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See detailRelative Contribution of Walking Speed, Ataxia and Gait asymmetry to the Composition of Gait in Multiple Sclerosis
PHAN BA, Remy ULg; Pierard, Sébastien ULg; LOMMERS, Emilie ULg et al

Poster (2013, October)

Introduction - Objective: Walking speed measured according to the T25FW is the most widely used descriptor of gait in MS clinical research and practice but other dimensions influencing gait variance exist ... [more ▼]

Introduction - Objective: Walking speed measured according to the T25FW is the most widely used descriptor of gait in MS clinical research and practice but other dimensions influencing gait variance exist according to alternative gait analysis methods. The relative importance of these different dimensions of gait relatively to its variance is unknown. Methods: We measured the performances of persons with MS and healthy subjects on the T25FW and the Timed 20-Meter Walk (T20MW) performed in tandem with a new gait analysis system (GAIMS). We performed a factorial analysis of variance to underline the main dimensions influencing gait variance and observed their composition. Findings - Conclusion: The main factor influencing gait variance in conventional walk tests is mostly composed of features related to walking speed. Balance, gait asymmetry and variability also participate to this variance but to a lesser extent. The inverse is observed in tests performed in tandem gait. [less ▲]

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See detailInfluence of the mode of walk on walking speed in multiple sclerosis: are you walking comfortably?
PHAN BA, Remy ULg; DELRUE, Gaël ULg; Pierard, Sébastien ULg et al

Poster (2013, June 10)

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 ... [more ▼]

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. [less ▲]

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See detailMotor fatigue measurement by distance-induced slow down of walking speed in multiple sclerosis
PHAN BA, Remy ULg; CALAY, Philippe ULg; GRODENT, Patrick ULg et al

in PLoS ONE (2012), 7(4), 34744

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 ... [more ▼]

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. [less ▲]

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See detailA corrected version of the Timed-25 Foot Walk Test with a dynamic start to capture the maximum ambulation speed in multiple sclerosis patients
Phan-Ba, Rémy ULg; CALAY, Philippe ULg; GRODENT, Patrick ULg et al

in NeuroRehabilitation (2012), 30(4), 261-266

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 ... [more ▼]

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. [less ▲]

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See detailMRI preclinical detection and asymptomatic course of a progressive multifocal leucoencephalopathy (PML) under natalizumab therapy.
Phan-Ba, Rémy ULg; LOMMERS, Emilie ULg; TSHIBANDA, Luaba ULg et al

in Journal of Neurology, Neurosurgery & Psychiatry (2012), 83

Early detection of progressive multifocal leucoencephalopathy (PML) in the setting of natalizumab therapy currently is performed by rapid evaluation of new symptoms occurring in treated patients. The role ... [more ▼]

Early detection of progressive multifocal leucoencephalopathy (PML) in the setting of natalizumab therapy currently is performed by rapid evaluation of new symptoms occurring in treated patients. The role of MR scanning has not been investigated but holds promise since MR detection is highly sensitive for PML lesions. The authors report a case of presymptomatic PML of the posterior fossa detected by MR scans. Immediate suspension of natalizumab and plasma exchanges resulted in a rapid decline of natalizumab serum concentration. Intravenous steroids started together with plasma exchanges followed by an oral tapering course were used to minimise the immune reconstitution inflammatory syndrome. No symptoms (beyond mild headache) developed, and the repeat PCR for JC Virus (JCV) DNA detection performed 10 weeks later was negative. This case suggests that: (1) periodic brain MR scans may detect signs of presymptomatic PML in MS patients treated with natalizumab, (2) corticosteroid management of inflammatory reaction may contribute to optimal control of the immune reconstitution inflammatory syndrome routinely seen with natalizumab-associated PML and (3) early radiological detection of PML can have an excellent outcome even in a clinically critical region and despite prior immunosuppressant exposure. The potential benefit of regular MR scanning just using the T2/FLAIR modalities could be further investigated in order to detect early natalizumab-associated PML, leading to benign outcomes. [less ▲]

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See detailComparison of the Timed 25-Foot and the 100-Meter Walk as Performance Measures in Multiple Sclerosis
Phan-Ba, Rémy ULg; Pace, Amy; CALAY, Philippe ULg et al

in Neurorehabilitation and neural repair (2011), 25(7), 672-9

BACKGROUND: Ambulation impairment is a major component of physical disability in multiple sclerosis (MS) and a major target of rehabilitation programs. Outcome measures commonly used to evaluate walking ... [more ▼]

BACKGROUND: Ambulation impairment is a major component of physical disability in multiple sclerosis (MS) and a major target of rehabilitation programs. Outcome measures commonly used to evaluate walking capacities suffer from several limitations. OBJECTIVES: To define and validate a new test that would overcome the limitations of current gait evaluations in MS and ultimately better correlate with the maximum walking distance (MWD). METHODS: The authors developed the Timed 100-Meter Walk Test (T100MW), which was compared with the Timed 25-Foot Walk Test (T25FW). For the T100MW, the subject is invited to walk 100 m as fast as he/she can. In MS patients and healthy control volunteers, the authors measured the test-retest and interrater intraclass correlation coefficient. Spearman rank correlations were obtained between the T25FW, the T100MW, the Expanded Disability Status Scale (EDSS), and the MWD. The coefficient of variation, Bland-Altman plots, the coefficient of determination, and the area under the receiver operator characteristic curve were measured. The mean walking speed (MWS) was compared between the 2 tests. RESULTS: A total of 141 MS patients and 104 healthy control volunteers were assessed. Minor differences favoring the T100MW over the T25FW were observed. Interestingly, the authors demonstrated a paradoxically higher MWS on a long (T100MW) rather than on a short distance walk test (T25FW). CONCLUSION: The T25FW and T100MW displayed subtle differences of reproducibility, variability, and correlation with MWD favoring the T100MW. The maximum walking speed of MS patients may be poorly estimated by the T25FW since MS patients were shown to walk faster over a longer distance. [less ▲]

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See detailNatalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis.
Belachew, Shibeshih ULg; Phan-Ba, Rémy ULg; Bartholome, Emmanuel et al

in European Journal of Neurology (2010), 18(2), 240-245

Background: 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 ... [more ▼]

Background: 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. [less ▲]

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See detailNatalizumab induced freedom from disease activity after failure to previous therapy in relapsing remitting multiple sclerosis.
Belachew, Shibeshih ULg; Bartholome E.; DELVAUX, Valérie ULg et al

Conference (2009, June)

Objectives: To analyze the efficacy of natalizumab after switching relapsing-remitting multiple sclerosis (RRMS) patients from other disease modifying treaments (DMTs). Background: Natalizumab (Tysabri ... [more ▼]

Objectives: To analyze the efficacy of natalizumab after switching relapsing-remitting multiple sclerosis (RRMS) patients from other disease modifying treaments (DMTs). Background: Natalizumab (Tysabri) is a monoclonal antibody directed against VLA4 that was recently approved for the treatment of RRMS. Due to safety concerns, the use should be restricted to highly active patients and/or patients with insufficient response to other DMTs. The pivotal trials were not designed to examine the effect of natalizumab as an escalation monotherapy. Methods: Prospective, open label, observational study. All patients initiating natalizumab had experienced at least 1 relapse in the previous year under DMTs and had at least 1 Gd-enhancing lesion on their brain MRI. Previous treatment with interferon-beta (IFN-beta) or glatiramer acetate (GA) were stopped at least one week and azathioprine or mitoxantrone at least 3 months before switching. The minimum therapy duration with natalizumab was 6 months for all patients. 21 RRMS patients were included in this analysis. The mean age of the patients was 25,5 yo with mean disease duration of 6,8 years. All patients were under IFN-beta (17) or GA (4) during at least the previous year before starting natalizumab therapy. Four patients had also received azathioprine and 1 patient mitoxantrone. Results: The mean relapse rate in the previous year was 2.15 (1-4), the mean EDSS at baseline was 3.3 (1,0-6.0), the mean number of Gd+ lesions at baseline 2,58 (1-6). Under tysabri treatment the annualized relapse rate dropped to 0,20. Eleven patients improved their EDSS (0,5 to 1,5 steps down), others remained stable at 6 months. The mean number of Gd+ T1 lesions dropped to 0,23 and the mean number of new T2 lesions was 0.25 on the control MRI at 6 months. 55% of patients were free from disease activity, i.e. had no relapses, no EDSS progression, no new T2 lesion and no Gd+ T1 lesions after 6 months of Tysabri. 5 patients experienced minor adverse events (1 zona, 2 flu-like symptoms, 1 gastroenteritis, 1 allergic reaction). Conclusion: Natalizumab was well tolerated and safe as escalation therapy when previous DMTs had failed to control disease progression in this group of highly active RRMS patients. These results suggest comparable efficacy to the phase III AFFIRM trial of natalizumab when the drug is used in a context of breakthrough disease. Although data from preliminary analyses are promising, long term investigations are warranted. [less ▲]

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See detailThe timed 100-meter walk test: an easy-t-use, sensitive tool to detect and evaluate restricted walking capacities in multiple sclerosis.
Belachew, Shibeshih ULg; CALAY, Philippe ULg; DELVAUX, Valérie ULg et al

Conference (2009, June)

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 ... [more ▼]

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. [less ▲]

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