Potential as a performance marker of disease severity and treatment effectiveness
Early axonal degeneration leads to progressive symptoms of heightened reflexes, muscle weakness and spasticity, which taken together lead on to subtle gait changes.
Computer simulation has been developed that is closely comparable to subtle gait changes in early-stage cases of SPG4 HSP, thus making gait a potential performance marker of disease severity and treatment effectiveness.
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: 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: 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: 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.
SOURCE: J Neuroeng Rehabil. 2023 Jul 15;20(1):90.
doi: 10.1186/s12984-023-01206-8. PMID: 37454121 © 2023. The Author(s).
Dysfunctional neuro-muscular mechanisms explain gradual gait changes in prodromal spastic paraplegia
Christian Lassmann 1 2 3 , Winfried Ilg 4 5 , Tim W Rattay 6 7 8 , Ludger Schöls 6 7 8 , Martin Giese 4 5 , Daniel F B Haeufle 9 5 10 11
1. Multi-level Modeling in Motor Control and Rehabilitation Robotics, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
2. Section Computational Sensomotorics, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
3. Department of Computer Engineering, Wilhelm-Schickard-Institute for Computer Science, University of Tuebingen, Tuebingen, Germany.
4. Section Computational Sensomotorics, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
5. Centre for Integrative Neuroscience (CIN), Tuebingen, Germany.
6. Department of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research, and Center for Neurology, University of Tuebingen, Tuebingen, Germany.
7. German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
8. Center for Rare Diseases (ZSE), University of Tuebingen, Tuebingen, Germany.
9. Multi-level Modeling in Motor Control and Rehabilitation Robotics, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
10. Institute for Modeling and Simulation of Biomechanical Systems, University of Stuttgart, Stuttgart, Germany.
11. Institute of Computer Engineering (ZITI), Heidelberg University, Heidelberg, Germany.
Can soft exoskeleton devices aid hsp?
Editor’s note: There was a flurry of exoskeleton prototypes to help mobility in people with impaired walking coming out of Japan over 10 years ago, but things didn’t really progress beyond research and testing. In more recent times there has been renewed interest, investment and research on walking aids for people with impaired mobility. The best that can be said at this stage is that, from the scientific evidence point of view, some devices “may” significantly help improve walking. More comprehensive studies would be needed to establish an evidence base for their use. Apart from effectiveness, major obstacles include comfort and convenience of these devices, and the big one, cost. Such studies rarely target a specific condition, rather they are likely to be tried on people with impaired walking caused by a number of things including spinal cord injury and a whole range of neurological disorders, both neurodevelopmental and neurodegenerative. It also seems to be the case that the level of effectiveness can vary significantly from person-to-person, reflecting the infinite range and type of walking impairment that people experience. It is probably fair to say that it is still some way off before devices that are reliably effective and affordable are readily available.