Dysfunctional neuro-muscular mechanisms explain gradual gait changes in prodromal spastic paraplegia.

Gait simulation HSP Hyperreflexia Movement disorder Prodromal SPG4 Spasticity

Journal

Journal of neuroengineering and rehabilitation
ISSN: 1743-0003
Titre abrégé: J Neuroeng Rehabil
Pays: England
ID NLM: 101232233

Informations de publication

Date de publication:
15 Jul 2023
Historique:
received: 24 10 2022
accepted: 19 06 2023
medline: 17 7 2023
pubmed: 16 7 2023
entrez: 15 7 2023
Statut: epublish

Résumé

In Hereditary Spastic Paraplegia (HSP) type 4 (SPG4) a length-dependent axonal degeneration in the cortico-spinal tract leads to progressing symptoms of hyperreflexia, muscle weakness, and spasticity of lower extremities. Even before the manifestation of spastic gait, in the prodromal phase, axonal degeneration leads to subtle gait changes. These gait changes - depicted by digital gait recording - are related to disease severity in prodromal and early-to-moderate manifest SPG4 participants. We hypothesize that dysfunctional neuro-muscular mechanisms such as hyperreflexia and muscle weakness explain these disease severity-related gait changes of prodromal and early-to-moderate manifest SPG4 participants. We test our hypothesis in computer simulation with a neuro-muscular model of human walking. We introduce neuro-muscular dysfunction by gradually increasing sensory-motor reflex sensitivity based on increased velocity feedback and gradually increasing muscle weakness by reducing maximum isometric force. By increasing hyperreflexia of plantarflexor and dorsiflexor muscles, we found gradual muscular and kinematic changes in neuro-musculoskeletal simulations that are comparable to subtle gait changes found in prodromal SPG4 participants. Predicting kinematic changes of prodromal and early-to-moderate manifest SPG4 participants by gradual alterations of sensory-motor reflex sensitivity allows us to link gait as a directly accessible performance marker to emerging neuro-muscular changes for early therapeutic interventions.

Sections du résumé

BACKGROUND BACKGROUND
In Hereditary Spastic Paraplegia (HSP) type 4 (SPG4) a length-dependent axonal degeneration in the cortico-spinal tract leads to progressing symptoms of hyperreflexia, muscle weakness, and spasticity of lower extremities. Even before the manifestation of spastic gait, in the prodromal phase, axonal degeneration leads to subtle gait changes. These gait changes - depicted by digital gait recording - are related to disease severity in prodromal and early-to-moderate manifest SPG4 participants.
METHODS METHODS
We hypothesize that dysfunctional neuro-muscular mechanisms such as hyperreflexia and muscle weakness explain these disease severity-related gait changes of prodromal and early-to-moderate manifest SPG4 participants. We test our hypothesis in computer simulation with a neuro-muscular model of human walking. We introduce neuro-muscular dysfunction by gradually increasing sensory-motor reflex sensitivity based on increased velocity feedback and gradually increasing muscle weakness by reducing maximum isometric force.
RESULTS RESULTS
By increasing hyperreflexia of plantarflexor and dorsiflexor muscles, we found gradual muscular and kinematic changes in neuro-musculoskeletal simulations that are comparable to subtle gait changes found in prodromal SPG4 participants.
CONCLUSIONS CONCLUSIONS
Predicting kinematic changes of prodromal and early-to-moderate manifest SPG4 participants by gradual alterations of sensory-motor reflex sensitivity allows us to link gait as a directly accessible performance marker to emerging neuro-muscular changes for early therapeutic interventions.

Identifiants

pubmed: 37454121
doi: 10.1186/s12984-023-01206-8
pii: 10.1186/s12984-023-01206-8
pmc: PMC10349428
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

90

Informations de copyright

© 2023. The Author(s).

Références

IEEE Trans Biomed Eng. 2007 Nov;54(11):1940-50
pubmed: 18018689
J Neuroeng Rehabil. 2014 Apr 30;11:78
pubmed: 24885302
Sci Rep. 2022 Jun 16;12(1):10075
pubmed: 35710689
Mov Disord. 2008 Nov 15;23(15):2232-8
pubmed: 18759344
PLoS Comput Biol. 2019 Oct 7;15(10):e1006993
pubmed: 31589597
Neurology. 2006 Aug 8;67(3):430-4
pubmed: 16894103
J Physiol. 2022 Jun;600(11):2691-2712
pubmed: 35442531
PLoS Comput Biol. 2021 May 19;17(5):e1008594
pubmed: 34010288
J Physiol. 2015 Aug 15;593(16):3493-511
pubmed: 25920414
Front Comput Neurosci. 2018 Oct 09;12:80
pubmed: 30356859
J Neurol. 2015 Aug;262(8):1961-71
pubmed: 26050637
Mov Disord. 2016 Dec;31(12):1891-1900
pubmed: 27782309
ACM Trans Graph. 2012 Jul;31(4):
pubmed: 26251560
Mov Disord. 2016 Oct;31(10):1527-1534
pubmed: 27430880
Mov Disord. 2022 Dec;37(12):2417-2426
pubmed: 36054444
Nat Genet. 1999 Nov;23(3):296-303
pubmed: 10610178
Eur J Paediatr Neurol. 2011 Mar;15(2):138-45
pubmed: 20829081
IEEE Trans Neural Syst Rehabil Eng. 2010 Jun;18(3):263-73
pubmed: 20378480
J Biomech. 2021 Jun 23;123:110530
pubmed: 34034014
J Neuroeng Rehabil. 2016 Jul 16;13(1):64
pubmed: 27423898
J Rehabil Med. 2010 Jul;42(7):656-63
pubmed: 20603696
Curr Neurol Neurosci Rep. 2006 Jan;6(1):65-76
pubmed: 16469273
J Rehabil Med. 2019 Jun 18;51(6):434-441
pubmed: 30968942
Lancet. 1983 May 21;1(8334):1151-5
pubmed: 6133167
Clin Neurophysiol. 2018 Mar;129(3):516-525
pubmed: 29353180
PLoS One. 2016 Oct 12;11(10):e0164623
pubmed: 27732632
Proc Biol Sci. 2021 Mar 10;288(1946):20202432
pubmed: 33653141
Clin Biomech (Bristol, Avon). 2017 Oct;48:63-72
pubmed: 28779695
PLoS One. 2015 Feb 06;10(2):e0117666
pubmed: 25658484
J Biomech Eng. 2013 Feb;135(2):021005
pubmed: 23445050
J Electromyogr Kinesiol. 2019 Apr;45:61-69
pubmed: 30836301
Acta Neuropathol. 2013 Sep;126(3):307-28
pubmed: 23897027
Gait Posture. 2012 Feb;35(2):266-71
pubmed: 22050971
Gait Posture. 2021 Jun;87:33-42
pubmed: 33882437
Brain. 2023 Mar 1;146(3):1093-1102
pubmed: 35472722

Auteurs

Christian Lassmann (C)

Multi-level Modeling in Motor Control and Rehabilitation Robotics, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. christian.lassmann@uni-tuebingen.de.
Section Computational Sensomotorics, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. christian.lassmann@uni-tuebingen.de.
Department of Computer Engineering, Wilhelm-Schickard-Institute for Computer Science, University of Tuebingen, Tuebingen, Germany. christian.lassmann@uni-tuebingen.de.

Winfried Ilg (W)

Section Computational Sensomotorics, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
Centre for Integrative Neuroscience (CIN), Tuebingen, Germany.

Tim W Rattay (TW)

Department of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research, and Center for Neurology, University of Tuebingen, Tuebingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
Center for Rare Diseases (ZSE), University of Tuebingen, Tuebingen, Germany.

Ludger Schöls (L)

Department of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research, and Center for Neurology, University of Tuebingen, Tuebingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
Center for Rare Diseases (ZSE), University of Tuebingen, Tuebingen, Germany.

Martin Giese (M)

Section Computational Sensomotorics, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
Centre for Integrative Neuroscience (CIN), Tuebingen, Germany.

Daniel F B Haeufle (DFB)

Multi-level Modeling in Motor Control and Rehabilitation Robotics, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
Centre for Integrative Neuroscience (CIN), Tuebingen, Germany.
Institute for Modeling and Simulation of Biomechanical Systems, University of Stuttgart, Stuttgart, Germany.
Institute of Computer Engineering (ZITI), Heidelberg University, Heidelberg, Germany.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH