Does MRI lesion activity regress in secondary progressive multiple sclerosis?

2010 ◽  
Vol 16 (4) ◽  
pp. 434-442 ◽  
Author(s):  
Y. Zhao ◽  
AJ Petkau ◽  
A. Traboulsee ◽  
A. Riddehough ◽  
DKB Li
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Short Term ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri ◽  
Short Term Trend

Background: The rate of new contrast-enhancing lesions (CELs) on monthly magnetic resonance imaging (MRI) scans has been shown to decrease over a 9-month period in placebo-treated patients with relapsing—remitting (RR) multiple sclerosis (RRMS). Objective: We examined this phenomenon in placebo-treated secondary progressive MS (SPMS) patients. Methods: Patients were chosen from two clinical trials. Monthly scans were taken at screening, baseline and months 1—9 for Cohort-1 and months 1—6 for Cohort-2. We examined the monthly new CEL rates according to initial CEL level: 0, 1—3, >3 CELs at screening, and presence and absence of pre-study relapses. Results: Respectively, 59, 21 and 14 of the 94 Cohort-1 patients, and 36, 17 and 9 of the 62 Cohort-2 patients had 0, 1—3 and >3 initial CELs. For Cohort-1, the monthly new CEL rates did not change during follow-up, regardless of initial CEL level. For Cohort-2, the monthly rate was unchanged in the 0 initial CEL subgroup, but decreased 33% (95% confidence interval: 8%, 52%) from months 1—3 to months 4—6 in the other two subgroups. For the combined cohorts, a decreasing rate was observed in the 12 patients with >3 initial CELs and pre-study relapses. Conclusions: The short-term trend of new CEL activity in placebo-treated SPMS patients may vary across cohorts.

Clinical and Magnetic Resonance Imaging Predictors of Disability in Primary and Secondary Progressive Multiple Sclerosis

1996 ◽  
Vol 1 (4) ◽  
pp. 218-222 ◽  
Author(s):  
NA Losseff ◽  
DPE Kingsley ◽  
WI McDonald ◽  
DH Miller ◽  
AJ Thompson
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Initial Study ◽  
Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Secondary Progressive ◽  
Short Period ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Study

The role of magnetic resonance imaging (MRI) in predicting disability in multiple sclerosis (MS) remains unclear. In this study 21 patients with primary and secondary progressive MS were reviewed 5 years following a serial MRI study of 6 months duration. In the secondary progressive group (n=11) there was a significant relationship between the occurrence of enhancing lesions and clinical relapses during the initial 6 months and increase in diability 5 years later. For both groups change in disability over the initial study period was predictive of outcome. These results suggest that the presence and frequency of gadolinium enhancement (a marker of inflammation) and changes in disability over a short period are predictive of future deterioration in progressive patients.

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

2014 ◽  
Vol 20 (12) ◽  
pp. 1654-1657 ◽  
Author(s):  
Ilana Katz Sand ◽  
Stephen Krieger ◽  
Colleen Farrell ◽  
Aaron E Miller
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Transition Period ◽  
Clinical Phenotype ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Diagnostic Uncertainty ◽  
Secondary Progressive ◽  
Relapsing Remitting

Secondary progressive multiple sclerosis (MS) is typically defined as deterioration independent of relapses for ≥ 6 months following an initial relapsing–remitting course; however, this definition is not always easily applied in clinical practice and the declaration of the change in clinical phenotype is often delayed. To identify the length of time required to re-classify relapsing–remitting MS (RRMS) patients whom have clinically transitioned to secondary progressive MS (SPMS) in clinical practice. We reviewed 123 patients with long-term follow-up and identified a sub-group whom transitioned from RRMS to SPMS, then characterized this transition period. There were 14/20 patients who transitioned during the follow-up period that had visits with uncertainty related to the clinical phenotype characterized by possible, but not definitive progression. The mean duration of this period of uncertainty was 2.9 ± 0.8 years. A period of diagnostic uncertainty regarding the transition from RRMS to SPMS existed in many of our patients. Potential reasons included the subtle nature of early progressive disease and caution in applying a progressive label, in light of the lack of evidence-based treatments as well as third-party payer concerns. Delay in definitive identification of an SPMS phenotype has a variety of implications related to patient care and research.

Modelling new enhancing MRI lesion counts in multiple sclerosis

2001 ◽  
Vol 7 (5) ◽  
pp. 298-304 ◽  
Author(s):  
M P Sormani ◽  
P Bruzzi ◽  
M Rovaris ◽  
F Barkhof ◽  
G Comi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Negative Binomial ◽  
Surrogate Marker ◽  
Parametric Models ◽  
Parametric Modelling ◽  
Resonance Imaging ◽  
Baseline Activity ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri

Magnetic resonance imaging (MRI) has been established as the most relevant paraclinical tool for diagnosing and monitoring multiple sclerosis (MS). In this context, counting the number of new enhancing lesions on monthly MRI scans is widely used as a surrogate marker of MS activity when evaluating the effect of treatments. In this study, we investigated whether parametric models based on mixed Poisson distributions (the Negative Binomial (NB) and the Poisson-Inverse Gaussian (P-IG) distributions) were able to provide adequate fitting of new enhancing lesion counts in MS. We found that the NB model gave good approximations in relapsing7remitting and secondary progressive MS patients not selected for baseline MRI activity, whereas the P-IG distribution modelled better new enhancing lesion counts in relapsing-remitting MS patients selected for baseline activity. This study shows that parametric modelling for MS new enhancing lesion counts is feasible. This approach should provide more targeted tools for the design and the analysis of MRI monitored clinical trials in MS.

scholarly journals Current advancements in promoting remyelination in multiple sclerosis

2018 ◽  
Vol 25 (1) ◽  
pp. 7-14 ◽  
Author(s):  
David Kremer ◽  
Rainer Akkermann ◽  
Patrick Küry ◽  
Ranjan Dutta
Keyword(s):  
Multiple Sclerosis ◽  
Precursor Cells ◽  
Resonance Imaging ◽  
Major Focus ◽  
Short Term ◽  
Myelin Repair ◽  
Relapsing Remitting ◽  
Oligodendrocyte Precursor ◽  
Magnetic Resonance Imaging Mri ◽  
Endogenous Process

Current multiple sclerosis (MS) therapies are effective in reducing relapse rate, short-term measures of disability, and magnetic resonance imaging (MRI) measures of inflammation in relapsing remitting MS (RRMS), whereas in progressive/degenerative disease phases these medications are of little or no benefit. Therefore, the development of new therapies aimed at reversing neurodegeneration is of great interest. Remyelination, which is usually a spontaneous endogenous process, is achieved when myelin-producing oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs). Even though these precursor cells are abundant in MS brains, their regeneration capacity is limited. Enhancing the generation of myelin-producing cells is therefore a major focus of MS research. Here we present an overview of the different advancements in the field of remyelination, including suitable animal models for testing remyelination therapies, approved medications with a proposed role in regeneration, myelin repair treatments under investigation in clinical trials, as well as future therapeutics aimed at facilitating myelin repair.

The predictive value of gadolinium enhancement for long term disability in relapsing-remitting multiple sclerosis-preliminary results

2001 ◽  
Vol 7 (1) ◽  
pp. 23-25 ◽  
Author(s):  
N A Losseff ◽  
D H Miller ◽  
D Kidd ◽  
A J Thompson
Keyword(s):  
Multiple Sclerosis ◽  
Median Number ◽  
Short Term ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Relapsing Remitting Multiple Sclerosis

As short-term MRI studies are increasingly being used to monitor disease activity in multiple sclerosis (MS) it is vital to establish if short-term MRI activity is predictive of long term clinical outcome. We followed up after 5 years a group of 10 benign (relapsing-remitting MS with a disease duration 410 years and EDSS 43) and 10 early relapsing-remitting patients who previously had monthly serial MRI scans for 6 months. In the early relapsing-remitting group median EDSS at entry to the initial serial study was three and in the benign group 2.5. At 5-year follow up, five of these 20 patients had developed a definite deterioration in EDSS. The median number of new enhancing lesions detected originally in the group that had deteriorated was 11 (7-17) compared to 0 (0-5) new enhancing lesions, for those who had not deteriorated (P50.05). There was a trend towards a higher baseline T2 lesion load in the group with a definite change in EDSS but this was not significant. This study suggests that short-term measurement of the number of gadolinium enhancing lesions may predict long term outcome in relapsing-remitting MS.

scholarly journals Contactin-1 and contactin-2 in cerebrospinal fluid as potential biomarkers for axonal domain dysfunction in multiple sclerosis

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881953 ◽  
Author(s):  
Madhurima Chatterjee ◽  
Marleen JA Koel-Simmelink ◽  
Inge MW Verberk ◽  
Joep Killestein ◽  
Hugo Vrenken ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Progressive Multiple Sclerosis ◽  
Clinically Isolated Syndrome ◽  
Resonance Imaging ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Contactin-1 and contactin-2 are important for the maintenance of axonal integrity. Objective To investigate the cerebrospinal fluid levels of contactin-1 and contactin-2 in multiple sclerosis patients and controls, and their potential use as prognostic markers for neurodegeneration. Methods Cerebrospinal fluid contactin-1 and contactin-2 were measured in relapsing–remitting multiple sclerosis ( n = 41), secondary progressive multiple sclerosis ( n = 26) and primary progressive multiple sclerosis patients ( n = 13) and controls ( n = 18), and in a second cohort with clinically isolated syndrome patients ( n = 88, median clinical follow-up period of 2.3 years) and controls ( n = 20). Correlations/linear regressions were analysed with other baseline cerebrospinal fluid axonal damage markers and cross-sectional/longitudinal magnetic resonance imaging features. Results Contactin-1 and contactin-2 levels were up to 1.4-fold reduced in relapsing–remitting multiple sclerosis (contactin-1: p = 0.01, contactin-2: p = 0.02) and secondary progressive multiple sclerosis (contactin-1: p = 0.05, contactin-2: p = 0.02) compared to controls. In clinically isolated syndrome patients, contactin-1 tended to increase when compared to controls ( p = 0.07). Both contactin-1 and contactin-2 correlated with neurofilament light, neurofilament heavy and magnetic resonance imaging metrics differently depending on the disease stage. In clinically isolated syndrome patients, baseline contactin-2 level (β = –0.42, p = 0.04) predicted the longitudinal decline in cortex volume. Conclusion Cerebrospinal fluid contactin-1 and contactin-2 reveal axonal dysfunction in various stages of multiple sclerosis and their inclusion to the biomarker panel may provide better insight into the extent of axonal damage/dysfunction.

scholarly journals Cerebrospinal fluid growth-associated protein 43 in multiple sclerosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Åsa Sandelius ◽  
Sofia Sandgren ◽  
Markus Axelsson ◽  
Clas Malmeström ◽  
Lenka Novakova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Resonance Imaging ◽  
Secondary Progressive ◽  
Highly Active ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying

AbstractNeurodegeneration in multiple sclerosis (MS) correlates with disease progression and reparative processes may be triggered. Growth-associated protein 43 (GAP-43) exhibits induced expression during axonal growth and reduced expression during MS progression. We aimed to evaluate if GAP-43 can serve as a biomarker of regeneration in relapsing-remitting MS (RRMS) and whether disease-modifying therapies (DMTs) influence GAP-43 concentration in cerebrospinal fluid (CSF). GAP-43 was measured using an enzyme-linked immunosorbent assay in 105 MS patients (73 RRMS, 12 primary progressive MS, 20 secondary progressive MS) and 23 healthy controls (HCs). In 35 of the patients, lumbar puncture, clinical assessment, and magnetic resonance imaging was performed before initiation of therapeutic intervention, and at follow-up. CSF GAP-43 concentration was significantly lower in progressive MS compared with HCs (p = 0.004) and RRMS (p =  < 0.001) and correlated negatively with disability (p = 0.026). However, DMTs did not alter CSF GAP-43. Interestingly, in RRMS CSF GAP-43 levels were higher in patients with signs of active inflammatory disease than in patients in remission (p = 0.042). According to CSF GAP-43 concentrations, regeneration seems reduced in progressive MS, increased during disease activity in RRMS but is unaffected by treatment of highly active DMTs.

Two-year follow-up study of primary and transitional progressive multiple sclerosis

2002 ◽  
Vol 8 (2) ◽  
pp. 108-114 ◽  
Author(s):  
G T Ingle ◽  
V L Stevenson ◽  
D H Miller ◽  
S M Leary ◽  
M Rovaris ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Time Points ◽  
Follow Up Study ◽  
Disease Mechanisms ◽  
Short Period ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Characteristics

This study documents changes in clinical and magnetic resonance imaging (MRI) characteristics in a large cohort of patients with primary and transitional progressive multiple sclerosis (PP and TPMS) over 2 years. Patients with PPMS and TPMS were recruited from six European centres and underwent clinical and MRI examination at three time points: baseline, year one and year two. Of the 190 patients recruited clinical data were available on 125 patients (66%, five centres) and MRI data were available on 113 patients (59%, four centres) at 2 years. Significant increases were seen in T2 load and T1 hypointensity, while brain and cord volume decreased. In PPMS significantly higher lesion loads were found in those who presented with non-cord syndromes when compared to cord presentation and there was a trend to greater brain atrophy in those who deteriorated clinically over the course of the study compared to those who remained stable. Significant cord atrophy was only seen in those with a cord presentation. Measurable changes in MRI parameters can be detected in PPMS patients over a relatively short period of time. MRI quantification is likely to be useful in elucidating disease mechanisms in PPMS and in the execution of clinical trials.

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