Efficacy of a Multi-segmental Robotic and Technological Upper Limb Rehabilitation Program, Compared With Traditional Therapy, in Individuals With Acute and Sub-acute Stroke: a Multicenter, Randomized, Controlled Clinical Trial.

Stroke is the first cause of disability in the world, with a very high social impact. Recovery is partial in 85% of stroke survivors, 35% of whom have a persisting serious disability. The increase in lifespan is leading to a rise in the incidence of stroke, and therefore to a rise in the number of people requiring a rehabilitation program. Rehabilitation programs are mainly focused on walking recovery, with insufficient attention being paid to upper limb recovery. Thirty to 60% of patients treated with conventional therapy present functional deficits of the paretic arm, resulting in an impairment of activities of daily living.

Robot-mediated therapy (RT) has been proposed in the literature as a viable approach for the rehabilitation of the upper limb. A first meta-analysis of 262 subjects showed that when the duration/intensity of conventional therapy (CT) is matched with that of the robot-assisted therapy, no difference exists between the two groups in terms of motor recovery, activities of daily living, strength or motor control; instead, when the RT is added to CT, a greater effectiveness can be observed, when compared with regular CT alone (5). A subsequent meta-analysis by Mehrholz et al., including 19 trials (involving 666 subjects), showed that RT was more effective than other interventions in improving patients' activities of daily living (SMD 0.43, 95% confidence interval (CI) 0.11 to 0.75, P = 0.009, I2 = 67%). In the same sample, stratified by time since disease onset, the analysis confirmed that RT was more effective in improving the activities of daily living in the 224 acute and sub-acute patients (within 3 months of stroke onset) (SMD 0.64, 95% CI 0.14 to 1.15, P=0.01, I2 =69%). The same findings were not confirmed in 334 chronic patients (more than 3 months after stroke) (SMD 0.85, 95% CI -0.27 to 1.97, P=0.14, I2 =94%). As for the other outcomes, robotic therapy was more effective in improving upper extremity function (SMD 0.45, 95% CI 0.20 to 0.69, P = 0.0004, I2 = 45%), but not muscular strength (SMD 0.48, 95% CI -0.06 to 1.03, P = 0.08, I2 = 79%). Finally, RT was well accepted by patients, there was no marked increase in the number of drop-outs, and serious adverse events were rare and unrelated to the robotic treatment (6).

In an update of their meta-analysis, published in 2015, the same research team confirmed that RT was more effective than other therapies in improving activities of daily living (SMD 0.37, 95% confidence interval (CI) 0.11 to 0.64, P = 0.005, I² = 62%), motor function (SMD 0.35, 95% CI 0.18 to 0.51, P < 0.0001, I² = 36%) and strength (SMD 0.36, 95% CI 0.01 to 0.70, P = 0.04, I² = 72%) of the upper limb. RT was well accepted by patients, there was no marked increase in the number of drop-outs (RD 0.00, 95% CI -0.02 to 0.03, P = 0.84, I² = 0%), and serious adverse events were rare and unrelated to the robotic treatment. However, the authors concluded that the evidence quality was low, highlighting the need for more rigorous studies.

It should be noted that the authors of the review highlighted the fact that the studies reviewed were heterogeneous in terms of study design (two arms, four arms, parallel groups or cross-over, duration of follow-up and selection criteria), of the devices used for the therapeutic treatment, of the patients' characteristics (time since disease onset), of the methodological protocols (methods of randomization, of the blindness of the outcome assessors to group allocation, and of the presence or absence of an intention to treat analysis).

However, the authors emphasized that limitations such as the inability to blind the therapist and participants, i.e. the so-called contamination (provision of the intervention to the control group), and co-intervention (when the same therapist unintentionally provides additional care to either treatment or comparison group) has often been present in rehabilitation studies. Moreover, they pointed out that sometimes the sample is selected according to comorbidities, age, spasticity or pain; instead, in clinical practice patients are often older, and the prevalence of comorbidity, pain, spasticity and/or limitations of articular function is higher than that reported in the studies analyzed. Therefore, inclusion criteria that allow the effects of a robotic treatment to be evaluated on a larger sample of patients with stroke, with clinical characteristics as close as possible to the real-world clinical setting, are desirable.