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SARS-CoV-2 vaccination with mRNA product BNT162b2 elicited high immunogenicity in healthy subjects in trials. This study aims to better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). We enrolled patients and healthy healthcare workers control group (HCW) that underwent mRNA BNT162b2 vaccination and measured the serum IgG anti-S-RBD response at booster dose (T1), one month after booster dose (T2) and up to 5 months (T3). Demographic, disease-specific and vaccination data were recorded. Vaccination response of 551 participants naïve to SARS-CoV-2 infection were included in HCW and 102 in the IMID group, analyzing separately those on anti-CD20. At T2 all naïve HCW developed anti-S-RBD-IgG, while 94% of IMID responded (p p = 0.031), T2 (p

Pregnancy represents an important event for women with multiple sclerosis (MS) and is often accompanied by post-partum disease reactivation. To date, the influence of this reproductive phase on long-term MS outcomes is still largely unexplored. The objective of the study was characterise a large real-world cohort of women with MS to evaluate the effects of pregnancy and breastfeeding on short- and long-term clinical and magnetic resonance imaging (MRI) outcomes while exploring the relationships with MRI measurements of brain atrophy. MS patients with and without pregnancy were recruited. Clinical relapses and MRI activity of the year before conception versus the year after delivery were evaluated. Regression models were performed to investigate the relationships between long-term MS outcomes (EDSS score and MRI brain measurements obtained by SIENAX software) and pregnancy and breastfeeding duration. Two hundred ten women with MS were enrolled; of them, 129 (61.4%) had at least one pregnancy. Of all pregnancies (n = 212), those that occurred after MS onset (90 [42.4%]) were examined to evaluate the short-term outcomes. A higher annualised relapse rate in the post-partum year versus the pre-conception year (0.54 ± 0.84 vs. 0.45 ± 0.71; p = 0.04) was observed. A regression analysis showed that clinical activity after delivery was associated with clinical activity of the year before conception (p = 0.001) as well as duration of breastfeeding (p = 0.022). Similarly, post-partum MRI activity was associated with pre-conception MRI activity (p = 0.026) and shorter breastfeeding duration (p = 0.013). Regarding long-term outcomes, having had at least one pregnancy during MS was associated with a lower EDSS score (p = 0.021), while no relationships were reported with MRI measurements. Conversely, a breastfeeding duration > 6 months was associated with lower white matter volume (p = 0.008). Our study underlines the importance of considering the effects of pregnancy and breastfeeding on short- and long-term MS outcomes. In the current therapeutic landscape, pregnancy planning and treatment optimisation in the post-partum period, in particular for women who choose to breastfeed, are fundamental for the management of these biological phases so central in a woman’s life.

Background and purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. Results: We studied 322 patients (mean age 36.8years, median EDSS score 3, median follow-up 1.94years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p&nbsp

To analyse the course of multiple sclerosis (MS) after fingolimod withdrawal in a multicentre cohort. Patients who discontinued fingolimod were included. Relapses, Expanded Disability Status Scale (EDSS), and new/gadolinium-enhancing lesions on magnetic resonance imaging (MRI) were assessed during the last year on fingolimod, and in the year after discontinuation. Wilcoxon test was used to analyse the difference in EDSS and relapses between the two periods, and to compare lymphocyte counts at discontinuation and 3 months later. Demographic and clinical variables were evaluated using univariable and multivariable logistic regression analyses. Patients were 230 (females 66.1%; mean age 38 years; median EDSS 3). Fingolimod was discontinued due to inefficacy in 57%, and 87.4% started another treatment. Relapse was observed in 33% of the patients in the year after discontinuation. Severe reactivation was observed in 15%. During the first 6 months after discontinuation, new/enhancing lesions were seen in 62/116 patients. Higher age at the fingolimod discontinuation was found to be associated with a lower probability of inflammatory activity (p = 0.001) and severe reactivation (p = 0.007) during the year after discontinuation. Lower lymphocyte count was a risk factor for clinical, radiological, and severe activity (p = 0.02, p = 0.002, p = 0.01, respectively). The main reason for the discontinuation of fingolimod was inefficacy. One-third of the patients had a relapse during the year after discontinuation, 15% experienced a severe reactivation, and approximately 50% of patients with available MRI scan had new/enhancing lesions. The risk factors for disease activity after discontinuation were low lymphocyte count and younger age.

The present work is aimed at presenting the data, methods and criteria that are being used for the assessment of ecosystem collapse risk in Italy.

Lead zirconate titanate (PZT) piezoceramics exhibit non-linear behaviour when large electric fields are applied. This causes the material properties to change through heating and increased mechanical and electrical losses. These may contribute to unexpected device behaviour and ultimately to failure. It is therefore of fundamental importance to characterise piezoelectric materials under high-power driving conditions for applications requiring large electric field. Ten different PZT compositions were investigated in the work presented here. Length-thickness-extensional (LTE) d 31 -mode plates were characterized under small signal excitation through electrical impedance spectroscopy, with curve fitting software (PRAP, TASI, Ontario, CAN) used to obtain the material properties. Subsequently, a high-power characterisation system was assembled, including a signal generator (33210A, Agilent, CA, USA), power amplifier (2100L, E & I, NY, USA), AC current probe (P6022, Tektronix, ORE, USA), differential voltage probe (GE8115, GE, GER), and DAQ (USB6346, National Instruments, TEX, USA). Bespoke software was used to acquire the electrical impedance through fast sine wave frequency sweeps in the range 1–200 $V_{pp}$ . This enabled evaluation of material properties with large electrical excitation. Additionally, a 1-D laser Doppler vibrometer (OFV 303, Polytec, GER), was integrated into the set-up to determine the transient vibrational response and determine the mechanical quality factor.

Mn:PIN-PMN-PT plates: [011]-poled (mm2 symmetry, d 32 -mode) were characterized at high-power excitation levels and at different temperatures. A bespoke high-power measurement system was utilized to acquire the electrical impedance at resonance. Results have shown that the resonant frequency/anti-resonant frequency downshifts with increasing driving voltage and temperature.

Objectives: The aim of this study was to characterize multiple sclerosis (MS) patients exposed to dimethyl fumarate (DMF) and to evaluate the predictors of therapeutic response. In addition, the study offers a picture of how DMF use has changed over the past few years in naive or switcher patients.Methods: In this observational monocentric study, we examined the prescription flow of DMF in MS patients categorized as naive or switchers (for safety/tolerability, ineffectiveness, and de-escalation strategy) from 2015 to 2019. Clinical and magnetic resonance imaging data of DMF-treated patients were analyzed, and NEDA-3 status at 24 months was evaluated by the three assessment components (absence of clinical relapses, no Expanded Disability Status Scale progression, no radiological activity). Determinants of therapeutic response were also evaluated using regression analysis.Results: The sample included 595 MS patients exposed to DMF categorized as naive (158; 26.5%) and switchers for reasons of safety/tolerability (198; 33.3%), inefficacy (175; 29.4%), and de-escalation strategy (64; 10.8%). A 15% increase in DMF use in naive and horizontal shift groups was observed in the last 3 years of observation, whereas there was a drop, with prescription passed from ~20% to p = 0.001] and being naive patients (HR = 1.38, p = 0.035) were associated with achievement of NEDA-3. Analogously, ARR in 2 years pretreatment affected the NEDA-3 achievement at 24 months in patients of the de-escalation group (HR = 0.07, p = 0.041), also indicating an effect related to the DMF initiation within 3 months (HR = 1.24, p = 0.029).Conclusion: Our findings confirm DMF as a handy drug with broad clinical utility, with greater benefits for naive patients and horizontal switchers. Additionally, an increase in the flow of DMF prescriptions in these two groups of patients was also observed in our cohort.

Metabolomic research has emerged as a promising approach to identify potential biomarkers in multiple sclerosis (MS). The aim of the present study was to determine the effect of interferon beta (IFN ß) on the metabolome of MS patients to explore possible biomarkers of disease activity and therapeutic response. Twenty-one MS patients starting IFN ß therapy (Rebif® 44 μg; s.c. 3 times per week) were enrolled. Blood samples were obtained at baseline and after 6, 12, and 24 months of IFN ß treatment and were analyzed by high-resolution nuclear magnetic resonance spectroscopy. Changes in metabolites were analyzed. After IFN ß exposure, patients were divided into responders and nonresponders according to the “no evidence of disease activity” (NEDA-3) definition (absence of relapses, disability progression, and magnetic resonance imaging activity), and samples obtained at baseline were analyzed to evaluate the presence of metabolic differences predictive of IFN ß response. The results of the investigation demonstrated differential distribution of baseline samples compared to those obtained during IFN ß exposure, particularly after 24 months of treatment (R(2)X = 0.812, R(2)Y = 0.797, Q(2) = 0.613, p = 0.003). In addition, differences in the baseline metabolome between responder and nonresponder patients with respect to lactate, acetone, 3-OH-butyrate, tryptophan, citrate, lysine, and glucose levels were found (R(2)X = 0.442, R(2)Y = 0.768, Q(2) = 0.532, p = 0.01). In conclusion, a metabolomic approach appears to be a promising, noninvasive tool that could potentially contribute to predicting the efficacy of MS therapies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-019-00721-8) contains supplementary material, which is available to authorized users.

Background and purpose: Tumefactive multiple sclerosis (TuMS) (i.e., MS onset presenting with tumefactive demyelinating lesions [TDLs]) is a diagnostic and therapeutic challenge. We performed a multicentre retrospective study to describe the clinical characteristics and the prognostic factors of TuMS. Methods: One hundred two TuMS patients were included in this retrospective study. Demographic, clinical, magnetic resonance imaging (MRI), laboratory data and treatment choices were collected. Results: TuMS was found to affect women more than men (female:male: 2.4), with a young adulthood onset (median age: 29.5years, range: 11–68 years, interquartile range [IQR]: 38 years). At onset, 52% of TuMS patients presented with the involvement of more than one functional system and 24.5% of them with multiple TDLs. TDLs most frequently presented with an infiltrative MRI pattern (38.7%). Cerebrospinal fluid immunoglobulin G oligoclonal bands were often demonstrated (76.6%). In 25.3% of the cases, more than one acute-phase treatment was administered, and almost one-half of the patients (46.6%) were treated with high-efficacy treatments. After a median follow-up of 2.3years (range: 0.1–10.7 years, IQR: 3.4 years), the median Expanded Disability Status Scale (EDSS) score was 1.5 (range: 0–7, IQR: 2). Independent risk factors for reaching an EDSS score ≥3 were a higher age at onset (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.03–1.14, p&nbsp

Importance Availability of new disease-modifying therapies (DMTs) and changes of therapeutic paradigms have led to a general improvement of multiple sclerosis (MS) prognosis in adults. It is still unclear whether this improvement also involves patients with pediatric-onset MS (POMS), whose early management is more challenging. Objective To evaluate changes in the prognosis of POMS over time in association with changes in therapeutic and managing standards. Design, Setting, and Participants Retrospective, multicenter, observational study. Data were extracted and collected in May 2019 from the Italian MS Registry, a digital database including more than 59 000 patients. Inclusion criteria were MS onset before age 18 years, diagnosis before January 2014, and disease duration of at least 3 years. Exclusion criteria were primary progressive MS, Expanded Disability Status Scale (EDSS) score of at least 8 one year after onset, unavailability of diagnosis date, and less than 2 EDSS score evaluations. Eligible patients were 4704 patients with POMS. According to these criteria, we enrolled 3198 patients, excluding 1506. Exposures We compared time to reach disability milestones by epoch of MS diagnosis (

Background Event-related potentials (ERPs) have been proposed as a neurophysiological biomarker to capture cognitive dysfunction in multiple sclerosis (MS). Few studies have evaluated the relationships between ERPs and brain atrophy as known marker of structural brain damage related to cognitive impairment (CI). Objectives To explore the relationships of brain atrophy, including of the cortex and deep grey matter, with ERP abnormalities and cognitive function, as defined using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). Results Seventy-eight patients with relapsing-remitting MS were enroled, of which 38 (48.7%) had CI. Independent t-test comparisons of the ERP parameters found a significant difference in P300 wave latency, with a latency of 343.7 ± 32.6 ms in the CI group vs. 320.3 ± 16.5 ms in the cognitively preserved (CP) group (p = 0.001). Significant differences in the MRI measurements, including the cortex (p = 0.02) and deep grey matter structures [thalamus (p = 0.001), amygdala (p = 0.030), and nucleus accumbens (p = 0.004)) were observed, with lower measurements in the CI group. Regression models were also performed to explore the impact of brain volumes on ERP parameters. This showed a relationship between P300 latency and the lower amygdala (p = 0.02) and hippocampus (p = 0.03) volumes, while the amplitude of the P300 was significantly associated with a lower cortex volume (p = 0.01). Conclusion Cortex volume emerged as the most significant predictor of the P300 amplitude. The amygdala and hippocampal volumes were found to influence P300 latency, highlighting the role of deep grey matter atrophy in ERPs for the first time. The combination of structural MRI and neurophysiological techniques, sensitive to diverse aspects of MS pathology, could improve the understanding of CI in MS and its neurodegenerative and inflammatory substrate.

Background: Cognitive impairment (CI) is common in people with multiple sclerosis (pwMS). The assessment of CI is based on neuropsychological tests and accurate anamnesis, involving the patients and caregivers (CG). This study aimed to assess the complex interplay between self-perception of CI, objective CI and the brain atrophy of MS patients, also exploring the possible differences with CI evaluated by caregivers.Methods: Relapsing pwMS were enrolled in this study. Subjects underwent neuropsychological examination using the Brief Cognitive Assessment for Multiple Sclerosis (BICAMS) and evaluation of self-reported cognitive status using the patient-version of the Multiple Sclerosis Neuropsychological Questionnaire (p-MSNQ). Depression and anxiety were also evaluated using the Back Depression Inventory-version II (BDI-II) and Zung Anxiety Scale. Brain MRI images were acquired and brain volumes estimated. For each patient that was enrolled, we spoke to a caregiver and collected their perception of the patient's CI using the MSNQ- Caregiver version.Results: Ninety-five MS subjects with their caregivers were enrolled. CI was detected in 51 (53.7%) patients. We found a significant correlation (p < 0.001) between BICAMS T scores and lower whole brain (Rho = 0.51), gray matter (Rho = 0.54), cortical gray matter (Rho = 0.51) volumes and lower p-MSNQ (Rho = 0.31), and cg-MSNQ (Rho = 0.41) scores. Multivariate logistic regression showed that p-MSNQ is related to a patient's anxiety to evaluate by Zung Score (p < 0.001) while cg-MSNQ to patient's brain volume (p = 0.01).Conclusion: Our data confirm that neuropsychological evaluation results are related to the perception of CI and brain volume measures and highlight the importance of the caregiver's perception for cognitive assessment of pwMS.

Background Bipolar disorder (BD) is frequently observed in patients affected by multiple sclerosis (MS), presenting a lifetime estimate of around 8%. However, uncertainty exists on the brain damage associated with this psychiatric comorbidity. This study aimed to investigate the effect of brain atrophy, particularly that of the subcortical grey matter (scGM) structures that notoriously regulate the affective functioning, on the co-occurrence of BD in patients with MS. Methods A group of patients with MS affected by BD and a control group of patients with MS without any mood/psychiatric disorder, as defined using standardised diagnostic tools (Advanced Neuropsychiatric Tools and Assessment Schedule), were recruited. The patients underwent brain MRI, and the volumes of the whole brain (WB), white matter (WM), and grey matter (GM) were estimated using SIENAX. Thus, the scGM volumes of the putamen, caudate, thalamus, hippocampus, amygdala, nucleus accumbens, and pallidus were estimated using the FIRST tool. Results The sample included 61 patients with MS, amongst whom 15 (24.6%) had BD. No differences in the WB, WM, and cortical GM volumes were observed between the patients with MS with and without BD. Conversely, the multiple regression analysis revealed a significant association of BD with lower volumes of the putamen (p = 0.032), nucleus accumbens (p = 0.029), and pallidus (p = 0.061; with a trend towards significance), independently from the demographic and MS clinical features. Conclusions Our preliminary results indicated that the nucleus accumbens and putamen are smaller in MS patients with BD. Further investigations in larger cohorts of MS patients with affective disorders are necessary to confirm these data and understand the structural brain damage underlying this psychiatric comorbidity.

Background: Multiple sclerosis (MS) is a chronic immunemediated disease of the central nervous system with a highly variable clinical presentation and disease progression. In this study, we investigate the metabolomics profile of patients affected by relapsing&ndash, remitting MS (RRMS)and primary progressive MS (PPMS), in order to find potential biomarkers to distinguish between the two forms. Methods: Cerebrospinal Fluid CSF and blood samples of 34 patients (RRMS n = 22, PPMS n = 12) were collected. Nuclear magnetic resonance (1H-NMR) and mass spectrometry (coupled with a gas chromatography and liquid chromatography) were used as analytical techniques. Subsequently, a multivariate statistical analysis was performed, the resulting significant variables underwent U-Mann&ndash, Whitney test and correction for multiple comparisons. Receiver Operating Characteristic ROC curves were built and the pathways analysis was conducted. Results: The analysis of the serum and the CSF of the two classes, allowed the identification of several altered metabolites (lipids, biogenic amines, and amino acids). The pathways analysis indicated the following pathways were affected: Glutathione metabolism, nitrogen metabolism, glutamine&ndash, glutamate metabolism, arginine&ndash, ornithine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis etc. Conclusion: The analysis allowed the identification of a set of metabolites able to classify RRMS and PPMS patients, each of whom express different patterns of metabolites in the two biofluids.

There is limited information on socio-professional attainment in pediatric-onset multiple sclerosis (POMS) compared with adult-onset MS (AOMS).To assess socio-professional outcomes in POMS and AOMS and variables influencing these outcomes.One-hundred-fifteen AOMS and 111 POMS patients underwent neuropsychological testing (Brief Repeatable Battery, Stroop test), assessment of cognitive reserve (CR) (education, National Adult reading Test -NART, Barratt Simplified Measure of Social Status), fatigue (Fatigue Severity Scale), depression (Montgomery-Åsberg Depression Rating Scale), socio-professional performance (Work and Social Adjustment Scale -WSAS). Prognostic factors were assessed using logistic and linear multivariable regression analyses.34.5% of patients showed CI without significant differences between AOMS and POMS. Cognitively impaired patients were older (p=0.024), had higher EDSS scores (p=0.041) and lower IQ (p0.001) compared with cognitively preserved patients. Better WSAS scores were associated with younger age (p=0.007), lower EDSS (p0.001) and higher educational levels (p=0.001). Fourteen POMS (13%) and six AOMS (5%) achieved a lower educational level compared with their parents (p=0.06). POMS exhibiting a lower than expected educational level, had a lower median IQ compared with the remaining subjects (101 vs 106.5; p=0.03). Unemployment rate was predicted by higher disability (p=0.044) and lower educational levels (p0.001). Occupational complexity was positively correlated to educational level (0.001) and NART scores (0.040).This study underscores the complex relationships between cognition and educational, socioeconomic and professional attainment in MS and supports a protective role of CR in both POMS and AOMS.

ObjectiveCladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data.MethodsData from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity.ResultsAll weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; p < 0.001), glatiramer acetate (RR = 0.49; p < 0.001), and dimethyl fumarate (RR = 0.6; p = 0.001); a similar ARR to that with fingolimod (RR = 0.74; p = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; p = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis.ConclusionIn patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity.Classification of evidenceThis study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.

Background: Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS). Objective: To investigate the effectiveness and safety of rituximab in relapsing–remitting (RR) and progressive MS. Methods: This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed. Results: A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p Conclusion: Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.

Background: Gait analysis is a reliable tool to characterise ambulation in Charcot-Marie-Tooth, the obtained are complex data makes its use scarce in clinical practice. The use of synthetic measure...

While cost estimation is a very positive tool for spatial conservation prioritisation, there are few examples where costs (in monetary terms) are applied. We present a repeatable method to estimate and map field values in monetary terms using common correlative models. We modelled, with a resolution of 1 km(2), the information obtained by several real estate’s agencies with a set of eleven environmental, climatic, and anthropogenic variables. Land cover was the main influencing factor, but further variables were affecting bids on field sales according to the socio-economic specificity of each administrative province. The estimated values were related to endemic plant species richness, their conservation status and altitudinal ranges. Richest areas in endemics have lower values given current market conditions and, within these endemic rich areas, values near the coast were generally higher than the rest of endemic-rich territories. Despite their limits, our method offers an alternative perspective on the challenges of simplifying the extrapolation of useful information for planning and disseminating the conservation of many ecosystem services providers.

BACKGROUND Frequently diagnosed in young adulthood, multiple sclerosis (MS) and several MS-related factors can influence patients' unemployment status and negatively affect work productivity and daily functioning. OBJECTIVE We examined MS patients' employment status and evaluated clinical features influencing it. Furthermore, we investigated patients' burdens due to visible and invisible MS symptoms through their worsening daily functioning. METHODS The study included outpatients affected by MS according to the 2010 McDonald criteria. The co-occurrence of invisible symptoms (fatigue, depression and apathy) was stated using validated, self-administered tools: Fatigue Severity Scale (FSS); Beck Depression Inventory-Second Edition (BDI-II); Apathy Evaluation Scale (AES). Impairment in daily functioning due to MS was assessed using the Work and Social Adjustment Scale (WSAS). Descriptive statistics, hierarchical regression analyses, Pearson's correlation, and the t-test were conducted. RESULTS Of the 123 participants, 52 (42.3%) were unemployed. Results showed employment to be positively associated with higher education levels (p 0.01); female gender (p 0.03) and higher disability (p 0.02) showed negative associations with employment. No associations were found between employment and fatigue or clinically relevant depressive and apathetic symptoms. High correlations were found between WSAS score and Expanded Disability Status Scale score (r = 565, p

Background The dual task paradigm (the simultaneous performance of motor and cognitive task) is used in a laboratory setting to evaluate walking impairments that affect patients’ daily lives. Although promising, it is poorly standardized and neither the cognitive task nor the motor task have been validated in a matched healthy control group (HC) for multiple sclerosis (MS). Objective Our aim was to set up a standardized instrument to evaluate cognitive motor interference in MS using the interference test par excellence: the stroop colour word test (SCWT). Methods Patients with MS and HC underwent 3D gait analysis with a dual task protocol, using the SCWT as a cognitive task. Gait performance impairment during the dual task was evaluated by dual task cost (DTC). A MANOVA was used to verify the effect of status (MS, HC) on DTC, calculated for the spatiotemporal parameter of the gait. Results In MS, the DTC was higher for the following gait parameters: speed (p = .013), cadence (p = .004), stride time (p = .005) stance phase (p Conclusion DTC is present in MS and HC, but the motor cost in MS is higher. The present work provides a useful and validated basis for future studies about cognitive motor interference in MS.

Paediatric onset multiple sclerosis (POMS) is associated with reduced brain and deep grey matter volume in comparison with that in healthy controls and individuals with adult onset multiple sclerosis (AOMS). The aim of our study was to evaluate the impact of POMS on adult brain volume with adjustment for other parameters, such as disease duration.We recruited 20 POMS and 40 AOMS patients and 20 healthy controls matched for age and sex. All study participants were adults at the time of inclusion in the study. All study subjects underwent brain magnetic resonance imaging (MRI) to evaluate whole brain, white matter, grey matter, cortical, and deep grey matter volumes. Clinical features, such as the Expanded Disability Status Scale (EDSS) score and disease duration, were also assessed.Brain (p = 0.01), grey matter (p = 0.01), and deep grey matter volume (p = 0.03) was significantly lower in POMS patients than in AOMS patients, while no differences were detected in the volume of white matter or cortical grey matter. A multiple linear regression analysis showed a relationship between brain volume (dependent variable) and the independent variables age (p 0.000) and paediatric onset (p 0.001), while other independent variables, including disease duration, sex, and disability, were not significantly different among groups. There were significant differences in thalamic volume among POMS and AOMS patients and healthy controls.Our data support the previous findings that POMS patients have reduced brain and deep grey matter volume, particularly thalamic volume, compared with sex- and age-matched AOMS patients and healthy controls. These findings appear to be independent of disease duration and other clinical features.

Several correlations between cognitive impairment (CI), radiologic markers and cognitive reserve (CR) have been documented in MS.To evaluate correlation between CI and brain volume (BV) considering CR as possibile mitigating factor.195 relapsing MS patients underwent a neuropsychological assessment using BICAMS. BV was estimated using SIENAX to obtain normalized volume of brain (NBV), white matter (NWV), gray matter (NGV) and cortical gray matter (CGV). CR was estimated using a previously validated tool.Pearson test showed a correlation between the symbol digit modality test (SDMT) score and NBV (r=0.38; p0.000) NGV(r=0.31; p0.000), CGV (r=0.35; p0.000) and CRI score(r=0.42; p0.000). Linear regression (dependent variable:SDMT) showed a relationship with CR scores (p=0.000) and NGV(p0.000). A difference was detected between cognitive impaired and preserved patients regarding mean of NBV(p=0.002), NGV(p=0.007), CGV(p=0.002) and CR Scores (p=0.007). Anova showed a association between the presence of CI (dependent variable) and the interaction term CRIQ × CGV (p=0.004) whit adjustment for age and disability evaluated by EDSS.Our study shows a correlation between cognition and BV, in particular gray matter volume. Cognitive reserve is also confirmed as an important element playing a role in the complex interaction to determine the cognitive functions in MS.

Background: For prioritising practical conservation measures in areas of high endemic plant diversity, a fine-scale hierarchy of sites needs to be established. In this context, conservation sites designed at local and regional levels are considered a network of interconnected areas.Aims: The main aim was to identify two hierarchical levels of a network of conservation sites, called ‘micro hotspots’ and ‘nano hotspots’, and test their efficiency for achieving conservation objectives across the island of Sardinia, Mediterranean Basin.Methods: We analysed the spatial distribution of endemic vascular plant species (EVPS) richness. Additionally, the area, perimeter, connectivity and surplus costs for the protection of all endemic plant populations were used as ranking criteria for a hierarchical classification.Results: We identified eight micro hotspots and 82 nano hotspots. Amongst the three possible solutions compared, the integrated network of micro and nano hotspots resulted in more effective conservation ...

Autologous hematopoietic stem cell transplantation (aHSCT) is used in aggressive relapsing and progressive multiple sclerosis (MS). The multicentre studies and case series reported have relatively short follow-up. To evaluate long-term effect and safety of HSCT in MS. Patients referred to the MS centre of Cagliari and undergoing HSCT were included. Variations in relapses and EDSS before and after HSCT were evaluated by Wilcoxon test. A descriptive analysis was made for other clinical data. Nine patients (female 6, males 3; 5 relapsing–remitting, 2 secondary progressive, 1 primary progressive, and 1 progressive relapsing) performed HSCT (1999–2006). The median follow-up was 11 years (11–18). Eight patients underwent aHSCT, seven using a low intensity conditioning regimen, and one an intermediate intensity. The primary progressive underwent allogeneic HSCT, due to onco hematological disease. The relapses number decreased in the 2 years following the procedure compared to the two preceding years (p = 0.041). New relapses or disease progressions were observed after a range of 7 (low intensity regimen)–118 (intermediate intensity) months. At last follow-up, the EDSS was stable in two patients, improved in two, and worse in five (maximum 2 EDSS in one patient). Six patients showed new lesions, and seven gadolinium-enhancing on brain MRI after a mean of 23.3 and 19.8 months, respectively. Two serious adverse events were reported: melanoma, and progressive multifocal leukoencephalopathy. Our results confirm in a long follow-up the efficacy of HSCT in reducing relapses and disability progression. The risk/benefit profile is better for intermediate intensity regimens.

SUMMARYRecent extinction rates suggest that humans are now causing the sixth mass extinction, and the Mediterranean islands are at the forefront of many of the environmental issues involved. This study provides an alternative approach for investigating documented local plant extinctions that occurred in Sardinia (western Mediterranean) during the last half century. A total of 190 local extinctions of 62 plant species were used to investigate the independent effects of eight ecological and anthropogenic variables and to model the areas of potential extinctions where plant conservation efforts could be focused. If all analysed plant species were considered together, ecological factors explained local extinctions more than anthropogenic factors. The independent effects of each factor considerably varied among species of different lifeforms and altitude ranges. Accordingly, distribution models of local extinctions outscored areas that are potentially rich in plant species with conservation interest, but which are particularly affected by humans. This paper suggests a reproducible, operational framework for analysing which extinction factors may play important roles in similar contexts and where they might be relevant.

Background. In people with multiple sclerosis (pwMS), disability is generally assessed on the basis of ambulation abilities, whereas upper limb motor dysfunctions are less frequently considered. Nevertheless, they can severely affect the quality of life of pwMS. To date, it remains mostly unknown whether a relationship exists between upper and lower limb impairments. Aim. To investigate the existence of a relationship between upper and lower limb impairments in pwMS based on two fundamental motor tasks, namely walking and hand-to-mouth (HTM) movement. Methods. Twenty-eight pwMS with Expanded Disability Status Scale (EDSS) scores in the range of 1–6, and 21 healthy controls (HC) underwent a kinematic analysis of gait and HTM movement performed with a motion capture system. The spatiotemporal parameters for the two tasks were calculated and correlated using Spearman’s rank correlation coefficients. Results. The pwMS performed worse than HC on both tasks. Small to large correlations were found between the total HTM movement duration and most of the gait parameters (rho, 0.35–0.68; p<0.05). Conclusions. Both upper and lower limb motor abilities in pwMS worsen as disability increases. Nevertheless, their relationship is only moderate. This finding emphasizes the need for specific tests to quantify disability considering the overall motor function in pwMS.

No postmarketing randomised clinical trials are available about alemtuzumab, and real-world data are limited. We aimed to analyse the efficacy and safety of alemtuzumab in a single-centre cohort of patients with relapsing–remitting MS. Patients who took alemtuzumab were enrolled. We collected the following data: age, sex, MS history, expanded disability status scale (EDSS), relapses, magnetic resonance imaging (MRI) parameters after alemtuzumab, and adverse events. EDSS scores before alemtuzumab and at the last follow-up were compared by Wilcoxon test. Time to first relapse was analysed after dividing the cohort on the basis of previous treatment. Ninety patients were enrolled [women 74.4%; naive 7; mean follow-up 27 months (SD 23)]. The EDSS was reduced from a median of 2.5 (IQR 1.5–4) before alemtuzumab to 2.0 (IQR 1.5–3.5) after (p = 0.025). The time to first relapse was shorter in patients shifting from a second-line therapy (p = 0.011). Over 2 years, 43.7% had no evidence of disease activity. We observed infusion-related reactions in 95.5% patients, including 11.1% with pneumonitis, thyroiditis in 11%, and thrombocytopenia in 3.3%. We confirmed the clinical and MRI efficacy of alemtuzumab in the clinical setting and the frequency of infusion-related reactions. Compared with that in clinical trials, higher number of patients developed pneumonitis during infusion.

Objective To evaluate disease activity according to rituximab (RTX) induction and maintenance regimens in a multicenter real-life dataset of NMOSD patients. Methods This is an observational-retrospective multicentre study including patients with NMOSD treated with RTX in 21 Italian and 1 Swiss centers. Demographics, relapse rate and adverse events over the follow-up were summarized taking into account induction strategy (two-1 g infusions at a 15-day interval (IND-A) vs. 375 mg/m2/week infusions for one month (IND-B)) and maintenance therapy (regimen A (M-A) with fixed time-points infusions vs. regimen B (M-B) based on cytofluorimetric driven reinfusion regimens, the least further subdivided according to CD19+ B cells (M-B1) or CD27+ memory B cells (M-B2) monitoring). Results 131 subjects were enrolled, 127 patients completed the induction regimen and 119 patients had at least one follow-up visit and were included in the outcome analysis. Median follow-up was 1.7 years (range 0.1–11.6). Annualized relapse rate (ARR) was 1.7 in the year before RTX start and decreased to 0.19 during the follow-up. Both ARR and Time to first relapse (TTFR) analysis showed a trend toward an increased disease activity for IND-B and M-A. No patients with MT-B2 experienced relapses during the follow-up. Number of relapses in the year before RTX initiation and having received a previous treatment were significantly associated with higher ARR and reduced TTFR in the multivariate analysis. Interpretation We confirm RTX efficacy in NMOSD patients. Use of specific induction and maintenance protocols is warranted in order to foster RTX efficacy and to reduce costs and side effects.

Background: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences. Objectives: To identify prognostic factors for early switch after first therapy choice. Methods: Newly diagnosed relapsing–remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models. Results: We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p Conclusion: Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.

Background: A high reactivation of multiple sclerosis (MS) was reported in patients treated with alemtuzumab after fingolimod. We aimed to understand whether this shift enhanced the risk for reactivation in a real-life cohort. Methods: Subjects with relapsing MS, shifting from fingolimod to alemtuzumab were enrolled. We collected the following data: age, sex, disease duration, relapses after fingolimod withdrawal, new T2/gadolinium (Gd)-enhancing lesions in the last magnetic resonance imaging (MRI) during fingolimod and in the first, while on alemtuzumab, lymphocyte counts at alemtuzumab start, and Expanded Disability Status Scale (EDSS) before and after alemtuzumab. Results: We enrolled 77 patients (women 61 (79%); mean age 36.2years (SD 9.6), and disease duration 12.3years (SD 6.8) at fingolimod discontinuation; median washout 1.8months). The annualised relapse rate was 0.89 during fingolimod, 1.32 during washout, and 0.15 after alemtuzumab (p = 0.001). The EDSS changed from a median of 3 (IQR 2–4) at the end of fingolimod to 2.5 after alemtuzumab (IQR 1.5–4) (p = 0.013). The washout length and the lymphocyte count before alemtuzumab were not associated with EDSS change after alemtuzumab (p = 0.59 and p = 0.33, respectively). MRI activity decreased after alemtuzumab compared to that during fingolimod (p = 0.001). At alemtuzumab start, lymphocyte counts were < 0.8 × 103/mL in 21 patients. Conclusions: In our cohort, alemtuzumab reduced relapse, new T2/Gd-enhancing lesions, and EDSS score, as compared to the previous periods (fingolimod/washout). These results were not related to washout length or lymphocyte counts. Therefore, a rapid initiation of alemtuzumab after fingolimod does not seem to be a risk factor for MS reactivation.

Background The relationship between cognitive assessment results in multiple sclerosis (MS) and performance in daily activities (DAs) remains unclear. Our study aimed to evaluate the relationship between cognitive functions (CF) measured by tests, performance in DAs, and the perception of CF in patients and their caregivers (CG) in MS. Methods The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was used to evaluate cognitive status. We created an ad hoc questionnaire (DaQ) to assess performance in DAs not requiring specific motor skills. We used the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) to measure each patient self-judgment and caregiver’s perception of CF. Results Forty-nine patients and their caregivers were included in the study. Significant correlations were found between the BICAMS and the DaQ (Symbol Digit Modalities Test (SDMT): r = − 0.48, p

Regional assessments could be more reliable than global ones, especially for species in peripheral parts of their range. In this sense, distribution criteria proposed by the IUCN, expressed by the Extent of Occurrence (EOO) and the Area of Occupancy (AOO), are of critical importance to evaluate the risk category at any scale. Our study was focused on the yellow gentian ( Gentiana lutea L. subsp. lutea ), a rhizomatous mountain plant of central and southern Europe, included in the Annex V of the Directive 92/43/EEC. The exhaustive and updated regional distribution and the recently published extinct localities, allowed for review of option to increase the number of criteria used for its regional conservation status assessment. In particular, the current restricted EOO and AOO extents and reductions occurred during the last three generations led this plant being considered as Endangered (EN), according to the IUCN sub-criteria A2, B1 and B2. Additionally, Species Distribution Models based on the extant localities and the respective current and future climate scenarios (2050 and 2070) predicted a decrease of its environmental niche reducing its altitudinal range towards higher elevations. This reduction was greater than 50% and confirmed the regional conservation status of EN, also according to the sub-criterion A3. This paper shows the reliability of regional risk assessment of peripheral and/or narrow populations, which is an effective tool for helping the development of the necessary conservation management, underling a diversified set of solutions for each specific past, present and future threat that could occur in each locality.

The TRACER multicenter retrospective study aimed to collect data on treatment adherence in a real-life setting, in order to identify predictors of adherence at baseline.We recruited 384 relapsing-remitting (RR) multiple sclerosis patients with at least 12 months of use of RebiSmart®. This electronic device records the performed injections and assesses adherence as the percentage of 'not missing doses', through the connection to the iMed database. Subjects with at least 80% of completed doses at the 12 month of therapy were defined 'treatment adherents'.After 12 months, 89.3% of patients were adherent; 93.2% of patients aged 26-40 years at baseline were adherent (vs 79% of the ≤25 and 87.5% of the ≥41 year olds; p = 0.006). Furthermore, 90.5% of patients with a baseline Expanded Disability Status Scale (EDSS) score4 showed ≥80% adherence (vs 71.4% in those with EDSS score ≥4; p = 0.016). Fifty-four percent of the patients who were not adherent after 3 months were also not adherent after 12 months (OR 16.8; CI 95%:7.1-39.8).Patients aged 26-40 years and with an EDSS score4 at baseline were the most adherent. The status of 'treatment adherent' in the first 3 months was predictive of higher adherence in the long term.

Background Cognitive dysfunctions are very frequent in people living with multiple sclerosis (MS). Several studies have previously indicated grey matter (GM) atrophy as useful predictor of patients’ cognitive impairment. However, considerable uncertainty exists about the possible impact of deep grey matter volumes on cognition. This study aimed to evaluate the relationship of the subcortical (sc) GM volumes with the presence and severity of global and selective cognitive impairment in MS. Methods A group of MS patients with relapsing remitting course were enrolled. Patients underwent a neuropsychological evaluation by using the Brief Repeatable Battery of Neuropsychological Tests (BRBN) and the Delis–Kaplan Executive Function System Sorting Test (D-KEFST); z scores were estimated and items with z score below 2 standard deviation were considered failed. Thus, brain MRIs images were acquired and measurements of whole brain (WB), white matter (WM), and cortical grey matter (GM) were obtained by SIENAX. After FIRST tool segmentation, volumes of subcortical GM structures were also estimated. Results The sample included 50 MS patients, of which 16/50 (32%) subjects were cognitively impaired. Multiple regression analyses found a significant association of severity of cognitive impairment, defined as number of failed neuropsychological tests, with lower volumes of cortex (p=0.003), thalamus (p=0.009), caudate (p=0.011), putamen (p=0.020), pallidus (p=0.012) and hippocampus (p=0.045), independently from other MS features. In addition, an association between accumbens volume and D-KEFS ST FSC and D-KEFS ST FSD z scores was observed (p Conclusions Our results indicated that volumes of several scGM structures, and in particular of thalamus, contribute to determine cognitive dysfunctions in MS, mainly influencing the executive functioning. Further investigations in larger MS cohorts with cognitive impairment are necessary to better understand the structural brain damage underlying this “invisible disability”.

Some studies have indicated the importance of considering smoking, vitamin D deficiency and obesity as negative prognostic factors for clinical and MRI outcomes in multiple sclerosis (MS). This study aimed to evaluate the possible effects of these modifiable risk factors on brain MRI lesion burden of patients with early MS, also exploring the influence on initial clinical features.MS patients were enrolled at diagnosis time and examined for smoking, body mass index (BMI), serum level of lipids and 25(OH) vitamin D. Brain MRIs' were acquired and lesion volume assessed by Jim software. Clinical data (disease course, disease duration, and EDSS score) were also collected.64 patients were enrolled, of these 4 (6.2%) had a primary progressive course. Mean age was 39.8 ± 11.1 years and mean EDSS 1.5 ± 1.1. Forty (62.5%) patients were smokers and 40 (62.5%) were overweight (BMI25). Insufficient levels of vitamin D (20 ng/mL) were reported in 36 (56.2%) patients, while 24 (37.5%) patients had an altered lipid profile with total cholesterol200 mg/dl and LDL100 mg/dl. No association between early clinical features and modifiable risk factors were reported. Multiple regression analysis showed an association between lesion burden and smoking status (p 0.003), while no association was reported with BMI, altered lipid profile and vitamin D insufficiency.Several risk factors may play a role in evolution of MS. Our results show that smoking status, probably due to chronic vascular and neurotoxic effects of the cigarette components, can affect the brain damage from the early stages of MS. No association was observed with the other explored modifiable risk factors, although an effect due to the small sample size cannot be excluded.

Some studies have indicated the importance of considering the presence of vascular comorbidities as negative prognostic factors for MRI outcomes in multiple sclerosis (MS). This study aimed to evaluate the possible influence of the most frequent vascular risk factors on brain volume in MS, also exploring the burden of their combined effects.MS patients with at least one vascular risk factor and a control group of MS patients were enrolled. Patients underwent brain MRI and the volumes of the whole brain (WB), white matter (WM), grey matter (GM), and cortical GM were estimated by SIENAX. Longitudinal atrophy was assessed by SIENA.The sample included 326 MS patients, of these 49 (15%) had diabetes mellitus, 44 (13.4%) hypertension and 50 (15.3%) were active smokers. Multiple regression analyses revealed that diabetes mellitus was associated with significant reductions in WB (p = 0.03), GM and cortical GM (p = 0.01) volumes. Similarly, reduced cortical GM volume was associated with hypertension (p 0.05). A strong relationship between the co-occurrence of multiple vascular risk factors and lower cortical GM volume (p = 0.007) was also identified. Ninety patients were included in the longitudinal study and a greater annualized brain volume loss was found in those with at least one vascular risk factor than in the control group (-1.05% vs. -0.58%, p = 0.005).Our results show that the vascular comorbidities affect brain atrophy, indicating that these conditions should be carefully monitored in patients with MS with a focus on limiting brain damage.

Cognitive impairment concerns a significant percentage of patients with multiple sclerosis (MS). A transient impairment of cognition with a simultaneous presence of non-symptomatic gadolinium (Gd)-enhancing lesions in patients with MS was previously described. Our study aimed to evaluate modifications in cognitive function before and after the occurrence of asymptomatic MRI gadolinium (Gd)-enhancing lesions in relapsing MS patients.All patients underwent a neuropsychological evaluation before (30-60 days) and after (30-60 days) brain MRI with Gd administration. Patients were classified as Gd positive (presence of enhancing-lesions) and Gd negative (absence of enhancing-lesions). We also recruited a healthy controls group underwent to the same neuropsychological assessment for two times with the same timing of MS patients.We included 84 relapsing-remitting patients and 40 healthy controls. Brain MRI results showed that 14/84 (16.7%) patients had asymptomatic Gd-enhancing-lesion. No significant variation in cognitive performance between baseline and follow-up was observed in patients with or without MRI-enhancing lesions. However, an increase between baseline and follow-up was observed in the mean scores of the Symbol Digit Modality Test (41.9 at baseline versus 46.7 at follow-up, p : 0.001). This increase was significantly lower in Gd positive patients compared to Gd negative patients (mean increase 1.1 in Gd positive versus 4.9 in Gd negative, p: 0.001) and to healthy controls groups (mean increase 7.2; p 0.001) CONCLUSIONS: In our study, the absence of a practice effect in Gd positive compared to Gd negative patients and to healthy controls suggests a possible role of focal inflammation on cognitive function of MS patients.

Background The principal biomarker of neurodegeneration in multiple sclerosis (MS) is believed to be brain volume, which is associated with cognitive functions and retinal nerve fibre layer (RNFL). A cross-sectional and longitudinal assessment of the relationship between RNFL, cognitive functions and brain volume. Methods At baseline, relapsing patients and healthy controls underwent 1.5 T MRI to estimate the normalized volume of brain (NBV), grey (NGV), white (NWV) and peripheral grey (pNGV) matter. Cognitive functions were evaluated by BICAMS, RNFL by Spectral-Domain OCT. Patients were re-evaluated after 12 months. Results Cognitive functions, brain volume, and RNFL differed between the group of 66 patients and that of 16 healthy controls. In the MS group, at baseline, an association was found between: p-NGV and symbol-digit (SDMT) (p = 0.022); temporal-RNFL and NBV (p = 0.007), NWV (p = 0.012), NGV (p = 0.048), and p-NGV (p = 0.021); papillo-macular bundle-RNFL and NBV (p = 0.013), NWV (p = 0.02), NGV (p = 0.049), and p-NGV (p = 0.032). Over the observational period, we found a reduction of brain volume (p

BACKGROUND AND PURPOSE Patients with multiple sclerosis (MS) have many pregnancy-related doubts and fears. Careful counselling is thus important. Mitoxantrone (MITO) is used in patients with aggressive MS and may affect reproductive capacity. The aim of this study was to investigate pregnancy planning and outcomes in patients with MS treated with MITO, both before and after the treatment. METHODS Patients with MS previously treated with MITO were recruited. Clinical, demographic and treatment data were recorded. A questionnaire regarding the planning and outcomes of all pregnancies was administered. Parametric and non-parametric tests were performed using SPSS 22 software. RESULTS A total of 238 patients (female/male, 158/80) were included; 106 subjects planned a pregnancy before MITO and 40 after MITO. Of these, respectively, 102 (97%) and 35 (85%) resulted in conception, 19 (19%) and 7 (18%) in miscarriage, 6 (6%) and 1 (3%) in abortion and 98 (96%) and 32 (91%) were full-term pregnancies. A total of 96 patients (40%) planned a pregnancy only before MITO (and not after), whereas 30 (13%) planned a pregnancy only after MITO (and not before) (P < 0.01). A total of 103 patients did not plan a pregnancy before MITO and 198 did not plan a pregnancy after MITO. The reasons included lack of interest or a partner, fear of MS and infertility. All of the babies born were healthy until the end of follow-up. CONCLUSIONS Mitoxantrone does not affect the ability to conceive or pregnancy outcomes. We found no differences in pregnancies, abortions or miscarriages before and after MITO. The tendency to plan pregnancies decreased significantly after MITO. Our findings may be useful for improving the quality of life of patients and the approach taken by neurologists.

Background: Few data are available on very long-term follow-up of pediatric multiple sclerosis (MS) patients treated with disease modifying treatments (DMTs). Objectives: To present a long-term follow-up of a cohort of Pediatric-MS patients starting injectable first-line agents. Methods: Data regarding treatments, annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, and serious adverse event were collected. Baseline characteristics were tested in multivariate analysis to identify predictors of disease evolution. Results: In total, 97 patients were followed for 12.5 ± 3.3 years. They started therapy at 13.9 ± 2.1 years, 88 with interferons and 9 with copaxone. During the whole follow-up, 82 patients changed therapy, switching to immunosuppressors/second-line treatment in 58% of cases. Compared to pre-treatment phase, the ARR was significantly reduced during the first treatment (from 3.2 ± 2.6 to 0.7 ± 1.5, p Conclusion: Pediatric-MS patients benefited from interferons/copaxone, but the majority had to switch to more powerful drugs. Starting therapy before 12 years of age could lead to a more favorable outcome.

Several studies indicated that multiple sclerosis (MS) is frequently associated with other autoimmune diseases. However, it is little known if the coexistence of these conditions may influence the radiologic features of MS, and in particular the brain volumes. To evaluate the effect of autoimmune comorbidities on brain atrophy in a large case–control MS population. A group of MS patients affected by a second autoimmune disorder, and a control MS group without any comorbidity, were recruited. Patients underwent a brain MRI and volumes of whole brain (WB), white matter (WM), and gray matter (GM) with cortical GM were estimated by SIENAX. The sample included 286 MS patients, of which 30 (10.5%) subjects with type 1 diabetes (T1D), 53 (18.5%) with autoimmune thyroiditis (AT) and 4 (0.1%) with celiac disease. Multiple regression analysis found an association between T1D and lower GM (p = 0.038) and cortical GM (p = 0.036) volumes, independent from MS clinical features and related to T1D duration (p

In this paper, we present a spatially explicit procedure for mapping and assessing coastal plant diversity value in the context of biodiversity monitoring and conservation planning. Our objective was to devise a replicable and easy to understand methodology framework, which can represent an expedient tool for coastal management and decision making at spatial scales between 1:25,000 and 1:50,000. For this purpose, we adopted a small number of key descriptors that refer to easily quantifiable information on species and habitats: plant species richness, species of conservation value, floristic consistency, habitat diversity, and habitats of conservation interest under the Council Directive 92/43/EEC. We built an expedient sampling strategy that combines systematic sampling by grid cells of fixed size with stratification per habitat type, and apply a plain equal weighting scoring system for assessing overall plant diversity. All floristic and habitat data were entered into a spatial database built within a GIS environment and referred to a 1 × 1 square km spatial grid overlaid on two selected test sites in southern Sardinia (Italy). The descriptors we chose were successful surrogates of plant diversity, as they were able to represent the known conservation importance of both test sites and of specific areas within them, both individually and in combination. In particular, our results show that integrating indicators at different levels of biodiversity enabled to represent aspects with marked differences in distribution as well as to compensate possible biases in data collection, as habitat data are more easily available than floristic information and spatially continuous even in less accessible areas. Being based on well-known criteria and policies, and on data that are most widely and consistently available, our assessment procedure proved effective and easily transferable, and provides a spatial reference framework for systematically evaluating and monitoring coastal plant diversity at national level and across the Mediterranean Basin.

Oligoclonal IgM (OCMB) and IgG (OCGB) bands were found to be associated with poor multiple sclerosis (MS) prognosis. We aimed to evaluate the prognostic value of OCMB/OCGB in a cohort of Sardinian MS patients. We recruited patients from the University of Cagliari. They underwent lumbar puncture for diagnostic purposes. Demographic and the following clinical data were recorded: clinical course; time to reach EDSS 3 and 6; EDSS at last follow-up; and MS treatments. The influence of gender, clinical course, age at onset, treatments, and OCGB/OCMB on reaching EDSS 3 was analysed using Cox regression. Kaplan–Meier curves were used to study the time to reach EDSS 3 considering OCMB/OCGB and therapies. The enrolled number of subjects was 503. The variables influencing the achievement of EDSS 3.0 were: male gender (p = 0.005); progressive course (p = 0.001); age at onset (p

Background and purpose There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS. Methods Patients with relapsing-remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis. Results A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound. Conclusions The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.