Neurorehabilitation and neural repair最新文献

BackgroundThe presence or absence of a motor evoked potential (MEP) in the post-stroke hemiparetic limb has been recommended by rehabilitation experts as a predictive biomarker which is ready for use in clinical trials. However, evidence remains limited for its prognostic value in the chronic stage.Objective:Determine if MEP status (MEP+ or MEP-) obtained within 1 week of starting treatment (baseline) predicts the magnitude of response to intervention in individuals with chronic, moderate-severe hemiparesis.MethodsThis is a retrospective analysis using data from a single-blind randomized controlled trial. Seventy-six individuals ≥6 months post-stroke with a baseline Fugl-Meyer Assessment of the Upper Extremity (FMUE) score of 23 to 40 underwent 30 hours of upper limb (UL) training over 6 weeks. Participants were stratified by baseline MEP status. The primary endpoint was change in FMUE score from baseline to post-test.ResultsSeventy-three participants provided FMUE scores and MEP status at baseline. Individuals who were MEP+ (n = 49) demonstrated a mean FMUE change score of 5.09 (standard deviation [SD] = 3.8) while MEP- (n = 24) individuals demonstrated a mean change score of 5.04 (SD = 4.0). There were no significant differences between the groups (mean difference = 0.05, P = .96, 95% confidence interval [-1.99, 2.09]).ConclusionsOur results demonstrate that MEP status at the start of an intervention in the chronic stage does not predict recovery for people with moderate-severe UL impairments. This finding directly challenges recent expert recommendations to stratify trial groups by MEP status, suggesting that such stratification may not effectively reduce variability or predict treatment response at the chronic stage.Clinical Trial Registration:ClinicalTrials.gov, ID: NCT03517657.

BackgroundThe Wolf Motor Function Test (WMFT) and its modified versions are widely used to assess upper limb (UL) function in stroke survivors. However, comprehensive evaluations of its psychometric properties are lacking.ObjectiveTo perform a systematic review with meta-analysis on the psychometric properties (following the COnsensus-based Standards for the selection of health Measurement INstruments [COSMIN] taxonomy) of the WMFT and modified versions in stroke survivors.MethodsSix databases were searched until May 2024 for studies examining at least one WMFT measurement property in stroke patients. Two independent reviewers conducted study selection, data extraction, and quality assessment using the COSMIN Risk of Bias checklist and quality of evidence (QoE) with the Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analyses synthesized psychometric properties reported in at least two studies.ResultsTwenty-five studies (N = 2044) were included. Regarding the WMFT Functional Ability Scale (FAS) and TIME scales, internal consistency (alpha ≥ .88), intra-rater (intraclass correlation coefficient [ICC] ≥ .97) and inter-rater (ICC ≥ .92) reliability, measurement error for TIME, construct validity (strong correlations [r ≥| .64|] with Fugl-Meyer Assessment and Action Research Arm Test), and responsiveness (ES ≥ 0.48) were rated sufficiently with QoE from very low to high. Measurement error for FAS was assessed as inconsistent with moderate QoE, and cross-cultural validity was rated as indeterminate with very low QoE. Content validity was not assessed. Few studies investigated the psychometric properties of the modified versions.ConclusionsWMFT demonstrates robust psychometric properties in assessing UL function in stroke survivors. While the WMFT-modified versions showed promising properties, further research is needed to use them. Future studies should focus on WMFT measurement error, content, and cross-cultural validity.Trial Review Registration:PROSPERO: CRD42021237425.

BackgroundDual-task capacity, which might be impaired poststroke, is needed for daily functions. Therefore, dual-task capacity should be assessed during rehabilitation. The Dual Overload Interference Test (DO-IT) is a new upper extremity (UE) protocol for assessment, combining The Box and Block Test with the Counting Backwards Test.ObjectivesTo validate DO-IT by comparing between (1) young and older healthy, (2) stroke and healthy participants. Additionally, to correlate DO-IT with (3) walking-cognitive dual-task assessment (healthy), and (4) standardized cognitive and EF assessments (stroke).MethodsA cross-sectional study included younger and older community-dwelling healthy individuals (N = 32), and younger and older individuals with stroke (N = 83). DO-IT was administered to all participants. The #blocks transferred (motor) and #correct numbers counted (cognitive) were recorded for single and dual conditions. The walking-cognitive dual-task test was administered to the healthy participants. Motor and cognitive costs were calculated as the difference between single and dual tasks. The Montreal Cognitive Assessment test (MoCA) and the Color Trail Test (CTT) assessed cognition post stroke.ResultsOlder healthy adults had significantly lower dual-task motor capacity compared to younger adults (median [interquartile range] blocks: older 26 [21-38], younger 46 [38-52], P < .01). Participants with stroke showed higher motor costs than healthy participants. Dual-task costs correlated between DO-IT to walking-cognitive (motor; r = .37-.41, cognitive; r = .41-.47, P < .05). DO-IT motor cost negatively correlated with MoCA (r = -.27, P < .05), and DO-IT motor performance correlated with MoCA/CTT-AB (r = .29-.60, P < .05).ConclusionsUE-Cognitive dual-task capacity is affected post-stroke. DO-IT shows potential for use in stroke rehabilitation and its validity should be further researched.

BackgroundAfter a central nervous system lesion, the ability to control muscle activation and relaxation in specific joint ranges may be impaired. The underlying mechanism of this sensorimotor impairment is related to a decreased ability to regulate the tonic stretch reflex threshold (TSRT) through descending and peripheral control processes. In dynamics, the reflex threshold and its velocity-sensitivity (μ) describe how movement in specific upper limb (UL) joint ranges is impaired after stroke.ObjectiveTo examine the relationships between measures of elbow flexor impairment using TSRT and μ, and clinical scores of spasticity and motor function. We hypothesized that TSRT and μ would be related to clinical spasticity and motor impairment scores in patients with acute and chronic stroke.MethodsTSRT, μ, and clinical data of the resistance to passive movement (Modified Ashworth Scale) and UL motor function (Fugl-Meyer Assessment [FMA]) were collected from 120 patients. Relationships between variables were determined using simple correlations and multiple regression analysis.ResultsTSRT and μ explained 72.0% of the variance in the FMA of the Upper Extremity [FMA-UE] describing only in-synergy and out-of-synergy movements and reflex function. TSRT explained 68.7% of the variance in the total score of the FMA-UE.ConclusionsThis study shows for the first time, a significant relationship between deficits in TSRT regulation and μ with UL motor impairment after stroke. TSRT and μ may be valuable clinical biomarkers of sensorimotor impairment for monitoring spontaneous or treatment-induced motor recovery.

BackgroundDeficits in dual-tasks (DT) are frequently observed post-concussion (ie, mild Traumatic Brain Injury). However, traditional DT may not be relevant to daily life. Walking while talking elicits DT costs in healthy adults and is part of daily life.ObjectiveWe investigated the effect of concussion on walking with extemporaneous speech and explored relationships between DT and acute symptoms.MethodsParticipants with recent concussion (<14 days post-injury) and controls completed 3 tasks: single-task gait without speaking (ST_G), single-task speaking without walking (ST_S), and walking while speaking (DT). Silent pauses in speech audio reflected cognitive performance, and gait was quantified using inertial sensors. We used linear mixed models to compare groups and conditions and explored associations with self-reported symptoms.ResultsBoth concussion (n = 19) and control (n = 18) groups exhibited longer speech pauses (P < .001), slower walking speeds (P < .001), and slower cadence (P < .001) during the DT compared to ST conditions. There were no group differences or interactions for speech pauses (P > .424). The concussion group slowed down more during DT than the control group (group × task P = .032). Vestibular symptoms strongly associated with ST speech pause duration (ρ = .72), ST gait speed (ρ = -.75), and DT gait speed (ρ = -.78).ConclusionsExtemporaneous speech is well-practiced but challenging to complete while walking post-concussion. Strong associations between DT outcomes and vestibular-related symptoms suggest DT deficits vary with post-concussion symptomology. DT deficits may be deleterious to daily tasks post-concussion.

BackgroundEarly identification of potential deficits is of utmost importance as early diagnosis and early treatment has been shown to be crucial to reduce disease activity and disease impact-leading to the notion of "Time matters" in multiple sclerosis (MS).ObjectiveThe aim of the present study was to compare physical-, cognitive-, and patient-reported outcomes in early phase MS patients with matched healthy controls (HC).MethodsThis cross-sectional study included 84 patients early in the disease course of MS (≤2 years from diagnosis) and 84 age- and sex-matched HC. All participants underwent a comprehensive test battery including physical-, cognitive-, and patient-reported outcomes.ResultsRelative deficits for patients with MS compared to HC corresponded to 7% to 35% in walking capacity (Timed 25-Foot Walk Test, 6 Spot Step Test, 6 Minute Walk Test), 5% for upper limb function (9 Hole Peg Test), 27% for aerobic capacity (maximal oxygen uptake), 17% to 38% for physical activity level (Baecke Sport Index and accelerometer counts/minute), 68% for fatigability (Walking Fatigability Index), 150% for fatigue (Modified Fatigue Impact Scale), 4% to 20% for cognitive function (Symbol Digit Modalities Test, Paced Auditory Serial Addition Test, and Selective Reminding Test), and lastly, 7% to 8% for quality of life (Short Form-36 health survey). Only the Symbol Digit Modalities Test and Selective Reminding Test Delayed did not differ between groups, statistically.ConclusionEarly phase MS patients present substantial deficits in physical-, cognitive-, and patient-reported outcomes compared to HC. These early impairments highlight the importance of early initiatives aimed at preserving and/or building of reserve capacity.

BackgroundHigh intensity interval training (HIIT) is a mode of aerobic exercise that can increase neurotrophin concentration, improve cardiovascular health, and enhance recovery post-stroke. However, HIIT is not commonly prescribed in stroke rehabilitation. Exploring the clinical utility of, and barriers and facilitators to, HIIT is necessary to optimize clinical use.ObjectiveTo identify perceptions of HIIT from people with stroke and health professionals working in stroke rehabilitation.MethodsPeople with stroke and health professionals in Australia were invited to participate in an online questionnaire. Participants were further invited to complete a one-on-one semi-structured interview. A Framework Analysis approach was applied to identify key themes.ResultsTwenty-six people with stroke (mean ± standard deviation = 49.2 ± 60.6 months post-stroke, 57.7% female) and 37 health professionals (2 medical and 35 allied health) completed questionnaires. Ten people with stroke (5 female) and 8 allied health professionals completed an interview. Aerobic exercise was not considered a priority after stroke, though participants were interested in HIIT. People with stroke reported a lack of understanding of the benefits of HIIT and use of the term "high intensity" as barriers to participation. Facilitators included education about safety of HIIT and referral to health professionals. Health professionals reported a lack of knowledge of HIIT prescription parameters and participant motivation as barriers to prescription. Facilitators included education of HIIT prescription and benefits and appropriate screening prior to commencement.ConclusionsPeople with stroke and health professionals are interested in HIIT after stroke. Increasing knowledge and confidence to participate in, and prescribe HIIT, may increase clinical use.

Background: There is a critical time window of post-stroke neuroplasticity when spontaneous behavioral recovery occurs. Potential factors responsible for this heightened plasticity are the reduction of parvalbumin-immunoreactive (PV+) interneuron inhibitory signaling and the disappearance of extracellular matrix synaptic stabilizers called perineuronal net(s; PNN/PNNs).

Objective: This study investigated whether behavioral recovery during this critical period following stroke is associated with changes in densities of PV+ interneurons and PNNs.MethodsMale, Sprague-Dawley rats received forelimb motor cortex stroke (n = 43) using endothelin-1, or vehicle injections (n = 44). Cohorts of rats underwent a battery of motor tests and were sacrificed within the post-stroke critical window on day 1, and 1, 2, 4, and 6 weeks. Using immunofluorescent labeling, PNNs (wisteria floribunda agglutinin; WFA+ cells), PV+ interneurons, and cells expressing both PV and PNNs were quantified in contra- and ipsilesional cortices to elucidate their spatial-temporal profiles following stroke.ResultsPV+ interneuron density decreased significantly at 1-day post-stroke in the lateral ipsilesional cortex, while the density of PNNs was significantly lower up to 4 weeks post-stroke in the lateral ipsilesional cortex and at 1 and 2 weeks post-stroke in the medial ipsilesional cortex. Reduction of combined PV+/PNN signaling coincided with spontaneous behavioral recovery.ConclusionsThese results suggest that post-stroke behavioral recovery corresponds to an early reduction in PV+/PNN co-labeled cells in conjunction with an early temporally-dependent reduction in PV+ interneuron signaling and chronic disappearance of PNNs. Interventions targeting PNNs or PV+ interneuron signaling have significant potential for extending the critical window of recovery following stroke.

Background: In humans, most spontaneous recovery from motor impairment after stroke occurs in the first 3 months. Studies in animal models show higher responsiveness to training over a similar time-period. Both phenomena are often attributed to a milieu of heightened plasticity, which may share some mechanistic overlap with plasticity associated with normal motor learning.

Objective: Given that neurorehabilitation approaches are frequently predicated on motor learning principles, here we asked if the sensitivity of trial-to-trial learning for 2 kinds of motor learning processes often involved during rehabilitation is also enhanced early post-stroke. In a cross-sectional design, we compared (1) reinforcement and (2) error-based learning in 2 groups: 1 tested within 3 months after stroke (early group, N = 35) another tested more than 6 months after stroke (late group, N = 30). These 2 forms of motor learning were assessed with variations of the same visuomotor rotation task. Critically, motor execution was matched between the 2 groups.

Results: Reinforcement learning was impaired in the early but not the late group, whereas error-based learning was unimpaired in either group. These findings could not be attributed to differences in baseline execution, cognitive impairment, gender, age, or lesion volume and location.

Discussion: The presence of a deficit in reinforcement motor learning in the first 3 months after stroke has important implications for rehabilitation.

Conclusion: It might be necessary to either increase reinforcement feedback given early after stroke, increase the dose of rehabilitation to compensate, or delay onset of rehabilitation approaches that may rely on reinforcement, for example, constraint-induced movement therapy, and instead emphasize other forms of motor training in the subacute time period.

Background: Spinal cord injury (SCI) can impair motor, sensory, and autonomic function. The formation of the glial scar comprises protective as well as inhibitory neurite outgrowth properties operated by the deposition of chondroitin sulfate proteoglycans (CSPG). Chondroitinase ABC (ChABC) can degrade CSPG and foster neuroaxonal plasticity as a therapeutic approach to restore locomotor function after SCI.

Objectives: To systematically review experimental ChABC treatments after SCI and assess their efficacy for locomotor function a comprehensive literature search was conducted following pre-registered Prospero Study protocol, selecting animal studies evaluating neurobehavioral outcomes after traumatic SCI followed by the calculation of normalized effect sizes applying meta-analysis and meta-regression methodology. Additional analyses were performed to investigate the impact of animal type, strain, sex, sample size, injury models, level of injury, and treatment duration.

Results: Within the overall analysis of 1066 animals, a considerable amount of heterogeneity was observed. A subgroup analysis comprising experiments applying the same neurobehavioral measurement (blood-brain barrier/Basso-Mouse-Scale [BMS]-subgroup) demonstrated a 15.9% (95% CI = 11.3%-20.6%) improvement in locomotor outcomes. Different experimental characteristics influenced neurological recovery, including sex, level of injury, used anesthetic, reported dosage of ChABC treatment, the timepoint of assessment and perioperative temperature control. Sensitivity analysis applying Trim and Fill identified 19 hypothetical missing experiments suggestive of reporting bias.

Conclusion: Reporting bias in experimental SCI research is prevalent and not limited to a specific intervention. ChABC treatment can exert beneficial effects on locomotor recovery after SCI.