Fatigability measured by dual-task conditions

Abstract

Introduction: Many MS clinical studies estimate the association between a treatment or other variable and the time to an event of interest. These times can be the time to next relapse, the time to disability progression or the time to EDSS landmarks. Time to event outcomes require specialized statistical techniques to properly estimate the associations. Objectives/Aims: To introduce statistical approaches for time to event outcomes in MS clinical studies, the assumptions required for these analyses, and sample size calculations. Methods: For this session, we will describe the special features of time to event outcomes in MS clinical studies through the use of examples from recent clinical trials and simulated datasets. The data-sets in this session will focus on the time to disability progression, which is a common outcome measure in progressive MS trials. Results: The most commonly used techniques for estimation of the associations between exposures and time to event outcomes include Kaplan-Meier curves, log rank tests, and Cox proportional hazards models. Each approach is valid in the presence of right censoring, which means that some subjects are not observed to have the event of interest. We will describe extensions to these techniques to account for different types of censoring as well as recurrent events. Finally, we will describe sample size calculations for the analysis of time to event outcomes. Conclusion: Many MS clinical studies have a time to event outcome as the primary outcome. The statistical techniques for these outcomes make several assumptions, but departures from the assumptions can be accounted for by using more complex approaches. Sample size calculations are also available in order to design studies with these outcomes. Introduction: Fatigue in multiple sclerosis (MS) can be distinguished between the subjective feeling of fatigue and fatigability, a decrease in performance over time. Further, people may experience motor and cognitive fatigability, either separately or in combination , which may limit activity performance and participation. Objectives/Aims: To describe methods of assessing and interventions to reduce cognitive fatigability in MS. Methods: In this educational session, after introducing a theoretical framework of fatigue and fatigability, we provide some examples of relevant and meaningful methods to assess cognitive fatigability in (virtual) reality situations to use in (future) clinical practice and research. Interventions targeting cognitive fatigability are described. Results: While subjective fatigue is assessed using questionnaires, cognitive fatigability is measured by the decline in performance during cognitive fatigue-inducing tasks. These tasks usually include neuropsychological tests like symbol digit modalities test (SDMT), paced auditory serial addition test (PASAT) or N-back task. However, these tasks do not reflect the complexity of real-life situations, therefore more ecological measures are indicated and may include virtual reality applications. Although sparse, interventions specifically designed for cognitive fatigability include pharmacological , magnetic stimulation or behavioral approaches. Conclusion: Assessing cognitive fatigue and fatigability is challenging , though important to provide tailormade (rehabilitation) interventions for people with MS. Introduction: Fatigability, or state fatigue, is defined as a change in performance over time, and can be abnormal in persons with MS (pwMS). It is prevalent in the motor domain at ICF body function level and during walking at ICF activity level in at least half of pwMS with moderate to severe disability. It is thought to also contribute to perception of fatigue or execution of activities of daily life. Objectives/Aims: The objective of the educational course is to understand how motor fatigability at body function level (f.e. decreased in maximal muscle force), and walking fatigability (f.e. reduced speed, changes in gait pattern) can be measured, what are underlying causes and what is the implication for rehabilitation programs. Methods: Based on literature review and experimental studies, measurement methods and cutoff scores are presented. Insights on concurrent validity with fatigue, perceived capacity and daily life performances are presented where applicable. Results: At body function level, static and dynamic fatigue indexes are available for lower and upper limbs with acceptable reliability. At activity level, methods for detecting abnormal slowing down (distance walked index) or changes in gait pattern and quality (f.e. reduced cadence or variability in step duration) are presented including reliability and cutoff scores. The definition of distance walked versus gait quality changes is discussed. The relations between indexes and fatigue (MFIS), perceived upper limb use (MAM) and walking (MSWS-12) or daily life physical activity (IPAQ, Pittsburgh fatigability scale) are presented Conclusion: Fatigability in the motor domain at body function level and during walking at activity level can be reliably measured and are advised to take into account in clinical reasoning and determining rehabilitation ingredients. Disclosure of interest: Lectures provided for Roche.