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1.
Neurol Ther ; 13(5): 1483-1504, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39222296

RESUMEN

INTRODUCTION: Nusinersen clinical trials have limited data on adolescents and adults with 5q-associated spinal muscular atrophy (SMA). We conducted a systematic literature review (SLR) and meta-analysis to assess effectiveness of nusinersen in adolescents and adults with SMA in clinical practice. METHODS: Our search included papers published 12/23/2016 through 07/01/2022 with ≥ 5 individuals ≥ 13 years of age and with ≥ 6 months' data on ≥ 1 selected motor function outcomes [Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), and Six-Minute Walk Test (6MWT)]. For meta-analysis, effect sizes were pooled using random-effects models. To understand treatment effects by disease severity, subgroup meta-analysis by SMA type and ambulatory status was conducted. RESULTS: Fourteen publications including 539 patients followed up to 24 months met inclusion criteria for the SLR. Patients were age 13-72 years and most (99%) had SMA Type II or III. Modest improvement or stability in motor function was consistently observed at the group level. Significant mean increases from baseline were observed in HFMSE [2.3 points (95% CI 1.3-3.3)] with 32.1% (21.7-44.6) of patients demonstrating a clinically meaningful increase (≥ 3 points) at 18 months. Significant increases in RULM were consistently found, with a mean increase of 1.1 points (0.7-1.4) and 38.3% (30.3-47.1) showing a clinically meaningful improvement (≥ 2 points) at 14 months. Among ambulatory patients, there was a significant increase in mean 6MWT distance of 25.0 m (8.9-41.2) with 50.9% (33.4-68.2) demonstrating a clinically meaningful improvement (≥ 30 m) at 14 months. The increases in HFMSE were greater for less severely affected patients, whereas more severely affected patients showed greater improvement in RULM. CONCLUSIONS: Findings provide consolidated evidence that nusinersen is effective in improving or stabilizing motor function in many adolescents and adults with a broad spectrum of SMA.


Motor neurons are specialized cells in the brain and spinal cord that control the function of muscles. People with spinal muscular atrophy (SMA) do not make enough survival motor neuron (SMN) protein, which motor neurons need to function. As a result, people with SMA experience decreased muscle function that gets worse over time. Nusinersen is a drug that increases the amount of SMN protein made in the brain and spinal cord. However, most clinical trials of nusinersen have been in infants and children with SMA. Less is known about the effects of nusinersen in teenagers and adults with SMA who may have less severe but still progressive forms of the disease. In this manuscript, we first conducted a thorough review and analysis of research published by investigators who treated teenagers and adults with nusinersen for up to 24 months. We then used an additional analysis, called a meta-analysis, that allowed us to combine the information from several articles, so that we could better understand whether nusinersen helped these patients. We looked at 3 tests that investigators used to see how nusinersen affected patients' motor function. The Hammersmith Functional Motor Scale­Expanded (HFMSE) assesses upper and lower limb motor function; the Revised Upper Limb Module (RULM) evaluates upper limb function; and the Six-Minute Walk Test (6MWT) measures the maximum distance a person can walk in 6 minutes. Our study showed that nusinersen can improve motor function or prevent motor function from getting worse in many teenagers and adults with SMA.

2.
Prog Rehabil Med ; 9: 20240029, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280961

RESUMEN

Objectives: There is a lack of evidence regarding the association between whole-body exercise and independence in urination and defecation. This study aimed to evaluate the effect of chair-stand exercise on improving urination and defecation independence in post-stroke patients with sarcopenia. Methods: A retrospective study was conducted on stroke patients admitted to a community rehabilitation hospital between 2015 and 2021. Patients diagnosed with sarcopenia who required assistance with bladder and bowel management were included. The primary outcomes were the Functional Independence Measure (FIM) scores for urination (FIM-Bladder) and defecation (FIM-Bowel) at discharge. Multiple regression analysis was used to examine the association between chair-stand exercise and the outcomes, adjusting for potential confounders. Results: Of 586 patients, 187 patients (mean age 79.3 years, 44.9% male) were included in the urination analysis, and 180 patients (mean age 79.3 years, 44.4% male) were included in the defecation analysis. Multiple regression analysis showed that the number of chair-stand exercises was independently positively associated with FIM-Bladder at discharge (ß=0.147, P=0.038) and FIM-Bladder gain (ß=0.168, P=0.038). Similarly, the number of chair-stand exercises was independently positively associated with FIM-Bowel at discharge (ß=0.149, P=0.049) and FIM-Bowel gain (ß=0.166, P=0.049). Conclusions: Chair-stand exercise was positively associated with improved urination and defecation independence in post-stroke patients with sarcopenia. Incorporating whole-body exercises, such as chair-stand exercise, in addition to conventional rehabilitation programs may help improve voiding independence, reduce incontinence, and enhance quality of life in these patients.

3.
Int J Clin Health Psychol ; 24(3): 100498, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39290876

RESUMEN

Objective: There is evidence that complex relationships exist between motor functions, brain structure, and cognitive functions, particularly in the aging population. However, whether such relationships observed in older adults could extend to other age groups (e.g., younger adults) remains to be elucidated. Thus, the current study addressed this gap in the literature by investigating potential associations between motor functions, brain structure, and cognitive functions in a large cohort of young adults. Methods: In the current study, data from 910 participants (22-35 yr) were retrieved from the Human Connectome Project. Interactions between motor functions (i.e., cardiorespiratory fitness, gait speed, hand dexterity, and handgrip strength), brain structure (i.e., cortical thickness, surface area, and subcortical volumes), and cognitive functions were examined using linear mixed-effects models and mediation analyses. The performance of different machine-learning classifiers to discriminate young adults at three different levels (related to each motor function) was compared. Results: Cardiorespiratory fitness and hand dexterity were positively associated with fluid and crystallized intelligence in young adults, whereas gait speed and handgrip strength were correlated with specific measures of fluid intelligence (e.g., inhibitory control, flexibility, sustained attention, and spatial orientation; false discovery rate [FDR] corrected, p < 0.05). The relationships between cardiorespiratory fitness and domains of cognitive function were mediated by surface area and cortical volume in regions involved in the default mode, sensorimotor, and limbic networks (FDR corrected, p < 0.05). Associations between handgrip strength and fluid intelligence were mediated by surface area and volume in regions involved in the salience and limbic networks (FDR corrected, p < 0.05). Four machine-learning classifiers with feature importance ranking were built to discriminate young adults with different levels of cardiorespiratory fitness (random forest), gait speed, hand dexterity (support vector machine with the radial kernel), and handgrip strength (artificial neural network). Conclusions: In summary, similar to observations in older adults, the current study provides empirical evidence (i) that motor functions in young adults are positively related to specific measures of cognitive functions, and (ii) that such relationships are at least partially mediated by distinct brain structures. Furthermore, our analyses suggest that machine-learning classifier has a promising potential to be used as a classification tool and decision support for identifying populations with below-average motor and cognitive functions.

4.
Front Neurol ; 15: 1379536, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39239398

RESUMEN

Objective: To investigate the psychometric properties of the Lift and Carry Test (LCT) time in people with stroke. Design: Cross-sectional design. Setting: University based neurorehabilitation laboratory. Participants: Twenty-four people with stroke and 24 healthy controls. Outcome measures: Lift and Carry Test (LCT), Fugl-Meyer Assessment of upper extremity and lower extremity, ankle dorsiflexor and plantarflexor muscle strength, Berg Balance Scale (BBS), Timed Up and Go (TUG) and Community Integration Measure. Results: The mean LCT time (29.70s) in people with stroke was more than double of that in healthy controls (13.70s). The LCT showed excellent intra-rater, inter-rater and test-retest reliability [intraclass correlation coefficient (ICC) = 0.943-1.000]. The LCT times demonstrated a significant negative correlation with the BBS score (rs = -0.771) and significant positive correlations with the TUG times (rs = 0.933). There was no significant correlation between LCT times and FMA score (p > 0.05). An optimal cut-off LCT time of 15.48 s (sensitivity = 95.8%, specificity = 87.5%) was identified to differentiate between people with stroke and healthy controls (area under the curve = 0.957). Conclusion: LCT is an excellent clinical test for examining advanced functional ability in people with stroke and distinguishing people with stroke from healthy controls.

5.
Cureus ; 16(8): e66667, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39262538

RESUMEN

In recent years, mental practice (MP), which involves repetitive motor imagery (MI), has been applied in rehabilitation to actively enhance exercise performance. MP is a method that involves repetitive MI, consciously evoking the intentions and content of the exercise without actual exercise. Combining actual exercise with MP promotes the development of exercise skills. However, it is possible that the MI recall ability differs greatly between individuals, affecting the therapeutic effect. In contrast, the vibration-induced illusory movement (VIM) task acts as a method to induce a motor illusion by somatosensory stimuli without actual motor. VIM, actual movement, and MI are thought to share a common neural basis in the brain. Therefore, it was hypothesized that the VIM task would complement the differences in MI recall in individual patients with hemiplegic stroke and may be a new treatment to enhance MI recall. Accordingly, in this study, we investigated the therapeutic effects of the VIM task in patients with hemiplegic stroke. In Study I, the therapeutic effect of the VIM task in 14 patients with post-stroke hemiplegia was evaluated by motor function assessment. In Study II, treatment effects were investigated by examining the ability of the same group of patients to recall MI and by neurophysiological examination of the electroencephalogram (EEG) during MI recall in four patients who consented to the study. Motor function and MI were assessed four times: before the intervention, after occupational therapy, after the VIM task (which used the motor illusion induced by tendon vibration), and one month after acceptance of therapy. Compared with occupational therapy, the VIM task showed a statistically significant improvement in upper limb function and MI ability. In addition, we found an increase in event-related desynchronization intensity during MI in the affected hemisphere only after the VIM task. It is possible that the VIM task facilitates motor function and MI. VIM task implementation of MI recall variability between individuals, which is a problem in mental practice, possible to increase the effectiveness of the brain-machine interface.

6.
Front Neurol ; 15: 1388718, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268070

RESUMEN

Background: Children and young people (CYP) with acquired brain injury (ABI) require early and effective neurorehabilitation to improve long-term functional outcomes. Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have been used to improve motor and sensory skills for children with cerebral palsy. However, there is limited evidence supporting its use in CYP with ABI. Objective: To systematically review the TMS and tDCS intervention effects on motor, sensory and other functional issues in CYP with ABI as reported in the literature. Methods: A comprehensive online bibliographic databases search was performed in various databases using keywords related to NIBS and CYP with ABI. Studies that examine the effect of NIBS intervention on motor function and other functional difficulties either as a primary or secondary objective were included in this review. Results: Fourteen studies (10 single case reports, one retrospective analysis, one case series, one randomised and one quasi-randomised controlled trial) published between 2006 and 2023 were identified. These studies examined the use of NIBS to manage motor disorders, hearing, vision, headaches, speech and language and memory issues. Seventy-six children with mild to severe ABI had received NIBS. The session frequency (3-20), duration (10-45 min) was variable, and NIBS delivered between 3 and 28 days. Conclusion: The literature describing NIBS interventions in CYP with ABI is scarce. An insufficient number of studies, inadequate information reported in them, and small sample sizes limit the ability to conclude how effective NIBS is in improving motor function and other functional issues in this cohort. Further studies are therefore necessary to examine the therapeutic effects of NIBS to manage various functional problems in the CYP with ABI.

7.
Front Hum Neurosci ; 18: 1409148, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268217

RESUMEN

Background: Upper limb motor impairment is a common consequence of stroke, and the effectiveness and underlying mechanisms of rehabilitation therapy for improving upper limb function remain uncertain. Functional near-infrared spectroscopy, a reliable wearable neuroimaging technique, holds promise for investigating brain activity during functional tasks. This study aims to explore the synchronous oxygenation characteristics of the central cortex and upper-limb flexors during a grasping task and investigate the rehabilitation mechanisms of upper limb motor function in individuals with stroke. Methods: Participants with stroke who demonstrate the ability to grasp and lift cubic wood blocks of different sizes (2.5cm3, 5cm3, and 10cm3) using their affected hand will be divided into three groups: A, B, and C. Each group will consist of twenty stroke patients, resulting in a total of sixty participants with stroke. Additionally, twenty matched healthy subjects will be enrolled as a control group. Comprehensive assessments will be conducted before and after the intervention, including blood oxygen parameter monitoring of the cerebral cortex and upper limb flexors using fNIRS during the grasping task. Other assessments will include MyotonPRO, the Modified Ashworth Scale, the upper extremity section of the Fugl-Meyer Assessment, the Action Research Arm Test, and the Modified Barthel Index. The study will be undertaken between January 2024 and September 2025. Conclusions: The results of this trial will provide an in-depth understanding of the Characteristics of central cortex and upper-limb flexors synchronous oxygenation during grasping task and how it may relate to the rehabilitation mechanism of upper limb motor function in people with stroke. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2400080619.

8.
J Alzheimers Dis ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39269840

RESUMEN

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder which primarily involves memory and cognitive functions. It is increasingly recognized that motor involvement is also a common and significant aspect of AD, contributing to functional decline and profoundly impacting quality of life. Motor impairment, either at early or later stages of cognitive disorders, can be considered as a proxy measure of cognitive impairment, and technological devices can provide objective measures for both diagnosis and prognosis purposes. However, compared to other neurodegenerative disorders, the use of technological tools in neurocognitive disorders, including AD, is still in its infancy. Objective: This report aims to evaluate the role of technological devices in assessing motor involvement across the AD spectrum and in other dementing conditions, providing an overview of the existing devices that show promise in this area and exploring their clinical applications. Methods: The evaluation involves a review of the existing literature in the PubMed, Web of Science, Scopus, and Cochrane databases on the effectiveness of these technologies. 21 studies were identified and categorized as: wearable inertial sensors/IMU, console/kinect, gait analysis, tapping device, tablet/mobile, and computer. Results: We found several parameters, such as speed and stride length, that appear promising for detecting abnormal motor function in MCI or dementia. In addition, some studies have found correlations between these motor aspects and cognitive state. Conclusions: Clinical application of technological tools to assess motor function in people with cognitive impairments of a neurodegenerative nature, such as AD, may improve early detection and stratification of patients.

9.
Artículo en Inglés | MEDLINE | ID: mdl-39270308

RESUMEN

Non-pharmacological interventions include physical activity, biofield energy therapy, reiki, Tai chi, and therapeutic touch. However, no reports analyzed the effectiveness of biofield therapy on cognition and motor function performance in adult subjects. The study aimed to investigate the impact of remote biofield energy healing therapy on cognition and motor functioning in adults with self-perceived neuropsychological impairments. This was a randomized double-blind clinical trial that involved 114 participants with self-perceived neuropsychological impairments. The participants were divided into three groups (control, sham control, and biofield intervention). Cognitive and motor function scores were assessed using the NIH Toolbox at baseline (day 0), day 90, and day 180. The biofield treatment group showed significant improvements in language function (p < 0.0001), working memory (p < 0.0001), and episodic memory (p < 0.0001) scores. Other cognitive functions also improved, although not statistically significant. The biofield intervention group also demonstrated significant enhancements (p < 0.05 to p < 0.0001) in locomotion, standing balance, dexterity, grip strength, and muscle endurance. No adverse effects were reported. The results suggest that remote biofield energy therapy is a safe, noninvasive intervention that improves cognitive and motor functions in adults. Further research is needed to understand its clinical benefits.

10.
Ann Med Surg (Lond) ; 86(9): 5425-5438, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39238962

RESUMEN

Background: Stroke is a major cause of adult disability, prompting the exploration of innovative rehabilitation methods. Virtual rehabilitation (VR), leveraging technological advances, has gained popularity as a treatment for stroke recovery. Methodology: The authors conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) published in English within the last decade, adhering to the PRISMA guidelines. The authors searched databases such as Medline/PubMed, and the Cochrane Library using specific search keywords and Medical Subject Headings (MeSH). The methodological quality was assessed using the PEDro scale, focusing on RCTs involving adult stroke patients undergoing VR rehabilitation, with outcomes related to motor function and quality of life. Results: The authors included 15 studies in our meta-analysis. VR rehabilitation offers several advantages over traditional therapy, such as enhanced feedback and increased patient motivation. Engaging VR environments helps improve focus during treatment, potentially boosting recovery from post-stroke impairments. VR therapies significantly benefit motor function, which can improve activities of daily living and overall quality of life. Conclusion: VR has demonstrated efficacy in improving motor function and quality of life for stroke survivors. Future research should explore patient variability and refine intervention methods. Incorporating VR into rehabilitation programs could optimize stroke recovery outcomes.

11.
Muscle Nerve ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39233378

RESUMEN

INTRODUCTION/AIMS: Available studies on scoliosis surgery in spinal muscular atrophy (SMA) have focused on the primary outcome of the procedure-the correction of the curve-whereas research focusing on secondary outcomes is scarce. We aimed to investigate postsurgical changes in respiratory function, motor function, weight, pain, and satisfaction. METHODS: We retrospectively reviewed the clinical notes of 32 disease-modifying treatment-naïve patients (26 SMA2, 6 nonambulant SMA3). We also performed investigator-developed phone interviews and conducted a focus group with families on postsurgical satisfaction. RESULTS: Mean annual rate of forced vital capacity percent decline improved in SMA2: -3.2% postsurgery versus -6.9% presurgery (p < .001), with similar trajectories in SMA3. Gross motor functional scores (Hammersmith Functional Motor Scale) available in 12/32 dropped immediately after surgery: median loss of 6.5 points, with relatively spared upper limb function. Weight z-scores postsurgery dropped in 16/32, requiring food supplements (5/16); one/16 lost >5% of total weight requiring gastrostomy. Postsurgical pain was frequently reported, especially hip pain (13/32). Overall, 10/10 patients/parents participating in the phone interview rated the procedure as very successful for posture and physical appearance. Nonetheless, 7/10 reported postsurgical pain, reduced mobility, and unmet care needs. The seven patients/parents attending the focus group highlighted lack of intensive physiotherapy programs, occupational therapy assistance, and psychological support as postsurgical unmet care needs. DISCUSSION: This study reports a positive impact of scoliosis surgery on respiratory function and overall satisfaction with posture and physical appearance. The observed negative impact on the other outcomes highlights the importance of multidisciplinary approaches to improve postoperative management.

12.
Drug Dev Res ; 85(6): e22254, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39234934

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. Syncytin-1 (Syn), an envelope glycoprotein encoded by the env gene of the human endogenous retrovirus-W family, has been resorted to be highly expressed in biopsies from the muscles from ALS patients; however, the specific regulatory role of Syn during ALS progression remains uncovered. In this study, C57BL/6 mice were injected with adeno-associated virus-overexpressing Syn, with or without Fasudil administration. The Syn expression was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry analysis. The histological change of anterior tibial muscles was determined by hematoxylin-eosin staining. Qualitative ultrastructural analysis of electron micrographs obtained from lumbar spinal cords was carried out. Serum inflammatory cytokines were assessed by enzyme linked immunosorbent assay (ELISA) assay and motor function was recorded using Basso, Beattie, and Bresnahan (BBB) scoring, climbing test and treadmill running test. Immunofluorescence and western blot assays were conducted to examine microglial- and motor neurons-related proteins. Syn overexpression significantly caused systemic inflammatory response, muscle tissue lesions, and motor dysfunction in mice. Meanwhile, Syn overexpression promoted the impairment of motor neuron, evidenced by the damaged structure of the neurons and reduced expression of microtubule-associated protein 2, HB9, neuronal nuclei and neuron-specific enolase in Syn-induced mice. In addition, Syn overexpression greatly promoted the expression of CD16/CD32 and inducible nitric oxide synthase (M1 phenotype markers), and reduced the expression of CD206 and arginase 1 (M2 phenotype markers). Importantly, the above changes caused by Syn overexpression were partly abolished by Fasudil administration. This study provides evidence that Syn-activated microglia plays a pivotal role during the progression of ALS.


Asunto(s)
1-(5-Isoquinolinesulfonil)-2-Metilpiperazina , Ratones Endogámicos C57BL , Microglía , Neuronas Motoras , Animales , Microglía/efectos de los fármacos , Microglía/metabolismo , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/metabolismo , Ratones , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Productos del Gen env , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/metabolismo , Proteínas Gestacionales/metabolismo , Masculino , Citocinas/metabolismo , Modelos Animales de Enfermedad , Actividad Motora/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/efectos de los fármacos
13.
Cureus ; 16(8): e66349, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39247036

RESUMEN

Patients with rare genetic muscle-wasting disorders (MWDs) often experience significant motor function impairments, making effective management strategies crucial for improving their quality of life. This systematic review and meta-analysis aimed to evaluate the impact of physiotherapeutic interventions on motor outcomes in this patient population.  A comprehensive literature search was conducted to identify randomized controlled trials (RCTs) and cohort-based studies that assessed physiotherapeutic interventions in patients with rare genetic MWDs. The primary outcome measure was the 6-minute walk test (6MWT). A random effects model was employed to calculate the mean difference (MD) and 95% confidence interval (CI).  Nine studies were selected for inclusion, and most demonstrated observable improvement in different facets of individuals with MWDs using physiotherapy. The meta-analysis of RCTs showed that physiotherapy statistically improved 6MWT performance (MD: -35.25 meters; 95% CI: -54.14 to -16.37) with low heterogeneity (Tau² = 0.00; Chi² = 0.48, df = 2, P = 0.79; I² = 0%). Similarly, the cohort-based studies demonstrated an overall MD (MD: -10.00; 95% CI: -11.07 to -8.93), with low heterogeneity (Tau² = 0.00; Chi² = 0.01, df = 1, P = 0.94; I² = 0%). Both analyses indicated significant improvements in 6MWT performance (RCTs: Z = 3.66, P = 0.0003; cohort-based: Z = 18.26, P < 0.00001). Physiotherapeutic interventions significantly enhanced motor function in patients with rare genetic MWDs, as evidenced by improved 6MWT performance. Exercise and intensive physiotherapy programs were particularly effective, although the benefits varied depending on the specific intervention and patient population. These findings support incorporating tailored physiotherapeutic strategies in MWD management to improve motor outcomes and overall quality of life.

14.
Front Neurol ; 15: 1408324, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114533

RESUMEN

After stroke, the poorer recovery of motor function of upper extremities compared to other body parts is a longstanding problem. Based on our recent functional MRI evidence on healthy volunteers, this perspective paper proposes systematic hand motor rehabilitation utilizing the plasticity of interhemispheric interaction between motor cortices and following its developmental rule. We first discuss the effectiveness of proprioceptive intervention on the paralyzed (immobile) hand synchronized with voluntary movement of the intact hand to induce muscle activity in the paretic hand. In healthy participants, we show that this bilateral proprioceptive-motor coupling intervention activates the bilateral motor cortices (= bilaterally active mode), facilitates interhemispheric motor-cortical functional connectivity, and augments muscle activity of the passively-moved hand. Next, we propose training both hands to perform different movements, which would be effective for stroke patients who becomes able to manage to move the paretic hand. This bilaterally different movement training may guide the motor cortices into left-right independent mode to improve interhemispheric inhibition and hand dexterity, because we have shown in healthy older adults that this training reactivates motor-cortical interhemispheric inhibition (= left-right independent mode) declined with age, and can improve hand dexterity. Transition of both motor cortices from the bilaterally active mode to the left-right independent mode is a developmental rule of hand motor function and a common feature of motor function recovery after stroke. Hence, incorporating the brain's inherent capacity for spontaneous recovery and adhering to developmental principles may be crucial considerations in designing effective rehabilitation strategies.

15.
Front Neurol ; 15: 1419791, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39105058

RESUMEN

Background and purpose: At 12 months in the phase 2 TOPAZ study, treatment with apitegromab was associated with both an improved motor function in patients with Type 2 or 3 spinal muscular atrophy (SMA) and with a favorable safety profile. This manuscript reports the extended efficacy and safety in the nonambulatory group of the TOPAZ study at 36 months. Methods: Patients who completed the primary study (NCT03921528) could enroll in an open-label extension, during which patients received apitegromab 20 mg/kg by intravenous infusion every 4 weeks. Patients were assessed periodically via the Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), World Health Organization (WHO) motor development milestones, Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) Daily Activities and Mobility domains, and Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue questionnaire. Results: Of the 58 patients enrolled in TOPAZ, 35 were nonambulatory (mean age 7.3 years). The mean change at 36 months in HFMSE score from baseline was +4.0 (standard deviation [SD]: 7.54), and + 2.4 (3.24) for RULM score (excluding n = 7 after scoliosis surgery). Caregiver-reported outcomes (PEDI-CAT and PROMIS Fatigue) showed improvements from baseline over 36 months. In addition, most patients (28/32) improved or maintained WHO motor milestones achieved at baseline. The most frequently reported treatment-emergent adverse events were pyrexia (48.6%), nasopharyngitis (45.7%), COVID-19 infection (40.0%), vomiting (40.0%), and upper respiratory tract infection (31.4%). Conclusion: The benefit of apitegromab treatment observed at 12 months was sustained at 36 months with no new safety findings.

16.
Mol Neurobiol ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102109

RESUMEN

This study was dedicated to investigating the effects of microRNA-128-3p (miR-128-3p) on neuronal apoptosis and neurobehavior in cerebral palsy (CP) rats via the Smurf2/YY1 axis.In vivo modeling of hypoxic-ischemic (HI) CP was established in neonatal rats. Neurobehavioral tests (geotaxis reflex, cliff avoidance reaction, and grip test) were measured after HI induction. The HI-induced neurological injury was evaluated by HE staining, Nissl staining, TUNEL staining, immunohistochemical staining, and RT-qPCR. The expression of miR-128-3p, Smurf2, and YY1 was determined by RT-qPCR and western blot techniques. Moreover, primary cortical neurons were used to establish the oxygen and glucose deprivation (OGD) model in vitro, cell viability was detected by CCK-8 assay, neuronal apoptosis was assessed by flow cytometry and western blot, and the underlying mechanism between miR-128-3p, Smurf2 and YY1 was verified by bioinformatics analysis, dual luciferase reporter assay, RIP, Co-IP, ubiquitination assay, western blot, and RT-qPCR.In vivo, miR-128-3p and YY1 expression was elevated, and Smurf2 expression was decreased in brain tissues of hypoxic-ischemic CP rats. Downregulation of miR-128-3p or overexpression of Smurf2 improved neurobehavioral performance, reduced neuronal apoptosis, and elevated Nestin and NGF expression in hypoxic-ischemic CP rats, and downregulation of Smurf2 reversed the effects of downregulation of miR-128-3p on neurobehavioral performance, neuronal apoptosis, and Nestin and NGF expression in hypoxic-ischemic CP rats, while overexpression of YY1 reversed the effects of Smurf2 on neurobehavioral performance, neuronal apoptosis, and Nestin and NGF expression in hypoxic-ischemic CP rats. In vitro, downregulation of miR-128-3p effectively promoted the neuronal survival, reduced the apoptosis rate, and decreased caspase3 protein expression after OGD, and overexpression of YY1 reversed the ameliorative effect of downregulation of miR-128-3p on OGD-induced neuronal injury. miR-128-3p targeted to suppress Smurf2 to lower YY1 ubiquitination degradation and decrease its expression.Inhibition of miR-128-3p improves neuronal apoptosis and neurobehavioral changes in hypoxic-ischemic CP rats by promoting Smurf2 to promote YY1 ubiquitination degradation and reduce YY1 expression.

17.
Neurol Sci ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39190170

RESUMEN

PURPOSE: A network meta-analysis was utilized to compare the rehabilitative effectiveness of different exercise interventions on motor function in cerebral palsy(CP) patients. METHODS: Computer searches were conducted across 9 databases, including PubMed, Cochrane Library, Scopus, Web of Science, Embase, and others, to identify randomized controlled trials focusing on different exercise interventions aimed at enhancing motor function in CP patients. The search spanned from the inception of the databases to January 31, 2024. RESULTS: 20 articles, encompassing 570 patients and evaluating three types of exercise interventions, were included in the analysis. Results showed that aerobic training, resistance training, and mixed training exhibited superior outcomes compared to the control group, as evidenced by improvements in Gross Motor Function Measure scores, muscle strength, gait speed, and 10-Meter Walk Test scores (P < 0.05). Furthermore, the network meta-analysis revealed that resistance training ranked highest in enhancing gross motor function and gait speed among CP patients, while mixed training was deemed most effective in improving muscle strength and 10-Meter Walk Test scores. CONCLUSION: Exercise interventions have been shown to significantly improve motor function in CP patients. Among these, resistance training and mixed training stand out for their effectiveness in enhancing walking capabilities. Resistance training is specifically aimed at improving gross motor function, while mixed training focuses on increasing muscle strength.

18.
J Stroke Cerebrovasc Dis ; : 107961, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39173684

RESUMEN

OBJECTIVES: Persistent lower limb dysfunction is a major challenge in post-stroke recovery. Repetitive transcranial magnetic stimulation is recognized for addressing post-stroke motor deficits. Our study explores the efficacy of combining rTMS with gait-adaptive training to enhance lower limb function and regulatory mechanisms in subacute stroke. MATERIALS AND METHODS: This randomized controlled trial enrolled 27 patients with subacute hemiparesis, dividing them into experimental and control groups. Both groups underwent gait-adaptability training 5 times/week for 4 weeks, with the experimental group receiving daily low-frequency transcranial magnetic stimulation before training. Primary outcomes included the pairwise derived brain symmetry index, lower-extremity Fugl-Meyer Assessment, 10-meter walk test, and Berg Balance Scale. Assessments occurred before and after the four-week intervention. RESULTS: The experimental and control groups showed significant improvements in the Fugl-Meyer Assessment, 10-meter walk test, and Berg Balance Scale after the 4-week intervention compared to baseline (all p<0.05). However, the experimental group demonstrated significantly greater improvements compared to the control group in the Fugl-Meyer Assessment (p=0.024) and the 10-meter walk test (p=0.033). Additionally, the experimental group exhibited a more pronounced decrease in the pairwise derived brain symmetry index (p=0.026) compared to the control group. Within the experimental group, the cortical subgroup's pairwise derived brain symmetry index was significantly lower than that of the control group (p=0.006). CONCLUSIONS: Combining low-frequency transcranial magnetic stimulation with Gait-Adaptive Training effectively enhances lower limb function and Regulatory mechanisms of the cerebral hemisphere in subacute stroke recovery, and it can provide rapid and effective rehabilitation effect compared with gait adaptation training alone.

19.
Clin Pediatr (Phila) ; : 99228241274295, 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39183559

RESUMEN

Our study utilized Rasch Analysis to examine the psychometric properties of 61-items fine motor function measure (FMFM) in children with cerebral palsy (CP). Partial credit model (PCM) was utilized to test the reliability and validity of FMFM. The response pattern of this samples displayed acceptable fitness to PCM. The analysis results supported the assumption of 1-dimensionality of FMFM. Disordered category thresholds were found in 30 items. Differential item functioning (DIF) was detected in 23 items. Participants with different CP subtypes in different age groups may perform in differently responses patterns. The Rasch analysis produces reliable evidence to support the clinical application of FMFM. Some items may produce inaccurate measurements originated from category structures. Difference in age groups and symptom topography may be associated with variation in fine motor ability among children with CP and leading to unnecessary assessment bias. Hence, FMFM items need modifications to calibrate the former item formulation.

20.
J Neuroeng Rehabil ; 21(1): 144, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39169408

RESUMEN

BACKGROUND: Children with unilateral cerebral palsy (CP) exhibit motor impairments predominantly on one side of the body, while also having ipsilesional and bilateral impairments. These impairments are known to persist through adulthood, but their extent have not been described in adults with CP. This study's aim is to characterize bilateral and unilateral upper limbs impairments in adults with CP. METHODS: Nineteen adults with CP (34.3 years old ± 11.5) performed three robotic assessments in the Kinarm Exoskeleton Lab, including two bilateral tasks (Object Hit [asymmetric independent goals task] and Ball on Bar [symmetric common goal task]) and one unilateral task (Visually Guided Reaching, performed with the more affected arm [MA] and less affected arm [LA]). Individual results were compared to sex, age and handedness matched normative data, describing the proportion of participants exhibiting impairments in each task-specific variable (e.g., Hand speed), each performance category (e.g., Feedforward control) and in global task performance. Associations were assessed using Spearman correlation coefficients between: 1: the results of the MA and LA of each limb in the unilateral task; and 2: the results of each limb in the unilateral vs. the bilateral tasks. RESULTS: The majority of participants exhibited impairments in bilateral tasks (84%). The bilateral performance categories (i.e., Bimanual) identifying bilateral coordination impairments were impaired in the majority of participants (Object Hit: 57.8%; Ball on Bar: 31.6%). Most of the participants were impaired when performing a unilateral task with their MA arm (63%) and a smaller proportion with their LA arm (31%). The Feedforward control was the unilateral performance category showing the highest proportion of impaired participants while displaying the strongest relationship between the MA and LA arms impairments (rs = 0.93). Feedback control was the unilateral performance category most often associated with impairments in bilateral tasks (6 out of 8 performance categories). CONCLUSIONS: Adults with CP experienced more impairment in bilateral tasks while still having substantial impairments in unilateral tasks. They frequently display Feedforward control impairments combined with a higher reliance on Feedback control during both bilateral and unilateral tasks, leading to poorer motor performance.


Asunto(s)
Parálisis Cerebral , Robótica , Extremidad Superior , Humanos , Parálisis Cerebral/fisiopatología , Parálisis Cerebral/complicaciones , Masculino , Femenino , Adulto , Extremidad Superior/fisiopatología , Robótica/instrumentación , Persona de Mediana Edad , Adulto Joven , Desempeño Psicomotor/fisiología , Dispositivo Exoesqueleto , Lateralidad Funcional/fisiología
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