BACKGROUND: Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS). OBJECTIVES: Provide experience with cladribine therapy in a real-world setting. METHODS: This is a registry-based retrospective observational cohort study. First, using data from the Czech nationwide registry ReMuS, we analysed patients who initiated cladribine from September 1, 2018 to December 31, 2021. Second, we analysed a subgroup of patients who initiated cladribine between September 1, 2018 to June 30, 2020, thus possessing a follow-up period of at least 2 years. We evaluated demographic and MS characteristics including disease-modifying therapies (DMTs) before and after cladribine administration, relapses, Expanded Disability Status Scale (EDSS), and adherence. RESULTS: In total, 617 patients (335 with follow-up of at least 2 years) started cladribine therapy in the study period (mean age 37.0, mean disease duration 8.4 years, 74.1% females). In most cases, cladribine was administered as a second-line drug, a total of 80.7% had been escalated from a platform DMT. During 2 years before cladribine initiation, the average annualised relapse rate (ARR) was .67. Following cladribine initiation, the ARR decreased to .28 in the first year and .22 in the second year. Overall, across the entire two-year treatment period, 69.0% of patients were relapse-free and the average ARR was .25. As for EDSS development, the median baseline EDSS was 2.5 and remained stable even after 24 months. The adherence to treatment ranged of around 90%. CONCLUSION: This nationwide study confirms the efficacy of cladribine in real-world settings, especially in patients who are not treatment-naïve. In addition, the study shows an exceptionally high adherence rate, a finding that underscores the invaluable role of cladribine, but also the value of registry-based studies in capturing real-world clinical practice.

• Klíčová slova
• Cladribine, adherence, annualised relapse rate, expanded disability status scale, high-efficacy disease-modifying therapy, multiple sclerosis,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Newly diagnosed people with multiple sclerosis frequently report fatigue, pain, depression and anxiety. Preventative programmes may be beneficial, but there is limited evidence of their effectiveness, especially long-term follow-up. METHODS: The programme consisted of 6-month face to face intervention (an introductory workshop, psychology-led group sessions and individual physical therapy) followed by 6-month self-guided therapy. Outcome measures were taken at baseline, 6 and 12 months. Primary outcomes measures were self-report questionnaires for fatigue, satisfaction with life and disease acceptance. Secondary outcomes were spirometry, spiroergometric parameters and neuroactive steroid levels. RESULTS: From 22 participants enrolled, 17 completed the first 6 months and 13 the follow-up. Fatigue measured on the Fatigue scale for motor and cognitive functions decreased significantly at 6 months (p = 0.035) and at follow-up (p = 0.007). The Modified Fatigue Impact Scale (p = 0.035) and Satisfaction With Life Scale (p = 0.007) significantly increased at follow-up. Spirometry, spiroergometric parameters, steroid hormones and neuroactive steroids levels did not change significantly. CONCLUSION: This programme reduces fatigue and improves satisfaction with life in this patient group with improvements sustained at 12 months. People who participated more frequently showed greater benefit. CLINICAL REHABILITATION IMPACT: The paper describes the effects of a complex preventative intervention for people with newly diagnosed Multiple Sclerosis. The study found that this programme reduces fatigue and improves satisfaction with life with long-term benefit (at 12-month follow up). The individuals who participated less frequently experienced fewer benefits.

• Klíčová slova
• aerobic training, cognitive behavioural therapy, fatigue, multiple sclerosis, neuroactive steroids, physical therapy, satisfaction with life,
• Publikační typ
• časopisecké články MeSH

Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990-2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep-wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population-all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.

• Klíčová slova
• Artificial intelligence, Behavioural patterns, Cytokine storm (COVID-19), Diabetes mellitus, Diabetic retinopathy, Expert recommendations, Flammer syndrome, Health policy, Health risk assessment, Health-to-disease transition, Healthcare economy, Individualised patient profile, Inflammation, Ischemic stroke, Mitochondrial health, Mitophagy, Patient-friendly non-invasive approach, Population screening, Predictive preventive personalised medicine (PPPM / 3PM), Primary and secondary care, Sleep medicine, Suboptimal health, Sudden cardiac arrest/death, Tear fluid analysis, Viromics and metabolomics,
• Publikační typ
• časopisecké články MeSH

Multiple sclerosis (MS) is a demyelinating and neurodegenerative autoimmune disease of the central nervous system (CNS) damaging myelin and axons. Diagnosis is based on the combination of clinical findings, magnetic resonance imaging (MRI) and analysis of cerebrospinal fluid (CSF). Metabolomics is a systematic study that allows us to track amounts of different metabolites in a chosen medium. The aim of this study was to establish metabolomic differences between the cerebrospinal fluid of patients in the early stages of multiple sclerosis and healthy controls, which could potentially serve as markers for predicting disease activity. We collected CSF from 40 patients after the first attack of clinical symptoms who fulfilled revised McDonald criteria of MS, and the CSF of 33 controls. Analyses of CSF samples were performed by using the high-performance liquid chromatography system coupled with a mass spectrometer with a high-resolution detector. Significant changes in concentrations of arginine, histidine, spermidine, glutamate, choline, tyrosine, serine, oleic acid, stearic acid and linoleic acid were observed. More prominently, Expanded Disability Status Scale values significantly correlated with lower concentrations of histidine. We conclude that these metabolites could potentially play a role as a biomarker of disease activity and predict presumable inflammatory changes.

• Klíčová slova
• CSF, MS, arginine, cerebrospinal fluid, histidine, metabolomics, multiple sclerosis,
• MeSH
• biologické markery mozkomíšní mok   MeSH
• centrální nervový systém MeSH
• histidin MeSH
• lidé MeSH
• mastné kyseliny MeSH
• metabolomika MeSH
• roztroušená skleróza * diagnostické zobrazování   mozkomíšní mok   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• histidin MeSH
• mastné kyseliny MeSH

BACKGROUND: A number of recent studies have shown that the intestinal microbiome, part of the brain-gut axis, is implicated in the pathophysiology of multiple sclerosis. An essential part of this axis, is the intestinal barrier and gastrointestinal disorders with intestinal barrier dysregulation appear to be linked to CNS demyelination, and hence involved in the etiopathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to evaluate the integrity of the intestinal barrier in patients with clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) using two serum biomarkers, claudin-3 (CLDN3), a component of tight epithelial junctions, and intestinal fatty acid binding protein (I-FABP), a cytosolic protein in enterocytes. METHODS: Serum levels of CLDN3 in 37 MS patients and 22 controls, and serum levels of I-FABP in 46 MS patients and 51 controls were measured using commercial ELISA kits. Complete laboratory tests excluded the presence of gluten-related disorders in all subjects. Thirty MS patients received either disease-modifying drugs (DMD), immunosuppression (IS) or corticosteroid treatment. RESULTS: CLDN3 levels were only significantly higher in the MS patients treated with DMD or IS compared to the control group (P=0.006). There were no differences in I-FABP serum levels between the groups. Serum CLDN3 levels did not correlate with serum I-FABP levels in CDMS, in CIS patients or controls. CONCLUSIONS: In multiple sclerosis patients, the intestinal epithelium may be impaired with increased permeability, but without significant enterocyte damage characterized by intracellular protein leakage. Based on our data, CLDN3 serum levels appear to assess intestinal dysfunction in MS patients but mainly in treated ones.

• Klíčová slova
• I-FABP, claudin-3, clinically isolated syndrome, intestinal permeability, multiple sclerosis,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS) the most common treatment strategy has been to start with low-moderate efficacy disease modifying therapy (LE-DMT) and to escalate to more efficacious treatments in cases of breakthrough disease activity. However, recent evidence suggests a better outcome in patients commencing with moderate-high efficacy DMT (HE-DMT) immediately after clinical onset. OBJECTIVE: The aim of this study is to compare disease activity and disability outcomes in patients treated with the two alternative strategies using the Swedish and Czech national multiple sclerosis registries, taking advantage of the fact that the relative frequency of each strategy differs markedly between these two countries. METHODS: Adult RRMS patients who initiated their first-ever DMT between 2013 and 2016 and were included in the Swedish MS register were compared with a similar cohort from the MS register of the Czech Republic using propensity score overlap weighting as a balancing method. The main outcomes of interest were time to confirmed disability worsening (CDW), time to achieve an expanded disability status scale (EDSS) value of 4, time to relapse, and time to confirmed disability improvement (CDI). To support the results, a sensitivity analysis focusing solely on patients from Sweden starting with HE-DMT and patients from the Czech Republic starting with LE-DMT was performed. RESULTS: In the Swedish cohort, 42% of patients received HE-DMT as initial therapy compared to 3.8% of patients in the Czech cohort. The time to CDW was not significantly different between the Swedish and Czech cohorts (p-value 0.2764), with hazard ratio (HR) of 0.89 and a 95% confidence interval (CI) of 0.77-1.03. Patients from the Swedish cohort exhibited better outcomes for all remaining variables. The risk of reaching EDSS 4 was reduced by 26% (HR 0.74, 95%CI 0.6-0.91, p-value 0.0327), the risk of relapse was reduced by 66% (HR 0.34, 95%CI 0.3-0.39, p-value <0.001), and the probability of CDI was three times higher (HR 3.04, 95%CI 2.37-3.9, p-value <0.001). CONCLUSION: The analysis of the Czech and the Swedish RRMS cohorts confirmed a better prognosis for patients in Sweden, where a significant proportion of patients received HE-DMT as initial treatment.

• Klíčová slova
• Escalation strategy, High-efficacy DMT, Multiple sclerosis, Registry study,
• MeSH
• dospělí MeSH
• lidé MeSH
• recidiva MeSH
• registrace MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   epidemiologie   MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Švédsko epidemiologie   MeSH

INTRODUCTION: The influence of breastfeeding and it´s duration on the course of multiple sclerosis (MS) is unclear. Here we analyzed a real-world data for breastfeeding women with MS and their disease course collected from a Czech national registry ReMuS. OBJECTIVES: To identify risk factors associated with not initiating breastfeeding after delivery, to analyze the impact of breastfeeding on the MS disease course, evaluate the assumption, that breastfeeding is not harmful in MS patients, and compare the disease course by breastfeeding status. MATERIALS AND METHODS: Using propensity score matching we compared Expanded Disability Status Scale (EDSS), confirmed disease worsening (CDW) and annual relapse rate (ARR) in breastfeeding and non-breastfeeding MS patients according to disease duration, disease modifying treatment (DMT) before pregnancy, last EDSS score before conception, age, and ARR during pregnancy. We also compared these parameters between breastfeeding patients not using a DMT and non-breastfeeding patients who resumed DMT within 3 months after delivery. EDSS, ARR, and CDW were collected at 12, 24, and 36 months after delivery. RESULTS: A total of 1681 pregnancies that ended in delivery were analyzed from 2013 through 2020. Change in ARR and EDSS values and 6-months CDW did not significantly differ between the analyzed groups. Compared with non-breastfeeding women who resumed DMT early after delivery, breastfeeding women with MS did not experience worse clinical outcomes even without initiating a DMT. DISCUSSION: Breastfeeding in Czech women with MS did not negatively affect the disease course and can be supported. Patients with MS can be treated with certain DMTs alongside breastfeeding and there is no need to stop breastfeeding, if the patient is clinically stable.

• Klíčová slova
• Breastfeeding, Czech national multiple sclerosis patient registry ReMuS, EDSS, Multiple sclerosis, Relapses,
• MeSH
• kojení MeSH
• lidé MeSH
• progrese nemoci MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• roztroušená skleróza * farmakoterapie   epidemiologie   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

This study examined the prevalence of acute and chronic myocardial injury according to standard criteria in patients after acute ischaemic stroke (AIS) and its relation to stroke severity and short-term prognosis. Between August 2020 and August 2022, 217 consecutive patients with AIS were enrolled. Plasma levels of high-sensitive cardiac troponin I (hs-cTnI) were measured in blood samples obtained at the time of admission and 24 and 48 h later. The patients were divided into three groups according to the Fourth Universal Definition of Myocardial Infarction: no injury, chronic injury, and acute injury. Twelve-lead ECGs were obtained at the time of admission, 24 and 48 h later, and on the day of hospital discharge. A standard echocardiographic examination was performed within the first 7 days of hospitalization in patients with suspected abnormalities of left ventricular function and regional wall motion. Demographic characteristics, clinical data, functional outcomes, and all-cause mortality were compared between the three groups. The National Institutes of Health Stroke Scale (NIHSS) at the time of admission and the modified Rankin Scale (mRS) 90 days following hospital discharge were used to assess stroke severity and outcome. Elevated hs-cTnI levels were measured in 59 patients (27.2%): 34 patients (15.7%) had acute myocardial injury and 25 patients (11.5%) had chronic myocardial injury within the acute phase after ischaemic stroke. An unfavourable outcome, evaluated based on the mRS at 90 days, was associated with both acute and chronic myocardial injury. Myocardial injury was also strongly associated with all-cause death, with the strongest association in patients with acute myocardial injury, at 30 days and at 90 days. Kaplan-Meier survival curves showed that all-cause mortality was significantly higher in patients with acute and chronic myocardial injury than in patients without myocardial injury (P < 0.001). Stroke severity, evaluated with the NIHSS, was also associated with acute and chronic myocardial injury. A comparison of the ECG findings between patients with and without myocardial injury showed a higher occurrence in the former of T-wave inversion, ST segment depression, and QTc prolongation. In echocardiographic analysis, a new abnormality in regional wall motion of the left ventricle was identified in six patients. Chronic and acute myocardial injury with hs-cTnI elevation after AIS are associated with stroke severity, unfavourable functional outcome, and short-term mortality.

• Klíčová slova
• Acute ischaemic stroke, Cardiovascular disease, Mortality, Myocardial injury, Stroke, Troponin,
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• časopisecké články MeSH

AIMS: Multiple sclerosis treatment strategies are changing in the Czech Republic. According to data from 2013-2021, the proportion of patients starting high-efficacy disease-modifying therapies is increasing. In this survey, we describe the actual data trends in multiple sclerosis (MS) patients beginning their first disease‑modifying therapies (DMTs) from 2013 to 2021. The secondary objective was to present the history, data collection, and scientific potential of the Czech National MS registry (ReMuS). METHODS: First, using descriptive statistics, we analysed the data for patients starting their first DMTs, either platform (including dimethyl fumarate) or high-efficacy DMTs (HE-DMTs), for each successive year. Second, a detailed description of the history, data collection, completeness, quality optimising procedures, and legal policies of ReMuS is provided. RESULTS: Based on the dataset from December 31, 2021, the total number of monitored patients with MS in ReMuS increased from 9,019 in 2013 (referred from 7 of 15 MS centres) to 12,940 in 2016 (referred from all 15 Czech MS centres) to 17,478 in 2021. In these years, the percentage of patients treated with DMTs in the registry ranged from 76 to 83%, but the proportion of patients treated with HE-DMTs changed from 16.2% in 2013 to 37.1% in 2021. During the follow-up period, a total of 8,491 treatment-naive patients received DMTs. The proportion of patients (all MS phenotypes) starting HE-DMTs increased from 2.1% in 2013 to 18.5% in 2021. CONCLUSION: Patient registries, including ReMuS, provide an essential quality data source, especially in light of the increasing percentage of patients on HE-DMTs. Although early initiation of HE-DMT can provide considerable benefits, it also carries greater potential risks. Consistent long-term follow-up of patients in real‑world clinical practice, which only registries allow, is therefore crucial to evaluate the efficacy and safety of therapeutic strategies, for epidemiological research and to assist decision making by healthcare providers and regulatory bodies.

• Klíčová slova
• disease-modifying therapy, epidemiology, high-efficacy therapy, multiple sclerosis, platform therapy, real-world data, registry, treatment initiation,
• Publikační typ
• časopisecké články MeSH