Use of Nintendo Wii Balance Board for posturographic analysis of Multiple Sclerosis patients with minimal balance impairment

Background: The Wii Balance Board (WBB) has been proposed as an inexpensive alternative to laboratory-grade Force Plates (FP) for the instrumented assessment of balance. Previous studies have reported a good validity and reliability of the WBB for estimating the path length of the Center of Pressure. Here we extend this analysis to 18 balance related features extracted from healthy subjects (HS) and individuals affected by Multiple Sclerosis (MS) with minimal balance impairment. Methods: Eighteen MS patients with minimal balance impairment (Berg Balance Scale 53.3 ± 3.1) and 18 age-matched HS were recruited in this study. All subjects underwent instrumented balance tests on the FP and WBB consisting of quiet standing with the eyes open and closed. Linear correlation analysis and Bland-Altman plots were used to assess relations between path lengths estimated using the WBB and the FP. 18 features were extracted from the instrumented balance tests. Statistical analysis was used to assess significant differences between the features estimated using the WBB and the FP and between HS and MS. The Spearman correlation coefficient was used to evaluate the validity and the Intraclass Correlation Coefficient was used to assess the reliability of WBB measures with respect to the FP. Classifiers based on Support Vector Machines trained on the FP and WBB features were used to assess the ability of both devices to discriminate between HS and MS. Results: We found a significant linear relation between the path lengths calculated from the WBB and the FP indicating an overestimation of these parameters in the WBB. We observed significant differences in the path lengths between FP and WBB in most conditions. However, significant differences were not found for the majority of the other features. We observed the same significant differences between the HS and MS populations across the two measurement systems. Validity and reliability were moderate-to-high for all the analyzed features. Both the FP and WBB trained classifier showed similar classification performance (>80%) when discriminating between HS and MS. Conclusions: Our results support the observation that the WBB, although not suitable for obtaining absolute measures, could be successfully used in comparative analysis of different populations

Pathological mitophagy disrupts mitochondrial homeostasis in Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy (LHON), a disease associated with a mitochondrial DNA mutation, is characterized by blindness due to degeneration of retinal ganglion cells (RGCs) and their axons, which form the optic nerve. We show that a sustained pathological autophagy and compartment-specific mitophagy activity affects LHON patient-derived cells and cybrids, as well as induced pluripotent-stem-cell-derived neurons. This is variably counterbalanced by compensatory mitobiogenesis. The aberrant quality control disrupts mitochondrial homeostasis as reflected by defective bioenergetics and excessive reactive oxygen species production, a stress phenotype that ultimately challenges cell viability by increasing the rate of apoptosis. We counteract this pathological mechanism by using autophagy regulators (clozapine and chloroquine) and redox modulators (idebenone), as well as genetically activating mitochondrial biogenesis (PGC1-α overexpression). This study substantially advances our understanding of LHON pathophysiology, providing an integrated paradigm for pathogenesis of mitochondrial diseases and druggable targets for therapy

tDCS and Robotics on Upper Limb Stroke Rehabilitation: Effect Modification by Stroke Duration and Type of Stroke

Objective. The aim of this exploratory pilot study is to test the effects of bilateral tDCS combined with upper extremity robot-assisted therapy (RAT) on stroke survivors. Methods. We enrolled 23 subjects who were allocated to 2 groups: RAT + real tDCS and RAT + sham-tDCS. Each patient underwent 10 sessions (5 sessions/week) over two weeks. Outcome measures were collected before and after treatment: (i) Fugl-Meyer Assessment-Upper Extremity (FMA-UE), (ii) Box and Block Test (BBT), and (iii) Motor Activity Log (MAL). Results. Both groups reported a significant improvement in FMA-UE score after treatment (p<0.01). No significant between-groups differences were found in motor function. However, when the analysis was adjusted for stroke type and duration, a significant interaction effect (p<0.05) was detected, showing that stroke duration (acute versus chronic) and type (cortical versus subcortical) modify the effect of tDCS and robotics on motor function. Patients with chronic and subcortical stroke benefited more from the treatments than patients with acute and cortical stroke, who presented very small changes. Conclusion. The additional use of bilateral tDCS to RAT seems to have a significant beneficial effect depending on the duration and type of stroke. These results should be verified by additional confirmatory studies

Action Observation Therapy for Arm Recovery after Stroke: A Preliminary Investigation on a Novel Protocol with EEG Monitoring

This preliminary study introduces a novel action observation therapy (AOT) protocol associated with electroencephalographic (EEG) monitoring to be used in the future as a rehabilitation strategy for the upper limb in patients with subacute stroke. To provide initial evidence on the usefulness of this method, we compared the outcome of 11 patients who received daily AOT for three weeks with that of patients who undertook two other approaches recently investigated by our group, namely intensive conventional therapy (ICT), and robot-assisted therapy combined with functional electrical stimulation (RAT-FES). The three rehabilitative interventions showed similar arm motor recovery as indexed by Fugl-Meyer’s assessment of the upper extremity (FMA_UE) and box and block test (BBT). The improvement in the FMA_UE was yet more favourable in patients with mild/moderate motor impairments who received AOT, in contrast with patients carrying similar disabilities who received the other two treatments. This suggests that AOT might be more effective in this subgroup of patients, perhaps because the integrity of their mirror neurons system (MNS) was more preserved, as indexed by EEG recording from central electrodes during action observation. In conclusion, AOT may reveal an effective rehabilitative tool in patients with subacute stroke; the EEG evaluation of MNS integrity may help to select patients who could maximally benefit from this intervention