Electrophysiological markers and predictors of the disease course in primary progressive multiple sclerosis

2013 ◽  
Vol 20 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Regina Schlaeger ◽  
Marcus D’Souza ◽  
Christian Schindler ◽  
Leticia Grize ◽  
Ludwig Kappos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Linear Regression Analysis ◽  
Surrogate Marker ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disease Course ◽  
Disease Evolution ◽  
Primary Progressive ◽  
Edss Score ◽  
The Relationship

Background: Currently no valid surrogate marker exists for primary progressive multiple sclerosis (PPMS). Objective: Our aim was to prospectively investigate multimodal evoked potentials (EPs) as markers and predictors of the disease course in PPMS. Methods: Twenty-two PPMS patients were prospectively examined with visual, somatosensory and motor EPs and Expanded Disability Status Scale (EDSS) assessments at baseline (T0) and at six-month intervals over three years. Spearman rank correlation was used to determine the relationship between EP measures and EDSS. The relationship between disease evolution and a numerical score derived from z-transformed EP-latencies ( s-EP-Q) and baseline characteristics was further assessed using multivariable linear regression analysis. Results: s-EP-Q correlated with EDSS score at all points in time in cross-sectional comparison (0.53≤rs ≤0.68; 0.0007≤p≤0.0232) and also longitudinally by trend ( rs=0.46, p=0.0740). The s-EP-QT0 correlated with the EDSS score at year 3 (T6) ( rs=0.77, p<0.0001). The s-EP-Q changes became statistically significant six months before corresponding changes were seen in the EDSS score. EDSST6 as predicted by EDSST6= −1.027+0.037* age+0.217* s-EP-QT0 + 0.695* EDSST0 correlated with the observed values ( rs=0.92, p<0.0001). Conclusions: Multimodal EPs correlate well with disability in PPMS, and allow some prediction of the disease course over three years. These findings support a role of EPs as surrogate markers in clinical trials in PPMS.

scholarly journals Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mario Amatruda ◽  
Maria Petracca ◽  
Maureen Wentling ◽  
Benjamin Inbar ◽  
Kamilah Castro ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disease Course ◽  
Primary Progressive ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
One Year ◽  
Multiple Sclerosis Patients

Abstract The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non-diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS-P, n = 9) or slow (PPMS-NP, n = 10) disease course based on worsening disability and/or MRI-visible appearance of new T2 lesions over a one-year-assessment. Partial least squares-discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelin-d18:1/14:0 and mono-hexosylceramide-d18:1/20:0 were differentially abundant in the plasma of PPMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lyso-phosphatidic acid-18:2 (LPA-18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPA-18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsing–remitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelin-d18:1/14:0, mono-hexosylceramide-d18:1/20:0, and LPA-18:2 may represent important targets for future studies aimed at understanding disease progression in MS.

scholarly journals A composite measure to explore visual disability in primary progressive multiple sclerosis

2017 ◽  
Vol 3 (2) ◽  
pp. 205521731770962
Author(s):  
Valentina Poretto ◽  
Maria Petracca ◽  
Catarina Saiote ◽  
Enricomaria Mormina ◽  
Jonathan Howard ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Linear Regression Analysis ◽  
Visual Pathway ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Primary Progressive Multiple Sclerosis ◽  
Inner Plexiform Layer ◽  
Visual Disability ◽  
Primary Progressive ◽  
Main Components

Background Optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can provide complementary information on visual system damage in multiple sclerosis (MS). Objectives The objective of this paper is to determine whether a composite OCT/MRI score, reflecting cumulative damage along the entire visual pathway, can predict visual deficits in primary progressive multiple sclerosis (PPMS). Methods Twenty-five PPMS patients and 20 age-matched controls underwent neuro-ophthalmologic evaluation, spectral-domain OCT, and 3T brain MRI. Differences between groups were assessed by univariate general linear model and principal component analysis (PCA) grouped instrumental variables into main components. Linear regression analysis was used to assess the relationship between low-contrast visual acuity (LCVA), OCT/MRI-derived metrics and PCA-derived composite scores. Results PCA identified four main components explaining 80.69% of data variance. Considering each variable independently, LCVA 1.25% was significantly predicted by ganglion cell-inner plexiform layer (GCIPL) thickness, thalamic volume and optic radiation (OR) lesion volume (adjusted R2 0.328, p = 0.00004; adjusted R2 0.187, p = 0.002 and adjusted R2 0.180, p = 0.002). The PCA composite score of global visual pathway damage independently predicted both LCVA 1.25% (adjusted R2 value 0.361, p = 0.00001) and LCVA 2.50% (adjusted R2 value 0.323, p = 0.00003). Conclusion A multiparametric score represents a more comprehensive and effective tool to explain visual disability than a single instrumental metric in PPMS.

Overview of London trial of intramuscular interferon-b1a in primary-progressive multiple sclerosis

2004 ◽  
Vol 10 (3_suppl) ◽  
pp. S56-S57 ◽  
Author(s):  
David H Miller ◽  
Siobhan M Leary ◽  
Alan J Thompson
Keyword(s):  
Multiple Sclerosis ◽  
Pilot Study ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Patient Cohort ◽  
Quantitative Mr ◽  
Double Blinded ◽  
Clinical Measures ◽  
The Relationship

This short monograph describes the rationale, design and outcome of a pilot study of beta interferon in patients with primary progressive MS. A total of 50 patients were studied for 2 years using a randomized, double-blinded, placebo -controlled design. There was an emphasis on using MRI measures to evaluate outcome. The study showed that with the numbers studied, useful data could be obtained on safety and on efficacy on certain MRI measures. A larger study would be required to evaluate treatment on disability in this patient cohort and further work is needed to elucidate the relationship between quantitative MR and clinical measures over the longer term.

The relationship of age with the clinical phenotype in multiple sclerosis

2016 ◽  
Vol 22 (13) ◽  
pp. 1750-1758 ◽  
Author(s):  
A Scalfari ◽  
C Lederer ◽  
M Daumer ◽  
R Nicholas ◽  
GC Ebers ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Age At Onset ◽  
Phase Evolution ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Relapsing Remitting ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

Background: The multiple sclerosis (MS) clinical course and relapses frequency before progression vary widely. Objective: To investigate the influence of age on the MS phenotype. Methods: Among 751 primary progressive (PP = 217) and secondary progressive (SP = 534) MS patients from the London Ontario database, we assessed the relationship of age on the relapse frequency and on the progressive phase evolution, and the impact of relapses on the age at onset of progression. Results: Age at onset did not influence the early attacks frequency, but patients younger at onset had larger number of total attacks before progression (age = 27.4, 31.0 and 32.8 mean years; ⩾4, 2–3 and 1 relapses, respectively) and longer latency to SP. Although frequent early relapses predicted younger age at SP onset, patients with no attacks (primary progressive multiple sclerosis (PPMS)), or 1, 2–3 and ⩾4 relapses during the relapsing-remitting phase started progressing at similar age (38.6, 41.3, 41.4 and 39.2 mean years, respectively). The age at onset of progressive phase did not affect its evolution. Conclusions: Age strongly influences the phenotype before progression. Relapsing-remitting patients younger at onset are more likely to display a predominantly inflammatory course, yet relapses number does not affect the age at onset of progression.

A patient with established primary progressive multiple sclerosis transitions to ‘secondary’ relapsing–remitting disease course following a fulminant demyelinating episode

2011 ◽  
Vol 17 (10) ◽  
pp. 1262-1264 ◽  
Author(s):  
Melih Tutuncu ◽  
Nuri O Demirci ◽  
Feriha Özer ◽  
Sabahattin Saip ◽  
Orhun H Kantarci ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immunosuppressive Treatment ◽  
Acute Disseminated Encephalomyelitis ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disease Course ◽  
Primary Progressive ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Demyelinating Disorders

Primary progressive multiple sclerosis (PPMS), relapsing remitting MS (RRMS) and acute disseminated encephalomyelitis (ADEM) are clinically and immunopathogenetically distinct phenotypes of inflammatory demyelinating disorders of the central nervous system. Progression following RRMS is well described as secondary progressive MS. We report a patient with unexpected transition from long established PPMS to clinically and radiologically active RRMS after an ADEM-like fulminant demyelinating episode despite an immunosuppressive treatment preceding relapses. We note clearly accelerated brain atrophy after the RRMS course ensues. The unique disease course in this patient illustrates the dissociation of the biology and disability impact of relapses and progression.

Decreased MMP-9 production in primary progressive multiple sclerosis patients

2004 ◽  
Vol 10 (4) ◽  
pp. 376-380 ◽  
Author(s):  
J Sastre-Garriga ◽  
M Comabella ◽  
L Brieva ◽  
A Rovira ◽  
M Tintoré ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Progressive Multiple Sclerosis ◽  
Regulatory Mechanisms ◽  
Primary Progressive Multiple Sclerosis ◽  
Healthy Controls ◽  
Primary Progressive ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
The Relationship

Background: An increase in MMP-9 levels has been found in relapsing-remitting (RR) multiple sclerosis (MS) showing correlation with magnetic resonance (MR) parameters mainly during relapses. However, data regarding primary progressive (PP) MS is scarce. Objectives: To determine both the pro and active forms of MMP-9 in PPMS and transitional progressive (TP) MS, RRMS and healthy controls (HC), and to assess the relationship between MMP-9 levels and clinical and radiological variables in PP/TPMS. Methods: 73 patients with PP/TPMS, 50 RRMS and 43 HC were studied. Levels of pro and active forms of MMP-9 in serum were measured with ELISA. EDSS and MSFC scores were recorded and T2- and T1-weighted MR scans were obtained at the time of blood sampling and one and two years later for PP/TP MS cases. Results: MMP-9 levels were 202.27 ng/ml for PP/TPMS, 242.20 ng/ml for RRMS and 274.49 ng/ml for HC. MMP-9 levels were significantly lower in PP/TPMS compared to RRMS(P-0.026) and HC (P- 0.001). No significant correlations were found between MMP-9 levels and clinical scores or radiological parameters. Conclusions: These results point to different regulatory mechanisms of MMP-9 production and/or activity between PP/TPMS and RRMS.

Sign in / Sign up

Export Citation Format

Share Document