PurposeIn this randomised controlled trial study, we aimed to preliminarily evaluate the effectiveness of purposeful activity-based electrical stimulation therapy (PA-EST) in improving independence in daily living in patients with stroke and moderate-to-severe upper limb hemiparesis.MethodsThis study was conducted in the rehabilitation ward of Kyoto Ohara Memorial Hospital, Japan. Sixteen rehabilitation ward inpatients who experienced stroke and moderate-to-severe upper limb hemiparesis were included. In this randomised controlled trial, the participants were randomly assigned to either PA-EST or conventional occupational therapy (COT) and received a 2-month intervention. The primary outcome measures included motor, cognitive, and total scores on the functional independence measure (FIM). The secondary outcome measures included the Motor Activity Log (MAL), Amount of Use and Quality of Movement (QOM) subscales, and the Upper Extremity, Lower Extremity, and Total Fugl-Meyer Assessment scores.FindingsTwo-way repeated measures analysis of variance revealed significant interactions for FIM-motor (p = 0.041), FIM-total (p = 0.029), and MAL-QOM (p = 0.005), with greater improvements in the PA-EST group than in the COT group. No significant interactions were observed for the other outcome measures.ConclusionsThis randomised controlled trial study provides preliminary evidence that PA-EST may enhance activities of daily living independence in patients with subacute-phase stroke and moderate-to-severe upper limb hemiparesis. These findings support the clinical utility of PA-EST as a novel intervention strategy for advancing stroke rehabilitation.
Vision is a multicomponential system where different aspects of visual processing rely on distinct neural circuits. This fundamental characteristic has profound implications for how we assess visual field defects. Classical gold standard perimetry focuses primarily on contrast detection. However, the size of the scotoma could be different when measured with kinetic perimetry since motion detection relies on different neural networks. Therefore, we developed and validated a high-precision eye-tracking kinetic perimetry as a complementary tool for evaluating visual field deficits in hemianopia. We emphasized methodological transparency and precise measurement of the transition zone between sighted and blind areas. Thirty-seven participants (17 with retrochiasmal lesions and 20 healthy controls) underwent test-retest evaluation using a kinetic perimetry system integrated with a Tobii Pro Spectrum eye tracker (0.03° RMS precision, 0.3° accuracy, 600 Hz sampling rate). Results demonstrated excellent test-retest reliability with adjusted ICC values exceeding 0.90 across all conditions. The application of an algorithm (LOESS) for noise reduction further improved measurement stability, with ICC increasing to 0.996 for controls and 0.988 for patients, while reducing standard deviation of errors from 4.69° to 1.52° in the affected visual field of patients. Based on these findings, we propose that a visual field enlargement exceeding 5° can be considered a meaningful change beyond the measurement variability of our perimetry. By embracing methodological transparency, including detailed disclosure of eye-tracking specifications and error measurements, and recognizing the multicomponential nature of vision, we aim to contribute to the understanding of visual field defects and their potential for recovery.
BackgroundRates of mental illness in adolescents are increasing at an alarming rate. At the same time, youth participation in physical activity is continually declining. International public health guidelines recommend that children spend at least 60 min/day in moderate-to-vigorous physical activity for optimal development of brain health. This study aimed to disentangle within-person effects of physical activity on mental health symptoms from stable, between-person differences using a four-wave random-intercepts cross-lagged panel model (RI-CLPM).MethodsData from the longitudinal Adolescent Brain Cognitive Development (ABCD) Study were used to follow pre-adolescent children (N = 6361) across development (10-14.2 years old). Physical activity was measured by youth-report. Internalizing and externalizing mental health behaviors were measured by the parent-reported Child Behavior Checklist. Bidirectional relationships between mental health and physical activity were assessed using RI-CLPM.ResultsFor internalizing symptoms, cross-lagged (within-person) random effects showed that higher physical activity at year 2 predicted fewer internalizing symptoms at year 3 (β= -0.037 [-0.062 to -0.012]), and from year 3 to year 4 (β = -0.045 [-0.068 to -0.022]). More internalizing symptoms at baseline predicted less physical activity from year 2 to year 3 (β = -0.076 [-0.125 to -0.027]), and from year 3 to year 4 (β = -0.075 [-0.118 to -0.031]). For externalizing symptoms, there were no significant cross-lagged or between-person effects.ConclusionIn this large, multi-wave longitudinal cohort, more physical activity was associated with fewer internalizing symptoms across early adolescent development. Additionally, higher internalizing symptoms were associated with lower physical activity across development. No associations were found with externalizing symptoms. Findings suggest that physical activity may alleviate internalizing symptoms during early adolescence, underscoring the need for promoting adherence to international physical activity guidelines in the complex management of adolescent mental health.
ObjectiveCyclophosphamide (CYP) is one of the chemotherapeutic agents known to cause neurotoxicity. The aim of this study was to experimentally investigate the potential therapeutic effect of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in the prevention of CYP-related neurotoxicity.MethodsA total of 18 rats were divided into three groups: Group 1: CYP, Group 2: CYP + stem cell, Group 3: control. Groups 1 and 2 received intraperitoneal (IP) CYP for 14 days, while the control group received IP saline. Subsequently, hUC-MSCs were administered to Group 2 as treatment. Mesenchymal stem cell (MSC) treatment was initiated only after completion of cyclophosphamide (CYP) administration to induce neurotoxicit. At the end of the first month, the animals were euthanized. Brain tissues were collected and examined using H&E, neurofilament immunostaining, and silver nitrate staining. Neurodegeneration and regeneration in the cerebral and cerebellar cortices were evaluated in a blinded histopathological manner. Histopathological evaluation of degeneration in the cerebral and cerebellar cortex, as well as cerebral gliosis, was performed and graded between 1 and 4 (0-25%: grade 1, 25-50%: grade 2, 50-75%: grade 3, 75-100%: grade 4).ResultsIn the CYP group (Group 1), degeneration in the cerebral and cerebellar cortex and a higher number of cerebral glial cells were significantly higher compared to the other groups (p < 0.001; p < 0.001; p < 0.001). In Group 2 (CYP + stem cell), evidence of regeneration was observed in the cerebral and cerebellar cortex, along with a reduction in cerebral glial cells (p < 0.001). The results of the stem cell-treated group were closer to those of the control group.ConclusionhUC-MSCs demonstrated a neuroprotective effect against CYP-induced neurotoxicity. Stem cell therapy may represent a promising approach to prevent the neurodegenerative effects of cytotoxic agents.
Executive function (EF) is improved following a single bout of exercise. Recently, it has been proposed the timing between exercise and rest intervals (i.e., exercise density) within a single bout of exercise (or across days or months of exercise) may serve as an important moderator in the expression and/or magnitude of an EF benefit. Here, participants (N = 25) completed separate interval exercise conditions - as well as a non-exercise control - wherein ten 1-min intervals of exercise (40% of 1 repetition max leg extensions at 0.25 Hz) were interspersed with 1-min (high-density: HD) or 2-min (low-density: LD) of rest. Prior to and following exercise (∼5-min), the antisaccade task (i.e., saccade mirror-symmetrical to a target) was used to assess the inhibitory control component of EF. Antisaccades were selected given the task's hands- and language-free nature and because they are mediated via EF networks showing task-dependent single-bout exercise changes. Peak systolic middle cerebral artery velocity (MCAvpeak), perceived exertion, arousal and neuromuscular fatigue were measured to identify a potential psychophysiological metric associated with a putative density-linked postexercise EF change. Frequentist and Bayesian statistics demonstrated that the LD - but not HD - condition produced a pre- to postexercise reduction in antisaccade reaction times (RTs), and across LD and HD conditions psychophysiological metrics did not demonstrate an association with postexercise antisaccade RT changes. Hence, results provide nascent evidence that density may moderate a single bout postexercise inhibitory control benefit and demonstrate that density may provide a framework to understand the interdependent psychophysiological mechanisms contributing to the benefit.
IntroductionRestoring normal gait function remains a major clinical challenge in post-stroke rehabilitation. Backward walking may increase neuromotor demands compared with forward walking and performing it on an incline may further augment task complexity. However, the feasibility, safety, and tolerability of backward incline walking in individuals with chronic stroke have not been systematically examined.ObjectiveTo evaluate the feasibility of a single-session treadmill-based backward incline walking protocol in individuals with chronic stroke, focusing on recruitment, adherence, safety, tolerability, and participant acceptability.MethodsDesignProspective, nonrandomized pilot feasibility study.SettingClinical Human Dynamic Laboratory at a university-affiliated rehabilitation program.ParticipantsSix individuals with chronic stroke (≥6 months post-event) were enrolled (median age 68 years, interquartile range [IQR] 56-73, median time since stroke of 19 months IQR [15-98]). Inclusion criteria included ambulatory ability with or without a single cane for ≥10-meter and absence of cognitive, orthopedic, or cardiopulmonary contraindications, and ability to tolerate 15 min of treadmill walking. All participants met these criteria and provided informed consent.InterventionParticipants completed three treadmill walking conditions delivered in a fixed order (level, forward incline, and backward incline walking), each for up to 15 min at self-selected speeds. Rest breaks and manual support were provided as needed.Main OutcomesFeasibility metrics included recruitment rate, protocol adherence, safety (adverse events), tolerability (rating of perceived exertion), and participant acceptability.Secondary Descriptive MeasuresOverground walking speed and spatiotemporal gait parameters recorded using an instrumented walkway before and after the treadmill conditions. These data were summarized descriptively without inferential statistical testing.ResultsRecruitment was feasible, with 40% of eligible individuals enrolled. All participants completed the single-session protocol without adverse events. Perceived exertion increased in our sample with task complexity and was highest during backward incline walking (median RPE = 6). Participant acceptability was high, with all individuals expressing willingness to repeat the protocol.SignificanceA single-session treadmill-based backward incline walking was feasible, safe, and well-tolerated in this pilot sample of ambulatory individuals with chronic stroke. These findings progression to adequately-powered, randomized studies designed to evaluate efficacy and to address order effects and individualized gait responses.
BACKGROUND:Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a neuromodulatory intervention to facilitate motor recovery after stroke. However, the frequency-specific effects of rTMS on lower-limb motor control and their neurophysiological correlates remain insufficiently clarified. OBJECTIVE:To compare the effects of low-frequency (1 Hz) rTMS applied over the contralesional (unaffected) lower-limb motor area of the primary motor cortex and high-frequency (10 Hz) rTMS applied over the ipsilesional (affected) lower-limb motor area on electroencephalographic (EEG) activity, affected-side lower-limb muscle activation, balance, and gait in individuals with chronic stroke. METHODS:Thirty-nine participants with chronic stroke were randomly assigned to a low-frequency rTMS group (n = 13), a high-frequency rTMS group (n = 13), or a sham group (n = 13). rTMS was delivered for 10 sessions over 2 weeks. Resting-state EEG (relative beta-band power at Cz), surface EMG of the affected-side rectus femoris, biceps femoris, tibialis anterior, and gastrocnemius during sit-to-stand, Timed Up and Go (TUG), 10-meter walk test (10MWT), and limits of stability (LOS) were assessed before and after the intervention. A 3 × 2 mixed-design analysis of variance (ANOVA) (group × time) was conducted. RESULTS:Significant group × time interactions were observed for rectus femoris activation (p < 0.001) and TUG performance (p = 0.037). Post hoc pairwise comparisons confirmed significantly greater improvements in TUG performance and rectus femoris activation in the low-frequency rTMS group than in the high-frequency and sham groups. Relative beta-band activity at Cz demonstrated a significant main effect of time (p < 0.001) without a significant interaction effect. Similarly, 10MWT and LOS showed significant time effects (p < 0.05) but no significant group × time interactions. No significant main effects of group were identified across outcomes. CONCLUSION:Short-term rTMS was associated with improvements in selected neuromuscular outcomes, while changes in resting cortical activity, gait speed, and postural stability appeared to reflect general time-related effects. Low-frequency rTMS demonstrated greater improvements in rectus femoris activation and TUG performance compared with high-frequency and sham stimulation. These findings suggest that frequency-specific rTMS may preferentially influence neuromuscular strategies underlying dynamic mobility rather than steady-state gait performance.
Stroke remains one of the leading causes of death and long-term disability worldwide, often resulting in persistent motor impairments that limit independence and quality of life. This special issue highlights recent advances in stroke assessment and rehabilitation driven by the convergence of engineering, neuroscience, and motor control. The contributions are organized around four themes: (1) the importance of rigorous theoretical and methodological foundations to improve reproducibility and clinical translation; (2) the role of neuroplasticity, neuromodulation, and cognition in enhancing recovery; (3) emerging insights into neurophysiological and motor control mechanisms across cortical and spinal levels; and (4) innovations in assessment tools and rehabilitation technologies, including accessible, low-cost, and real-world solutions. Collectively, these studies demonstrate how interdisciplinary approaches are advancing both the science and practice of stroke rehabilitation, with an emphasis on clinically feasible strategies that can improve functional recovery and outcomes for individuals living with stroke.
Recent studies have shown that supplemental sensory feedback systems have potential to mitigate functional impairment after neuromotor injury through mechanisms of sensory augmentation or replacement. In this proof-of-concept case series, we evaluated multi-session 3-dimensional kinesthetic vibrotactile feedback training as a means to enhance the accuracy and efficiency of goal-directed reaching in the absence of visual feedback in survivors of stroke. A motion capture system converted real-time position of the contralesional hand within a Cartesian frame of reference into spatiotemporal patterns of vibrotactile feedback provided to the non-moving, ipsilesional arm. Seven survivors of stroke underwent 9 hours of reach-to-grasp training under conditions that encouraged them to learn a mapping from hand position to patterns of vibrotactile feedback. We then assessed their ability to use that feedback to improve the accuracy and efficiency of reaches performed without concurrent visual feedback. Within-subject comparisons to baseline performance revealed heterogeneous learning effects on reaching both with and without supplemental vibrotactile feedback. When reaching with the supplemental feedback after training, three participants significantly improved reach accuracy, two significantly improved temporal efficiency, and three significantly improved spatial efficiency (although one significantly worsened with regard to spatial efficiency). Further, all but one of the participants who exhibited post-training performance changes during movements made with the supplemental feedback also exhibited similar post-training performance changes during movements made without the supplemental feedback. These results suggest that while a subset of stroke survivors may accrue benefits from using the form of supplemental vibrotactile kinesthetic feedback described in the paper, the effects of such training resulted primarily from ancillary benefits provided by the 9 hours of intensive reach-to-grasp training with the feedback, rather than from the ongoing use of the feedback itself. Despite the mixed kinematic results, responses to standard surveys of subjective experience suggest that training with the vibrotactile display had acceptable usability and was both motivating and satisfying to use. We conclude that while the wearable technology may provide a positive user experience, practical benefits (e.g., increased reach accuracy or efficiency) may accrue more from hours of focused reach training than from the additional sensory information provided by the vibrotactile interface. (National Clinical Trial Number: NCT03298243; clinicaltrials.gov/study/NCT03298243).
Constipation is a common but often overlooked issue among stroke survivors, despite its adverse impact on recovery. Herein, we describe an unexpected improvement in constipation following aerobic exercise during the rehabilitation of a patient in the subacute stage of stroke. A man in his 70 s with moderate right-sided hemiparesis following a pontine infarction was admitted for inpatient rehabilitation. Despite maintaining a stable diet and fluid intake, as well as regular use of laxatives, he experienced persistent constipation (one to three bowel movements per week). After 4 weeks of standard rehabilitation, an aerobic exercise regimen was introduced, comprising 30-min sessions on a recumbent ergometer performed five times per week at 50% of the heart rate reserve. No changes were made to his medication, diet, or other therapies during the aerobic exercise period. After initiating aerobic exercise, the patient's bowel movement frequency increased rapidly to four to six times per week, with a marked reduction in constipation symptoms evident from the first week of intervention. To evaluate the effectiveness of aerobic exercise, the percentage of non-overlapping data (PND) was calculated. The PND was 75%, indicating that the intervention was effective. This improvement was sustained both during and after the aerobic exercise period. No other potential confounding factors were identified. This case highlights a temporal association between moderateintensity aerobic exercise and improved constipation in a patient with stroke, suggesting that exercise may warrant investigation as a potential adjunctive intervention. However, the retrospective, single-case design precludes causal inference, and the observed improvements could reflect natural variation or unmeasured confounders. A plausible mechanistic
Intermuscular coherence (IMC), especially in the beta band, has been widely used as a non-invasive approach to estimate the strength of corticospinal connectivity. The corticospinal tract is frequently damaged as a result of stroke, which may impair the strength of corticospinal connectivity, particularly that contributing to manual dexterity. Here we investigated acute adaptations in IMC and manual dexterity in fifteen chronic stroke survivors and seven age-matched healthy controls who performed exercise to task-failure with their non-paretic hand (or dominant hand for healthy controls). Dexterity (measured by Box-and-Blocks Test, BBT) and IMC were tested at baseline, following exercise to task-failure, and every 45 min until 4 h after task-failure (7 times in total). At baseline, paretic hand beta and gamma band IMC were significantly reduced in stroke survivors (P's = 0.006). Additionally, at baseline paretic hand (or non-dominant hand for healthy controls) BBT performance and gamma band IMC revealed significant positive correlations in both stroke survivors (R2 = 0.40, P = 0.010) and the whole sample (R2 = 0.33, P = 0.005). Paretic hand BBT performance increased immediately and at 225 min after task-failure compared with baseline (P's = 0.017 and 0.014, respectively). Paretic hand beta band IMC increased immediately and remained significantly elevated at 45 min after task-failure (P = 0.045 and 0.005, respectively) while paretic hand gamma band IMC was increased at 135 min after task-failure (P = 0.051). Taken together, our results suggest increased strength of corticospinal connectivity to the paretic hand as an acute adaptation to non-paretic hand exercise to task-failure. Concurrent facilitation of paretic hand manual dexterity and strengthened ipsilesional corticospinal connectivity suggests this approach should be explored as a strategy to promote recovery of corticospinal connectivity and paretic hand motor function in neurorehabilitation.
BACKGROUND:Spinal cord injury (SCI) is a devastating condition characterized by inflammation, oxidative stress, and neuronal damage. These factors contribute significantly to the secondary injury phase, exacerbating tissue degeneration and impairing recovery. While many therapeutic approaches focus on reducing these detrimental processes, the use of natural products like Moringa peregrina (M.P), a plant known for its antioxidant and anti-inflammatory properties, remains underexplored. This study investigates the neuroprotective effects of the alcoholic extract of Moringa peregrina leaves on SCI, evaluating its impact on oxidative stress, inflammation, and both structural and functional recovery. MATERIALS AND METHODS:In this study, fifty-four male Wistar rats were randomly assigned to three groups: laminectomy (sham), SCI (injection of saline intraperitoneally for 21 days), and SCI + Moringa peregrina (150 mg/kg of M.P extract injected intraperitoneally for 21 days). Motor function was assessed using the Basso, Beattie, and Bresnahan (BBB) scale throughout the study period. At 21 days post-injury, we measured the activity of antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], total antioxidant capacity [TAC]), the oxidative stress marker malondialdehyde (MDA), and inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-18), alongside nuclear factor kappa B (NF-κB). Histological analyses were performed using hematoxylin and eosin (H&E) and cresyl violet staining to evaluate neuronal damage and tissue density. RESULTS:Intraperitoneal administration of Moringa peregrina extract significantly reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-18) and the oxidative stress marker MDA, while enhancing the activity of SOD, GPx, CAT, and TAC. These changes were associated with a marked reduction in NF-κB expression. Histological analysis revealed less cellular damage and increased tissue density in the SCI + Moringa peregrina group compared to the SCI group, indicating preserved neuronal structure. Furthermore, motor function recovery was significantly improved in the SCI + Moringa peregrina group, as evidenced by higher BBB scores compared to the untreated SCI group. CONCLUSION:The findings of this study demonstrate that the alcoholic extract of Moringa peregrina leaves exerts neuroprotective effects through modulation of oxidative stress, inflammation, and structural preservation. The improvement in both motor function and spinal cord tissue integrity highlights the potential therapeutic value of Moringa peregrina in the treatment of SCI.
In keeping with the topic of this special issue, "Breakthroughs in Stroke Rehabilitation: Bridging Engineering, Neuroscience, and Motor Control," this commentary addresses the recent emergence of computer vision motion capture (CVMC, aka markerless motion capture) with a realistic check-in on its current measurement performance and future utility as a clinical assessment tool. These are heady times. It would be understandable to misinterpret early demonstrations of CVMC in clinical research as a suggestion that this innovative tool is ready for clinical deployment. In reality, benchmarks for CVMC measurements are still being established, and cultivation of targeted clinical practice approaches informed by motion analysis remains aspirational. In this commentary, we reframe the CVMC conversation by first acknowledging the current state of CVMC as a technology still in development. We then consider the path to a long-term goal: targeted stroke rehabilitation in clinical practice informed by the quantification of movement function. In lighthearted spirit, we channel Douglas Adams' book series, "The Hitchhikers Guide to the Galaxy" (HG2G; Adams, 1979-1992), providing clinician hitchhikers some recommendations to deftly navigate the CVMC landscape on their intergalactic motion capture travels between lab and clinic. And so, just as Ford Prefect, the friendly alien researcher in the HG2G book series would say to reassure new hitchhikers: "You just come along with me and have a good time. The Motion Capture Galaxy's a fun place. You'll need to have a fish in your ear." - Ford Prefect (adapted from Adams; Book 1, Chapter 5).
Environmental changes in response to COVID-19 may negatively impact the development, behavior, and mental health of children with Autism spectrum disorder (ASD). Thus, it is necessary to investigate the changed behavioral goals provided.This narrative review examined studies that investigated changes in intervention methods and behavioral goals for children with ASD during COVID-19. This study searched five databases and identified ten articles meeting the inclusion criteria. These articles were evaluated for risk of bias and quality of evidence level. Behavioral goals and intervention methods were reviewed.The selected articles included two non-randomized single-group studies, six single-experiment studies, and two case studies. Behavioral goals included mask wearing, social participation and play, and behavioral regulation. Interventions included telehealth, social participation training, play-based sibling intervention, early intensive behavioral, differential reinforcement, and treatment extension for tolerating.This review identifies the need to change in intervention methods and behavioral goals for children with ASD to adapt to environmental changes due to COVID-19.
Rehabilitation devices are technologies that can automate repetitive features of therapy using force generation elements like motors to render training forces or gamified environments to improve user engagement (e.g., rehabilitation robots). These devices have received considerable attention from researchers and clinicians over the past several decades as a means to increase dosage of intensive rehabilitation following a stroke. However, the commercial results of these efforts often manifest as highly motorized, expensive, and bulky devices that are unsuitable for the majority of clinical or home environments. Indeed, as access to rehabilitation resources begins to reveal itself as a critical obstacle to recovery for many stroke survivors, it is important for researchers to examine alternative approaches to facilitate device adoption. A handful of researchers have attempted to bridge this gap with increasing success by designing affordable and portable devices for post-stroke rehabilitation. However, the methods employed to lower device cost are quite varied; therefore, a synthesis of these approaches could benefit other researchers. In this review, we discussed the field of rehabilitation robots and provided a review of 37 existing low-cost devices for stroke rehabilitation. These devices engage patients using a variety of actuation methods to produce training forces: Active (controllable actuator that adds or dissipates energy e.g., motors, stimulators), Passive (uncontrollable actuator that only dissipates energy e.g., springs, cables), Semi-Passive (controllable actuator that only dissipates energy e.g., brakes) and Augmented Feedback (no actuator). Following this review, we outline certain unexplored areas of low-cost devices that may be fruitful areas of future exploration.
Plantarflexor strength and voluntary activation are key metrics for characterizing lower extremity function in stroke survivors. However, the extent to which stroke and/or aging affects these neuromuscular properties remains unclear. This study addressed this gap by testing plantarflexor strength and voluntary activation in fifty-two (stroke: 19, older: 15, young: 18) participants. Testing was done bilaterally in stroke survivors and on the dominant leg of the control participants using the central activation ratio (CAR) and interpolated twitch technique (ITT) with triplets. Stroke survivors demonstrated significantly reduced raw and mass-normalized plantarflexor strength on both legs compared with controls, and on their more affected leg compared with the less affected leg (all p's ≤ 0.02). Regardless of technique, voluntary activation was significantly lower only in the more affected leg compared with the less affected leg and control leg (all p's ≤ 0.02). Older adults also demonstrated lower plantarflexor strength (p ≤ 0.01), but not voluntary activation, compared with young adults. These findings indicate that both stroke and aging affect plantarflexor strength; however, voluntary activation is only affected by stroke. Additionally, quantification technique influenced voluntary activation estimates, with CAR consistently demonstrating higher activation relative to ITT. Collectively, these findings highlight the need for targeting plantarflexor strength and voluntary activation during post-stroke rehabilitation.
IntroductionPost-acute COVID-19 vaccination syndrome (PACVS) emerges as a syndrome of persistent symptoms of a multisystemic nature, even in previously healthy people. Its pathophysiology involves a neural phase characterized by the neuroimmune reflex and persistent secondary neurogenic inflammation. Frequent manifestations such as dysautonomia, neurological alterations, and musculoskeletal symptoms have been described.ObjectiveTo review the current evidence on PACVS and explore the therapeutic potential of Neuraltherapeutic Medicine (NTM), illustrated with a clinical case.Material and methodsA targeted literature review search was conducted in MEDLINE (up to June 2024) using the terms "post-COVID-19 vaccination syndrome", "covid vaccine adverse effects", "inflammatory reflex" and "neural therapy". In addition, a clinical case of a 75-year-old patient with persistent musculoskeletal pain post-vaccination, treated with NTM, was documented.ResultsThe pathophysiology of PACVS includes neuroimmune mechanisms such as response, neurogenic inflammation, and autonomic dysfunction. NTM has shown the ability to modulate the nervous system by desensitizing sources of irritation. In the case presented, the application of 0.5% procaine to the vaccination site and contralateral reflex zone resulted in complete resolution of pain within 48 h and sustained functional improvement during the three months of follow-up.ConclusionsNTM could represent a therapeutic option in the management of PACVS and other syndromes involving neurogenic inflammation. Controlled studies are required to validate its efficacy and establish standardized protocols.
Homosynaptic depression (HD) refers to the reduction in the magnitude of the monosynaptic spinal reflex resulting from prior activation of the circuit, often evoked with the H-reflex. Previous literature has reported HD of the soleus H-reflex is reduced post-stroke. However, it remains unclear if HD plays a role in functional impairments. The goal of this study was to characterize HD of the soleus H-reflex in individuals with post-stroke gait impairments and examine the relationship with functional measures of gait. Our results revealed that individuals after stroke experienced reduced depression at longer (8s) interstimulus intervals compared to age-matched neurologically intact individuals. However, we did not observe a difference in the change in HD across interstimulus intervals between groups, contrary to previous reports. This finding could not be explained by age of participants. In addition, we found a strong correlation between faster gait speed and reduced change in depression in individuals after stroke. While the underlying mechanisms linking HD with gait are unclear, this finding represents the first piece of evidence of the potential role of HD in function. Further research is needed to understand the parameters that guide HD and clarify how useful the mechanism is for improving the assessment and treatment of post-stroke impairments.
Ischemic stroke, a leading cause of neurological disability and mortality, involves a multifactorial cascade of oxidative stress, mitochondrial dysfunction, and inflammation. Yet, conventional paradigms centered on apoptosis and necrosis fail to fully explain the inflammatory amplification that drives secondary brain injury-underscoring the emerging significance of pyroptosis as a distinct and targetable death program. This review delineates the mechanistic architecture of pyroptosis in ischemic stroke, integrating canonical (NLRP3-caspase-1-GSDMD) and noncanonical (caspase-4/5/11-GSDMD) inflammasome cascades with apoptosis-, necroptosis-, and ferroptosis-linked pathways within a unified PANoptotic continuum. Upstream regulators-such as mitochondrial ROS-TXNIP coupling, STING-mediated innate immune signaling, and astrocytic LCN2/24p3R activation-coordinate oxidative stress with neuroinflammatory propagation and blood-brain barrier disruption. Pharmacological inhibition of inflammasomes (MCC950, CY-09, OLT1177), caspases (VX-765, Ac-YVAD-CMK), or gasdermins (disulfiram, necrosulfonamide) markedly reduces IL-1β/IL-18 release and preserves neurovascular integrity in preclinical models, highlighting pyroptosis as a therapeutically tractable axis in ischemic stroke. Despite these advances, challenges remain in defining temporal-cellular specificity and achieving clinical translation. Integrating single-cell multi-omics, spatial imaging, and nanocarrier-based delivery systems may enable precise, phase-adaptive modulation of pyroptosis, transforming destructive inflammation into controlled neurovascular recovery.
In this open-label single-arm study, we tested the preliminary therapeutic effects of a four-week mindfullness-based intervention (MBI) tailored for fibromyalgia, including weekly online group meetings and daily mindfulness practices. Forty-six patients completed the intervention. The primary outcome was pain intensity scored on a numerical rating scale (NRS). Secondary outcomes included verbal fluency and self-reports of affective pain, quality of life, sleep quality, mood, emotion regulation, and psychological impairment. Transcranial magnetic stimulation was used to measure mindfulness-induced cortical excitability changes. Participants reported statistically reduced pain intensity post-training, with only 15.3% of the patients demonstrating clinically meaningful pain relief. A moderate improvement in quality of life, with only 45.6% clinical responders, were noted. Small-to-medium improvements in affective pain level, mindfulness level, and resilience as well as increase in long-interval intracortical inhibition-a measure of GABABergic inhibition-were observed. The study introduces a novel MBI tailored for fibromyalgia. Nonetheless, given the current study design and the lack of clinical significance of the findings despite statistical significance, the results are insufficient to draw firm conclusions regarding its potential therapeutic efficacy. Future sham-controlled randomized clinical trials are necessary to validate and expand upon these results.
