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BACKGROUND: The 'dual syndrome' hypothesis states that two cognitive subtypes can be distinguished in mild cognitive impairment in Parkinson's disease (PD-MCI): a frontostriatal one, characterized by attentional and/or executive deficits, and a posterior cortical one, characterized by visuospatial, memory and/or language deficits. The latter type has been associated with a higher risk of earlier development of PD dementia. The functional bases of these subtypes remain partly unknown.OBJECTIVE: To identify EEG modifications associated with PD-MCI subtypes.METHODS: 75 non-demented PD patients underwent a comprehensive neuropsychological assessment and a high-density EEG. They were classified as having normal cognition (PD-NC; n = 37), PD-MCI with a frontostriatal subtype (PD-FS; n = 11) or PD-MCI with a posterior cortical subtype (PD-PC; n = 27). Two EEG analyses were performed: (a) spectral powers quantification and (b) functional connectivity analysis.RESULTS: PD-FS patients displayed spectral and functional EEG alterations, namely (a) higher powers in the theta and delta bands, (b) lower powers in the beta2 band and (c) lower functional connectivity in the beta2 band compared to PD-NC and PD-PC patients. These alterations were mainly located in the frontal, limbic and parietal regions. There were no significant differences between PD-NC and PD-PC.CONCLUSION: EEG alterations previously reported in PD-MCI may only concern the frontostriatal subtype, and not the posterior-cortical subtype. This provides evidence for the dual syndrome hypothesis and emphasizes the importance of identifying PD-MCI subtypes. It also shows the promising potential of EEG to discriminate between PD-MCI subtypes.

Our objective was to evaluate the potential additional value of electroencephalogram (EEG) and evoked potentials in neonates with hypoxic-ischemic encephalopathy to predict their disability at 1 and 2 years old.30 full-term infants after perinatal asphyxia who underwent therapeutic hypothermia were evaluated at 1 year and 2 years for disability using International Classification of Functioning, Disability and Health classification. Scores for EEG, sensory evoked potentials and brainstem auditory evoked potentials were evaluated after withdrawal of therapeutic hypothermia that lasted 72 h. A regression approach was investigated to build models allowing to distinguish neonates according to their disability at 1 and 2 years. Two models were built, the first by considering the clinical data and EEG before and after therapeutic hypothermia and the second by incorporating evoked potentials recording.Adding EEG and evoked potentials data after rewarming improved dramatically the accuracy of the model considering outcome at 1 and 2 years.We propose to record systematically EEG and evoked potentials following rewarming to predict the outcome of neonates with hypoxic ischemic encephalopathy. Combination of altered evoked potentials with no improvement of EEG after rewarming appeared to be a robust criterion for a poor outcome.

Objective To evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study. Methods Six ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to the center. Clinical evaluation of patients included the revised ALS Functional Rating Scale (ALSFRS-R) and upper motor neuron (UMN) score. Results TST amplitude ratio was decreased in 62% of patients whereas conventional TMS amplitude ratio was decreased in 25% of patients and central motor conduction time was increased in 16% of patients. TST amplitude ratio was correlated with ALSFRS-R and UMN score. TST amplitude ratio results were not different between the centers. Conclusions TST is a TMS technique applicable in daily clinical practice in ALS centers for the detection of UMN dysfunction, more sensitive than conventional TMS and related to the clinical condition of the patients. Significance This multicenter study shows that TST can be a routine clinical tool to evaluate UMN dysfunction at the diagnostic assessment of ALS patients.

Background Gait initiation is an automatized motor program that is preceded by anticipatory postural adjustments (APAs). During attentional tasks, these APAs can be modulated, producing multiple APAs. However, the role of the peripheral nervous system in the regulation of these APAs is unknown. Research question The objective of our study was to investigate whether APAs are also regulated by peripheral nervous afferents. Methods We assessed 21 patients suffering from chronic inflammatory demyelinating neuropathy and 20 healthy controls. Participants initiated gait with the right or left leg either freely (in the standard condition) or according to a visual trigger (i.e., the select condition). Kinetic and kinematic parameters of APAs and step initiation were recorded. Results The select condition was related to a higher rate of multiple APAs compared to the standard condition, and was more attention-consuming in both groups. The group with a neuropathy showed longer APAs than the control group, associated with a longer time to recover from multiple APAs. Consequently, the step execution time was delayed in patients with a peripheral neuropathy. Significance The impairment of the peripheral nervous system is therefore responsible for an alteration of the mechanisms underlying the recovery from multiple APAs during gait initiation. Our results are in favor of a role of proprioceptive afferents in the early peripheral regulation of motor errors. Further study on gait initiation in peripheral nervous disease could be helpful to better explore sensory-motor coupling in tasks requiring balance control.

International audience; INTRODUCTION: There is a growing interest in personality evaluation in Parkinson's disease (PD), following observations of specific temperaments in PD patients. Therefore, our objective was to evaluate personality dimensions from the Temperament and Character Inventory (TCI) in a cohort of fluctuating PD patients considered for deep brain stimulation. METHODS: Fluctuating PD patients from the PREDISTIM cohort were included. Description of TCI dimensions and comparison with a French normative cohort were performed. Pearson correlations between TCI dimensions and motor, behavioral and cognitive variables were investigated. Structural and internal consistency analysis of the TCI were further assessed. RESULTS: The 570 PD patients presented significant higher scores in Harm Avoidance, Reward Dependence, Persistence, Self-Directedness and Cooperativeness and significant lower scores in Self-Transcendence compared to the French normative cohort; only Novelty Seeking scores were not different. Harm Avoidance and Self-directedness scores were correlated with PDQ-39 total, HAMD, HAMA scores, and anxiolytic/antidepressant treatment. Novelty Seeking scores were correlated with impulsivity. Pearson correlations between TCI dimensions, principal component analysis of TCI sub-dimensions and Cronbach's alpha coefficients showed adequate psychometric proprieties. CONCLUSION: The TCI seems to be an adequate tool to evaluate personality dimensions in PD with good structural and internal consistencies. These fluctuating PD patients also have specific personality dimensions compared to normative French population. Moreover, Harm Avoidance and Self-Directedness scores are associated with anxio-depressive state or quality of life and, and Novelty Seeking scores with impulsivity.

Objective To describe EEG patterns of critical Coronavirus Disease 2019 (COVID-19) patients with suspicion of encephalopathy and test their association with clinical outcome. Methods EEG after discontinuation of sedation in all patients, and somesthesic evoked potentials and brainstem auditive evoked potentials when EEG did not show reactivity, were performed. Clinical outcome was assessed at day 7 and 14 after neurophysiological explorations. Results 33 patients were included for analysis. We found slowed background activity in 85% of cases, unreactive activity in 42% of cases, low-voltage activity in 21% of cases and rhythmic or periodic delta waves in 61% of cases. EEG epileptic events were never recorded. Clinical outcome at day 14 was associated with unreactive background activity and tended to be associated with rhythmic or periodic delta waves and with low-voltage activity. Results of multimodal evoked potentials were in favor of a preservation of central nervous system somatosensory and auditory functions. Conclusions Among critical COVID-19 patients with abnormal arousal at discontinuation of sedation, EEG patterns consistent with encephalopathy are found and are predictive for short term clinical outcome. Significance The abnormal EEG with presence of periodic discharges and lack of reactivity could be related to encephalopathy linked to COVID-19.

To identify relevant quantitative parameters for early classification of neonatal hypoxic-ischemic encephalopathy (HIE) severity from conventional EEGs.Ninety EEGs, recorded in full-term infants within 6 h of life after perinatal hypoxia, were visually classified according to the French EEG classification into three groups of increasing HIE severity. Physiologically significant EEG features (signal amplitude, continuity and frequency content) were automatically quantified using different parameters. The EEG parameters selection was based on their ability to reproduce the visual EEG classification. Post hoc analysis based on clinical outcome was performed.Six EEG parameters were selected, with overall EEG classification performances between 61% and 70%. All parameters differed significantly between group 3 (severe) and groups 1 (normal-mildly abnormal) and 2 (moderate) EEGs (p 0.001). Amplitude and discontinuity parameters were different between the 3 groups (p 0.01) and were also the best predictors of clinical outcome. Conversely, pH and lactate did not differ between groups.This study provides quantitative EEG parameters that are complementary to visual analysis as early markers of neonatal HIE severity. These parameters could be combined in a multiparametric algorithm to improve their classification performance. The absence of relationship between pH lactate and HIE severity reinforces the central role of early neonatal EEG.

Objective Although a number of clinical factors have been linked to falls in Parkinson’s disease (PD), the diagnostic value of gait parameters remains subject to debate. The objective of this retrospective study was to determine to what extent the combination of gait parameters with clinical characteristics can distinguish between fallers and non-fallers. Methods Using a video motion system, we recorded gait in 174 patients with PD. The patients’ clinical characteristics (including motor status, cognitive status, disease duration, dopaminergic treatment and any history of falls or freezing of gait) were noted. The considered kinematic gait parameters included indices of gait bradykinesia and hypokinesia, asymmetry, variability, and foot clearance. After a parameters selection using an ANCOVA analysis, support vector machine algorithm was used to build classification models for distinguishing between fallers and non-fallers. Two models were built, the first included clinical data only while the second incorporated the selected gait parameters. Results The “clinical-only” model had an accuracy of 94% for distinguishing between fallers and non-fallers. The model incorporating additional gait parameters including stride time and foot clearance performed even better, with an accuracy of up to 97%. Conclusion Although fallers differed significantly from non-fallers with regard to disease duration, motor impairment or dopaminergic treatment, the addition of gait parameters such as foot clearance or stride time to clinical variables increased the model’s discriminant power. Significance: This predictive model now needs to be validated in prospective cohorts.

International audience; Background and purpose: Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat functional neurological disorders. Here, the aim was to assess the efficacy of rTMS to treat functional paralysis in a controlled randomized trial.Methods: Patients received two sessions of active or sham 0.25 Hz rTMS (60 stimuli each), with a 1-day interval, applied over the motor cortex contralateral to the paralysis. The primary outcome was the number of patients with an increase in motor score between baseline and after the second rTMS session, rated by two investigators blinded to the treatment allocation. Secondary outcomes were changes in global and fine motor scores between groups after rTMS, and the occurrence of adverse events.Results: Sixty-two patients (46 female; mean [SD] age, 35.2 [13.9] years) were enrolled and randomized. Thirteen out of 32 (41%) and 11/30 (37%) patients had increased motor strength after active or sham rTMS, respectively (p = 0.80). Changes in both global and fine motor scores after rTMS relative to baseline were also not significantly different between treatment groups (median difference in the global motor score 0.62 [0.83] and 0.37 [0.61], and in the fine motor scores 0.12 [0.18] and 0.08 [0.11], in active and sham rTMS groups, respectively; p = 0.14). Six serious adverse events, consisting of three cephalalgia in the active group and two cephalalgia and one asthenia in the sham group, were observed.Conclusions: Two sessions of sham or active low frequency rTMS were effective to improve functional paralysis, suggesting a placebo effect of this non-invasive brain stimulation technique.

Pompe disease is a progressive myopathy that combines motor, respiratory, and cardiac impairments. The 6-min walk test is the gold standard for assessing disease severity at the motor level. The objective of this study was to better determine the parameters that influence the total distance covered in patients with Pompe disease.We performed a retrospective review of 15 patients with late-onset Pompe disease who were followed regularly at a single referral center. Logistic regression was used to investigate the links between motor, respiratory and cardiac variables and 6-min walk test performance.When considering baseline clinical and demographic variables, a seven-step backward elimination regression analysis yielded a model with two predictors (age and the use of an assistive device) that explained 85.5% of the variance. When considering the cardiorespiratory variables monitored during gait, a three-step backward elimination regression analysis showed that two predictors (heart rate recovery and the baseline partial pressure of carbon dioxide) explained 42.2% of the variance.Our results highlighted the importance of respiratory and cardiac adaptation during exercise (along with motor ability) during the 6-min walk test in patients with Pompe disease. Further studies of larger cohorts are necessary to validate the model, which might enable investigators to determine whether intra-individual fluctuations in 6-min walk test performance are related to physiological parameters and/or to other variables such as the patient's level of motivation during the test.

International audience; The aims of this narrative review are to provide scientific support to characterize the postural instability commonly observed in Parkinson's disease (PD), and to emphasize how bottom-up rehabilitation programs stimulating the sole of the foot can improve postural stability in PD. Postural instability is a typical characteristic of individuals with PD, which increases the frequency of falls and may worsen their consequences. It thus seems relevant to diagnose these alterations as early as possible, in order to develop specific rehabilitative treatment. The association between sensitivity of the sole of the foot and postural instability in individuals with PD is linked to the key role of peripheral alterations of the sensorimotor system in balance and motor symptoms. By enhancing sensory feedback coming from the feet, bottom-up stimulation allows patients to improve their sensorimotor control. In clinical practice, health practitioners can use sensory stimulation to improve postural control. By improving postural stability, a decrease in fall risk can be achieved and the secondary impairments associated with falls prevented.

With about one third of adults aged 65 years and older being reported worldwide to fall each year, and an even higher prevalence with advancing age, aged-related falls and the associated disabilities and mortality are a major public health concern. In this context, identification of fall risk in healthy older adults is a key component of fall prevention. Since dual-task outcomes rely on the interaction between cognition and motor control, some studies have demonstrated the role of dual-task walking performance or costs in predicting future fallers. However, based on previous reviews on the topic, (1) discriminative and (2) predictive powers of dual tasks involving gait and a concurrent task are still a matter of debate, as is (3) their superiority over single tasks in terms of fall-risk prediction. Moreover, less attention has been paid to dual tasks involving postural control and transfers (such as gait initiation and turns) as motor tasks. In the present paper, we therefore systematically reviewed recent literature over the last 7 years in order to answer the three above mentioned questions regarding the future of lab-based dual tasks (involving posture, gait initiation, gait and turning) as easily applicable tests for identifying healthy older adult fallers. Despite great heterogeneity among included studies, we emphasized, among other things, the promising added value of dual tasks including turns and other transfers, such as in the Timed Up and Go test, for prediction of falls. Further investigation of these is thus warranted. 50;6

The pathophysiology of freezing of gait in people with Parkinson's disease (PD) remains unclear, despite its association with motor, cognitive, limbic and sensory-perceptual impairments. Resting-state electroencephalography (EEG) may provide functional information for a better understanding of freezing of gait by studying spectral power and connectivity between brain regions in different frequency bands.High-resolution EEG was recorded in 36 patients with PD (18 freezers, 18 non-freezers), and 18 healthy controls during a 5-min resting-state protocol with eyes open, followed by a basic spectral analysis in the sensor space and a more advanced analysis of functional connectivity at the source level.Freezers showed a diffusely higher theta-band relative spectral power than controls. This increased power was correlated with a deficit in executive control. Concerning resting-state functional connectivity, connectivity strength within a left fronto-parietal network appeared to be higher in freezers than in controls in the theta band, and to be correlated with freezing severity and a history of falls.We have shown that spectral power and connectivity analyses of resting-state EEG provide useful and complementary information to better understand freezing of gait in PD. The higher connectivity strength seen within the left ventral attention network in freezers is in keeping with an excessive guidance of behavior by external cues, due to executive dysfunction, and spectral analysis also found changes in freezers that was closely correlated with executive control deficits. This exaggerated influence of the external environment might result in behavioral consequences that contribute to freezing of gait episodes. These findings should be further investigated with a longitudinal study.

OBJECTIVE: To identify markers of Parkinson's disease (PD) related anxiety, using high density electroencephalography (hd-EEG).METHODS: 108 patients participated in the study. They were divided into two groups: with and without clinically relevant anxiety, according to their score on the Parkinson Anxiety Scale. Resting-state hd-EEG was recorded. Spectral and functional connectivity characteristics were compared between the two groups.RESULTS: Thirty-three patients (31%) had significant anxiety symptoms. In the spectral analysis, relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without. Functional connectivity analysis showed a stronger connectivity between the left insula and several regions of the right prefrontal cortex in patients with anxiety than in those without.CONCLUSION: This study shows the pivotal role of the insula and frontal cortex in the pathophysiology of anxiety in PD and extends the results of previous studies using magnetic resonance imaging or positron emission tomography imaging.

International audience; Patients with Parkinson’s disease (PD patients) have been shown to exhibit abnormally low levels of synergy in their posture control. The goal of this study is to determine how synergic interactions between vision and posture are affected in PD patients. These synergic interactions were expected to be impaired because PD affects the basal ganglia, which are involved in the modulation of both types of movement. Twenty patients (mean age: 60) on levodopa and 20 age-matched-controls (mean age: 61) performed a precise visual task (searching for targets in an image) and an unprecise control task (randomly looking at an image) in which images were projected onto a large panoramic display. Lower back, upper back, head and eye movements were recorded simultaneously. To test behavioural synergies, Pearson correlations between eye and postural movements were analysed. The relationships between eye movements and upper and lower back movements were impaired in the patients. The age-matched controls did not show any significant correlations between eye and postural movements. Overall, our results showed that the PD patients failed to adjust and control their postural stability for success in the visual task. The impaired synergy between eye and postural movements was not related to clinical variables - probably because our patients had early-stage PD. Our results showed that impairments in synergy can occur very early in PD. Hence, the analysis of this synergy might provide a better understanding of postural instability, visual task performance in the upright stance, and perhaps the risk of falls in PD patients.

BACKGROUND Duchenne Muscular Dystrophy (DMD), the most common neuromuscular disease in children, is a severe, progressive disease that affects skeletal muscle. Abnormal gait patterns in children with DMD result from compensatory adaptations of their locomotor system to maintain free ambulation in response to the slow, progressive muscle weakness, contractures and osteoarticular changes caused by the disease. Identification of gait abnormalities can be challenging because current understanding of how gait patterns changes progressively in children with DMD is limited. 3D gait analysis could thus increase understanding about the effects of the disease on gait, guide treatments and help to predict key milestones, such as ambulation loss. This latter event is important because it is an endpoint for clinical trials and studies of DMD disease progression. OBJECTIVE The primary aim of this study was to analyze the gait characteristics of children with Duchenne Muscular Dystrophy (DMD) during their last 2 years of free ambulation. The secondary aim was to explore the capacity of gait variables to predict the time of loss of ambulation. METHODS The gait of eighteen children with DMD and fourteen age-matched control children was recorded using a 3D optoelectronic system. Statistical parametric mapping was used to compare kinematic and kinetic variables between groups. Multivariate regression was used to identify predictors of the time of ambulation loss among spatiotemporal, kinematic and kinetic variables. RESULTS Compared with the controls, anterior pelvic tilt was increased during the whole gait cycle, hip flexion was increased during the second part of stance phase and of the entire swing, knee flexion was increased during swing, dorsiflexion was reduced during stance, and plantar flexion occurred in swing in the DMD group. Maximal ground reaction force, ankle dorsiflexion moment at initial contact, knee power absorption and generation during loading response, and maximal power generation of the hip at the end of stance were all reduced. A combination of gait variables, mostly kinetic, predicted the duration before ambulation loss to be less than three months. CONCLUSIONS The gait of children with DMD who are close to losing ambulation is characterized by specific deviations. The time of ambulation loss was accurately predicted by 3D gait variables, particularly kinetic. Combined with data from the clinical examination, 3D gait analysis provides valuable information to guide physical therapy, including targeted muscle strengthening and stretching, to help patients maintain free ambulation as long as possible.

Introduction Freezing of gait (FOG) in Parkinson's disease (PD) is associated with an altered posture during quiet stance as well as an impaired preparation and execution of the gait initiation process. We aimed to investigate whether an altered initial posture impacts anticipatory postural adjustments (APAs) and first-step execution during gait initiation in people with PD with FOG (PD + FOG). Methods Twenty-seven PD+FOG, 30 PD patients without FOG and 27 age-matched healthy controls performed self-generated gait initiation. Initial mean center of pressure (COP) position prior to APA onset, characteristics of APAs and features of first-step execution were investigated. Results Contrarily to controls, PD patients showed a COP that was initially positioned more towards the stance leg (p = 0.007). Moreover, significantly smaller backward COP shift, longer duration of swing-foot unloading phase, and lower first-step length and velocity characterized PD+FOG compared to controls. While size and duration of backward COP shift during APA and lateral COP shift during the unloading phase were main predictors of first-step length and velocity in all groups, the medio-lateral shift of the initial COP position in PD+FOG was a main predictor of first-step execution (β = −0.191, p = 0.001 for velocity). Conclusion In PD+FOG, the more the COP was initially positioned towards the stance foot, the slower and shorter the first step. The initial medio-lateral COP position may be a compensatory strategy to address postural instability of PD+FOG. A specific training regarding postural control prior to gait preparation and execution could improve functional mobility in PD+FOG.

Fil: Rascol, Olivier. Université de Toulouse. NeuroToul COEN Center. Services de Pharmacologie Clinique et Neurosciences. Centre d’Investigation Clinique; Francia Fil: Negre-Pages, Laurence. LN Pharma; Francia Fil: Negre-Pages, Laurence. Hôpital la Colombière. Département d’Information Médicale. Unité de Recherche Clinique et Epidémiologie; Francia Fil: Damier, Philippe. Université de Nantes. Department of Neurology; Francia Fil: Delval, Arnaud. Université de Lille. Department of Neurology; Francia Fil: Derkinderen, Pascal. Université de Lille. Department of Neurology; Francia Fil: Destée, Alain. Université de Lille. Department of Neurology; Francia Fil: Fabbri, Margherita.University of Turin. Department of Neuroscience; Italia Fil: Meissner, Wassilios G. NS-Park/FCRIN Network. Service de Neurologie; Francia Fil: Meissner, Wassilios G. Université de Bordeaux. Institut des Maladies Neurodégénératives; Francia Fil: Meissner, Wassilios G. University of Otag. Departament Medicine. New Zealand Brain Research Institute; Nueva Zelanda Fil: Rachdi, Amine. Université de Toulouse. NeuroToul COEN Center. Services de Pharmacologie Clinique et Neurosciences. Centre d’Investigation Clinique; Francia Fil: Tison, François. University of Otag. Departament Medicine. New Zealand Brain Research Institute; Nueva Zelanda Fil: Tison, François. Université de Toulouse. NeuroToul COEN Center. Services de Pharmacologie Clinique et Neurosciences. Centre d’Investigation Clinique; Francia Fil: Pérez Lloret, Santiago. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Pérez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Pérez Lloret, Santiago. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina Abstract: Introduction: We describe excessive buccal saliva (EBS) prevalence in patients with Parkinson’s Disease (PD) and controls of the COPARK study, its changes between “ON” and OFF” conditions and over time, its impact on Health-related Quality of life (HRQoL), and factors associated with this condition. Methods: We studied 671 ambulatory PD patients and 177 age/sex-matched controls. We defined “sialorrhea” as UPDRS item #6 (salivation)=1 or 2; and “drooling” as item #6=3 or 4. SCOPA-Aut drooling score (item #2) was also available in a subset (45%) of the cohort. HRQoL was assessed by the PDQ-39 and SF-36 scales. Twenty-four months follow-up data was available in 401/671 patients. Results: EBS as assessed by UPDRS was present in 38% of PD patients in the “ON” condition (“Sialorrhea”: 35%; “drooling”: 3%). There were also more PD patients reporting “drooling” than controls according to the SCOPA-Aut (49% vs 19%, p

Parkinson's disease (PD) affects the automatic control of body movements. In our study, we tested PD-related impairments in automatic postural control in quiet upright stance. Twenty PD patients (mean age: 60 ± 8 years; Hoehn and Yahr: 2.00 ± 0.32, on-drug) and twenty age-matched controls (61 ± 7 years) were recruited. We studied interrelations between center-of-pressure movements, body movements (head, neck, and lower back), eye movements and variability of pupil size. Participants performed two fixation tasks while standing, during which they looked at: (a) a cross surrounded by a white background; and (b) a cross surrounded by a structured visual background (images used: rooms in houses). PD patients exhibited stronger and weaker correlations between eye and center-of-pressure/body movement variables than age-matched controls in the white and structured fixation tasks, respectively. Partial correlations, controlling for variability of pupil size showed that PD patients used lower and greater attentional resources than age-matched controls to control their eye and center-of-pressure/body movements simultaneously in the white fixation and structured fixation tasks, respectively. In the white fixation task, PD patients used attentional resources to optimize visuomotor coupling between eye and body movements to control their posture. In the structured fixation task, the salient visual stimuli distracted PD patients’ attention and that possibly affected postural control by deteriorating the automatic visuomotor coupling. In contrast, age-matched controls were able to use surrounding visual background to improve the automatic coupling between eye and center-of-pressure movements to control their posture. These results suggest that cluttered environments may distract PD patients and deteriorate their postural control. 52;12

International audience; Gait is often considered as an automatic movement but cortical control seems necessary to adapt gait pattern with environmental constraints. In order to study cortical activity during real locomotion, electroencephalography (EEG) appears to be particularly appropriate. It is now possible to record changes in cortical neural synchronization/desynchronization during gait. Studying gait initiation is also of particular interest because it implies motor and cognitive cortical control to adequately perform a step. Time-frequency analysis enables to study induced changes in EEG activity in different frequency bands. Such analysis reflects cortical activity implied in stabilized gait control but also in more challenging tasks (obstacle crossing, changes in speed, dual tasks…). These spectral patterns are directly influenced by the walking context but, when analyzing gait with a more demanding attentional task, cortical areas other than the sensorimotor cortex (prefrontal, posterior parietal cortex, etc.) seem specifically implied. While the muscular activity of legs and cortical activity are coupled, the precise role of the motor cortex to control the level of muscular contraction according to the gait task remains debated. The decoding of this brain activity is a necessary step to build valid brain–computer interfaces able to generate gait artificially.

International audience; Motor programme for gait initiation can vary as a function of attentional resources. The objective of the present study was to determine whether alertness, orientation and executive control can modulate cortical activation during step initiation. The attention network test (ANT) was used to control the influence of different attentional components on kinetic characteristics of step initiation and the associated cortical activity. Thirty healthy adults performed ANT combined with step initiation. The step execution time (SET) and anticipatory postural adjustments (APAs) were recorded. Movement-related cortical potentials (MRCPs) and event-related spectral perturbations (ERSPs) after response emission were analysed according to the presence or absence of cueing or conflict resolution. Step reaction time and thus SET were significantly shorter with cueing, whereas APA duration and SET were longer during conflict resolution. Moreover, alertness was related to a higher rate of anticipated responses, and conflicting situations were associated with a greater amount of multiple APAs. Attentional load did not affect MRCPs but ERSPs: trials with a cue showed earlier posterior alpha and beta desynchronisations before APA onset. Furthermore, we found earlier, more pronounced and longer alpha- and beta-band desynchronisations over the sensorimotor cortex for trials with incongruent flankers. Our results showed that attention has an impact on step initiation. A specific pattern of response-locked ERSPs seems to mirror behavioural effects of attentional load on step initiation. This new paradigm combining ANT and step initiation is, therefore, promising to investigate the interaction between attention and gait initiation in pathological populations.

Immediate-release (IR) amantadine has been marketed for Parkinson’s disease (PD) therapy for 50 years, while two novel extended-release formulations have only recently reached the market in the US. The aim of this study was to describe amantadine IR utilization patterns in the French COPARK cohort, at baseline and after 2 years of follow-up. Overall, 683 PD patients from the COPARK survey were evaluated. All patients were assessed in a standardized manner (demographics, treatments, Unified Parkinson’s Disease Rating Scale [UPDRS], Hospital Anxiety and Depression Scale, Pittsburg Questionnaire and health-related quality-of-life scales (Short Form-36 [SF-36], 39-item Parkinson’s Disease Questionnaire [PDQ-39]). Longitudinal data were only available for 401/683 patients (59%) with a median (P25–75) follow-up period of 23 months (18–31). Patients were assessed in the same way as in the baseline visit. At baseline, amantadine was prescribed to 61/683 (9%) patients (median dose 200 mg/day, range 100–300 mg/day). Amantadine was initiated after a median of 7 years from PD diagnosis, and its prescription was correlated with the presence of dyskinesia (logistic regression odds ratio [OR] 3.72, 95% confidence interval [CI] 1.95–7.08) and hallucinations (UPDRS I.2) [OR 1.57, 95% CI 1.08–2.29]. After 2 years, the amantadine prescription increased from 33 (8%) patients at baseline to 54 (14%) patients in the subset of 401 patients analysed twice (p = 0.001). Among the 33 patients receiving amantadine at baseline, 9 (27%) stopped amantadine, 5 (15%) increased the dose, 6 (18%) reduced the dose and 13 (40%) stayed at the same doses. Treatment was initiated in 30/54 new patients (55%). Patients who started amantadine or increased its dose (n = 35) had more levodopa-induced dyskinesias at baseline (OR 7.02, 95% CI 3.09–15.90) and higher Mini-Mental State Examination score at follow-up (OR 1.37, 95% CI 1.06–1.79). Undergoing deep brain stimulation was related to stopping or downtitrating amantadine (OR 22.02, 95% CI 4.24–114.44; n = 15). In this cohort, amantadine was used in 10% of patients. Its use increased during follow-up, despite the fact that one-third of patients who received amantadine at baseline stopped taking it. Amantadine prescription was mainly correlated with the presence of dyskinesia.

Introduction/Background The posterior parietal cortex (PPC) is a key structure for visual attention and upper limb function, two features that could be impaired after stroke, and could be implied in their recovery. If it is well established that stroke is responsible for intra- and interhemispheric connectivity troubles, little is known about those existing for the contralesional PPC. Material and method In this study, we aimed at mapping the functional (using resting state fMRI) and structural (using diffusion tensor imagery) networks associated with 3 subparts of the PPC of the contralesional hemisphere (the anterior intraparietal sulcus (aIPS), the posterior intraparietal sulcus (pIPS) and the superior parieto-occipital cortex (SPOC)) in 12 chronic stroke patients compared to 13 healthy controls. We also aimed at assessing the relationship between connectivity and the severity of visuospatial and motor deficiencies. Results We showed that intrahemispheric functional connectivity between the contralesional PPC and posterior frontal regions (especially premotor areas) was altered, as were interhemispheric functional and structural connexions between each part of the contralesional PPC and their homologous area in the ipsilesional hemisphere. Neglect severity was associated with several alterations in intra- and interhemispheric connectivity, the behavioral/connectivity correlations were far less evident for motor deficiency. Conclusion The results of this exploratory study shed a new light on the influence of the contralesional PPC in post-stroke patients, they have to be confirmed and refined in further larger studies.

ObjectiveTo assess, in a cross-sectional study, the feasibility and immediate efficacy of laser shoes, a new ambulatory visual cueing device with practical applicability for use in daily life, on freezing of gait (FOG) and gait measures in Parkinson disease (PD).MethodsWe tested 21 patients with PD and FOG, both “off” and “on” medication. In a controlled gait laboratory, we measured the number of FOG episodes and the percent time frozen occurring during a standardized walking protocol that included FOG provoking circumstances. Participants performed 10 trials with and 10 trials without cueing. FOG was assessed using offline video analysis by an independent rater. Gait measures were recorded in between FOG episodes with the use of accelerometry.ResultsCueing using laser shoes was associated with a significant reduction in the number of FOG episodes, both “off” (45.9%) and “on” (37.7%) medication. Moreover, laser shoes significantly reduced the percent time frozen by 56.5% (95% confidence interval [CI] 32.5–85.8; p = 0.004) when “off” medication. The reduction while “on” medication was slightly smaller (51.4%, 95% CI −41.8 to 91.5; p = 0.075). These effects were paralleled by patients' positive subjective experience on laser shoes' efficacy. There were no clinically meaningful changes in the gait measures.ConclusionsThese findings demonstrate the immediate efficacy of laser shoes in a controlled gait laboratory, and offer a promising intervention with potential to deliver in-home cueing for patients with FOG.Classification of evidenceThis study provides Class III evidence that for patients with PD, laser shoes significantly reduce FOG severity (both number and duration of FOG episodes).

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation. Funding The European Commission FP7 NeurOmics project; CHDI Foundation; the Medical Research Council UK; the Brain Research Trust; and the Guarantors of Brain.

International audience; Patients with Parkinson's disease have better functional status and motor performance under on-drug conditions. However, the administration of levodopa leads to greater postural sway. The present study's primary objective was to determine whether this on-drug problem may be related to a lack of adjustment in postural control mechanisms and body segment rotations. Fourteen patients with Parkinson's disease and 14 controls performed two gaze-shift tasks (40° to the left and 40° to the right, at 0.125 and 0.25Hz) and a stationary gaze task in two sessions (an off-drug session and an on-drug session for the patients, and two off-drug sessions for the controls). At baseline, the "on-drug" patients indeed swayed significantly more than the controls during the gaze-shift tasks. As expected, acute L-dopa administration did not increase eye, head, neck and lower back rotation of the patients during the gaze-shift tasks. Unexpectedly, levodopa appeared to enable the patients to significantly increase the contribution of their postural control mechanisms (relative to controls) during the gaze-shift tasks. However, and as expected, this adjustment was not great enough to enable the patients to maintain their postural sway as well as the controls did. Overall, the administration of levodopa seemed to destabilize the patients - especially with regard to the lower back region. In addition, the patients used hypermetric eye rotations during the gaze-shift tasks under both off- and on-drug conditions. If they had not used these compensatory eye rotations, their unsafe behavior at the hip level might have been even more pronounced. Future research should focus on this lower back weakness.

La qualite de la marche est un element fondamental de la qualite de vie et de l’autonomie des personnes âgees (Woo et al., 1999). Des index simples ont ete developpes et montrent qu’il existe une correlation etroite entre vitesse de marche et esperance de vie. Les troubles de la marche sont presents des le debut de la maladie de Parkinson et constituent un des plaintes majeures des patients ; ils mettent initialement en jeu un processus d’hypokinesie de la marche que le patient a tendance a naturellement compenser en augmentant sa cadence. Neanmoins, ces processus cognitifs de compensation ont un cout eleve chez les patients : c’est l’impossibilite de realiser une double tâche, ou la survenue, lors d’un stress d’un blocage brutal de la marche appele freezing, responsable de chutes et de perte d’autonomie. Nous souhaitons utiliser la derniere generation de systeme d’analyse de la marche de facon repetee et ecologique chez des patients parkinsoniens volontaires a differents stades de la maladie afin de detecter les modifications simples et subtiles de leur pattern de marche qui vont annoncer la degradation de cette derniere, et predire la survenue des sources de handicap majeur que sont les freezing de la marche et les chutes. Notre equipe mene une etude pilote clinique bicentrique dans les centres experts Parkinson (Lille, Bordeaux). L’objectif premier de ce projet est le developpement d’un outil qui detecte les modifications de marche predictives du freezing et des chutes chez le patient parkinsonien, en environnement ecologique, c.-a-d. hors d’un laboratoire de recherche et en vie reelle. Plusieurs etapes sont necessaires a la realisation de ce projet : – acquerir, les donnees de marche de 30 patients parkinsoniens a differents stades evolutifs de leur maladie (repartis en 3 groupes : 2 ans, 5 ans, 8 ans d’evolution) pendant 5 jours ; – renouveler les analyses pour chaque patient a un an, afin de detecter les modifications des parametres de marche ; – construire un modele predictif et interactif de survenue des troubles de la marche base sur les donnees cliniques couples aux enregistrements de la marche, en utilisant une population de sujets controles apparies en âge (donnees Feet Me). Les premiers resultats seront presentes en avant-premiere au cours du congres de la SOFPEL a Montreal.

Introduction La maladie de Pompe est une myopathie liee a un deficit en alpha-glucosidase acide. Elle se manifeste dans la forme tardive par une myopathie de la ceinture pelvienne et/ou une insuffisance respiratoire. L’alpha-alglucosidase recombinante a montre dans les etudes pivotales une amelioration du test de marche de 6 minutes d’environ 30 metres versus placebo, pour une base a 330 ± 130 metres. L’objectif de ce travail etait d’essayer de determiner les correlats de la distance parcourue par les patients atteints d’une maladie de Pompe de forme tardive. Nous faisions l’hypothese que l’atteinte respiratoire pouvait influencer la fatigabilite lors de cette epreuve de marche. Materiel et methodes Nous avons enregistre 14 patients traites au centre de reference des maladies neuromusculaires de Lille. La consigne etait de marcher le plus longtemps possible pendant 6 minutes, sur un couloir long de 100 metres. Afin d’enregistrer les caracteristiques cinematiques, des semelles embarquees Feetme® avec centrale inertielle ont ete utilisees. Resultats Certains patients presentaient une vitesse constante et d’autres une vitesse de decroissance lineaire au cours du temps. Il semblait exister une association avec l’atteinte respiratoire. (Resultats plus complets a venir) Discussion–conclusion La distance parcourue sur 6 minutes semblait etre liee a differents facteurs : performances motrices, fatigabilite, atteinte respiratoire. Il pourrait etre plus interessant de definir des parametres plus specifiques pour mieux quantifier la reponse au traitement. Cette donnee brute a l’echelle d’une population semblait trop heterogene.

International audience; Parietofrontal (PF) networks link the posterior parietal cortex to premotor and prefrontal areas, and are involved in the control of many motor and cognitive behaviors in healthy humans. In recent years, electrophysiological experiments have provided a better understanding of the functional specificity and temporal involvement of the PF networks’ different components during the planning of visually guided upper limb movements. In particular, transcranial magnetic stimulation has been used to temporarily inactivate a cortical area (virtual lesions) or to assess connectivity using paired-pulse protocols)). This approach has shed new light on the neural mechanisms that underlie the planning stages of the reaching and grasping phases of transitive movements. Reaching and grasping were often presented as two distinct processes; in fact, the respective involvement of dorsolateral and dorsomedial networks may depend on the movement's complexity and the need for precise coordination between the two phases. The dorsolateral parietofrontal network (linking the anterior part of the intraparietal sulcus to the ventral premotor cortex) is involved in the grasping phase (i.e. hand shape and grip force scaling), whereas the dorsomedial part (from the posterior part of the intraparietal sulcus and the superior parieto-occipital cortex to the dorsal premotor cortex) appears to be involved not only in the reaching phase but also in more complex visually guided grasping movements. Changes in parietofrontal connectivity following brain injury might explain the impairments in visually guided upper limb movements observed in patients (such as optic ataxia and the motor component of spatial neglect). Lastly, parietofrontal changes may reflect neuronal plasticity in motor function recovery.

BACKGROUND Impulse control disorders (ICDs) in Parkinson's disease (PD) are related to treatment with dopamine agonists, which is thought to deregulate the dopaminergic mesolimbic pathway and impair reward evaluation. EEG studies in healthy controls (HCs) have suggested that the increase in theta power observed after negative outcome is a marker of reward processing. OBJECTIVE To compare outcome-locked, event-related spectral perturbation in a gambling task in PD patients with and without ICDs and in HCs. METHODS Twelve PD patients with ICDs, 12 PD patients without ICDs and 14 HCs underwent EEG while performing a gambling task. The groups were compared in terms of (i) the peak EEG power in the theta (4-7 Hz), alpha (8-14 Hz) and beta (15-30 Hz) frequency bands between 200 and 500 ms after the outcome, and (ii) time-frequency plots at Fz, FCz and Cz. RESULTS Positive outcomes were associated with greater theta power than negative outcomes in patients without ICDs and in HCs, but not in patients with ICDs. Patients with ICDs and HCs displayed greater theta power following unexpectedly high outcomes. HCs displayed greater beta power following high amplitude than low amplitude outcomes, whereas patients with ICD showed the opposite pattern. CONCLUSIONS In PD, ICDs are associated with (i) weaker modulation of frontocentral theta power by reward valence, (ii) greater frontocentral theta power following unexpected, high outcomes, and (iii) a reversal of the effect of risk on beta oscillations. These observations are consistent with an impairment in prediction error computation in the medial prefrontal cortex.

Objective To investigate the efficiency of intermittent theta-burst stimulation (iTBS) to alleviate the symptoms of freezing of gait (FoG) in Parkinson’s disease (PD). Methods We performed a cross-over, sham-controlled study of patients with severe PD, bilateral motor signs and debilitating, severe FoG, that was levodopa-sensitive but not controlled by optimal dopatherapy. We applied iTBS to the left premotor cortex and measured FoG, gait initiation and continuous gait, before and immediately after the iTBS session. All patients received sham and true iTBS with a one-week interval and in randomized order. Results 15 patients were included in the study. Recordings were performed under usual medication and all patients always showed unresponsive freezing. The pre- and post-stimulation gait trajectories did not differ in terms of the mean trajectory completion time or the percent time with FoG. The percent time with FoG was 6% greater after sham stimulation and 3% lower after iTBS (p > 0.05). Visual cueing modified gait initiation and continuous gait but these latter were not influenced by rTMS. Conclusions The present study provides Class I evidence that iTBS of the left premotor cortex does not alleviate FoG in PD.

Objective To determine whether or not modulation of the excitability of the M1 region controlling the lower limb (using repetitive transcranial magnetic stimulation; TMS) would change the TA’s activity during gait and the effect of aging on this change. Methods In three separate sessions, participants underwent different repetitive TMS (rTMS) protocols (sham stimulation, intermittent theta-burst stimulation (TBS) and continuous TBS) delivered over the M1 region controlling the lower limb muscles, using a focal, figure-of-eight coil. Before and after rTMS, the TA’s activity was recorded using surface electrodes while participants walked at a freely chosen speed and at an imposed speed on a treadmill. Cortical excitability was assessed by characterizing input–output (IO) curves, after fitting the relationship between motor evoked potential amplitude and stimulus intensity with a Boltzmann sigmoidal equation. Results We did not observe any effects of rTMS in terms of TA activation during locomotion, gait parameters or IO curves in either healthy young adults or elderly adults. Elderly patients presented lower excitability of cortical TA representation area. Conclusion Modulation of TA activity by TBS was ineffective contrary to what is observed for upper limbs. Interindividual variability in the effects of rTMS on TA activation, activation of the TA before the rTMS and/or differences in the depth of the cortical representation of the TA could have influenced the results and should be taken into account for further studies.

Introduction Les composantes de l’attention visuospatiale ont demontre leur capacite a moduler specifiquement l’initiation du pas et peuvent etre analysees conjointement au sein du meme paradigme : l’Attention Network Test (ANT). Cependant, les patients souffrant de la maladie de Parkinson avec freezing de la marche presentent un deficit du controle executif qui pourrait deteriorer l’initiation du pas. Cette etude vise a une meilleure comprehension de l’interaction entre attention et initiation de la marche chez les parkinsoniens freezers et non-freezers, a travers l’observation de modulations (1) comportementales et (2) cortico-motrices. Materiel et methodes Quatorze freezers, 15 non-freezers et 15 temoins ont realise une tâche attentionnelle adaptee de l’ANT combinee a l’initiation du pas. L’activite corticale pendant la preparation (ajustements posturaux anticipes [APAs]) et l’execution du pas a ete enregistree a l’aide d’une electroencephalographie a haute resolution. Resultats Bien que le temps d’execution du pas ait ete plus long pour les parkinsoniens, les effets des indices et cibles n’etaient pas significativement differents entre les groupes. Les patients presentaient une desynchronisation liee au mouvement d’amplitude reduite comparee aux controles et plus tardive pour les freezers. Globalement, l’activite induite associee a l’effet du controle executif differait entre parkinsoniens et temoins au niveau du cortex sensorimoteur. Conclusion Les tâches de resolution de conflit entrainent une alteration de l’initiation du pas similaire chez les freezers, non-freezers et temoins. L’electroencephalographie durant l’ANT combine a l’initiation du pas semble etre pertinente pour une meilleure comprehension de l’influence de l’attention sur l’initiation du pas dans la maladie de Parkinson.

Introduction Many clinical factors have been associated with falling in PD but the utility of gait analysis remains uncertain. To determine if additional use of clinical characteristics of the disease combined with gait parameters distinguish PD fallers from non-fallers Material and methods One hundred and seventy-four subjects were recorded during stabilized with a videomotion system. Clinical characteristics included UPDRS 3, disease duration, MMSE, occurrence of falls and freezing of gait. Kinematic parameters of gait first include gait speed, stride length and time, gait asymmetry, gait variability, foot clearance. A classification approach was investigated to build models allowing distinguishing fallers from non-fallers. Two different models were built, one by considering only the clinical data: age, disease duration, UPDRS III and MMSE scores and the second by adding to these data, gait analysis data. Support vectors machines (SVM) algorithm was used to build the models. The models were learned to tune their parameters using 4/5 of the patients’ data, randomly selected and validated blindly of the remaining 1/5 data. Results Clinical factors have an accuracy of 0.91 to distinguish fallers from non-fallers. Adding some relevant parameters such as stride length, foot clearance, variability improves this accuracy of 0.95. This was confirmed with a test sample with an accuracy of 0.87. Discussion/conclusion Fallers distinguished from non-fallers by disease duration and motor impairment but adding gait measurement improves the accuracy of the clinical data. Further research should concentrate to validate these models in prospective cohorts.

Background Cognitive symptoms are common in patients with Parkinson's disease. Characterization of a patient's cognitive profile is an essential step toward the identification of predictors of cognitive worsening. Objective The aim of this study was to investigate the use of the combination of resting-state EEG and data-mining techniques to build characterization models. Methods Dense EEG data from 118 patients with Parkinson's disease, classified into 5 different groups according to the severity of their cognitive impairments, were considered. Spectral power analysis within 7 frequency bands was performed on the EEG signals. The obtained quantitative EEG features of 100 patients were mined using 2 machine-learning algorithms to build and train characterization models, namely, support vector machines and k-nearest neighbors models. The models were then blindly tested on data from 18 patients. Results The overall classification accuracies were 84% and 88% for the support vector machines and k-nearest algorithms, respectively. The worst classifications were observed for patients from groups with small sample sizes, corresponding to patients with the severe cognitive deficits. Whereas for the remaining groups for whom an accurate diagnosis was required to plan the future healthcare, the classification was very accurate. Conclusion These results suggest that EEG features computed from a daily clinical practice exploration modality in-that it is nonexpensive, available anywhere, and requires minimal cooperation from the patient-can be used as a screening method to identify the severity of cognitive impairment in patients with Parkinson's disease. (c) 2018 International Parkinson and Movement Disorder Society