ABSTRACT
Purpose: The aim of this study was to evaluate the effects of aerobic training on motor cortical areas in multiple sclerosis (MS) patients, based on task-based functional magnetic resonance imaging (t-fMRI) as well as on brain activity at rest, according to resting state functional MRI (rs-fMRI) studies. Material and methods: Multiple sclerosis patients were divided into 2 groups consisting of 14 participants each: the MS study group and the MS control group. All MS patients underwent clinical assessment and MRI examination, twice: in the MS study group at the time of inclusion in the study and after a 4-week period of aerobic training, whereas in the MS control group it happened at the time of inclusion and after a period of one month without exercise rehabilitation. The MRI study protocol included rs-fMRI and t-fMRI sequences, which were the grounds for an analysis of resting state networks (RSN) as well as peak level and cluster level parameters within motor cortex areas - the primary motor cortex, premotor area, and supplementary motor area, respectively. Results: In the MS study group, aerobic training improved the clinical condition and decreased the functional correlation between the sensorimotor network and the salience network. Also, significant decreases of the mean cluster level (72.42 vs. 38.35) and peak level values (10.89 vs. 7.64) were observed in the contralateral primary motor cortex in this group of patients between examinations. Conclusions: Aerobic training not only improves physical performance but also contributes to changes in brain activity - both within RSN and motor cortex areas in MS patients.
ABSTRACT
Purpose: The aim of this study was to assess the activity of motor cortical areas and the resting brain activity in a group of multiple sclerosis (MS) patients compared to a group of healthy individuals according to task-based functional magnetic resonance imaging (t-fMRI), resting state functional MRI (rs-fMRI), and volumetric MRI studies. Material and methods: The study enrolled 28 MS patients and 20 healthy volunteers who underwent MRI examinations. Primary motor cortex (M1), premotor area (PMA), supplementary motor area, as well as resting state networks (RSN's) and volumes of selected brain structures were subjected to a detailed analysis. Results: In MS patients, a motor task more often resulted in the activation of ipsilateral M1 cortex (observed in 39% of the studied group) as well as the PMA cortex (observed in 32% of MS patients). No differences in resting brain activity were found between the studied groups. Significant differences were observed in volumetric parameters of the total brain volume (healthy volunteers vs. MS patients, respectively): (1197 cm³ vs. 1150 cm³) and volumes of the grey matter (517 cm³ vs. 481 cm³), cerebellum (150 cm³ vs. 136 cm³), thalamus (16.3 cm³ vs. 12.6 cm³), putamen (8.9 cm³ vs. 7.7 cm³), and globus pallidus (4.57 cm³ vs. 3.57 cm³). Conclusions: In the MS patients, the motor task required significantly more frequent activation of the primary and secondary ipsilateral motor cortex compared to the group of healthy volunteers. The rs-fMRI study showed no differences in activity patterns within the RSN's. Differences in the total cerebral volume and the volume of the grey matter, cerebellum, thalamus, putamen, and globus pallidus were observed.
ABSTRACT
Multiple sclerosis (MS) still poses a challenge in terms of complex etiology, not fully effective methods of treatment, and lack of healing agents. This neurodegenerative condition considerably affects the comfort of life by causing difficulties with movement and worsening cognition. Neuron, astrocyte, microglia, and oligodendrocyte activity is engaged in multiple pathogenic processes associated with MS. These cells are also utilized in creating in vitro cellular models for investigations focusing on MS. In this article, we present and discuss a summary of different in vitro models useful for MS research and describe their development. We discuss cellular models derived from animals or humans and present in the form of primary cell lines or immortalized cell lines. In addition, we characterize cell cultures developed from induced pluripotent stem cells (iPSCs). Culture conditions (2D and 3D cultures) are also discussed.
Subject(s)
Induced Pluripotent Stem Cells , Multiple Sclerosis , Multiple Sclerosis/pathology , Multiple Sclerosis/metabolism , Humans , Animals , Induced Pluripotent Stem Cells/cytology , Oligodendroglia/metabolism , Oligodendroglia/pathology , Cell Culture Techniques/methods , Neurons/metabolism , Neurons/pathology , Astrocytes/metabolism , Astrocytes/pathology , Microglia/pathology , Microglia/metabolism , Models, BiologicalABSTRACT
Inflammation plays an important role in numerous central nervous system (CNS) disorders. Its role is ambiguous-it can induce detrimental effects, as well as repair and recovery. In response to injury or infection, resident CNS cells secrete numerous factors that alter blood-brain barrier (BBB) function and recruit immune cells into the brain, like neutrophils. Their role in the pathophysiology of CNS diseases, like multiple sclerosis (MS) and stroke, is highly recognized. Neutrophils alter BBB permeability and attract other immune cells into the CNS. Previously, neutrophils were considered a homogenous population. Nowadays, it is known that various subtypes of these cells exist, which reveal proinflammatory or immunosuppressive functions. The primary goal of this review was to discuss the current knowledge regarding the important role of neutrophils in MS and stroke development and progression. As the pathogenesis of these two disorders is completely different, it gives the opportunity to get insight into diverse mechanisms of neutrophil involvement in brain pathology. Our understanding of the role of neutrophils in CNS diseases is still evolving as new aspects of their activity are being unraveled. Neutrophil plasticity adds another level to their functional complexity and their importance for CNS pathophysiology.
ABSTRACT
Biomarkers of atherosclerotic plaque instability are needed. This study aimed to evaluate the level of chemokine CXCL1 (CXC motif ligand 1) in plasma and atherosclerotic plaques in patients with carotid stenosis and correlate that with plaque morphology. The study group included 82 patients (30 women and 52 men) aged 50-90 years (mean 68.1 ± 8.9) who underwent elective carotid endarterectomy. The obtained atherosclerotic plaques were macroscopically and microscopically assessed according to the American Heart Association (AHA) classification. Fifty-one (62.2%) and 31 (37.8%) of the plaques were unstable and stable, respectively. The mean concertation of CXCL1 in plaques in asymptomatic and symptomatic patients was 0.00 (±0.00) vs 88.90 (±95.19) pg/ml, respectively (P = 0.000). The mean plasma concentration of CXCL1 in the study group was 42.40 (±85.79) pg/ml, while in the control group (healthy volunteers without lesions in the carotid arteries) it was 0.00 pg/mL (±0.00) (P = 0.000). The mean plasma CXCL1 concertation in asymptomatic and symptomatic patients was 22.08 (±49.13) versus 67.72 (±107.91) pg/ml, respectively (P = 0.031). Significantly higher CXCL1 concentration in atherosclerotic plaques and plasma in symptomatic patients compared with asymptomatic patients probably resulted from unstable lesions in the carotid arteries.
ABSTRACT
CLINICAL RATIONALE FOR THE STUDY: The rapid spread of SARS-CoV-2 throughout the world has highlighted the importance of vaccinations to control the pandemic and to protect people at risk for severe disease courses. Disease-modifying therapies (DMT) in multiple sclerosis (MS), whether immunomodulatory or immunosuppressive, may affect the immune response. Therefore, the question arose as to whether these vaccinations would be effective. AIM OF THE STUDY: We planned a study to assess the immune response to SARS-CoV-2 vaccines by type of therapy. MATERIAL AND METHODS: Participants were recruited from 14 Polish MS centres. The data was obtained by neurologists using a questionnaire. We collected data on 353 MS patients (269 females, 84 males) who received complete primary SARS-CoV-2 vaccination. All persons with MS (PwMS) were treated with disease-modifying therapies. RESULTS: 305 out of 353 PwMS (86.4%) were positive for IgG Abs against SARS-CoV-2 S domain S1 Ag after vaccination. A strong immune response was noted in 129 PwMS (36.5%). The rate of seroconversion after SARS-CoV-2 vaccination in PwMS who received immunomodulatory DMTs (interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab) was 91.5%, in PwMS receiving immune reconstruction therapy (alemtuzumab, cladribine) was 92%, and in immunosuppressive DMTs (fingolimod, ocrelizumab), the seroconversion rate was 59%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study shows that, in PwMS receiving immunomodulatory therapy, the immune response to vaccination is generally excellent. Even in immunosuppressive patients, seroconversion is satisfactory.
Subject(s)
COVID-19 , Multiple Sclerosis , Female , Male , Humans , Multiple Sclerosis/drug therapy , Poland , COVID-19 Vaccines , Seroconversion , COVID-19/prevention & control , SARS-CoV-2 , Immunosuppressive Agents/therapeutic useABSTRACT
Astrocytes are considered to be the dominant cell fraction of the central nervous system. They play a supportive and protective role towards neurons, and regulate inflammatory processes; they thus make suitable targets for drugs and supplements, such as polyphenolic compounds. However, due to their wide range, knowledge of their anti-inflammatory potential remains relatively incomplete. The aim of this study was therefore to determine whether myricetin and chrysin are able to decrease chemokine release in reactive astrocytes. To assess the antioxidant and anti-inflammatory potential of polyphenols, human primary astrocytes were cultured in the presence of a reactive and neurotoxic astrocyte-inducing cytokine mixture (TNF-α, IL-1a, C1q), either alone or in the presence of myricetin or chrysin. The examined polyphenols were able to modify the secretion of chemokines by human cortical astrocytes, especially CCL5 (chrysin), CCL1 (myricetin) and CCL2 (both), while cell viability was not affected. Surprisingly, the compounds did not demonstrate any antioxidant properties in the astrocyte cultures.
ABSTRACT
It is well known that neurodegenerative diseases' development and progression are accelerated due to oxidative stress and inflammation, which result in impairment of mitochondrial function, cellular damage, and dysfunction of DNA repair systems. The increased consumption of antioxidants can postpone the development of these disorders and improve the quality of patients' lives who have already been diagnosed with neurodegenerative diseases. Prolonging life span in developed countries contributes to an increase in the incidence ratio of chronic age-related neurodegenerative disorders, such as PD (Parkinson's disease), AD (Alzheimer's disease), or numerous forms of age-related dementias. Dietary supplementation with neuroprotective plant-derived polyphenols might be considered an important element of healthy aging. Some polyphenols improve cognition, mood, visual functions, language, and verbal memory functions. Polyphenols bioavailability differs greatly from one compound to another and is determined by solubility, degree of polymerization, conjugation, or glycosylation resulting from chemical structure. It is still unclear which polyphenols are beneficial because their potential depends on efficient transport across the BBB (blood-brain barrier), bioavailability, and stability in the CNS (central nervous system). Polyphenols improve brain functions by having a direct impact on cells and processes in the CNS. For a direct effect, polyphenolic compounds must be able to overcome the BBB and accumulate in brain tissue. In this review, the latest achievements in studies (animal models and clinical trials) on the effect of polyphenols on brain activity and function are described. The beneficial impact of plant polyphenols on the brain may be summarized by their role in increasing brain plasticity and related cognition improvement. As reversible MAO (monoamine oxidase) inhibitors, polyphenols are mood modulators and improve neuronal self-being through an increase in dopamine, serotonin, and noradrenaline amounts in the brain tissue. After analyzing the prohealth effects of various eating patterns, it was postulated that their beneficial effects result from synergistic interactions between individual dietary components. Polyphenols act on the brain endothelial cells and improve the BBB's integrity and reduce inflammation, thus protecting the brain from additional injury during stroke or autoimmune diseases. Polyphenolic compounds are capable of lowering blood pressure and improving cerebral blood flow. Many studies have revealed that a nutritional model based on increased consumption of antioxidants has the potential to ameliorate the cognitive impairment associated with neurodegenerative disorders. Randomized clinical trials have also shown that the improvement of cognitive functions resulting from the consumption of foods rich in flavonoids is independent of age and health conditions. For therapeutic use, sufficient quantities of polyphenols must cross the BBB and reach the brain tissue in active form. An important issue in the direct action of polyphenols on the CNS is not only their penetration through the BBB, but also their brain metabolism and localization. The bioavailability of polyphenols is low. The most usual oral administration also conflicts with bioavailability. The main factors that limit this process and have an effect on therapeutic efficacy are: selective permeability across BBB, gastrointestinal transformations, poor absorption, rapid hepatic and colonic metabolism, and systemic elimination. Thus, phenolic compounds have inadequate bioavailability for human applications to have any beneficial effects. In recent years, new strategies have been attempted in order to exert cognitive benefits and neuroprotective effects. Converting polyphenols into nanostructures is one of the theories proposed to enhance their bioavailability. The following nanoscale delivery systems can be used to encapsulate polyphenols: nanocapsules, nanospheres, micelles, cyclodextrins, solid lipid nanoparticles, and liposomes. It results in great expectations for the wide-scale and effective use of polyphenols in the prevention of neurodegenerative diseases. Thus far, only natural polyphenols have been studied as neuroprotectors. Perhaps some modification of the chemical structure of a given polyphenol may increase its neuroprotective activity and transportation through the BBB. However, numerous questions should be answered before developing neuroprotective medications based on plant polyphenols.
Subject(s)
Neurodegenerative Diseases , Polyphenols , Animals , Humans , Polyphenols/chemistry , Neurodegenerative Diseases/drug therapy , Antioxidants/pharmacology , Endothelial Cells/metabolism , Inflammation/drug therapyABSTRACT
Astrocytes, the most abundant group of glia cells in the brain, provide support for neurons and indicate multiple various functions in the central nervous system (CNS). Growing data additionally describe their role in the regulation of immune system activity. They exert their function not only by direct contact with other cell types, but also through an indirect method, e.g., by secreting various molecules. One such structure is extracellular vesicles, which are important mediators of crosstalk between cells. In our study, we observed that the impact of exosomes derived from astrocytes with various functional phenotype differently affect the immune response of CD4+ T cells, both from healthy individuals and from patients with multiple sclerosis (MS). Astrocytes, by modulating exosome cargo, impacts the release of IFN-γ, IL-17A and CCL2 in our experimental conditions. Considering the proteins concentration in cell culture supernatants and the cellular percentage of Th phenotypes, it could be stated that human astrocytes, by the release of exosomes, are able to modify the activity of human T cells.
Subject(s)
Exosomes , Multiple Sclerosis , Humans , Astrocytes/metabolism , Exosomes/metabolism , Multiple Sclerosis/metabolism , Central Nervous System , ImmunityABSTRACT
Physical rehabilitation and physical activity are known non-pharmacological methods of treating multiple sclerosis. Both lead to an improvement in physical fitness in patients with movement deficits while improving cognitive function and coordination. These changes occur through the induction of brain plasticity. This review presents the basics of the induction of brain plasticity in response to physical rehabilitation. It also analyzes the latest literature evaluating the impact of traditional physical rehabilitation methods, as well as innovative virtual reality-based rehabilitation methods, on the induction of brain plasticity in patients with multiple sclerosis.
ABSTRACT
Plasma from patients with Parkinson's disease (PD) is a valuable source of information indicating altered metabolites associated with the risk or progression of the disease. Neurotoxicity of dopaminergic neurons, which is triggered by aggregation of α-synuclein, is the main pathogenic feature of PD. However, a growing body of scientific reports indicates that metabolic changes may precede and directly contribute to neurodegeneration. Identification and characterization of the abnormal metabolic pattern in patients' plasma are therefore crucial for the search for potential PD biomarkers. The aims of the present study were (1) to identify metabolic alterations in plasma metabolome in subjects with PD as compared with the controls; (2) to find new potential markers, some correlations among them; (3) to identify metabolic pathways relevant to the pathophysiology of PD. Plasma samples from patients with PD (n = 25) and control group (n = 12) were collected and the gas chromatography-time-of-flight-mass spectrometry GC-TOFMS-based metabolomics approach was used to evaluate the metabolic changes based on the identified 14 metabolites with significantly altered levels using univariate and multivariate statistical analysis. The panel, including 6 metabolites (L-3-methoxytyrosine, aconitic acid, L-methionine, 13-docosenamide, hippuric acid, 9,12-octadecadienoic acid), was identified to discriminate PD from controls with the area under the curve (AUC) of 0.975, with an accuracy of 92%. We also used statistical criteria to identify the significantly altered level of metabolites. The metabolic pathways involved were associated with linoleic acid metabolism, mitochondrial electron transport chain, glycerolipid metabolism, and bile acid biosynthesis. These abnormal metabolic changes in the plasma of patients with PD were mainly related to the amino acid metabolism, TCA cycle metabolism, and mitochondrial function.
ABSTRACT
For a long time, astrocytes were considered a passive brain cell population. However, recently, many studies have shown that their role in the central nervous system (CNS) is more active. Previously, it was stated that there are two main functional phenotypes of astrocytes. However, nowadays, it is clear that there is rather a broad spectrum of these phenotypes. The major goal of this study was to evaluate the production of some inflammatory chemokines and neurotrophic factors by primary human astrocytes after pro- or anti-inflammatory stimulation. We observed that only astrocytes induced by inflammatory mediators TNFα/IL-1a/C1q produced CXCL10, CCL1, and CXCL13 chemokines. Unstimulated astrocytes and those cultured with anti-inflammatory cytokines (IL-4, IL-10, or TGF-ß1) did not produce these chemokines. Interestingly, astrocytes cultured in proinflammatory conditions significantly decreased the release of neurotrophic factor PDGF-A, as compared to unstimulated astrocytes. However, in response to anti-inflammatory cytokine TGF-ß1, astrocytes significantly increased PDGF-A production compared to the medium alone. The production of another studied neurotrophic factor BDNF was not influenced by pro- or anti-inflammatory stimulation. The secretory response was accompanied by changes in HLA-DR, CD83, and GFAP expression. Our study confirms that astrocytes differentially respond to pro- and anti-inflammatory stimuli, especially to inflammatory cytokines TNF-α, IL-1a, and C1q, suggesting their role in leukocyte recruitment.
ABSTRACT
Epilepsy is a common brain disorder characterized by a heterogenous etiology. Its main features are recurrent seizures. Despite many clinical studies, about 30% of cases are refractory to treatment. Recent studies suggested the important role of immune-system elements in its pathogenesis. It was suggested that a deregulated inflammatory process may lead to aberrant neural connectivity and the hyperexcitability of the neuronal network. The aim of our study was the analysis of the expression of inflammatory mediators in a mouse model of epilepsy and their impact on the neurodegeneration process located in the brain. We used the KA-induced model of epilepsy in SJL/J mice and performed the analysis of gene expression and protein levels. We observed the upregulation of IL1ß and CXCL12 in the early phase of KA-induced epilepsy and elevated levels of CCL5 at a later time point, compared with control animals. The most important result obtained in our study is the elevation of CXCL2 expression at both studied time points and its correlation with the neurodegeneration observed in mouse brain. Increasing experimental and clinical data suggest the influence of peripheral inflammation on epileptogenesis. Thus, studies focused on the molecular markers of neuroinflammation are of great value and may help deepen our knowledge about epilepsy, leading to the discovery of new drugs.
ABSTRACT
Epigenetic modifications play a key role in gene regulation and expression and are involved in numerous cellular processes. Due to the limited research on nucleosides in Parkinson's disease (PD), it is very important to consider epigenetic factors and their role in the development of PD. The aim of this study was to investigate and compare the levels of modified nucleosides, such as O-methylguanosine, N6-methyl-2'-deoxyadenosine, 1-methyladenosine, 1-methylguanine, 7-methylguanine, 3-methyladenine and 7-methylguanosine in the urine of Parkinson's disease (PD) patients and the control group, and to verify that the results obtained differ in a subgroup of patients with parkinsonian syndromes. The study group comprised 18 patients with diagnosed idiopathic Parkinson's disease and four parkinsonian syndromes. The control group consisted of 30 age- and sex-matched neurological patients without confirmation by neuroimaging brain damage and extrapyramidal symptoms. The levels of nucleosides were determined by validated liquid chromatography coupled with the mass spectrometry (LC-MS/MS) method using the multiple reaction monitoring (MRM) mode. Lower levels of O-methylguanosine, 3-methyladenine, 1-methylguanine, N6-methyl-2'-deoxyadenosine and a higher level of 7-methylguanine in the urine of 22 PD patients were observed. Moreover, elevated levels of 1-methyladenosine, 7-methylguanine, and O-methylguanosine were observed in the parkinsonian syndrome subgroup. These preliminary results may indicate that modified nucleosides describe metabolic disturbances in the metabolism of purine, which was the most severely affected pathway that mediated the detrimental effects of neuroinflammation on PD.
Subject(s)
Chromatography, Liquid , Parkinson Disease/urine , Parkinsonian Disorders/urine , Tandem Mass Spectrometry , Urinalysis/methods , Aged , Case-Control Studies , Female , Humans , Male , Middle AgedABSTRACT
Epidemiological data indicate that a diet rich in plant polyphenols has a positive effect on brain functions, improving memory and cognition in humans. Direct activity of ingested phenolics on brain neurons may be one of plausible mechanisms explaining these data. This also suggests that some phenolics can cross the blood-brain barrier and be present in the brain or cerebrospinal fluid. We measured 12 phenolics (a combination of the solid-phase extraction technique with high-performance liquid chromatography) in cerebrospinal fluid and matched plasma samples from 28 patients undergoing diagnostic lumbar puncture due to neurological disorders. Homovanillic acid, 3-hydroxyphenyl acetic acid and caffeic acid were detectable in cerebrospinal fluid reaching concentrations (median; interquartile range) 0.18; 0.14 µmol/L, 4.35; 7.36 µmol/L and 0.02; 0.01 µmol/L, respectively. Plasma concentrations of caffeic acid (0.03; 0.01 µmol/L) did not correlate with those in cerebrospinal fluid (ρ = -0.109, p = 0.58). Because food (fruits and vegetables) is the only source of caffeic acid in human body fluids, our results indicate that the same dietary phenolics can cross blood-brain barrier in humans, and that transportation of caffeic acid through this barrier is not the result of simple or facilitated diffusion.
Subject(s)
Blood-Brain Barrier/drug effects , Caffeic Acids/blood , Caffeic Acids/cerebrospinal fluid , Caffeic Acids/pharmacology , Polyphenols/pharmacology , Adult , Blood-Brain Barrier/metabolism , Chromatography, High Pressure Liquid , Diet, Western , Female , Fruit/chemistry , Homovanillic Acid/blood , Homovanillic Acid/cerebrospinal fluid , Humans , Male , Middle Aged , Nervous System Diseases/blood , Nervous System Diseases/cerebrospinal fluid , Polyphenols/blood , Polyphenols/cerebrospinal fluid , Solid Phase Extraction , Vegetables/chemistryABSTRACT
PURPOSE: The management of patients with disorders of consciousness (DOC) constitutes a challenge for clinicians. CASE REPORT: We present the case of a 66-year-old man who developed coma with subsequent DOC after a severe traumatic brain injury. Behavioural assessment constitutes the gold standard in the evaluation of patients with DOC. In the case presented herein the neuropsychological findings were ambiguous, and the patient underwent functional magnetic resonance imaging (fMRI) to determine whether he was in a vegetative state or minimally conscious state. Three paradigms: passive, active, and resting state fMRI were used to study the brain activity in our patient. CONCLUSIONS: fMRI provided reliable evidence of preserved minimal consciousness. The neuroimaging techniques used in our patient were vital for his further treatment.
ABSTRACT
Regulatory T cells (Tregs) play a significant role in limiting damage of tissue affected by autoimmune process, which has been demonstrated in various experimental models for multiple sclerosis (MS) (mostly experimental autoimmune encephalomyelitis - EAE), rheumatoid arthritis, and type 1 diabetes. In this study, we demonstrated that Tregs increasingly migrate to central nervous system (CNS) during subsequent phases of EAE (preclinical, initial attack, and remission). In contrast, in peripheral tissues (blood, lymph nodes, and spleen), a significant accumulation of Tregs is mostly present during EAE remission. Moreover, an increased expression of CCR6 on Tregs in the CNS, blood, lymph nodes, and spleen in all phases of EAE was observed. The highest expression of CCR6 on Tregs from the CNS, lymph nodes, and spleen was noted during the initial attack of EAE, whereas in the blood, the peak expression of CCR6 was detected during the preclinical phase. The presence of Tregs in the CNS during EAE was confirmed by immunohistochemistry. To analyze additional functional significance of CCR6 expression on Tregs for EAE pathology, we modulated the clinical course of this MS model using Tregs with blocked CCR6. EAE mice, which received CCR6-deficient Tregs showed significant amelioration of disease severity. This observation suggests that CCR6 on Tregs may be a potential target for future therapeutic interventions in MS.
ABSTRACT
OBJECTIVES: Fingolimod is indicated for the treatment of relapsing-remitting multiple sclerosis (RRMS) patients with highly aggressive disease characterized by frequent relapses and active magnetic resonance imaging. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. Fingolimod in licensed in Europe since 2011 but with a growing number of disease-modifying drugs (DMD) becoming available for RRMS, it is important to gather real-world evidence data regarding long-term effectiveness in treated patients with MS. The aim of this study was to assess fingolimod effectiveness in a real life Polish group of RRMS patients receiving fingolimod as second line treatment. PATIENTS AND METHODS: The observational study with retrospective data collection was performed at 13 sites that were asked to document eligible patients in consecutive chronological order to avoid selection bias. Demographic and clinical data from 253 adult patients with RRMS treated with fingolimod were analyzed. RESULTS: Mean treatment time with fingolimod was 42 months. Relapses reduction during 3 years treatment period was observed (2.0 v 0.2) and majority of patients were free of relapses. Mean EDSS score was stable during the time of observation. The proportion of patients who were free from any clinical disease activity, i.e. without relapses and disability progression, was over 70%. During the first and second year of observation significant reduction of new MRI lesions was observed. CONCLUSION: In the Polish group of patients with RRMS treated with fingolimod, the majority of them showed freedom from relapses, disability progression and reduction of new MRI lesions. Switching from injectable immunomodulatory drugs to fingolimod is associated with fewer relapses and lower disability progression.
Subject(s)
Fingolimod Hydrochloride/therapeutic use , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Disabled Persons/rehabilitation , Disease Progression , Female , Humans , Male , Middle Aged , Poland , RecurrenceABSTRACT
PURPOSE: The study aimed to identify biomarkers predictive of cryptogenic stroke in patients aged <65. MATERIALS AND METHODS: We investigated 520 patients with ischemic stroke. Out of them we assigned 65 patients to the cryptogenic stroke group (age 54 (47-58), 42% male) and 36 without stroke to the control group (age 53 (47-58), 61% male). In all patients we assessed carotid intima-media thickness (cIMT) and the levels of biomarkers which might be involved in the underlying biological mechanism of ischemic stroke. RESULTS: There were no differences between stroke and control groups in the levels of syndecan 4, resistin, leptin, low-density lipoprotein cholesterol, triglycerides, prothrombin time, or activated partial thromboplastin time. There was no statistically significant difference in cIMT between groups. The level of high-density lipoprotein cholesterol was statistically significantly lower in the cryptogenic stroke group than in the controls (1.1â¯mmol/L (0.95-1.46) vs 1.37 (1.19-1.6) pâ¯=â¯0.02). Patients in the stroke group had higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) (391â¯pg/ml (107-1249) vs 109 (46-236); pâ¯=â¯0.003), interleukin 6 (2.6â¯pg/ml (0.8-8.1) vs 0.7 (0.4-1.2) pâ¯=â¯0.002) and asymmetric dimethylarginine (ADMA) (0.44⯵mol/L (0.39-0.55) vs 0.36 (0.32-0.4); pâ¯=â¯0.0002) than the control group. In the multivariate analysis Il-6 was the only biomarker statistically significant associated with the occurrence of cryptogenic stroke (odds ratio 1.918, 95% confidence interval 1.029-3.575; pâ¯=â¯0.04). CONCLUSIONS: Endothelial dysfunction assessed by increased level of ADMA affects the inflammatory state in patients with cryptogenic stroke. Increase in the inflammatory cytokine IL-6 by 1â¯pg/ml almost doubles the risk of stroke.
Subject(s)
Cytokines/metabolism , Inflammation/metabolism , Stroke/metabolism , Biomarkers/metabolism , Female , Humans , Inflammation/immunology , Interleukin-6/metabolism , Male , Middle Aged , Multivariate Analysis , Stroke/immunologyABSTRACT
BACKGROUND: Epidemiologic data on primary progressive multiple sclerosis (PPMS) in Poland are limited. The aim of this study was to assess selected clinical and socio-demographic factors of Polish patients with PPMS and compare this form and relapsing-remitting (RRMS) and secondary progressive (SPMS) forms. METHODS: Patients who attended follow-up visits under the Registry of Patients with Multiple Sclerosis (RejSM) were enrolled in the study in the autumn of 2017. The prevalence of individual types of the disease was compared and the clinical, demographic, and social differences between RRMS, PPMS and SPMS were analyzed. RESULTS: Of the 8,045 registered patients, current data as on December 31, 2017 was obtained from 4,398 patients. The RRMS form was seen in 2,925 patients (66.5%); secondary progressive form, in 1.051 patients (23.9%); and PPMS, in 422 patients (9.6%). The first symptoms of PPMS appeared almost 10 years later than in patients with RRMS (39.2⯱â¯11.4â¯vs. 29.8⯱â¯9.8). The period from the first symptoms to diagnosis was more than twice as long in patients with PPMS (5.8⯱â¯3.4) than RRMS (2.4⯱â¯1.6). SPMS was diagnosed on average after 14 years of RRMS (46.2⯱â¯13.5). The RRMS form was more frequently found in women (2.4:1), while the PPMS form was almost equal in both sexes (1.2:1). The average degree of disability based on the Expanded Disability Status Scale was 3.2⯱â¯2.1 for RRMS, 4.6⯱â¯2.4 for PPMS and 5.2⯱â¯3.6 for SPMS. The dominant symptom in PPMS was paresis of the lower limbs (86%). Patients with PPMS had higher education and higher instance of marriage than those with RRMS or SPMS. CONCLUSIONS: PPMS occurs in about 10% of Polish patients with multiple sclerosis, and the first symptoms appear at around 40 years of age with the same frequency in both sexes. PPMS diagnosis takes more than twice the time for RRMS.