Home-based exergames to improve cognitive function in Multiple Sclerosis: the EXTREMUS Study ​

Background. Motor and cognitive dysfunctions are common and disabling features in multiple sclerosis (MS) that remain challenging to be treated. Exergaming is an emerging tool in neurorehabilitation, which promotes motor functions and fitness level. Evidence in general population and in other neurological conditions suggests that exergames may be beneficial also for cognitive functions, as playing action video games requires the engagement of high-level domains for visuo-motor integration and spatial attention. Objective. To test if home-based exergaming is not inferior to cognitive rehabilitation delivered by a software application (app) for mobile devices and both interventions are superior to a placebo-analogue (sham) cognitive intervention. The hypothesis is that exergames offer a comprehensive approach to improve both motor and cognitive domains. Methods. This is a multicenter, randomized, sham-controlled, single blind, parallel arm study. People with MS (pwMS) will be randomized in a 1:1:1 ratio to receive 1) an 8-week home-based training with exergames, specifically with Nintendo Wii (intervention of interest) or 2) adaptive COGNI-TRAcK (comparator intervention) or 3) sham COGNI-TRAcK (placebo-analogue intervention). Assessments will be conducted at study enrolment (baseline), at the end of the 8-week intervention period (immediate post-training, Week 8) and after 16 weeks from randomization (post-training follow-up, Week 16). At each point in the assessment, Brief International Cognitive Assessment for MS (BICAMS) and the Stroop Color Word Test (SCWT). In addition, pwMS were assessed with the 29-item Multiple Sclerosis Impact Scale (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the 2-Minute Walking Test (2MWT), the Timed Up&Go test (TUG) and by a static posturography under single- (ST) and dual-task (DT) conditions were conducted. Results. Sixty-nine pwMS were assessed for eligibility in this pre-planned interim analysis; of these, 47 were randomized to the three treatment groups. The three treatment groups were comparable in terms of demographic and clinical characteristics at baseline (all p values >0.2). Preliminary analyses show statistically significant results between the SHAM group and the ADAPTIVE group (p=0.04) for the Symbol Digit Modalities Test (SDMT), the information processing speed assessment test that is part of BICAMS; the improvement observed between the EXERGAMES group and the SHAM group, did not reach statistical significance (p=0.06). TUG among the three groups showed statistically significant improvement between the EXERGAMES group and the SHAM group (p=0.01) and the ADAPTIVE group (p<0.001). Regarding fatigue, statistically significant results emerged between the SHAM group and the ADAPTIVE group (p=0.04) and between the ADAPTIVE group and the EXERGAMES group (p=0.01). In the EXERGAMES group, there was an improvement in balance measured by posturography the ST and DT conditions (p=0.01 and p=0.02). Discussion. Although this is only preliminary data, some interesting results emerged from the study. First, both COGNI-TRAcK and Nintendo Wii-treated patients experienced improvements in SDMT compared to the SHAM group. In addition, the study found that patients undergoing home rehabilitation with the Nintendo Wii also achieved improvements in the motor domain. Second, it appears that rehabilitation training with exergames can bring improvements in some specific domains of QoL and fatigue. The results obtained for fatigue in people with MS show that exergames are significantly effective in improving after the intervention, compared with the other groups. These results indicate that rehabilitation with exergames, which requires simultaneous physical and cognitive effort on the part of the patient, promotes not only the strengthening of motor functions, but also the efficiency of brain networks, particularly those dedicated to attention.