Longitudinal changes in magnetisation transfer ratio in secondary progressive multiple sclerosis: data from a randomised placebo controlled trial of lamotrigine

2011 ◽  
Vol 259 (3) ◽  
pp. 505-514 ◽  
Author(s):  
T. Hayton ◽  
J. Furby ◽  
K. J. Smith ◽  
D. R. Altmann ◽  
R. Brenner ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Magnetisation Transfer ◽  
Magnetisation Transfer Ratio ◽  
Longitudinal Changes ◽  
Transfer Ratio ◽  
Secondary Progressive

scholarly journals Magnetisation transfer ratio abnormalities in primary and secondary progressive multiple sclerosis

2019 ◽  
Vol 26 (6) ◽  
pp. 679-687 ◽  
Author(s):  
James William L Brown ◽  
Azmain Chowdhury ◽  
Baris Kanber ◽  
Ferran Prados Carrasco ◽  
Arman Eshaghi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Healthy Controls ◽  
Magnetisation Transfer ◽  
Magnetisation Transfer Ratio ◽  
Transfer Ratio ◽  
Secondary Progressive ◽  
Normal Appearing White Matter ◽  
Meningeal Inflammation ◽  
Cortical Grey Matter

Background: In relapse-onset multiple sclerosis (MS), tissue abnormality – as assessed with magnetisation transfer ratio (MTR) imaging – is greater in the outer cortical and inner periventricular layers. The cause of this remains unknown but meningeal inflammation has been implicated, particularly lymphoid follicles, which are seen in secondary progressive (SP) but not primary progressive (PP) MS. Cortical and periventricular MTR gradients might, therefore, differ in PPMS and SPMS if these follicles are responsible. Objective: We assessed cortical and periventricular MTR gradients in PPMS, and compared gradients between people with PPMS and SPMS. Methods: Using an optimised processing pipeline, periventricular normal-appearing white matter and cortical grey-matter MTR gradients were compared between 51 healthy controls and 63 people with progressive MS (28 PPMS, 35 SPMS). Results: The periventricular gradient was significantly shallower in healthy controls (0.122 percentage units (pu)/band) compared to PPMS (0.952 pu/band, p < 0.0001) and SPMS (1.360 pu/band, p < 0.0001). The cortical gradient was also significantly shallower in healthy controls (−2.860 pu/band) compared to PPMS (−3.214 pu/band, p = 0.038) and SPMS (−3.328 pu/band, p = 0.016). Conclusion: Abnormal periventricular and cortical MTR gradients occur in both PPMS and SPMS, suggesting comparable underlying pathological processes.

scholarly journals Longitudinal changes of cerebral glutathione (GSH) levels associated with the clinical course of disease progression in patients with secondary progressive multiple sclerosis

2016 ◽  
Vol 23 (7) ◽  
pp. 956-962 ◽  
Author(s):  
In-Young Choi ◽  
Phil Lee ◽  
Abbey J Hughes ◽  
Douglas R Denney ◽  
Sharon G Lynch
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Disease Progression ◽  
Clinical Status ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Multiple Quantum ◽  
Longitudinal Changes ◽  
Secondary Progressive ◽  
Motor Strength

Background: Increased oxidative stress leads to loss of glutathione (GSH). We have reported lower cerebral GSH in patients with secondary progressive multiple sclerosis (SPMS), indicating the involvement of oxidative stress in multiple sclerosis (MS) pathophysiology. Objective: This study expanded upon our earlier work by examining longitudinal changes in cerebral GSH in patients with SPMS in relation to their clinical status. Methods: A total of 13 patients with SPMS (Expanded Disability Status Scale (EDSS) = 4.0–6.5; MS duration = 21.2 ± 8.7 years) and 12 controls were studied over 3–5 years. GSH mapping was acquired from frontal and parietal regions using a multiple quantum chemical shift imaging technique at 3 T. Clinical assessments of the patient’s disability included EDSS, gait, motor strength, ataxia, tremor, brainstem function and vision changes. Results: Brain GSH concentrations in patients were lower than those in controls for both baseline and 3- to 5-year follow-ups. Longitudinal GSH changes of patients were associated with their neurologist’s blinded appraisal of their clinical progression. Patients judged to have worsening clinical status had significantly greater declines in frontal GSH concentrations than those with stable clinical status. Conclusion: GSH provides a distinct measure associated with the disease progression in SPMS, possibly due to its dynamic alignment with pathogenic processes of MS related to oxidative stress.

scholarly journals A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis

2015 ◽  
Vol 22 (4) ◽  
pp. 533-543 ◽  
Author(s):  
J Kuhle ◽  
M Hardmeier ◽  
G Disanto ◽  
K Gugleta ◽  
M Ecsedi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Analysis Of Covariance ◽  
Long Term Effects ◽  
Long Term Outcome ◽  
Secondary Progressive

Objectives: To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). Methods: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. Results: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R2: 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited ( R2: 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. Conclusions: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.

Reliability of Outcome Measures in Clinical Trials in Secondary Progressive Multiple Sclerosis

Neurology ◽  
2020 ◽  
Vol 96 (1) ◽  
pp. e111-e120 ◽  
Author(s):  
Marcus W. Koch ◽  
Jop Mostert ◽  
Pavle Repovic ◽  
James D. Bowen ◽  
Bernard Uitdehaag ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Outcome Measures ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Disability Progression ◽  
Secondary Progressive ◽  
Randomized Controlled ◽  
Disability Status ◽  
Over Time

ObjectiveTo investigate the reliability of clinical outcomes in secondary progressive multiple sclerosis (SPMS) trials, we compared the frequency of progression and improvement events on different clinical outcome measures in the placebo arms of 2 large randomized controlled trial (RCT) datasets.MethodsUsing original trial data from the placebo arms of IMPACT (International MS Secondary Progressive Avonex Controlled Trial) and ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis), 2 large RCTs in SPMS, we compared disability progression and similarly defined improvement with and without 3- or 6-month confirmation on the outcome measures Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and their combinations.ResultsIn both datasets, the EDSS showed the highest rates of improvement over time, and the smallest difference between progression and improvement rates, followed by the T25FW and the 9HPT. For the T25FW and 9HPT, improvement rates were fairly stable over time and remained at below or around the 10% level. For the EDSS, improvement rates increased in parallel with disability progression rates.ConclusionsAll investigated outcome measures in SPMS showed some evidence of random variation and measurement error, the T25FW and 9HPT less so than the more established outcome EDSS. Our findings are relevant for the design and critical appraisal of trials in SPMS.

Sign in / Sign up

Export Citation Format

Share Document