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Journal of Neurology

, Volume 265, Issue 9, pp 2125–2136 | Cite as

Extrapyramidal deficits in ALS: a combined biomechanical and neuroimaging study

  • Maryse Feron
  • Annabelle Couillandre
  • Eya Mseddi
  • Nicolas Termoz
  • Malek Abidi
  • Eric Bardinet
  • Daniel Delgadillo
  • Timothée Lenglet
  • Giorgia Querin
  • Marie-Laure Welter
  • Nadine Le Forestier
  • François Salachas
  • Gaelle Bruneteau
  • Maria del Mar Amador
  • Rabab Debs
  • Lucette Lacomblez
  • Vincent Meininger
  • Mélanie Pélégrini-Issac
  • Peter Bede
  • Pierre-François Pradat
  • Giovanni de Marco
Original Communication

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.

Keywords

Amyotrophic lateral sclerosis Gait impairment Postural instability Magnetic resonance imaging Basal ganglia 

Notes

Acknowledgements

The authors are grateful for the generosity and kindness of all participating patients and healthy controls. We also thank Xavier Devrelle, Sophien Mehdi, and Sara Fernandez-Vidal (ICM Foundation) for their assistance in data recording. We thank the Center for Clinical Investigation (Instititut du Cerveau et de la Moellle Epiniere, Paris, France) and Vanessa Brochard for their role in the organisation and management of the study.

Funding

This study was funded by a grant from the Association for Research on ALS (ARSLA) and the Institut National pour la Santé et la Recherche Médicale (INSERM). The research leading to these results has also received support from the programme ‘‘Investissements d’avenir’’ ANR-10-IAIHU-06.

Compliance with ethical standards

Conflicts of interest

The authors have no actual or potential conflict of interest to disclose, including any financial, personal, or other relationships with other individuals or organisations within 3 years of beginning the submitted work that could inappropriately influence, or be perceived to influence, their work. Marie-Laure Welter received research support from the ‘Institut du Cerveau et de la Moelle. Epinière’ (ICM) Foundation and the Agence Nationale de la Recherche. Nicolas Termoz received research support from the Laboratoire CeRSM—EA 2931. Peter Bede is supported by the Health Research Board (HRB—Ireland; HRB EIA-2017-019), the Irish Institute of Clinical Neuroscience IICN—Novartis Ireland Research (IICN—2016), the Iris O’Brien Foundation, the Perrigo Clinician-Scientist Research Fellowship, and the Research Motor Neuron (RMN-Ireland) Foundation Ireland. Pierre-François Pradat received research support from the French Association for Research in ALS (ARSla), the Institute for Research in Spinal Cord and Brain (IRME), the French Association for Myopathie (AFM-Telethon), Paris Institute of Translational Neuroscience (IHU-A-ICM), the Thierry Latran foundation, the Target ALS foundation and the Institut National pour la Santé et la Recherche Médicale (INSERM). Giovanni de Marco received research support from the Laboratoire CeRSM—EA 2931 and COMUE Université Paris Lumières.

Ethics approval

All procedures performed in this study were fully approved by the local, institutional ethics committee (CPP Ile-de-France Paris VI; INSERM promotion RBM C12-13) and were in accordance with the 1964 Helsinki Declaration and its later amendments. This study does not involve any methods or experiments with animals.

Informed consent

All study participants provided informed consent prior to inclusion in the study.

Glossary

ALS

Amyotrophic lateral sclerosis

APA

Anticipatory postural adjustment

CoM

Centre of mass

CoP

Centre of foot pressure

EP

Execution phase

FO

Foot-off of the swing leg

FO2

Foot-off of the stance leg

GM

Grey matter

HC

Healthy control

MRI

Magnetic resonance imaging

CN

Caudate nucleus

L

Stride length

NPI-ALS

ALS patients without postural instability

PI-ALS

ALS patients with postural instability

PD

Parkinson’s disease

PU

Putamen

VBM

Voxel-based morphometry

V1

Minimum vertical velocity of the CoM

V2

CoM vertical velocity of the CoM at time of foot contact

Vm

Maximum anteroposterior velocity of the CoM

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Maryse Feron
    • 1
  • Annabelle Couillandre
    • 1
    • 2
  • Eya Mseddi
    • 1
  • Nicolas Termoz
    • 1
    • 2
  • Malek Abidi
    • 1
  • Eric Bardinet
    • 3
    • 4
    • 5
    • 6
  • Daniel Delgadillo
    • 7
  • Timothée Lenglet
    • 8
  • Giorgia Querin
    • 8
    • 9
  • Marie-Laure Welter
    • 3
    • 4
    • 5
    • 10
    • 11
  • Nadine Le Forestier
    • 8
    • 12
  • François Salachas
    • 8
  • Gaelle Bruneteau
    • 8
  • Maria del Mar Amador
    • 8
  • Rabab Debs
    • 8
  • Lucette Lacomblez
    • 8
    • 9
  • Vincent Meininger
    • 13
  • Mélanie Pélégrini-Issac
    • 9
  • Peter Bede
    • 8
    • 9
    • 14
  • Pierre-François Pradat
    • 2
    • 8
    • 9
    • 15
  • Giovanni de Marco
    • 1
    • 2
  1. 1.Laboratoire CeRSM – EA 2931 Paris OuestNanterreFrance
  2. 2.COMUE Université Paris LumièresParisFrance
  3. 3.Sorbonne Université, Institut du Cerveau et de la Moelle épinière (ICM), UMR-S975ParisFrance
  4. 4.Inserm, U975ParisFrance
  5. 5.CNRS, UMR 7225ParisFrance
  6. 6.Institut du Cerveau et de la Moelle Epinière, Centre de Neuroimagerie de Recherche (CENIR)ParisFrance
  7. 7.Service de Neuro-OncologieAssistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Pitié-Salpêtrière/Charles FoixParisFrance
  8. 8.Département de NeurologieAssistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Pitié-Salpêtrière/Charles FoixParisFrance
  9. 9.Sorbonne Université, CNRS, INSERM, Laboratoire d’Imagerie Biomédicale, LIBParisFrance
  10. 10.Institut du Cerveau et de la Moelle Epinière, Plateforme d’Analyse du Mouvement (PANAM)ParisFrance
  11. 11.Neurophysiology Department, CHU Charles NicolleUniversité de RouenRouenFrance
  12. 12.Département de recherche en éthiqueUniversité Paris-Sud-SaclayLe Kremlin-BicêtreFrance
  13. 13.Hôpital des Peupliers, Ramsay générale de santéParisFrance
  14. 14.Computational Neuroimaging Group, Academic Unit of NeurologyTrinity CollegeDublinIreland
  15. 15.Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research InstituteUlster University, C-TRIC, Altnagelvin HospitalLondonderryUK

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