Phantosmia during proton radiation and differences in frequency of phantosmia rates based on proton craniospinal irradiation technique for pediatric brain tumor patients.

BACKGROUND: Unusual olfactory perception, often referred to as "phantosmia" or "cacosmia" has been reported during brain radiotherapy (RT), but is infrequent and does not typically interfere with the ability to deliver treatment. We seek to determine the rate of phantosmia for patients treated with proton craniospinal irradiation (CSI) and identify any potential clinical or treatment-related associations. METHODS: We performed a retrospective review of 127 pediatric patients treated with CSI, followed by a boost to the brain for primary brain tumors in a single institution between 2016 and 2021. Proton CSI was delivered with passive scattering (PS) proton technique (n = 53) or pencil beam scanning technique (PBS) (n = 74). Within the PBS group, treatment delivery to the CSI utilized a single posterior (PA) field (n = 24) or two posterior oblique fields (n = 50). We collected data on phantom smell, nausea/vomiting, and the use of medical intervention. RESULTS: Our cohort included 80 males and 47 females. The median age of patients was 10 years (range: 3-21). Seventy-one patients (56%) received concurrent chemotherapy. During RT, 104 patients (82%) developed worsening nausea, while 63 patients (50%) reported episodes of emesis. Of those patients who were awake during CSI (n = 59), 17 (29%) reported phantosmia. In the non-sedated group, we found a higher rate of phantosmia in patients treated with PBS (n = 16, 42%) than PS (n = 1, 4.7%) (p = .002). Seventy-eight patients (61%) required medical intervention after developing nausea/vomiting or phantosmia during RT. Two patients required sedation due to the malodorous smell during CSI. We did not find any significant difference in nausea/vomiting based on treatment technique. CONCLUSION: Proton technique significantly influenced olfactory perception with greater rates of phantosmia with PBS compared to PS. Prospective studies should be performed to determine the cause of these findings and determine techniques to minimize phantosmia during radiation therapy.

Characteristics of higher depressive tendency in the patients with olfactory disorder.

OBJECTIVE: Most patients with olfactory dysfunction experience stress and anxiety because of the inconvenience and changes caused by the loss of olfaction. However, psychological assessment is not performed routinely in patients with olfactory dysfunction, and the characteristics of these patients with psychological depression are unclear. METHODS: In this study, we used the Self-rating Depression Scale to evaluate the degree of depression in patients who visited our clinic with olfactory dysfunction and examine the characteristics of these patients with strong depressive tendencies. Patients who visited our clinic between April 2019 and March 2020 with complaints of olfactory dysfunction were included in the study. RESULTS: A total of 180 patients (79 male and 101 female) underwent olfactory examination and completed the Self-rating Depression Scale. Eighty-six and 94 patients were included in the low depression and high depression groups, respectively. Binomial logistic regression analysis showed significant positive associations of Self-rating Depression Scale scores with female sex and the presence of parosmia/phantosmia (p < 0.05). CONCLUSION: In our study, approximately half of the patients with olfactory dysfunction had depressive tendencies especially in female and parosmia/phantosmia patients. We believe that psychological assessments, such as that with the SDS, can help identify patients with olfactory dysfunction who may be at a greater risk of developing depression.

Abnormal visual and olfactory sensations during radiation therapy: a prospective study.

PURPOSE: Patients sometimes report phosphene and phantosmia during radiation therapy (RT). However, the detail features and related factors are not well understood. Our prospective study aimed to investigate the characteristics of phantosmias and phosphenes, to identify factors that influence the occurrence, intensity and hedonic (pleasantness/unpleasantness) ratings of such sensations during RT. METHODS: We included a total of 106 patients (37 women), who underwent RT in regions of the brain, ear, nose, throat (ENT), and other areas of the body for a duration of 43 ± 5 days. Medical history and treatment parameters were collected in a structured medical interview. Olfactory function was measured using the Sniffin' Stick Odor Identification Test at baseline. Phantosmia and phosphene were recorded weekly based on a self-report questionnaire. RESULTS: There were 37% of the patients experiencing phantosmias, 51% experiencing phosphenes, and 29% simultaneously experiencing both sensations. Phosphenes were typically perceived as a flashily blue, white and/or purple light, phantosmias were typically perceived as a chemical-like, metallic or burnt smell. Younger age (F = 7.81, p < 0.01), radiation in the brain region (χ2 = 14.05, p = 0.02), absence of taste problems (χ2 = 10.28, p = 0.01), and proton RT (χ2 = 10.57, p = 0.01) were related to these abnormal sensations. History of chemical/dust exposure predicted lower intensity (B = -1.52, p = 0.02) and lower unpleasantness (B = 0.49, p = 0.03) of phantosmia. In contrast, disease (tumor) duration (B = 0.11, p < 0.01), food allergy (B = 2.77, p < 0.01), and epilepsy (B = -1.50, p = 0.02) influence phosphenes intensity. Analgesics intake predicted a higher pleasantness of the phosphenes (B = 0.47, p < 0.01). CONCLUSIONS: Phantosmias and phosphenes are common during RT. The treatment settings and individual arousal level influence the occurrence, intensity and hedonic of such abnormal sensations. Phantosmias and phosphenes may involve more central neural than peripheral mechanism, and they could be elicited with activation of areas that are not regarded to be part of the olfactory or visual network.

Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19-related olfactory disorders.

It is estimated that 20%-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of 4 possible odors. Those who completed the test (N = 287) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder only (anosmia or hyposmia, N = 135), qualitative olfactory disorder only (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia, and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

Phantom smells: a prevalent COVID-19 symptom that progressively sets in.

PURPOSE: One of the long-term symptoms of COVID-19 is phantosmia, a type of Olfactory Disorder (OD) that has deleterious impacts on patients' quality of life. The aim of this article was to study how this poorly understood qualitative OD manifests itself in the COVID-19. METHODS: 4691 patients with COVID-19 responded to our online questionnaire focusing on COVID-19-related OD. We first analyzed the prevalence of phantosmia in this population. Then, with the help of Natural Language Processing techniques, we investigated the qualitative descriptions of phantom smells by the 1723 respondents who reported phantosmia. RESULTS: The prevalence of phantosmia was of 37%. Women were more likely to report phantosmia than men, as well as respondents for whom OD was described as fluctuating rather than permanent, lasted longer, was partial rather than total and appeared progressively rather than suddenly. The relationship between OD duration and phantosmia followed a logarithmic function, with a prevalence of phantosmia increasing strongly during the first 2 months of the disease before reaching a plateau and no decrease over the 15 months considered in this study. Qualitative analyses of phantosmia descriptions with a sentiment analysis revealed that the descriptions were negatively valenced for 78% of the respondents. Reference to "tobacco" was more frequent in non-smokers. Source names and odor characteristics were used differently according to age and OD duration. CONCLUSION: The results of this descriptive study of phantosmia contribute to the current efforts of the medical community to better understand and treat this rapidly increasing COVID-19-related OD.

Recovery from 3 Years of Daily Olfactory Distortions after Short-Term Treatment with GABA-Analogue.

This case report describes a healthy 47-year-old man with a 3 years history of daily unpleasant olfactory distortions with severe negative effects on the quality of life. The distorted smoke-like smell occurred every day and was most prominent in the evenings resulting in severe discomfort as the patient felt suffocated by the smoke when falling asleep. The distorted smell had no odour triggers and was classified as phantosmia. Patient history, nasal endoscopy, neurological and otolaryngological examination, depression screening, cognitive testing, and CT scan revealed no obvious aetiology, resulting in the diagnosis of idiopathic phantosmia. Quantitate olfactory function was normal. Based on anecdotal evidence in the literature, the patient was treated with a GABA-analogue (pregabalin 50 mg × 3) for 4 weeks. During this treatment, the olfactory distortions completely disappeared for the first time in 3 years and had not reoccurred after 7 months of follow-up. GABA-analogues may be a potential treatment for some of the patients suffering from olfactory distortions. While this constitutes a single case report without controls and phantosmia can disappear spontaneously, there is no proof of causality. However, given the long duration of symptoms, temporal relationship with treatment on the sudden disappearance of phantosmia, and long follow-up without recurrence, this highlights the need for further studies on GABA-analogues as a potential treatment of idiopathic phantosmia. Consequently, larger studies and systematic evaluation of potential effects in different patient groups are warranted before routine treatment with GABA-analogues is advised.

Olfactory Nomenclature: An Orchestrated Effort to Clarify Terms and Definitions of Dysosmia, Anosmia, Hyposmia, Normosmia, Hyperosmia, Olfactory Intolerance, Parosmia, and Phantosmia/Olfactory Hallucination.

BACKGROUND: Definitions are essential for effective communication and discourse, particularly in science. They allow the shared understanding of a thought or idea, generalization of knowledge, and comparison across scientific investigation. The current terms describing olfactory dysfunction are vague and overlapping. SUMMARY: As a group of clinical olfactory researchers, we propose the standardization of the terms "dysosmia," "anosmia," "hyposmia," "normosmia," "hyperosmia," "olfactory intolerance," "parosmia," and "phantosmia" (or "olfactory hallucination") in olfaction-related communication, with specific definitions in this text. KEY MESSAGES: The words included in this paper were determined as those which are most frequently used in the context of olfactory function and dysfunction, in both clinical and research settings. Despite widespread use in publications, however, there still exists some disagreement in the literature regarding the definitions of terms related to olfaction. Multiple overlapping and imprecise terms that are currently in use are confusing and hinder clarity and universal understanding of these concepts. There is a pressing need to have a unified agreement on the definitions of these olfactory terms by researchers working in the field of chemosensory sciences. With the increased interest in olfaction, precise use of these terms will improve the ability to integrate and advance knowledge in this field.

Establishing UK research priorities in smell and taste disorders: A James Lind alliance priority setting partnership.

OBJECTIVES: To determine the top 10 research priorities in Smell and Taste Disorders (SATD). DESIGN: After steering group was established, an electronic survey was disseminated to determine the list of questions. After removing out-of-scope responses, the remainder were consolidated to create summary questions. A literature search was conducted to remove already answered questions. A second survey was used to determine the top questions that formed the subject of final debate at a workshop attended by clinicians and patients to determine the top 10 priorities. SETTING: A James Lind Alliance Priority Setting Partnership (JLAPSP) was established by FifthSense to identify the top 10 research questions in SATDs in the United Kingdom. PARTICIPANT: All stakeholders in SATDs (patients, healthcare professionals, family, carers, researchers). MAIN OUTCOME MEASURES: Final 10 research priorities. RESULTS: The 665 respondents to the initial survey provided 1698 research questions. Thirteen were out-of-scope and removed; remaining 1685 were then consolidated to form 147 summary questions. Following literature search and discussion with the steering group, 37 questions remained for the second survey, which 235 people responded. The top ten priorities agreed upon in the workshop covered themes of improved understanding of pathophysiologlogy, improving health services, and managing long-term effects of smell/taste disorders. The most important research question agreed was "How can we further our understanding of the mechanism of disease in the nerve pathways that affect smell and taste disorders, including where parosmia and phantosmia exist." CONCLUSION: We report the top 10 research priorities in smell and taste disorders. These priorities will now empower researchers to secure research funding and provide the basis of the FifthSense research hub.

A New Mystery: Phantosmia after COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) has developed as a pandemic and has caused millions of deaths worldwide. Multiple studies have implicated anosmia and ageusia as symptoms associated with COVID-19. In this case report we present the cases who suffer from phantosmia after COVID-19 infection. As the prevalence of the virus increases, the symptomatology profile continues to be updated. More studies are needed to better understand this disease.

Consequences of gaining olfactory function after lifelong anosmia.

We present a rare case in which a patient has gained her smell after lifelong anosmia. The patient was objectively tested and diagnosed with functional anosmia at age 13 and reported they were experiencing a new sensation of smell at age 22. Our results show an electrophysiological signal for two unimodal odorants. The patient had a retronasal score in the hyposmic range and self-reported the ability to smell non-trigeminal odors, but reported being disturbed by the presence of the new sense and co-occurrence of phantosmia. We discuss our case in routes of neurogenesis and non-forming memory association with odors.

Apparently Minor Head Trauma Can Lead to Anosmia: A Case Report.

We report the case of a 49-year-old female patient who suffered from anosmia following an apparently mild head trauma when bumping into a door at her home. She reported no other accompanying symptoms after the injury that day. Olfactory function was completely lost, which was noted the day after the trauma. Gustatory function remained normal. Magnetic resonance imaging indicated lesions/bleeding in the right frontal lobe and in the area of the olfactory sulcus/bulb. The present case indicates that in case of apparently mild head trauma with anosmia, an MRI scan of the head should be performed because of suspect brain damage. This case also points to the deeper question how to gauge severity of head trauma.

Phantosmia as the first presentation of a cavernous sinus - clinoidal meningioma.

Cavernous sinus meningiomas (CSM) are complex skull base lesions that, due to their particular anatomical location, render surgical management difficult. Their symptomatology is versatile, and the clinical outcome is difficult to predict. We present the case of a 57-year old female patient who experienced phantosmia - an abnormal, persistent, olfactory sensation of cigarette smell for 18 months. MRI was performed and revealed a left cavernous sinus meningioma, extending into the left temporal fossa, with olfactory and optic nerve distortion. To our knowledge, this is the first reported case of phantosmia as the initial presentation of a lesion in the cavernous sinus.

An unmet need: Patients with smell and taste disorders.

OBJECTIVES: There are large numbers of patients with olfactory disturbance in the UK and shortfalls in assessment and support amongst mainstream practice in both primary and secondary care leading to significant quality-of-life impairment and potential missed diagnoses. The aim of this study was to determine the key themes which can be identified from the accounts of anosmia sufferers and to identify important areas to target for future research or service development. DESIGN: Qualitative analysis of written patient accounts from patients corresponding with a tertiary smell and taste clinic in the UK. This qualitative study utilised unstructured written patient accounts from consenting patients experiencing olfactory disturbances received by the smell and taste clinic. Framework analysis was performed using Nvivo 10 software. SETTING: Tertiary smell and taste clinic. PARTICIPANTS: Consenting patients who contacted the smell and taste clinic with accounts of their experiences. MAIN OUTCOME MEASURES: Themes generated by qualitative analysis with Nvivo software. RESULTS: Accounts submitted by 71 participants were included in the analysis; age range 31-80 years, 45 females, 26 males. Themes identified include negative emotional impact, feelings of isolation, impaired relationships and daily functioning, impact on physical health and the difficulty and financial burden of seeking help. CONCLUSIONS: Olfactory disturbances have a wide-ranging impact on the lives of sufferers, compounded by a lack of knowledge of the disorder amongst clinicians. There is a role for further support and education both for sufferers and for clinicians, as well as a need to improve our understanding of olfactory disturbance.

The Association Between Diabetes and Olfactory Function in Adults.

Diabetes is a significant chronic disease that in limited studies has been linked with olfactory dysfunction. We investigated the cross-sectional association between diabetes and olfactory dysfunction in 3151 adults aged ≥40 years who participated in US National Health and Nutrition Examination Survey 2013-2014 with information on olfactory dysfunction and diabetes. Diabetes was defined from fasting serum glucose ≥126 mg/dL, oral glucose tolerance test ≥200 mg/dL, HbA1c levels ≥6.5%, physician-diagnosed diabetes, or current use of oral hypoglycemic agents and/or insulin. Self-reported olfactory dysfunction was defined as a positive answer to any of the following questions: 1) "Have you had problem with smell in the past 12 months?"; 2) "Have you had a change in the ability to smell since age 25?", or 3) "Do you have phantom smells?". Participants were considered to have severe hyposmia or anosmia if they had <5 correct answers in the 8-item pocket smell test. Analyses were adjusted for the main confounders, including olfactory dysfunction risk factors. Compared to non-diabetics, diabetics under insulin treatment showed a higher prevalence of phantom odors [OR(95% CI): 2.42 (1.16; 5.06)] and a non-significant higher prevalence of severe hyposmia/anosmia [OR(95% CI): 1.57 (0.89; 2.78)]. Amongst diabetics, there was a significant trend to severe hyposmia/anosmia for those on more aggressive treatments [OR (95% CI) including oral and insulin treatment compared to those who reported no use of drug treatment, respectively: 1.33 (0.60; 2.96) and 2.86 (1.28; 6.40); P trend 0.01]. No association was observed between diabetes duration and prevalence of olfactory dysfunction.

Phantom Smells: Prevalence and Correlates in a Population-Based Sample of Older Adults.

Loss of olfactory function is common in old age, but evidence regarding qualitative olfactory dysfunction in the general older population is scarce. The current study investigates the prevalence and correlates of phantom smell experiences (phantosmia) in a population-based study (Swedish National Study on Aging and Care in Kungsholmen [SNAC-K]) of Swedish adults (n = 2569) aged between 60 and 90 years. Phantosmia was assessed through a standardized interview and defined as reporting having experienced an odor percept in the absence of any stimuli in the surrounding environment that could emit the odor. The relationships between phantosmia and demographic, genetic, health-related, and behavioral variables were analyzed with hierarchical logistic regression analyses. The overall prevalence of phantom smells was 4.9%, and was associated with female gender, carrying the met allele of the BDNF gene, higher vascular risk burden, and reporting distorted smell sensations (parosmia). Olfactory dysfunction was, however, not related to phantosmia. The most frequently reported phantom smell was smoky/burnt. A novel finding was that some individuals reported phantom smells with an autobiographical connotation. The results from this study indicate that the prevalence of phantosmia in the general older population is not negligible and that some factors that are beneficial for preserved olfactory function, such as female gender and the BDNF met allele, are also associated with the occurrence of phantom smells.

Prevalence and Risk Factors of Self-Reported Smell and Taste Alterations: Results from the 2011-2012 US National Health and Nutrition Examination Survey (NHANES).

Chemosensory problems challenge health through diminished ability to detect warning odors, consume a healthy diet, and maintain quality of life. We examined the prevalence and associated risk factors of self-reported chemosensory alterations in 3603 community-dwelling adults (aged 40+ years), from the nationally representative, US National Health and Nutrition Examination Survey (NHANES) 2011-2012. In this new NHANES component, technicians surveyed adults in the home about perceived smell and taste problems, distortions, and diminished abilities since age 25 (termed "alterations"), and chemosensory-related health risks and behaviors. The prevalence of self-reported smell alteration was 23%, including phantosmia at 6%; taste was 19%, including dysgeusia at 5%. Prevalence rates increased progressively with age, highest in those aged 80+ years (smell, 32%; taste, 27%). In multivariable logistic regression, controlling for sociodemographics, health behaviors, and chemosensory-related conditions, the strongest independent risk factor for smell alteration was sinonasal symptoms (odds ratio [OR] = 2.06; 95% confidence interval [CI]: 1.63-2.61), followed by heavy drinking, loss of consciousness from head injury, family income ≤110% poverty threshold, and xerostomia. For taste, the strongest risk factor was xerostomia (OR = 2.65; 95% CI: 1.97-3.56), followed by nose/facial injury, lower educational attainment, and fair/poor health. Self-reported chemosensory alterations are prevalent in US adults, supporting increased attention to decreasing their modifiable risks, managing safety/health consequences, and expanding chemosensory screening/testing and treatments.

Phantosmia and Migraine With and Without Headache.

Phantosmia is a rare migraine aura. We present two cases of phantosmias occurring before migraine headaches and also without headaches. To our knowledge, these are the third and fourth cases of phantosmias ever reported due to migraine aura without headache.

The impact of olfactory disorders in the United kingdom.

Olfactory disorders are believed to affect 5% of the general population and have been shown to bear significant psychosocial consequences to sufferers. Although more common than blindness and profound deafness in the United Kingdom, the impact of these disorders has not been assessed to date and the plight of British patients has yet to be quantified. In 2012, a patient support organization, Fifth Sense, was founded to provide information and support to sufferers of chemosensory disorders. Following a recent members conference, a survey of the membership was conducted anonymously using a series of questions based on an existing olfactory disorders questionnaire. From 496 respondents, this has demonstrated high rates of depression (43%) and anxiety (45%), impairment of eating experience (92%), isolation (57%), and relationship difficulties (54%). Women appear to have significantly more issues than men in terms of social and domestic dysfunction relating to olfactory loss (P = 0.01). Qualitative disorders also affected more than 1 in 5 members with parosmia reported in 19% and phantosmia in 24%. This paper discusses the details of the British story of anosmia and other related disorders as depicted by those most affected.

Comparison of Patient Characteristics and Olfactory Sensitivity for Trigger Odorants in Parosmia and Phantosmia.

OBJECTIVES: This study aimed to determine the characteristics of patients with qualitative olfactory dysfunction (qualOD) and whether individuals with parosmia exhibit increased olfactory sensitivity to previously reported odorous triggers of parosmia. METHODS: This study included individuals aged ≥18 years, divided into quantitative OD only, parosmia, and phantosmia groups. Data collected included: clinical-demographic data, "Sniffin' Sticks" scores, questionnaires (depression scale, importance of olfaction), and information about parosmia and phantosmia. A proportion of patients underwent trigger odor threshold testing for 2-Furfurylthiol [FFT] found in coffee and 2,6-nonadienal [Nonadienal] found in cucumber. RESULTS: Those with parosmia were typically younger women, with shorter OD duration due to post-viral OD (PVOD), hyposmic/normosmic, and experienced parosmia more severely. Parosmia was 3.5 times more likely in PVOD. Those with phantosmia were older, with longer OD duration due to idiopathic OD, hyposmic/anosmic, and experienced phantosmia less severely. There were no significant differences between FFT and Nonadienal threshold scores in patients with parosmia, phantosmia, or only quantitative OD, but all groups had significantly increased olfactory sensitivity for trigger odors compared to phenyl ethyl alcohol (PEA). CONCLUSION: Parosmia and phantosmia patients have distinct characteristics. This may provide clinicians with a better understanding of possible olfactory outcomes in these patients. The higher olfactory sensitivity of all groups to trigger odors compared to PEA raises interesting points about parosmia triggers and odors in the context of warning for danger, in relation to the pathophysiology of parosmia that may be worth exploring in future studies. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3277-3285, 2024.

The Prognostic Value of Olfactory Dysfunction in Patients with COVID-19: The COVIDORA Study.

BACKGROUND: Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between olfac-tory dysfunction (OD) and the evolution of disease severity. The main aim was to assess whether OD is a predictive factor of COVID-19 severity based on the patient's medical management (outpa-tient care, standard hospital admission, and ICU admission). METHODS: A national, prospective, mul-ticenter cohort study was conducted in 20 public hospitals and a public center for COVID-19 screen-ing. During the first wave of the pandemic, from 6 April to 11 May 2020, all patients tested positive for COVID-19 confirmed by RT-PCR underwent two follow-up ENT consultations within 10 days of symptom onset. The main outcome measures were the evolution of medical management (out-patient care, standard hospital admission, and ICU admission) at diagnosis and along the clinical course of COVID-19 disease. RESULTS: Among 481 patients included, the prevalence of OD was 60.7%, and it affected mostly female patients (74.3%) under 65 years old (92.5%), with fewer comor-bidities than patients with normal olfactory function. Here, 99.3% (290/292) of patients with OD presented with non-severe COVID-19 disease. Patients reporting OD were significantly less hospi-talized than the ones managed as outpatients, in either a standard medical unit or an ICU. Conclu-sions: As regards the clinical course of COVID-19 disease, OD could predict a decreased risk of hospitalization during the first wave of the pandemic.