BACKGROUND: Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS). OBJECTIVES: Provide experience with cladribine therapy in a real-world setting. METHODS: This is a registry-based retrospective observational cohort study. First, using data from the Czech nationwide registry ReMuS, we analysed patients who initiated cladribine from September 1, 2018 to December 31, 2021. Second, we analysed a subgroup of patients who initiated cladribine between September 1, 2018 to June 30, 2020, thus possessing a follow-up period of at least 2 years. We evaluated demographic and MS characteristics including disease-modifying therapies (DMTs) before and after cladribine administration, relapses, Expanded Disability Status Scale (EDSS), and adherence. RESULTS: In total, 617 patients (335 with follow-up of at least 2 years) started cladribine therapy in the study period (mean age 37.0, mean disease duration 8.4 years, 74.1% females). In most cases, cladribine was administered as a second-line drug, a total of 80.7% had been escalated from a platform DMT. During 2 years before cladribine initiation, the average annualised relapse rate (ARR) was .67. Following cladribine initiation, the ARR decreased to .28 in the first year and .22 in the second year. Overall, across the entire two-year treatment period, 69.0% of patients were relapse-free and the average ARR was .25. As for EDSS development, the median baseline EDSS was 2.5 and remained stable even after 24 months. The adherence to treatment ranged of around 90%. CONCLUSION: This nationwide study confirms the efficacy of cladribine in real-world settings, especially in patients who are not treatment-naïve. In addition, the study shows an exceptionally high adherence rate, a finding that underscores the invaluable role of cladribine, but also the value of registry-based studies in capturing real-world clinical practice.
- Publikační typ
- časopisecké články MeSH
Cerebral tumors and multiple sclerosis (MS) can show overlapping clinical and magnetic resonance imaging (MRI) features and even occur concurrently. Due to the emergence of new symptoms, not usually MS related, an MRI was conducted in a 29-year-old woman with relapsing-remitting MS and showed a significant size progression of a parieto-occipital lesion, with mild clinical correlates, such as blurred vision, difficulty in speaking, and headache. Contrast-enhanced MRI and fluorothymidine positron-emission tomography (PET) did not point toward neoplasm, a lesion biopsy, however, showed astrocytoma, which was confirmed as grade III astrocytoma after the radical resection of the tumor. In the case of an atypical lesion, a tumor should be considered in patients with MS. A small fraction of high-grade gliomas show no enhancement on MRI and no hypermetabolism on PET. Biopsy proved to be the essential step in a successful diagnostic workup. To the best of our knowledge, this is the first case of anaplastic astrocytoma with these radiological features reported in a patient with MS.
- Publikační typ
- kazuistiky MeSH
BACKGROUND: In multiple sclerosis (MS), dysphagia is an important and common clinical symptom. Although often overlooked and underdiagnosed, it can have a significant impact on a patient's life, including social integration, and it can lead to malnutrition, aspiration pneumonia, and suffocation, i.e., life-threatening complications. Early detection of dysphagia is essential to prevent these risks. However, the optimal screening method and the inter-relationship between different methods used for dysphagia screening are not clear. The aim of this study was to compare the diagnostic performance of a simple question about swallowing problems, the DYsphagia in MUltiple Sclerosis (DYMUS) swallowing questionnaire, and the Timed Water Swallowing Test (TWST) to detect dysphagia in people with relapsing-remitting MS (RRMS). METHODS: Patients with MS were asked about subjective swallowing difficulties and, regardless of their response, completed the DYMUS questionnaire and underwent the TWST at their routine follow-up visit. Patients with at least one positive screening method were offered an objective assessment of swallowing function using the Fiberoptic Endoscopic Evaluation of Swallowing (FEES). The results were statistically analyzed and correlated with demographic and MS-related parameters. RESULTS: Of the 304 people with RRMS enrolled in the study, 46 (15.1 %) reported having subjective difficulty swallowing when asked a simple question. The DYMUS questionnaire was positive in 59 (19.4 %) of the 304 patients; 51 (16.8 %) had an abnormality on the TWST. A clear correlation (r = 0.351, p < 0.01) was found between the DYMUS and TWST results, but a significant proportion of patients (about half) had an abnormality on only one of these tests. The positivity of at least one of the screening methods used (DYMUS or TWST) had a better chance of identifying a patient with dysphagia than a simple question (p < 0.001). Of the patients with a positive result for difficulty swallowing, 37 underwent FEES, which confirmed dysphagia in 94.6% of this subgroup. Patients with higher Expanded Disability Status Scale (EDSS) scores, female gender, and older age were at higher risk of developing dysphagia. CONCLUSION: The DYMUS questionnaire and TWST had a confirmed potential to identify more patients with dysphagia than a simple question about swallowing problems. However, our study found only a partial overlap between DYMUS and TWST; a combination of these two methods was more sensitive in identifying patients with MS at risk of dysphagia. Furthermore, the screening showed excellent specificity: almost 95 % of the positively screened patients had dysphagia confirmed by objective methods. Age, female gender, and a higher EDSS score appear to be potential risk factors for dysphagia in patients with MS.
Multiple sclerosis (MS) is a chronic neurodegenerative disease that affects the central nervous system (CNS). Currently, MS treatment is limited to several Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved medications that slow disease progression by immunomodulatory action. Fingolimod and siponimod have similar mechanisms of action, and consequently, their therapeutic effects may be comparable. However, while fingolimod is mainly used for relapsing-remitting MS (RRMS), siponimod, according to EMA label, is recommended for active secondary progressive MS (SPMS). Clinicians and scientists are analysing whether patients can switch from fingolimod to siponimod and identifying the advantages or disadvantages of such a switch from a therapeutic point of view. In this review, we aim to discuss the therapeutic effects of these two drugs and the advantages/disadvantages of switching treatment from fingolimod to siponimod in patients with the most common forms of MS, RRMS and SPMS.
- MeSH
- chronicko-progresivní roztroušená skleróza * farmakoterapie chemicky indukované MeSH
- fingolimod hydrochlorid škodlivé účinky MeSH
- hodnocení rizik MeSH
- imunosupresiva škodlivé účinky MeSH
- lidé MeSH
- neurodegenerativní nemoci * chemicky indukované farmakoterapie MeSH
- recidiva MeSH
- roztroušená skleróza * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Klíčová slova
- Okrelizumab,
- MeSH
- antigeny CD20 farmakologie imunologie MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * aplikace a dávkování farmakologie klasifikace terapeutické užití MeSH
- intravenózní podání metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- recidiva MeSH
- roztroušená skleróza diagnóza farmakoterapie klasifikace MeSH
- výběr pacientů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease that secondarily leads to axonal loss and associated brain atrophy. Disease-modifying drugs (DMDs) have previously been studied for their ability to affect specific immunity. This study investigates the effect of interferon beta-1a (INF) and glatiramer acetate (GA) administration on changes in innate immunity cell populations. METHODS: Sixty Caucasian female patients with relapsing-remitting MS undergo blood sample testing for 15 blood parameters at baseline, 1 month, 3 months, and 6 months after treatment by GA or IFN (started as their first-line DMD). RESULTS: A statistically significant difference in the change after 6 months was found in the parameter monocytes (relative count) in the group of patients treated with IFN. The median increase was 27.8%. Changes in many of the other 15 parameters studied were 10-20%. CONCLUSION: Innate immunity has long been neglected in MS immunopathology. The findings suggest that IFN treatment may modulate the immune response in MS by affecting monocyte function and may provide insight into the mechanisms of action of IFN in MS.
- MeSH
- glatiramer acetát terapeutické užití MeSH
- interferon beta 1a terapeutické užití MeSH
- interferon beta terapeutické užití MeSH
- lidé MeSH
- peptidy terapeutické užití MeSH
- přirozená imunita MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie patologie MeSH
- roztroušená skleróza * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: The influence of breastfeeding and it ́s duration on the course of multiple sclerosis (MS) is unclear. Here we analyzed a real-world data for breastfeeding women with MS and their disease course collected from a Czech national registry ReMuS. OBJECTIVES: To identify risk factors associated with not initiating breastfeeding after delivery, to analyze the impact of breastfeeding on the MS disease course, evaluate the assumption, that breastfeeding is not harmful in MS patients, and compare the disease course by breastfeeding status. MATERIALS AND METHODS: Using propensity score matching we compared Expanded Disability Status Scale (EDSS), confirmed disease worsening (CDW) and annual relapse rate (ARR) in breastfeeding and non-breastfeeding MS patients according to disease duration, disease modifying treatment (DMT) before pregnancy, last EDSS score before conception, age, and ARR during pregnancy. We also compared these parameters between breastfeeding patients not using a DMT and non-breastfeeding patients who resumed DMT within 3 months after delivery. EDSS, ARR, and CDW were collected at 12, 24, and 36 months after delivery. RESULTS: A total of 1681 pregnancies that ended in delivery were analyzed from 2013 through 2020. Change in ARR and EDSS values and 6-months CDW did not significantly differ between the analyzed groups. Compared with non-breastfeeding women who resumed DMT early after delivery, breastfeeding women with MS did not experience worse clinical outcomes even without initiating a DMT. DISCUSSION: Breastfeeding in Czech women with MS did not negatively affect the disease course and can be supported. Patients with MS can be treated with certain DMTs alongside breastfeeding and there is no need to stop breastfeeding, if the patient is clinically stable.
- MeSH
- kojení MeSH
- lidé MeSH
- progrese nemoci MeSH
- recidiva MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie MeSH
- roztroušená skleróza * farmakoterapie epidemiologie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Paraneoplastické, autoimunitní a idiopatického syndromy mozkového kmene a mozečku jsou nejčastěji paraneoplastického původu a rozvoj v jejich diagnostice a léčbě souvisí s objevením onkoneurálních protilátek a protilátek proti povrchovým antigenům struktur nervového systému a s využitím zobrazovacích metod. Znalost klinických obrazů umožňuje včasnou diagnostiku a v některých případech i úspěšnou léčbu.
Paraneoplastic, autoimmmune and idiopathic syndromes of brainstem and cerebellum are usually of paraneoplastic origin. The diagnostics are based on the detection of onconeural antibodies, neural cell surface antibodies and imaging methods. The early diagnostics is based on the index of clinical suspicion and enables effective treatment in some cases.
- MeSH
- autoimunitní nemoci nervového systému imunologie klasifikace patologie MeSH
- diferenciální diagnóza MeSH
- encefalitida klasifikace patologie MeSH
- lidé MeSH
- mozeček patologie MeSH
- mozkový kmen patologie MeSH
- nemoci mozku * diagnóza imunologie klasifikace patologie terapie MeSH
- paraneoplastické neurologické syndromy etiologie patologie MeSH
- syndrom opsoklonus-myoklonus diagnóza imunologie klasifikace patologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS) the most common treatment strategy has been to start with low-moderate efficacy disease modifying therapy (LE-DMT) and to escalate to more efficacious treatments in cases of breakthrough disease activity. However, recent evidence suggests a better outcome in patients commencing with moderate-high efficacy DMT (HE-DMT) immediately after clinical onset. OBJECTIVE: The aim of this study is to compare disease activity and disability outcomes in patients treated with the two alternative strategies using the Swedish and Czech national multiple sclerosis registries, taking advantage of the fact that the relative frequency of each strategy differs markedly between these two countries. METHODS: Adult RRMS patients who initiated their first-ever DMT between 2013 and 2016 and were included in the Swedish MS register were compared with a similar cohort from the MS register of the Czech Republic using propensity score overlap weighting as a balancing method. The main outcomes of interest were time to confirmed disability worsening (CDW), time to achieve an expanded disability status scale (EDSS) value of 4, time to relapse, and time to confirmed disability improvement (CDI). To support the results, a sensitivity analysis focusing solely on patients from Sweden starting with HE-DMT and patients from the Czech Republic starting with LE-DMT was performed. RESULTS: In the Swedish cohort, 42% of patients received HE-DMT as initial therapy compared to 3.8% of patients in the Czech cohort. The time to CDW was not significantly different between the Swedish and Czech cohorts (p-value 0.2764), with hazard ratio (HR) of 0.89 and a 95% confidence interval (CI) of 0.77-1.03. Patients from the Swedish cohort exhibited better outcomes for all remaining variables. The risk of reaching EDSS 4 was reduced by 26% (HR 0.74, 95%CI 0.6-0.91, p-value 0.0327), the risk of relapse was reduced by 66% (HR 0.34, 95%CI 0.3-0.39, p-value <0.001), and the probability of CDI was three times higher (HR 3.04, 95%CI 2.37-3.9, p-value <0.001). CONCLUSION: The analysis of the Czech and the Swedish RRMS cohorts confirmed a better prognosis for patients in Sweden, where a significant proportion of patients received HE-DMT as initial treatment.
- MeSH
- dospělí MeSH
- lidé MeSH
- recidiva MeSH
- registrace MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie epidemiologie MeSH
- roztroušená skleróza * farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Švédsko MeSH
BACKGROUND: The QuantiFERON®-Monitor (QFM) is an assay that measures interferon-γ production and was developed to provide an objective marker of complex immune response. In this study, we evaluated the use of the QFM test in patients with two forms of multiple sclerosis (MS), relapsing-remitting form treated with fingolimod (fMS) and secondarily progressive form not treated pharmacologically (pMS), and in healthy controls (HC). We hypothesized that IFN-γ levels would be lower in those subjects who are relatively more immunosuppressed and higher in those with normal or activated immune function. METHODS: This single-center observational study was conducted from November 2020 to October 2021 and compared results in three groups of patients: 86 healthy controls, 96 patients with pMS, and 78 fMS. Combination of lyophilized stimulants was added to 1 ml heparinized whole blood within 8 hr of collection. Plasmatic IFN-γ was measured using the ELISA kit for the QFM and data were obtained in IU/ml. RESULTS: The results showed that controls had nearly 2-fold higher levels of IFN-γ (QFM score) in median (q25, q75) 228.00 (112.20, 358.67) than the MS patient groups: pMS 144.80 (31.23, 302.00); fMS 130.50 (39.95, 217.07) which is statistically significant difference P-value: HC vs. pMS = 0.0071; HC vs. fMS = 0.0468. This result was also confirmed by a validation analysis to exclude impact of variable factors, such as disease duration and Expanded Disability Status Scale scores. CONCLUSIONS: Results showed that controls had higher levels of IFN-γ production than the MS patient groups and suggest that MS patients included in this study have a lower ability of immune system activation than HC. Results confirm that fingolimod is able to suppress production of IFN-γ. The fact that the QFM score of MS patients is significantly lower than that of HC may indicate a dysfunctional state of the immune system in baseline conditions.
