Maryse Feron1, Annabelle Couillandre1,2, Eya Mseddi1, Nicolas Termoz1,2, Malek Abidi1, Eric Bardinet3,4,5,6, Daniel Delgadillo7, Timothée Lenglet8, Giorgia Querin8,9, Marie-Laure Welter3,4,5,10,11, Nadine Le Forestier8,12, François Salachas8, Gaelle Bruneteau8, Maria Del Mar Amador8, Rabab Debs8, Lucette Lacomblez8,9, Vincent Meininger13, Mélanie Pélégrini-Issac9, Peter Bede8,9,14, Pierre-François Pradat15,16,17,18, Giovanni de Marco1,2. 1. Laboratoire CeRSM - EA 2931 Paris Ouest, Nanterre, France. 2. COMUE Université Paris Lumières, Paris, France. 3. Sorbonne Université, Institut du Cerveau et de la Moelle épinière (ICM), UMR-S975, 75013, Paris, France. 4. Inserm, U975, 75013, Paris, France. 5. CNRS, UMR 7225, 75013, Paris, France. 6. Institut du Cerveau et de la Moelle Epinière, Centre de Neuroimagerie de Recherche (CENIR), 75013, Paris, France. 7. Service de Neuro-Oncologie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Pitié-Salpêtrière/Charles Foix, 75013, Paris, France. 8. Département de Neurologie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Pitié-Salpêtrière/Charles Foix, 75013, Paris, France. 9. Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, 75006, Paris, France. 10. Institut du Cerveau et de la Moelle Epinière, Plateforme d'Analyse du Mouvement (PANAM), 75013, Paris, France. 11. Neurophysiology Department, CHU Charles Nicolle, Université de Rouen, Rouen, France. 12. Département de recherche en éthique, Université Paris-Sud-Saclay, Le Kremlin-Bicêtre, France. 13. Hôpital des Peupliers, Ramsay générale de santé, Paris, France. 14. Computational Neuroimaging Group, Academic Unit of Neurology, Trinity College, Dublin, Ireland. 15. COMUE Université Paris Lumières, Paris, France. pierre-francois.pradat@psl.aphp.fr. 16. Département de Neurologie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Pitié-Salpêtrière/Charles Foix, 75013, Paris, France. pierre-francois.pradat@psl.aphp.fr. 17. Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, 75006, Paris, France. pierre-francois.pradat@psl.aphp.fr. 18. Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, C-TRIC, Altnagelvin Hospital, Londonderry, UK. pierre-francois.pradat@psl.aphp.fr.
Abstract
INTRODUCTION: Extrapyramidal deficits are poorly characterised in amyotrophic lateral sclerosis (ALS) despite their contribution to functional disability, increased fall risk and their quality-of-life implications. Given the concomitant pyramidal and cerebellar degeneration in ALS, the clinical assessment of extrapyramidal features is particularly challenging. OBJECTIVE: The comprehensive characterisation of postural instability in ALS using standardised clinical assessments, gait analyses and computational neuroimaging tools in a prospective study design. METHODS: Parameters of gait initiation in the anticipatory postural adjustment phase (APA) and execution phase (EP) were evaluated in ALS patients with and without postural instability and healthy controls. Clinical and gait analysis parameters were interpreted in the context of brain imaging findings. RESULTS: ALS patients with postural instability exhibit impaired gait initiation with an altered APA phase, poor dynamic postural control and significantly decreased braking index. Consistent with their clinical profile, "unsteady" ALS patients have reduced caudate and brain stem volumes compared to "steady" ALS patients. INTERPRETATION: Our findings highlight that the ALS functional rating scale (ALSFRS-r) does not account for extrapyramidal deficits, which are major contributors to gait impairment in a subset of ALS patients. Basal ganglia degeneration in ALS does not only contribute to cognitive and behavioural deficits, but also adds to the heterogeneity of motor disability.
INTRODUCTION:Extrapyramidal deficits are poorly characterised in amyotrophic lateral sclerosis (ALS) despite their contribution to functional disability, increased fall risk and their quality-of-life implications. Given the concomitant pyramidal and cerebellar degeneration in ALS, the clinical assessment of extrapyramidal features is particularly challenging. OBJECTIVE: The comprehensive characterisation of postural instability in ALS using standardised clinical assessments, gait analyses and computational neuroimaging tools in a prospective study design. METHODS: Parameters of gait initiation in the anticipatory postural adjustment phase (APA) and execution phase (EP) were evaluated in ALSpatients with and without postural instability and healthy controls. Clinical and gait analysis parameters were interpreted in the context of brain imaging findings. RESULTS:ALSpatients with postural instability exhibit impaired gait initiation with an altered APA phase, poor dynamic postural control and significantly decreased braking index. Consistent with their clinical profile, "unsteady" ALSpatients have reduced caudate and brain stem volumes compared to "steady" ALSpatients. INTERPRETATION: Our findings highlight that the ALS functional rating scale (ALSFRS-r) does not account for extrapyramidal deficits, which are major contributors to gait impairment in a subset of ALSpatients. Basal ganglia degeneration in ALS does not only contribute to cognitive and behavioural deficits, but also adds to the heterogeneity of motor disability.
Authors: Jacqueline Montes; Bin Cheng; Beverly Diamond; Carolyn Doorish; Hiroshi Mitsumoto; Paul H Gordon Journal: Amyotroph Lateral Scler Date: 2007-10
Authors: Ioannis Ugo Isaias; Mariangela Dipaola; Marlies Michi; Alberto Marzegan; Jens Volkmann; Marina L Rodocanachi Roidi; Carlo Albino Frigo; Paolo Cavallari Journal: PLoS One Date: 2014-04-17 Impact factor: 3.240
Authors: Peter Bede; Rangariroyashe H Chipika; Eoin Finegan; Stacey Li Hi Shing; Mark A Doherty; Jennifer C Hengeveld; Alice Vajda; Siobhan Hutchinson; Colette Donaghy; Russell L McLaughlin; Orla Hardiman Journal: Neuroimage Clin Date: 2019-10-24 Impact factor: 4.881
Authors: Eoin Finegan; Stacey Li Hi Shing; Rangariroyashe H Chipika; Mark A Doherty; Jennifer C Hengeveld; Alice Vajda; Colette Donaghy; Niall Pender; Russell L McLaughlin; Orla Hardiman; Peter Bede Journal: Neuroimage Clin Date: 2019-11-12 Impact factor: 4.881