Full length articleReal-world walking in multiple sclerosis: Separating capacity from behavior
Introduction
Habitual physical activity (HPA) measurement has emerged as a walking outcome in MS [1] and Parkinson’s disease [2], with broad applications in health care [3], [4]. HPA improves upon available mobility measurements by quantifying the impact of disease on real-world functioning. Currently, HPA is commonly reported as (1) daily step counts or movement counts; or (2) amount of moderate physical activity (MPA) and vigorous physical activity (VPA). However, physical activity in all people, including those with chronic disease, is affected by a multitude of personal, environmental, and social factors [5], [6]. As a result, these statistics fail to distinguish subjects’ real-world walking capacity – which quantifies their ability to walk under real-world conditions, and is directly affected by MS – from physical activity behaviors not immediately attributable to disease. This dilemma that has been recognized [7], but not yet solved. Total daily activity is easy to calculate, but difficult to interpret when both disability and activity behaviors are variable.
Studies evaluating HPA in MS have borne out this concern. Although MS subjects are active less often then controls [8], [9], physical activity statistics (MPA and VPA) are correctly viewed as measures of activity behaviors, not precise measures of the impact of disease on subjects’ ability to be active. Daily step counts are the best known measure of real-world walking capacity, as shown by statistically significant correlations to the six-minute walk (6 MW), timed 25-foot walk (T25FW), and MS Walking Scale (MSWS-12) [10], [11]. However, daily counts explain less than half of the variance in these outcomes [10], [11], and they do not reliably change when patient-reported walking ability changes [12]. Although daily counts have been established as valid walking outcomes, they are most accurately viewed as imprecise measures of both walking capacity and activity behaviors.
To address these limitations, we set out to establish new HPA statistics that isolate the direct impact of disease from activity behaviors. We hypothesize that the maximum step rate (MSR) along with the habitual walking step rate (HWSR), a statistic derived through personalized activity modeling (PAM), can meet this objective, providing clinicians with real-world capacity outcomes in MS and potentially other chronic diseases. This hypothesis is validated in MS through correlational analysis to the aforementioned walking outcomes, which in turn sheds new light on the real-world meaning of existing measures.
Section snippets
Recruitment and study procedures
Study procedures were approved by the University of Virginia (UVa) Institutional Review Board, and written consent was obtained. Subjects with clinically definite MS [13], were recruited from the UVa Neurology Department outpatient clinic population along with healthy controls. All subjects were age 18–64 years and able to ambulate for six minutes, possibly with an assistive device. Those with neurological impairment from other diagnoses, orthopedic limitations, morbid obesity, or known cardiac
Subject demographics and outcome measures
In total, 88 subjects with MS [13] and 38 control subjects were recruited (Table 1). Among MS subjects, 52.3% had mild disability (EDSS 0–2.5), 35.2% moderate (EDSS 3.0–4.0), and 12.5% severe (EDSS ≥ 4.5). A higher proportion were female among MS subjects (83.0%) compared to controls (71.1%), though this difference was not statistically significant. Education was similar between groups, but age, employment status, years since symptom onset and diagnosis, and clinical outcomes showed statistically
Discussion
Our population spanned the full range of ambulatory MS-related disability by EDSS (range 1–6.5) and MSWS-12 (range 0–100), with approximately equal numbers of control subjects, mild MS subjects, and moderate to severe MS subjects. Beyond this range (EDSS > 6.5), HPA measurement is not appropriate.
The striking correlations between the MSR and all four walking outcomes support it as a valid measure of walking capacity. Correlation was strongest for 6 MW step rate and distance, respectively, followed
Conflict of interest
MME, SDP, and JCL have nothing to report. MDG reports grants from Biogen Idec, grants from Novartis, other from Acorda, other from Biogen Idec, other from Novartis, personal fees from Novartis, and personal fees from Sarepta outside the submitted work.
Acknowledgments
MDG is funded by the National Institutes of Health − National Institute of Neurologic Disorders and Stroke (K23NS062898). Additional funding was provided by the Broadband Wireless Access and Applications Center, an NSF-supported industry-university cooperative research center (NSF award #1266311), and a gift from the ziMS Foundation. We owe special thanks to Margaret Keller, the CNS of our clinical research program, and Kristina Sheridan, who inspired much of this work.
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Conducted all statistical analyses.