Myla D. Goldman

Evaluation of the six-minute walk in multiple sclerosis subjects and healthy controls

Objective To assess the characteristics of the 6-min walk (6MW) in multiple sclerosis (MS) subjects of varied disability, and controls. To assess the correlation of 6MW to subjective measures of fatigue, health status and ambulation using the modified fatigue impact scale (MFIS), short form-36 Health Questionnaire physical component score and MS walking scale (MSWS). Methods Forty MS expanded disability status scale [(EDSS) 0—6.5] and 20 control subjects were recruited from a MS outpatient clinic. Subjects completed survey material and three 6MWs with 1-h interval rest in a single study visit. Results There was no practice effect or fatigability with repeat 6MW tests with a one-h rest period between test sessions. The 6MW had excellent intra-[intraclass correlation coefficient (ICC) = 0.95] and inter-rater (ICC = 0.91) reliability. MS subjects demonstrated reduced 6MW distance and speed compared with controls (P < 0.0001). Within the MS population 6MW distance was significantly reduced with increasing disability (P = 0.05). Compared with the EDSS, the 6MW had a stronger correlation to subjective measures of ambulation and physical fatigue: MSWS (r = -0.81 versus 0.69) and MFISphy (0.66 versus 0.63). Conclusions The 6MW is a feasible, reproducible, and reliable measure in MS. MS subjects demonstrate motor fatigue in both 6MW distance and speed compared with controls. In MS subjects there is an inverse relationship between motor fatigue and disability. 6MW has a strong correlation to subjective measures of ambulation and physical fatigue. Multiple Sclerosis 2008; 14: 383—390. http://msj.sagepub.com

Validity of performance scales for disability assessment in multiple sclerosis.

Researchers increasingly use self-reported health status assessments, but these require validation. Performance Scales (PS) is a self-report measure for multiple sclerosis (MS)-associated disability, assessing mobility, bowel/bladder, fatigue, sensory, vision, cognition, spasticity and hand function. The criterion validity of the total PS score was established using the Expanded Disability Status Scale (EDSS), but the construct and criterion validity of the individual subscales have not been established. We assessed the criterion and construct validity of the PS subscales. Forty-four patients with MS completed PS, and these criterion measurements: neurological examination (EDSS), the Multiple Sclerosis Functional Composite (MSFC), contrast acuity testing, and the Multiple Sclerosis Quality of Life Inventory. We assessed criterion and construct validity with Spearman rank correlations between PS subscales and the other measurements. PS correlated with the MSFC (r = -0.58, P < 0.0001). The mobility, hand, vision, fatigue and bladder subscales correlated with their criterion measures (r = 0.59—0.77, P < 0.0001). The sensory subscale correlated weakly with the sensory functional system score (r = 0.39, P = 0.01 ), and the cognitive subscale did not correlate with the PASAT (r = -0.17, P = 0.26). This study supports the criterion and construct validity of PS overall, and its mobility, hand, vision, fatigue, and bladder subscales. Further assessment of the cognitive, sensory and spasticity subscales is needed. Multiple Sclerosis 2007; 13: 1176—1182. http://msj.sagepub.com

Possible clinical outcome measures for clinical trials in patients with multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease with both clinical and pathological heterogeneity. The complexity of the MS population has offered challenges to the measurement of MS disease progression in therapeutic trials. The current standard clinical outcome measures are relapse rate, Expanded Disability Severity Scale (EDSS), and the MS Functional Composite (MSFC). These measures each have strengths and some weakness. Two additional measures, the six-minute walk and accelerometry, show promise in augmenting current measures. MS therapeutics is a quickly advancing field which requires sensitive clinical outcome measures that can detect small changes in disability that reliably reflect long-term changes in sustained disease progression in a complex population. A single clinical outcome measure of sustained disease progression may remain elusive. Rather, an integration of current and new outcome measures may be most appropriate and utilization of different measures depending on the MS population and stage of the disease may be preferred.

Walking impairment in patients with multiple sclerosis: exercise training as a treatment option

Multiple sclerosis (MS) is a chronic disease of the central nervous system that culminates in the progression of physical and cognitive disability over time. Walking impairment is a ubiquitous feature of MS and a sentinel characteristic of the later or advanced stages of the disease. This paper presents a conceptual rationale along with empirical evidence for exercise training as a rehabilitation approach for managing walking impairment and improving walking function in persons with MS. Conceptually, MS is associated with a decrease in physical activity, which, in turn, can result in deconditioning across multiple domains of physiological functioning. The resulting deconditioning feeds back and further drives physical inactivity until a threshold is reached that likely initiates the progression of walking impairment in MS. Empirically, physical activity and exercise training have been associated with beneficial effects on walking function in persons with MS. This is based on cross-sectional, longitudinal, and experimental research that included diversity in the breadth of measures of walking, persons with MS, and exercise/physical activity characteristics. Of particular importance, future researchers might consider examining the combinatory effects of exercise training plus pharmacological agents on walking mobility in MS. Collectively, exercise training and physical activity might hold significant potential for the management of progressive mobility disability in MS.

Clinically meaningful performance benchmarks in MS Timed 25-Foot Walk and the real world

Objective: Identify and validate clinically meaningful Timed 25-Foot Walk (T25FW) performance benchmarks in individuals living with multiple sclerosis (MS). Methods: Cross-sectional study of 159 MS patients first identified candidate T25FW benchmarks. To characterize the clinical meaningfulness of T25FW benchmarks, we ascertained their relationships to real-life anchors, functional independence, and physiologic measurements of gait and disease progression. Candidate T25FW benchmarks were then prospectively validated in 95 subjects using 13 measures of ambulation and cognition, patient-reported outcomes, and optical coherence tomography. Results: T25FW of 6 to 7.99 seconds was associated with a change in occupation due to MS, occupational disability, walking with a cane, and needing “some help” with instrumental activities of daily living; T25FW ≥8 seconds was associated with collecting Supplemental Security Income and government health care, walking with a walker, and inability to do instrumental activities of daily living. During prospective benchmark validation, we trichotomized data by T25FW benchmarks (<6 seconds, 6–7.99 seconds, and ≥8 seconds) and found group main effects on 12 of 13 objective and subjective measures (p < 0.05). Conclusions: Using a cross-sectional design, we identified 2 clinically meaningful T25FW benchmarks of ≥6 seconds (6–7.99) and ≥8 seconds. Longitudinal and larger studies are needed to confirm the clinical utility and relevance of these proposed T25FW benchmarks and to parse out whether there are additional benchmarks in the lower (<6 seconds) and higher (>10 seconds) ranges of performance.

Accelerometry and Its Association With Objective Markers of Walking Limitations in Ambulatory Adults With Multiple Sclerosis

OBJECTIVE To validate accelerometry based on its correlations with 6-minute walk distance (6MWD) and oxygen cost of walking as objective markers of walking limitations in multiple sclerosis (MS). DESIGN Cross-sectional. SETTING Laboratory and general community. PARTICIPANTS Ambulatory participants with MS (N=26) who resided in the local community. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Patient Determined Disease Steps (PDDS) scale and Multiple Sclerosis Walking Scale-12 (MSWS-12); 6-minute walk test while wearing a portable metabolic unit for measuring the 6MWD and oxygen cost of walking; accelerometer during the waking hours of a 7-day period. RESULTS The average of total daily movement counts from the accelerometer correlated significantly and strongly with MSWS-12 scores (ρ=-.681, P=.001), PDDS scores (ρ=-.609, P=.001), 6MWD (ρ=.519, P=.003), and oxygen cost of walking (ρ=-.541, P=.002). CONCLUSIONS We provide evidence that further supports the validity of accelerometry as a measure of walking limitations in ambulatory persons with MS.

Oxygen cost of treadmill and over-ground walking in mildly disabled persons with multiple sclerosis

Walking impairment is a ubiquitous feature of multiple sclerosis (MS) and the O2 cost of walking might quantify this dysfunction in mild MS. This paper examined the difference in O2 cost of walking between persons with MS who have mild disability and healthy controls and the correlation between the O2 cost of walking and disability. Study 1 included 18 persons with mild MS and 18 controls and indicated that the O2 cost of walking was significantly higher in MS than controls and that disability was significantly associated with the O2 cost of slow, moderate, and fast treadmill walking. Study 2 included 24 persons with mild MS and indicated that disability was significantly correlated with O2 cost of comfortable, fast, and slow over-ground walking. We provide evidence that the O2 cost of walking is an indicator of walking dysfunction in mildly disabled persons with MS and should be considered in clinical research and practice.

Multiple Sclerosis Walking Scale-12 and oxygen cost of walking

BACKGROUND The 12-item multiple sclerosis walking scale (MSWS-12) has been validated against self-report and clinical markers, but has not been validated with a physiological marker of locomotor impairment. OBJECTIVE This study further validates the MSWS-12 based on its correlation with the oxygen cost (O(2) cost) of walking as a physiological marker of locomotor impairment in persons with multiple sclerosis (MS). METHODS Participants (N=24) with MS completed the MSWS-12 and then wore a portable metabolic unit for measuring the O(2) cost of walking during three 6-min walk (6MW) tests. The first 6MW test involved the participants comfortable walking speed (CWS), whereas the second and third 6MW tests were undertaken above (faster walking speed, FWS) and below (slower walking speed, SWS) the participants CWS (i.e., +/-5mph CWS). RESULTS MSWS-12 scores correlated strongly with O(2) cost of walking during the 6MW tests undertaken at CWS (r=.641, p=.001), FWS (r=.616, p=.001), and SWS (r=.639, p=.001). INTERPRETATION We provide evidence that further confirms the validity of the MSWS-12 as a measure of the impact of MS on walking.

Real-life walking impairment in multiple sclerosis: preliminary comparison of four methods for processing accelerometry data

This study further validates accelerometers as a measure of walking impairment in persons with multiple sclerosis. We examined total movement counts and three novel methods of processing accelerometer data (i.e. standard deviation, approximate entropy and detrended fluctuation analysis) for quantifying real-life walking impairment in this population. A total of 70 individuals with a definite diagnosis of multiple sclerosis completed a battery of patient-rated measures of walking impairment and then wore an ActiGraph accelerometer for 7 days. The data were analyzed using multivariate analysis of variance and bivariate correlation analysis. The results indicated that total daily movement counts and standard deviation of daily movement counts differed between groups of persons with mild, moderate, and severe self-reported disability status and who were independently ambulatory or ambulatory with assistance. Those two metrics for the accelerometer data further demonstrated strong correlations with patient-rated measures of walking impairment. By comparison, there were smaller and often non-significant differences in approximate entropy and detrended fluctuation analysis metrics for the accelerometer data as a function of disability and ambulatory status, and only moderate correlations with patient-rated measures of walking impairment. The results confirm that the metric of total daily movement counts correlates with level of disability, ambulatory status, and patient reports of walking impairment in persons with multiple sclerosis. We further demonstrate that variability, indexed by the standard deviation of daily movement counts, correlates with multiple sclerosis-related disability, ambulatory status, and self-reported walking impairment. Such results provide preliminary evidence that variability in accelerometer counts is not simply noise and may provide important information about multiple sclerosis-related walking impairment.

Evidence for the different physiological significance of the 6- and 2-minute walk tests in multiple sclerosis

BackgroundResearchers have recently advocated for the 2-minute walk (2MW) as an alternative for the 6-minute walk (6MW) to assess long distance ambulation in persons with multiple sclerosis (MS). This recommendation has not been based on physiological considerations such as the rate of oxygen consumption (V·O2) over the 6MW range.ObjectiveThis study examined the pattern of change in V·O2 over the range of the 6MW in a large sample of persons with MS who varied as a function of disability status.MethodNinety-five persons with clinically-definite MS underwent a neurological examination for generating an Expanded Disability Status Scale (EDSS) score, and then completion of the 6MW protocol while wearing a portable metabolic unit and an accelerometer.ResultsThere was a time main effect on V·O2 during the 6MW (p = .0001) such that V·O2 increased significantly every 30 seconds over the first 3 minutes of the 6MW, and then remained stable over the second 3 minutes of the 6MW. This occurred despite no change in cadence across the 6MW (p = .84).ConclusionsThe pattern of change in V·O2 indicates that there are different metabolic systems providing energy for ambulation during the 6MW in MS subjects and steady state aerobic metabolism is reached during the last 3 minutes of the 6MW. By extension, the first 3 minutes would represent a test of mixed aerobic and anaerobic work, whereas the second 3 minutes would represent a test of aerobic work during walking.