Assessment of Body Motion and Muscle Weakness: Outcome Evaluation in Frail Elderly and DMD Subjects

Muscle weakness is a common symptom in elderly population and in children with Duchenne muscular dystrophy (DMD), causing impaired mobility. DMD is a devastating degenerative disease caused by a mutation in the dystrophin gene, leading to the absence of the corresponding protein. Children with DMD experience with disease progression a gradual decline in their ability to perform functional tasks. Precise methods of measurement are necessary to more accurately establish the effect of treatment and find the temporal trend in functional motor status. With regard to the aging population, it is largely recognized that there is a substantial need for an accurate health assessment. Thus, it can have significant implications for older patients' care planning and future quality of life. Despite ongoing research, the development of reliable and objective outcome measures in this population is still a major challenge. The development of these outcome measures is further complicated by certain aspects such as frailty, comorbidity, and heterogeneity in this population. The assessment of health's status in aged population and DMD children is not only useful for the prediction of health decline with age, but also for the evaluation of the outcomes of early treatments in both populations. In DMD, large research efforts are made to find efficient treatments to slow/stop the disease progression. Finding appropriate outcome measures which reflect an improvement or stabilization in functional ability of the subject is also another challenge that clinicians are currently facing. The research aims of this thesis were: (i) to provide new and accurate measures/outcomes in order to assess the effect of treatment and to determine the temporal trend in functional motor status in two types of disorders related to muscle weakness (frailty and Duchenne muscular dystrophy); (ii) to analyze relevant body movements such as postural transitions and gait in laboratory as well as in real-world conditions/environment; (iii) to compare the objective outcomes obtained by analyzing body movements to the relevant clinical scores. New objective parameters have been proposed to quantify the sit-to-stand and stand-to-sit movements. In regard to the one of the most functional demanding daily tasks which is the ability to rise from a chair (sit-to-stand transition), these parameters showed high sensitivity to change. From a clinical point of view, they separated successfully frail elderly subjects from healthy elderly subjects, as well as different evaluations of frail elderly before and after the rehabilitation program. The new parameters developed in the current study may capture more subtle functional changes that might help for prediction of adverse events during the disability development. A new algorithm was designed for detection of the sit-to-stand and stand-to-sit postural transitions patterns in real-life conditions based only on one body-worn inertial sensor. For the first time a technical validation was proposed with real-world data and its superiority compared to existing controlled validation protocols was shown. The proposed algorithm provides a simple method to detect and characterize postural transitions in healthy subjects and also in disorders such as chronic pain and frail elderly subjects. We showed that gait parameters obtained during long distance walking separated successfully the DMD patients from age-matched healthy children. The study showed the potential of such parameters to distinguish between different stages of the disease and open new perspectives for an objective assessment of the efficacy of some new therapies associated with Duchenne muscular dystrophy. We believe that these research investigations may have applicability in both clinical and research fields related to elderly, DMD children and probably other neuromuscular disorders.


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