Clinical Outcome Measures for Multiple Sclerosis

Background: To assess disease progression in multiple sclerosis (MS) several outcome measures are available. The interrelation of changes on different scales has not been studied extensively and the concept of combining scales has only recently been introduced in MS. Objective: To explore combining different clinical outcome measures in the evaluation of disease progression in MS. Methods: In 553 patients we studied the presence of relevant changes according to standard definitions on the Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), Timed 25-Foot Walk (T25FW) and the Multiple Sclerosis Impact Scale (MSIS-29). We examined ‘exclusive worsening’ (worsening on one measure while not worsening on any other measure) and ‘opposing changes’ (worsening on one measure while improving on another measure). Finally, we investigated the impact of combining assessments. Results: Based on the EDSS alone, 140 patients progressed. However, almost twice as many (275) showed worsening on any of the clinical outcome measures. Exclusive worsening was observed in 37 patients on the EDSS, 13 on the 9HPT, 39 on the T25FW and 44 on the MSIS physical. Of all worsened patients 76 (28%) showed opposing changes, a phenomenon predominantly observed when combining physician-based and patient-derived outcome measures. Conclusion: When assessing disease progression in MS, sensitivity to change can be increased by combining different outcome measures. The added value is especially present when combining measures from different perspectives. However, further research is needed to evaluate the optimal way to combine outcome measures before implementing this strategy in clinical studies.

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The added value of cognition-targeted exercise versus symptom-targeted exercise for multiple sclerosis fatigue: A randomized controlled pilot trial

PLoS ONE ◽

10.1371/journal.pone.0258752 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0258752

Author(s):

Azza Alketbi ◽

Salah Basit ◽

Nouran Hamza ◽

Lori M. Walton ◽

Ibrahim M. Moustafa

Keyword(s):

Multiple Sclerosis ◽

Clinical Outcome ◽

Outcome Measures ◽

Recruitment Rate ◽

Control Group ◽

Entire Study ◽

Randomized Controlled ◽

Significant Difference ◽

Intervention Protocol

Background Fatigue is considered one of the most common symptoms of multiple sclerosis (MS) and lacks a current standardized treatment. Therefore, the aim of this study was to examine the feasibility and effectiveness of a cognition-targeted exercise versus symptom-targeted exercise for MS fatigue. Methods In this Pilot, parallel-group, randomized controlled trial, sixty participants with multiple sclerosis, were randomly assigned to either a Cognition-Targeted Exercise (CTE) (N = 30, mean age 41) or a Symptom-Targeted Exercise (STE) (N = 30, mean age 42). The participants in the experimental group received eight, 50-minute sessions of weekly Cognitive Behavior Therapy (CBT) in addition to a CTE Program; whereas, participants in the control group received eight, 50-minute sessions of weekly CBT in addition to the standardized physiotherapy program (STE Program). Feasibility was assessed through recruitment rate, participant retention, adherence and safety, in addition to clinical outcome measures, including: (1) Modified Fatigue Impact Scale (MFIS), (2) Work and Social Adjustment Scale (WSAS), (3) Hospital Anxiety and Depression Scale (HADS), and Perceived Stress Scale (PSS). All outcome measures were assessed at baseline (pretreatment), following completion of the eight visit intervention protocol, and at 3-months follow-up. Results The recruitment rate was 60% and 93% of participants completed the entire study. The recruited participants complied with 98% of the required visits. No adverse events were recorded. A Generalized Estimation Equation Model revealed a significant difference over time as an interaction term during the post and follow up visit for all clinical outcome measures (p < .001). Conclusion The addition of CTE to CBT exhibited positive and more lasting influence on MS fatigue outcomes compared to Symptom-Targeted Exercise (STE). Feasibility and efficacy data from this pilot study provide support for a full-scale RCT of CTE as an integral component of Multiple Sclerosis fatigue management.

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Clinical Outcome Measures and Rating Scales in Multiple Sclerosis Trials

Mayo Clinic Proceedings ◽

10.4065/72.11.1070 ◽

1997 ◽

Vol 72 (11) ◽

pp. 1070-1079 ◽

Cited By ~ 28

Author(s):

Dean M. Wingerchuk ◽

John H. Noseworthy ◽

Brian G. Weinshenker

Keyword(s):

Multiple Sclerosis ◽

Clinical Outcome ◽

Outcome Measures ◽

Rating Scales

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Clinical Outcome Measures for Research in Multiple Sclerosis

Journal of Neuro-Ophthalmology ◽

10.1097/00041327-200112000-00014 ◽

2001 ◽

Vol 21 (4) ◽

pp. 296-301 ◽

Cited By ~ 36

Author(s):

Laura J. Balcer

Keyword(s):

Multiple Sclerosis ◽

Clinical Outcome ◽

Outcome Measures

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Diffusion tensor imaging in early relapsing-remitting multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/135245850100700504 ◽

2001 ◽

Vol 7 (5) ◽

pp. 290-297 ◽

Cited By ~ 9

Author(s):

Colette M Griffin ◽

Declan T Chard ◽

Olga Ciccarelli ◽

Raj Kapoor ◽

Gareth J Barker ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Outcome ◽

Outcome Measures ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Region Of Interest ◽

Volume Ratio ◽

Early Disease ◽

Normal Appearing White Matter ◽

Relapsing Remitting

Diffusion tensor magnetic resonance imaging (DTI) indices are abnormal in patients with established multiple sclerosis (MS). The objective of this study was to examine the diffusion characteristics of MS lesions, normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in MS patients with early relapsing-remitting disease. A further objective was to investigate the relationship between three DTI parameters (fractional anisotropy (FA), mean diffusivity (MD) and volume ratio (VR)) and clinical outcome measures (Kurtzke expanded disability status scale (EDSS) and MS Functional Composite Measure) in early disease. DTI was performed in 28 patients and 27 controls. Analysis was carried out using a region of interest (ROI) approach. ROIs were placed in 12 NAWM and nine NAGM regions. Significant differences were found in FA, MD and VR between lesions and NAWM (P<0.001 for all three DTI parameters). No significant differences were found between patients and controls when examining NAWM or NAGM, although there was a trend for abnormal NAWM FA and VR in some regions. No correlation was found between DTI parameters in lesions, NAWM or NAGM and the clinical outcome measures. The lack of significant DTI abnormality in the NAWM and NAGM may reflect a lack of pathological change or a limited sensitivity of DTI using ROI methodology. Previous studies have shown abnormalities in T1 relaxation time, magnetisation transfer ratio (MTR) and N-Acetyl aspartate (NAA) in this cohort of patients, and as such, DTI using a region of interest (ROI) approach may not be as sensitive as other MR techniques in detecting subtle changes in normal appearing brain tissue in early disease.

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Developing clinical outcome measures in multiple sclerosis: an evolving process

Multiple Sclerosis Journal ◽

10.1191/1352458502ms846ed ◽

2002 ◽

Vol 8 (5) ◽

pp. 357-358 ◽

Cited By ~ 6

Author(s):

Alan J Thompson

Keyword(s):

Multiple Sclerosis ◽

Clinical Outcome ◽

Outcome Measures

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The measure tells the tale: Clinical outcome measures in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458517690825 ◽

2017 ◽

Vol 23 (5) ◽

pp. 626-627 ◽

Cited By ~ 3

Author(s):

Hanneke E Hulst ◽

Alan J Thompson ◽

Jeroen JG Geurts

Keyword(s):

Multiple Sclerosis ◽

Clinical Outcome ◽

Outcome Measures

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The Multiple Sclerosis Functional Composite: a new clinical outcome measure for multiple sclerosis trials

Multiple Sclerosis Journal ◽

10.1191/1352458502ms845oa ◽

2002 ◽

Vol 8 (5) ◽

pp. 359-365 ◽

Cited By ~ 140

Author(s):

R A Rudick ◽

G Cutter ◽

S Reingold

Keyword(s):

Multiple Sclerosis ◽

Clinical Trials ◽

Cognitive Function ◽

Clinical Outcome ◽

Outcome Measures ◽

Standard Therapy ◽

Outcome Measure ◽

Task Force ◽

Multiple Sclerosis Functional Composite ◽

Clinical Outcome Measure

With the advent and widespread use of partially effective disease modifying drug therapies for multiple sclerosis (MS), future clinical trials will undoubtedly test experimental interventions against standard therapy, or will test combinations of drugs against standard therapy. In either case, incremental progress in slowing disability progression in future MS clinical trials will require much larger sample sizes, more sensitive outcome measures, or a combination of the two. Because improved clinical outcome methods would likely accelerate progress in MS therapeutics, the National Multiple Sclerosis Society (NMSS) convened an international task force in 1994 to recommend improved clinical outcome measures. As the result of a two-year process of discussion and data analysis, the task force recommended the Multiple Sclerosis Functional Composite (MSFC) as a new clinical outcome measure for future MS trials. MSFC consists of timed tests of walking, arm function, and cognitive function, expressed as a single score along a continuous scale. The task force recommended that MSFC be included in future MS trials, and recommended a series of validation studies. Subsequent studies have provided evidence that MSFC correlates moderately with Expanded Disability Status Scale (EDSS), and that correlation is driven by strong correlations with the ambulatory function component; arm function and cognitive function correlate at lower levels with EDSS. The MSFC correlates better than EDSS with magnetic resonance imaging (MRI) variables, including brain atrophy, and shows significant correlation with patient-reported disease-related quality of life (QOL). MSFC and short-term change in MSFC correlate with future clinical and MRI status, and the strength of the correlations compares favorably with well-known cardiovascular risk factors. The studies in aggregate indicate that MSFC and MSFC change are clinically meaningful, and that MSFC has substantial advantages over alternative clinical outcome measures for MS clinical trials.

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