## 4 Discussion
These improvements are most evident in prevalent pyramidal impaired subjects who were unable to maintain the effects of rehabilitation after three months [29]. The robotic training with the Haptic Master Robot was used in an RCT [32] and in a prospective cohort study [37]. In addition to traditional therapy, it showed significant improvements in the quality of the movement execution in wheelchair-bound populations and demonstrated reported beneficial effects on daily use without any adjunct impact on clinical outcome measures [32]. By increasing the number of sessions (from 3 to 5 weeks) and by utilizing the intervention on a less impaired population [37], significant improvements were also noted in clinical parameters such as active ROM in the shoulder and the strength and motor capacity of the upper limbs, unlike in stroke patients [37]. Two case series studies explored the effects of Armeo Spring. An 8-week long training program (3 times per week for 30 min/session) that was implemented supplementary to conventional therapy in high-level disability PwMS (EDSS 7.0-8.5) was able to improve the functional capacity of the upper limbs, even after a 2-month follow-up [34]. [PERSON] combined the use of the Armeo Spring with functional electric stimulation (FES). This system assisted patients in following a specified trajectory path, employing an iterative learning control to improve accuracy and maximize voluntary effort. An improvement of the proximal upper limb was reported in a small group who underwent a training program for 18 treatment sessions over 10 weeks [31]. Finally, an RCT did not find the superiority of the hand-robot Amadeo on conventional therapy for clinical measures, even if only the robot-assisted group reported significant improvement in arm use and an enhancement in extensor carpi activation [30]. In conclusion, end-effector robotic devices may represent a therapeutic opportunity, improving manual dexterity, coordination, functional capacity, and the efficiency of upper limb motor strategies in PwMS [29; 30; 32; 33; 36; 37]. However, the literature does not highlight statistically significant benefits of RAT compared to [30] or in addition to conventional rehabilitation [32]. Most of the included studies show that the clinical assessment does not always confirm improvements in instrumental measurements. A possible explanation could be related to the fact that kinematic and motor activity impairments can be present with a normal upper limb function [39]. Moreover, robotic-driven measurements can offer a more detailed picture of the execution of everyday daily living activities [40]. The included studies highlight that the improvements are not always maintained until the follow-up, except for arm function [30; 34], probably because there may be no automatic transfer of the improved task performance to the overall upper limb functionality. The use of real objects during purposeful, functional tasks involving the whole upper limb can be a good solution to generalize motor tasks to daily living activities. In this direction, using a planar robot with real object manipulation has effectively ameliorated grasping function in PwMS [33]. Robot-assisted therapy has been proposed to induce neuroplastic changes and motor recovery mainly through two different paradigms: adaptive or assistive [18]. Even though the assistive approach is usually the most commonly applied approach in arm robotic therapy, the evidence in PwMS is more focused on the adaptive approach with a solid neurophysiological rationale [29; 33; 35; 36]. This is based on the idea that PwMS preserve their ability to adapt to a novel dynamic environment, an ability that is related to the feed-forward component of control [9; 36]. The robot did not assist subjects during the movement execution but provided an unfamiliar dynamic environment. The subjects are required to adapt by learning to predict the effects of perturbating forces.