Background Impairment of walking and the resultant reduction in physical function together with pathological fatigue are major concerns for patients with Multiple Sclerosis (MS). Patients are in need of interventions to improve walking. Slow–release 4–aminopyridine (Fampridine; Fampyra) improves walking speed in approximately 35% of MS patients. The Timed 25–Foot Walk (T25FW) is used to measure response to treatment. There are concerns that the T25FW is a poor estimate of walking speed, and only able to provide a snapshot of walking impairment under controlled circumstances. Funding bodies have raised uncertainties regarding the possibility of increased falls with Fampridine.

Objectives T25FW is not the most pragmatic measure of either walking impairment and or Fampridine efficacy. Alternative objective outcome measures including accelerometry or longer walking distance tests may be more informative of patients' walking ability in real–life situations. We therefore set out to evaluate objective and subjective outcome measures of walking impairment, falls risk and fatigability for use in MS patients.

Methods Thirty–two MS patients underwent a battery of objective and subjective assessments, including 48–hour accelerometry. Appropriate statistical tests were selected for data analysis. Pearson correlation coefficient and Spearman's rho were used for parametric and non–parametric data, respectively. Group mean comparisons were made using the un–paired t–test and one–way analysis of variance (ANOVA) on parametric data, and Mann–Whitney U test and Kruskal–Wallis test on non–parametric data.

Results The study group consisted of 13 women and 19 male (5 primary progressive, 19 secondary progressive, and 8 relapsing–remitting; EDSS range 2.5–7). Median age was 48.5, (range 30–68). All patients had fallen in the past 6 months, and 19 used an assistive device at all times. The mean duration since MS diagnosis was 8.3 years (SD=6.6).

T25FW, 2–minute walk (2MWT) and average daily activity measured by accelerometry showed significant correlations with all other objective measures of walking impairment. The MS walking scale–12 (MSWS–12) correlated significantly with T25FW and 2MWT.

The Activities–specific Balance Confidence (ABC) scale scores increased significantly with higher falls frequency (p=0.03). Assistive device use was significantly associated with worse scores on all subjective and objective tools, and with falls frequency. Accelerometry was a discriminator of physical fatigability in MS patients, when comparing the average activity in the morning with the average activity in the afternoon. Patients in this study suffering from fatigue were less active in the afternoon compared to the early morning (p=0.01).

Conclusions The 2MWT and accelerometry are good objective measures of walking disability in addition to the T25FW. Accelerometry provides additional real–life data regarding activity during the day, and offers information regarding the impact of fatigue on a patient. The MSWS–12 subjectively measures impact of walking disability and the ABC score predicts falls. The use of an assistive device identifies walking disability and predicts risk of falls. Given the uncertainty regarding falls risk in patients using fampridine, physicians should consider using these tools to monitor patients under consideration for the drug.