Sample
The sample was recruited through neurology practices located in the USA, and testing occurred in a single MS center. The three inclusion criteria were (a) neurologist confirmed diagnosis of MS [19] (b) capacity for independent ambulation or ambulation with an assistive device and (c) willingness to voluntarily complete testing. Those who had a relapse in the past 30 days were excluded from participation. Participants were recruited through an email flyer that was distributed among participants in a database from previous studies conducted in the laboratory over the past five years and through local media, promotional flyers and medical records. Overall, 190 people were contacted, 124 were screened and recruited, but 28 cancelled and were unable to be re-scheduled. The final sample included 96 patients who satisfied inclusion criteria and participated.
Measures
Timed 25-foot walk (T25FW)
The T25FW was administered as a measure of walking speed. This assessment consisted of the participant walking 25 feet, with or without an assistive device, as quickly and safely as possible in a hallway clear of obstacles. The main outcome measure was the mean time (s) to complete two trials of the T25FW [20]; shorter times reflect faster walking speed.
Timed-Up-and-Go (TUG)
The TUG was administered as a measure of walking mobility [21] as it involves standing up, walking, turning, and sitting down. The TUG consisted of the participant sitting on a chair, standing up with arms crossed over the chest, walking around an object placed 10 feet in front of the chair, and returning to a seated position on the chair as quickly and safely as possible. The participants completed two trials and the main outcome was mean time (s) to complete the TUG [21] (i.e., time from arising from the chair to the moment sitting back on the chair); shorter times reflect better walking mobility.
Six-minute walk
The 6 MW was included as a measure of walking endurance. The 6 MW was performed using a rectangular and carpeted course with four hallways that each exceeded 50 m in length and that were clear of obstructions and foot traffic. The participants walked around the entire course during the 6 MW in a clockwise pattern. We provided standardised instructions and emphasised walking as far and as fast as possible for 6 minutes [22]. Distance was recorded in meters (m) using a measuring wheel (Stanley MW50, New Briton, CT); longer distances reflect better walking endurance.
Multiple sclerosis walking scale-12
The MSWS-12 is a 12-item PRO of the impact of MS on walking [23]. Example items are “In the past two weeks, how much has MS limited your ability to walk?” and “In the past two weeks, how much has MS slowed down your walking?” The 12-items on the MSWS-12 are rated on a scale ranging between 1 (Not at all) and 5 (Extremely). The total MSWS-12 score is computed by summing the individual item scores, subtracting the minimum possible score (12), dividing by the maximal score (48), and then multiplying the result by 100 [23]. The MSWS-12 score ranges between 0 and 100; lower scores indicate less perceived walking impairment.
Abbreviated Late-Life Function and Disability Inventory (LL-FDI)
The abbreviated LL-FDI is a multidimensional, PRO of functional limitations and disability with psychometric evidence of validity in persons with MS [24]. The functional limitations component of the abbreviated LL-FDI was included in this study and contains 15 items partitioned into three, five-item subscales, namely advanced lower extremity function (ALEF), basic lower extremity function (BLEF), and upper extremity function (UEF). An example item for the ALEF subscale was “How much difficulty do you have with going up and down a flight of stairs outside, without using a handrail?” An example item for the BLEF subscale was “How much difficulty do you have using a step stool to reach into a high cabinet?” An example item for the UEF subscale was “How much difficulty do you have unscrewing the lid off a previously unopened jar without using any devices?”. The 15-items were rated on a 5-point ordinal scale of 1 (none) and 5 (cannot do) and were reverse-scored (i.e., 1 was re-coded into 5, whereas 5 was recorded into 1) and then averaged to form composite measures of ALEF, BLEF, and UEF. Scores for each five-item subscale range between 5 and 25, and higher scores reflect fewer functional limitations.
Free-living accelerometry
ActiGraph accelerometers (model GT3X; ActiGraph) measure steps/day as an indication of free-living ambulation in MS [25]. The ActiGraph accelerometers were worn on a belt over the hip and measured steps using a solid state digital accelerometer that generates an electrical signal proportional to the force acting upon it during movement. The steps were recorded over one-minute intervals, stored in the accelerometer’s memory and later downloaded using a personal computer. Steps per one-minute interval were summed over the course of the day into steps/day. Raw accelerometer data were checked against participant recorded wear times from a log sheet and only valid days (≥ 10 hours of wear time without periods of continuous zeros exceeding 60 minutes) were included in the analysis. The outcome of steps/day was averaged over 3 or more available days of data, and higher scores reflect greater community ambulation.
Cognitive processing speed
The 3-second Paced Auditory Serial Additional Test (PASAT) and the Symbol Digit Modalities Test (SDMT) were included as measures of cognitive processing speed. These tests are relatively quick assessments and valid in MS [26, 27]. The PASAT emphasises auditory processing speed and working memory, whereas the SDMT involves visual/spatial processing speed and working memory; detailed procedures for the PASAT and SDMT are provided elsewhere [28]. The main outcome measure of the PASAT was the total number of correct responses given out of a possible 60 [26]. The main outcome measure of the SDMT was the total number of correctly provided numbers (maximum of 110) in the 90 second period [27]. Higher scores on both assessments reflect faster cognitive processing speed.
Procedure
The procedure was approved for human subjects research by the University of Illinois College of Medicine at Peoria Institutional Review Board and all participants provided written informed consent. The data were collected from each participant during one session in a single clinical setting. There was no standardization of the exact ordering of tests as more than one person underwent testing per session. Rather, we varied the administration of tests such that there was ample seated rest between the administration of walking outcomes (i.e., each walking outcome was followed by a seated rest period and administration of a non-ambulatory outcome as an approach for avoiding motor fatigue). The participants provided demographic information, completed the PDDS, MSWS-12, and LL-FDI, and underwent a neurological examination for generating FS and Expanded Disability Status Scale (EDSS) scores [1]. This was accompanied by completion of the SDMT and PASAT, T25FW, TUG, and 6 MW tests. The participants were then provided with an accelerometer, belt, log, and instructions for wearing the motion sensor during the waking hours of the next seven days, along with a pre-stamped and pre-addressed envelope for its return. All participants received $20 remuneration upon return of the motion sensor.
Validation framework
To establish criterion validity, the correlation between PDDS and EDSS scores were examined as the EDSS is the most common and accepted measure of disability status in MS. To establish the convergent and divergent aspects of construct validity, we examined the correlations between PDDS scores with FS scores and other clinical outcomes. The correlations with measures related to mobility (i.e., pyramidal functions, cerebellar functions, sensory functions, 6 MW, T25FW, TUG, steps/day, BLEF and ALEF) provided information on the convergent validity of the PDDS, whilst comparisons with outcomes related to other, non-mobility constructs (i.e. optic functions, brainstem functions, bowel/bladder functions, mental status function, demographic variables, UEF, SDMT and PASAT) provide information on the divergent validity of the PDDS.
Data analysis
The data were analysed using IBM SPSS statistics version 19.0. Descriptive statistics were computed as median (range, IQR), unless otherwise noted. The associations between variables were examined using Spearman rho rank-order correlation coefficients (ρ) given that the EDSS and PDDS are both ordered-categorical variables. This approach further avoids the effects of outliers and non-normality on the correlation coefficients [29]. Values for correlation coefficients of .1, .3, and .5 were interpreted as small, moderate, and large, respectively [30]. We examined the significance of differences in the magnitude of dependent correlations between PDDS and EDSS scores with other variables [31]; the significance of differences was based on an alpha value of .05.