Assessment of motor phenotype in Amyotrophic Lateral Sclerosis using a force plate – a new biomarker for clinical studies?

Background: Assessment of severity of symptoms in patients with Amyotrophic Lateral Sclerosis (ALS) in the setting of clinical studies is usually performed using categorical clinical scales such as the ALS-FRS (functional rating scale) (Cedarbaum 1997). Objective measures of disease phenotype are desirable to quantitatively and sensitively assess clinical severity in ALS. Assessment of motor phenotype dysfunction may serve as a useful surrogate marker that is easy to assess even in out-patient settings.

Objective: To investigate whether patients with ALS (1) exhibit impairments in the stability of stance compared to controls that can quantitatively be assessed using a force plate and (2) to assess whether these measures correlate to the severity of disease as assessed clinically by the ALS-FRS.

Subjects and methods: Patients with ALS (n=15) and age-and-sex-matched controls (n=17) were standing on a force plate (Satel, France) with eyes open and eyes closed for 25.6 seconds. Subjects were instructed to stand still without moving. Stability of center of mass (COM) location was assessed by the variables “surface“, “distance“, and “velocity“ reflecting COM mobility. All subjects were assessed using the ALS-FRS. Statistics were performed using non-parametric Mann-Whitney test and Spearman correlations (SPSS 15.0).

Results: The measures surface, velocity and distance were significantly increased in patients with ALS compared to controls (p<0.01 for all conditions with eyes open and closed). With eyes closed velocity correlated to the severity of clinical symptoms in the patients as assessed by the ALS-FRS (r=0,535, p<0.05).

Conclusion: Assessment of stability of stance using a force plate provides objective and quantitative readouts of motor phenotype dysfunction in ALS. The measure velocity of COM dislocation was correlated to the severity of ALS as expressed in the ALS-FRS after loss of visual feedback. A possible use of the force plate as a surrogate marker for clincial trials in ALS warrants further exploration, e.g., in a blinded multicenter follow-up study.