Immunohistochemical method for the diagnosis of olfactory disturbance

To confirm the diagnosis and determine the cause of the olfactory disturbance, we used an immunohistochemical method to examine biopsy specimens of the olfactory mucosa from a patient who complained of anosmia after head injury. Neuron-specific enolase immunoreactivity was found in the olfactory vesicles and dendrites of the receptor cells in the olfactory epithelium. S-100 protein immunoreactivity was found in the ductal cells of Bowman's gland in the olfactory epithelium and in the acinar cells of Bowman's gland in the lamina propria. This suggests that the olfactory receptor cells and Bowman's gland were normal. The olfactory disturbance in this patient was not caused by nerve transection due to the head injury, but by already existing chronic sinusitis. Immunohistochemical methods are useful for diagnosing olfactory disturbance when used in combination with biopsy of olfactory mucosa.     

Clinical observations on parosmia]

We reviewed the clinical records of 15 patients with parosmia examined in our department from April 1987 to September 1990. Seven (29.2%) of 24 patients with olfactory disturbance caused by traumatic injury complained of parosmia. Eight (23.2%) of 34 patients with olfactory disturbance caused by influenza also showed parosmia. The incidence of parosmia between two groups was not statistically significant (p greater than 0.05). Parosmia was observed in none of 42 patients with olfactory disturbance caused by nasal-paranasal diseases. All patients (n:15) always perceived odors as unpleasent. Twelve of them had spontaneous parosmia, and three patients recognized the unpleasant smell when an odor came. In comparison with the auditory system, we speculated that spontaneous parosmia resembles tinnitus. The cause of tinnitus is recognized as a disturbance of the auditory nerve (the first order neuron). Tinnitus is rare in patients with conductive hearing loss, and cases of olfactory disturbance of the "respiratory dysosmia" did not complain of parosmia. Post-traumatic olfactory disturbance is caused by transection of the fila olfactoria, which is part of an olfactory neuron, while post-inflammatory olfactory disturbance is caused by damage to olfactory receptor cells. Furthermore, the fact that the incidence of parosmia between the two groups was not statistically significant suggests the same etiological mechanism in receptor cells. We consider that parosmia is caused by damage to olfactory sensory neurons.     

Measurement of chemosensory function

Although hundreds of thousands of patients seek medical help annually for disorders of taste and smell, relatively few medical practitioners quantitatively test their patients' chemosensory function, taking their complaints at face value. This is clearly not the approach paid to patients complaining of visual, hearing, or balance problems. Accurate chemosensory testing is essential to establish the nature, degree, and veracity of a patient's complaint, as well as to aid in counseling and in monitoring the effectiveness of treatment strategies and decisions. In many cases, patients perseverate on chemosensory loss that objective assessment demonstrates has resolved. In other cases, patients are malingering. Olfactory testing is critical for not only establishing the validity and degree of the chemosensory dysfunction, but for helping patients place their dysfunction into perspective relative to the function of their peer group. It is well established, for example, that olfactory dysfunction is the rule, rather than the exception, in members of the older population. Moreover, it is now apparent that such dysfunction can be an early sign of neurodegenerative diseases such as Alzheimer's and Parkinson's. Importantly, older anosmics are three times more likely to die over the course of an ensuring five-year period than their normosmic peers, a situation that may be averted in some cases by appropriate nutritional and safety counseling. This review provides the clinician, as well as the academic and industrial researcher, with an overview of the available means for accurately assessing smell and taste function, including up-to-date information and normative data for advances in this field.     

Chemosensory function in Wegener’s granulomatosis: a preliminary report

Despite the fact that Wegener’s granulomatosis affects the nasal and paranasal cavities and the cranial nerves regularly, chemosensory impairments have not been reported. The objective of this study is to test the three chemosensory systems, olfaction, taste, and intranasal trigeminal function in Wegener disease patients. We tested olfactory, gustatory, and intranasal trigeminal function in nine patients (5 women, 4 men, mean age 57 years) with confirmed Wegener’s granulomatosis. Olfaction was tested with the Sniffin’Sticks, gustatory function with the “Taste strips” and intranasal trigeminal function with a lateralization task. One patient had anosmia (11%), four patients had hyposmia (44%) and four patients were normosmic (45%). Gustatory testing function showed pathological taste strip results in five patients (55%) and normal results in three patients (33%). One patient did not undergo taste testing. Intranasal trigeminal function was lowered in five patients (56%) and normal in four patients (44%). Neither previous nasal surgery status nor endoscopic status was associated to a higher frequency in pathological scores for any of the three chemical senses. In conclusion, these preliminary results suggest a consistent affection in chemosensory functions in Wegener’s granulomatosis patients.     

Objective screening for olfactory and gustatory dysfunction during the COVID‐19 pandemic: A prospective study in healthcare workers using self‐administered testing

BackgroundSmell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID‐19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID‐19 patients suggests that self‐reported measures are insufficient for capturing patients with chemosensory dysfunction.ObjectivesThe purpose of this study was to quantify the impact of recent COVID‐19 infection on chemosensory function and demonstrate the use of at‐home objective smell and taste testing in an at‐risk population of healthcare workers.MethodsTwo hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self‐administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one‐month follow‐up surveys were completed.ResultsAmong subjects with prior SARS‐CoV‐2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self‐reported smell and taste loss were both strong predictors of COVID‐19 positivity. Subjects with evidence of recent SARS‐CoV‐2 infection (<45 days) had significantly lower olfactory scores but equivalent gustatory scores compared to other subjects. There was a time‐dependent increase in smell scores but not in taste scores among subjects with prior infection and chemosensory symptoms. The overall infection rate was 4.4%, with 2.5% reported by PCR swab.ConclusionHealthcare workers with recent SARS‐CoV‐2 infection had reduced olfaction and normal gustation on self‐administered objective testing compared to those without infection. Rates of infection and chemosensory symptoms in our cohort of healthcare workers reflect those of the general public.     

Clinical study of flavor disturbance

OBJECTIVE: We have observed that, in cases of smell loss, patients often complain of taste loss as well even though they actually have normal gustatory acuity according to gustatory tests; we have defined such symptoms as "flavor disturbance". The clinical features of flavor disturbance are reported in this paper. MATERIAL AND METHODS: A total of 297 patients (99 males, 198 females; mean age 55.5 years) were treated for olfactory disturbance at the hospital of Hyogo College of Medicine between July 1995 and August 2001. Sixty-six out of 297 patients (22.5%) also experienced taste disturbance, and 49 of these 66 cases were evaluated by means of smell and taste tests. These 49 patients who complained of taste and smell loss were classified into two groups according to the results of their smell and taste tests. Patients who only complained of olfactory disturbance were also reviewed. RESULTS: There was no relationship between the severity of olfactory disturbance and the degree of flavor disturbance. The incidence of flavor disturbance was high in patients with sudden olfactory disturbance after upper respiratory tract infection or head trauma and low in those with slowly progressive olfactory disturbance. The symptoms of flavor disturbance improved regardless of whether smell was improved or not. CONCLUSIONS: The patients with flavor disturbance tended to misrecognize that they had taste loss because of sudden smell loss, and there were more of these cases than we expected. When patients with smell and taste loss are treated, flavor disturbance should also be considered.     

Effects of head injury on olfaction and taste

Traumatic events such as motor vehicle accidents, falls, or assaults can lead to dysfunction in olfaction or gustation. Mechanisms of posttraumatic olfactory dysfunction include direct injury to the sinonasal tract or olfactory epithelium, shearing effect on olfactory fibers at the cribriform plate, or brain contusion or intraparenchymal hemorrhage. Posttraumatic gustatory dysfunction is rare, but may occur as a result of direct injury to the tongue, injury to cranial nerves VII or IX, or brain contusion or hemorrhage. Evaluation of head-injured patients presenting with olfactory or gustatory complaints should include a thorough history, including assessment for pre-and posttraumatic chemosensory dysfunction and potential mechanisms of injury, complete head and neck examination including nasal endoscopy and cranial nerve testing, and focused radiographic imaging, usually CT of the sinuses and skull base. Formal olfactory and gustatory testing may be performed using various techniques, although in cases potentially involving litigation, methodologies able to detect malingering should be used. Treatable causes of chemosensory disturbance, most notably conductive olfactory losses caused by chronic rhinosinusitis or nasal obstruction, should be ruled out. In the event of neurosensory deficits, recovery may occur up to 12 to 18 months after the traumatic event. All patients should be counseled regarding the risks of their chemosensory deficits, and given suggestions for appropriate compensatory strategies.     

Effects of drugs on olfaction and taste

The fact that so many varied medications reportedly affect taste and smell is a testament to the complexity of the gustatory and olfactory systems. The reception, transduction, propagation, and perception of a chemical tastant or odorant requires the effective operation of numerous mechanisms--all of which may be susceptible in one way or another to a prescribed medication. Just as a diuretic may block the apical ion channels on a taste bud, or an antifungal can inhibit cytochrome p450-dependent enzymes at the level of the receptors, a chemotherapeutic agent can destroy mitosis in a replicating receptor cell and a steroid can lead to candidal overgrowth on the tongue surface. Medications not only have a perceivable taste themselves at times, but they can alter the mechanisms responsible for the ultimate perception of tastes and smells--either by direct or secondary means. It should be emphasized, as noted earlier in this article, that while many medications are to blame for the impairment or distortion of the gustatory or olfactory systems, it is not uncommon that the underlying medical problem for which they are prescribed is actually the culprit. Examples include epilepsy, migraines, hypothyroidism, schizophrenia, infections, and cancer. In fact, simple partial seizures emanating from regions of the brain such as the amygdala, hippocampus, parietal operculum, and rolandic operculum can lead to the chemosensory sensations that are most commonly considered unpleasant, such as "rotten apples," "cigarette," "peculiar," or "vomitus". While removing or changing an offending medication can reverse the effects on smell or taste perception, it is important to remember that lasting impairment may occur. This is vital for a physician to recognize prior to prescribing a medication. It is also necessary to report this to patients who may be devastated by chemosensory alterations after starting a new medication (eg, pastry chef, perfumist, wine specialist, plumber). Among the "risks" in a risks/benefits discussion with a patient regarding the use of a new medication, alterations in olfaction and taste appear to play an increasingly recognized role.     

Intrinsic chemosensory signal recorded from the human nasal mucosa in patients with smell loss

Physiological investigation of olfactory receptor function in hyposmic or anosmic patients is rare. Pioneers examined the electro-olfactogram in patients with olfactory disturbance. Although the electro-olfactogram is an established method to record olfactory responses from human olfactory epithelium, the response is only measured at specific sites of the olfactory mucosa. In contrast to that the response of the olfactory epithelium to chemosensory stimuli can be studied in a specific nasal area by means of intrinsic optical signal recording. Five functionally anosmic patients were included in the present study. In all patients, responses could be obtained following trigeminal stimulation with CO₂. In some patients, responses could be obtained after olfactory stimulation with H₂S and PEA. The present data show that in the studied patients trigeminal function seems to be preserved, while it appears that in some patients olfactory function is preserved to a certain degree.     

Future directions in chemosensory research

The past two decades have witnessed phenomenal growth in chemosensory research in the basic sciences and clinical studies. Although chemosensory disorders today are recognized more widely for their marked impacts on QOL and public safety, the increased research focus has yet to translate into significant therapeutic advances for human olfactory or gustatory dysfunction. Nevertheless, it should be expected that active chemosensory research eventually will yield discoveries necessary to generate better treatment options for otolaryngologists and other physicians caring for smell and taste loss patients. As the understanding of chemosensory biology and disease pathophysiology grows, there is great promise that medical science will conquer the frustrating and debilitating health problems posed by olfactory and gustatory dysfunction. Moreover, it is likely that the lessons gained through chemosensory research will apply broadly to a range of human diseases affecting sensory modalities and the central nervous system.     

Severe chemotherapy-induced parosmia

BACKGROUND: Smell and taste disorders are among the side effects of chemo- and radiotherapy. Although direct radionecrosis of the salivary glands and the taste buds might explain the chemosensory problems after radiotherapy, the olfactory and gustatory complaints seen after chemotherapy remain unexplained. The patients reporting olfactory symptoms rarely complain about qualitative olfactory disorders such as parosmia or phantosmia. Quantitative olfactory loss such as anosmia and hyposmia seem to be more frequent. METHODS: We present the case of a 63-year-old woman with chemotherapy-induced parosmia leading to severe nutrition and appetite problems resulting in a life-threatening weight loss. RESULTS: With the aid of a simple nose clip the parosmia could be abolished and oral food intake became possible again. Parosmia resolved gradually over an observation period of 9 months, in parallel to an increase of olfactory sensitivity. The patient progressively gained appetite and weight. CONCLUSION: Parosmia can occur as a severe and potentially life-threatening complication of chemotherapy. This rare presentation of parosmia illustrates the importance of olfactory testing with an adequate recognition of the underlying problem and a consecutive treatment.     

Are there sex-related differences in responses to repetitive olfactory/trigeminal stimuli?

Sex differences in olfactory sensitivity have been reported since the late 1800’s with women typically outperforming men on tests of odor detection, discrimination or identification. It is not known whether women adapt differently than men to olfactory and trigeminal stimuli. Seventeen healthy volunteers participated (9 female, 8 male, mean age 22 years) in the study. As established by an odor identification test (UPSIT, score ≥38) all subjects had normal olfactory function. Event-related potentials (ERPs) were recorded in response to olfactory (25% v/v phenyl ethyl alcohol) and trigeminal (44% v/v CO₂) stimuli using a computer controlled olfactometer (flow 8 L/min; stimulus duration 200 ms). Stimuli were applied at four intervals (5, 10, 20, and 60 s). Amplitudes and latencies of ERP peaks P1, N1, and P2 were measured. Stimulus intensity also rated using visual analogue scales subjects. When compared to phenyl ethyl alcohol, the slightly more intense CO₂ produced larger amplitudes and shorter latencies. Both, ratings and ERP amplitudes P2 decreased with decreasing interval between stimuli. Responses to the trigeminal and olfactory stimuli changed similarly in relation to repetitive stimulation. Women had larger ERP amplitudes P2. No sex-related difference for ratings and ERP in relation to repeated stimulation amplitudes was observed. Although women exhibit larger ERP amplitudes to chemosensory stimuli compared to men, the present data indicate on both psychophysical and electrophysiological levels that there is no major difference between young, healthy men and women in relation to short-term adaptation to suprathreshold chemosensory stimulation.     

Prevalence and causes of severe taste loss in a chemosensory clinic population

Although complete or near-complete olfactory loss has been extensively documented and described, few published reports have documented severe generalized gustatory loss (across qualities and neural fields) with rigorous psychophysical testing, and none have explored the prevalence or causes of such losses in a large clinical population. This study retrospectively reviews our chemosensory clinic's experience of 1,176 patients evaluated for complaints of chemosensory dysfunction in order to address these issues. Our series confirms that despite the complex, bilateral innervation and regenerative capacity of the gustatory system, severe generalized taste loss does occur as a clinical entity, albeit rarely: only 0.85% (n = 10) of our patients evidenced such a deficit, as compared to 32% (n = 371) who were found to have a profound olfactory deficit. Combinations of systemic and/or acute events may underlie many cases of severe taste loss, and in half of our cases, these patients evidenced moderate to complete smell loss as well.     

上呼吸道感染后嗅觉障碍患者化学感觉功能评估

目的:观察上呼吸道感染后嗅觉障碍（post-viral olfactory dysfunction,PVOD）患者的嗅觉功能、鼻内三叉神经功能和味觉功能变化,探讨PVOD患者化学感觉功能变化的相关性。方法:回顾性分析2019年1—12月在北京安贞医院耳鼻咽喉头颈外科嗅觉味觉中心就诊的PVOD患者42例,其中男20例,女...     

Evaluation of smell and taste in patients with Wegener’s granulomatosis

Although a reduced olfactory/gustatory function affects patients in all parts of life, this problem has not received much attention in Wegener’s granulomatosis (WG). The aim of this study was to assess the smell/taste function of WG patients. Demographic data of 16 WG patients (9 males, 7 females) were obtained. They all subjectively assessed their taste/smell function on visual analogue scale. Olfactory/gustatory functions of the patients were tested with ‘Sniffin’ Sticks and ‘Taste’ strips, respectively. The results were then compared with those from sex and age-matched control group (n = 16) and normative data. WG patients subjectively assessed their olfactory (p = 0.03) and gustatory (p = 0.02) function to be lower than control group. All the olfactory scores (odour identification, odour discrimination and threshold) in both genders were significantly below the scores in the control group. WG patients were hyposmic. For taste (total taste score, as well as scores for the qualities sweet, sour, salty and bitter), WG patients did not significantly differ from controls and were normogeusic. However, the gustatory scores showed the tendency of reduction as compared to the control group. In conclusion, WG patients truly suffer from olfactory/taste dysfunction, but this is worse with olfaction. It is, therefore, imperative that physicians should make their patients to be aware of these sensory dysfunctions and educate them on methods to cope with it for better quality of life.     

Olfactory impairment and Parkinson's disease-like symptoms observed in the common marmoset following administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

OBJECTIVE: Although olfactory disturbance appears to occur in the early stages of Parkinson's disease (PD) in humans, little is known about its mechanism. The aim of this study was to make a PD model using injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset and to discover the mechanism of olfactory disturbance in this animal. MATERIAL AND METHODS: Olfactory disturbance induced by MPTP in the common marmoset was observed by behavioral, biochemical and immunohistochemical means. RESULTS: Administration of MPTP caused common marmosets to enter an akinetic state within a few days and to show signs of impaired olfactory function. Biochemical study showed a decrease in dopamine levels, especially in tissue samples from the caudate nucleus and putamen. Immunohistochemical analysis revealed a lack of tyrosine hydroxylase immunoreactivity, not only in the substantia nigra, caudate nucleus and putamen but also in the olfactory tubercle. CONCLUSION: These results demonstrate that MPTP causes both PD-like symptoms and olfactory disturbance in the common marmoset. The olfactory disturbance observed in these animals may be due to the lack of dopamine in the olfactory tubercle.     

Objective assessment of terbinafine-induced taste loss

OBJECTIVES: Terbinafine (Lamisil), a widely prescribed oral antifungal agent, reportedly induces taste loss in 0.6% to 2.8% of those taking the drug. However, many so-called taste problems reflect olfactory problems, and the sole empirical study published on this topic, based on whole-mouth testing of a single subject, found no terbinafine-related deficit. In this study, we quantitatively assessed, using well-validated taste and smell tests, chemosensory function in six patients complaining of taste disturbance after terbinafine treatment and compared their test scores to those of six age-, race-, and sex-matched normal controls. METHODS: Taste function was measured using a 96-trial regional test that assesses sweet, sour, bitter, and salty taste perception within the anterior (cranial nerve [CN] VII) and posterior (CN IX) lingual taste bud fields. Smell function was bilaterally evaluated using the 40-item University of Pennsylvania Smell Identification Test. RESULTS: Taste function for sweet-, sour-, and bitter-tasting stimuli was significantly depressed in both the anterior and posterior lingual regions. For sodium chloride, the decrements were confined to the posterior region. Olfactory function was within normal limits. CONCLUSION: These findings 1) support anecdotal case reports of taste loss after terbinafine use, 2) demonstrate that all four major taste qualities are affected, and 3) suggest that olfactory dysfunction is not involved. Because self-report markedly underestimates chemosensory deficits, more extensive quantitative testing of patients receiving terbinafine will likely reveal a much higher prevalence of terbinafine-induced taste loss than currently reported. Since being older than 65 years of age and having a low body mass index are reportedly risk factors for terbinafine-induced taste loss, physicians should be particularly on the alert for elderly persons taking this medication who may become depressed or alter their food intake in response to decreased taste sensation.     

Fish-odor syndrome presenting as dysosmia

We describe a patient who had perceived an unpleasant odor or taste for at least 20 years. Several other physicians had unsuccessfully treated her for infections, mucus membrane dryness and inflammation, chronic tonsillitis, and psychiatric disorders. Her workup at the State University of New York Health Science Center at Syracuse Olfactory Referral Center included a thorough history, examinations (including endoscopic studies of her nose, pharynx, and lungs), roentgenograms, taste testing, olfactory testing, and selective anesthesia of her chemosensory areas. The perception occurred only during exhalation, and appeared to be binasal. These findings, together with her morning mucus sample having a strong fishlike odor, prompted us to suspect a metabolic problem. Further testing at the Monell-Jefferson Chemosensory Clinical Research Center, Philadelphia, Pa, confirmed that she had trimethylaminuria. It is important to consider this and other treatable conditions when evaluating individuals with olfactory complaints.