Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis.

peer reviewedBackground: Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy of natalizumab on disability status and ambulation after switching patients with RRMS from other disease-modifying treatments (DMTs). Methods: A retrospective, observational study was carried out. All patients (n = 45) initiated natalizumab after experiencing at least 1 relapse in the previous year under interferon-beta (IFNB) or glatiramer acetate (GA) treatments. The patients also had at least 1 gadolinium-enhancing (Gd+) lesion on their baseline brain MRI. Expanded Disability Status Scale (EDSS) scores, and performance on the Timed 25-Foot Walk Test and on the Timed 100-Metre Walk Test were prospectively collected every 4 weeks during 44 weeks of natalizumab treatment. Brain MRI scans were performed after 20 and 44 weeks of treatment. Results: Sixty-two per cent of patients showed no clinical and no radiological signs of disease activity, and 29% showed a rapid and confirmed EDSS improvement over 44 weeks of natalizumab therapy. Patients with improvement on the EDSS showed similar levels of baseline EDSS and active T1 lesions, but had a significantly higher number of relapses, and 92% of them had experienced relapse-mediated sustained EDSS worsening in the previous year. A clinically meaningful improvement in ambulation speed was observed in approximately 30% of patients. Conclusions: These results indicate that natalizumab silences disease activity and rapidly improves disability status and walking performance, possibly through delayed relapse recovery in patients with RRMS who had shown a high level of disease activity under other DMTs

Motor Fatigue Measurement by Distance-Induced Slow Down of Walking Speed in Multiple Sclerosis

Background: Motor fatigue and ambulation impairment are prominent clinical features of people with multiple sclerosis (pMS). We hypothesized that a multimodal and comparative assessment of walking speed on short and long distance would allow a better delineation and quantification of gait fatigability in pMS. Objectives: To compare 4 walking paradigms: the timed 25-foot walk (T25FW), a corrected version of the T25FW with dynamic start (T25FW+), the timed 100-meter walk (T100MW) and the timed 500-meter walk (T500MW). Methods: Thirty controls and 81 pMS performed the 4 walking tests in a single study visit. Results: The 4 walking tests were performed with a slower WS in pMS compared to controls even in subgroups with minimal disability. The finishing speed of the last 100-meter of the T500MW was the slowest measurable WS whereas the T25FW+ provided the fastest measurable WS. The ratio between such slowest and fastest WS (Deceleration Index, DI) was significantly lower only in pMS with EDSS 4.0-6.0, a pyramidal or cerebellar functional system score reaching 3 or a maximum reported walking distance !4000m. Conclusion: The motor fatigue which triggers gait deceleration over a sustained effort in pMS can be measured by the WS ratio between performances on a very short distance and the finishing pace on a longer more demanding task. The absolute walking speed is abnormal early in MS whatever the distance of effort when patients are unaware of ambulation impairment. In contrast, the DI-measured ambulation fatigability appears to take place later in the disease course

Interview sur les effets des boissons énergisantes

info:eu-repo/semantics/publishe

Interview sur le Motilium

info:eu-repo/semantics/publishe

A corrected version of the Timed-25 Foot Walk Test with a dynamic start to capture the maximum ambulation speed in multiple sclerosis patients

Background : No clinical test is currently available and validated to measure the maximum walking speed (WS) of multiple sclerosis (MS) patients. Since the Timed 25-Foot Walk Test (T25FW) is performed with a static start, it takes a significant proportion of the distance for MS patients to reach their maximum pace. Objectives : In order to capture the maximum WS and to quantify the relative impact of the accelerating phase during the first meters, we compared the classical T25FW with a modified version (T25FW+) allowing a dynamic start after a 3 meters run-up. Methods : Sixty-four MS patients and 30 healthy subjects performed successively the T25FW and the T25FW+. Results : The T25FW+ was performed faster than the T25FW for the vast majority of MS and healthy subjects. In the MS population, the mean relative gain of speed due to the dynamic start on T25FW+ was independent from the EDSS and from the level of ambulation impairment. Compared to healthy subjects, the relative difference between dynamic versus static start was more important in the MS population even in patients devoid of apparent gait impairment according to the T25FW. Conclusion : The T25FW+ allows a more accurate measurement of the maximum WS of MS patients, which is a prerequisite to reliably evaluate deceleration over longer distance tests. Indirect arguments suggest that the time to reach the maximum WS may be partially influenced by the cognitive impairment status. The maximum WS and the capacity of MS patients to accelerate on a specific distance may be independently regulated and assessed separately in clinical trials and rehabilitation programs

Improved probabilistic segmentation of white matter lesions in multiple sclerosis

Multimodal and quantitative assessment of progressive forms of multiple sclerosis: a clinical and MRI study

The timed 100-meter walk test: an easy-t-use, sensitive tool to detect and evaluate restricted walking capacities in multiple sclerosis.

Objectives: The primary aim of this study was to develop a quantitative ambulation test that correlates with the maximal walking distance in multiple sclerosis (MS) patients. Background: The timed 25-foot walk (T25FW) weakly correlates with overall walking capacities of MS patients. We developed the timed 100-meter walk test (T100T), which besides reflecting speed may be more sensitive to other walking parameters such as gait and spasticity-related fatigue. Methods: In the T100T, the patient is instructed to walk as fast as possible on a distance of 100 meters. Eighty-eight MS patients with an EDSS score from 0 to 5.5 and 60 normal controls performed the T100T and the T25FW. In addition, 30 normal controls and 30 patients performed the tests twice. Results: T25FW (R2= 0.79) and T100T (R2 = 0.89) correlated with the nonlinear distribution of EDSS scores. The correlation between T100T and T25FW values was high (r2 = 0.81) for the low (0 to 3.0) and high (3.5-5.5) scores of EDSS. The intra-class correlations were excellent and similar for both tests. The range of T100T values in MS patients (40.4 to 114.7 seconds) was 10-fold wider than that of the T25FW (3.0 to 9.1 seconds). The univariate distribution analyses demonstrated that abnormal T100T values appear to be more sensitive than T25FW to predict walking limitations. Finally, the correlation with the reported and/or actual maximal walking distance without aid and rest was significantly better for T100T. Conclusions : The T100T proves to be superior to the T25FW in terms of discriminatory power for the detection and evaluation of restricted walking capacities in MS. The T100T should be of interest for clinical trials studying disability worsening and improvement across the spectrum of EDSS. It may provide more sensitive measure for ambulation change in quantifying progressive MS pathology

Construction and pre-validation of a cognitive ergonomics questionnaire for work holding in multiple sclerosis patients : The QUIPSEP

We describe how we build and pre-validate a cognitive ergonomics questionnaire for multiple sclerosis patients actually employed, the QUIPSEP. This questionnaire must help us better manage our patients and thei potentiel difficulties in work situation from a cognitive ergonomic point of view

Influence of the mode of walk on walking speed in multiple sclerosis: are you walking comfortably?

Introduction : Walking speed (WS) is the most frequent gait variable taken into account when measuring gait dysfunction in neurological diseases. Influences of the mode of walk instructed to the subject, i.e. « as fast as possible » (AFAP) or « at a comfortable pace » (PrP) have not been well characterized in multiple sclerosis (MS). Objectives : to compare those 2 mode of walk in a population of persons with MS (pMS) and healthy volunteers (HV). Methods: WS was measured with a new automated device along a 25 foot distance (T25FW) as part of a multimodal evaluation of gait in an MS ambulatory department. Results: Baseline demographics between HV and pMS were comparable. Our first results demonstrate that (i) WS is obviously significantly higher in AFAP than in PrP both for pMS and HV (p < 0.001 for all comparisons) and (ii) the relative difference between AFAP and PrP WS is significantly higher in HV than in pMS (p < 0.001). The AFAP-PrP WS correlation is higher in pMS (r = 0.87, p < 0.001) than in HV (r = 0.51, p < 0.001). Finally, the relative difference between AFAP and PrP WS is significantly and negatively correlated with the PrP WS in HV (r = -0.41, p < 0.001) and pMS with mild to moderate disability (EDSS 0-3.5, r = -0.49, p < 0.01) but not in pMS with high disability (EDSS 4-5.5, r = 0.008). Conclusions : these results suggests that heatlhy subjects have access to a higher range of PrP WS than pMS and questions the regulation of PrP WS that might be under psychological or behavioural influences. The demonstration of a lower PrP-AFAP difference in MS suggests that pMS are either adopting a natural WS closer to their maximum WS, or alternatively that they can’t reach their maximum WS because of neurological impairments. Our results also emphasize the importance of the instructed mode of walk in the quantification of gait disorders both for routine clinical practice and clinical trials