Olfactory dysfunction decreased local field potential in the reward system and increased EtOH consumption in mice.

The relationship between olfactory dysfunction and alcohol intake is unobvious. Chronic alcohol intake results in reduced olfactory acuity and olfactory discrimination and addiction in humans. However, alcohol is a beverage with distinctive odors, which usually works as a cue to induce addictive memories and craving behavior. Whether olfactory impairment increase or decrease alcohol consumption remains an important but unclear issue. In this study, we measured ethanol (EtOH) consumption in the two-bottle choice EtOH drinking test, two bottle choice EtOH/sucrose drinking test and the drinking in the dark (DID) test during the olfactory loss. We also recorded local field potentials (LFPs) from the brain reward system, the ventral tegmental area (VTA), nucleus accumbens (NAc), and piriform cortex (Pir) one and four weeks after the induction of olfactory epithelium lesions using zinc sulfate (ZnSO4) in mice. The results showed that the EtOH consumption and preference were increased during the period of olfactory dysfunction. 1 week after the olfactory injury, LFP powers in the reward system at low- and high-gamma bands decreased significantly, coherence between the Pir and the reward system was also decrease. 4 weeks after the ZnSO4 treatment, LFP powers were reversed, but the coherence between VTA and NAc was decreased, indicating lasting effects post-recovery. This study demonstrates that olfactory dysfunction increased EtOH consumption in mice, which was accompanied by decreased LFP power and coherence in the reward system, which suggest that olfactory deficits changed activities in the reward system and could alter reward-seeking behaviors, which provide insights into the neurobiology of alcohol addiction.

The Effect of Platelet-Rich Plasma and Hyaluronic Acid Nasal Injections in the Treatment of Traumatic Olfactory Dysfunction.

Objective: Platelet-rich plasma (PRP) has been injected into the olfactory cleft to treat olfactory dysfunction related to coronavirus disease 2019. In this study, we aimed to evaluate the effect of PRP combined with hyaluronic acid (HA) nasal injection in the treatment of traumatic olfactory dysfunction. Methods: Patients who had lost olfactory function after experiencing head trauma and were willing to receive PRP and HA nasal injections for treatment were enrolled. Before nasal injection, 10 cc of blood was drawn from the patients. The drawn blood was injected into a centrifuge tube for processing, and finally, 5 cc of the PRP mixed with HA was drawn out using an empty syringe. The PRP mixed with HA was injected into the upper part of the middle nasal septum and the medial side of the middle turbinate of the patient's nasal cavity under a nasal endoscope. The olfactory function of each patient was evaluated by the phenyl ethyl alcohol (PEA) odor detection threshold test before and at both 1 and 3 months after nasal injection and the traditional Chinese version of the University of Pennsylvania Smell Identification Test at 3 months after nasal injection. Results: A total of 28 patients received PRP and HA nasal injections between August and December of 2023 and came back for evaluation of the effect. In all, 20 (71.4%) patients felt their olfactory function improved 1 month after injection, and 24 of 28 (85.7%) patients reported their olfactory function improved at 3 months after injection. The bilateral or unilateral PEA threshold decreased in 22 (78.6%) patients 1 month after injection, and decreased in 15 (53.6%) patients 3 months after injection. Conclusions: Our results show that PRP and HA nasal injections were associated with favored patient-reported outcomes and improved the olfactory threshold in the treatment of traumatic olfactory dysfunction.

Soluble Epoxide Hydrolase Inhibitor Ameliorates Olfactory Dysfunction, Modulates Microglia Polarization, and Attenuates Neuroinflammation after Ischemic Brain Injury.

Olfactory bulb (OB) microglia activation and inflammation can lead to olfactory dysfunction, which often occurs after an ischemic stroke. Inhibition of soluble epoxide hydrolase (sEH) attenuates neuroinflammation in brain injuries by reducing the degradation of anti-inflammatory epoxyeicosatrienoic acids. However, whether sEH inhibitors can ameliorate olfactory dysfunction after an ischemic stroke remains unknown. Ischemic brain injury and olfactory dysfunction were induced by middle cerebral artery occlusion (MCAO) in Wistar Kyoto rats. The rats were administered 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a selective sEH inhibitor. Olfactory function, cerebral infarct volume, and the degree of degeneration, microglial polarization and neuroinflammation in OB were evaluated. Following treatment with AUDA, rats subjected to MCAO displayed mild cerebral infarction and OB degeneration, as well as better olfactory performance. In OB, AUDA triggered a modulation of microglial polarization toward the M2 anti-inflammatory type, reduction in proinflammatory mediators, and enhancement of the antioxidant process. The effectiveness of AUDA in terms of anti-inflammatory, neuroprotection and anti-oxidative properties suggests that it may have clinical therapeutic implication for ischemic stroke related olfactory dysfunction.

Intranasal Insulin for Treatment of Persistent Post-COVID-19 Olfactory Dysfunction: A Scoping Review.

Olfactory dysfunction has emerged as a prominent symptom of COVID-19, persisting in a subset of patients even after recovery. This scoping review aims to explore the potential of intranasal insulin as a treatment modality for persistent post-COVID-19 olfactory dysfunction. A comprehensive literature search was conducted to gather relevant studies examining the role of intranasal insulin in treating olfactory dysfunction, particularly in post-COVID-19 cases. Studies were included investigating intranasal insulin's mechanisms, efficacy, safety, and clinical outcomes. The review synthesizes findings from various studies suggesting the therapeutic potential of intranasal insulin in improving olfactory function. Research highlights the influence of intranasal insulin on neuroprotection, neurogenesis, and synaptic plasticity within the olfactory system, providing insights into its mechanisms of action. Furthermore, preliminary clinical evidence suggests improvements in olfactory sensitivity and intensity following intranasal insulin administration in post-COVID-19 patients with persistent olfactory dysfunction. While initial findings are encouraging, further rigorous investigations, including clinical trials with larger cohorts, are essential to validate these observations, ascertain optimal dosage regimens, and establish the safety and efficacy of intranasal insulin. This review provides a foundation for future research directions aimed at harnessing the therapeutic potential of intranasal insulin in addressing olfactory dysfunction following COVID-19.

A Pilot Study of the Computerized Brief Smell Identification Test.

Objectives: A self-administered Computerized Brief Smell Identification Test (cB-SIT) was developed recently to perform the olfactory identification test under computer control. The aim of this study was to evaluate the clinical applicability of the cB-SIT as compared with the traditional Brief Smell Identification Test (B-SIT). Methods: Sixty healthy volunteers with self-reported normal olfactory function, 30 hyposmic patients, and 30 anosmic patients were enrolled from June 2023 to May 2024. All enrolled participants received both B-SIT and cB-SIT in a random order to measure their odor identification ability. Thirty healthy volunteers took the second B-SIT and cB-SIT at least one week later. Results: The score was significantly different in both B-SIT and cB-SIT among healthy volunteers, hyposmic, and anosmic patients. The correct answer rate was significantly different in 10 items of the B-SIT and in 7 items of the cB-SIT among the three groups, but the post hoc test showed significant differences in correct answer rates between healthy volunteers and hyposmic patients in 7 items of both the B-SIT and cB-SIT. Test-retest results showed the score of the second B-SIT test was significantly higher than that of the first test, but the scores of the two tests of the cB-SIT were not significantly different. In the B-SIT, the lemon odorant had a higher correct answer rate in the second test than in the first test, but in the cB-SIT, the correct answer rate was not significantly different between the first and second tests in all 12 items. Conclusions: Our findings demonstrate that the cB-SIT was similar to the B-SIT and can be administered in the diagnosis of patients with olfactory dysfunction.

Neuroimaging evaluations of olfactory, gustatory, and neurological deficits in patients with long-term sequelae of COVID-19.

The World Health Organization indicated that around 36 million of patients in the European Region showed long COVID associated with olfactory and gustatory deficits. The precise mechanism underlying long COVID clinical manifestations is still debated. The aim of this study was to evaluate potential correlations between odor threshold, odor discrimination, odor identification, and the activation of specific brain areas in patients after COVID-19. Sixty subjects, 27 patients (15 women and 12 men) with long COVID and a mean age of 40.6 ± 13.4 years, were compared to 33 age-matched healthy controls (20 women and 13 men) with a mean age of 40.5 ± 9.8 years. Our data showed that patients with long COVID symptoms exhibited a significant decrease in odor threshold, odor discrimination, odor identification, and their sum TDI score compared to age-matched healthy controls. In addition, our results indicated significant correlations between odor discrimination and the increased activation in the right hemisphere, in the frontal pole, and in the superior frontal gyrus. This study indicated that the resting-state fMRI in combination with the objective evaluation of olfactory and gustatory function may be useful for the evaluation of patients with long COVID associated with anosmia and hyposmia.

Four odorants for olfactory training are enough: a pilot study.

BACKGROUND:  Olfactory training (OT) is commonly used for the treatment of olfactory disorders. Nevertheless, there is an ongoing debate about the most effective OT regimen. We aimed to compare the effects of OT with 7 items (rose, lemon, eucalyptus, cloves, stewed apple, balm, mint) to 4-item-OT (rose, lemon, eucalyptus, cloves) over 3 months. Methods: Participants were 40 patients with olfactory dysfunction receiving 4-item-OT or 7-item-OT and 60 gender- and age-matched individuals with normal sense of smell receiving no OT, 4-item-OT, or 7-item-OT. Before and after the OT we assessed n-butanol odor thresholds, discrimination, and identification (TDI score), additionalthresholds for (R)-(-)-carvone, ß-damascenone, salicyclic acid benzylester, the degree of phantosmia and parosmia, cognitive function, and ratings of olfactory function. Results: In both patient groups, the TDI score increased with the use of OT, regardless of the number of odors used (p < 0.001; 3.48 ± 4.21 and lower than control groups). The clinically significant increase of 5.5 points in TDI score correlated with change of ratings of parosmia (r 0.62; p < 0.01) and with ratings of olfactory dysfunction (r = 0.51; p < 0.05). CONCLUSION:  Concluding, OT over a 3-months period with 4 or 7 odors appears to produce similar results, although the sample size has to be considered.

Network pharmacology and experimental validation reveal the mechanisms of sniffing essential oil of Acori Tatarinowii rhizoma in treating olfactory dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Acorus tatarinowii Rhizoma, a traditional Chinese medicine known for open the orifices and transform phlegm, is used in the treatment of brain disorders. The essential oil of Acorus tatarinowii Rhizoma (EOAT) has demonstrated neuroprotective properties clinically. However, research into its effect on Olfactory Dysfunction (OD) remains limited. AIM OF THE STUDY: This study aimed to investigate the effects and mechanisms of sniffing EOAT on improving olfactory function in a 3-Methylindole (3-MI)-induced OD mouse model. MATERIALS AND METHODS: The research involved intraperitoneal injection of 3-MI to induce OD in mice. The effects of EOAT treatment were assessed on olfactory function, olfactory bulb (OB) pathology, inflammatory factors, olfactory marker protein (OMP), microglial activation, and related pathway proteins and mRNA. RESULTS: Based on the GC-MS analysis results of EOAT and network pharmacology studies, we predicted 18 targets associated with the treatment of OD. SLC6A3, MAOB, DRD1, and PTGS2 were identified as the core targets of EOAT against OD. Molecular docking and KEGG enrichment results indicated that EOAT may exert anti-inflammatory effects by acting on the core target PTGS2, with its anti-inflammatory mechanism possibly related to the PI3K/Akt signaling pathway. Subsequent animal experiments confirmed that inhalation of EOAT significantly increased the body weight of OD model mice, shortened the foraging time, enhanced the expression of OMP in OB, reduced damage to the OB cells, and improved olfactory function. Meanwhile, EOAT significantly alleviated the inflammatory response in OB of OD model mice, inhibited the activation of microglial cells, and suppressed the expression of PI3K/Akt signaling pathway proteins and mRNA. CONCLUSION: EOAT inhalation could improve olfactory function in 3-MI-induced OD model. The underlying mechanism may be related to the modulation of the PI3K/Akt signaling pathway.

Evaluating ChatGPT as a Patient Education Tool for COVID-19-Induced Olfactory Dysfunction.

Objective: While most patients with COVID-19-induced olfactory dysfunction (OD) recover spontaneously, those with persistent OD face significant physical and psychological sequelae. ChatGPT, an artificial intelligence chatbot, has grown as a tool for patient education. This study seeks to evaluate the quality of ChatGPT-generated responses for COVID-19 OD. Study Design: Quantitative observational study. Setting: Publicly available online website. Methods: ChatGPT (GPT-4) was queried 4 times with 30 identical questions. Prior to questioning, Chat-GPT was "prompted" to respond (1) to a patient, (2) to an eighth grader, (3) with references, and (4) no prompt. Answer accuracy was independently scored by 4 rhinologists using the Global Quality Score (GCS, range: 1-5). Proportions of responses at incremental score thresholds were compared using χ 2 analysis. Flesch-Kincaid grade level was calculated for each answer. Relationship between prompt type and grade level was assessed via analysis of variance. Results: Across all graded responses (n = 480), 364 responses (75.8%) were "at least good" (GCS ≥ 4). Proportions of responses that were "at least good" (P < .0001) or "excellent" (GCS = 5) (P < .0001) differed by prompt; "at least moderate" (GCS ≥ 3) responses did not (P = .687). Eighth-grade level (14.06 ± 2.3) and patient-friendly (14.33 ± 2.0) responses were significantly lower mean grade level than no prompting (P < .0001). Conclusion: ChatGPT provides appropriate answers to most questions on COVID-19 OD regardless of prompting. However, prompting influences response quality and grade level. ChatGPT responds at grade levels above accepted recommendations for presenting medical information to patients. Currently, ChatGPT offers significant potential for patient education as an adjunct to the conventional patient-physician relationship.

Comparing smell identification ability among different motor subtypes of Parkinson's disease using the Vietnamese Smell Identification Test and the Brief Smell Identification Test.

Introduction: Olfactory dysfunction is one of the most common non-motor symptoms of Parkinson's disease (PD). The association between smell identification ability and motor subtypes of PD is not uniform in previous studies. This study aimed to compare the odor identification ability among different motor subtypes of PD in Vietnamese participants. Methods: Patients who were diagnosed with PD according to the International Parkinson's Disease and Movement Disorder Society 2015 Diagnostic Criteria and had normal cognitive function were recruited. Participants were divided into akinetic-rigid (AR), tremor-dominant (TD), and mixed (MX) motor subgroups using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score. Olfactory identification ability was evaluated using the Vietnamese Smell Identification Test (VSIT) and the Brief Smell Identification Test (BSIT). Cognitive status was assessed using the Mini-Mental State Examination (MMSE). Age, age at PD onset, disease duration, smell identification ability, and cognitive function were compared among the three PD motor subtypes. Results: The AR subgroup was the most common motor subtype (n = 164, 75.2 %), followed by TD (n = 39, 17.9 %), and MX (n = 15, 6.9 %) subtypes. Age, age at PD onset, sex, disease duration, and MMSE score were not significantly different between the three motor subgroups (all p > 0.05). The median (IQR) VSIT scores of AR, TD, and MX subgroups were 5.00 [4.00;7.00], 5.00 [3.50;7.00], and 5.00 [3.00;6.00], respectively. The median (IQR) BSIT scores of AR, TD, and MX subgroups were 6.00 [4.00;7.00], 5.00 [4.00;7.00], and 5.00 [4.50;7.00], respectively. The VSIT and the BSIT scores were not significantly different among the three motor subtypes (all p > 0.05). Conclusion: Smell identification ability assessed in both the VSIT and BSIT did not differ across the three motor subtypes of PD.

Effects of Corticosteroid Treatment on Olfactory Dysfunction in LATY136F Knock-In Mice.

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition affecting multiple organs, including the pancreas, salivary glands, lungs, kidneys, skin, and lymph nodes. Clinically, it is characterized by elevated serum IgG and IgG4 levels and tissue infiltration by IgG4-positive plasma cells, lymphocytes, fibrosis, and phlebitis obliterans. IgG4-RD is linked to increased Th2-dominant cytokines, contributing to eosinophilia, elevated serum IgG4, and fibrosis. A notable feature is its good response to corticosteroid therapy. To investigate the effects of corticosteroid treatment on olfactory dysfunction in LATY136F knock-in mice, which exhibited increased production of Th2-type IgG1 (the murine homolog of human IgG4) and developed multiorgan tissue lesions similar to those observed in IgG4-RD patients. METHODS: LATY136F knock-in mice (n=24) were divided into groups that received prednisolone or saline at different ages. Olfactory function was assessed using a behavioral test with cycloheximide. Histological and immunohistochemical analyses were performed to evaluate the olfactory epithelium thickness as well as the presence of mature and immature olfactory neurons. RESULTS: Corticosteroid-treated mice exhibited significantly improved olfactory function compared to the controls. Histological analysis revealed a significant increase in olfactory epithelium thickness and mature (olfactory marker protein-positive) and immature (growth-associated protein 43-positive) olfactory neurons in the treated groups compared with the control group. CONCLUSION: Corticosteroid treatment effectively improved olfactory dysfunction and promoted olfactory epithelium regeneration in LATY136F knock-in mice, suggesting the potential therapeutic benefits of corticosteroid treatment for patients with IgG4-RD experiencing olfactory dysfunction. However, further research on topical nasal steroid therapy in untreated patients is warranted. The results support further investigation into topical nasal steroid therapies for treating olfactory dysfunction in untreated patients, potentially influencing clinical practice and patient management strategies for IgG4-RD globally.

Neurological soft signs and olfactory dysfunction in patients with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is a serious disorder with a lifetime prevalence of 2.7-5.9% and is thought to correlate with altered neuroplasticity. The aim of the present study is to investigate possible associations of BPD (-severity) and alterations in neurological soft signs (NSS) and olfactory function. METHODS: For the monocentric observational study, 39 female subjects with a BPD diagnosis and 19 female healthy control subjects were recruited. The groups were matched by age. Olfactory functions were examined using Sniffin' Sticks. NSS were assessed by a standardized test with 50 items. RESULTS: BPD subjects have higher NSS scores in group comparison. By contrast, there are no alterations in the total score of olfactory function, while the BPD subjects scored higher in smell identification. Within the BPD group, the total NSS score was discovered to have a negative correlation with olfactory function. BPD subjects taking antipsychotics show more NSS than those without. We found no significant influence of posttraumatic stress disorder on the NSS or olfactory function. The BPD-severity correlates with NSS. LIMITATIONS: Due to the cross-sectional design, we did not have a follow up examination. The sample size was small, and all patients had psychiatric comorbidities. Additionally, we did not perform MRI to connect our findings with possible structural abnormalities. CONCLUSIONS: Our study confirmed altered NSS in BPD patients, whereas no impairment in the olfactory function was found. Further research is required to establish NSS and smell tests as clinical screening tools in BPD patients and to uncover the disorder's impact on neuroplasticity.

The Association of Odor Identification With Nutritional Status and Systemic Inflammation in Patients With Advanced Chronic Kidney Disease.

OBJECTIVES: Anorexia is common in patients with chronic kidney disease (CKD) and could lead to protein-energy wasting (PEW). An altered sense of smell, a reflection of olfactory dysfunction, is a potential mechanism that exacerbates the impact of anorexia on PEW. In this study, we examined the extent of the altered sense of smell and its association with PEW in patients with moderate-to-advanced CKD. METHODS: We studied 139 individuals (34 healthy subjects- controls, 50 patients with stage 3-4 CKD, and 55 patients on maintenance hemodialysis (MHD)) using the odor identification test (Sniffin' Sticks odor screening test containing 12 different smells). The odor identification test was scored as either correct or incorrect, and each participant's total odor score was calculated. Malnutrition inflammation score (MIS) was used to assess PEW. RESULTS: Patients with CKD had higher C-reactive protein and lower serum albumin concentrations compared to healthy individuals. Total odor scores were different between groups, with controls having the highest scores and MHD patients having the lowest scores. A similar difference was observed in MIS, and MHD patients displayed the worst nutritional score (P ≤ .001). The number of participants with severe olfactory dysfunction (≤6 correct answers) was significantly higher in the CKD and MHD groups compared to the controls (P ≤ .01). There was an inverse trend between the total odor score and the MIS score for the study population. However, this relationship was not statistically significant (r = -0.124, P = .21). CONCLUSION: This cross-sectional study suggests that olfactory dysfunction, as assessed by the odor identification test, is altered in patients with advanced CKD, most notably in ones on MHD. Although the diminished sense of smell was observed alongside development of PEW, we explicitly noted that there is no statistically significant correlation.

Subjective and objective effects of radioiodine therapy on the sense of smell.

PURPOSE: Evaluating the impact of radioiodine therapy (RIT) on olfactory function in thyroid cancer patients through quantitative and qualitative olfactory tests. METHOD: In this cohort study, patients with thyroid cancer were included. Demographic, clinical, and laboratory data were collected. To subjectively evaluate the olfactory changes aftter RIT, the Visual Analog Scale (VAS), Self-Reported Mini-Olfactory Questionnaire (self-MOQ), and the University of Washington Quality of Life Questionnaire (UW-QOL) were assessed. Out of UW-QOL questions those related to saliva, taste, and overall health condition were analysed. For objective assessment, patients underwent both the Butanol Threshold Test (BTT) and the a version of Smell Identification Test (SIT). Patients were assessed before, one month, and six months after RIT. RESULTS: Ninety eight patients were included (Male = 17). A statistically significant decrement was observed in olfaction based on the VAS, between the baseline and one (pvalue = 0.015) and six months (pvalue = 0.031) of follow-up. Additionally, saliva (pvalue = 0.001), taste (pvalue = 0.000), and overall health condition (pvalue = 0.010) significantly decreased one-month after RIT. The measures were not different between the baseline and 6-month follow up and the improvement of index of taste was significant from 1-month to 6-months follow ups (pvalue = 0.000). However, none of the objective tests (the BTT and the SIT) indicated a significant decline in olfaction during the follow up. CONCLUSION: A subjective RIT related decrease in smell function, taste, and saliva production was documented without any objective olfactory dysfunction.

Impaired olfactory system in metabolic imbalance-related neuropathology.

Olfactory dysfunction, influenced by factors such as aging and environmental stress, is linked to various neurological disorders. The olfactory bulb's connections to brain areas like the hypothalamus, piriform cortex, entorhinal cortex, and limbic system make olfactory dysfunction a contributor to a range of neuropathological conditions. Recent research has underscored that olfactory deficits are prevalent in individuals with both metabolic syndrome and dementia. These systemic metabolic alterations correlate with olfactory impairments, potentially affecting brain regions associated with the olfactory bulb. In cases of metabolic syndrome, phenomena such as insulin resistance and disrupted glucose metabolism may result in compromised olfactory function, leading to multiple neurological issues. This review synthesizes key findings on the interplay between metabolic-induced olfactory dysfunction and neuropathology. It emphasizes the critical role of olfactory assessment in diagnosing and managing neurological diseases related to metabolic syndrome.

Incidence and influencing factors of olfactory dysfunction in patients 1 week after endoscopic transsphenoidal resection of pituitary tumor: a cross-sectional study of 158 patients.

Objective: To investigate the current situation of olfactory dysfunction in patients after endoscopic transsphenoidal resection of pituitary tumors, and analyze its influencing factors, to provide references for clinical nursing and rehabilitation. Methods: A cross-sectional study design and convenience sampling method were used to investigate 158 patients with pituitary tumors treated by endoscopic transsphenoidal pituitary tumor resection in the Department of Neurosurgery of three Grade-A general hospitals in Sichuan Province from January 2022 and June 2023. The olfactory function of patients was evaluated 1 week after surgery, and the general clinical data and olfactory related data of patients were collected, and the influencing factors of olfactory disorder were analyzed by logistic regression. Results: The incidence of olfactory dysfunction was 73.42%. analysis revealed that the formation of blood scabs, nasal cavity adhesion, cerebrospinal fluid leakage and operation time were independent risk factors for olfactory dysfunction in patients after transsphenoidal pituitary tumor resection (p < 0.05). Conclusion: The incidence of olfactory dysfunction is high in patients after endoscopic transsphenoidal resection of pituitary tumors, suggesting that medical staff should pay close attention to and identify patients with olfactory dysfunction based on the guidance of disease knowledge and skills, develop targeted nursing interventions, and promote the improvement of patients' olfactory function and quality of life.

Olfactory perceptual fingerprints of people with olfactory dysfunction and healthy controls.

Objectives: An olfactory perceptual fingerprint (OPF) defines one's olfactory perception using perceptual descriptor ratings (such as odor pleasantness, intensity) for a set of odors. OPFs have been shown to distinguish patients with COVID-related olfactory dysfunction (OD) and healthy controls with 86% accuracy. However, all participants rated the same odorants. With the aim to evaluate whether the OPFs are indeed odorant independent, previously published dataset by Lötsch et al. was reanalyzed. Furthermore, this independent dataset was used to check whether the OPFs separate patients with OD due to various causes from controls. Methods: The study included 104 controls and 42 patients, who were randomized into four odor sets with 10 odorants each. Odorants were presented using a computer-controlled olfactometer and evaluated on scales from 1 (not at all) to 5 (very) using perceptual descriptors pleasant, intensive, familiar, edible, irritating, cold/warm, and painful. Results: Permutational multivariate analysis of variance showed that the odor set did not have a significant effect on the OPFs, confirming that the OPFs are indeed odorant independent. On the other hand, both diagnosis and age affected the OPFs (p < .001) and explained around 11% and 5% of the variance of the OPFs, respectively. Furthermore, a supervised machine learning method, random forest classifier, showed that OPF can distinguish patients and controls with 80% accuracy. Conclusion: OPFs are odorant independent. Patients perceived odors as less familiar, less intense, and less edible than controls. Other perceptual descriptors were much less important for the separation of patients and controls. Level of evidence: 3.

Neurological Complications of COVID-19 Infection: A Comprehensive Review.

The COVID-19 pandemic is well on its way to reaching endemic status across the globe. While the medical community's understanding of the respiratory complications induced by COVID-19 is improving, there is still much to be learned about the neurological manifestations associated with COVID-19 infection. This review aimed to compile relevant, available evidence of COVID-19-induced neurological complications and to provide information for each complication regarding symptomology, progression patterns, demographic risk factors, treatment, and causative mechanism of action when available. Data for this review was collected using a confined search on PubMed using the keywords ["COVID-19" OR "SARS-CoV-2"] AND ["neurological complications" OR "olfactory symptoms" OR "gustatory symptoms" OR "myalgia" OR "headache" OR "dizziness" OR "stroke" OR "seizures" OR "meningoencephalitis" OR "cerebellar ataxia" OR "acute myelitis" OR "Guillain Barré Syndrome" OR "Miller Fisher Syndrome" OR "Posterior Reversible Encephalopathy Syndrome"] between 2019 and 2023. A wide range of neurological manifestations impact a significant percentage of COVID-19 patients, and a deeper understanding of these manifestations is necessary to ensure adequate management. The most common neurological complications identified consist of olfactory and gustatory dysfunctions, myalgia, headache, and dizziness, while the most severe complications include stroke, seizures, meningoencephalitis, Guillain-Barré syndrome, Miller Fisher syndrome, acute myelitis, and posterior reversible encephalopathy syndrome. While this review effectively provides a roadmap of the neurological risks posed to COVID-19 patients, further research is needed to clarify the precise incidence of these complications and to elucidate the mechanisms responsible for their manifestation.

Comparative imaging study of patients with persistent olfactory dysfunction due to mild COVID-19 using structural and functional MRI.

INTRODUCTION: Persistent post-COVID olfactory dysfunction continues to be studied due to the controversy in its pathophysiology and neuroimaging. MATERIALS AND METHODS: The patients had confirmed mild COVID-19 infection with olfactory dysfunction of more than one month of evolution and they were compared to controls with normal olfaction, assessed using the Sniffin' Sticks Olfactory Test and underwent brain, magnetic resonance imaging (MRI) of the olfactory bulb and olfactory function. RESULTS: A total of 8 patients and 2 controls participated. The average age of the patients was 34.5 years (SD 8.5), and that of the controls was 28.5 (SD 2.1). The average score in the patients' olfactory test was 7.9 points (SD 2.2). In brain and olfactory bulb MRI tests, no morphological differences were found. When evaluated by functional MRI, none of the patients activated the entorhinal area in comparison to the controls, who did show activation at this level. Activation of secondary olfactory areas in cases and controls were as follows: orbitofrontal (25% vs 100%), basal ganglia (25% vs 50%) and insula (38% vs 0%) respectively. CONCLUSIONS: There were no observed morphological changes in the brain MRI. Unlike the controls, none of the patients activated the entorhinal cortex in the olfactory functional MRI.