Publications by authors named "Luc Defebvre"

157 Publications

Three cases of adult-onset Brown-Vialetto-Van Laere syndrome: Novel variants in SLC52A3 gene and MRI abnormalities.

Neuromuscul Disord 2021 08 26;31(8):752-755. Epub 2021 Jun 26.

Univ. Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, F-59000 Lille, France; Centre de référence des maladies neuromusculaires Nord Est Ile de France, Lille University Medical Centre, Lille, France; Neurology Department, Lille University Medical Center, Lille, France.

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.
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http://dx.doi.org/10.1016/j.nmd.2021.06.009DOI Listing
August 2021

Role of the peripheral nervous system for an appropriate postural preparation during gait initiation in patients with a chronic inflammatory demyelinating polyneuropathy: A pilot study.

Gait Posture 2021 Aug 4;90:29-35. Epub 2021 Aug 4.

Univ. Lille, Inserm U1172- Lille Neurosciences Cognition, CHU Lille, F-59000, Lille, France.

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.
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http://dx.doi.org/10.1016/j.gaitpost.2021.08.001DOI Listing
August 2021

Optimization of postural control in precise gaze shifts and laser pointing.

Hum Mov Sci 2021 Oct 28;79:102853. Epub 2021 Jul 28.

CHRU Lille, Unité INSERM 1172, Service de Neurophysiologie Clinique, Hôpital Salengro, F-59000 Lille, France.

Young adults are known to reduce their postural sway to perform precise visual search and laser pointing tasks. We tested if young adults could reduce even more postural and/or center of pressure sway to succeed in both tasks simultaneously. The methodology is novel because published pointing tasks usually require continuously looking at the pointed target and not exploring an image while pointing elsewhere at the same time. Twenty-five healthy young adults (23.2 ± 2.5 years) performed six visual tasks. In the free-viewing task, participants randomly explored images with no goal. In two visual search tasks, participants searched to locate objects (easy search task) or graphical details (hard search task). Participants additionally pointed a laser beam into a central circle (2°) or pointed the laser turned off. Postural sway and center of pressure sway were reduced complementarily - in various variables - to perform the visual search and pointing tasks. Unexpectedly, the pointing task influenced more strongly postural sway and center of pressure sway than the search tasks. Overall, the participants adopted a functional strategy in stabilizing their posture to succeed in the pointing task and also to fully explore images. Therefore, it is possible to inverse the strength of effects found in the literature (usually stronger for the search task) in modulating the experimental methodology. In search tasks more than in free-viewing tasks, participants mostly rotated their eyes and head, and not their full body, to stabilize their posture. These results could have implications for shooting activities, video console games and rehabilitation most particularly.
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http://dx.doi.org/10.1016/j.humov.2021.102853DOI Listing
October 2021

A French survey on the lockdown consequences of COVID-19 pandemic in Parkinson's disease. The ERCOPARK study.

Parkinsonism Relat Disord 2021 08 13;89:128-133. Epub 2021 Jul 13.

Service de Neurologie, Centre Hospitalier Universitaire, Toulouse, France; France CHU de Toulouse, Université de Toulouse-Toulouse 3, INSERM, UMR1214 Toulouse NeuroImaging Centre "TONIC," Center of Excellence in Neurodegeneration (CoEN), NeuroToul, Centre Expert Parkinson de Toulouse, Centre d'Investigation Clinique CIC1436, NS-Park/FCRIN Network, Services de Neurologie et de Pharmacologie Clinique, UMR 1048 Institute for Cardiovascular Diseases, Toulouse, France.

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. .
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http://dx.doi.org/10.1016/j.parkreldis.2021.07.013DOI Listing
August 2021

Parkinson's disease-related changes in the behavioural synergy between eye movements and postural movements.

Eur J Neurosci 2021 08 28;54(3):5161-5172. Epub 2021 Jun 28.

Univ. Lille, Unité INSERM 1172, CHU Lille, Lille, France.

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 was 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.
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http://dx.doi.org/10.1111/ejn.15351DOI Listing
August 2021

Posterior Cortical Cognitive Deficits Are Associated With Structural Brain Alterations in Mild Cognitive Impairment in Parkinson's Disease.

Front Aging Neurosci 2021 13;13:668559. Epub 2021 May 13.

Lille Neuroscience and Cognition, Lille University, Inserm, Lille University Medical Centre, Lille, France.

: Cognitive impairments are common in patients with Parkinson's disease (PD) and are heterogeneous in their presentation. The "dual syndrome hypothesis" suggests the existence of two distinct subtypes of mild cognitive impairment (MCI) in PD: a frontostriatal subtype with predominant attentional and/or executive deficits and a posterior cortical subtype with predominant visuospatial, memory, and/or language deficits. The latter subtype has been associated with a higher risk of developing dementia. : The objective of this study was to identify structural modifications in cortical and subcortical regions associated with each PD-MCI subtype. : One-hundred and fourteen non-demented PD patients underwent a comprehensive neuropsychological assessment as well as a 3T magnetic resonance imaging scan. Patients were categorized as having no cognitive impairment ( = 41) or as having a frontostriatal ( = 16), posterior cortical ( = 25), or a mixed ( = 32) MCI subtype. Cortical regions were analyzed using a surface-based Cortical thickness (CTh) method. In addition, the volumes, shapes, and textures of the caudate nuclei, hippocampi, and thalami were studied. Tractometric analyses were performed on associative and commissural white matter (WM) tracts. : There were no between-group differences in volumetric measurements and cortical thickness. Shape analyses revealed more abundant and more extensive deformations fields in the caudate nuclei, hippocampi, and thalami in patients with posterior cortical deficits compared to patients with no cognitive impairment. Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were also observed in the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the striato-parietal tract, and the anterior and posterior commissural tracts. Texture analyses showed a significant difference in the right hippocampus of patients with a mixed MCI subtype. : PD-MCI patients with posterior cortical deficits have more abundant and more extensive structural alterations independently of age, disease duration, and severity, which may explain why they have an increased risk of dementia.
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http://dx.doi.org/10.3389/fnagi.2021.668559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155279PMC
May 2021

Fluoxetine for the Symptomatic Treatment of Multiple System Atrophy: The MSA-FLUO Trial.

Mov Disord 2021 07 1;36(7):1704-1711. Epub 2021 Apr 1.

Service de Neurologie des Maladies Neurodégénératives, French Reference Center for MSA, NS-Park/FCRIN Network, CHU Bordeaux, Bordeaux, France.

Background: There are no effective treatments for multiple system atrophy (MSA).

Objective: The objective of this study was to assess the efficacy and safety of the serotonin reuptake inhibitor fluoxetine (40 mg/d) for the symptomatic treatment of MSA.

Methods: This was a double-blind, parallel-group, placebo-controlled, randomized trial in patients with "probable" MSA. The primary outcome was the change from baseline to week 12 in the mean total score of the Unified MSA Rating Scale (UMSARS Parts I + II). Secondary outcomes included change from baseline to week 6 in total UMSARS, and change from baseline to week 12 in the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction, Beck Depression Inventory, and different domains of the MSA-Quality of Life Questionnaire. Exploratory outcomes included change from baseline to week 12 in the UMSARS Parts I and II separately and change from baseline to week 24 in the total UMSARS score.

Results: A total of 81 patients were randomly assigned, with no significant difference in the primary outcome (-2.13 units [95% confidence interval, CI, -4.55 to 0.29]; P = 0.08). There was a greater reduction on fluoxetine in the change from baseline to 12-week in UMSARS Part II (exploratory outcome: -1.41 units [95% CI, -2.84; 0.03]; p = 0.05) and in MSA-QoL emotional/social dimension (secondary outcome: -6.99 units [95% CI, -13.40; -0.56]; p < 0.03). A total of 5 deaths occurred (3 on fluoxetine and 2 on placebo).

Conclusion: The MSA-FLUO failed to demonstrate fluoxetine superiority over placebo on the total UMSARS score, whereas trends in motor and emotional secondary/exploratory outcomes deserve further investigation. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28569DOI Listing
July 2021

Cognitive Behavioral Therapy for Anxiety in Parkinson's Disease: A Randomized Controlled Trial.

Mov Disord 2021 Feb 22. Epub 2021 Feb 22.

Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, the Netherlands.

Background: Anxiety disorders are among the most prevalent and disabling neuropsychiatric syndromes in patients with Parkinson's disease (PD), but no randomized controlled treatment trials of anxiety have been published to date.

Objective: The aim of this study was to assess the effectiveness of cognitive behavioral therapy (CBT) in the treatment of anxiety in patients with PD.

Methods: Forty-eight patients with PD with anxiety were randomized 1:1 between CBT and clinical monitoring only (CMO). The CBT program was developed to specifically address anxiety symptoms in PD and consisted of 10 weekly sessions. Assessments were conducted by blinded assessors at baseline, at the end of the intervention, after 3 months, and after 6 months (CBT group only). Main outcome measures were the Hamilton Anxiety Rating Scale (HARS) and the Parkinson Anxiety Scale (PAS).

Results: Both the CBT and CMO groups showed clinically relevant improvement. Although there was no between-group difference in outcome on the Hamilton Anxiety Rating Scale (6.7-point reduction in the CBT group versus 3.9-point reduction in the CMO group; P = 0.15), there was both a statistically significant and a clinically relevant between-group difference on the total PAS in favor of CBT (9.9-point reduction in the CBT group versus 5.2-point reduction in the CMO group; P = 0.012), which was due to improvement on the PAS subscales for episodic (situational) anxiety and avoidance behavior. This greater improvement was maintained at 3- and 6-month follow-ups.

Conclusion: CBT is an effective treatment for anxiety in patients with PD and reduces situational and social anxiety, as well as avoidance behavior. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28533DOI Listing
February 2021

Parkinson's disease: Content analysis of patient online discussion forums. A prospective observational study using Netnography.

Patient Educ Couns 2021 08 28;104(8):2060-2066. Epub 2021 Jan 28.

Department of General Practice, University of Lille, Lille, France; CN2R-Centre National de Ressources et de Résilience, Lille, France.

Objectives: To assess the users' characteristics, discussion contents, and the atmosphere of virtual peer communities.

Methods: A qualitative, prospective study was conducted using the Netnography method. The most popular, publicly accessible French discussion forums were investigated. The web users' quotes were collected from May to October 2018. Data analysis triangulation was performed by two researchers using the NVivo 12® software.

Results: The users discussed their experience with Parkinson's disease (PD) in a warm atmosphere. 23 discussion threads were analysed: 302 messages posted by 70 users (70% were females; the average illness duration was 6 years); 115 encoded nodes were created. Five user profiles appeared: leader, follower, expert, mixed, and undetermined. Common preoccupations were a lack of time and listening from the physicians' side. Three themes emerged: managing symptoms, living with PD, and sharing illness experiences. Users sought actively for a cure to limit or stop disease evolution, using alternative and complementary therapies to optimize their daily condition.

Conclusions: Online forums foster person's informal learnings about coping with PD. Healthcare professionals can use these learnings to optimize person-centred support.

Practice Implications: During consultations, healthcare professionals should invite persons to discuss their online activity, informal learnings, beliefs and expectations towards therapeutic strategies.
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http://dx.doi.org/10.1016/j.pec.2021.01.028DOI Listing
August 2021

Texture-based markers from structural imaging correlate with motor handicap in Parkinson's disease.

Sci Rep 2021 02 1;11(1):2724. Epub 2021 Feb 1.

Université de Lille, INSERM, U1172, CHU-Lille, Lille Neuroscience Cognition Research Centre, 1 place de Verdun, 59000, Lille, France.

There is a growing need for surrogate biomarkers for Parkinson's disease (PD). Structural analysis using magnetic resonance imaging with T1-weighted sequences has the potential to quantify histopathological changes. Degeneration is typically measured by the volume and shape of morphological changes. However, these changes appear late in the disease, preventing their use as surrogate markers. We investigated texture changes in 108 individuals, divided into three groups, matched in terms of sex and age: (1) healthy controls (n = 32); (2) patients with early-stage PD (n = 39); and (3) patients with late-stage PD and severe L-dopa-related complications (n = 37). All patients were assessed in off-treatment conditions. Statistical analysis of first- and second-order texture features was conducted in the substantia nigra, striatum, thalamus and sub-thalamic nucleus. Regions of interest volumetry and voxel-based morphometry were performed for comparison. Significantly different texture features were observed between the three populations, with some showing a gradual linear progression between the groups. The volumetric changes in the two PD patient groups were not significantly different. Texture features were significantly associated with clinical scores for motor handicap. These results suggest that texture features, measured in the nigrostriatal pathway at PD diagnosis, may be useful in predicting clinical progression of motor handicap.
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http://dx.doi.org/10.1038/s41598-021-81209-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851138PMC
February 2021

Initial center of pressure position prior to anticipatory postural adjustments during gait initiation in people with Parkinson's disease with freezing of gait.

Parkinsonism Relat Disord 2021 03 22;84:8-14. Epub 2021 Jan 22.

Department of Neurology, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.parkreldis.2021.01.012DOI Listing
March 2021

Do kinematic gait parameters help to discriminate between fallers and non-fallers with Parkinson's disease?

Clin Neurophysiol 2021 02 19;132(2):536-541. Epub 2020 Dec 19.

Univ. Lille, Inserm, U1172 - Lille Neuroscience and Cognition, F-59000 Lille, France; Neurology and Movement Disorders Department, Lille University Medical Center, F-59000 Lille, France; Lille Center of Excellence for Neurodegenerative Diseases, LiCEND, France.

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.
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http://dx.doi.org/10.1016/j.clinph.2020.11.027DOI Listing
February 2021

Accuracy of non-guided versus ultrasound-guided injections in cervical muscles: a cadaver study.

J Neurol 2021 May 5;268(5):1894-1902. Epub 2021 Jan 5.

CHU Lille, Radiologie et Imagerie Musculo-squelettique, F-59000, Lille, France.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: Our results indicate that US-guided injections are more accurate than non-guided injections in most cervical muscles.
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http://dx.doi.org/10.1007/s00415-020-10365-wDOI Listing
May 2021

Erratum to 'Can dual-task paradigms predict falls better than single task? - A systematic literature review' [Neurophysiol Clin 50 (2020) 401-40].

Neurophysiol Clin 2020 Dec 23. Epub 2020 Dec 23.

Univ. Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, Department of Clinical Neurophysiology, F-59000 Lille, France. Electronic address:

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http://dx.doi.org/10.1016/j.neucli.2020.12.004DOI Listing
December 2020

Nucleus Basalis of Meynert Stimulation for Lewy Body Dementia: A Phase I Randomized Clinical Trial.

Neurology 2021 02 16;96(5):e684-e697. Epub 2020 Nov 16.

From the Departments of Neurology (D.M., D.W., R.L., D.H.), Neurophysiology (J.B., M.-L.W.), and Neurosurgery (S.D.), Rouen University Hospital and University of Rouen; INSERM U1239 (D.M.), Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan; Department of Neurology C (T.D., S.T.), Hopital Neurologique Pierre Wertheimer, University of Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Sud Charles Mérieux; Department of Neurology (L.D., K.D.), Lille University Hospital, INSERM 1171; Department of Neurology (J.-L.H.), CIC-INSERM 1402, CHU de Poitiers; Université de Poitiers (J.-L.H.); Department of Neurology (O.G., P.K.), Amiens University Hospital; Department of Neurology (O.M.), Caen University Hospital; Department of Biostatistics (A.G.), Rouen University Hospital; Department of Nuclear Medicine (M.C., P.V.), Henri Becquerel Cancer Center and Rouen University Hospital; and QuantIF-LITIS [EA (Equipe d'Accueil) 4108-FR CNRS 3638] (M.C., P.V.), Faculty of Medicine, University of Rouen, France.

Objectives: Nucleus basalis of Meynert deep brain stimulation (NBM-DBS) has been proposed for patients with dementia. Here, we aim to assess the safety and effects of NBM-DBS in patients with Lewy body dementia (LBD), in a randomized, double-blind, crossover clinical trial.

Methods: Six patients with mild to moderate LBD (mean [SD] age, 62.2 [7.8] years) were included, operated on for bilateral NBM-DBS, and assigned to receive either active or sham NBM-DBS followed by the opposite condition for 3 months. The primary outcome was the difference in the total free recalls of the Free and Cued Selective Reminding Test (FCSRT) between active and sham NBM-DBS. Secondary outcomes were assessments of the safety and effects of NBM-DBS on cognition, motor disability, sleep, and PET imaging.

Results: There was no significant difference in the FCSRT score with active vs sham NBM-DBS. The surgical procedures were well tolerated in all patients, but we observed significant decreases in Stroop and Benton scores after electrode implantation. We observed no significant difference in other scales between active and sham NBM-DBS. With active NBM-DBS relative to baseline, phonemic fluency and motor disability significantly decreased. Lastly, the superior lingual gyrus metabolic activity significantly increased with active NBM-DBS.

Conclusions: NBM-DBS does not appear to be totally safe for patients with LBD with no evidence of cognitive benefit.

Clinicaltrialsgov Identifier: NCT01340001.

Classification Of Evidence: This study provides Class II evidence that, for patients with LBD operated on for bilateral NBM-DBS, active NBM-DBS stimulation compared to sham stimulation did not significantly change selective recall scores.
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http://dx.doi.org/10.1212/WNL.0000000000011227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884989PMC
February 2021

Can dual-task paradigms predict Falls better than single task? - A systematic literature review.

Neurophysiol Clin 2020 Nov 8;50(6):401-440. Epub 2020 Nov 8.

Univ. Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, Department of Clinical Neurophysiology, F-59000 Lille, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.neucli.2020.10.008DOI Listing
November 2020

Postural instability in Parkinson's disease: Review and bottom-up rehabilitative approaches.

Neurophysiol Clin 2020 Nov 7;50(6):479-487. Epub 2020 Nov 7.

Département de Kinésiologie, Faculté de Médecine, Université Laval, Québec, Québec, Canada; Centre Interdisciplinaire de Recherche en Réadaptation et Intégration Sociale (CIRRIS), Québec, Québec, Canada.

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.
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http://dx.doi.org/10.1016/j.neucli.2020.10.013DOI Listing
November 2020

Anxiety in Parkinson's disease is associated with changes in the brain fear circuit.

Parkinsonism Relat Disord 2020 11 19;80:89-97. Epub 2020 Sep 19.

Univ. Lille, Inserm, CHU Lille, Lille Neurosciences and Cognition, Lille, France; Neurology and Movement Disorders Department, Lille University Medical Centre, Lille, France.

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.
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http://dx.doi.org/10.1016/j.parkreldis.2020.09.020DOI Listing
November 2020

Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia.

Sci Rep 2020 08 18;10(1):13933. Epub 2020 Aug 18.

Sorbonne University, 75005, Paris, France.

Myoclonus-dystonia (MD) is a syndrome characterized by myoclonus of subcortical origin and dystonia, frequently associated with psychiatric comorbidities. The motor and psychiatric phenotypes of this syndrome likely result from cortico-striato-thamalo-cerebellar-cortical pathway dysfunction. We hypothesized that reactive and proactive inhibitory control may be altered in these patients. Using the Stop Signal Task, we assessed reactive and proactive inhibitory control in MD patients with (n = 12) and without (n = 21) deep brain stimulation of the globus pallidus interna and compared their performance to matched healthy controls (n = 24). Reactive inhibition was considered as the ability to stop an already initiated action and measured using the stop signal reaction time. Proactive inhibition was assessed through the influence of several consecutive GO or STOP trials on decreased response time or inhibitory process facilitation. The proactive inhibition was solely impaired in unoperated MD patients. Patients with deep brain stimulation showed impairment in reactive inhibition, independent of presence of obsessive-compulsive disorders. This impairment in reactive inhibitory control correlated with intrinsic severity of myoclonus (i.e. pre-operative score). The results point to a dissociation in reactive and proactive inhibitory control in MD patients with and without deep brain stimulation of the globus pallidus interna.
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http://dx.doi.org/10.1038/s41598-020-70926-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434767PMC
August 2020

New insight into Parkinson's disease-related impairment of the automatic control of upright stance.

Eur J Neurosci 2020 12 11;52(12):4851-4862. Epub 2020 Jul 11.

CHRU Lille, Unité INSERM 1172, Service de Neurophysiologie Clinique, Hôpital Salengro, Lille, France.

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.
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http://dx.doi.org/10.1111/ejn.14870DOI Listing
December 2020

Functional correlates of cognitive slowing in Parkinson's disease.

Parkinsonism Relat Disord 2020 07 19;76:3-9. Epub 2020 May 19.

Lille Neuroscience and Cognition, UMR 1172, Team1 Degenerative and vascular cognitive disorders, Lille, France; Lille University Medical Center, Department of Neurology, Lille, France. Electronic address:

Although attentional impairments (particularly cognitive slowing) are frequent in Parkinson's disease (PD), the mechanisms underlying these phenomena have not been fully characterized. The MRI-compatible version of the Symbol Digit Modalities Test (SDMT) has been applied to healthy individuals but not previously to patients with PD. We sought to assess functional changes in brain activation patterns associated with cognitive slowing in PD. Eighteen patients with PD and 11 matched healthy controls (HCs) were enrolled. High-resolution three-dimensional T1-weighted images and blood-oxygen-level-dependent images were acquired during the SDMT. SDMT-related brain networks for the HC and PD groups were extracted from one-sample T-test maps. In each hemisphere, correlated regions were identified by selecting 120 voxels around the peak of each significant cluster (p<0.001). Regions of interest were then analyzed. When performing the SDMT, both groups displayed activation in the frontal, parietal and occipital regions known to be involved in attention. In the PD group, activation was lower in several parts of the cerebellum, left and right occipital cortices, and right supramarginal gyrus. In eight of these regions, fMRI activation was positively correlated with performance in the SDMT task. Our results suggest that the right supramarginal gyrus (an important interface for information integration), the cerebellum, and the left and right occipital cortices are involved in cognitive slowing in PD. A lower level of brain activation was associated with greater cognitive impairment.
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http://dx.doi.org/10.1016/j.parkreldis.2020.05.006DOI Listing
July 2020

Dyspnea: A Missing Item of the MDS-UPDRS Part I?

Mov Disord 2020 06 25;35(6):1079. Epub 2020 Mar 25.

Movement Disorders Department, Parkinson's Disease Center, Lille University Medical Center, Lille, France.

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http://dx.doi.org/10.1002/mds.28036DOI Listing
June 2020

Intraventricular dopamine infusion alleviates motor symptoms in a primate model of Parkinson's disease.

Neurobiol Dis 2020 06 20;139:104846. Epub 2020 Mar 20.

Medical Pharmacology Department, Univ Lille, Inserm, CHU Lille, UMR_S1171, Lille F-59000, France. Electronic address:

Background: Continuous compensation of dopamine represents an ideal symptomatic treatment for Parkinson's disease (PD). The feasibility in intracerebroventricular administration (i.c.v.) of dopamine previously failed because of unresolved dopamine oxidation.

Objectives: We aim to test the feasibility, safety margins and efficacy of continuous i.c.v. of anaerobic-dopamine (A-dopamine) with a pilot translational study in a non-human primate model of PD.

Methods: Continuous and circadian i.c.v. of A-dopamine was administered through a micro-pump connected to a subcutaneous catheter implanted into the right frontal horn of 8 non-human primates treated with 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP). A-dopamine was assessed at acute doses previously reported for dopamine as well as evaluating the long term therapeutic index of A-dopamine in comparison to anaerobically prepared L-dopa or methyl ester L-dopa.

Results: Over 60 days of a continuous circadian i.c.v. of A-dopamine improved motor symptoms (therapeutic index from 30 to 70 mg/day) without tachyphylaxia. No dyskinesia was observed even with very high doses. Death after 1 to 10 days (without neuronal alteration) was only observed with doses in excess of 160 mg whereas L-dopa i.c.v. was not effective at any dose. The technical feasibility of the administration regimen was confirmed for an anaerobic preparation of dopamine and for administration of a minimal infusion volume by micro-pump at a constant flow that prevented obstruction.

Conclusion: Continuous circadian i.c.v. of A-dopamine appears to be feasible and shows efficacy without dyskinesia with a safe therapeutic index.
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http://dx.doi.org/10.1016/j.nbd.2020.104846DOI Listing
June 2020

Cortical Oscillations during Gait: Wouldn't Walking be so Automatic?

Brain Sci 2020 Feb 9;10(2). Epub 2020 Feb 9.

UMR-S1172, Lille Neuroscience & Cognition, Inserm, University Lille, 59000 Lille, France.

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.
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http://dx.doi.org/10.3390/brainsci10020090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071606PMC
February 2020

A new paradigm to study the influence of attentional load on cortical activity for motor preparation of step initiation.

Exp Brain Res 2020 Mar 5;238(3):643-656. Epub 2020 Feb 5.

Univ. Lille, Inserm, Lille Neuroscience & Cognition, UMR-S1172, Degenerative and Vascular Cognitive Disorders, F-59000, Lille, France.

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.
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http://dx.doi.org/10.1007/s00221-020-05739-5DOI Listing
March 2020

L’art de se déplacer dans la ville.

Neurophysiol Clin 2019 12;49(6):405-406

CIAMS, Université Paris-Sud, Orsay, France.

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http://dx.doi.org/10.1016/j.neucli.2019.11.005DOI Listing
December 2019

Texture features of magnetic resonance images: A marker of slight cognitive deficits in Parkinson's disease.

Mov Disord 2020 03 23;35(3):486-494. Epub 2019 Nov 23.

Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Lille (CHU Lille), Degenerative & Vascular Cognitive Disorders, Lille, France.

Background: Cognitive impairment is a frequent nonmotor symptom of Parkinson's disease. Depending on severity, patients are considered to have mild cognitive impairment or dementia. However, among the cognitively intact patients, some may have deficits in a less severe range. The early detection of such subtle symptoms may be important for the initiation of care strategies.

Objective: To identify imaging markers of early cognitive symptoms, potentially before usual signs, such as atrophy, become manifest.

Methods: A total of 102 patients with Parkinson's disease and 17 age-matched cognitively intact healthy controls underwent extensive neuropsychological assessment and T1-weighted magnetic resonance imaging. Parkinson's disease patients were separated into 3 groups according to their cognitive status: intact, with slight slowing, and with mild deficits in executive functions. Texture features as measured by first-order and second-order statistics were computed in the following 6 brain regions: the hippocampus, thalamus, amygdala, putamen, caudate nucleus, and pallidum. They were tested between the groups, and their correlation with cognition was examined. Volumetric measurements were made for comparison.

Results: Texture analysis showed significant between-group differences for 2 features-skewness and entropy in the hippocampus, the thalamus, and the amygdala-and the volume analysis revealed no between-group difference. These features were significantly correlated with cognitive performance.

Conclusion: These results support the assumption that signal alterations associated with Parkinson's disease-related cognitive decline can be captured very early by texture analysis. As these changes appear to reflect clinical phenomena, texture analysis may be a promising marker for helping cognitive phenotyping in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27931DOI Listing
March 2020
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