## 4 Discussion
In fact, in the phase from FS to MKF-C, the knee tended to extend rather than flex, similar to PwMS (Figure 4C,D). The low walking speed is also reflected in the knee-ankle diagram, highlighting a reduced area and perimeter. In contrast, when HCs walked at 3 km/h (i.e., the usual walking speed in healthy subjects) the knee flexed, and the hip extended between FS and MKF-C. Additionally, the shape and dimension of hip-knee and knee-ankle diagrams in the representative example (Figure 5A,B) were similar to those of the averaged values (Figure 5C,D). In fact, the variability within and between subjects decreased by increasing the speed of walking, particularly the CV within subjects (ranging from 6 to 14%); however, the CV of areas (hip-knee and knee-ankle diagrams) between subjects tended to remain high (ranging from 30 to 40%) (Table 3). The variability of the areas (hip-knee and knee-ankle) between the subjects was likely determined by the individual combinations selected by the subjects between step length and frequency. These results are consistent with the activation differences in proximal (VL and BF) and distal (TA and LG) leg muscles between PwMS and HC. In the present study, the high activation of the VL and BF indicates a stiff knee during the stance phase (appreciable in the hip-knee diagram, green line), which causes PwMS to compensate for the deficit with the ankle muscles (TA and LG). The reduced muscle activation of the TA and LG is responsible for nonfunctional limb distal control, which alters ankle positioning in the initial phase of the stride and the subsequent propulsion, thereby reducing the contribution to the forwards momentum of the body [18]. Therefore, altered muscle activation could be explained by a different recruitment pattern of motor units in proximal vs. distal muscles [19] and represents a compensatory strategy that could increase when the balance is impaired in PwMS [20]. The potential points of concern in the present study include the following. First, the sample size was relatively small (N = 20), and post hoc analysis demonstrated that the computed statistical power was equal to 0.16/0.19 to detect a small effect size (\(\sim\)0.10) and a significant difference (\(p<0.05\)) between PwMS and HCs when perimeters and areas were determined in the hip-knee angle. The achieved power of 0.16/0.19 corresponds to a likelihood of only 16/9% for revealing a real difference with a sample size of N = 200; therefore, a larger sample size would have been unlikely to lead to a different result, indicating that the more sensitive parameter to detect gait alteration in PwMS is the knee-ankle diagram. Second, EMG activity was recorded in the muscles of only one leg (the weakest in PwMS and the dominant in HCs). Regarding the latter limitation, we emphasize that recording the EMG activity in both leg muscles would make it possible to better describe the pattern of activation and the interactions between the weakest and strongest leg muscles during the gait cycles. To summarize, the results of the present study confirm the feasibility of angle-angle diagrams to provide individual quantitative and qualitative information regarding ROM and coordination while PwMS are walking. Future investigations should confirm this preliminary study by exploring the sensitivity of the angle-angle diagram to describe and quantify gait modifications in longitudinal protocols. Therefore, it is reasonable to suggest that the information provided by the angle-angle diagram could be used to detect individual gait alterations and assess the effectiveness of exercise and/or pharmacological interventions in PwMS. Conceptualization, R.D.G. and L.R. ; software, L.R., D.D.L. and S.L.G. ; validation, R.T. and R.D.G. ; formal analysis, F.M. and R.D.G. ; investigation, R.D.G., D.D.L., S.L.G. and E.P. ; data curation, R.T.; writing--original draft preparation, R.D.G. and D.D.L. ; writing--review and editing, R.D.G., E.P. and R.T.; supervision, R.D.G. and E.P. All authors have read and agreed to the published version of the manuscript.