A randomized clinical control study on the efficacy of three-dimensional upper limb robotic exoskeleton training in chronic stroke.

BACKGROUND: Although robotics assisted rehabilitation has proven to be effective in stroke rehabilitation, a limited functional improvements in Activities of Daily Life has been also observed after the administration of robotic training. To this aim in this study we compare the efficacy in terms of both clinical and functional outcomes of a robotic training performed with a multi-joint functional exoskeleton in goal-oriented exercises compared to a conventional physical therapy program, equally matched in terms of intensity and time. As a secondary goal of the study, it was assessed the capability of kinesiologic measurements-extracted by the exoskeleton robotic system-of predicting the rehabilitation outcomes using a set of robotic biomarkers collected at the baseline. METHODS: A parallel-group randomized clinical trial was conducted within a group of 26 chronic post-stroke patients. Patients were randomly assigned to two groups receiving robotic or manual therapy. The primary outcome was the change in score on the upper extremity section of the Fugl-Meyer Assessment (FMA) scale. As secondary outcome a specifically designed bimanual functional scale, Bimanual Activity Test (BAT), was used for upper limb functional evaluation. Two robotic performance indices were extracted with the purpose of monitoring the recovery process and investigating the interrelationship between pre-treatment robotic biomarkers and post-treatment clinical improvement in the robotic group. RESULTS: A significant clinical and functional improvements in both groups (p < 0.01) was reported. More in detail a significantly higher improvement of the robotic group was observed in the proximal portion of the FMA (p < 0.05) and in the reduction of time needed for accomplishing the tasks of the BAT (p < 0.01). The multilinear-regression analysis pointed out a significant correlation between robotic biomarkers at the baseline and change in FMA score (R2 = 0.91, p < 0.05), suggesting their potential ability of predicting clinical outcomes. CONCLUSION: Exoskeleton-based robotic upper limb treatment might lead to better functional outcomes, if compared to manual physical therapy. The extracted robotic performance could represent predictive indices of the recovery of the upper limb. These results are promising for their potential exploitation in implementing personalized robotic therapy. Clinical Trial Registration clinicaltrials.gov, NCT03319992 Unique Protocol ID: RH-UL-LEXOS-10. Registered 20.10.2017, https://clinicaltrials.gov/ct2/show/NCT03319992.

Predictive value of electroencephalography connectivity measures for motor training outcome in multiple sclerosis: an observational longitudinal study.

BACKGROUND: Neurophysiological investigations represent powerful tools to shed light on brain plasticity in multiple sclerosis (MS) patients. AIM: We investigated the relationship between electroencephalography (EEG)-based connectivity, the extent of brain lesions and changes in motor performance after an intensive task-oriented circuit training (TOCT). DESIGN: Observational longitudinal study. SETTING: Outpatients training program. POPULATION: Sixteen MS patients (10F; mean age =51.4 years; range: 27-67; mean disease duration =15.1 years; range: 2-26; mean Expanded Disability Status Scale 4.4; range: 3.5-5.5), were included in our study. METHODS: MS patients with mild gait impairment were evaluated through functional scales and submitted to TOCT. Resting-state EEG was performed before (T0) and after (T1) rehabilitation. Alpha-band weighted Phase Lag Index (wPLI) and broadband weighted Symbolic Mutual Information (wSMI) connectivity analyses were performed. White matter lesion load was measured using MRI prior to the TOCT. Neurophysiological and structural parameters were then related to behavioral changes. RESULTS: Dynamic Gait Index significantly improved after TOCT (F(1,14) =13.10, P=0.003). Moreover, the interaction between TOCT and age was observed for changes in Timed Up and Go (TUG) performance (F(1,14) = 7.75, P=0.015), indicating that older patients only benefited in this measure. Regarding the relationship between EEG connectivity and TOCT outcome, we observed positive correlations between changes in TUG and strength (P=0.017) and efficiency (Pone-tail =0.029) of alpha-band wPLI connectivity at T0. Such correlation was mainly driven by antero-posterior regional interactions (P=0.038), rather than by inter-hemispheric connectivity (P=0.089). Moreover, we observed a positive correlation between performance improvements and wSMI connectivity at T1 (P=0.001) as well as the difference between T0 and T1 (P=0.005). Lesion load percentage was not related to functional improvement after TOCT (Pone-tail=0.137). CONCLUSIONS: Results of the current study demonstrated that baseline alpha-band wPLI connectivity predicts TOCT outcome in MS patients. Moreover, broadband wSMI tracks neural changes that accompany treatment-related variations in motor performance. CLINICAL REHABILITATION IMPACT: Our findings suggest that EEG-based connectivity measures may represent a potential tool for customizing rehabilitative management of the disease.

Delta Power Is Higher and More Symmetrical in Ischemic Stroke Patients with Cortical Involvement.

A brain injury resulting from unilateral stroke critically alters brain functionality and the complex balance within the cortical activity. Such modifications may critically depend on lesion location and cortical involvement. Indeed, recent findings pointed out the necessity of applying a stratification based on lesion location when investigating inter-hemispheric balance in stroke. Here, we tested whether cortical involvement could imply differences in band-specific activity and brain symmetry in post stroke patients with cortico-subcortical and subcortical strokes. We explored brain activity related to lesion location through EEG power analysis and quantitative Electroencephalography (qEEG) measures. Thirty stroke patients in the subacute phase and 10 neurologically intact age-matched right-handed subjects were enrolled. Stroke patients were equally subdivided in two groups based on lesion location: cortico-subcortical (CS, mean age ± SD: 72.21 ± 10.97 years; time since stroke ± SD: 31.14 ± 11.73 days) and subcortical (S, mean age ± SD: 68.92 ± 10.001 years; time since stroke ± SD: 26.93 ± 13.08 days) group. We assessed patients' neurological status by means of National Institutes of Health Stroke Scale (NIHSS). High density EEG at rest was recorded and power spectral analysis in Delta (1-4 Hz) and Alpha (8-14 Hz) bands was performed. qEEG metrics as pairwise derived Brain Symmetry Index (pdBSI) and Delta/Alpha Ratio (DAR) were computed and correlated with NIHSS score. S showed a lower Delta power in the Unaffected Hemisphere (UH) compared to Affected Hemisphere (AH; z = -1.98, p < 0.05) and a higher Alpha power compared to CS (z = -2.18, p < 0.05). pdBSI was negatively correlated with NIHSS (R = -0.59, p < 0.05). CS showed a higher value and symmetrical distribution of Delta band activity (z = -2.37, p < 0.05), confirmed also by a higher DAR value compared to S (z = -2.48, p < 0.05). Patients with cortico-subcortical and subcortical lesions show different brain symmetry in the subacute phase. Interestingly, in subcortical stroke patient brain activity is related with the clinical function. qEEG measures can be explicative of brain activity related to lesion location and they could allow precise definition of diagnostic-therapeutic algorithms in stroke patients.

Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation.

Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration.

Neurophysiological Characterization of Subacute Stroke Patients: A Longitudinal Study.

Various degrees of neural reorganization may occur in affected and unaffected hemispheres in the early phase after stroke and several months later. Recent literature suggests to apply a stratification based on lesion location and to consider patients with cortico-subcortical and subcortical strokes separately: different lesion location may also influence therapeutic response. In this study we used a longitudinal approach to perform TMS assessment (Motor Evoked Potentials, MEP, and Silent Period, SP) and clinical evaluations (Barthel Index, Fugl-Meyer Assessment for upper limb motor function and Wolf Motor Function Test) in 10 cortical-subcortical and 10 subcortical ischemic stroke patients. Evaluations were performed in a window between 10 and 45 days (t0) and at 3 months after the acute event (t1). Our main finding is that 3 months after the acute event patients affected by subcortical stroke presented a reduction in contralateral SP duration in the unaffected hemisphere; this trend is related to clinical improvement of upper limb motor function. In conclusion, SP proved to be a valid parameter to characterize cortical reorganization patterns in stroke survivors and provided useful information about motor recovery within 3 months in subcortical patients.

Quantitative assessment of early biomechanical modifications in diabetic foot patients: the role of foot kinematics and step width.

BACKGROUND: Forefoot ulcers (FU) are one of the most disabling and relevant chronic complications of diabetes mellitus (DM). In recent years there is emerging awareness that a better understanding of the biomechanical factors underlying the diabetic ulcer could lead to improve the management of the disease, with significant socio-economic impacts. Our purpose was to try to detect early biomechanical factors associated with disease progression. METHODS: Thirty subjects (M/F: 22/8; mean age ± SD: 61,84 ± 10 years) with diagnosis of type II DM were included. The participants were divided into 3 groups (10 subjects per group) according to the stage of evolution of the disease: Group 1, subjects with newly diagnosed type II DM, without clinical or instrumental diabetic peripheral neuropathy (DPN) nor FU (group called "DM"); Group 2, with DPN but without FU (group called "DPN"); Group 3, with DPN and FU (group called "DNU"). All subjects underwent 3-D Gait Analysis during walking at self-selected speed, measuring spatio-temporal, kinematic and kinetic parameters and focusing on ankle and foot joints. The comparative analysis of values between groups was performed using 1-way ANOVA. We also investigated group to group differences with Tukey HSD test. The results taken into consideration were those with a significance of P < 0,05. 95 % confidence interval was also calculated. RESULTS: A progressive and significant trend of reduction of ROM in flexion-extension of the metatarso-phalangeal joint (P = 0.0038) and increasing of step width (P = 0.0265) with the advance of the disease was evident, with a statistically significant difference comparing subjects with recently diagnosed diabetes mellitus and subjects with diabetic neuropathy and foot ulcer (P = 0.0048 for ROM and P = 0.0248 for step width at Tukey's test). CONCLUSIONS: The results provide evidence that foot segmental kinematics, along with step width, can be proposed as simple and clear indicators of disease progression. This can be the starting point for planning more targeted strategies to prevent the occurrence and the recurrence of a FU in diabetic subjects.

An EMG-Controlled Robotic Hand Exoskeleton for Bilateral Rehabilitation.

This paper presents a novel electromyography (EMG)-driven hand exoskeleton for bilateral rehabilitation of grasping in stroke. The developed hand exoskeleton was designed with two distinctive features: (a) kinematics with intrinsic adaptability to patient's hand size, and (b) free-palm and free-fingertip design, preserving the residual sensory perceptual capability of touch during assistance in grasping of real objects. In the envisaged bilateral training strategy, the patient's non paretic hand acted as guidance for the paretic hand in grasping tasks. Grasping force exerted by the non paretic hand was estimated in real-time from EMG signals, and then replicated as robotic assistance for the paretic hand by means of the hand-exoskeleton. Estimation of the grasping force through EMG allowed to perform rehabilitation exercises with any, non sensorized, graspable objects. This paper presents the system design, development, and experimental evaluation. Experiments were performed within a group of six healthy subjects and two chronic stroke patients, executing robotic-assisted grasping tasks. Results related to performance in estimation and modulation of the robotic assistance, and to the outcomes of the pilot rehabilitation sessions with stroke patients, positively support validity of the proposed approach for application in stroke rehabilitation.

A Beautician's Dystonia: Long-Lasting Effect of Botulinum Toxin.

Treatment options for dystonia are not curative but symptomatic; the treatment of choice for focal dystonias is repeated botulinum toxin injections. Here, we present the case of a 46-year-old beautician with focal dystonia in her left hand that affected her ability to work. Pharmacological treatment with clonazepam and gabapentin failed to resolve her symptoms and was discontinued due to side effects (sleepiness, gastrointestinal disorders). Intramuscular injection of botulinum toxin (incobotulinumtoxinA, Xeomin) into the extensor digitorum communis (35 U), flexor carpi radialis (35 U), and flexor digitorum superficialis (30 U) muscles resulted in complete resolution of symptoms at clinical assessments at 1, 3, 6, and 10 months after the injections, confirmed by the results of surface electromyography 10 months after treatment. The patient was able to work again 1 month after treatment. No reinjection has been necessary at the last evaluation (12 months after treatment). In conclusion, botulinum toxin is an effective treatment for focal dystonia that can have long-lasting effects and can improve patients' ability to work and quality of life.

Clinical evidences of brain plasticity in stroke patients.

Emerging findings deriving from neuromodulation and neuroradiology are providing us new insights about plas- ticity and functional reorganization of the brain after stroke, but the direct clinical assessment of motor function should still be considered an indispensable tool for the evaluation of the effects of plasticity in stroke patients. Recovery of motor function can be spontaneous or guided by training. Substantial functional recovery can occur spontaneously especially in the first month post-stroke. Instead, the guided recovery may take more time and may rely on a number of rehabilitation techniques which proved to be capable of stimulating cerebral plasticity. Even the time course of these processes is a decisive element. First, it is important to correlate the trends of plasticity after stroke, from the enhancement of earlier periods to the later stages, to the behavioral changes observed. Furthermore, it is crucial to distinguish recovery of function occurring through improvement of motor deficit from compensatory mechanisms, distinction that has also an effect on timing of recovery. Another relevant question is the maintenance over time of the improvements reached with the treatment, feature on which various clinical studies have been conducted in acute and chronic stroke patients. Further studies are needed to allow us to get a more precise definition of the potentiality of functional recovery and of the mechanisms underlying the recovery depending on its levels and timing. Understanding the mechanisms, the effects and the limits of neural plasticity may eventually help enhancing the recovery process in stroke patients, significantly improving the quality of life of these patients. Then, a greater attention towards the clinical implica- tions of the changes related to plasticity can be a crucial element to further improve the therapeutic options used in neurorehabilitation.

NIBS-driven brain plasticity.

Through plasticity the brain is able to change its function and to rearrange following injury or environmental changes. In recent years, it was shown that non-invasive brain stimulation (NIBS) techniques, especially transcra- nial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can contribute to understand how these plastic changes occur. Additionally, the literature suggests that TMS and tDCS may be used as interven- tional strategies to improve neurorehabilitation efforts and arguably recovery of motor function after brain lesions. This review focuses on the use of NIBS in experimental protocols for evaluation and modulation of brain plastic- ity, the factors contributing to the inter-individual variability of response, proposed mechanisms and difficulties in translating findings from small proof of principle studies through the pipeline to clinical practice.