INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease that secondarily leads to axonal loss and associated brain atrophy. Disease-modifying drugs (DMDs) have previously been studied for their ability to affect specific immunity. This study investigates the effect of interferon beta-1a (INF) and glatiramer acetate (GA) administration on changes in innate immunity cell populations. METHODS: Sixty Caucasian female patients with relapsing-remitting MS undergo blood sample testing for 15 blood parameters at baseline, 1 month, 3 months, and 6 months after treatment by GA or IFN (started as their first-line DMD). RESULTS: A statistically significant difference in the change after 6 months was found in the parameter monocytes (relative count) in the group of patients treated with IFN. The median increase was 27.8%. Changes in many of the other 15 parameters studied were 10-20%. CONCLUSION: Innate immunity has long been neglected in MS immunopathology. The findings suggest that IFN treatment may modulate the immune response in MS by affecting monocyte function and may provide insight into the mechanisms of action of IFN in MS.

• Klíčová slova
• Glatiramer acetate, Innate immunity, Interferon beta-1a, Monocytes, Multiple sclerosis,
• MeSH
• glatiramer acetát terapeutické užití   MeSH
• interferon beta 1a terapeutické užití   MeSH
• interferon beta terapeutické užití   MeSH
• lidé MeSH
• peptidy terapeutické užití   MeSH
• přirozená imunita MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   patologie   MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glatiramer acetát MeSH
• interferon beta 1a MeSH
• interferon beta MeSH
• peptidy MeSH

BACKGROUND: The QuantiFERON®-Monitor (QFM) is an assay that measures interferon-γ production and was developed to provide an objective marker of complex immune response. In this study, we evaluated the use of the QFM test in patients with two forms of multiple sclerosis (MS), relapsing-remitting form treated with fingolimod (fMS) and secondarily progressive form not treated pharmacologically (pMS), and in healthy controls (HC). We hypothesized that IFN-γ levels would be lower in those subjects who are relatively more immunosuppressed and higher in those with normal or activated immune function. METHODS: This single-center observational study was conducted from November 2020 to October 2021 and compared results in three groups of patients: 86 healthy controls, 96 patients with pMS, and 78 fMS. Combination of lyophilized stimulants was added to 1 ml heparinized whole blood within 8 hr of collection. Plasmatic IFN-γ was measured using the ELISA kit for the QFM and data were obtained in IU/ml. RESULTS: The results showed that controls had nearly 2-fold higher levels of IFN-γ (QFM score) in median (q25, q75) 228.00 (112.20, 358.67) than the MS patient groups: pMS 144.80 (31.23, 302.00); fMS 130.50 (39.95, 217.07) which is statistically significant difference P-value: HC vs. pMS = 0.0071; HC vs. fMS = 0.0468. This result was also confirmed by a validation analysis to exclude impact of variable factors, such as disease duration and Expanded Disability Status Scale scores. CONCLUSIONS: Results showed that controls had higher levels of IFN-γ production than the MS patient groups and suggest that MS patients included in this study have a lower ability of immune system activation than HC. Results confirm that fingolimod is able to suppress production of IFN-γ. The fact that the QFM score of MS patients is significantly lower than that of HC may indicate a dysfunctional state of the immune system in baseline conditions.

• MeSH
• ELISA MeSH
• fingolimod hydrochlorid terapeutické užití   MeSH
• imunitní systém MeSH
• interferon gama MeSH
• lidé MeSH
• relabující-remitující roztroušená skleróza * MeSH
• roztroušená skleróza * diagnóza   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• fingolimod hydrochlorid MeSH
• interferon gama MeSH

PURPOSE: To identify the clinical and paraclinical markers of employment status in multiple sclerosis (MS). METHODS: This was a cross-sectional sub-study investigating 1226 MS patients. To minimalized confounding effect, two groups of patients, matched by sex, age, and education, were selected: 307 patients with full time employment and 153 unemployed patients receiving disability pension. We explored associations between employment status and Expanded Disability Status Scale (EDSS), 25 Foot Walk Test (25FWT), Nine Hole Peg Test (9HPT), Brief International Cognitive Assessment for MS (BICAMS), Paced Auditory Serial Addition Test (PASAT), Beck Depression Inventory (BDI), SLOAN charts (SLOAN), and brain volumetric MRI measures. RESULTS: Both groups differed significantly on all variables of interest (p < 0.001). In the univariate analyses, EDSS, SDMT (Symbol Digit Modalities Test) adjusted for BDI, 25FWT, and 9HPT best explained variability in vocational status. In multivariate analyses, the combination of EDSS, 25FWT, SDMT, BDI, and corpus callosum fraction (CCF) explained the greatest variability. As a next step, after patients were matched by EDSS, differences in SDMT, 25FWT (both p < 0.001), 9HPT, CCF, and T2 lesion volume were still present (all p < 0.005) between both groups. The best multivariate model consisted of SDMT, BDI, and T2 lesion volume. CONCLUSIONS: EDSS, walking ability, cognitive performance, and MRI volumetric parameters are independently associated with employment status.

• Klíčová slova
• Cognitive impairment, Employment status, Gait impairment, MRI, Multiple sclerosis, Work disability,
• MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• neuropsychologické testy MeSH
• posuzování pracovní neschopnosti MeSH
• průřezové studie MeSH
• roztroušená skleróza * komplikace   MeSH
• zaměstnanost MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). T cells and B lymphocytes are involved in the development of this disease. METHODS: The following biomarkers were determined in peripheral blood in 28 patients treated with glatiramer acetate (GA) and 21 patients treated with interferon beta 1-a (IFN): IL-10, BAFF, Mx1, IgG, IgG1, IgG2, IgG3 and IgG4 (at baseline and after 6 months of treatment). All participants had confirmed MS diagnosis. OBJECTIVES: The primary objective is to assess a percentual change of biomarkers after 6 months since the first-line treatment initiation with GA or IFN. The secondary objective is to explore correlations between the baseline biomarkers' values (levels). RESULTS: A positive trend was observed in the increase in IL-10 concentration by 30.33 % (IFN) and by 15.65 % (GA). In the IFN group, we observed a statistically significant increase in the BAFF protein concentration by 29.9% (P < 0.001). We found that Mx1 protein levels did not change with the administration of GA, which can be explained by the different mechanisms of action of GA. The serum levels of IgG immunoglobulins and both IgG1 and IgG4 subclasses in both groups of patients were increased. Thus, our data were in accordance with the generally accepted assumption that both IFN and GA are capable of modulating the B cell system. CONCLUSIONS: Our results suggest that treatment with IFN and GA has a more pronounced influence on the B cell system of MS.

• Klíčová slova
• BAFF, Glatiramer acetate, IL-10, IgG, Interferon beta-1a, Multiple sclerosis, Mx1,
• MeSH
• biologické markery MeSH
• glatiramer acetát terapeutické užití   MeSH
• interferon beta 1a MeSH
• lidé MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• T-lymfocyty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• glatiramer acetát MeSH
• interferon beta 1a MeSH

Anterior circulation stroke (ACS) is associated with typical symptoms, while posterior circulation stroke (PCS) may cause a wide spectrum of less specific symptoms. We aim to assess the correlation between the initial presentation of acute ischemic stroke (AIS) symptoms and the treatment timeline. Using a retrospective, observational, single-center study, the set consists of 809 AIS patients treated with intravenous thrombolysis (IVT) and/or endovascular treatment (EVT). We investigate the impact of baseline clinical AIS symptoms and the affected vascular territory on recanalization times in patients treated with IVT only and EVT (±IVT). Regarding the IVT-only group, increasing the National Institutes of Health Stroke Scale (NIHSS) score on admission and speech difficulties are associated with shorter (by 1.59 ± 0.76 min per every one-point increase; p = 0.036, and by 24.56 ± 8.42 min; p = 0.004, respectively) and nausea/vomiting with longer (by 43.72 ± 13.13 min; p = 0.001) onset-to-needle times, and vertigo with longer (by 8.58 ± 3.84 min; p = 0.026) door-to-needle times (DNT). Regarding the EVT (±IVT) group, coma is associated with longer (by 22.68 ± 6.05 min; p = 0.0002) DNT, anterior circulation stroke with shorter (by 47.32 ± 16.89 min; p = 0.005) onset-to-groin time, and drooping of the mouth corner with shorter (by 20.79 ± 6.02 min; p = 0.0006) door-to-groin time. Our results demonstrate that treatment is initiated later in strokes with less specific symptoms than in strokes with typical symptoms.

• Klíčová slova
• acute ischemic stroke, clinical outcome, clinical symptoms, endovascular therapy, intravenous thrombolysis, recanalization times,
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND PURPOSE: A high variability of brain MRI volume change measurement renders challenging its interpretation in multiple sclerosis (MS). Occurrence and clinical relevance of observed apparent brain volume increase (BVI) in MS patients have not been investigated yet. The objective was to quantify the prevalence and factors associated with BVI. METHODS: We examined 366 MS patients (2,317 scans) and 44 controls (132 scans). Volumetric analysis of brain volume changes was performed by SIENA and ScanView. BVI was defined as brain volume change >0%. We compared characteristics of patients with and without BVI. RESULTS: BVI was found in 26.3% (from 1,951) longitudinal scans (SIENA). If BVI occurred, a probability that BVI will be repeated consecutively more than or equal to two times was 15.9%. The repeated BVI was associated with clinical disease activity in 50% of cases. BVI was associated with shorter time and lower T2 lesion volume increase between two MRI scans, and higher normalized brain volume (all P < .0001). A proportion of scans with BVI was higher when analyzed by ScanView (35.3%) and in controls (36.4% by SIENA). CONCLUSIONS: BVI occurs in a great proportion of MR scans over short-term follow-up and is not associated with disease stabilization. Although BVI can be caused by several factors, the results indicate that measurement error may contribute to BVI in the majority of cases. Clinicians should be aware of the frequent occurrence of apparent BVI, interpret brain volume changes in MS patients with great caution, and use methods with precise quantification of brain volume changes.

• Klíčová slova
• Brain atrophy, MRI, interpretation, multiple sclerosis, volume increase,
• MeSH
• dospělí MeSH
• interpretace obrazu počítačem * MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• roztroušená skleróza diagnostické zobrazování   patologie   MeSH
• velikost orgánu MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The role of the immune system as an integral component of the inflammatory response in the pathophysiology of migraine remains unclear. The aim of this study was to evaluate the differences in immune system parameters (acquired immunity parameters) in patients with episodic migraine (EM) and in healthy controls. In EM patients, we aimed to determine whether the changes found in peripheral blood parameters were related to migraine severity according to the standardised MIDAS and HIT-6 tests. Forty-nine patients with EM and 50 healthy controls were included in this study. The authors compared different lymphocyte parameters obtained by multicolor flow cytometry in the EM and control groups by performing statistical tests. The relationship between the changes in peripheral blood parameters and migraine severity in EM patients was investigated using correlation and regression analysis. EM patients showed higher values than healthy controls, especially in nine parameters: relative count of lymphocytes, relative and absolute counts of CD3 T cells, relative and absolute counts of CD8 suppressor cytotoxic T cells, relative and absolute counts of CD4 + TEMRA (terminally differentiated helper T lymphocytes), absolute count of CD8 naïve T cells, and absolute count of CD19 switched memory B cells. Among the lymphocyte parameters, CD4 + TEM (effector memory helper T lymphocytes) and CD8 + TEMRA (terminally differentiated cytotoxic T lymphocytes) were statistically significantly associated with HIT-6. Patients with a CD4 + TEM value below 15 had a high probability (90%) that the HIT-6 value would be higher than 60. The results of this study show that EM patients have changes in immune system parameters measured in the peripheral blood. Changes in the abundance of CD4 + TEM could be used as a biomarker for disease severity.

• MeSH
• biologické markery MeSH
• dospělí MeSH
• imunitní systém imunologie   metabolismus   MeSH
• imunofenotypizace MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• migréna diagnóza   etiologie   metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• náchylnost k nemoci * MeSH
• průtoková cytometrie MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• T-lymfocyty - podskupiny imunologie   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH

PURPOSE: To evaluate the effect of intravitreal aflibercept injections in treatment-naive type 3 neovascularization using a fixed treatment regime during the first year of therapy. METHODS: Fourteen eyes of 14 patients diagnosed with type 3 neovascularization were studied. All patients were treated with intravitreal aflibercept injections using a fixed treatment regime of 3 consecutive monthly dosages followed by 2-month interval injections. Results were assessed after a 12-month follow-up period. Changes of best corrected visual acuity (BCVA), central retinal thickness (CRT), central macular volume (CMV), and retinal pigment epithelium (RPE) atrophy at fundus autofluorescence and infrared reflectance images were recorded and analyzed. RESULTS: BCVA improved from 60.3 ± 11.7 ETDRS letters at the baseline to 70.9 ± 10.3 ETDRS letters at 12-months follow-up (p = 0.036). Also, CRT and CMV statistically improved after the treatment (from 425 ± 117 to 308 ± 117 µm [p = 0.031] and from 9.52 ± 1.90 to 8.29 ± 0.95 mm3 [p = 0.073], respectively). In 4 patients, development and progression of RPE atrophy were observed, and it was associated with the presence of serous pigment epithelium detachment at the baseline. Furthermore, the development of a fibrotic lesion eccentric to the fovea was observed in 5 patients, without significant impairment of BCVA (p = 0.290). CONCLUSION: Intravitreal aflibercept administered in a fixed treatment regime during the first year of therapy may be effective for the improvement and stabilization of BCVA in eyes with type 3 neovascularization. However, RPE atrophy and subretinal/intraretinal fibrosis can develop during the treatment.

• Klíčová slova
• Aflibercept, Age-related macular degeneration, Anti-vascular endothelial growth factor, Optical coherence tomography, Retinal angiomatous proliferation, Type 3 neovascularization,
• MeSH
• injekce intravitreální MeSH
• lidé středního věku MeSH
• lidé MeSH
• macula lutea patologie   MeSH
• následné studie MeSH
• optická koherentní tomografie MeSH
• receptory vaskulárního endoteliálního růstového faktoru aplikace a dávkování   antagonisté a inhibitory   MeSH
• rekombinantní fúzní proteiny aplikace a dávkování   MeSH
• retinální pigmentový epitel patologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vlhká makulární degenerace diagnóza   farmakoterapie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zraková ostrost * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aflibercept MeSH Prohlížeč
• receptory vaskulárního endoteliálního růstového faktoru MeSH
• rekombinantní fúzní proteiny MeSH

BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. The cause of MS is still unknown, and the role of innate immunity is still poorly understood. OBJECTIVE: The goal of this study was to understand whether, compared to healthy controls, the elements of innate immunity are altered in the blood of MS patients in the remitting phase. METHODS: A total of 77 naïve MS patients and 50 healthy controls were included in this cohort study. Peripheral blood samples were collected and analyzed. All the calculations were performed with the statistical system R (r-project.org). RESULTS: The results showed that MS patients had significantly lower relative representations of granulocytes than healthy controls, while the relative representations of monocytes remained unchanged. CD64- and PD-L1-positive granulocytes exhibited a nonsignificant decreasing trend, while granulocytes with other membrane markers remained noticeably unchanged. CONCLUSION: The results of this study suggest that studies of the causes of MS and its treatment should also be focused on the elements of the innate immune response.

• Klíčová slova
• CD64, PD-L1, granulocytes, monocytes, multiple sclerosis, relapsing-remitting,
• Publikační typ
• časopisecké články MeSH

Background: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system. Well-established drugs used for MS patients after the first demyelinating event in the Czech Republic include glatiramer acetate (GA), interferon beta-1a (IFNβ-1a), IFN beta-1b (IFNβ-1b), peginterferon beta-1a (peg-IFNβ-1a), and teriflunomide. Objective: The objective of this observational study was to compare the effectiveness of the abovementioned drugs in patients with MS who initiated their therapy after the first demyelinating event. Patients were followed for up to 2 years in real clinical practice in the Czech Republic. Methods: A total of 1,654 MS patients treated after the first demyelinating event and followed up for 2 years were enrolled. Evaluation parameters (endpoints) included the annualized relapse rate (ARR), time to next relapse, change in the Expanded Disability Status Scale (EDSS) score, and time of confirmed disease progression (CDP). When patients ended the therapy before the observational period, the reason for ending the therapy among different treatments was compared. Results: No significant difference was found among the groups of patients treated with IFNβ-1a/1b, GA, or teriflunomide for the following parameters: time to the first relapse, change in the EDSS score, and the proportion of patients with CDP. Compared to IFNβ-1a (44 mcg), a significant increase in the percentage of relapse-free patients was found for GA, but this treatment effect was not confirmed by the validation analysis. Compared to the other drugs, there was a significant difference in the reasons for terminating GA therapy. Conclusion: Small differences were found among GA, IFNβ and teriflunomide therapies, with no significant impact on the final outcome after 2 years. Therefore, in clinical practice, we recommend choosing the drug based on individual potential risk from long-term therapy and on patient preferences and clinical characteristics.

• Klíčová slova
• DMD, clinical practice, long-term therapy, multiple sclerosis, treatment,
• Publikační typ
• časopisecké články MeSH