Tato kazuistika popisuje léčbu pacienta s relabující-remitující formou roztroušené sklerózy (RR-RS), který zároveň trpí Crohnovou nemocí. Po počáteční terapii glatiramer-acetátem a interferonem beta-1a došlo u pacienta k pokračující aktivitě onemocnění, která si vyžádala změnu léčby. S ohledem na potřebu vysoce účinné terapie a pacientovu preferenci méně častých návštěv zdravotnického zařízení byla v dubnu 2022 zahájena léčba ponesimodem. Po více než dvouleté léčbě pacient zůstává klinicky stabilní, bez nových atak či progrese nemoci, a Crohnova nemoc je v remisi. Pacient dobře toleruje léčbu a vede plnohodnotný život, což potvrzuje účinnost a bezpečnost ponesimodu jako vhodné volby pro pacienty s aktivní RS a komorbiditami.
This case report describes the treatment of a patient with relapsing-remitting multiple sclerosis (RR-RS) who also suffers from Crohn's disease. After initial therapy with glatiramer acetate and interferon beta-1a, the patient had ongoing disease activity that required a change in treatment. Considering the need for highly effective therapy and the patient's preference for less frequent visits to the medical facility, treatment with ponesimod was started in April 2022. After more than two years of treatment, the patient remains clinically stable, without new relapses or disease progression, and Crohn's disease is in remission. The patient tolerates the treatment well and leads a full life, which confirms the efficacy and safety of ponesimod as a suitable choice for patients with active MS and comorbidities.
- Klíčová slova
- ponesimod,
- MeSH
- Crohnova nemoc diagnóza farmakoterapie MeSH
- demyelinizační nemoci diagnostické zobrazování MeSH
- dospělí MeSH
- kvalita života MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- progrese nemoci MeSH
- receptory sfingosin-1-fosfátu * antagonisté a inhibitory terapeutické užití MeSH
- relabující-remitující roztroušená skleróza * diagnóza farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Because secondary progressive multiple sclerosis (SPMS) is associated with worse prognosis, early predictive tools are needed. We aimed to use systematic literature review and advanced methods to create and validate a clinical tool for estimating individual patient risk of transition to SPMS over five years. METHODS: Data from the Jacobs Multiple Sclerosis Center (JMSC) and the Multiple Sclerosis Center Amsterdam (MSCA) was collected between 1994 and 2022. Participants were relapsing-remitting adult patients at initial evaluation. We created the tool in four stages: (1) identification of candidate predictors from systematic literature review, (2) ordinal cutoff determination, (3) feature selection, (4) feature weighting. RESULTS: Patients in the development/internal-validation/external-validation datasets respectively (n = 787/n = 522/n = 877) had a median age of 44.1/42.4/36.6 and disease duration of 7.7/6.2/4.4 years. From these, 12.6 %/10.2 %/15.4 % converted to SPMS (median=4.9/5.2/5.0 years). The DAAE Score was named from included predictors: Disease duration, Age at disease onset, Age, EDSS. It ranges from 0 to 12 points, with risk groups of very-low=0-2, low=3-7, medium=8-9, and high≥10. Risk of transition to SPMS increased proportionally across these groups in development (2.7 %/7.4 %/18.8 %/40.2 %), internal-validation (2.9 %/6.8 %/26.8 %/36.5 %), and external-validation (7.5 %/9.6 %/22.4 %/37.5 %). CONCLUSION: The DAAE Score estimates individual patient risk of transition to SPMS consistently across datasets internationally using clinically-accessible data. With further validation, this tool could be used for clinical risk estimation.
- MeSH
- chronicko-progresivní roztroušená skleróza * diagnóza MeSH
- dospělí MeSH
- hodnocení rizik metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- progrese nemoci * MeSH
- relabující-remitující roztroušená skleróza diagnóza MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
- MeSH
- azathioprin aplikace a dávkování MeSH
- centrální nervový systém diagnostické zobrazování patologie MeSH
- diferenciální diagnóza * MeSH
- dospělí MeSH
- hormony kůry nadledvin aplikace a dávkování MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- paréza etiologie mozkomíšní mok MeSH
- recidiva MeSH
- relabující-remitující roztroušená skleróza diagnóza MeSH
- vaskulitida centrálního nervového systému * diagnostické zobrazování farmakoterapie patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The initial phase of multiple sclerosis (MS), often known as clinically isolated syndrome (CIS), is a critical period for identifying individuals at high risk of progressing to full-blown MS and initiating timely treatment. In this study, we aimed to evaluate the prognostic value of C-X-C motif chemokine ligand 13 (CXCL13) and interleukin-8 (IL-8) as potential markers for CIS patients' conversion to MS. Our study encompassed patients with CIS, those with relapsing-remitting MS (RRMS), and control subjects, with sample analysis conducted on both cerebrospinal fluid (CSF) and serum. Patients were categorized into four groups: CIS-CIS (no MS development within 2 years), CIS-RRMS (conversion to RRMS within 2 years), RRMS (already diagnosed), and a control group (CG) with noninflammatory central nervous system disorders. Results showed significantly elevated levels of CXCL13 in CSF across all patient groups compared with the CG (p < 0.0001, Kruskal-Wallis test). Although CXCL13 concentrations were slightly higher in the CIS-RRMS group, statistical significance was not reached. Similarly, significantly higher levels of IL-8 were detected in CSF samples from all patient groups compared with the CG (p < 0.0001, Kruskal-Wallis test). Receiver operating characteristic analysis in the CIS-RRMS group identified both CXCL13 (area under receiver operating characteristic curve = .959) and IL-8 (area under receiver operating characteristic curve = .939) in CSF as significant predictors of CIS to RRMS conversion. In conclusion, our study suggests a trend towards elevated CSF IL-8 and CSF CXCL13 levels in CIS patients progressing to RRMS. These findings emphasize the importance of identifying prognostic markers to guide appropriate treatment strategies for individuals in the early stages of MS.
- MeSH
- biologické markery mozkomíšní mok krev MeSH
- chemokin CXCL13 * mozkomíšní mok krev MeSH
- demyelinizační nemoci mozkomíšní mok MeSH
- dospělí MeSH
- interleukin-8 * mozkomíšní mok krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- prognóza MeSH
- progrese nemoci * MeSH
- relabující-remitující roztroušená skleróza * mozkomíšní mok krev diagnóza MeSH
- roztroušená skleróza mozkomíšní mok krev diagnóza 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
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.
Ozanimod je modulátor receptorů pro sfingosin-1fosfát (S1P) selektivní k receptorům typu 1 a 5 (S1PR1 a S1PR5), zatímco vůči typům 2, 3 a 4 vykazuje afinitu minimální nebo žádnou. Je indikován pro léčbu relaps-remitentní formy roztroušené sklerózy a ulcerózní kolitidy. U těchto nemocí prokázal dobrou účinnost i bezpečnostní profil. Jeho mechanismus účinku spočívá především ve snížení migrace lymfocytů do místa zánětu centrální nervové soustavy a střev. Podává se perorálně jedenkrát denně v udržovací dávce 0,92 mg, v úvodu léčby se používá týdenní režim eskalace dávky. Nejčastějšími nežádoucími účinky jsou lymfopenie, nazofaryngitidy a elevace jaterních enzymů. Významné lékové interakce mohou nastat při kombinaci s imunosupresivy a bradykardizujícími léky, a také s induktory cytochromu P450, CYP2C8.
Ozanimod is a modulator of sphingosine-1-phosphate (S1P) receptors selective for types 1 and 5 (S1PR1 and S1PR5), whereas it shows minimal or no affinity for types 2, 3 and 4. It is indicated for the treatment of reiapsing-remitting forms of multiple sclerosis and ulcerative colitis. It has shown good efficacy and safety profile in these diseases. Its mechanism of action is primarily to reduce the migration of lymphocytes to the site of inflammation in the central nervous system and intestine. It is administered orally once a day at a maintenance dose of 0.92 mg, with a weekly dose escalation regimen at the start of treatment. The most common adverse effects are lymphopenia, nasopharyngitis, and elevation of liver enzymes. Significant drug interactions may occur when combined with immunosuppressive and bradycardic drugs as well as with cytochrome P450, CYP2C8 inducers.
- Klíčová slova
- ozanimod,
- MeSH
- farmakokinetika MeSH
- inhibice migrace buněk účinky léků MeSH
- klinická studie jako téma MeSH
- lékové interakce MeSH
- nežádoucí účinky léčiv klasifikace MeSH
- receptory sfingosin-1-fosfátu * klasifikace terapeutické užití účinky léků MeSH
- relabující-remitující roztroušená skleróza diagnóza farmakoterapie MeSH
- ulcerózní kolitida diagnóza farmakoterapie MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- alemtuzumab terapeutické užití MeSH
- imunosupresivní léčba metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- relabující-remitující roztroušená skleróza * diagnóza terapie MeSH
- transplantace hematopoetických kmenových buněk MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Early diagnosis and treatment of patients with multiple sclerosis (MS) are associated with better outcomes; however, diagnostic delays remain a major problem. OBJECTIVE: Describe the prevalence, determinants and consequences of delayed diagnoses. METHODS: This single-centre ambispective study analysed 146 adult relapsing-remitting MS patients (2016-2021) for frequency and determinants of diagnostic delays and their associations with clinical, cognitive, imaging and biochemical measures. RESULTS: Diagnostic delays were identified in 77 patients (52.7%), including 42 (28.7%) physician-dependent cases and 35 (24.0%) patient-dependent cases. Diagnosis was delayed in 22 (15.1%) patients because of misdiagnosis by a neurologist. A longer diagnostic delay was associated with trends towards greater Expanded Disability Status Scale (EDSS) scores (B = 0.03; p = 0.034) and greater z-score of the blood neurofilament light chain (B = 0.35; p = 0.031) at the time of diagnosis. Compared with patients diagnosed at their first clinical relapse, patients with a history of >1 relapse at diagnosis (n = 63; 43.2%) had a trend towards greater EDSS scores (B = 0.06; p = 0.006) and number of total (B = 0.13; p = 0.040) and periventricular (B = 0.06; p = 0.039) brain lesions. CONCLUSION: Diagnostic delays in MS are common, often determined by early misdiagnosis and associated with greater disease burden.
- MeSH
- dospělí MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek patologie MeSH
- opožděná diagnóza MeSH
- prevalence MeSH
- recidiva MeSH
- relabující-remitující roztroušená skleróza * diagnóza epidemiologie patologie MeSH
- roztroušená skleróza * diagnóza epidemiologie patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE: The lack of reliable diagnostic and/or prognostic biomarkers for multiple sclerosis (MS) is the major obstacle to timely and accurate patient diagnosis in MS patients. To identify new proteins associated with MS we performed a detailed proteomic analysis of cerebrospinal fluid (CSF) of patients newly diagnosed with relapsing-remitting MS (RRMS) and healthy controls. MATERIAL: Reflecting significantly higher prevalence of MS in women we included only women patients and controls in the study. To eliminate a potential effect of therapy on the CSF composition, only the therapy-naïve patients were included. METHODS: Pooled CSF samples were processed in a technical duplicate, and labeled with stable-isotope coded TMT tags. To maximize the proteome coverage, peptide fractionation using 2D-LC preceded mass analysis using Orbitrap Fusion Tribrid Mass Spectrometer. Differential concentration of selected identified proteins between patients and controls was verified using specific antibodies. RESULTS: Of the identified 900 CSF proteins, we found 69 proteins to be differentially abundant between patients and controls. In addition to several proteins identified as differentially abundant in MS patients previously, we observed several linked to MS for the first time, namely eosinophil-derived neurotoxin and Nogo receptor. CONCLUSIONS: Our data confirm differential abundance of several previously proposed protein markers, and provide indirect support for involvement of copper-iron disbalance in MS. Most importantly, we identified two new differentially abundant CSF proteins that seem to be directly connected with myelin loss and axonal damage via TLR2 signaling and Nogo-receptor pathway in women newly diagnosed with RRMS.
- MeSH
- biologické markery mozkomíšní mok MeSH
- lidé MeSH
- mozkomíšní mok chemie metabolismus MeSH
- proteiny v mozkomíšním moku mozkomíšní mok MeSH
- proteom analýza metabolismus MeSH
- proteomika MeSH
- relabující-remitující roztroušená skleróza * diagnóza MeSH
- roztroušená skleróza * diagnóza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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
