Alexander TH, Davidson TM. Intranasal zinc and anosmia: the zinc-induced anosmia syndrome. Laryngoscope 2006;116:217-20.
OBJECTIVE: Commercial preparations of intranasal zinc gluconate gel are marketed as a remedy for the common cold. However, intranasal zinc has been reported as a cause of anosmia in humans and animals. Seventeen patients presenting with anosmia after the use of intranasal zinc gluconate are described. METHODS: The authors conducted a retrospective case series of patients presenting to a nasal dysfunction clinic and conducted complete history and physical examination on all patients, including nasal endoscopy. All patients underwent detailed odor threshold and identification testing. RESULTS: Threshold and identification testing revealed impaired olfaction in all patients. Inflammatory and traumatic causes of anosmia were excluded based on history, physical examination, and imaging. All patients diagnosed with zinc-induced anosmia or hyposmia reported sniffing deeply when applying the gel. This was followed by an immediate sensation of burning lasting minutes to hours. Loss of sense of smell was then perceived within 48 hours. Seven of 17 patients never developed symptoms of an upper respiratory infection. CONCLUSIONS: The zinc-induced anosmia syndrome, characterized by squirt, sniff, burn, and anosmia, occurs after the exposure of olfactory epithelium to zinc cation. It can be distinguished from postviral anosmia based on history.

Wise JB, Moonis G, Mirza N. Magnetic resonance imaging findings in the evaluation of traumatic anosmia. Ann Otol Rhinol Laryngol 2006;115:124-7.
OBJECTIVES: Head trauma is a common cause of anosmia, but diagnosis is typically late, owing to more life-threatening sequelae of the injury. Herein, we describe our workup for a case of traumatic anosmia and the magnetic resonance imaging (MRI) findings both at the time of injury and at the 18-month follow-up. METHODS: We present a case report and a review of the literature. RESULTS: A 33-year-old woman presented to our institution with a chief complaint of loss of smell and taste following an occipital blow to her head that occurred when she was hit by a car while riding a bicycle. We present the findings of MRI performed at the time of the injury and at the 18-month follow-up. We describe the clinical progression of her disease, from symptoms of parosmic and phantosmic episodes accompanied by dysgeusia to total anosmia at the 18-month follow-up. CONCLUSIONS: We advocate the use of MRI, coupled with otolaryngology consultation and formal olfactory testing, in the diagnosis, management, and counseling of patients with anosmia sustained from head injury.

Salerno-Kennedy R, Cusack S, Cashman KD. Olfactory function in people with genetic risk of dementia. Ir J Med Sci 2005;174:46-50.
BACKGROUND: Screening for sensorial impairment is a secondary objective in the context of neurodegenerative diseases, including dementias. For example, olfactory dysfunction is among the first signs of Alzheimer's disease.There has been no study of olfactory function in Irish subjects at risk of dementia. AIM: To investigate olfactory function in non-demented Irish persons, who carry genetic risk factors for dementia. METHODS: Thirty-eight Irish adult subjects, who are at risk of dementia, were recruited. Cognitive performance and olfactory function were assessed and apolipoprotein E (APOE) genotype determined. RESULTS: Three and six subjects had a Mini Mental State Examination (MMSE) and Brief Smell Identification Test (B-SIT) score, respectively, outside the normal range. While five out of the fifteen epsilon-4 allele positive subjects had B-SIT scores outside the normal range, only one out of the twenty-three epsilon-4 allele negative subjects had; the difference in this frequency was significant (P=0.025). There was no significant difference (P=0.266) in the frequency of abnormal MMSE scores between epsilon-4 allele groups. CONCLUSION: Further investigation is required to explore the reasons for the higher prevalence of olfactory dysfunction in epsilon-4 allele positive subjects.

Jackman AH, Doty RL. Utility of a three-item smell identification test in detecting olfactory dysfunction. Laryngoscope 2005;115:2209-12.
OBJECTIVE: Physicians rarely assess smell function, largely because of time considerations. Therefore, there is clinical need for very brief cranial nerve I screening tests. Although a few such tests exist, none have been adequately validated. The goal of this study was to empirically assess the utility of a three-item microencapsulated odor identification test in detecting olfactory dysfunction. SETTING: Smell and taste center at a university medical center. METHODS: The test was administered to 224 consecutive patients (98 men and 126 women ranging in age from 15-88 years). As part of their overall assessment, the well-validated 40-item University of Pennsylvania Smell Identification Test (UPSIT) was also administered. Sensitivity, specificity, and both negative and positive predictive values of the three-item test were established relative to UPSIT dysfunction categories. Test-retest reliability was determined in a subset of 39 patients. RESULTS: The three-item test was abnormal in 99% (67/68) of patients with anosmia, 85% (35/41) of those with severe microsmia, 76% (31/41) of those with moderate microsmia, and 50% (17/34) of those with mild microsmia. Of the 40 normosmic patients, 62.5% (25/40) correctly identified all odors, 25% (10/40) two odors, and 12.5% (5/40) one odor. None of the normosmic patients missed all three items. Using a cut-off score of 2, the test’s sensitivity and specificity were 99% and 40%, respectively, for detecting total anosmia. The corresponding negative and positive predictive values were 98% and 43%. For detecting anosmia and severe microsmia, these values were 93%, 45%, 88%, and 63%. For detecting any olfactory pathology, they were 82%, 63%, 42%, and 91%. The test-retest reliability was 0.87. CONCLUSION: The brief three-item test used in this study was found to be highly sensitive in identifying olfactory loss in patients with chemosensory complaints, particularly those with severe dysfunction. Although only moderately specific, its high reliability and negative predictive value suggests it may be an appropriate screening test for olfactory loss.

Landis BN, Frasnelli J, Reden J, et al. Differences between orthonasal and retronasal olfactory functions in patients with loss of the sense of smell. Arch Otolaryngol Head Neck Surg 2005;131:977-81.
OBJECTIVE: To investigate differences between orthonasal and retronasal olfaction in patients with loss of the sense of smell without taste complaints. DESIGN: Electrophysiological and psychophysical testing of orthonasal and retronasal olfactory functions. SETTING: Outpatient clinics. PATIENTS: A series of 18 patients who had olfactory loss due to various reasons but no taste complaints. MAIN OUTCOME MEASURES: Orthonasal and retronasal olfactory functions assessed by olfactory event-related potentials and psychophysical smell tests. RESULTS: Psychophysical testing revealed retronasal olfaction to be normal or slightly altered, whereas orthonasal olfaction was either absent or severely compromised. Findings from nasal endoscopic examinations and computed tomographic scans were within the reference range in all subjects. In response to orthonasal stimulation there were neither detectable olfactory event-related potentials nor any with small amplitudes, whereas olfactory event-related potentials in response to retronasal stimulation were clearly present in some patients. CONCLUSION: These clinical observations, together with the psychophysical and electrophysiological findings, suggest that orthonasal and retronasal olfaction might be processed differently.

Ishimaru T. [Recent clinical trends in smell disorder] No To Shinkei 2005;57:659-66. [Article in Japanese.] No abstract available.

Eibenstein A, Fioretti AB, Lena C, et al. Modern psychophysical tests to assess olfactory function. Neurol Sci 2005;26:147-55.
The sense of smell significantly contributes to quality of life. In recent years much progress has been made in understanding the biochemistry, physiology and pathology of the human olfactory system. Olfactory disorders may arise not only from upper airway phlogosis but also from neurodegenerative disease. Hyposmia may precede motor signs in Parkinson's disease and cognitive deficit in Alzheimer’'s disease. These findings suggest the complementary role of olfactory tests in the diagnosis and management of neurodegenerative diseases. In this report we present a review of modern olfactory tests and their clinical applications. Although rarely employed in routine clinical practice, the olfactory test evaluates the ability of odour identification and is a useful diagnostic tool for olfaction evaluation. Olfactory screening tests are also available. In this work we strongly recommend the importance of an ENT evaluation before the test administration and dissuade from a self-administration of an olfactory test.

Landis BN, Knecht M, Huttenbrink KB, et al. [Clinical aspects of dysosmia and presentation of European Olfactory Test of sniffin’ sticks: a review.] J Otolaryngol 2005;34:86-92. [Article in French]
The medical community has neglected olfactory dysfunction for a long time. However, over the last two decades, remarkable progress has been made in terms of understanding the sense of smell and both the assessment and diagnosis of olfactory dysfunction. Currently, there are only a few validated olfactory tests. The most commonly used one is the University of Pennsylvania Smell Identification Test. Owing to its cultural biases, this test is mostly used in the United States. Sniffin’ Sticksare one of the first European tests to be widely used. Since their development in 1996, they have been applied in numerous studies and have found increasing use in otolaryngology clinics. The goal of this article is to present Sniffin’ Sticks and to provide a review of clinical olfactory research during recent years.

Aiba T, Inoue Y, Matsumoto K, et al. Magnetic resonance imaging for diagnosis of congenital anosmia. Acta Otolaryngol Suppl 2004;(554):50-4.
Magnetic Resonance Imaging (MRI) was performed on 9 patients who lacked a sense of smell since birth. Seven of them, including two patients with Kallmann syndrome, exhibited abnormality of the olfactory bulb, olfactory tract, olfactory sulcus, or rectus gyrus, with some variation among patients in type and degree of abnormality. The other two patients exhibited normal olfactory pathway morphology, and for them the possibility of acquired sensorineural anosmia could not be ruled out. MRI is useful for determining whether patients with congenital anosmia have olfactory pathway anomalies. Many patients with congenital anosmia and hypoplasty or aplasty of the olfactory pathway nevertheless had no gonadal or endocrinological disorders.

Blomqvist EH, Bramerson A, Stjarne P, Nordin S. Consequences of olfactory loss and adopted coping strategies. Rhinology 2004;42:189-94.
The aims of this study were to investigate the effects of loss of smell as regards the quality of life and the coping strategies used. METHODS: Seventy-two patients with anosmia (46%) or hyposmia (54%) filled in the validated Multi-Clinic Smell and Taste Questionnaire, the validated General Well-being Schedule (GWBS), and answered other questions shown to be of good validity. RESULTS: Several kinds of negative effects, risks associated with the loss, interference with daily routines and deteriorations in well-being were common. Physical health, financial security, profession, partnership, friendship, emotional stability and leisure were also deemed to be negatively affected and GWBS scores show compromised psychological well-being. The importance of olfaction seemed to be more noticeable after the loss of smell, and several kinds of problem- and emotion-focused coping strategies were adopted by these patients. CONCLUSIONS: We found that the loss of smell had substantial adverse effects on the quality of life and that high priority should be given to its diagnosis and treatment and to further research in this field. Furthermore, a combination of problem- and emotion-focused coping strategies may be suggested to patients who have recently lost the sense of smell.

Kern RC, Conley DB, Haines GK 3rd, Robinson AM. Treatment of olfactory dysfunction, II: studies with minocycline. Laryngoscope 2004;114:2200-4.
OBJECTIVES/HYPOTHESIS: The treatment of anosmia has changed minimally since the early 1970s, despite dramatic advances in the understanding of the molecular biology of olfaction. Recent studies from the authors’ laboratory have suggested that most common causes of clinical olfactory dysfunction, including rhinosinusitis, appear to be associated with increased apoptotic death of olfactory sensory neurons. This appears to result in a decline in the number of functioning mature olfactory sensory neurons, despite the capacity of the olfactory epithelium for regeneration. The current study evaluated the ability of the antibiotic minocycline to inhibit olfactory sensory neuron apoptosis. This drug is known to inhibit apoptosis separate from its anti-infective properties. Olfactory sensory neuron apoptosis was triggered by surgical deafferentation (“bulbectomy”), the standard experimental model. Earlier studies have indicated that bulbectomy and sinusitis invoke similar proteolytic enzyme cascades in olfactory sensory neurons. STUDY DESIGN: Histological analysis of animal olfactory tissue. METHODS: Mice underwent unilateral olfactory bulbectomy to induce apoptotic olfactory sensory neuron death, with and without 45 mg/kg intraperitoneal minocycline given 12 hours before surgery and every 12 hours until death. Mice were killed at 2 and 4 days after bulbectomy and assessed for activation of capsase-3 and olfactory sensory neuron survival by immunohistochemical analysis. RESULTS: Minocycline resulted in partial suppression of cell death at 2 days after surgery when compared with untreated animals. CONCLUSION: Minocycline inhibits olfactory sensory neuron death in the face of a potent pro-apoptotic stimulus. This drug is well tolerated and is currently undergoing human trials for the management of a variety of neurological disorders associated with apoptosis. The current results suggest that minocycline may be efficacious in the management of peripheral olfactory loss as well.

Benvenuti S, Ranvaud R. Olfaction and the homing ability of pigeons raised in a tropical area in Brazil. J Exp Zoolog A Comp Exp Biol 2004;301:961-7.
Several workers have investigated the effect of anosmia on pigeon navigation in different geographical locations because it has been suggested that homing behavior is based on different cues, such as olfactory cues, the Earth’s magnetic field or infrasound, and that in the absence of one cue another would be used. In this situation, no cue is universally indispensable, including olfactory ones. In order to extend such observations to a novel biome, we observed the behaviour of 192 young inexperienced birds raised in southeastern Brazil, a tropical area where olfactory tests had never been run before. The birds were released from eight symmetrically distributed sites 17 to 44 km from the loft. Half of these birds (experimentals) had been made temporarily anosmic by washing their olfactory mucosae with 4% solution of ZnSO4 the day before release, while controls were treated with Ringer solution. The results of release tests showed that anosmia totally impaired the navigational performance of experimental birds, which were unable to home from sites at relatively short distances from home (34-44 km) and whose pooled initial bearings produced a (negative) homeward component not significantly different from 0. Homing performance of controls was significantly better, and their pooled vanishing bearings had a significant homeward component, in spite of much scatter in individual releases. We conclude that pigeon homing in the study area depends on olfactory information, even though local environmental conditions in the interior of the State of Sao Paulo, as in several other parts of the world, do not appear to be as favorable as Italy for the development of efficient olfactory navigation.

Woodley SK, Baum MJ. Differential activation of glomeruli in the ferret’s main olfactory bulb by anal scent gland odours from males and females: an early step in mate identification. Eur J Neurosci 2004;20:1025-32.
Peripheral anosmia was previously found to disrupt sex discrimination and partner preference in male and female ferrets. Here we show directly that volatile anal scent gland odourants from male and female ferrets activated overlapping but distinguishable clusters of glomeruli located in the ventral-caudal portion of the main olfactory bulb (MOB) of breeding ferrets of both sexes. No glomerular activation was seen in the accessory olfactory bulb (AOB). The profile of MOB glomerular activation induced in oestrous females by male anal scents was very similar to that induced by direct contact with a male during mating, and oestrogen treatment failed to alter the profile of glomerular activation induced in ovo-hysterectomized females by male anal scents. In rodents, ‘atypical’ MOB glomeruli, which have dense acetylcholinesterase (AChE) activity in the neuropil, may be activated by body odours from conspecifics. No such AChE-staining ‘atypical’ glomeruli were found in the ferret’s MOB, suggesting that in this carnivore they do not constitute a subset of MOB glomeruli that respond to body odourants. In ferrets of both sexes, volatile body odourants that are detected by the main as opposed to the vomeronasal-AOB accessory olfactory system may play a critical role in mate identification.

Forster G, Damm M, Gudziol H, et al. [Testing the sense of smell using validated procedures] Z Arztl Fortbild Qualitatssich 2004;98:279-81. [Article in German]
There is a growing interest into the investigation of smell disorders in both research and clinical practice. For psychophysical (“subjective”) investigations related to the sense of smell a variety of test kits are available, namely the various “Sniffin’ Sticks” kits, the UPSIT (University of Pennsylvania Smell Identification Test) or the CCSIT (Cross-Cultural Smell Identification Test). Recording of olfactory evoked potentials (OEPs) and respiration olfactometry can be used for diagnosing smell dysfunctions in a more objective way.

Nishida K, Kobayashi M, Adachi M, et al. [A case report on congenital anosmia] Nippon Jibiinkoka Gakkai Kaiho 2004;107:665-8. [Article in Japanese]
We report 2 cases of congenital anosmia, in a 13-year-old girl and the other in a 10-year-old boy. They reported having no concept of smell. The girl has no complications but the boy has congenital microphthalmia and is completely blind. They showed scale-out results on both T & T olfactometry and intravenous Alinamin test. Brain MRI detected hypoplasia or lack of the olfactory bulbs, tracts, and olfactory sulci in the frontal lobe of the brain in both patients. Neither had endocrinal dysfunction. In the boy, we biopsied the nasal mucosa in the olfactory cleft and found it had no olfactory epithelial cells at all. We found MRI to be the most useful imaging for diagnosing congenital olfactory disturbance.

Ghadami M, Majidzadeh-A K, Morovvati S, et al. Isolated congenital anosmia with morphologically normal olfactory bulb in two Iranian families: a new clinical entity? Am J Med Genet 2004;127A:307-9.
Congenital total loss of the sense of smell occurs as a part of a syndrome or isolated anosmia. Kallmann syndrome is the most well known congenital anosmia associated with hypogonadotropic hypogonadism. Isolated congenital anosmia (ICA) is a very rare condition and appears to be due to changes in the olfactory epithelium or to aplasia of the olfactory nerve, bulb, and tract. Here we report two unrelated Iranian families with ICA. One family consisted of nine affected members, and the other family contained three affected members. Clinical history, physical examination, and smell testing by intravenous injection of combined vitamins (Alinamin trade mark, Takeda Pharmaceutical Co. Ltd., Japan) confirmed the disease in each affected member. No signs of hypogonadism or other neurological disorders were observed in any affected members. Family analysis with the complete ascertainment method under assumption of the same condition in the two families suggested that the disease is not inconsistent with an autosomal dominant mode with incomplete penetrance. The inheritance in one family appears unusual, i.e., there were no affected individuals in the third generation. When only two upper generations in the family are concerned, the segregation ratio was 0.39 +/- 0.11. Male-to-male transmissions were observed and both sexes were affected in both families. Magnetic resonance imaging (MRI) of the olfactory bulb and sulcus revealed no evidence of morphological changes in all affected members, suggesting that these patients have either a defect in the olfactory epithelium or a functional defect in the olfactory cortex.

Bonfils P, Malinvaud D, Bozec H, Halimi P. Olfactory disorders. Ann Otolaryngol Chir Cervicofac 2004;121:67-74.[Article in French]
Smell and taste problems are of major importance to those who suffer from olfactory disorders. The inability to determine the presence of odors in the home and the markedly reduced capacity or incapacity to appreciate food flavors are key reasons given for limited social interaction. Patients experiencing distorted smells and tastes may avoid food, which results in weight loss and possible malnutrition. We present an overview of smell disorders, based on physiological considerations, with specific attention to clinical characteristics of conditions most commonly causing smell disorders.

Bramerson A, Johansson L, Ek L, et al. Prevalence of olfactory dysfunction: the Skovde population-based study. Laryngoscope 2004;114:733-7.
OBJECTIVES/HYPOTHESIS: Patients with olfactory dysfunction appear repeatedly in ear, nose, and throat practices, but the prevalence of such problems in the general adult population is not known. Therefore, the objectives were to investigate the prevalence of olfactory dysfunction in an adult Swedish population and to relate dysfunction to age, gender, diabetes mellitus, nasal polyps, and smoking habits. STUDY DESIGN: Cross-sectional, population-based epidemiological study. METHODS: A random sample of 1900 adult inhabitants, who were stratified for age and gender, was drawn from the municipal population register of Skovde, Sweden. Subjects were called to clinical visits that included questions about olfaction, diabetes, and smoking habits. Examination was performed with a smell identification test and nasal endoscopy. RESULTS: In all, 1387 volunteers (73% of the sample) were investigated. The overall prevalence of olfactory dysfunction was 19.1%, composed of 13.3% with hyposmia and 5.8% with anosmia. A logistic regression analysis showed a significant relationship between impaired olfaction and aging, male gender, and nasal polyps, but not diabetes or smoking. In an analysis of a group composed entirely of individuals with anosmia, diabetes mellitus and nasal polyps were found to be risk factors, and gender and smoking were not. CONCLUSION: The sample size of the population-based study was adequate, with a good fit to the entire population, which suggests that it was representative for the Swedish population. Prevalence data for various types of olfactory dysfunction could be given with reasonable precision, and suggested risk factors analyzed. The lack of a statistically significant relationship between olfactory dysfunction and smoking may be controversial.

Mann NM, Lafreniere D. Anosmia and nasal sinus disease. Otolaryngol Clin North Am 2004;37:289-300, vi.
Smell loss associated with nasal sinus disease can be a frustrating condition for patients and their physicians. A better understanding of the causes and pathophysiology of olfactory dysfunction can provide a framework from which the physician can plan appropriate treatment and counsel patients as to probable outcomes. This article reviews the pathophysiology of smell loss and the diagnostic paradigms and treatment approaches for the more common causes of anosmia.

Kovacs T. Mechanisms of olfactory dysfunction in aging and neurodegenerative disorders. Ageing Res Rev 2004;3:215-32.
Although olfaction is the primal sense in animals, its importance in humans is underappreciated. Extensive literature demonstrates that aging is accompanied by olfactory loss and hyposmia/anosmia which is also a feature of several neurodegenerative disorders. Alzheimer's and Parkinson's diseases are characterized by severe olfactory deficits, while problems of olfactory discrimination are less prominent features in several other disorders. Olfactory loss is accompanied by structural abnormalities of the olfactory epithelium, the olfactory bulb and the central olfactory cortices. This review summarizes our present knowledge about the pathological changes in the olfactory system during aging and in various neurodegenerative diseases.

Kern RC, Conley DB, Haines GK 3rd, Robinson AM. Pathology of the olfactory mucosa: implications for the treatment of olfactory dysfunction. Laryngoscope 2004;114:279-85.
OBJECTIVE: The pathology of the olfactory mucosa is poorly understood; however, most cases of hyposmia and anosmia appear to be associated with a decline in the number of functioning mature olfactory sensory neurons (OSNs). Under normal conditions, OSNs undergo apoptotic cell death at a baseline rate likely secondary to their exposed location in the nose. Regeneration of mature OSNs from precursors in the epithelium allows the animal to maintain an adequate number of neurons necessary for olfactory sensation. In many cases of olfactory dysfunction, this balance is apparently disturbed, with a net loss of OSNs. The current study will examine normal and diseased olfactory tissue for the presence of data demonstrating that the preferred mechanism of OSN cell death is apoptotic in both health and disease. The potential therapeutic implications will be discussed. STUDY DESIGN: Histologic analysis of human and animal olfactory tissue. METHODS: Normal and diseased human and animal olfactory mucosa were assessed for immunohistochemical evidence of apoptosis. RESULTS: Increased activity of the apoptotic effector enzyme caspase-3 was demonstrated in diseased olfactory mucosa in comparison with normal controls. CONCLUSION: These results indicate that a common pathway may mediate OSN cell death from a diverse set of pathologic insults including aging, trauma, and sinusitis. Interference with this pathway of cell death is currently the subject of intense pharmacotherapeutic research for the management of stroke and meningitis. These drugs may ultimately prove useful in the treatment of clinical olfactory dysfunction.

Michael W. Anosmia treated with acupuncture. Acupunct Med 2003;21:153-4.
This is a report detailing the successful treatment of a case of anosmia with acupuncture. The patient was managed conventionally for two years with no sign of improvement. She regained the sense of smell following one session of acupuncture. Such patients should be investigated for any detectable organic cause prior to treatment with acupuncture.

Welge-Luessen A, Wolfensberger M. Reversible anosmia after amikacin therapy. Arch Otolaryngol Head Neck Surg 2003;129:1331-3.
Olfactory disorders are among the rare adverse effects of antibiotic therapy. To date, olfactory losses or distortions have been reported after the use of doxycycline, amoxicillin, clarithromycin, roxithromycin, kanamycin sulfate, and streptomycin sulfate. We describe what we believe to be the first case of transient anosmia associated with the use of intravenous amikacin sulfate. The appearance of the disorder and its subsequent resolution were demonstrated by psychometric testing as well as by chemosensory evoked potentials. Based on the well-documented temporal course of the anosmia, there is a probable causal correlation between the administration of amikacin and the appearance of the olfactory disturbance. However, the exact pathogenesis of the anosmia is still a matter of conjecture.

Holbrook EH, Leopold DA. Anosmia: diagnosis and management. Curr Opin Otolaryngol Head Neck Surg 2003;11:54-60.
Disorders of the sense of smell can be frustrating for both the patient and physician. Ongoing research in this field has provided insight into the possible mechanisms for smell loss; however, therapy is still limited. Commercially distributed smell testing kits and newer screening tests using material available in all clinical settings have made diagnosis and measurement of the degree of impairment available to all physicians. A detailed history and physical examination are the most powerful tools in the evaluation of smell disorders, whereas imaging studies are reserved for preoperative planning or detailed assessment of positive physical findings.

Greisen O, Lambertsen K. [Congenital anosmia]. Ugeskr Laeger 2003;165:2399-400. [Article in Danish]
A 72-year-old woman with congenital familiar lack of smell is described. General ENT and otoneurological examination were normal. The ability to smell was totally absent. By MR scan normal conditions were found in the nose, paranasal sinuses, the cribriform plate in the anterior cranial fossa and in the brain especially in the olfactory bulbs. Microscopic examinations of biopsy specimens from the olfactory region showed no signs of olfactory epithelium.

McBride K, Slotnick B, Margolis FL. Does intranasal application of zinc sulfate produce anosmia in the mouse? An olfactometric and anatomical study. Chem Senses 2003;28:659-70.
Mice pre-trained in an olfactometer were tested daily on odor detection and discrimination tasks after irrigation of their olfactory epithelium in each naris with 50 micro l of 5% zinc sulfate or saline. Anterograde transport of a wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) conjugate from the epithelium to the olfactory bulb was used to assess anatomical connectivity in these and in mice that were used only for histological analyses. One day after treatment, saline controls performed at high levels of accuracy in detecting vapor from solutions of 5-0.01% ethyl acetate and in an odor discrimination task but most ZnSO(4)-treated mice performed at chance for 5-30 days before showing recovery. Although dense WGA-HRP reaction product was found in the accessory olfactory bulb, there was little or no evidence for axonal transport to glomeruli of the main olfactory bulb in the first 4-8 days after treatment. These results demonstrate that intranasal application of ZnSO(4) to mice produces a brief but essentially total disruption of functional connections from the olfactory epithelium to the main olfactory bulb and a corresponding transient anosmia.

Mann NM. Head injury and anosmia. Conn Med 2003;67:545-7.
Anosmia is a frequent complication of head injury. One hundred eighty-one patients with head trauma and accompanying smell impairment were examined in the University of Connecticut Chemosensory Clinic from 1986 to 2002. The literature is reviewed.

Hummel T, Futschik T, Frasnelli J, Huttenbrink KB. Effects of olfactory function, age, and gender on trigeminally mediated sensations: a study based on the lateralization of chemosensory stimuli. Toxicol Lett 2003;140-141:273-80.
The present investigation aimed to compare trigeminal nasal function of anosmic and hyposmic patients to healthy controls. Further, we aimed to study effects of age and gender on trigeminally mediated sensations following intranasal chemosensory stimulation. Participants were 35 patients with olfactory dysfunction (n=13: functional anosmia; n=22: hyposmia; age 28-69 years, mean age 56 years). Their results were compared with 17 normosmic subjects (28-82 years, mean 52 years). To analyze effects of age and gender in healthy subjects, an additional 24 healthy subjects were included (19-27 years; mean 24 years). Olfactory function was assessed using the ‘Sniffin’ Sticks’ test kit (butanol odor threshold, odor discrimination, odor identification). The subjects’ ability to lateralize odors was investigated for benzaldehyde and eucalyptol. Patients with olfactory dysfunction had lower scores in the lateralization task than controls (P<0.001) indicating decreased trigeminal sensitivity. Among anosmic patients scores were not different in relation to different causes of olfactory dysfunction (P>0.29). There was a weak, but significant, correlation between localization of eucalyptol and duration of olfactory dysfunction (P=0.017). When investigating normosmic subjects only, no gender-related difference was apparent for lateralization scores. However, older subjects had lower scores than younger ones (P<0.01). Results of partial correlational analyses controlling for age suggested a relation between the trigeminal and the olfactory systems. In conclusion, results of the present study indicate that patients with olfactory dysfunction have lower trigeminal sensitivity compared with normosmic controls. This seems to be independent of the cause of olfactory loss. The deficit appears to improve with duration of the olfactory dysfunction, possibly indicating adaptive mechanisms. Further, the data suggest an age-related decrease of intranasal trigeminal sensitivity in healthy subjects. Analyses additionally indicate a correlation between olfactory and trigeminal sensitivity.

Malaspina D, Coleman E. Olfaction and social drive in schizophrenia. Arch Gen Psychiatry 2003;60:578-84.
BACKGROUND: The neurobiology of social dysfunction in schizophrenia is unknown, but smell identification deficits (SIDs) exist in schizophrenia, and olfaction is related to social affiliation in other mammals. The SIDs have been linked with negative symptoms and the deficit syndrome, but any specificity of SIDs for social dysfunction is unstudied. Low intelligence might explain this relationship, if it is associated with both negative symptoms and SIDs. We examined whether SIDs in schizophrenia were related broadly to negative symptoms, as are a number of other neuropsychological measures, or whether they might show a more specific relationship with social drive. METHODS: Smell Identification Test scores, Wechsler Adult Intelligence Scale-Revised IQ, symptomatology assessed with the Positive and Negative Syndrome Scale, and the deficit syndrome were determined in 70 patients with DSM-IV schizophrenia. RESULTS: The SIDs were related to negative symptoms and the deficit syndrome, but the association of SIDs with diminished social drive explained both relationships. Smell identification was also related to Wechsler Adult Intelligence Scale-Revised IQ, but intelligence was independent of the relationship of SID and social drive. The worse Smell Identification Test scores in male patients were attributable to a greater preponderance of men with the deficit syndrome. CONCLUSIONS: These analyses demonstrated independent relationships of Smell Identification Test scores to social drive and intelligence that together accounted for almost 50% of the variance in Smell Identification Test scores. There may be common neural substrates for the low social drive and SIDs in schizophrenia.

Hawkes C. Olfaction in neurodegenerative disorder. Mov Disord 2003;18:364-72.
There has been an increase of interest in olfactory dysfunction since it was realised that anosmia was a common feature of idiopathic Parkinson's disease (PD) and Alzheimer-type dementia (AD). It is an intriguing possibility that the first sign of a disorder hitherto regarded as one of movement or cognition may be that of disturbed smell sense. In this review of PD, parkinsonian syndromes, essential tremor, AD, motor neurone disease (MND) and Huntington's chorea (HC) the following observations are made: 1) olfactory dysfunction is frequent and often severe in PD and AD; 2) normal smell identification in PD is rare and should prompt review of diagnosis unless the patient is female with tremor-dominant disease; 3) anosmia in suspected progressive supranuclear palsy and corticobasal degeneration is atypical and should likewise provoke diagnostic review; 4) hyposmia is an early feature of PD and AD and may precede motor and cognitive signs respectively; 5) subjects with anosmia and one ApoE-4 allele have an approximate 5-fold increased risk of later AD; 6) impaired smell sense is seen in some patients at 50% risk of parkinsonism; 7) smell testing in HC and MND where abnormality may be found, is not likely to be of clinical value; and 8) biopsy of olfactory nasal neurons shows non-specific changes in PD and AD and at present will not aid diagnosis.

Temmel AF, Quint C, Schickinger-Fischer B, et al. Characteristics of olfactory disorders in relation to major causes of olfactory loss. Arch Otolaryngol Head Neck Surg 2002;128:635-41.
OBJECTIVE: To investigate the consequences of olfactory loss and explore specific questions related to the effect of duration of olfactory loss, degree of olfactory sensitivity, and cause of the olfactory loss. PATIENTS: A total of 278 consecutive patients with hyposmia or anosmia were examined. RESULTS: Causes of olfactory loss were categorized as follows: trauma (17%), upper respiratory tract infection (URI) (39%), sinonasal disease (21%), congenital anosmia (3%), idiopathic causes (18%), or other causes (3%). Our data suggest that (1) recovery rate was higher in URI olfactory loss than in olfactory loss from other causes; (2) likelihood of recovery seemed to decrease with increased duration of olfactory loss; and (3) the elderly are more prone to URI olfactory loss than younger patients. Regarding changes in quality of life (QoL), we found that (1) in most patients olfactory loss caused food-related problems; (2) loss in QoL did not change with duration of olfactory loss; (3) younger patients had more complaints than older ones, and women had more complaints than men; (4) complaint scores were higher in hyposmic patients than in anosmic patients; and (5) self-rated depression did not relate to measured olfactory function. CONCLUSIONS: Among many complaints of olfactory loss, the predominant ones were food related. This loss in QoL seemed to be of greater importance in younger than in older people, and women seem to be affected more strongly than men.

Thomas HJ, Fries W, Distel H. [Evaluation of olfactory stimuli by depressed patients] Nervenarzt 2002;73:71-7. [Article in German]
Anhedonia, a cardinal sign of depression, is discussed to originate from a transmitter dysbalance in the central dopaminergic reward system. This system involves neuroanatomically many structures of the olfactory system. Hence the question arises whether anhedonia can be quantified when depressive patients judge smells hedonically. Sensory evaluation of olfactory stimuli by 16 depressive patients was compared that of an age-matched control group. In the group comparison, mono- and birhinal sensory thresholds as well as judgment of intensity were not significantly different. For four of the eight smells, the hedonic judgments were found to be identical between the group of depressives and controls, with the remaining smells not significantly different. There were no differences in the consistency of ranking of smells. In a longitudinal (test-retest) assessment there were again no differences in intensity, familiarity, and hedonic quality of the smells. The findings suggest that changes in the dopaminergic transmitter balance during the state of depression causing anhedonia affect neither olfactory perception nor the hedonic judgement of smells. Contrary to the clinical picture, anhedonia thus seems not to arise at the level of sensory perception yet but should be considered a more complex construct of disturbed central processing.

Mann NM. Management of smell and taste problems. Cleve Clin J Med 2002;69:329-36.
Lost or impaired smell or taste should be taken seriously, as it puts a person at higher risk for toxic exposures, such as gas leaks, smoke, and rotting food, and it also takes away the enjoyment of some of life’s pleasures, such as the fragrance of flowers or the taste of good food or fine wine. In many patients, the loss follows a viral upper respiratory tract infection, and the only real treatment is to reassure patients that the problem may resolve if the damaged sensory cells regenerate. In other patients, the loss has more subtle causes and deserves a careful investigation and appropriate treatment. This article reviews the proper steps to take when investigating and treating chemosensory difficulties.

Murphy C, Schubert CR, Cruickshanks KJ, et al. Prevalence of olfactory impairment in older adults. JAMA. 2002;288:2307-12.
CONTEXT: Older adults represent the fastest-growing segment of the US population, and prevalences of vision and hearing impairment have been extensively evaluated. However, despite the importance of sense of smell for nutrition and safety, the prevalence of olfactory impairment in older US adults has not been studied. OBJECTIVE: To determine the prevalence of olfactory impairment in older adults. DESIGN, SETTING, AND PARTICIPANTS: A total of 2491 Beaver Dam, Wis, residents aged 53 to 97 years participating in the 5-year follow-up examination (1998-2000) for the Epidemiology of Hearing Loss Study, a population-based, cross-sectional study. MAIN OUTCOME MEASURES: Olfactory impairment, assessed by the San Diego Odor Identification Test and self-report. RESULTS: The mean (SD) prevalence of impaired olfaction was 24.5% (1.7%). The prevalence increased with age; 62.5% (95% confidence interval [CI], 57.4%-67.7%) of 80- to 97-year-olds had olfactory impairment. Olfactory impairment was more prevalent among men (adjusted prevalence ratio, 1.92; 95% CI, 1.65-2.19). Current smoking, stroke, epilepsy, and nasal congestion or upper respiratory tract infection were also associated with increased prevalence of olfactory impairment. Self-reported olfactory impairment was low (9.5%) and this measure became less accurate with age. In the oldest group, aged 80 to 97 years, sensitivity of self-report was 12% for women and 18% for men. CONCLUSIONS: This study demonstrates that prevalence of olfactory impairment among older adults is high and increases with age. Self-report significantly underestimated prevalence rates obtained by olfaction testing. Physicians and caregivers should be particularly alert to the potential for olfactory impairment in the elderly population.

Ho TP, Carrie S. Congenital anosmia. Int J Clin Pract 2001;55:418-419.
We present two cases demonstrating congenital anosmia. In both cases, magnetic resonance imaging (MRI) has served to highlight an interesting clinical oddity. To date, there has only been one study of the use of MRI in the assessment of patients with congenital anosmia who do not have Kallmann's syndrome.

Kurosawa K. [Anosmia, congenital]. Ryoikibetsu Shokogun Shirizu 2001;:207-8. [Article in Japanese] No abstract available.

Saini S, Barr H, Bessant C. Sniffing out disease using the artificial nose. Biologist 2001;48:229-33.
Is there information in the odours that we emit and that circulate around us? More importantly, can doctors gain knowledge of disease by smelling their patients? Machines that emulate the mammalian nose have picked up the scent of several diseases and may drastically change diagnostic procedure.

Page one

Page three