Specific gait changes in prodromal hereditary spastic paraplegia type 4 - preSPG4 study

Type of Publication:
hereditary spastic paraplegia, prodromal, SPG4, motor biomarker, gait analysis
Laßmann, Christian
Ilg, Winfried
Schneider, Marc
Völker, Maximilian
Haeufle, Daniel
Schüle, Rebecca
Giese, Martin A.
Synofzik, Matthis
Schöls, Ludger
Rattay, Tim W.
Movement Disorders 2022

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