scholarly journals Greater loss of axons in primary progressive multiple sclerosis plaques compared to secondary progressive disease

Brain ◽  
2009 ◽  
Vol 132 (5) ◽  
pp. 1190-1199 ◽  
Author(s):  
E. C. Tallantyre ◽  
L. Bo ◽  
O. Al-Rawashdeh ◽  
T. Owens ◽  
C. H. Polman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Secondary Progressive

Mitoxantrone as a potential therapy for primary progressive multiple sclerosis

2004 ◽  
Vol 10 (3_suppl) ◽  
pp. S58-S61 ◽  
Author(s):  
Olaf Stüve ◽  
Mariko Kita ◽  
Daniel Pelletier ◽  
Robert J Fox ◽  
Jerome Stone ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Western Europe ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Pharmacological Properties ◽  
Phase 2 ◽  
Double Blind ◽  
Primary Progressive ◽  
Secondary Progressive ◽  
Phase 2 Trial

Mitoxantrone (Novantrone®) was the first drug approved in western Europe and North A merica for treatment of secondary progressive multiple sclerosis (SPMS) and progressive relapsing MS (PRMS). Pharmacological properties of mitoxantrone, its role in SPMS, the study rational and design of an ongoing multi-centre, double blind, randomized, placebo -controlled phase 2 trial will be outlined in this article.

028 Treating progressive multiple sclerosis

2018 ◽  
Vol 89 (6) ◽  
pp. A12.1-A12
Author(s):  
Jordana Hughes ◽  
Vilija Jokubaitis ◽  
Mark Slee ◽  
Jeannette Lechner-Scott ◽  
Anneke Van der Walt ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Hazard Ratio ◽  
Primary Progressive Multiple Sclerosis ◽  
Disability Progression ◽  
Primary Progressive ◽  
Effect Of Therapy ◽  
Multivariable Regression ◽  
Multivariable Regression Models

IntroductionWe showed that the available immunotherapies do not modify disability outcomes when used in secondary progressive multiple sclerosis. However, these therapies are effective in advanced active multiple sclerosis. Primary progressive multiple sclerosis may present with or without superimposed relapses. Significance of these relapses for disability accumulation and treatment remains contested. We aimed to examine the effect of the available immunotherapies in primary progressive multiple sclerosis.Methods1427 eligible patients with primary progressive multiple sclerosis from MSBase were studied. Confirmed disability progression of disability was compared between treated and untreated propensity score-matched cohorts. Multivariable regression models were used to compare disability accrual between primary progressive multiple sclerosis with and without superimposed relapses. Finally, the effect of therapy on disability accrual in cohorts with and without superimposed relapses was analysed.Results173 treated and 373 untreated patients were matched. No differences in the risk of disability progression (p=0.79) and improvement (p=0.98) were observed over the median 3 year follow-up.The likelihood of disability progression was relatively lower in patients with superimposed relapses (hazard ratio=0.83, p<0.01). We observed an association between the proportion of time on immunotherapy and the hazard of disability progression in active (hazard ratio=0.96, p=0.01) but not in the inactive primary progressive disease (p=0.21).ConclusionSuperimposed relapses in primary progressive multiple sclerosis represent a favourable prognostic marker, associated with slower disability accrual. This is most likely attributed to the effectiveness of immunotherapy in active primary progressive disease. Relapse activity, therefore, is a treatable modifier of disability accrual in primary progressive disease.

Circulating microRNAs as biomarkers in progressive multiple sclerosis

2016 ◽  
Vol 23 (3) ◽  
pp. 403-412 ◽  
Author(s):  
Julia Vistbakka ◽  
Irina Elovaara ◽  
Terho Lehtimäki ◽  
Sanna Hagman
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Progressive Multiple Sclerosis ◽  
Body Fluids ◽  
Primary Progressive Multiple Sclerosis ◽  
Circulating Mirnas ◽  
Circulating Micrornas ◽  
Primary Progressive ◽  
Secondary Progressive ◽  
Exceptional Stability

Background: In multiple sclerosis (MS), microRNA (miRNA) dysregulation is mostly reported in different immune cells, but less information is available on circulating miRNAs that exert strong biomarker potential due to their exceptional stability in body fluids. Objective: The aim of this study was to profile expression of circulating miRNAs in primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) and assess their association with neurological worsening. Methods: The expressions of 84 different miRNAs were profiled in serum of 83 subjects (62 MS and 21 controls) using miScript miRNA techniques. First, they were screened on 18 PPMS and 10 controls; thereafter, 10 most aberrantly expressed miRNAs were validated on a larger cohort. Results: In comparison with controls, upregulation of miR-191-5p was found in both progressive MS subtypes, while miR-376c-3p was overexpressed only in PPMS. Additionally, upregulation of miR-128-3p and miR-24-3p was detected in PPMS when compared to controls and SPMS. Progression index correlated with miR-128-3p in PPMS and miR-375 in SPMS. Conclusion: We detected overexpression of four miRNAs that have not been previously associated with progressive forms of MS. The increased expression of circulating miR-191-5p seems to be associated with progressive forms of MS, while miR-128-3p seems to be associated mostly with PPMS.

scholarly journals Charting a global research strategy for progressive MS—An international progressive MS Alliance proposal

2021 ◽  
pp. 135245852110597
Author(s):  
Alan J Thompson ◽  
William Carroll ◽  
Olga Ciccarelli ◽  
Giancarlo Comi ◽  
Anne Cross ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Biomarker Discovery ◽  
Steering Committee ◽  
Progressive Multiple Sclerosis ◽  
Research Strategy ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Secondary Progressive ◽  
Underlying Mechanisms ◽  
Global Research

Background: Progressive forms of multiple sclerosis (MS) affect more than 1 million individuals globally. Recent approvals of ocrelizumab for primary progressive MS and siponimod for active secondary progressive MS have opened the therapeutic door, though results from early trials of neuroprotective agents have been mixed. The recent introduction of the term ‘active’ secondary progressive MS into the therapeutic lexicon has introduced potential confusion to disease description and thereby clinical management. Objective: This paper reviews recent progress, highlights continued knowledge and proposes, on behalf of the International Progressive MS Alliance, a global research strategy for progressive MS. Methods: Literature searches of PubMed between 2015 and May, 2021 were conducted using the search terms “progressive multiple sclerosis”, “primary progressive multiple sclerosis”, “secondary progressive MS”. Proposed strategies were developed through a series of in-person and virtual meetings of the International Progressive MS Alliance Scientific Steering Committee. Results: Sustaining and accelerating progress will require greater understanding of underlying mechanisms, identification of potential therapeutic targets, biomarker discovery and validation, and conduct of clinical trials with improved trial design. Encouraging developments in symptomatic and rehabilitative interventions are starting to address ongoing challenges experienced by people with progressive MS. Conclusion: We need to manage these challenges and realise the opportunities in the context of a global research strategy, which will improve quality of life for people with progressive MS.

Primary progressive multiple sclerosis: a distinct syndrome?

1996 ◽  
Vol 2 (3) ◽  
pp. 137-141 ◽  
Author(s):  
GV McDonnell ◽  
SA Hawkins
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Progressive Decline ◽  
Primary Progressive ◽  
Therapeutic Trials ◽  
Relapsing Remitting ◽  
Progressive Course

Multiple sclerosis (MS) has long been recognised to have both a relapsing-remitting and progressive course. More recently patients with progressive disease have been further sub-divided into those with a progressive course from onset (primary progressive MS) and those with progressive decline following an initially relapsing-remitting period (secondary progressive MS). Diversity in MS may not however be restricted to clinical course. There is growing evidence that the subgroups of MS also differ with respect to clinical features, epidemiology, pathogenesis, genetics and neuroimaging appearances. In this review we outline the criteria variously applied in the classification of MS patients, addressing the need for a dear nomenclature. We evaluate the proposition that primary progressive MS has a prof ile distinct from other MS categories, contrasting the separate differential diagnoses and examining the implications for future therapeutic trials.

The pathology of primary progressive multiple sclerosis

2002 ◽  
Vol 8 (2) ◽  
pp. 93-97 ◽  
Author(s):  
W Brück ◽  
C Lucchinetti ◽  
H Lassmann
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Current Knowledge ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Underlying Pathology ◽  
Clinical Subtype

The present review will focus on the current knowledge of the pathology of primary progressive multiple sclerosis lesions. Multiple sclerosis (MS) is an inflammatory demyelinating disease with a broad clinical variability. The main disease courses are relapsing-remitting, secondary progressive and primary progressive MS. Pathological studies examining the specific underlying pathology of a defined clinical subtype are rare. Here, we focus on the phatological characteristics of the MS lesions and summarize the current findings of the phatology of primary progressive MS with respect to inflammation, oligodendrocyte/myelin pathology, axon destruction and immunopathology of the lesions.

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