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Abstract:

Background In Hereditary Spastic Paraplegia (HSP) type 4 (SPG4) a length-dependent axonal degeneration in the cortico-spinal tract leads to progressing symptoms of hyperrefexia, 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 We hypothesize that dysfunctional neuro-muscular mechanisms such as hyperrefexia and muscle weak- ness explain these disease severity-related gait changes of prodromal and early-to-moderate manifest SPG4 partici- pants. 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 refex sensitivity based on increased velocity feedback and gradually increasing muscle weakness by reducing maximum isometric force. Results By increasing hyperrefexia of plantarfexor and dorsifexor muscles, we found gradual muscular and kin- ematic changes in neuro-musculoskeletal simulations that are comparable to subtle gait changes found in prodromal SPG4 participants. Conclusions Predicting kinematic changes of prodromal and early-to-moderate manifest SPG4 participants by grad- ual alterations of sensory-motor refex sensitivity allows us to link gait as a directly accessible performance marker to emerging neuro-muscular changes for early therapeutic interventions. Keywords Gait simulation, Spasticity, Hyperrefexia, Prodromal, SPG4, HSP, Movement disorder

Authors: Laßmann, Christian; Ilg, Winfried; Rattay, Tim W. Schöls, Ludger Giese, Martin A.; Haeufle, Daniel F. B.

Research Areas: Clinical Movement Control and real-life Behavior Analysis for Assistive Systems

Type of Publication: Article

Journal: Journal of NeuroEngineering and Rehabilitation. Jul 15;20(1):90

Year: 2023

Month: July

Abstract:

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 subjects. 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 subjects. 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 subjects. Predicting kinematic changes of prodromal and early-to-moderate manifest SPG4 subjects 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.

Authors: Laßmann, Christian; Ilg, Winfried; Rattay, Tim W. Schöls, Ludger Giese, Martin A.; Haeufle, Daniel

Research Areas: Clinical Movement Control and real-life Behavior Analysis for Assistive Systems

Type of Publication: Article

Abstract:

Background: In hereditary spastic paraplegia type 4 (SPG4), subclinical gait changes might occur years before patients realize gait disturbances. The prodromal phase of neurodegenerative disease is of particular interest to halt disease progression by future interventions before impairment has manifested. Objectives: Identification of specific movement abnormalities before manifestation of gait impairment and quantification of disease progression in the prodromal phase. Methods: 70 subjects participated in gait assessment, including 30 prodromal SPAST mutation carriers, 17 patients with mild-to-moderate manifest SPG4, and 23 healthy controls. Gait was assessed by an infrared-camera-based motion capture system to analyze features like range of motion and continuous angle trajectories. Those features were correlated with disease severity as assessed by the Spastic Paraplegia Rating Scale (SPRS) and neurofilament light chain (NfL) as a fluid biomarker indicating neurodegeneration. Results: Compared to healthy controls, we found an altered gait pattern in prodromal mutation carriers during the swing phase in segmental angles of the lower leg (p

Authors: Laßmann, Christian; Ilg, Winfried; Schneider, Marc Völker, Maximilian Haeufle, Daniel Sch\"ule, Rebecca Giese, Martin A.; Synofzik, Matthis Schöls, Ludger Rattay, Tim W.

Research Areas: Clinical Movement Control and real-life Behavior Analysis for Assistive Systems

Type of Publication: Article