scholarly journals Elevated sCD40L in Secondary Progressive Multiple Sclerosis in Comparison to Non-progressive Benign and Relapsing Remitting Multiple Sclerosis

2021 ◽  
Vol 13 ◽  
pp. 117957352110507
Author(s):  
Qi Wu ◽  
Qin Wang ◽  
Jennifer Yang ◽  
Jacob WS Martens ◽  
Elizabeth A Mills ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Plasma Levels ◽  
Disease Onset ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: The long-term prognosis of relapsing-remitting multiple sclerosis (RRMS) is usually unfavorable as most patients transition to secondary progressive multiple sclerosis (SPMS) with accumulative disability. A rare form of non-progressive multiple sclerosis (MS) also exists, known as benign MS (BMS or NPMS), which lacks disease progression defined as Expanded Disability Status Scale (EDSS) ≤3 after 15 years of disease onset without treatment. Purpose: Our study aims to identify soluble plasma factors predicting disease progression in multiple sclerosis (MS). Research Design and Study Sample: We utilized Luminex multiplex to analyze plasma levels of 33 soluble factors, comparing 32 SPMS patients to age-, sex-, and disease duration-matched non-progressive BMS patients, as well as to RRMS patients and healthy controls. Results: Plasma levels of EGF, sCD40L, MCP1/CCL2, fractalkine/CX3CL1, IL-13, Eotaxin, TNFβ/LTα, and IL-12p40 were significantly different between the various types of MS. Plasma sCD40L was significantly elevated in SPMS compared to BMS and RRMS. The combination of MCP1/CCL2 and sCD40L discriminated between RRMS and SPMS. MCP1/CCL2 was found to be the most effective classifier between BMS and RRMS, while BMS was most effectively distinguished from SPMS by the combination of sCD40L and IFNγ levels. Conclusions: These differences may facilitate personalized precision medicine and aid in the discovery of new therapeutic targets for disease progression through the improvement of patient stratification.

scholarly journals Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies

2018 ◽  
Vol 4 (2) ◽  
pp. 205521731878334 ◽  
Author(s):  
Francisco Coret ◽  
Francisco C Pérez-Miralles ◽  
Francisco Gascón ◽  
Carmen Alcalá ◽  
Arantxa Navarré ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Disease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis. Objective To explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing–remitting multiple sclerosis patients. Methods Our study included 204 patients treated for relapsing–remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan–Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion, and multivariate survival analysis with a Cox regression model was used to analyse prognostic factors. Results Relapsing–remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1–18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0. Conclusions The favourable influence of disease-modifying therapies on long-term disability in relapsing–remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

scholarly journals Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 84 ◽  
Author(s):  
Stephanie Herman ◽  
Torbjörn Åkerfeldt ◽  
Ola Spjuth ◽  
Joachim Burman ◽  
Kim Kultima
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Progression ◽  
High Resolution Mass Spectrometry ◽  
Progressive Multiple Sclerosis ◽  
Pyrimidine Metabolism ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

To better understand the pathophysiological differences between secondary progressive multiple sclerosis (SPMS) and relapsing-remitting multiple sclerosis (RRMS), and to identify potential biomarkers of disease progression, we applied high-resolution mass spectrometry (HRMS) to investigate the metabolome of cerebrospinal fluid (CSF). The biochemical differences were determined using partial least squares discriminant analysis (PLS-DA) and connected to biochemical pathways as well as associated to clinical and radiological measures. Tryptophan metabolism was significantly altered, with perturbed levels of kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin in SPMS patients compared with RRMS and controls. SPMS patients had altered kynurenine compared with RRMS patients, and altered indole-3-acetate compared with controls. Regarding the pyrimidine metabolism, SPMS patients had altered levels of uridine and deoxyuridine compared with RRMS and controls, and altered thymine and glutamine compared with RRMS patients. Metabolites from the pyrimidine metabolism were significantly associated with disability, disease activity and brain atrophy, making them of particular interest for understanding the disease mechanisms and as markers of disease progression. Overall, these findings are of importance for the characterization of the molecular pathogenesis of SPMS and support the hypothesis that the CSF metabolome may be used to explore changes that occur in the transition between the RRMS and SPMS pathologies.

Paraneoplastic cerebellar degeneration mimicking development of secondary progressive multiple sclerosis in a patient with relapsing–remitting multiple sclerosis

2010 ◽  
Vol 17 (4) ◽  
pp. 498-500
Author(s):  
RM Gracien ◽  
M Kordulla ◽  
U Ziemann
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Cerebellar Degeneration ◽  
Secondary Progressive Multiple Sclerosis ◽  
Paraneoplastic Cerebellar Degeneration ◽  
Diagnostic Challenge ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Paraneoplastic cerebellar degeneration (PCD) is a rare non-metastatic complication of cancer mediated by T lymphocytes and auto-antibodies directed against Purkinje cells of the cerebellum. We report a patient with relapsing–remitting multiple sclerosis who developed a progressive cerebellar syndrome with dysarthria, ataxic gait and vertigo mimicking development of secondary progressive multiple sclerosis but caused by anti-Yo antibody positive PCD associated with ovarian cancer, presenting an unusual diagnostic challenge.

White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis

2016 ◽  
Vol 22 (11) ◽  
pp. 1429-1437 ◽  
Author(s):  
Kim A Meijer ◽  
Nils Muhlert ◽  
Mara Cercignani ◽  
Varun Sethi ◽  
Maria A Ron ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Cognitive Domains ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Tract Damage

Background: While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. Objective: The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. Methods: Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). Results: A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance ( R2 = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. Conclusion: Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients.

Diagnostic uncertainty during the transition to secondary progressive multiple sclerosis: Multicenter study in Argentina

2020 ◽  
pp. 135245852092458 ◽  
Author(s):  
Juan Ignacio Rojas ◽  
Liliana Patrucco ◽  
Ricardo Alonso ◽  
Orlando Garcea ◽  
Norma Deri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Onset ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Multicenter Cohort Study ◽  
Diagnostic Uncertainty ◽  
Secondary Progressive ◽  
Kaplan Meier ◽  
Relapsing Remitting ◽  
Time Required

Background: A period of diagnostic uncertainty often characterizes the clinical transition from relapsing to secondary progressive multiple sclerosis (SPMS). Objective: The aim of this study was to describe the length of time required to reclassify relapsing-remitting MS (RRMS) patients who have clinically transitioned to SPMS (diagnosis uncertainty). Methods: This is a retrospective multicenter cohort study conducted in Argentina, identifying in every center all patients with diagnosis of MS who transitioned from RRMS to SPMS during the follow-up. We identified the dates of the last definitive RRMS and first definitive SPMS diagnoses for diagnostic uncertainty. The time required to reclassify RRMS who transitioned to SPMS and the time from disease onset to reclassify SPMS were calculated using the Kaplan–Meier method. Results: A total of 170 patients were included, where the mean age at disease onset (first symptom) was 36 ± 6 years; the length of time required to reclassify RRMS patients who transitioned to SPMS was 3.3 ± 1.1 years (range = 1–7 years); and the time from disease onset to classify SPMS was 19.4 ± 8.5 years (range = 16–35 years). Conclusion: A period of diagnostic uncertainty regarding the transition from RRMS to SPMS was present in many of our patients, with a mean time of 3.3 years.

scholarly journals Living with secondary progressive multiple sclerosis in Europe: perspectives of multiple stakeholders

2021 ◽  
Vol 11 (1) ◽  
pp. 9-19
Author(s):  
Øivind Torkildsen ◽  
Ralf A Linker ◽  
Jose MM Sesmero ◽  
Simone Fantaccini ◽  
Rainel Sanchez-de la Rosa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Diagnostic Tools ◽  
Patient Journey ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Assessment Guidelines ◽  
Research Findings ◽  
Relapsing Remitting Multiple Sclerosis

The transition from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (SPMS) remains a clinical challenge owing to the heterogeneous course of the disease, indistinct disease progression and lack of availability of validated biomarkers and diagnostic tools. This article summarizes the outcomes from an international expert group meeting conducted to validate the preliminary research findings gathered through interviews with primary healthcare stakeholders and pharmaceutical representatives, and to understand the current and future patient journey of SPMS across seven European countries. We highlight the uncertainty in SPMS diagnosis and management and, consequently, the need for uniform assessment guidelines, enhanced awareness and a collaborative effort between the stakeholders associated with SPMS patient care and the pharmaceutical industry.

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