Inflammatory natalizumab-associated PML: baseline characteristics, lesion evolution and relation with PML-IRIS

BACKGROUND AND OBJECTIVE: Natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) patients may show imaging signs suggestive of inflammation at diagnosis ('inflammatory PML'), reminiscent of PML-immune reconstitution inflammatory syndrome (PML-IRIS). We investigated the imaging characteristics of inflammatory NTZ-PML lesions and PML-IRIS to determine differentiating and overlapping features. METHODS: We scored the presence, localisation and pattern of imaging characteristics of inflammation on brain MRI scans of inflammatory NTZ-PML patients. The imaging characteristics were followed up until the occurrence of PML-IRIS. RESULTS: Ten out of the 44 NTZ-PML patients included showed signs suggestive of inflammation at the time of diagnosis. The inflammation pattern at diagnosis was similar to the pattern seen at PML-IRIS, with contrast enhancement representing the most frequent sign of inflammation (90% at diagnosis, 100% at PML-IRIS). However, the severity of inflammation differed, with absence of swelling and low frequency of perilesional oedema (10%) at diagnosis, as compared with the PML-IRIS stage (40%). CONCLUSION: Patterns of inflammation at the time of PML diagnosis and at the PML-IRIS stage overlap but differ in their severity of inflammation. This supports histopathological evidence that the inflammation seen at both stages of the same disease shares a similar underlying pathophysiology, representing the immune response to the JC virus to a variable extend

Empathy in multiple sclerosis-correlates with cognitive, psychological and occupational functioning

Background Recent studies report deficits in social cognition in individuals with multiple sclerosis (MS). Social cognitive skills such as empathy are important for adequate social and occupational functioning. Our objectives are: (1) to examine whether empathy differs between individuals with MS and healthy controls, (2) to examine relations between empathy and cognitive, psychological and occupational functioning. Methods 278 individuals with MS (relapsing-remitting subtype) and 128 healthy controls from the MS@Work study participated in this investigation. The participants completed questionnaires about demographics, cognitive, psychological and occupational functioning, and underwent neurological and neuropsychological examinations. Mann-Whitney U-tests were used to examine group differences in empathy. Pearson and Spearman rank correlation analyses were used to examine relations between empathy and the other measures. Results Empathy did not differ between individuals with MS and healthy controls. In individuals with MS, higher empathy was correlated with a higher educational level (X2(df) = 13.2(2), p = 0.001), better verbal learning (r = 0.20, p = 0.001), less symptoms of depression (r=−0.21, p = 0.001), higher extraversion (r = 0.25, p ≤ 0.001), agreeableness (r = 0.55, p ≤ 0.001) and conscientiousness (r = 0.27, p ≤ 0.001) and better occupational functioning in terms of work scheduling and output demands (r = 0.23, p = 0.002) and less cognitive/psychological work barriers (r = −0.21, p = 0.001). In healthy controls, higher empathy was correlated with less symptoms of depression (r = −0.34, p ≤ 0.001), less fatigue (r = −0.37, p ≤ 0.001), higher agreeableness (r = 0.59, p ≤ 0.001) and better occupational functioning in terms of work ability as compared to lifetime best (r = 0.28, p = 0.001) and less cognitive/psychological work barriers (r = −0.34, p ≤ 0.001). Empathy did not differ between unemployed and employed individuals with MS or healthy controls. Conclusion Empathy did not differ between individuals with MS and healthy controls. Within both investigated groups, higher empathy was weakly to moderately correlated with less symptoms of depression, higher agreeableness and better occupational functioning. We also found unique correlations for empathy within the investigated groups. Longitudinal studies are needed to further examine social cognition in relation to cognitive, psychological and occupational functioning in both individuals with MS and healthy controls. It would be particularly interesting to concurrently examine changes in the brain network involved with social cognition

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

The capability set for work - correlates of sustainable employability in workers with multiple sclerosis

BACKGROUND: The aim of this study was to examine whether work capabilities differ between workers with Multiple Sclerosis (MS) and workers from the general population. The second aim was to investigate whether the capability set was related to work and health outcomes. METHODS: A total of 163 workers with MS from the MS@Work study and 163 workers from the general population were matched for gender, age, educational level and working hours. All participants completed online questionnaires on demographics, health and work functioning. The Capability Set for Work Questionnaire was used to explore whether a set of seven work values is considered valuable (A), is enabled in the work context (B), and can be achieved by the individual (C). When all three criteria are met a work value can be considered part of the individual's 'capability set'. RESULTS: Group differences and relationships with work and health outcomes were examined. Despite lower physical work functioning (U = 4250, p = 0.001), lower work ability (U = 10591, p = 0.006) and worse self-reported health (U = 9091, p ≤ 0.001) workers with MS had a larger capability set (U = 9649, p ≤ 0.001) than the general population. In workers with MS, a larger capability set was associated with better flexible work functioning (r = 0.30), work ability (r = 0.25), self-rated health (r = 0.25); and with less absenteeism (r = - 0.26), presenteeism (r = - 0.31), cognitive/neuropsychiatric impairment (r = - 0.35), depression (r = - 0.43), anxiety (r = - 0.31) and fatigue (r = - 0.34). CONCLUSIONS: Workers with MS have a larger capability set than workers from the general population. In workers with MS a larger capability set was associated with better work and health outcomes. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. The study is registered at the Dutch CCMO register ( https://www.toetsingonline.nl ). This study is approved by the METC Brabant, 12 February 2014. First participants are enrolled 1st of March 2014

A Dutch validation study of the Multiple Sclerosis Work difficulties questionnaire in relapsing remitting multiple sclerosis

Health and self-regulatio

Self-reported occupational functioning in persons with relapsing-remitting multiple sclerosis: does personality matter?

Health and self-regulatio

Aplicação de deficientes físicos nas atividades da Polícia Militar do Paraná

Orientador: Ivan Santa MariaMonografia (Especialização) - Universidade Federal do Paraná,Setor de Ciências Sociais Aplicadas, Departamento de Contabilidade, Curso de Especialização em Administração PolicialResumo: O presente trabalho monográfico abordou o problema da aplicabilidade de policiais-militares em atividades consideradas meio na Organização, sendo que os mesmos poderiam ser substituídos por deficientes físicos em algumas funções básicas, como telefonista, recepcionista, digitador e outros, redundando num maior emprego de policiaismilitares nas ruas. Para tanto, buscou primeiramente retratar a realidade na PMPR; caracterizar atividades de cunho civil e de cunho militar na atividade meio; além de onde e como aplicar a pessoa portadora de deficiência física. Na parte do desenvolvimento, foram abordadas conceituações básicas, como atividade Policial Militar, atividades-meio e atividades-fim da Polícia Militar, cunho civil e militar na atividade-meio. Na seqüência, abordaram-se aspectos da pessoa portadora de deficiência, sendo navegado em assuntos a respeito da antigüidade, do renascimento, a política demográfica, deficiência em si, Programa Nacional de Direitos Humanos, a realidade social do deficiente e sua situação atual. Tratou-se também dos deficientes físicos e a Polícia Militar, em que buscou-se evidenciar o que existe em legislação peculiar e cargos privativos de militares. Quanto aos direitos dos deficientes, relatou-se a respeito dos tratados internacionais e a legislação brasileira. Ainda no capítulo referente ao desenvolvimento retratou-se a respeito do PSAV - Prestador de Serviço Auxiliar Voluntário (Deficientes Físicos); APR - Associação Paranaense de Reabilitação; ADFP -Associação dos Deficientes Físicos do Paraná; empresas que abrem caminhos para deficientes; uma importante matéria veiculada na Gazeta do Povo com o título "700 Deficientes podem Perder o Emprego", postura esta defendida pelo Estado como sendo o serviço prestado de grande importância econômica e social. Um capítulo tratou sobre a presença de pessoal civil na Polícia Militar, com seus fundamentos legais e doutrinários. Chegou-se ao final do desenvolvimento retratando como seria uma possível implantação da alocação de deficientes físicos em certas atividades-meio da Polícia Militar do Paraná Finalizou o presente estudo tratando das considerações finais, em que algumas propostas foram colocadas, ressaltando-se a importância de primeiramente serem readequadas as instalações físicas das Unidades Policiais-Militares para o ideal recebimento destes funcionário

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche