The role of sensory systems in the association between balance and walking in people with multiple sclerosis.

BACKGROUND: In Multiple Sclerosis, it has been demonstrated that balance is related to performances in walking tasks at different levels of complexity. However, it is unknown how the different sensory systems involved in balance control contribute to walking. This observational study investigates the associations between somatosensory, vestibular, and visual systems and measures of self-reported walking and walking capacity at different complexity levels (i.e. low, medium, and high). METHODS: People with MS with EDSS<6 were assessed through the Sensory Organization Test (SOT), 12-Item MS Walking Scale (MSWS-12), Timed 25-Foot Walk (T25FW), Timed Up-and-Go Test (TUG), and Six-Spot-Step-Test (SSST). T25FW, TUG and SSST are measures of low, medium and high walking capacity, respectively. RESULTS: Forty-five PwMS were enrolled (EDSS: 3.4 ± 1.3). Capacity/ability walking measures were moderate-to-highly significantly associated (p < 0.01). Balance measures from SOT showed significant correlation (p < 0.05) between vestibular system and all the walking measures; between visual system and T25FW, SSST and MSWS-12; between the degree to which the patient relies on the visual system to maintain balance with conflicting visual surroundings information (VIS PREF) and T25FW and TUG. In the multivariate analyses, only VIS PREF significantly correlated (p < 0.05) with T25FW (std. Beta=0.42) and TUG (std. Beta=0.38). CONCLUSIONS: Vestibular and visual systems are associated with walking capacity. However, tasks with higher complexity levels require more visual attention towards ground obstacles, as often seen in real-life activities, whereas simpler walking tasks seem to require visual attention towards the surroundings.

The six spot step test is superior in detecting walking capacity impairments compared to short- and long-distance walk tests in persons with multiple sclerosis.

Background: Walking capacity is important not only to persons with multiple sclerosis but also to clinical practice and research. The present study aims to compare the extent of impairments (relative to healthy controls) across three commonly used walking capacity outcomes in persons with multiple sclerosis. Methods: In a two-hospital cross-sectional study, walking capacity was assessed using the timed-25-footwalk-test (timed 25-ft walk test; 'walking speed'), the six-minute-walk-test ('walking endurance') and the six-spot-step-test ('walking balance and coordination'). Data were compared to normative reference data in healthy controls. Results: A total of 228 persons with multiple sclerosis (68% females) were involved in the study: age 53.7 ± 11.6 y (range 26-81 y); patient-determined-disease-steps 3 [IQR; 1; 4] (range 0-7); time since diagnosis 12.6 ± 9.9 y (range 0-49 y); MS-phenotype (relapse remitting MS, secondary progressive MS, primary progressive MS) 146/39/41; and co-morbidity n = 80 (35%). Compared to healthy controls, deficits were observed across all walking capacity outcomes (p < 0.001): timed 25-foot walk test -26 [-30; -23]%, 6 minute-walk-test -36 [-39; -32]% and six-spot-step-test -44 [-47; -40]%. Deficits differed across walking capacity outcomes (p < 0.001). Conclusion: Altogether, persons with multiple sclerosis performed substantially worse than healthy controls across all three walking capacity outcomes. The results showed that the six-spot-step-test was superior to the timed 25-foot walk test and the 6 minute-walk-test in detecting walking capacity impairments in persons with multiple sclerosis.

The subjective minimal important change for the Six Spot Step Test in people with multiple sclerosis - The Danish MS Hospitals Rehabilitation study.

INTRODUCTION: The Six Spot Step Test has shown good psychometric properties in terms of validity and reliability in people with multiple sclerosis. Yet, the responsiveness and minimal important change are unknown. The objective was to investigate the responsiveness of the Six Spot Step Test against the perceived change of walking limitations and establish estimates for the minimal important change in people with multiple sclerosis. METHODS: The Six Spot Step Test was performed before and after four weeks of specialised multidisciplinary inpatient rehabilitation by 142 adults with mild to severe multiple sclerosis. Responsiveness was determined based on anchor- and distribution-based methods, using the Multiple Sclerosis Walking Scale-12 as external criterion. In a supplementary analysis, the Six-Minute Walking Test was used as an external criterion. RESULTS: The correlation between the baseline (r = 0.56, p < 0.01) and discharge (r = 0.55, p < 0.01) Multiple Sclerosis Walking Scale-12 and Six Spot Step Test scores were acceptable. Furthermore, the change scores were weakly associated (r = 0.1, p = 0.27). This trend was similar for the Six-Minute Walking Test when used as anchor. The smallest detectable change was estimated to 1.7 seconds. An improvement in the Six Spot Step Test exceeding 2.1 (95% CI - 0.9 to 5.0) sec and 4.9 (95% CI 1.2-8.6) sec may be considered clinically important on a group level based on the Multiple Sclerosis Walking Scale-12 and the Six-Minute Walking Test, respectively. CONCLUSION: In a sample of mild to severely disabled people with multiple sclerosis, the Six Spot Step Test showed fair responsiveness against a subjective and objective criterion, indicating a minimal important change between ≥ 2.1 and ≥ 4.9 seconds, respectively. However, a weak association between the change in the Six Spot Step Test and the subjective and objective external criterion calls for cautious interpretation. Hence, the results should be further verified against a valid external criterion.

The lived experience of uncertainty in everyday life with MS.

PURPOSE: This article examines how issues of control, certainty, and uncertainty are experienced and managed in everyday life with multiple sclerosis (MS) and explores the ways in which people living with MS make sense of these experiences. MATERIALS AND METHODS: Qualitative interviews with 23 women and men diagnosed with MS and four relatives were carried out in Denmark. Drawing on the notion of "phenomenological uncertainty," a thematic approach was used to analyse the interview data. RESULTS: Three themes characterise participants' experience of uncertainty: the body and issues of control; symptom fluctuations and disease progression; understanding and interpreting embodied MS experiences. Shared, between the themes, is a focus on the body and multi-faceted bodily aspects of uncertainty across diverse temporalities. CONCLUSION: Phenomenological uncertainty shapes and pervades the everyday lived experience of MS in the present and future. Gaining a sense of control and certainty in the face of daily uncertainty demands ongoing self-surveillance, and the evaluation and reconciliation of fluctuating MS symptom expressions and disease progression with personal needs, abilities, and management strategies.IMPLICATIONS FOR REHABILITATIONRehabilitation professionals and physicians should consider the lived experience of uncertainty in everyday life with MS in all their contacts with people living with MS.The multi-faceted uncertainties experienced by people living with MS should be actively acknowledged and incorporated in discussions of MS rehabilitation options and when integrating MS guideline content into activities-of-daily-living advice.Discussions of MS medical treatment options should actively consider and integrate the multi-faceted uncertainties experienced by people living with MS.

Lower extremity muscle power - A critical determinant of physical function in aging and multiple sclerosis.

BACKGROUND AND PURPOSE: In aging, lower extremity muscle power is undoubtedly one of the most important parameters of neuromuscular function implicating lower extremity physical function (e.g. walking capacity). However, no previous studies have examined the combined effects of aging and multiple sclerosis (MS) on lower extremity muscle power concomitant with lower extremity physical function. The aim of this cross-sectional study was to examine potential decrements in pwMS vs. healthy controls (HC) across the adult lifespan in these outcomes. METHODS: In the present explorative cross-sectional study, n = 42 pwMS (females n = 29 (69%); age = 53 ± 12 years (mean ± SD), range 31-78; patient determined disease steps score = 3.7 ± 1.7, range 0-7) and n = 49 age-matched HC (females n = 34 (69%); age = 56 ± 16 years, range 24-78) were enrolled, and divided into groups of young (≤ 44 years), middle-aged (45-59 years), and old (≥ 60 years). Muscle power was obtained from bilateral leg press (PowerLegPressPeak) and maximal chair rise (PowerChairRise) using a linear encoder. Associations were assessed between muscle power and measurements of lower extremity physical function (5 x sit-to-stand (5STS); timed 25-foot-walk-test (T25FWT)). RESULTS: Muscle power was reduced in pwMS vs. HC (PowerLegPressPeak -23[-34:-12]% (mean[95%CI]); PowerChairRise -26[-35:-17]%) and was negatively associated with advanced age in both pwMS (decline per decade -0.40 W.kg-1 and -2.53 W.kg-1, respectively) and HC (decline per decade -0.42 W.kg-1 and -2.03 W.kg-1, respectively). Muscle power was strongly associated with physical function in pwMS (r2range = 0.45-0.61, p < 0.01) yet only moderately associated in HC (r2range = 0.18-0.39, p < 0.01). CONCLUSION: The combined effects of MS and aging reveal substantial decrements in lower extremity muscle power that is accompanied by (and strongly associated with) decrements in lower extremity physical function. Consequently, lower extremity muscle power should be viewed as a clinically important factor (i.e. a critical determinant of lower extremity physical function) in pwMS. We propose that lower extremity muscle power should be specifically targeted by preventive and rehabilitative exercise strategies, especially in older pwMS.

Personalised inpatient multidisciplinary rehabilitation elicits clinically relevant improvements in physical function in patients with multiple sclerosis - The Danish MS Hospitals Rehabilitation Study.

PURPOSE: Evidence of the effects of inpatient multidisciplinary rehabilitation (MDR) on physical function in patients with multiple sclerosis (MS) is limited, particularly whether clinically relevant improvements can be achieved. The aim of this study, therefore, was to investigate the effects of personalised inpatient MDR on the physical function of MS patients. METHODS: Embedded in the Danish MS Hospitals Rehabilitation Study, a pragmatic study was performed in MS patients undergoing four weeks of inpatient MDR specifically targeting physical function. Outcomes were assessed at baseline (n = 142), at discharge (n = 137) and at six months follow-up (n = 126) using the six-minute walk test (6MWT), six-spot step test (SSST), five times sit to stand test (5STS), nine-hole peg test (NHPT), dynamic gait index (DGI) and 12-item MS walking scale (MSWS). RESULTS: From Baseline-to-Discharge, significant and clinically relevant improvements were found in all measures of walking capacity (6MWT, SSST, 5STS, DGI and MSWS; p < 0.05) along with significant (but not clinically relevant) improvements in upper extremity function (NHPT; p < 0.05). Whilst comparable improvements were observed within subgroups of MS phenotype (relapsing-remitting [RR] vs. secondary + primary progressive [SP + PP]), disease severity (moderate [EDSS2.5-5.5] vs. severe [EDSS6.0-7.5]) and age (young/middle-aged [Age24-59] vs. old [Age60-65]), an attenuated adaptation was nevertheless observed for 6MWT in the most affected and vulnerable subgroups (i.e. SP + PP, EDSS6.0-7.5 and Age60-65). The significant improvements in walking capacity and upper extremity function persisted at six months follow-up but did not exceed anymore the thresholds regarded as clinically relevant. CONCLUSION: The results provide novel evidence that personalised inpatient MDR targeting physical function in MS patients elicits significant and clinically relevant improvements in physical function.

Associations between fatigue impact and lifestyle factors in people with multiple sclerosis - The Danish MS hospitals rehabilitation study.

BACKGROUND: The lack of medical treatment options to reduce fatigue in patients with multiple sclerosis (MS) emphasize the importance of identifying potential non-pharmacological modifiable factors, as this may help advance current treatment strategies. The aim of this study was to identify potential modifiable lifestyle factors as well as patient- and disease-related characteristics, that are associated with fatigue in a large sample of clinically well-characterized patients with MS. METHODS: This study was a secondary analysis of a pragmatic randomized controlled trial of inpatient multidisciplinary rehabilitation in Denmark. MS patients aged 18 to 65 years and with a disease severity score ≤ 7.5 according to the Expanded Disability Status Scale participated. Data on patient- and disease-related characteristics, fatigue impact (Modified Fatigue Impact Scale (MFIS)), and on lifestyle factors (tobacco smoking, alcohol intake, and physical activity), were collected at baseline. A linear mixed model was used to compare MFIS total, physical, cognitive, and psychosocial scores across subgroups of selected characteristics. Regression analyses were used to examine associations between lifestyle factors and MFIS total, physical, cognitive, and psychosocial scores. RESULTS: In the sample of 417 MS patients, median age was 51 years, 69% were female, median time since diagnosis was 8 years, with 41% having relapsing remitting MS. Higher MFIS total scores were observed in MS patients with shorter time since diagnosis, being a tobacco smoker, and not undertaking regular physical activity. Somewhat similar findings were observed for MFIS subscores (physical, cognitive, psychosocial), especially MFIS physical scores. In the multivariate analyses, physical activity was significantly associated with fatigue impact on total, physical and psychosocial functioning. Tobacco smoking was significantly associated with fatigue impact on psychosocial functioning. Alcohol intake was not associated with fatigue impact. None of the lifestyle factors were associated with fatigue impact on cognitive functioning. In the adjusted models time since diagnosis was significantly associated with fatigue impact on total, physical and cognitive functioning, as was disease severity with fatigue impact on physical and cognitive functioning. CONCLUSION: Physical activity showed the most pronounced associations with fatigue impact on physical and psychosocial functioning, while the impact on cognitive functioning showed a trend. Tobacco smoking contributed significantly to impact on psychosocial functioning, while alcohol intake did not contribute to fatigue impact. Introducing or supporting maintenance of physical activity/exercise and cessation of tobacco smoking seems to be a useful approach for rehabilitation services to help patients with MS manage fatigue.

Can inpatient multidisciplinary rehabilitation improve health-related quality of life in MS patients on the long term - The Danish MS Hospitals Rehabilitation Study.

BACKGROUND: Inpatient multidisciplinary rehabilitation (MDR) can improve health-related quality of life (HRQoL) in multiple sclerosis (MS) patients. However, the evidence of a long-term benefit is limited. OBJECTIVES: To investigate the long-term effectiveness of inpatient MDR on HRQoL in MS patients. METHODS: We conducted a randomized controlled partial crossover trial with 427 MS patients. RESULTS: Statistical significant long-term improvements in HRQoL were found in three of the six outcome measures at 12-month follow-up. Three in four suggested minimal clinically important differences (MCIDs) were unmet. CONCLUSION: These results indicate that the administration of inpatient MDR may lead to long-lasting improvements in HRQoL in MS patients.

Test-retest agreement and reliability of the Six Spot Step Test in persons with multiple sclerosis.

BACKGROUND: The Six Spot Step Test (SSST) extends traditional walking outcomes in persons with multiple sclerosis (PwMS) by further challenging components of coordination and balance. Nonetheless, the test-retest agreement of the SSST has not been investigated. OBJECTIVE: To determine the within-day, day-to-day, and inter-rater agreement and reliability of the SSST in PwMS. A secondary aim was to investigate the validity of handheld timing. METHODS: A total of 38 PwMS with an Expanded Disability Status Scale (EDSS) <6.5 completed two SSSTs with a 5-minute break in-between. After 2 days, this procedure was repeated. Bland-Altman analysis was performed to determine the 95% Limits of Agreement (LOA) and Intraclass Correlation Coefficient (ICC) was calculated. In a subgroup of 18 PwMS, the SSSTs were video-recorded and timed by a second investigator. RESULTS: The relative LOA within and between days were ±15% and ±19%, while ICC were 0.987 and 0.983, respectively. A minor learning effect was found over four tests. The handheld timing error was ±0.5 seconds when compared to video-based timing. CONCLUSION: The SSST has an acceptable within- and between-day agreement and reliability. For interventional purposes, a change of >19% can be regarded as a real change. Valid timing can be performed by a handheld stopwatch.

Can we trust self-reported walking distance when determining EDSS scores in patients with multiple sclerosis? The Danish MS hospitals rehabilitation study.

BACKGROUND: In multiple sclerosis (MS), the Expanded Disability Status Scale (EDSS) reflects disease severity. Although parts of the EDSS are dependent on actual walking distance, self-reported statements are often applied. OBJECTIVES: The purpose of the present study was, therefore, to compare self-reported walking distance to actual walking distance to outline how this influences EDSS scoring. METHODS: MS patients with EDSS 4.0-7.5 (n = 273) were included from the Danish MS hospitals rehabilitation study (n = 427). All patients subjectively classified their maximal walking distance according to one of seven categories (>500; 300-499; 200-299; 100-199; 20-99; 5-19; 0-4 m). Subsequently, actual maximal walking distance was assessed and EDSS was determined from both self-reported walking distance (EDSSself-report) and actual walking distance (EDSSactual). RESULTS: In 145 patients (53%), self-reported walking distance was misclassified when compared to the actual walking distance. Misclassification was more frequent in patients using walking aids (64% vs. 44%, p < 0.05) and in patients with primary progressive MS (69%, p < 0.05). Misclassification of walking distance corresponded to incorrect EDSS scores (EDSSself-report vs EDSSactual) of ⩾0.5 point in 24%. CONCLUSION: In MS patients with EDSS 4.0-7.5, 53% misclassified their walking distance yielding incorrect EDSS scores in 24%. Therefore, correct EDSS determination must be based on measurement of actual walking distance.

Prevalence of Walking-Related Motor Fatigue in Persons With Multiple Sclerosis: Decline in Walking Distance Induced by the 6-Minute Walk Test.

OBJECTIVE: To investigate the individual occurrence of walking-related motor fatigue in persons with multiple sclerosis (PwMS), according to disability level and disease phenotype.Study design This was a cross-sectional, multinational study.Participants They were 208 PwMS from 11 centers with Expanded Disability Status Scale (EDSS) scores up to 6.5. METHODS: The percentage change in distance walked (distance walked index, DWI) was calculated between minute 6 and 1 (DWI(6-1)) of the 6-Minute Walk Test (6MWT). Its magnitude was used to classify participants into 4 subgroups: (1) DWI(6-1)[≥5%], (2) DWI(6-1)[5%; -5%], (3) DWI(6-1)[-5%; > -15%], and (4) DWI(6-1)[≤-15%]. The latter group was labeled as having walking-related motor fatigue. PwMS were stratified into 5 subgroups based on the EDSS (0-2.5, 3-4, 4.5-5.5, 6, 6.5) and 3 subgroups based on MS phenotype (relapsing remitting [RR], primary progressive [PP], and secondary progressive [SP]). RESULTS: The DWI6-1was ≥5% in 16 PwMS (7.7%), between 5% and -5% in 70 PwMS (33.6%), between -5% and -15% in 58 PwMS (24%), and ≤-15% in 64 PwMS (30.8%). The prevalence of walking-related motor fatigue (DWI(6-1)[≤-15%]) was significantly higher among the progressive phenotype (PP = 50% and SP = 39%; RR = 15.6%) and PwMS with higher disability level (EDSS 4.5-5.5 = 48.3%, 6 = 46.3% and 6.5 = 51.5%, compared with EDSS 0-2.5 = 7.8% and 3-4 = 16.7%;P< .05). Stepwise multiple regression analysis indicated that EDSS, but not MS phenotype, explained a significant part of the variance in DWI(6-1)(R(2)= 0.086;P< .001). CONCLUSION: More than one-third of PwMS showed walking-related motor fatigue during the 6MWT, with its prevalence greatest in more disabled persons (up to 51%) and in those with progressive MS phenotype (up to 50%). Identification of walking-related motor fatigue may lead to better-tailored interventions.

Within-day variability on short and long walking tests in persons with multiple sclerosis.

OBJECTIVE: To compare within-day variability of short (10 m walking test at usual and fastest speed; 10MWT) and long (2 and 6-minute walking test; 2MWT/6MWT) tests in persons with multiple sclerosis. DESIGN: Observational study. SETTING: MS rehabilitation and research centers in Europe and US within RIMS (European network for best practice and research in MS rehabilitation). SUBJECTS: Ambulatory persons with MS (Expanded Disability Status Scale 0-6.5). INTERVENTION: Subjects of different centers performed walking tests at 3 time points during a single day. MAIN MEASURES: 10MWT, 2MWT and 6MWT at fastest speed and 10MWT at usual speed. Ninety-five percent limits of agreement were computed using a random effects model with individual pwMS as random effect. Following this model, retest scores are with 95% certainty within these limits of baseline scores. RESULTS: In 102 subjects, within-day variability was constant in absolute units for the 10MWT, 2MWT and 6MWT at fastest speed (+/-0.26, 0.16 and 0.15m/s respectively, corresponding to +/-19.2m and +/-54 m for the 2MWT and 6MWT) independent on the severity of ambulatory dysfunction. This implies a greater relative variability with increasing disability level, often above 20% depending on the applied test. The relative within-day variability of the 10MWT at usual speed was +/-31% independent of ambulatory function. CONCLUSIONS: Absolute values of within-day variability on walking tests at fastest speed were independent of disability level and greater with short compared to long walking tests. Relative within-day variability remained overall constant when measured at usual speed.

Heat sensitive persons with multiple sclerosis are more tolerant to resistance exercise than to endurance exercise.

BACKGROUND: Heat sensitivity (HS) is reported by 58% of all persons with multiple sclerosis (MS), causing symptom exacerbation possibly limiting exercise participation. OBJECTIVE: The purpose of this study was to test the hypotheses that (a) a relationship between exercise-induced changes in core-temperature (C(temp)) and changes in symptom intensity exists, and (b) that resistance exercise (RE), as a consequence of a minor increase in core temperature, will induce a lesser worsening of symptoms than endurance exercise (EE) in HS persons with MS. METHODS: On two separate days, 16 HS persons with MS randomly completed a session of RE and EE, or EE and RE, respectively. Testing was conducted pre, post and one hour after exercise and consisted of Visual Analogue Scale (VAS) scoring (fatigue, spasticity, pain, strength, walking and balance), the 5-time sit-to-stand (5STS), the Multiple Sclerosis Functional Composite (MSFC) and Body Sway. Composite scores describing average subjective symptom intensity (SI) and total number of symptoms (SN) were calculated from VAS scores. RESULTS: C(temp) (0.9±0.4°C vs 0.3±0.1°C, p<0.001), SI (1.7±1.9 cm vs 0.6±1.5 cm, p<0.05) and SN (1.6±1.9 vs 0.6±2.1, p<0.05) increased significantly more during EE than RE. Changes in C(temp) correlated to changes in SI (r=0.50, p<0.01). No differences were observed in 5STS, MSFC and Body Sway scores after EE when compared to RE. CONCLUSION: An exercise-induced increase in C(temp) is associated with increased number and severity of perceived symptoms in HS persons with MS. Based on these findings it is expected that HS persons with MS do tolerate RE better than EE.

Validity and variability of the 5-repetition sit-to-stand test in patients with multiple sclerosis.

PURPOSE: To investigate; (i) the relationship between the 5STS-test and lower extremity muscle strength and balance, and (ii) the variability of the 5STS-test in multiple sclerosis (MS) patients. METHOD: 22 MS patients were divided into two groups (Group A and Group B) who completed one 5STS familiarization test session and two testing sessions. In Group A, session 1 also included assessment of lower extremity muscle strength. Session 2 and 3 involved completion of two 5STS-tests and assessment of balance. In Group B, session 2 and 3 involved completion of two rounds of two 5STS-tests separated by a 30 min break. RESULTS: Significant correlations were found between the 5STS-test and isometric and isokinetic knee flexor and extensor muscle strength of the most affected leg (R = -0.60 to -0.77), and between the 5STS-test and balance performance (R = 0.69). Intra-assessor day-to-day variability, intra-assessor test-retest variability and intra-assessor variability within test were 25.5, 22.3, and 23.1%, respectively. Inter-assessor variability within test and inter-assessor variability were 23.4 and 5.9%, respectively. CONCLUSIONS: The 5STS-test is related to lower extremity muscle strength and to balance performance in MS patients. For interventional purposes, a change of >25% can be regarded as a real change.