Discussion
spasticity
The present pilot study was aimed at verifying the possible effects originated by 4-week nabiximols treatment on upper limb functioning of PwMS with moderate-severe spasticity. In particular, such assessment was carried out both from a clinical point of view (by investigating gross and fine manual dexterity with tests widely employed in MS) and by analyzing the kinematic parameters associated with a functional task (i.e., HTM) obtained using quantitative techniques for movement analysis, following an approach previously employed in several studies aimed at exploring the effect of nabiximols on gait performance [The results of the kinematic analysis suggest that the 4-week treatment had a positive impact on the ability of the tested PwMS to perform the HTM task. In particular, the overall time required to complete the task, which at the baseline was 1.83 s (in line with what previously observed in similar studies on PwMS [It was also interesting to observe that the improvements associated with the treatment are not restricted to the kinematic parameters of HTM but also involve the gross and fine manual dexterity performance, thus indicating that the observed effects are not task-specific but are likely to extend to the overall upper limb functioning. In particular, for the BBT the observed increase was, on average, of 3 blocks/min (+ 6%) while for the 9HPT the time necessary to complete the test reduced by 2.9 s (− 10%). However, it should be noted that both changes, although significant, remain below the threshold identified as representative of a clinically meaningful difference (which are 6 blocks/min for BBT and 15–20% for the 9HPT [Summarizing, the integration of the objective instrumental data and the clinical assessment indicates a certain degree of improvement in the upper limb functioning induced by nabiximols. At the same time, the study confirmed the subjective perception of the reduction of the severity of the spasticity symptoms (together with other positive aspects associated with sleep quality and bladder function) that were, so far, the main outcomes considered in most previous studies of nabiximols in PwMS. Even though, unfortunately, there is scarcity of similar data in the literature, our findings appear somehow consistent with those reported in the review by Arroyo et al. [From a clinical point of view, the findings of the present study are of some relevance since they suggest that the objective kinematic analysis can effectively integrate the results of the clinical tests to provide a more realistic and comprehensive view of the possible positive effects associated with the nabiximols treatment. In fact, while conventional tests like 9HPT and BBT are still necessary to evaluate any pharmacologic treatment targeted to UL, considering the large amount of existing data on PwMS that can be used as reference, the data originated by the instrumental analysis of HTM is likely to reflect the actual impact of the treatment under more ecological conditions.Some limitations of the study should be acknowledged: at first, given the nature of the pilot study, the sample here tested was small and thus generalization of the results is limited. Secondly, even though the kinematic analysis of HTM is objective and hardly influenced by voluntary behavior of the participants, the lack of a control group did not allow to assess the possible impact of placebo effects. Third, the follow-up time (1 month) might be too short to fully capture the improvement possibilities of the treatment, as the antispastic effect of nabiximols has been shown to increase up to the third month [