Retinal degeneration in MOG antibody Associated Disease (MOGAD): a longitudinal OCT study

Background and aims.Since in MOGAD(MOG antibody Associated Disease)data about prognostic meaning of MOG ab titres and retinal degeneration are still lacking, we analysed longitudinal dynamics of MOG antibodies and of GCL and RNFL thicknesses, acquired through OCT scans in a cohort of MOGAD patients. We compared GCL and RNFL thicknesses and dynamics between MOGAD patients and a cohort of multiple sclerosis(MS) patients. Methods.Prospective and retrospective interventistic monocentric study. MOGAD and MS patients referring to Mondino Foundation underwent periodic clinical and serological follow-up(FU)and OCT scans. Results.MOGAD cohort was made up of 16 patients, with mean age of 38 years, mean EDSS of 1.8, mean FU duration of 49 months. 8/16 patients showed a relapsing form of disease.MOG ab titres dynamics were similar between monophasic and relapsing patients. However, in 5/8 relapsing patients clinical relapse occurred in concomitance with increasing in MOGab titres. We didn’t find correlation between MOG antibody titres at baseline and mean GCL-RNFL thicknesses,and between MOG ab titres and OCT thicknesses variation rates. Patients were divided in groups according to history of optic neuritis(ON): MOG-ON+(N=11) and MOG-ON-(N=5). Mean MOG antibody titres at baseline were similar between groups, as baseline OCT thicknesses. We didn’t find differences in GCL-RNFL variation rates between groups.We didn’t find correlations between MOG dynamics and GCL-RNFL thinning rates considering eyes with and without ON. Considering whole cohort of MOGAD, we found association between annualized GCL variation rate and relapsing course of disease(p=0.01). This result also applied when splitting our cohort into MOG-ON+and MOG-ON-subgroups. Considering EDSS variation at FU, annualized CGL variation rate was higher in patients with disability progression(p=0.03). MS cohort was made up of 21 patients, with mean age of 34 years,mean EDSS of 1,mean FU duration of 40 months. Demographic features were similar between MOGAD and MS,except for baseline EDSS, which was higher in MOGAD and sex(F/M ratio was higher in RRMS cohort). Considering patients with ON, GCL-RNFL baseline thicknesses and thinning rates were similar between MOGAD and MS.Considering eyes without history of ON, we found a higher annualized GCL variation rate in MOGAD(p=0.03). This result applied when considering group of unaffected eyes(p=0.05), but didn’t apply when considering group of fellow eyes. Discussion and conclusions. Even if MOG ab titres dynamics didn’t differ between monophasic and relapsing patients, the occurrence of clinical relapses is preceded by an increasing in MOG ab titres. Thus, monitoring MOG-ab titres could have a prognostic utility. In MOGAD cohort, retinal degeneration was higher in relapsing patients, independently of the occurrence of ON. Thus, retinal degeneration could be accelerated by inflammatory events, independently of the district in which they occur. MOG ab titres didn’t correlate with retinal degeneration. Thus, monitoring MOG ab titres might not reflect severity of retinal degeneration, even in eyes with history of ON. All patients experiencing disability progression show increased MOG ab titres at FU and faster GCL thinning rates. As titres increased during relapses and retinal degeneration accelerates after inflammatory episodes, these data highlight the concept that retinal degeneration and disability progression could be result of recurrent relapses. Retinal degeneration is similar in MOGAD and MS eyes with ON as in fellow eyes. Thus, we could infer that retinal degeneration is independent of the triggering ON. Moreover, in fellow eyes, a similar physiopathological mechanism could occur. In eyes without ON retinal degeneration is higher in MOGAD than in MS.This data question if, even in MOGAD, a pure neurodegenerative process could exist thus considering that disability progression could not be caused only by clinical relapses

A preliminary evaluation of chemical interaction between sanitizing products and silk

The ongoing Coronavirus crisis involved almost all sectors as well as museums, collections, and historical sites all over the world. Even though artworks do not have the ability to spread the virus, the pandemic officially introduced in cultural sites alcohol-based products (even by visitors for personal use) as these products were indicated to be able to inactivate the virus and were imposed by many local authorities. In this context, the need to conciliate the safety of the visitors and the protection of artworks represents a challenging task. The possibility that accumulation of vapour coming from the sanitizing solutions or from accidental spills, potentially caused also by visitors, should be considered. The study focuses specifically on the possible interactions between sanitizing alcohol-based products and silk, since this material is present in many cultural sites all over the world on upholsteries and tapestries. The recommended sanitising solution (75% ethanol, 20% water, 5% benzalkonium chloride) selected by the Italian Ministry for Cultural Heritage (MIBACT) was considered. Pure distilled water, absolute ethanol and water/ethanol blends in different concentrations were also tested. Chemical and morphological variations on the silk have been evaluated with Scanning Electron Microscopy - SEM, Atomic Force Microscopy - AFM and portable instruments (contact microscope, colorimeter, Infrared and Raman spectroscopy). IR and Raman analyses did not detect significant chemical changes in silk. However, Raman spectra showed, after immersion treatments, minor variations in the intensity of peaks attributed to dyes. Residues of benzalkonium chloride after immersion tests in sanitising solution are present, confirmed also by SEM and AFM analyses. Even if chemical spectroscopic changes were not relevant, the colour of few samples seemed to consistently fade after immersion treatments, thus affecting the visual appearance of textiles.The ongoing Coronavirus crisis involved almost all sectors as well as museums, collections, and historical sites all over the world. Even though artworks do not have the ability to spread the virus, the pandemic officially introduced in cultural sites alcohol-based products (even by visitors for personal use) as these products were indicated to be able to inactivate the virus and were imposed by many local authorities. In this context, the need to conciliate the safety of the visitors and the protection of artworks represents a challenging task. The possibility that accumulation of vapour coming from the sanitizing solutions or from accidental spills, potentially caused also by visitors, should be considered. The study focuses specifically on the possible interactions between sanitizing alcohol-based products and silk, since this material is present in many cultural sites all over the world on upholsteries and tapestries. The recommended sanitising solution (75% ethanol, 20% water, 5% benzalkonium chloride) selected by the Italian Ministry for Cultural Heritage (MIBACT) was considered. Pure distilled water, absolute ethanol and water/ethanol blends in different concentrations were also tested. Chemical and morphological variations on the silk have been evaluated with Scanning Electron Microscopy - SEM, Atomic Force Microscopy - AFM and portable instruments (contact microscope, colorimeter, Infrared and Raman spectroscopy). IR and Raman analyses did not detect significant chemical changes in silk. However, Raman spectra showed, after immersion treatments, minor variations in the intensity of peaks attributed to dyes. Residues of benzalkonium chloride after immersion tests in sanitising solution are present, confirmed also by SEM and AFM analyses. Even if chemical spectroscopic changes were not relevant, the colour of few samples seemed to consistently fade after immersion treatments, thus affecting the visual appearance of textiles

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Beyond Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibodies: Alternative Causes of Optic Neuritis

Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain during eye movements. Typical ON is associated with Multiple Sclerosis (MS) and is generally mild and steroid-responsive. Atypical forms are characterized by unusual features, such as prominent optic disc edema, poor treatment response, and bilateral involvement, and they are often associated with autoantibodies against aquaporin-4 (AQP4) or Myelin Oligodendrocyte Glycoprotein (MOG). However, in some cases, AQP4 and MOG antibodies will return as negative, plunging the clinician into a diagnostic conundrum. AQP4- and MOG-seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis are greatly different. The aim of this review is to describe the possible rarer etiologies of non-MS-related and AQP4- and MOG-IgG-seronegative inflammatory ON and discuss their diagnoses and treatments

The Potential Role of SARS-CoV-2 Infection and Vaccines in Multiple Sclerosis Onset and Reactivation: A Case Series and Literature Review

: The recent SARS-CoV-2 pandemic and related vaccines have raised several issues. Among them, the potential role of the viral infection (COVID-19) or anti-SARS-CoV-2 vaccines as causal factors of dysimmune CNS disorders, as well as the safety and efficacy of vaccines in patients affected by such diseases and on immune-active treatments have been analyzed. The aim is to better understand the relationship between SARS-CoV-2 infection/vaccines with dysimmune CNS diseases by describing 12 cases of multiple sclerosis/myelitis onset or reactivation after exposure to SARS-CoV-2 infection/vaccines and reviewing all published case reports or case series in which MS onset or reactivation was temporally associated with either COVID-19 (8 case reports, 3 case series) or anti-SARS-CoV-2 vaccines (13 case reports, 6 case series). All the cases share a temporal association between viral/vaccine exposure and symptoms onset. This finding, together with direct or immune-based mechanisms described both during COVID-19 and MS, claims in favor of a role for SARS-CoV-2 infection/vaccines in unmasking dysimmune CNS disorders. The most common clinical presentations involve the optic nerve, brainstem and spinal cord. The preferential tropism of the virus together with the presence of some host-related genetic/immune factors might predispose to the involvement of specific CNS districts

The Impact of Graphene Oxide on Polycaprolactone PCL Surfaces: Antimicrobial Activity and Osteogenic Differentiation of Mesenchymal Stem Cell

In dentistry, bone regeneration requires osteoinductive biomaterial with antibacterial properties. Polycaprolactone (PCL) may be combined with different nanofillers including reduced graphene oxide (rGO). Here, the amount of rGO filler was defined to obtain a biocompatible and antibacterial PCL-based surface supporting the adhesion and differentiation of human mesenchymal stem cells (MSCs). Compounds carrying three different percentages of rGO were tested. Among all, the 5% rGO-PCL compound is the most bacteriostatic against Gram-positive bacteria. All scaffolds are biocompatible. MSCs adhere and proliferate on all scaffolds; however, 5% rGO-PCL surface supports the growth of cells and implements the expression of extracellular matrix components necessary to anchor the cells to the surface itself. Moreover, the 5% rGO-PCL surface has superior osteoinductive properties confirmed by the improved alkaline phosphatase activity, mineral matrix deposition, and osteogenic markers expression. These results suggest that 5% rGO-PCL has useful properties for bone tissue engineering purposes

Effects of yogurt dietary supplementation on the intestinal ecosystem of a population of Emperor tamarins (Saguinus imperator)

Providing hidden food is a method of nutritional and environmental enrichment for captive animals and yogurt is sometimes used with this purpose for non-human primates. Objective of the present study was to evaluate the effect of feeding fresh yogurt on the intestinal ecosystem of Emperor tamarins (Saguinus imperator). A population of nine adult/juvenile emperor tamarins received during the whole trial a diet mainly consisting of different fruits. During the first 30 d, the diet did not contain any yogurt; during the following 28 d, every two days, a total of 300 g of fresh fruit yogurt was provided to the animals. A fresh fecal sample was collected from each animal the day before administration of yogurt started (Day 0) and again after 21 and 28 days for chemical and bacterial determinations. Throughout the study, all tamarins remained in good health and no clinical signs of intestinal discomfort were observed. During yogurt supplementation, fecal pH, moisture and ammonia resulted unchanged respect to the beginning of the study. Similarly, fecal volatile fatty acids were not affected by the yogurt intake. On the contrary, fecal spermine concentration resulted significantly decreased at Day 28 respect to Day 0 (4.4 vs. 30.1 nmol/g of feces; P < 0.05). Furthermore, the consumption of yogurt resulted in reduced fecal concentrations of coliforms, enterococci and lactobacilli on Rogosa Agar (respectively,-1.9,-1.5 and-2.8 log CFU/g of feces; P < 0.05). Results from the present study showed that emperor tamarins can tolerate high amounts of yogurt in their diet without showing any signs of lactose malabsorption (for example, soft feces or diarrhea). On the other hand, yogurt ingestion failed to exert any major influence on the animals' intestinal microbiota

Early prediction of unfavorable evolution after a first clinical episode suggestive of multiple sclerosis: the EUMUS score

BackgroundPredicting disease progression in patients with the first clinical episode suggestive of multiple sclerosis (MS) is crucial for personalized therapeutic approaches. This study aimed to develop the EUMUS score for accurately estimating the risk of early evidence of disease activity and progression (EDA).MethodsRetrospective analysis was conducted on data from 221 patients with a first clinical MS episode collected from four Italian MS centers. Various variables including socio-demographics, clinical features, cerebrospinal fluid analysis, evoked potentials, and brain MRI were considered. A prognostic multivariate regression model was identified to develop the EUMUS score. The optimal cutoff for predicting the transition from no evidence of disease activity (NEDA3) to EDA was determined. The accuracy of the prognostic model and score were tested in a separate UK MS cohort.ResultsAfter 12 months, 61.54% of patients experienced relapses and/or new MRI lesions. Younger age (OR 0.96, CI 0.93-0.99; p = 0.005), MRI infratentorial lesion(s) at baseline (OR 2.21, CI 1.27-3.87; p = 0.005), positive oligoclonal bands (OR 2.89, CI 1.47-5.69; p = 0.002), and abnormal lower limb somatosensory-evoked potentials (OR 2.77, CI 1.41-5.42; p = 0.003) were significantly associated with increased risk of EDA. The EUMUS score demonstrated good specificity (72%) and correctly classified 80% of patients with EDA in the independent UK cohort.ConclusionsThe EUMUS score is a simple and useful tool for predicting MS evolution within 12 months of the first clinical episode. It has the potential to guide personalized therapeutic approaches and aid in clinical decision-making