It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.
- MeSH
- chronicko-progresivní roztroušená skleróza * epidemiologie etiologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- recidiva MeSH
- rizikové faktory MeSH
- roztroušená skleróza * epidemiologie etiologie MeSH
- studie případů a kontrol MeSH
- věk při počátku nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Austrálie MeSH
BACKGROUND: For persons with multiple sclerosis (pwMS), exercise is known to be safe and effective at treating several symptoms and it may even be disease-modifying. However, exercise can trigger heat intolerance, exercise-induced heat sensitivity (EIHS), which may cause some pwMS to refrain from exercise. No review has yet summarized the existing knowledge on EIHS in pwMS. Therefore, the purpose of the present review was to clarify the terminology, summarize both the prevalence of EIHS and the current knowledge of underlying mechanisms, and provide an overview of existing treatment options and clinical management of EIHS in pwMS. METHODS: A scoping review was performed. RESULTS: As no clear definition could be identified in the literature, we propose a definition of EIHS. Aspects related to EIHS are reported in 29-80 % of all pwMS. The mechanisms underlying EIHS are not well understood but seem to include axon demyelination, CNS lesions, abnormal sudomotor function and sweating, abnormal afferent thermosensory function, disease stability, and abnormal neuropsychological responses. The severity of EIHS depends on the applied exercise modality, intensity, and format, and can be further reduced when applying different cooling interventions or garments before and/or during exercise. CONCLUSION: EIHS appears frequently in pwMS, but the underlying mechanisms are still only sparsely understood. EIHS severity depends on exercise-related factors and can be reduced by cooling interventions.
- MeSH
- cvičení * fyziologie MeSH
- lidé MeSH
- prevalence MeSH
- roztroušená skleróza * terapie patofyziologie epidemiologie MeSH
- vysoká teplota škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- lidé MeSH
- rizikové faktory MeSH
- roztroušená skleróza * epidemiologie etiologie patologie MeSH
- T-lymfocyty imunologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
INTRODUCTION: Fabry disease (FD) can be undiagnosed in the context of multiple sclerosis (MS) due to similar clinical and paraclinical features. Our study aimed to determine the prevalence (and the necessity of screening) of FD among patients with possible or definite MS. METHODS: In this prospective monocentric observational study, we included consecutive patients enrolled between May 2017 and May 2019 after the first clinical event suggestive of MS. All patients underwent FD screening using dried blood spots in a stepwise manner combining genetic and enzyme testing. Patients were followed until May 2022. RESULTS: We included 160 patients (73.1% female, mean age 33.9 years). The 2017 revised McDonald's criteria for definite MS were fulfilled by 74 (46.3%) patients at the time of study recruitment and 89 (55.6%) patients after 3-5 years of follow-up. None of the patients had a pathogenic GLA variant, and four (2.5%) had a variant of unknown significance (p.A143T, p.S126G, 2 × p.D313Y). In two of these patients, the intrathecal synthesis of oligoclonal bands was absent, and none had hyperproteinorachia or pleocytosis in cerebrospinal fluid. Detailed examination of FD organ manifestations revealed only discrete ocular and kidney involvement in two patients. CONCLUSION: The prevalence of FD in the population of suspected or definite MS patients does not appear to be high. Our results do not support routine FD screening in all patients with a possible diagnosis of MS, but there is an urgent need to search for red flags and include FD in the differential diagnosis of MS.
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- Fabryho nemoc * diagnóza epidemiologie MeSH
- lidé MeSH
- nepoznaná diagnóza MeSH
- prospektivní studie MeSH
- roztroušená skleróza * diagnóza epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
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.
- MeSH
- big data MeSH
- lidé MeSH
- mezinárodní spolupráce MeSH
- registrace * MeSH
- roztroušená skleróza * epidemiologie terapie MeSH
- šíření informací MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Roztroušená skleróza (RS) je autoimunitní onemocnění, na jehož rozvoji se podílí více faktorů. V současné době se stále více studií věnuje podílu genetiky na rozvoji RS. Studie, které mapovaly rozsáhlé soubory pacientů s RS a kontrol, identifikovaly 236 nezávislých genetických variant asociovaných se zvýšeným rizikem rozvoje RS. Žádná z těchto variant se nenachází výhradně u pacientů s RS. Riziko RS je primárně zprostředkováno mírnými změnami genové regulace, které mají za následek změny funkcí periferních a tkáňově vázaných buněk imunitního systému. Každý genetický rizikový faktor sám o sobě představuje malé riziko, jejich kombinací vzniká individuální genetické riziko rozvoje RS. Tato polygenicita tedy určuje riziko vzniku RS u každého jedince. Jakým způsobem se spolupodílí environmentální faktory a které, zůstává otázkou. Studium genetického pozadí spolu s epidemiologickými studiemi s využitím metody mendelovské randomizace nabízí možnosti k prokázání kauzality těchto vlivů. Současný výzkum se zaměřuje na rozšíření kohort, jejich rozmanitost, jejich podrobnější studium a převedení zjištěných asociací pro pochopení patofyziologie RS.
Multiple sclerosis (MS) is an autoimmune disease in which multiple factors contribute to its development. Currently, more and more studies are devoted to the role of genetics in the development of MS. Studies that mapped large sets of MS patients and controls identified 236 independent genetic variants associated with an increased risk of developing MS. None of these variants are found exclusively in MS patients. MS is primarily mediated by mild changes in gene regulation that result in changes in the functions of peripheral and tissue-bound cells of the immune system. Each genetic risk factor alone represents a small risk, the combination of which creates an individual genetic risk of developing MS. This polygenicity therefore determines the risk of developing MS in every individual. How environmental factors contribute remains a question. The study of genetic background together with epidemiologic studies using Mendelian randomization offer possibilities to demonstrate the causality of these effects. Current research focuses on expanding the cohorts, their diversity, studying them in more detail and translating the associations to understanding the pathophysiology of MS.
- MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- roztroušená skleróza * epidemiologie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- COVID-19 * MeSH
- cvičení MeSH
- kvalita života MeSH
- lidé MeSH
- pandemie MeSH
- roztroušená skleróza * komplikace epidemiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
BACKGROUND: In 2018 multiple sclerosis (MS) care unit (MSCU) recommendations were defined. Nevertheless, the information on MS care, and whether MS centres fulfil the international recommendation is limited. Thus our objectives were to assess whether centres meet the MSCU recommendations and gain a comprehensive overview of MS care in Central-Eastern European countries. METHODS: A self-report questionnaire assessing aspects of the MSCU recommendations, disease-modifying therapy (DMT) and registry use and the patient number was assembled and sent to nine Central-Eastern European countries. Furthermore, one Danish and one German centre were contacted as a reference. RESULTS: In 9/9 countries, MS care was pursued in centres by MS neurologists and MS nurses. In Austria and the Czech Republic, management of MS was conducted under strict regulations displaying a referral centre system, fundamentally similar to but independent of the MSCU criteria. Several centres fulfilled all aspects of the MSCU criteria, while others had similar insufficiencies consisting of a speech therapist, continence, pain and spasticity specialist, neuro-ophthalmologist, and oto-neurologist. In 9/9 countries, DMTs were reimbursed. However, some centres did not provide every available DMT. A national registry was available in 4/9 countries with mandatory registry use only in Austria and the Czech Republic. CONCLUSION: In countries where MSCU recommendations are not fulfilled, a strictly regulated centre system similar to the Austrian and Czech model with a registry-based quality control might ensure appropriate care for people with MS.
- MeSH
- lidé MeSH
- neurologie * MeSH
- průzkumy a dotazníky MeSH
- roztroušená skleróza * epidemiologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
- Evropa MeSH
