Motor Function Research Articles

Predictors of Death or Severe Impairment in Neonates With Hypoxic-Ischemic Encephalopathy

Outcomes after hypoxic-ischemic encephalopathy (HIE) are variable. Predicting death or severe neurodevelopmental impairment (NDI) in affected neonates is crucial for guiding management and parent communication. To predict death or severe NDI in neonates who receive hypothermia for HIE. This prognostic study included participants enrolled in a large US clinical trial conducted in US neonatal intensive care units who were born between January 2017 and October 2019 and followed up to age 2 years. Eligible participants were neonates with moderate-severe HIE born at 36 weeks or more gestation and with 2-year outcome data. Data were analyzed June 2023. External validation was performed with a UK cohort. Clinical, electroencephalography (EEG), and magnetic resonance imaging (MRI) variables were curated and examined at 24 hours and following cooling. Death or severe NDI at age 2 years. Severe NDI was defined as Bayley Scales of Infant Toddler Development cognitive score below 70, Gross Motor Function Classification System score of 3 or higher, or quadriparesis. Model performance metrics were derived from training, internal, and external validation datasets. Among 424 neonates (mean [SD] gestational age, 39.1 [1.4] weeks; 192 female [45.3%]; 28 Asian [6.6%], 50 Black [11.8%], 311 White [73.3%]), 105 (24.7%) had severe encephalopathy at enrollment. Overall, 59 (13.9%) died and 46 (10.8%) had severe NDI. In the 24-hour model, the combined presence of 3 clinical characteristics-(1) severely abnormal EEG, (2) pH level of 7.11 or below, and (3) 5-minute Apgar score of 0-had a specificity of 99.6% (95% CI, 97.5%-100%) and a positive predictive value (PPV) of 95.2% (95% CI, 73.2%-99.3%). Validation model metrics were 97.9% (95% CI, 92.7%-99.8%) for internal specificity, with a PPV of 77.8% (95% CI, 43.4%-94.1%), and 97.6% (95% CI, 95.1%-99.0%) for external specificity, with a PPV of 46.2% (95% CI, 23.3%-70.8%). In the postcooling model, specificity for T1, T2, or diffusion-weighted imaging (DWI) abnormality in at least 2 of 3 deep gray regions (ie, thalamus, caudate, putamen and/or globus pallidus) plus a severely abnormal EEG within the first 24 hours was 99.1% (95% CI, 96.8%-99.9%), with a PPV of 91.7% (95% CI, 72.8%-97.8%). Internal specificity in this model was 98.9% (95% CI, 94.1%-100%), with a PPV of 92.9% (95% CI, 64.2%-99.0%); external specificity was 98.6% (95% CI, 96.5%-99.6%), with a PPV of 83.3% (95% CI, 64.1%-93.4%). In this prognostic study of neonates with moderate or severe HIE who were treated with therapeutic hypothermia, simple models using readily available clinical, EEG, and MRI results during the hospital admission had high specificity and PPV for death or severe NDI at age 2 years.

Early pain findings in infants with brachial plexus birth injury: Relationship with function and comorbidities, and cut-off point for fractures

BackgroundInfants with birth brachial plexus injury (BPBI) may have various comorbidities such as fractures, torticollis, plagiocephaly, central nervous system disorders. In infants with BPBI, it is important to identify fractures, which are common among comorbidities, objectively assess pain, and investigate factors that may be associated with pain. AimThe aim of this study is to determine the pain level, comorbidities, and motor function in infants with BPBI and to examine the relationship between these parameters. The second aim is to determine the cut-off value of the pain score that may be a sign of fracture in patients with BPBI, in order to suspect and predict a fracture in the shoulder region and to request additional examinations. Subjects and measurements59 infants with BPBI aged 15–90 days were included in the study. Comorbidities, active joint movements, and total upper extremity function assessed with the Active Movement Scale and pain scores measured with the FLACC Pain Scale were retrospectively analyzed. In addition, pain, comorbidities and motor function were investigated according to types of Narakas, which indicates the degree of nerve injury. ResultsOf the 59 participants, 18 (30.5 %) had at least one comorbidity and 12 (20.3 %) had fractures. The number of comorbidities (p = 0.41), the number of fractures (p = 0.84), and the level of pain (p = 0.71) did not differ by types of Narakas. There was a moderate negative correlation between pain level and upper extremity motor function in upper trunk injuries (p < 0.5, −0.67 < r < −0.46). There was a difference in pain level measured by palpation (p < 0.01) and passive joint movement (p < 0.01) in infants with and without comorbidities. To suspect a fracture in the shoulder region and to request further evaluation, the cut-off value of the Flacc pain level, which may predict a fracture, was 3.5 points for palpation and passive shoulder abduction and 4.5 points for passive external rotation. ConclusionThis is the first study in the BPBI to measure pain in infants using a quantifiable and widely used assessment. Pain level was ranked from high to low as infants with fractures, infants with comorbidities other than fractures and infants without comorbidities. Increased pain adversely affects motor function and pain above the cut-off values is a predictor of fracture.

Costunolide ameliorates rotenone-induced Parkinson's disease in rat model via activation of SIRT-1/p-AMPK cascade and suppression of IL-6/STAT3 axis

Costunolide (COST), a sesquiterpene lactone, has demonstrated promising potential in molecular docking studies targeting key proteins associated with Parkinson's disease (PD), particularly AMP-activated protein kinase (AMPK) and sirtuin-1 (SIRT1). Building on these preliminary findings, this study was designed to explore the in vivo neuroprotective effects of COST in a rotenone-induced PD model, aiming to substantiate its therapeutic efficacy. The evaluation focused on motor function, oxidative stress markers, neuroinflammatory indicators, and the balance between autophagy and apoptosis, alongside histopathological examination.Treatment with COST displayed an enhancement in motor performance, as observed by improved results in both the open-field and narrow beam walk tests. Concurrently, COST preserved dopaminergic neurons in the substantia nigra and boosted tyrosine hydroxylase immunoreactivity. Furthermore, COST reduced oxidative stress status via increasing SIRT-1 and PGC-1α content. Notably, COST suppressed neuroinflammation by inhibiting the IL-6R/STAT3/NFκBp65 /IL-6 signaling pathway. Additionally, COST stimulated autophagy via the activation of p-AMPK/ULK1/Beclin-1 cascade, facilitating the removal misfolded protein, α-synuclein. COST also reduced apoptosis by increasing Bcl-2 and decreasing Bax levels. In conclusion, COST exhibited promising neuroprotective effects against rotenone-induced PD in a rat model. This protection is mediated through the activation of the SIRT1/PGC-1α and p-AMPK/ULK1/Beclin-1 pathways, alongside the inhibition of the IL-6R/STAT3/NFκBp65 axis. Collectively, these mechanisms attenuated oxidative stress and neuroinflammation while restoring the balance between apoptosis and autophagy, positioning COST as a potential therapeutic candidate for Parkinson's disease.

Neurologic Music Therapy's Impact on Neurological Disorders.

Neurologic music therapy (NMT) represents a groundbreaking, interdisciplinary approach that combines the therapeutic properties of music with neuroscientific principles to treat a range of neurological and psychiatric conditions. This interdisciplinary approach, increasingly recognized in clinical and research settings, leverages advances in neuroimaging to explore how music affects the structure and activity of the brain. This review provides an in-depth exploration of the multifaceted effects of NMT on brain function, highlighting its role in promoting neuroplastic changes and enhancing cognitive, emotional and motor functions in diverse patient groups. This review consolidates current knowledge on NMT and provides insights into how music affects brain structure and function and the mechanisms of action. The article then discusses the application and research results of NMT in various diseases such as stroke, Alzheimer's disease and Parkinson's disease. Its potential in personalizing therapeutic interventions and its ability to improve treatment access and effectiveness in various settings are highlighted.

Photobiomodulation reduces spinal cord edema by decreasing the expression of AQP4 in the astrocytes of male spinal cord injury rats via the JAK2/STAT3 signaling pathway.

BackgroundSpinal cord swelling commonly occurs following SCI. Previous studies suggest that PBM may reduce inflammation and scar formation after SCI. However, whether PBM can alleviate post-spinal cord injury edema and its underlying mechanisms have not yet been reported. This study aims to investigate the effects of PBM on spinal cord swelling in rats following SCI and explore the underlying mechanisms. MethodsA rat model of SCI was established, and the rats received continuous PBM therapy for two weeks. Tissue hydration, motor function, AQP4 expression, and pathological changes in the spinal cord were evaluated at different time points. In vitro, astrocytes were subjected to PBM and treated with either cucurbitacin I or TGN020 following OGD. ResultsThe results indicate that PBM reduces tissue swelling in rats with SCI, improves motor function recovery, and inhibits the upregulation of AQP4 and GFAP associated with SCI. In vitro, PBM reduces abnormal activation of the JAK2/STAT3 signaling pathway in astrocytes, leading to decreased AQP4 synthesis and astrocyte activation. ConclusionsThese findings suggest that PBM reduces spinal cord swelling in rats after injury. This effect is associated with the inhibition of JAK2/STAT3 signaling pathway activation in astrocytes and the reduction in AQP4 expression.

Effects of Pediatric Endurance and Limb Strengthening (PEDALS) Program Versus Lower Limb Strength Training in Diplegic Cerebral Palsy

Objective: To evaluate the comparative effects of pediatric endurance and limb strengthening (PEDALS) program versus lower limb strength training in diplegic cerebral palsy(CP). Methodology: It was a Randomized clinical trial and a sample of 24 cerebral palsy (CP) patients was drawn through a consecutive sampling technique. One group of 12 patients received the PEDALS program and other group B of 12 patients received lower limb strength training. Group A PEDALS program was applied for 30 minutes, 3 days/week for 12 weeks, total 36 session and Group B lower limb strength training was applied 6-8rep, 1-3sets for3 days/week for 12 weeks, total 36 session. Outcome was measured with GMFM-88, Six-minute walk test and goniometer pre and post treatment. Results: Mean age for both group were 9.95±2.21. Mean value for total GMFM score for Group A was 64.916±8.129 and mean value for Group B was 65.33±9.92 with p-value &gt; 0.05. Mean value for six minute test for Group A was 199.58±13.55 and for Group B was 195.50±15.71 with p-value &gt;0.05 and ROM for Group Aand Group B p-value&gt;0.05. Conclusion: Result shows that PEDALS program as well as lower limb strength training is effective in improving endurance, gross motor function and ROM in diplegic CP. Keywords: Cerebral palsy, endurance, pediatric, strength, training.

Tributyl phosphate inhibits neurogenesis and motor functions during embryonic development in zebrafish

Tributyl phosphate inhibits neurogenesis and motor functions during embryonic development in zebrafish

Capillary Electrophoresis-Frontal Analysis (CE-FA) and Molecular Docking Studies on the Albumin-Binding Properties of Dopamine and Serotonin.

Dopamine and serotonin are neurotransmitters that are crucial for numerous physiological processes, including mood regulation, reward, and motor function. Dysregulation of these neurotransmitters is associated with various neuropsychiatric disorders. Albumin in plasma modulates the bioavailability of drugs and free concentrations of bioactive constituents. This study aimed to characterize the interactions of dopamine and serotonin with bovine serum albumin. Capillary electrophoresis in the frontal analysis mode was utilized as an effective method to assess dopamine-bovine serum albumin and serotonin-bovine serum albumin affinity. The free neurotransmitter plateaus were distinctly separated from the bovine serum albumin-neurotransmitter complex plateaus. Free dopamine and serotonin concentrations were determined by monitoring the heights of their respective plateaus. In contrast, the bound concentrations were calculated from the difference between the total and free plateau heights. Dopamine and serotonin were found to bind to bovine serum albumin at independent sites with binding constant values of 1.90×103 and 2.90×103L/mol, respectively. Additionally, an in silico molecular docking approach revealed the binding sites for dopamine and serotonin near the glutamic acid-291 and serine-428 residues of bovine serum albumin, respectively.

Disease Progression of GNE Myopathy and Its Relationship With Genotype: A Retrospective, Observational Study in Chinese Patients.

Studies on the natural disease progression of detailed motor dysfunction in patients with GNE myopathy are rare. This study aimed to investigate motor function involvement during disease progression and its relationship with the genotype among Chinese patients with GNE myopathy. This retrospective observational cohort study included all patients with genetically confirmed GNE myopathy enrolled at Peking University First Hospital between 2000 and 2023. Patients with GNE myopathy were stratified into 2 subgroups based on with or without p.D207V mutation. Data on clinically significant muscular problems were collected from patients' medical history and follow-up assessments to evaluate motor function using the GNE Myopathy Functional Activity Scale and the modified Rankin Scale. Eighty-three patients with GNE myopathy were included, with a median age at examination of 36 years (range 25-57) and a median age at onset (AAO) of 26 years (range 16-46). The Kaplan-Meier curves revealed that patients with the p.D207V mutation experienced a significantly later AAO (27 years [95% CI 25-29]) and onset age of wheelchair dependency (50 years [95% CI 46-54]) compared with those without the mutation, who had an AAO of 24 years (95% CI 22-26) and an onset age of wheelchair dependency of 45 years (95% CI 36-54). Multivariate Cox regression analysis, adjusted for sex and disease duration, revealed that patients without the p.D207V mutation had a higher risk of wheelchair dependency, with an adjusted hazard ratio of 2.361 (95% CI 1.030-5.411). Barthel indexes (BIs) were negatively correlated with the disease duration and positively correlated with AAOs. Patients with GNE with earlier AAO exhibited a shorter disease duration of developing functional dependency (BIs <60) than did those with later AAOs. Our results provide insights into the motor function involvement observed during disease progression in Chinese patients with GNE myopathy, and relatively mild disease severity was observed in those with the p.D207V mutation.

Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment

Charcot-Marie-Tooth disease type 1A (CMT1A) is a demyelinating disease caused by PMP22 duplication and an exceedingly rare hereditary peripheral neuropathy, with an incidence of 1 in 2500. Currently, no cure exists for CMT1A; however, various therapeutic approaches are under development. Considering the known therapeutic effects of mesenchymal stem cells (MSCs) and the relation of blood sugar levels with nerve damage in CMT, this study aimed to confirm the therapeutic effects of MSCs and insulin on CMT, using both in-vitro and in-vivo models. CMT1A in-vitro models were exposed to Wharton's jelly-derived MSCs (WJ-MSCs) or insulin, and the resulting proliferation changes were measured. CMT1A mice were treated with WJ-MSCs or insulin, and their phenotypic changes were observed. We observed improvements in myelination of Schwann cells in vitro and motor function in vivo. Insulin also showed therapeutic efficacy by promoting Schwann cell proliferation. Furthermore, combination therapy using insulin and WJ-MSCs was more effective than WJ-MSCs or insulin alone. Insulin promoted the proliferation of Schwann cells and WJ-MSCs through activation of the ATK and PI3K-MAPK signaling pathways. Overall, this study is the first to confirm the therapeutic efficacy of WJ-MSCs and insulin in CMT1A, and their synergistic effect without causing insulin resistance.

Risk assessment of complex organoarsenic species in food.

The European Commission asked EFSA for a risk assessment on complex organoarsenic species in food. They are typically found in marine foods and comprise mainly arsenobetaine (AsB), arsenosugars and arsenolipids. For AsB, no reference point (RP) could be derived because of insufficient toxicity data. AsB did not show adverse effects in the two available repeat dose toxicity tests in rodents. It has not shown genotoxicity in in vitro assays. There is no indication of an association with adverse outcomes in human studies. The highest 95th percentile exposure for AsB was observed in 'Toddlers' with an estimate of 12.5 μg As/kg bw per day (AsB expressed as elemental arsenic). There is sufficient evidence to conclude that AsB at current dietary exposure levels does not raise a health concern. For glycerol arsenosugar (AsSugOH) a RP of 0.85 mg As/kg bw per day was derived based on the BMDL10 values for cognitive and motor function in mice. A margin of exposure (MOE) of ≥ 1000 would not raise a health concern. The highest 95th percentile estimate of exposure for AsSugOH (for adult consumers of red seaweed Nori/Laver) was 0.71 μg As/kg bw per day (AsSugOH expressed as elemental arsenic), which results in an MOE > 1000, not raising a health concern. Based on qualitative consideration of all identified uncertainties, it is regarded likely that the dietary exposures to AsB and AsSugOH do not raise a health concern. No conclusions could be drawn regarding other arsenosugars. No risk characterisation could be conducted for arsenolipids, due to the lack of data.

Mechanistic insights into “Three Methods and Three Acupoints” Tuina therapy for improving spinal microcirculation and motor function in sciatic nerve injury model rats

Mechanistic insights into “Three Methods and Three Acupoints” Tuina therapy for improving spinal microcirculation and motor function in sciatic nerve injury model rats

Reactivation of mTOR signaling slows neurodegeneration in a lysosomal sphingolipid storage disease.

Sandhoff disease, a lysosomal storage disorder, is caused by pathogenic variants in the HEXB gene, resulting in the loss of β-hexosaminidase activity and accumulation of sphingolipids including GM2 ganglioside. This accumulation occurs primarily in neurons, and leads to progressive neurodegeneration through a largely unknown process. Lysosomal storage diseases often exhibit dysfunctional mTOR signaling, a pathway crucial for proper neuronal development and function. In this study, Sandhoff disease model mice exhibited reduced mTOR signaling in the brain. To test if restoring mTOR signaling could improve the disease phenotype, we genetically reduced expression of the mTOR inhibitor Tsc2 in these mice. Sandhoff disease mice with reactivated mTOR signaling displayed increased survival rates and motor function, especially in females, increased dendritic-spine density, and reduced neurodegeneration. Tsc2 reduction also partially rescued aberrant synaptic function-related gene expression. These findings imply that enhancing mTOR signaling could be a potential therapeutic strategy for lysosomal-based neurodegenerative diseases.

Neurometabolite and cognitive changes in hypothyroid patients in response to treatment: In-vivo 1H MRS Study.

The disturbances in thyroid hormones lead to altered brain metabolism, function, and cognition. Neuroimaging studies have shown structural and functional changes in hypothyroidism. Present study investigates the neuro-metabolite changes in dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) and associated decline cognitive function in hypothyroid patients before and after thyroxine treatment. We performed neuropsychological test and 1H MRS in hypothyroid patients (n=25) and controls (n=30). In addition, follow-up data was also collected from 19 patients treated with levo-thyroxine for 32 weeks. The concentration of the neurometabolites were calculated using LCModel. MRS data were analysed using analysis of covariance (ANCOVA), with age and gender as covariates. A paired t-test was conducted to compare the baseline hypothyroid with the follow-up. Partial correlations were utilised to assess possible associations between neuropsychological scores and neurometabolites with age and gender as covariates. Spearman correlation was performed between thyroid hormone levels and neurometabolites. Hypothyroid patients showed an impairment in delayed recall, immediate recall of semantic, visual retention, recognition of objects memory, attention, and motor function at baseline, which improved significantly after thyroxine therapy. At baseline, patients with hypothyroidism exhibited significantly higher levels of choline compounds (GPC+PCh) [Cho]. No significant normalisation of Cho levels was observed, despite achieving euthyroidism with thyroxine treatment. Cho levels showed a positive correlation with TSH in PPC and a negative correlation with T4 in DLPFC and PCC. Cho levels also showed negative correlations with delayed recall, immediate recall of semantic, visual retention memory and MMSE scores. The MRS findings show increased levels of Cho in hypothyroid patients compared to healthy controls. These Cho levels are not reversible within 32 weeks of treatment, suggesting that a longer follow-up may be needed to see if levels can be normalised.

Efficacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the D-A-CH-region: a population-based observational study

Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0-90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n=16, nusinersen: n=154, both: n=2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

Optimizing the Performance of DC Electric Smart Gate Motor using Ziegler Nichols Tuning Methods

One of the primary functions of the DC motor is exemplified in its utilization for the automated operation of irrigation gates, which involves a variety of DC motor models. The DC motor chosen was influenced by the particular operational requirements of the irrigation gate. The ability to support the massive weight of the gate as well as the extreme pressure produced by river water currents are among these requirements. The gate motor utilized functions at a sluggish pace of 20 revolutions per minute. The approach employed involves tuning utilizing the Ziegler-Nichols (ZN) method. The (Proportional-Integral-Derivative) PID controller is designed to precisely manage a DC motor's position, improving the motor's overall performance. The parameters were designed to be Kp = 17, Ti = 1, and Td = 0.1. The Simulation derived from the analysis of MATLAB step response data are side by side with algorithm utilized to certain the dynamic response of the closed-loop configuration. Essential Specifications such as rise time and settling time, both measured in seconds, will be integrated into the simulation outcomes. The utilization of the (ZN) based algorithm for adjusting the gain constants of the PID control system tends to yield superior outcomes in comparison to that under a unity feedback control system .The rising time was 12.6, but when performance improved, it dropped to 0.713. This improvement is also applicable to the settling time, which decreased from 22.4 to 1.13. The holistic evaluation demonstrates that the (ZN) method yields superior performance in contrast to a system employing unity feedback control.

Effect of alemtuzumab on fatigue, quality of life, and patient/caregiver-reported outcomes in relapsing-remitting multiple sclerosis – a real-world evidence study

BackgroundAlemtuzumab is approved in the European Union for treating highly active relapsing-remitting multiple sclerosis (RRMS). Patient-reported outcomes measure the treatment impact on quality of life (QoL), including fatigue, a common symptom in multiple sclerosis (MS). Chronic diseases like MS also affect the patient's caregiver. Thus, understanding the impact on both patients and caregivers is essential for a comprehensive view of MS treatment outcomes. MethodsThis multi-center prospective, observational study assessed RRMS patients undergoing alemtuzumab treatment, and their caregivers across three European countries (Denmark, Norway, and Italy). The study visits were conducted at baseline, and at Months 3, 6, 12, 18, 24, and 36 (± 1 month). The primary endpoint assessed the effect of alemtuzumab on MS-related fatigue (Fatigue Scale for Motor and Cognitive Functions [FSMC] score). Secondary endpoints included changes in cognition (Symbol Digit Modalities Test [SDMT]), depression (Beck Depression Inventory-Version II [BDI-II]), QoL (29-item Multiple Sclerosis Impact Scale [MSIS-29]), treatment satisfaction (Treatment Satisfaction Questionnaire for Medication [TSQM]), working capacity/daily life activity (Health-Related Productivity Questionnaire [HRPQ]), and clinical evaluation (number of relapses, improvement in Expanded Disability Status Scale [EDSS] score, and need for re-treatment with alemtuzumab/any other treatment). Exploratory endpoints included caregiver perception of patient's QoL, caregiver QoL, and caregiver burden. The sample size (N=80) was determined based on the 2-sided t-test at 5% significance level. Data were analyzed descriptively. Safety was also evaluated. ResultsOf 87 enrolled patients, 72.4% (n=63) completed all follow-ups. Significant improvement was observed in fatigue (p<0.01), with a median (min, max) FSMC score change of -7.3 (-56.0, 34.0) units at the end-of-study (EOS), and clinically relevant improvement (≥ 9 units) noted in approximately 12.5 months. SDMT (3-5 units, p<0.05), BDI-II (median score of 9.5, i.e., no depression, p<0.01), and MSIS-29 (median change in physical and psychological impact scores -9.2, p<0.01 and -14.8, p<0.001, respectively) improved significantly from baseline to EOS. Global treatment satisfaction (p<0.001), effectiveness (p<0.05), and side effects (p<0.05) significant improved exept at EOS, whereas treatment convenience remained same throughout the study. The percentage of patients with at least one relapse was similar each year of the study (10.8%-13.2%). A statistically significant improvement (p<0.05) in EDSS was reported over time. At EOS, 4.5% patients needed retreatment with alemtuzumab. Caregivers also reported improvement in patients’ QoL over time, but the median change from baseline (physical and psychological impact scores: -10.0 and -14.8, respectively) was not statistically significant (p>0.05). Caregivers reported similar QoL and caregiver burden at baseline and EOS, apart from an increase in emotional QoL. Headache (51.2%), pyrexia (44.2%), and rash (34.9%) were the most common adverse events (AEs). Majority of the AEs were either mild or moderate, apart from 25 severe AEs. Three patients discontinued prematurely, of which one patient died of sepsis related to treatment. ConclusionThis real-world study showed beneficial impact of alemtuzumab on fatigue, cognition, depression, QoL, and treatment satisfaction. Improvement in patient disability, and caregiver-reported outcomes indicated enhanced patients’ QoL.

Relationship Between Body Mass Index, Selective Voluntary Motor Control and Functional Independence in Children With Cerebral Palsy

Objectives: This study detects the relationship between body mass index (BMI), selective voluntary motor control (SVMC) and functional independence in children with spastic diplegic cerebral palsy (CP). Methods: A total of 84 children with spastic diplegic CP (levels II and III of gross motor function classification system [GMFCS]), aged 6-9 years with a mean age of 7.09±0.68 participated in this correlational study. BMI, selective control assessment of the lower extremity and pediatric functional independence measure (WEE FIM) were used to assess BMI, SVMC and functional independence, respectively. Results: The data demonstrated the presence of a positive strong significant correlation between selective control assessment of the lower extremity and WEE FIM. On the other hand, there was a negative, significant correlation between WEE FIM and BMI. In addition, a negative moderate considerable correlation between BMI and selective control assessment of the lower extremity was detected Discussion: Functional independence is significantly correlated with BMI and SVMC in children with spastic diplegic CP. BMI and SVMC are major factors that influence functional independence in these children. So, they are highly recommended to be part of the evaluation of the functional independence of children with spastic diplegia in clinical settings and research.

TAT-PPA1 protects against oxidative stress-induced loss of dopaminergic neurons.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) of the midbrain, resulting in severe motor impairments. Inorganic pyrophosphatase 1 (PPA1) plays a key role in various biological processes, and this study introduces a cell-penetrating PPA1 fusion protein (TAT-PPA1) to explore its transduction into cells and brain tissues. TAT-PPA1 effectively penetrates SH-SY5Y cells and the SN region of PD animal models without toxicity, exhibiting protective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-)-induced cell death. TAT-PPA1 revealed an inhibitory influence on the MAPK signaling pathway and MPTP-induced reactive oxygen species (ROS) production. TAT-PPA1 suppresses JNK, AKT, p53, ERK, and p38 phosphorylation, showcasing its multifaceted role in cell survival pathways. In the MPTP-induced PD animal model, TAT-PPA1 prevents dopaminergic cell death and enhances motor function. This study shows that TAT-PPA1 protects against oxidative stress and cell death in neurodegenerative diseases, suggesting potential as a PD treatment.

Role of BDNF-TrkB signaling in the improvement of motor function and neuroplasticity after ischemic stroke in rats by transcranial direct current stimulation

Role of BDNF-TrkB signaling in the improvement of motor function and neuroplasticity after ischemic stroke in rats by transcranial direct current stimulation