Research: new outcome measure?

Motor disability in MS is commonly assessed by the Expanded Disability Status Scale (EDSS). Categorical rating scales are limited by subjective error and inter-rater variability. Therefore, objective and quantitative measures of motor disability may be useful to supplement the EDSS in the setting of clinical trials.

It was previously shown that grip-force-variability (GFV) is increased in MS. We hypothesized that GFV may be an objective measure of motor disability in MS. To investigate whether the increase in GFV in MS is correlated to the clinical disability as assessed by the EDSS and to microstructural changes in the brain as assessed by diffusion tensor imaging, GFV was recorded in a grasping and lifting task in 27 MS patients and 23 controls using a grip-device equipped with a force transducer. The EDSS was assessed by neurologists experienced in MS. Patients underwent diffusion tensor imaging at 3T to assess the fractional anisotropy (FA) of the cerebral white matter as a measure of microstructural brain integrity. GFV was increased in MS and correlated to changes in the FA of white matter in the vicinity of the somatosensory and visual cortex. GFV also correlated with the EDSS. GFV may be a useful objective measure of motor dysfunction in MS linked to disability and structural changes in the brain. Our data suggests that GFV should be further explored as an objective measure of motor dysfunction in MS. It could supplement the EDSS, e.g., in proof of concept studies.

 

The EDSS scale of mobility is used by the regulators to determine whether drugs are active or not. However this is a very crude instrument and is perhaps part of the problem with progress in MS drug development as it a non-linear (the differences from point to point do not occur at the same rate) motor scale that is insensitive to change so trials tend to be of long duration. We have been saying for some time that we need to be more ingenious about how we monitor clinical trials. This study looks at the strength in grip and see that this declines in MSers. They say there is a correlation with EDSS, but this is going to be a loose correlation as grip strength examines arm function and EDSS is concentrated on leg movement function. The types of outcomes may help to determine if we can see xhange quicker. It remains to be seen if GFV willl be part of the armoury of new outcome meansures in future trials.

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