Altered Gait in Charcot Neuropathic Mice: A Kinematic Analysis

Abstract

Category: Diabetes; Hindfoot Introduction/Purpose: Charcot arthropathy is known to cause neurodegenerative as well as physical skeletal changes that can affect gait. A verified model of inducing Charcot arthropathy in mouse hindlegs exists, but clinical data has yet to be gathered from this model. This is a pilot study with the purpose of gathering clinical data on mouse gait and joint reactive forces that occur over time as a result of Charcot arthropathy utilizing MatLab software. Methods: Eleven wild-type 25-week-old C57BL/6J were included in this study. Group A (n= 6) was fed a high-fat 60% kcal diet starting at the age of 6 weeks and underwent a verified running protocol to induce microtrauma leading to hind-paw Charcot-type arthropathy. Sensory testing and fasting blood glucose levels confirmed the presence of hyperglycemia and neuropathy in Group A. Group B (n= 5) was fed a normal diet and did not complete a running protocol. At week 0 and week 16 of the study, brightly colored dots were placed on mice hindlimbs to mark the hip, knee, ankle, and tarsal joints. The mice were placed on the treadmill at a constant speed of 10 m/sec and were recorded in slow motion for 2-3 full gait cycles. MATLAB was used to measure gait angles and coordinates in space by following the corresponding colored dot for each joint on the mouse (Figure 1). Results: The control mice did not have significant changes in range of motion of the knee, ankle, or midfoot while walking between weeks 0 and 16. In contrast, the mice fed a high-fat diet had statistically significant differences in ankle range of motion (p=0.0275), nearly significant differences in knee range of motion (p=0.0991), and insignificant differences in midfoot range of motion between weeks 0 and 16. In addition, the differences between range of motion of the knee of the control vs. C57BL/6J mice were significantly different between groups at both weeks 0 (p=0.0016) and 16 (p=0.0201). In the ankle, the difference was statistically significant at week 0 (p=0.0275) but not week 16 (p=0.7066), presumably due to a large standard deviation in ankle range of motion. Conclusion: Results of this gait analysis indicate that mice with Charcot-like arthropathic changes demonstrated gait differences that affected the range of motion of the knees and ankles of the mice, but not the midfoot. These changes could be due to the neuropathic abnormalities induced in mouse feet that would cause gait changes. Future studies will include a larger sample size of mice with gait analysis done at intermediate time points to further quantify how gait changes over time with Charcot arthropathy.