version of the OSIT-J can be used to assess
olfactory function in US patients.
Brämerson A, Nordin S, Bende M. Clinical experience with patients with
olfactory complaints, and their quality of life. Acta Otolaryngol 2007;127(2):167-74.
A special consulting team for patients with olfactory disorders would be
able to verify, describe, and explain the characteristics of the disorders,
also in cases where a patient experiences a disorder, but has a normal sense
of smell. OBJECTIVES. The general purpose of this paper was to present our experience
with patients seeking medical attention for olfactory disorders, and to describe
how quantitative and qualitative olfactory disorders are diagnosed, what the
etiologies are, and how quality of life is compromised in patients with olfactory
disorders. SUBJECTS AND METHODS. This investigation was performed prospectively
over a 10-year period by one physician responsible for the consulting team for
patients with olfactory disorders. Based on a standardized clinical examination,
a structured interview, and assessment of olfactory function, its aim was to
diagnose quantitative and qualitative disorders in 303 consecutive patients.
Health-related quality of life was assessed with the Nottingham Health Profile
(NHP) in about one-third of patients. RESULTS. In the majority of patients,
a reduced sense of smell was found after testing. Often, but not always, this
was combined with qualitative disorders. Dominating etiologies were infections,
nasal polyposis, head trauma, and aging. Patients complaining of olfactory disorders
experience a significantly reduced quality of life regarding the impact of their
health problem on paid employment, household work, and social and family life.
Demarquay G, Ryvlin P, Royet JP. [Olfaction and neurological diseases: a
review of the literature]. Rev Neurol (Paris) 2007;163(2):155-67. [Article in
French]
Olfactory disorders are often misjudged and rarely rated in the clinical
setting. They are nevertheless described in a wide range of neurological disorders,
and their evaluation can be useful for diagnosis. Usually irreversible olfactory
dysfunction is a well-known complication after head trauma. Severe changes in
olfactory tests are observed in Parkinson’s disease. Dysfunction is present
at disease onset and evidenced with all behavioral tests. Regarding other parkinsonian
syndromes, olfactory performances are severely impaired in Lewy body disease,
less pronounced in multiple system atrophy and usually preserved in corticobasal
degeneration. Olfactory deficits are an early feature in Alzheimer’s disease
and worsen with disease progression. Rarely reported by patients, they must
be searched for with olfactory tests. Though epilepsy is mainly known for its
olfactory hallucinatory disorders, alterations of olfactory abilities are also
described, especially in mesial temporal epilepsy. Disorders of olfactory perception
are finally reported in patients with multiple sclerosis and migraine. After
a reminder of anatomical data on the olfactory system, and the different methods
of testing used to rate olfactory performances, the current review focuses on
the type of olfactory dysfunction and damaged brain areas of the olfactory system
encountered in the main neurological diseases.
Turgut B, Turkcuoglu P, Guler M, et al. Anosmia as an adverse effect of dorzolamid. Acta Ophthalmol Scand 2007;85(2):228-9. No abstract available.
Hutton JL, Baracos VE, Wismer WV. Chemosensory dysfunction is a primary
factor in the evolution of declining nutritional status and quality of life
in patients with advanced cancer. J Pain Symptom Manage 2007;33(2):156-65.
Alterations in taste and smell functions have been reported in cancer patients.
Although these senses are known to be particularly affected by chemotherapy,
many features of chemosensory perception in cancer patients remain obscure.
The relative importance of chemosensory changes in the etiology of malnutrition
and wasting is not known. To assess this relationship, self-perceived taste
and smell function were evaluated using a validated questionnaire in 66 patients
with advanced cancer receiving palliative care (median survival 7.4 months).
Participants also completed 3-day food records to assess dietary intake, and
the Functional Assessment of Anorexia/Cachexia Therapy questionnaire to assess
quality of life (QOL). Total chemosensory complaint scores ranged from 0 to
14 on a 16-point scale. Only 14% of the subjects reported no chemosensory complaints
of any kind, whereas 86% reported some degree of chemosensory abnormality. The
most common complaints were persistent bad taste in the mouth, taste distortion,
and heightened sensitivity to odors. Subjects with severe chemosensory complaints
showed substantially lower energy intakes (by 900-1,100 kcal/day), higher rates
of weight loss, and lower QOL scores than subjects with mild or moderate chemosensory
complaints. Severe chemosensory dysfunction is persistent well beyond the window
of active therapy in patients with advanced cancer and represents a primary
factor relating to malnutrition, wasting, and poor QOL. Further research is
required to identify appropriate strategies to alleviate this important group
of symptoms, to determine whether intervention will improve QOL, and to match
foods and diet to the unique chemosensory profile of advanced cancer patients.
Iannilli E, Gerber J, Frasnelli J, Hummel T. Intranasal trigeminal function
in subjects with and without an intact sense of smell. Brain Res 2007;1139:235-44.
The intranasal trigeminal system is involved in the perception of odors.
To investigate the cerebral processing of sensory information from the trigeminal
nerve in detail we studied subjects with and without olfactory function using
functional magnetic resonance imaging. A normosmic group (n=12) was compared
with a group of anosmic subjects (n=11). For trigeminal stimulation gaseous
CO(2) was used. Following right-sided stimulation with CO(2) controls exhibited
a stronger right-sided cerebral activation than anosmic subjects. Stronger activation
was found in controls compared to anosmic subjects for the right prefrontal
cortex, the right somatosensory cortex (SI), and the left parietal insula. In
contrast, relatively higher activation was found in anosmic subjects for the
left supplementary motor area in the frontal lobe, the right superior and middle
temporal lobe, the left parahippocampal gyrus in the limbic lobe, and the sub-lobar
region of the left putamen and right insula which was mostly due to a decreased
BOLD signal of controls in these areas. Additional conjunction analysis revealed
that activated areas common to the two groups were the cerebellum and the right
premotor frontal cortex. These data suggest that the processing of the trigeminally
mediated information is different in the presence or absence of an intact sense
of smell, pointing towards the intimate connection between the two chemosensory
systems.
Trotier D, Bensimon JL, Herman P, et al. Inflammatory obstruction of the
olfactory clefts and olfactory loss in humans: a new syndrome? Chem Senses 2007;32(3):285-92.
The first step in the olfactory perception is the activation by odorants
of sensory neurones in the olfactory epithelium. In humans, this sensory epithelium
is located at 2 narrow passages, the olfactory clefts, at the upper part of
the nasal cavities. Little is known about the physiology of these clefts. We
examined, in 34 patients, the impact of obstructed clefts upon detection and
postlearning identification of 5 odorants. The location and extension of the
obstructions were assessed using endoscopy, CT scans, and MRI. The inflammatory
obstruction was usually bilateral, extending anteroposteriorly, and confined
to the clefts, with no sign of obstruction or any inflammatory disease in the
rest of the nasal cavities and sinuses. When tested with 5 odorants, these patients
showed greatly impaired olfaction compared with a group of 73 normosmic subjects.
The majority of these 34 patients had sensory deficits equivalent to that found
in another group of 41 congenital anosmic patients, where inspection with MRI
indicated the lack of olfactory bulbs. This study demonstrates that the olfactory
clefts, in human, function as an entity that is different from other regions
of the nasal cavity and is the target for local inflammatory events that are
apparently not responding to corticoid and antibiotic treatments.
Katotomichelakis M, Balatsouras D, Tripsianis G, et al. Normative values
of olfactory function testing using the ‘sniffin’ sticks.’ Laryngoscope
2007;117(1):114-20.
OBJECTIVES: Quantitative olfactory assessment is often neglected in clinical
practice, although olfactory loss can assist to diagnosis and may lead to significant
morbidity. “Sniffin’ Sticks” is a modern test of nasal chemosensory
performance that is based on penlike odor-dispensing devices. It consists of
three tests of olfactory function: odor threshold, odor discrimination, and
odor identification. The results of this test may be presented as a composite
threshold-discrimination-identification (TDI) score. The aim of this study was
first to develop normative data of olfactory function for the Greek population
using this test and second to relate olfactory performance to age, sex, and
side examined. STUDY DESIGN: The authors conducted a prospective clinical trial.
METHODS: A total of 93 healthy subjects were included in the study, 48 males
and 45 females, mean age of 44.5 years (range, 6-84 years). RESULTS: A database
of normal values for olfactory testing was established for the Greek population.
Females performed better than males and older subjects performed less efficiently
in all tests. We also found a right nostril advantage compared with the left.
Additionally, scores obtained from bilateral presentation were similar with
scores obtained from the nostril with the better performance. CONCLUSIONS: The
“Sniffin’ Sticks” can be used effectively in the Greek population
to evaluate olfactory performance. Mean values of olfactory tests obtained were
better in comparison with data from settings located in central and northern
Europe.
Rombaux P, Weitz H, Mouraux A, et al. Olfactory function assessed with orthonasal
and retronasal testing, olfactory bulb volume, and chemosensory event-related
potentials. Arch Otolaryngol Head Neck Surg 2006;132(12):1346-51.
OBJECTIVE: To investigate whether differences in olfactory function between
healthy individuals and patients with olfactory loss could be detected by various
diagnostic tests. DESIGN: Psychophysical testing of orthonasal and retronasal
olfactory functions, magnetic resonance imaging of olfactory bulb (OB) volume,
and chemosensory event-related potential (ERP) measurement performed between
January 1, 2005, and October 31, 2005. SETTING: Academic tertiary referral medical
center. PATIENTS: Eleven healthy individuals with normal olfactory function
(NL) and 11 patients with nasal polyposis (NP), 11 with posttraumatic olfactory
loss (PT), and 11 with postinfectious olfactory loss (PI) were included in this
study. MAIN OUTCOME MEASURES: Orthonasal and retronasal olfactory test results,
magnetic resonance imaging-based OB volume, and ERPs to both olfactory and intranasal
trigeminal stimulation. RESULTS: Orthonasal and retronasal testing revealed
that NL individuals had higher scores than patients with NP, PT, or PI. Retronasal
scores were higher in NP patients compared with PT and PI patients. The OB volumes
were higher in NL individuals compared with NP, PT, and PI patients. The OB
volumes in PT patients were significantly lower than those from NP and PI patients.
Olfactory ERPs were different between NL individuals and NP, PT, and PI patients,
and trigeminal ERPs were significantly different when comparing NL individuals
with NP patients. For the entire cohort, a significant correlation was found
between orthonasal testing and OB volume, between retronasal testing and OB
volume, and between both orthonasal and retronasal testing and olfactory ERP
amplitudes. Olfactory ERPs were recorded in the 11 NL individuals and in 3 NP,
3 PT, and 4 PI patients, defined as responders. Orthonasal and retronasal test
scores, OB volume, and olfactory ERPs were significantly larger in responders
compared with nonresponders. CONCLUSIONS: Significant differences in various
tests that evaluate olfactory function were detectable in a cohort of NL individuals
and NP, PT, and PI patients. This finding suggests that these diagnostic tools
provide information in terms of the clinical assessment of olfactory function.
Future studies will investigate their combined use in terms of the prognosis
of olfactory function in patients with olfactory loss.
Frasnelli J, Schuster B, Hummel T. Interactions between Olfaction and the
Trigeminal System: What Can Be Learned from Olfactory Loss. Cereb Cortex 2006
Dec 5; [Epub ahead of print].
The olfactory and the trigeminal systems have a close relationship. Most
odorants also stimulate the trigeminal nerve. Further, subjects with no sense
of smell exhibit a decreased trigeminal sensitivity with unclear underlying
mechanisms. Previous studies indicated that single stages of trigeminal processing
may differently be affected by olfactory loss. A better knowledge of adaptive
and compensatory changes in the trigeminal system of subjects with acquired
anosmia (AA) will improve the understanding of interactive processes between
the 2 sensory systems. Thus, we aimed to assess trigeminal function on different
levels of processing in subjects with AA. Subjects with AA showed larger electrophysiological
responses to irritants obtained from the mucosa than healthy controls. On central
levels, however, they exhibited smaller event-related potentials and psychophysical
measures to irritants. Over 9 months, they exhibited an increase in trigeminal
sensitivity. Subjects with recovering olfactory function showed an even more
increased peripheral responsiveness to irritants. These data suggest dynamic
mechanisms of mixed sensory adaptation/compensation in the interaction between
the olfactory and trigeminal systems, where trigeminal activation is increased
on mucosal levels in subjects with AA and amplified on central levels in subjects
with a functioning olfactory system.
Bonanni E, Borghetti D, Fabbrini M, et al. Quantitative EEG analysis in
post-traumatic anosmia. Brain Res Bull 2006;71(1-3):69-75.
Many objective and quantitative methods have been developed to create a
procedure or a device to prove, describe and quantify olfactory deficit and
anosmia, especially after a head trauma. Electrophysiological testing throughout
olfactoelectroencephalography (olfactoEEG) is based on brain activity desynchronisation,
and on the subsequent disappearance of alpha activity on the posterior regions
after an olfactory stimulus. Yet traditional evaluation of EEG can be difficult,
because of little or hardly detectable alpha activity on the posterior regions
(‘alpha rare’). The aim of this study was to evaluate the Olfactory
Stop Reaction (OSR) by means of frequency band power calculation and subsequent
topographical mapping in patients with post-traumatic anosmia, who presented
‘alpha rare’ EEG. Twenty-five consecutive patients, affected by anosmia
caused by head trauma, were submitted to an EEG recording with olfactory stimulation.
After signal processing and analysis, an Olfactory Stop Reaction was detected
in 17 out of 25 patients; moreover, in these patients we detected a significant
decrease in alpha band power in the occipital regions and an increase in theta
band power on midline frontal and central regions after olfactory stimulation.
In the remaining eight patients, no significant variation in band power was
observed. In conclusion, an objective evaluation of the olfactory function with
this method of automatic EEG signal analysis allows the limits given by psychophysical
methods and traditional EEG to be overcome and attempts to fulfil the requirements
for standardization of olfactory function evalution.
Strous RD, Shoenfeld Y. To smell the immune system: olfaction, autoimmunity
and brain involvement. Autoimmun Rev 2006;6(1):54-60.
Aside from its recognition and warning functions, olfaction serves many
purposes in the CNS and remains one of the most important means of communication
with the environment. In addition to olfactory tract input, the olfactory bulb
also receives and provides input to other brain centers that modify neuronal
activity. Research in the field of immunology as well as in various brain illnesses
is beginning to indicate the increasing relevance of smell in pathophysiology.
Much of this is based on the many intricate interactions that exist between
the immune system and the nervous system, and evidence exists that there may
be something unique about the olfactory system that is inextricably related
to immunological function. In addition, accumulating evidence confirms the existence
of olfactory dysfunction in brain disease, much of which appears at early stages
including multiple sclerosis, Alzheimer’s Disease, Parkinson’s Disease,
schizophrenia and depression. Such observations may further suggest that under
certain circumstances, olfactory abnormalities may be associated with autoimmune
conditions. Since the organization of the olfactory system is so sensitive,
impairment may be noted at an early stage. This may become important in the
prediction of certain brain illnesses. While preliminary evidence may suggest
a role for olfaction in the management and alleviation of various disorders,
investigation of its clinical relevance remains limited.
Verma P, Verma S, Jani P. Overcoming anosmia following total laryngectomy. Clin Otolaryngol. 2006 Oct;31(5):468-9. No abstract available.
