Fabry disease presenting with sudden hearing loss and otosclerosis : a case report

Introduction: Fabry disease is an X-linked lysosomal storage disorder resulting in a multiple-system disorder with a wide spectrum of physical signs and symptoms, predominantly affecting the central and peripheral nervous systems, skin, heart, kidneys, and eyes. Case presentation: We describe the case of a 26-year-old European Caucasian man who had Fabry disease and who presented with episodic sudden unilateral hearing loss and was treated with glucocorticoids, pentoxifylline, hyperbaric oxygen, and fluoride because of concomitant audiometric evidence of otosclerosis. This case demonstrates the partial and transient beneficial effect of standard treatment for sudden hearing loss not related to Fabry disease and analyzes the possible connection between typical Fabry disease inner-ear lesions and otosclerosis. Whereas hearing loss has been described in connection with Fabry disease, otosclerosis-associated hearing loss in Fabry disease has not yet been described. Conclusions: Although progressive hearing loss in patients with Fabry disease seems to be influenced by replacement therapy, few data concerning treatment of sudden hearing loss are available. The lack of literature concerning the pathogenesis of the otological involvement in Fabry disease makes it impossible to identify a connection between the latter and otosclerosis. Therefore, this report may help to reinforce the importance of a thorough evaluation of hearing in patients with Fabry disease and may be of help with therapeutic decisionmaking

Pmca-generated prions from the olfactory mucosa of patients with fatal familial insomnia cause prion disease in mice

Background: Fatal Familial Insomnia (FFI) is a genetic prion disease caused by the D178N mutation in the prion protein gene (PRNP) in coupling phase with methionine at PRNP 129. In 2017, we have shown that the olfactory mucosa (OM) collected from FFI patients contained traces of PrPSc detectable by Protein Misfolding Cyclic Amplification (PMCA). Methods: In this work, we have challenged PMCA-generated products obtained from OM and brain homogenate of FFI patients in BvPrP-Tg407 transgenic mice expressing the bank vole prion protein to test their ability to induce prion pathology. Results: All inoculated mice developed mild spongiform changes, astroglial activation, and PrPSc deposition mainly affecting the thalamus. However, their neuropathological alterations were different from those found in the brain of BvPrP-Tg407 mice injected with raw FFI brain homogenate. Conclusions: Although with some experimental constraints, we show that PrPSc present in OM of FFI patients is potentially infectious. Funding: This work was supported in part by the Italian Ministry of Health (GR-2013-02355724 and Ricerca Corrente), MJFF, ALZ, Alzheimer’s Research UK and the Weston Brain Institute (BAND2015), and Euronanomed III (SPEEDY) to FM; by the Spanish Ministerio de Economía y Competitividad (grant AGL2016-78054-R [AEI/FEDER, UE]) to JMT and JCE; AM-M was supported by a fellowship from the INIA (FPI-SGIT-2015-02)

PMCA-Based Detection of Prions in the Olfactory Mucosa of Patients With Sporadic Creutzfeldt–Jakob Disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder caused by the conformational conversion of the prion protein (PrPC) into an abnormally folded form, named prion (or PrPSc). The combination of the polymorphism at codon 129 of the PrP gene (coding either methionine or valine) with the biochemical feature of the proteinase-K resistant PrP (generating either PrPSc type 1 or 2) gives rise to different PrPSc strains, which cause variable phenotypes of sCJD. The definitive diagnosis of sCJD and its classification can be achieved only post-mortem after PrPSc identification and characterization in the brain. By exploiting the Real-Time Quaking-Induced Conversion (RT-QuIC) assay, traces of PrPSc were found in the olfactory mucosa (OM) of sCJD patients, thus demonstrating that PrPSc is not confined to the brain. Here, we have optimized another technique, named protein misfolding cyclic amplification (PMCA) for detecting PrPSc in OM samples of sCJD patients. OM samples were collected from 27 sCJD and 2 genetic CJD patients (E200K). Samples from 34 patients with other neurodegenerative disorders were included as controls. Brains were collected from 26 sCJD patients and 16 of them underwent OM collection. Brain and OM samples were subjected to PMCA using the brains of transgenic mice expressing human PrPC with methionine at codon 129 as reaction substrates. The amplified products were analyzed by Western blot after proteinase K digestion. Quantitative PMCA was performed to estimate PrPSc concentration in OM. PMCA enabled the detection of prions in OM samples with 79.3% sensitivity and 100% specificity. Except for a few cases, a predominant type 1 PrPSc was generated, regardless of the tissues analyzed. Notably, all amplified PrPSc were less resistant to PK compared to the original strain. In conclusion, although the optimized PMCA did not consent to recognize sCJD subtypes from the analysis of OM collected from living patients, it enabled us to estimate for the first time the amount of prions accumulating in this biological tissue. Further assay optimizations are needed to faithfully amplify peripheral prions whose recognition could lead to a better diagnosis and selection of patients for future clinical trials

Odontogenic rhinosinusitis and sinonasal complications of dental disease or treatment: prospective validation of a classification and treatment protocol

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%

Efficacia e tollerabilit\ue0 di moxifloxacina nelle sinusiti recidivanti e croniche dell\u2019adulto e dell\u2019anziano

Risultano oggi sempre pi\uf9 numerose le segnalazioni di infezioni delle alte vie respiratorie che presentano resistenze alle comuni terapie antibiotiche eseguite con derivati della penicillina o cefalosporine. Sotto questa luce l\u2019agente eziologico che oggi sembra rivestire maggior pericolosit\ue0 \ue8 lo Streptococcus pneumoniae (Paradisi e Coll., 2001; Cunha,2002). Negli ultimi anni nuove molecole sono state introdotte nella pratica clinica per la terapia delle infezioni causate da pneumococchi penicillino-resistenti. Studi sia in vitro che in vivo hanno dimostrato l\u2019efficacia clinica di farmaci della classe dei fluorochinoloni (levofloxacina, moxifloxacina, gatifloxacina) su ceppi di pneumococchi penicillino-resistenti (Paradisi e Coll., 2001). La moxifloxacina, in particolare, ha dimostrato un\u2019ottima disponibilit\ue0 nella mucosa dei seni paranasali con una concentrazione locale superiore a quella ematica in presenza di infezioni sinusali. Tale elevata disponibilit\ue0 si realizza sulla mucosa sia mascellare che etmoidale, cos\uec come nei polipi nasali (Gehanno e Coll., 2002). In letteratura cominciano ad essere riportati studi comparativi sull\u2019efficacia dei nuovi chinoloni nelle infezioni delle alte vie respiratorie. Rakkar e Coll., nel 2001 valutarono 475 pazienti adulti con sinusite acuta trattati con moxifloxacina e controllati con amoxicillina e acido clavulanico. I risultati nei due bracci sperimentali furono sostanzialmente sovrapponibili sia dal punto di vista dell\u2019efficacia che degli effetti collaterali anche se moxifloxacina dimostrava una guarigione pi\uf9 rapida (con benefici gi\ue0 alla terza giornata di trattamento). Il limite degli studi fin qui realizzati sembrerebbe legato alla selezione dei casi (spesso non particolarmente rilevanti sul piano clinico) ed al giudizio diagnostico sull\u2019avvenuta guarigione. Su queste basi gli Autori hanno attuato uno studio preliminare in aperto su casi complessi di sinusite volto ad evidenziare l\u2019efficacia di Moxifloxacina su casi di sinusite acuta ricorrente o cronica riacutizzata. Sono stati arruolati 29 casi ed i risultati, che appaiono favorevoli, saranno discussi nel poster. In particolare pu\uf2 essere ricordata la presenza di effetti collaterali rilevanti solo in 1/29 casi e, modesti, in un ulteriore 1/29 casi. La guarigione, controllata endoscopicamente, \ue8 stata completa in 26/28 casi che avevano completato la terapia e parziale (netto miglioramento) in un ulteriore 1/28

Incontinentia pigmenti : case report

IP is an uncommon X-linked dominant disorder (incidence: 1/40.000 newborn). It is caused by mutations in NEMO. It is characterized by cutaneous lesions and dental, ocular, neurologic, nails, hair disorders. The ocular and neurologic sequelae represent the major morbidity in IP. We present a case-report with classical cutaneous features diagnostic for IP. The clinical, ophtalomologic and neurologic examinations revealed no other pathological manifestation

Proposal for a protocol for the staging of incontinentia pigmenti in pediatric age

Incontinentia Pigmenti (IP) is an X-linked dominant disorder of skin with neurologic and ophthalmologic involvement. IP predominantly affects females because the mutations are usually lethal in males in utero. IP is characterized by abnormalities of neuroectodermal tissues. IP is caused by mutations in a gene called NEMO, which is required to activate the NF-kB pathway. We present a diagnostic protocol for IP and a meta-analysis of the clinical spectrum of IP in 82 patients cited by MEDLINE in the European literature from 2000 to 2006. [References: 31

Isolated olfactory cleft involvement in SARS-CoV-2 infection: prevalence and clinical correlates

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 \ub1 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 \ub1 4 vs. 9 \ub1 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