Objective assessment of motor dysfunction in ALS using grip force and 3D position analysis – new biomarkers for clinical studies?

Background: Objective and quantitative surrogate markers for assessment of stage and progression of patients with Amyotrophic Lateral Sclerosis (ALS) are desirable. Analysis of isometric grip forces was shown to be a measure for disease severity and disease progression, e.g., in Huntington's Disease (for review see Reilmann et al. 2004).

Objective: To investigate whether coordination of isometric grip forces and 3D object stability in a precision grip task are altered in ALS and correlate to disease severity.

Subjects and methods: Patients with ALS (n=14) and age-and-sex-matched healthy controls (n=17) were instructed to grasp and hold an object (weight 250g and 500g) equipped with pre-calibrated force transducers (Mini-30, ATI, USA) in the precision grip. Object position (x, y, z) and orientation (roll, pitch, yaw) were recorded using a 3D position sensor (Fastrack, Polhemus, USA). Data was recorded and analyzed using a flexible laboratory computer system (SC/ZOOM, University of Umeå, Sweden). Grip force variability (=GFV, i.e. coefficient of variation of grip forces) and 3D object stability were calculated during a 15s period. Patients were clinically assessed using the ALS-Functional Rating Scale (ALS-FRS) (Cedarbaum 1997). Statistics were performed using ANOVA and Spearman correlation analysis (SPSS 13.0).

Results: GFV was significantly increased in patients with ALS in both the 250g (p<0,01) and 500g (p<0,05) object weight. Transport time of the object was not significantly increased in patients compared to control, but was correlated to the severity of disease as assessed with the ALS-FRS (r=-0,564, p<0,05 for 250g and r=-0,792, p<0.001 for 500g) with patients clinically more affected exhibiting longer transport times. Object instability as assessed by the orientation index (derived from Polhemus data) was increased in patients with ALS (p<0,001 for 250g and p<0,001 for 500g) and was correlated to disease severity (=ALS-FSR; r=-0,579, p<0,05 for 250g and r=-0,613, p<0,05 for 500g).

Conclusion: The results of this cross-sectional study suggest that assessment of isometric grip forces and 3D object stability may provide objective and quantitative measures of severity of motor dysfunction in ALS. A possible use of these measures as surrogate markers in ALS should be assessed in follow-up studies.

Acknowledgment: R.R. was supported by grant IMF-RE-120225 from the “Innovative Medizinische Forschung“, Faculty of Medicine, University of Münster