Defining tibial anterior muscle morphology in first-ever chronic stroke patients using three-dimensional freehand ultrasound.

BACKGROUND: Drop foot is common post-stroke, elevating fall risks and mobility limitations. It is caused by weakness and lack of control of the tibialis anterior muscle (TA), for which various rehabilitation treatments are used. A reliable objective estimate of changes in TA muscle morphology and composition can enhance treatment optimization. OBJECTIVES: We aimed to ascertain 3D freehand ultrasound (3DfUS) reliability in measuring TA muscle volume, length, and echo intensity in stroke patients and healthy controls and its validity by comparing these features across legs, between patients and controls, and between clinical subgroups (i.e. patients with and without ankle contracture, spastic muscle overactivity, and foot dorsiflexor paresis). METHODS: We included 9 stroke patients and 9 healthy controls to define reliability and 26 stroke patients and 28 healthy controls to define validity. For reliability, data were collected and processed by 2 different operators and processors. For inter- and intra-rater reliability, intra-class correlation coefficient (ICC) and standard error of measurement (SEM) were used. For validity, Wilcoxon-Signed-Ranked and Mann-Whitney U tests were used for comparisons between groups and subgroups. RESULTS: All measurements showed good to excellent inter- and intra-rater reliability (ICC: 0.816 to 0.997, SEM: 0.5% to 7.8%). Comparison analyses revealed no differences in muscle features among legs, groups, or subgroups. CONCLUSION: While the 3DfUS is a reliable method to define TA morphology and composition, its clinical validity needs further investigation into factors influencing muscle property changes across various age groups and post-stroke time points. MESH TERMS: Stroke; Skeletal muscle morphology; muscle composition; 3D freehand ultrasonography, Anterior Tibial Muscle.

Neurorehabilitation including Virtual-Reality-Based Balance Therapy: Factors Associated with Training Response.

BACKGROUND: Virtual reality (VR) therapy is increasingly used and has shown encouraging effects. Yet, it is unknown which patients respond best to VR-based balance therapy as part of neurorehabilitation. METHODS: Data from 30 persons with stroke and 51 persons with multiple sclerosis who performed three to four weeks of VR-based balance therapy during in-patient rehabilitation were analysed. Participants were divided into responders and nonresponders based on achievement of the minimal clinically important difference in functional balance post intervention. Measures of balance, trunk function, mobility, gait, motivation, and exergame parameters were compared between groups. RESULTS: Post intervention, all clinical measurements significantly improved (p < 0.05; effect size: 0.45-0.59). Participants that achieved the minimal clinically important difference in functional balance (n = 49; 60%) had significantly lower preintervention functional and dynamic balance (median(IQR): 39(27-46) versus 45(37-50); p = 0.02 and 11(6-15) versus 16(11-18); p = 0.03). They spent less time on higher difficulty exercises (11(8-17) versus 14.5(10-12); p = 0.03) and demonstrated increased motivation over time compared with nonresponders (1(-1-5) versus -2(-7-3); p = 0.03). CONCLUSION: Lower baseline balance ability, spending more time on adequately challenging exercises, and increased motivation potentially influence response to therapy. These factors can support the personalisation of VR-based balance therapy.

The feasibility of the adapted H-GRASP program for perceived and actual daily-life upper limb activity in the chronic phase post-stroke.

(Purpose: Assessing feasibility and initial impact of the Home-Graded Repetitive Arm Supplementary Program combined with in-home accelerometer-based feedback (AH-GRASP) on perceived and actual daily-life upper limb (UL) activity in stroke survivors during the chronic phase with good UL motor function but low perceived daily-life activity. Material and methods: A 4-week intervention program (4 contact hours, 48 h self-practice) encompassing task-oriented training, behavioral techniques, phone-based support, monitoring, and weekly feedback sessions using wrist-worn accelerometery was implemented using a pre-post double baseline repeated measures design. Feasibility, clinical assessments, patient-reported outcomes, and accelerometer data were investigated. Results: Of the 34 individuals approached, nineteen were included (recruitment rate 56%). Two dropped out, one due to increased UL pain (retention rate 89%). Seven (41%) achieved the prescribed exercise target (120 min/day, six days/week). Positive patient experiences and improvements in UL capacity, self-efficacy, and contribution of the affected UL to overall activity (p < 0.05, small to large effect sizes) were observed. Additionally, seven participants (41%) surpassed the minimal clinically important difference in perceived UL activity.Conclusions: A home-based UL exercise program with accelerometer-based feedback holds promise for enhancing perceived and actual daily-life UL activity for our subgroup of chronic stroke survivors.

Implementing a home-based exercise program with accelerometer-based feedback and telephone supervision may effectively improve upper limb activity after stroke.This program is most suitable for individuals with mild upper limb impairment and should be tailored to their abilities, preferences, and limitations to enhance engagement.The AH-GRASP program shows promising recruitment and retention rates, safety, and positive patient experiences.To improve adherence, consider dividing exercises into shorter sessions that accommodate patient's schedules, attention and endurance levels.

Does somatosensory discrimination therapy alter sensorimotor upper limb function differently compared to motor therapy in children and adolescents with unilateral cerebral palsy: study protocol for a randomized controlled trial.

BACKGROUND: Besides motor impairments, up to 90% of the children and adolescents with unilateral cerebral palsy (uCP) present with somatosensory impairments in the upper limb. As somatosensory information is of utmost importance for coordinated movements and motor learning, somatosensory impairments can further compromise the effective use of the impaired upper limb in daily life activities. Yet, intervention approaches specifically designated to target these somatosensory impairments are insufficiently investigated in children and adolescents with uCP. Therefore, the aim of this randomized controlled trial (RCT) is to compare the effectiveness of somatosensory discrimination therapy and dose-matched motor therapy to improve sensorimotor upper limb function in children and adolescents with uCP, who experience somatosensory impairments in the upper limb. We will further explore potential behavioral and neurological predictors of therapy response. METHODS: A parallel group, evaluator-blinded, phase-II, single-center RCT will be conducted for which 50 children and adolescents with uCP, aged 7 to 15 years, will be recruited. Participants will be randomized to receive 3 weekly sessions of 45 minutes of either somatosensory discrimination therapy or upper limb motor therapy for a period of 8 weeks. Stratification will be performed based on age, manual ability, and severity of tactile impairment at baseline. Sensorimotor upper limb function will be evaluated at baseline, immediately after the intervention and after 6 months follow-up. The primary outcome measure will be bimanual performance as measured with the Assisting Hand Assessment. Secondary outcomes include a comprehensive test battery to objectify somatosensory function and measures of bimanual coordination, unimanual motor function, and goal attainment. Brain imaging will be performed at baseline to investigate structural brain lesion characteristics and structural connectivity of the white matter tracts. DISCUSSION: This protocol describes the design of an RCT comparing the effectiveness of somatosensory discrimination therapy and dose-matched motor therapy to improve sensorimotor upper limb function in children and adolescents with uCP. The results of this study may aid in the selection of the most effective upper limb therapy, specifically for children and adolescents with tactile impairments. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06006065). Registered on August 8, 2023.

Error Enhancement for Upper Limb Rehabilitation in the Chronic Phase after Stroke: A 5-Day Pre-Post Intervention Study.

A large proportion of chronic stroke survivors still struggle with upper limb (UL) problems in daily activities, typically reaching tasks. During three-dimensional reaching movements, the deXtreme robot offers error enhancement forces. Error enhancement aims to improve the quality of movement. We investigated clinical and patient-reported outcomes and assessed the quality of movement before and after a 5 h error enhancement training with the deXtreme robot. This pilot study had a pre-post intervention design, recruiting 22 patients (mean age: 57 years, mean days post-stroke: 1571, male/female: 12/10) in the chronic phase post-stroke with UL motor impairments. Patients received 1 h robot treatment for five days and were assessed at baseline and after training, collecting (1) clinical, (2) patient-reported, and (3) kinematic (KINARM, BKIN Technologies Ltd., Kingston, ON, Canada) outcome measures. Our analysis revealed significant improvements (median improvement (Q1-Q3)) in (1) UL Fugl-Meyer assessment (1.0 (0.8-3.0), p < 0.001) and action research arm test (2.0 (0.8-2.0), p < 0.001); (2) motor activity log, amount of use (0.1 (0.0-0.3), p < 0.001) and quality of use (0.1 (0.1-0.5), p < 0.001) subscale; (3) KINARM-evaluated position sense (-0.45 (-0.81-0.09), p = 0.030) after training. These findings provide insight into clinical self-reported and kinematic improvements in UL functioning after five hours of error enhancement UL training.

Standardized measurement of balance and mobility post-stroke: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

BACKGROUND: Mobility is a key priority for stroke survivors. Worldwide consensus of standardized outcome instruments for measuring mobility recovery after stroke is an essential milestone to optimize the quality of stroke rehabilitation and recovery studies and to enable data synthesis across trials. METHODS: Using a standardized methodology, which involved convening of 13 worldwide experts in the field of mobility rehabilitation, consensus was established through an a priori defined survey-based approach followed by group discussions. The group agreed on balance- and mobility-related definitions and recommended a core set of outcome measure instruments for lower extremity motor function, balance and mobility, biomechanical metrics, and technologies for measuring quality of movement. RESULTS: Selected measures included the Fugl-Meyer Motor Assessment lower extremity subscale for motor function, the Trunk Impairment Scale for sitting balance, and the Mini Balance Evaluation System Test (Mini-BESTest) and Berg Balance Scale (BBS) for standing balance. The group recommended the Functional Ambulation Category (FAC, 0-5) for walking independence, the 10-meter Walk Test (10 mWT) for walking speed, the 6-Minute Walk Test (6 MWT) for walking endurance, and the Dynamic Gait Index (DGI) for complex walking. An FAC score of less than three should be used to determine the need for an additional standing test (FAC < 3, add BBS to Mini-BESTest) or the feasibility to assess walking (FAC < 3, 10 mWT, 6 MWT, and DGI are "not testable"). In addition, recommendations are given for prioritized kinetic and kinematic metrics to be investigated that measure recovery of movement quality of standing balance and walking, as well as for assessment protocols and preferred equipment to be used. CONCLUSIONS: The present recommendations of measures, metrics, technology, and protocols build on previous consensus meetings of the International Stroke Recovery and Rehabilitation Alliance to guide the research community to improve the validity and comparability between stroke recovery and rehabilitation studies as a prerequisite for building high-quality, standardized "big data" sets. Ultimately, these recommendations could lead to high-quality, participant-specific data sets to aid the progress toward precision medicine in stroke rehabilitation.

Standardized measurement of balance and mobility post-stroke: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

BACKGROUND: Mobility is a key priority for stroke survivors. Worldwide consensus of standardized outcome instruments for measuring mobility recovery after stroke is an essential milestone to optimize the quality of stroke rehabilitation and recovery studies and to enable data synthesis across trials. METHODS: Using a standardized methodology, which involved convening of 13 worldwide experts in the field of mobility rehabilitation, consensus was established through an a priori defined survey-based approach followed by group discussions. The group agreed on balance- and mobility-related definitions and recommended a core set of outcome measure instruments for lower extremity motor function, balance and mobility, biomechanical metrics, and technologies for measuring quality of movement. RESULTS: Selected measures included the Fugl-Meyer Motor Assessment lower extremity subscale for motor function, the Trunk Impairment Scale for sitting balance, and the Mini Balance Evaluation System Test (Mini-BESTest) and Berg Balance Scale (BBS) for standing balance. The group recommended the Functional Ambulation Category (FAC, 0-5) for walking independence, the 10-meter Walk Test (10 mWT) for walking speed, the 6-Minute Walk Test (6 MWT) for walking endurance, and the Dynamic Gait Index (DGI) for complex walking. An FAC score of less than three should be used to determine the need for an additional standing test (FAC < 3, add BBS to Mini-BESTest) or the feasibility to assess walking (FAC < 3, 10 mWT, 6 MWT, and DGI are "not testable"). In addition, recommendations are given for prioritized kinetic and kinematic metrics to be investigated that measure recovery of movement quality of standing balance and walking, as well as for assessment protocols and preferred equipment to be used. CONCLUSIONS: The present recommendations of measures, metrics, technology, and protocols build on previous consensus meetings of the International Stroke Recovery and Rehabilitation Alliance to guide the research community to improve the validity and comparability between stroke recovery and rehabilitation studies as a prerequisite for building high-quality, standardized "big data" sets. Ultimately, these recommendations could lead to high-quality, participant-specific data sets to aid the progress toward precision medicine in stroke rehabilitation.

Defining characteristics of independent walking persons after stroke presenting with different arm swing coordination patterns.

BACKGROUND: Persons after stroke present with an altered arm swing during walking. Given the known influence of the arm swing on gait, it is important to identify the characteristics of persons with stroke with different arm-to-leg coordination patterns during walking. METHODS: Twenty-five persons after stroke walked on a self-paced treadmill at comfortable walking speed. The frequency of shoulder movements per stride was detected by Fast Fourier transform analysis on the kinematic data for hemiplegic shoulder movements in the sagittal plane. An independent-sample t-test or Mann-Whitney U test was used to compare clinical and biomechanical parameters between identified subgroups. RESULTS: Two earlier described subgroups based on the number of shoulder flexion-extension movements during one stride could be confirmed. Participants in the 1:1 ratio subgroup (one arm swing during one stride, N = 15) presented with a less upper limb impairment and less spasticity of the elbow extensors (p = 0.012) than the participants in the 2:1 ratio subgroup (two arm swings during one stride, N = 9). Although not significant, the participants in the 1:1 subgroup also seemed to have less spasticity of the shoulder internal rotators (p = 0.06) and a less walking variability based on the standard deviation of the step width. Further research on a greater sample should confirm these findings. CONCLUSION: Fast Fourier transform analysis was used to identify subgroups based on sagittal shoulder kinematics during walking. The clinical and gait related differences between the identified subgroups can be taken into account in future research investigating post-stroke gait interventions aiming to improve the arm swing.

In-depth quantification of bimanual coordination using the Kinarm exoskeleton robot in children with unilateral cerebral palsy.

BACKGROUND: Robots have been proposed as tools to measure bimanual coordination in children with unilateral cerebral palsy (uCP). However, previous research only examined one task and clinical interpretation remains challenging due to the large amount of generated data. This cross-sectional study aims to examine bimanual coordination by using multiple bimanual robotics tasks in children with uCP, and their relation to task execution and unimanual performance. METHODS: The Kinarm exoskeleton robot was used in 50 children with uCP (mean age: 11 years 11 months ± 2 years 10 months, Manual Ability Classification system (MACS-levels: l = 27, ll = 16, lll = 7)) and 50 individually matched typically developing children (TDC). All participants performed three tasks: object-hit (hit falling balls), ball-on-bar (balance a ball on a bar while moving to a target) and circuit task (move a cursor along a circuit by making horizontal and vertical motions with their right and left hand, respectively). Bimanual parameters provided information about bimanual coupling and interlimb differences. Differences between groups and MACS-levels were investigated using ANCOVA with age as covariate (α < 0.05, [Formula: see text]). Correlation analysis (r) linked bimanual coordination to task execution and unimanual parameters. RESULTS: Children with uCP exhibited worse bimanual coordination compared to TDC in all tasks (p ≤ 0.05, [Formula: see text] = 0.05-0.34). The ball-on-bar task displayed high effect size differences between groups in both bimanual coupling and interlimb differences (p < 0.001, [Formula: see text] = 0.18-0.36), while the object-hit task exhibited variations in interlimb differences (p < 0.001, [Formula: see text] = 0.22-0.34) and the circuit task in bimanual coupling (p < 0.001, [Formula: see text] = 0.31). Mainly the performance of the ball-on-bar task (p < 0.05, [Formula: see text] = 0.18-0.51) was modulated by MACS-levels, showing that children with MACS-level lll had worse bimanual coordination compared to children with MACS-level l and/or II. Ball-on-bar outcomes were highly related to task execution (r = - 0.75-0.70), whereas more interlimb differences of the object-hit task were moderately associated with a worse performance of the non-dominant hand (r = - 0.69-(- 0.53)). CONCLUSION: This study gained first insight in important robotic tasks and outcome measures to quantify bimanual coordination deficits in children with uCP. The ball-on-bar task showed the most discriminative ability for both bimanual coupling and interlimb differences, while the object-hit and circuit tasks are unique to interlimb differences and bimanual coupling, respectively.

Validity of a sensorimotor adaptation of the Action Research Arm Test (sARAT) in chronic stroke.

PURPOSE: After stroke, upper limb somatosensation can be impaired which affects motor control. Vision is often used to compensate for this. A clinical assessment which assesses the combined sensorimotor function in the absence of vision would be beneficial in studies targeting sensorimotor improvement. METHODS AND MATERIALS: We adapted the Action Research Arm Test (ARAT) to be performed without vision and called this modified version the sensorimotor ARAT (sARAT). Sixty healthy participants and 22 participants with chronic stroke performed the ARAT, sARAT, Fugl-Meyer upper extremity assessment (FM-UE) and Erasmus modified Nottingham sensory assessment (EmNSA). Discriminative validity of sARAT was evaluated by comparing performance between healthy participants and participants with chronic stroke. Convergent validity was evaluated by correlating sARAT with FM-UE and EmNSA. RESULTS: Participants with stroke performed worse on the sARAT compared to healthy participants (p < 0.001), with median scores of 52 (IQR 32-57) and 57 (IQR 57-57), respectively. The sARAT showed high correlations with FM-UE and EmNSA (r = 0.80-0.90). CONCLUSIONS: The sARAT shows good discriminative and convergent validity in people with chronic stroke. It allows a quick assessment of the combined upper limb sensorimotor function, by performing the well-known ARAT with the eyes closed.

The sensorimotor adaptation of the Action Research Arm Test (sARAT) is a clinical assessment of upper limb activity which is performed with the eyes closed.Combining the gold standard ARAT with the sensorimotor adaptation sARAT can inform about the influence of somatosensory impairments on upper limb activity in stroke survivors when vision is blocked.The sARAT shows good discriminative and convergent validity in persons with chronic stroke.

The differential effect of age on upper limb sensory processing, proprioception, and motor function.

Sensory processing consists in the integration and interpretation of somatosensory information. It builds upon proprioception but is a distinct function requiring complex processing by the brain over time. Currently little is known about the effect of aging on sensory processing ability or the influence of other covariates such as motor function, proprioception, or cognition. In this study, we measured upper limb passive and active sensory processing, motor function, proprioception, and cognition in 40 healthy younger adults and 54 older adults. We analyzed age differences across all measures and evaluated the influence of covariates on sensory processing through regression. Our results showed larger effect sizes for age differences in sensory processing (r = 0.38) compared with motor function (r = 0.18-0.22) and proprioception (r = 0.10-0.27) but smaller than for cognition (r = 0.56-0.63). Aside from age, we found no evidence that sensory processing performance was related to motor function or proprioception, but active sensory processing was related to cognition (ß = 0.30-0.42). In conclusion, sensory processing showed an age-related decline, whereas some proprioceptive and motor abilities were preserved across age.NEW & NOTEWORTHY Sensory processing consists in the integration and interpretation of sensory information by the brain over time and can be affected by lesion while proprioception remains intact. We investigated how sensory processing can be used to reproduce and identify shapes. We showed that the effect of age on sensory processing is more pronounced than its effect on proprioception or motor function. Age and cognition are related to sensory processing, not proprioception or motor function.

Motor rehabilitation after stroke: European Stroke Organisation (ESO) consensus-based definition and guiding framework.

PURPOSE: To propose a consensus-based definition and framework for motor rehabilitation after stroke. METHODS: An expert European working group reviewed the literature, attaining internal consensus after external feedback. FINDINGS: Motor rehabilitation is defined as a process that engages people with stroke to benefit their motor function, activity capacity and performance in daily life. It is necessary for people with residual motor disability whose goal is to enhance their functioning, independence and participation. Motor rehabilitation operates through learning- and use-dependent mechanisms. The trajectory of motor recovery varies across patients and stages of recovery. Early behavioral restitution of motor function depends on spontaneous biological mechanisms. Further improvements in activities of daily living are achieved by compensations. Motor rehabilitation is guided by regular assessment of motor function and activity using consensus-based measures, including patient-reported outcomes. Results are discussed with the patient and their carers to set personal goals. During motor rehabilitation patients learn to optimize and adapt their motor, sensory and cognitive functioning through appropriately dosed repetitive, goal-oriented, progressive, task- and context-specific training. Motor rehabilitation supports people with stroke to maximize health, well-being and quality of life. The framework describes the International Classification of Functioning, Disability and Health in the context of stroke, describes neurobiological mechanisms of behavioral restitution and compensation, and summarizes recommendations for clinical assessment, prediction tools, and motor interventions with strong recommendations from clinical practice guidelines (2016-2022). CONCLUSIONS: This definition and framework may guide clinical educators, inform clinicians on current recommendations and guidelines, and identify gaps in the evidence base.

Altered Dynamic Resting State Functional Connectivity Associated With Somatosensory Impairments in the Upper Limb in the Early Sub-Acute Phase Post-Stroke.

BACKGROUND.: Altered dynamic functional connectivity has been associated with motor impairments in the acute phase post-stroke. Its association with somatosensory impairments in the early sub-acute phase remains unexplored. OBJECTIVE.: To investigate altered dynamic functional connectivity associated with somatosensory impairments in the early sub-acute phase post-stroke. METHODS.: We collected resting state magnetic resonance imaging and clinical somatosensory function of the upper limb of 20 subacute stroke patients and 16 healthy controls (HC). A sliding-window approach was used to identify 3 connectivity states based on the estimated dynamic functional connectivity of sensorimotor related networks. Network components were subdivided into 3 domains: cortical and subcortical sensorimotor, as well as cognitive control network. Between-group differences were investigated using independent t-tests and Mann-Whitney-U tests. Analyzes were performed with correction for age, head motion and time post-stroke and corrected for multiple comparisons. RESULTS.: Stroke patients spent significantly less time in a weakly connected network state (state 3; dwell time: pstate3 = 0.003, meanstroke = 53.02, SDstroke = 53.13; meanHC = 118.92, SDHC = 72.84), and stayed shorter but more time intervals in a highly connected intra-domain network state (state 1; fraction time: pstate 1 < 0.001, meanstroke = 0.46, SDstroke = 0.26; meanHC = 0.26, SDHC = 0.21) compared to HC. After 8 weeks of therapy, improvements in wrist proprioception were moderately associated with decreases in dwell and fraction times toward a more normalized pattern. CONCLUSION.: Changes in temporal properties of large-scale network interactions are present in the early rehabilitation phase post-stroke and could indicate enhanced neural plasticity. These findings could augment the understanding of cerebral reorganization after loss of neural tissue specialized in somatosensory functions.

Trunk training following stroke.

BACKGROUND: Previous systematic reviews and randomised controlled trials have investigated the effect of post-stroke trunk training. Findings suggest that trunk training improves trunk function and activity or the execution of a task or action by an individual. But it is unclear what effect trunk training has on daily life activities, quality of life, and other outcomes. OBJECTIVES: To assess the effectiveness of trunk training after stroke on activities of daily living (ADL), trunk function, arm-hand function or activity, standing balance, leg function, walking ability, and quality of life when comparing with both dose-matched as non-dose-matched control groups. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, and five other databases to 25 October 2021. We searched trial registries to identify additional relevant published, unpublished, and ongoing trials. We hand searched the bibliographies of included studies. SELECTION CRITERIA: We selected randomised controlled trials comparing trunk training versus non-dose-matched or dose-matched control therapy including adults (18 years or older) with either ischaemic or haemorrhagic stroke. Outcome measures of trials included ADL, trunk function, arm-hand function or activity, standing balance, leg function, walking ability, and quality of life. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two main analyses were carried out. The first analysis included trials where the therapy duration of control intervention was non-dose-matched with the therapy duration of the experimental group and the second analysis where there was comparison with a dose-matched control intervention (equal therapy duration in both the control as in the experimental group).  MAIN RESULTS: We included 68 trials with a total of 2585 participants. In the analysis of the non-dose-matched groups (pooling of all trials with different training duration in the experimental as in the control intervention), we could see that trunk training had a positive effect on ADL (standardised mean difference (SMD) 0.96; 95% confidence interval (CI) 0.69 to 1.24; P < 0.001; 5 trials; 283 participants; very low-certainty evidence), trunk function (SMD 1.49, 95% CI 1.26 to 1.71; P < 0.001; 14 trials, 466 participants; very low-certainty evidence), arm-hand function (SMD 0.67, 95% CI 0.19 to 1.15; P = 0.006; 2 trials, 74 participants; low-certainty evidence), arm-hand activity (SMD 0.84, 95% CI 0.009 to 1.59; P = 0.03; 1 trial, 30 participants; very low-certainty evidence), standing balance (SMD 0.57, 95% CI 0.35 to 0.79; P < 0.001; 11 trials, 410 participants; very low-certainty evidence), leg function (SMD 1.10, 95% CI 0.57 to 1.63; P < 0.001; 1 trial, 64 participants; very low-certainty evidence), walking ability (SMD 0.73, 95% CI 0.52 to 0.94; P < 0.001; 11 trials, 383 participants; low-certainty evidence) and quality of life (SMD 0.50, 95% CI 0.11 to 0.89; P = 0.01; 2 trials, 108 participants; low-certainty evidence). Non-dose-matched trunk training led to no difference for the outcome serious adverse events (odds ratio: 7.94, 95% CI 0.16 to 400.89; 6 trials, 201 participants; very low-certainty evidence). In the analysis of the dose-matched groups (pooling of all trials with equal training duration in the experimental as in the control intervention), we saw that trunk training had a positive effect on trunk function (SMD 1.03, 95% CI 0.91 to 1.16; P < 0.001; 36 trials, 1217 participants; very low-certainty evidence), standing balance (SMD 1.00, 95% CI 0.86 to 1.15; P < 0.001; 22 trials, 917 participants; very low-certainty evidence), leg function (SMD 1.57, 95% CI 1.28 to 1.87; P < 0.001; 4 trials, 254 participants; very low-certainty evidence), walking ability (SMD 0.69, 95% CI 0.51 to 0.87; P < 0.001; 19 trials, 535 participants; low-certainty evidence) and quality of life (SMD 0.70, 95% CI 0.29 to 1.11; P < 0.001; 2 trials, 111 participants; low-certainty evidence), but not for ADL (SMD 0.10; 95% confidence interval (CI) -0.17 to 0.37; P = 0.48; 9 trials; 229 participants; very low-certainty evidence), arm-hand function (SMD 0.76, 95% CI -0.18 to 1.70; P = 0.11; 1 trial, 19 participants; low-certainty evidence), arm-hand activity (SMD 0.17, 95% CI -0.21 to 0.56; P = 0.38; 3 trials, 112 participants; very low-certainty evidence). Trunk training also led to no difference for the outcome serious adverse events (odds ratio (OR): 7.39, 95% CI 0.15 to 372.38; 10 trials, 381 participants; very low-certainty evidence). Time post stroke led to a significant subgroup difference for standing balance (P < 0.001) in non-dose-matched therapy. In non-dose-matched therapy, different trunk therapy approaches had a significant effect on ADL (< 0.001), trunk function (P < 0.001) and standing balance (< 0.001). When participants received dose-matched therapy, analysis of subgroup differences showed that the trunk therapy approach had a significant effect on ADL (P = 0.001), trunk function (P < 0.001), arm-hand activity (P < 0.001), standing balance (P = 0.002), and leg function (P = 0.002). Also for dose-matched therapy, subgroup analysis for time post stroke resulted in a significant difference for the outcomes standing balance (P < 0.001), walking ability (P = 0.003) and leg function (P < 0.001), time post stroke significantly modified the effect of intervention.  Core-stability trunk (15 trials), selective-trunk (14 trials) and unstable-trunk (16 trials) training approaches were mostly applied in the included trials. AUTHORS' CONCLUSIONS: There is evidence to suggest that trunk training as part of rehabilitation improves ADL, trunk function, standing balance, walking ability, upper and lower limb function, and quality of life in people after stroke. Core-stability, selective-, and unstable-trunk training were the trunk training approaches mostly applied in the included trials. When considering only trials with a low risk of bias, results were mostly confirmed, with very low to moderate certainty, depending on the outcome.

Transcranial direct current stimulation enhances motor learning in Parkinson's disease: a randomized controlled trial.

Writing training has shown clinical benefits in Parkinson's disease (PD), albeit with limited retention and insufficient transfer effects. It is still unknown whether anodal transcranial direct current stimulation (atDCS) can boost consolidation in PD and how this interacts with medication. To investigate the effects of training + atDCS versus training + sham stimulation on consolidation of writing skills when ON and OFF medication. Second, to examine the intervention effects on cortical excitability. In this randomized sham-controlled double-blind study, patients underwent writing training (one session) with atDCS (N = 20) or sham (N = 19) over the primary motor cortex. Training was aimed at optimizing amplitude and assessed during online practice, pre- and post-training, after 24-h retention and after continued learning (second session) when ON and OFF medication (interspersed by 2 months). The primary outcome was writing amplitude at retention. Cortical excitability and inhibition were assessed pre- and post-training. Training + atDCS but not training + sham improved writing amplitudes at retention in the ON state (p = 0.017, g = 0.75). Transfer to other writing tasks was enhanced by atDCS in both medication states (g between 0.72 and 0.87). Also, training + atDCS improved continued learning. However, no online effects were found during practice and when writing with a dual task. A post-training increase in cortical inhibition was found in the training + atDCS group (p = 0.039) but not in the sham group, irrespective of medication. We showed that applying atDCS during writing training boosted most but not all consolidation outcomes in PD. We speculate that atDCS together with medication modulates motor learning consolidation via inhibitory processes ( https://osf.io/gk5q8/ , 2018-07-17).

Longitudinal Synaptic Density PET with 11 C-UCB-J 6 Months After Ischemic Stroke.

OBJECTIVE: The purpose of this study was to explore longitudinal changes in synaptic density after ischemic stroke in vivo with synaptic vesicle protein 2A (SV2A) positron emission tomography (PET). METHODS: We recruited patients with an ischemic stroke to undergo 11 C-UCB-J PET/MR within the first month and 6 months after the stroke. We investigated longitudinal changes of partial volume corrected 11 C-UCB-J standardized uptake value ratio (SUVR; relative to centrum semiovale) within the ischemic lesion, peri-ischemic area and unaffected ipsilesional and contralesional grey matter. We also explored crossed cerebellar diaschisis at 6 months. Additionally, we defined brain regions potentially influencing upper limb motor recovery after stroke and studied 11 C-UCB-J SUVR evolution in comparison to baseline. RESULTS: In 13 patients (age = 67 ± 15 years) we observed decreasing 11 C-UCB-J SUVR in the ischemic lesion (ΔSUVR = -1.0, p = 0.001) and peri-ischemic area (ΔSUVR = -0.31, p = 0.02) at 6 months after stroke compared to baseline. Crossed cerebellar diaschisis as measured with 11 C-UCB-J SUVR was present in 11 of 13 (85%) patients at 6 months. The 11 C-UCB-J SUVR did not augment in ipsilesional or contralesional brain regions associated with motor recovery. On the contrary, there was an overall trend of declining 11 C-UCB-J SUVR in these brain regions, reaching statistical significance only in the nonlesioned part of the ipsilesional supplementary motor area (ΔSUVR = -0.83, p = 0.046). INTERPRETATION: At 6 months after stroke, synaptic density further declined in the ischemic lesion and peri-ischemic area compared to baseline. Brain regions previously demonstrated to be associated with motor recovery after stroke did not show increases in synaptic density. ANN NEUROL 2023;93:911-921.

In Vivo Detection of Neurofibrillary Tangles by 18F-MK-6240 PET/MR in Patients With Ischemic Stroke.

BACKGROUND AND OBJECTIVES: The risk of developing Alzheimer disease is increased after stroke, and this association may not solely be driven by traditional vascular risk factors. Neuronal death leads to the release of tau proteins, which can become dephosphorylated, rephosphorylated, or hyperphosphorylated in the setting of ischemia, possibly leading to formation of neurofibrillary tangles (NFT). Therefore, a potential synergistic effect between development of tauopathy and cerebrovascular lesion burden may contribute to cognitive decline after stroke. We explored the spatial and temporal distribution of NFT after ischemic stroke in vivo by using 18F-MK-6240 PET. METHODS: We included patients with a first ischemic stroke to undergo longitudinal 18F-MK-6240 PET/MR within 2-4 weeks and 6 months after stroke. For cross-sectional analyses, we also included age-matched healthy controls. We delineated 5 volumes of interest based on T2 FLAIR and T1 MR data: the ischemic lesion, 3 consecutive peri-ischemic areas, and the remaining ipsilesional hemisphere. We performed region-based voxel-wise partial volume correction on the PET data and calculated standardized uptake value ratios (SUVRs) with the cerebellum as the reference region. RESULTS: We did not quantify PET scans of patients within the first month after stroke (n = 17; median age 73 years [interquartile range {IQR}: 62-82 years]) because the signal intensity was influenced by blood-brain barrier breakdown hampering a reliable data analysis. At 6 months after the event (n = 13; median age 71 years [IQR: 60-79 years]), 18F-MK-6240 SUVR was increased in the ischemic lesion compared with 20 age-matched healthy controls (median age 71.5 years [IQR: 66-76 years]; ratiolesion/controls = 1.62 ± 0.54; 1-sample t test: p = 0.0015) and gradually decreased in the surrounding tissue (1-way within-subject analysis of variance [F{1.2, 14.8} = 18.0, p = 0.00043]). DISCUSSION: These findings suggest that NFT may form after ischemic stroke and spread in the peri-ischemic brain parenchyma. Further follow-up is required to gain more insight into the spatial and temporal dynamics of this tauopathy after ischemic stroke.

Multimodal and multidomain lesion network mapping enhances prediction of sensorimotor behavior in stroke patients.

Beyond the characteristics of a brain lesion, such as its etiology, size or location, lesion network mapping (LNM) has shown that similar symptoms after a lesion reflects similar dis-connectivity patterns, thereby linking symptoms to brain networks. Here, we extend LNM by using a multimodal strategy, combining functional and structural networks from 1000 healthy participants in the Human Connectome Project. We apply multimodal LNM to a cohort of 54 stroke patients with the aim of predicting sensorimotor behavior, as assessed through a combination of motor and sensory tests. Results are two-fold. First, multimodal LNM reveals that the functional modality contributes more than the structural one in the prediction of sensorimotor behavior. Second, when looking at each modality individually, the performance of the structural networks strongly depended on whether sensorimotor performance was corrected for lesion size, thereby eliminating the effect that larger lesions generally produce more severe sensorimotor impairment. In contrast, functional networks provided similar performance regardless of whether or not the effect of lesion size was removed. Overall, these results support the extension of LNM to its multimodal form, highlighting the synergistic and additive nature of different types of network modalities, and their corresponding influence on behavioral performance after brain injury.