Big Multiple Sclerosis Data network: an international registry research network.

BACKGROUND: The Big Multiple Sclerosis Data (BMSD) network ( https://bigmsdata.org ) was initiated in 2014 and includes the national multiple sclerosis (MS) registries of the Czech Republic, Denmark, France, Italy, and Sweden as well as the international MSBase registry. BMSD has addressed the ethical, legal, technical, and governance-related challenges for data sharing and so far, published three scientific papers on pooled datasets as proof of concept for its collaborative design. DATA COLLECTION: Although BMSD registries operate independently on different platforms, similarities in variables, definitions and data structure allow joint analysis of data. Certain coordinated modifications in how the registries collect adverse event data have been implemented after BMSD consensus decisions, showing the ability to develop together. DATA MANAGEMENT: Scientific projects can be proposed by external sponsors via the coordinating centre and each registry decides independently on participation, respecting its governance structure. Research datasets are established in a project-to-project fashion and a project-specific data model is developed, based on a unifying core data model. To overcome challenges in data sharing, BMSD has developed procedures for federated data analysis. FUTURE PERSPECTIVES: Presently, BMSD is seeking a qualification opinion from the European Medicines Agency (EMA) to conduct post-authorization safety studies (PASS) and aims to pursue a qualification opinion also for post-authorization effectiveness studies (PAES). BMSD aspires to promote the advancement of real-world evidence research in the MS field.

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis.

OBJECTIVE: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). METHODS: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. RESULTS: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. INTERPRETATION: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021;89:780-789.

First Wave of COVID-19 Pandemic in Italy: Data and Evidence.

INTRODUCTION: Unexpectedly, Italy was the first Western country to face COVID-19 outbreak, but promptly it was the first one to adopt stringent procedures to stem the spread of infection. The objective of this study was to describe the epidemiological situation and comorbidities in Italy, in addition to containment measures and health system and social protection strengthening ones applied in this country. METHODS: Available population data were collected, managed, and analysed from the daily reports on COVID-19 published every day, from 1 February to 8 June 2020. RESULTS: Lombardia, a northern region of Italy, is considered the epicentre for the wave of the infection with the first diagnosed case, but in a few weeks other regions were involved (with Piemonte, Emilia-Romagna, and Veneto covering more than 70% of the Italian total cases). In the European context, after 3 months of containing measures of the sanitary emergency, Italy is the fourth country for the number of total positive cases (with 235,278 total case as at 8 June 2020), after Russia, the United Kingdom, and Spain, whereas it is the second for the number of deaths (with 33,964 deaths as at 8 June 2020), only after the United Kingdom. Regarding incidence, the curve of daily new cases shows an increasing trend up to 22 March 2020 with 6557 new daily cases and then a decreasing trend up to 280 as at 8 June. This turnaround can be explained by the application of national lockdown starting from 9 March and by the following 14 days of incubation of infection. Profiles of subjects at major risk of poor prognosis and death for COVID-19 are elderly (mean age of 80 years) and with three or more comorbidities. These characteristics can partially explain the high lethality rate for coronavirus observed in Italy, which is the European country with the highest share of elderly. In addition, other possible explanations of this high lethality are differences in testing policies among countries that influence the number of asymptomatic or pauci-symptomatic patients diagnosed as coronavirus positive, together with differences in definition and in the way of recording deaths for coronavirus. In the absence of a vaccine, severe nonpharmaceutical interventions (NPIs), including national lockdown, quarantine, social distancing, and use of facial masks, have been applied with success to reduce the virus spread and the burden on the National Health System. In addition to these stringent containment measures to fight the pandemic, other policies have been adopted searching to ensure economic sustainability, social safety, and stability. CONCLUSION: Italy was the first Western country with a wide spread of COVID-19, but it was the first one to introduce containment restrictions, tightening them week by week and subjecting the 60 million people living in the country to unprecedented limitations. Many measurements have been adopted by the government, such as lockdown during the early stages of infection and subsequent social distancing and wearing face masks in public areas. Italians were compliant with all the measures ordered by the government and their discipline reflected in the COVID numbers: the curve of daily new cases after a peak at the end of March now shows a consistent decreasing trend up. In this phase of current reduction of virus diffusion, it is crucial to accommodate the need to continue protecting citizens from the risk of infection with the undeferrable, although gradual, restart of the economic and social system. This new scenario requires an active collaboration among all the actors: statutory bodies, employers, civil society, and the third sector.

MAM-36 and ABILHAND as outcome measures of multiple sclerosis hand disability: an observational study.

BACKGROUND: Impaired upper limb functionality and dexterity are common in people with multiple sclerosis (PwMS) and lead to increased dependency and reduced quality of life. AIM: The aim of this study was to compare the ability of the Manual Abilites Measure 36 (MAM-36) and the ABILHAND questionnaire to recognize an involvement of the upper limbs in PwMS, and to compare their results with those of other patient reported outcomes (PRO) evaluating disability, functional independence, symptoms of anxiety and depression, fatigue and quality of life. DESIGN: The study design was observational. SETTING: The setting of the study was outpatient. POPULATION: The study population included fifty-one PwMS (mean age of 56.31 years, age range of 33-82 years, 72.5% of patients were females). METHODS: For each patient were collected MAM-36, ABILHAND questionnaire, expanded disability status scale (EDSS), Functional Independence measure (FIM), Hospital Anxiety and Depression Scale (HADS), Modified Fatigue Impact Scale (MFIS) and Life Satisfaction Index (LSI). RESULTS: A strong correlation between MAM-36 and the ABILHAND questionnaire (Spearman r: 0.79; P<0.0001) were found. We obtained a significant correlation between MAM-36 and EDSS (Spearman r: -0.5; P=0.0002), FIM (Spearman r: 0.55; P<0.0001); we did not observe a correlation with MFIS (Spearman r: -0.33; P=0.02); moreover we found a similar trend between ABILHAND and EDSS (Spearman r: -0.47; P=0.0005), FIM (Spearman r: 0.61; P<0.0001), MFIS (Spearman r: -0.41; P=0.002). CONCLUSIONS: In PwMS the assessment of upper limbs is fundamental since it closely related to the level of disability of the person. Both MAM-36 and ABILHAND Questionnaire are equally able to detect upper limb dysfunctions in PwMS. CLINICAL REHABILITATION IMPACT: Both MAM-36 and ABILHAND can be used for upper limbs evaluation, within a multidimensional approach that seems to be the best way to evaluate PwMS.

Impact of the COVID-19 pandemic on persons with multiple sclerosis: Early findings from a survey on disruptions in care and self-reported outcomes.

OBJECTIVE: To describe the disruptions in care experienced by persons with Multiple Sclerosis in Italy due to the COVID-19 pandemic and the self-reported impact on their health and wellbeing. METHODS: A cross-sectional online survey was completed by 2722 persons with Multiple Sclerosis, after Italy instituted a national lockdown in response to the pandemic. RESULTS: Persons with Multiple Sclerosis reported that the pandemic caused broad disruptions to usual health and social care services, which impacted on their health and wellbeing. Disruptions in care were consistently associated with negative self-reported impacts on the expected progression of the disease, on out-of-pocket expenditure and on carer's stress. Psychological consequences were associated with interruption to usual psychological support, and concerns about the safety of care delivered in person. CONCLUSIONS: The quality of life of persons with Multiple Sclerosis depends greatly on prompt access to a broad range of health and care services. Negative psychological impacts reported by persons with Multiple Sclerosis with less severe disabilities show that accessible integrated services are crucial for maintenance of their wellbeing. Most persons with Multiple Sclerosis with more severe disability experienced negative impacts on perceived health. Their carers compensating for lack of social input resulted in care overburden. As continuity of care is crucial for persons with Multiple Sclerosis, as well as for persons with chronic conditions in general, strategies must be in place to ensure it is included in future pandemic response plans.

EAN Guideline on Palliative Care of People with Severe, Progressive Multiple Sclerosis.

Background and Purpose: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. Methods: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients-Intervention-Comparator-Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score >6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. Results: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. Conclusions: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs.

An "all-wheel drive" proposal to accelerate clinical research in common and rare neurological diseases.

The complex biology of neurological diseases calls for collaborative efforts that may increase the success rate of clinical research. Models have been proposed, but concrete actions remain insufficient. Based on recent considerations from basic science, from science of patient input and from an analysis of scientific resources in Italy, we here explain why our country may represent an appropriate environment for such actions. Furthermore, we sketch operational framework and business model to be applied in order to accelerate, in parallel, the development of therapies in common and rare diseases.

Increasing prevalence of multiple sclerosis in Tuscany, Italy.

BACKGROUND AND RATIONALE: An increase of prevalence and incidence of multiple sclerosis (MS) has been reported in several countries, especially taking into account a long-term evaluation. This increasing trend often reflects improved case identification and ascertainment due to the refinement of diagnostic criteria. The aim of this study was to update the prevalence rate of MS in Tuscany (central Italy) as of 2017, and to assess if there has been an increasing trend of prevalence in this Region considering a short period of analysis, from 2014 to 2017. METHODS: To capture prevalent cases, a case-finding algorithm based on administrative data, previously created and validated, was used. As data sources, we considered hospital discharge records, drug-dispensing records, disease-specific exemptions from copayment to health care, home and residential long-term care, and inhabitant registry. RESULTS: As of January 1, 2017, 7809 cases were identified, of which 69.4% were females and 30.6% were males. Considering temporal variation, an increasing trend was observed, with standardized rates rising from 189.2 in 2014 to 208.7 per 100,000 in 2017. CONCLUSIONS: Results confirm that prevalence increases every year, probably mainly due to the difference between incidence and mortality, resulting in an increasing trend. Moreover, administrative data may accurately identify MS patients in a routinary way and monitor this cohort along disease care pathways.

MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with a degenerative component, leading to irreversible disability. Mesenchymal stem cells (MSC) have been shown to prevent inflammation and neurodegeneration in animal models of MS, but no large phase II clinical trials have yet assessed the exploratory efficacy of MSC for MS. METHODS/DESIGN: This is an academic, investigator-initiated, randomized, double-blind, placebo-compared phase I/II clinical trial with autologous, bone-marrow derived MSC in MS. Enrolled subjects will receive autologous MSC at either baseline or at week 24, through a cross-over design. Primary co-objectives are to test safety and efficacy of MSC treatment compared to placebo at 6 months. Secondary objectives will evaluate the efficacy of MSC at clinical and MRI levels. In order to overcome funding constraints, the MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study has been designed to merge partially independent clinical trials, following harmonized protocols and sharing some key centralized procedures, including data collection and analyses. DISCUSSION: Results will provide patients and the scientific community with data on the safety and efficacy of MSC for MS. The innovative approach utilized to obtain funds to support the MESEMS trial could represent a new model to circumvent limitation of funds encountered by academic trials. TRIAL REGISTRATION: Andalusia: NCT01745783 , registered on Dec 10, 2012. Badalona: NCT02035514 EudraCT, 2010-024081-21. Registered on 2012. Canada: ClinicalTrials.gov, NCT02239393 . Registered on September 12, 2014. Copenhagen: EudraCT, 2012-000518-13 . Registered on June 21, 2012. Italy: EudraCT, 2011-001295-19, and ClinicalTrials.gov, NCT01854957 . Retrospectively registered on May 16, 2013. London: Eudra CT 2012-002357-35, and ClinicalTrials.gov, NCT01606215 . Registered on May 25, 2012. Salzburg: EudraCT, 2015-000137-78 . Registered on September 15, 2015. Stockholm: ClinicalTrials.gov, NCT01730547 . Registered on November 21, 2012. Toulouse: ClinicalTrials.gov, NCT02403947 . Registered on March 31, 2015.

Steps towards Collective Sustainability in Biomedical Research.

The optimism surrounding multistakeholder research initiatives does not match the clear view of policies that are needed to exploit the potential of these collaborations. Here we propose some action items that stem from the integration between research advancements with the perspectives of patient-advocacy organizations, academia, and industry.

Multiple sclerosis spatial cluster in Tuscany.

Tuscany (Central Italy) is a high-risk area for multiple sclerosis (MS) with a prevalence of 188 cases per 100,000 at 2011, and it is characterized by a heterogeneous geographic distribution of this disease. Our objective was to update prevalence at 2013 and to evaluate the presence of spatial clusters in Tuscany. The MS prevalence was evaluated on 31 December 2013 using a validated case-finding algorithm, based on administrative data. To identify spatial clusters, we calculated standardized morbidity ratios (SMRs) for each Tuscan administrative municipality. In addition to the classical approach, we applied the hierarchical Bayesian model to overcome random variability due to the presence of small number of cases per municipality. We identified 7330 MS patients (2251 males and 5079 females) with an overall prevalence of 195.4/100,000. The SMR for each Tuscan municipality ranged from 0 to 271.4, but this approach produced an extremely non-homogeneous map. On the contrary, the Bayesian map was much smoother than the classical one. The posterior probability (PP) map showed prevalence clusters in some areas in the province of Massa-Carrara, Pistoia, and Arezzo, and in the municipalities of Siena, Florence, and Barberino Val d'Elsa. Our prevalence data confirmed that Tuscany is a high-risk area, and we observed an increasing trend during the time. Using the Bayesian method, we estimated area-specific prevalence in each municipality reducing the random variation and the effect of extreme prevalence values in small areas that affected the classical approach.

Multiple Sclerosis Epidemiology in Europe.

Multiple sclerosis is characterized by a non-homogeneous distribution around the world. Some authors in past described a latitude gradient, with increasing risk from the equator to North and South Poles, but this theory is still controversial. Regarding Europe, there are many articles in the literature concerning the epidemiology of this disease but, unfortunately, they are not always comparable due to different methodologies, they do not cover all countries in the continent, and most of them reported data of small areas and rarely at a national level. In 2012 there were 20 national registries that could help to describe the epidemiology of the disease and, in addition, there is an European Register for Multiple Sclerosis that collect data from already existing national or regional MS registries and databases. Another valid alternative to obtain epidemiological data, also at national level, in a routinely and cost-saving way is through administrative data that are of increasing interest in the last years.

Motor Imagery as a Function of Disease Severity in Multiple Sclerosis: An fMRI Study.

Motor imagery (MI) is defined as mental execution without any actual movement. While healthy adults usually show temporal equivalence, i.e., isochrony, between the mental simulation of an action and its actual performance, neurological disorders are associated with anisochrony. Unlike in patients with stroke and Parkinson disease, only a few studies have investigated differences of MI ability in multiple sclerosis (MS). However, the relationship among disease severity, anisochrony and brain activation patterns during MI has not been investigated yet. Here, we propose to investigate MI in MS patients using fMRI during a behavioral task executed with dominant/non-dominant hand and to evaluate whether anisochrony is associated with disease severity. Thirty-seven right-handed MS patients, 17 with clinically isolated syndrome (CIS) suggestive of MS and 20 with relapsing-remitting MS (RR-MS) and 20 right-handed healthy controls (HC) underwent fMRI during a motor task consisting in the actual or imaged movement of squeezing a foam ball with the dominant and non-dominant hand. The same tasks were performed outside the MRI room to record the number of actual and imagined ball squeezes, and calculate an Index of performance (IP) based on the ratio between actual and imagined movements. IP showed that a progressive loss of ability in simulating actions (i.e., anisochrony) more pronounced for non-dominant hand, was found as function of the disease course. Moreover, anisochrony was associated with activation of occipito-parieto-frontal areas that were more extensive at the early stages of the disease, probably in order to counteract the changes due to MS. However, the neural engagement of compensatory brain areas becomes more difficult with more challenging tasks, i.e., dominant vs. non-dominant hand, with a consequent deficit in behavioral performance. These results show a strict association between MI performance and disease severity, suggesting that, at early stages of the disease, anisochrony in MI could be considered as surrogate behavioral marker of MS severity.

Funding Medical Research Projects: Taking into Account Referees' Severity and Consistency through Many-Faceted Rasch Modeling of Projects' Scores.

The funding policy of research projects often relies on scores assigned by a panel of experts (referees). The non-linear nature of raw scores and the severity and inconsistency of individual raters may generate unfair numeric project rankings. Rasch measurement (many-facets version, MFRM) provides a valid alternative to scoring. MFRM was applied to the scores achieved by 75 research projects on multiple sclerosis sent in response to a previous annual call by FISM-Italian Foundation for Multiple Sclerosis. This allowed to simulate, a posteriori, the impact of MFRM on the funding scenario. The applications were each scored by 2 to 4 independent referees (total = 131) on a 10-item, 0-3 rating scale called FISM-ProQual-P. The rotation plan assured "connection" of all pairs of projects through at least 1 shared referee.The questionnaire fulfilled satisfactorily the stringent criteria of Rasch measurement for psychometric quality (unidimensionality, reliability and data-model fit). Arbitrarily, 2 acceptability thresholds were set at a raw score of 21/30 and at the equivalent Rasch measure of 61.5/100, respectively. When the cut-off was switched from score to measure 8 out of 18 acceptable projects had to be rejected, while 15 rejected projects became eligible for funding. Some referees, of various severity, were grossly inconsistent (z-std fit indexes less than -1.9 or greater than 1.9). The FISM-ProQual-P questionnaire seems a valid and reliable scale. MFRM may help the decision-making process for allocating funds to MS research projects but also in other fields. In repeated assessment exercises it can help the selection of reliable referees. Their severity can be steadily calibrated, thus obviating the need to connect them with other referees assessing the same projects.

Azathioprine versus beta interferons for relapsing-remitting multiple sclerosis: a multicentre randomized non-inferiority trial.

UNLABELLED: For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis. However its efficacy was usually considered marginal and following approval of ß interferons for this indication it was no longer recommended as first line treatment, even if presently no conclusive direct ß interferon-azathioprine comparison exists. To compare azathioprine efficacy versus the currently available ß interferons in relapsing-remitting multiple sclerosis, a multicenter, randomized, controlled, single-blinded, non-inferiority trial was conducted in 30 Italian multiple sclerosis centers. Eligible patients (relapsing-remitting course; ≥ 2 relapses in the last 2 years) were randomly assigned to azathioprine or ß interferons. The primary outcome was annualized relapse rate ratio (RR) over 2 years. Key secondary outcome was number of new brain MRI lesions. Patients (n = 150) were randomized in 2 groups (77 azathioprine, 73 ß interferons). At 2 years, clinical evaluation was completed in 127 patients (62 azathioprine, 65 ß interferons). Annualized relapse rate was 0.26 (95% Confidence Interval, CI, 0.19-0.37) in the azathioprine and 0.39 (95% CI 0.30-0.51) in the interferon group. Non-inferiority analysis showed that azathioprine was at least as effective as ß interferons (relapse RRAZA/IFN 0.67, one-sided 95% CI 0.96; p<0.01). MRI outcomes were analyzed in 97 patients (50 azathioprine and 47 ß interferons). Annualized new T2 lesion rate was 0.76 (95% CI 0.61-0.95) in the azathioprine and 0.69 (95% CI 0.54-0.88) in the interferon group. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p = 0.03) in the azathioprine than in the interferon group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year. The results of this study indicate that efficacy of azathioprine is not inferior to that of ß interferons for patients with relapsing-remitting multiple sclerosis. Considering also the convenience of the oral administration, and the low cost for health service providers, azathioprine may represent an alternative to interferon treatment, while the different side effect profiles of both medications have to be taken into account. TRIAL REGISTRATION: EudraCT 2006-004937-13.

Multiple sclerosis registries in Europe - results of a systematic survey.

BACKGROUND: Identification of MS registries and databases that are currently in use in Europe as well as a detailed knowledge of their content and structure is important in order to facilitate comprehensive analysis and comparison of data. METHODS: National MS registries or databases were identified by literature search, from the results of the MS Barometer 2011 and by asking 33 national MS societies. A standardized questionnaire was developed and sent to the registries' leaders, followed by telephone interviews with them. RESULTS: Twenty registries were identified, with 13 completing the questionnaire and seven being interviewed by telephone. These registries differed widely for objectives, structure, collected data, and for patients and centres included. Despite this heterogeneity, common objectives of the registries were epidemiology (n=10), long-term therapy outcome (n=8), healthcare research (n=9) and support/basis for clinical trials (n=8). While physician-based outcome measures (EDSS) are used in all registries, data from patients' perspectives were only collected in six registries. CONCLUSIONS: The detailed information on a large number of national MS registries in Europe is a prerequisite to facilitating harmonized integration of existing data from MS registries and databases, as well as comprehensive analyses and comparison across European populations.

Upper limb motor rehabilitation impacts white matter microstructure in multiple sclerosis.

Upper limb impairments can occur in patients with multiple sclerosis, affecting daily living activities; however there is at present no definite agreement on the best rehabilitation treatment strategy to pursue. Moreover, motor training has been shown to induce changes in white matter architecture in healthy subjects. This study aimed at evaluating the motor behavioral and white matter microstructural changes following a 2-month upper limb motor rehabilitation treatment based on task-oriented exercises in patients with multiple sclerosis. Thirty patients (18 females and 12 males; age=43.3 ± 8.7 years) in a stable phase of the disease presenting with mild or moderate upper limb sensorimotor deficits were randomized into two groups of 15 patients each. Both groups underwent twenty 1-hour treatment sessions, three times a week. The "treatment group" received an active motor rehabilitation treatment, based on voluntary exercises including task-oriented exercises, while the "control group" underwent passive mobilization of the shoulder, elbow, wrist and fingers. Before and after the rehabilitation protocols, motor performance was evaluated in all patients with standard tests. Additionally, finger motor performance accuracy was assessed by an engineered glove. In the same sessions, every patient underwent diffusion tensor imaging to obtain parametric maps of fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. The mean value of each parameter was separately calculated within regions of interest including the fiber bundles connecting brain areas involved in voluntary movement control: the corpus callosum, the corticospinal tracts and the superior longitudinal fasciculi. The two rehabilitation protocols induced similar effects on unimanual motor performance, but the bimanual coordination task revealed that the residual coordination abilities were maintained in the treated patients while they significantly worsened in the control group (p=0.002). Further, in the treatment group white matter integrity in the corpus callosum and corticospinal tracts was preserved while a microstructural integrity worsening was found in the control group (fractional anisotropy of the corpus callosum and corticospinal tracts: p=0.033 and p=0.022; radial diffusivity of the corpus callosum and corticospinal tracts: p=0.004 and p=0.008). Conversely, a significant increase of radial diffusivity was observed in the superior longitudinal fasciculi in both groups (p=0.02), indicating lack of treatment effects on this structure, showing damage progression likely due to a demyelination process. All these findings indicate the importance of administering, when possible, a rehabilitation treatment consisting of voluntary movements. We also demonstrated that the beneficial effects of a rehabilitation treatment are task-dependent and selective in their target; this becomes crucial towards the implementation of tailored rehabilitative approaches.

The effect of Nintendo® Wii® on balance in people with multiple sclerosis: a pilot randomized control study.

Improvement of sensory strategies is a relevant part of balance rehabilitation in multiple sclerosis (MS). This study aimed to Assess the effectiveness of visual-feedback exercises in improving balance in MS. We divided 36 patients into Wii and control-treated groups that underwent balance rehabilitation. Outcomes were obtained for Berg Balance Scale (BBS), Modified Fatigue Impact Scale, and sway area under conditions of opened and closed eyes. BBS showed a statistically significant improvement (from 49.6 to 54.6 points, p < 0.05) in the Wii group. Interactive visual-feedback exercises such as Wii could be more effective than the current standard protocol in improving balance disorders in MS.

Presenting evidence-based health information for people with multiple sclerosis: the IN-DEEP project protocol.

BACKGROUND: Increasingly, evidence-based health information, in particular evidence from systematic reviews, is being made available to lay audiences, in addition to health professionals. Research efforts have focused on different formats for the lay presentation of health information. However, there is a paucity of data on how patients integrate evidence-based health information with other factors such as their preferences for information and experiences with information-seeking. The aim of this project is to explore how people with multiple sclerosis (MS) integrate health information with their needs, experiences, preferences and values and how these factors can be incorporated into an online resource of evidence-based health information provision for people with MS and their families. METHODS: This project is an Australian-Italian collaboration between researchers, MS societies and people with MS. Using a four-stage mixed methods design, a model will be developed for presenting evidence-based health information on the Internet for people with MS and their families. This evidence-based health information will draw upon systematic reviews of MS interventions from The Cochrane Library. Each stage of the project will build on the last. After conducting focus groups with people with MS and their family members (Stage 1), we will develop a model for summarising and presenting Cochrane MS reviews that is integrated with supporting information to aid understanding and decision making. This will be reviewed and finalised with people with MS, family members, health professionals and MS Society staff (Stage 2), before being uploaded to the Internet and evaluated (Stages 3 and 4). DISCUSSION: This project aims to produce accessible and meaningful evidence-based health information about MS for use in the varied decision making and management situations people encounter in everyday life. It is expected that the findings will be relevant to broader efforts to provide evidence-based health information for patients and the general public. The international collaboration also permits exploration of cultural differences that could inform international practice.

Multiple sclerosis in twins from continental Italy and Sardinia: a nationwide study.

Knowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high-prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium-prevalence) and Sardinia (high-prevalence), we ascertained 216 pairs from 34,549 patients. This gives a twinning rate of 0.62% among MS patients, significantly less than that of the general population. In continental Italy, probandwise concordance was 14.5% (95% confidence interval, 5.1-23.8) for monozygotic and 4.0% (95% confidence interval, 0.8-7.1) for dizygotic twins. Results in Sardinia resemble those in northern populations but in limited numbers. Monozygotic concordance was 22.2% (95% confidence interval, 0-49.3) probandwise, but no concordant dizygotic pairs were identified. A questionnaire on 80 items possibly related to disease cause was administered to 70 twin pairs, 135 sporadic patients, and 135 healthy volunteers. Variables positively (7) or negatively (2) associated with predisposition and concordance in twins largely overlapped and were mainly linked to infection. If compared with previous studies, our data demonstrate that penetrance in twins appears to correlate with MS prevalence. They highlight the relevance of nonheritable variables in Mediterranean areas. The apparent underrepresentation of MS among Italian twins draws attention to protective factors, shared by twins, that may influence susceptibility.