Altered isometric force control during object release in patients with Huntington's Disease

Background: Objective markers for the severity of motor dysfunction are warranted for clinical trials in patients with Huntington's Disease (HD). Specific impairments in the control of isometric grip forces were found in grasping, holding, and transport tasks in HD. In previous studies we identified „grip force variability“ (GFV) as a measure correlated (1) to the clinical severity of the disease as assessed in the UHDRS, (2) to the amount of neurodegeneration in MRI volumetry, and (3) to the CAG repeat length when corrected for the age of patients. Thus GFV may be a surrogate marker to objectively assess the severity of HD. While the initiation and maintenance of grip forces in grasping and lifting has intensively been investigated in HD, it is unknown if specific impairments occur during object release in HD.

Objective: To investigate whether impairments of isometric force control can be objectively assessed during the replacement and release of an object in patients with HD compared to controls.

Methods: 16 patients with genetically confirmed HD and 15 controls were instructed to grasp, lift, hold and replace an object on a table using the precision grip. Replacement of the object was initiated by an auditory cue. Thirteen trials were performed with 250g and 500g object weights. Grip forces were recorded using precalibrated force transducers (Nano 17, ATI, USA). Object position was recorded using an electromagnetic position sensor (Fastrack, Polhemus, USA). Data recording and analysis was performed using a flexible laboratory computer system (SC/ZOOM, University of Umea, Sweden). Statistical analysis was performed using MANOVA (SPSS 10.1).

Results: HD patients showed a normal object replacement phase. However, after object replacement HD patients exhibited a prolonged unload phase and load force decrease phase (p<0.05 for both object weights), and a prolonged digit release phase (p<0.01 for both weights).

Conclusions: Isometric force release in HD patients shows robust impairments in the timing of force coordination, i.e. bradykinesia and sequencing problems in the final phases of grip release. Further studies are warranted to investigate whether these impairments are useful surrogates to assess the overall severity of motor dysfunction and the stage of disease in HD.

Acknowledgement: Supported by grant IMF RE-120225, Innovative Medical Research Fund, Faculty of Medicine, University of Muenster (RR)