Neurophysiological and Clinical Effects of Upper Limb Robot-Assisted Rehabilitation on Motor Recovery in Patients with Subacute Stroke: A Multicenter Randomized Controlled Trial Study Protocol.

BACKGROUND: The efficacy of upper limb (UL) robot-assisted therapy (RAT) on functional improvement after stroke remains unclear. However, recently published randomized controlled trials have supported its potential benefits in enhancing the activities of daily living, arm and hand function, and muscle strength. Task-specific and high-intensity exercises are key points in facilitating motor re-learning in neurorehabilitation since RAT can provide an assisted-as-needed approach. This study aims to investigate the clinical effects of an exoskeleton robotic system for UL rehabilitation compared with conventional therapy (CT) in people with subacute stroke. As a secondary aim, we seek to identify patients' characteristics, which can predict better recovery after UL-RAT and detects whether it could elicit greater brain stimulation. METHODS: A total of 84 subacute stroke patients will be recruited from 7 Italian rehabilitation centers over 3 years. The patients will be randomly allocated to either CT (control group, CG) or CT plus UL-RT through an Armeo®Power (Hocoma AG, CH, Volketswil, Switzerland) exoskeleton (experimental group, EG). A sample stratification based on distance since onset, DSO (DSO ≤ 30; DSO > 30), and Fugl-Meyer Assessment (FM)-UL (FM-UL ≤ 22; 22 < FM-UL ≤ 44) will be considered for the randomization. The outcomes will be recorded at baseline (T0), after 25 + 3 sessions of intervention (T1), and at 6 months post-stroke (T2). The motor functioning assessed by the FM-UL (0-66) will be considered the primary outcome. The clinical assessments will be set based on the International Classification of Function, Disability and Health (ICF). A patient satisfaction questionnaire will be evaluated in the EG at T1. A subgroup of patients will be evaluated at T0 and T1 via electroencephalography. Their brain electrical activity will be recorded during rest conditions with their eyes closed and open (5 min each). CONCLUSION: The results of this trial will provide an in-depth understanding of the efficacy of early UL-RAT through a whole arm exoskeleton and how it may relate to the neural plasticity process. The trial was registered at ClinicalTrial.gov with the registration identifier NCT04697368.

Robot-Assisted Training for Upper Limb in Stroke (ROBOTAS): An Observational, Multicenter Study to Identify Determinants of Efficacy.

BACKGROUND: The loss of arm function is a common and disabling outcome after stroke. Robot-assisted upper limb (UL) training may improve outcomes. The aim of this study was to explore the effect of robot-assisted training using end-effector and exoskeleton robots on UL function following a stroke in real-life clinical practice. METHODS: A total of 105 patients affected by a first-ever supratentorial stroke were enrolled in 18 neurorehabilitation centers and treated with electromechanically assisted arm training as an add-on to conventional therapy. Both interventions provided either an exoskeleton or an end-effector device (as per clinical practice) and consisted of 20 sessions (3/5 times per week; 6-8 weeks). Patients were assessed by validated UL scales at baseline (T0), post-treatment (T1), and at three-month follow-up (T2). The primary outcome was the Fugl-Meyer Assessment for the upper extremity (FMA-UE). RESULTS: FMA-UE improved at T1 by 6 points on average in the end-effector group and 11 points on average in the exoskeleton group (p < 0.0001). Exoskeletons were more effective in the subacute phase, whereas the end-effectors were more effective in the chronic phase (p < 0.0001). CONCLUSIONS: robot-assisted training might help improve UL function in stroke patients as an add-on treatment in both subacute and chronic stages. Pragmatic and highmethodological studies are needed to confirm the showed effectiveness of the exoskeleton and end-effector devices.

Efficacy of repetitive transcranial magnetic stimulation combined with visual scanning treatment on cognitive and behavioral symptoms of left hemispatial neglect in right hemispheric stroke patients: study protocol for a randomized controlled trial.

BACKGROUND: Left hemispatial neglect (LHN) is a neuropsychological syndrome often associated with right hemispheric stroke. Patients with LHN have difficulties in attending, responding, and consciously representing the right side of space. Various rehabilitation protocols have been proposed to reduce clinical symptoms related to LHN, using cognitive treatments, or on non-invasive brain stimulation. However, evidence of their benefit is still lacking; in particular, only a few studies focused on the efficacy of combining different approaches in the same patient. METHODS: In the present study, we present the SMART ATLAS trial (Stimolazione MAgnetica Ripetitiva Transcranica nell'ATtenzione LAteralizzata dopo Stroke), a multicenter, randomized, controlled trial with pre-test (baseline), post-test, and 12 weeks follow-up assessments based on a novel rehabilitation protocol based on the combination of brain stimulation and standard cognitive treatment. In particular, we will compare the efficacy of inhibitory repetitive-transcranial magnetic stimulation (r-TMS), applied over the left intact parietal cortex of LHN patients, followed by visual scanning treatment, in comparison with a placebo stimulation (SHAM control) followed by the same visual scanning treatment, on visuospatial symptoms and neurophysiological parameters of LHN in a population of stroke patients. DISCUSSION: Our trial results may provide scientific evidence of a new, relatively low-cost rehabilitation protocol for the treatment of LHN. TRIAL REGISTRATION: ClinicalTrials.gov NCT04080999 . Registered on September 2019.

Brain and behaviour in post-acute stroke: Reduction in seeking and posterior cingulate neuronal variability.

INTRODUCTION: Stroke is a complex event on both behavioral and neuronal grounds. Recent investigations evidence the central role of subcortical damage on the post-stroke brain and behavior reorganization. We have conducted an exploratory study combining anatomical lesion analysis, functional analysis of resting state fMRI, and behavioral assessment with focus on exploration as represented by SEEKING. METHOD: 24 stroke inpatients were studied immediately after their clinical stabilization post-stroke; neuronal variability in fMRI along with behavioral outcomes were assessed. These outcomes were compared with a control group of 22 healthy subjects. RESULTS: First, we observed predominant subcortical lesions in our sample with all stroke patients showing subcortical lesions and only some exhibiting additional cortical lesions. Second, we observed significantly reduced neuronal variability in the posterior cingulate cortex (PCC) that did not show any structural damage. Third, our stroke subjects showed reduced SEEKING which was related to reduced PCC neuronal variability in an abnormal way (compared to healthy subjects). This last outcome was assessed by considering the subset of 11 stroke subjects for which fMRI and behavioral outcomes were jointly measured. CONCLUSIONS: Taken together, our findings suggest that damage in subcortical regions may play a central role in abnormalities in both cortical activity (PCC) and associated behavior of post-stroke reorganization. Accounting for these aspects may have significant implications to optimize multidisciplinary rehabilitation processes, particularly during the early steps of recovery, reducing the impact of stroke on the patient and caregiver quality of life.

SEEKING and depression in stroke patients: an exploratory study.

The concept of SEEKING describes a predisposition to search enthusiastically for rewards in the environment. While SEEKING and its underlying functional anatomy have been extensively investigated in animals, such processes in humans, especially brain-damaged individuals, remain understudied. We therefore conducted an exploratory behavioral study in stroke patients to investigate the effects of brain lesions that anatomically could be interpreted to impact the SEEKING system and predicted relationships to depression. Patients with lesions in anterior, medial, and/or subcortical lesions showed significantly lower SEEKING scores and higher depression scores than nonlesioned subjects in the control group. Based on our data and related work on animals, we propose central involvement of the anterior subcortical-cortical midline system as core of the limbic system in SEEKING in humans.