References of "Garraux, Gaëtan"
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See detailBrain mechanisms underlying automatic and unconscious control of motor action
D'Ostilio, Kevin ULg; GARRAUX, Gaëtan ULg

in Frontiers in Human Neuroscience (2012)

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See detailAutomatic multiclass classification of 18FDG-PET scans for the distinction between Parkinson’s disease and atypical parkinsonian syndromes
Phillips, Christophe ULg; Schrouff, Jessica ULg; Luxen, André ULg et al

Poster (2012, June 10)

Part of the difficulty in the early diagnosis of Parkinson’s disease (PD) is in differentiating it from atypical parkinsonian disorders (APS) that have a poorer prognosis such as multiple system atrophy ... [more ▼]

Part of the difficulty in the early diagnosis of Parkinson’s disease (PD) is in differentiating it from atypical parkinsonian disorders (APS) that have a poorer prognosis such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). 18flurodeoxyglucose (FDG) positron emission tomography (PET) has been recommended for the early differentiation between PD and APS [1]. Here, 120 FDG PET scans (42, 31, 26 and 21 for the PD, MSA, PSP and CBS resp.) were acquired on average 3.5 years after symptoms onset (because the initial clinical features were outside the prevailing perception for PD) to look, without any a priori assumption, for cerebral FDG uptake patterns that discriminate either between the PD and APS classes, or between the four PD, MSA, PSP and CBS classes. The diagnostic used to label the scans was defined by clinical criteria on average 4.5 years after PET assessment. [less ▲]

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See detailNEURAL CORRELATES OF GAIT HYPOKINESIA IN PARKINSON'S DISEASE: AN FMRI STUDY
Cremers, Julien ULg; Stamatakis, Julien; D'Ostilio, Kevin ULg et al

Poster (2012, May 05)

Introduction: Brisk walking (BW) is an efficient tool to study gait hypokinesia whose pathogenesis remains poorly understood in Parkinson's disease (PD). Aims: Assuming that brain regions recruited during ... [more ▼]

Introduction: Brisk walking (BW) is an efficient tool to study gait hypokinesia whose pathogenesis remains poorly understood in Parkinson's disease (PD). Aims: Assuming that brain regions recruited during imagined gait strongly overlap with those recruited during real gait, we used mental imagery of BW as a paradigm to study the neural correlates of gait hypokinesia in PD with BOLD fMRI. Methods: 15 'on-drugs' PD patients and 15 controls matched for age and gender were instructed to imagine themselves in two situations: comfortable walking (CW) and BW on a 25 meter-path. Imagined speed reserve (ISR), defined as the difference between imagined BW and CW speeds, was measured as a control of behavioral performance. The first-level individual contrast images representing the comparison between BW and CW were entered into second-level analyses with the corresponding ISRs as correlation regressors. Results: ISRs and their real counterparts measured offline were significantly decreased in patients relatively to controls. They strongly positively correlated in patients (Pearson's r = 0.88) and controls (Pearson's r = 0.59). Between-group comparison of individual contrasts BW minus CW in correlation with their corresponding ISRs showed that increasing imagined gait speed was strongly associated with increased activity of the left posterior parietal cortex (PPC) in controls and with decreased activity of this region in the patients. Conclusions: Our findings suggest that gait hypokinesia is related to an impaired function of the left PPC in PD. The left PPC may represent a target for therapeutic interventions aimed at alleviating gait disturbances in PD. [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 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 detailDissociation between unconscious motor response facilitation and conflict in medial frontal areas.
D'Ostilio, Kevin ULg; GARRAUX, Gaëtan ULg

in European Journal of Neuroscience (2012), 35(2), 332-340

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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 multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants.
Sharma, Manu; Ioannidis, John P. A.; Aasly, Jan O. et al

in Journal of Medical Genetics (2012), 49(11), 721-6

BACKGROUND: Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease . Although additional missense ... [more ▼]

BACKGROUND: Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease . Although additional missense variants were described, their pathogenic role yet remains inconclusive. METHODS AND RESULTS: We performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort. CONCLUSIONS: Our study apart from identifying the p.Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide. [less ▲]

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See detail3D Analysis of Normal and Pathological Gait Based on Low-Cost Wireless Accelerometers
Boutaayamou, Mohamed ULg; Schwartz, Cédric ULg; Bruls, Olivier ULg et al

in URSI Benelux Forum 2012 “Antennas: multiple designs, multiple applications” (2012)

We describe the principle and use of a new low-cost, wireless, 3-axis accelerometer-based device that records acceleration signals and automatically analyses them to characterize normal and pathological ... [more ▼]

We describe the principle and use of a new low-cost, wireless, 3-axis accelerometer-based device that records acceleration signals and automatically analyses them to characterize normal and pathological gait. [less ▲]

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See detailNeural correlates of hypokinetic gait in Parkinson’s disease: An fMRI study
Cremers, Julien ULg; Stamatakis, Julien; D'Ostilio, Kevin ULg et al

Poster (2012)

Objective: To investigate the neural correlates of hypokinetic gait in Parkinson’s disease (PD) using functional magnetic resonance imaging (fMRI). Background: Although hypokinetic gait is frequent and ... [more ▼]

Objective: To investigate the neural correlates of hypokinetic gait in Parkinson’s disease (PD) using functional magnetic resonance imaging (fMRI). Background: Although hypokinetic gait is frequent and has a negative impact on quality of life in PD, its underlying mechanisms remain poorly understood. Assuming that the brain regions recruited during real and imagined gait strongly overlap, mental imagery of brisk gait may be a successful approach to study hypokinetic gait in PD. Methods: Fifteen ‘‘on-drugs’’ PD patients (8 males; mean age 5 65.1 6 9.4 years) and fifteen controls matched for age, gender and mental imagery skills were trained to perform video-taped trials of comfortable and brisk gait on a 25 meter-path. The study was organ- ized as a block-design fMRI experiment where subjects were instructed to rehearse themselves performing comfortable and brisk gait and to press a key to indicate when they completed each 25 meter-imagined gait trial. The imagined speed reserve (ISR) defined as the difference between imagined brisk and comfortable gait speeds was measured as a control of behavioral performance. Imaging data processing and analyses were performed using SPM8. The first-level individual contrast images representing the comparison between brisk and comfortable gait were entered as two separate groups (controls vs patients) in an ANOVA with the corresponding ISRs as correlation regressors. Results: Compared with controls, patients showed hypokinetic gait during real gait training as their increase in speed during brisk relatively to comfortable gait was related to an increase in step ca- dence (r50.87; p<0.001) but not in step length (r50.11). ISRs meas- ured during fMRI and their real counterparts measured offline strongly correlated in patients (r50.88; p<0.001) and controls (r50.59; p50.02). Between-group comparison (p<0.001, uncorrected) of fMRI data showed that increasing imagined gait speed was strongly associated with increased activity of the left posterior parietal cortex in controls and with decreased activity of this region in patients. Conclusions: Our findings suggest that hypokinetic gait in PD is related to the impaired functioning of the left posterior parietal cortex. This area may represent a target for therapeutic interventions aimed at alleviating gait disturbances in PD. [less ▲]

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See detailLarge-scale replication and heterogeneity in Parkinson disease genetic loci.
Sharma, Manu; Ioannidis, John P. A.; Aasly, Jan O. et al

in Neurology (2012), 79(7), 659-67

OBJECTIVE: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The ... [more ▼]

OBJECTIVE: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. METHODS: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. RESULTS: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. CONCLUSION: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. [less ▲]

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See detailDu coaching physique pour mieux endurer la maladie de Parkinson
Garraux, Gaëtan ULg

in Mouvements (2012), 12(2), 41-50

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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 detailPartial trisomy 4q associated with young-onset dopa-responsive parkinsonism.
Garraux, Gaëtan ULg; CABERG, Jean-Hubert ULg; Vanbellinghen, Jean-Francois et al

in Archives of Neurology (2012), 69(3), 398-400

OBJECTIVE: To describe a patient who developed a young-onset, dopa-responsive parkinsonism linked to a de novo heterozygous interstitial duplication 4q. DESIGN: Case report. SETTING: Movement Disorder ... [more ▼]

OBJECTIVE: To describe a patient who developed a young-onset, dopa-responsive parkinsonism linked to a de novo heterozygous interstitial duplication 4q. DESIGN: Case report. SETTING: Movement Disorder Outpatient Clinic at the University Hospital Centre, Liege, Belgium. Patient A 31-year-old woman. MAIN OUTCOME MEASURES: Clinical, neuroimaging, and genetic data. RESULTS: The duplicated region contains 150 known genes, including the alpha-synuclein (SNCA) gene locus. Motor and 6-[(18)F]fluoro-L-dopa positron emission tomography features are similar to those previously reported in heterozygote SNCA duplication carriers. Altered expression of other genes contained in the duplicated region may contribute to clinical features that are uncommon in the phenotypic spectrum of SNCA multiplications such as delayed developmental psychomotor milestones during infancy and musculoskeletal abnormalities. CONCLUSION: This case report provides new insights on the genetic basis of parkinsonism. [less ▲]

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See detailBrain energization in response to deep brain stimulation of subthalamic nuclei in Parkinson's disease.
Garraux, Gaëtan ULg; Bahri, Mohamed Ali ULg; Lemaire, Christian ULg et al

in Journal of Cerebral Blood Flow & Metabolism (2011)

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment in a subgroup of medically refractory patients with Parkinson's disease (PD). Here, we compared resting-state (18)F ... [more ▼]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment in a subgroup of medically refractory patients with Parkinson's disease (PD). Here, we compared resting-state (18)F-fluorodeoxyglucose (FDG) positron emission tomography images in the stimulator off (DBS_OFF) and on (DBS_ON) conditions in eight PD patients in an unmedicated state, on average 2 years after bilateral electrode implantation. Global standardized uptake value (SUV) significantly increased by approximately 11% in response to STN-DBS. To avoid any bias in the voxel-based analysis comparing DBS_ON and DBS_OFF conditions, individual scan intensity was scaled to a region where FDG-SUV did not differ significantly between conditions. The resulting FDG-SUV ratio (FDG-SUVR) was found to increase in many regions in response to STN-DBS including the target area of surgery, caudate nuclei, primary sensorimotor, and associative cortices. Contrary to previous studies, we could not find any regional decrease in FDG-SUVR. These findings were indirectly supported by comparing the extent of areas with depressed FDG-SUVR in DBS_OFF and DBS_ON relatively to 10 normal controls. Altogether, these novel results support the prediction that the effect of STN-DBS on brain activity in PD is unidirectional and consists in an increase in many subcortical and cortical regions.Journal of Cerebral Blood Flow & Metabolism advance online publication, 6 April 2011; doi:10.1038/jcbfm.2011.41. [less ▲]

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See detailAutomatic Stimulus-Induced Medial Premotor Cortex Activation without Perception or Action
D'Ostilio, Kevin ULg; Garraux, Gaëtan ULg

in PLoS ONE (2011), 6(2),

Who has ever been surprised to return to the bowl of salted peanuts without realizing it, even after having eating a moderate number and deciding to stop? Using rapid event-related functional magnetic ... [more ▼]

Who has ever been surprised to return to the bowl of salted peanuts without realizing it, even after having eating a moderate number and deciding to stop? Using rapid event-related functional magnetic resonance imaging (fMRI) in healthy volunteers, we investigated the neural correlates of automatic processes induced by subliminal stimuli. We demonstrated that the automatic activation of motor programs elicited unconsciously in the medial premotor cortex was normally restricted to specific contexts set by the environment, but can occur below the threshold of awareness even when no movement was executed. This novel finding expands our view on brain mechanisms underlying unconscious motor control and provides new evidence that activation of the motor preparation system and consciousness are not obligatory linked. [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 detailGait feature extraction in Parkinson's disease using low-cost accelerometers
Stamatakis, Julien; Cremers, Julien ULg; Maquet, Didier ULg et al

Poster (2011)

The clinical hallmarks of Parkinson’s disease (PD) are movement poverty and slowness (i.e. bradykinesia), muscle rigidity, limb tremor or gait disturbances. Parkinson’s gait include slowness, shuffling ... [more ▼]

The clinical hallmarks of Parkinson’s disease (PD) are movement poverty and slowness (i.e. bradykinesia), muscle rigidity, limb tremor or gait disturbances. Parkinson’s gait include slowness, shuffling, short steps, freezing of gait (FoG) and/or asymmetries in gait. There are currently no validated clinical instruments or device that allow a full characterization of gait disturbances in PD. As a step towards this goal, a four accelerometer-based system is proposed to increase the number of parameters that can be extracted to characterize parkinsonian gait disturbances such as FoG or gait asymmetries. After developing the hardware, an algorithm has been developed, that automatically epoched the signals on a stride-by-stride basis and quantified, among others, the gait velocity, the stride time,the stance and swing phases, the single and double support phases or the maximum acceleration at toe-off, as validated by visual inspection of video recordings during the task. The results obtained in a PD patient and an healthy volunteer are presented. The FoG detection will be improved using time-frequency analysis and the system is about to be validated with a state-of-the-art 3D movement analysis system. [less ▲]

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See detailBrain perfusion patterns in familial frontotemporal lobar degeneration.
Seelaar, H.; Papma, J. M.; Garraux, Gaëtan ULg et al

in Neurology (2011), 77(4), 384-92

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) is a clinically, genetically, and pathologically heterogeneous disorder. The aim of this study was to compare clinical features and perfusion patterns ... [more ▼]

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) is a clinically, genetically, and pathologically heterogeneous disorder. The aim of this study was to compare clinical features and perfusion patterns on SPECT of patients with familial FTLD-TAR DNA binding protein 43 kDa (TDP) and MAPT mutations. METHODS: Patients were included if they had MAPT or GRN mutations, positive family history with pathologically proven FTLD in the patient or first-degree relative, or were part of FTD-MND families. All patients and 10 age- and gender-matched controls underwent measurement of brain perfusion using (99m)Tc-HMPAO SPECT. We used SPM8 to perform image processing and voxel-based group analyses (p < 0.001). Gender and age were included as nuisance variables in the design matrices. RESULTS: Of the 29 patients with familial FTLD, 19 had familial FTLD-TDP (GRN mutations in 6), and 10 had MAPT mutations. At clinical presentation, familial FTLD-TDP patients were older at onset (p = 0.030) and had more memory deficits (p = 0.011), whereas patients with MAPT had more naming deficits (p < 0.001) and obsessive-compulsive behavior (p = 0.001). The between-groups SPECT analyses revealed significantly less perfusion in the right frontal lobe, precuneus, cuneus, and inferior parietal lobule in familial FTLD-TDP, whereas significantly less perfusion was found in the left temporal and inferior frontal gyri in MAPT. Post hoc analysis of familial FTLD-TDP with unknown genetic defect vs MAPT revealed less perfusion in the right frontal and parietal lobe. CONCLUSION: Familial FTLD-TDP shows relatively more posterior hypoperfusion, including the precuneus and inferior parietal lobule, possibly related to significant memory impairment. Patients with MAPT were characterized by impaired perfusion of the temporal regions and naming deficits. [less ▲]

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