Restorative neurology and neuroscience最新文献

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system, leading to inflammation, demyelination, and neurodegeneration. Although disease-modifying therapies (DMTs) have shown efficacy in reducing relapse rates, they offer limited benefit in addressing cognitive symptoms and overall disease burden. The ketogenic diet (KD), a high-fat, low-carbohydrate dietary approach, has emerged as a promising adjunctive strategy. Recent research suggests that KD may modulate key inflammatory pathways, enhance mitochondrial function, and reduce oxidative stress through mechanisms involving ketone bodies such as β-hydroxybutyrate. These effects have been linked to improvements in fatigue, cognition, quality of life, and markers of neuronal injury in individuals with MS. Furthermore, KD may positively influence the gut microbiome, insulin sensitivity, and myelin repair processes. Despite encouraging results, challenges such as dietary adherence, nutrient deficiencies, gastrointestinal side effects, and cardiovascular risks limit widespread adoption. Current evidence is largely based on short-term studies with limited diversity and variable dietary protocols. Future research should focus on long-term safety, standardized guidelines, and personalized strategies to better integrate KD into comprehensive MS care.

The purpose of this study was to explore the relationship between brain excitability indexed using different transcranial magnetic stimulation (TMS) measures and post-stroke fatigue (PSF) in individuals with mild to moderate motor impairment. We used single- and paired-pulse TMS to obtain various TMS outcomes from 24 participants with chronic stroke: resting motor threshold (RMT), motor evoked potential amplitude (MEP), Input-Output Curve (IOC) slope, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). IO curve slope (ρ = -0.61, p = 0.02) and SICI (ρ = -0.51, p = .03) measured from the ipsilesional hemisphere correlated with PSF. Other TMS measures were not significantly correlated with PSF measures. Findings suggest that higher levels of fatigue were associated with lower brain excitability. Together with previous studies, our findings suggest that level of motor impairment and the tool used to assess fatigue might influence the relationship between brain excitability and PSF.

Peripheral facial paralysis results in complete loss of contractibility in facial muscles, atrophy and asymmetry. Patients performed functional electrical stimulation (FES) home training twice daily over 1 year to show its effect and define stimulation parameters. A specific response was obtained in all 10 patients. Since the mean phase duration (PD) could be reduced (155.0 ± 55.0 to 51.0 ± 12.4 msec), this allowed the mean stimulation frequency to be increased (1.3 ± 0.5 to 5.0 Hz ± 1.5 Hz). The PD reduction to generate the same charge increased the voltage (16.2 ± 2.5 to 27.2 V ± 5.9). A suitable combination of PD and amplitude elicited a selective response without activation of other facial muscles using a PD of ≥ 25 ms (> 25 000 µs). FES changes the stimulation parameters for improving the training effect on denervated facial muscles. It prevents denervation atrophy and stops facial asymmetry.

Clinical assessments of the post-stroke upper limbs have several limitations in that they focus primarily on unilateral movements, rely on observer-based ordinal scales, and give limited insight into movement quality. Human pose estimation uses computer vision to extract motion data from videos, making it a clinically feasible tool to assess movement and overcome many challenges of traditional clinical assessments. Our objective of this work was to demonstrate the use of video-based pose estimation to enhance the assessment of bilateral tasks in individuals post-stroke through visualizations and quantitative metrics. Using single camera video recordings of the Chedoke Hand and Arm Activity Inventory in two individuals with chronic stroke and one neurologically intact individual, we demonstrate differences in movement patterns including increased compensatory movements of proximal joints and asymmetries. We were able to detect differences that the traditional assessment scoring could not, demonstrating the potential of computer vision to enhance clinical assessment.

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 GABA_Bergic 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.

Background: After stroke, impaired bimanual coordination reduces quality of life, where precise coordination of force between arms is essential for daily activities. Effective coordination relies on balanced interhemispheric communication, which induces crossed facilitation between primary motor cortices (M1). Intracortical inhibition influences both crossed facilitation and bimanual coordination in neurologically intact individuals. This study examines whether GABA_B-mediated inhibition in ipsilesional M1 influences crossed facilitation from contralesional M1 and its relationship with bimanual coordination post-stroke.

Methods: Thirteen chronic stroke participants performed dynamic and isometric bimanual force grip task. In the dynamic task, the paretic hand maintained 30% of maximal voluntary contraction while the non-paretic hand varied force levels (low-mid-high). Cross-covariance coefficient between hands measured interference from non-paretic hand to paretic hand. In the isometric task, transcranial magnetic stimulation assessed crossed facilitation via motor evoked potential (MEP) and intracortical inhibition via cortical silent period (CSP) in ipsilesional M1 under varying bimanual force conditions (paretic: rest, 5%, 30%; non-paretic: rest, 10%, 30%, 70%).

Results: Results showed variable bimanual interference post-stroke, with greater interference in less impaired individuals and under high non-paretic force. Crossed facilitation increased with higher force asymmetry and lower paretic effort, particularly in less impaired participants, but became more variable as paretic effort increased (during PH 30%: NPH 70%). Under the high asymmetry condition, GABA_B-mediated disinhibition was most pronounced and greater crossed facilitation was associated with increased bimanual interference.

Conclusion: These findings suggest that reduced inhibitory tone may contribute to the regulation of crossed facilitation, and bimanual coordination deficits may be driven by excessive crossed facilitation. Future work will examine other ipsilesional factors regulating crossed facilitation, as targeted asymmetric training and neuromodulation may help improve bimanual coordination in individuals with moderate-to-mild motor impairment.

Stroke motor rehabilitation research is critical for improving functional recovery and quality of life. However, the success of therapeutic interventions is highly dependent on the theoretical basis and methodological rigor of the studies that evaluate them. This paper outlines ten essential recommendations/guidelines for stroke motor rehabilitation research aimed at enhancing the scientific quality and reliability of findings. Our recommendations span issues related to mechanistic understanding, methodological rigor, and transparency, while providing specific suggestions for implementation in the context of stroke motor rehabilitation research. To improve our mechanistic understanding of how and why an intervention works, these guidelines emphasize the importance of having a clear scientific rationale for the active ingredient in the proposed therapy (e.g., physical or occupational therapy), ensuring manipulation checks for key therapeutic components, and assessing outcomes at multiple levels using the ICF framework. To improve methodological rigor, the paper also highlights the necessity of adequately dose-matched control groups, minimizing baseline imbalances and biased treatment effects through randomization and blinding, and employing larger sample sizes to minimize the risk of false-positive trials. Finally, to enhance transparency and reproducibility, we advocate for pre-registering outcomes and protocols, performing robustness checks, presenting data in multiple formats, and the publication of open data. We anticipate that following these recommendations will pave the way for more reliable, impactful results that advance the development of effective therapeutic interventions.