OBJECTIVE: To compare the effectiveness of glatiramer acetate (GA) vs intramuscular interferon beta-1a (IFN-β-1a), we applied a previously published statistical method aimed at identifying patients' profiles associated with efficacy of treatments. METHODS: Data from 2 independent multiple sclerosis datasets, a randomized study (the Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis [CombiRx] trial, evaluating GA vs IFN-β-1a) and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors. RESULTS: The overall ARR ratio of GA to IFN-β-1a in the CombiRx trial was 0.72. The response score (made up of a linear combination of age, sex, relapses in the previous year, disease duration, and Expanded Disability Status Scale score) detected differential response of GA vs IFN-β-1a: in the trial, patients with the largest benefit from GA vs IFN-β-1a (lower score quartile) had an ARR ratio of 0.40 (95% confidence interval [CI] 0.25-0.63), those in the 2 middle quartiles of 0.90 (95% CI 0.61-1.34), and those in the upper quartile of 1.14 (95% CI 0.59-2.18) (heterogeneity p = 0.012); this result was validated on MSBase, with the corresponding ARR ratios of 0.58 (95% CI 0.46-0.72), 0.92 (95% CI 0.77-1.09,) and 1.29 (95% CI 0.97-1.71); heterogeneity p < 0.0001). CONCLUSIONS: We demonstrate the possibility of a criterion, based on patients' characteristics, to choose whether to treat with GA or IFN-β-1a. This result, replicated on an independent real-life cohort, may have implications for clinical decisions in everyday clinical practice.

• MeSH
• adjuvancia imunologická aplikace a dávkování   MeSH
• databáze faktografické trendy   MeSH
• dospělí MeSH
• glatiramer acetát aplikace a dávkování   MeSH
• imunosupresiva aplikace a dávkování   MeSH
• injekce intramuskulární MeSH
• interferon beta 1a aplikace a dávkování   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• relabující-remitující roztroušená skleróza diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• glatiramer acetát MeSH
• imunosupresiva MeSH
• interferon beta 1a MeSH

IMPORTANCE: Multiple sclerosis (MS) is usually diagnosed in women during their childbearing years. Currently, no consensus exists on whether pregnancy can delay the first episode of demyelination or clinically isolated syndrome (CIS). OBJECTIVE: To investigate the association of pregnancy with time to CIS onset. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study collected reproductive history (duration of each pregnancy, date of delivery, length of breastfeeding) on all participants between September 1, 2016, and June 25, 2019. Adult women being treated at the MS outpatient clinics of 4 tertiary hospitals in 2 countries (Charles University and General University Hospital in Prague, Czech Republic; Royal Melbourne Hospital in Melbourne, Australia; Alfred Hospital in Melbourne, Australia; and John Hunter Hospital in Newcastle, Australia) were recruited to participate in the study. Preexisting data (date of CIS onset, date of birth, sex, date of clinical onset, and Expanded Disability Status Scale result) were collected from MSBase, an international registry of long-term prospectively collected data on patients with MS. Data analyses were performed from June 1, 2019, to February 3, 2020. EXPOSURES: Gravida (defined as any pregnancy, including pregnancy that ended in miscarriage and induced abortion) and parity (defined as childbirth after gestational age of more than 20 weeks, including livebirth and stillbirth) before CIS onset. MAIN OUTCOMES AND MEASURES: Time to CIS onset. The following were assessed: (1) whether women with previous pregnancies and childbirths had a delayed onset of CIS compared with those who had never been pregnant and those who had never given birth, and (2) whether a dose response existed, whereby a higher number of gravidity and parity was associated with a later onset of CIS. RESULTS: Of the 2557 women included in the study, the mean (SD) age at CIS onset was 31.5 (9.7) years. Of these women, before CIS onset, 1188 (46%) had at least 1 pregnancy and 1100 (43%) had at least 1 childbirth. The mean (SD) age at first pregnancy was 23.3 (4.5) years and at first childbirth was 23.8 (4.5) years. Women with previous pregnancies and childbirths had a later onset of CIS compared with those who had never been pregnant (HR, 0.68; 95% CI, 0.62-0.75; P < .001), with a median delay of 3.3 (95% CI, 2.5-4.1) years. Women who had given birth also had a later CIS onset compared with women who had never given birth (HR 0.68; 95% CI, 0.61-0.75; P < .001), with a similar median delay of 3.4 (95% CI, 1.6-5.2) years. A higher gravidity and parity number was not associated with delay in CIS onset. CONCLUSIONS AND RELEVANCE: This study suggests an association between previous pregnancies and childbirths and timing of CIS onset, but having more pregnancies or childbirths did not appear to be associated with a later CIS onset. Further studies are needed to help explain the mechanisms behind the associations between pregnancy and onset of multiple sclerosis.

• MeSH
• demyelinizační nemoci epidemiologie   MeSH
• dospělí MeSH
• gravidita * MeSH
• kohortové studie MeSH
• lidé MeSH
• roztroušená skleróza epidemiologie   MeSH
• těhotenství MeSH
• věk při počátku nemoci * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

OBJECTIVE: To determine whether serum neurofilament light chain (sNfL) levels are associated with recent MRI activity in patients with relapsing-remitting MS (RRMS). METHODS: This observational study included 163 patients (405 samples) with early RRMS from the Study of Early interferon-beta1a (IFN-β1a) Treatment (SET) cohort and 179 patients (664 samples) with more advanced RRMS from the Genome-Wide Association Study of Multiple Sclerosis (GeneMSA) cohort. Based on annual brain MRI, we assessed the ability of sNfL cutoffs to reflect the presence of combined unique active lesions, defined as new/enlarging lesion compared with MRI in the preceding year or contrast-enhancing lesion. The probability of active MRI lesions among patients with different sNfL levels was estimated with generalized estimating equations models. RESULTS: From the sNfL samples ≥90th percentile, 81.6% of the SET (OR = 3.4, 95% CI = 1.8-6.4) and 48.9% of the GeneMSA cohort samples (OR = 2.6, 95% CI = 1.7-3.9) was associated with radiological disease activity on MRI. The sNfL level between the 10th and 30th percentile was reflective of negligible MRI activity: 1.4% (SET) and 6.5% (GeneMSA) of patients developed ≥3 active lesions, 5.8% (SET) and 6.5% (GeneMSA) developed ≥2 active lesions, and 34.8% (SET) and 11.8% (GeneMSA) showed ≥1 active lesion on brain MRI. The sNfL level <10th percentile was associated with even lower MRI activity. Similar results were found in a subgroup of clinically stable patients. CONCLUSIONS: Low sNfL levels (≤30th percentile) help identify patients with MS with very low probability of recent radiologic disease activity during the preceding year. This result suggests that in future, sNfL assessment may substitute the need for annual brain MRI monitoring in considerable number (23.1%-36.4%) of visits in clinically stable patients.

• MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladý dospělý MeSH
• neurofilamentové proteiny krev   MeSH
• progrese nemoci * MeSH
• relabující-remitující roztroušená skleróza krev   diagnóza   patologie   MeSH
• senzitivita a specificita MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• neurofilament protein L MeSH Prohlížeč
• neurofilamentové proteiny MeSH

IMPORTANCE: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date. OBJECTIVES: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions. DATA SOURCES: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC. STUDY SELECTION: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex. DATA EXTRACTION AND SYNTHESIS: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept. MAIN OUTCOME AND MEASURE: The cNfL levels adjusted for age and sex across diagnoses. RESULTS: Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes. CONCLUSIONS AND RELEVANCE: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.

• Publikační typ
• časopisecké články MeSH

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that leads to inflammation, demyelination and ultimately axonal degeneration. In most cases, it is preceded by its precursor, clinically isolated syndrome (CIS) with conversion rates to clinically definite MS (CDMS) of roughly 20-75%. Neurologists are therefore faced with the challenge of initiating a disease-modifying therapy (DMT) as early as possible to favorably influence the course of the disease. During the past 20 years, a multitude of drugs have been incorporated into our therapeutic armamentarium for MS and CIS. Choosing the right drug for an individual patient is complex and should be based not only on the drug's overall efficacy to prevent disease progression but also its specific adverse reaction profile, the severity of individual disease courses and, finally, patient compliance in order to adequately weigh associated risks and benefits. Here, we review the available data on the efficacy, safety and tolerability of DMTs tested for CIS and discuss their value regarding a delay of progression to CDMS.

• MeSH
• látky ovlivňující centrální nervový systém terapeutické užití   MeSH
• lidé MeSH
• progrese nemoci MeSH
• roztroušená skleróza farmakoterapie   MeSH
• syndrom MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• látky ovlivňující centrální nervový systém MeSH

OBJECTIVES: Multiple sclerosis (MS) often occurs in young women and the effect of obstetric anesthesia/analgesia on the disease is poorly understood. No previous study has investigated the course of the disease in women in labor in the Czech Republic. The aim of this study was to evaluate the occurrence or absence of relapses in the 6-month postpartum period in MS parturients with and without obstetric anesthesia/analgesia. MATERIALS AND METHODS: We retrospectively studied all deliveries (n = 58,455) at the University Hospital Brno from 2004 to 2013 and identified those of the women with an ICD-10 code G35 (MS) recorded anytime in their medical history (n = 428). We included only deliveries of women with confirmed diagnosis at the time of labor (n = 70). Statistical analysis was performed using the Fischer Exact Test. RESULTS: There were 70 deliveries of 65 women, including 45 vaginal deliveries and 25 Cesarean deliveries (16 under general anesthesia, 8 with epidural anesthesia and 1 with spinal anesthesia). Epidural obstetric analgesia was performed in 11 deliveries. There was no statistically significant difference in relapses between the vaginal delivery group (n = 15; 33%) and Cesarean section group (n = 10; 40%), p = 0.611. CONCLUSION: Neither delivery mode (vaginal vs Caesarean) nor type of obstetric anesthesia/analgesia was found to have any impact on the course of MS at 6 months postpartum in women with this condition.

• Klíčová slova
• cesarean section, labor, multiple sclerosis, obstetric anesthesia, pregnancy, relapse,
• MeSH
• analgézie porodnická metody   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• poporodní období MeSH
• porodnická anestezie metody   MeSH
• progrese nemoci MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• roztroušená skleróza epidemiologie   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

Vitamin D receptor polymorphisms have been the target of many studies focusing on multiple sclerosis. However, previously reported results have been inconclusive. The objective of this study was to investigate the association between five vitamin D receptor polymorphisms (EcoRV, FokI, ApaI, TaqI, and BsmI) and multiple sclerosis susceptibility and its course. The study was carried out as a case-control and genotype-phenotype study, consisted of 296 Czech multiple sclerosis patients and 135 healthy controls. Genotyping was carried out using polymerase chain reaction and restriction analysis. In multiple sclerosis men, allele and/or genotype distributions differed in EcoRV, TaqI, BsmI, and ApaI polymorphisms as compared to controls (EcoRV, pa = 0.02; Taq, pg = 0.02, pa = 0.02; BsmI, pg = 0.02, pa = 0.04; ApaI, pg = 0.008, pa = 0.005). In multiple sclerosis women, differences in the frequency of alleles and genotypes were found to be significant in ApaI (controls vs multiple sclerosis women: pg = 0.01, pa = 0.05). Conclusive results were observed between multiple sclerosis women in the case of EcoRV [differences in Expanded Disability Status Scale (p = 0.05); CT genotype was found to increase the risk of primary progressive multiple sclerosis 5.5 times (CT vs CC+TT pcorr = 0.01, sensitivity 0.833, specificity 0.525, power test 0.823)] and FokI [borderline difference in Multiple Sclerosis Severity Score (p = 0.05)]. Our results indicate that the distribution of investigated vitamin D receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and progression in the Czech population. The association between disease risk and polymorphisms was found to be stronger in men. The association of disease progression with polymorphisms was observed only in women.

• Klíčová slova
• EDSS, MSSS, Multiple sclerosis, Single-nucleotide polymorphism, Vitamin D receptor,
• MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• receptory kalcitriolu genetika   MeSH
• roztroušená skleróza genetika   patologie   MeSH
• senioři MeSH
• sexuální faktory MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• receptory kalcitriolu MeSH
• VDR protein, human MeSH Prohlížeč

BACKGROUND AND OBJECTIVE: Once-daily oral fingolimod is approved in the EU as escalation treatment for adult patients with highly active relapsing multiple sclerosis (MS). The efficacy and safety profiles of fingolimod have been well established in a large clinical development programme and several papers reflecting the experience with fingolimod in real-world settings have been published to date. The GOLEMS study was designed to evaluate the efficacy, safety and tolerability of fingolimod and the impact of fingolimod treatment on disability progression and work capability in patients with MS in routine clinical practice in the Czech Republic. METHODS: GOLEMS was a national, multicentre, non-interventional, single-arm study conducted to analyse the outcomes of a minimum of 12 months of fingolimod therapy on primary and secondary endpoints. The primary endpoint was to assess the proportion of relapse-free patients and severity of MS relapses in patients treated with fingolimod for 12 months. Secondary endpoints included assessment of changes in disability progression evaluated by the Expanded Disability Status Scale (EDSS) score and work capability assessment measured through voluntary completion of the WPAI-GH questionnaire. The predictive factors for relapse-free status during fingolimod treatment were also analysed. RESULTS: Of the 240 enrolled patients, 219 completed the 12-month treatment period at the time of final analysis. In the efficacy set (N = 237), the proportion of relapse-free patients increased from 47 patients (19.6 %; 95 % confidence interval [CI] 14.8-25.2) in the year before fingolimod initiation to 152 patients (64.1 %; 95 % CI 58.0-70.2) after 1 year of fingolimod treatment. Of the 85 patients who experienced at least one relapse after 1 year of fingolimod treatment, 53 (62.4 %; 95 % CI 51.7-71.9) reported only one relapse, while 25 (29.4 %; 95 % CI 20.8-39.8) and seven (8.2 %; 95 % CI 4.0-16.0) patients had ≥2 relapses, respectively. No significant changes were observed in EDSS scores over the 12-month treatment period compared with baseline. The absolute number of relapses during 2 years before initiation of fingolimod treatment and baseline EDSS scores were identified as significant independent predictors for 'being relapse-free' during the 12-month fingolimod treatment period. No trend was established in work capability or number of missed days at work due to the large proportion of missing data. Of 240 enrolled patients, 27 (11.3 %) patients discontinued the study at or before the 12-month visit, 16 (6.7 %) discontinued because of adverse events related to study drug. Only six (2.5 %) patients reported serious adverse events related to the study drug. CONCLUSION: The results confirm the favourable safety and efficacy profile of fingolimod under real-world conditions, consistent with phase III trials.

• MeSH
• dospělí MeSH
• fingolimod hydrochlorid aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• posuzování pracovní neschopnosti MeSH
• práce MeSH
• progrese nemoci MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   MeSH
• stanovení cílového parametru MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• fingolimod hydrochlorid MeSH
• imunosupresiva MeSH

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, which often causes progressive neurological disability. In addition to motor and sensory dysfunction, cognitive decline and fatigue are frequent manifestations of the disease. Fatigue is probably the most common symptom, with up to 90% of MS individuals reporting fatigue at some point. Cognitive impairment affects about 50% of patients and may be present at all MS stages. The aim of this observational study was to evaluate changes in cognition, fatigue, and disability status in 300 relapsing-remitting MS (RRMS) patients, treated with subcutaneous (sc) interferon (IFN) β-1a over 2 years. METHODS: The study was designed as an observational, multicentre, prospective, single-arm, phase IV study carried out in 13 MS centres in the Czech Republic. Cognition status was assessed using the Paced Auditory Serial Addition Task (PASAT), fatigue using the Fatigue Descriptive Scale (FDS), and disability using the Expanded Disability Status Scale (EDSS), at baseline, and after 6, 12 and 24 months. The percentage of patients with changed versus stable cognition, fatigue status and disability was calculated at each time point and the changes in these scores were evaluated. RESULTS: The proportion of patients with cognitive improvement was higher compared with those with a stable or decreased PASAT scores at all time points, and the average cognitive performance improved during the follow-up period. Also the proportion of patients with stable or improved fatigue and EDSS scores was higher compared with those in which FDS or EDSS scores declined, this was found at all time points of the analysed sample. However, the direct effect of IFN β-1a on cognition and fatigue cannot be concluded from this study. CONCLUSIONS: The results of this observational study have demonstrated a stable or improved cognitive performance, fatigue status, and disability level in the majority of RRMS patients treated with sc IFN β-1a over a two-year follow-up period, in a real life setting, in the Czech Republic.

• Klíčová slova
• cognitive impairment, fatigue, interferon β-1a, multiple sclerosis, treatment,
• Publikační typ
• časopisecké články MeSH

Early diagnosis and treatment of multiple sclerosis (MS) in the initial stages of the disease can significantly retard its progression. The aim of the present study was to identify changes in the cerebrospinal fluid proteome in patients with relapsing-remitting MS and clinically isolated MS syndrome who are at high risk of developing MS (case group) compared to healthy population (control) in order to identify potential new markers, which could ultimately aid in early diagnosis of MS. The protein concentrations of each of the 11 case and 15 control samples were determined using a bicinchoninic acid assay. Nanoscale liquid chromatography coupled with tandem mass spectrometry was used for protein identification. Proteomics data were processed using the Perseus software suite and R. The results were filtered using the Benjamini-Hochberg procedure for the false discovery rate (FDR) correction (FDR<0.05). The results showed that, 26 proteins were significantly dysregulated in case samples compared to the controls. Nine proteins were found to be significantly less abundant in case samples, while the abundance of 17 proteins was significantly increased in case samples compared to controls. Three of the proteins were previously linked to RR MS, including immunoglobulin (Ig) γ-1 chain C region, Ig heavy chain V-III region BRO and Ig κ chain C region. Three proteins that were uniquely expressed in patients with RR MS were identified and these proteins may serve as prognostic biomarkers for identifying patients with a high risk of developing RR MS.

• Klíčová slova
• biomarkers, cerebrospinal fluid, clinically isolated syndrome, multiple sclerosis, proteins, proteomic analysis,
• Publikační typ
• časopisecké články MeSH