Discriminant BOLD Activation Patterns during Mental Imagery in Parkinson’s Disease

in Proceedings of MLINI 2012 (in press)

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 ▲]

Preserved automatic inhibition effect after 1 Hz repetitive transcranial magnetic stimulation over the supplementary motor area

Poster (2013, March)

Preserved automatic inhibition effect after 1 Hz repetitive transcranial magnetic stimulation over the supplementary motor area

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 ▲]

Etude IRM par tenseur de diffusion (DTI) des anomalies microstructurelles de la matière blanche dans la maladie de Parkinson

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 ▲]

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

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 ▲]

Comparison of the Timed 25-Foot and the 100-Meter Walk as Performance Measures in Multiple Sclerosis

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 ▲]

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

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 ▲]

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

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 ▲]

La vignette thérapeutique de l'étudiant. La maladie de Parkinson debutante

in Revue Médicale de Liège (2009), 64(4), 228-32

We present a discussion on the treatment options in the case of a patient seen at the outpatient abnormal movement clinic for a resting tremor of both hands. Signs and symptoms of the parkinsonian ... [more ▼]

We present a discussion on the treatment options in the case of a patient seen at the outpatient abnormal movement clinic for a resting tremor of both hands. Signs and symptoms of the parkinsonian syndrome are summarized as well as the current treatment options of early Parkinson's disease. [less ▲]

Etude en stimulation magnétique transcrânienne de la récupération motrice des AVC

Doctoral thesis (2005)