People with newly diagnosed multiple sclerosis benefit from a complex preventative intervention-a single group prospective study with follow up.

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.

The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation.

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.

Metabolomics of Cerebrospinal Fluid Amino and Fatty Acids in Early Stages of Multiple Sclerosis.

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.

Impaired intestinal permeability in patients with multiple sclerosis.

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.

Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries.

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.

Is breastfeeding in MS harmful or not? An answer from real-world Czech data.

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.

Prevalence of myocardial injury in patients after acute ischaemic stroke according to standard criteria.

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.

The Czech National MS Registry (ReMuS): Data trends in multiple sclerosis patients whose first disease-modifying therapies were initiated from 2013 to 2021.

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 disease­modifying 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 real­world 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.

Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications-risks and mitigation.

Proliferative diabetic retinopathy (PDR) the sequel of diabetic retinopathy (DR), a frequent complication of diabetes mellitus (DM), is the leading cause of blindness in the working-age population. The current screening process for the DR risk is not sufficiently effective such that often the disease is undetected until irreversible damage occurs. Diabetes-associated small vessel disease and neuroretinal changes create a vicious cycle resulting in the conversion of DR into PDR with characteristic ocular attributes including excessive mitochondrial and retinal cell damage, chronic inflammation, neovascularisation, and reduced visual field. PDR is considered an independent predictor of other severe diabetic complications such as ischemic stroke. A "domino effect" is highly characteristic for the cascading DM complications in which DR is an early indicator of impaired molecular and visual signaling. Mitochondrial health control is clinically relevant in DR management, and multi-omic tear fluid analysis can be instrumental for DR prognosis and PDR prediction. Altered metabolic pathways and bioenergetics, microvascular deficits and small vessel disease, chronic inflammation, and excessive tissue remodelling are in focus of this article as evidence-based targets for a predictive approach to develop diagnosis and treatment algorithms tailored to the individual for a cost-effective early prevention by implementing the paradigm shift from reactive medicine to predictive, preventive, and personalized medicine (PPPM) in primary and secondary DR care management.

Acute ischaemic stroke: recent advances in reperfusion treatment.

During the last 5-7 years, tremendous progress was achieved in the reperfusion treatment of acute ischaemic stroke during its first few hours from symptom onset. This review summarizes the latest evidence from randomized clinical trials and prospective registries with a focus on endovascular treatment using stent retrievers, aspiration catheters, thrombolytics, and (in selected patients) carotid stenting. Novel approaches in prehospital (mobile interventional stroke teams) and early hospital (direct transfer to angiography) management are described, and future perspectives ('all-in-one' laboratories with angiography and computed tomography integrated) are discussed. There is reasonable chance for patients with moderate-to-severe acute ischaemic stroke to survive without permanent sequelae when the large-vessel occlusion is removed by means of modern pharmaco-mechanic approach. Catheter thrombectomy is now the golden standard of acute stroke treatment. The role of cardiologists in stroke is expanding from diagnostic help (to reveal the cause of stroke) to acute therapy in those regions where such up-to-date Class I. A treatment is not yet available.

Ischemic stroke of unclear aetiology: a case-by-case analysis and call for a multi-professional predictive, preventive and personalised approach.

Due to the reactive medical approach applied to disease management, stroke has reached an epidemic scale worldwide. In 2019, the global stroke prevalence was 101.5 million people, wherefrom 77.2 million (about 76%) suffered from ischemic stroke; 20.7 and 8.4 million suffered from intracerebral and subarachnoid haemorrhage, respectively. Globally in the year 2019 - 3.3, 2.9 and 0.4 million individuals died of ischemic stroke, intracerebral and subarachnoid haemorrhage, respectively. During the last three decades, the absolute number of cases increased substantially. The current prevalence of stroke is 110 million patients worldwide with more than 60% below the age of 70 years. Prognoses by the World Stroke Organisation are pessimistic: globally, it is predicted that 1 in 4 adults over the age of 25 will suffer stroke in their lifetime. Although age is the best known contributing factor, over 16% of all strokes occur in teenagers and young adults aged 15-49 years and the incidence trend in this population is increasing. The corresponding socio-economic burden of stroke, which is the leading cause of disability, is enormous. Global costs of stroke are estimated at 721 billion US dollars, which is 0.66% of the global GDP. Clinically manifested strokes are only the "tip of the iceberg": it is estimated that the total number of stroke patients is about 14 times greater than the currently applied reactive medical approach is capable to identify and manage. Specifically, lacunar stroke (LS), which is characteristic for silent brain infarction, represents up to 30% of all ischemic strokes. Silent LS, which is diagnosed mainly by routine health check-up and autopsy in individuals without stroke history, has a reported prevalence of silent brain infarction up to 55% in the investigated populations. To this end, silent brain infarction is an independent predictor of ischemic stroke. Further, small vessel disease and silent lacunar brain infarction are considered strong contributors to cognitive impairments, dementia, depression and suicide, amongst others in the general population. In sub-populations such as diabetes mellitus type 2, proliferative diabetic retinopathy is an independent predictor of ischemic stroke. According to various statistical sources, cryptogenic strokes account for 15 to 40% of the entire stroke incidence. The question to consider here is, whether a cryptogenic stroke is fully referable to unidentifiable aetiology or rather to underestimated risks. Considering the latter, translational research might be of great clinical utility to realise innovative predictive and preventive approaches, potentially benefiting high risk individuals and society at large. In this position paper, the consortium has combined multi-professional expertise to provide clear statements towards the paradigm change from reactive to predictive, preventive and personalised medicine in stroke management, the crucial elements of which are:Consolidation of multi-disciplinary expertise including family medicine, predictive and in-depth diagnostics followed by the targeted primary and secondary (e.g. treated cancer) prevention of silent brain infarctionApplication of the health risk assessment focused on sub-optimal health conditions to effectively prevent health-to-disease transitionApplication of AI in medicine, machine learning and treatment algorithms tailored to robust biomarker patternsApplication of innovative screening programmes which adequately consider the needs of young populations.

Metabolomics of Cerebrospinal Fluid in Multiple Sclerosis Compared With Healthy Controls: A Pilot Study.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) leading to the loss of myelin and axons. Diagnosis is based on clinical findings, MRI, and analysis of cerebrospinal fluid (CSF). CSF is an ultrafiltrate of plasma and reflects inflammatory processes in the CNS. The aim of this study was to perform metabolomics analysis of CSF in patients after the first attack of MS and healthy controls and try to find new specific analytes for MS including those potentially predicting disease activities at the onset. Methods: We collected CSF from 19 patients (16 females, aged 19-55 years) after the first attack of clinical symptoms who fulfilled revised McDonald criteria of MS and CSF of 19 controls (16 females, aged 19-50 years). Analyses of CSF samples were provided using the high-performance liquid chromatography system coupled with a mass spectrometer with a high-resolution detector (TripleTOF 5600, AB Sciex, Canada). Results: Approximately 130 selected analytes were identified, and 30 of them were verified. During the targeted analysis, a significant decrease in arginine and histidine and a less significant decrease in the levels of asparagine, leucine/isoleucine, and tryptophan, together with a significant increase of palmitic acid in the patient group, were found. Conclusion: We observed significant differences in amino and fatty acids in the CSF of newly diagnosed patients with MS in comparison with controls. The most significant changes were observed in levels of arginine, histidine, and palmitic acid that may predict inflammatory disease activity. Further studies are necessary to support these findings as potential biomarkers of MS.

Influence of Hyperglycaemia and CRP on the Need for Mechanical Ventilation in Guillain-Barré Syndrome.

Objectives: Elevated blood glucose and CRP (C-reactive protein) are usually related to a worsened clinical outcome in neurological diseases. This association in Guillain-Barré syndrome (GBS) has been studied rarely. We tried to analyse if hyperglycaemia and CRP at admission may influence the outcome of GBS, including mechanically ventilated (MV) patients. Methods: We retrospectively studied 66 patients (40 males, 19-93 years, average 56 years) without diabetes mellitus and free of corticoid treatment, who fulfilled the clinical criteria for diagnosis of GBS. Hyperglycaemia (the level of fasting plasma glucose, FPG) was defined as blood glucose level >5.59 mmol/L according to our laboratory. CRP >5 mg/L was considered as an abnormally elevated value. Results: At admission, 32 GBS patients (48%) had hyperglycaemia according to FPG level. A severe form of GBS (>4 according to Hughes GBS scale) was observed in 17 patients (26%); and 8 of them (47%) had hyperglycaemia. Fourteen patients (21%) were MV, and in 10 of them (71%) hyperglycaemia was present. CRP was significantly increased in MV patients. The linear model revealed a significant relationship between CRP and glycemia (p = 0.007) in subjects without MV (p = 0.049). In subjects with MV the relationship was not significant (p = 0.2162, NS). Conclusion: In the acute phase of GBS at admission, hyperglycaemia and higher CRP occur relatively frequently, and may be a risk factor for the severity of GBS. Stress hyperglycaemia due to impaired glucose homeostasis could be one explanation for this condition.

Modulation of Motor Cortex Activity After Intrathecal Baclofen Delivery in Chronic Thoracic Spinal Cord Injury.

Objectives: Intrathecal baclofen (ITB) is commonly used for reduction of spasticity in chronic spinal cord injury (SCI). Its clinical effect is well-known; however, exact mechanisms of long-term effect of continuous ITB administration (cITBa) on modulation of cortical processes have not been elucidated. The aim of this study was to evaluate changes in motor cortex activation for healthy upper limbs in comparison to impaired lower limbs by functional magnetic resonance imaging (fMRI). Methods: Ten subjects (eight males, 20-69 years) with thoracic SCI presenting no voluntary movements of lower limbs (except one) were enrolled in the fMRI study. fMRI at 1.5T with a finger tapping paradigm and mental movement simulating foot flexion on the dominant side were performed before, 3 months, and 1 year after start of cITBa. fMRI data processing was carried out using FMRI Expert Analysis Tool (FEAT), part of FSL. A second-level analysis was carried out using FLAME stages 1 and 2. The level of spasticity was assessed with the Modified Ashworth scale (MAS). Results: Continuous ITB significantly decreased limb spasticity in all the subjects (group MAS spasticity dropped from 3 to 0.3). The second-level analysis (Z > 1.6, cluster significance threshold p =0.05) revealed increased activation of the primary sensorimotor cortex of the foot between baseline and 3 months, and 3 months and 1 year. Conclusion: Increased sensorimotor cortex activation with spasticity reduction after cITBa may reflect distant functional reorganization because of long-term mediated neuroplastic changes in the sensorimotor cortex. Better understanding of modulation of brain function in SCI after cITBa may influence the field of neurorehabilitation.

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) in Patients after Acute Stroke: Relation to Stroke Severity, Myocardial Injury, and Impact on Prognosis.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to be associated with poor prognosis after cardiovascular events. We aimed to assess the dynamic changes in TRAIL levels and the relation of TRAIL level to stroke severity, its impact on the short-term outcomes, and its association with markers of cardiac injury in patients after acute stroke. METHODS: Between August 2020 and August 2021, 120 consecutive patients, 104 after acute ischemic stroke (AIS), 76 receiving reperfusion therapy, and 16 patients after intracerebral hemorrhage (ICH) were enrolled in our study. Blood samples were obtained from patients at the time of admission, 24 h later, and 48 h later to determine the plasma level of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitive Troponin I (hs-TnI). Twelve-lead ECGs were obtained at the time of admission, 24 h later, 48 h later, and at the release of the patients. Evaluations were performed using the National Institutes of Health Stroke Scale (NIHSS) at the time of admission and using the modified Rankin Scale (mRS) 90 days following the patient's discharge from the hospital. RESULTS: We observed a connection between lower TRAIL levels and stroke severity evaluated using the NIHSS (p = 0.044) on the first day. Lower TRAIL showed an association with severe disability and death as evaluated using the mRS at 90 days, both after 24 (p = 0.0022) and 48 h (p = 0.044) of hospitalization. Moreover, we observed an association between lower TRAIL and NT-proBNP elevation at the time of admission (p = 0.039), after 24 (p = 0.043), and after 48 h (p = 0.023) of hospitalization. In the ECG analysis, lower TRAIL levels were associated with the occurrence of premature ventricular extrasystoles (p = 0.043), and there was an association with prolonged QTc interval (p = 0.052). CONCLUSIONS: The results show that lower TRAIL is associated with stroke severity, unfavorable functional outcome, and short-term mortality in patients after acute ischemic stroke. Moreover, we described the association with markers of cardiac injury and ECG changes.

Analysis of the Group of Pediatric Patients With Relapsing-Remitting Multiple Sclerosis: Data From the Czech National Registry.

Importance: Multiple sclerosis can also affect children. Approximately 3-10% of patients develop multiple sclerosis before the age of 16. Objective: The aim of this analysis is to describe the characteristics of pediatric patients with multiple sclerosis who started their treatment with disease-modifying drugs in 2013-2020, with data obtained from the Czech National Registry of patients with multiple sclerosis. Design and Setting: A method of retrospective analysis conducted with 134 pediatric patients with multiple sclerosis was used. Results: The findings reveal that the mean age at the date of the introduction of the first disease-modifying drugs treatment is 15.89 years, and gender does not play any role. In addition, moderate (51.6%) and mild (45.2%) relapses are predominant in these young patients. Seventy five percent of patients will not experience a confirmed progression of the expanded disability status scale within 54.7 months from starting the treatment. Furthermore, the results confirm that the first-choice treatment is interferon beta-a and glatiramer acetate, which is common for adult patients. However, some factors, such as a low efficacy or a lack of tolerance may impact on treatment discontinuation in children. Conclusion: More research should be performed on novel disease-modifying drugs for this target group.

Clinical and radiological factors predicting stroke outcome after successful mechanical intervention in anterior circulation.

The recanalization effect of large-vessel occlusion (LVO) in anterior circulation is well documented but only some patients benefit from endovascular treatment. We analysed clinical and radiological factors determining clinical outcome after successful mechanical intervention. We included 146 patients from the Prague 16 study enrolled from September 2012 to December 2020, who had initial CT/CTA examination and achieved good recanalization status after mechanical intervention (TICI 2b-3). One hundred and six (73%) patients achieved a good clinical outcome (modified Rankin Scale 0-2 in 3 months). It was associated with age, leptomeningeal collaterals (LC), onset to intervention time, ASPECTS, initial NIHSS, and leukoaraiosis (LA) in univariate analysis. The regression model identified good collateral status [odds ratio (OR) 5.00, 95% confidence interval (CI) 1.91-13.08], late thrombectomy (OR 0.24, 95% CI 0.09-0.65), LA (OR 0.44, 95% CI 0.19-1.00), ASPECTS (OR 1.45, 95% CI 1.08-1.95), and NIHSS score (OR 0.86, 95% CI 0.78-0.95) as independent outcome determinants. In the late thrombectomy subgroup, 14 out of 33 patients (42%) achieved a favourable clinical outcome, none of whom with poor collateral status. The presence of LC and absence of LA predicts a good outcome in acute stroke patients after successful recanalization of LVO in anterior circulation. Late thrombectomy was associated with higher rate of unfavourable clinical outcome. Nevertheless, collateral status in this subgroup was validated as a reliable selection criterion.

Direct transfer of acute stroke patients to angiography suites equipped with flat-detector computed tomography: literature review and initial single-centre experience.

Background: Time is brain! This paradigm is forcing the development of strategies with potential to shorten the time from symptom onset to recanalization. One of these strategies is to transport select patients with acute ischaemic stroke directly to an angio-suite equipped with flat-detector computed tomography (FD-CT) to exclude intracranial haemorrhage, followed directly by invasive angiography and mechanical thrombectomy if large-vessel occlusion (LVO) is confirmed. Aim: To present existing published data about the direct transfer (DT) of stroke patients to angio-suites and to describe our initial experience with this stroke pathway. Methods: We performed a systematic PubMed search of trials that described DT of stroke patients to angio-suites and summarized the results of these trials. In January 2020, we implemented a new algorithm for acute ischaemic stroke care in our stroke centre. Select patients suitable for DT (National Institute of Health Stroke Scale score ≥10, time from symptom onset to door <4.5 h) were referred by neurologists directly to an angio-suite equipped with FD-CT. Patients treated using this algorithm were analysed and compared with patients treated using the standard protocol including CT and CT angiography in our centre. Results: We identified seven trials comparing the DT protocol with the standard protocol in stroke patients. Among the 628 patients treated using the DT protocol, 104 (16.5%) did not have LVO and did not undergo endovascular treatment (EVT). All the trials demonstrated a significant reduction in door-to-groin time with DT, compared with the standard protocol. This reduction ranged from 22 min (DT protocol: 33 min; standard protocol: 55 min) to 59 min (DT protocol: 22 min; standard protocol: 81 min). In three of five trials comparing the 90-day modified Rankin scale scores between the DT and standard imaging groups, this reduction in ischaemic time translated into better clinical outcomes, whereas the two other trials reported no such difference in scores. Between January 2020 and October 2021, 116 patients underwent EVT for acute ischaemic stroke in our centre. Among these patients, 65 (56%) met the criteria for DT (National Institutes of Health Stroke Scale score >10, symptom onset-to-door time <4.5 h), but only 7 (10.8%) were transported directly to the angio-suite. The reasons that many patients who met the criteria were not transported directly to the angio-suite were lack of personnel trained in FD-CT acquisition outside of working hours, ongoing procedures in the angio-suite, contraindication to the DT protocol due to atypical clinical presentation, and neurologist's decision for obtain complete neurological imaging. All seven patients who were transported directly to the angio-suite had LVOs. The median time from door-to-groin-puncture was significantly lower with the DT protocol compared with the standard protocol {29 min [interquartile range (IQR): 25-31 min] vs. 71 min [IQR: 55-94 min]; P < 0.001}. None of the patients had symptomatic intracranial haemorrhage in the DT protocol group, compared with 7 (6.4%) patients in the standard protocol group. Direct transfer of acute ischaemic stroke patients to the angio-suite equipped with FD-CT seems to reduce the time from patient arrival in the hospital to groin puncture. This reduction in the ischaemic time translates into better clinical outcomes. However, more data are needed to confirm these results.

Is pregnancy in MS patients safe and what is its impact on MS course? Real World evidence of 1533 pregnancies in Czech Republic.

BACKGROUND: A special care of MS women planning a pregnancy is highly demanding especially in the terms of disease modifying treatment (DMD) decisions and counselling regarding periods of conception, pregnancy and postpartum period. OBJECTIVE: To provide data about impact of pregnancy, delivery or miscarriage/artificial abortion on MS disease course in Czech women with MS based on analysis of retrospective data from the Czech national registry ReMuS. METHODS: The analysis focused on women with MS with at least one record of pregnancy in the registry. Clinical data (EDSS, relapses) were collected prior to conception, during pregnancy and after delivery or miscarriage/artificial abortion. These data were analysed according to baseline characteristics of DMD treatment prior to conception and according to breastfeeding status. RESULTS: A total of 1 533 pregnancies were analysed from the period of 2013 until 31st December 2019. The occurrence of relapses and worse EDSS was significantly related to the treatment with escalation therapy prior to conception. Relapses were significantly more frequent in women who breastfed less than 3 months than in women who breastfed more than 3 months or did not breastfeed at all. Patients treated with either fingolimod or natalizumab prior to pregnancy were significantly more likely to develop relapses during pregnancy. CONCLUSION: Pregnancy and postpartum period were generally safe for Czech women with MS. Better disease outcomes were observed in those who had been treated with first line injectable DMDs prior to conception and those who either breastfed more than 3 months or did not breastfeed at all. We confirmed the assumption of rebound phenomenon of MS after discontinuation of treatment due to planned pregnancy both for fingolimod and natalizumab.