Research

Title: A Novel Semiautomated Pipeline to Measure Brain Atrophy and Lesion Burden in Multiple Sclerosis: A Long-Term Comparative Study

Author: UHER, Tomas, KRASENSKY, Jan, VANECKOVA, Manuela, SOBISEK, Lukas, SEIDL, Zdenek, HAVRDOVA, Eva, BERGSLAND, Niels, DWYER, Michael G., HORAKOVA, Dana, ZIVADINOV, Robert.

Year: 2017

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
UHER, Tomas, KRASENSKY, Jan, VANECKOVA, Manuela, SOBISEK, Lukas, SEIDL, Zdenek, HAVRDOVA, Eva, BERGSLAND, Niels, DWYER, Michael G., HORAKOVA, Dana, ZIVADINOV, Robert. A Novel Semiautomated Pipeline to Measure Brain Atrophy and Lesion Burden in Multiple Sclerosis: A Long-Term Comparative Study. Journal of Neuroimaging, 2017, roč. 27, č. 6, s. 620-629, http://onlinelibrary.wiley.com/doi/10.1111/jon.12445/full

Abstract:
BACKGROUND AND PURPOSE

Lesion burden and brain volume changes are frequent end points in research but nowadays are becoming important in the clinical practice of multiple sclerosis (MS). The objective of this study was to investigate the correlation between magnetic resonance imaging (MRI) measures obtained by in-house developed ScanView software and commonly used volumetric techniques for assessment of T2 lesion and whole brain volumes and their changes.

METHODS

Together 3,340 MRI scans from 209 patients after first demyelinating event suggestive of MS, 181 relapsing-remitting MS patients and 43 controls were analyzed. The average number of MRI scans and follow-up duration was 8.2 and 6.5 years, respectively. All MRI scans were performed in a single center but independently analyzed in two neuroimaging centers. Volumetric analysis by ScanView software was applied in Prague. Commonly used techniques, such as SIENA, SIENAX, and Jim software, were applied in Buffalo. Correlations between MRI measures were evaluated using correlation coefficients. Intraindividual variability of longitudinal MRI data was estimated by mean squared error.

RESULTS

The associations of the cross-sectional and longitudinal MRI measures between commonly used techniques and ScanView were significant (r/rho = .83-.95). The associations of cross-sectional MRI measures were stronger (r/rho = .90-.95) compared with longitudinal ones (r = .83). Standardized intraindividual variability of whole brain % volume change was greater in ScanView compared with SIENA (mean squared error .32 vs. .21; P < .001).

CONCLUSIONS

We found relatively strong correlations of cross-sectional and longitudinal data obtained by both techniques. However, SIENA showed lower intraindividual variability than the ScanView method in measuring whole brain volume loss over time.

Keywords (CZ): MRI, volumetrie, T2 objem lézí, atrofie mozku, roztroušená skleróza

Keywords (EN): MRI, volumetry, T2 lesion volume, brain atrophy, multiple sclerosis

Title: Acute management should be optimized in patients with less specific stroke symptoms: findings from a retrospective observational study

Author: HALÚSKOVÁ, Simona, HERZIG, Roman, KRAJÍČKOVÁ, Dagmar, HAMZA, Abduljabar, KRAJINA, Antonín, CHOVANEC, Vendelín, LOJÍK, Miroslav, RAUPACH, Jan, RENC, Ondřej, ŠIMUNEK, Libor, VÍTKOVÁ, Eva, SOBÍŠEK, Lukáš, VALIŠ, Martin

Year: 2021

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
HALÚSKOVÁ, Simona, HERZIG, Roman, KRAJÍČKOVÁ, Dagmar, HAMZA, Abduljabar, KRAJINA, Antonín, CHOVANEC, Vendelín, LOJÍK, Miroslav, RAUPACH, Jan, RENC, Ondřej, ŠIMUNEK, Libor, VÍTKOVÁ, Eva, SOBÍŠEK, Lukáš, VALIŠ, Martin. Acute management should be optimized in patients with less specific stroke symptoms: findings from a retrospective observational study. J. Clin. Med., 2021, roč. 10, číslo: 5, s. 1143. https://doi.org/10.3390/jcm10051143 .

Abstract:
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.

Keywords (CZ): akutní ischemická mrtvice, klinické symtomy, trombóza, endovaskulární terapie, čas rekanalizace, klinické výstupy

Keywords (EN): acute ischemic stroke; clinical symptoms; intravenous thrombolysis; endovascular therapy; recanalization times; clinical outcome

Title: Additive Effect of Spinal Cord Volume, Diffuse and Focal Cord Pathology on Disability in Multiple Sclerosis.

Author: ANDĚLOVÁ, Michaela, UHER, Tomáš, KRÁSENSKÝ, Jan, SOBÍŠEK, Lukáš, KUSOVÁ, Eliška, SRPOVÁ, Barbora, FRIEDOVÁ, Lucie, LÍZROVÁ PREININGEROVÁ, Jana, KUBALA HAVRDOVÁ, Eva, HORÁKOVÁ, Dana, VANĚČKOVÁ, Manuela.

Year: 2019

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
ANDĚLOVÁ, Michaela, UHER, Tomáš, KRÁSENSKÝ, Jan, SOBÍŠEK, Lukáš, KUSOVÁ, Eliška, SRPOVÁ, Barbora, FRIEDOVÁ, Lucie, LÍZROVÁ PREININGEROVÁ, Jana, KUBALA HAVRDOVÁ, Eva, HORÁKOVÁ, Dana, VANĚČKOVÁ, Manuela. Additive Effect of Spinal Cord Volume, Diffuse and Focal Cord Pathology on Disability in Multiple Sclerosis. Frontiers in Neurology, 2019, roč. 10, č. 820, doi: 10.3389/fneur.2019.00820.

Abstract:
Introduction
Spinal cord (SC) pathology is strongly associated with disability in multiple sclerosis (MS). We aimed to evaluate the association between focal and diffuse SC abnormalities and spinal cord volume and to assess their contribution to physical disability in MS patients.
Methods
This large sample-size cross-sectional study investigated 1,249 patients with heterogeneous MS phenotypes. Upper cervical-cord cross-sectional area (MUCCA) was calculated on an axial 3D-T2w-FatSat sequence acquired at 3T using a novel semiautomatic edge-finding tool. SC images were scored for the presence of sharply demarcated hyperintense areas (focal lesions) and homogenously increased signal intensity (diffuse changes). Patients were dichotomized according EDSS in groups with mild (EDSS up to 3.0) and moderate (EDSS ≥ 3.5) physical disability. Analysis of covariance was used to identify factors associated with dichotomized MUCCA. In binary logistic regression, the SC imaging parameters were entered in blocks to assess their individual contribution to risk of moderate disability. In order to assess the risk of combined SC damage in terms of atrophy and lesional pathology on disability, secondary analysis was carried out where patients were divided into four categories (SC phenotypes) according to median dichotomized MUCCA and presence/absence of focal and/or diffuse changes.
Results
MUCCA was strongly associated with total intracranial volume, followed by presence of diffuse SC pathology, and disease duration. Compared to the reference group (normally appearing SC, MUCCA>median), patients with the most severe SC changes (SC affected with focal and/or diffuse lesions, MUCCA Conclusion
Low cervical SC volume is a strong independent predictor of physical disability in MS patients. The contribution of focal SC lesions and diffuse changes to the worse disability outcomes is limited and present especially in patients with low SC volume.

Keywords (CZ): magnetická rezonance, mícha, fokální léze, dufúzní abnormality, míšní rezervy

Keywords (EN): magnetic resonance imaging, spinal cord, focal lesions, diffuse abnormalities, spinal cord reserve

Title: Assessment of Functional Capacity of Immune System in Patients with Multiple Sclerosis using QuantiFERON Monitor

Author: PAVELEK, Zbyšek, SOUČEK, Ondřej, KREJSEK, Jan, atd.

Year: 2023

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
PAVELEK, Zbyšek, SOUČEK, Ondřej, KREJSEK, Jan, SEJKOROVA, Ilona, VYSATA, Oldrich, KLIMOVA, Blanka, ANGELUCCI, Francesco, STOURAC, Pavel, VALIS, Martin, PETERKA, Marek, SOBISEK, Lukas, NOVOTNY, Michal. Assessment of Functional Capacity of Immune System in Patients with Multiple Sclerosis using QuantiFERON Monitor. Journal of Immunology Research, 2023, roč. 2023, Article ID 4653627, 8 pages, https://doi.org/10.1155/2023/4653627.

Abstract:
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.

Objectives:
In this study, we were the first researchers to evaluate the use of the QFM test in patients with two forms of MS, fMS [14] and pMS not treated pharmacologically, 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.

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.

Keywords (CZ): roztroušená skleróza, Quantiferon

Keywords (EN): multiple sclerosis, Quantiferon

Title: CD4+/CD45RO+: A Potential Biomarker of the Clinical Response to Glatiramer Acetate

Author: VALIŠ, Martin, SOBÍŠEK, Lukáš, PAVELEK, Zbyšek, atd.

Year: 2019

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
VALIŠ, Martin, SOBÍŠEK, Lukáš, VYŠATA, Oldřich, KLÍMOVÁ, Blanka, ANDRÝS, Ctirad, VOKURKOVÁ, Doris, MASOPUST, Jiří, PAVELEK, Zbyšek. CD4+/CD45RO+: A Potential Biomarker of the Clinical Response to Glatiramer Acetate. Cells, 2019, roč. 8, číslo 5, s. 456-458.

Abstract:
Glatiramer acetate (GA) is an effective treatment for the earliest stages of multiple sclerosis (MS)—clinically isolated syndrome (CIS) or clinically definite MS (CDMS). Objective: This study aims to determine the differences in the lymphocyte population (at baseline and the course of five years) between confirmed sustained progression (CSP) and non-CSP groups and to identify potential biomarkers among these parameters that can predict a positive response to the treatment. Methods:
Twelve male and 60 female patients were included in the study. Peripheral blood samples were collected before and five years after treatment with GA. The authors compared lymphocyte parameters between the CSP and non-CSP groups by statistical analyses. Univariate and penalized logistic regression models were fitted to identify the best lymphocyte parameters at baseline and their combination for potential biomarkers. Subsequently, the ROC analysis was used to identify cut-offs for selected parameters.
Results:
The parameter CD4+/CD45RO+ was identified as the best single potential biomarker, demonstrating the ability to identify patients with CSP. Moreover, a combination of four lymphocyte parameters at baseline, relative lymphocyte counts, CD3+/CD69+, CD4+/CD45RO+, and CD4+/CD45RA+ab, was identified as a potential composite biomarker. This combination explains 23% of the variability in CSP, which is better than the best univariate parameter when compared to CD4+/CD45RO+ at baseline.
Conclusions:
The results suggest that other biomarkers can help monitor the conditions of patients and predict a favourable outcome.

Keywords (CZ): roztroušená skleróza, glatiramer acetát, biomarker, CD4+/CD45RO+, pacienti, progrese nemoci

Keywords (EN): multiple sclerosis, glatiramer acetate, biomarker, CD4+/CD45RO+, patients, disease progression

Title: Cognitive clinico-radiological paradox in early stages of multiple sclerosis

Author: UHER, Tomáš, KRÁSENSKÝ, Jan, SOBÍŠEK, Lukáš, BLÁHOVÁ DUŠÁNKOVÁ, Jana, SEIDL, Zdeněk, HAVRDOVÁ, Eva, SORMANI, Maria Pia, HORÁKOVÁ, Dana, KALINČÍK, Tomáš, VANĚČKOVÁ, Manuela.

Year: 2018

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
UHER, Tomáš, KRÁSENSKÝ, Jan, SOBÍŠEK, Lukáš, BLÁHOVÁ DUŠÁNKOVÁ, Jana, SEIDL, Zdeněk, HAVRDOVÁ, Eva, SORMANI, Maria Pia, HORÁKOVÁ, Dana, KALINČÍK, Tomáš, VANĚČKOVÁ, Manuela. Cognitive clinico-radiological paradox in early stages of multiple sclerosis. Annals of Clinical and Translational Neurology, 2018, roč. 5, č. 1, s. 81-91, http://onlinelibrary.wiley.com/doi/10.1002/acn3.512/epdf

Abstract:
Objective: To investigate whether the strength of the association between magnetic resonance imaging (MRI) metrics and cognitive outcomes differs between various multiple sclerosis subpopulations.

Methods: 1052 patients were included in this large cross-sectional study. Brain MRI (T1 and T2 lesion volume and brain parenchymal fraction) and neuropsychological assessment (Brief International Cognitive Assessment for Multiple Sclerosis and Paced Auditory Serial Addition Test) were performed.

Results: Weak correlations between cognitive domains and MRI measures were observed in younger patients (age≤30 years; absolute Spearman ' s rho=0.05-0.21), with short disease duration (<2 years; rho=0.01-0.21), low Expanded Disability Status Scale [EDSS] (≤1.5; rho=0.08-0.18), low T2 lesion volume (lowest quartile; <0.59 ml; rho=0.01-0.20) and high brain parenchymal fraction (highest quartile; >86.66; rho=0.01-0.16). Stronger correlations between cognitive domains and MRI measures were observed in older patients (age>50 years; rho=0.24-0.50), with longer disease duration (>15 years; rho=0.26-0.53), higher EDSS (≥5.0; rho=0.23-0.39), greater T2 lesion volume (highest quartile; >5.33 ml; rho=0.16-0.32) and lower brain parenchymal fraction (lowest quartile; <83.71; rho=0.13-0.46). The majority of these observed results were confirmed by significant interactions (P≤0.01) using continuous variables.

Interpretation: The association between structural brain damage and functional cognitive impairment is substantialy weaker in multiple sclerosis patients with a low disease burden. Therefore, disease stage should be taken into consideration when interpreting associations between structural and cognitive measures in clinical trials, research studies and clinical practice.

Keywords (CZ): MRI, volumetrie, T2 objem lézí, atrofie mozku, roztroušená skleróza

Keywords (EN): MRI, volumetry, T2 lesion volume, brain atrophy, multiple sclerosis

Title: Combining clinical and magnetic resonance imaging markers enhances prediction of 12-year disability in multiple sclerosis

Author: UHER, Tomáš, VANEČKOVÁ, Manuela, SOBÍŠEK, Lukáš, TÝBLOVÁ, Michaela, SEIDL, Zdeněk, KRÁSENSKÝ, Jan, RAMASAMY, Deepa, HAVRDOVÁ, Eva, KALINČIK, Tomáš, HORÁKOVÁ, Dana

Year: 2017

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
UHER, Tomáš, VANEČKOVÁ, Manuela, SOBÍŠEK, Lukáš, TÝBLOVÁ, Michaela, SEIDL, Zdeněk, KRÁSENSKÝ, Jan, RAMASAMY, Deepa, HAVRDOVÁ, Eva, KALINČIK, Tomáš, HORÁKOVÁ, Dana. Combining clinical and magnetic resonance imaging markers enhances prediction of 12-year disability in multiple sclerosis. Multiple Sclerosis Journal [online]. 2017, roč. 23, č. 1, s. 51–61. ISSN 1352-4585. DOI: https://doi.org/10.1177/1352458516642314

Abstract:
Background:

Disease progression and treatment efficacy vary among individuals with multiple sclerosis. Reliable predictors of individual disease outcomes are lacking.

Objective:

To examine the accuracy of the early prediction of 12-year disability outcomes using clinical and magnetic resonance imaging (MRI) parameters.

Methods:

A total of 177 patients from the original Avonex-Steroids-Azathioprine study were included. Participants underwent 3-month clinical follow-ups. Cox models were used to model the associations between clinical and MRI markers at baseline or after 12 months with sustained disability progression (SDP) over the 12-year observation period.

Results:

At baseline, T2 lesion number, T1 and T2 lesion volumes, corpus callosum (CC), and thalamic fraction were the best predictors of SDP (hazard ratio (HR) = 1.7–4.6; p ≤  0.001–0.012). At 12 months, Expanded Disability Status Scale (EDSS) and its change, number of new or enlarging T2 lesions, and CC volume % change were the best predictors of SDP over the follow-up (HR = 1.7–3.5; p ≤  0.001–0.017). A composite score was generated from a subset of the best predictors of SDP. Scores of ≥4 had greater specificity (90%–100%) and were associated with greater cumulative risk of SDP (HR = 3.2–21.6; p < 0.001) compared to the individual predictors.

Conclusion:

The combination of established MRI and clinical indices with MRI volumetric predictors improves the prediction of SDP over long-term follow-up and may provide valuable information for therapeutic decisions.

Keywords (CZ): roztroušená skleróza, magnetická rezonance, disabilita, prediktory, mozková atrofie, léze

Keywords (EN): multiple sclerosis, magnetic resonance imaging, disability, predictors, brain atrophy, lesions

Title: Combining clinical and magnetic resonance imaging markers enhances prediction of 12-year employment status in multiple sclerosis patients

Author: KADRNOŽKOVÁ, Lucie, VANĚČKOVÁ, Manuela, SOBÍŠEK, Lukáš, atd.

Year: 2018

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
KADRNOŽKOVÁ, Lucie, VANĚČKOVÁ, Manuela, SOBÍŠEK, Lukáš, KRÁSENSKÝ, Jan, BEŇOVÁ, Barbora, KUČEROVÁ, Karolína, MOTÝL, Jiří, ANDĚLOVÁ, Michaela, NOVOTNÁ, Klára, LÍZROVÁ PREININGEROVÁ, Jana, HAVRDOVÁ, Eva, HORÁKOVÁ, Dana, UHER, Tomáš. Combining clinical and magnetic resonance imaging markers enhances prediction of 12-year employment status in multiple sclerosis patients. Journal of the Neurological Science, 2018, roč. 388, Číslo 15, s. 87-93.

Abstract:
Background
Multiple sclerosis (MS) is frequently diagnosed in the most productive years of adulthood and is often associated with worsening employment status. Reliable predictors of employment status change are lacking.

Objective
To identify early clinical and magnetic resonance imaging (MRI) markers of employment status worsening in MS patients at 12-year follow-up.

Methods
A total of 145 patients with early relapsing-remitting MS from the original Avonex-Steroids-Azathioprine (ASA) study were included in this prospective, longitudinal, observational cohort study. Cox models were conducted to identify MRI and clinical predictors (at baseline and during the first 12 months) of worsening employment status (patients either (1) working full-time or part-time with no limitations due to MS and retaining this status during the course of the study, or (2) patients working full-time or part-time with no limitations due to MS and switching to being unemployed or working part-time due to MS).

Results
In univariate analysis, brain parenchymal fraction, T1 lesion volume, and T2 lesion volume were the best MRI predictors of worsening employment status over the 12-year follow-up period. MS duration at baseline (hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.03-1.18; p = 0.040) was the only significant clinical predictor. Having one extra milliliter of T1 lesion volume was associated with a 53% greater risk of worsening employment status (HR = 1.53, 95% CI 1.16-2.02; p = 0.018). A brain parenchymal fraction decrease of 1% increased the risk of worsening employment status by 22% [HR = 0.78, 95% CI 0.65-0.95; p = 0.034].

Conclusion
Brain atrophy and lesion load were significant unique predictors of worsening employment status in MS patients. Using a combination of clinical and MRI markers may improve the early prediction of an employment status change over long-term follow-up.

Keywords (CZ): roztroušená skleróza, zaměstnanost, magnetická rezonance, práce, longitudinální studie, mozková atrofie, objem lézí

Keywords (EN): Multiple sclerosis, Employment, Magnetic Resonance Imaging, Work, Longitudinal studies, Brain Atrophy, Lesion load

Title: Comparison of Therapies in MS Patients After the First Demyelinating Event in Real Clinical Practice in the Czech Republic: Data From the National Registry ReMuS

Author: PAVELEK, Zbyšek, SOBÍŠEK, Lukáš, ŠARLÁKOVÁ, Jana, POTUŽNÍK, Pavel, PETERKA, Marek, ŠTĚTKÁŘOVÁ, Ivana, ŠTOURAČ, Pavel, MAREŠ, Jan, HRADÍLEK, Pavel, AMPAPA, Radek, GRUNERMELOVÁ, Markéta, VACHOVÁ, Marta, RECMANOVÁ, Eva, ANGELUCCI, Francesco, HALÚSKOVÁ, Simona, VALIŠ, Martin

Year: 2020

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
PAVELEK, Zbyšek, SOBÍŠEK, Lukáš, ŠARLÁKOVÁ, Jana, POTUŽNÍK, Pavel, PETERKA, Marek, ŠTĚTKÁŘOVÁ, Ivana, ŠTOURAČ, Pavel, MAREŠ, Jan, HRADÍLEK, Pavel, AMPAPA, Radek, GRUNERMELOVÁ, Markéta, VACHOVÁ, Marta, RECMANOVÁ, Eva, ANGELUCCI, Francesco, HALÚSKOVÁ, Simona, VALIŠ, Martin. Comparison of Therapies in MS Patients After the First Demyelinating Event in Real Clinical Practice in the Czech Republic: Data From the National Registry ReMuS. Front. Neurol., 2021, https://doi.org/10.3389/fneur.2020.593527.

Abstract:
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.

Keywords (CZ): roztroušená skleróza, léčba, dlouhodobá terapie, klinická praxe, DMD

Keywords (EN): multiple sclerosis, treatment, long-term therapy, clinical practice, DMD

Title: Do eyes with and without optic neuritis in multiple sclerosis age equally?

Author: LIZROVA PREININGEROVA, J., GRISHKO, A., SOBISEK, L., ANDELOVA, M., BENOVA, B., KUCEROVA, K., HAVRDOVA KUBALA, E.

Year: 2018

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
LIZROVA PREININGEROVA, J., GRISHKO, A., SOBISEK, L., ANDELOVA, M., BENOVA, B., KUCEROVA, K., HAVRDOVA KUBALA, E. Do eyes with and without optic neuritis in multiple sclerosis age equally? Neuropsychiatric desease and treatment. 2018, roč. 14. s. 2281-2285.

Abstract:
Purpose:

Anterior visual pathway reflects axonal loss caused by both optic neuritis (ON) and neurodegeneration in multiple sclerosis (MS). Although the axonal injury post-ON is thought to be complete by 6 months of onset, most studies using optical coherence tomography (OCT) to evaluate retinal changes as a marker of neurodegeneration exclude eyes with a history of ON or consider them separately. The objective of this study was to assess whether the eyes post-ON (>6 months) show in later years different rate of chronic retinal changes than the fellow eyes not affected by ON.

Patients and methods:

Fifty-six patients with MS with a history of ON in one eye (ON eyes) and no ON in the fellow (FL) eye, who were followed by OCT for >2 years, were selected from a cohort of patients with MS. Paired eye analysis was performed.

Results:

Mean interval post-ON at baseline was 5.65 (SD 5.05) years. Mean length of follow-up by OCT was 4.57 years. There was no statistical difference in absolute or relative thinning of retinal nerve fiber layer in peripapillary area between the ON and FL eyes.

Conclusion:

This study has shown that we do not need to exclude eyes with a history of ON from longitudinal studies of neurodegeneration in MS, provided that we use data outside of the frame of acute changes post-ON. Long-term changes of peripapillary retinal nerve fiber layer in ON and FL eyes are equal.

Keywords (CZ): roztroušená skleróza; neurodegenerace; oční koherenční tomograf; sítnici

Keywords (EN): multiple sclerosis; neurodegeneration; optical coherence tomography; retina

Title: Fingolimod v reálné klinické praxi

Author: TICHÁ, V., SOBÍŠEK, Lukáš, HAVRDOVÁ, E.

Year: 2017

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
TICHÁ, V., SOBÍŠEK, Lukáš, HAVRDOVÁ, E. Fingolimod v reálné klinické praxi. Česká a slovenská neurologie a neurochirurgie. 2017, č. 2, s. 213–219. ISSN 1210-7859. DOI: https://doi.org/10.14735/amcsnn2017213 . web: http://www.csnn.eu/ceska-slovenska-neurologie-clanek/fingolimod-v-realne-klinicke-praxi-60567

Abstract:
Cíl:

Retrospektivní zhodnocení klinické účinnosti fingolimodu v prvním a druhém roce léčby u pacientů s aktivní roztroušenou sklerózou.

Soubor a metodika:

Jeden rok bylo léčeno 223 pacientů a 109 z nich dva roky fingolimodem. Na fingolimod bylo převedeno 126 pacientů z interferonu beta nebo glatiramer acetátu, 3 pacienti nebyli dosud léčeni a 94 pacientů bylo převedeno z natalizumabu.

Výsledky:

Četnost relapsů poklesla ve skupině pacientů převedených z interferonu beta nebo glatiramer acetátu o 72 % během prvního roku a o 64 % během prvních 2 let a ve skupině převedené z natalizumabu o 25 % v prvním roce a o 31 % během prvních 2 let. První rok léčby nemělo žádný relaps 66 % pacientů, během 2 let léčby bylo bez relapsu 50,5 % pacientů. Stabilní nebo zlepšené EDSS mělo v obou podskupinách během 1 i 2 let léčby 80 % pacientů. Potvrzenou šestiměsíční progresi EDSS nemělo 94,6 % pacientů z celé skupiny a bez známek klinické aktivity nemoci bylo v prvním roce 64,6 % a prvních 2 letech 50 % pacientů. Při wash-out periodě kratší než 63 dnů po ukončení natalizumabu se vyskytl relaps v prvních 6 měsících u 16,7 % pacientů a při wash-out periodě delší než 63 dnů u 25 % pacientů.

Závěr:

Fingolimod je účinný pro eskalaci léčby u pacientů selhávajících na Disease Modifying Drug nebo jako lék první volby u pacientů s vysokou aktivitou nemoci. Ve většině případů je účinnou alternativou léčby pro ty pacienty, kteří ukončí léčbu natalizumabem.

Keywords (CZ): roztroušená skleróza, fingolimod, natalizumab, eskalace

Keywords (EN): multiple sclerosis, fingolimod, natalizumab, escalation

Title: Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach

Author: UHER, Tomáš, VANĚČKOVÁ, Manuela, SORMANI, M. T., KRÁSENSKÝ, Jan, SOBÍŠEK, Lukáš, BLÁHOVÁ DUŠÁNKOVÁ, J., SEIDL, Zdeněk, HAVRDOVÁ, Eva, KALINČIK, Tomáš, BENEDICT, R. H. B., HORÁKOVÁ, Dana

Year: 2017

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
UHER, Tomáš, VANĚČKOVÁ, Manuela, SORMANI, M. T., KRÁSENSKÝ, Jan, SOBÍŠEK, Lukáš, BLÁHOVÁ DUŠÁNKOVÁ, J., SEIDL, Zdeněk, HAVRDOVÁ, Eva, KALINČIK, Tomáš, BENEDICT, R. H. B., HORÁKOVÁ, Dana. Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach. European Journal of Neurology [online]. 2017, roč. 24, č. 1, s. 292–301. ISSN 1351-5101. DOI: https://doi.org/10.1111/ene.13200

Abstract:
Background and purpose

While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients.

Methods

Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24).

Results

The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds ratio (OR) of 6.5 (95% CI 4.4–9.5). Low BPF together with high T2-LV identified in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1–3.8) and low BPF (OR 2.6; 95% CI 1.4–4.7).

Conclusions

The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment.

Keywords (CZ): roztroušená skleróza, magnetická rezonance, disabilita, prediktory, mozková atrofie, léze

Keywords (EN): multiple sclerosis, magnetic resonance imaging, disability, predictors, brain atrophy, lesions

Title: Innate Immune System and Multiple Sclerosis. Granulocyte Numbers are Reduced in Patients Affected by Relapsing-Remitting Multiple Sclerosis during the Remission Phase

Author: PAVELEK, Zbyšek, AGNELUCCI, Francesco, SOUČEK, Ondřej, KREJSEK, Jan, SOBÍŠEK, Lukáš, KLÍMOVÁ, Blanka, ŠARLÁKOVÁ, Jana, HALÚSKOVÁ, Simona, KUČA, Kamil, VALIŠ, Martin

Year: 2020

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
PAVELEK, Zbyšek, AGNELUCCI, Francesco, SOUČEK, Ondřej, KREJSEK, Jan, SOBÍŠEK, Lukáš, KLÍMOVÁ, Blanka, ŠARLÁKOVÁ, Jana, HALÚSKOVÁ, Simona, KUČA, Kamil, VALIŠ, Martin. Innate Immune System and Multiple Sclerosis. Granulocyte Numbers are Reduced in Patients Affected by Relapsing-Remitting Multiple Sclerosis during the Remission Phase. J. Clin Med., 2020, roč. 9, číslo 5, s. 1468.

Abstract:
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.

Keywords (CZ): CD64, PD-L1, granulocyty, monocyty, roztroušená skleróza, relaps-remitentní

Keywords (EN): CD64, PD-L1, granulocytes, monocytes, multiple sclerosis, relapsing-remitting

Title: Interpretation of brain volume increase in multiple sclerosis

Author: UHER, Tomas, BERGSLAND, Niels, KRASENSKY, Jan, DWYER, Michael G., ANDELOVA, Michaela, SOBISEK, Lukas, KUBALA HAVRDOVA, Eva, HORAKOVA, Dana, ZIVADINOV, Robert, VANECKOVA, Manuela

Year: 2020

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
UHER, Tomas, BERGSLAND, Niels, KRASENSKY, Jan, DWYER, Michael G., ANDELOVA, Michaela, SOBISEK, Lukas, KUBALA HAVRDOVA, Eva, HORAKOVA, Dana, ZIVADINOV, Robert, VANECKOVA, Manuela. Interpretation of brain volume increase in multiple sclerosis. J. Neuroimaging, 2020, číslo: 00, s. 1-7.

Abstract:
BACKGROUND:

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).

CONCLUSION:

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.

Keywords (CZ): atrofie mozku, interpretace, MRI, roztroušená skleróza, zvýšení objemu

Keywords (EN): Brain atrophy, interpretation, MRI, multiple sclerosis, volume increase

Title: Is no evidence of disease activity an achievable goal in MS patients on intramuscular interferon beta-1a treatment over long-term follow-up?

Author: UHER, Tomáš, HAVRDOVÁ, Eva, SOBÍŠEK, Lukáš, KRÁSENSKÝ, Jan, VANĚČKOVÁ, Manuela, SEIDL, Zdeněk, TÝBLOVÁ, Michaela, RAMASAMY, Deepat, ZIVADINOV, Robert, HORÁKOVÁ, Dana

Year: 2017

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
UHER, Tomáš, HAVRDOVÁ, Eva, SOBÍŠEK, Lukáš, KRÁSENSKÝ, Jan, VANĚČKOVÁ, Manuela, SEIDL, Zdeněk, TÝBLOVÁ, Michaela, RAMASAMY, Deepat, ZIVADINOV, Robert, HORÁKOVÁ, Dana. Is no evidence of disease activity an achievable goal in MS patients on intramuscular interferon beta-1a treatment over long-term follow-up? Multiple Sclerosis Journal [online]. 2017, roč. 23, č. 2, s. 242–252. ISSN 1352-4585. DOI: https://doi.org/10.1177/1352458516650525

Abstract:
Background:

No evidence of disease activity (NEDA) has been proposed as a new treatment goal in multiple sclerosis (MS). NEDA-3 status is defined as the absence of magnetic resonance imaging (MRI; new/enlarging/enhancing lesions and increased whole brain volume loss in NEDA-4) and clinical disease activity.

Objectives:

To investigate the persistence of NEDA status over long-term follow-up in MS patients treated with weekly intramuscular interferon beta-1a.

Methods:

We included 192 patients after the first demyelinating event suggestive of MS, that is, clinically isolated syndrome (CIS) and 162 relapsing-remitting MS (RRMS) patients.

Results:

NEDA-3 status was observed in 40.1% of CIS and 20.4% of RRMS patients after 1 year. After 4 years, 10.1% of CIS patients had NEDA-3 status. After 10 years, none of the RRMS patients had NEDA-3 status. Only 4.6% of CIS and 1.0% of RRMS patients maintained NEDA-4 status after 4 years. Loss of NEDA-3 status after the first year was associated with a higher risk of disability progression (hazard ratio (HR) = 2.3–4.0; p = 0.005–0.03) over 6 years.

Conclusions:

Despite intramuscular interferon beta-1a treatment, loss of NEDA status occurred in the vast majority of individuals. Loss of NEDA status during the first year was associated with disability progression over long-term follow-up; however, specificity for individual patient was low.

Keywords (CZ): roztroušená skleróza, žádná aktivita nemoci, interferony, magnetická rezonance, atrofie mozku

Keywords (EN): multiple sclerosis, no evidence of disease activity, interferons, magnetic resonance imaging, brain atrophy

Title: Lymphocyte populations and their change during five-year glatiramer acetate treatment

Author: PAVELEK, Zbyšek, VYŠATA, Oldřich, SOBÍŠEK, Lukáš, KLÍMOVÁ, Blanka, ANDRÝS, Ctirad, VOKURKOVÁ, Doris, MAZUROVÁ, Radka, ŠŤOURAČ, Pavel, VALIŠ, Martin.

Year: 2018

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
PAVELEK, Zbyšek, VYŠATA, Oldřich, SOBÍŠEK, Lukáš, KLÍMOVÁ, Blanka, ANDRÝS, Ctirad, VOKURKOVÁ, Doris, MAZUROVÁ, Radka, ŠŤOURAČ, Pavel, VALIŠ, Martin. Lymphocyte populations and their change during five-year glatiramer acetate treatment. Neurologia i Neurochirurgia Polska, 2018. roč. 52, Číslo: 5: s. 587– 592.

Abstract:
Background

The goal of this study was to determine the characteristics that are affected in patients treated with glatiramer acetate (GA).

Methods

A total of 113 patients were included in this study. Patients were treated with glatiramer acetate (subcutaneous injection, 20 mg, each day). Peripheral blood samples were obtained just prior to treatment as well as 5 years after GA treatment. All the calculations were performed with the statistical system R (r-project.org).

Results

After 5 years of treatment, a significant decrease was found in the absolute and relative CD3+/CD69+ counts, the absolute and relative CD69 counts, the relative CD8+/CD38+ count and the relative CD38 count. A significant increase was found in the absolute and relative CD5+/CD45RA+ counts and the absolute CD5+/CD45RO+ count after 5 years of treatment.

Conclusion

This study presents some parameters that were affected by long-term GA treatment.

Keywords (CZ): Roztroušená skleróza, lymfocyty, Glatiramir acetát, parametry, léčba

Keywords (EN): Multiple sclerosis, Lymphocytes, Glatiramer acetate, Parameters, Treatment

Title: Monitoring of Lymphocyte Populations During Treatment with Interferon-β-1b to Predict Multiple Sclerosis Disability Progression.

Author: VALIŠ, Martin, VYŠATA, Oldřich, SOBÍŠEK, Lukáš, KLÍMOVÁ, Blanka, ANDRÝS, Ctirad, VOKURKOVÁ, Doris, PAVELEK, Zbyšek.

Year: 2019

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
VALIŠ, Martin, VYŠATA, Oldřich, SOBÍŠEK, Lukáš, KLÍMOVÁ, Blanka, ANDRÝS, Ctirad, VOKURKOVÁ, Doris, PAVELEK, Zbyšek. Monitoring of Lymphocyte Populations During Treatment with Interferon-β-1b to Predict Multiple Sclerosis Disability Progression. Journal of Interferon & Cytokine Research, 2019, roč. 39, č. 3, s. 164 – 173.

Abstract:
The authors aim to understand how lymphocyte populations could predict the course of multiple sclerosis (MS) in people treated with interferon-β (IFN-β). Twenty-five male patients and 72 female patients were analyzed in the study. Peripheral blood samples were taken before and 5 years after the treatment with IFN-β. Lymphocyte subsets were analyzed by flow cytometry. The authors compared lymphocyte parameters between confirmed sustained progression (CSP) and non-CSP groups by using Welch's one-way analysis of means or a chi-square test of independence. A penalized (lasso) logistic regression model was fitted to identify the combination of lymphocyte parameters for potential biomarkers. The combination of lymphocyte counts, relative CD3+/CD25+ cells, absolute CD8 T cells, absolute CD8+/CD38+ cells, absolute CD38+ cells, and relative CD5+/CD19+ cells was identified as potential biomarker for the IFN-β treatment to monitor MS development in relation to CSP. The results suggest that other biomarkers aid in patient observation, predict a favorable outcome, and assist in the decision-making process for the early therapy escalation

Keywords (CZ): roztroušená skleróza, interferon- β, biomarkery, lymfocyty

Keywords (EN): multiple sclerosis, interferon-β, biomarkers, lymphocytes

Title: Multiple sclerosis and immune system biomarkers: Novel comparison in glatiramer acetate and interferon beta-1a-treated patient groups

Author: PAVELEK, Zbyšek, NOVOTNÝ, Michal, SOUČEK, Ondřej, atd.

Year: 2021

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
PAVELEK, Zbyšek, NOVOTNÝ, Michal, SOUČEK, Ondřej, KREJSEK, Jan, SOBÍŠEK, Lukáš, SEJKOROVÁ, Ilona, MASOPUST, Jiří, KUCA, Kamil, VALIŠ, Martin, KLÍMOVÁ, Blanka, ŠŤOURAČ, Pavel. Multiple sclerosis and immune system biomarkers: Novel comparison in glatiramer acetate and interferon beta-1a-treated patient groups. Multiple Sclerosis and Related Disorders, 2021, roč. 53, https://doi.org/10.1016/j.msard.2021.103082.

Abstract:
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.

Keywords (CZ): roztroušená skleróza, BAFF, IL-10, Mx1, IgG, Glatiramer Acetát, Interferon beta-1a

Keywords (EN): multiple sclerosis, BAFF, IL-10, Mx1, IgG, Glatiramer Acetate, Interferon beta-1a

Title: One-Year Results of Fixed Aflibercept Treatment Regime in Type 3 Neovascularization.

Author: ERNEST, Jan, MANETHOVÁ, Kateřina, KOLÁŘ, Petr, SOBÍŠEK, Lukáš, SACCONI, Riccardo, QUERQUES, Giuseppe.

Year: 2020

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
ERNEST, Jan, MANETHOVÁ, Kateřina, KOLÁŘ, Petr, SOBÍŠEK, Lukáš, SACCONI, Riccardo, QUERQUES, Giuseppe. One-Year Results of Fixed Aflibercept Treatment Regime in Type 3 Neovascularization. Ophthalmologica, 2020, roč. 243, č. 1, s. 58 – 65.

Abstract:
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.

Keywords (CZ): aflibercept, degenerace makuly spojení stárnutím, anit-VEGF, optická koherenční tomografie, retinální angiomatózní proliferace, neovaskularizace typu

Keywords (EN): aflibercept, age-related macular degeneration, anti-VEGF, optical coherence tomography, retinal angiomatous proliferation, type 3 neovascularization

Title: Ovlivňují iniciální klinické symptomy výsledný stav pacientů s ischemickým iktem a rekanalizační léčbou?

Author: Halúsková S, Herzig R, Krajíčková D, Hamza A, Krajina A, Chovanec V, Lojík M, Raupach J, Renc O, Šimůnek L, Vítková E, Sobíšek L, Vališ M

Year: 2021

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
Halúsková S, Herzig R, Krajíčková D, Hamza A, Krajina A, Chovanec V, Lojík M, Raupach J, Renc O, Šimůnek L, Vítková E, Sobíšek L, Vališ M. Ovlivňují iniciální klinické symptomy výsledný stav pacientů s ischemickým iktem a rekanalizační léčbou? Cesk Slov Neurol N 2021; 84/117(5): 456–64. doi: 10.48095/cccsnn2021456.

Abstract:
Cíl:
Cílem bylo posoudit závislost 90denního výsledného klinického stavu na úvodních symptomech ischemické CMP (iCMP) u pacientů léčených intravenózní trombolýzou (IVT) a/nebo endovaskulární terapií (EVT).

Soubor a metodika:
V retrospektivní observační jednocentrové studii jsme v souboru 809 pacientů s iCMP léčených IVT a/nebo EVT zkoumali vliv iniciálních symptomů iCMP, dosažených časů a stupně rekanalizace na 90denní výsledný klinický stav.

Výsledky:
Ve skupině IVT byly jako významné negativní prediktory dobrého 90denního výsledného klinického stavu identifikovány věk (poměr šancí [OR] = 0,94, 95% interval spolehlivosti [CI]: 0,91–0,96), vstupní neurologický deficit (OR = 0,91, 95% CI: 0,86–0,96) a přítomnost parézy končetin (OR = 0,51, 95% CI: 0,25–0,97). Ve skupině EVT (± IVT) byly věk (OR = 0,93, 95% CI: 0,91–0,95) a iniciální neurologický deficit (OR = 0,84, 95% CI: 0,80–0,89) identifikovány jako významné negativní prediktory a úspěšná rekanalizace (OR = 4,31, 95% CI: 2,44–7,81) jako významný pozitivní prediktor dobrého 90denního výsledného klinického stavu (ve všech případech p < 0,05).

Závěry:
Naše výsledky prokázaly, že přítomnost parézy končetin byla spojena s horším výsledným klinickým stavem u pacientů léčených pouze IVT, zatímco přítomnost dalších symptomů iCMP neměla vliv na 90denní výsledný klinický stav u pacientů s rekanalizační léčbou.

Keywords (CZ): endovaskulární terapie, intravenózní trombolýza, akutní ischemická cévní mozková příhoda, klinické symptomy, výsledný klinický stav

Keywords (EN): acute ischemic stroke, clinical symptoms, intravenous thrombolysis, endovascular therapy, clinical outcome

Title: Quantification of Gait Abnormalities in Healthy-Looking Multiple Sclerosis Patients (with Expanded Disability Status Scale 0-1.5)

Author: NOVOTNÁ, K., SOBÍŠEK, Lukáš, HORÁKOVÁ, D., HAVRDOVÁ, E., LIZROVA PREININGEROVA, J.

Year: 2016

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
NOVOTNÁ, K., SOBÍŠEK, Lukáš, HORÁKOVÁ, D., HAVRDOVÁ, E., LIZROVA PREININGEROVA, J. Quantification of Gait Abnormalities in Healthy-Looking Multiple Sclerosis Patients (with Expanded Disability Status Scale 0-1.5). European Neurology [online]. 2016, roč. 76, č. 3–4, s. 99–104. ISSN 0014-3022. DOI: https://doi.org/10.1159/000448091. Dostupné také z: https://www.ncbi.nlm.nih.gov/pubmed/27497974

Abstract:
BACKGROUND:

Gait impairment is a common symptom in multiple sclerosis (MS) patients, but there is a lack of evidence about gait performance in the group of MS patients with no apparent disability. The aim of our study was to evaluate gait characteristics in MS patients with no apparent impairment of walking and with an Expanded Disability Status Scale (EDSS 0-1.5), and to determine whether any abnormalities are detectable by common clinical tests.

METHODS:

This was an observational study of 64 MS patients with an EDSS 0-1.5 and 47 age- and sex-matched healthy controls. We measured their performance in the timed 25-foot walk test (T25FWT) and the 2-minute walk test (2MWT). The spatiotemporal parameters of gait were measured using a GAITRite instrument.

RESULTS:

MS patients with no apparent disability (EDSS 0-1.5) performed worse in T25FWT and 2MWT than normal controls. During the self-selected walking speed test on GAITRite, MS patients had a prolonged double support phase, and during the fast walking speed test, they had lower cadence and decreased step length.

Keywords (CZ): roztroušená skleróza, chůze, chůzové testy, disabilita

Keywords (EN): multiple sclerosis, gait, walking tests, disability

Title: Serum lipid profile changes predict neurodegeneration in interferon-ß1a-treated multiple sclerosis patients.

Author: UHER, Tomáš, FELLOWS, Kelly, HORÁKOVÁ, Dana, ZIVADINOV, Robert, VANĚČKOVÁ, Manuela, SOBÍŠEK, Lukáš, TÝBLOVÁ, Michaela, SEIDL, Zdeněk, KRÁSENSKÝ, Jan, BERGSLAND, Niels, WEINSTOCK-GUTTMAN, Bianca, HAVRDOVÁ, Eva, RAMANATHAN, Murali.

Year: 2017

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
UHER, Tomáš, FELLOWS, Kelly, HORÁKOVÁ, Dana, ZIVADINOV, Robert, VANĚČKOVÁ, Manuela, SOBÍŠEK, Lukáš, TÝBLOVÁ, Michaela, SEIDL, Zdeněk, KRÁSENSKÝ, Jan, BERGSLAND, Niels, WEINSTOCK-GUTTMAN, Bianca, HAVRDOVÁ, Eva, RAMANATHAN, Murali. Serum lipid profile changes predict neurodegeneration in interferon-ß1a-treated multiple sclerosis patients. Journal of Lipid Research [online]. 2017, roč. 58, č. 2. 40 s. ISSN 0022-2275. DOI: https://doi.org/10.1194/jlr.M072751

Abstract:
The purpose of this work was to determine whether changes in cholesterol profiles after interferon-β (IFN-β)1a treatment initiation following the first demyelinating event suggestive of multiple sclerosis are associated with clinical and MRI outcomes over 4 years. A group of 131 patients (age: 27.9 ± 7.8 years, 63% female) with serial 3-monthly clinical and 12-monthly MRI follow-ups over 4 years were investigated. Serum cholesterol profiles, including total cholesterol (TC), HDL cholesterol (HDL-C), and LDL cholesterol (LDL-C) were obtained at baseline, 1 month, 3 months, and every 6 months thereafter. IFN-β1a initiation caused rapid decreases in serum HDL-C, LDL-C, and TC within 1 month of IFN-β1a initiation (all P < 0.001) that returned slowly toward baseline. In predictive mixed model analyses, greater percent decreases in HDL-C after 3 months of IFN-β1a treatment initiation were associated with less brain atrophy over the 4 year time course, as assessed by percent brain volume change (P < 0.001), percent gray matter volume change (P < 0.001), and percent lateral ventricle volume change (P = 0.005). Decreases in cholesterol biomarkers following IFN-β1a treatment are associated with brain atrophy outcomes over 4 years. Pharmacological interventions targeting lipid homeostasis may be clinically beneficial for disrupting neurodegenerative processes.

Keywords (CZ): cholesterol, léčebná terapie, HDL, zánět, LDL, roztroušená skleróza

Keywords (EN): cholesterol, drug therapy, HDL, inflammation, LDL, multiple sclerosis

Title: Srovnání účinnosti subkutánně podávaného interferonu β-1a 44 μg, dimetyl fumarátu a fingolimodu v reálné klinické praxi – multicentrická observační studie

Author: PAVELEK, Zbyšek, SOBÍŠEK, Lukáš, HORÁKOVÁ, Dana, VALIŠ, Martin.

Year: 2018

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
PAVELEK, Zbyšek, SOBÍŠEK, Lukáš, HORÁKOVÁ, Dana, VALIŠ, Martin. Srovnání účinnosti subkutánně podávaného interferonu β-1a 44 μg, dimetyl fumarátu a fingolimodu v reálné klinické praxi – multicentrická observační studie. Cesk Slov Neurol N, 2018. roč. 81, Číslo: 114(4): s. 457– 465.

Abstract:
Úvod:
Roztroušená skleróza je chronické zánětlivé a neurodegenerativní onemocnění postihující CNS. Mezi etablované léky pro relaps-remitentní RS (RR RS) patří interferon (IFN) β-1a44 μg, dimetyl fumarát (DMF) a fingolimod. Cílem projektu, resp. výstupem z analýzy z registru ReMuS, bylo srovnat účinnost subkutánně podávaného IFN β-1a 44 μg, DMF a fingolimodu u pacientů s RR RS, u nichž byla zahájena tato léčba do 90 dní od počátku relapsu, v reálné klinické praxi v ČR.

Soubor a metodika:
Do projektu bylo zahrnuto celkem 279 pacientů s RR RS, kteří prodělali při léčbě 1. linie (IFN β-1a 22 μg 3× týdně, IFN β-1a 30 μg 1× týdně , IFN β-1b 250 μg obden, teriflunomid 14 mg denně, glatiramer acetát 20 mg denně nebo glatiramer acetát 40 mg 3× týdně) jeden relaps a kterým byla léčba změněna buď na IFN β-1a 44 μg nebo DMF či fingolimod. Sledovanými parametry byly roční počet relapsů (annualized relapse rate; ARR), doba do dalšího relapsu, zastoupení pacientů bez relapsu a změna Expanded Disability Status Scale (EDSS) po roce od změny léčby u jednotlivých preparátů.

Výsledky:
Po změně terapie došlo u všech třech sledovaných preparátů během roční observace k signifikantnímu zlepšení analyzovaných parametrů. Při porovnání skupiny pacientů s léčbou IFN β-1a 44 μg (83 pa cientů) vs. fingolimod nebo DMF (196 pa cientů) bylo ve druhé skupině významnější zlepšení v parametru ARR a změna EDSS. Po spárování pacientů na terapii IFN β-1a 44 μg se skupinou léčenou DMF nebo fingolimodem v poměru 1 : 1 metodou propensity score matching (83 vs. 83 pacientů) zůstal signifi kantní vliv na zlepšení sledovaných parametrů před změnou terapie a po ní v obou skupinách, neprokázali jsme ale již signifikantní rozdíl efektu mezi skupinami.

Závěr: IFN β-1a 44 μg, DMF i fingolimod prokázaly svou účinnost v rámci eskalace léčby na vybrané skupině pacientů v parametrech změna EDSS a čas do dalšího relapsu.

Keywords (CZ): roztroušená skleróza, interferon β-1a 44 μg, dimetyl fumarát, fingolimod

Keywords (EN): Multiple sclerosis, interferon β-1a 44 μg, dimethyl fumarate, fingolimod

Title: Thalamic Iron Differentiates Primary-Progressive and Relapsing-Remitting Multiple Sclerosis.

Author: BURGETOVÁ, A., DUŠEK. P., VANĚČKOVÁ, M., HORÁKOVÁ, D., LANGKAMMER, C., KRÁSENSKÝ, J., SOBÍŠEK, L., MATRAS, P., MAŠEK, M., SEIDL, Z.

Year: 2017

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
BURGETOVÁ, A., DUŠEK. P., VANĚČKOVÁ, M., HORÁKOVÁ, D., LANGKAMMER, C., KRÁSENSKÝ, J., SOBÍŠEK, L., MATRAS, P., MAŠEK, M., SEIDL, Z. Thalamic Iron Differentiates Primary-Progressive and Relapsing-Remitting Multiple Sclerosis. Americal Journal of Neuroradiology. 2017, roč. 38, č.6 , s. 1079-1086. DOI: https://doi.org/10.3174/ajnr.A5166

Abstract:
BACKGROUND AND PURPOSE: Potential differences between primary progressive and relapsing remitting multiple sclerosis are the subject of ongoing controversial discussions. The aim of this work was to determine whether and how primary-progressive and relapsing-remitting multiple sclerosis subtypes differ regarding conventional MR imaging parameters, cerebral iron deposits, and their association with clinical status.

MATERIALS AND METHODS: We analyzed 24 patients with primary-progressive MS, 80 with relapsing-remitting MS, and 20 healthy controls with 1.5T MR imaging for assessment of the conventional quantitative parameters: T2 lesion load, T1 lesion load, brain parenchymal fraction, and corpus callosum volume. Quantitative susceptibility mapping was performed to estimate iron concentration in the deep gray matter.

RESULTS: Decreased susceptibility within the thalamus in relapsing-remitting MS compared with primary-progressive MS was the only significant MR imaging difference between these MS subtypes. In the relapsing-remitting MS subgroup, the Expanded Disability Status Scale score was positively associated with conventional parameters reflecting white matter lesions and brain atrophy and with iron in the putamen and caudate nucleus. A positive association with putaminal iron and the Expanded Disability Status Scale score was found in primary-progressive MS.

CONCLUSIONS: Susceptibility in the thalamus might provide additional support for the differentiation between primary-progressive and relapsing-remitting MS. That the Expanded Disability Status Scale score was associated with conventional MR imaging parameters and iron concentrations in several deep gray matter regions in relapsing-remitting MS, while only a weak association with putaminal iron was observed in primary-progressive MS suggests different driving forces of disability in these MS subtypes.

Keywords (CZ): roztroušení skleróza, MRI, QSM, železo, hluboká šedá hmota, léze, EDSS, primárně progresivní RS, relaps remitentní RS

Keywords (EN): Multiple sclerosis, MRI, QSM, Iron, Deep gray matter, Lesion load, Expanded Disability Status Scale, Primary progressive MS, Relapsing remitting MS

Title: Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

Author: KALINČÍK Tomáš, MANOUCHEHRINIA, Ali, SOBÍŠEK, Lukáš, a kol.

Year: 2017

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
KALINČÍK Tomáš, MANOUCHEHRINIA, Ali, SOBÍŠEK, Lukáš, a kol. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response. Brain, 2017, roč. 140, č. 9, s. 2426–2443, https://doi.org/10.1093/brain/awx185

Abstract:
Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were:

(i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and

(ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study.

Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry.

In the training cohort (n= 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n= 1196) of the resulting predictive models was high (480%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2–4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation.

External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease- modifying therapies at the time of their commencement.

Keywords (CZ): roztroušená skleróza; predikce; disabilita; relapsy; precizní medicína

Keywords (EN): multiple sclerosis; prediction; disability; relapses; precision medicine

Title: What Variability of Treatment Effect of Fampridine Can We Expect in People with Multiple Sclerosis?

Author: NOVOTNÁ, Klára, PREININGEROVÁ LÍZROVÁ, Klára, SOBÍŠEK, Lukáš, HAVRDOVÁ, Eva.

Year: 2017

Field: Medical research

Publication type: paper (Web of Knowledge - JCR, Scopus)

Citation:
NOVOTNÁ, Klára, PREININGEROVÁ LÍZROVÁ, Klára, SOBÍŠEK, Lukáš, HAVRDOVÁ, Eva. What Variability of Treatment Effect of Fampridine Can We Expect in People with Multiple Sclerosis? Journal of Multiple Sclerosis, 2017, roč. 4, č. 3, s. 1-5, https://www.omicsonline.org/open-access/what-variability-of-treatment-effect-of-fampridine-can-we-expect-in-people-with-multiple-sclerosis-2376-0389-1000206.pdf

Abstract:
Background:

Gait impairment represents one of the most common symptoms of multiple sclerosis (MS). Fampridine is the first symptomatic treatment aimed at improving gait.An objective measurement of the mobility improvement from treatment initiation has been recommended to evaluate treatment response.

Objective:

In this retrospective observational study, we evaluated what improvement in walking speed can be expected in people with multiple sclerosis (MS) treated with Fampridine in clinical practice, with respect to specific disability levels (EDSS 4.0-7.0).

Methods:

The mobility tests including the Timed 25 foot walk test (T25FW), Timed Up and Go test (TUG) and Step test (ST) were performed just before and 3 h after administration of Fampridine 10 mg tablet.

Results:

One hundred and thirty one (131) people with MS (15 with primary progressive, 40 with secondary progressive and 76 people with relapsing-remitting MS). The mean age was 48 years (SD 9.8), mean MS duration was 19, 8 years, 58% were women. The range of treatment response of Fampridine, measured with the T25FW test, varied from 11-41%. Contrary to prior reports, the baseline T25FW and the percentage of improvement in T25FW was significantly correlated.

Conclusion:

Assessment of treatment response outside of a clinical trial is challenging and may require different outcome measures compared to RCT. For MS patients with moderate disability seems TUG test or Step test more appropriate for quantifying treatment response.

Keywords (CZ): Roztroušená skleróza; Chůze; Disabilita; Symptomatická léčba; Fampridine

Keywords (EN): Multiple sclerosis; Gait; Disability; Symptomatic treatment; Fampridine