Publications by authors named "Francesco Patti"

227 Publications

Natalizumab administration in multiple sclerosis patients during active SARS-CoV-2 infection: a case series.

BMC Neurol 2021 Nov 29;21(1):462. Epub 2021 Nov 29.

Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", section of Neurosciences, University of Catania, via Santa Sofia 78, 95123, Catania, Italy.

Background: The Coronavirus disease 2019 (COVID-19) caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a pandemic, affecting the therapeutic management for Multiple Sclerosis (MS). Any decision regarding the discontinuation of high-potency agents for moderate and highly active MS should be carefully evaluated, taking into account the potential risk of rebound of the disease. In particular, no data about clinical outcome of patients with MS receiving Natalizumab (NTZ) during active COVID-19 infection have been reported yet.

Cases Presentation: We reported on 6 patients treated with NTZ for relapsing MS during active COVID-19 infection, who recovered without reporting any worsening or new symptoms. Most of the patients were asymptomatic, with the exception of one patient who had a slight worst COVID-19 clinical course. No patients received O2-therapy or required intensive care. No neurological complications were observed.

Conclusions: This paper reported the clinical outcome of patients with MS receiving NTZ during active COVID-19 infection. This case series suggests that treatment with NTZ during pandemic is relatively safe and might be continued in selected patients who are infected by COVID-19, thereby reducing the risk of MS disease rebound.
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http://dx.doi.org/10.1186/s12883-021-02421-3DOI Listing
November 2021

Spinal needle and post-dural puncture headache.

Neurol Sci 2021 Nov 20. Epub 2021 Nov 20.

Department "GF Ingrassia", Section Neuroscience, University of Catania, Via Santa Sofia 87, 95123, Catania, Italy.

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http://dx.doi.org/10.1007/s10072-021-05745-7DOI Listing
November 2021

Changes in John Cunningham virus index in Multiple Sclerosis patients treated with different disease-modifying therapies.

Curr Neuropharmacol 2021 Nov 11. Epub 2021 Nov 11.

Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", section of neurosciences; University of Catania, Catania, Italy.

Background: Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection caused by John Cunningham virus (JCV) reactivation, potentially associated to natalizumab (NTZ) treatment for Multiple Sclerosis (MS). The anti-JCV antibodies titre (JCV index) increases during NTZ treatment; however, the effects of other disease modifying therapies (DMTs) on JCV index have not been fully explored.

Objective: to evaluate changes in JCV index during treatment with several DMTs.

Methods: This longitudinal study evaluated JCV index before starting DMT (T0) and on DMT (T1).

Results: A total of 260 (65.4% females, mean age 43±11.3 ) were enrolled: 68 (26.2%) treated with fingolimod (FTY), 65 (25%), rituximab or ocrelizumab (RTX/OCR), 37 (14.2%), dimethyl-fumarate (DMF), 29 (11.2%), cladribine (CLD), 23 (8.8%), teriflunomide (TFM), 20 (7.7%), interferon or glatiramer acetate (IFN/GA), and 18 (6.9%) alemtuzumab (ALM). At T1, the percentage of patients with JCV index <0.90 was significantly increased in the ALM group (16.7% versus 66.7%, p=0.05), the percentage of patients with JCV index >1.51 was significantly reduced in RTX/OCR group (51.6% versus 37.5%, p=0.04). In the FTY group, a significant reduction in percentage of patients with JCV index <0.90 was also found (23.5% versus 1.4%, p=0.0006). The mean JCV index was reduced in RTX/OCR and ALM groups, while a significant increase was observed in the FTY group.

Conclusion: DMTs with a T and/or B depleting mechanism of action induced a significant reduction of the JCV index. These results may suggest new possible sequencing strategies potentially maximizing disease control, while reducing PML risk.
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http://dx.doi.org/10.2174/1570159X19666211111123202DOI Listing
November 2021

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

Neurol Neuroimmunol Neuroinflamm 2022 01 9;9(1). Epub 2021 Nov 9.

From the Department of Health Sciences (M.P.S., I.S., L.C.), University of Genova; IRCCS Ospedale Policlinico San Martino (M.P.S., M.I.), Genoa; Centro Sclerosi Multipla ASST Spedali Civili di Brescia (C.C., N.D.R.), Montichiari; Neurology Unit (M.F.), Neurorehabilitation Unit (M.F.), and Neurophysiology Unit (M.F.), IRCCS San Raffaele Scientific Institute, Milan; Neuroimaging Research Unit (M.F.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan; Vita-Salute San Raffaele University (M.F.), Milan; Department of Neurology and Multiple Sclerosis Center (M.R.), ASST "Papa Giovanni XXIII", Bergamo; Multiple Sclerosis Center (P.I.), Ospedale Guglielmo da Saliceto, Piacenza; Regional Referral Multiple Sclerosis Centre (M.C.), Department of Neurology, University Hospital San Luigi, Orbassano, Torino; AISM Rehabilitation Center (G.B.), Italian MS Society, Genoa; Centro Sclerosi Multipla (E.C.), ATS Sardegna; Dipartimento Scienze Mediche e Sanità Pubblica (E.C.), Università di Cagliari; IRCCS Istituto delle Scienze Neurologiche di Bologna (C.S.), UOSI Riabilitazione Sclerosi Multipla; MS Center (P. Cavalla), Department of Neuroscience, City of Health and Science University Hospital of Turin; Centro SM UOC Neurologia (I. Pesci), Fidenza, AUSL PR; Multiple Sclerosis Research Center (A.Z.), IRCCS Mondino Foundation, Pavia; Multiple Sclerosis Centre (P. Confalonieri), Neuroimmunology Department-"Carlo Besta" Neurological Institute, Milan; Multiple Sclerosis Clinical and Research Unit (G.A.M.), Department of Systems Medicine, Tor Vergata University, Rome; Department of Neurology Multiple Sclerosis Center (P.P.), University of Padua; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI) (M.I.), University of Genoa; Department of Basic Medical Sciences, Neurosciences and Sense Organs (M.T.), University of Bari; Federico II University of Naples (V.B.M.); Department of Advanced Medical and Surgical Sciences (G.T.), University of Campania, Napoli; Università Vita Salute San Raffaele (G.C.), Casa di Cura Privata Del Policlinico, Milan; Research Department (M.A.B.), Italian Multiple Sclerosis Foundation, Genoa; Department of Life Sciences (M.A.B.), University of Siena; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, University of Catania; Centro Sclerosi Multipla (F.P.), Policlinico Catania, University of Catania; Department of Neuroscience, Mental Health and Sensory Organs (M.S.), Sapienza University of Rome; and Unit of Neurology (M.S.), IRCCS Neuromed, Pozzilli, Isernia, Italy.

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 χ 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 ( < 0.001), RR = 2.19 for ICU admission ( < 0.001), and RR = 2.43 for death ( < 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, = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, = 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.
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http://dx.doi.org/10.1212/NXI.0000000000001105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579249PMC
January 2022

The effect of air pollution on COVID-19 severity in a sample of patients with multiple sclerosis.

Eur J Neurol 2021 Nov 4. Epub 2021 Nov 4.

Department of Health Sciences, University of Genova, Genova, Italy.

Background And Purpose: Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m (PM2.5), may contribute to severe COVID-19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID-19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID-19 severity amongst PwMS.

Methods: Data were retrieved from an Italian web-based platform (MuSC-19) which includes PwMS with COVID-19. PM2.5 2016-2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID-19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID-19 severity.

Results: In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID-19 course (odds ratio 1.90; p = 0.009).

Conclusions: Even if several other factors explain the unfavourable course of COVID-19 in PwMS, the role of air pollutants must be considered and further investigated.
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http://dx.doi.org/10.1111/ene.15167DOI Listing
November 2021

Multiple Sclerosis, COVID-19 and Vaccines: Making the Point.

Neurol Ther 2021 Dec 8;10(2):627-649. Epub 2021 Oct 8.

Department G. F. Ingrassia, Section of Neurosciences, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy.

On 11 March 2020, the World Health Organization declared the coronavirus disease 19 (COVID-19) outbreak a pandemic. In this context, several studies and clinical trials have been conducted since then, and many are currently ongoing, leading to the development of several COVID-19 vaccines with different mechanisms of action. People affected by multiple sclerosis (MS) have been considered high-risk subjects in most countries and prioritized for COVID-19 vaccination. However, the management of MS during the COVID-19 pandemic has represented a new challenge for MS specialists, particularly because of the initial lack of guidelines and differing recommendations. Despite an initial hesitation in prescribing disease-modifying drugs (DMDs) in naïve and already treated patients with MS, most national neurology associations and organizations agree on not stopping treatment. However, care is needed especially for patients treated with immune-depleting drugs, which also require some attentions in programming vaccine administration. Many discoveries and new research results have accumulated in a short time on COVID-19, resulting in a need for summarizing the existing evidence on this topic. In this review, we describe the latest research results on the immunological aspects of SARS-CoV-2 infection speculating about their impact on COVID-19 vaccines' mechanisms of action and focused on the management of MS during the COVID pandemic according to the most recent guidelines and recommendations. Finally, the efficacy of COVID-19 and other well-known vaccines against infectious disease in patients with MS on DMDs is discussed.
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http://dx.doi.org/10.1007/s40120-021-00288-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500471PMC
December 2021

Eculizumab in refractory generalized myasthenia gravis previously treated with rituximab: subgroup analysis of REGAIN and its extension study.

Muscle Nerve 2021 Dec 14;64(6):662-669. Epub 2021 Oct 14.

Department of Medical and Surgical Sciences and Advanced Technologies, G.F. Ingrassia, University of Catania, Catania, Italy.

Introduction/aims: Individuals with refractory generalized myasthenia gravis (gMG) who have a history of rituximab use and experience persistent symptoms represent a population with unmet treatment needs. The aim of this analysis was to evaluate the efficacy and safety of eculizumab in patients with refractory anti-acetylcholine receptor antibody-positive (AChR ) gMG previously treated with rituximab.

Methods: This post hoc subgroup analysis of the phase 3 REGAIN study (NCT01997229) and its open-label extension (OLE; NCT02301624) compared baseline characteristics, safety, and response to eculizumab in participants who had previously received rituximab with those who had not. Rituximab use was not permitted within the 6 months before screening or during REGAIN/OLE.

Results: Of 125 REGAIN participants, 14 had received rituximab previously (7 received placebo and 7 received eculizumab). In the previous-rituximab group, 57% had used at least four other immunosuppressants compared with 16% in the no-previous-rituximab group. Myasthenia Gravis Activities of Daily Living total scores from eculizumab baseline to week 130 of eculizumab treatment improved in both the previous-rituximab and no-previous-rituximab groups (least-squares mean -4.4, standard error of the mean [SEM] 1.0 [n = 9] and least-squares mean -4.6, SEM 0.3 [n = 67], respectively; difference = 0.2, 95% confidence interval -1.88 to 2.22). In addition, in both groups, most patients who were treated with eculizumab for 130 weeks achieved a Myasthenia Gravis Foundation of America post-intervention status of minimal manifestations (66.7% and 65.0%, respectively). The eculizumab safety profile was similar between groups and consistent with its established profile.

Discussion: Eculizumab is an effective therapy for patients with refractory AChR gMG, irrespective of whether they had received rituximab treatment previously.
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http://dx.doi.org/10.1002/mus.27422DOI Listing
December 2021

Long-term outcomes in patients presenting with optic neuritis: Analyses of the MSBase registry.

J Neurol Sci 2021 Nov 3;430:118067. Epub 2021 Sep 3.

Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA. Electronic address:

Background: Short-term outcomes of optic neuritis (ON) have been well characterized. Limited data exists on longer-term visual outcomes in patients who present with ON. The large MSBase registry allows for characterization of long-term visual outcomes after ON.

Methods: Via the MSBase Registry, data on patients from 41 centers was collected during routine clinical and research visits. Physical and visual disability were measured using the expanded disability status scale (EDSS) and the visual function score (VFS). Inclusion criteria for this analysis included age ≥ 18 years, clinically isolated syndrome (CIS), ON-onset, baseline visit within 6 months of onset, and at least one follow-up visit. Survival analysis was used to evaluate the association of disease-modifying treatment with time to conversion to clinically definite MS or sustained EDSS/VFS progression.

Results: Data from 60,933 patients were obtained from the MSBase registry in July 2019. Of these, 1317 patients met inclusion criteria; 935 were treated at some point in disease course, while 382 were never treated. At baseline, mean age was 32.3 ± 8.8 years, 74% were female, median EDSS was 2 (IQR 1-2), and median VFS was 1 (IQR 0-2). Median follow-up time was 5.2 years (IQR 2.4-9.3). Treatment was associated with reduced risk and delayed conversion to clinically definite MS (HR = 0.70, p < 0.001), sustained EDSS progression (HR = 0.46, p < 0.0001) and sustained VFS (HR = 0.41, p < 0.001) progression.

Conclusions: In the MSBase cohort, treatment after ON was associated with better visual and neurological outcomes compared to no treatment. These results support early treatment for patients presenting with ON as the first manifestation of MS.
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http://dx.doi.org/10.1016/j.jns.2021.118067DOI Listing
November 2021

Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts.

CNS Drugs 2021 11 18;35(11):1217-1232. Epub 2021 Sep 18.

Neurology Unit, Garibaldi Hospital, Catania, Italy.

Introduction: Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined.

Objective: The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest.

Methods: Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients' sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed with weighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score.

Results: A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15-41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65-0.88); in those aged ≤ 38 years (0.64; 0.54-0.76); in those with disease duration ≤ 7 years (0.63; 0.53-0.76); in those with EDSS score < 4 (0.75; 0.64-0.88), < 6 (0.80; 0.70-0.91), and ≥ 6 (0.52; 0.31-0.86); and in patients with pre-baseline relapses (0.74; 0.64-0.86). A higher probability of confirmed disability improvement on natalizumab versus fingolimod (hazard ratio [HR]; 95% CI) was observed among women (1.36; 1.10-1.66); those aged > 38 years (1.34; 1.04-1.73); those with disease duration > 7 years (1.33; 1.01-1.74); those with EDSS score < 6 (1.21; 1.01-1.46) and ≥ 6 (1.93; 1.11-3.34); and patients with no new MRI lesion (1.73; 1.19-2.51).

Conclusions: Overall, in women, younger patients, those with shorter disease durations, and patients with pre-treatment relapses, natalizumab was associated with a lower frequency of multiple sclerosis relapses than fingolimod. It was also associated with an increased chance of recovery from disability among most patients, particularly women and those with no recent MRI activity.
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http://dx.doi.org/10.1007/s40263-021-00860-7DOI Listing
November 2021

Clinical characteristics of middle-aged and older patients with MS treated with interferon beta-1b: post-hoc analysis of a 2-year, prospective, international, observational study.

BMC Neurol 2021 Aug 23;21(1):324. Epub 2021 Aug 23.

Bayer AG, Berlin, Germany.

Background: Despite trends towards the increased age of patients living with multiple sclerosis (MS), little is known about the response of older adults with MS to disease-modifying therapies (DMTs). Thus, a post-hoc analysis was undertaken using data from a 2-year, international, non-interventional, prospective cohort study (NCT00787657; BEACON: BEtaferon prospective study on Adherence, COping and Nurse support) of patients above the age of 40 years with MS and starting interferon beta-1b (IFNB-1b) treatment within 6 months before study entry.

Methods: Middle-aged and older patients with MS were divided into two sub-groups: 41-50 years and > 50 years. Treatment with IFNB-1b started within 6 months before study entry. Patients were followed-up for a 2-year observation period. Assessments included disease history and course, annualised relapse rate (ARR), Expanded Disability Scale Score (EDSS), treatment adherence, Hospital Anxiety and Depression Scale (HADS), and adverse events (AE).

Results: At baseline, the intention-to-treat (ITT) population (n = 481) aged 41-50 years (n = 327) and > 50 years (n = 154), had mean (standard deviation [SD]) ages of 45.1 (2.8) and 56.2 (4.2) years, maximum age of 72 years, and duration of MS since onset of symptoms of 3.9 (5.2) and 5.9 (7.1) years, respectively. At baseline, the proportion of patients with relapsing-remitting MS (RRMS) was 96.3 and 94.9 %, and secondary progressive MS (SPMS) was 3.7 and 5.1 %, in the 41-50 and > 50 years sub-groups, respectively. The ARR in the 2 years before study start was 0.93 (0.48) and 0.86 (0.54) for the 41-50 and > 50 years groups, respectively, and decreased since study start to 0.20 (1.09) and 0.07 (0.37), respectively. The percentage of patients with anxiety and depression, as measured by HADS, were stable over the study period. Polypharmacy (five or more medications) was seen in 32.3 and 41.2 % of patients aged 41-50 and > 50 years. No unexpected AEs were reported.

Conclusions: This study provides observational data on patients between 40 and 72 years of age, suggesting that IFNB-1b can be an effective and well-tolerated treatment option in MS patients of advanced age.

Trial Registration: ClinicalTrials.gov, NCT00787657.
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http://dx.doi.org/10.1186/s12883-021-02347-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381478PMC
August 2021

Study protocol on advance care planning in multiple sclerosis (ConCure-SM): intervention construction and multicentre feasibility trial.

BMJ Open 2021 08 13;11(8):e052012. Epub 2021 Aug 13.

Unit of Neuroepidemiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy

Introduction: Multiple sclerosis (MS) is the most common cause of progressive neurological disability in young adults. The use of advance care planning (ACP) for people with progressive MS (pwPMS) remains limited. The ConCure-SM project aims to assess the effectiveness of a structured ACP intervention for pwPMS. The intervention consists of a training programme on ACP for healthcare professionals caring for pwPMS, and a booklet to be used during the ACP conversation. Herein, we describe the first two project phases.

Methods: In phase 1 we translated and adapted, to the Italian legislation and MS context, the ACP booklet of the National ACP Programme for New Zealand. Acceptability, comprehensibility and usefulness of the booklet were assessed via 13 personal cognitive interviews with pwPMS and significant others (SOs), and one health professional focus group. Based on these findings, we will revise the booklet. In phase 2 we will conduct a single-arm pilot/feasibility trial with nested qualitative study. Participants will be 40 pwPMS, their SOs, health professionals from six MS and rehabilitation centres in Italy. In the 6 months following the ACP conversation, we will assess completion of an advance care plan document (primary outcome), as well as safety of the intervention. Secondary outcomes will be a range of measures to capture the full process of ACP; patient-carer congruence in treatment preferences; quality of patient-clinician communication and caregiver burden. A qualitative process evaluation will help understand the factors likely to influence future implementation and scalability of the intervention.

Ethics And Dissemination: The project is coleaded by a neurologist and a bioethicist. Phase 1 has received ethical approvals from each participating centre, while phase 2 will be submitted to the centres in May 2021. Findings from both phases will be disseminated widely through peer-reviewed publications, conferences and workshops.

Trial Registration Number: ISRCTN48527663; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2021-052012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365819PMC
August 2021

Job satisfaction among physicians and nurses involved in the management of multiple sclerosis: the role of happiness and meaning at work.

Neurol Sci 2021 Aug 7. Epub 2021 Aug 7.

Department of Biomedical and Clinical Sciences L. Sacco, Università degli Studi di Milano, Milan, Italy.

Objective: Health professionals caring for persons with multiple sclerosis (MS) are faced with increasingly complex working conditions that can undermine their job satisfaction and the quality of their healthcare services. The aim of this study was to delve into health professionals' job satisfaction by assessing the predictive role of happiness and meaning at work. Specifically, it was hypothesized that job meaning would moderate the relationship between job happiness and satisfaction.

Methods: The study hypothesis was tested among 108 healthcare professionals (53 physicians and 55 nurses) working in eight MS centers in Italy. Participants were administered the Eudaimonic and Hedonic Happiness Investigation and the Job Satisfaction Questionnaire. Hierarchical regression analysis was performed to test the moderating role of job meaning between job happiness and satisfaction.

Results: A significant interaction effect of job happiness and meaning on job satisfaction was identified for both physicians and nurses. When work was attributed low meaning, participants experiencing high job happiness were more satisfied with their work than those reporting low happiness; by contrast, when work was perceived as highly meaningful, participants' levels of job happiness did not significantly contribute to job satisfaction.

Conclusions: Focusing on the interplay between job happiness and meaning, findings bring forward practical suggestions for the preservation and promotion of job satisfaction among health professionals working with MS patients. Particularly, they suggest the need to strengthen those job-related aspects that may enhance job meaning, thus providing health professionals with significant reasons to persevere in their work in the face of daily challenges.
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http://dx.doi.org/10.1007/s10072-021-05520-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346783PMC
August 2021

Prevalence and predictors of bowel dysfunction in a large multiple sclerosis outpatient population: an Italian multicenter study.

J Neurol 2021 Aug 4. Epub 2021 Aug 4.

MS Center-I Division of Neurology, Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italia, piazza Miraglia, 2, 80138, Naples, Italy.

Introduction: Bowel dysfunction (BD) is reported as a common and disabling symptom in multiple sclerosis (MS) patients. To date, no studies have explored the prevalence of these symptoms in a large multicenter outpatient setting. The aims of the present study are to assess: (i) the prevalence of BD in a large multicenter Italian MS population, and (ii) the correlation between clinico-demographic variables and the severity of BD.

Methods: Each of the nine participating center screened MS patients prospectively: 1100 subjects were enrolled. All patients underwent the Expanded Disability Status Scale (EDSS) and completed the Neurogenic Bowel Dysfunction score (NBDs). Multivariable linear and logistic regression models were used to assess the association between NBDs and several clinico-demographic variables.

Results: Fourteen percent of MS patients showed a moderate/severe BD (NBDs > 10); this percentage increased in patients with high disability, ranging from 26 to 32%. Moderate/severe BD was more frequent in MS patients with: progressive phenotypes, higher disability, older age, and longer disease duration. NBDs severity was predicted by female sex, ambulation impairment and bladder symptoms.

Conclusion: This study confirms the relatively high prevalence of moderate/severe BD in a large, multicenter, unselected, outpatient MS population. BD appears to be mainly associated to female sex and MS-related disability.
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http://dx.doi.org/10.1007/s00415-021-10737-wDOI Listing
August 2021

SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study.

Mult Scler 2021 Jul 30:13524585211035318. Epub 2021 Jul 30.

Department of Neuroscience, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy/Unit of Neurology, IRCCS Neuromed, Isernia, Italy.

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available.

Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test.

Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model.

Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20,  = 0.002).

Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.
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http://dx.doi.org/10.1177/13524585211035318DOI Listing
July 2021

Italian translation and psychometric validation of the ABILHAND-26 and its correlation with upper limb objective and subjective measures in multiple sclerosis subjects.

Mult Scler Relat Disord 2021 Oct 21;55:103160. Epub 2021 Jul 21.

Dept. of Rehabilitation, CRRF "Mons. Luigi Novarese", Moncrivello, VC, Italy.

Background: Upper limb (UL) function is affected in about 50% of people with Multiple Sclerosis (PwMS). In the last decade, Patient Reported Outcome Measures (PROM) are playing an important role in clinical trial and practice. ABILIHAND-26 is a PROM that assess self-perceived manual ability defined as the capacity to manage daily activities using the upper limbs. The aim of the study is to translate the ABILHAND-26 into Italian, to explore its psychometric properties examining the associations with demographics, clinical variables, 9-Hole Peg Test (9-HPT) and Manual Ability Measures-36 (MAM-36).

Materials And Methods: Subjects were recruited in five Italian neurological centers. They were evaluated through ABILHAND-26, 9-HPT and MAM-36. Confirmatory factor analysis and Rasch analysis were adopted to investigate the psychometric properties of the ABILHAND-26.

Results: Two hundred and forty-five patients were recruited. Rasch analyses showed adequate functioning and supported the unidimensionality of the scale. ABILHAND-26 showed negative correlations with age and disease duration, moderate negative correlation with EDSS and the 9-HPT scores for both arms and strong positive associations (ρ ≥ .84) with the MAM-36. Difference in ABILHAND-26 scores only emerged when comparing patients with severe disability (EDSS ≥ 6) with patients with either mild or moderate disability. t) and when comapring relapsing-remitting and secondary progressive patients.

Conclusion: The Italian version of the ABILHAND-26 is now available. It shows adequate reliability of the score, moderate criterion validity and strong convergent validity. ABILHAND-26 could represent a valid assessment for self-perceived ability to perform manual activity, especially for PwMS with moderate-to-high level of disability.
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http://dx.doi.org/10.1016/j.msard.2021.103160DOI Listing
October 2021

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

Ann Clin Transl Neurol 2021 08 7;8(8):1738-1744. Epub 2021 Jul 7.

Department of Neurology, CIC INSERM 1434, CHU de Strasbourg, Strasbourg, 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.
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http://dx.doi.org/10.1002/acn3.51408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351392PMC
August 2021

First-line therapies in late-onset multiple sclerosis: An Italian registry study.

Eur J Neurol 2021 Dec 30;28(12):4117-4123. Epub 2021 Jul 30.

Department "G.F. Ingrassia,", MS Center University of Catania, Catania, Italy.

Background And Purpose: The diagnosis of late-onset (age ≥50 years old) relapsing remitting multiple sclerosis (LORRMS) has been increasingly described in clinical practice, whereas data focusing on the specific therapeutic management of LORRMS are scarce. Our objective was to compare the effectiveness of injectable and oral first-line disease-modifying therapies (DMTs) in a cohort of LORRMS patients with time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation.

Methods: This is a multicenter, observational, retrospectively acquired cohort study on LORRMS-naïve patients from the Italian MS Register who started either injectable or oral first-line DMTs between January 1, 2013 and December 31, 2017. LORRMS patients were divided into two groups, namely the injectable group (IG) and oral group (OG). Cox models adjusted with inverse probability-weighted propensity score were built for the investigated outcomes.

Results: Of a cohort of 3989 patients, 302 were enrolled (203 in the IG and 99 in the OG). The two cohorts did not differ in baseline characteristics. Time to first relapse did not show any difference between the two groups (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 0.50-2.46, p = 0.797). Furthermore, no differences were found between the two groups with respect to the risk of CDP (HR: 1.04; 95% CI: 0.35-3.06, p = 0.939), nor for the risk of DMT discontinuation (HR: 0.90; 95% CI: 0.17-2.08, p = 0.425).

Conclusions: Real-world data from the Italian MS Register suggested that both injectables and oral first-line DMTs similarly controlled the investigated outcomes in LORRMS.
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http://dx.doi.org/10.1111/ene.15006DOI Listing
December 2021

Effects of High- and Low-Efficacy Therapy in Secondary Progressive Multiple Sclerosis.

Neurology 2021 08 30;97(9):e869-e880. Epub 2021 Jun 30.

From the CORe (I.R., C.M., T.K.), Department of Medicine, University of Melbourne; Melbourne MS Centre (I.R., K.B., C.M., T.K.), Department of Neurology, Royal Melbourne Hospital, Australia; Rennes University (E.L.), EHESP, REPERES EA 7449; Univ Rennes (E.L.), CHU Rennes, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes); Université de Lyon (R.C.), Université Claude Bernard Lyon 1; Hospices Civils de Lyon (R.C.), Service de Neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Bron; Observatoire Français de la Sclérose en Plaques (R.C.), Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292; EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis (R.C.), state-approved foundation, Bron, France; Department of Neurology and Center of Clinical Neuroscience (D.H., E.H.), First Faculty of Medicine, Charles University; General University Hospital (D.H., E.H.), Prague, Czech Republic; Hospital Universitario Virgen Macarena (G.I., S.E.M.), Sevilla, Spain; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia; Multiple Sclerosis Center (F.P.), University of Catania, Italy; Centre hospitalier universitaire de Rennes (G.E.), Hôpital Pontchaillou, Service de neurologie, CIC1414 INSERM; Nancy University Hospital (M.D.), Department of Neurology; Université de Lorraine (M.D.), APEMAC, Nancy, France; Aix Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, France; Dokuz Eylul University (S.O.), Konak/Izmir, Turkey; Department of Neurosciences, Psychology, Drugs and Child Health Area (NEUROFARBA) (M.P.A.), Section Neurosciences, University of Florence, Italy; CHU Clermont-Ferrand (P.C.), Department of Neurology; Université Clermont Auvergne (P.C.), Inserm, Neuro-Dol, Clermont-Ferrand, France; CISSS Chaudière-Appalache (P.G.), Lévis, Canada; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology (K.B., O.S., H.B.), Box Hill Hospital, Monash University; The Alfred Hospital (O.S.), Melbourne, Australia; CHU de Toulouse (J.C.), Hôpital Pierre-Paul Riquet, Department of Neurology, CRC-SEP, Toulouse Cedex 9, France; Department of Neurology (O.G.), Zuyderland Medical Center, Sittard-Geleen, the Netherlands; Neuro Rive-Sud (F.G.), Quebec, Canada; School of Medicine and Public Health (J.L.-S.), University Newcastle; Department of Neurology (J.L.-S.), John Hunter Hospital, Hunter New England Health, Newcastle; Central Clinical School (H.B.), Monash University; Department of Neurology (H.B.), The Alfred Hospital, Melbourne, Australia; Service de neurologie (S.V.), sclérose en plaques, pathologies de la myéline et neuro-inflammation; Hôpital Neurologique Pierre Wertheimer (S.V.), Hospices Civils de Lyon, Lyon/Bron; France Centre des Neurosciences de Lyon (S.V.), Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292; and Université Claude Bernard Lyon 1 (S.V.), Faculté de médecine Lyon Est, France.

Objective: To compare the clinical effectiveness of high- and low-efficacy treatments in patients with recently active and inactive secondary progressive multiple sclerosis (SPMS) after accounting for therapeutic lag.

Methods: Patients treated with high-efficacy (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-efficacy (interferon beta, glatiramer acetate, teriflunomide) therapies after SPMS onset were selected from MSBase and Observatoire Français de la Sclérose en Plaques (OFSEP), 2 large observational cohorts. Therapeutic lag was estimated for each patient from their demographic and clinical characteristics. Propensity score was used to match patients treated with high- and low-efficacy therapies. Outcomes after the period of therapeutic lag was disregarded were compared in paired, pairwise-censored analyses.

Results: One thousand patients were included in the primary analysis. Patients with active SPMS treated with high-efficacy therapy experienced less frequent relapses than those on low-efficacy therapy (hazard ratio [HR] 0.7, = 0.006). In patients with inactive SPMS, there was no evidence for a difference in relapse frequency between groups (HR 0.8, = 0.39). No evidence for a difference in the risk of disability progression was observed.

Conclusion: In treated patients with SPMS, high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active but not those with inactive SPMS. However, more potent therapies do not offer an advantage in reducing disability progression in this patient group.

Classification Of Evidence: This study provides Class III evidence that high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active SPMS, although we did not find a difference in disability progression between patients treated with high- and low-efficacy therapy.
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http://dx.doi.org/10.1212/WNL.0000000000012354DOI Listing
August 2021

PML risk is the main factor driving the choice of discontinuing natalizumab in a large multiple sclerosis population: results from an Italian multicenter retrospective study.

J Neurol 2021 Jun 28. Epub 2021 Jun 28.

Neurosciences Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.

Background: Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients.

Materials And Methods: The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as "lack of efficacy", "progressive multifocal leukoencephalopathy (PML) risk" or "other".

Results: Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1 years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy [1682 (32.7% of 5151) vs 221 (4.3%), p < 0.001]; other reasons were identified for 99 (1.9%) patients. Patients discontinuing treatment were older, had longer disease duration and worse EDSS at the time of NTZ initiation and at last follow-up on NTZ treatment. The JCV index and EDSS at baseline were predictors for stopping therapy (HR 2.94, 95% CI 1.22-4.75; p = 0.02; HR 1.36, 95% CI 1.18-5.41; p = 0.04).

Conclusions: Roughly 60% of MS patients stayed on NTZ treatment during the observation period. For those patients in whom NTZ discontinuation was required, it was mainly due to PML concerns.
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http://dx.doi.org/10.1007/s00415-021-10676-6DOI Listing
June 2021

Pregnancy in multiple sclerosis women with relapses in the year before conception increases the risk of long-term disability worsening.

Mult Scler 2021 Jun 16:13524585211023365. Epub 2021 Jun 16.

Division Neurological Rehabilitation, Department of NEUROFARBA, University of Florence, Florence, Italy/IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.

Background: The influence of pregnancy on long-term disability in multiple sclerosis (MS) is still controversial.

Objective: To assess the risk of long-term disability worsening after pregnancy in MS women as compared with a propensity-score (PS) matched group of MS women without pregnancy.

Methods: In the setting of the Italian Pregnancy Dataset, MS patients with (pregnancy group (PG)) and without pregnancy (control group (CG)) were recruited. Time to disability worsening on the Expanded Disability Status Scale (EDSS) was assessed through a multivariable Cox regression model.

Results: The PS-matching retained 230 PG and 102 CG patients. After a follow-up of 6.5 +/- 3.1 years, disability worsening occurred in 87 (26.2%) women. In the multivariable analysis, disability worsening was associated with pregnancy in women with relapses in the year before conception (adjusted hazard ratio (aHR) = 1.74; 95% confidence interval (CI) 1.06-2.84; = 0.027), higher EDSS (aHR = 1.39; 95% CI 1.12-1.74; = 0.003), younger age (aHR = 0.95; 95% CI 0.91-0.99; = 0.022) and shorter DMD exposure over the follow-up ( < 0.008).

Conclusion: Pregnancy in MS women with relapses in the year before conception increases the risk of long-term disability worsening. Our findings underscore the importance of counselling in MS women facing a pregnancy that should be planned after a period of clinical stability, favouring treatment optimization in patients with recent disease activity.
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http://dx.doi.org/10.1177/13524585211023365DOI Listing
June 2021

The effectiveness of natalizumab vs fingolimod-A comparison of international registry studies.

Mult Scler Relat Disord 2021 Aug 8;53:103012. Epub 2021 May 8.

KTU Medical Faculty Farabi Hospital, Trabzon, Turkey.

Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening.

Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting.

Results: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod.

Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.
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http://dx.doi.org/10.1016/j.msard.2021.103012DOI Listing
August 2021

Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies.

Ther Adv Neurol Disord 2021 31;14:17562864211019574. Epub 2021 May 31.

Dipartimento di Neurologia, Neurofisiologia e Neuroriabilitazione, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

Background And Aims: No consensus exists on how aggressively to treat relapsing-remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC).

Methods: RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups.

Results: The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5-11.7) years. Mean annual delta-EDSS values were all significantly ( < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01-0.19,  = 0.03) at 1 year to 0.30 (0.07-0.53,  = 0.009) at 5 years and to 0.67 (0.31-1.03,  = 0.0003) at 10 years.

Conclusion: Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time.
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http://dx.doi.org/10.1177/17562864211019574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170278PMC
May 2021

Early-Onset Alcohol Dependence and Multiple Sclerosis: Diagnostic Challenges.

Int J Environ Res Public Health 2021 05 24;18(11). Epub 2021 May 24.

Section of Neurosciences, Department "GF. Ingrassia", University of Catania, Via S. Sofia, 78, 95123 Catania, Italy.

Multiple sclerosis (MS) is an inflammatory demyelinating disorder characterized by the progressive disruption of the myelin sheath around the nerve fibres. The early initiation of disease-modifying treatments is crucial for preventing disease progression and neurological damage. Unfortunately, a diagnostic delay of several years is not uncommon, particularly in the presence of physical and mental comorbidities. Among psychiatric comorbidities, the role of alcohol misuse is still under debate. In this paper, we discuss a case of early-onset alcohol dependence and its possible role in delaying the initiation of a specific therapy for MS. The differential diagnosis between idiopathic and secondary neurodegenerative disorders is often challenging. When dealing with patients reporting an early-onset substance abuse (likely to present organic damage), clinicians may be prone to formulate a diagnosis of secondary neuropathy, particularly when facing non-specific symptoms. This case report highlights the need for in-depth medical investigations (including imaging) in the presence of neurological signs suggesting a damage of the central nervous system, prompting a differential diagnosis between idiopathic and secondary neurodegenerative conditions. Indeed, a timely diagnosis is crucial for the initiation of specific therapies positively affecting the outcome.
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http://dx.doi.org/10.3390/ijerph18115588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197265PMC
May 2021

Risk of Persistent Disability in Patients With Pediatric-Onset Multiple Sclerosis.

JAMA Neurol 2021 Jun;78(6):726-735

Multiple Sclerosis Center, Gallarate Hospital, ASST Valle Olona, Gallarate (VA), Italy.

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 (<1993, 1993-1999, 2000-2006, and 2007-2013), adjusting for possible confounders linked to EDSS evaluations and clinical disease activity. We then analyzed the difference among the 4 diagnosis epochs regarding demographic characteristics, clinical disease activity at onset, and DMTs management.

Main Outcomes And Measures: Disability milestones were EDSS score 4.0 and 6.0, confirmed in the following clinical evaluation and in the last available visit.

Results: We enrolled 3198 patients with POMS (mean age at onset, 15.2 years; 69% female; median time to diagnosis, 3.2 years; annualized relapse rate in first 1 and 3 years, 1.3 and 0.6, respectively), with a mean (SD) follow-up of 21.8 (11.7) years. Median survival times to reach EDSS score of 4.0 and 6.0 were 31.7 and 40.5 years. The cumulative risk of reaching disability milestones gradually decreased over time, both for EDSS score of 4.0 (hazard ratio [HR], 0.70; 95% CI, 0.58-0.83 in 1993-1999; HR, 0.48; 95% CI, 0.38-0.60 in 2000-2006; and HR, 0.44; 95% CI, 0.32-0.59 in 2007-2013) and 6.0 (HR, 0.72; 95% CI, 0.57-0.90; HR, 0.44; 95% CI, 0.33-0.60; and HR, 0.30; 0.20-0.46). In later diagnosis epochs, a greater number of patients with POMS were treated with DMTs, especially high-potency drugs, that were given earlier and for a longer period. Demographic characteristics and clinical disease activity at onset did not change significantly over time.

Conclusions And Relevance: In POMS, the risk of persistent disability has been reduced by 50% to 70% in recent diagnosis epochs, probably owing to improvement in therapeutic and managing standards.
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http://dx.doi.org/10.1001/jamaneurol.2021.1008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094039PMC
June 2021

Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis.

Neurology 2021 Apr 20. Epub 2021 Apr 20.

Liverpool Hospital, Australia.

Objective: To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort.

Methods: Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses.

Results: We included 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in third trimester, and increased to 0.59 (0.51-0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28-0.49) and 0.29 (0.22-0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41-0.91], p=0.016). 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum.

Conclusion: Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation, with early re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.
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http://dx.doi.org/10.1212/WNL.0000000000012084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253565PMC
April 2021

Male fertility in relapsing-remitting multiple sclerosis patients treated with natalizumab and ocrelizumab: A prospective case-control study.

Mult Scler 2021 Dec 19;27(14):2284-2287. Epub 2021 Apr 19.

Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia" , University of Catania, Italy.

Scarce data are available about the impact of natalizumab (NTZ) and ocrelizumab (OCR) on male fertility in relapsing-remitting multiple sclerosis (RRMS). In this case-control prospective study, the gonadal steroids and the sperm parameters have been analysed at the time of the RRMS diagnosis and after 12 months from the beginning of the investigated therapies. Sixteen men with RRMS and sixteen matched healthy controls were included. At enrolment and after 12 months on therapy, the gonadal steroids and the sperm parameters of men with RRMS did not differ from the healthy controls. In conclusion, therapy with NTZ and OCR had no impact on fertility status in our cohort of men with RRMS. Further randomized and prospective studies are needed.
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http://dx.doi.org/10.1177/13524585211009208DOI Listing
December 2021

Exit Strategies in Natalizumab-Treated RRMS at High Risk of Progressive Multifocal Leukoencephalopathy: a Multicentre Comparison Study.

Neurotherapeutics 2021 04 12;18(2):1166-1174. Epub 2021 Apr 12.

Department "G.F. Ingrassia", MS Center, Organization University of Catania, Catania, Italy.

The main aim of the study is to evaluate the efficacy and safety profile of ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab (NTZ) exit strategies in relapsing-remitting multiple sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML). This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA from January 1st, 2019, to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity-score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs). Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. Patients from the 3 groups did not show differences for baseline characteristics, also after post hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpB 0.485, CI 95% 0.264-0.893, p = 0.020). This result was confirmed also for 12-month MRI activity (ExpB 0.248 CI 95% 0.065-0.948, p = 0.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile.
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http://dx.doi.org/10.1007/s13311-021-01037-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423885PMC
April 2021

Exploring polypharmacy phenomenon in newly diagnosed relapsing-remitting multiple sclerosis: a cohort ambispective single-centre study.

Ther Adv Chronic Dis 2021 27;12:2040622320983121. Epub 2021 Feb 27.

Department "G.F. Ingrassia"; University of Catania, Catania, Italy.

Aims: We aimed to examine the frequency of polypharmacy in a large cohort of patients at the time of diagnosis of relapsing-remitting multiple sclerosis (RRMS) and to explore its effects on discontinuation of first disease-modifying treatment (DMT) using survival analysis.

Methods: This was a cohort ambispective single-centre study. We enrolled RRMS patients starting their first DMT between 1st January 2013 and 31st December 2015. According to the number of medicines prescribed (except DMTs), we divided the patients into three groups: no-poly RRMS, minor-poly RRMS (from one to three medications), and major-poly RRMS (more than three medications).

Results: A total of 392 RRMS patients were enrolled (mean age 41.1). The minor-poly RRMS group included 61 patients (15.6%) and the major-poly RRMS group included 112 (28.6%). Individuals in these groups were older and had higher median body mass index (BMI) than patients in the no-poly RRMS group ( < 0.05). Upon multinomial regression analysis, older age at onset was associated with minor and major polypharmacy (OR 1.050, CI 1.010-1.093,  = 0.015 and OR 1.063, CI 1.026-1.101,  = 0.001, respectively) and higher BMI was associated with major polypharmacy (OR 1.186, CI 1.18-1.29,  = 0.001). The rates of discontinuation of first DMT were similar among the three groups (50.7% for no-Poly RRMS, 50.8% for minor-Poly RRMS, and 53.3% for major-Poly RRMS,  = 0.264). At log-Rank test, there were no differences among the three groups ( = 0.834).

Conclusion: Polypharmacy was more common in older RRMS patients with high BMI.
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http://dx.doi.org/10.1177/2040622320983121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923988PMC
February 2021

Therapeutic recommendations and seasonal influenza vaccine for multiple sclerosis patients in treatment with ocrelizumab: an expert consensus.

J Neurol 2021 Apr 20;268(4):1540-1543. Epub 2021 Feb 20.

Neurology and Neurophysiopathology Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, Italy.

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http://dx.doi.org/10.1007/s00415-021-10466-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896178PMC
April 2021

Injectable Versus Oral First-Line Disease-Modifying Therapies: Results from the Italian MS Register.

Neurotherapeutics 2021 04 2;18(2):905-919. Epub 2021 Feb 2.

Department "G.F. Ingrassia", MS center, University of Catania, Policlinico G. Rodolico, V. Santa Sofia 78, 95123, Catania, Italy.

The current study aims to compare injectable and oral first-line disease-modifying therapies (DMTs) for time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation using a cohort of relapsing remitting multiple sclerosis (RRMS) patients, with data extracted from the Italian MS Register. This multicenter, observational, retrospectively acquired, and propensity-adjusted cohort study utilized RRMS-naïve patients from the Italian MS Register who started either injectable or oral first-line DMTs between January 1, 2010, and December 31, 2017, to evaluate the impact on disability outcomes in patients. Enrolled patients were divided into two groups, namely the injectable group (IG) and the oral group (OG). Of a cohort of 11,416 patients, 4602 were enrolled (3919 in the IG and 683 in the OG). The IG had a higher rate of women (67.3% vs 63.4%, p < 0.05) and a lower mean age (36.1 ± 10.9 vs 38.9 ± 11.8, p < 0.001). The event time to first relapse demonstrated a lower risk in the OG (HR = 0.58; CI 95% 0.48-0.72, p < 0.001). However, no differences were found between the two groups with respect to the risk of CDP (HR = 0.94; CI 95% 0.76-1.29, p = 0.941), while a lower risk of DMT was found in the OG (HR = 0.72; CI 95% 0.58-0.88, p = 0.002) for the event time to discontinuation. Real-world data from the Italian MS Register suggests that first-line oral DMTs are associated with a lower risk of experiencing a new relapse and of therapy discontinuation compared to injectable DMTs.
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http://dx.doi.org/10.1007/s13311-020-01001-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423935PMC
April 2021
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