Grip-force variability in asymptomatic carriers of the Huntington gene – a biomarker for presymptomatic clinical studies?

Abstract

Aims: Isometric grip force variability (GFV) in Huntington's Disease (HD) was shown to correlate with (1) the severity of motor deficits in HD as assessed in the UHDRS (Gordon et al. 2000), (2) the CAG-repeat length when normalized for age (Reilmann et al. 2004), and (3) the degree of atrophy observed in the caudate nucleus on MRI volumetry (Reilmann et al 2005). Furthermore grip force variability was shown to increase in the course of HD (Reilmann et al. 2001). Objective: To investigate whether GFV in a grasping and holding task is pathologically increased in clinically asymptomatic carriers of the Huntington gene. Subjects and methods: HD gene carriers (n=13) and age-and-sex-matched healthy controls (n=13) were instructed to grasp and lift an object (weight 250g or 500g) in the precision grip and hold it next to a marker 10cm high for 30 seconds. Thirteen trials were performed in each weight condition. Grip and lift forces were recorded using force transducers (Mini-30, ATI, USA). Object position was recorded using a 3D-tracking device (Fastrack, Polhemus, USA). Data was recorded and analyzed using a flexible laboratory computer system (SC/ZOOM, University of Umea, Sweden). Mean grip force and its coefficient of variation were calculated during a 20s period in the static holding phase. Gene carriers were clinically assessed by the UHDRS and exhibited total motor scores <4, i.e. presymptomatic stage. Statistics were performed using ANOVA (SPSS 13.0). Results: Grip force variability in the static holding phase was increased in HD gene carriers compared to healthy controls in the 250g object condition (p<0.05). The difference in the 500g object condition did not reach statistical significance (p=0.07). Conclusion: Assessment of isometric grip forces may enable investigators to detect and objectively quantify impairments in motor dysfunction in subjects prior to clinical manifestation of HD. Similar to symptomatic HD patients, impairments in grip force control are more evident in the lighter object condition (see Gordon et al. 2000, Fellows et al. 1997). A possible use of GFV as a surrogate marker in neuroprotective treatment trials in asymptomatic HD gene carriers warrants further exploration, e.g. in a blinded follow-up study. Acknowledgment: The study was supported by grant IMF-RE-120225 from the “Innovative Medizinische Forschung“, Faculty of Medicine, University of Munster to RR