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In Parkinson’s disease, neurophysiological abnormalities within the primary motor cortex have been shown to contribute to cardinal symptoms such as bradykinesia, but the exact modalities are still uncertain. Here, we propose that such impairment could involve alterations of mechanisms shaping motor activity specifically during voluntary movement preparation. Indeed, several past studies in healthy populations have suggested that a strong suppression of corticospinal excitability called “preparatory suppression” – propels movement execution by increasing motor neural gain. Thus, we hypothesized that a gradual alteration to this mechanism may contribute to progressive motor slowness in Parkinson’s disease. We also predicted a benefit of dopamine medication in restoring correct motor neural activity during action preparation. To test these hypotheses, we investigated preparatory suppression on two consecutive days in 29 Parkinson’s disease patients (ON and OFF medication) and 29 matched healthy controls. Single-pulse transcranial magnetic stimulation was applied over both primary motor cortices, eliciting concurrent motor-evoked potentials in the two hands, while subjects were either at rest or prepared a left- or right-hand response in an instructed-delay choice reaction time task. Preparatory suppression was assessed by expressing the amplitude of motor potentials evoked during movement preparation relative to those obtained at rest. These neurophysiological measures were cross-analysed with task behaviour and clinical data. Contrary to healthy controls, Parkinson’s disease patients showed a lack of preparatory suppression, which appeared to depend on disease progression, but not on dopamine medication. Indeed, in relatively early disease stages, patients still exhibited partial preparatory suppression, while in later stages, they lacked it completely and even exhibited a tendency for corticospinal facilitation in the hand selected for movement execution. As expected

Les céphalées représentent un motif fréquent de consultation médicale, environ 2% de toutes les admissions en salle d’urgence, plus de 5 % en médecine générale (1,2). Elles s’intègrent dans des tableaux cliniques très variés, parfois bénins et parfois graves. Il est dès lors particulièrement important de détecter les patients qui présentent des céphalées secondaires et chez lesquels des examens complémentaires sont indispensables pour faire le diagnostic, voire pour choisir le traitement optimal et de les distinguer des patients qui présentent des céphalées primaires pour lesquelles aucun bilan complémentaire n’est indiqué. Dans le cas des céphalées secondaires, il est également important de choisir le bilan complémentaire adéquat et de définir la fenêtre de temps optimale pour le réaliser, la précocité du diagnostic et du traitant pouvant influencer le pronostic du patient.

Safinamide is a recent multimodal antiparkinsonian drug that inhibits monoamine oxidase B and modulates the glutamatergic system with positive effects on motor and nonmotor symptoms of Parkinson's disease (PD). This post-hoc analysis of the European SYNAPSES study provides first-time data on the use of safinamide in routine clinical practice in Belgium. To describe the efficacy and safety of safinamide in Belgian PD patients in real-life conditions. Post-hoc analysis of the Belgian cohort from the European SYNAPSES trial, which was an observational, multicenter, retrospective-prospective cohort study. Patients were followed up to 12 months. Analyses were performed in the overall population and according to different criteria such as the age limit (> 75 years), presence or absence of relevant comorbidities, presence or absence of psychiatric conditions such as depression and anxiety, patients on levodopa monotherapy or levodopa in combination with other treatments, patients on rasagiline before inclusion or not. Of the 172 patients included, 29.2% were > 75 years, 58.9% had relevant comorbidities and 32.7% had psychiatric conditions. Almost all the patients reported motor (98.8%) or non-motor (86.3%) symptoms. During the study, 36.3% of patients reported drug-related reactions. The adverse drug reactions were those already described in the patients' information leaflet. The majority were mild or moderate and completely resolved and no differences were detected between the subgroups of patients. Almost 35% of the patients demonstrated a clinically significant improvement in the UPDRS and 50% of the patients with wearing-off at baseline, did not report wearing-off anymore after one year of treatment. Patients under levodopa monotherapy compared to patients receiving levodopa combined with other antiparkinsonian treatments benefit more from safinamide treatment. Patients switched from rasagiline to safinamide seemed also to benefit more from safinamide treatment. The st

BACKGROUND: In Parkinson's disease (PD), neurophysiological abnormalities within the primary motor cortex (M1) have been shown to contribute to bradykinesia, but exact modalities are still uncertain. We propose that such motor slowness could involve alterations in mechanisms underlying movement preparation, especially the suppression of corticospinal excitability-called "preparatory suppression"-which is considered to propel movement execution by increasing motor neural gain in healthy individuals. METHODS: On two consecutive days, 29 PD patients (on and off medication) and 29 matched healthy controls (HCs) underwent transcranial magnetic stimulation over M1, eliciting motor-evoked potentials (MEPs) in targeted hand muscles, while they were either at rest or preparing a left- or right-hand response in an instructed-delay choice reaction time task. Preparatory suppression was assessed by expressing MEP amplitudes during movement preparation relative to rest. RESULTS: Contrary to HCs, PD patients showed a lack of preparatory suppression when the side of the responding hand was analyzed, especially when the latter was the most affected one. This deficit, which did not depend on dopamine medication, increased with disease duration and also tended to correlate with motor impairment, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III (both total and bradykinesia scores). CONCLUSIONS: Our novel findings indicate that preparatory suppression fades in PD, in parallel with worsening motor symptoms, including bradykinesia. Such results suggest that an alteration in this marker of intact movement preparation could indeed cause motor slowness and support its use in future studies on the relation between M1 alterations and motor impairment in PD. © 2022 International Parkinson and Movement Disorder Society.

Variability raises considerable interest as a promising and sensitive marker of dysfunction in physiology, in particular in neurosciences. Both internally (e.g., pathology) and/or externally (e.g., environment) generated perturbations and the neuro-mechanical responses to them contribute to the fluctuating dynamics of locomotion. Defective internal gait control in Parkinson’s disease (PD), resulting in typical timing gait disorders, is characterized by the breakdown of the temporal organization of stride duration variability. Influence of external cue on gait pattern could be detrimental or advantageous depending on situations (healthy or pathological gait pattern, respectively). As well as being an interesting rehabilitative approach in PD, treadmills are usually implemented in laboratory settings to perform instrumented gait analysis including gait variability assessment. However, possibly acting as an external pacemaker, treadmill could modulate the temporal organization of gait variability of PD patients which could invalidate any gait variability assessment. This study aimed to investigate the immediate influence of treadmill walking (TW) on the temporal organization of stride duration variability in PD and healthy population. Here, we analyzed the gait pattern of 20 PD patients and 15 healthy age-matched subjects walking on overground and on a motorized-treadmill (randomized order) at a self-selected speed. The temporal organization and regularity of time series of walking were assessed on 512 consecutive strides and assessed by the application of non-linear mathematical methods (i.e., the detrended fluctuation analysis and power spectral density; and sample entropy, for the temporal organization and regularity of gait variability, respectively). A more temporally organized and regular gait pattern seems to emerge from TW in PD while no influence was observed on healthy gait pattern. Treadmill could afford the necessary framework to regulate gait rhythmicity i

Fatigue is a frequent complaint among healthy population and one of the earliest and most debilitating symptoms in Parkinson's disease (PD). Earlier studies have examined the role of dopamine and serotonin in pathogenesis of fatigue, but the plausible role of noradrenalin (NA) remains underexplored. We investigated the relationship between fatigue in Parkinsonian patients and the extent of degeneration of Locus Coeruleus (LC), the main source of NA in the brain. We quantified LC and Substantia Nigra (SN) atrophy using neuromelanin-sensitive imaging, analyzed with a novel, fully automated algorithm. We also assessed patients' fatigue, depression, sleep disturbance and vigilance. We found that LC degeneration correlated with the levels of depression and vigilance but not with fatigue, while fatigue correlated weakly with atrophy of SN. These results indicate that LC degeneration in Parkinson's disease is unlikely to cause fatigue, but may be involved in mood and vigilance alterations.

Recent transcranial magnetic stimulation studies have shown that the motor output pathway shows a profound inhibition during the preparation of an action. This phenomenon, called “preparatory inhibition”, remains incompletely understood, as it is still unclear which neural structures support it and what function it exactly serves during action preparation. In the current study, we tested this preparatory inhibition in Parkinson’s disease (PD) patients and matched healthy control subjects. The aim was to better understand the role of basal ganglia (which are dysfunctional in PD) and the influence of dopamine replacement therapy on motor inhibition during action preparation.

Movement disorders following heart surgery are very unusual. Post-pump chorea is mainly a pediatric complication of heart surgery, typically manifesting after a latent period of normality and is usually related with long extracorporeal circulation time and deep hypothermia. We report a 73-year-old woman, without risk factors predisposing to paroxysmal movement disorders, presenting acute choreoathetoid movements 5 days after aortic valvular replacement with normal extracorporeal circulation time and perioperative normothermia.

Objective: Huntington's disease (HD) is characterized by motor and cognitive impairments including memory, executive, and attentional functions. However, because earlier studies relied on multidetermined attentional tasks, uncertainty still abounds regarding the differential deficit across attentional subcomponents. Likewise, the evolution of these deficits during the successive stages of HD remains unclear. The present study simultaneously explored 3 distinct networks of attention (alerting, orienting, executive conflict) in preclinical and clinical HD. Method: Thirty-eight HD patients (18 preclinical) and 38 matched healthy controls completed the attention network test, an integrated and theoretically grounded task assessing the integrity of 3 attentional networks. Results: Preclinical HD was not characterized by any attentional deficit compared to controls. Conversely, clinical HD was associated with a differential deficit across the 3 attentional networks under investigation, showing preserved performance for alerting and orienting networks but massive and specific impairment for the executive conflict network. This indexes an impaired use of executive control to resolve the conflict between task-relevant stimuli and interfering task-irrelevant ones. Conclusion: Clinical HD does not lead to a global attentional deficit but rather to a specific impairment for the executive control of attention. Moreover, the absence of attentional deficits in preclinical HD suggests that these deficits are absent at the initial stages of the disease. In view of their impact on everyday life, attentional deficits should be considered in clinical contexts. Therapeutic programs improving the executive control of attention by neuropsychology and neuromodulation should be promoted

INTRODUCTION: This registry evaluated the 24-month safety and efficacy of levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's disease (PD) patients under routine clinical care. METHODS: Motor fluctuations, dyskinesia, non-motor symptoms, quality of life, and safety were evaluated. Observations were fully prospective for treatment-naïve patients (60% of patients) and partially retrospective for patients with ≤12 months of pre-treatment with LCIG (40% of patients). Hours of "On" and "Off" time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale part IV items 32 and 39. RESULTS: Overall, 375 patients were enrolled by 75 movement disorder centers in 18 countries and 258 patients completed the registry. At 24 months LCIG treatment led to significant reductions from baseline in "Off" time (hours/day) (mean ± SD = -4.1 ± 3.5, P < 0.001), "On" time with dyskinesia (hours/day) (-1.1 ± 4.8, P = 0.006), Non-Motor Symptom Scale total (-16.7 ± 43.2, P < 0.001) and individual domains scores, and Parkinson's Disease Questionnaire-8 item total score (-7.1 ± 21.0, P < 0.001). Adverse events deemed to have a possible/probable causal relationship to treatment drug/device were reported in 194 (54%) patients; the most frequently reported were decreased weight (6.7%), device related infections (5.9%), device dislocations (4.8%), device issues (4.8%), and polyneuropathy (4.5%). CONCLUSIONS: LCIG treatment led to sustained improvements in motor fluctuations, non-motor symptoms particularly sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of life in advanced PD patients over 24 months. Safety events were consistent with the established safety profile of LCIG.

Objective: Huntington’s disease (HD) is characterized by motor and cognitive impairments including memory, executive, and attentional functions. However, because earlier studies relied on multidetermined attentional tasks, uncertainty still abounds regarding the differential deficit across attentional subcomponents. Likewise, the evolution of these deficits during the successive stages of HD remains unclear. The present study simultaneously explored 3 distinct networks of attention (alerting, orienting, executive conflict) in preclinical and clinical HD. Method: Thirty-eight HD patients (18 preclinical) and 38 matched healthy controls completed the attention network test, an integrated and theoretically grounded task assessing the integrity of 3 attentional networks. Results: Preclinical HD was not characterized by any attentional deficit compared to controls. Conversely, clinical HD was associated with a differential deficit across the 3 attentional networks under investigation, showing preserved performance for alerting and orienting networks but massive and specific impairment for the executive conflict network. This indexes an impaired use of executive control to resolve the conflict between task-relevant stimuli and interfering task-irrelevant ones. Conclusion: Clinical HD does not lead to a global attentional deficit but rather to a specific impairment for the executive control of attention. Moreover, the absence of attentional deficits in preclinical HD suggests that these deficits are absent at the initial stages of the disease. In view of their impact on everyday life, attentional deficits should be considered in clinical contexts. Therapeutic programs improving the executive control of attention by neuropsychology and neuromodulation should be promoted.

Huntington’s disease (HD) is centrally characterized by motor, neurocognitive and psychiatric symptoms, but impaired emotional decoding abilities have also been reported. However, more complex affective abilities are still to be explored, and particularly empathy, which is essential for social relations and is impaired in various psychiatric conditions. This study evaluates empathic abilities and social skills in pre-clinical and clinical HD, and explores the distinction between two empathy sub-components (emotional-cognitive). Thirty-six HD patients (17 pre-clinical) and 36 matched controls filled in the Empathy Quotient Scale, while controlling for psychopathological comorbidities. At the clinical stage of HD, no global empathy impairment was observed but rather a specific deficit for the cognitive sub-component, while emotional empathy was preserved. A deficit was also observed for social skills. Pre-clinical HD was not associated with any empathy deficit. Emotional deficits in clinical HD are thus not limited to basic emotion decoding but extend towards complex interpersonal abilities. The dissociation between impaired cognitive and preserved emotional empathy in clinical HD reinforces the proposal that empathy subtypes are sustained by distinct processes. Finally, these results underline the extent of distinct affective and social impairments in HD and the need to grasp them in clinical contexts.

Introduction Timing gait disorders of Parkinson’s disease (PD) are characterized by unstructured gait vari- ability. Recently, the breakdown of the temporal organization of stride duration variability (i.e. long-range autocorrelations; LRA) was associated to dynamic instability in PD. To improve timing gait in PD, synchro- nization of walking with rhythmic auditory stimulation (RAS) like music or metronome is largely used in clinical settings. Purpose To assess the LRA modulation of PD gait pattern according to the structure of RAS. Method Nine patients performed overground walking trials at a comfortable speed while listening di erent structures of RAS (counterbalanced order across patients): isochronic, randomly uctuating, uctuating ac- cording to an LRA structure and no RAS. Each structure was adapted to the patient’s gait cadence as previ- ously measured in a 10 meter-walking test. Temporal organization (LRA) of stride duration variability, gait ca- dence, speed and stride length were measured on 512 consecutive gait cycles. e presence of LRA was based on scaling properties of the series variability (Hurst exponent) and the shape of the power spectral density (á exponent). ose measures were compared across the four conditions using a one-way-repeated ANOVA. Results Our results show that temporal organization of PD gait may be modulated using di erent audi- tory structures. Adequate correlation between LRA of gait and auditory cue indicates strong adaptation and synchronization of the gait to the RAS. However, LRA were systematically lower during auditory conditions compared to spontaneous walking session, up to the disappearance of LRA during isochronic RAS. Further- more, gait cadence, speed and stride length were not statistically di erent across di erent conditions. Discussion and conclusions Isochronic auditory stimuli (e.g. metronome) do not seem to be an optimal way to improve timing gait in PD, as it induces the disappearance of LRA. Future work will inve

Background Deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) is a recognised treatment for advanced Parkinson’s disease (PD). We present our results of 10 consecutive patients implanted under general anaesthesia (GA) using intraoperative robotic three-dimensional (3D) fluoroscopy (Artis Zeego; Siemens, Erlangen, Germany). Method Ten patients (nine men, one woman) with a mean age of 57.6 (range, 41–67) years underwent surgery between October 2013 and January 2015. The mean duration of PD was 9.2 [1, 2, 3, 4, 5, 6, 7, 8, 9, 10] year. The procedure was performed under GA: placement of the stereotactic frame, implantation of the electrodes (Lead 3389; Medtronic, Minnesota, MN, USA) and 3D intraoperative fluoroscopic control (Artis Zeego) with image fusion with the preoperative MRI scans. All patients were evaluated preoperatively and 6 months postoperatively. Results The mean operative time was 240.1 (185–325) min. The mean Unified Parkinson’s Disease Rating Scale (UPDRS) II OFF medication decreased from 23.9 preoperatively to 15.7 postoperatively. The mean OFF medication UPDRS III decreased from 41 to 11.6 and the UPDRS IV decreased from 10.6 to 7. The mean preoperative and postoperative L-Dopa doses were 1,178.5 and 696.5 mg, respectively. Two complications were recorded: one episode of transient confusion (24 h) and one internal pulse generator (IPG) infection. Conclusions With improvement in preoperative magnetic resonance imaging (MRI) and the ability to control the position of the leads intraoperatively using Artis Zeego, we now perform this procedure under GA. Our results are comparable to others reported. The significant decrease in the duration of surgery could be associated with a reduced rate of complications (infection, loss of patient collaboration). However, this observation needs to be confirmed.

Introduction: Activating the upper body during walking, Nordic walking (NW) may be used as an external cueing to improve spatiotemporal parameters of gait, such as stride length or gait variability, in Parkinson disease (PD). Structured gait variability, revealed by the presence of long-range autocorrelations (LRA), was associated to dynamic stability of gait. Dynamic stability has been de ned as the ability to maintain functional locomotion despite the presence of internal or external disturbances, which is a feature of healthy locomotor system. Purpose: To assess bene cial e ects of NW on dynamic stability of gait and spatiotemporal gait parameters in PD. Methods: Fourteen mild to moderate PD patients performed 2×12min overground walking sessions (with and without pole in a randomized order) at a comfortable speed. Gait speed, cadence, step length and tem- poral organization (i.e. LRA) of stride duration variability were studied on 512 consecutive gait cycles using a unidimensional accelerometer placed on the malleola of the most a ected side. e presence of LRA was determined using the Rescaled Range Analysis (Hurst exponent) and the power spectral density (á exponent). To assess NW in uence on PD gait, a paired t-test was used. Results: All patients presented LRA during both walking sessions. However, Hurst and á exponents were sig- ni cantly higher during NW (p<0,001). While gait speed remained unchanged between two walking sessions, gait cadence decreased (p=0,009) and step length increased signi cantly (p=0,003). Discussion and conclusions: is study demonstrates that Nordic walking can improve the dynamic stabil- ity of gait in PD. Involving a voluntary intersegmental coordination, such improvement could also be due to the upper body rhythmic movements acting as rhythmical external cue to bypass their defective basal ganglia circuitries. erefore, Nordic walking may constitute a powerful way to manage gait disorders in PD.

"Objectives: Activating the upper body during walking, Nordic walking (NW) may be used as an external cueing to improve spatiotemporal parameters of gait, such as stride length or gait variability, in Parkinson disease (PD)..."

La sémiologie neurologique est extrêmement riche, caractérisée par une grande abondance de signes et de syndromes. L’examen neurologique sera toujours orienté par l’anamnèse, dont on ne saurait souligner assez l’importance. Un examen clinique neurologique standard sera réalisé de façon systématique et sera ensuite complété selon les premières observations. Certains éléments font impérativement partie de l’examen clinique systématique. Parmi ceux-ci figurent l’examen des réflexes ostéo-tendineux et du réflexe cutané plantaire, l’examen de la motricité, non seulement de la force mais également du tonus musculaire et de la marche. On y ajoutera l’examen de différents modes de la sensibilité, la réalisation des épreuves cérébelleuses et certains éléments de l’examen des paires crâniennes, dont la motricité de la face et l’oculomotricité., [The neurological examination by the general practitioner] The neurological symptomatology is extremely rich and characterized by numerous signs and syndromes. The neurological examination should always be preceded and guided by a careful anamnesis, the relevance of which cannot be sufficiently stressed. A standard clinical neurological examination must be performed systematically and will then be further extended according to the initial observations. Certain elements should be considered an essential part of the routine clinical examination, such as the review of tendon reflexes and plantar reflex, as well as the examination of motor skills, which should include not only strength but also muscle tone and gait. Routine clinical examination should also comprise the following: examination of different sensitivity modes, performance of cerebellar tests, and examination of certain features pertaining to cranial nerves like the movements of the face and eyes.

"Objectives: unstructured gait variability is a hallmark of timing gait disorders of Parkinson's disease (PD). Recently, complex temporal structure of stride duration variability has been demonstrated in healthy gait pattern, displaying long-range autocorrelations (LRA)..."