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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 detailImpaired automatic and unconscious motor processes in Parkinson's disease
D'Ostilio, Kevin ULg; CREMERS, Julien ULg; DELVAUX, Valérie ULg et al

in Scientific Reports (2013)

While it is increasingly recognized that voluntary movements are produced by an interaction between conscious and unconscious processes, the role of the latter in Parkinson’s disease has received little ... [more ▼]

While it is increasingly recognized that voluntary movements are produced by an interaction between conscious and unconscious processes, the role of the latter in Parkinson’s disease has received little attention to date. Here, we administered a subliminal masked prime task to 15 Parkinson’s disease patients and 15 age-matched healthy elderly subjects. Compatibility effects were examined by manipulating the direction of the arrows and the interstimuli interval. Analysis of the positive compatibility effect revealed performance differences between the most and the least affected hand in Parkinson’s disease patients. Additionally, patients did not show the same tendency toward a negative compatibility effect as compared to elderly controls. These novel findings provide evidence supporting the role of basal ganglia circuits in controlling the balance between automatic motor response facilitation and inhibition. [less ▲]

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See detailLes troubles du contrôle des impulsions associés au traitement dopaminergique substitutif antiparkinsonien
DEPIERREUX, Frédérique ULg; CREMERS, Julien ULg; SKAWINIAK, Eva ULg et al

in Revue Médicale de Liège (2013), 68(mai-juin), 221-225

Summary : In some patients, impulse control behaviours can be triggered by dopaminergic replacement therapy, particularly dopamine agonist drugs: hobbyism, punding (stereotyped behaviours), compulsive ... [more ▼]

Summary : In some patients, impulse control behaviours can be triggered by dopaminergic replacement therapy, particularly dopamine agonist drugs: hobbyism, punding (stereotyped behaviours), compulsive buying, binge eating disorder, pathological gamgling, hypersexuality, hedonistic homeostatic dysregulation syndrome ... The pathogenesis of these behaviours is not well understood, but likely involves aberrant changes in the dopaminergic pathways that mediate motivation i.e., a dopaminergic “overdose” in meso-cortico-limbic circuits. An early diagnosis is difficult, but mandatory to prevent the occurrence of devastating familial, marital, professional, socio-economic, medical and medico-legal consequences. Their management is not yet well standardized. Patients and caregivers should be warned about impulse control behaviours before starting dopamine agonists and monitoring for such behaviours while on therapy is requested. [less ▲]

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See detailPreserved automatic inhibition effect after 1 Hz repetitive transcranial magnetic stimulation over the supplementary motor area
D'Ostilio, Kevin ULg; CREMERS, Julien ULg; DELVAUX, Valérie ULg et al

Poster (2013)

Background: It is widely accepted that medial frontal regions are involved in voluntary action control. Indeed, Sumner et al. (2007) have recently suggested that one of the mechanisms through which the ... [more ▼]

Background: It is widely accepted that medial frontal regions are involved in voluntary action control. Indeed, Sumner et al. (2007) have recently suggested that one of the mechanisms through which the supplementary motor area (SMA) contributes to voluntary control is automatic and unconscious motor inhibition. In this study, they administered a visuo-motor subliminal masked prime task (Eimer & Schlaghecken, 2003) to two patients with micro-lesions of the SMA and demonstrated an absence of automatic and unconscious inhibition as evoked by masked prime stimuli. This finding has been supported by neuroimaging data (D'Ostilio et al., 2012). Here, the aim of our research was to corroborate this result by means of a “virtual lesion” approach. Methods: For this purpose, we examined the effects of 1 Hz rTMS (train of 20 min; stimulus intensity 120 % of resting motor threshold) over the SMA of ten healthy volunteers, previously localized by functional magnetic resonance imaging (fMRI), on reaction time (RT) performance in the subliminal masked prime task. The functional localizer experiment consisted of four blocks of sequential finger tapping and 15 s of rest after each block. Imaging data were analyzed with SPM 8 and then were imported into the Brainsight software version 2.1.5. With such system, we were able to navigate across the subjects’ brain. The peak voxel in the SMA for each subject (at a statistical threshold of p < 0.05 uncorrected) was used as a target point for the rTMS session. Results: The mean motor threshold was 50.9 % of maximal stimulator output (SD: ± 4.86 %). Wilcoxon tests showed a significant effect of compatibility on RTs (sham: Z = 2.7, p = 0.007; rTMS: Z = 2.8, p = 0.005) and accuracy rate (sham: Z = 2.5, p = 0.01; rTMS: Z = 2.1, p = 0.03), subjects being slower and making more errors in compatible trials (sham: 391.64 ± 52 ms, 87.3 % of accuracy; rTMS: 396.66 ± 37 ms, 86.3 % of accuracy) in comparison to incompatible trials (sham: 357.45 ± 36 ms, 92.5 % of accuracy; rTMS: 356.25 ± 28 ms, 92.7 % of accuracy), suggesting motor inhibition. However, this NCE was preserved after rTMS over the SMA (RTs: Z = 0.87, p = 0.39; accuracy rate: Z = 0.71, p = 0.47). Conclusions: We conclude that long trains of low intensity 1 Hz rTMS did not affect the modulation of RT by subliminal stimuli, suggesting that the SMA might not be mandatory for the implementation of this automatic process. The limitation of this study is relative to the neural efficacy argument because we are not sure that TMS was strong enough to disturb the redundant organizational processing in the SMA or that other regions were not able to compensate for the virtually lesioned area. [less ▲]

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See detailDiscriminant BOLD Activation Patterns during Mental Imagery in Parkinson’s Disease
Schrouff, Jessica ULg; Cremers, Julien ULg; D'Ostilio, Kevin ULg et al

in Proceedings of MLINI 2012 (2012, December 07)

Using machine learning based models in clinical applications has become current practice and can prove useful to provide information at the subject’s level, such as predicting an (early) diagnosis or ... [more ▼]

Using machine learning based models in clinical applications has become current practice and can prove useful to provide information at the subject’s level, such as predicting an (early) diagnosis or monitoring the evolution of a disease. However, the performance of these models depends on the choice of a biomarker to detect the presence or absence of a disease. Choosing a biomarker is not straightforward, especially in the case of Parkinson’s disease when compared to healthy subjects. In the present work, we investigated the mental imagery of gait as a biomarker of Parkinson’s disease and showed that the signal in the mesencephalic locomotor region during the mental imagery of gait at a comfortable pace can discriminate significantly between idiopathic Parkinson’s disease patients and healthy subjects. Although there is room for improvement, the results of this preliminary study are promising. [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 detailEtude IRM par tenseur de diffusion (DTI) des anomalies microstructurelles de la matière blanche dans la maladie de Parkinson
Coolen, Tim; Cremers, Julien ULg; André, Elodie ULg et al

Poster (2012, March 21)

Introduction L’imagerie par résonance magnétique (IRM) conventionnelle du cerveau est réputée normale dans la maladie de Parkinson (MP), mais l’essor récent de techniques avancées offre de nouvelles ... [more ▼]

Introduction L’imagerie par résonance magnétique (IRM) conventionnelle du cerveau est réputée normale dans la maladie de Parkinson (MP), mais l’essor récent de techniques avancées offre de nouvelles perspectives, notamment l’IRM par tenseur de diffusion (DTI). Les études précédentes en la matière, hétérogènes dans leurs méthodes, montrent des résultats discordants. Ici, nous avons utilisé la DTI pour rechercher, sans hypothèse a priori, la présence d’anomalies microstructurelles au sein des principaux tracti de matière blanche dans la MP. Méthodes Soixante et un volumes en pondération de diffusion ont été acquis avec un système Allegra 3T (Siemens, Erlangen, Allemagne) au moyen d’une séquence DTI doublement refocalisée (1) chez 27 patients parkinsoniens non déments (durée moyenne d’évolution après le diagnostic : 5 ± 4.2 ans) et 25 contrôles d’âge (MP: 68,7±8,4; C: 65,1±8,8) et de genre similaires. Pour chaque sujet, les valeurs d’anisotropie fractionnelle (FA) et de diffusivité moyenne (MD) ont été extraites à partir d’un modèle du tenseur obtenu au moyen du logiciel ExploreDTI (2) faisant appel à la méthode RESTORE (3). Nous avons ensuite utilisé le module TBSS (v1.2) du logiciel FSL (4) pour conformer les images des scalaires dans un espace tridimensionnel commun puis rechercher, voxel-par-voxel, des différences entre les 2 groupes au sein du squelette de la matière blanche. Les résultats obtenus à l’issue d’un test par permutations (N=10000) ont été corrigés pour des comparaisons multiples. Résultats L’analyse des cartes de FA montre des valeurs significativement (P<0.05) plus élevées chez les patients dans plusieurs régions (5): fibres sous-corticales péri-rolandiques droites, parties du faisceau arqué droit, fibres du faisceau longitudinal inférieur et /ou fronto-occipital inférieur droit, fibres sous-corticales préfrontales gauches, partie postérieure du genou corps calleux. La comparaison inverse ne révèle aucun résultat significatif ni l’analyse des cartes de MD. Conclusions Ces résultats sont en accord avec les modèles physiopathologiques selon lesquels le primum movens dans la MP se situe dans une dysfonction synaptique et axonale (6,7). Une augmentation des valeurs de FA de la matière blanche dans la MP est en contradiction avec la plupart mais pas toutes (8,9) les études précédentes. L’hypothèse d’une diminution relative des fibres de croisement dans ces régions chez les patients mérite d’être testée au moyen de méthodes d’acquisition et d’analyse plus élaborées. Références 1. Nagy Z, et al. Magn Reson Med 2008; 60(5):1256-1260. 2. Leemans A, et al. Proc Intl Soc Mag Reson Med 17 2009;3537. (Abstract). 3. Chang LC, et al. Magn Reson Med 2005;3(5):1088-1095. 4. Smith SM et al. Neuroimage 2006; 31(4):1487-1505. 5. Catani M, et al. Cortex 2008; 44(8):1105-1132. 6. Schulz-Schaeffer WJ. Acta Neuropathol 2010; 120(2):131-143. 7. Cheng HC, et al. Ann Neurol 2010; 67(6):715-725. 8. Tessa C, et al. AJNR 2008; 29(4):674-680. 9. Wang JJ et al. Radiology 2011; 261(1):210-217. Remerciements Ce travail est financé par le Fonds de la Recherche Scientifique (FNRS-FRS) de la Communauté Française de Belgique. [less ▲]

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See detailBrain activation pattern related to gait disturbances in Parkinson's disease.
Cremers, Julien ULg; D'Ostilio, Kevin ULg; Stamatakis, Julien et al

in Movement Disorders : Official Journal of the Movement Disorder Society (2012), 27(12), 1498-505

Gait disturbances represent a therapeutic challenge in Parkinson's disease (PD). To further investigate their underlying pathophysiological mechanisms, we compared brain activation related to mental ... [more ▼]

Gait disturbances represent a therapeutic challenge in Parkinson's disease (PD). To further investigate their underlying pathophysiological mechanisms, we compared brain activation related to mental imagery of gait between 15 PD patients and 15 age-matched controls using a block-design functional MRI experiment. On average, patients showed altered locomotion relatively to controls, as assessed with a standardized gait test that evaluated the severity of PD-related gait disturbances on a 25-m path. The experiment was conducted in the subjects as they rehearsed themselves walking on the same path with a gait pattern similar as that during locomotor evaluation. Imagined walking times were measured on a trial-by-trial basis as a control of behavioral performance. In both groups, mean imagined walking time was not significantly different from that measured during real gait on the path used for evaluation. The between-group comparison of the mental gait activation pattern with reference to mental imagery of standing showed hypoactivations within parieto-occipital regions, along with the left hippocampus, midline/lateral cerebellum, and presumed pedunculopontine nucleus/mesencephalic locomotor area, in patients. More specifically, the activation level of the right posterior parietal cortex located within the impaired gait-related cognitive network decreased proportionally with the severity of gait disturbances scored on the path used for gait evaluation and mental imagery. These novel findings suggest that the right posterior parietal cortex dysfunction is strongly related to the severity of gait disturbances in PD. This region may represent a target for the development of therapeutic interventions for PD-related gait disturbances. (c) 2012 Movement Disorder Society. [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 detailConstruction and validation of the Dynamic Parkinson Gait Scale (DYPAGS).
Cremers, Julien ULg; PHAN BA, Remy ULg; DELVAUX, Valérie ULg et al

in Parkinsonism & Related Disorders (2012)

The dynamic evaluation of Parkinson's disease (PD)-related episodic gait disturbances in routine is challenging. Therefore, the aim of our study was to assess the reliability/validity of the Dynamic ... [more ▼]

The dynamic evaluation of Parkinson's disease (PD)-related episodic gait disturbances in routine is challenging. Therefore, the aim of our study was to assess the reliability/validity of the Dynamic Parkinson Gait Scale (DYPAGS) composed of eight relevant items for the objective quantification of PD gait features: walking forwards/backwards/with dual-task, turning to both sides, imaginary obstacle avoidance with both legs and passing through narrow spaces. The scale was validated on thirty-five patients with mild to severe parkinsonism in their habitual "on-state". A shorter 6 item-version was designed on the basis of a principal component analysis. No significant floor/ceiling effect was detected. The internal consistency was excellent. The levels of interrater agreement, precision and minimal detectable change were adequate. The criterion-related validity was demonstrated by strong correlations with the DYPAGS scores and those at the gait subscales of the Tinetti Mobility Test and MDS-UPDRS. The construct validity was assessed by moderate-strong correlations with the Freezing of Gait Questionnaire, mobility index of the PD Questionnaire (PDQ-39), disease duration and levodopa equivalent daily doses. Statistical analyses using the coefficient of determination showed that both DYPGAS versions were superior to the other instruments to identify patients with gait disturbances with poorer response to dopaminergic treatment. Full and short DYPAGS are reliable instruments for the quantification of "on" PD-related episodic gait disturbances. The full version is sensitive to detect subtle disturbances in mild parkinsonism. The shorter one is easily administered and reliably quantifies gait disturbances in moderate to severe parkinsonism. We recommend their use for research and clinical practice. [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 detailLa demence chez le patient parkinsonien: facteurs de risque, diagnostic et traitement.
BAKAY, Sara ULg; BECHET, Sophie ULg; BARJONA MORGADO DE MOURA, Aude ULg et al

in Revue Médicale de Liège (2011), 66(2), 75-81

Aside from limb tremor, bradykinesia, rigidity and gait disturbances, Parkinson's disease (PD) is also characterized by non-motor symptoms. A cognitive decline can occur early in the disease course and ... [more ▼]

Aside from limb tremor, bradykinesia, rigidity and gait disturbances, Parkinson's disease (PD) is also characterized by non-motor symptoms. A cognitive decline can occur early in the disease course and undoubtedly impact of the patient's quality of life. Dementia affects 80% of patients 20 years after disease onset but a small subgroup of patients remain free of dementia even after decades with PD. Risk factors and diagnosis of dementia can be easily assessed using bed-side clinical instruments. Advances in genetics and imagery will allow improving the diagnosis and therapeutic strategy dementia in Parkinson's disease. [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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