Objective motor phenotype assessment in multiple sclerosis: deficits in grip force coordination correlate to changes in diffusion tensor imaging

Background: Complex motor deficits are common symptoms in patients with Multiple Sclerosis (MS). Objective and quantitative measures of motor phenotype may increase the sensitivity of clinical trials. We previously found increased grip force variability in patients with MS and correlation of deficits in grip force variability to the EDSS. Diffusion Tensor Imaging (DTI) and analysis of fractional anisotropy (FA) are reliable methods to investigate microstructural damage of the white matter tissue in MS.

Objective: To investigate whether the severity of deficits in grip force control in patients with MS assessed by grip force variability correlates with structural damage in primary and secondary motor areas as assessed by FA in DTI.

Subjects and methods: 27 patients with MS grasped and lifted an object (500g weight) in the precision grip (between thumb and index finger) of the right hand (dominant hand in all but one patient). They were instructed to hold the device stable for 30 seconds next to a marker. Cueing tones indicated start and end of each of 10 trials. Data was collected and analyzed using SC/ZOOM (Dept. of Neurophysiology, University of Umea, Sweden). Grip force variability (expressed as coefficient of variation [%]) was calculated in a 20s. static period prior to object release. All patients underwent 3.0 Tesla DTI-MRI. Voxel and region of interest (ROI) based FA-analysis was performed. ROI statistics were performed using Pearson correlation analysis (SPSS 13.0). Results were considered significant at p<0.01 (cluster size 10 voxel).

Results: Grip force variability (coef. var.) was negatively correlated to the FA of parietal white matter tissue (ROI) in both hemispheres. Best correlation on voxel level was found in the contralateral primary motor cortex (r=-0.65; p<0.001).

Conclusion: In this study, patients exhibiting higher levels of pathological grip force variability also expressed a higher grade of microstructural damage in the white matter as assessed by voxel based analysis of FA. These results suggest a link between objective peripheral motor phenotype assessment and central damage. However, several studies correlating clinical severity as assessed by categorical scales such as the EDSS and FA in DTI-MRI showed no conclusive results. We conclude that grip force variability is a useful quantitative surrogate marker of motor phenotype in MS and hypothesize that it may have a higher sensitivity to assess motor dysfunction than the EDSS.