Background Parkinson’s disease (PD) is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms. PD is characterized by intraneuronal accumulation of abnormal α-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of either α-synuclein, as in the case of Multiple System Atrophy (MSA) or tau, as in the case of Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP), in other disease-specific brain regions. Definite diagnosis of all these diseases can be formulated only neuropathologically by detection and localization of α-synuclein or tau aggregates in the brain. Compelling evidence suggests that trace-amount of these proteins can appear in peripheral tissues, including receptor neurons of the olfactory mucosa (OM). Methods We have set and standardized the experimental conditions to extend the ultrasensitive Real Time Quaking Induced Conversion (RT-QuIC) assay for OM analysis. In particular, by using human recombinant α-synuclein as substrate of reaction, we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induce α-synuclein aggregation, and compared their seeding ability to that of OM samples collected from patients with clinical diagnoses of CBD and PSP. Results Our results showed that a significant percentage of MSA and PD samples induced α-synuclein aggregation with high efficiency, but also few samples of patients with the clinical diagnosis of CBD and PSP caused the same effect. Notably, the final RT-QuIC aggregates obtained from MSA and PD samples owned peculiar biochemical and morphological features potentially enabling their discrimination. Conclusions Our study provide the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities for α-synuclein. Additional studies are required for (i) estimating sensitivity and specificity of the technique and for (ii) evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms. RT-QuIC analyses of OM and cerebrospinal fluid (CSF) can be combined with the aim of increasing the overall diagnostic accuracy of these diseases, especially in the early stages. Electronic supplementary material The online version of this article (10.1186/s40035-019-0164-x) contains supplementary material, which is available to authorized users.

Purpose Odontogenic sinusitis and sinonasal complications of dental disease or treatment (SCDDT) represent a heterogeneous group of conditions that often require multidisciplinary care. The present study aims to prospectively validate a classification and treatment protocol for SCDDT patients. Methods One hundred twenty-eight consecutive patients (73 females and 45 males, mean age 52.4 years) affected by SCDDT not responding to dental and medical therapy were classified and surgically treated according to the proposed protocol. The protocol classified patients into three aetiology-based groups (preimplantologic, implantologic, and related to traditional dental diseases and procedures, respectively). The groups were further divided into classes according to the presence of oro-antral communications and/or dislocated dental hardware. Each condition was treated according to the class-related, protocol-defined treatment, by either a transnasal or combined transnasal/transoral approach. All patients were successfully classified according to our protocol. None of the proposed classes were redundant, and no condition fell outside the definitions. Results The surgical treatment protocol proved to be adequate and effective, in that 125 of the 128 patients completely recovered after surgical treatment. Conclusions The term SCDDT and the consequent classification proposed by the authors appear, therefore, to be nosologically correct. Furthermore, the protocol-related proposed treatment appears to be clinically sound, with a success rate nearing 98%.

Complete presurgery evaluation with endoscopy and a computed tomography (CT) scan in SCDDT patients is essential. SCDDT patients not responding to medical and dental treatment should be addressed with a planned approach targeting the extramaxillary extension, which may necessitate a combined oral and endonasal approach. It is unclear whether disease in the maxillary sinus contralateral to the primary maxillary sinus demonstrating odontogenic-induced disease is incidental, associated, or represents a subclinical odontogenic infection.

Background Detection of the pathological and disease-associated alpha-synuclein (αSynD) in the brain is required to formulate the definitive diagnosis of multiple system atrophy (MSA) and Parkinson’s disease (PD). We recently showed that αSynD can be detected in the olfactory mucosa (OM) of MSA and PD patients. For this reason, we have performed the first interlaboratory study based on α-synuclein Real-Time Quaking-Induced Conversion (αSyn_RT-QuIC) analysis of OM samples collected from PD and MSA patients with the parkinsonian (MSA-P) and cerebellar (MSA-C) phenotypes. Methods OM samples were prospectively collected from patients with a probable diagnosis of MSA-P (n = 20, mean disease duration 4.4 years), MSA-C (n = 10, mean disease duration 4 years), PD (n = 13, mean disease duration 8 years), and healthy control subjects (HS) (n = 11). Each sample was analyzed by αSyn_RT-QuIC in two independent specialized laboratories, one located in Italy (ITA-lab) and one located in the USA (USA-lab). Both laboratories have developed and used harmonized αSyn_RT-QuIC analytical procedures. Results were correlated with demographic and clinical data. Results The αSyn_RT-QuIC analysis reached a 96% interrater agreement of results (IAR) between laboratories (Kappa = 0.93, 95% CI 0.83–1.00). In particular, αSyn_RT-QuIC seeding activity was found in the OM of 9/13 patients with PD (sensitivity 69%, IAR 100%) and 18/20 patients with MSA-P (sensitivity 90%, IAR 100%). Interestingly, samples collected from patients with MSA-C did not induce αSyn_RT-QuIC seeding activity, except for one subject in USA-lab. Therefore, we found that MSA-P and MSA-C induced opposite effects. Regardless of disease diagnosis, the αSyn_RT-QuIC seeding activity correlated with some clinical parameters, including the rigidity and postural instability. Conclusions Our study provides evidence that OM-αSynD may serve as a novel biomarker for accurate clinical diagnoses of PD, MSA-P, and MSA-C. Moreover, αSyn_RT-QuIC represents a reliable assay that can distinguish patients with MSA-P from those with MSA-C, and may lead to significant advancements in patients stratification and selection for emerging pharmacological treatments and clinical trials.

Fatal Familial Insomnia (FFI) is a genetic prion disease caused by a point mutation in the prion protein gene (PRNP) characterized by prominent thalamic atrophy, diffuse astrogliosis and moderate deposition of PrPSc in the brain. Here, for the first time, we demonstrate that the olfactory mucosa (OM) of patients with FFI contains trace amount of PrPSc detectable by PMCA and RT-QuIC. Quantitative PMCA analysis estimated a PrPSc concentration of about 1 × 10−14 g/ml. In contrast, PrPSc was not detected in OM samples from healthy controls and patients affected by other neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease and frontotemporal dementia. These results indicate that the detection limit of these assays is in the order of a single PrPSc oligomer/molecule with a specificity of 100%.

Lymphoepithelial carcinoma is a very rare tumour of the larynx, with an exhaustive review of the literature having disclosed only 33 documented cases. The relationship between lymphoepithelial carcinoma of the larynx and Epstein-Barr virus is still controversial. We describe one new case of this tumour involving the supraglottis. The patient was treated with supraglottic laryngectomy and left modified neck dissection. Three years and 4 months later, the right side of the neck was found positive for metastatic disease and a right modified neck dissection was performed. No evidence of disease was exhibited 4 years after the diagnosis of metastatic disease. The diagnostic problems and therapy associated with this rare tumour are discussed.

SUMMARY The term odontogenic sinusitis (OS) has proved less and less suitable to describe a series of pathological conditions related to dental procedures. We have introduced the term and classification ‘sinonasal complications of dental disease or treatment’ (SCDDT). This study aimed to review our cases and evaluate whether the classification used is applicable to everyday clinical practice. The sample was composed of patients treated for SCDDT from 2002 to 2018 in our Department of Otorhinolaryngology. All presented signs and symptoms of sinusitis and had a recent history of dental disease or treatment. All patients underwent multidisciplinary evaluation, flexible endoscopy and computed tomography (CT) scan. Patients were allocated into three groups depending on the aetiology of the complication, following the classification proposed by Felisati et al. The sample comprised 480 patients (44% men, 56% women) with a mean age of 52.36 years. Of these, 43 patients (9%) belonged to group 1 (class A), 105 (21%) to group 2 (50, 2A; 5, 2B; 27, 2C; 23, 2D) and 332 (70%) to group 3 (119, 3A; 213, 3B). A total of 454 patients (94.5%) had unilateral maxillary opacification, while only 26 cases (5.4%) started as bilateral inflammation. Nine of the latter cases (34.6%) presented a bilateral odontogenic focus, while the other 17 (65.4%) had a history of unilateral dental pathology. The results of this study suggest that SCDDT is a complex entity that needs a careful diagnostic approach based on CT scans and presurgical endoscopy.

Purpose Smell alterations are a symptom of COVID-19 and have been associated with olfactory cleft mucosal thickening (OCMT). Although their pathogenesis is unclear, evidences link them to viral neuroinvasive potential. This study aims at estimating the prevalence of OCMT in CT scans of COVID-19 patients and investigating its clinical correlates. Methods In a single-institution retrospective cross-sectional study, we included all patients hospitalized for COVID-19 undergoing head CT scan for any reason. Exclusion criteria were history of recent head trauma or chronic rhinosinusitis; opacification > 2 mm in any sinonasal space other than the olfactory cleft; CT performed during/after invasive ventilation or feeding via nasogastric tube. We recorded the prevalence of OCMT and related it to age, sex, need for invasive ventilation during hospital stay, outcome, length of hospital stay, diffusion of lung SARS-CoV-19 lesions and outcome. Results 63 eligible patients were identified (39 male, 24 female; median age 77.82 ± 17.77 years). OCMT was identified in 16 patients (25.4%; 95% CI 15.3-37.9%). Patients with OCMT had longer hospital stays (median 16 ± 4 vs. 9 ± 14.5 days, p = .009, Mann-Whitney U test) and required invasive ventilation more frequently than patients without mucosal thickening (OR 4.89, 95% CI 0.96-24.89, p = .063, Fisher's test). No other difference was observed. Conclusion OCMT affects nearly one in four patients hospitalized for COVID-19. It is associated with a worse disease course irrespective of age, sex and diffusion of lung lesions, although with no direct effect on survival.