Corticospinal Suppression Underlying Intact Movement Preparation Fades in Parkinson's Disease.

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.

Does Nordic Walking restore the temporal organization of gait variability in Parkinson's disease?

BACKGROUND: Gait disorders of Parkinson's disease (PD) are characterized by the breakdown of the temporal organization of stride duration variability that was tightly associated to dynamic instability in PD. 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 PD. The aim of this study was to evaluate the beneficial effects of NW on temporal organization of gait variability and spatiotemporal gait variables in PD. METHODS: Fourteen mild to moderate PD participants and ten age-matched healthy subjects performed 2 × 12 min overground walking sessions (with and without pole in a randomized order) at a comfortable speed. Gait speed, cadence, step length and temporal organization (i.e. long-range autocorrelations; LRA) of stride duration variability were studied on 512 consecutive gait cycles using a unidimensional accelerometer placed on the malleola of the most affected side in PD patients and of the dominant side in healthy controls. The presence of LRA was determined using the Rescaled Range Analysis (Hurst exponent) and the Power Spectral Density (α exponent). To assess NW and disease influences on gait, paired t-tests, Z-score and a two-way (pathological condition x walking condition) ANOVA repeated measure were used. RESULTS: Leading to significant improvement of LRA, NW enhances step length and reduces gait cadence without any change in gait speed in PD. Interestingly, LRA and step length collected from the NW session are similar to that of the healthy population. CONCLUSION: This cross-sectional controlled study demonstrates that NW may constitute a powerful way to struggle against the randomness of PD gait and the typical gait hypokinesia. 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. ETHICS COMMITTEE'S REFERENCE NUMBER: B403201318916 TRIAL REGISTRATION: NCT02419768.

STN DBS for Parkinson's disease: results from a series of ten consecutive patients implanted under general anaesthesia with intraoperative use of 3D fluoroscopy to control lead placement.

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 [1-10] 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.

Effectiveness and safety of safinamide in routine clinical practice in a Belgian Parkinson's disease population: an open-label, levodopa add-on study.

BACKGROUND: 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. OBJECTIVE: To describe the efficacy and safety of safinamide in Belgian PD patients in real-life conditions. METHODS: 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. RESULTS: 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. CONCLUSION: The study confirms the excellent safety and efficacy profile of safinamide, particularly in more vulnerable groups of patients such as the elderly and patients with significant comorbidities or psychiatric conditions such as depression or anxiety.

Treatments for progressing Parkinson's disease: a clinical case scenario study.

OBJECTIVE: A 'case scenario' study on clinical decisions in progressing Parkinson's disease (PD) was developed to complement scientific evidence with the collective judgment of a panel of experts. METHODS: The opinions of 9 experts in movement disorders on the appropriateness of 9 common pharmacological treatments for 33 hypothetical patient profiles were compared to those of 14 general neurologists. Before rating the case scenarios, all participants received a document integrating European and US guidelines for the treatment of patients with advanced PD. Case scenarios showing disagreement or with inconsistencies in appropriateness ratings were discussed at a feedback meeting. A tool for interactive discussion on the clinical case scenarios included was developed based on the outcome of the study. RESULTS: Current guidelines are often insufficient to adequately guide the management of patients with progressing PD. The case scenario study did not reveal major differences in opinions between experts in movement disorders and general neurologists about the appropriateness of certain drug choices for specific case scenarios. However in about 1 out of 5 treatment decisions where experts stated appropriateness or inappropriateness, the general neurologists panel had no or dispersed opinions. CONCLUSIONS: This study reveals more uncertainty about treatment of advanced PD in general neurologists compared with experts in movement disorders and underlines the need for additional support for guiding treatment decisions in clinical practice.

Gait Complexity and Regularity Are Differently Modulated by Treadmill Walking in Parkinson's Disease and Healthy Population.

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 in PD. Overall, the results support the hypothesis of a greater dependence to regulatory inputs as an explanatory factor of treadmill influence observed in PD. Also, since treadmill misrepresents the gait as more healthy than it is, the present findings underline that gait analysis using treadmill devices should be cautiously considered in PD and especially for gait variability assessment in gait lab.

Locus Coeruleus atrophy doesn't relate to fatigue in Parkinson's disease.

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.

Choreoathetotic syndrome following cardiac surgery.

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.

Attentional impairments in Huntington's disease: A specific deficit for the executive conflict.

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. (PsycINFO Database Record

Temporal organization of stride duration variability as a marker of gait instability in Parkinson's disease.

OBJECTIVE: Gait instability and fall risk are major concerns in Parkinson's disease. This study shows that the temporal organization of gait variability can represent a marker of gait instability that complements standard assessment of motor deficits in Parkinson's disease. METHODS: Temporal organization (long-range autocorrelation; LRA) of stride duration variability, collected from 20 persons with Parkinson's disease walking overground at a comfortable speed, was studied. The presence of LRA was based on the scaling properties of the series variability and the shape of the power spectral density. Simultaneously, measures of neurological impairment (MDS-UPDRS), balance (BESTest), and balance confidence (ABC-Scale) were collected. To precisely identify the relationship between LRA and functional measures, correlation coefficients were applied. RESULTS: Degradation of LRA was strongly correlated with other clinical scores, in such a way that the temporal organization of gait variability was more random for patients presenting with greater motor impairments. Importantly, these measures were relatively independent of age, and gait speed, thus they can be applied to a wide clinical population.  Conclusion: The findings of this study emphasize that temporal organization of gait variability is related to degree of functional impairment in Parkinson's disease. LRA may thus be regarded as an objective and quantitative measure of gait stability for both clinical practice and research.

Dissociating emotional and cognitive empathy in pre-clinical and clinical Huntington's disease.

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.

Rating Parkinson's Disease: A Contemporary Eye to Archival Patients.

In this article, we present a detailed analysis of archival films of 12 different patients with Parkinson's disease (PD). This unique collection of films was made by Arthur Van Gehuchten (1861-1914), the first professor of neurology in Belgium at the turn of the 20th century. These extraordinarily well-preserved century-old documents are a precise iconography of PD before encephalitis lethargica swept the world and with clinical features unaffected by treatments such as levodopa. In view of the universal interest of the International Parkinson and Movement Disorder Society-sponsored revision of the UPDRS (MDS-UPDRS) in evaluating patients with PD, we based our analysis on this scale. Of course, given the lack of detailed clinical files and the impossibility of rating a number of items, rating disease severity in a strict clinimetric sense could not be achieved. However, we did this exercise in order to place these one-century-old cases in a modern perspective. In most patients, we could score numerous items of the motor examination part of the MDS-UPDRS. These archival documents constitute a superb lesson in the semiology of PD, which keeps today its fresh didactical value.

Pharmacological blockade of dopamine D2 receptors by aripiprazole is not associated with striatal sensitization.

The partial agonist profile of novel antipsychotics such as aripiprazole has hardly been demonstrated in biochemical assays on animal tissues. As it is established that responses induced by dopamine D2 receptor agonists are increased in models of dopaminergic sensitization, this paradigm was used in order to facilitate the detection of the partial agonist properties of aripiprazole. At variance with all other partial and full agonists tested, the partial agonist properties of aripiprazole were not revealed in guanosine 5'-O-(γ-[³5S]thiotriphosphate ([³5S]GTPγS) binding assays on striatal membranes from haloperidol-treated rats. Hence,aripiprazole behaved as an antagonist, efficiently inhibiting the functional response to dopamine. Similarly, in behavioural assays, aripiprazole dose-dependently inhibited the stereotypies elicited by apomorphine. However, at variance with haloperidol, repeated administrations of aripiprazole(3 weeks) at the doses of 10 and 30 mg/kg did not induce any up-regulation or hyperfunctionality of the dopamine D2 receptors in the striatum. These data highlight the putative involvement of other pharmacological targets for aripiprazole that would support in the prevention of secondary effects commonly associated with the blockade of striatal dopamine D2 receptors. Hence, in additional experiments, aripiprazole was found to efficiently promote [³5S]GTPγS binding in hippocampal membranes through the activation of 5-HT(1A) receptors. Further experiments investigating the second messenger cascades should be performed so as to establish the functional properties of aripiprazole and understand the mechanism underlying the prevention of dopamine receptor regulation in spite of the observed antagonism.