Particular features of gait identified
The importance of a reliable predictor of disease onset cannot be overstated where there is a significant likelihood that the best that can be hoped for from candidate treatments is stopping disease progression. This is the case for SPG4.
This study shows that certain gait features are promising biomarkers of very early-stage disease onset in SPG4, with the prospect that potential treatments begun at this point may prevent the disease developing to any appreciable extent.
Background: In hereditary spastic paraplegia type 4 (SPG4), subclinical gait changes might occur years before patients experience gait disturbances. This prodromal phase of neurodegenerative disease is of particular interest to halt disease progression by future interventions before impairment has manifested.
Objective: The objective of this study was to identify specific movement abnormalities before the manifestation of gait impairment and quantify disease progression in the prodromal phase.
Methods: Seventy subjects participated in gait assessment, including 30 prodromal SPAST pathogenic variant carriers, 17 patients with mild-to-moderate manifest SPG4, and 23 healthy control subjects. An infrared-camera-based motion capture system assessed gait to analyze features such as range of motion and continuous angle trajectories. Those features were correlated with disease severity as assessed by the Spastic Paraplegia Rating Scale, neurofilament light chain as a fluid biomarker indicating neurodegeneration, and motor-evoked potentials.
Results: Compared with healthy control subjects, we found an altered gait pattern in prodromal pathogenic variant carriers during the swing phase in the segmental angle of the foot (Dunn’s post hoc test, q = 3.1) and heel ground clearance (q = 2.8). Furthermore, range of motion of segmental angle was reduced for the foot (q = 3.3). These changes occurred in prodromal pathogenic variant carriers without quantified leg spasticity in clinical examination. Gait features correlated with neurofilament light chain levels, central motor conduction times of motor-evoked potentials, and Spastic Paraplegia Rating Scale score.
Conclusions: Gait analysis can quantify changes in prodromal and mild-to-moderate manifest SPG4 patients. Thus, gait features constitute promising motor biomarkers characterizing the subclinical progression of spastic gait and might help to evaluate interventions in early disease stages. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
SOURCE: Mov Disord. 2022 Aug 29. doi: 10.1002/mds.29199. Online ahead of print. PMID: 36054444 © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Specific Gait Changes in Prodromal Hereditary Spastic Paraplegia Type 4: preSPG4 Study
Christian Laßmann 1 2 3 , Winfried Ilg 1 4 , Marc Schneider 1 4 , Maximilian Völker 5 , Daniel F B Haeufle 3 4 6 , Rebecca Schüle 5 7 8 , Martin Giese 1 4 , Matthis Synofzik 5 7 8 , Ludger Schöls 5 7 8 , Tim W Rattay 5 7 8
1. Section Computational Sensomotorics, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
2. Department of Computer Engineering, Wilhelm-Schickard-Institute for Computer Science, University of Tübingen, Tübingen, Germany.
3. Multi-level Modeling in Motor Control and Rehabilitation Robotics, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
4. Centre for Integrative Neuroscience (CIN), Tübingen, Germany.
5. Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, and Center of Neurology, University of Tübingen, Tübingen, Germany.
6. Computational Biophysics and Biorobotics, Institute for Modelling and Simulation of Biomechanical Systems, University of Stuttgart, Stuttgart, Germany.
7. German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
8. Center for Rare Diseases (ZSE) University of Tübingen, Tübingen, Germany.