Decline In Motor Function Research Articles

Risk factors for motor decline following parasagittal and falx meningioma resection in the middle third

ObjectiveThe resection of parasagittal and falx meningiomas in the middle third superior sagittal sinus (SSS) is associated with a high risk of postoperative motor deficits. This study discusses the risk factors affecting postoperative motor decline and recovery of motor function after follow-up.MethodsThe results of a single-institution retrospective cohort study of parasagittal and falx meningioma resection in the middle third between 2016 and 2023 were reviewed, and parameters were screened as potential predictors. Variables of interest included postoperative motor decline and outcome after follow-up. Univariate and multivariate analyses were performed to identify risk factors.ResultsAmong 87 patients who underwent resection of parasagittal (63.2%) or falx (36.8%) middle third meningiomas, 14.9% (13/87) experienced postoperative motor decline. Among the 36 patients (41.4%) with preoperative motor deficits, 66.3% improved, 17.0% unchanged, and 16.7% (6/36) worsened following surgery. Among the 51 patients without preoperative motor deficits, 13.7% (7/51) developed new weakness. The predictors of postoperative motor decline were major venous involvement (p = 0.022), falx meningioma (p = 0.031), loss of the brain-tumor interface (p=0.033) and WHO grade II-III (p = 0.032).ConclusionsThe resection of parasagittal and falx meningiomas in the middle third carries a high rate of postoperative morbidity and deserves perioperative planning. Alternative surgical strategies, such as preserving the brain-tumor arachnoid interface and minority residual tumors, may prevent motor decline in a subset of high-risk patients.

Exploring the Pathophysiology, Diagnosis, and Treatment Options of Multiple Sclerosis.

The complicated neurological syndrome known as multiple sclerosis (MS) is typified by demyelination, inflammation, and neurodegeneration in the central nervous system (CNS). Managing this crippling illness requires an understanding of the complex interactions between neurophysiological systems, diagnostic techniques, and therapeutic methods. A complex series of processes, including immunological dysregulation, inflammation, and neurodegeneration, are involved in the pathogenesis of MS. Gene predisposition, autoreactive T cells, B cells, and cytokines are essential participants in the development of the disease. Demyelination interferes with the ability of the CNS to transmit signals, which can cause a variety of neurological symptoms, including impaired motor function, sensory deficiencies, and cognitive decline. Developing tailored therapeutics requires understanding the underlying processes guiding the course of the disease. Neuroimaging, laboratory testing, and clinical examination are all necessary for an accurate MS diagnosis. Evoked potentials and cerebrospinal fluid studies assist in verifying the diagnosis, but magnetic resonance imaging (MRI) is essential for identifying distinctive lesions in the CNS. Novel biomarkers have the potential to increase diagnostic precision and forecast prognosis. The goals of MS treatment options are to control symptoms, lower disease activity, and enhance quality of life. To stop relapses and reduce the course of the disease, disease-modifying treatments (DMTs) target several components of the immune response. DMTs that are now on the market include interferons, glatiramer acetate, monoclonal antibodies, and oral immunomodulators; each has a unique mode of action and safety profile. Symptomatic treatments improve patients' general well-being by addressing specific symptoms, including pain, sphincter disorders, fatigue, and spasticity. Novel treatment targets, neuroprotective tactics, and personalized medicine techniques will be the main focus of MS research in the future. Improving long-term outcomes for MS patients and optimizing disease treatment may be possible by utilizing immunology, genetics, and neuroimaging developments. This study concludes by highlighting the complexity of multiple MS, including its changing therapeutic landscape, diagnostic problems, and neurophysiological foundations. A thorough grasp of these elements is essential to improving our capacity to identify, manage, and eventually overcome this intricate neurological condition.

Effect of Hyaluronan Molecular Weight on the Stability and Biofunctionality of Microfibers Assembled by Interfacial Polyelectrolyte Complexation.

Nervous system disorders are characterized by a progressive loss of function and structure of neurons that ultimately leads to a decline in cognitive and motor functions. In this study, we used interfacial polyelectrolyte complexation (IPC) to produce fibers for neural tissue regeneration. IPC is a processing method that allows spinning of sensitive biopolymers. The rate of spinning and the properties of the used biopolymers (charge and molecular weight) influence different characteristics of the fibers such as size and stability, among others. We used two major components of the neuronal stem cell niche, the polycationic collagen (Col) and the polyanionic hyaluronic acid (HA), to obtain bioactive fibers. We tested HA with different molecular weights and found that HA with medium and high molecular weights (350 and 1200 kDa, respectively) enabled drawing of microfibers with a homogeneous distribution of Col and HA, whereas low-molecular-weight HA (40 kDa) did not allow spinning. The obtained microfibers showed high swelling ability in a physiological buffer: their diameters increased more than 5-fold from their dry state. At these conditions, the tensile storage moduli of the fibers were similar to nervous tissues. Collagenase and hyaluronidase did not change the morphology of the fibers for up to 3 days but reduced their moduli 2- to 3-fold. Assays with PC12 neuronal-like cells showed that IPC microfibers support cell adhesion and viability regardless of the molecular weight of the used HA.

Associations Between Muscle Thickness, Motor Function, and Echo Intensity in Community-Dwelling Older Japanese Men and Women.

Purpose Muscle atrophy progresses with age. The motor function may be estimated by measuring the muscle mass; however, if muscle quality deteriorates due to an increase in connective tissue within the muscle, a decline in motor function may be missed by measuring muscle mass alone. Therefore, it is important to understand the relationship between muscle mass, muscle quality, and motor function. This study aimed to clarify how changes in muscle thickness, measured using ultrasound imaging, in older people are related to motor function and echo intensity. Patients and methods The thickness and echo intensity of the four quadriceps muscles were measured using an ultrasound imaging device in 110 community-dwelling older individuals. Correlations between muscle thickness, motor functions such as walking and muscle strength, and echo intensity were analyzed in each sex. Partial correlation analysis was conducted using age as a control variable. Results A significant correlation was observed between muscle thickness and motor function in both men and women. There was no significant negative correlation between muscle thickness and echo intensity of the same muscle in men, except between each muscle thickness and the vastus medialis (p < 0.001 or p = 0.007), between the sum of the four muscle thicknesses and vastus medialis thickness (p = 0.02), and between the vastus medialis thickness and echo intensity (p < 0.006). In women, a significant correlation was observed for all muscles. Partial correlation analysis revealed a similarly significant correlation between muscle thickness and echo intensity in men and women. Conclusion We observed sex differences in the relationship between muscle thickness and echo intensity. This suggests that, even after adjusting for age-related factors, women may show more pronounced changes in muscle quality than men, with increased echo intensity due to increased intramuscular connective tissue with muscle atrophy.

Delineating sex-dependent and anatomic decline of motor functions in the SOD1G93A mouse model of amyotrophic lateral sclerosis.

The transgenic SOD1G93A mouse model is the most widely used animal model of amyotrophic lateral sclerosis (ALS), a fatal disease of motor neuron degeneration. While genetic background influences onset and progression variability of motor dysfunction, the C57BL/6 background most reliably exhibits robust ALS phenotypes; thus, it is the most widely used strain in mechanistic studies. In this model, paresis begins in the hindlimbs and spreads rostrally to the forelimbs. Males experience earlier onset, greater disease severity, and shorter survival than females. However, the influence of sex on patterns of declining motor function between forelimbs and hindlimbs as well as among distinct, spinal-innervated muscle groups within each limb are not fully understood. To provide a higher resolution framework of degenerating motor function across the body, we conducted more comprehensive, limb-dependent and independent measures of motor decline over the course of disease. Subsequently, we compared the timing and intensity of these features across sex, and we consider to what extent these patterns are conserved in clinical observations from human ALS patients. We found male mice experienced earlier and less localized onset than females. We also report distinct motor features decline at different rates between sexes. Finally, mice showed differences in correlation between the decline of left- and right-side measures of the hindlimb. Consequently, our findings reinforce and refine the utility of the SOD1 mouse in modeling more highly resolved, sex-specific differences in ALS patient motor behavior. This may better guide preclinical studies in stratifying patients by sex and anatomical site of onset.

Neurophysiologic Innovations in ALS: Enhancing Diagnosis, Monitoring, and Treatment Evaluation.

Amyotrophic lateral sclerosis (ALS) is a progressive disease of both upper motor neurons (UMNs) and lower motor neurons (LMNs) leading invariably to decline in motor function. The clinical exam is foundational to the diagnosis of the disease, and ordinal severity scales are used to track its progression. However, the lack of objective biomarkers of disease classification and progression delay clinical trial enrollment, muddle inclusion criteria, and limit accurate assessment of drug efficacy. Ultimately, biomarker evidence of therapeutic target engagement will support, and perhaps supplant, more traditional clinical trial outcome measures. Electrophysiology tools including nerve conduction study and electromyography (EMG) have already been established as diagnostic biomarkers of LMN degeneration in ALS. Additional understanding of the motor manifestations of disease is provided by motor unit number estimation, electrical impedance myography, and single-fiber EMG techniques. Dysfunction of UMN and non-motor brain areas is being increasingly assessed with transcranial magnetic stimulation, high-density electroencephalography, and magnetoencephalography; less common autonomic and sensory nervous system dysfunction in ALS can also be characterized. Although most of these techniques are used to explore the underlying disease mechanisms of ALS in research settings, they have the potential on a broader scale to noninvasively identify disease subtypes, predict progression rates, and assess physiologic engagement of experimental therapies.

Native learning ability and not age determines the effects of brain stimulation

Healthy aging often entails a decline in cognitive and motor functions, affecting independence and quality of life in older adults. Brain stimulation shows potential to enhance these functions, but studies show variable effects. Previous studies have tried to identify responders and non-responders through correlations between behavioral change and baseline parameters, but results lack generalization to independent cohorts. We propose a method to predict an individual’s likelihood of benefiting from stimulation, based on baseline performance of a sequential motor task. Our results show that individuals with less efficient learning mechanisms benefit from stimulation, while those with optimal learning strategies experience none or even detrimental effects. This differential effect, first identified in a public dataset and replicated here in an independent cohort, was linked to one’s ability to integrate task-relevant information and not age. This study constitutes a further step towards personalized clinical-translational interventions based on brain stimulation.

The Effect of glna Loss on the Physiological and Pathological Phenotype of Parkinson's Disease C. elegans.

Parkinson's disease (PD) is a common neurodegenerative disease. Glutamate(Glu) excitotoxicity is one of the main pathogenesis of PD. Glutaminase (Gls) is an enzyme primarily responsible for catalyzing the hydrolysis and deamidation of glutamine (Gln) to produce Glu and ammonia. Inhibiting the function of Gls may have a beneficial effect on the treatment of PD by reducing the production of Glu. The homologous gene of Gls in C. elegans is glna. To explore the effects of glna loss on physiological and pathological phenotype of PD C. elegans, and to provide new ideas and references for the research and treatment of PD. We used PD C. elegans UA44 and QIN27 to detect development and lifespan, behavior, degeneration of dopaminergic neurons, lipid levels, ROS levels, expression levels of common amino acids. Glna loss had no significant impact on the development and lifespan of PD C. elegans. Glna loss saved part of the decline of motor function, including the head thrash frequency and the body bend frequency, and the difference was significant. There was a trend of improvement in some motor behaviors, such as the ethanol avoidance experiment, while no improvement was observed in other experiments. Glna loss slowed down the degeneration of dopaminergic neurons. Glna loss increased the lipid levels and ROS levels in C. elegans. Glna loss decreased Glu content and increased Gln content in C. elegans. The effect of glna loss on PD C. elegans may be the result of multiple factors, such as the tissue types of α-syn expression in C. elegans, the PD C. elegans model used, the adverse effects of glna loss on other systems, and the changes in ROS levels in C. elegans. The specific mechanisms causing these phenomena are still unclear and need to be further explored. Glna loss has a certain protective effect on dopaminergic neurons in PD C. elegans, while the improvement effect on movement and behavior is limited.

Dipeptidyl peptidase 4 as an injury-responsive protein in the mouse sciatic nerve

Dipeptidyl peptidase 4 (DPP4) is a membrane-bound protease known for its roles in immunity and metabolism; however, its function in the nervous system remains largely unexplored. We found that DPP4 is predominantly expressed in the Schwann cells of the sciatic nerve, and its systemic depletion in postnatal mice resulted in a decline in motor function. Importantly, the inhibition of its proteolytic activity did not affect axon regeneration, indicating that DPP4's protease activity may not be directly involved in axon regeneration. Instead, we observed a reduction in DPP4 protein levels in the sciatic nerve after injury and increased in serum postinjury, suggesting that DPP4 may be shed into circulation, potentially mediating systemic responses following injury. These findings highlight DPP4's importance in sensory function and its potential role in systemic responses after peripheral nerve injury.

Novel nerve regeneration assessment method using adult zebrafish with crush spinal cord injury.

Zebrafish (Danio rerio), an alternative to rodents, are widely used in neurological, genetic, and toxicology research. The zebrafish larval spinal cord injury model has been used in neural mechanistic analyses owing to its high regenerative capacity and throughput; however, it also had several limitations in imitating rodents. Therefore, we investigated the use of adult zebrafish as an alternative model to rodents for evaluating nerve regeneration. Here, we established a novel spinal cord regeneration evaluation method, which was based on the maximum swimming speed of adult zebrafish in a custom-built hydrodynamic-based aquarium. The spinal cords of adult male zebrafish were crushed using forceps, and maximum swimming speed and histological spinal cord regeneration were evaluated. Spinal cord-injured zebrafish showed a significant decline in motor function, followed by recovery at 3weeks postoperatively, accompanied by histological regeneration. Spinal cord regeneration can be indirectly assessed by monitoring maximum swimming speed. They were also fed a diet containing fig extract, which can promote peripheral nerve regeneration; they were fed daily starting 1week before the operation. Maximum swimming speed was measured time-dependently until 3weeks postoperatively. Fig-consuming fish showed improved recovery of maximum swimming speed compared to the controls, which was consistent with the histological analysis. In summary, we established a spinal cord regeneration assessment system using adult zebrafish in a customized aquarium, which enables researchers to evaluate spinal cord regeneration in adult zebrafish similar to that of rodent experiments, contributing to faster and easier screening of neuroregenerative technology.

LDHzyme-assisted high-performance on-site tracking of levodopa pharmacokinetics for Parkinson's disease management

Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons and the consequent decline in motor and cognitive functions. The primary therapeutic agent levodopa necessitates precise dosing due to its narrow therapeutic window and complex pharmacokinetics. This study presents the development of a novel CuCoFe-LDHzyme-based sweat sensor for real-time monitoring of levodopa concentration in PD patients. Employing differential pulse voltammetry (DPV) technique, the sensor demonstrates high sensitivity and selectivity, achieving a detection limit of 28.1nM. The sensor's design allows for non-invasive, continuous monitoring, significantly enhancing patient convenience compared to traditional blood sampling methods. Through pH correction, precise quantification of levodopa in sweat is accomplished, and a strong correlation (Pearson coefficient=0.833) with blood levodopa levels is established. The pharmacokinetic profile of levodopa is reconstructed in real-time, offering a promising tool for optimizing PD treatment regimens. This study highlights the potential of CuCoFe-LDHzyme sensors to advance personalized treatment strategies, aiming to improve the quality of life for PD patients by providing clinicians with real-time data for medication adjustments.

Anxiety, memory, and social impairments in the YAC128 mouse model of Huntington’s disease

Background Huntington’s disease (HD) is an autosomal dominant hereditary disorder, caused by an expansion of polyglutamine in the huntingtin protein. HD is characterized by a progressive decline in motor functions. This decline includes involuntary movements (chorea) and the worsening of controlled motions caused mainly by neuronal dysfunction in the striatum. In addition to the deterioration of motor symptoms, HD patients also suffer from cognitive changes, mood swings, apathy, depression, outbursts of anger, psychosis, and social withdrawal. Objective A comprehensive examination of cognitive, affective, and social changes in the HD mouse model is required for the development of combined therapy for both motor and non-motor deficits in HD. Methods The behavioral tests for anxiety, memory, and social traits were used in this study. Results YAC128 HD transgenic mice exhibited anxiolytic behavior in the novel brightly illuminated environment of the open field and light-dark place preference tests. Moreover, YAC128 HD mice also suffered from a decline in their recognition memory during the novel object recognition test. YAC128 HD mice demonstrated reduced exploration interest during the open field with a non-social target as well as during the first day of the three-chamber social test. Social interaction was also impaired in YAC128 HD mice as it was shown in the social interaction with resident intruder test. Conclusions YAC128 HD mouse model may be used as a model system to test the possible treatments for both motor and non-motor symptoms including memory loss, agitation and social withdrawal.

Lycium barbarum Extract Enhanced Neuroplasticity and Functional Recovery in 5xFAD Mice via Modulating Microglial Status of the Central Nervous System.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with limited treatment options. This study aimed to investigate the effects of Lycium barbarum extract (LBE), a Chinese herb, on the central nervous system (CNS)-including the retina, brain, and spinal cord-in 5xFAD transgenic mice after the onset of AD. Starting at 6 months of age, 5xFAD mice received daily intragastric gavage of LBE (2 g/kg) for 2 months. At 8 months, behavioral tests were conducted to assess cognition, motor function, and visual function. These included the Morris water maze, novel object recognition, and Y-maze tests for cognition; the beam walking balance and clasping tests for motor function; and electroretinogram (ERG) for visual function. Immunohistochemistry, western blotting, and ELISA were used to evaluate Aβ deposition, microglial morphology, neuroinflammation, and neuroprotective signaling pathways. Primary microglia and the IMG cell line were used to study LBE's effects on Aβ uptake and degradation invitro. After 2 months of LBE treatment, the decline in cognition, motor, and visual functions in 5xFAD mice was significantly slowed. Microglia in the brain, spinal cord, and retina exhibited a neuroprotective state, with reduced Aβ deposition, decreased inflammatory cytokine levels (e.g., TNF-α, IL-1β, IL-6), increased Arg-1/iNOS ratio, and enhanced phagocytic capacity. LBE also promoted Aβ uptake and degradation in primary microglia and the IMG cell line. Neuroprotective signals such as p-Akt, p-Erk1/2, and p-CREB were elevated. Additionally, LBE treatment restored synaptic protein expression and enhanced neuroplasticity. The findings suggest that LBE treatment can enhance neuroplasticity, reduce systemic inflammation, and improve phagocyte clearance of Aβ deposition via inducing a neuroprotective microglial phenotype throughout CNS. As an upper-class Chinese medicine, appropriate intake of LBE may serve as a beneficial antiaging strategy for AD.

Brain age in genetic and idiopathic Parkinson's disease.

The brain-age gap, i.e. the difference between the brain age estimated from structural MRI data and the chronological age of an individual, has been proposed as a summary measure of brain integrity in neurodegenerative diseases. Here, we aimed to determine the brain-age gap in genetic and idiopathic Parkinson's disease and its association with surrogate markers of Alzheimer's disease and Parkinson's disease pathology and with rates of cognitive and motor function decline. We studied 1200 cases from the Parkinson's Progression Markers Initiative cohort, including idiopathic Parkinson's disease, asymptomatic and clinical mutation carriers in the leucine-rich repeat kinase 2 gene (LRRK2) and the glucocerebrosidase gene (GBA), and normal controls using a cohort study design. For comparison, we studied 187 Alzheimer's disease dementia cases and 254 controls from the Alzheimer's Disease Neuroimaging Initiative cohort. We used Bayesian ANOVA to determine associations of the brain-age gap with diagnosis, and baseline measures of motor and cognitive function, dopamine transporter activity and CSF markers of Alzheimer's disease type amyloid-β42 and phosphotau pathology. Associations of brain-age gap with rates of cognitive and motor function decline were determined using Bayesian generalized mixed effect models. The brain-age gap in idiopathic Parkinson's disease patients was 0.7 years compared to controls, but 5.9 years in Alzheimer's disease dementia cases. In contrast, asymptomatic LRRK2 individuals had a 1.1. year younger brain age than controls. Across all cases, the brain-age gap was associated with motor impairment and (in the clinically manifest PD cases) reduced dopamine transporter activity, but less with CSF amyloid-β42 and phosphotau. In idiopathic Parkinson's disease cases, however, the brain-age gap was associated with lower CSF amyloid-β42 levels. In sporadic and genetic Parkinson's disease cases, a higher brain-age gap was associated with faster decline in episodic memory, and executive and motor function, whereas in asymptomatic LRRK2 cases, a smaller brain-age gap was associated with faster cognitive decline. In conclusion, brain age was sensitive to Alzheimer's disease like rather than Parkinson's disease like brain atrophy. Once an individual had idiopathic Parkinson's disease, their brain age was associated with markers of Alzheimer's disease rather than Parkinson's disease. Asymptomatic LRRK2 cases had seemingly younger brains than controls, and in these cases, younger brain age was associated with poorer cognitive outcome. This suggests that the term brain age is misleading when applied to disease stages where reactive brain changes with apparent volume increases rather than atrophy may drive the calculation of the brain age.

Efficacy of Nusinersen Treatment in Type 1, 2, and 3 Spinal Muscular Atrophy: Real-World Data from a Single-Center Study.

Spinal muscular atrophy (SMA) is an inherited neuromuscular disease characterized by progressive muscle weakness and atrophy due to the absence of the survival motor neuron 1 (SMN1) gene. SMA is classified into types 0 through 4 based on the age of symptom onset and the severity of motor function decline. Recent advances in SMA treatment, including nusinersen, onasemnogene abeparvovec, and risdiplam, have significantly improved the prognosis of SMA patients. This study evaluated the safety and efficacy of nusinersen in pediatric patients with SMA types 1, 2, and 3 in a real-world clinical setting. This prospective observational single-center study assessed the treatment effects of nusinersen in 23 pediatric patients with genetically confirmed SMA over a 22-month observation period. All the participants received intrathecal loading doses of 12 mg of nusinersen on days 1, 14, 28, and 63, followed by maintenance doses every four months. Functional assessments were conducted using the CHOP-INTEND scale. Data were collected during routine patient visits, including clinical laboratory tests and vital sign parameters, and adverse events were recorded. The inclusion criteria were defined by the national reimbursement program for nusinersen treatment in Poland. Initially, 37 patients ranging from 1 month old to 18 years old were included, but 23 were ultimately observed due to changes in treatment regimens or assessment scales. The patients showed significantly improved CHOP-INTEND scores over the 22-month period. At 6 months, the average increase was 4.2 points, continuing to 17.8 points at 22 months. By the end of the study, 100% of patients showed either stabilization or improvement, with significant clinical improvements observed in several patients. Nusinersen was generally well-tolerated, with post-lumbar puncture headache and lower back pain being the most common adverse events. Nusinersen treatment significantly enhances motor function in pediatric patients with SMA types 1, 2, and 3. This study demonstrates the importance of early and sustained treatment, with most patients showing the continuous improvement or stabilization of motor function. These findings support the use of nusinersen as an effective therapy for SMA; however, further research is needed to understand the long-term outcomes and optimize treatment strategies.

Apolipoprotein C3-rich low-density lipoprotein (AC3RL) exacerbates cerebral ischaemic stroke injury by increasing BBB leakage via LOX-1

Abstract Background Ischaemic stroke causes the abrupt reduction or cessation of blood flow to the brain results in a cascade of events that can compromise blood-brain barrier (BBB) integrity. We revealed that an increase in apolipoprotein C3 (ApoC3)-rich low-density lipoprotein (AC3RL) is associated with endothelial cell apoptosis and inflammatory responses, indicating that AC3RL is one of the risk factors for cardiovascular events. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) triggers a cascade of events within endothelial cells that leads to endothelial dysfunction. Purpose We aimed to investigate whether AC3RL affects BBB permeability via the LOX-1, and thus increases brain damage. Methods We collected the whole blood from normal and patients with ischaemic events and separated them by centrifugation. AC3RL were collected using FPLC. We performed middle cerebral artery occlusion (MCAO) surgery to induce ischaemic stroke using B6 (C57BL/6) and LOX-1-/- mice injected with AC3RL. Triphenyl tetrazolium chloride (TTC) and Evans blue stains were accessed to confirm brain injury and BBB permeability. Results FPLC results showed that patients with ischaemic events presented higher levels of AC3RL compared to normal people. TTC stain showed the increased area of ischaemic penumbra damage in B6 mice with AC3RL injection, and LOX-1-/- mice with AC3RL injection were significantly protected. Evans blue dye leakage was observed in the brain tissues of B6 mice with AC3RL injection. LOX-1-/- mice with AC3RL injection revealed a decrease in BBB permeability. The modified neurological severity score (mNSS) method revealed a significant rise in B6 mice with AC3RL injection, which suggested a decline in motor and nervous function. LOX-1-/- mice with AC3RL injection significantly improved in motor and neurological functioning. Conclusions We demonstrate that AC3RL, through its effects on LOX-1, is associated with an increased risk of BBB damage after stroke. Therefore, pharmacological inhibition of AC3RL-LOX-1 interaction will be the main strategy to reduce severe brain damage. Figure 1: (A) AC3RL percentage (%) in individuals. Normal: healthy people, Ischemic event: patients who have experienced an ischemic event. **p &amp;lt; 0.001 vs. Normal group. (B, C) TTC stain of brain tissue after euthanasia to pinpoint the site of brain damage. The white portion of the mice brains indicated the site of the injury. (D, E) Evans blue dye leakage study in mice brains exhibited BBB permeability changes. (F) Assessment of mice's motor and neurological performance using the mNSS. Data are expressed as the mean ± SEM. **p &amp;lt; 0.001, ****p &amp;lt; 0.0001 vs. sham group, ##p &amp;lt; 0.001 vs. B6 I.V. AC3RL group.Graphical abstractFigure 1.

Sirt6 Mono-ADP-Ribosylates YY1 to Promote Dystrophin Expression for Neuromuscular Transmission.

The degeneration of the neuromuscular junction (NMJ) and the decline in motor function are common features of aging, but the underlying mechanisms have remained largely unclear. This study reveals that Sirt6 is reduced in aged mouse muscles. Ablation of Sirt6 in skeletal muscle causes a reduction of Dystrophin levels, resulting in premature NMJ degeneration, compromised neuromuscular transmission, and a deterioration in motor performance. Mechanistic studies show that Sirt6 negatively regulates the stability of the Dystrophin repressor YY1 (Yin Yang 1). Specifically, Sirt6 mono-ADP-ribosylates YY1, causing its disassociation from the Dystrophin promoter and allowing YY1 to bind to the SMURF2 E3 ligase, leading to its degradation. Importantly, supplementation with nicotinamide mononucleotide (NMN) enhances the mono-ADP-ribosylation of YY1 and effectively delays NMJ degeneration and the decline in motor function in elderly mice. These findings provide valuable insights into the intricate mechanisms underlying NMJ degeneration during aging. Targeting Sirt6 could be a potential therapeutic approach to mitigate the detrimental effects on NMJ degeneration and improve motor function in the elderly population.

Safety and efficacy of viltolarsen in ambulatory and nonambulatory males with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by mutations in the dystrophin gene, causing motor and pulmonary function decline. Viltolarsen is indicated for patients with dystrophin gene mutations amenable to exon 53 skipping. Here, we report safety, motor function, and the first pulmonary function results from the open-label, phase II Galactic53 trial of viltolarsen (NCT04956289). Male participants aged ≥ 8years with DMD received 80mg/kg intravenous viltolarsen once weekly for 48weeks. Results from participants receiving viltolarsen were compared with an external control cohort group-matched for multiple variables. All treatment-emergent adverse events were mild or moderate, 4 were considered treatment-related, and no participants discontinued. Participants receiving viltolarsen experienced clinically meaningful benefits in pulmonary function with higher percent predicted forced vital capacity and higher peak cough flow at Week 49 compared with the control cohort for both ambulatory and nonambulatory participants. Viltolarsen also stabilized upper limb motor function over the Treatment Period. These results support viltolarsen as an important part of the treatment armamentarium for both ambulatory as well as nonambulatory patients with DMD.

Motor function and gait decline in individuals with cerebral palsy during adulthood: a narrative review of potential physiological determinants.

Cerebral palsy (CP) is the most common childhood-onset disability. The evolution of gait according to severity is well known amongst children and thought to peak between 8 and 12years of age among those walking without assistive devices. However, among adults, clinical experience as well as scientific studies report, through clinical assessments, questionnaires and interviews, increasing walking difficulties leading to an increased dependency of assistive devices in everyday ambulation. For many individuals with CP, this change will occur around 30-40years, with the risk of losing mobility increasing with age. This narrative review aims to first provide objective evidence of motor function and gait decline in adults with CP when ageing, and then to offer mechanistic hypotheses to explain those alterations. Many studies have compared individuals with CP to the typically developing population, yet the evolution with ageing has largely been understudied. Comorbid diagnoses comprise one of the potential determinants of motor function and gait decline with ageing in people with CP, with the first manifestations happening at an early age and worsening with ageing. Similarly, ageing appears to cause alterations to the neuromuscular and cardiovascular systems at an earlier age than their typically developing (TD) peers. Future studies should, however, try to better understand how the physiological particularities of CP change with ageing that could pave the way for better strategies for maintaining function and quality of life in people with CP.

Latent class analysis of communication methods and devices among Japanese patients with amyotrophic lateral sclerosis: a cross-sectional survey

ABSTRACT Augmentative and alternative communication (AAC) is used to support individuals with communication impairments, such as those with amyotrophic lateral sclerosis (ALS). The selection of AAC for patients with ALS involves a variety of factors, sometimes leading to the utilization of multiple AAC methods. This study aimed to survey patients with ALS in Japan, focusing on objectives: to describe the actual state of AAC usage among these patients and to investigate potential classifications in their choice of communication methods, along with identifying influential latent factors. Data from 102 patients with ALS were analysed using descriptive statistics and latent class analysis. A latent class analysis revealed four distinct classifications: class I, replacing unaid communication with AAC (n = 46, 45.1%); class II, with minimal AAC use (n = 24, 23.5%); class III, centred around no-tech/low-tech AAC (n = 17, 16.7%); and class IV combining unaid communication with various AACs (n = 15, 14.7%). These classifications were influenced by age at diagnosis, TPPV use, gastrostomy use, and the Revised ALS Functional Rating Scale. The characteristics of each class revealed a correlation between increased medical needs, such as bulbar palsy, motor and respiratory function decline, and the necessity for AAC. Notably, patients diagnosed at an older age and those with severe bulbar palsy, like those seen in bulbar-onset ALS, require early communication support due to early onset of communication impairments. Additionally, introducing AAC in the early stages of ALS suggests that learning diverse communication methods can contribute to the maintenance of communication.