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BACKGROUND: Cognitive behavioral therapy (CBT) reduces anxiety symptoms in patients with Parkinson's disease (PD).OBJECTIVE: The objective of this study was to identify changes in functional connectivity in the brain after CBT for anxiety in patients with PD.METHODS: Thirty-five patients with PD and clinically significant anxiety were randomized over two groups: CBT plus clinical monitoring (10 CBT sessions) or clinical monitoring only (CMO). Changes in severity of anxiety symptoms were assessed with the Parkinson Anxiety Scale (PAS). Resting-state functional brain MRI was performed at baseline and after the intervention. Functional networks were extracted by an Independent Component Analysis (ICA). Functional connectivity (FC) changes between structures involved in the PD-related anxiety circuits, such as the fear circuit (involving limbic, frontal, and cingulate structures) and the cortico-striato-thalamo-cortical limbic circuit, and both within and between functional networks were compared between groups and regressed with anxiety symptoms changes.RESULTS: Compared to CMO, CBT reduced the FC between the right thalamus and the bilateral orbitofrontal cortices and increased the striato-frontal FC. CBT also increased the fronto-parietal FC within the central executive network (CEN) and between the CEN and the salience network. After CBT, improvement of PAS-score was associated with an increased striato-cingulate and parieto-temporal FC, and a decreased FC within the default-mode network and between the dorsal attentional network and the language network.CONCLUSION: CBT in PD-patients improves anxiety symptoms and is associated with functional changes reversing the imbalance between PD-related anxiety circuits and reinforcing cognitive control on emotional processing.

INTRODUCTION: Parkinson's disease (PD) is a heterogeneous disorder with great variability in motor and non-motor manifestations. It is hypothesized that different motor subtypes are characterized by different neuropsychiatric and cognitive symptoms, but the underlying correlates in cerebral connectivity remain unknown. Our aim is to compare brain network connectivity between the postural instability and gait disorder (PIGD) and tremor-dominant (TD) subtypes, using both a within- and between-network analysis.METHODS: This cross-sectional resting-state fMRI study includes 81 PD patients, 54 belonging to the PIGD and 27 to the TD subgroup. Group-level spatial maps were created using independent component analysis. Differences in functional connectivity were investigated using dual regression analysis and inter-network connectivity analysis. An additional voxel-based morphometry analysis was performed to examine if results were influenced by grey matter atrophy.RESULTS: The PIGD subgroup scored worse than the TD subgroup on all cognitive domains. Resting-state fMRI network analyses suggested that the connection between the visual and sensorimotor network is a potential differentiator between PIGD and TD subgroups. However, after correcting for dopaminergic medication use these results were not significant anymore. There was no between-group difference in grey matter volume.CONCLUSION: Despite clear motor and cognitive differences between the PIGD and TD subtypes, no significant differences were found in network connectivity. Methodological challenges, substantial symptom heterogeneity and many involved variables make analyses and hypothesis building around PD subtypes highly complex. More sensitive visualisation methods combined with machine learning approaches may be required in the search for characteristic underpinnings of PD subtypes.

To explore possible forms of domestic violence suffered by men with Parkinson's disease (PD).A qualitative study was conducted through face-to face interviews, followed by a conceptual content analysis. Forms of violence were predetermined as code categories according to a classification of mistreatment and a lack within Maslow's hierarchy of needs. Data triangulation was performed by two researchers using the "long table" method according to Kruegeramp; Casey.Eleven men with PD were interviewed to identify experienced forms of domestic violence. Since PD, the men felt neglected by their partners, lived in the fear of the partner's reactions, described a mutual sexual and physical distance, suffered from mockeries, humiliations, physical violence, and had a feeling of abandon while facing and managing PD.Domestic violence against men with PD exists and should be screened during communication with healthcare professionals.Domestic violence has different faces and is not always identified by the victims themselves. Spouses with profiles at risk for domestic violence against men with PD should be identified. Domestic violence can be triggered by female gender, alcoholism, anxiety and depression, a low educational level, low interest in and low knowledge about PD.

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.

International audience; Introduction The public health issue of the Parkinson's disease (PD) has led to a great deal of research that has highlighted the individual challenges faced by the person with the Parkinson's disease (PwPD) and the caregiving spouse. Few studies, however, have sought to understand the functioning of couples facing PD, by differentiating each stage, each of which has its own issues. In particular, the “honeymoon period”, characterized by a symptomatic respite allowed by the effectiveness of treatments for motor symptoms, has been poorly documented, especially at the dyadic level. Design and Method This qualitative study, based on Interpretative Phenomenological Analysis, aimed to understand the experience of couples and their functioning at this stage. Fifteen couples participated in separate semi-structured interviews for each partner. The analyses highlighted four dyadic dynamics, which call into question the relevance of the term “honeymoon” to describe the experience of couples. Results While some couples appear to adjust by means of flexible functioning and a positive reinterpretation of this experience, other dyads oscillate between rigid hyperprotection in the face of perceived distress or a vicious circle of control/avoidance and, in some cases, gradually slipping towards the erosion of the relationship. Discussion These results show that the relational difficulties suffered by partners at this stage should be taken into account as soon as possible after the diagnosis. Strengthening the communication and the togetherness between partners, as well as working on dyadic emotional regulation, are particularly relevant options for these couples.

International audience; Background: Parkinson’s disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes. Objective: To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS. Secondarily, we sought to identify MRI structural markers associated with cognitive impairment in these subgroups. Methods: Baseline data from the French multicentric PREDISTIM cohort were used. Candidates to STN-DBS were classified according to their cognitive performance in normal cognition (PD-NC) or PD-MCI. The latter included frontostriatal (PD-FS) and posterior cortical (PD-PC) subtypes. Between-group comparisons were performed on demographical and clinical variables as well as on T1-weighted MRI sequences at the cortical and subcortical levels. Results: 320 patients were included: 167 (52%) PD-NC and 153 (48%) PD-MCI patients. The latter group included 123 (80%) PD-FS and 30 (20%) PD-PC patients. There was no between-group difference regarding demographic and clinical variables. PD-PC patients had significantly lower global efficiency than PD-FS patients and significantly worse performance on visuospatial functions, episodic memory, and language. Compared to PD-NC, PD-MCI patients had cortical thinning and radiomic-based changes in the left caudate nucleus and hippocampus. There were no significant differences between the PD-MCI subtypes. Conclusion: Among the candidates to STN-DBS, a significant proportion has PD-MCI which is associated with cortical and subcortical alterations. Some PD-MCI patients have posterior cortical deficits, a subtype known to be at higher risk of dementia.

Background The "dual syndrome hypothesis" distinguished two subtypes in mild cognitive impairment (MCI) in Parkinson's disease: frontostriatal, characterized by attentional and executive deficits; and posterior cortical, characterized by visuospatial, memory, and language deficits. Objective The aim was to identify resting-state functional modifications associated with these subtypes. Methods Ninety-five nondemented patients categorized as having normal cognition (n = 31), frontostriatal (n = 14), posterior cortical (n = 20), or mixed (n = 30) cognitive subtype had a 3 T resting-state functional magnetic resonance imaging scan. Twenty-four age-matched healthy controls (HCs) were also included. A group-level independent component analysis was performed to identify resting-state networks, and the selected components were subdivided into 564 cortical regions in addition to 26 basal ganglia regions. Global intra- and inter-network connectivity along with global and local efficiencies was compared between groups. The network-based statistics approach was used to identify connections significantly different between groups. Results Patients with posterior cortical deficits had increased intra-network functional connectivity (FC) within the basal ganglia network compared with patients with frontostriatal deficits. Patients with frontostriatal deficits had reduced inter-network FC between several networks, including the visual, default-mode, sensorimotor, salience, dorsal attentional, basal ganglia, and frontoparietal networks, compared with HCs, patients with normal cognition, and patients with a posterior cortical subtype. Similar results were also found between patients with a mixed subtype and HCs. Conclusion MCI subtypes are associated with specific changes in resting-state FC. Longitudinal studies are needed to determine the predictive potential of these markers regarding the risk of developing dementia. (c) 2021 International Parkinson and Movement Disorder Society

Background Patient education is essential in Parkinson's disease (PD). However, it is not known which aspects of patient education are associated with an improvement in quality of life (QoL). Objective To identify factors that predicted an improvement in QoL in PD patients that participate in an education program. Methods EduPark is a community-hospital patient education program. PD Patients that had participated in the program between September 2013 and March 2017 were retrospectively included. QoL was prospectively evaluated (using the PDQ-8 questionnaire) before and after the patient's participation. We used mixed linear models (adjusted for the initial value of the PDQ-8) to determine socio-demographic and clinical variables that predicted the change in the PDQ-8 score. Results A total of 181 patients were included (mean ± standard deviation age: 62.9 ± 8.2 years; disease duration: 9.1 ± 5.3 years). 76.7% of the 103 patients having undergone a cognitive evaluation did not display cognitive impairment . We did not identify any factors that predicted the program's impact on the patient's QoL. Participation in the program was associated with a significant decrease (improvement) in the PDQ-8 score (39.4 ± 17.81 before and 35.6 ± 15.9 afterwards, P Conclusion We did not identify any factors that were predictive of the patient education program's impact on QoL in patients with PD. Participation in the program was associated with a significant improvement in QoL. Our results suggest that Patient Education Programs should be more widely prescribed and developed in the management of PD.

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.

Brown-Vialetto-Van Laere syndrome is a rare, autosomal, recessive neurological condition caused by variants in the riboflavin transporter genes SLC52A2 and SLC52A3. Here, we report on three cases. Case 1 was a 35-year-old woman from a consanguineous family who presented with progressive deafness, subacute multiple cranial nerve impairments (III, VII, IX, XII), and MRI abnormalities (including as hypersignal from the cranial nerves). The patient was homozygous for a novel SLC52A3variant. Case 2 was the woman's brother, who presented similar symptoms. Case 3 was an 18-year-old woman experiencing progressive hearing loss, bilateral steppage gait and a cranial nerves impairment (VII and XII). MRI revealed hypersignal in the root nerves and cauda equina. A novel heterozygous variant in SLC52A3 was identified. A subacute history of polyradiculoneuropathy along with progressive deafness, cranial nerve impairment, and MRI abnormalities should raise suspicion for Brown-Vialetto-Van Laere syndrome.

Background In 2020 the coronavirus disease 19 (COVID-19) pandemic imposed a total and sudden lockdown. We aimed to investigate the consequences of the first COVID-19 lockdown (mid-March – mid-April 2020) on motor and non-motor symptoms (NMS) in a cohort of French people with Parkinson's disease (PwP). Methods PwP were enrolled either by an on-line survey sent from the national France Parkinson association (FP) to reach the French community of PwP or as part of outpatients' telemedicine visits followed by an hospital-based Parkinson Expert Center (PEC). All patients were evaluated using the same standardized questionnaire assessing motor and NMS (including a list of most disabling, new or worsened symptoms and Patient's Global Impression-Improvement scales [PGI-I]) psycho-social queries and quality of life. Results 2653 PwP were included: 441 (16.6%) in the PEC group and 2122 (83.4%) in the community-based group. Physiotherapy was interrupted among 88.6% of the patients. 40.9% referred a clinical modification of their symptoms. Based on the questionnaire, pain (9.3%), rigidity (9.1%) and tremor (8.5%) were the three most frequently new or worsened reported symptoms. Based on the PGI-I, the motor symptoms were the most affected domain, followed by pain and psychic state. PwP in community-based group tended to have more frequent worsening for motor symptoms, motor complications, pain and confusion than those of the PEC group. Conclusions The first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. .

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.

Hypersomnia is a rare neurologic disorder characterized by an excessive daytime sleepiness with long naps, despite an undisturbed nocturnal sleep. The impaired daytime alertness and sleep inertia are different from general fatigue. This disorder is often classified as idiopathic. Here, we report the case of a young patient presenting both a mitochondrial disease and a hypersomnia. We discuss the links between the two pathologies and propose to systematically investigate personal and familial mitochondrial features in case of hypersomnia, to offer suitable genetic tests. Conversely, fatigue could be one of the complaints reported by patients with a confirmed mitochondrial disease, which is multifactorial. Sleep quality and somnolence should be examined in these patients as specific treatments exist for this debilitating disorder.

Levels of expression or of phosphorylation of leucine-rich repeat kinase 2 (LRRK2) and its Rab substrates have the potential for use as disease or pharmacodynamic biomarkers. LRRK2 phosphorylation levels at the S910-S935-S955-S973 phosphosites are reduced for most disease mutant forms of LRRK2, while for phospho-S1292, phospho-T72-Rab8 and phospho-T73-Rab10 levels are increased for most mutants. In addition, all of these 5 phosphosites on LRRK2 are rapidly dephosphorylated upon LRRK2 inhibitor treatment, considered potential therapeutics. The main objective of this study is therefore to characterize leucine-rich repeat kinase 2 (LRRK2) and Rab8/10 in human, non-human primate and rat urine for use as potential disease or pharmacodynamic biomarkers. With urine collected from human subjects as well as animals, we have applied an ultracentrifugation based fractionation protocol to isolate small extracellular vesicles (EVs). We used western blot with antibodies directed against LRRK2, LRRK2 phosphorylation sites as well as Rab8 and Rab10 total and phosphorylated proteins in order to measure these LRRK2 and Rab epitopes in urinary EVs (uEVs). We confirm the presence of LRRK2 and Rab8/10 in human and non-human primate (NHP) uEVs, including total LRRK2 as well phosphorylated forms of LRRK2 pS910, pS935, pS955, pS973, pS1292 and phosphorylated Rab8 and Rab10. We also confirm LRRK2 and Rab expression in rodent uEVs. We quantified LRRK2 and Rab epitopes in human cohorts and found in a first cohort that pS1292-LRRK2 levels were elevated in individuals carrying the LRRK2 G2019S mutation, but did not differ significantly between healthy and PD groups, whether for LRRK2 G2019S carriers or not. In a second cohort, we found that PD was associated to an increase in Rab8 levels and a decrease in S910-LRRK2 and S935-LRRK2 phosphorylation rates. In animals, we found that acute treatment with LRRK2 kinase inhibitor led to decreases in Rab10 phosphorylation rates and to a decrease in pS935-LRRK2 rates in uEVs from NHPs. The identification of changes in LRRK2 phosphorylation at heterologous phosphorylation sites in uEVs of PD patients further reinforces the potential of the LRRK2-Rab pathway as a source of PD biomarkers in uEVs.

Neuroferritinopathy is a rare inherited neurodegenerative disease with brain iron accumulation characterized by brain iron overload resulting in progressive movement disorders. No treatment is currently available.We assessed conservative iron chelation with deferiprone at 30 mg/kg/day on the disease progression with controlled periods of discontinuation.Four patients with confirmed molecular diagnosis of neuroferritinopathy were given deferiprone at different stages of disease progression and with clinical and biological monitoring to control benefit and risk.The four patients showed slight to high improvement. In one case, we managed to stabilize disease progression for more than 11 years. In another case, we were able to reverse symptoms after a few months of treatment. The earliest the treatment was started, the most efficient it was on disease progression.Conservative iron chelation should be further assessed in neuroferritinopathy. © 2022 International Parkinson and Movement Disorder Society.

International audience; OBJECTIVES: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. RESULTS: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). CONCLUSIONS: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.

Summary Background Progressive supranuclear palsy is a neurodegenerative disorder associated with tau protein aggregation. Tilavonemab (ABBV-8E12) is a monoclonal antibody that binds to the N-terminus of human tau. We assessed the safety and efficacy of tilavonemab for the treatment of progressive supranuclear palsy. Methods We did a phase 2, multicentre, randomised, placebo-controlled, double-blind study at 66 hospitals and clinics in Australia, Canada, France, Germany, Italy, Japan, Spain, and the USA. Participants (aged ≥40 years) diagnosed with possible or probable progressive supranuclear palsy who were symptomatic for less than 5 years, had a reliable study partner, and were able to walk five steps with minimal assistance, were randomly assigned (1:1:1) by interactive response technology to tilavonemab 2000 mg, tilavonemab 4000 mg, or matching placebo administered intravenously on days 1, 15, and 29, then every 28 days through to the end of the 52-week treatment period. Randomisation was done by the randomisation specialist of the study sponsor, who did not otherwise participate in the study. The sponsor, investigators, and participants were unaware of treatment allocations. The primary endpoint was the change from baseline to week 52 in the Progressive Supranuclear Palsy Rating Scale (PSPRS) total score in the intention-to-treat population. Adverse events were monitored in participants who received at least one dose of study drug. Prespecified interim futility criteria were based on a model-based effect size of 0 or lower when 60 participants had completed the 52-week treatment period and 0·12 or lower when 120 participants had completed the 52-week treatment period. This study is registered at ClinicalTrials.gov, number NCT02985879. Findings Between Dec 12, 2016, and Dec 31, 2018, 466 participants were screened, 378 were randomised. The study was terminated on July 3, 2019, after prespecified futility criteria were met at the second interim analysis. A total of 377 participants received at least one dose of study drug and were included in the efficacy and safety analyses (2000 mg, n=126; 4000 mg, n=125; placebo, n=126). Least squares mean change from baseline to week 52 in PSPRS was similar in all groups (between-group difference vs placebo: 2000 mg, 0·0 [95% CI –2·6 to 2·6], effect size 0·000, p>0·99; 4000 mg, 1·0 [–1·6 to 3·6], –0·105, p=0·46). Most participants reported at least one adverse event (2000 mg, 111 [88%]; 4000 mg, 111 [89%]; placebo, 108 [86%]). Fall was the most common adverse event (2000 mg, 42 [33%]; 4000 mg, 54 [43%]; placebo, 49 [39%]). Proportions of patients with serious adverse events were similar among groups (2000 mg, 29 [23%]; 4000 mg, 34 [27%]; placebo, 33 [26%]). Fall was the most common treatment-emergent serious adverse event (2000 mg, five [4%]; 4000 mg, six [5%]; placebo, six [5%]). 26 deaths occurred during the study (2000 mg, nine [7%]; 4000 mg, nine [7%]; placebo, eight [6%]) but none was drug related. Interpretation A similar safety profile was seen in all treatment groups. No beneficial treatment effects were recorded. Although this study did not provide evidence of efficacy in progressive supranuclear palsy, the findings provide potentially useful information for future investigations of passive immunisation using tau antibodies for progressive supranuclear palsy. Funding AbbVie Inc.

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; BackgroundExcessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide.ObjectiveThe aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS.MethodsThe method involved a randomized, double-blind, placebo-controlled, crossover trial testing two doses of THN102 (200 mg/d modafinil with 2 mg/d [200/2] or 18 mg/d flecainide [200/18]) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score.ResultsBoth doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (least square means vs. placebo [95% confidence interval, CI]: −1.4 [−2.49; −0.31], P = 0.012) but did not change significantly with the 200/18 dosage.ConclusionsTHN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD. © 2021 International Parkinson and Movement Disorder Society

People with Parkinson’s disease (PwPD) have complex healthcare pathways (HCPW) and expect person-centred interdisciplinary care coordination.Our study aimed to provide insight to patients’ and heal...

The col-cap concept encouraged neurologists to inject a large group of muscles in the treatment of cervical dystonia. This includes deep muscles such as the obliquus capitis inferior or the semispinalis capitis, and muscles close to vascular or neurological structures such as scalene muscles. Our aim was to determine the accuracy of injections in cervical muscles using ultrasonography (US) or palpation of anatomical landmarks. A mix of paint, gelatin and iodized contrast agent was injected in nine pairs of cervical muscles of human cadavers, according to two injection techniques: US-guided and non-guided. The dye was localized on 1 cm-thick, frozen slices. A total of 102 muscles was injected in the US-guided group (n = 8). The global accuracy was 88.2%. The lowest accuracy was in the OCI (41.7%); trying to avoid the vertebral artery, injections were too medial. A total of 54 muscles was injected in the non-guided group (n = 3). The global accuracy was 48.0%; moreover, some dye was found in four blood vessels. The embalming process produced texture changes, making difficult the palpation of bony landmarks. Our results indicate that US-guided injections are more accurate than non-guided injections in most cervical muscles.

Resume L’atteinte respiratoire fait partie des aspects les moins etudies dans la maladie de Parkinson, qu’il s’agisse de la plainte fonctionnelle (en l’occurrence la dyspnee) ou de la dynamique ventilatoire objectivee par des explorations fonctionnelles respiratoires (EFR). Pourtant, l’inconfort respiratoire, ou dyspnee, est frequemment rapporte par les patients. Une meilleure analyse semiologique de ce symptome pourrait permettre de determiner certains mecanismes sous-jacents, notamment de distinguer la part perceptive et emotionnelle de la dyspnee, et donc d’orienter au mieux la prise en charge neurologique, psychologique et meme orthophonique ou kinesitherapeutique. L’existence ou non d’une atteinte de la musculature respiratoire ou des volumes pulmonaires dans la maladie de Parkinson fait encore debat mais l’etude objective de la fonction ventilatoire pourrait aider a ameliorer certains symptomes de la maladie comme la dysarthrie ou la dysphagie.

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

Background Anxiety is frequent in Parkinson's disease (PD) and has a negative impact on disease symptoms and quality of life. The underlying mechanisms remain largely unknown. The aim of this study was to identify anatomical and functional changes associated to PD-related anxiety by comparing the volume, shape and texture of the amygdala, the cortical thickness as well as the functional connectivity (FC) of the fear circuit in patients with and without clinically relevant anxiety. Methods Non-demented PD patients were recruited, and anxiety was quantified using the Parkinson Anxiety Scale. Structural MRI was used to compare cortical thickness and amygdala structure and resting-state functional MRI to compare FC patterns of the amygdala and resting-state functional networks in both groups. Results We included 118 patients: 34 with (A+) and 84 without (A-) clinically relevant anxiety. Clusters of cortical thinning were identified in the bilateral fronto-cingulate and left parietal cortices of the A+ group. The texture and the shape of the left amygdala was different in the A+ group but the overall volume did not differ between groups. FC between the amygdala and the whole brain regions did not differ between groups. The internetwork resting-state FC was higher between the “fear circuit” and salience network in the A+ group. Conclusion Anxiety in PD induces structural modifications of the left amygdala, atrophy of the bilateral fronto-cingulate and the left parietal cortices, and a higher internetwork resting-state FC between the fear circuit and the salience network.