Fig. 1

Study Design—Can dysfunctional neuro-muscular mechanisms explain gradual gait changes of prodromal and early-to-moderate manifest SPG4 patients? We first used data of an instrumented gait analysis to investigate gait changes of healthy controls (green), prodromal SPG4 (blue), and manifest SPG4 (red) patients. We identified characteristic changes for the three different groups, which were recently published [7]. Secondly, we introduced and gradually manipulated neuro-muscular mechanisms, i.e. hyperreflexia (muscle spindle velocity feedback, orange), muscle weakness (reduced isometric force, light blue), and their combination in a neuro-musculoskeletal model and expected to predict relative gait changes, as in experimental data