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1. Factors that predict a change in quality of life among Parkinson's disease patients participating in a patient education program

Author

D. Haidon, Nicolas Carrière, S. Peres, A. Faillon, Kathy Dujardin, C. Derollez, Luc Defebvre, and Maeva Kyheng

Subjects
medicine.medical_specialty, Parkinson's disease, Disease, 03 medical and health sciences, 0302 clinical medicine, Patient Education as Topic, Quality of life, Surveys and Questionnaires, medicine, Humans, In patient, 030212 general & internal medicine, Cognitive impairment, Aged, Retrospective Studies, Cognitive evaluation theory, business.industry, Parkinson Disease, Middle Aged, medicine.disease, humanities, Neurology, Quality of Life, Physical therapy, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study, Patient education
Abstract

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.

Published
2021

2. 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

Author

Patrick Vermersch, Romain Lapoulvereyrie, Madli Bayot, Arnaud Delval, Luc Defebvre, and Céline Tard

Subjects
medicine.medical_specialty, education, Biophysics, Pilot Projects, Chronic inflammatory demyelinating polyneuropathy, Motor program, Physical medicine and rehabilitation, Peripheral Nervous System, mental disorders, medicine, Humans, Orthopedics and Sports Medicine, Gait, Postural Balance, Balance (ability), Proprioception, business.industry, Rehabilitation, medicine.disease, Biomechanical Phenomena, Peripheral, Peripheral neuropathy, medicine.anatomical_structure, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Peripheral nervous system, business, psychological phenomena and processes
Abstract

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.

Published
2021

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

Author

Luc Defebvre, Cécile Acquaviva, Fanny Gauvrit, Anne Frédérique Dessein, Christine Vianey-Saban, Claire-Marie Dhaenens, Guillaume Carey, Sylvie Nguyen, Grégory Kuchcinski, and Céline Tard

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Adolescent, Consanguineous family, Hearing Loss, Sensorineural, Bulbar Palsy, Progressive, Progressive deafness, Brown–Vialetto–Van Laere syndrome, medicine, Humans, Genetics (clinical), business.industry, Cranial nerves, Membrane Transport Proteins, Steppage gait, Cauda equina, Polyradiculoneuropathy, Progressive hearing loss, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Mutation, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), business
Abstract

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.

Published
2021

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

Author

Claire Thalamas, Luc Defebvre, Frédérique Fluchère, Matthieu Bereau, David Maltête, Philippe Damier, Clémence Leung, Fabienne Ory-Magne, Claire Thiriez, David Grabli, Guillaume Baille, Giovanni Castelnovo, Christine Brefel Courbon, Anne Doé De Maindreville, Nicolas Carrière, Vanessa Rousseau, Agnès Sommet A, Olivier Rascol, Margherita Fabbri, and Marie Fuzzatti

Subjects
Telemedicine, medicine.medical_specialty, Parkinson's disease, Coronavirus disease 2019 (COVID-19), Pain, Disease, Motor symptoms, Cohort Studies, Quality of life, Surveys and Questionnaires, Tremor, Pandemic, Humans, Medicine, Pandemics, Physical Therapy Modalities, business.industry, Remote Consultation, COVID-19, Parkinson Disease, medicine.disease, Muscle Rigidity, Neurology, Communicable Disease Control, Quarantine, Cohort, Quality of Life, Physical therapy, France, Neurology (clinical), Geriatrics and Gerontology, business
Abstract

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. .

Published
2021

5. Idiopathic Hypersomnia in a Patient Suffering from MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes): a New Mitochondrial Feature?

Author

Christelle Charley Monaca, Anne-Frédérique Dessein, Grégory Kuchcinski, Claire-Marie Dhaenens, Céline Tard, Claire Douillard, and Luc Defebvre

Subjects
Pediatrics, medicine.medical_specialty, business.industry, Mitochondrial disease, Sleep inertia, Encephalopathy, Excessive daytime sleepiness, medicine.disease, Alertness, Mitochondrial myopathy, Lactic acidosis, mental disorders, medicine, medicine.symptom, business, Somnolence
Abstract

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.

Published
2021

6. Neurologic manifestations associated with COVID-19: a multicentre registry

Author

Elodie Meppiel, Nathan Peiffer-Smadja, Alexandra Maury, Imen Bekri, Cécile Delorme, Virginie Desestret, Lucas Gorza, Geoffroy Hautecloque-Raysz, Sophie Landre, Annie Lannuzel, Solène Moulin, Peggy Perrin, Paul Petitgas, François SellaI, Adrien Wang, Pierre Tattevin, Thomas de Broucker, Sophie Abgrall, Fanny Alby-Laurent, Thibault Allou, Joséphine Amevigbe, Hanifa Amarguellay, Nabil Alloussi, Guillaume Baille, Mathilde Barbaz, Lamia Bencherif, Samia Bensaadi, Guillaume Beraud, Alexandra Bizot, Laure Bottin, Fabrice Bruneel, Jean-Philippe Camdessanche, Jeanne Chauffier, Jean-Philippe Csajaghy, Chloé De Broucker, Thomas De Broucker, Luc Defebvre, Elodie Dembloque, Nathalie Derache, Olivier Dereeper, Céline Derollez, Cécile Descotes-Genon, Mathilde Devaux, Lydie Dubuc, Gilles Edan, Andréa Fickl, Thibault Fraisse, Michel Gugenheim, Karolina Hankiewicz, Yves Hansmann, Carole Henry, Stéphanie Jobard, Fanny Jouan, Arnaud Kwiatkowski, Thibault Lalu, Johan Leguilloux, Camille Lejeune, Clémence Liegeois, Sophie Mahy, Jonathan Marey, Laure Michel, Rita Mitri, Chloé Moulin, Asma Omarjee, Canan Ozsancak, Fernando Pico, Marie Poupard, Valérie Rabier, Camille Rizzato, Caroline Roos, Julien Saison, Naomi Sayre, Nicolas Sedillot, François Sellal, Jérôme Servan, Caroline Storey, Laurent Suchet, Paul Tarteret, Mathilde Thiebaut, Claudia Vaduva, David Varlan, Virginie Zarrouk, Centre Hospitalier de Saint-Denis [Ile-de-France], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre Hospitalier de Versailles André Mignot (CHV), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Hôpital Foch [Suresnes], Hôpitaux Civils de Colmar, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Centre Hospitalier Universitaire de Reims (CHU Reims), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Pontchaillou [Rennes], Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]

Subjects
Male, 0301 basic medicine, Microbiology (medical), Registry, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030106 microbiology, Encephalopathy, Nervous System, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Registries, 030212 general & internal medicine, Pleocytosis, Aged, Retrospective Studies, medicine.diagnostic_test, SARS-CoV-2, business.industry, Mortality rate, Brain, COVID-19, Retrospective cohort study, Magnetic resonance imaging, General Medicine, Neurologic manifestations, Middle Aged, medicine.disease, Thrombosis, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Neurological manifestations, Female, Original Article, France, Nervous System Diseases, business, Encephalitis
Abstract

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.

Published
2021

7. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial

Author

Wassilios G. Meissner, Roberto Eleopra, Taku Hatano, Francisco Grandas, Joseph F. Quinn, Justyna Sarna, Hui Zheng, Osamu Onodera, John T. Slevin, Theresa A. Zesiewicz, Anwar Ahmed, Erika Driver-Dunckley, Tao Xie, Hidek Mochizuki, Deborah A. Hall, John O`Sullivan, Peter A. Ljubenkov, Carlo Colosimo, Tomoko Oeda, Luc Defebvre, Diana R. Kerwin, Hana Florian, Deli Wang, Hoi-Kei Lon, David S. Geldmacher, Nahome Fisseha, Jennifer Hui, Elizabeth Peckham, Noriko Nishikawa, Jean-Christophe Corvol, Günter U. Höglinger, Jared Brosch, Fabienne Ory-Magne, Alberto Albanese, Kumar Budur, Yvette Bordelon, Zbigniew K. Wszolek, Stefano Ruggieri, Akio Kikuchi, James H. Bower, Kelly Bertram, Antonio Daniele, Daryl Wile, Ikuko Aiba, Rajeev Kumar, Lawrence S. Honig, Daniel Claassen, Victor S.C. Fung, Renato P. Munhoz, Beatrice Rendenbach-Mueller, Michael Gold, Ziyi Jin, Albert C. Ludolph, Nuno Mendonca, Ronald B. Postuma, John C. Morgan, Alexandre Eusebio, Aldo Quattrone, Antoine Duquette, Pablo Mir Rivera, Irene Litvan, Thomas E. Kimber, Michele Tagliati, Paola Cudia, Stefan Lorenzl, Takashi Kimura, Zoltan Mari, Hideki Oizumi, Nikolaus R. McFarland, Davis C. Ryman, Lawrence I. Golbe, and Paul E Schulz

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, drug therapy [Supranuclear Palsy, Progressive], Population, Placebo-controlled study, MAPT protein, human, tau Proteins, adverse effects [Antibodies, Monoclonal, Humanized], Antibodies, Monoclonal, Humanized, Placebo, Progressive supranuclear palsy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, medicine, Clinical endpoint, Humans, ddc:610, Adverse effect, education, Aged, education.field_of_study, business.industry, tilavonemab, therapeutic use [Antibodies, Monoclonal, Humanized], Middle Aged, Interim analysis, medicine.disease, immunology [tau Proteins], Settore MED/26 - NEUROLOGIA, Treatment Outcome, 030104 developmental biology, Administration, Intravenous, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

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.

Published
2021

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

Author

Luc Defebvre, David Devos, Nacim Betrouni, Jordan Labidi, Caroline Moreau, Arnaud Delval, Céline Tard, and Kathy Dujardin

Subjects
Male, medicine.medical_specialty, Parkinson's disease, Video Recording, STRIDE, Poison control, Kinematics, Sensitivity and Specificity, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Gait (human), Hypokinesia, Physiology (medical), medicine, Humans, 0501 psychology and cognitive sciences, Aged, Analysis of covariance, business.industry, 05 social sciences, Parkinson Disease, Retrospective cohort study, Middle Aged, medicine.disease, Sensory Systems, Biomechanical Phenomena, Neurology, Accidental Falls, Female, Neurology (clinical), medicine.symptom, Gait Analysis, business, human activities, 030217 neurology & neurosurgery
Abstract

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.

Published
2021

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

Author

Luc Defebvre, Xavier Demondion, Alexandre Kreisler, and Camille Gerrebout

Subjects
medicine.medical_specialty, Neurology, Vertebral artery, Scalene muscles, Palpation, Injections, 03 medical and health sciences, 0302 clinical medicine, Cadaver, medicine.artery, medicine, Humans, 030212 general & internal medicine, Cervical dystonia, Ultrasonography, Interventional, Ultrasonography, Neuroradiology, medicine.diagnostic_test, business.industry, Cervical muscles, Muscles, Anatomy, medicine.disease, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

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.

Published
2021

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

Author

Martin Simoneau, Luc Defebvre, Arnaud Delval, Frédéric Viseux, Laboratoire d'Automatique, de Mécanique et d'Informatique industrielles et Humaines - UMR 8201 (LAMIH), Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Interdisciplinaire de Recherche en Réadaptation et Intégration Sociale (CIRRIS), Université Laval [Québec] (ULaval), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), and Lille Neurosciences & Cognition - U 1172 (LilNCog)

Subjects
medicine.medical_specialty, Parkinson's disease, [SDV]Life Sciences [q-bio], medicine.medical_treatment, "Postural control", Postural instability, Sensory system, Disease, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Feedback, Sensory, Physiology (medical), Humans, Medicine, 0501 psychology and cognitive sciences, Postural Balance, Balance (ability), Sensory stimulation therapy, Rehabilitation, "Foot sole", Foot, business.industry, 05 social sciences, Parkinson Disease, "Parkinson’s disease", General Medicine, medicine.disease, "Cutaneous feedback", Neurology, Postural stability, "Bottom-up rehabilitation", Accidental Falls, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

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.

Published
2020

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

Author

Gilles Allali, Céline Tard, Arnaud Delval, Madli Bayot, Kathy Dujardin, Cédrick T. Bonnet, Etienne Allart, Lucile Dissaux, Luc Defebvre, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Lille Neurosciences & Cognition - U 1172 (LilNCog), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille, Inserm, CHU Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer [JPArc - U1172 Inserm], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc], Lille Neurosciences & Cognition (LilNCog) - U 1172, Lille Neurosciences & Cognition - U 1172 [LilNCog], Troubles cognitifs vasculaires et dégénératifs, 415060|||Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 [SCALab], Albert Einstein College of Medicine [New York], and Geneva University Hospital [HUG]

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Posture, Turns, Context (language use), Walking, gait, posture, gait initiation (GI), turns, dual task (DT), attention, falls, ageing, Timed Up and Go test, 050105 experimental psychology, Task (project management), 03 medical and health sciences, 0302 clinical medicine, Gait (human), Physical medicine and rehabilitation, Physiology (medical), medicine, Humans, Attention, 0501 psychology and cognitive sciences, Postural Balance, Gait, Aged, 05 social sciences, Motor control, Cognition, General Medicine, Gait initiation (GI), ddc:616.8, Ageing, Systematic review, Neurology, Time and Motion Studies, Dual task (DT), Accidental Falls, Falls, Neurology (clinical), Psychology, 030217 neurology & neurosurgery, Fall prevention
Abstract

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

Published
2020

12. Texture features of magnetic resonance images

Author

Renaud Lopes, Nacim Betrouni, Luc Defebvre, Albert F.G. Leentjens, Kathy Dujardin, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), and RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience

Subjects
0301 basic medicine, medicine.medical_specialty, cognitive deficits, Parkinson's disease, magnetic resonance imaging (MRI), Caudate nucleus, PROGRESSION, Neuropsychological Tests, Audiology, ATROPHY, VALIDATION, 03 medical and health sciences, Cognition, 0302 clinical medicine, medicine, Humans, Dementia, Cognitive Dysfunction, Neuropsychological assessment, Cognitive decline, RATING-SCALE, texture analysis, medicine.diagnostic_test, business.industry, Putamen, DEMENTIA, Parkinson Disease, IMPAIRMENT, PERFORMANCE, Executive functions, medicine.disease, Magnetic Resonance Imaging, PROCESSING SPEED, 030104 developmental biology, Neurology, ONSET, Neurology (clinical), Cognition Disorders, business, 030217 neurology & neurosurgery
Abstract

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.

Published
2020

13. Grey matter abnormalities are associated only with severe cognitive decline in early stages of Parkinson's disease

Author

Anja J.H. Moonen, Luc Defebvre, Paul A. M. Hofman, Amée F. Wolters, Christine Delmaire, Kathy Dujardin, Frank C.G. van Bussel, Renaud Lopes, Albert F.G. Leentjens, Annelien Duits, Neurochirurgie, MUMC+: MA AIOS Neurologie (9), RS: MHeNs - R3 - Neuroscience, MUMC+: MA Niet Med Staf Psychologie (9), Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), Beeldvorming, and MUMC+: DA BV Medisch Specialisten Radiologie (9)

Subjects
medicine.medical_specialty, Parkinson's disease, Cognitive Neuroscience, DIAGNOSTIC-CRITERIA, Motor Disorders, Experimental and Cognitive Psychology, Audiology, Grey matter, Neuropsychological Tests, SURFACE-BASED ANALYSIS, 050105 experimental psychology, VALIDATION, White matter, 03 medical and health sciences, 0302 clinical medicine, Cognition, VISUAL HALLUCINATIONS, medicine, Dementia, Humans, 0501 psychology and cognitive sciences, Cognitive Dysfunction, Disabled Persons, Neuropsychological assessment, Cognitive decline, Gray Matter, RATING-SCALE, medicine.diagnostic_test, DEMENTIA, 05 social sciences, Neuropsychology, Parkinson Disease, LEWY BODY, IMPAIRMENT, medicine.disease, Magnetic Resonance Imaging, Grey matter changes, ALZHEIMERS-DISEASE, Neuropsychology and Physiological Psychology, medicine.anatomical_structure, Cross-Sectional Studies, Psychology, CORTICAL THICKNESS, 030217 neurology & neurosurgery
Abstract

Cognitive impairment is common in Parkinson's disease (PD), yet with large heterogeneity in the range and course of deficits. In a cross-sectional study, 124 PD patients underwent extensive clinical and neuropsychological assessment as well as a 3T MRI scan of the brain. Our aim was to identify differences in grey matter volume and thickness, as well as cortical folding, across different cognitive profiles as defined through a data-driven exploratory cluster analysis of neuropsychological data. The identified cognitive groups ranged from cognitively intact patients to patients with severe deficits in all cognitive domains, whilst showing comparable levels of motor disability and disease duration. Each group was compared to the cognitively intact PD group using voxel- and vertex-based morphometry. Results revealed widespread age-related grey matter abnormalities associated with progressive worsening of cognitive functions in mild PD. When adjusted for age, significant differences were only seen between cognitively intact and severely affected PD patients and these were restricted to the right posterior cingulate and the right precuneus. Reduced cortical thickness was seen in the right inferior temporal gyrus and reduced folding in the right temporal region. As these differences were not associated with age, we assume that they are associated with underlying pathology of the cognitive decline. Given the limited involvement of grey matter differences, and the absence of differences in vascular changes across the groups, we hypothesize a more important role for white matter tract changes in cognitive decline in PD. (C) 2019 Elsevier Ltd. All rights reserved.

Published
2020

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

Author

Tarkeshwar Singh, Cédrick T. Bonnet, Arnaud Delval, Luc Defebvre, Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Pennsylvania State University (Penn State), Penn State System, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université de Lille, CNRS, CHU Lille, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 [SCALab], Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193, Lille Neurosciences & Cognition (LilNCog) - U 1172, Pennsylvania State University [Penn State], and Université de Lille, LillOA

Subjects
medicine.medical_specialty, Levodopa, Parkinson's disease, Eye Movements, Movement, Posture, Postural instability, automatic vs. higher order behaviours, Parkinson's disease-related impairments, eye and postural movements, synergic model, visual performance, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Physical medicine and rehabilitation, Basal ganglia, Humans, Medicine, Postural Balance, 030304 developmental biology, 0303 health sciences, business.industry, General Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Eye movement, Visual task, Parkinson Disease, Mean age, [SCCO] Cognitive science, Middle Aged, medicine.disease, Postural stability, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

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

Published
2021

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

Author

Quentin Devignes, Romain Viard, Nacim Betrouni, Guillaume Carey, Gregory Kuchcinski, Luc Defebvre, Albert F. G. Leentjens, Renaud Lopes, Kathy Dujardin, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), JMH Conception F- 68100 Mulhouse, France, Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), NS-Park/FCRIN Network, UMS 015, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and DUJARDIN, Kathy

Subjects
cognition, Aging, Pathology, medicine.medical_specialty, Parkinson's disease, Cognitive Neuroscience, DIAGNOSTIC-CRITERIA, tractometry, shape analysis, Neurosciences. Biological psychiatry. Neuropsychiatry, Context (language use), behavioral disciplines and activities, SURFACE-BASED ANALYSIS, VALIDATION, White matter, Fractional anisotropy, medicine, image texture analysis, Dementia, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuropsychological assessment, RATING-SCALE, Original Research, volumetry, medicine.diagnostic_test, business.industry, DEMENTIA, Cognition, Fascicle, cortical thickness, medicine.disease, medicine.anatomical_structure, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, RC321-571, Neuroscience
Abstract

Context: 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.Objective: The objective of this study was to identify structural modifications in cortical and subcortical regions associated with each PD-MCI subtype.Methods: 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 (n = 41) or as having a frontostriatal (n = 16), posterior cortical (n = 25), or a mixed (n = 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.Results: 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.Conclusion: 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.

Published
2021

17. Visual Sensory Processing is Altered in Myoclonus Dystonia

Author

Bertrand Degos, Luc Defebvre, Cécile Delorme, Christine Tranchant, Yulia Worbe, Pierre Krystkoviak, Marie Vidailhet, David Grabli, Eavan McGovern, Clément Tarrano, Jean-Christophe Corvol, Pierre Pouget, Stéphane Thobois, Jean‐Michel Pedespan, Romain Valabregue, Emmanuel Roze, Vanessa Brochard, Nicolas Wattiez, Jean-Luc Houeto, Adrian Degardin, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Myoclonus, 0301 basic medicine, medicine.medical_specialty, Visual sensory, Sensory processing, Movement, medicine.medical_treatment, Sensory system, Audiology, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Discrimination threshold, Dystonia, Movement Disorders, business.industry, Left primary visual cortex, Middle Aged, medicine.disease, nervous system diseases, 030104 developmental biology, Visual cortex, medicine.anatomical_structure, Neurology, Dystonic Disorders, Visual Perception, Female, Neurology (clinical), medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

BACKGROUND: Abnormal sensory processing, including temporal discrimination threshold, has been described in various dystonic syndromes. OBJECTIVE: To investigate visual sensory processing in DYT-SGCE and identify its structural correlates. METHODS: DYT-SGCE patients without DBS (DYT-SGCE-non-DBS) and with DBS (DYT-SGCE-DBS) were compared to healthy volunteers in three tasks: a temporal discrimination threshold, a movement orientation discrimination, and movement speed discrimination. Response times attributed to accumulation of sensory visual information were computationally modelized, with mu parameter indicating sensory mean growth rate. We also identified the structural correlates of behavioral performance for temporal discrimination threshold. RESULTS: Twenty-four DYT-SGCE-non-DBS, 13 DYT-SGCE-DBS, and 25 healthy volunteers were included in the study. In DYT-SGCE-DBS, the discrimination threshold was higher in the temporal discrimination threshold (P = 0.024), with no difference among the groups in other tasks. The sensory mean growth rate (mu) was lower in DYT-SGCE in all three tasks (P < 0.01), reflecting a slower rate of sensory accumulation for the visual information in these patients independent of DBS. Structural imaging analysis showed a thicker left primary visual cortex (P = 0.001) in DYT-SGCE-non-DBS compared to healthy volunteers, which also correlated with lower mu in temporal discrimination threshold (P = 0.029). In DYT-SGCE-non-DBS, myoclonus severity also correlated with a lower mu in the temporal discrimination threshold task (P = 0.048) and with thicker V1 on the left (P = 0.022). CONCLUSION: In DYT-SGCE, we showed an alteration of the visual sensory processing in the temporal discrimination threshold that correlated with myoclonus severity and structural changes in the primary visual cortex. (c) 2019 International Parkinson and Movement Disorder Society.

Published
2019

18. Idiopathic Normal-Pressure Hydrocephalus: Diagnostic Accuracy of Automated Sulcal Morphometry in Patients With Ventriculomegaly

Author

Renaud Lopes, Christine Delmaire, Caroline Jacquiez, Julien Dumont, Luc Defebvre, Marc Baroncini, Jean-Pierre Pruvo, Jérôme Hodel, François Machuron, Grégory Kuchcinski, Hélène Behal, Régis Bordet, Xavier Leclerc, Thibaud Lebouvier, and Michel Bottlaender

Subjects
Cerebral atrophy, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Cognitive disorder, Magnetic resonance imaging, medicine.disease, 030218 nuclear medicine & medical imaging, Hydrocephalus, Calcarine sulcus, 03 medical and health sciences, 0302 clinical medicine, Normal pressure hydrocephalus, medicine, Surgery, Cingulate sulcus, Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery, Ventriculomegaly
Abstract

Background Idiopathic normal-pressure hydrocephalus (iNPH) is a treatable cause of gait and cognitive impairment. iNPH should be differentiated from ventriculomegaly secondary to brain atrophy to choose the best therapeutic option (ventriculoperitoneal shunt vs medical management). Objective To determine the diagnostic accuracy of automated sulcal morphometry to differentiate patients with iNPH from patients with ventriculomegaly of neurodegenerative origin. Methods Thirty-eight consecutive patients with iNPH (shunt responsive n = 31, nonresponsive n = 7), 35 with vascular cognitive disorder, and 25 age- and sex-matched healthy controls were prospectively included and underwent cognitive evaluation and 3T brain magnetic resonance imaging. Sulcal opening of 10 sulci of interest was retrospectively measured using an automated surface-based approach from the 3-dimensional T1-weighted images. Receiver-operating characteristic curve analyses determined the best parameter to identify iNPH patients. Results The best parameter to discriminate shunt-responsive iNPH from patients with vascular cognitive disorder and healthy controls was the ratio between calcarine sulcus and cingulate sulcus opening with an area under the curve of 0.94 (95% CI: 0.89, 0.99). A cut-off value of 0.95 provided the highest sensitivity (96.8%) and specificity (83.3%). Conclusion This preliminary study showed that automated sulcal morphometry may help the neurosurgeon to identify iNPH patients and to exclude other causes of ventriculomegaly.

Published
2019

19. Dyspnea: An underestimated symptom in Parkinson's disease

Author

Luc Defebvre, Kathy Dujardin, Cécile Chenivesse, François Machuron, Caroline Moreau, Thierry Perez, Guillaume Baille, David Devos, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Movement disorders, Parkinson's disease, Heart disease, [SDV]Life Sciences [q-bio], Physical examination, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, Humans, Medicine, Prospective Studies, Depression (differential diagnoses), Aged, medicine.diagnostic_test, business.industry, Parkinson Disease, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Dyspnea, 030104 developmental biology, Neurology, Cohort, Female, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Introduction Dyspnea is one of the least well-characterized non-motor symptoms (NMS) associated with Parkinson's disease (PD). Objective To determine the frequency of dyspnea in a large, single-center cohort of consecutive PD patients with no history of lung or heart disease, and to compare clinical features in dyspneic vs. non-dyspneic patients. Methods Patients with abnormal cardiovascular and pulmonary results in a clinical examination were excluded. A positive response to at least one question ("In the last month, have you suffered from breathlessness?" and "In the last month, have you had trouble breathing normally?") was considered to signify the experience of dyspnea. MDS-UPDRS, global cognitive performance, non-motor symptoms and quality of life were assessed. Results In the cohort of 153 non-demented PD patients (mean age ± standard deviation: 63.9 ± 7.4; mean disease duration: 9.2 ± 6.1 years), the mean [95% confidence interval (CI)] frequency of dyspnea was 39.2% (31.5-47). After adjustment for disease severity, PD patients with dyspnea had a significantly higher Movement Disorders Society Unified Parkinson's Disease Rating Scale part I, II and IV scores, a higher HAD anxiety and depression scores and a significantly higher 8-item Parkinson's Disease Questionnaire. Conclusion Dyspnea is a frequent NMS in PD. Its pathophysiology and prognostic value need more investigation.

Published
2019

20. Suggestive association between OPRM1 and impulse control disorders in Parkinson's disease

Author

Mathieu Anheim, Ouhaid Lagha-Boukbiza, Emmanuel Roze, Florence Cormier-Dequaire, Paul Krack, Alexis Brice, Lucette Lacomblez, Jean-Christophe Corvol, Solène Ansquer, Samir Bekadar, Sophie Tezenas du Montcel, Isabelle Benatru, Bénédicte Lebrun-Vignes, Pierre-Michel Llorca, Olivier Rascol, Graziella Mangone, Luc Defebvre, David Maltête, Ana Marques‐Raquel, Fabienne Ory-Magne, Anna Castrioto, Marie Vidailhet, Franck Durif, Said Lebbah, Eugénie Lhommée, Jean-Philippe Azulay, Fanny Charbonnier-Beaupel, Alexandre Kreisler, Suzanne Lesage, Antoine Pelissolo, Christine Tranchant, David Grabli, Christine Brefel-Courbon, Mélissa Tir, and Pierre Krystkowiak

Subjects
0301 basic medicine, Oncology, Candidate gene, medicine.medical_specialty, Parkinson's disease, Population, Disease, Logistic regression, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Internal medicine, Medicine, Family history, education, education.field_of_study, business.industry, medicine.disease, 3. Good health, Impulse control, 030104 developmental biology, Bonferroni correction, Neurology, symbols, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

BACKGROUND Impulse control disorders are frequently associated with dopaminergic therapy in Parkinson's disease. Genetic studies have suggested a high heritability of impulse control disorders in the general population and in PD. The aim of this study was to identify candidate gene variants associated with impulse control disorders and related behaviors in PD. METHODS We performed a multicenter case-control study in PD patients with (cases) or without impulse control disorders and related behaviors despite significant dopamine agonist exposure of >300 mg levodopa-equivalent daily dose during 12 months (controls). Behavioral disorders were assessed using the Ardouin scale. We investigated 50 variants in 24 candidate genes by a multivariate logistic regression analysis adjusted for sex and age at PD onset. RESULTS The analysis was performed on 172 cases and 132 controls. Cases were younger (60 ± 8 vs 63 ± 8 years; P

Published
2018

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

Author

Marc Vérin, Anne Pavy-Le Traon, Vanessa Rousseau, Margherita Fabbri, Alexandra Foubert-Samier, Wassilios G. Meissner, François Tison, Philippe Couratier, Agnès Sommet, Luc Defebvre, Valérie Cochen De Cock, Santiago Perez-Lloret, Franck Durif, Christine Tranchant, Claire Thalamas, Jean-Philippe Azulay, Philippe Remy, Jean-Christophe Corvol, Philippe Damier, Olivier Rascol, Jean-Luc Houeto, Christian Geny, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), EuroMov - Digital Health in Motion (Euromov DHM), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Montpellier (UM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Limoges, Centre hospitalier universitaire de Nantes (CHU Nantes), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Euromov (EuroMov), Université de Montpellier (UM), CHI Créteil, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), CHU Pontchaillou [Rennes], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), NS-Park/FCRIN Network, UMS 015, Centre d’Excellence en Maladies Neurodégénératives (NeuroToul), CHU Toulouse [Toulouse], Clinique Beau Soleil [Montpellier], Pontifical Catholic University of Argentina (UCA), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Nord Laennec [CHU Nantes], Lille Neurosciences & Cognition - U 1172 (LilNCog), CHU Lille, CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Les Hôpitaux Universitaires de Strasbourg (HUS), University of Otago [Dunedin, Nouvelle-Zélande], Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)

Subjects
0301 basic medicine, medicine.medical_specialty, Serotonin reuptake inhibitor, [SDV]Life Sciences [q-bio], multiple system atrophy, ENSAYO CLINICO, Placebo, law.invention, 03 medical and health sciences, NEUROBIOLOGIA, 0302 clinical medicine, Atrophy, Randomized controlled trial, Double-Blind Method, Rating scale, law, Internal medicine, Surveys and Questionnaires, medicine, ATROFIA MULTISISTÉMICA, Humans, symptomatic treatment, Fluoxetine, business.industry, Beck Depression Inventory, fluoxetine, ENFERMEDADES NEURODEGENERATIVAS, Parkinson Disease, clinical trial, medicine.disease, Confidence interval, 3. Good health, ENFERMEDAD DE PARKINSON, 030104 developmental biology, Treatment Outcome, Neurology, Quality of Life, placebo, TRATAMIENTO MEDICO, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Fil: Rascol, Olivier. Universidad de Toulouse. Hospital Universitario de Toulouse; Francia Fil: Rascol, Olivier. Centro NeuroToul COEN; Francia Fil: Rascol, Olivier. Clínica de Toulouse. Centro de Investigación. Departamentos de Neurociencias y Farmacología Clínica; Francia Fil: Cochen De Cock, Valérie. Clínica Beau Soleil. Departamento de Neurología; Francia Fil: Cochen De Cock, Valérie. Universidad de Montpellier. EuroMov Digital Health in Motion; Francia Fil: Pavy-Le Traon, Anne. Centro de referencia de atrofia multisistémica; Francia Fil: Pavy-Le Traon, Anne. Universidad de Toulouse. Hospital Universitario de Toulouse. Instituto de Enfermedades Cardiovasculares y Metabólicas. Centro de Investigación Clínica de Toulouse. Departamento de Neurociencias; Francia Fil: Foubert-Samier, Alexandra. Universidad de Toulouse. Hospital Universitario de Toulouse. Instituto de Enfermedades Cardiovasculares y Metabólicas. Departamento de Neurociencias, Centro de investigación Clínica de Toulouse; Francia Fil: Thalamas, Claire. Universidad de Toulouse. Hospital Universitario de Toulouse. Centro de Investigación Clínica de Toulouse; Francia Fil: Thalamas, Claire. Hospital Universitario de Burdeos; Francia Fil: Sommet, Agnès. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Pérez Lloret, Santiago. Universidad Abierta Interamericana. Centro de Investigaciones Biomédicas; Argentina Fil: Pérez Lloret, Santiago. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina Fil: Fabbri, Margherita. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Azulay, Jean Philippe. Universidad de Aix-Marsella. Sistema de Hospitales Universitarios Públicos de Marsella; Francia Fil: Corvol, Jean-Christophe. Universidad de la Sorbona; Francia Fil: Corvol, Jean-Christophe. Hospital de la Pitié-Salpêtrière; Francia Fil: Corvol, Jean-Christophe. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Couratier, Philippe. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Damier, Philippe. Hospital Nord Laennec. Centro de Investigación Clínica; Francia Fil: Defebvre, Luc. Universidad en Lille; Francia Fil: Defebvre, Luc. Hospital Universitario de Marsella. Departamento de Neurología y Patología del Movimiento; Francia Fil: Durif, Franck. Centro Hospitalario Universitario, Clermont-Ferrand. Departamento de Neurología; Francia Fil: Durif, Franck. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Geny, Christian. Universidad de Montpellier. Departamento de Neurología; Francia Fil: Houeto, Jean-Luc. Centro Hospitalario Universitario de Limoges; Francia Fil: Houeto, Jean-Luc. Centro de referencia de atrofia multisistémica. Departamento de Neurología. Centro de Expertos en Parkinson; Francia Fil: Rascol, Olivier. Centro de referencia de atrofia multisistémica; Francia Fil: Remy, Philippe. Red Francesa de Infraestructura de Investigación Clínica. Centros Expertos en Parkinson; Francia Fil: Remy, Philippe. Instituto de Investigaciones Biomédicas Mondor; Francia Fil: Tranchant, Christine. Hospital Universitario de Estrasburgo. Red Francesa de Infraestructura de Investigación Clínica. Departamento de Neurología; Francia Fil: Verin, Marc. Universidad de Rennes. Hospital Universitario de Rennes. Red Francesa de Infraestructura de Investigación Clínica. Centro de expertos en Parkinson; Francia Fil: Tison, François. Centro de referencia de atrofia multisistémica. Departamento de Neurología de Enfermedades Neurodegenerativas; Francia Fil: Meissner, Wassilios G. Instituto de Investigación del Cerebro; Nueva Zelanda Fil: Meissner, Wassilios G. Universidad de Otago. Departamento de Medicina; Nueva Zelanda Abstract: 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.

Published
2021

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

Author

Nacim Betrouni, Caroline Moreau, David Devos, Renaud Lopes, Gregory Kuchcinski, Romain Viard, Luc Defebvre, Marie Chupin, Anne-Sophie Rolland, Nicolas Carrière, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Departement de Neuroradiologie [Lille], Gestionnaire, HAL Sorbonne Université 5, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Inserm, Université de Lille, Lille Neurosciences & Cognition (LilNCog) - U 1172, and Lille Neurosciences & Cognition - U 1172 [LilNCog]

Subjects
Male, Pathology, medicine.medical_specialty, Dyskinesia, Drug-Induced, Parkinson's disease, Science, Thalamus, Nigrostriatal pathway, Substantia nigra, Disease, Striatum, Texture (music), Article, 030218 nuclear medicine & medical imaging, Antiparkinson Agents, Levodopa, 03 medical and health sciences, 0302 clinical medicine, Engineering, medicine, Image Processing, Computer-Assisted, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Gray Matter, Aged, Multidisciplinary, medicine.diagnostic_test, business.industry, Brain, Magnetic resonance imaging, Parkinson Disease, Middle Aged, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Nerve Degeneration, Medicine, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, 030217 neurology & neurosurgery, Biomarkers, Neuroscience
Abstract

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.

Published
2021

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

Author

Anne-Claire Leterme, Mark L. Kuijf, Anja J.H. Moonen, Dominique Servant, Marjolein E. de Vugt, Annelien Duits, Kathy Dujardin, Bérengère Flinois, Sebastian Köhler, Luc Defebvre, Anne E.P. Mulders, Albert F.G. Leentjens, MUMC+: MA Niet Med Staf Psychologie (9), Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: MHeNs - R3 - Neuroscience, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), and MUMC+: MA Med Staf Spec Psychiatrie (9)

Subjects
0301 basic medicine, medicine.medical_specialty, Movement disorders, Hamilton Anxiety Rating Scale, medicine.medical_treatment, Anxiety, behavioral disciplines and activities, law.invention, s disease, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Intervention (counseling), medicine, HARS, Humans, Cognitive Behavioral Therapy, business.industry, Social anxiety, Parkinson Disease, Anxiety Disorders, Cognitive behavioral therapy, parkinson&#700, 030104 developmental biology, Treatment Outcome, Neurology, randomized controlled trial, Physical therapy, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

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.

Published
2021

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

Author

Madli Bayot, Caroline Moreau, Luc Defebvre, Clint Hansen, Walter Maetzler, Arnaud Delval, Christian Schlenstedt, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Christian-Albrechts University of Kiel, European Project: 721577,H2020-MSCA-ITN-2016,Keep Control(2017), Université de Lille, Inserm, CHU Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer [JPArc - U1172 Inserm], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc], Lille Neurosciences & Cognition (LilNCog) - U 1172, Lille Neurosciences & Cognition - U 1172 [LilNCog], Lille Neurosciences & Cognition - U 1172 (LilNCog), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Parkinson's disease, genetic structures, Posture, Postural instability, freezing of gait (FOG), gait initiation, Postural control, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Gait (human), anticipatory postural adjustments (APAs), Parkinson’s disease (PD), medicine, Humans, Gait initiation, Postural Balance, Gait Disorders, Neurologic, Aged, business.industry, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Parkinson Disease, Middle Aged, medicine.disease, Biomechanical Phenomena, 030104 developmental biology, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Center of pressure (fluid mechanics)
Abstract

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.

Published
2021
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25. Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia

Author

Vanessa Brochard, Cyril Atkinson-Clement, Yulia Worbe, David Grabli, Stéphane Thobois, Jean‐Michel Pedespan, Nicolas Wattiez, Christine Tranchant, Romain Valabregue, Pierre Krystkoviak, Emmanuel Roze, Bertrand Degos, Clément Tarrano, Emmanuelle Apartis, Charlotte Rosso, Cécile Delorme, Camille-Albane Porte, Luc Defebvre, Jean-Luc Houeto, Marie Vidailhet, Eavan McGovern, Jean-Christophe Corvol, Pierre Pouget, Adrian Degardin, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), St Vincent's University Hospital, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hospices Civils de Lyon (HCL), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpitaux Paris Seine-Saint-Denis [Bobigny], CHU de Bordeaux Pellegrin [Bordeaux], CHU Amiens-Picardie, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Tourcoing, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Normandie Université (NU)-Normandie Université (NU), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Lille, Service de Neurologie [CHU Saint-Antoine], Atkinson-Clement, Cyril, Service de pédiatrie, CHU Pellegrin, Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie et pathologie du mouvement, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), and ANR-18-CE37-0008,CADETS,Cognition et développement cérébral chez adolescents avec Syndrome de Gilles de la Tourette(2018)

Subjects
Male, Myoclonus, 0301 basic medicine, Deep Brain Stimulation, medicine.medical_treatment, lcsh:Medicine, Stop signal, Synaptic Transmission, Comorbidities, [SCCO]Cognitive science, 0302 clinical medicine, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Dystonia, Multidisciplinary, Inhibition, Psychological, Dystonic Disorders, Proactive Inhibition, Neurological manifestations, Facilitation, Female, medicine.symptom, Adult, medicine.medical_specialty, Deep brain stimulation, Dissociative Disorders, Globus Pallidus, Inhibitory postsynaptic potential, Article, Young Adult, 03 medical and health sciences, Internal medicine, Reaction Time, medicine, Humans, Movement disorders, Reactive inhibition, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:R, Reactive Inhibition, [SCCO] Cognitive science, medicine.disease, nervous system diseases, 030104 developmental biology, Endocrinology, nervous system, lcsh:Q, business, Neurological disorders, 030217 neurology & neurosurgery
Abstract

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.

Published
2020

26. New insight into Parkinson’s disease‐related impairment of the automatic control of upright stance

Author

Yann Romain Kechabia, Tarkeshwar Singh, Luc Defebvre, Cédrick T. Bonnet, Arnaud Delval, Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Georgia [USA], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Lille Neurosciences & Cognition - U 1172 (LilNCog), Université de Lille, LillOA, Université de Lille, CNRS, CHU Lille, Lille Neurosciences & Cognition (LilNCog) - U 1172, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 [SCALab], and Service de neurophysiologie clinique [CHRU Lille]

Subjects
medicine.medical_specialty, Visual perception, Parkinson's disease, Eye Movements, Automatic control, genetic structures, Movement, media_common.quotation_subject, Posture, Upright stance, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Physical medicine and rehabilitation, Eye-body coordinated movements, Humans, Contrast (vision), Medicine, Postural Balance, Aged, 030304 developmental biology, media_common, Attentional resources, 0303 health sciences, business.industry, General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Eye movement, Parkinson Disease, Body movement, Automatic postural control, Middle Aged, medicine.disease, QUIET, Fixation (visual), Parkinson’s disease, business, 030217 neurology & neurosurgery
Abstract

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

Published
2020

27. Anatomy-guided injections of botulinum neurotoxin in neck muscles: how accurate is needle placement?

Author

Alexandre Kreisler, Luc Defebvre, A. Degardin, Eugénie Mutez, and Clémence Simonin

Subjects
medicine.medical_specialty, Injections, Intramuscular, 03 medical and health sciences, 0302 clinical medicine, Neck Muscles, Medicine, Humans, 030212 general & internal medicine, Cervical dystonia, Botulinum Toxins, Type A, Torticollis, Ultrasonography, Dystonia, Splenius capitis muscle, business.industry, Ultrasound, Imaging guidance, medicine.disease, Neck muscles, Botulinum neurotoxin, Neurology, Neuromuscular Agents, Needle placement, Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery
Abstract

BACKGROUND AND PURPOSE In cervical dystonia, the accuracy of botulinum neurotoxin (BoNT) injections may influence the response to the treatment. METHODS We used ultrasound to evaluate the accuracy of anatomy-guided injections of BoNT in the neck muscles. RESULTS A total of 56 consecutive patients and 332 injections were evaluated. The overall accuracy was 76.6%. The lowest accuracy (67.9%) was observed for the splenius capitis muscle. CONCLUSIONS Anatomic guidance of BoNT injections in the neck muscles is often inaccurate. Imaging guidance may improve the accuracy of BoNT injections in cervical dystonia.

Published
2020

28. Expanding the phenotype of SCA19/22: Parkinsonism, cognitive impairment and epilepsy

Author

Jean-Christophe Cuvellier, Marie Delliaux, Kathy Dujardin, Delphine Dellacherie, Bernard Sablonnière, Isabelle Strubi-Vuillaume, David Devos, Luc Defebvre, Vincent Huin, Audrey Riquet, Marine Brion, Caroline Moreau, Jean-Marie Cuisset, HUIN, Vincent, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neurologie et Pathologies du Mouvement [CHU Lille], Service de neuropédiatrie [CHU Lille], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Biologie Pathologie et Génétique, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut d'Immunologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille

Subjects
Male, 0301 basic medicine, Pediatrics, Parkinson's disease, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, Mesh:Adult, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SCCO]Cognitive science, Epilepsy, Mesh:Adolescent, 0302 clinical medicine, Medicine, Child, Neurogenetics, Mesh:Epilepsy/genetics, Mesh:Aged, Spinocerebellar Degenerations, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, Parkinsonism, Mesh:Spinocerebellar Degenerations/complications, Cognition, Middle Aged, Mesh:Cognitive Dysfunction/genetics, Pedigree, 3. Good health, Phenotype, Neurology, Spinocerebellar ataxia, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Adult, Mesh:Female, medicine.medical_specialty, Adolescent, Cognitive disorders, Mesh:Child, Mesh:Male, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, 03 medical and health sciences, Parkinsonian Disorders, Mesh:Middle Aged, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Mesh:80 and over, Humans, Cognitive Dysfunction, Quantitative Biology - Genomics, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Genetic testing, Genomics (q-bio.GN), [SDV.GEN]Life Sciences [q-bio]/Genetics, Cerebellar ataxia, business.industry, Mesh:Pedigree, Mesh:Phenotype, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SCCO] Cognitive science, medicine.disease, Neuropsychiatric disorder, Mesh:Humans, 030104 developmental biology, KCND3 mutation, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mesh:Parkinsonian Disorders/genetics, Parkinson''s disease, FOS: Biological sciences, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

International audience; BACKGROUND: Spinocerebellar ataxia types 19 and 22 (SCA19/22) are rare conditions in which relatively isolated cerebellar involvement is frequently associated with cognitive impairment. Here, we report on new clinical features and provide details of the cognitive profile in two SCA19/22 families.METHODS: Two families displaying an autosomal-dominant form of cerebellar ataxia underwent clinical examinations and genetic testing.RESULTS: In addition to the classical clinical features of SCA, a wide spectrum of cognitive disorders (including visuospatial impairments) was observed. Eight patients had mild Parkinsonism, and five had epilepsy. Genetic testing showed that the KCND3 mutation (c.679_681delTTC, p.F227del) was present in both families.CONCLUSIONS: Our findings broaden the phenotypic spectrum of SCA19/22, and suggest that KCND3 should be included in the list of candidate genes for epilepsy, Parkinsonism and cognitive impairment.

Published
2017

29. Identification of genetic variants associated with Huntington's disease progression

Author

Davina J Hensman Moss, Antonio F Pardiñas, Douglas Langbehn, Kitty Lo, Blair R Leavitt, Raymund Roos, Alexandra Durr, Simon Mead, Peter Holmans, Lesley Jones, Sarah J Tabrizi, A Coleman, R Dar Santos, J Decolongon, A Sturrock, E Bardinet, C Jauff Ret, D Justo, S Lehericy, C Marelli, K Nigaud, R Valabrègue, SJA van den Bogaard, E M Dumas, J van der Grond, EP t'Hart, C Jurgens, M-N Witjes-Ane, N Arran, J Callaghan, C Stopford, C Frost, R Jones, N Hobbs, N Lahiri, R Ordidge, G Owen, T Pepple, J Read, M Say, E Wild, A Patel, N C Fox, C Gibbard, I Malone, H Crawford, D Whitehead, S Keenan, D M Cash, C Berna, N Bechtel, S Bohlen, A Hoff Man, P Kraus, E Axelson, C Wang, T Acharya, S Lee, W Monaco, C Campbell, S Queller, K Whitlock, M Campbell, E Frajman, C Milchman, A O'Regan, I Labuschagne, J Stout, B Landwehrmeyer, D Craufurd, R Scahill, S Hicks, C Kennard, H Johnson, A Tobin, HD Rosas, R Reilmann, B Borowsky, C Pourchot, S C Andrews, Anne-Catherine Bachoud-Lévi, Anna Rita Bentivoglio, Ida Biunno, Raphael Bonelli, Jean-Marc Burgunder, Stephen Dunnett, Joaquim Ferreira, Olivia Handley, Arvid Heiberg, Torsten Illmann, G. Bernhard Landwehrmeyer, Jamie Levey, Maria A. Ramos-Arroyo, Jørgen Nielsen, Susana Pro Koivisto, Markku Päivärinta, Raymund A.C. Roos, A Rojo Sebastián, Sarah Tabrizi, Wim Vandenberghe, Christine Verellen-Dumoulin, Tereza Uhrova, Jan Wahlström, Jacek Zaremba, Verena Baake, Katrin Barth, Monica Bascuñana Garde, Sabrina Betz, Reineke Bos, Jenny Callaghan, Adrien Come, Leonor Correia Guedes, Daniel Ecker, Ana Maria Finisterra, Ruth Fullam, Mette Gilling, Lena Gustafsson, Olivia J Handley, Carina Hvalstedt, Christine Held, Kerstin Koppers, Claudia Lamanna, Matilde Laurà, Asunción Martínez Descals, Saül Martinez-Horta, Tiago Mestre, Sara Minster, Daniela Monza, Lisanne Mütze, Martin Oehmen, Michael Orth, Hélène Padieu, Laurent Paterski, Nadia Peppa, Martina Di Renzo, Amandine Rialland, Niini Røren, Pavla Šašinková, Erika Timewell, Jenny Townhill, Patricia Trigo Cubillo, Wildson Vieira da Silva, Marleen R van Walsem, Carina Whalstedt, Marie-Noelle Witjes-Ané, Grzegorz Witkowski, Abigail Wright, Daniel Zielonka, Eugeniusz Zielonka, Paola Zinzi, Raphael M. Bonelli, Sabine Lilek, Karen Hecht, Brigitte Herranhof, Anna Holl, Hans-Peter Kapfhammer, Michael Koppitz, Markus Magnet, Nicole Müller, Daniela Otti, Annamaria Painold, Karin Reisinger, Monika Scheibl, Helmut Schöggl, Jasmin Ullah, Eva-Maria Braunwarth, Florian Brugger, Lisa Buratti, Eva-Maria Hametner, Caroline Hepperger, Christiane Holas, Anna Hotter, Anna Hussl, Christoph Müller, Werner Poewe, Klaus Seppi, Fabienne Sprenger, Gregor Wenning, Andrea Boogaerts, Godelinde Calmeyn, Isabelle Delvaux, Dirk Liessens, Nele Somers, Michel Dupuit, Cécile Minet, Dominique van Paemel, Pascale Ribaï, Dimphna van Reijen, Jirí Klempír, Veronika Majerová, Jan Roth, Irena Stárková, Lena E. Hjermind, Oda Jacobsen, Jørgen E. Nielsen, Ida Unmack Larsen, Tua Vinther-Jensen, Heli Hiivola, Hannele Hyppönen, Kirsti Martikainen, Katri Tuuha, Philippe Allain, Dominique Bonneau, Marie Bost, Bénédicte Gohier, Marie-Anne Guérid, Audrey Olivier, Adriana Prundean, Clarisse Scherer-Gagou, Christophe Verny, Blandine Babiloni, Sabrina Debruxelles, Charlotte Duché, Cyril Goizet, Laetitia Jameau, Danielle Lafoucrière, Umberto Spampinato, Rekha Barthélémy, Christelle De Bruycker, Maryline Cabaret Anne-Sophie Carette, Eric Decorte Luc Defebvre, Marie Delliaux, Arnaud Delval, Alain Destee, Kathy Dujardin, Marie-Hélène Lemaire, Sylvie Manouvrier, Mireille Peter, Lucie Plomhouse, Bernard Sablonnière, Clémence Simonin, Stéphanie Thibault-Tanchou, Isabelle Vuillaume, Marcellin Bellonet, Hassan Berrissoul, Stéphanie Blin, Françoise Courtin, Cécile Duru, Véronique Fasquel, Olivier Godefroy, Pierre Krystkowiak, Béatrice Mantaux, Martine Roussel, Sandrine Wannepain, Jean-Philippe Azulay, Marie Delfini, Alexandre Eusebio, Frédérique Fluchere, Laura Mundler, Mathieu Anheim, Celine Julié, Ouhaid Lagha Boukbiza, Nadine Longato, Gabrielle Rudolf, Christine Tranchant, Marie-Agathe Zimmermann, Christoph Michael Kosinski, Eva Milkereit, Daniela Probst, Kathrin Reetz, Christian Sass, Johannes Schiefer, Christiane Schlangen, Cornelius J. Werner, Harald Gelderblom, Josef Priller, Harald Prüß, Eike Jakob Spruth, Gisa Ellrichmann, Lennard Herrmann, Rainer Hoffmann, Barbara Kaminski, Peter Kotz, Christian Prehn, Carsten Saft, Herwig Lange, Robert Maiwald, Matthias Löhle, Antonia Maass, Simone Schmidt, Cecile Bosredon, Alexander Storch, Annett Wolz, Martin Wolz, Philipp Capetian, Johann Lambeck, Birgit Zucker, Kai Boelmans, Christos Ganos, Walburgis Heinicke, Ute Hidding, Jan Lewerenz, Alexander Münchau, Jenny Schmalfeld, Lars Stubbe, Simone Zittel, Gabriele Diercks, Dirk Dressler, Heike Gorzolla, Christoph Schrader, Pawel Tacik, Michael Ribbat, Bernhard Longinus, Katrin Bürk, Jens Carsten Möller, Ida Rissling, Mark Mühlau, Alexander Peinemann, Michael Städtler, Adolf Weindl, Juliane Winkelmann, Cornelia Ziegler, Natalie Bechtel, Heike Beckmann, Stefan Bohlen, Eva Hölzner, Ralf Reilmann, Stefanie Rohm, Silke Rumpf, Sigrun Schepers, Natalia Weber, Matthias Dose, Gabriele Leythäuser, Ralf Marquard, Tina Raab, Alexandra Wiedemann, Andrea Buck, Julia Connemann, Carolin Geitner, Andrea Kesse, Bernhard Landwehrmeyer, Christina Lang, Franziska Lezius, Solveig Nepper, Anke Niess, Ariane Schneider, Daniela Schwenk, Sigurd Süßmuth, Sonja Trautmann, Patrick Weydt, Claudia Cormio, Vittorio Sciruicchio, Claudia Serpino, Marina de Tommaso, Sabina Capellari, Pietro Cortelli, Roberto Galassi, Giovanni Rizzo, Roberto Poda, Cesa Scaglione, Elisabetta Bertini, Elena Ghelli, Andrea Ginestroni, Francesca Massaro, Claudia Mechi, Marco Paganini, Silvia Piacentini, Silvia Pradella, Anna Maria Romoli, Sandro Sorbi, Giovanni Abbruzzese, Monica Bandettini di Poggio, Giovanna Ferrandes, Paola Mandich, Roberta Marchese, Alberto Albanese, Daniela Di Bella, Anna Castaldo, Stefano Di Donato, Cinzia Gellera, Silvia Genitrini, Caterina Mariotti, Lorenzo Nanetti, Dominga Paridi, Paola Soliveri, Chiara Tomasello, Giuseppe De Michele, Luigi Di Maio, Marco Massarelli, Silvio Peluso, Alessandro Roca, Cinzia Valeria Russo, Elena Salvatore, Pierpaolo Sorrentino, Enrico Amico, Mariagrazia Favellato, Annamaria Griguoli, Irene Mazzante, Martina Petrollini, Ferdinando Squitieri, Barbara D'Alessio, Chiara Esposito, Rita Bentivoglio, Marina Frontali, Arianna Guidubaldi, Tamara Ialongo, Gioia Jacopini, Carla Piano, Silvia Romano, Francesco Soleti, Maria Spadaro, Monique S.E. van Hout, Marloes E. Verhoeven, Jeroen P.P. van Vugt, A. Marit de Weert, J.J.W. Bolwijn, M. Dekker, B. Kremer, K.L. Leenders, J.C.H. van Oostrom, Simon J.A. van den Bogaard, Eve M. Dumas, Ellen P. 't Hart, Berry Kremer, C.C.P. Verstappen, Olaf Aaserud, Jan Frich C, Ragnhild Wehus, Kathrine Bjørgo, Madeleine Fannemel, Per F. Gørvell, Eirin Lorentzen, Lars Retterstøl, Bodil Stokke, Inga Bjørnevoll, Sigrid Botne Sando, Artur Dziadkiewicz, Malgorzata Nowak, Piotr Robowski, Emilia Sitek, Jaroslaw Slawek, Witold Soltan, Michal Szinwelski, Magdalena Blaszcyk, Magdalena Boczarska-Jedynak, Ewelina Ciach-Wysocka, Agnieszka Gorzkowska, Barbara Jasinska-Myga, Gabriela Klodowska-Duda, Gregorz Opala, Daniel Stompel, Krzysztof Banaszkiewicz, Dorota Bocwinska, Kamila Bojakowska-Jaremek, Malgorzata Dec, Malgorzata Krawczyk, Monika Rudzinska, Elzbieta Szczygiel, Andrzej Szczudlik, Anna Wasielewska, Magdalena Wójcik, Anna Bryl, Anna Ciesielska, Aneta Klimberg, Jerzy Marcinkowski, Husam Samara, Justyna Sempolowicz, Anna Gogol, Piotr Janik, Hubert Kwiecinski, Zygmunt Jamrozik, Jakub Antczak, Katarzyna Jachinska, Wioletta Krysa, Maryla Rakowicz, Przemyslaw Richter, Rafal Rola, Danuta Ryglewicz, Halina Sienkiewicz-Jarosz, Iwona Stepniak, Anna Sulek, Elzbieta Zdzienicka, Karolina Zieora-Jakutowicz, Joaquim J Ferreira, Miguel Coelho, Tiago Mendes, Anabela Valadas, Carlos Andrade, Miguel Gago, Carolina Garrett, Maria Rosália Guerra, Carmen Durán Herrera, Patrocinio Moreno Garcia, Miquel Aguilar Barbera, Dolors Badenes Guia, Laura Casas Hernanz, Judit López Catena, Pilar Quiléz Ferrer, Ana Rojo Sebastián, Gemma Tome Carruesco, Jordi Bas, Núria Busquets, Matilde Calopa, Misericordia Floriach Robert, Celia Mareca Viladrich, Jesús Miguel Ruiz Idiago, Antonio Villa Riballo, Esther Cubo, Cecilia Gil Polo, Natividad Mariscal, Perez Jessica Rivadeneyra, Francisco Barrero, Blas Morales, María Fenollar, Rocío García-Ramos García, Paloma Ortega, Clara Villanueva, Javier Alegre, Mónica Bascuñana, Juan Garcia Caldentey, Marta Fatás Ventura, Guillermo García Ribas, Justo García de Yébenes, José Luis López-Sendón Moreno, Fernando Alonso Frech, Pedro J García Ruíz, Asunción Martínez-Descals, Rosa Guerrero, María José Saiz Artiga, Vicenta Sánchez, María Fuensanta Noguera Perea, Lorenza Fortuna, Salvadora Manzanares, Gema Reinante, María Martirio Antequera Torres, Laura Vivancos Moreau, Sonia González González, Luis Menéndez Guisasola, Carlos Salvador, Esther Suaréz San Martín, Inés Legarda Ramirez, Aranzazú Gorospe, Mónica Rodriguez Lopera, Penelope Navas Arques, María José Torres Rodríguez, Barbara Vives Pastor, Itziar Gaston, Maria Dolores Martinez-Jaurrieta, Jose Manuel Garcia Moreno, Carolina Mendez Lucena, Fatima Damas, Hermoso Eva Pacheco Cortegana, José Chacón Peña, Luis Redondo, Fátima Carrillo, María Teresa Cáceres, Pablo Mir, María José Lama Suarez, Laura Vargas-González, Maria E. Bosca, Francisco Castera Brugada, Juan Andres Burguera, Anabel Campos, Garcia Carmen Peiró Vilaplana, Peter Berglund, Radu Constantinescu, Gunnel Fredlund, Ulrika Høsterey-Ugander, Petra Linnsand, Liselotte Neleborn-Lingefjärd, Magnus Wentzel, Ghada Loutfi, Carina Olofsson, Eva-Lena Stattin, Laila Westman, Birgitta Wikström, Yanik Stebler, Alain Kaelin, Irene Romero, Michael Schüpbach, Sabine Weber Zaugg, Maria Hauer, Roman Gonzenbach, Hans H. Jung, Violeta Mihaylova, Jens Petersen, Roisin Jack, Kirsty Matheson, Zosia Miedzybrodzka, Daniela Rae, Sheila A Simpson, Fiona Summers, Alexandra Ure, Vivien Vaughan, Shahbana Akhtar, Jenny Crooks, Adrienne Curtis, Jenny de Souza, John Piedad, Hugh Rickards, Jan Wright, Elizabeth Coulthard, Louise Gethin, Beverley Hayward, Kasia Sieradzan, Matthew Armstrong, Roger A. 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García, Martínez-Descals, Asunciã³n, Guerrero, Rosa, Artiga, María José Saiz, Sã¡nchez, Vicenta, Perea, María Fuensanta Noguera, Fortuna, Lorenza, Manzanares, Salvadora, Reinante, Gema, Torres, María Martirio Antequera, Moreau, Laura Vivanco, González González, Sonia, Guisasola, Luis Menéndez, Salvador, Carlo, Martã­n, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazãº, Lopera, Mónica Rodriguez, Arques, Penelope Nava, Rodrã­guez, María José Torre, Pastor, Barbara Vive, Gaston, Itziar, Martinez-Jaurrieta, Maria Dolore, Moreno, Jose Manuel Garcia, Lucena, Carolina Mendez, Damas, Fatima, Cortegana, Hermoso Eva Pacheco, Peã±a, José Chacón, Redondo, Lui, Carrillo, Fã¡tima, Teresa Cáceres, Marã­a, Mir, Pablo, Suarez, María José Lama, Vargas-González, Laura, Bosca, Maria E., Brugada, Francisco Castera, Burguera, Juan Andre, Campos, Anabel, Vilaplana, Garcia Carmen Peiró, Berglund, Peter, Constantinescu, Radu, Fredlund, Gunnel, Høsterey-Ugander, Ulrika, Linnsand, Petra, Neleborn-Lingefjärd, Liselotte, Wentzel, Magnu, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikstrã¶m, Birgitta, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schã¼pbach, Michael, Weber Zaugg, Sabine, Hauer, Maria, Gonzenbach, Roman, Jung, Hans H., Mihaylova, Violeta, Petersen, Jen, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A, Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza, Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Armstrong, Matthew, Barker, Roger A., O'Keefe, Deidre, Di Pietro, Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Kershaw, Ann, Mason, Sarah, Paterson, Nicole, Raymond, Lucy, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Clenaghan, Catherine, Hunt, Sarah, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Edwards, Maureen, Carrie, Ho, Hughes, Teresa, Mcgill, Marie, Pearson, Pauline, Porteous, Mary, Smith, Paul, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Burrows, Liz, Chu, Carol, Fletcher, Amy, Gallantrae, Deena, Hamer, Stephanie, Harding, Alison, Klã¶ppel, Stefan, Kraus, Alison, Laver, Fiona, Lewis, Monica, Longthorpe, Mandy, Markova, Ivana, Raman, Ashok, Robertson, Nicola, Silva, Mark, Thomson, Aileen, Wild, Sue, Yardumian, Pam, Evans, Carole, Gallentrae, Deena, Hobson, Emma, Jamieson, Stuart, Musgrave, Hannah, Rowett, Liz, Toscano, Jean, Bourne, Colin, Clapton, Jackie, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Grant, Janet, Gross, Diana, Hallam, Caroline, Middleton, Julia, Murch, Ann, Thompson, Catherine, Alusi, Sundu, Davies, Rhy, Foy, Kevin, Gerrans, Emily, Pate, Louise, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Bruno, Stefania, Doherty, Karen, Haider, Salman, Hensman, Davina, Lahiri, Nayana, Novak, Marianne, Patel, Aakta, Rosser, Elisabeth, Taylor, Rachel, Warner, Thoma, Wild, Edward, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Rogers, Dawn, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iri, Verstraelen, Nichola, Westmoreland, Leann, Armstrong, Richard, Dixon, Kathryn, Nemeth, Andrea H, Siuda, Gill, Valentine, Ruth, David, Harrison, Hughes, Max, Parkinson, Andrew, Soltysiak, Beverley, Bandmann, Oliver, Bradbury, Alyson, Gill, Paul, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Kazoka, Mbombe, O'Donovan, Kirsty, Taylor, Cat, Tidswell, Katherine, Quarrell, Oliver, Lau, Puay Ngoh, Pica, Emmanul, Tan, Louis, Amsterdam Neuroscience - Neurodegeneration, Neurology, Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Moss, Davina J Hensman, Lo, Kitty, Pardiñas, Antonio F, Santos, R Dar, Ret, C Jauff, Valabrègue, R., Witjes-Ane, M. -N., Man, A Hoff, Bachoud-Lévi, Anne-Catherine, Nielsen, Jørgen, Päivärinta, Markku, Sebastián, A Rojo, Wahlström, Jan, Garde, Monica Bascuñana, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saül, Mütze, Lisanne, Padieu, Hélène, Røren, Niini, Šašinková, Pavla, Witjes-Ané, Marie-Noelle, Müller, Nicole, Schöggl, Helmut, Müller, Christoph, Minet, Cécile, Ribaï, Pascale, Klempír, Jirí, Majerová, Veronika, Stárková, Irena, Nielsen, Jørgen E., Hyppönen, Hannele, Gohier, Bénédicte, Guérid, Marie-Anne, Duché, Charlotte, Lafoucrière, Danielle, Barthélémy, Rekha, Lemaire, Marie-Hélène, Sablonnière, Bernard, Simonin, Clémence, Thibault-Tanchou, Stéphanie, Blin, Stéphanie, Courtin, Françoise, Duru, Cécile, Fasquel, Véronique, Mantaux, Béatrice, Fluchere, Frédérique, Julié, Celine, Prüß, Harald, Löhle, Matthia, Münchau, Alexander, Bürk, Katrin, Möller, Jens Carsten, Mühlau, Mark, Städtler, Michael, Hölzner, Eva, Leythäuser, Gabriele, Süßmuth, Sigurd, Marchese, Roberta, DI MAIO, Luigi, ’t Hart, Ellen P., Bjørgo, Kathrine, Gørvell, Per F., Retterstøl, Lar, Bjørnevoll, Inga, Wójcik, Magdalena, Guerra, Maria Rosália, Herrera, Carmen Durán, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastián, Ana Rojo, Busquets, Núria, Idiago, Jesús Miguel Ruiz, Fenollar, María, García, Rocío García-Ramo, Bascuñana, Mónica, Ventura, Marta Fatá, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Ruíz, Pedro J García, Martínez-Descals, Asunción, Artiga, María José Saiz, Sánchez, Vicenta, Perea, María Fuensanta Noguera, Torres, María Martirio Antequera, González González, Sonia, Guisasola, Luis Menéndez, Martín, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazú, Lopera, Mónica Rodriguez, Rodríguez, María José Torre, Peña, José Chacón, Carrillo, Fátima, Teresa Cáceres, María, Suarez, María José Lama, Vargas-González, Laura, Vilaplana, Garcia Carmen Peiró, Høsterey-Ugander, Ulrika, Neleborn-Lingefjärd, Liselotte, Wikström, Birgitta, Schüpbach, Michael, Ho, Carrie, Klöppel, Stefan, Harrison, David, Cardiff University, University of Iowa [Iowa City], University of British Columbia (UBC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UCL, Institute of Neurology [London], National Oceanography Centre [Southampton] (NOC), University of Southampton, Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), TRACK-HD investigators, Pardinas, Antonio F, Langbehn, Douglas, Lee, S Hong, TRACK-HD Investigators, and REGISTRY Investigators

Subjects
0301 basic medicine, Oncology, Registrie, Genome-wide association study, Longitudinal Studie, Disease, Bioinformatics, Severity of Illness Index, Principal Component Analysi, Longitudinal Studies, Registries, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Huntington disease, DNA-Binding Proteins, Settore MED/26 - NEUROLOGIA, Adult, Genome-Wide Association Study, Humans, Huntington Disease, MutS Homolog 3 Protein, Principal Component Analysis, Disease Progression, Neurology (clinical), huntingtin gene, age of onest, Huntington’s disease, Human, medicine.medical_specialty, cag repeat, instability, DNA-Binding Protein, Clinical Neurology, Principal component analysis, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, Huntington's disease, Internal medicine, medicine, SNP, genome-wide association study, medicine.disease, R1, meta-analysis, Minor allele frequency, 030104 developmental biology, Age of onset, Trinucleotide repeat expansion, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

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

Published
2017

30. Levodopa has primarily negative influences on postural control in patients with Parkinson's disease

Author

Arnaud Delval, Luc Defebvre, Sébastien Szaffarczyk, Cédrick T. Bonnet, Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, CHU Lille, CNRS, Inserm, Université de Lille, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 [SCALab], Troubles cognitifs dégénératifs et vasculaires - U1171, Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille, LillOA, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
Male, Parkinson's disease, genetic structures, [SDV]Life Sciences [q-bio], Poison control, 02 engineering and technology, postural control mechanisms, Postural control, Levodopa, [SCCO]Cognitive science, Behavioral Neuroscience, off- and on-drug sessions, visual tasks, 0302 clinical medicine, MESH: Parkinson Disease/physiopathology, Postural Balance, MESH: Levodopa/pharmacology, body sway, MESH: Aged, MESH: Head/physiopathology, MESH: Middle Aged, Parkinson Disease, Middle Aged, MESH: Postural Balance/drug effects, body rotation, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, MESH: Psychomotor Performance/physiology, medicine.symptom, Psychology, medicine.drug, Adult, medicine.medical_specialty, Weakness, 0206 medical engineering, 03 medical and health sciences, Physical medicine and rehabilitation, MESH: Psychomotor Performance/drug effects, Injury prevention, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Behavior/physiology, MESH: Postural Balance/physiology, Aged, Behavior, MESH: Humans, MESH: Adult, medicine.disease, 020601 biomedical engineering, Gaze, MESH: Male, Parkinson''s disease, Parkinson’s disease, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Off- and on-drug sessions, Body rotation, Postural control mechanisms, Body sway, Visual tasks, Head, Psychomotor Performance, MESH: Female, 030217 neurology & neurosurgery
Abstract

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

Published
2017

31. Les maladies neurologiques à expression psychiatrique : importance de l’examen neurologique

Author

Ali Amad, Luc Defebvre, Alexandre Haroche, Pierre-Alexis Geoffroy, and Thomas Fovet

Subjects
03 medical and health sciences, Psychiatry and Mental health, medicine.medical_specialty, 0302 clinical medicine, 030214 geriatrics, Arts and Humanities (miscellaneous), Daily practice, medicine, Psychiatry, Psychology, 030217 neurology & neurosurgery, Applied Psychology, 3. Good health
Abstract

In daily clinical psychiatric practice, it is necessary to be able to identify neurological disorders that can be expressed by psychiatric symptoms. The aim of this article is to briefly review neurological disorders that may have psychiatric manifestations, emphasizing the importance of neurologic examination in psychiatry. Another objective is to present an easy to follow neurologic examination to help the clinician for daily practice.

Published
2017

32. Clinical features of amyotrophic lateral sclerosis and their prognostic value

Author

Luc Defebvre, Caroline Moreau, Véronique Danel-Brunaud, Céline Tard, and David Devos

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Pathology, Disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Amyotrophic lateral sclerosis, business.industry, Amyotrophic Lateral Sclerosis, Disease progression, Nutritional status, Progressive muscular atrophy, Prognosis, medicine.disease, Clinical trial, 030104 developmental biology, Neurology, Respiratory failure, Disease Progression, Body region, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

In classic amyotrophic lateral sclerosis (ALS), the relative degree of impairment of cortical vs spinal motor neurons serving the different body regions is highly variable. This means that an accurate, systematic assessment of the patient's clinical presentation is essential for both the diagnosis and prognosis. The patient's phenotype, rate of disease progression, time of onset (if early) of respiratory failure and nutritional status all have prognostic value, and should be specified in the nosological classification of the disease.

Published
2017

33. Ethical considerations and palliative care in patients with amyotrophic lateral sclerosis: A review

Author

David Devos, Luc Defebvre, S. Vandoolaeghe, Caroline Moreau, Véronique Danel-Brunaud, L. Chevalier, and L. Touzet

Subjects
Advance care planning, medicine.medical_specialty, Palliative care, Psychological intervention, Disease, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Ethics, Medical, 030212 general & internal medicine, Amyotrophic lateral sclerosis, Intensive care medicine, Psychiatry, Terminal Care, business.industry, Amyotrophic Lateral Sclerosis, Palliative Care, medicine.disease, Caregivers, Withholding Treatment, Neurology, Anticipation (artificial intelligence), General partnership, Quality of Life, Neurology (clinical), business, 030217 neurology & neurosurgery, Executive dysfunction
Abstract

Amyotrophic lateral sclerosis (ALS) is not a curable disease, but it is treatable. By definition, much of the care provided to ALS patients is palliative, even though active life-sustaining strategies are available to prolong survival. Healthcare professionals must develop communication skills that help patients cope with the inexorable progression of the disease and the inevitability of death. Symptomatic treatments as well as respiratory insufficiency and nutritional life-sustaining therapies must be regularly evaluated as the disease progresses, without losing sight of the burden placed on the patient's non-professional caregivers. The decision-making process regarding tracheostomy with invasive ventilation (TIV) is of greater complexity. Providing full information is crucial. Several long interviews are necessary to explain, discuss and allow assimilation of the information. Also, physicians should be careful not to focus exclusively on the biomedical aspects of disease, as ALS patients generally welcome the opportunity to discuss end-of-life issues with their physicians. Psychological factors, education level and cognitive status (especially the level of executive dysfunction) have a major influence on their decisions. However, as many patients do not complete advance directives with regard to TIV, advance care planning may instead be suggested in anticipation of emergency interventions. This should be discussed by healthcare professionals and the patient, and based on the wishes of the patient and caregiver(s), and communicated to all healthcare professionals. Many healthcare professionals are involved in the management of an ALS patient: they include not only those at ALS centers who provide diagnosis, follow-up and treatment initiation (particularly for respiratory and nutritional care), but also the medical and social care networks involved in disability support and home care. Specialist palliative care teams can work in partnership with ALS centers early in the course of the disease, with the center coordinating information-sharing and collaborative discussions.

Published
2017

34. Tactile Temporal Discrimination Is Impaired in Myoclonus‐Dystonia

Author

Luc Defebvre, Clément Tarrano, Pierre Krystkoviak, Eavan McGovern, Jean-Christophe Corvol, Cyril Atkinson-Clement, Stéphane Thobois, Jean‐Michel Pedespan, Adrian Degardin, Jean-Charles Lamy, Yulia Worbe, Cécile Delorme, Emmanuelle Apartis, Vanessa Brochard, Marie Vidailhet, David Grabli, Christine Tranchant, Jean-Luc Houeto, Emmanuel Roze, Bertrand Degos, Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Neurochirurgie [CHU Pitié-Salpêtrière], Service de neurophysiologie clinique (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie et pathologie du mouvement, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de physiologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Myoclonus, Dystonia, 0303 health sciences, medicine.medical_specialty, business.industry, Audiology, medicine.disease, [SCCO]Cognitive science, 03 medical and health sciences, 0302 clinical medicine, Neurology, Dystonic Disorders, Touch, medicine, Humans, Neurology (clinical), medicine.symptom, business, Temporal discrimination, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

International audience

Published
2020

35. Functional correlates of cognitive slowing in Parkinson's disease

Author

David Devos, Guillaume Grolez, Renaud Lopes, Luc Defebvre, Kathy Dujardin, Romain Viard, Caroline Moreau, and Grégory Kuchcinski

Subjects
0301 basic medicine, Brain activation, Male, Cerebellum, medicine.medical_specialty, Parkinson's disease, Audiology, Neuropsychological Tests, computer.software_genre, 03 medical and health sciences, 0302 clinical medicine, Voxel, medicine, Humans, Cognitive Dysfunction, Aged, Cerebral Cortex, medicine.diagnostic_test, business.industry, Cognitive disorder, Cognition, Symbol digit modalities test, Parkinson Disease, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, medicine.anatomical_structure, Neurology, Female, Neurology (clinical), Geriatrics and Gerontology, business, Functional magnetic resonance imaging, computer, 030217 neurology & neurosurgery
Abstract

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 (puncorrected

Published
2019

36. What can we learn from fMRI capture of visual hallucinations in Parkinson’s disease?

Author

Renaud Jardri, David Roman, Stéphanie Lefebvre, Luc Defebvre, Guillaume Baille, Christine Delmaire, Delphine Pins, Kathy Dujardin, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Inserm, CHU Lille, Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Troubles cognitifs dégénératifs et vasculaires - U1171, 415060|||Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 [SCALab], Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 [SCALab], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), and Université de Lille, LillOA

Subjects
Male, medicine.medical_specialty, Parkinson's disease, Hallucinations, Cognitive Neuroscience, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Disease, Audiology, 050105 experimental psychology, 03 medical and health sciences, Behavioral Neuroscience, Cellular and Molecular Neuroscience, 0302 clinical medicine, default-mode network, medicine, Humans, two-step method, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Cognitive decline, Default mode network, Neuroradiology, Aged, Cerebral Cortex, hallucination capture, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, [SCCO.NEUR] Cognitive science/Neuroscience, Neuropsychology, Brain, Parkinson Disease, connectivity, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Visual Hallucination, Functional imaging, Psychiatry and Mental health, Neurology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background: With disease progression, patients with Parkinson’s disease (PD) may have chronic visual hallucinations (VH). The mechanisms behind this invalidating non-motor symptom remain largely unknown, namely because it is extremely difficult to capture hallucination events. This study aimed to describe the patterns of brain functional changes when VH occur in PD patients. Methods: Nine PD patients were enrolled because of their frequent and chronic VH (> 10/day). Patients with severe cognitive decline (MMSE

Published
2019

37. Safety and effectiveness of levodopa-carbidopa intestinal gel for advanced Parkinson's disease: A large single-center study

Author

David Seguy, Nicolas Carrière, Caroline Moreau, Maeva Kyheng, Alexandre Kreisler, Guillaume Grolez, Luc Defebvre, David Devos, Eugénie Mutez, A-S Blaise, Kathy Dujardin, and Guillaume Baille

Subjects
Adult, Male, medicine.medical_specialty, Parkinson's disease, Movement disorders, Drug-Related Side Effects and Adverse Reactions, medicine.medical_treatment, Single Center, Severity of Illness Index, Endoscopy, Gastrointestinal, Antiparkinson Agents, Levodopa, 03 medical and health sciences, 0302 clinical medicine, Catheters, Indwelling, Percutaneous endoscopic gastrostomy, Internal medicine, Medicine, Humans, 030212 general & internal medicine, Adverse effect, Infusion Pumps, Aged, Retrospective Studies, Aged, 80 and over, Gastrostomy, business.industry, Carbidopa, Parkinson Disease, Middle Aged, medicine.disease, Mental Status and Dementia Tests, Discontinuation, Drug Combinations, Treatment Outcome, Neurology, Intestinal Absorption, Clinical Global Impression, Female, Neurology (clinical), France, medicine.symptom, business, Gels, 030217 neurology & neurosurgery
Abstract

Background Treatment with levodopa-carbidopa intestinal gel (LCIG) can effectively relieve motor and non-motor symptoms in advanced Parkinson's disease (PD). However, adverse events (AEs) are frequent. Objective To describe AEs associated with LCIG treatment and the main reasons for treatment discontinuation. We also looked for factors that were potentially predictive of serious AEs and assessed the effectiveness of and satisfaction with LCIG. Method We retrospectively analyzed data on AEs in patients treated with LCIG at a French university medical center. For patients still receiving treatment at last follow-up, effectiveness was assessed according to the Clinical Global Impression (CGI) scale and the Movement Disorders Society – Unified Parkinson's Disease Rating Scale motor score. Results Of the 63 patients treated with LCIG for a mean (range) of 19 months (8–47), 57 (90%) experienced at least one AE (340 AEs in total). Most of the AEs (in 69.8% of the patients) were related to percutaneous endoscopic gastrostomy with a jejunal tube (PEG-J) or affected the gastrointestinal tract (granuloma, leakage, or a local infection). Device-related AEs (such as PEG-J removal and device occlusion) were frequent (in 63.5% of patients). Forty-three patients (68%) required at least one additional endoscopic procedure. Dopatherapy-related AEs occurred in 30 patients (48%). Most of the AEs occurred long after treatment initiations, and only a small proportion led to discontinuation. On the CGI scale, 53 patients (84.4%) considered that their condition had improved during LCIG treatment. Conclusion Despite the high frequency of AEs, patients with advanced PD gain clinical benefit from treatment with LCIG. This treatment requires a competent, multidisciplinary team on site.

Published
2019

38. Psychosocial Impact of dysarthria: the patient-reported outcome as part of the clinical management

Author

Luc Defebvre, Serge Pinto, Joaquim J. Ferreira, Jean-Philippe Azulay, Camille Robieux, Alban Letanneux, Alexandre Eusebio, Danièle Robert, Lauriane Véron-Delor, Guillaume Baille, Manon Berthelot, Marie-Charlotte Cuartero, Cyril Atkinson-Clement, Caroline Moreau, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Cognitions Humaine et ARTificielle (CHART), Université Paris 8 Vincennes-Saint-Denis (UP8)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École supérieure du professorat et de l'éducation - Académie de Créteil (UPEC ESPE Créteil), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Aix Marseille Université (AMU), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut de Neurosciences de la Timone (INT), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris 8 Vincennes-Saint-Denis (UP8)-École Pratique des Hautes Études (EPHE), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris 8 Vincennes-Saint-Denis (UP8)-École pratique des hautes études (EPHE)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Troubles cognitifs dégénératifs et vasculaires (U1171), INSERM-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), CHU Lille, CNRS, Inserm, Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U1171, and Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV]

Subjects
Adult, Male, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Psychometrics, Intelligibility (communication), Audiology, Psychosocial impact, Severity of Illness Index, 050105 experimental psychology, 03 medical and health sciences, Dysarthria, 0302 clinical medicine, medicine, Humans, Psychology, Speech, 0501 psychology and cognitive sciences, Patient Reported Outcome Measures, Voice Handicap Index, Aged, Dystonia, Aged, 80 and over, Cerebellar ataxia, business.industry, 05 social sciences, Communication Barriers, Speech Intelligibility, Discriminant validity, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Neurodegenerative Diseases, Middle Aged, medicine.disease, Mental Status and Dementia Tests, nervous system diseases, Phenotype, Neurology, Self-assessment, Voice, Patient-reported outcome, Female, Neurology (clinical), medicine.symptom, business, Psychosocial, 030217 neurology & neurosurgery
Abstract

Background: Dysarthria in neurological disorders can have psychosocial consequences. The dysarthric speaker’s perspective towards the disorder’s psychosocial impact is essential in its global assessment and management. For such purposes, assessment tools such as the Dysarthria Impact Profile (DIP) are indispensable. Objective: We aimed to confirm the relevance of using the DIP to quantify the psychosocial consequences of dysarthria in neurological diseases. Methods: We studied 120 participants, 15 healthy controls and 105 patients with different kinds of dysarthria induced by several neurological disorders (Parkinson’s disease [PD], Huntington’s disease, dystonia, cerebellar ataxia, progressive supranuclear palsy [PSP], multiple system atrophy, lateral amyotrophic sclerosis). All participants underwent a cognitive evaluation and a speech intelligibility assessment and completed three self-reported questionnaires: the 36-Item Short Form Health Survey, the Voice Handicap Index (VHI), and the DIP. Results: The psychometric properties of the DIP were confirmed, including internal consistency (α = 0.93), concurrent validity (correlation with the VHI: r = –0.77), and discriminant validity (accuracy = 0.93). Psychosocial impact of dysarthria was revealed by the DIP for all patients. Intelligibility loss was found strongly correlated with the psychosocial impact of dysarthria: for a similar level of intelligibility impairment, the DIP total score was similar regardless of the pathological group. However, our findings suggest that the psychosocial impact measured by the DIP could be partially independent from the severity of dysarthria (indirectly addressed here via speech intelligibility): the DIP was able to detect patients without any intelligibility impairment, but with a psychosocial impact. Conclusions: All patients reported a communication complaint, attested by the DIP scores, despite the fact that not all patients, notably PD, ataxic, and PSP patients, had an intelligibility deficit. The DIP should be used in clinical practice to contribute to a holistic evaluation and management of functional communication in patients with dysarthria.

Published
2019

39. Ventilatory Dysfunction in Parkinson’s Disease

Author

Christelle Monaca Charley, Kathy Dujardin, David Devos, Caroline Moreau, Guillaume Baille, Luc Defebvre, Thierry Perez, and Anna Maria De Jesus

Subjects
Male, Spirometry, medicine.medical_specialty, ventilatory function, Parkinson's disease, Review, Disease, Hypoxemia, 03 medical and health sciences, Cellular and Molecular Neuroscience, Sleep Apnea Syndromes, 0302 clinical medicine, Internal medicine, Respiratory muscle, Humans, Medicine, Lung volumes, 030212 general & internal medicine, Hypoxia, pathophysiology, medicine.diagnostic_test, business.industry, Parkinson Disease, Respiration Disorders, medicine.disease, Respiratory Muscles, Hypoventilation, Dyspnea, Parkinson’s disease, Cardiology, Female, Neurology (clinical), medicine.symptom, Lung Volume Measurements, business, 030217 neurology & neurosurgery
Abstract

In contrast to some other neurodegenerative diseases, little is known about ventilatory dysfunction in Parkinson's disease (PD). To assess the spectrum of ventilation disorders in PD, we searched for and reviewed studies of dyspnea, lung volumes, respiratory muscle function, sleep breathing disorders and the response to hypoxemia in PD. Among the studies, we identified some limitations: (i) small study populations (mainly composed of patients with advanced PD), (ii) the absence of long-term follow-up and (iii) the absence of functional evaluations under "off-drug" conditions. Although there are many reports of abnormal spirometry data in PD (mainly related to impairment of the inspiratory muscles), little is known about hypoventilation in PD. We conclude that ventilatory dysfunction in PD has been poorly studied and little is known about its frequency and clinical relevance. Hence, there is a need to characterize the different phenotypes of ventilation disorders in PD, study their relationships with disease progression and assess their prognostic value.

Published
2016

40. Impulse Control Disorders in Parkinson’s Disease are Associated with Alterations in Reward-Related Cortical Oscillations

Author

Philippe Derambure, Kathy Dujardin, Luc Defebvre, Arnaud Delval, Nicolas Carrière, and Jean-Louis Bourriez

Subjects
Male, medicine.medical_specialty, Parkinson's disease, Prefrontal Cortex, Mesolimbic pathway, Electroencephalography, Audiology, 050105 experimental psychology, Executive Function, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Reward, Dopamine, medicine, Humans, 0501 psychology and cognitive sciences, Prefrontal cortex, Aged, medicine.diagnostic_test, business.industry, 05 social sciences, Dopaminergic, Parkinson Disease, Middle Aged, medicine.disease, Brain Waves, Impulse control, Disruptive, Impulse Control, and Conduct Disorders, Dopamine Agonists, Cortical oscillations, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

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

Published
2016

41. Single session intermittent theta-burst stimulation on the left premotor cortex does not alleviate freezing of gait in Parkinson’s disease

Author

Arnaud Delval, Hervé Devanne, Luc Defebvre, and Céline Tard

Subjects
Male, 0301 basic medicine, Levodopa, medicine.medical_specialty, Parkinson's disease, genetic structures, medicine.medical_treatment, Prefrontal Cortex, Pilot Projects, Stimulation, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Humans, Prefrontal cortex, Gait Disorders, Neurologic, Aged, Cross-Over Studies, General Neuroscience, Parkinson Disease, Middle Aged, medicine.disease, Transcranial Magnetic Stimulation, Crossover study, Gait, Left premotor cortex, Biomechanical Phenomena, Transcranial magnetic stimulation, Treatment Outcome, 030104 developmental biology, Physical therapy, Female, Psychology, 030217 neurology & neurosurgery, medicine.drug
Abstract

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

Published
2016

42. Movement disorders and stroke

Author

Pierre Krystkowiak and Luc Defebvre

Subjects
Myoclonus, medicine.medical_specialty, Movement disorders, Lesion, 03 medical and health sciences, 0302 clinical medicine, Chorea, Internal medicine, Basal ganglia, medicine, Humans, 030212 general & internal medicine, Parkinson Disease, Secondary, Stroke, Asterixis, Dystonia, Dyskinesias, Movement Disorders, Prognosis, medicine.disease, Neurology, Anesthesia, Cardiology, Neurology (clinical), medicine.symptom, Psychology, 030217 neurology & neurosurgery
Abstract

Stroke may be associated with different types of movement disorders, such as hyperkinetic syndromes (hemichorea-hemiballism, unilateral asterixis, limb-shaking, dystonia, tremor, myoclonus) and hypokinetic syndromes (especially vascular parkinsonism). However, movement disorders are rare and transient in acute stroke and, as a permanent consequence, are more often delayed. While ischemic and hemorrhagic strokes can happen at any level of the frontal-subcortical motor system, they can be explained most of the time by a dysfunction in the basal ganglia motor circuit. However, only brain MRI allows the involved structure(s) to be precisely located, and each syndrome is specific to the type of lesion. Treatment is above all symptomatic. Only limb-shaking syndrome requires urgent surgical treatment because of the low-perfusion hemodynamic state. The functional prognosis depends on the type of movement disorder.

Published
2016

43. Influence of repetitive transcranial magnetic stimulation on tibialis anterior activity during walking in humans

Author

Alexandre Caux-Dedeystere, Arnaud Delval, Luc Defebvre, Hervé Devanne, Philippe Derambure, and Mélanie Rambour

Subjects
Adult, medicine.medical_specialty, medicine.medical_treatment, Stimulation, Walking, Stimulus (physiology), 050105 experimental psychology, Lower limb, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Humans, 0501 psychology and cognitive sciences, Elderly adults, Evoked potential, Treadmill, Muscle, Skeletal, Gait, Aged, General Neuroscience, 05 social sciences, Age Factors, Middle Aged, Transcranial Magnetic Stimulation, Transcranial magnetic stimulation, Primary motor cortex, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract

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

Published
2016

44. Les nouvelles voies de recherche thérapeutique dans la sclérose latérale amyotrophique (SLA)

Author

Caroline Moreau, V. Brunaud-Danel, Luc Defebvre, and David Devos

Subjects
0301 basic medicine, Gynecology, 03 medical and health sciences, medicine.medical_specialty, 030104 developmental biology, 0302 clinical medicine, business.industry, Medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Resume La sclerose laterale amyotrophique est une maladie neurodegenerative de l’adulte definie par la demonstration clinique et a l’electromyogramme d’une perte progressive et irreversible des motoneurones centraux et peripheriques. Le delai entre les premieres manifestations cliniques de la maladie et le diagnostic est en moyenne de 1 an, delai que l’on peut difficilement reduire en l’absence de biomarqueur du diagnostic. Aucun traitement medicamenteux ne permet de controler l’evolution de la maladie en dehors du riluzole au benefice certain mais modeste, ameliore si utilise precocement. L’amelioration du pronostic fonctionnel et vital obtenue ces dernieres annees est surtout le resultat d’une prise en charge medicale pluridisciplinaire, des progres de la ventilation non invasive, et d’un meilleur controle de l’etat nutritionnel. Les resultats des etudes therapeutiques medicamenteuses sont helas tres decevants. Les principales raisons sont les inconnues sur les mecanismes et les causes du dysfonctionnement neuromusculaire, l’heterogeneite clinique des malades se pretant a la recherche (formes a debut et predominance bulbaires ou spinales, formes spastiques ou peripheriques, formes lentes ou rapides, formes avec ou sans atteinte fronto-temporale cognitive ou comportementale, formes sporadiques ou familiales) et la grande variabilite du pronostic, allant de quelques mois a plus de 10 ans. La genetique est a ce jour la cle majeure pour ameliorer notre comprehension des dysfonctionnements des motoneurones dans la SLA, en particulier la formation d’agregats proteiques cellulaires anormaux, la perturbation des processus d’autophagie cellulaire et la neuro-inflammation. Des alterations du metabolisme lipidique et des mecanismes d’adaptation a l’hypoxemie jouent aussi probablement un role dans l’evolution de la maladie.

Published
2016

45. Do kinematic parameters of gait discriminate fallers and non-fallers in Parkinson's disease?

Author

Jordan Labidi, Arnaud Delval, Caroline Moreau, Kathy Dujardin, Luc Defebvre, David Devos, Nacim Betrouni, and Céline Tard

Subjects
medicine.medical_specialty, Parkinson's disease, business.industry, General Medicine, Kinematics, Stride length, medicine.disease, Gait speed, Gait asymmetry, Gait (human), Physical medicine and rehabilitation, Neurology, Physiology (medical), Gait analysis, Updrs iii, Medicine, Neurology (clinical), business, human activities
Abstract

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

Published
2019

46. Descriptive analysis of the French NS-Park registry: Towards a nation-wide Parkinson's disease cohort?

Author

Christine Brefel-Courbon, Stéphane Thobois, Gilles Defer, Christine Tranchant, Jean-Christophe Corvol, Bertrand Degos, Mohamed Doulazmi, Teodor Danaila, Estelle Dellapina, Frederic Torny, Véronique Chaigneau, Anne Doé De Maindreville, Christian Geny, Wassilios G. Meissner, Luc Defebvre, Nicolas Carrière, David Maltête, Louise-Laure Mariani, Marie Vidailhet, Olivier Rascol, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Euromov (EuroMov), Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Excellence en Maladies Neurodégénératives (NeuroToul), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Dupuytren [CHU Limoges], Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CCSD, Accord Elsevier, Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), and Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
0301 basic medicine, Adult, Male, Pediatrics, medicine.medical_specialty, Parkinson's disease, [SDV]Life Sciences [q-bio], Population, Disease, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Parkinsonian Disorders, Medicine, Humans, Registries, National database registry, education, Aged, Aged, 80 and over, education.field_of_study, business.industry, Parkinson Disease, Middle Aged, medicine.disease, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], 030104 developmental biology, Clinical research, Neurology, Cohort, Anxiety, Feasibility Studies, Female, Neurology (clinical), France, Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery, Cohort study
Abstract

Introduction Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's. The French clinical research network for PD (NS-Park) has created a national patient registry to i)report medical activity of Parkinson Expert Centers (PECs) to the Ministry of Health, ii)facilitate PD patients pre-screening for clinical trials, iii) provide a source for pharmaco-epidemiology studies. Objective Assess the French Parkinsonian population at a nation-wide level and discover new clinical characteristics. Methods In this feasibility study, PECs prospectively collected clinical data in a standardized manner. The population main clinical characteristics are described, focusing on motor and non-motor symptoms and treatments, assessing its representativeness. By using an unbiased clustering with multiple correspondence analysis (MCA), we also investigate potential relationships between multiple variables like symptoms and treatments, as clues for future studies. Results Between 2012 and 2016, among 11,157 included parkinsonian syndromes, 9454 (85%) had PD. MCA identified various profiles depending on disease duration. Occurrences of motor complications, axial signs, cognitive disorders and Levodopa use increase over time. Neurovegetative symptoms, psychiatric disorders, sleep disturbances and impulse control disorders (ICDs) seem stable over time. As expected, ICDs were associated to dopaminergic agonist use but other associations, such as ICDs and sleep disturbances for instance, or anxiety and depression, were found. Conclusions Our results report one of the biggest PD registries ever reported and demonstrate the feasibility of implementing a nation-wide registry of PD patients in France, a potent tool for future longitudinal studies and clinical trials’ population selection, and for pharmaco-epidemiology and cost-effectiveness studies.

Published
2018

47. Electroencephalography-based machine learning for cognitive profiling in Parkinson's disease: Preliminary results

Author

Kathy Dujardin, Laurence Chaton, Anja J.H. Moonen, Luc Defebvre, Albert F.G. Leentjens, Nacim Betrouni, Arnaud Delval, Annelien Duits, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Niet Med Staf Psychologie (9), Psychiatrie & Neuropsychologie, and MUMC+: MA Med Staf Spec Psychiatrie (9)

Subjects
0301 basic medicine, Male, medicine.medical_specialty, cognitive deficits, Parkinson's disease, Support Vector Machine, IMPACT, PHENOTYPES, Disease, Electroencephalography, Quantitative eeg, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Cognition, medicine, Profiling (information science), Humans, EEG, Aged, medicine.diagnostic_test, business.industry, DEMENTIA, Small sample, Parkinson Disease, IMPAIRMENT, Middle Aged, medicine.disease, quantitative EEG, Support vector machine, 030104 developmental biology, Neurology, Female, Neurology (clinical), business, characterization models, Cognition Disorders, 030217 neurology & neurosurgery, Algorithms
Abstract

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

Published
2018

48. Small effect size leads to reproducibility failure in resting-state fMRI studies

Author

Xiao Hu, Jan Kassubek, Moran Gilat, Ze-Juan Jia, Minming Zhang, Hu Liu, Alessandro Tessitore, Fabrizio Esposito, Renaud Lopes, Qian Li, Di Nardo Federica, Z. Jane Wang, Jiu-Quan Zhang, Stephen A. Coombes, Luc Defebvre, David E. Vaillancourt, Tomáš Slavíček, Shu-Leong Ho, Martin Gorges, Kathy Dujardin, Grainne M. McAlonan, Gioacchino Tedeschi, Nicolas Carrière, Tao Wu, Shirley Yy Pang, Hui Fang Shang, Ni-Ni Mao, Mark Hallett, Irena Rektorová, Alessia Sarica, Xi-Nian Zuo, Jian Wang, Yan-Ling Zhang, Xia Wu, Weiguo Liu, Roxana G. Burciu, Martin J. McKeown, Xiaopeng Song, Christine Delmaire, Delong Zhang, Guo-Guang Fan, Xiao-Fei Hu, Nailin Yao, Aiping Liu, James M. Shine, Saurabh Garg, Biao Huang, Fay B. Horak, Barek Barton, Jing Yang, Lei Yan, Yu-Feng Zang, Na Zhao, Tara M. Madhyastha, Priyank Shukla, Lenka Krajcovicova, Aldo Quattrone, Bo-Yu Chen, Jun Chen, Jing Li, Yuting Lou, Christy Jones, Chao-Gan Yan, Ajay S. Kurani, Yi-Xuan Feng, Wei Luo, Bo Liu, Antonio Cerasa, Lu-Qing Wei, Wan-Qun Yang, Xi-Ze Jia, Peiyu Huang, Jue Wang, Xiaojun Xu, Brett W. Fling, and Cai-Hong Zhou

Subjects
0303 health sciences, Reproducibility, medicine.medical_specialty, neuroimaging, medicine.diagnostic_test, Resting state fMRI, business.industry, Homogeneity (statistics), fmri, Audiology, 16. Peace & justice, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, resting-state, Autism spectrum disorder, parkinson, Multiple comparisons problem, medicine, Metric (unit), business, Functional magnetic resonance imaging, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Thousands of papers using resting-state functional magnetic resonance imaging (RS-fMRI) have been published on brain disorders. Results in each paper may have survived correction for multiple comparison. However, since there have been no robust results from large scale meta-analysis, we do not know how many of published results are truly positives. The present meta-analytic work included 60 original studies, with 57 studies (4 datasets, 2266 participants) that used a between-group design and 3 studies (1 dataset, 107 participants) that employed a within-group design. To evaluate the effect size of brain disorders, a very large neuroimaging dataset ranging from neurological to psychiatric isorders together with healthy individuals have been analyzed. Parkinson’s disease off levodopa (PD-off) included 687 participants from 15 studies. PD on levodopa (PD-on) included 261 participants from 9 studies. Autism spectrum disorder (ASD) included 958 participants from 27 studies. The meta-analyses of a metric named amplitude of low frequency fluctuation (ALFF) showed that the effect size (Hedges’ g) was 0.19 - 0.39 for the 4 datasets using between-group design and 0.46 for the dataset using within-group design. The effect size of PD-off, PD-on and ASD were 0.23, 0.39, and 0.19, respectively. Using the meta-analysis results as the robust results, the between-group design results of each study showed high false negative rates (median 99%), high false discovery rates (median 86%), and low accuracy (median 1%), regardless of whether stringent or liberal multiple comparison correction was used. The findings were similar for 4 RS-fMRI metrics including ALFF, regional homogeneity, and degree centrality, as well as for another widely used RS-fMRI metric namely seed-based functional connectivity. These observations suggest that multiple comparison correction does not control for false discoveries across multiple studies when the effect sizes are relatively small. Meta-analysis on un-thresholded t-maps is critical for the recovery of ground truth. We recommend that to achieve high reproducibility through meta-analysis, the neuroimaging research field should share raw data or, at minimum, provide un-thresholded statistical images.

Published
2018
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49. MRI of the cervical spinal cord predicts respiratory dysfunction in ALS

Author

Alain Duhamel, Gregory Kuchcinski, David Devos, Caroline Moreau, Renaud Lopes, Jean-Christophe Devedjian, Patrice Jissendi-Tchofo, Maeva Kyheng, Thierry Perez, Pierre-François Pradat, Régis Bordet, Guillaume Grolez, Charlotte Laloux, Maud Pétrault, Véronique Danel-Brunaud, Florent Auger, Kelly Timmerman, Pierre Besson, Luc Defebvre, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, CNRS, Inserm, Institut Pasteur de Lille, Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Troubles cognitifs dégénératifs et vasculaires - U1171, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Université de Lille, LillOA, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
0301 basic medicine, Internal capsule, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Respiratory Tract Diseases, lcsh:Medicine, Mice, Superoxide Dismutase-1, 0302 clinical medicine, Amyotrophic lateral sclerosis, Respiratory system, lcsh:Science, Motor Neurons, Medulla Oblongata, Multidisciplinary, medicine.diagnostic_test, Motor Cortex, Magnetic Resonance Imaging, White Matter, 3. Good health, medicine.anatomical_structure, Spinal Cord, Disease Progression, Cardiology, Neurodegeneration, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.medical_specialty, Neuroprotection, Article, White matter, 03 medical and health sciences, Atrophy, Phénomènes atmosphériques, Internal medicine, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business.industry, lcsh:R, Cervical Cord, Magnetic resonance imaging, medicine.disease, Spinal cord, Disease Models, Animal, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, 030104 developmental biology, lcsh:Q, business, 030217 neurology & neurosurgery
Abstract

For patients with amyotrophic lateral sclerosis (ALS), the primary therapeutic goal is to minimize morbidity. Non-invasive ventilation improves survival. We aim to assess whether Magnetic Resonance Imaging (MRI) of the cervical spinal cord predicts the progression of respiratory disorders in ALS. Brain and spinal MRI was repeatedly performed in the SOD1G86R mouse model, in 40 patients and in healthy controls. Atrophy, iron overload, white matter diffusivity and neuronal loss were assessed. In Superoxide Dismutase-1 (SOD1) mice, iron accumulation appeared in the cervical spinal cord at symptom onset but disappeared with disease progression (after the onset of atrophy). In ALS patients, the volumes of the motor cortex and the medulla oblongata were already abnormally low at the time of diagnosis. Baseline diffusivity in the internal capsule was predictive of functional handicap. The decrease in cervical spinal cord volume from diagnosis to 3 months was predictive of the change in slow vital capacity at 12 months. MRI revealed marked abnormalities at the time of ALS diagnosis. Early atrophy of the cervical spinal cord may predict the progression of respiratory disorders, and so may be of value in patient care and as a primary endpoint in pilot neuroprotection studies., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

50. Self-perceived and actual ability in the functional reach test in patients with Parkinson’s disease

Author

Myriam Noël, Luc Defebvre, Gilles Ryckewaert, Marion Luyat, Céline Tard, Mélanie Rambour, Arnaud Delval, Psychologie : Interactions, Temps, Emotions, Cognition (PSITEC) - ULR 4072 (PSITEC), Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
Adult, 030506 rehabilitation, medicine.medical_specialty, Activities of daily living, Parkinson's disease, Adolescent, Movement, [SDV]Life Sciences [q-bio], Posture, Poison control, Mesh:Young Adult, Mesh:Adult, Mesh:Parkinson Disease/physiopathology, Mesh:Parkinson Disease/psychology, Occupational safety and health, Young Adult, [SCCO]Cognitive science, 03 medical and health sciences, Mesh:Adolescent, 0302 clinical medicine, Physical medicine and rehabilitation, Motor imagery, Mesh:Middle Aged, Injury prevention, Mesh:Distance Perception, Humans, Medicine, Young adult, Mesh:Aged, Aged, Mesh:Movement, business.industry, Distance Perception, General Neuroscience, Parkinson Disease, Functional reach test, Middle Aged, Displacement (psychology), medicine.disease, Mesh:Humans, Mesh:Imagination, Parkinson''s disease, Imagination, Physical therapy, Falls, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract

International audience; Falls frequently occur during daily activities such as reaching for an object in patients with Parkinson's disease (PD). Misjudgment is also reported to be one of the circumstances that lead to falls. The functional reach test is an indicator of dynamic balance. The primary objective was to establish whether there is a difference between self-perceived and actual ability to perform the functional reach test in patients with PD who have never fallen. Three groups of participants (all with no history of falls) were studied: young adults, elderly adults and PD patients. The participants first estimated their maximum reaching distance (but without performing the action, i.e. as a motor imagery task) and then actually performed the functional reach test (i.e. as a motor task). No significant overestimation or underestimation was observed. The reaching distance was lower in PD than in the two other groups. There were no differences between PD patients and elderly adults in terms of the forward centre of pressure displacement. Seven PD patients reported a fall in the year following the experiment. The fallers had a longer history of disease. Finally, PD patients adequately estimated their ability in the functional reach test and did not adopt an "at risk" strategy and appeared to be quite conservative (as were healthy elderly adults) in their postural control behavior. Ability to estimate self-performance is preserved in PD patients with no clinical impairments of postural control although they are at risk of future falls.

Published
2015

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