Neurorehabilitation and neural repair最新文献

AimsSerum soluble low-density lipoprotein receptor-related protein 1 (sLRP1) has been implicated in the severity of ischemia-reperfusion injury in experimental stroke models. Its potential prognostic value in ischemic stroke recovery warrants further investigation. This study aims to explore the association between serum sLRP1 levels and functional outcome improvement from 3 to 12 months following acute ischemic stroke (AIS).MethodsWe included patients hospitalized for AIS within 24 hours of symptom onset. Serum sLRP1 levels at admission were analyzed for their association with functional outcome improvement, defined as a ≥1-point decrease in the modified Rankin Scale (mRS) score between 3 and 12 months. Multivariate binary logistic regression was employed to adjust for potential confounders. Improvements in predictive performance by including sLRP1 were assessed using the net reclassification index (NRI) and integrated discrimination improvement (IDI).ResultsA total of 171 patients were enrolled (median age: 65 years; 64.9% male). Functional outcome improvement was observed in 53 patients (31.0%). After adjusting for confounding factors, patients in the second and third tertiles of sLRP1 had significantly lower odds of functional outcome improvement compared to those in the lowest tertile (Tertile 2, odds ratio [OR] 0.19, 95% confidence interval [CI]: 0.08-0.49, P = .001; Tertile 3, OR 0.10, 95% CI: 0.03-0.27, P < .001). Incorporating sLRP1 into predictive models alongside conventional factors significantly enhanced reclassification accuracy (NRI = 46%, P = .004; IDI = 4%, P = .014).ConclusionsLower serum sLRP1 levels at admission are independently associated with functional outcome improvement after AIS. These findings suggest that modulating sLRP1 may represent a promising therapeutic strategy to enhance recovery in stroke patients.

BackgroundPhysical activity (PA) supports physical, cognitive, and mental health, yet is often limited in persons with multiple sclerosis (PwMS) due to mobility, cognitive, and psychological factors. Practical methods to identify those meeting PA recommendations are needed. This study aimed to develop a clinically useful approach combining patient-reported outcomes and objective measures to determine whether PwMS meet step count goals.MethodsParticipants completed mobility assessments (static balance, reactive balance, forward walking [FW], and backward walking [BW]), cognitive testing, and self-report measures. Fitbit tracked PA for 3 months, categorizing participants based on whether they met the MS daily step goal (7500 steps).ResultsForty-five PwMS (age: 51.16 ± 11.12 years; median Patient Determined Disease Steps: 1; 84% female) participated, with 15 meeting the daily step goal. Participants who met the step count goal reported significantly lower mobility limitations (MS Walking Scale-12, P = .01) and concern about falling (Falls Efficacy Scale-International, P < .01) compared to those who did not. Significant differences were also observed for BW at both comfortable and fast speeds (P < .01), FW at both speeds (P = .01), and reactive balance (P = .04). No differences were observed for cognition. Logistic regression identified BW at both comfortable (0.89 m/s) and fast speeds (1.25 m/s) as the strongest predictors of achieving the daily step goal, with predictive accuracies of 80% and 82.2%, respectively.ConclusionBW is a clinically relevant predictor of achieving daily step goals in PwMS. Established cut-off values-0.89 m/s for comfortable and 1.25 m/s for fast BW-demonstrated strong predictive accuracy. These findings highlight the utility of BW as a mobility measure to inform interventions and promote PA in clinical practice.

BackgroundStroke is a leading cause of upper-extremity (UE) motor impairments worldwide. Transcranial direct current stimulation (TDCS) may enhance UE recovery, but response variability remains a challenge.ObjectiveThis randomized, double-blinded feasibility and pilot clinical trial evaluated effects of patient-tailored TDCS versus sham on UE recovery in subacute stroke.MethodsPatients with subacute ischemic stroke and UE impairment were randomized to receive either anodal TDCS or sham stimulation, during UE rehabilitation 3 times weekly for 4 weeks. Electrode placement was patient-tailored and optimized using electric field modeling and targeted the ipsilesional primary motor hand area (M1-HAND). Primary outcome was Fugl-Meyer Assessment of UE (FMA-UE) score at end-of-intervention (EOT) and 12-weeks follow-up. Feasibility and exploratory clinical outcomes were also assessed.Results24 participants were randomized into real (n = 12, mean age 63 years) and sham TDCS (n = 12, mean age 68 years). FMA-UE improved at EOT in both groups, but improvement was significantly larger in the real TDCS group (mean difference 4.5 points, 95% confidence interval (CI) -5.34-14.31, P = .011). The differences diminished at 12-week follow-up. Median compliance was 95.8 and 100%, for real- and sham-TDCS groups, respectively, with no severe adverse events.ConclusionsPatient-tailored anodal TDCS over the ipsilesional M1-HAND may boost recovery of UE impairment in subacute stroke versus sham TDCS. This trial identified a clinically feasible framework for optimizing protocols of patient-tailored TDCS for larger-scale stroke trials. Despite the complex trial setup, the favorable safety profile supports future large-scale studies with improved stratification by UE impairment.

BackgroundThe Time to Walking Independently after Stroke (TWIST) prediction tool is designed to predict the number of post-stroke weeks at which patients are expected to achieve walking independence. The external validation of the TWIST tool's clinical applicability and generalizability has been desired.ObjectiveWe performed a geographic external validation of TWIST prediction in a multicenter prospective cohort.Patients and MethodsAdult post-stroke patients with lower-limb weakness and inability to walk independently were enrolled. Each patient's TWIST score (max. score: 4 points) was calculated using age, knee-extension strength, and the Berg Balance Scale score at 1 week post-stroke. The TWIST score predicts independent walking by 4, 6, 9, 16, or 26 weeks post-stroke, and we calculated the overall fit, calibration, and discrimination at each of these timepoints to assess the model's performance.ResultsThe validation cohort consisted of 145 patients (median age 73 years, 44% women, 36% moderate-severe stroke). At 9 and 26 post-stroke weeks, 60.7% and 72.4% of the patients achieved walking independence. The overall fit explained a moderate proportion of the outcome's variance (Nagelkerke R² = 0.28-0.49), and the discrimination performance was good (c-statistic >0.75). Calibration performance showed over-prediction at all timepoints (calibration-in-the-large = -1.62 to -0.34). Higher TWIST scores (3 or 4 points) over-predicted early post-stroke; lower TWIST scores (1 or 2 points) became increasingly over-predictive over time.ConclusionsThe TWIST prediction tool optimistically predicted walking independence in Japanese patients with stroke. Further validation studies are necessary to assess this tool's precise clinical impact and generalizability.Clinical Trial Registration URL:https://www.umin.ac.jp/UMIN000050588.

The expanding application of spinal stimulation therapies in spinal cord injury (SCI) rehabilitation necessitates a critical reexamination of cardiovascular (CV) responses to these interventions. A key question arises: How should blood pressure (BP) responses to stimulation be interpreted, and does the conventional definition of autonomic dysreflexia (AD) adequately capture these phenomena? Researchers remain divided-some classify BP elevations during stimulation as AD, while others attribute them to intentional neuromodulation targeting sympathetic preganglionic neurons. This review scrutinizes the various AD definitions in the literature, including the conventional threshold (systolic BP increase >20 mmHg), revealing substantial limitations in research contexts. While symptomatic AD occurs in only 4-7% of stimulation study participants, asymptomatic BP increases are considerably more frequent. This established threshold lacks robust physiological rationale and creates significant interpretive challenges, particularly when evaluating interventions designed to modulate BP responses. The current limitations of guideline-based definitions of AD challenge research interpretation and clinical translation. Although several publications describe AD as "unregulated" or "uncontrolled," it has not yet been incorporated into formal guideline definitions. This review underscores the need for a collaborative effort to refine AD definitions in research, particularly in the context of spinal stimulation. Future consensus development should address whether uniform thresholds should apply across different contexts, how to integrate heart rate dynamics and absolute BP values alongside symptomatic status, and how to meaningfully distinguish therapeutic BP modulation from adverse autonomic responses. This is essential for standardizing research approaches, optimizing stimulation parameters, and ensuring efficacy and safety as spinal stimulation technologies advance clinically.

BackgroundNeurorehabilitation is among the most vibrant areas of biomedical research. Its main strategy has been skill-specific practice, which often fails to produce adequate recovery. Now, new recognition of central nervous system (CNS) plasticity, new understanding of skills, and new technologies provide new strategies that enhance the efficacy of practice.ObjectivesThe substrate of a skill is a network of neurons and synapses that extends from cortex to spinal cord and is now called a heksor. A heksor changes continually to maintain the key features of its skill, the attributes that make the skill satisfactory. Muscle activity and kinematics may change; key features are maintained. Heksors share neurons and synapses. Through their concurrent changes, they keep the CNS in a negotiated equilibrium that enables each to maintain its skill. When CNS damage occurs, the goal is to enable damaged heksors to repair themselves.ResultsTwo new strategies enhance the efficacy of skill-specific practice. One increases plasticity. A damaged heksor shapes the additional plasticity through practice. The other targets beneficial plasticity to a critical site in a damaged heksor. This improves practice, enabling the heksor to achieve wider beneficial plasticity. In animals and humans, protocols that combine these strategies with practice enhance lasting recovery.ConclusionsThe challenge is to develop, optimize, and validate these combined protocols. Computational modeling can accelerate the process. Controlled trials and comprehensive outcome assessments are essential. Pre-morbid factors and physiological measures may identify biomarkers that can predict efficacy or guide patient-specific protocol design. Many combined protocols will be noninvasive and suitable for home use.

BackgroundConcern about falling (CAF) is highly prevalent in multiple sclerosis (MS) and is linked to poor motor, cognitive, and psychological functioning. Although CAF has been associated with impairments in these domains, the unique and combined contributions of motor, cognitive, psychological, and neural factors remain unclear. This study used a comprehensive approach to identify behavioral and neural predictors of CAF.MethodsForty-three individuals with MS completed motor, cognitive, and psychological assessments, and underwent a structural magnetic resonance imaging scan. Linear regression models examined domain-specific predictors of CAF, controlling for disease severity. A discriminant function analysis (DFA) evaluated the combined predictive value of all variables in classifying individuals into high versus low CAF groups based on a median split.ResultsCAF was significantly associated with impairments across all behavioral domains (|r| = .32-.78). Regression models explained 57% to 74% of variance in CAF. Greater physical fatigue (β = .46), slower backward walking speed (β = -.41), slower processing speed (β = -.44), impaired task-switching (β = .32), higher anxiety (β = .38), and avoidance behavior (β = .58) predicted greater CAF. Hippocampal and cerebellar volumes were not significant predictors after accounting for disease severity. DFA classified participants with high accuracy (73.9% low CAF; 65.0% high CAF).ConclusionCAF in MS reflects a complex interplay of physical, cognitive, and emotional factors. While structural brain measures were not independently predictive, the combined influence of motor, cognitive, and psychological factors highlight the need for multidomain assessments and treatments to reduce CAF and its negative consequences in MS.

Background: Persistent post-stroke ankle impairment hinders functional recovery. Brain-computer interface (BCI)-controlled ankle robot show rehabilitation potential, but their efficacy and underlying neuroplasticity remain unclear.

Objective: To assess BCI-controlled ankle robot training on post-stroke lower-limb motor recovery and neuroplasticity using quantitative EEG (qEEG).

Methods: Thirty-two stroke patients were randomized to BCI (n = 16, 40-minute BCI-robot training) or control (n = 16, 40-minute ankle-robot training) groups, receiving 5 sessions/week for 2 weeks. Outcomes included Fugl-Meyer Assessment-Lower Extremity (FMA-LE), Berg Balance Scale (BBS), Functional Ambulatory Category (FAC), Modified Ashworth Scale (MAS), active range of motion (AROM), and muscle strength. QEEG assessed the relative power of the delta (rδ), theta (rθ), alpha (rα), beta (rβ) bands, spectral power ratios, pairwise-derived Brain Symmetry Index (pdBSI), and functional connectivity.

Results: Both groups showed significant within-group improvements in dorsiflexion AROM, dorsiflexor strength, FMA-LE, BBS, and FAC (P < .05). The BCI group demonstrated significantly greater FMA-LE improvement than controls (∆FMA-LE, P = .007) and reduced calf spasticity (MAS; P = .038). QEEG analysis in the BCI group revealed decreased rδ (P = .005), increased rα (P = .017), reduced DAR and DTABR (P < .05), reduced interhemispheric asymmetry (pdBSI-δ; P = .018), and enhanced Cz-parietal connectivity in α and β bands (P < .05).

Conclusion: BCI-controlled ankle robot training significantly improved lower-limb motor function and reduced spasticity post-stroke. Associated neurophysiological changes, characterized by reduced slow-wave power and asymmetry, increased alpha power, and functional connectivity, indicated beneficial neuroplastic reorganization.Clinical trial registration number: China Clinical Trail Registry (ChiCTR2300074381; URL: http://www.chictr.org.cn).

Background: Pelvic floor dysfunction (PFD) is a frequent yet underrecognized complication of neurological disorders such as multiple sclerosis (MS), Parkinson's disease (PD), and stroke. Its multifactorial pathophysiology involves complex neural mechanisms affecting bladder, bowel, and sexual function, often resulting in decreased quality of life and psychosocial distress.

Objective: This focused mini-review aims to synthesize current evidence on the pathophysiology, clinical features, and rehabilitation approaches for neurogenic PFD in major neurological conditions.

Methods: A targeted literature search was performed in PubMed, Scopus, and Web of Science databases to identify clinical and experimental studies published between 1990 and 2025 addressing urinary and PFD in neurological populations. Special attention was given to rehabilitation-based interventions such as pelvic floor muscle training (PFMT), biofeedback, neuromuscular electrical stimulation (NMES), and percutaneous tibial nerve stimulation.

Findings: Neurogenic PFD is highly prevalent, with up to 90% of MS patients, 60% of PD patients, and nearly half of stroke survivors experiencing urinary symptoms. Conservative rehabilitation, particularly PFMT combined with biofeedback and NMES, improves muscle function, reduces incontinence frequency, and enhances quality of life. However, standardized rehabilitation protocols are lacking, and adherence remains a major barrier.

Conclusion: Evidence supports a multidisciplinary rehabilitation approach integrating PFMT and adjunct modalities for neurogenic PFD. Further large-scale randomized studies are required to establish standardized, evidence-based clinical guidelines.