Local budesonide therapy in the management of persistent hyposmia in suspected non-severe COVID-19 patients: Results of a randomized controlled trial.

OBJECTIVES: Consequences of COVID-19 on olfactory functions remained unclear during the pandemic. We assessed the efficacy of local budesonide in addition to olfactory rehabilitation when managing non-severe COVID-19 patients with persistent hyposmia. METHODS: A multicentric, randomized, superiority trial was conducted (ClinicalTrials.gov NCT04361474). The experimental group (EG) received budesonide and physiological saline nasal irrigations administered via three syringes of 20 ml in each nasal cavity in the morning and evening for 30 days. The control group (CG) received a similar protocol without budesonide. Patients were included if they were >18 years old, with a SARS-CoV-2 infection and presenting an isolated hyposmia persisting 30 days after symptom onset. The primary endpoint was the percentage of patients with improvement of more than two points on the ODORATEST score after 30 days of treatment. RESULTS: In total, 123 patients were included and randomized (EG: 62 vs CG: 61). Two patients from the EG met the primary endpoint with no statistical difference between the two groups (P = 0.5). CONCLUSION: To our knowledge, this is the first study evaluating local budesonide for COVID-19 related hyposmia treatment even though previous trials were performed with other local corticosteroids. Local budesonide efficacy was not demonstrated for persistent hyposmia related to COVID-19.

Recurrent vestibulopathy: are cVEMP, oVEMP and inner ear MRI useful to distinguish patients with Menière's disease and vestibular migraine?

PURPOSE: The aim of this study was to assess the rate of endolymphatic hydrops (EH) on MRI and the rate of otolithic dysfunction with cVEMP and oVEMP, in patients with recurrent vertigo such as Menière's disease (MD), vestibular migraine (VM) and vestibular Menière's disease (vMD). METHODS: In this retrospective study, we performed 3D-FLAIR sequences with delayed acquisition in 20 MD, 20 VM and 20 vMD patients. Each subject was then assessed for the presence of EH on MRI. All patients underwent pure-tone audiometry, cVEMP and oVEMP. RESULTS: In MD patients, EH was observed in 18 (90%) out of 20 patients while EH was observed in only 1 MV (5%) and 1 vMD (5%) patients. We found significant differences between groups for the presence of EH on MRI (p = 0.001). MD patients had significant higher PTA level (p < 0.001) and oVEMP impairment than MV and vMD (p = 0.08 and p = 0.06, respectively). However, no significant differences were observed for cVEMP impairment, either asymmetric ratio (p = 0.36) and 1000/500 ratio (p = 0.20). CONCLUSIONS: Concerning cVEMP, we observed no significant differences between VM, vMD and MD. However, we observed higher oVEMP impairment, PTA level and EH on MRI in MD patients. We believe that MRI could be used to differentiate MD from VM patients with cochlear symptoms. However, in cases of migraine associated with recurrent vertigo and without cochlear symptoms, we believe that MRI is not a useful tool to differentiate between VM and vMD.

MRI characteristics of intralabyrinthine schwannoma on post-contrast 4 h-delayed 3D-FLAIR imaging.

PURPOSE: The purpose of this study was to describe the MRI characteristics of intralabyrinthine schwannoma (ILS) on post contrast three-dimensional (3D) fluid-attenuation-inversion-recovery (FLAIR) images obtained four hours after intravenous administration of a gadolinium-based contrast agent (4h-3D-FLAIR). MATERIALS AND METHODS: This IRB-approved retrospective multi-center study included patients presenting with typical ILS from January 2016 to October 2020. All medical charts were systematically collected. All MRI examinations, including 4h-3D-FLAIR images, were reviewed by two board-certified neuroradiologists. Main outcome measures were location, signal intensity and associated anomalies of ILS. RESULTS: Twenty-seven out of 8730 patients (0.31%) referred for the investigation of a cochleovestibular disorder had a final diagnosis of ILS. There were 13 men and 14 women with a mean age of 52 ± 17 (SD) years (age range: 20-86 years). The most common clinical presentation was unilateral progressive sensorineural hearing loss (16/27; 59%). All ILS were unilateral and 15 (15/27; 55%) were intracochlear. All ILS presented as a hypointense filling defect within the labyrinth on T2-weighted images that enhanced on post-contrast T1-weighted images. On 4h-3D-FLAIR images, all ILS presented as a hypointense filling defect, associated with diffuse perilymphatic hyperintensity. Two patients (2/27; 7%) presented with ipsilateral endolymphatic hydrops. CONCLUSION: ILS displays consistent features on post-contrast 4h-3D-FLAIR images. ILS should not be confused with endolymphatic hydrops and requires a systematic analysis of the corresponding T2-weighted images.

Loss of smell in patients with COVID-19: MRI data reveal a transient edema of the olfactory clefts.

OBJECTIVE: To assess the physiopathology of olfactory function loss (OFL) in patients with coronavirus disease 2019 (COVID-19), we evaluated the olfactory clefts (OC) on MRI during the early stage of the disease and 1 month later. METHODS: This was a prospective, monocentric, case-controlled study. Twenty severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-infected patients with OFL were included and compared to 20 age-matched healthy controls. All infected patients underwent olfactory function assessment and 3T MRI, performed both at the early stage of the disease and at the 1-month follow-up. RESULTS: At the early stage, SARS-CoV2-infected patients had a mean olfactory score of 2.8 ± 2.7 (range 0-8), and MRI displayed a complete obstruction of the OC in 19 of 20 patients. Controls had normal olfactory scores and no obstruction of the OC on MRI. At the 1 month follow-up, the olfactory score had improved to 8.3 ± 1.9 (range 4-10) in patients, and only 7 of 20 patients still had an obstruction of the OC. There was a correlation between olfactory score and obstruction of the OC (p = 0.004). CONCLUSION: OFL in SARS-CoV2-infected patients is associated with a reversible obstruction of the OC.

Efficacy of local budesonide therapy in the management of persistent hyposmia in COVID-19 patients without signs of severity: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the efficacy of local intranasal treatment with budesonide (nasal irrigation), in addition to olfactory rehabilitation, in the management of loss of smell in COVID-19 patients without signs of severity and with persistent hyposmia 30 days after the onset of symptoms. To search for an association between the presence of an obstruction on MRI and the severity of olfactory loss, at inclusion and after 30 days of treatment. TRIAL DESIGN: Two center, open-label, 2-arm (1:1 ratio) parallel group randomized controlled superiority trial. PARTICIPANTS: Inclusion criteria - Patient over 18 years of age; - Patient with a suspected SARS-CoV-2 infection, whether or not confirmed by PCR, or close contact with a PCR-confirmed case, typical chest CT scan (unsystematic frosted glass patches with predominantly sub-pleural appearance, and at a later stage, alveolar condensation without excavation or nodules or masses) or positive serology ; - Patient with isolated sudden onset hyposmia persisting 30 days after the onset of symptoms of CoV-2 SARS infection; - Affiliate or beneficiary of a social security scheme; - Written consent to participate in the study. Non-inclusion criteria - Known hypersensitivity to budesonide or any of the excipients; - Hemostasis disorder or epistaxis; - Oral-nasal and ophthalmic herpes virus infection; - Long-term corticosteroid treatment; - Treatment with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone and HIV protease inhibitors); - Severe forms of SARS-CoV-2 with respiratory or other signs; - Hyposmia persisting for more than 90 days after the onset of symptoms - Other causes of hyposmia found on interrogation or MRI; - Patient benefiting from a legal protection measure; - Pregnant or breastfeeding women. The participants will be recruited from: Hôpital Fondation Adolphe de Rothschild and Hôpital Lariboisière in Paris, France INTERVENTION AND COMPARATOR: Intervention: Experimental group: Nasal irrigation with budesonide and physiological saline (Budesonide 1mg/2mL diluted in 250mL of physiological saline 9°/00): 3 syringes of 20mL in each nasal cavity, morning and evening, for 30 days, in addition to olfactory rehabilitation twice a day. CONTROL GROUP: Nasal irrigation with physiological saline 9°/00 only: 3 syringes of 20cc in each nasal cavity, morning and evening, for 30 days, in addition to olfactory rehabilitation twice a day. MAIN OUTCOMES: Percentage of patients with an improvement of more than 2 points on the ODORATEST score after 30 days of treatment. RANDOMISATION: Patients will be randomized (1:1) between the experimental and control groups, using the e-CRF. The randomization list will be stratified by centre. BLINDING (MASKING): Participants and caregivers are aware of the group assignment. People assessing the outcomes are blinded to the group assignment Numbers to be randomised (sample size) 120 patients are planned to be randomized into two groups of 60 patients. TRIAL STATUS: MDL_2020_10. Version number 2, May 22, 2020. Recruitment started on May 22, 2020. The trial will finish recruiting by August 2020. TRIAL REGISTRATION: EUDRACT number: 2020-001667-85; date of trial registration: 15 May 2020 Protocol registered on ClinicalTrial.gov, registration number: NCT04361474 ; date of trial registration: 24 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.