scholarly journals NR1H3 p.Arg415Gln Is Not Associated To Multiple Sclerosis Risk

2016 ◽  
Author(s):  
◽  
Chris Cotsapas
Keyword(s):  
Multiple Sclerosis ◽  
Sample Size ◽  
False Positive ◽  
Progressive Disease ◽  
Low Frequency ◽  
Common Variant ◽  
Primary Progressive ◽  
Disease Subtype ◽  
Multiple Sclerosis Risk

AbstractA recent study by Wang et al claims the low-frequency variant NR1H3 p.Arg415Gln is pathological for multiple sclerosis and determines a patient’s likelihood of primary progressive disease. We sought to replicate this finding in the International MS Genetics Consortium (IMSGC) patient collection, which is 13-fold larger than the collection of Wang et al, but we find no evidence that this variant is associated either with MS or disease subtype. Wang et al also report a common variant association in the region, which we show captures the association the IMSGC reported in 2013. Therefore, we conclude that the reported low-frequency association is a false positive, likely generated by insufficient sample size. The claim of NR1H3 mutations describing a Mendelian form of MS - of which no examples exist - can therefore not be substantiated by data.

scholarly journals Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Cell ◽  
2018 ◽  
Vol 175 (6) ◽  
pp. 1679-1687.e7 ◽  
Author(s):  
Mitja Mitrovič ◽  
Nikolaos A. Patsopoulos ◽  
Ashley H. Beecham ◽  
Theresa Dankowski ◽  
An Goris ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Low Frequency ◽  
Multiple Sclerosis Risk

scholarly journals Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes

2016 ◽  
Vol 23 (9) ◽  
pp. 1258-1267 ◽  
Author(s):  
Luis Ruano ◽  
Emilio Portaccio ◽  
Benedetta Goretti ◽  
Claudia Niccolai ◽  
Milton Severo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Progressive Multiple Sclerosis ◽  
Multivariable Logistic Regression Analysis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Disease Subtype ◽  
Clinical Onset ◽  
Disease Subtypes ◽  
In Cis

Background: There is limited and inconsistent information on the clinical determinants of cognitive impairment (CI) in multiple sclerosis (MS). Objective: The aim of this study was to compare the prevalence and profile of CI across MS disease subtypes and assess its clinical determinants. Methods: Cognitive performance was assessed through the Brief Repeatable Battery and the Stroop test in consecutive patients with MS referred to six Italian centers. CI was defined as impairment in ⩾ 2 cognitive domains. Results: A total of 1040 patients were included, 167 with clinically isolated syndrome (CIS), 759 with relapsing remitting (RR), 74 with secondary progressive (SP), and 40 with primary progressive (PP) disease course. The overall prevalence of CI was 46.3%; 34.5% in CIS, 44.5% in RR, 79.4% in SP, and 91.3% in PP. The severity of impairment and the number of involved domains were significantly higher in SP and primary progressive multiple sclerosis (PPMS) than in CIS and RR. In multivariable logistic regression analysis, the presence of CI was significantly associated with higher Expanded Disability Status Scale (EDSS) and older age. Conclusion: CI is present in all MS subtypes since the clinical onset and its frequency is increased in the progressive forms, but these differences seem to be more associated with patient age and physical disability than to disease subtype per se.

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.

scholarly journals Soluble E-selectin in multiple sclerosis: raised concentrations in patients with primary progressive disease.

1996 ◽  
Vol 60 (1) ◽  
pp. 20-26 ◽  
Author(s):  
G Giovannoni ◽  
J W Thorpe ◽  
D Kidd ◽  
B E Kendall ◽  
I F Moseley ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Primary Progressive ◽  
Soluble E Selectin

Intracellular cytokine profile in T-cell subsets of multiple sclerosis patients: different features in primary progressive disease

2001 ◽  
Vol 7 (3) ◽  
pp. 145-150 ◽  
Author(s):  
J. Killestein ◽  
B.F. den Drijver ◽  
W.L. van der Graaff ◽  
B.M.J. Uitdehaag ◽  
C.H. Polman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Progressive Disease ◽  
Cytokine Profile ◽  
T Cell Subsets ◽  
Intracellular Cytokine ◽  
Primary Progressive ◽  
Multiple Sclerosis Patients

scholarly journals Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Cell ◽  
2020 ◽  
Vol 180 (2) ◽  
pp. 403
Author(s):  
Mitja Mitrovič ◽  
Nikolaos A. Patsopoulos ◽  
Ashley H. Beecham ◽  
Theresa Dankowski ◽  
An Goris ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Low Frequency ◽  
Multiple Sclerosis Risk

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

scholarly journals Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Cell ◽  
2019 ◽  
Vol 178 (1) ◽  
pp. 262 ◽  
Author(s):  
Mitja Mitrovič ◽  
Nikolaos A. Patsopoulos ◽  
Ashley H. Beecham ◽  
Theresa Dankowski ◽  
An Goris ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Low Frequency ◽  
Multiple Sclerosis Risk

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.

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