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Keywords = cerebral palsy

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16 pages, 2713 KiB  
Review
Aquatic Therapy in Children and Adolescents with Disabilities: A Scoping Review
by Anna Ogonowska-Slodownik, Oliwia Jakobowicz, Lyndsay Alexander, Andresa R. Marinho-Buzelli, Catherine Devion and Natalia Morgulec-Adamowicz
Children 2024, 11(11), 1404; https://doi.org/10.3390/children11111404 - 20 Nov 2024
Viewed by 317
Abstract
Globally, around 1 in 10 children aged 0–17 years have moderate-to-severe disabilities. The aquatic environment provides hydrostatic and hydrodynamic characteristics that make exercise and therapy feasible for children and adolescents with disabilities. The objective of this scoping review is to understand the extent [...] Read more.
Globally, around 1 in 10 children aged 0–17 years have moderate-to-severe disabilities. The aquatic environment provides hydrostatic and hydrodynamic characteristics that make exercise and therapy feasible for children and adolescents with disabilities. The objective of this scoping review is to understand the extent and type of evidence in relation to the use of aquatic therapy in children and adolescents with disabilities. The eligibility criteria were as follows: participants—children and/or adolescents with disabilities aged from 6 to 18 years old; concept—aquatic therapy interventions; context—any available setting. The databases searched included MEDLINE, CINAHL, EMBASE, PsycINFO, AMED, Eric, Scopus, Web of Science, Epistemonikos, and one register, Cochrane Central Register of Controlled Trials. In total, 52 reports met the inclusion criteria. Most of the studies included children/adolescents with autism spectrum disorder (ASD; 46.7%)—442 participants in 21 studies in total. The majority of interventions were based on aquatic exercise (35%). Most often, interventions were conducted for 8 weeks, with 2 sessions a week lasting 60 min. The most common type of intervention for children and adolescents with ASD and Down syndrome was swimming. Participants with attention deficit hyperactivity disorder, neuromuscular disorders, and cerebral palsy were more often treated with aquatic exercises. This scoping review could guide practitioners, clinicians, and researchers on what type, setting, and content of aquatic therapy interventions, including exercise types, intervention duration, number of sessions, frequency, facility, and provider, are used with children and adolescents with disabilities. Full article
(This article belongs to the Special Issue Advances in Rehabilitation of Children with Disabilities: 2nd Edition)
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<p>PRISMA flow chart [<a href="#B27-children-11-01404" class="html-bibr">27</a>].</p>
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<p>Map with the number of studies published in different countries.</p>
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<p>Number of publications, number of participants, and types of disabilities published since 2012. Note: The size of the bubbles represents the number of participants; ASD—autism spectrum disorder; ADHD—attention deficit hyperactivity disorder; CP—cerebral palsy; DS—down syndrome; NMD—neuromuscular disorder.</p>
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<p>Characteristics of the aquatic interventions. ASD—autism spectrum disorder; ADHD—attention deficit hyperactivity disorder; CP—cerebral palsy; DS—down syndrome; NMD—neuromuscular disorder; NR—not reported. [<a href="#B11-children-11-01404" class="html-bibr">11</a>,<a href="#B13-children-11-01404" class="html-bibr">13</a>,<a href="#B15-children-11-01404" class="html-bibr">15</a>,<a href="#B28-children-11-01404" class="html-bibr">28</a>,<a href="#B29-children-11-01404" class="html-bibr">29</a>,<a href="#B30-children-11-01404" class="html-bibr">30</a>,<a href="#B31-children-11-01404" class="html-bibr">31</a>,<a href="#B32-children-11-01404" class="html-bibr">32</a>,<a href="#B33-children-11-01404" class="html-bibr">33</a>,<a href="#B34-children-11-01404" class="html-bibr">34</a>,<a href="#B35-children-11-01404" class="html-bibr">35</a>,<a href="#B36-children-11-01404" class="html-bibr">36</a>,<a href="#B37-children-11-01404" class="html-bibr">37</a>,<a href="#B38-children-11-01404" class="html-bibr">38</a>,<a href="#B39-children-11-01404" class="html-bibr">39</a>,<a href="#B40-children-11-01404" class="html-bibr">40</a>,<a href="#B41-children-11-01404" class="html-bibr">41</a>,<a href="#B42-children-11-01404" class="html-bibr">42</a>,<a href="#B43-children-11-01404" class="html-bibr">43</a>,<a href="#B44-children-11-01404" class="html-bibr">44</a>,<a href="#B45-children-11-01404" class="html-bibr">45</a>,<a href="#B46-children-11-01404" class="html-bibr">46</a>,<a href="#B47-children-11-01404" class="html-bibr">47</a>,<a href="#B48-children-11-01404" class="html-bibr">48</a>,<a href="#B49-children-11-01404" class="html-bibr">49</a>,<a href="#B50-children-11-01404" class="html-bibr">50</a>,<a href="#B51-children-11-01404" class="html-bibr">51</a>,<a href="#B52-children-11-01404" class="html-bibr">52</a>,<a href="#B53-children-11-01404" class="html-bibr">53</a>,<a href="#B54-children-11-01404" class="html-bibr">54</a>,<a href="#B55-children-11-01404" class="html-bibr">55</a>,<a href="#B56-children-11-01404" class="html-bibr">56</a>,<a href="#B57-children-11-01404" class="html-bibr">57</a>,<a href="#B58-children-11-01404" class="html-bibr">58</a>,<a href="#B59-children-11-01404" class="html-bibr">59</a>,<a href="#B60-children-11-01404" class="html-bibr">60</a>,<a href="#B61-children-11-01404" class="html-bibr">61</a>,<a href="#B62-children-11-01404" class="html-bibr">62</a>,<a href="#B63-children-11-01404" class="html-bibr">63</a>,<a href="#B64-children-11-01404" class="html-bibr">64</a>,<a href="#B65-children-11-01404" class="html-bibr">65</a>,<a href="#B66-children-11-01404" class="html-bibr">66</a>,<a href="#B67-children-11-01404" class="html-bibr">67</a>,<a href="#B68-children-11-01404" class="html-bibr">68</a>,<a href="#B69-children-11-01404" class="html-bibr">69</a>,<a href="#B70-children-11-01404" class="html-bibr">70</a>,<a href="#B71-children-11-01404" class="html-bibr">71</a>,<a href="#B72-children-11-01404" class="html-bibr">72</a>,<a href="#B73-children-11-01404" class="html-bibr">73</a>,<a href="#B74-children-11-01404" class="html-bibr">74</a>,<a href="#B75-children-11-01404" class="html-bibr">75</a>,<a href="#B76-children-11-01404" class="html-bibr">76</a>,<a href="#B77-children-11-01404" class="html-bibr">77</a>].</p>
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<p>Specialists delivering aquatic interventions.</p>
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<p>Type of disability and the type of intervention. Note: Thicker line represent more studies; ASD—autism spectrum disorder; ADHD—attention deficit hyperactivity disorder; CP—cerebral palsy; DS—down syndrome; NMD—neuromuscular disorder.</p>
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20 pages, 935 KiB  
Review
Upper Limb Therapy for Infants and Young Children with Unilateral Cerebral Palsy: A Clinical Framework
by Susan Greaves and Brian Hoare
J. Clin. Med. 2024, 13(22), 6873; https://doi.org/10.3390/jcm13226873 - 15 Nov 2024
Viewed by 784
Abstract
Early detection and rehabilitation interventions are essential to optimise motor function in infants and young children with unilateral cerebral palsy. In this paper we report a clinical framework aimed at enhancing upper limb therapy for infants and young children with unilateral cerebral palsy [...] Read more.
Early detection and rehabilitation interventions are essential to optimise motor function in infants and young children with unilateral cerebral palsy. In this paper we report a clinical framework aimed at enhancing upper limb therapy for infants and young children with unilateral cerebral palsy during a sensitive period of brain development. We describe two major therapeutic approaches based on motor learning principles and evidence: constraint-induced movement therapy and bimanual therapy. These two therapies have demonstrated efficacy in older children and emerging evidence is available for their application to infants younger than 2 years of age. To provide clinicians with guidance as to when to implement these therapies, we discuss the key consideration when undertaking upper limb therapy programs. In addition, we describe the factors to consider when choosing which approach may be suitable for an individual child and family. Detailed strategies for implementing these therapies in infants and young children of different ability levels are given. Full article
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<p>Unimanual action-focused goals targeted using constraint-induced movement therapy.</p>
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<p>Bimanual action-focused goals targeted using bimanual therapy.</p>
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10 pages, 837 KiB  
Article
Bladder and Bowel Dysfunction Rehabilitation in Children with Acquired Brain Injury
by Rita Chiminello, Chiara Pellegrino, Noemi Deanesi, Giulia Barone, Ida Barretta, Gaia Paolella, Maria Luisa Capitanucci, Antonio Maria Zaccara, Maria Laura Sollini, Giacomo Esposito, Donatella Lettori, Gessica Della Bella, Enrico Castelli and Giovanni Mosiello
Children 2024, 11(11), 1382; https://doi.org/10.3390/children11111382 - 14 Nov 2024
Viewed by 338
Abstract
Objective: To evaluate neurogenic bladder and bowel dysfunction (NBBD) in children with cerebral palsy (CP) and acquired brain injury (ABI), a condition considered less frequent in those patients than in children with spinal cord injury (SCI), and to study the relationship between NBBD [...] Read more.
Objective: To evaluate neurogenic bladder and bowel dysfunction (NBBD) in children with cerebral palsy (CP) and acquired brain injury (ABI), a condition considered less frequent in those patients than in children with spinal cord injury (SCI), and to study the relationship between NBBD and disability grade in this population. Study Design: We retrospectively reviewed the clinical data of all patients (aged 3–18 years old) admitted during a three-month observation in our neurorehabilitation department. Data collected were as follows: demographic parameters; disability status (Wee-FIM Scale, Gross Motor Function Classification System (GMFCS) and the Communication Function Classification System); and gastrointestinal and urological symptoms (diaries, Bristol scale, Pad Test and International Consultation on Incontinence Modular Questionnaire). Results: Sixty patients were enrolled (31 females, 29 males): 30 CP, 17 ABI, 3 SCI, and 10 others with neurological diseases. All presented urinary incontinence without gender differences. CP and ABI had major incidences of bowel dysfunction (50% and 64.7%, respectively) and SCI of urinary tract infections (66.6%) and enuresis (100%). A major incidence of symptoms was recorded in patients with higher GMFCS levels (level 3-4-5). Conclusions: NBBD has a high frequency in children with CP and ABI, as in SCI. More attention is needed from pediatricians and pediatric urologists for this clinical entity. Further studies are needed to better understand clinical relevance and, therefore, to establish specific management. Full article
(This article belongs to the Section Pediatric Nephrology & Urology)
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<p>Average Wee-FIM scores divided by pathology (<span class="html-italic">p</span> value for operation in ANOVA).</p>
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<p>Distribution of GMFCS levels for each group of patients.</p>
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<p>Distribution of CFCS levels for each group of patients.</p>
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16 pages, 4416 KiB  
Article
Raloxifene Protects Oxygen-Glucose-Deprived Astrocyte Cells Used to Mimic Hypoxic-Ischemic Brain Injury
by Nicolás Toro-Urrego, Juan P. Luaces, Tamara Kobiec, Lucas Udovin, Sofía Bordet, Matilde Otero-Losada and Francisco Capani
Int. J. Mol. Sci. 2024, 25(22), 12121; https://doi.org/10.3390/ijms252212121 - 12 Nov 2024
Viewed by 321
Abstract
Perinatal asphyxia (PA) is a clinical condition characterized by oxygen supply suspension before, during, or immediately after birth, and it is an important risk factor for neurodevelopmental damage. Its estimated 1/1000 live births incidence in developed countries rises to 5–10-fold in developing countries. [...] Read more.
Perinatal asphyxia (PA) is a clinical condition characterized by oxygen supply suspension before, during, or immediately after birth, and it is an important risk factor for neurodevelopmental damage. Its estimated 1/1000 live births incidence in developed countries rises to 5–10-fold in developing countries. Schizophrenia, cerebral palsy, mental retardation, epilepsy, blindness, and others are among the highly disabling chronic pathologies associated with PA. However, so far, there is no effective therapy to neutralize or reduce PA-induced harm. Selective regulators of estrogen activity in tissues and selective estrogen receptor modulators like raloxifene have shown neuroprotective activity in different pathological scenarios. Their effect on PA is yet unknown. The purpose of this paper is to examine whether raloxifene showed neuroprotection in an oxygen–glucose deprivation/reoxygenation astrocyte cell model. To study this issue, T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37 °C in a hypoxia chamber with 1% O2 for 3, 6, 12, and 24 h. Cultures were supplemented with raloxifene 10, and 100 nM during both glucose and oxygen deprivation and reoxygenation periods. Raloxifene 100 nM and 10 nM improved cell survival—65.34% and 70.56%, respectively, compared with the control cell groups. Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifene cotreatment. Raloxifene co-treatment reduced superoxide production by 72.72% and peroxide production by 57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-h oxygen–glucose deprivation followed by 3, 6, and 9 h of reoxygenation, respectively. Therefore, raloxifene improved cell survival and mitochondrial membrane potential and reduced lipid peroxidation and reactive oxygen species (ROS) production, suggesting a direct effect on mitochondria. In this study, raloxifene protected oxygen–glucose-deprived astrocyte cells, used to mimic hypoxic–ischemic brain injury. Two examiners performed the qualitative assessment in a double-blind fashion. Full article
(This article belongs to the Special Issue New Trends in Molecular Research of Aneurysm and Brain Injury)
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<p>Raloxifene decreased OGD-induced cell death. (<b>A</b>) T98G cells were treated with different concentrations of raloxifene during 6 h of OGD and 3 h of reoxygenation, and cell viability was assessed by MTT assay. Data are represented as the mean ± SEM of four independent experiments. Control (101.99 ± 1.85); OGD/R (52.59 ± 2.02); OGD/R + 100 nM raloxifene (65.34 ± 2.03); OGD/R + 10 nM raloxifene (70.56 ± 2.36). Data were examined by analysis of variance, followed by the post hoc Dunnet’s test for between-group comparisons and Tukey’s test for multiple comparisons, * <span class="html-italic">p</span> &lt; 0.005. (<b>B</b>) Cell surface quantification with different concentrations of raloxifene during 6 h of OGD and 3 h of reoxygenation. Data are represented as the mean ± SEM of four independent experiments. Control (225.3 ± 13.01); OGD/R (278.7 ± 18.51); OGD/R + 100 nM raloxifene (318.2 ± 21.86); OGD/R + 10 nM raloxifene (277.1 ± 18.16). Data were examined by analysis of variance, followed by the post hoc Dunnet’s test for between-group comparisons and Tukey’s test for multiple comparisons, * <span class="html-italic">p</span> &lt; 0.005. (<b>C</b>–<b>F</b>) Raloxifene reduced morphological alterations induced by oxygen–glucose deprivation/reoxygenation. Representative microphotographs showing the morphology of cells exposed to (<b>C</b>) DMEM, (<b>D</b>) OGD/R, (<b>E</b>) OGD/R + Ral 100 nM, and (<b>F</b>) OGD/R + Ral 10 nM. Scale bar 50 µm.</p>
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<p>Raloxifene reduced superoxide production at 6 h of OGD and 3 h of reoxygenation. (<b>A</b>) Mean fluorescence values of dihydroethidium (DHE) intensity. (<b>B</b>–<b>E</b>) Representative fluorescence micrographs of dihydroethidium (DHE) staining in T98G cells exposed to (<b>B</b>) DMEM, (<b>C</b>) OGD/R, (<b>D</b>) OGD/R + Ral 100 nM with 6 h of OGD and 3 h of reoxygenation, and (<b>E</b>) OGD/R + Ral 10 nM with 6 h of OGD and 3 h of reoxygenation. *** <span class="html-italic">p</span> &lt; 0.0001. Scale bar 50 µm.</p>
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<p>Raloxifene reduced peroxide production at 6 h of OGD and 6 h of reoxygenation. The figure shows the representative fluorescence microphotographs of 2′,7′-Dichlorofluorescin Diacetate (DCFDA) staining of T98G cells exposed to (<b>A</b>) Control, (<b>B</b>) OGD/R, (<b>C</b>) OGD/R, OGD/R + Ral 100 nM with 6 h of OGD and 6 h of reoxygenation, (<b>D</b>) OGD/R, OGD/R + Ral 10 nM with 6 h of OGD and 6 h of reoxygenation, and (<b>E</b>) the mean fluorescence values of DCFDA intensity measured by flow cytometry. Data are represented as the mean ± SEM of five independent experiments. Control (55.51 ± 1.03); OGD/R (131.00 ± 4.01); OGD/R + 100 nM raloxifene (75.15 ± 6.60); OGD/R + 10 nM raloxifene (72.38 ± 7.82). Data were examined by analysis of variance, followed by the post hoc Dunnet’s test for between-group comparisons and Tukey’s test for multiple comparisons **** <span class="html-italic">p</span> &lt; 0.0001. Scale bar 50 µm.</p>
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<p>Raloxifene attenuated mitochondrial membrane potential loss at 6 h of OGD and 3 h of reoxygenation. (<b>A</b>) The figure shows the mean fluorescence values. (<b>B</b>–<b>E</b>) Representative fluores-cence micrographs of tetra-methyl rhodamine methyl ester (TMRM) staining in T98G cells exposed to (<b>B</b>) OGD/R, (<b>C</b>) DMEM, (<b>D</b>) OGD/R + Ral 100 nM with 6 h of OGD and 3 h of reoxygenation, and (<b>E</b>) OGD/R + Ral 10 nM with 6 h of OGD and 3 h of reoxygenation. *** <span class="html-italic">p</span> &lt; 0.0001. Scale bar 50 µm.</p>
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<p>Raloxifene preserved mitochondrial mass in T98G cells exposed to 6 h of OGD and 3 h of reoxygenation. The figure shows the mitochondrial mass in T98G cells exposed to 6 h of oxygen–glucose deprivation (OGD) to 3 h (<b>A</b>–<b>D</b>), 6 h (<b>E</b>–<b>H</b>), and 9 h (<b>I</b>–<b>L</b>) of reoxygenation. The representative microphotographs of acridine orange (NAO) fluorescence in T98G astrocytic cells exposed to (<b>A</b>) DMEM, (<b>B</b>) OGD/R, (<b>C</b>) OGD/R + Ral 100 nM with 3 h of reoxygenation, and (<b>D</b>) OGD/R + Ral 10 nM with 3 h of reoxygenation. (<b>M</b>) Mean fluorescence values of NAO intensity in this period of insult. Data are represented as the mean ± SEM of five independent experiments. Control (6671.00 ± 86.18); OGD/R (1903.00 ± 155.30); OGD/R + 100 nM raloxifene (2940.00 ± 142.90); OGD/R + 10 nM raloxifene (3163.00 ± 119.80). (<b>E</b>) DMEM, (<b>F</b>) OGD/R, (<b>G</b>) OGD/R + Ral 100 nM with 6 h of reoxygenation, and (<b>H</b>) OGD/R + Ral 10 nM with 6 h of reoxygenation. (<b>N</b>) Mean fluorescence values of NAO intensity in this period of insult. Data are represented as the mean ± SEM of five independent experiments. Control (416.7.00 ± 39.47); OGD/R (183.1 ± 17.70); OGD + 100 nM raloxifene (238.4 ± 26.43); OGD + 10 nM raloxifene (314.6 ± 27.45) (<b>I</b>) DMEM, (<b>J</b>) OGD/R, (<b>K</b>) OGD/R + Ral 100 nM with 9 h of reoxygenation, and (<b>L</b>) OGD/R + Ral 10 nM with 9 h of reoxygenation. (<b>O</b>) Mean fluorescence values of NAO intensity in this period of insult. Data are represented as the mean ± SEM of five independent experiments. Control (452.20 ± 22.28); OGD/R (330.42 ± 23.45); OGD/R + 100 nM raloxifene (404.71 ± 12.34); OGD/R + 10 nM raloxifene (374.64 ± 19.78). Data were examined by analysis of variance, followed by the post hoc Dunnet’s test for between-group comparisons and Tukey’s test for multiple comparisons, * <span class="html-italic">p</span> &lt; 0.005, ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001. Scale bar 50 µm.</p>
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15 pages, 2201 KiB  
Article
Application of the Gait Kinematics Index in Patients with Cerebral Palsy
by Katarzyna Jochymczyk-Woźniak, Karolina Wawak, Robert Michnik and Katarzyna Nowakowska-Lipiec
Appl. Sci. 2024, 14(22), 10312; https://doi.org/10.3390/app142210312 - 9 Nov 2024
Viewed by 459
Abstract
Due to the complexity of the medical issues connected with cerebral palsy (CP), the classification of gait pathologies seems rather difficult. The aim of this study was to asses the usefulness of the Gait Kinematics Index (GKI) from a clinical point of view [...] Read more.
Due to the complexity of the medical issues connected with cerebral palsy (CP), the classification of gait pathologies seems rather difficult. The aim of this study was to asses the usefulness of the Gait Kinematics Index (GKI) from a clinical point of view in the population of patients with CP. The assessment of the possibilities of using the GKI in a group of patients with CP was conducted on the basis of the correlation of its results with the Gillette Gait Index (GGI) and Gait Deviation Index (GDI) values. The distribution of the index values was also evaluated with attention paid to the CP types and treatment methods. Analyses were performed on the basis of the gait test results in a group of 56 healthy children and 72 patients with CP. The GKI values for patients with CP were 1.55 ± 0.66, as opposed to 0.77 ± 0.17 for the reference group. A strong linear correlation was found between the values of the GKI and GGI (r = 0.8 ÷ 0.85), as well as between the GKI and GDI (r = −0.89 ÷ 0.9), obtained in children with CP. In addition, significant differences were found between the results obtained in all the groups of children with CP divided by treatment method (rehabilitation, botulinum, rhizotomy, p < 0.05), whereas in the groups of children divided by CP type, significant differences (p < 0.05) were found solely between diplegia and hemiplegia and between hemiplegia and quadriplegia. The results obtained were the same in the case of the GKI, GGI and GDI. To conclude, the results presented in this work confirm the clinical utility of the GKI in the population of patients with CP. Full article
(This article belongs to the Special Issue Biomechanics and Motor Control on Human Movement Analysis)
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<p>(<b>a</b>) Measurement stand BTS Smart, (<b>b</b>) patient during measurements.</p>
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<p>Scatter plot depicting dependence between indices, regression equations, and R<sup>2</sup> values: (<b>a</b>) GKI and GGI and (<b>b</b>) GKI and GDI.</p>
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<p>Scatter plot presenting dependence between the GKI and GGI, regression equations and R<sup>2</sup> values in the case of (<b>a</b>) right lower limb in patients with CP and (<b>b</b>) left lower limb in patients with CP.</p>
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<p>Scatter plot presenting dependence between the GKI and GDI, regression equations and R<sup>2</sup> values in the case of (<b>a</b>) right lower limb in patients with CP and (<b>b</b>) left lower limb in patients with CP.</p>
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<p>Distribution of results of (<b>a</b>) GKI, (<b>b</b>) GGI and (<b>c</b>) GDI in children treated with the different methods.</p>
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<p>Distribution of results of (<b>a</b>) GKI, (<b>b</b>) GGI and (<b>c</b>) GDI in children with different CP types.</p>
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18 pages, 811 KiB  
Article
Feasibility of Home-Based Early Infant Hybrid Therapy in Children with Unilateral Cerebral Palsy
by Rocío Palomo-Carrión, Helena Romay-Barrero, Elena Pinero-Pinto, Rita-Pilar Romero-Galisteo, María Coello-Villalón, Asunción Ferri-Morales, Purificación López-Muñoz and Cristina Lirio-Romero
J. Clin. Med. 2024, 13(22), 6725; https://doi.org/10.3390/jcm13226725 - 8 Nov 2024
Viewed by 352
Abstract
Background: The first stage of childhood is characterized by great neuronal plasticity. In Unilateral Cerebral Palsy (UCP), it is essential to carry out early treatment, with family involvement. The aim of this study was to investigate the feasibility of Early Infant Hybrid [...] Read more.
Background: The first stage of childhood is characterized by great neuronal plasticity. In Unilateral Cerebral Palsy (UCP), it is essential to carry out early treatment, with family involvement. The aim of this study was to investigate the feasibility of Early Infant Hybrid Therapy (eI-Hybrid) applied at home with family involvement in children with UCP aged 9–18 months, and to assess its preliminary effectiveness on bimanual functional performance. Methods: A single group of 10 children (12.8 months, SD = 3.4) performed the eI-Hybrid therapy. The main outcome was measured with the mini Assisting Hand Assessment scale (mini-AHA), functional goals were measured with the Goal Attainment Scale (GAS), and satisfaction expectations on intensive therapy were also recorded. Three measures were performed (week 0, week 10, and month 6). A repeated-measures ANOVA test was performed on the mini-AHA in order to observe the statistically significant differences in pairwise comparison. Results: Ten children completed the study and the parents’ expectations were fulfilled, indicating high caregiver compliance and high adherence to the treatment. Clinically relevant changes were observed between pre- and post-intervention measurements in BFP (pre: 41.9 (SD: 7.7), post: 50.9 (SD: 6.0) and in the follow-up at 6 months (50.3 (SD:5.6); p < 0.001). Families reported a high satisfaction. Conclusions: infant hybrid treatment is feasible to be performed at home with the family’s involvement, obtaining improvements in the affected upper limb for early-age UCP. Full article
(This article belongs to the Section Clinical Pediatrics)
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<p>Long-sleeved T-shirt restriction in left upper limb for use of affected upper limb, inducing shoulder flexion into specific activity to touch balloons.</p>
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<p>Infant hybrid flowchart.</p>
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23 pages, 3203 KiB  
Perspective
The Importance of Including Maternal Immune Activation in Animal Models of Hypoxic–Ischemic Encephalopathy
by Bailey Collins, Elise A. Lemanski and Elizabeth Wright-Jin
Biomedicines 2024, 12(11), 2559; https://doi.org/10.3390/biomedicines12112559 - 8 Nov 2024
Viewed by 538
Abstract
Hypoxic–ischemic encephalopathy (HIE) is a perinatal brain injury that is the leading cause of cerebral palsy, developmental delay, and poor cognitive outcomes in children born at term, occurring in about 1.5 out of 1000 births. The only proven therapy for HIE is therapeutic [...] Read more.
Hypoxic–ischemic encephalopathy (HIE) is a perinatal brain injury that is the leading cause of cerebral palsy, developmental delay, and poor cognitive outcomes in children born at term, occurring in about 1.5 out of 1000 births. The only proven therapy for HIE is therapeutic hypothermia. However, despite this treatment, many children ultimately suffer disability, brain injury, and even death. Barriers to implementation including late diagnosis and lack of resources also lead to poorer outcomes. This demonstrates a critical need for additional treatments for HIE, and to facilitate this, we need translational models that accurately reflect risk factors and interactions present in HIE. Maternal or amniotic infection is a significant risk factor and possible cause of HIE in humans. Maternal immune activation (MIA) is a well-established model of maternal infection and inflammation that has significant developmental consequences largely characterized within the context of neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. MIA can also lead to long-lasting changes within the neuroimmune system, which lead to compounding negative outcomes following a second insult. This supports the importance of understanding the interaction of maternal inflammation and hypoxic–ischemic outcomes. Animal models have been invaluable to understanding the pathophysiology of this injury and to the development of therapeutic hypothermia. However, each model system has its own limitations. Large animal models such as pigs may more accurately represent the brain and organ development and complexity in humans, while rodent models are more cost-effective and offer more possible molecular techniques. Recent studies have utilized MIA or direct inflammation prior to HIE insult. Investigators should thoughtfully consider the risk factors they wish to include in their HIE animal models. In the incorporation of MIA, investigators should consider the type, timing, and dose of the inflammatory stimulus, as well as the timing, severity, and type of hypoxic insult. Using a variety of animal models that incorporate the maternal–placental–fetal system of inflammation will most likely lead to a more robust understanding of the mechanisms of this injury that can guide future clinical decisions and therapies. Full article
(This article belongs to the Special Issue Understanding Diseases Affecting the Central Nervous System)
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<p>LPS and Poly(I:C) bind to toll-like receptors, which initiates intracellular pathways, initiating the transcription of proinflammatory genes.</p>
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<p>MIA initiates inflammation, which disrupts neurodevelopmental processes, leading to increased rates of ASD, schizophrenia, and epilepsy.</p>
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<p>Microglia exhibit different phenotypes, transcriptional markers, and functions depending on developmental timing and activation state. There are some caveats to the transcriptional markers presented in <a href="#biomedicines-12-02559-f003" class="html-fig">Figure 3</a>. Most developmental microglia have transcriptomes similar to homeostatic microglia. However, a subset referred to as proliferative-region-associated microglia (PAMs) have distinct transcriptional markers referenced here [<a href="#B133-biomedicines-12-02559" class="html-bibr">133</a>]. * Tmem119 and Hexb are often referred to as homeostatic markers. However, the expression of these genes does not change in proinflammatory microglia [<a href="#B134-biomedicines-12-02559" class="html-bibr">134</a>]. Therefore, it is more accurate to refer to these as general microglia markers. ** Many commonly used microglia identifiers are upregulated in proinflammatory microglia [<a href="#B135-biomedicines-12-02559" class="html-bibr">135</a>].</p>
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<p>HIE model comparison.</p>
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11 pages, 2575 KiB  
Article
Load Modulation Affects Pediatric Lower Limb Joint Moments During a Step-Up Task
by Vatsala Goyal, Keith E. Gordon and Theresa Sukal-Moulton
Biomechanics 2024, 4(4), 653-663; https://doi.org/10.3390/biomechanics4040047 - 6 Nov 2024
Viewed by 396
Abstract
Introduction: Performance in a single step has been suggested to be a sensitive measure of movement quality in pediatric clinical populations. Although there is less information available in children with typical development, researchers have postulated the importance of analyzing the effect of body [...] Read more.
Introduction: Performance in a single step has been suggested to be a sensitive measure of movement quality in pediatric clinical populations. Although there is less information available in children with typical development, researchers have postulated the importance of analyzing the effect of body weight modulation on the initiation of stair ascent, especially during single-limb stance where upright stability is most critical. The purpose of this study was to investigate the effect of load modulation from −20% to +15% of body weight on typical pediatric lower limb joint moments during a step-up task. Methods: Fourteen participants between 5 and 21 years who did not have any neurological or musculoskeletal concerns were recruited to perform multiple step-up trials. Peak extensor support and hip abduction moments were identified during the push-off and pull-up stance phases. Linear regressions were used to determine the relationship between peak moments and load. Mixed-effects models were used to estimate the effect of load on hip, knee, and ankle percent contributions to peak support moments. Results: There was a positive linear relationship between peak support moments and load in both stance phases, where these moments scaled with load. There was no relationship between peak hip abduction moments and load. While the ankle and knee were the primary contributors to the support moments, the hip contributed more than expected in the pull-up phase. Discussion: Clinicians can use these results to contextualize movement differences in pediatric clinical populations, including in those with cerebral palsy, and highlight potential target areas for rehabilitation for populations such as adolescent athletes. Full article
(This article belongs to the Special Issue Personalized Biomechanics and Orthopedics of the Lower Extremity)
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<p>A participant in the experimental set-up with retro-reflective markers.</p>
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<p>Representative kinetic (<b>A</b>,<b>C</b>) and kinematic (<b>B</b>,<b>D</b>) profiles from one participant during a no-load step up for the trailing leg (<b>A</b>,<b>B</b>) and the leading leg (<b>C</b>,<b>D</b>). On each <span class="html-italic">x</span>-axis, 0% corresponds to the start of a step-up trial at leading leg lift-off while 100% corresponds to the end of the trial at trailing leg initial contact with the step. On each <span class="html-italic">y</span>-axis, a positive magnitude indicates joint flexion/abduction while a negative magnitude indicates joint extension/adduction. Average hip abduction moments are in red. Individual lower limb sagittal plane moments are in gray, including the hip (gray dash), knee (gray dash–dot), and ankle (gray dot). The sum of these individual joint moments equals the extensor support moments shown in blue. Shaded regions represent one standard deviation. The black boxes on plots (<b>A</b>,<b>C</b>) indicate the push-off and pull-up stance phases, respectively.</p>
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<p>Peak support moments vs. load for the (<b>A</b>) push-off and (<b>B</b>) pull-up stance phases. All values are divided by their respective values in the no-load condition. The linear regression for both stance phases showed a significant relationship between the two variables, with y = 0.817x + 0.973 for the push-off phase (R<sup>2</sup> = 0.278) and y = 0.933x + 1.02 for the pull-up phase (R<sup>2</sup> = 0.498).</p>
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<p>Individual hip (orange), knee (yellow), and ankle (green) percent contributions to peak extensor support moment at the time of peak support moment for all loading conditions in the push-off stance phase (<b>A</b>,<b>C</b>,<b>E</b>) and the pull-up stance phase (<b>B</b>,<b>D</b>,<b>F</b>). A negative percent contribution represents a joint moment in flexion, while a positive percent contribution represents a joint moment in extension. Significant pairwise comparisons are shown by black brackets (corrected <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Peak hip abduction moments (red) and peak support moments (blue) vs. age for the no-load condition during the push-off and pull-up stance phases. Each point represents an individual no-load trial. All moment values are divided by participant weight, and colored arrows on the far left show the direction of increasing moment magnitude. Pearson’s correlation was significant for all relationships, with r-values of (<b>A</b>) +0.830, (<b>B</b>) +0.833, (<b>C</b>) +0.304, and (<b>D</b>) +0.358. Results indicate that the magnitude of peak hip abduction increases with age, while the magnitude of peak support moment decreases with age.</p>
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28 pages, 1717 KiB  
Systematic Review
Effectiveness of Robotic Devices for Medical Rehabilitation: An Umbrella Review
by Kei Kiyono, Shigeo Tanabe, Satoshi Hirano, Takuma Ii, Yuki Nakagawa, Koki Tan, Eiichi Saitoh and Yohei Otaka
J. Clin. Med. 2024, 13(21), 6616; https://doi.org/10.3390/jcm13216616 - 4 Nov 2024
Viewed by 962
Abstract
Background/Objectives: Clinical trials have investigated the efficacy of rehabilitation robotics for various pathological conditions, but the overall impact on rehabilitation practice remains unclear. We comprehensively examined and analyzed systematic reviews (SRs) of randomized controlled trials (RCTs) investigating rehabilitative interventions with robotic devices. Methods: [...] Read more.
Background/Objectives: Clinical trials have investigated the efficacy of rehabilitation robotics for various pathological conditions, but the overall impact on rehabilitation practice remains unclear. We comprehensively examined and analyzed systematic reviews (SRs) of randomized controlled trials (RCTs) investigating rehabilitative interventions with robotic devices. Methods: Four databases were searched using term combinations of keywords related to robotic devices, rehabilitation, and SRs. The SR meta-analyses were categorized into “convincing”, “highly suggestive”, “suggestive”, “weak”, or “non-significant” depending on evidence strength and validity. Results: Overall, 62 SRs of 341 RCTs involving 14,522 participants were identified. Stroke was most frequently reported (40 SRs), followed by spinal cord injury (eight SRs), multiple sclerosis (four SRs), cerebral palsy (four SRs), Parkinson’s disease (three SRs), and neurological disease (any disease causing limited upper- and lower-limb functioning; three SRs). Furthermore, 38, 21, and 3 SRs focused on lower-limb devices, upper-limb devices, and both upper- and lower-limb devices, respectively. Quantitative synthesis of robotic intervention effects was performed by 51 of 62 SRs. Robot-assisted training was effective for various outcome measures per disease. Meta-analyses offering suggestive evidence were limited to studies on stroke. Upper-limb devices were effective for motor control and activities of daily living, and lower-limb devices for walking independence in stroke. Conclusions: Robotic devices are useful for improving impairments and disabilities in several diseases. Further high-quality SRs including RCTs with large sample sizes and meta-analyses of these RCTs, particularly on non-stroke-related diseases, are required. Further research should also ascertain which type of robotic device is the most effective for improving each specific impairment or disability. Full article
(This article belongs to the Special Issue Innovations in Neurorehabilitation)
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<p>PRIOR flowchart. EEG, electroencephalography; EMG, electromyography; RCT, randomized controlled trials; tDCS, transcranial direct current stimulation.</p>
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<p>Number of systematic reviews (SRs), randomized controlled trials (RCTs), and participants according to diseases. Dark blue, upper-limb devices; blue, lower-limb devices; light blue, upper- and lower-limb devices. Number of SRs (<b>A</b>), RCTs (<b>B</b>), and participants (<b>C</b>). SRs on neurological disease included RCTs investigating stroke, cerebral palsy, and brain injury. Duplicates were excluded from RCTs (<b>B</b>) and corresponding participants (<b>C</b>).</p>
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<p>Number of robotic devices according to diseases. (<b>A</b>) Upper-limb devices; (<b>B</b>) lower-limb devices.</p>
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11 pages, 724 KiB  
Article
Epilepsy in Cerebral Palsy: Unraveling Prevalence, Risk Factors, and Subtype Associations in a Large-Scale Population Study
by Reem Abdullah Alyoubi and Ahmed Abu-Zaid
Medicina 2024, 60(11), 1809; https://doi.org/10.3390/medicina60111809 - 4 Nov 2024
Viewed by 494
Abstract
Background and Objective: Cerebral palsy (CP) constitutes a group of enduring movement disorders arising from non-progressive brain damage, often accompanied by epilepsy. This study aims to explore the prevalence of epilepsy in CP patients, dissecting demographic characteristics, healthcare parameters, and nuanced risk factors. [...] Read more.
Background and Objective: Cerebral palsy (CP) constitutes a group of enduring movement disorders arising from non-progressive brain damage, often accompanied by epilepsy. This study aims to explore the prevalence of epilepsy in CP patients, dissecting demographic characteristics, healthcare parameters, and nuanced risk factors. Materials and Methods: The study employed the National Inpatient Sample (NIS) database (2016–2019, four years). CP patients were identified through ICD-10 codes, excluding non-CP patients and those with missing values. Baseline characteristics of CP patients, such as age, subtype distribution, and types of epilepsy, were tabulated, and disparities were assessed using the chi-squared test. Univariate and multivariate logistic regression analyses were conducted to examine predictors of epilepsy according to CP subtypes and infant-related conditions. Data were presented as odds ratios (OR) with corresponding 95% confidence intervals (CI). Results: In this comprehensive analysis of 88,138 CP patients, 44,901 with epilepsy and 43,237 without epilepsy, disparities between those with and without epilepsy were uncovered, revealing distinct demographic patterns and healthcare characteristics. Spastic diplegic CP showed the strongest association with epilepsy (adjusted OR = 1.88, 95% CI [1.73–2.04], p < 0.0001), underscoring the significance of subtype-specific considerations. Perinatal infection emerged as a noteworthy risk factor for epilepsy development (adjusted OR = 1.61, 95% CI [1.17–2.23], p = 0.004). Conclusions: The study provides nuanced insights into the prevalence and associations of epilepsy in CP patients. Specific CP subtypes and perinatal factors play pivotal roles in epilepsy risk. These findings offer a foundation for tailored clinical management and support services, addressing the complex needs of individuals with CP and epilepsy. Full article
(This article belongs to the Section Neurology)
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<p>Graphical summary of the three specific objectives of the current research. CP: cerebral palsy; OR: odds ratio.</p>
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10 pages, 720 KiB  
Article
Follow-Up of Neonatal Hearing Screening in the Risk Factor Group for Hearing Loss: Results from a Tertiary Medical Center
by Miriam Geal Dor, Menachem Gross and Cahtia Adelman
Children 2024, 11(11), 1336; https://doi.org/10.3390/children11111336 - 31 Oct 2024
Viewed by 480
Abstract
Introduction: Universal newborn hearing screening has been successfully implemented in many places around the world, and it is recommended that cases with risk factors for hearing loss be followed-up regardless of hearing screening results. However, there is a need for clarity regarding the [...] Read more.
Introduction: Universal newborn hearing screening has been successfully implemented in many places around the world, and it is recommended that cases with risk factors for hearing loss be followed-up regardless of hearing screening results. However, there is a need for clarity regarding the recommended rate of follow-up and which tests should be performed. The aim of this study was to assess the audiologic follow-up program for the group with risk factors. Method: Our retrospective study involved children of various ages with a risk factor for hearing loss who passed the initial neonatal hearing test but were later diagnosed with hearing loss. Out of 113,708 children born at Hadassah University Medical Center during the years 2013–2021, 6763 were at risk of hearing loss, and their follow-up audiologic test results were studied. Results: Audiologic testing including ABR, OAE, tympanometry and behavioral audiometry was performed in 1534 of 6763 (23%) of the risk factor group that returned to the hospital. In total, 73 children (4.7%) were diagnosed with hearing loss, 54 of whom failed the initial screening and 19 who had passed it. Further examination of the children that passed the initial screening and were later diagnosed with a hearing loss revealed that four cases had been missed in screening (one familial mild hearing loss, one familial progressive loss, one premature infant with a high tone loss, and one NICU graduate with CNS involvement). Another nine cases had late-onset hearing loss (three meningitis, five CMV, and one with a mitochondrial disease). An additional six cases were diagnosed late, and the age of onset of the hearing loss was unknown (two intubated, two with hydrocephalus, one with Cerebral Palsy, and one with general developmental delay). Conclusions: These results reveal the importance of implementing a refined protocol for monitoring hearing in the high-risk group of children that pass neonatal hearing screening with respect to which hearing tests should be conducted, at what age, and the duration of follow-up. Also, barriers to follow-up must be dealt with, and parents should be more involved in the monitoring process. Full article
(This article belongs to the Special Issue Research Advances in Ear and Hearing Disorders in Children)
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<p>The distribution of the different risk factor categories with the rate of infants that returned for follow-up in each risk factor group.</p>
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<p>Length of follow-up by age of the 1534 subjects that returned in the risk factor group (m = months; y = years).</p>
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<p>Hearing evaluation results of the 1534 subjects that returned for follow-up in the risk factor group.</p>
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17 pages, 2622 KiB  
Article
Feasibility of a Virtual Reality System in Speech Therapy: From Assessment to Tele-Rehabilitation in Children with Cerebral Palsy
by Gloria Mangani, Veronica Barzacchi, Clara Bombonato, Jessica Barsotti, Elena Beani, Valentina Menici, Carolina Ragoni, Giuseppina Sgandurra and Benedetta Del Lucchese
Children 2024, 11(11), 1327; https://doi.org/10.3390/children11111327 - 30 Oct 2024
Viewed by 663
Abstract
Background/Objectives: New advances in technologies are opening the possibility to support functional evaluation and rehabilitation in the field of speech therapy. Among available systems, a virtual reality rehabilitation system (VRRS, Khymeia) is a multi-domain ecosystem. Despite it being used in a limited number [...] Read more.
Background/Objectives: New advances in technologies are opening the possibility to support functional evaluation and rehabilitation in the field of speech therapy. Among available systems, a virtual reality rehabilitation system (VRRS, Khymeia) is a multi-domain ecosystem. Despite it being used in a limited number of studies, its use in speech-therapy has shown potential for promoting linguistic and literacy skills. Methods: This pilot study aims to assess the feasibility of single-session speech assessment with the VRRS in twenty-eight children with cerebral palsy (CP) by means of ad hoc questionnaires. Moreover, we evaluated the feasibility and the effects of an intensive tele-rehabilitation treatment with the VRRS in a subgroup of three children with unilateral CP. Results: Feasibility was generally good when using the VRRS for assessments. Both clinicians and children found it to have good usability, although acceptability scores were higher for children than clinicians. For tele-rehabilitation, overall improvements were observed in both linguistic and learning (reading and writing) skills. Conclusions: This study paves the way for VRRS use in speech-therapy tele-rehabilitation for children with CP and language and learning difficulties. Full article
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<p>(<b>a</b>) VRRS Home Kit Tablet: A case provided to patients and their families, equipped with a tablet and a set of integrated motion sensors, allowing for home tele-rehabilitation pathways. (<b>b</b>) Example of language domain’ exercise available within the wide library of the medical device.</p>
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<p>Mean usability and acceptability box-plot of children and clinicians responses to feasibility assessment questionnaires.</p>
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<p>Clinicians, parents, and children responses to feasibility-training questionnaires.</p>
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<p>Raw scores of lexical abilities at T0 and T1.</p>
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<p>Raw scores of metaphonological abilities at T0 and T1.</p>
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<p>(<b>a</b>) Raw scores of reading speed at T0 and T1. (<b>b</b>) Raw scores of reading accuracy at T0 and T1.</p>
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<p>Raw scores of writing accuracy at T0 and T1.</p>
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11 pages, 1078 KiB  
Article
Assessing the Efficacy of Lokomat Training in Pediatric Physiotherapy for Cerebral Palsy: A Progress Evaluation
by Michalina Błażkiewicz and Anna Hadamus
J. Clin. Med. 2024, 13(21), 6417; https://doi.org/10.3390/jcm13216417 - 26 Oct 2024
Viewed by 551
Abstract
Background: Gait disturbances in children with cerebral palsy can increase the hindrance caused by loss of independence and social engagement. The Lokomat, developed by Hocoma, shows promise as a supplementary tool for gait rehabilitation. This study investigates the impact of Lokomat training [...] Read more.
Background: Gait disturbances in children with cerebral palsy can increase the hindrance caused by loss of independence and social engagement. The Lokomat, developed by Hocoma, shows promise as a supplementary tool for gait rehabilitation. This study investigates the impact of Lokomat training on gait parameters and trends observed during training. Methods: A total of 26 children (13 male individuals) with a diagnosis of cerebral palsy (CP), aged 4 to 23 years, were enrolled in the study. Patients participated in a standard comprehensive rehabilitation program with additional Lokomat training sessions. Gait function was assessed using the Timed Up and Go Test (TUG) and the 10 m walking test (10mWT) at the beginning and end of the rehabilitation period. Changes in Lokomat parameters (step number, session duration, speed, body weight support, and guidance force) were also analysed. Results: The median duration of the 10mWT and TUG significantly decreased across the groups after the treatment program. The highest increases were observed for the number of steps taken. Across the entire cohort, the linear trend curves for distance and number of steps exhibited near-perpendicular alignment with the horizontal axis, suggesting significant improvement in these parameters. A consistent trend was noted for speed, with the trend line aligned parallel with the horizontal axis. Decreasing trends were observed for body weight support and guidance force. Conclusions: Therapy with the Lokomat functioning as the active gait orthosis can be used as a form of support to the standard rehabilitation protocol for patients with CP. Full article
(This article belongs to the Section Clinical Neurology)
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<p>The Lokomat Pro 6 (Hocoma AG, Volketswil, Switzerland) (picture provided from the manufacturer’s resources).</p>
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<p>The study protocol.</p>
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<p>An example of three linear trend functions without free expression demonstrates how the slope of their graphs changes based on the value of the directional coefficient.</p>
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14 pages, 513 KiB  
Article
Motor and Cognitive Trajectories in Infants and Toddlers with and at Risk of Cerebral Palsy Following a Community-Based Intervention
by Kanishka Baduni, Allison McIntyre, Caitlin P. Kjeldsen, Larken R. Marra, William C. Kjeldsen, Melissa M. Murphy, Owais A. Khan, Zhulin He, Kristin Limpose and Nathalie L. Maitre
Children 2024, 11(11), 1283; https://doi.org/10.3390/children11111283 - 24 Oct 2024
Viewed by 583
Abstract
Background: Early motor development is fundamental in driving cognitive skill acquisition. Motor delays in children with cerebral palsy (CP) often limit exploratory behaviors, decreasing opportunities or the quality of cognitive development, emphasizing the importance of early intervention. This study aimed to assess immediate [...] Read more.
Background: Early motor development is fundamental in driving cognitive skill acquisition. Motor delays in children with cerebral palsy (CP) often limit exploratory behaviors, decreasing opportunities or the quality of cognitive development, emphasizing the importance of early intervention. This study aimed to assess immediate and 5-month motor and cognitive changes in infants and toddlers at risk of or with CP after participation in a community-based program. Methods: Twenty-two children (mean age: 22 ± 7 months) classified using the Gross Motor Function Classification System (GMFCS) and mini-Manual Ability Classification System (mini-MACS) participated in a 6-day community-based activity program, with outcomes assessed using the Developmental Assessment of Young Children (DAYC-2). Results: Participants who met their motor goals post-participation had significantly higher cognitive scores (p = 0.006) 5 months after the program. Participants with higher functional motor abilities (GMFCS levels I–II, p = 0.052; mini-MACS levels I–II, p = 0.004) demonstrated better cognitive scores at 5 months, adjusted for baseline scores, than those with lower functional motor abilities. Conclusions: This study highlights the impact of motor improvements following an evidence-based community program on later cognitive development. Prospective studies investigating the mechanisms and mediation of cognitive progress in children with CP should investigate the effects of early motor interventions on long-term developmental trajectories. Full article
(This article belongs to the Section Pediatric Neurology & Neurodevelopmental Disorders)
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<p>Changes in DAYC-2 raw scores across assessment timepoints, not controlled for age, for (<b>a</b>) cognitive score and (<b>b</b>) motor scores (means are indicated by +). * Statistically Significant differences between groups across all time-points.</p>
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9 pages, 1222 KiB  
Brief Report
IL-1 Blockade Mitigates Autism and Cerebral Palsy Traits in Offspring In-Utero Exposed to Group B Streptococcus Chorioamnionitis
by Taghreed A. Ayash, Marie-Julie Allard, Mathilde Chevin and Guillaume Sébire
Int. J. Mol. Sci. 2024, 25(21), 11393; https://doi.org/10.3390/ijms252111393 - 23 Oct 2024
Viewed by 1179
Abstract
Group B Streptococcus (GBS) is one of the most common bacteria responsible for placental and neonatal infection and inflammation resulting in lifelong neurobehavioral impairments. In particular, GBS-induced chorioamnionitis is known in preclinical models to upregulate inflammatory pathways, primarily through the activation of the [...] Read more.
Group B Streptococcus (GBS) is one of the most common bacteria responsible for placental and neonatal infection and inflammation resulting in lifelong neurobehavioral impairments. In particular, GBS-induced chorioamnionitis is known in preclinical models to upregulate inflammatory pathways, primarily through the activation of the interleukin-1 (IL-1) pathway, leading to brain injury and subsequent neurodevelopmental issues. Previous studies from our laboratory using Lewis rat pups have shown that male offspring exposed in utero to GBS chorioamnionitis develop brain injuries leading to neurobehavioral impairments such as autistic traits. In the present study, we aimed to explore whether blocking the IL-1 pathway could prevent or mitigate these neurodevelopmental impairments in adulthood. Using our established preclinical model, we administered IL-1 receptor antagonist (IL-1Ra) to dams with GBS-induced chorioamnionitis. Here, we show that IL-1Ra administration to dams reversed autistic and cerebral palsy traits in male adult offspring exposed in utero to GBS. Hence, IL-1 blockade could serve as a therapeutic intervention against pathogen-induced neurodevelopmental disorders. This research supports the need for future human randomized controlled trials to assess IL-1 blockade administered during pregnancy or in newborns as a strategy to reduce the long-term neurobehavioral consequences of prenatal infections, such as autism, cerebral palsy, learning disabilities, and other neurodevelopmental disorders. Full article
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<p>Effect of the IL-1Ra treatment on maternal and pup weight gain and litter size. (<b>a</b>) Mean maternal weight gain (g) between gestational day (G)18 and G22 from n = 8–11 dams per experimental group; (<b>b</b>) mean male pup weight (g) from postnatal day (P)1 to P9 with n = 8–14 pups per experimental group; (<b>c</b>) mean number of pups per litter in 13–17 litters per experimental group. Data were expressed as mean ± SEM, using one-way or two-way ANOVA. ns: non-significant. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 refers to GBS compared to control. # <span class="html-italic">p</span> &lt; 0.05, ### <span class="html-italic">p</span> &lt; 0.001 refers to GBS + IL-1Ra compared to control.</p>
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<p>Effect of IL-1Ra on neurobehavioral impairments in offspring exposed in utero to GBS chorioamnionitis. (<b>a</b>) The latency before social interaction and (<b>b</b>) the number of social episodes were assessed during a 5 min period in an open-field apparatus at P40. (<b>c</b>) The travelled distance and (<b>d</b>) number of lines crossed were measured during a 5 min period in the open field at P80. Pairs of animals (from 4 to 6 litters) per experimental group were used for the social interaction test. n = 4–9 animals per experimental group from 4–5 litters were used for the open-field test. n = 3–6 animals per experimental group from 4–5 litters were used for IL-1ß titers. Data were expressed as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, using one-way ANOVA. (<b>e</b>) A significant correlation was found between IL-1ß blood titers at P1 and the distance travelled at P80 in males but not females, using the Spearman correlation test, <span class="html-italic">p</span> &lt; 0.05.</p>
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