Search Results (1,603)

Background/Objectives: Brain-derived neurotrophic factor (BDNF) and antioxidant networks mediated by Selenoprotein P (SEPP1) are core drivers of structural neuroplasticity and blood–brain barrier integrity, yet their co-regulatory behavior during subacute stroke neurorehabilitation remains poorly understood. This pilot study quantified concurrent changes in serum BDNF and SEPP1 during rehabilitation. Methods: Sixteen subacute post-stroke patients with mild stroke severity were assigned to an intensive multi-modal neurorehabilitation protocol incorporating high-intensity interval training (Treated, n = 7) or standard care (Control, n = 9); the biomarker sampling window averaged 73.4 days. Fasting venous blood was collected at baseline and post-intervention and analyzed by ELISA. Results: BDNF changes (ΔBDNF) differed significantly between arms (U = 57.0, p = 0.0081): the Treated cohort showed a uniform decrease (mean Δ: −0.240 ± 0.103 ng/mL), while Controls showed stabilization or a slight increase (mean Δ: +0.118 ± 0.339 ng/mL). ΔBDNF and ΔSEPP1 were significantly, positively correlated across the cohort (ρ = 0.596, p = 0.015). Conclusions: The BDNF decline in the Treated group is consistent with the “central sink” hypothesis, but may more plausibly reflect stress/cortisol-mediated suppression induced by the high training intensity, contrasting with increases typically reported after moderate-intensity subacute-phase exercise. The collinear coupling with SEPP1 suggests a link between neurotrophic synthesis and antioxidant buffering during post-stroke tissue remodeling, though this correlational finding does not by itself establish a single, coordinated mechanism. Full article

Objectives: To determine the prevalence of visual deficits among inpatients with acquired brain injury, to examine the agreement between objective screenings and patient-reported visual deficits, and to investigate patient characteristics associated with visual deficits. Methods: This cross-sectional study included data on screened and patient-reported visual deficits in patients with acquired brain injury admitted for inpatient rehabilitation. The screenings were conducted by occupational therapists. Visual acuity and visual field were assessed in 2014–2023, and complemented by assessment of ocular motility and patient-reported deficits in 2021–2023. Predictive values were calculated for the agreement between screening results and patient-reported symptoms. Logistic regression models were applied to investigate the association between clinical characteristics and visual deficits. Results: 2814 patients were screened, 65% were men, the median age was 64 years, and the most common diagnosis was stroke (66%). In screened patients 32% had reduced visual acuity, 18% had ocular motility deficits, and 15% had visual field deficits. Of 975 patients providing self-reports, 38% reported vision problems. A total of 28% of patients who did not report visual deficits, had visual deficits in the objective screening. Lower functional level was associated with greater odds of having any visual deficits. Traumatic and anoxic brain injuries were associated with lower odds of visual field deficits compared with stroke. Conclusions: The high proportion of patients with visual deficits underlines that these are common consequences following acquired brain injury. Objective screening and patient-reported deficits offer overlapping yet distinct insights into visual deficits. Knowledge of clinical characteristics associated with visual deficits may help recognize high-risk subgroups. Full article

Background/Objectives: Rehabilitation robotics is increasingly used in neurorehabilitation, yet evidence on how robotic services are organized, maintained and scaled in routine care remains fragmented. This mapping review examined service-delivery models, implementation determinants, strategies, outcomes, workflows and resource signals for robotic rehabilitation in service-linked clinical care. Methods: Six search sources were queried from inception to 21 February 2026. Eligible reports were studies addressing rehabilitation robotics within clinical pathways and reporting an implementation-relevant element. Data from 55 studies were systematically charted and mapped to CFIR determinants, ERIC strategies and Proctor implementation outcomes. Design-appropriate appraisal was applied once per included report to contextualize methodological confidence. Results: Staffing and supervision were reported in 50 studies (90.9%), workflow and scheduling in 43 (78.2%), safety governance in 32 (58.2%) and training and competency in 29 (52.7%). Feasibility was mapped in 40 studies (72.7%), acceptability in 31 (56.4%) and adoption in 23 (41.8%), whereas sustainability, penetration, technical support, documentation infrastructure and implementation cost were less consistently reported. Two randomized trials were appraised with RoB 2 and four non-randomized comparative studies with ROBINS-I; the remaining 49 reports received design-appropriate methodological or reporting appraisal. Conclusions: Routine-care rehabilitation robotics is best understood as a service configuration rather than a device alone. Transferable implementation requires explicit reporting of workforce, workflow, safety, documentation, technical support, infrastructure, cost, equity and sustainment. Frequencies indicate reporting presence, not practical importance or causal influence. The proposed workflow, logic model and minimum reporting set are evidence-informed, inductively derived proposals requiring prospective validation. Full article

Background: Spasticity is one of the most disabling manifestations of multiple sclerosis (MS), contributing to limitations in walking and transfers, pain, progressive functional limitation, and reduced quality of life. Despite advances in rehabilitation, pharmacological therapies, botulinum toxin injections, and intrathecal baclofen, many patients continue to experience refractory focal or multifocal spasticity requiring alternative therapeutic approaches. Percutaneous cryoneurolysis has recently emerged as a minimally invasive peripheral neuromodulation technique capable of selectively reducing pathological muscle overactivity through reversible axonotmesis while preserving the structural framework necessary for nerve regeneration. Growing clinical experience has expanded its application across several neurological disorders; however, its role in MS has not yet been comprehensively defined. Methods: A structured narrative review was conducted through comprehensive searches of PubMed/MEDLINE, Scopus, and Web of Science. Original clinical studies evaluating percutaneous cryoneurolysis for neurological spasticity were identified and critically synthesized. Because disease-specific evidence in MS remains limited, studies involving other upper motor neuron disorders, including stroke, cerebral palsy, traumatic brain injury, and spinal cord injury, were also considered to provide a broader overview of current clinical applications, procedural techniques, safety, and functional outcomes. Results: The available evidence includes case reports, case series, and prospective and retrospective observational studies, together with recent evidence syntheses. Across different neurological conditions, ultrasound-guided cryoneurolysis has consistently demonstrated technical feasibility and a favorable safety profile, with reported reductions in spasticity, improvements in passive range of motion, pain reduction, facilitation of positioning and nursing care, and, in selected studies, improved functional performance. Recent observational cohorts and prospective studies have expanded the evidence base by providing larger patient populations and longer follow-up, while systematic evidence syntheses have confirmed the growing clinical interest in this technique. Nevertheless, substantial heterogeneity persists regarding patient selection, target nerves, procedural protocols, outcome measures, and duration of follow-up. Evidence specifically addressing patients with MS remains limited and is currently derived primarily from individual case reports and small clinical series. Conclusions: Current evidence suggests that percutaneous cryoneurolysis represents a promising minimally invasive adjunctive treatment for selected patients with focal or multifocal neurological spasticity, including those with multiple sclerosis. However, the available evidence remains predominantly observational, and randomized controlled trials comparing cryoneurolysis with established therapies are still lacking. Future multicenter prospective studies, standardized treatment protocols, and disease-specific investigations are required to better define patient selection, long-term efficacy, safety, and the role of cryoneurolysis within contemporary multidisciplinary spasticity management. Full article

In recent years, the application of virtual reality (VR) in rehabilitation medicine has gained increasing attention. VR is generally classified into two types: non-immersive and immersive systems. Non-immersive VR allows patients to interact with virtual environments through screens while maintaining a connection with the real world. Several studies have reported that the combined application of non-immersive VR and adjunctive technologies such as transcranial direct current stimulation and hand exoskeleton devices could facilitate functional recovery of hemiparetic limbs after stroke. In contrast, immersive VR is applied with the use of head-mounted displays to encompass the user’s visual field, providing a high level of immersion and an enhanced sense of presence. This enhanced experience has been shown to promote patients’ attention and motivation, which are important factors in motor learning. Emerging evidence suggests that immersive VR is effective for improving upper limb motor function in post-stroke hemiparetic patients. Furthermore, rehabilitative training performed in immersive virtual environments may facilitate the transfer of acquired motor skills to real activities of daily living. Future research should aim to generate high-quality evidence through large-scale, multicenter randomized controlled trials to better establish the clinical efficacy and optimal implementation of VR-based interventions in stroke rehabilitation. Full article

Synaptic failure is the most accurate pathological correlate of cognitive and motor decline in neurodegenerative diseases. However, the molecular logic governing selective synaptic vulnerability in Alzheimer’s (AD) and Parkinson’s (PD) remains a fundamental enigma. This review dissects the hierarchical organization of the synaptome, arguing that synaptic decay is not a generic process of attrition but a specific collapse of subsynaptic domains (SSDs) and trans-synaptic nanocolumns, considered here within the framework of the tetrapartite synapse, which comprises the presynaptic and postsynaptic compartments together with glia and the perisynaptic extracellular matrix. We use the term pathological convergence in a restricted sense, to denote that, although the primary aggregates differ, the two diseases converge on the same postsynaptic scaffolding hubs and on a comparable loss of condensate fluidity. We propose a biophysical model where the Post-Synaptic Density (PSD) matrix, governed by liquid–liquid phase separation (LLPS), may undergo a pathological liquid-to-solid transition—characterized by condensate maturation and the formation of insoluble protein aggregates—driven by proteotoxic species. Specifically, we analyze how Aβ-mediated zinc sequestration disrupts the Shank-SAM scaffold hierarchy in AD, while α-synuclein aggregates arrest presynaptic vesicle dynamics and mitochondrial homeostasis in PD. Furthermore, we explore the emerging frontier of “Precision Synaptopharmacology,” highlighting how targeted modulation of protein–protein interaction (PPIs), synthetic synaptic organizers (e.g., CPTX), and phase-stabilizing chaperones can restore nanocolumn alignment and synaptic fluidity. We also set out the principal limitations of these strategies, including blood–brain barrier delivery, off-target effects, the immaturity of condensate-directed pharmacology and the incomplete translation of rodent findings to human disease, and we consider the vascular and peripheral contributions that modify the synaptic environment. By integrating recent advances in super-resolution microscopy, systems biology, and activity-based neurorehabilitation, we provide a comprehensive framework for shifting neuroprotective strategies toward the precision engineering and functional recovery of synaptic nano-architecture. Full article

Background/Objectives. Headache and migraine were exacerbated by light during an episode, with light also serving as a diathesis for pain between episodes. Such interictal photosensitivity has been hypothesized to reflect heightened sensitivity to blue-cyan (BC) light, due to activation of melanopsin-based intrinsically photosensitive retinal ganglion cells (ipRGCs). This study examined evidence for wavelength-selective photosensitivity and its relation to headaches/migraine and accompanying functional sequelae. Methods. Individuals with persistent post-traumatic headache (N = 325) were assessed for photosensitivity with an analysis of filtered wavelengths that resulted in relief. A subsample (n = 209) wore precision tinted lenses that matched their individual wavelength photosensitivity profile for over a 1–3-month follow up period and were assessed on a variety of persistent functional complaints. Results. Analysis of wavelengths associated with photosensitivity did not support differential sensitivity to the BC range, revealing greater sensitivity to light below 440 nm and less sensitivity above 680 nm, but with a coefficient of variation of 94.7%, consistent with extremely high individual variation. Individuals who showed near elimination of photosensitivity (97.9%) had decreased self-reported headache frequency (92.6%), as well as reported diminished physical, emotional and cognitive complaints, with these functional outcomes unrelated to the magnitude of BC filtering. Conclusions. These results suggested (1) wavelengths evoking photosensitivity were highly individually variable and (2) interictal exposure to a variety of wavelengths may have contributed to post-traumatic head pain and associated impaired global function, pointing toward common central origins. Full article

Neurorehabilitation units (NRUs) are long-term care settings associated with multiple risk factors for carriage and infection by multidrug-resistant organisms (MDROs), including prolonged hospitalization, the use of invasive medical devices, high antibiotic exposure, and multiple comorbidities. We report the case of a patient admitted to an NRU for rehabilitation after cerebral hemorrhage who developed complex co-colonization by several MDROs, including Pseudomonas aeruginosa producing either FIM or VIM metallo-β-lactamases, Acinetobacter baumannii producing OXA-23 serine-carbapenemase, Klebsiella pneumoniae producing either KPC or OXA-48 serine-carbapenemases or both, Proteus mirabilis producing VEB extended-spectrum β-lactamase, and vancomycin-resistant Enterococcus faecium of the VanA type. During the 22-month hospitalization, the patient experienced several infection episodes, some of which were apparently related with colonizing MDROs. This case highlights that co-colonization by multiple MDROs may occur in patients admitted to NRUs in endemic settings, and emphasizes the importance of implementing targeted infection prevention and control strategies in these healthcare environments. Full article

Background/Objectives: The sit-to-stand task is widely used to assess functional performance after stroke; however, how upper-limb involvement is addressed methodologically during this transition remains unclear. This study aimed to map how upper-limb postural orientation has been considered, operationalised and controlled during sit-to-stand assessment in individuals after stroke, with particular attention to experimental protocols, assessment instruments, and biomechanical outcome measures. Methods: A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, and the literature search was performed using PubMed, Web of Science, ScienceDirect and Google Scholar. Results: Across the 10 included studies, 264 unique individuals after stroke were assessed from eight independent samples (sample-weighted mean age: 60.2 years). Three studies shared the same participant cohort and were counted once in all aggregate figures. Most studies adopted cross-sectional observational designs (n = 7), and laboratory-based biomechanical settings were the most common assessment context (n = 6). Upper-limb conditions were explicitly reported in all studies but were predominantly constrained or standardised, most frequently with the arms crossed over the chest (n = 4). Only four studies compared different upper-limb conditions. Instrumented assessments primarily relied on 3D motion analysis systems and force platforms, whereas clinical assessments focused mainly on temporal performance measures. Comprehensive 3D analyses of upper-limb contribution and multi-segmental coordination remain scarce. Conclusions: This scoping review reveals limited and methodologically heterogeneous evidence on upper-limb involvement during sit-to-stand assessment after stroke, underscoring the need for greater methodological clarity and biomechanical characterisation. Full article

Purpose: Upper extremity motor impairments following stroke substantially limit independence in daily living. Hand-tracking virtual reality (VR) rehabilitation systems may support intensive task-oriented practice while enhancing motivation; however, evidence integrating objective kinematic indicators with usability and patient-reported outcomes for controller-free consumer-grade VR remains limited. The primary aim of this single-arm pilot study was to evaluate the feasibility, safety (tolerability), and usability of a hand-tracking VR rehabilitation system delivered as an adjunct to conventional physiotherapy in individuals with stroke; describing its preliminary in-game kinematic profile and exploring participants’ experiences through open-ended feedback were secondary aims. The study was explicitly not designed or powered to test clinical efficacy. Materials and Methods: Ten individuals with stroke completed a 20-session (8-week) single-arm pilot intervention; all participants concurrently received standard hospital-based physiotherapy (median 3 sessions/week, ∼45 min/session). Early-phase (sessions 1–5) and late-phase (sessions 16–20) within-subject performance were compared using the Wilcoxon signed-rank test with Holm–Bonferroni correction across four pre-specified primary outcomes. Movement smoothness was assessed using the Spectral Arc Length (SPARC), usability was evaluated using the System Usability Scale (SUS), and cybersickness was monitored with the Simulator Sickness Questionnaire (SSQ). Results: Sixteen patients were screened, of whom fourteen started the intervention and ten completed the 8-week per-protocol program (intervention completion rate, 10/14 = 71.4%; per-protocol session adherence among the ten completers, 200/200 = 100%; no SSQ-defined adverse events). Within-subject comparisons showed a $+10.6$-point increase in success rate (adjusted $p=0.020$), a $+0.10$ m/s increase in mean movement speed (adjusted $p=0.020$), a $-341$ ms reduction in pause duration (adjusted $p=0.022$), and a $+27.0$-point Hodges–Lehmann median-difference increase in SS-QOL (95% CI $14.0$–$41.0$; participant-level median $\mathsf{\Delta }$$+18.5$; adjusted $p=0.020$). The mean SUS score was $78.5\pm 5.4$, indicating “good” usability. Thematic analysis of post-intervention open-ended feedback identified three themes—motivation and engagement, the value of feedback, and design and comfort suggestions—that converged with the high adherence and good usability ratings. Correlations between VR-derived kinematic change and clinical change were non-significant trends ($p\ge 0.12$). Conclusions: A controller-free hand-tracking VR system was found to be feasible, well tolerated, and rated as having good usability when delivered as an adjunct to conventional therapy. Because the study used a single-arm design, included only ten participants, and did not control for the confounding effect of concurrent conventional physiotherapy or natural recovery, the observed within-subject changes cannot be causally attributed to the VR intervention and should be interpreted as exploratory feasibility signals. Adequately powered randomized controlled trials with stroke-specific clinical scales (e.g., FMA-UE, ARAT) are required before clinical efficacy can be claimed. Full article

Background: Robotic rehabilitation systems for upper-limb stroke rehabilitation have been developed across diverse robotic platforms, yet cross-study comparisons remain challenging due to heterogeneous system designs and classification approaches. This brief narrative review proposes a paradigm-driven framework, categorizing robotic rehabilitation systems based on underlying therapeutic interaction principles (e.g., mirror, bimanual, mirror–bimanual hybrid) rather than implementation modality alone. Methods: A structured MEDLINE/PubMed literature search was performed to identify representative studies describing robotic system characteristics, rehabilitation task structures, clinical outcomes, and mechanistic insights within mirror, bimanual, and hybrid rehabilitation paradigms. Findings: Among the reviewed studies, mirror-based systems emphasize sensory representation and interhemispheric modulation, whereas bimanual systems target coordination and motor learning through bilateral interaction. Hybrid systems integrate these approaches by combining mirrored feedback with active bilateral engagement. Emerging neuroimaging evidence, particularly resting-state fMRI, may help relate clinical improvements to neural network changes, providing a mechanism-informed perspective on rehabilitation outcomes. Conclusions: This review highlights substantial progress in robotic upper-limb stroke rehabilitation, with current systems increasingly integrating multimodal feedback and task-oriented interaction within mirror, bimanual, and hybrid rehabilitation paradigms. Limitations include variability across studies due to differences in robotic system implementation, task design, duration, stroke chronicity, and patient engagement. Full article

Background: Peak oxygen uptake (VO₂peak), as measured by cardiopulmonary exercise testing (CPET), is considered the gold standard for assessing cardiorespiratory fitness (CRF). However, CPET is not always feasible in rehabilitation settings. The 6-min walk test (6MWT) is simple and widely used, yet its relationship with CPET-derived measures in patients with subacute cerebral infarction remains unclear. Methods: A total of 122 patients with subacute cerebral infarction underwent both the 6MWT and CPET. VO₂peak, CPET-derived peak heart rate (CPET HRpeak), 6-min walk distance (6MWD), 6MWTpeak heart rate (6MWT HRpeak), and the ratio of 6MWT HRpeak to age-predicted maximal heart rate were assessed. Results: In multivariate linear regression analysis, 6MWD was independently associated with VO₂peak (unstandardized coefficient B = 0.010, p < 0.001). Partial correlation analyses adjusting for age, sex, and β-blocker use showed that CPET HRpeak was positively correlated with 6MWD (ρ = 0.361, p < 0.001) and 6MWT HRpeak (ρ = 0.217, p = 0.018). The ratio of 6MWT HRpeak to age-predicted maximal heart rate did not mediate the association between 6MWD and VO₂peak. Conclusions: In patients with subacute cerebral infarction, 6MWD was independently associated with VO₂peak, while both 6MWD and 6MWT HRpeak were positively correlated with CPET HRpeak. These findings suggest that the 6MWT may help assess CRF when CPET is not available. Full article

Background: Stroke remains a leading cause of long-term disability worldwide. Post-stroke spasticity (PSS) is increasingly recognized as a complex complication resulting from the interaction between neural hyperexcitability and non-neural muscular adaptations, including fibrosis, altered muscle architecture, and increased stiffness. Consequently, effective management requires a comprehensive approach targeting both components. Musculoskeletal ultrasound (MSK US) has emerged as a practical tool for muscle characterization, treatment targeting, and longitudinal monitoring within neurorehabilitation programs. Aim: To propose a clinical practice framework integrating serial MSK US into multimodal PSS management and to illustrate its application through a proof-of-concept clinical case. Methods: The proposed framework combines standardized clinical assessment, serial MSK US evaluation, BoNT-A injections, physical modalities (neuromuscular electrical stimulation and extracorporeal shock wave therapy), and task-oriented rehabilitation. Ultrasound findings, including muscle echogenicity, architecture, and Modified Heckmatt Scale (MHS) characteristics, were integrated with clinical outcomes and rehabilitation goals to support individualized decision-making. Results: Serial MSK US provided complementary information regarding muscle quality and potential non-neural contributors to spasticity syndrome, supporting treatment planning and follow-up. Although only modest morphological changes were observed over time, the illustrative case showed favorable changes in clinical assessments including spasticity, motor performance, gait, and functional independence following the multimodal intervention. Conclusions: This proof-of-concept framework highlights the potential role of serial MSK US as a practical decision-support and monitoring tool within multimodal PSS management. Integrating clinical assessment with ultrasound-informed evaluation of both neural and non-neural components may facilitate more individualized rehabilitation strategies and optimize functional outcomes. Further studies are warranted to validate and standardize this approach. Full article

Background: Problematic school attendance in adolescence is a heterogeneous phenomenon with academic, emotional, and developmental consequences. Although relational factors are increasingly recognised, the literature remains conceptually fragmented, with overlapping constructs such as social isolation, loneliness, social withdrawal, and peer difficulties examined under partially distinct frameworks. Objective: This systematic review aimed to synthesize empirical evidence on the association between social isolation, related constructs, and problematic school attendance during adolescence. Methods: Following PRISMA 2020 guidelines, searches were conducted in PubMed, Scopus, and Embase (final search: 20 January 2026). Eligible studies were observational or qualitative empirical investigations involving adolescents aged 11–18 years and examining at least one relational construct (objective/subjective social isolation, loneliness, social withdrawal, peer rejection) together with at least one school attendance outcome (school refusal, withdrawal, truancy, avoidance, dropout). Risk of bias was assessed with design-specific JBI tools and findings were synthesized narratively. Results: Eleven studies met the inclusion criteria: six cross-sectional, four longitudinal/cohort, and one qualitative. Loneliness, bullying, school alienation, and social isolation at school were most consistently associated with school refusal and absenteeism, whereas peer acceptance, reciprocal friendships, teacher emotional support, and school belonging were associated with reduced dropout intentions, higher graduation rates, and better school transition. Longitudinally, loneliness and low teacher support preceded increases in intention to quit, while supportive relationships appeared to protect against later disengagement. Conclusions: Social isolation and related constructs are meaningfully associated with problematic school attendance in adolescence. Social isolation and related constructs appear to be meaningfully associated with problematic school attendance in adolescence, although the evidence base remains limited and heterogeneous. These findings suggest that a relational perspective may usefully complement existing approaches to attendance difficulties, and point to the need for longitudinal, multi-informant studies disentangling subjective, interpersonal, and institutional disconnection across distinct attendance profiles. Full article

Background: Advanced endovascular procedures are increasingly used for ischemic stroke, but real-world evidence from middle-income settings remains limited, particularly regarding survival, disability, and neurorehabilitation. This study examined mortality, recorded disability, procedure-related differences, and neurorehabilitation exposure among patients receiving high-technology stroke care in Almaty, Kazakhstan. Methods: We conducted a retrospective cohort study of 328 adults with ischemic stroke who underwent endovascular or stent-based procedures between 2014 and 2024. Survival was assessed using Kaplan–Meier analysis and Cox proportional-hazards regression. Binary mortality status and recorded disability were examined using logistic regression. Procedure codes were grouped as mechanical thrombectomy/endovascular removal, intracranial stenting, and embolization/coiling/other procedures. Results: Neurorehabilitation was received by 39% of patients and was associated with better crude survival (1 year survival 93.6% vs. 76.7%; 5-year survival 69.0% vs. 60.7%; log-rank p = 0.001). In the adjusted Cox model, older age (HR = 1.069, 95% CI 1.046–1.092, p < 0.001) and greater total bed-day burden (HR = 1.071, 95% CI 1.029–1.116, p = 0.001) were associated with higher mortality hazard. Binary neurorehabilitation was not independently associated with survival (p = 0.803). Male sex was the only consistent factor associated with recorded disability (fully adjusted OR = 2.662, 95% CI 1.261–5.617, p = 0.010). Conclusions: Older age and bed-day burden were the most stable mortality-related factors. Neurorehabilitation was linked to better crude survival but not adjusted survival or recorded disability. Procedure-related and disability findings should be considered exploratory because baseline stroke severity and validated functional scales were unavailable. Full article